A colonoscopia é atualmente o padrão ouro para investigação da mucosa dos cólons, reto e íleo terminal. Para sua realização, há necessidade de uso de soluções para limpeza do cólon que, em geral, são mal toleradas pelos pacientes. Os objetivos do presente estudo foram comparar duas soluções de preparo intestinal para colonoscopia, quanto à efetividade, tolerabilidade, aceitabilidade e segurança em pacientes que se submeteriam a colonoscopia eletivamente, no Centro de Diagnóstico em Gastroenterologia do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. Trata-se de estudo unicêntrico, prospectivo, com alocação aleatória dos pacientes. Cem pacientes pareados por sexo e idade foram randomizados em dois grupos. O grupo I recebeu bisacodil mais 1 litro de Polietilenoglicol (PEG) na véspera e 1 litro no dia do exame. O grupo II recebeu bisacodil na véspera e 1 litro de manitol 10% no dia do exame. A mesma dieta foi orientada nos dois grupos. A qualidade do preparo foi graduada através das escalas de Boston e Ottawa. A tolerabilidade e aceitabilidade foram aferidas por questionários previamente estudados. Quanto à segurança, foram ava liadas: variação de sinais vitais antes e após o preparo e complicações. Noventa e seis pacientes (96%) completaram o estudo. Não se observou diferença na qualidade do preparo entre os grupos(p = 0,059). Quanto à tolerabilidade, o grupo I (PEG) apresentou frequência significativamente menor de náusea, vômito, dor abdominal e distensão abdominal (p < 0,05). A aceitabilidade foi significativamente melhor com o grupo I (PEG) (p < 0,05). Em relação à segurança, o grupo I (PEG) apresentou-se mais seguro. No presente estudo, podemos concluir que ambos os preparos são semelhantes em eficácia (p > 0,05) e a solução de PEG apresentou melhor tolerabilidade, aceitabilidade e segurança em comparação ao preparo com manitol (p < 0,05). / Colonoscopy is currently the gold standard to examine the colon, the rectum, and the terminal ileum. To perform a colonoscopy, is necessary to use solutions to clean the colon that are generally poorly tolerated by the patients. The study aims to compare the effectiveness, tolerability, acceptability and safety of two solutions used for intestinal preparation for elective colonoscopy examination in the Diagnosis Center Of Hospital das Clinicas, Faculty of Medicine, University of São Paulo. It is a Prospective study carried out in a single center, with random allocation of the patients. One hundred patients that were paired based on sex and age were randomized into two groups. Group I received bisacodyl plus 1 liter of polyethylene glycol (PEG) the night before and 1 liter on the day of the exam. Group II received bisacodyl the night before and 1 liter of a 10% mannitol solution on the day of the exam. The patients diet was the same for both groups. The quality of the preparation was graded based on the Boston and Ottawa scales. Tolerability and acceptability were measured using previously validated questionnaires. In terms of safety, variations in vital signs before and after the preparation were recorded, as well as any complications. Ninety-six patients (96%) completed the study. No difference was observed in the quality of the preparation between the two preparation methods (p = 0,059). As for tolerability, group II (the mannitol preparation group) presented a significantly higher frequency of nausea, vomiting, abdominal pain and abdominal distension (p < 0,05). Acceptability was significantly better in group I (p < 0,05). The PEG solution was also shown to be safer than mannitol. Based on the present study, the following conclusions can be made: 1) Both methods of preparation had similar efficiencies (p > 0,05); 2) PEG method showed higher tolerability, acceptability and safety compared to the mannitol method (p < 0,05).

A colonoscopia é atualmente o padrão ouro para investigação da mucosa dos cólons, reto e íleo terminal. Para sua realização, há necessidade de uso de soluções para limpeza do cólon que, em geral, são mal toleradas pelos pacientes. Os objetivos do presente estudo foram comparar duas soluções de preparo intestinal para colonoscopia, quanto à efetividade, tolerabilidade, aceitabilidade e segurança em pacientes que se submeteriam a colonoscopia eletivamente, no Centro de Diagnóstico em Gastroenterologia do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. Trata-se de estudo unicêntrico, prospectivo, com alocação aleatória dos pacientes. Cem pacientes pareados por sexo e idade foram randomizados em dois grupos. O grupo I recebeu bisacodil mais 1 litro de Polietilenoglicol (PEG) na véspera e 1 litro no dia do exame. O grupo II recebeu bisacodil na véspera e 1 litro de manitol 10% no dia do exame. A mesma dieta foi orientada nos dois grupos. A qualidade do preparo foi graduada através das escalas de Boston e Ottawa. A tolerabilidade e aceitabilidade foram aferidas por questionários previamente estudados. Quanto à segurança, foram ava liadas: variação de sinais vitais antes e após o preparo e complicações. Noventa e seis pacientes (96%) completaram o estudo. Não se observou diferença na qualidade do preparo entre os grupos(p = 0,059). Quanto à tolerabilidade, o grupo I (PEG) apresentou frequência significativamente menor de náusea, vômito, dor abdominal e distensão abdominal (p < 0,05). A aceitabilidade foi significativamente melhor com o grupo I (PEG) (p < 0,05). Em relação à segurança, o grupo I (PEG) apresentou-se mais seguro. No presente estudo, podemos concluir que ambos os preparos são semelhantes em eficácia (p > 0,05) e a solução de PEG apresentou melhor tolerabilidade, aceitabilidade e segurança em comparação ao preparo com manitol (p < 0,05). / Colonoscopy is currently the gold standard to examine the colon, the rectum, and the terminal ileum. To perform a colonoscopy, is necessary to use solutions to clean the colon that are generally poorly tolerated by the patients. The study aims to compare the effectiveness, tolerability, acceptability and safety of two solutions used for intestinal preparation for elective colonoscopy examination in the Diagnosis Center Of Hospital das Clinicas, Faculty of Medicine, University of São Paulo. It is a Prospective study carried out in a single center, with random allocation of the patients. One hundred patients that were paired based on sex and age were randomized into two groups. Group I received bisacodyl plus 1 liter of polyethylene glycol (PEG) the night before and 1 liter on the day of the exam. Group II received bisacodyl the night before and 1 liter of a 10% mannitol solution on the day of the exam. The patients diet was the same for both groups. The quality of the preparation was graded based on the Boston and Ottawa scales. Tolerability and acceptability were measured using previously validated questionnaires. In terms of safety, variations in vital signs before and after the preparation were recorded, as well as any complications. Ninety-six patients (96%) completed the study. No difference was observed in the quality of the preparation between the two preparation methods (p = 0,059). As for tolerability, group II (the mannitol preparation group) presented a significantly higher frequency of nausea, vomiting, abdominal pain and abdominal distension (p < 0,05). Acceptability was significantly better in group I (p < 0,05). The PEG solution was also shown to be safer than mannitol. Based on the present study, the following conclusions can be made: 1) Both methods of preparation had similar efficiencies (p > 0,05); 2) PEG method showed higher tolerability, acceptability and safety compared to the mannitol method (p < 0,05).

Class of 2015 Abstract / Objectives: To compare and evaluate effects on kidney function of mannitol dieresis versus saline diuresis on kidney function with cisplatin therapy. Methods: Patient charts documented between January 2010 and July 2013 were obtained and reviewed from a database of a university associated medical center. The patient’s lowest creatinine clearance (CrCl) and potassium levels during any time in therapy were compared against the baseline. Statistical testing for primary and secondary outcomes was calculated using the Independent-Samples T-Test. Results: A total of 140 patients were reviewed – 68 patients were included in the mannitol arm, 72 in the saline arm. All baseline characteristics reviewed were not statistically different between groups except for sex, which was skewed towards males in the saline arm of the study. Baseline CrCl was 97.14 ml/min in the mannitol arm, and 93.69 ml/min in the saline arm (p=0.91). The average change in CrCl was found to be -16.72 ml/min (95% CI, -21.85 to -11.59) in the mannitol arm, -14.00 ml/min (95% CI, -18.82 to -9.20) in the saline arm; this was not statistically different (p=0.41). There was an average change of -0.31 mmol/L in blood potassium levels in mannitol patients, and a change of 0.014 mmol/L in saline patients; this was found to be significantly different (p<0.01). Conclusions: In this single-center retrospective study, there appeared to be no benefit in using mannitol diuresis over saline diuresis. The use of mannitol incurs additional cost and place additional restrictions on administration.

The incidence of CF related diabetes is on the rise as patient life expectancy continues to improve. Sugars elevated in diabetics include glucose, fructose, and mannose. These sugars, in addition to mannitol (recently approved as an inhaled osmolyte) are the basis for this study, aimed at assessing the impact these clinically relevant sugars have on virulence in Burkholderia multivorans. B. multivorans is a member of the Burkholderia cepacia complex (Bcc), and is the most frequent cause of Bcc infection in CF patients. Using an exopolysaccharide-deficient knockout in macrophage and Galleria mellonella infection models, biofilm formation, and adhesion assays, this study has identified exopolysaccharide-dependent and -independent phenotypes. Sequencing of B. multivorans C1576, a CF outbreak isolate, identified three putative adhesins in clinical isolate C1576 but not present in the sequenced environmental strain ATCC17616. Mannitol promoted adhesion and enhanced expression of these adhesins. This study characterised these adhesins and assessed the distribution within other clinical and environmental isolates of B. multivorans and the Bcc. Additionally, transcriptomic profiling of B. multivorans assessed the sugar response and EPS regulation during growth on clinically relevant sugars. Where possible, links were made between phenotypic studies and transcriptome data. B. multivorans EPS derived from fructose and mannitol was subjected to composition analysis using mass spectrometry, and assessed for biological activity. Still relevant to CF related diabetes, the ability of some members of the Bcc to bind insulin was assessed. Results indicated that a minority of strains bound insulin. Furthermore, by using flow cytometry cell sorting and fluorescence microscopy, results also showed only a small number of cells within a given population that bound insulin. In all, this study has added to the knowledge base of B. multivorans but more work is needed to fully understand virulence strategies exploited by this CF pathogen.

Submitted by (lucia.rodrigues@ufrpe.br) on 2017-02-13T15:29:49Z No. of bitstreams: 1 Edmilson Clarindo de Siqueira.pdf: 4674633 bytes, checksum: c618a0d261dbc9f5432627199fd82f3a (MD5) / Made available in DSpace on 2017-02-13T15:29:49Z (GMT). No. of bitstreams: 1 Edmilson Clarindo de Siqueira.pdf: 4674633 bytes, checksum: c618a0d261dbc9f5432627199fd82f3a (MD5) Previous issue date: 2012-04-13 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / In this study we investigated the resolution of rac-1,2-propanediol and rac-2,3- isopropylidene glycerol using chiral amines (R)- and (S)-1-phenylethylamine (27). The alcohols are esterified to form hemi-phthalates, and treated with the enantiomers of 27 resulting in the following salts (R)-27.(±)-52 and (S)-27.(±)-52 in good yields. However, salts (R)-27.(±)-33 and (S)-27.(±)-33 did not form crystalline material. In addition we studied the resolution of (±)-14 and (±)-31 through the use of amino acids benzyl esters and brucine as auxiliaries. Attempts to obtain the benzyl ester of L-tryptophan (59) were negative; attempts to obtain benzyl esters of Lphenylalanine (58) and L-lysine (57) were also negative. In the case of brucine (35) there was no noticeable diastereoisomeric enrichment during repeated crystallizations. As an extension to this, we performed dehydration of D-mannitol (40) in an acid medium. Modifications of the published method resulted in obtaining a new derivative, the 2,5-anhydro-1,3-O-benzyl-D-mannitol (81) whose structure was established via x-ray study. / Neste trabalho foi avaliada a resolução dos alcoóis rac-1,2-propanodiol (14) e rac-2,3-isopropilideno glicerol (31) pelas aminas quirais (R)- e (S)-1-feniletilamina (27) via processo de dessimetrização: os alcoóis foram esterificados, na forma de ftalatos, e tratados com os enantiômeros de 27 que resultou nos seguintes sais (R)-27.(±)-52 e (S)-27.(±)-52 em bons rendimentos. Todavia, os sais (R)-27.(±)-33 e (S)-27.(±)-33 não foram isolados em sua forma cristalina. Adicionalmente, foi estudada a resolução de (±)-14 e (±)-31 através do uso de aminoácidos, na sua forma benzílica, e brucina como auxiliares quirais. Tentativas de obter o éster benzil de L-triptofano (59), foram negativas. Alternativas de usar Lfenilalanina (58) e L-lisina (57) também foram negativas. Condizente com este tipo de resolução foi ensaiada também o alcalóide brucina (35), porém não houve enriquecimento diastereoisomérico durante repetidas cristalizações. Como extensão ao trabalho realizado com os alcoóis, foi investigada a desidratação do D-manitol (40) em meio ácido. Modificações desta metodologia conduziram à obtenção de um novo derivado deste substrato, o 2,6-anidro-1,3-di-Obenzil- D-manitol (81), que foi caracterizado por raios-X.

This thesis examines the overarching theme of inhaled corticosteroid (ICS) dose response effects on a variety of asthma outcome measures; with further importance placed on the application of these findings to personalising ICS dosing for the individual asthmatic. The introduction provides a detailed summary of the current recommendations for the treatment of adult asthma, with particular reference to the mechanism of action and clinical utility of ICS for the treatment of asthma. Current methods of assessing ICS dose response are presented, as well as the common influences that affect these responses. Novel therapeutic theories and the identification of specific asthmatic phenotypes are also introduced, in order to demonstrate the shift towards personalising treatment for asthma. The first two studies examine the dose response of ICS on two specific factors that influence asthma. The third study presents an examination of pharmacological manipulation of the ICS dose response using an additional agent. The following two studies address: how asthma outcomes relate to each other in patients receiving ICS; in addition to an overall assessment of the ICS dose response across a broad range of both ICS moieties and outcome measures. The final study examines for any detrimental effect of an ICS dose ramp on bone metabolism, an important potential long-term adverse effect of higher ICS dosing. The discussion draws together all the results obtained in relation to ICS dose response in asthma, and how these apply to current clinical practice for the individual patient. Furthermore, hypotheses are generated for areas of future study based on the findings from this work.

L'induction par un hôte d'un stress oxydatif chez un parasite représente l'une des stratégies de défense chimique les plus répandues. Chez les Brassicacées, famille de plantes comprenant des espèces à fort intérêt agronomique comme le chou ou le colza, ou d'intérêt scientifique comme Arabidopsis thaliana, le stress oxydatif peut être généré soit par des formes actives d'oxygène libérées au niveau de la zone d'agression lors du burst oxydatif soit par des molécules issues du métabolisme secondaire de la plante telles que les isothiocyanates (ITC). Bien que fortement exposé à un tel stress lors de l'infection, Alternaria brassicicola, champignon pathogène nécrotrophe inféodé aux Brassicacées, est capable d'accomplir son cycle parasitaire et donc de s'y adapter. Cette thèse met en évidence que la tolérance du champignon aux stress oxydatif est partiellement dépendante du métabolisme du mannitol qui participe à la résistance des conidies lors du burst oxydatif in planta ou à la protection contre les dommages intracellulaires des FAO générées par les ITC lors des phases précoces de l'interaction. Les travaux réalisés montrent également que la charge fongitoxique des dérivés des glucosinolates peut être inhibée par leur conjugaison au glutathion via des Glutathion-Stransférases (GST) spécifiques. L'altération du métabolisme du mannitol ou l'inactivation de ces GST diminue significativement le pouvoir pathogène d'A. brassicicola et la régulation de ces voies métaboliques est donc à considérer dans l'optique de développer de nouvelles stratégies de protection des cultures.

<p>Directive EC 2003/89/EC of the European Parliament and of the Council states that certain</p><p>ingredients and products derived there of known to cause allergen reactions must always be</p><p>declared. Furthermore labelling is mandatory irrespective of the amount included. The National</p><p>Food Administration therefore needs methods for monitoring the presence of allergens in food.</p><p>Methods already exist for most of the allergens on the EU-list, but an operational method for</p><p>celery (Apium graveolens) is missing.</p><p>A specific DNA-method was developed, based on TaqMan Real-Time PCR with the celery</p><p>mannitol dehydrogenase gene as target sequence. The analysis was started with homogenisation</p><p>of the sample followed by extraction of DNA. The Real-Time PCR method was shown to be</p><p>specific for celery, producing a 113 bp fragment with two celery varieties and negative results</p><p>with other closely selected species commonly present together with celery in food products (12</p><p>samples). The detection limit was 2-20 pg DNA, which corresponds to 1-7 haploid genome</p><p>copies. When evaluated with model samples of celery in meat, a detection limit of less than</p><p>0,01 % was determined. When used to analyse food products from the market, six out of seven</p><p>products declared to contain celery were correctly identified as positive.</p>

<p>The toxicity of perfluorooctane sulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) was measured. When Caco-2 cells from human adenocarcinoma are cultivated on a filter a monolayer is formed with properties similar to human duodenum epithelium. The Caco-2 cells grown on filter were exposed to the environmental contaminants PFOS and PFOA. The effects on the Caco-2 epithelium were examined by four different methods: trans-epithelial resistance (TEER), leakage of the intracellular protein lactate dehydrogenase (LDH), 14C-mannitol passage through the epithelium and protein content of the epithelium. TEER and C-mannitol passage show the Caco-2 cellmonolayer integrity, LDH leakage gives information of cytotoxicity and protein content of the epithelium shows cell adhension to the filter.</p><p>In the first study TEER decreased at the highest concentrations of PFOS and PFOA (1Mm). The 14C-mannitol passage increased at the highest PFOS concentration. No cytotoxicity was shown and protein-loss was not observed. The second study with PFOS doses of 0, 1, 10, 100 and 500µM and 1 and 10mM showed that the effect of PFOS on TEER was dose-dependent. The 14C-mannitol passage was very high at the highest PFOS-concentration (10mM) and a dose-response was indicated. No cytotoxicity was demonstrated and protein-quantity was not affected. In the third study it was demonstrated that the toxicity of PFOS did not depend on the different concentrations of the oil-emulsion used to dissolve PFOS and PFOA.</p>

Directive EC 2003/89/EC of the European Parliament and of the Council states that certain ingredients and products derived there of known to cause allergen reactions must always be declared. Furthermore labelling is mandatory irrespective of the amount included. The National Food Administration therefore needs methods for monitoring the presence of allergens in food. Methods already exist for most of the allergens on the EU-list, but an operational method for celery (Apium graveolens) is missing. A specific DNA-method was developed, based on TaqMan Real-Time PCR with the celery mannitol dehydrogenase gene as target sequence. The analysis was started with homogenisation of the sample followed by extraction of DNA. The Real-Time PCR method was shown to be specific for celery, producing a 113 bp fragment with two celery varieties and negative results with other closely selected species commonly present together with celery in food products (12 samples). The detection limit was 2-20 pg DNA, which corresponds to 1-7 haploid genome copies. When evaluated with model samples of celery in meat, a detection limit of less than 0,01 % was determined. When used to analyse food products from the market, six out of seven products declared to contain celery were correctly identified as positive.