Made available in DSpace on 2014-10-09T12:32:51Z (GMT). No. of bitstreams: 0 / Made available in DSpace on 2014-10-09T14:10:05Z (GMT). No. of bitstreams: 1 03526.pdf: 2946019 bytes, checksum: 162913e7d1135b3db6d5a5d5f9493dcc (MD5) / Tese (Doutoramento) / IPEN/T / Instituto de Quimica, Universidade de Sao Paulo - IQ/USP

Made available in DSpace on 2015-05-14T13:00:12Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 1253693 bytes, checksum: 473208aa372beaf58b2dc01deecdc9be (MD5) Previous issue date: 2010-03-08 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / Organic nitrates are nitric oxide (NO) donors used in the treatment of cardiovascular diseases mimicking the role of endogenous NO. This study evaluated organic nitrates newly synthesized from glycerin, which cardiovascular actions had not yet been investigated. Therefore, the cardiovascular effects produced by organic nitrates derived from glycerin: 2-nitrate-1,3-dimethoxypropan (NDMP), 2-nitrate-1,3-diethoxypropan (NDEP), 2-nitrate-1 ,3-dipropoxypropan (NDPP) and 2-nitrate-1,3-dibutoxypropan (NDBP) in rats were investigated using in vitro and in vivo approaches. For in vitro studies, animals were euthanized and the superior mesenteric artery was isolated. Artery rings were kept in tanks with Tyrode at 37 ° C aerated with carbogen, then were attached to a force transducer (Fort 10, WPI, Sarasota, USA) coupled to a data acquisition system data (Miobath-4, WPI, Sarasota, USA) under a tension of 0.75 g for 1 hour. After this period, preparations were pre-contracted with phenylephrine (FEN) 10 μM or KCl 80 mM and then increasing concentrations of organic nitrates were cumulatively added. The nitrate with the most promising effects was selected for further studies and concentration-response curves of the compound selected in the presence of HDX, a hijacker of NO; ODQ, inhibitor of soluble guanylyl cyclase, KCl 20 mM, a modulator of potassium efflux, and blockers for calcium-sensitive potassium channel (TEA, 1 mM), blockers for ATP-sensitive potassium channel (GLIB, 1 M) and blockers for voltage-operated potassium channel (4-AP, 1 mM) were obtained. All compounds showed vasorelaxant activity endothelium-independent in superior mesenteric artery rings, being the NDBP was the most potent agent with Emax = 105.4 ± 2.7% in rings pre-contracted with FEN and Emax = 82, 7 ± 7.9% in KCl 80 mM induced contraction. The vasorelaxation was significantly attenuated in the presence of HDX and ODQ with Emax = 62.8 ± 14.9% and Emax = 15.2 ± 9.2%, respectively. In the presence of KCl 20 mM the vasorelaxat response was also reduced [Emax = 70.6 ± 15.02%] as well as in the presence of TEA [Emax = 87.97 ± 5.78%]; GLIB [Emax = 78, 2 ± 6.5%] and 4-AP, a lesser extent [Emax = 94.65 ± 6.6%]. For in vivo studies, we investigated the changes in blood pressure (BP) and heart rate (HR) in conscious rats treated acutely with NDBP. Intravenous administration of NDBP (2, 5, 10, 15 and 20 mg/kg, randomly) produced hypotension (-6 ± 1.7, -22 ± 6.8, -58 ± 3.7, -70 ± 5.5, -77 ± 5.4 mmHg) and bradycardia (-12 ± 5, -40 ± 19.7, -133 ± 18.6, -179 ± 23.5, and -266 ± 12.4 bpm) in a dose-dependent manner. Thus, the vasorrelaxant response produced by NDBP possibly involves the NO release and subsequent activation of the CGs/GMPc/PKG pathway and BKCa, KATP and KV channels. These mechanism of action may be contributing to hypotension and bradycardia showed in non-anesthetized normotensive rats. / Os nitratos orgânicos são doadores de óxido nítrico (NO) utilizados no tratamento de doenças cardiovasculares mimetizando o papel do NO endógeno. Neste estudo foram avaliados nitratos orgânicos recém-sintetizados a partir da glicerina cujas ações cardiovasculares ainda não haviam sido investigadas. Portanto, os efeitos cardiovasculares do 2-nitrato-1,3-dimetoxipropano (NDMP), 2-nitrato-1,3-dietoxipropano (NDEP), 2-nitrato-1,3-dipropoxipropano (NDPP) e 2-nitrato-1,3-dibutoxipropano (NDBP) em ratos normotensos foram observados, utilizando técnicas in vitro e in vivo. Para os estudos in vitro, os animais foram eutanasiados e a artéria mesentérica superior foi isolada. Anéis de artéria mesentérica superior isolada de rato foram mantidos em cubas contendo Tyrode a 37 ºC gaseificado com carbogênio, em seguida foram fixados a um transdutor de força (FORT 10, WPI, Sarasota, EUA), acoplado a um sistema de aquisição de dados (Miobath-4, WPI, Sarasota, EUA) sob tensão de 0,75 g, durante 1 hora. Após este período, as preparações foram pré-contraídas com fenilefrina (FEN) 10 μM ou KCl 80 mM e, em seguida, concentrações crescentes dos nitratos orgânicos, foram adicionadas cumulativamente. O nitrato com efeito mais promissor foi selecionado para estudos subsequentes e foram obtidas curvas concentração-resposta do composto na presença de HDX, sequestrador de NO; ODQ, inibidor da ciclase de guanilil solúvel; KCl 20 mM, modulador do efluxo de potássio; e bloqueadores de canais para K+ sensíveis ao cálcio (TEA, 1 mM), ao ATP (GLIB, 1 M) e operados por voltagem (4-AP, 1 mM). Todos os compostos apresentaram atividade vasorrelaxante em anéis de artéria mesentérica superior isolada de rato independente do endotélio funcional, sendo o NDBP o mais potente com Emáx = 105,4 ± 2,7 % em anéis pré-contraídos com FEN e Emáx = 82,7 ± 7,9 % na contração induzida por KCL 80 mM. O vasorrelaxamento foi significativamente atenuado na presença de HDX e ODQ, com Emáx = 62,8 ± 14,9 % e Emáx = 15,2 ± 9,2 %, respectivamente. Na presença de KCl 20 mM a resposta vasorrelaxante também foi reduzida [Emáx = 70,6 ± 15,02 %], bem como na presença do TEA [Emáx = 87,97 ± 5,78 %]; GLIB [Emáx = 78,2 ± 6,5 %] e 4-AP, em menor proporção [Emáx = 94,65 ± 6,6 %]. Para os estudos in vivo, foram investigadas as alterações na pressão arterial (PA) e frequência cardíaca (FC) em ratos não-anestesiados tratados agudamente com o NDBP. A administração aleatória do NDBP (2, 5, 10, 15 e 20 mg/kg, i. v) produziu hipotensão (-6 ± 1,7; -22 ±6,8; -58 ± 3,7; -70 ± 5,5; -77 ± 5,4 mmHg) e bradicardia (-12 ± 5; -40 ± 19,7; -133 ± 18,6; -179 ± 23,5; e -266 ± 12,4 bpm) de maneira dose-dependente. Deste modo, a resposta vasorrelaxante promovida pelo NDBP possivelmente envolve a liberação de NO e posterior ativação da via CGs/GMPc/PKG e canais para K+ do tipo BKCa; KATP e KV. Este mecanismo de ação pode estar contribuindo para a hipotensão e bradicardia observadas em animais normotensos não-anestesiados.

The influence of precipitation on runoff characteristics of tile drainage systems and nitrate concentrations in drainage water were evaluated in this thesis. The Jeninsky stream catchment is located at the foothill of Sumava Mountains near the border checkpoint Dolni Dvoriste. Extensive agriculture (pasture) is practised in the catchment as well as surrounding areas. Above mentioned evaluated characteristics were measured on two closure profiles of tile drained subcatchments. Discharges were measured continously, water quality was sampled forthnigtly. Evaluated hydrologic year 2007 was rich in rainfall {--} the precipitation amounted to 892 mm, which is classified as a wet year, despite of 41 days long dry period. Runoff characteristics don{\crq}t vary much in both subcatchments, due to similar area and land use on researched catchments. Long dry period did not cause zero discharges. The progress of nitrate concentrations in subcatchments is characterized by low variations in values. Relatively low values (90-percentil of nitrate concentrations in individual catchments belong to II. and III. class of water quality limits set by Czech legislative) occured in the catchment. These values correspond or slightly exceed values monitored on surrounding simirarly used areas, but are significantly lower than values monitored in areas, where intensive agriculture is practised. This confirms positive influence of grassing on nitrate pollution of drainage and surface water.

Water quality of small streams in agricultural landscape is mostly classified as polluted or very polluted. The reason of enhanced mineralization of organic mass in soil can be found in changed physical, chemical and biochemical properties of soil profile, which negatively display in mineralization of organic mass and nitrogen release to soil water. Analysis of water quality in agricultural river-basin prove that quality of surface water in areas with high nitrate loadings did not significantly improve in recent years. Nitrates in water are a distinct anthropogenic factor, which defines well disturbance in natural environment. This thesis deals with analysis of time series of nitrate concentrations in the Kopaninsky stream catchment in Bohemo-Moravian Highland. Further the progress in nitrate concentration and its seasonal component is researched.

The object of this research was follow up the cumulation of nitrates in individual kinds of vegetables. Analysed was 240 samples of root crops, cole crops and potatoes distributed in the trade network in Humpolec in the years 2008 - 2010. The measurement results show that all the vegetables went beyond the nitrate permitted limit, according to a law n. 53/2002. The most frequently it was in potatoe samples (50 % samples). The next was a carrot (27 %), kohlrabi (25 %), broccoli (24 %) and celery (17 %). From aspect cumulation of nitrates is parsley unchallenged kind of vegetable. Permitted limit was transcendent in 10 % about less than 1 %. The origin of the vegetables was detected as well. Czech republic had the worst results (52,5 %) because of the high nitrate concentration in potatoes. It is grown by a domestic growers. Spain had 20 % in broccoli and kohlrabi. It is imported to our market. Although the high nitrate concentration in some vegetable samples the vegetable influence the human health in a positive way and it doesn?t make health hazard.

Introdução: O tratamento com nitrato fixo em pacientes com angina estável é comum na prática clínica. Contudo, os eventos adversos podem interferir na qualidade de vida relacionada à saúde (QVRS) e adesão ao tratamento medicamentoso. O objetivo do estudo foi comparar a QVRS e adesão ao tratamento em grupos de pacientes com angina estável em retirada e manutenção de nitrato. Métodos: Ensaio clínico randomizado conduzido com pacientes com angina estável em dois grupos: intervenção com retirada de nitrato e introdução de placebo e controle com manutenção de nitrato. Ambos os grupos receberam três avaliações: basal, 30 dias e 120 dias no período de quatro meses. A QVRS foi mensurada pelo Short Form Health Survey (SF-36) e Seattle Angina Questionnaire (SAQ), e a adesão foi aferida pela escala de Morisky e contagem de comprimidos. Resultados: 105 pacientes foram randomizados (51: placebo e 54: nitrato). Após quatro meses, observou-se maiores escores nos domínios de dor (63+19; 67+23; 72+24; P=0,004) e aspecto social (87+19; 91+21; 91+19; P=0,002) do SF-36 e no escore de limitação física (74+11; 78+10; 78+8; P=0,006) do SAQ no grupo nitrato, e redução do escore de estabilidade da angina (81+19; 72+20; 72+24; P=0,031) no grupo placebo. Contudo, o tamanho de efeito foi igual ou inferior a 0,42 nesses domínios. A adesão aferida no final entre os grupos foi significativamente maior no grupo intervenção (94% vs 80%; P=0,041) com a escala de Morisky, mas não houve diferença entre os grupos na contagem da medicação. Conclusão: Pacientes com angina estável em uso de nitrato em comparação aos pacientes com uso de placebo não tiveram comprometimento clinicamente relevante da QVRS, porém demonstraram pior adesão ao tratamento na escala de Morisky. / Background: Long-term nitrate treatment of stable angina is associated with adverse events and can interfere with health-related quality of life (HRQoL) and medication adherence. The aim of the present study was to compare HRQoL and adherence to treatment in patients with stable angina undergoing nitrate withdrawal and maintenance. Methods: Randomized clinical trial. Patients were allocated into an intervention group (nitrate withdrawal followed by introduction of placebo) or a control group (nitrate maintenance). The assessments were performed at baseline, 30 days, and 120 days with the Short Form Health Survey (SF-36) and the Seattle Angina Questionnaire (SAQ). Treatment adherence was measured by the Morisky scale and pill count. Results: 51 participants were randomized for replacement of nitrate with placebo and 54 for maintenance of treatment with nitrate. After four months, SF-36 scores increased for the bodily pain (P=0.004) and social functioning (P=0.002) in the nitrate maintenance group. Increased SAQ scores were also noted for physical limitations (P=0.006) in the nitrate maintenance group. SAQ score for angina stability (P=0.031) decreased in the placebo group. However, the effect size was small ! 0.42 in those domains. At the end of the study, adherence was significantly higher in the placebo group (P=0.041), but no difference was detected between the groups with the pill count method. Conclusion: HRQoL was similar in patients with stable angina using nitrate regularly as compared to patients undergoing nitrate withdrawal. However, adherence to treatment was lower in nitrate users according to the Morisky scale.

A amônia presente em galpões fechados de criação de frangos afeta a saúde tanto dos animais como dos tratadores, além de ser um grave problema ambiental. O processo aqui recomendado faz uso de um material com grande capacidade de retenção tanto da amônia gasosa como na forma de seu hidróxido, NH4OH. Este absorvedor, um trocador catiônico sólido, preparado para a retenção seletiva da amônia, é inodoro, insípido e atóxico. Uma vez saturado com amônia, passa por um tratamento químico para a remoção deste composto, podendo ser reutilizado muitas vezes sem perda de sua capacidade retentora, tornando o processo mais econômico. A remoção deste material pode-se dar na forma de um sal de amônio que poderá ser utilizado como fertilizante. Ressalta-se ainda que a amônia recuperada nestes galpões avícolas, quando submetida a uma decomposição térmica catalítica, gera hidrogênio para uso em células a combustível, podendo fornecer energia elétrica no próprio local do trabalho. / The process here stressed uses a cátion exchange material. The aim of the present work has been to prepare a suitable cation exchanger material with excepecinally high selectivity for ammonia, as the cation NH4+ or as aqueous ammonia solution containing NH4OH hyroxide as well. Aliquots of the abovementioned exchangers were set up inside an chiken farm production near São Paulo city. Periodically the exchanger was removed to the laboratory and eluted with a convenient acid to regenerate the exchanger for the new cicle. The ammonia retention was quite high and presents no dificulty for its elution. The selected exchanger is a solid material, non toxic, without smell and have good physical properties. The first results encouraged us and our plants to do large experiments that in progress. This process is a contribution to remediation of the avicola local, removing the ammonia gas and suppressing grettly its smell and bad effect to the animals and even to workers

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