No description available.

No description available.

Estudos termoanalíticos de alguns aditivos alimentares da classe dos realçadores de sabor foram desenvolvidos visando avaliar sua estabilidade e resistência durante o preparo de alimentos a quente assim como investigar os eventuais intermediários de decomposição que poderiam resultar destes processos. Os sais foram obtidos de fontes industriais ou sintetizados e submetidos à caracterização por análise elementar, espectrometria vibracional na região do infra-vermelho, termogravimetria/termogravimetria derivada, análise térmica diferencial e em alguns casos, calorimetria exploratória diferencial. Foram estudados o ácido glutâmico e seus sais de amônio, lítio e sódio mono e dissubstituídos. Em todos os casos observou-se uma conversão a piroglutamato após desidratação dos sais monossubstituídos, a qual ocorre via a a-carboxila. A estabilidade térmica destes sais foi da ordem de 190-200 °C. No caso dos sais dissubstituídos de lítio e sódio não houve conversão ao piroglutamato pois as duas carboxilas estão salificadas. Os glutamatos de magnésio, cálcio estrôncio e bário, também foram preparados e investigados quanto ao seu comportamento térmico. Os sais se formaram na estequiometria 2:1 (ligante:metal), apresentando águas de hidratação em número característico e foram estáveis até 190- 200 °C. Finalmente foram estudados os mecanismos de decomposição térmica do inosinato-monofosfato de sódio e do guanilato-monofosfato de sódio, dois nucleotídeos que apresentam a propriedade de realçar o sabor de alimentos. Ambos apresentaram elevado grau de hidratação, para o qual foi possível distinguir mecanismos característicos de desidratação. A decomposição dos sais anidros ocorreu com saída do grupo purínico, seguida da decomposição do restante da molécula e formação de pirofosfato de sódio como resíduo final. / Thermal analytical studies of some food addictives of the flavor enhancer class were developed in order to evaluate their stability and resistance to the hot cooking process, as well as to identify the intermediaries of thermal decomposition that could remain at the end of such processes. The salts were obtained from industrial sources or synthesized and characterized by elemental analysis, infra-red spectroscopy, thermogravimetry/derivative thermogravimetry, differential thermal analysis and in some opportunities to differential scanning calorimetry. The glutamic acid and its ammonium, lithium and sodium salts mono and disubstituted were investigated. In all cases a conversion to pyroglutamate has been observed in the free acid and its monosubstituted salts after dehydration. The conversion undergoes by the ?-carboxyl group. The thermal stability was observed to be as high as 190-200 °C. In the case of the lithiu m and sodium dissubstituted salts any conversions to pyroglutamates were observed, once both carboxyl groups were salified. Magnesium, calcium, strontium and barium glutamates has also been synthesized and investigated in relation to its thermal behavior. The salts were formed in the 2:1 stoichiometry (ligand:metal), presenting hydration waters in a characteristic content and showed to be stable up to 190-200 °C. Finally the thermal decomposition mechanisms of dissodium inosinatemonophosphate and dissodium guanilate-monophosphate two nucleotides with flavor enhancement properties in food were also investigated. Both presented high degree of hydration, to which it was possible to propose a water release mechanism. The decomposition of the anhydrous salts occurred with release of the purine group followed by the decomposition of the rest of the molecule generating sodium pyrophosphate as residue.

INTRODUÇÃO. O termo Lesão Pulmonar Aguda (LPA) é usado para descrever a resposta pulmonar à lesão que ocorre diretamente ou indiretamente nos pulmões. A quebra da barreira alvéolo-capilar determina o influxo de líquido rico em proteínas para dentro dos espaços alveolares, sendo necessária a reabsorção desse líquido no processo de resolução da LPA. A infusão intravenosa de Ácido Oleico (AO) em ratos provoca agudamente edema alveolar difuso e focos hemorrágicos intra-alveolares, sendo um bom modelo de indução. Estudos relatam que o Azul de Metileno (AM) atenua tais lesões, com efeito protetor, no tecido pulmonar, e reduz o edema presente na LPA em animais com sepse através da inibição da guanilato ciclase solúvel (GCs), uma enzima ativadora da via NO-GMPc. OBJETIVO. Estudar a repercussão da inibição da GCs pelo AM na permeabilidade capilar pulmonar ministrando-o antes e após a indução da lesão pulmonar por AO. MÉTODO. Ratos Wistar foram divididos em 5 grupos: Sham com infusão de salina em bolus; AM com infusão de AM por 2h; AO com infusão de AO em bolus, AM/AO com infusão de AM por 2h, sendo que, após 5 min do início, recebeu AO simultaneamente em bolus e AO/AM com infusão de AO em bolus e, após 2h, infusão de AM por mais 2h. Após 4h foi realizada a coleta de materiais (sangue, lavado bronco-alveolar e tecido pulmonar) para análise do NO plasmático e tecidual, gasometria arterial, cálculo do peso úmido/peso seco (PU/PS) e histologia do tecido pulmonar de todos os grupos. A estatística utilizada foi a análise de variância (one-way ANOVA) com p<0.05. RESULTADO. Não foi encontrado hipoxemia grave após 4h de lesão. O grupo AO apresenta um aumento no número de proteínas no lavado bronco-alveolar e na relação PU/PS comparado aos grupos controle: Sham e AM, confirmando a presença de lesão e alteração de permeabilidade pulmonar. Os grupos tratados com AM apresentaram melhora na permeabilidade pulmonar, porém, apenas o grupo pré-tratamento (AM/AO) apresentou diferença estatística na redução do extravasamento de proteínas no lavado. Não foram encontradas diferenças significativas no NO plasmático e tecidual. Na microscopia, a congestão capilar foi intensa, acompanhada de múltiplos focos de edema alveolar, exsudato intra-alveolar proteico, áreas de hemorragia e infiltrado inflamatório neutrofílico, tanto no interstício quanto nos septos alveolares.Os grupos tratados com AM apresentaram diminuição das áreas de edema, exsudação e hemorragia, porém, com maior evidência no grupo AM/AO. CONCLUSÃO. O AM diminui a permeabilidade pulmonar quando administrado de maneira precoce amenizando os danos causados pela LPA induzida por AO. / BACKGROUND. The term Acute Lung Injury (ALI) is used to describe the response to lung injury that occurs directly or indirectly in the lungs. The rupture of the alveolar - capillary barrier determines the influx of protein-rich fluid into the alveolar spaces, the reabsorption of this fluid in the process of resolving the ALI is required. Intravenous infusion of oleic acid (OA) in rats acutely causes diffuse alveolar edema and intra-alveolar hemorrhagic foci, being a good role model induction. Studies have reported that Methylene Blue (MB) attenuates such injuries, with a protective effect in lung tissue and reduce edema present in the ALI present in with sepsis by inhibition of soluble guanylate cyclase (sGC), an activator of the enzyme NO- cGMP pathway. OBJECTIVE. To study the effect of inhibition of sGC by MB in pulmonary capillary permeability ministering to the before and after induction of lung injury by OA. METHOD. Wistar rats were divided into 5 groups: Sham infused with saline bolus, MB infused with MB for 2hrs, OA infused with OA bolus, MB/OA infused with MB for 2hrs, and after 5 min from the beginning, simultaneously received OA bolus and OA/MB infused with OA bolus and after 2hrs, MB infusion for 2hrs. After 4hrs the collection of materials was performed (blood, bronchoalveolar lavage and lung tissue) for analysis of plasma and tissue NO, arterial blood gases, calculation of the wet weight/dry weight (WW/DW) and histology of lung tissue from all groups. The statistic used was analysis of variance (one-way ANOVA) with p<0.05. RESULTS. Not found severe hypoxemia after 4hrs of injury. The OA group shows an increase in the number of proteins in bronchoalveolar lavage and in WW/DW ratio compared to the control groups: Sham and MB, confirming the presence of injury and alterations of lung permeability. The groups treated with MB showed improvement in lung permeability, however, only the pretreatment group (MB/OA) showed statistical significance in reducing the leakage of protein in the lavage. No significant differences were found in plasma and tissue NO. In microscopy, capillary congestion was intense, accompanied by multiple foci of alveolar edema, intra-alveolar proteinaceous exudates, areas of hemorrhage and neutrophilic inflammatory infiltrate in both the interstitium and in the alveolar septa. The groups treated with MB showed reduction in areas of edema, exudation and hemorrhage, however, most obviously in MB/OA group. CONCLUSION. The MB decreases lung permeability when administered as early as possible, mitigating the damage caused by OA-induced ALI.

Abstract not available

Primary cilia are evolutionarily conserved organelles required in a number of signalling pathways influencing the development and behaviour of a diverse range of organisms. More recently, studies into a new class of human diseases known as ciliopathies have helped to shed light on the critical role of this once-ignored signalling centre. Bardet-Biedl syndrome (BBS) proteins localize to the primary cilium and participate in cilium biogenesis and function. BBS is a pleiotropic human disorder with variable severity that is suitable as a disease model for investigating the pathogenesis of a number of common ciliopathy features such as photoreceptor degeneration, renal cysts, and obesity. The C. elegans genome encodes a number of BBS proteins which undergo intraflagellar transport (IFT) at the primary cilium. Given the conservation between C. elegans and human BBS proteins, I hypothesize the existence of unidentified conserved genetic pathways related to the functions of these proteins. Using C. elegans, I characterize novel features of bbs mutants while identifying sources of genomic variation that may elucidate the variability of human BBS features. I show that C. elegans bbs mutants exhibit smaller body size, delayed development, and decreased exploration behaviour. Moreover, I identify a role for the soluble guanylate cyclases GCY-35/GCY-36 in modifying these bbs phenotypes. I conclude that BBS proteins non-cell autonomously influence a set of body cavity neurons in which GCY-35/GCY-36 function genetically upstream of a cGMP-dependent protein kinase (PKG), EGL-4, to control body size. Furthermore, the role of GCY-35/GCY-36 is unique amongst a large number of guanylate cyclases and BBS proteins may influence body size via an IFT-independent function. I explore the biological functions of EGL-4 and conclude that it may regulate body size through multiple cellular mechanisms. I also examine potential candidate genes related to cGMP production and turnover, confirming that additional cGMP-related factors can influence body size although not necessarily in body cavity neurons. In conclusion, I propose a model where BBS-expressing sensory neurons influence body size and development through cGMP-PKG signalling in body cavity neurons while functioning in parallel with additional sensory neurons (possibly BBS-independent) that use similar cGMP-PKG signalling dynamics.

Primary cilia are evolutionarily conserved organelles required in a number of signalling pathways influencing the development and behaviour of a diverse range of organisms. More recently, studies into a new class of human diseases known as ciliopathies have helped to shed light on the critical role of this once-ignored signalling centre. Bardet-Biedl syndrome (BBS) proteins localize to the primary cilium and participate in cilium biogenesis and function. BBS is a pleiotropic human disorder with variable severity that is suitable as a disease model for investigating the pathogenesis of a number of common ciliopathy features such as photoreceptor degeneration, renal cysts, and obesity. The C. elegans genome encodes a number of BBS proteins which undergo intraflagellar transport (IFT) at the primary cilium. Given the conservation between C. elegans and human BBS proteins, I hypothesize the existence of unidentified conserved genetic pathways related to the functions of these proteins. Using C. elegans, I characterize novel features of bbs mutants while identifying sources of genomic variation that may elucidate the variability of human BBS features. I show that C. elegans bbs mutants exhibit smaller body size, delayed development, and decreased exploration behaviour. Moreover, I identify a role for the soluble guanylate cyclases GCY-35/GCY-36 in modifying these bbs phenotypes. I conclude that BBS proteins non-cell autonomously influence a set of body cavity neurons in which GCY-35/GCY-36 function genetically upstream of a cGMP-dependent protein kinase (PKG), EGL-4, to control body size. Furthermore, the role of GCY-35/GCY-36 is unique amongst a large number of guanylate cyclases and BBS proteins may influence body size via an IFT-independent function. I explore the biological functions of EGL-4 and conclude that it may regulate body size through multiple cellular mechanisms. I also examine potential candidate genes related to cGMP production and turnover, confirming that additional cGMP-related factors can influence body size although not necessarily in body cavity neurons. In conclusion, I propose a model where BBS-expressing sensory neurons influence body size and development through cGMP-PKG signalling in body cavity neurons while functioning in parallel with additional sensory neurons (possibly BBS-independent) that use similar cGMP-PKG signalling dynamics.

Thesis (Ph. D.)--University of Washington, 2003. / Vita. Includes bibliographical references (leaves 98-113).

Thesis (Ph. D.)--University of Washington, 2001. / Vita. Includes bibliographical references (leaves 118-135).

Estudos termoanalíticos de alguns aditivos alimentares da classe dos realçadores de sabor foram desenvolvidos visando avaliar sua estabilidade e resistência durante o preparo de alimentos a quente assim como investigar os eventuais intermediários de decomposição que poderiam resultar destes processos. Os sais foram obtidos de fontes industriais ou sintetizados e submetidos à caracterização por análise elementar, espectrometria vibracional na região do infra-vermelho, termogravimetria/termogravimetria derivada, análise térmica diferencial e em alguns casos, calorimetria exploratória diferencial. Foram estudados o ácido glutâmico e seus sais de amônio, lítio e sódio mono e dissubstituídos. Em todos os casos observou-se uma conversão a piroglutamato após desidratação dos sais monossubstituídos, a qual ocorre via a a-carboxila. A estabilidade térmica destes sais foi da ordem de 190-200 °C. No caso dos sais dissubstituídos de lítio e sódio não houve conversão ao piroglutamato pois as duas carboxilas estão salificadas. Os glutamatos de magnésio, cálcio estrôncio e bário, também foram preparados e investigados quanto ao seu comportamento térmico. Os sais se formaram na estequiometria 2:1 (ligante:metal), apresentando águas de hidratação em número característico e foram estáveis até 190- 200 °C. Finalmente foram estudados os mecanismos de decomposição térmica do inosinato-monofosfato de sódio e do guanilato-monofosfato de sódio, dois nucleotídeos que apresentam a propriedade de realçar o sabor de alimentos. Ambos apresentaram elevado grau de hidratação, para o qual foi possível distinguir mecanismos característicos de desidratação. A decomposição dos sais anidros ocorreu com saída do grupo purínico, seguida da decomposição do restante da molécula e formação de pirofosfato de sódio como resíduo final. / Thermal analytical studies of some food addictives of the flavor enhancer class were developed in order to evaluate their stability and resistance to the hot cooking process, as well as to identify the intermediaries of thermal decomposition that could remain at the end of such processes. The salts were obtained from industrial sources or synthesized and characterized by elemental analysis, infra-red spectroscopy, thermogravimetry/derivative thermogravimetry, differential thermal analysis and in some opportunities to differential scanning calorimetry. The glutamic acid and its ammonium, lithium and sodium salts mono and disubstituted were investigated. In all cases a conversion to pyroglutamate has been observed in the free acid and its monosubstituted salts after dehydration. The conversion undergoes by the ?-carboxyl group. The thermal stability was observed to be as high as 190-200 °C. In the case of the lithiu m and sodium dissubstituted salts any conversions to pyroglutamates were observed, once both carboxyl groups were salified. Magnesium, calcium, strontium and barium glutamates has also been synthesized and investigated in relation to its thermal behavior. The salts were formed in the 2:1 stoichiometry (ligand:metal), presenting hydration waters in a characteristic content and showed to be stable up to 190-200 °C. Finally the thermal decomposition mechanisms of dissodium inosinatemonophosphate and dissodium guanilate-monophosphate two nucleotides with flavor enhancement properties in food were also investigated. Both presented high degree of hydration, to which it was possible to propose a water release mechanism. The decomposition of the anhydrous salts occurred with release of the purine group followed by the decomposition of the rest of the molecule generating sodium pyrophosphate as residue.