Pacientes submetidos à revascularização do miocárdio (RM), frequentemente utilizam beta-bloqueadores no pré-operatório para o controle da angina pectoris, e continuam o tratamento após a cirurgia, para a redução de mortalidade e complicações cardiovasculares perioperatórias. Entretanto, a circulação extracorpórea (CEC), empregada na maioria das cirurgias cardíacas, pode alterar as concentrações plasmáticas e a disposição cinética de muitos fármacos, e consequentemente seus efeitos terapêuticos. O atenolol é um beta-bloqueador altamente hidrossolúvel, de absorção incompleta e eliminação renal-dependente. O objetivo deste estudo foi o de investigar a influência da CEC sobre as concentrações plasmáticas do atenolol no intra-operatório de cirurgia cardíaca, além de comparar a sua farmacocinética no pré e pós-operatório de RM com CEC, em pacientes com insuficiência coronariana. Investigou-se ainda, a variabilidade das concentrações plasmáticas do atenolol no período que antecede a cirurgia cardíaca. Na primeira etapa, avaliaram-se 19 pacientes coronarianos, em terapia crônica com atenolol PO, submetidos à cirurgia cardíaca com ou sem CEC. Na segunda parte, investigaram-se os períodos pré e pós-cirúrgico de 7 pacientes submetidos à RM com CEC e tratados com atenolol PO em regime de doses múltiplas. Todos os pacientes investigados apresentavam função renal dentro da normalidade ou leve disfunção renal, decorrente da idade e da insuficiência coronariana. O monitoramento do atenolol plasmático no intra-operatório de RM e o estudo farmacocinético realizado antes e após a revascularização, exigiram coletas de amostras sangüíneas seriadas. A quantificação do atenolol em plasma foi realizada através da cromatografia líquida de alta eficiência com detector de fluorescência e consistiu num procedimento analítico rápido, simples e de baixo custo. Apenas 200 L de plasma foram utilizados em cada análise cromatográfica. O estudo de validação demonstrou que o método desenvolvido apresenta alta linearidade, sensibilidade e seletividade adequadas, alta recuperação, boa precisão e exatidão, além de estabilidade e robustez. Conclui-se que a circulação extracorpórea altera as concentrações do atenolol no intra-operatório de RM, visto que o decaimento das concentrações plasmáticas mostrou-se mais pronunciado na ausência da CEC. Entretanto, apesar das maiores concentrações obtidas ao final da cirurgia com CEC, o atenolol mostra-se seguro, em virtude do baixo acúmulo do fármaco administrado em regime de doses múltiplas. Além disso, a disposição cinética do atenolol permaneceu inalterada, quando os períodos pré e pós-operatórios foram comparados; entretanto, registrou-se uma tendência à normalização do volume de distribuição e da depuração plasmática do atenolol após a revascularização. Adicionalmente, a ausência de correlação entre meia-vida biológica e volume aparente de distribuição sugere que, tanto no pré quanto no pós-operatório, as concentrações do atenolol dependem apenas da sua depuração plasmática. Finalmente, verificou-se que o atenolol apresenta baixa variabilidade inter-pacientes nos regimes posológicos empregados no tratamento da insuficiência coronariana. / Patients submitted to coronary artery bypass grafting (CABG) surgery frequently are using beta-blockers agents for the control of angina pectoris, and continue the treatment after the surgery to reduce the mortality and cardiovascular events. However, the technique of cardiopulmonary bypass (CPB), used in most cardiac surgeries with cardioplegia, causes important changes in the plasma concentrations and pharmacokinetics of many drugs and may also alter their therapeutic effects. Atenolol is a hydrophilic beta-blocker characterized by incomplete absorption, a relatively small volume of distribution and a renal function-dependent elimination. The objective of this study was to investigate the effects of CPB on the plasma concentrations of atenolol during the intra-operative period of cardiac surgery, as well as, to compare the pharmacokinetics of atenolol in the pre and post-operative periods of revascularization with CPB, in patients with coronary insufficiency. In addition, it was investigated the variability of plasma atenolol concentrations before the cardiac surgery. In the first part of the study, it was investigated 19 coronary patients, under chronic therapy with atenolol and submitted to cardiac surgery performed with and without CPB. At the second part, it was evaluated the pre and post-operative periods from 7 patients submitted to the CABG surgery with CPB, who were chronically treated with atenolol in a multiple regimen. All enrolled patients presented normal or slightly reduced renal function as a result of age and underlying disease. A serial blood samples collection was required for monitoring of plasma atenolol concentrations at the intra-operative period and also for pharmacokinetic study at the pre and post-CABG. The quantification of plasma atenolol was performed using high-performance liquid chromatography with fluorescence detection and consisted of a relatively rapid, simple and low-cost analytical procedure. Only 200 µL of plasma was used for each chromatographic analysis. Validation of this analytical method showed high linearity, adequate sensitivity and selectivity, high recovery, good accuracy and precision, in addition to stability and a guarantee of robustness. It was concluded that the CPB changes plasma atenolol concentrations in the intra-operative period, since a marked decrease in plasma atenolol concentrations was observed in patients undergoing cardiac surgery without CPB. Thus, despite the lower decline in plasma levels observed in patients submitted to CPB, atenolol can be used safely, due to the low accumulation of the drug administrated at multiple dose regimens. In addition, pharmacokinetics of atenolol remained unaltered when pre and post-operative periods were compared; although it was observed a tendency of normalization of volume of distribution and plasma clearance of atenolol after the revascularization. Moreover, the lack of correlation between biological half-life and apparent volume of distribution suggests that, in both periods, plasma atenolol concentration only depends on its plasma clearance. Finally, it was verified a small inter-patient variability of atenolol in the dose regimens used for the control of coronary insufficiency.

In this thesis, the photochemical and photocatalytic degradation of atenolol (ATL) and 2-phenylbenzimidazole-5-sulfonic acid (PBSA) have been investigated in aqueous solutions. Our results show that direct photolysis of ATL is weak and the indirect photolysis, e.g., induced by photosensitizers such as nitrate, may contributed to its major loss process in natural sunlit waters. In the case of PBSA, direct photolysis is found to be important while the indirect photolysis may play a less important role in its elimination in natural surface waters. The photolytic reactions (either direct or indirect) generally obey pseudo-first-order kinetics and can be influence by the solution pH, the co-existence of other water constituents such as dissolved organic matter (DOM) and bicarbonate ion (HCO3-). The photolytic degradation lead to a variety of intermediates and products. However, the reduction in TOC of the photolysis is usually found to be insignificant compared to the disappearance of the mother compound. Nevertheless, the observed decrease in toxicity toward fresh water species D. magna in nitrate-induced photodegradation of ATL implies indirect photolysis of ATL is possibly an important way to reduce the toxicity to ecosystem. It should be noted that direct and indirect photodegradation may process through different pathways and mechanism as observed in the photolysis of PBSA in this work. Photocatalytic oxidation of ATL and PBSA were carried out in illuminated aqueous TiO2 suspensions. Photocatalytic reactions normally follow pseudo-first-order kinetics. The kinetics are strongly affected by the photocatalyst type, the photocatalyst dosage, the solution pH value and the substrate concentration. Hydroxyl radical (HO*) was determined to be the major reactive specie responsible for the remarkable degradation of mother compounds. The degradation efficiency is largely influenced by the water matrices as well as the formation and transformation of intermediates. It should be noted that Degussa P25 showed the highest photocatalytic activity for oxidizing ATL and PBSA compared to pure anatase or rutile catalyst such as Hombikat UV 100, Millennium PC 500 and Aldrich rutile, which is in line with previous reports. The photocatalytic degradation of mother compounds results in the formation of various intermediates (e.g., formic, oxalic, malonic acid) and inorganic ions (e.g., NH4+, NO3-, SO42-). TOC decreases much more slowly as compared to the disappearance of the mother compounds, however, complete mineralization could be obtained with longer irradiation time

Dans ce travail, nous avons étudié la dégradation photochimique et photocatalytique de l'aténolol (ATL) et du 2-phénylbenzimidazole-5-sulfonique acide (PBSA) soit dans des solutions aqueuses de qualité milli-Q dopée ou non avec des espèces présentes dans les eaux naturelles (ions bicarbonate, nitrate, substances humiques) soit dans de l'eau naturelle (eau du Rhône). Nos résultats ont montré que la photolyse directe de l'ATL est faible, l'ATL présentant une faible absorbance pour les longueurs d'onde supérieures à 290 nm. C'est donc la photolyse induite par exemple par des photo-sensibilisateurs tels que le nitrate qui peuvent contribuer à son processus de dégradation dans les eaux naturelles ensoleillées. En revanche, dans le cas du PBSA, la photolyse directe a été jugée importante alors que la photolyse indirecte jouerait un rôle moindre dans les eaux de surface naturelles, cette dégradation étant fortement inhibé par la présence des ions hydrogénocarbonates. Dans les deux cas, les réactions de photolyse (directs ou indirects) obéissent généralement à des cinétiques de pseudo-premier ordre et peuvent être influencées par le pH de la solution, la coexistence d'autres constituants de l'eau tels que la matière organique dissoute (MOD) et de l'ion bicarbonate (HCO3-). L'oxydation photocatalytique de l'ATL et du PBSA ont également été étudiés dans des solutions aqueuses de TiO2 en suspension. Nous avons montré que les cinétiques étaient fortement dépendantes du type et de la concentration en photocatalyseur, du pH de la solution et de la concentration en substrat. Dans les deux cas, le radical hydroxyle serait la principale espèce réactive responsable de la dégradation de ces composés. Ici aussi, l'efficacité de la dégradation est largement influencée par les constituants de la matrice de l'eau. Il convient de noter que le TiO2 Degussa P25 a montré l'activité photocatalytique le plus élevée par rapport aux autres catalyseurs de type Hombikat UV 100, le PC 500 de millennium et le rutile d'Aldrich. En ce qui concerne la minéralisation des polluants, les mesures de COTmètre montrent une diminution beaucoup plus lente par rapport à la disparition des composés parents, cependant, la minéralisation complète peut être obtenue avec une plus longue durée d'irradiation / In this thesis, the photochemical and photocatalytic degradation of atenolol (ATL) and 2-phenylbenzimidazole-5-sulfonic acid (PBSA) have been investigated in aqueous solutions. Our results show that direct photolysis of ATL is weak and the indirect photolysis, e.g., induced by photosensitizers such as nitrate, may contributed to its major loss process in natural sunlit waters. In the case of PBSA, direct photolysis is found to be important while the indirect photolysis may play a less important role in its elimination in natural surface waters. The photolytic reactions (either direct or indirect) generally obey pseudo-first-order kinetics and can be influence by the solution pH, the co-existence of other water constituents such as dissolved organic matter (DOM) and bicarbonate ion (HCO3-). The photolytic degradation lead to a variety of intermediates and products. However, the reduction in TOC of the photolysis is usually found to be insignificant compared to the disappearance of the mother compound. Nevertheless, the observed decrease in toxicity toward fresh water species D. magna in nitrate-induced photodegradation of ATL implies indirect photolysis of ATL is possibly an important way to reduce the toxicity to ecosystem. It should be noted that direct and indirect photodegradation may process through different pathways and mechanism as observed in the photolysis of PBSA in this work. Photocatalytic oxidation of ATL and PBSA were carried out in illuminated aqueous TiO2 suspensions. Photocatalytic reactions normally follow pseudo-first-order kinetics. The kinetics are strongly affected by the photocatalyst type, the photocatalyst dosage, the solution pH value and the substrate concentration. Hydroxyl radical (HO•) was determined to be the major reactive specie responsible for the remarkable degradation of mother compounds. The degradation efficiency is largely influenced by the water matrices as well as the formation and transformation of intermediates. It should be noted that Degussa P25 showed the highest photocatalytic activity for oxidizing ATL and PBSA compared to pure anatase or rutile catalyst such as Hombikat UV 100, Millennium PC 500 and Aldrich rutile, which is in line with previous reports. The photocatalytic degradation of mother compounds results in the formation of various intermediates (e.g., formic, oxalic, malonic acid) and inorganic ions (e.g., NH4+, NO3-, SO42-). TOC decreases much more slowly as compared to the disappearance of the mother compounds, however, complete mineralization could be obtained with longer irradiation time

Os fármacos são essenciais para a preservação da saúde do homem e de animais e também na prevenção de doenças. Entretanto, seu alto consumo associado ao descarte incorreto e aos tratamentos ineficientes de águas e efluentes podem trazer grandes prejuízos ao meio ambiente como, por exemplo, a resistência bacteriana. O objetivo deste trabalho foi estudar a remoção de ampicilina (AMP), atenolol (ATN) e paracetamol (PAR), fármacos de três classes distintas, em soluções aquosas através da técnica de adsorção em carvão ativado granular (CAG). Foram realizados experimentos de adsorção em batelada avaliando o efeito dos parâmetros pH, tempo de contato e concentração de sólido adsorvente. O comportamento cinético da adsorção dos fármacos em carvão ativado granular foi avaliado por meio dos modelos de pseudo-primeira ordem, pseudosegunda ordem e difusão intrapartícula. Ainda, isotermas de equilíbrio para estes sistemas foram construídas em diferentes temperaturas (15, 25 e 35 °C) e analisadas através dos modelos de Langmuir, Freundlich e Sips. O processo de adsorção também foi avaliado através de ensaios termodinâmicos. A adsorção em coluna de leito fixo foi avaliada utilizando planejamentos experimentais para os fármacos e os efeitos da massa do leito de adsorvente (0,5 – 1,5 g) e da vazão de alimentação (10 – 15 mL min-1) foram estudados Ainda, a fim de se avaliar o comportamento dos fármacos quando em mistura, foram realizados ensaios de adsorção em batelada e em coluna de leito fixo da mistura de ampicilina e paracetamol. Os melhores resultados encontrados nos ensaios de adsorção batelada foram: pH 6 e concentração de sólido adsorvente de 10 g L-1 para os três fármacos. O tempo de adsorção mais adequado foi de 90 minutos para o ATN e 120 min para AMP e PAR. Nessas condições foi possível obter remoções de 90 %, 94 % e 96 % para a ampicilina, atenolol e paracetamol, respectivamente. O modelo cinético que melhor descreveu o processo de adsorção foi o de pseudo-primeira ordem, para os fármacos ampicilina e paracetamol, e pseudo-segunda ordem para o atenolol. As isotermas obtidas para os fármacos indicaram que o processo de adsorção é de natureza endotérmica, ou seja, a adsorção é favorecida com o aumento da temperatura. Para a AMP, o melhor ajuste das isotermas foi obtido pelo modelo de Langmuir nas temperaturas de 15 ºC e 25 ºC e pelo modelo de Sips na temperatura de 35 ºC. Para o ATN, o melhor ajuste foi obtido pelo modelo de Freundlich e, para o PAR, o modelo de Sips, nas três temperaturas estudadas. Os ensaios termodinâmicos indicaram que o processo de adsorção dos fármacos é favorável e espontâneo e comprovou a natureza endotérmica do processo Em relação aos resultados obtidos na adsorção em coluna de leito fixo foi observado que os tempos de ruptura e de saturação aumentam com o aumento da massa de sólido presente no leito e diminuem com o aumento da vazão. A massa de adsorvente apresentou efeito negativo sobre a fração de leito utilizado e foi significativa no processo de adsorção dos três fármacos. Já a vazão de alimentação só foi significativa na adsorção em leito fixo da AMP e apresentou efeito positivo na fração de leito utilizado. Os maiores volumes de efluente tratado foram obtidos com a maior massa de sólido utilizada (1,5 g) e com a menor vazão de alimentação testada (10 mL min-1). Na adsorção multicomponente em batelada, verificou-se que há concorrência entre os fármacos pelos sítios ativos do CAG disponíveis para adsorção. Os resultados obtidos nos ensaios das isotermas de adsorção mostraram que o comportamento dos fármacos em mistura é o mesmo que quando comparados individualmente. Os modelos que melhor se ajustaram aos dados experimentais foram os mesmos obtidos nos ensaios monocomponente, Langmuir para a AMP e Sips para o PAR. Da mesma forma que para os experimentos em coluna monocomponente, os ensaios multicomponentes demostraram que os tempos de ruptura e de saturação são maiores para o PAR. Entretanto, esses valores são menores do que na adsorção individual indicando que houve concorrência entre os fármacos pelos sítios do adsorvente. Os resultados encontrados indicam que a adsorção é uma alternativa viável para a remoção de fármacos, contribuindo, assim, para o avanço das pesquisas relacionadas ao tratamento de efluentes contaminados por estes poluentes. / Drugs are essential for preservation of human and animal health as well as for disease prevention. However, its high consumption associated with incorrect disposal and inefficient treatment of water and effluents can cause great damage to the environment such as bacterial resistance, for example. The objective of this work was to study the removal of ampicillin (AMP), atenolol (ATN) and paracetamol (PAR), drugs of three different classes, in aqueous solutions by adsorption technique in granular activated carbon (GAC). Adsorption experiments were carried out in batch evaluating the effect of parameters pH, contact time and concentration of solid adsorbent. The kinetic behavior of the adsorption of drugs in granular activated carbon was evaluated through the pseudofirst order, pseudo-second order and intraparticle diffusion models. Furthermore, equilibrium isotherms for these systems were made at different temperatures (15, 25 and 35 ° C) and analyzed using the Langmuir, Freundlich and Sips models. The adsorption process was also evaluated through thermodynamic tests. The fixed bed column adsorption was evaluated by experimental planning for drugs and the effects of mass of the adsorbent bed (0.5 to 1.5 g) and feed rate (10 - 15 ml min-1) were studied Also, in order to evaluate the behavior of the drugs when in mixture, adsorption tests were carried out in batch and in fixed bed column for the mixture of ampicillin and paracetamol. The best results found in the batch adsorption tests were: pH 6 and concentration of adsorbent solid of 10 g L-1 for the three drugs. The most suitable adsorption time was 90 minutes for ATN and 120 min for AMP and PAR. Under these conditions it was possible to obtain removals of 90%, 94% and 96% for ampicillin, atenolol and paracetamol respectively. The kinetic model that best described the adsorption process was the pseudo-first order for the ampicillin and paracetamol drugs and pseudo-second order for atenolol. The isotherms obtained for the drugs indicated that the adsorption process is of endothermic nature, that is, the adsorption is favored with the increase in temperature. For the AMP, the best isotherm adjustment was obtained by the Langmuir model at temperatures of 15 °C and 25 °C and by the Sips model at temperature of 35 °C. For the ATN, the best fit was obtained by the Freundlich model and, for PAR, the Sips model at the three temperatures studied. The thermodynamic tests indicated that the adsorption process of the drugs was favorable and spontaneous and confirmed the endothermic nature of the process Regarding the results obtained in adsorption in fixed bed column, it was observed that rupture and saturation times increase with the increase of the mass of solid present in the bed and decrease with the increase of flow. The adsorbent mass had a negative effect on the used bed fraction and was significant in the adsorption process of the three drugs. The feed flow was only significant in the adsorption in fixed bed of the AMP and had positive effect in the used bed fraction. The highest volumes of treated effluent were obtained with the largest mass of solid used (1,5 g) and with the lowest feed rate tested (10 mL min-1). In multicomponent adsorption in batch, it was found that there is competition between the drugs by the active sites of GAC available for adsorption. The results obtained in the adsorption isotherms tests showed that the behavior of the drugs in mixture is the same as when compared individually. The models that best fit the experimental data were the same ones obtained in the monocomponent tests, Langmuir for AMP and Sips for PAR. Similarly as for the monocomponent column experiments, the multicomponent tests showed that the break and saturation times are larger for the PAR. However, these values are lower than in individual adsorption indicating that there was competition between the drugs for the sites of the adsorbent. The results indicate that adsorption is a viable alternative for the removal of drugs, thus contributing to the advancement of research related to the treatment of effluents contaminated by these pollutants.

In Part I we found that the CYP2C9 genotype appears to influence the diastolic blood pressure response to the angiotensin II-receptor antagonist irbesartan in patients with hypertension and left ventricular hypertrophy. Those with the *1/*2 genotype (slower metabolism) responded better than those with the *1/*1 genotype (normal metabolism), likely due to a slower elimination of the drug. We further found that a +9/-9 exon 1 polymorphism of the B2 bradykinin receptor gene – shown to affect mRNA expression - appears to influence the regression of left ventricular mass during therapy with irbesartan or the beta-blocker atenolol in the same patients. Subjects with the -9/-9 genotype (higher mRNA expression) had a greater regression than carriers of the +9 allele. In Part II we found that women on digoxin therapeutic drug monitoring have higher serum digoxin concentrations (SDCs) as compared to men (1.54±0.04 [nmol/L±SE] vs 1.20±0.05 [nmol/L±SE], p<0.001), which could be of importance since an SDC >1.4 nmol/L has been associated with increased mortality. We further found that coadministration of P-glycoprotein inhibitors with digoxin was common (47%) among the same patients, and that the SDC increased in a stepwise fashion with the number of P-glycoprotein inhibitors (20-60%). Lastly, we found that patients admitted to Swedish coronary care units with atrial fibrillation without heart failure and who had been given digoxin had a higher 1-year mortality than those not given digoxin (RR 1.44 [95% CI 1.29-1.60], adjustment made for potential confounders). In conclusion, Part I represents a further step in the pharmacogenomic prospect of tailoring antihypertensive therapy. Part II indicates that heightened attention to the digoxin-dose is warranted in women, that there is a need for awareness about P-glycoprotein interactions with digoxin, and that long-term therapy with digoxin is an independent risk factor for death among patients with atrial fibrillation without heart failure.

Os fármacos são essenciais para a preservação da saúde do homem e de animais e também na prevenção de doenças. Entretanto, seu alto consumo associado ao descarte incorreto e aos tratamentos ineficientes de águas e efluentes podem trazer grandes prejuízos ao meio ambiente como, por exemplo, a resistência bacteriana. O objetivo deste trabalho foi estudar a remoção de ampicilina (AMP), atenolol (ATN) e paracetamol (PAR), fármacos de três classes distintas, em soluções aquosas através da técnica de adsorção em carvão ativado granular (CAG). Foram realizados experimentos de adsorção em batelada avaliando o efeito dos parâmetros pH, tempo de contato e concentração de sólido adsorvente. O comportamento cinético da adsorção dos fármacos em carvão ativado granular foi avaliado por meio dos modelos de pseudo-primeira ordem, pseudosegunda ordem e difusão intrapartícula. Ainda, isotermas de equilíbrio para estes sistemas foram construídas em diferentes temperaturas (15, 25 e 35 °C) e analisadas através dos modelos de Langmuir, Freundlich e Sips. O processo de adsorção também foi avaliado através de ensaios termodinâmicos. A adsorção em coluna de leito fixo foi avaliada utilizando planejamentos experimentais para os fármacos e os efeitos da massa do leito de adsorvente (0,5 – 1,5 g) e da vazão de alimentação (10 – 15 mL min-1) foram estudados Ainda, a fim de se avaliar o comportamento dos fármacos quando em mistura, foram realizados ensaios de adsorção em batelada e em coluna de leito fixo da mistura de ampicilina e paracetamol. Os melhores resultados encontrados nos ensaios de adsorção batelada foram: pH 6 e concentração de sólido adsorvente de 10 g L-1 para os três fármacos. O tempo de adsorção mais adequado foi de 90 minutos para o ATN e 120 min para AMP e PAR. Nessas condições foi possível obter remoções de 90 %, 94 % e 96 % para a ampicilina, atenolol e paracetamol, respectivamente. O modelo cinético que melhor descreveu o processo de adsorção foi o de pseudo-primeira ordem, para os fármacos ampicilina e paracetamol, e pseudo-segunda ordem para o atenolol. As isotermas obtidas para os fármacos indicaram que o processo de adsorção é de natureza endotérmica, ou seja, a adsorção é favorecida com o aumento da temperatura. Para a AMP, o melhor ajuste das isotermas foi obtido pelo modelo de Langmuir nas temperaturas de 15 ºC e 25 ºC e pelo modelo de Sips na temperatura de 35 ºC. Para o ATN, o melhor ajuste foi obtido pelo modelo de Freundlich e, para o PAR, o modelo de Sips, nas três temperaturas estudadas. Os ensaios termodinâmicos indicaram que o processo de adsorção dos fármacos é favorável e espontâneo e comprovou a natureza endotérmica do processo Em relação aos resultados obtidos na adsorção em coluna de leito fixo foi observado que os tempos de ruptura e de saturação aumentam com o aumento da massa de sólido presente no leito e diminuem com o aumento da vazão. A massa de adsorvente apresentou efeito negativo sobre a fração de leito utilizado e foi significativa no processo de adsorção dos três fármacos. Já a vazão de alimentação só foi significativa na adsorção em leito fixo da AMP e apresentou efeito positivo na fração de leito utilizado. Os maiores volumes de efluente tratado foram obtidos com a maior massa de sólido utilizada (1,5 g) e com a menor vazão de alimentação testada (10 mL min-1). Na adsorção multicomponente em batelada, verificou-se que há concorrência entre os fármacos pelos sítios ativos do CAG disponíveis para adsorção. Os resultados obtidos nos ensaios das isotermas de adsorção mostraram que o comportamento dos fármacos em mistura é o mesmo que quando comparados individualmente. Os modelos que melhor se ajustaram aos dados experimentais foram os mesmos obtidos nos ensaios monocomponente, Langmuir para a AMP e Sips para o PAR. Da mesma forma que para os experimentos em coluna monocomponente, os ensaios multicomponentes demostraram que os tempos de ruptura e de saturação são maiores para o PAR. Entretanto, esses valores são menores do que na adsorção individual indicando que houve concorrência entre os fármacos pelos sítios do adsorvente. Os resultados encontrados indicam que a adsorção é uma alternativa viável para a remoção de fármacos, contribuindo, assim, para o avanço das pesquisas relacionadas ao tratamento de efluentes contaminados por estes poluentes. / Drugs are essential for preservation of human and animal health as well as for disease prevention. However, its high consumption associated with incorrect disposal and inefficient treatment of water and effluents can cause great damage to the environment such as bacterial resistance, for example. The objective of this work was to study the removal of ampicillin (AMP), atenolol (ATN) and paracetamol (PAR), drugs of three different classes, in aqueous solutions by adsorption technique in granular activated carbon (GAC). Adsorption experiments were carried out in batch evaluating the effect of parameters pH, contact time and concentration of solid adsorbent. The kinetic behavior of the adsorption of drugs in granular activated carbon was evaluated through the pseudofirst order, pseudo-second order and intraparticle diffusion models. Furthermore, equilibrium isotherms for these systems were made at different temperatures (15, 25 and 35 ° C) and analyzed using the Langmuir, Freundlich and Sips models. The adsorption process was also evaluated through thermodynamic tests. The fixed bed column adsorption was evaluated by experimental planning for drugs and the effects of mass of the adsorbent bed (0.5 to 1.5 g) and feed rate (10 - 15 ml min-1) were studied Also, in order to evaluate the behavior of the drugs when in mixture, adsorption tests were carried out in batch and in fixed bed column for the mixture of ampicillin and paracetamol. The best results found in the batch adsorption tests were: pH 6 and concentration of adsorbent solid of 10 g L-1 for the three drugs. The most suitable adsorption time was 90 minutes for ATN and 120 min for AMP and PAR. Under these conditions it was possible to obtain removals of 90%, 94% and 96% for ampicillin, atenolol and paracetamol respectively. The kinetic model that best described the adsorption process was the pseudo-first order for the ampicillin and paracetamol drugs and pseudo-second order for atenolol. The isotherms obtained for the drugs indicated that the adsorption process is of endothermic nature, that is, the adsorption is favored with the increase in temperature. For the AMP, the best isotherm adjustment was obtained by the Langmuir model at temperatures of 15 °C and 25 °C and by the Sips model at temperature of 35 °C. For the ATN, the best fit was obtained by the Freundlich model and, for PAR, the Sips model at the three temperatures studied. The thermodynamic tests indicated that the adsorption process of the drugs was favorable and spontaneous and confirmed the endothermic nature of the process Regarding the results obtained in adsorption in fixed bed column, it was observed that rupture and saturation times increase with the increase of the mass of solid present in the bed and decrease with the increase of flow. The adsorbent mass had a negative effect on the used bed fraction and was significant in the adsorption process of the three drugs. The feed flow was only significant in the adsorption in fixed bed of the AMP and had positive effect in the used bed fraction. The highest volumes of treated effluent were obtained with the largest mass of solid used (1,5 g) and with the lowest feed rate tested (10 mL min-1). In multicomponent adsorption in batch, it was found that there is competition between the drugs by the active sites of GAC available for adsorption. The results obtained in the adsorption isotherms tests showed that the behavior of the drugs in mixture is the same as when compared individually. The models that best fit the experimental data were the same ones obtained in the monocomponent tests, Langmuir for AMP and Sips for PAR. Similarly as for the monocomponent column experiments, the multicomponent tests showed that the break and saturation times are larger for the PAR. However, these values are lower than in individual adsorption indicating that there was competition between the drugs for the sites of the adsorbent. The results indicate that adsorption is a viable alternative for the removal of drugs, thus contributing to the advancement of research related to the treatment of effluents contaminated by these pollutants.

The main aim of this study was to investigate the efficiency of wastewater treatment plant (WWTP) in České Budějovice for the elimination of selected pharmaceuticals (carbamazepine, diclofenac, atenolol, metoprolol, sotalol, bisoprolol, valsartan, verapamil and tramadol) over a long time period (March 2011 - February 2012). Time-proportional 24 hours pooled samples of wastewater from influent and effluent of the WWTP were used to assess the efficiency of WWTP. The concentrations of target compounds were determined by using in line SPE/LC-MS/MS analysis. The average annual concentrations in the effluent of WTP were in the range of 0,019 microgram/l (verapamil) to 1,00 microgram/l (atenolol). Average annual efficiencies of pharmaceutical elimination in WWTP based on pooled samples were found in the case of carbamazepine (-22 %), tramadol (-15 %), sotalol (-1 %), diclofenac (15 %), metoprolol (16 %), verapamil (43 %), bisoprolol (48 %) and valsartan (85 %). The statistical analysis of daily results in the winter and in the summer period showed significantly higher efficiency of the WWTP in the summer for 5 target compounds (diclofenac, atenolol, valsartan, sotalol and bisoprolol). Removal efficiency for the rest of pharmaceuticals did not show significant differences. Elevated temperature and longer irradiation period in summer can positively affect biodegradation or increased photolysis respectively.

Made available in DSpace on 2014-06-11T19:27:47Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-08-20Bitstream added on 2014-06-13T19:15:14Z : No. of bitstreams: 1 cursino_nm_me_araca.pdf: 2792202 bytes, checksum: 7bc02b29243b06952aa21b86edc0566a (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / A hipertensao arterial representa um fator de risco sistemico e condicao desfavoravel para tratamentos dentarios, especialmente aqueles que necessitam de reparacao ossea. O objetivo deste estudo foi avaliar o reparo alveolar em ratos espontaneamente hipertensos (SHR) e o efeito do atenolol sobre este processo. Wistar e SHR tratados ou nao com 100mg/kg/dia (atenolol), foram submetidos a extracao do dente incisivo superior direito e sacrificados aos 7, 14, 21, 28 e 42 dias apos a cirurgia. As hemi-maxilas foram removidas e as imagens radiograficas foram realizadas. A analise radiografica foi obtida por meio do sistema digital Digora. Analises histologicas, histomorfometricas e reacoes imunoistoquimicas foram feitas em cortes histologicos de 5ƒÊm de espessura, os quais foram corados com hematoxilina-eosina ou submetidos a imunomarcacao para RANK, RANKL, OPG e proteinas MMP-9. A analise histologica foi realizada por microscopia optica e a analise histomorfometrica pelo software RGB / Leica Qwin Color. Os resultados densitometricos e histomorfometricos foram analisados pela Anova two-way. Na analise imunoistoquimica, utilizando um microscopio optico, foram atribuidos scores as imagens. Os resultados foram analisados pelos testes estatisticos Kruskal-Wallis e Mann Whitney. As diferencas entre os resultados foram consideradas significativas quando p<0,05. Reducao da densidade mineral ossea (DMO), menor porcentagem de osso e menor espessura do trabeculado osseo foram observadas nos periodos finais do reparo alveolar em SHR. Aumento da imunomarcacao para RANKL, RANK e MMP-9 foi observado em 28 dias apos a cirurgia no alveolo em SHR. Consistente efeito do atenolol foi observado no reparo alveolar de ratos hipertensos. O atenolol aumentou a DMO observada na maioria dos periodos analisados e aumentou a espessura do trabeculado... / Hypertension represents a systemic risk factor and unfavorable condition for dental treatments, especially treatments that require bone healing. The purpose of this study was to evaluate the alveolar wound healing in spontaneously hypertensive rats (SHR) and the atenolol effect on this process. Normotensive Wistar rats and SHR, untreated or treated with atenolol (100mg/kg/day), were submitted to the extraction of the upper right incisive tooth and sacrificed at 7, 14, 21, 28 and 42 days after surgery. The hemi-jaws were extracted and the radiographic images were obtained. Radiographic analysis was performed by using the digital system Digora. Histological, histomorphometric and immunohistochemical reactions were done in histological sections, 5 μm thick, stained with hematoxylin and eosin or subjected to immunolabeling to RANK, RANKL, OPG and MMP-9 proteins. Histological analysis was performed by light microscopy and histomorphometric analysis by Leica Qwin Color/RGB software. The densitometric and histomorphometric results were also analyzed by two-way ANOVA. In immunohistochemical analysis, using an optical microscopy, scores were assigned to the images. Results were analyzed by Kruskal-Wallis and Mann Whitney statistical tests. Differences between results were considered significant when p <0.05. Reduced bone mineral density (BMD), lower bone percentage and less thickness of trabecular bone was observed in the final periods of alveolar bone healing in SHR. Increased RANKL, RANK and MMP-9 immunolabeling were observed at 28 days after surgery in SHR alveolus. Consistent atenolol effect was observed on alveolar bone healing of hypertensive rats. Atenolol increased the BMD observed in most of the periods analyzed and increased trabecular bone thickness at 28 and 42 days in SHR alveolus. Increased OPG immunolabeling... (Complete abstract click electronic access below)

Os fármacos são essenciais para a preservação da saúde do homem e de animais e também na prevenção de doenças. Entretanto, seu alto consumo associado ao descarte incorreto e aos tratamentos ineficientes de águas e efluentes podem trazer grandes prejuízos ao meio ambiente como, por exemplo, a resistência bacteriana. O objetivo deste trabalho foi estudar a remoção de ampicilina (AMP), atenolol (ATN) e paracetamol (PAR), fármacos de três classes distintas, em soluções aquosas através da técnica de adsorção em carvão ativado granular (CAG). Foram realizados experimentos de adsorção em batelada avaliando o efeito dos parâmetros pH, tempo de contato e concentração de sólido adsorvente. O comportamento cinético da adsorção dos fármacos em carvão ativado granular foi avaliado por meio dos modelos de pseudo-primeira ordem, pseudosegunda ordem e difusão intrapartícula. Ainda, isotermas de equilíbrio para estes sistemas foram construídas em diferentes temperaturas (15, 25 e 35 °C) e analisadas através dos modelos de Langmuir, Freundlich e Sips. O processo de adsorção também foi avaliado através de ensaios termodinâmicos. A adsorção em coluna de leito fixo foi avaliada utilizando planejamentos experimentais para os fármacos e os efeitos da massa do leito de adsorvente (0,5 – 1,5 g) e da vazão de alimentação (10 – 15 mL min-1) foram estudados Ainda, a fim de se avaliar o comportamento dos fármacos quando em mistura, foram realizados ensaios de adsorção em batelada e em coluna de leito fixo da mistura de ampicilina e paracetamol. Os melhores resultados encontrados nos ensaios de adsorção batelada foram: pH 6 e concentração de sólido adsorvente de 10 g L-1 para os três fármacos. O tempo de adsorção mais adequado foi de 90 minutos para o ATN e 120 min para AMP e PAR. Nessas condições foi possível obter remoções de 90 %, 94 % e 96 % para a ampicilina, atenolol e paracetamol, respectivamente. O modelo cinético que melhor descreveu o processo de adsorção foi o de pseudo-primeira ordem, para os fármacos ampicilina e paracetamol, e pseudo-segunda ordem para o atenolol. As isotermas obtidas para os fármacos indicaram que o processo de adsorção é de natureza endotérmica, ou seja, a adsorção é favorecida com o aumento da temperatura. Para a AMP, o melhor ajuste das isotermas foi obtido pelo modelo de Langmuir nas temperaturas de 15 ºC e 25 ºC e pelo modelo de Sips na temperatura de 35 ºC. Para o ATN, o melhor ajuste foi obtido pelo modelo de Freundlich e, para o PAR, o modelo de Sips, nas três temperaturas estudadas. Os ensaios termodinâmicos indicaram que o processo de adsorção dos fármacos é favorável e espontâneo e comprovou a natureza endotérmica do processo Em relação aos resultados obtidos na adsorção em coluna de leito fixo foi observado que os tempos de ruptura e de saturação aumentam com o aumento da massa de sólido presente no leito e diminuem com o aumento da vazão. A massa de adsorvente apresentou efeito negativo sobre a fração de leito utilizado e foi significativa no processo de adsorção dos três fármacos. Já a vazão de alimentação só foi significativa na adsorção em leito fixo da AMP e apresentou efeito positivo na fração de leito utilizado. Os maiores volumes de efluente tratado foram obtidos com a maior massa de sólido utilizada (1,5 g) e com a menor vazão de alimentação testada (10 mL min-1). Na adsorção multicomponente em batelada, verificou-se que há concorrência entre os fármacos pelos sítios ativos do CAG disponíveis para adsorção. Os resultados obtidos nos ensaios das isotermas de adsorção mostraram que o comportamento dos fármacos em mistura é o mesmo que quando comparados individualmente. Os modelos que melhor se ajustaram aos dados experimentais foram os mesmos obtidos nos ensaios monocomponente, Langmuir para a AMP e Sips para o PAR. Da mesma forma que para os experimentos em coluna monocomponente, os ensaios multicomponentes demostraram que os tempos de ruptura e de saturação são maiores para o PAR. Entretanto, esses valores são menores do que na adsorção individual indicando que houve concorrência entre os fármacos pelos sítios do adsorvente. Os resultados encontrados indicam que a adsorção é uma alternativa viável para a remoção de fármacos, contribuindo, assim, para o avanço das pesquisas relacionadas ao tratamento de efluentes contaminados por estes poluentes. / Drugs are essential for preservation of human and animal health as well as for disease prevention. However, its high consumption associated with incorrect disposal and inefficient treatment of water and effluents can cause great damage to the environment such as bacterial resistance, for example. The objective of this work was to study the removal of ampicillin (AMP), atenolol (ATN) and paracetamol (PAR), drugs of three different classes, in aqueous solutions by adsorption technique in granular activated carbon (GAC). Adsorption experiments were carried out in batch evaluating the effect of parameters pH, contact time and concentration of solid adsorbent. The kinetic behavior of the adsorption of drugs in granular activated carbon was evaluated through the pseudofirst order, pseudo-second order and intraparticle diffusion models. Furthermore, equilibrium isotherms for these systems were made at different temperatures (15, 25 and 35 ° C) and analyzed using the Langmuir, Freundlich and Sips models. The adsorption process was also evaluated through thermodynamic tests. The fixed bed column adsorption was evaluated by experimental planning for drugs and the effects of mass of the adsorbent bed (0.5 to 1.5 g) and feed rate (10 - 15 ml min-1) were studied Also, in order to evaluate the behavior of the drugs when in mixture, adsorption tests were carried out in batch and in fixed bed column for the mixture of ampicillin and paracetamol. The best results found in the batch adsorption tests were: pH 6 and concentration of adsorbent solid of 10 g L-1 for the three drugs. The most suitable adsorption time was 90 minutes for ATN and 120 min for AMP and PAR. Under these conditions it was possible to obtain removals of 90%, 94% and 96% for ampicillin, atenolol and paracetamol respectively. The kinetic model that best described the adsorption process was the pseudo-first order for the ampicillin and paracetamol drugs and pseudo-second order for atenolol. The isotherms obtained for the drugs indicated that the adsorption process is of endothermic nature, that is, the adsorption is favored with the increase in temperature. For the AMP, the best isotherm adjustment was obtained by the Langmuir model at temperatures of 15 °C and 25 °C and by the Sips model at temperature of 35 °C. For the ATN, the best fit was obtained by the Freundlich model and, for PAR, the Sips model at the three temperatures studied. The thermodynamic tests indicated that the adsorption process of the drugs was favorable and spontaneous and confirmed the endothermic nature of the process Regarding the results obtained in adsorption in fixed bed column, it was observed that rupture and saturation times increase with the increase of the mass of solid present in the bed and decrease with the increase of flow. The adsorbent mass had a negative effect on the used bed fraction and was significant in the adsorption process of the three drugs. The feed flow was only significant in the adsorption in fixed bed of the AMP and had positive effect in the used bed fraction. The highest volumes of treated effluent were obtained with the largest mass of solid used (1,5 g) and with the lowest feed rate tested (10 mL min-1). In multicomponent adsorption in batch, it was found that there is competition between the drugs by the active sites of GAC available for adsorption. The results obtained in the adsorption isotherms tests showed that the behavior of the drugs in mixture is the same as when compared individually. The models that best fit the experimental data were the same ones obtained in the monocomponent tests, Langmuir for AMP and Sips for PAR. Similarly as for the monocomponent column experiments, the multicomponent tests showed that the break and saturation times are larger for the PAR. However, these values are lower than in individual adsorption indicating that there was competition between the drugs for the sites of the adsorbent. The results indicate that adsorption is a viable alternative for the removal of drugs, thus contributing to the advancement of research related to the treatment of effluents contaminated by these pollutants.