Thesis (Ph.D.)--University of Alabama at Birmingham, 2009. / Title from PDF title page (viewed on July 1, 2010). Includes bibliographical references.

Bakgrund: Diabetes mellitus typ II (DMT2) är en kronisk sjukdom som ökar i antal både i Sverige och runtom i världen. Att få diagnosen DMT2 innebär att personen får ett ansvar för egenvård och att utföra livsstilsförändringar. Om personen inte följer sin behandling och ändrar sin livsstil kan det medföra flertals komplikationer så som hjärt- och kärlproblematik.Syfte: Var att beskriva personers upplevelse av att leva med DMT2.Metod: Litteraturöversikt med 14 artiklar med kvalitativ ansats.Resultat: Resultatet har huvudkategorierna psykisk, fysisk och social påverkan i vardagslivet samt synen på livsstilsförändringar med respektive underkategorier. Personer som lever med DMT2 upplevde blandade känslor och blev olika påverkade. Att ha DMT2 krävde livsstilsförändringar som kunde ses som en möjlighet eller svårighet. Personer beskrev vikten av stöd och vad sjuksköterskans roll innebär för hanterbarheten av sjukdomen.Slutsats: Litteraturöversikten bidrog med förståelse och kunskap om hur personer som lever med DMT2 upplever sitt liv och sjukdomen. Kunskapen från litteraturöversikten gav även en förståelse för varför personer inte följer deras rekommendationer, deras behov av omvårdnad och stöd. / Background: Diabetes mellitus type II (DMT2) is a chronic disease that increases in numbers both in Sweden and around the world. To diagnose DMT2 means that the person is given a responsibility for self-care and lifestyle changes. If the person does not follow his treatment and changes his lifestyle, it can cause plural complications such as cardiovascular problems.Purpose: To describe people's experience of living with DMT2.Method: Literature review with 14 articles with qualitative approaches.Result: The result has the main category of psychological, physical and social influences in everyday life with the respective subcategories and the view on lifestyle changes. People living with DMT2 experienced mixed feelings and were affected differently. Having DMT2 required lifestyle changes that could be seen as an opportunity or difficulty. Individuals described the importance of support and what the nurse's role means for the manageability of the disease.Conclusion: The literature review contributed to understanding and knowledge about how people living with DMT2 experience their lives and the disease. The knowledge from the literature review also gave an understanding of why people do not follow their recommendations, their needs for nursing and support.

Introdução: As mucopolisaccaridoses tipo I (MPS I), tipo II (MPS II) e tipo VI (MPS VI) são doenças lisossômicas (DL) para as quais está disponível a terapia de reposição enzimática (TRE) com laronidase, idursulfase e galsufase, respectivamente. Objetivo Primário: Analisar a frequência anual de intervenções médicas (número de consultas, internações, cirurgias, exames solicitados, medicamentos prescritos, equipamentos de uso crônico e outras formas de terapia) em uma amostra de pacientes brasileiros com MPS I, II e VI e, desta forma, contribuir para o conhecimento dos aspectos farmacoeconômicos relacionados a essas doenças. Metodologia: Estudo exploratório, retrospectivo, de base hospitalar, baseado em revisão de prontuário, com amostragem por conveniência, e que foi realizado em duas etapas (etapas 1 e 2). Um instrumento específico para a coleta de dados de ambas as etapas foi construído pela equipe do estudo, que é multidisciplinar. Os desfechos de interesse foram as frequências anuais de intervenções médicas (consultas, exames, cirurgias, internações, medicamentos utilizados, outras formas de terapia). A etapa 1 consistiu em estudo pré-experimental, realizado no Serviço de Genética Médica do Hospital de Clínicas de Porto Alegre (SGM-HCPA), e que comparou as variáveis de interesse, para o mesmo grupo de pacientes, entre o período pré e pós-TRE. Os critérios de inclusão dessa etapa foram: ter diagnóstico confirmado de MPS I; estar em acompanhamento regular no SGM-HCPA desde o diagnóstico; estar em TRE por pelo menos um ano; e não ter participado de ensaio clínico envolvendo TRE ou ter realizado transplante de células-tronco hematopoiéticas. A etapa 2 foi transversal, multicêntrica (centros incluídos: SGMHCPA, Departamento de Genética Médica da Universidade Estadual de Campinas - UNICAMP, Pontifícia Universidade Católica de Campinas – PUC-Campinas, e Departamento de Pediatria da Universidade Estadual do Rio de Janeiro - UERJ), e comparou as variáveis de interesse entre grupos diferentes de pacientes (aqueles recebendo TRE e aqueles não recebendo TRE). Para essa etapa, foram considerados somente os dados relativos a 2010, sendo os seguintes os critérios de inclusão dos pacientes: ter diagnóstico confirmado de MPS I, II e VI; não estar participando de nenhum ensaio clínico envolvendo TRE ou ter realizado transplante de células-tronco hematopoiéticas; estar em TRE por pelo menos 12 meses antes do início da coleta, ou em acompanhamento por pelo 12 meses antes do início da coleta. Resultados: Etapa 1 - Nove pacientes (graves=3; atenuados=6) com MPS I foram incluídos no estudo, com mediana de idade de diagnóstico de 4,4 anos. Somente o número de cirurgias/ano/paciente foi dependente do tempo de doença (p=0,0004) e da gravidade do fenótipo (p=0,014). Com relação às comparações pré e pós-TRE, as variáveis que apresentaram diferença significativa (média do número/ano/paciente) foram: exames (pré-TRE=10,2+2,7; pós-TRE=22,5+2,1; p=0,005) e internações (pré-TRE=0,05+0,04; pós-TRE=0,30+0,11; p=0,013). Para as demais variáveis, não foi encontrada associação. Etapa 2 - Trinta e quatro pacientes com MPS I (n=12), II (n=17) e VI (n=5) foram incluídos no estudo. Desses, sete não utilizavam TRE (grupo “sem TRE") e 27 faziam uso de tratamento específico (grupo “com TRE"). Não foi encontrada correlação significativa entre tempo de doença e as variáveis estudadas. Considerando a amostra total, foi encontrada diferença entre o grupo “sem TRE” e o grupo “com TRE” em relação à mediana de internações hospitalares e de cirurgias realizadas [1(0-2) vs. 0 (0-1), p=0,015; e 0 (0-2) vs. 0 (0-0), p=0,040, respectivamente]. Para as crianças/adolescentes (<18 anos), não foi encontrada diferença estatística entre os grupos. Os pacientes com comprometimento cognitivo utilizavam mais medicamentos que os demais (p=0,024). Encontrou-se correlação negativa entre as variáveis duração da TRE e número anual de internações (r= -0,504; p=0,007). Discussão/ Conclusões: Este é um dos primeiros estudos a avaliar aspectos relacionados à farmaconomia da TRE para as MPS. De acordo com os resultados obtidos na etapa 2, verifica-se que, desconsiderando-se o custo associado às infusões, o custo do tratamento de pacientes com MPS parece ser menor para aqueles pacientes que utilizam a TRE do que para os pacientes que fazem somente tratamento sintomático. Entretanto, de acordo com a etapa 1 do estudo, a TRE parece não impedir a evolução da doença, pelo menos em relação à MPS I, e, assim, a cada ano de vida do paciente ocorreria um incremento do custo associado ao tratamento. Estudos adicionais, com maior tamanho amostral, deverão ser realizados para confirmar nossos achados. / Introduction: The mucopolysaccharidoses type I (MPS I), II (MPS II) and VI (MPS VI) are lysosomal disorders (LSD) for which enzyme replacement therapy (ERT) with laronidase, idursulfase and galsulfase, respectively, are available. Principal objective: To analyze the annual frequency of medical interventions (number of medical appointments, hospital admissions, surgical procedures, exams performed, medications prescribed, ancillary therapies and the use of medical devices) in a sample of Brazilian patients with MPS I, II and VI, and thus, contribute to the understanding of some pharmacoeconomic aspects related to these diseases. Methodology: Retrospective, exploratory, hospital-based study, based on medical records review, with convenience sampling, which was conducted in two steps (steps 1 and 2). A specific data collection instrument for both steps was designed by the study team, which is multidisciplinary. The chosen outcomes were: annual frequencies of medical interventions (medical appointments, exams, surgical procedures, hospital admissions, medications used and ancillary therapies). Step 1 was a pre-experimental study conducted at the Medical Genetics Service of Hospital de Clínicas de Porto Alegre (SGM-HCPA), and compared the variables of interest between the pre and post-ERT periods for the same group of patients. The patient inclusion criteria were: a biochemical diagnosis of MPS I and regular follow-up at SGM-HCPA since diagnosis; ERT for at least 1 year; no enrollment in any clinical trials involving ERT, and no history of hematopoietic stem cell transplantation. Step 2 was a cross-sectional and multicentric estudy (Centers included: SGM-HCPA), the Department of Medical Genetics of Universidade Estadual de Campinas - UNICAMP, Pontifícia Universidade Católica de Campinas - PUC-Campinas, and the Department of Pediatrics at Universidade Estadual do Rio de Janeiro – UERJ, which compared the variables of interest between different groups of patients (those receiving and those not receiving ERT). For this step only data from 2010 were considered. The inclusion patient criteria were: a biochemical diagnosis of MPS I, II or VI; no enrollment in any clinical trials involving ERT, and no history of hematopoietic stem cell transplantation, to be on ERT for at least 12 months before the start of data collection or to undergo regular follow-up for at least 12 months before the start of data collection. Results: Step 1 – Nine MPS I patients (severe=3; attenuated phenotype=6) were included in the study with median age at diagnosis was 4.4 years. Only the number/year/patient of surgeries was found to be dependent on length of disease (p=0.0004) and on severity of phenotype (p=0.014). Regarding pre- and post-ERT comparisons, the variables for which a significant difference was detected (mean number/year/patient) were exams (pre-ERT, 10.2±2.7; post-ERT, 22.5±2.1; p=0.005) and hospital admissions (pre-ERT, 0.05±0.04; post-ERT, 0.30±0.11; p=0.013). For the other variables, no association was found. Step 2: Thirty-four patients with MPS I, II and VI were included (I=12, II=17, VI=5). From them, 27 on ERT (“ERT group”) and 7 receiving supportive care only (“non-ERT group”). There were no significant correlation between length of disease and any of the variables of interest. There were significant between-group differences in the median number of hospital admissions and surgical procedures, both of which were higher in the non-ERT group [1(0-2) vs. 0 (0-1), p=0,015; e 0 (0-2) vs. 0 (0-0), p=0,040, respectively]. There were no significant between-group differences when only children and adolescents (<18 years) were taken into account. Patients with cognitive involvement used more medications than the others (p=0.024). A correlation was detected between time on ERT and the hospital admissions variable (r= -0.504; p=0.007). Discussion/conclusions: This was one of the first studies to evaluate aspects related to pharmacoeconomics of ERT for MPS. According to the results of step 2, and not acknowledging the costs associated with recombinant enzyme infusions, patients with MPS who undergo ERT generate less cost to SUS than patients on symptomatic treatment. On the other hand, according to the results of step 1, ERT seems not to stop the disease progress, at least in respect to MPS I, and thus, for each year of a patient life occurred an increase in cost associated with treatment. Additional studies with larger sample size are needed to confirm our findings.

This study was conducted to estimate power of tests in Analysis of Variance (ANOVA) in beef cattle experiments, determine sample size and classify the coefficient of variation. Data was collected from thesis and dissertations of the Program of Post-Graduation in Animal Science of Federal University of Santa Maria (PPGZ-UFSM) among the years of 1991 to 2012, in beef cattle production area using ANOVA. Power was estimated by assumption of non central F distribution to the alternative hypothesis in ANOVA. The number of replications for treatments was estimated by power of 80% and interval of [0,4 ; 2,0] to effect size. Classification of coefficient of variation was based on proposed by Garcia (1989) using mean and standard deviation, and Costa et al. (2002) using median and pseudo-sigma. Power of tests shows two frequency peaks of experiments with low and high power. The recommended average number of replication per treatments was among 7 and 10 replications. Classification of coefficient of variation was proposed by low, medium and high, differently from literature that considers the intervals low, medium, high and very high. / Este estudo foi realizado com o objetivo de determinar o poder do teste F em Análise de Variância (ANOVA) para experimentos com bovinos de corte, determinar o tamanho ideal de amostra e classificar o coeficiente de variação. Os dados foram utilizados de dissertações e teses publicadas do Programa de Pós-Graduação em Zootecnia da Universidade Federal de Santa Maria (PPGZ-UFSM) nos anos de 1991 à 2012, na área de bovinocultura de corte empregando ANOVA. O poder do teste foi determinado assumindo distribuição F de Fisher não central sob hipótese alternativa para a estatística de teste F na ANOVA. O número de repetições por tratamentos foi estimado com base no poder do teste de 80% e o intervalo [0,4 ; 2,0] para o tamanho do efeito. A classificação do coeficiente de variação foi baseada nas metodologias propostas por Garcia (1989) usando média e desvio padrão, e Costa et al. (2002) utilizando mediana e pseudo-sigma. As estimações de poder do teste apresentaram picos de frequências de alto e baixo poder. O número médio recomendado de repetições por tratamentos oscilou entre 7 e 10 repetições. Foi proposta a classificação do coeficiente de variação em baixo, médio e alto, diferindo da classificação da literatura que considera os intervalos baixo, médio, alto e muito alto.

Introdução: As mucopolisaccaridoses tipo I (MPS I), tipo II (MPS II) e tipo VI (MPS VI) são doenças lisossômicas (DL) para as quais está disponível a terapia de reposição enzimática (TRE) com laronidase, idursulfase e galsufase, respectivamente. Objetivo Primário: Analisar a frequência anual de intervenções médicas (número de consultas, internações, cirurgias, exames solicitados, medicamentos prescritos, equipamentos de uso crônico e outras formas de terapia) em uma amostra de pacientes brasileiros com MPS I, II e VI e, desta forma, contribuir para o conhecimento dos aspectos farmacoeconômicos relacionados a essas doenças. Metodologia: Estudo exploratório, retrospectivo, de base hospitalar, baseado em revisão de prontuário, com amostragem por conveniência, e que foi realizado em duas etapas (etapas 1 e 2). Um instrumento específico para a coleta de dados de ambas as etapas foi construído pela equipe do estudo, que é multidisciplinar. Os desfechos de interesse foram as frequências anuais de intervenções médicas (consultas, exames, cirurgias, internações, medicamentos utilizados, outras formas de terapia). A etapa 1 consistiu em estudo pré-experimental, realizado no Serviço de Genética Médica do Hospital de Clínicas de Porto Alegre (SGM-HCPA), e que comparou as variáveis de interesse, para o mesmo grupo de pacientes, entre o período pré e pós-TRE. Os critérios de inclusão dessa etapa foram: ter diagnóstico confirmado de MPS I; estar em acompanhamento regular no SGM-HCPA desde o diagnóstico; estar em TRE por pelo menos um ano; e não ter participado de ensaio clínico envolvendo TRE ou ter realizado transplante de células-tronco hematopoiéticas. A etapa 2 foi transversal, multicêntrica (centros incluídos: SGMHCPA, Departamento de Genética Médica da Universidade Estadual de Campinas - UNICAMP, Pontifícia Universidade Católica de Campinas – PUC-Campinas, e Departamento de Pediatria da Universidade Estadual do Rio de Janeiro - UERJ), e comparou as variáveis de interesse entre grupos diferentes de pacientes (aqueles recebendo TRE e aqueles não recebendo TRE). Para essa etapa, foram considerados somente os dados relativos a 2010, sendo os seguintes os critérios de inclusão dos pacientes: ter diagnóstico confirmado de MPS I, II e VI; não estar participando de nenhum ensaio clínico envolvendo TRE ou ter realizado transplante de células-tronco hematopoiéticas; estar em TRE por pelo menos 12 meses antes do início da coleta, ou em acompanhamento por pelo 12 meses antes do início da coleta. Resultados: Etapa 1 - Nove pacientes (graves=3; atenuados=6) com MPS I foram incluídos no estudo, com mediana de idade de diagnóstico de 4,4 anos. Somente o número de cirurgias/ano/paciente foi dependente do tempo de doença (p=0,0004) e da gravidade do fenótipo (p=0,014). Com relação às comparações pré e pós-TRE, as variáveis que apresentaram diferença significativa (média do número/ano/paciente) foram: exames (pré-TRE=10,2+2,7; pós-TRE=22,5+2,1; p=0,005) e internações (pré-TRE=0,05+0,04; pós-TRE=0,30+0,11; p=0,013). Para as demais variáveis, não foi encontrada associação. Etapa 2 - Trinta e quatro pacientes com MPS I (n=12), II (n=17) e VI (n=5) foram incluídos no estudo. Desses, sete não utilizavam TRE (grupo “sem TRE") e 27 faziam uso de tratamento específico (grupo “com TRE"). Não foi encontrada correlação significativa entre tempo de doença e as variáveis estudadas. Considerando a amostra total, foi encontrada diferença entre o grupo “sem TRE” e o grupo “com TRE” em relação à mediana de internações hospitalares e de cirurgias realizadas [1(0-2) vs. 0 (0-1), p=0,015; e 0 (0-2) vs. 0 (0-0), p=0,040, respectivamente]. Para as crianças/adolescentes (<18 anos), não foi encontrada diferença estatística entre os grupos. Os pacientes com comprometimento cognitivo utilizavam mais medicamentos que os demais (p=0,024). Encontrou-se correlação negativa entre as variáveis duração da TRE e número anual de internações (r= -0,504; p=0,007). Discussão/ Conclusões: Este é um dos primeiros estudos a avaliar aspectos relacionados à farmaconomia da TRE para as MPS. De acordo com os resultados obtidos na etapa 2, verifica-se que, desconsiderando-se o custo associado às infusões, o custo do tratamento de pacientes com MPS parece ser menor para aqueles pacientes que utilizam a TRE do que para os pacientes que fazem somente tratamento sintomático. Entretanto, de acordo com a etapa 1 do estudo, a TRE parece não impedir a evolução da doença, pelo menos em relação à MPS I, e, assim, a cada ano de vida do paciente ocorreria um incremento do custo associado ao tratamento. Estudos adicionais, com maior tamanho amostral, deverão ser realizados para confirmar nossos achados. / Introduction: The mucopolysaccharidoses type I (MPS I), II (MPS II) and VI (MPS VI) are lysosomal disorders (LSD) for which enzyme replacement therapy (ERT) with laronidase, idursulfase and galsulfase, respectively, are available. Principal objective: To analyze the annual frequency of medical interventions (number of medical appointments, hospital admissions, surgical procedures, exams performed, medications prescribed, ancillary therapies and the use of medical devices) in a sample of Brazilian patients with MPS I, II and VI, and thus, contribute to the understanding of some pharmacoeconomic aspects related to these diseases. Methodology: Retrospective, exploratory, hospital-based study, based on medical records review, with convenience sampling, which was conducted in two steps (steps 1 and 2). A specific data collection instrument for both steps was designed by the study team, which is multidisciplinary. The chosen outcomes were: annual frequencies of medical interventions (medical appointments, exams, surgical procedures, hospital admissions, medications used and ancillary therapies). Step 1 was a pre-experimental study conducted at the Medical Genetics Service of Hospital de Clínicas de Porto Alegre (SGM-HCPA), and compared the variables of interest between the pre and post-ERT periods for the same group of patients. The patient inclusion criteria were: a biochemical diagnosis of MPS I and regular follow-up at SGM-HCPA since diagnosis; ERT for at least 1 year; no enrollment in any clinical trials involving ERT, and no history of hematopoietic stem cell transplantation. Step 2 was a cross-sectional and multicentric estudy (Centers included: SGM-HCPA), the Department of Medical Genetics of Universidade Estadual de Campinas - UNICAMP, Pontifícia Universidade Católica de Campinas - PUC-Campinas, and the Department of Pediatrics at Universidade Estadual do Rio de Janeiro – UERJ, which compared the variables of interest between different groups of patients (those receiving and those not receiving ERT). For this step only data from 2010 were considered. The inclusion patient criteria were: a biochemical diagnosis of MPS I, II or VI; no enrollment in any clinical trials involving ERT, and no history of hematopoietic stem cell transplantation, to be on ERT for at least 12 months before the start of data collection or to undergo regular follow-up for at least 12 months before the start of data collection. Results: Step 1 – Nine MPS I patients (severe=3; attenuated phenotype=6) were included in the study with median age at diagnosis was 4.4 years. Only the number/year/patient of surgeries was found to be dependent on length of disease (p=0.0004) and on severity of phenotype (p=0.014). Regarding pre- and post-ERT comparisons, the variables for which a significant difference was detected (mean number/year/patient) were exams (pre-ERT, 10.2±2.7; post-ERT, 22.5±2.1; p=0.005) and hospital admissions (pre-ERT, 0.05±0.04; post-ERT, 0.30±0.11; p=0.013). For the other variables, no association was found. Step 2: Thirty-four patients with MPS I, II and VI were included (I=12, II=17, VI=5). From them, 27 on ERT (“ERT group”) and 7 receiving supportive care only (“non-ERT group”). There were no significant correlation between length of disease and any of the variables of interest. There were significant between-group differences in the median number of hospital admissions and surgical procedures, both of which were higher in the non-ERT group [1(0-2) vs. 0 (0-1), p=0,015; e 0 (0-2) vs. 0 (0-0), p=0,040, respectively]. There were no significant between-group differences when only children and adolescents (<18 years) were taken into account. Patients with cognitive involvement used more medications than the others (p=0.024). A correlation was detected between time on ERT and the hospital admissions variable (r= -0.504; p=0.007). Discussion/conclusions: This was one of the first studies to evaluate aspects related to pharmacoeconomics of ERT for MPS. According to the results of step 2, and not acknowledging the costs associated with recombinant enzyme infusions, patients with MPS who undergo ERT generate less cost to SUS than patients on symptomatic treatment. On the other hand, according to the results of step 1, ERT seems not to stop the disease progress, at least in respect to MPS I, and thus, for each year of a patient life occurred an increase in cost associated with treatment. Additional studies with larger sample size are needed to confirm our findings.

Submitted by Fabio Sobreira Campos da Costa (fabio.sobreira@ufpe.br) on 2016-09-12T14:41:29Z No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Tese_2016_Eryvelton PPGCF_UFPE.pdf: 2235912 bytes, checksum: 48691df62258c8f06d762a37dfc7ad5a (MD5) / Made available in DSpace on 2016-09-12T14:41:30Z (GMT). No. of bitstreams: 2 license_rdf: 1232 bytes, checksum: 66e71c371cc565284e70f40736c94386 (MD5) Tese_2016_Eryvelton PPGCF_UFPE.pdf: 2235912 bytes, checksum: 48691df62258c8f06d762a37dfc7ad5a (MD5) Previous issue date: 2016-03-11 / CAPEs / A crescente substituição dos alimentos in natura por produtos industrializados (ricos em carboidratos simples, lipídios, elevado teor em sódio e baixo teor em fibras), associados a um estilo de vida sedentário, vem contribuindo para o aumento da prevalência de pessoas obesas e consequentemente pré-dispostas ao desenvolvimento da Síndrome Metabólica (SM), condição clínica que compreende alterações específicas, incluindo obesidade abdominal, resistência à insulina, dislipidemia e hipertensão. Várias opções terapêuticas convencionais, bem como espécies vegetais com propriedades medicinais, têm sido utilizadas no tratamento dos distúrbios verificados na SM. Nesse contexto, a Parkinsonia aculeata L., indicada popularmente para o controle do diabetes, vem sendo estudada quanto ao seu perfil fitoquímico e farmacológico, revelando resultados promissores em modelos animais de diabetes e de dislipidemias. Dessa forma, o objetivo deste estudo foi avaliar os efeitos bioquímicos e moleculares do extrato hidroalcoólico (HA) e partição (HAP - HA/acetato de etila) de P. aculeata sobre o perfil glicêmico de ratos Wistar com SM induzida por Dieta Ocidentalizada (DO). Foram acompanhados 42 ratos Wistar machos pós-desmame (21 dias), divididos inicialmente em dois grupos, que receberam dieta padrão para roedores (Presence®- DP) ou DO durante 150 dias. Em seguida, esses animais foram divididos em seis subgrupos, os quais foram tratados por gavagem durante 30 dias consecutivos, com HA ou HAP (130 ou 65 mg/kg/dia), Metformina (500 mg/kg/dia) ou água destilada (10 ml/kg/dia). A evolução ponderal de todos os animais foi avaliada semanalmente até os 150 dias de consumo das dietas. Aos 90, 120 e 150 dias foram registradas as dimensões corporais e teste de tolerância oral à glicose (TTOG) e aos 150 dias, o teste de resistência à insulina (TRI), perfil lipídico, hematológico e de proteínas séricas. A evolução ponderal continuou sendo avaliada uma vez por semana durante os 30 dias de tratamento e ao final todas as variáveis supracitadas foram novamente avaliadas. Posteriormente, os animais foram anestesiados e eutanasiados por decapitação. Em seguida, foram determinados o peso dos órgãos (coração e fígado), dos tecidos (adiposo, abdominal e epididimal), os níveis séricos de corticosterona, IL-6, IL-8, TNF-α, insulina e a concentração do glicogênio hepático e muscular. Nossos resultados mostraram que os animais submetidos à DO apresentaram sinais de SM (aumento da circunferência abdominal, dislipidemia, hiperglicemia), com diferença (p<0,05) média de 23,01% ± 0,78% no peso a partir da 10ª semana, chegando a 23,85% ± 0,96% na 22ª semana. Aos 150 dias, todos os subgrupos DO apresentaram nítida tolerância à glicose nos tempos de 60, 90 e 120 minutos, e o TRI através do Kitt revelou um aumento médio (p<0,05) no tempo de meia vida da glicose de 75,63%, comparados ao grupo DP. Os subgrupos DO apresentaram aumento médio (p<0,05) de colesterol e triglicerídeos de 23,59% e 38,75%, respectivamente, comparados aos do grupo DP. O tratamento com a partição HAP (130 mg/kg), mesmo com a continuidade do consumo da DO pelos animais (do 150º ao 180º dia), trouxe os níveis de colesterol, de triglicerídeos, da glicemia de jejum, das concentrações séricas de insulina, de IL-6 e de TNF-α, bem como das concentrações de glicogênio muscular e hepático, a valores comparáveis aos do grupo DP. Adicionalmente o tratamento com HAP (130 mg/kg) promoveu o aumento (p<0,05) nos níveis de HDL-c. Contudo, o tratamento com HA (130 ou 65 mg/kg) ou HAP (130 ou 65 mg/kg) não modificou o peso do tecido hepático, adiposo abdominal ou epididimal. Finalmente, concluímos que a DO induz um quadro característico de SM (obesidade central, dislipidemia, hiperglicemia de jejum, elevados níveis de IL-6 e de TNF-α) em ratos Wistar e que o tratamento com o HAP (130 mg/kg) foi capaz de restabelecer a homeostase glicêmica e lipídica, além de reduzir a liberação de citocinas pró-inflamatórias, que contribuem para o estado de inflamação crônica de baixo grau existente em indivíduos obesos. / The increasing substitution of fresh food for processed products (with high levels in simple carbohydrates, lipids, sodium and low levels in fiber), associated with a sedentary lifestyle, has contributed to the increasing prevalence of overweight people and consequently predisposed to the development of the Metabolic Syndrome (MS), which is a clinical condition with several specific changes, including abdominal obesity, insulin resistance, dyslipidemia and hypertension. Many conventional treatment options, like plant species with medicinal properties, have been used in the treatment of disorders observed in MS. In this context, Parkinsonia aculeata L., popularly indicated for diabetes control, has been studied both in phytochemical and pharmacological profiles, showing promising results in animal models of diabetes and dyslipidemia. Therefore, the aim of this study was to evaluate the biochemical and molecular effects of hydroalcoholic extract (HA) and partition (HAP - HA/ethyl acetate) of P. aculeata on the glycemic profile of Wistar rats with MS, induced by Westernized Diet (WD). Forty-two Wistar male rats were observed after ablactating (21 days), initially divided into two groups, which received standard rodent feed (Presence® - SD), or WD by 150 days. Then these animals were divided into six subgroups, which were treated by gavage for 30 consecutive days with HA or HAP (130 or 65 mg/kg/day), Metformin (500 mg/kg/day) or distilled water (10 ml/kg/day). Once a week, until 150 days of diet consumption, the weight gain of those animals was evaluated weekly until the end of 150 days consuming these diets. At 90, 120 and 150 days body dimensions and oral glucose tolerance test (OGTT) were registered and at 150 days, Insulin resistance test (IRT), lipid and hematology profile and serum proteins. The weight gain was remained evaluating once a week for the 30 days of treatment and in the end of it, all parameters mentioned above were evaluated again. Later, the animals were anesthetized and euthanized by decapitation. Then the weight of the organs (heart and liver), tissues (fat, abdominal and epididymal) and serum levels of corticosterone, IL-6, IL-8, TNF-α, insulin and hepatic and muscle glycogen concentration were measured. Our results showed that animals submitted to westernized diet showed signs of metabolic syndrome (abdominal obesity increase, dyslipidemia, hyperglycemia), with difference (p<0.05) average of 23.01% ± 0.78% in weight from the 10th week, reaching 23.85% ± 0.96% at 22 weeks. After 150 days, all the WD subgroups revealed visible glucose tolerance at 60, 90 and 120 minutes, and IRT through Kitt showed an average increase (p<0.05) in the half-life of 75.63% glucose, compared to the SD group. The WD subgroups demonstrated an average increase (p<0.05) of cholesterol (23.59%) and triglyceride (38.75%), compared to the SD group. The treatment with the HAP130 partition, even with the continuity of WD consumption by the animals (from 150 to 180 days), brought the levels of cholesterol, triglycerides, fasting blood glucose, concentration of serum insulin, IL-6, TNF-α, muscle and liver glycogen to comparable values of the SD group. Additionally, the treatment with HAP (130 mg/kg) caused an increase (p<0.05) in HDL-c levels. However, the treatment with HA (130 or 65 mg/kg) or HAP (130 or 65 mg/kg) hasn´t changed the weight of epididymal, liver and abdominal fat tissues. Finally, we conclude that the WD induces a characteristic chart of MS (central obesity, dyslipidemia, fasting hyperglycemia, high levels of IL-6 and TNF-α) in rats Wistar and the treatment with HAP (130 mg/kg) was able to restore glycemic and lipid homeostasis and to reduce the release of pro-inflammatory cytokines, which contribute to a low level chronic inflammation state in obese individuals.

Objetivo: O objetivo deste estudo foi avaliar, em pacientes portadores de diabete melito tipo 2 (DM 2) e em indivíduos saudáveis (C), o efeito agudo e crônico do exercício físico aeróbio intenso (TFA) sobre o insulto oxidativo e defesas antioxidantes plasmáticas, bem como o reflexo sobre a habilidade das HDL2 e HDL3 em inibir a oxidação das LDL in vitro. Métodos: O consumo máximo de oxigênio no pico de exercício (VO2 pico) foi medido respiração a respiração, durante teste de esforço máximo, realizado antes e após as 18 sem de TFA supervisionado. Colesterol total (CT), triglicérides (TG), glicose plasmática e insulina foram determinados antes e após TFA. Também foram determinadas a concentração de substâncias reativas ao ácido tiobarbitúrico (TBARS), o perfil antioxidante total e a atividade sérica da paraoxonase-1. As HDL2 e HDL3 foram isoladas do plasma por ultracentrifugação em gradiente descontínuo de densidade. Para determinar o lag time de oxidação de LDL (LAG) e a razão máxima de formação de dienos conjugados (RDC), as HDL2 e HDL3, isoladas nos diferentes períodos experimentais, foram incubadas com pool de LDL de doadores saudáveis, na presença de CuSO4 (10µmol/mL) a 37°C, com leitura a 234 nm, durante 4 h. CT, TG, fosfolípides e apolipoproteína A-I foram determinados nas subfrações de HDL. Resultados: O VO2 pico aumentou em ambos os grupos após TFA. Não se observou variação significativa de peso, TG, HDL colesterol (HDLc), insulina e índice HOMA entre os grupos, tampouco após o treinamento físico. Antes do período de TFA, o CT e o LDL colesterol plasmáticos do grupo C foram maiores que o do grupo DM 2, diferença que não se manteve após o período de treinamento físico. HbA1c e glicemia foram maiores no grupo DM 2, antes e após TFA. O TFA não alterou a HbA1c no grupo DM 2. Na presença de HDL3, o LAG foi semelhante entre os grupos antes do TFA, porém apenas no grupo DM 2 houve aumento do LAG e redução na RDC, mediante incubação com HDL3 isolada após TFA. Na presença de HDL2, o LAG foi menor no grupo DM 2 quando comparado ao grupo C, antes do TFA. Após TFA esta diferença desapareceu. Não houve alteração na RDC em ambos os grupos após TFA. Não houve diferença entre os grupos na composição da HDL3 antes e após TFA. No período basal, a HDL2 do grupo DM 2 apresentou concentrações menores de CT e livre, desaparecendo a diferença após o TFA. Após TFA, observou-se redução no TBARS apenas no DM 2. O TFA não alterou a atividade da paraoxonase-1 e o perfil antioxidante total no plasma em ambos os grupos. Conclusão: O TFA reduziu a peroxidação lipídica no plasma, corrigiu o efeito antioxidante da HDL2 e melhorou o da HDL3 em indivíduos portadores de DM 2. Estes eventos foram independentes de alteração na sensibilidade à insulina e da concentração e composição de HDL no plasma / Objective: The objective of this study was to analyze in type 2 diabetes mellitus (DM 2) and in healthy controls subjects (C) the role of acute and aerobic exercise training (AET) on plasma oxidative stress and antioxidant defenses as well as the HDL2 and HDL3 ability to inhibit the in vitro LDL oxidation. Methods: Peak oxygen uptake (VO2 peak) was measured breath to breath during a maximal cardiopulmonary exercise test before (basal period) and after a 18-wk supervised AET. HDL2 and HDL3 isolated in both periods by discontinuous density gradient ultracentrifugation were incubated with a healthy donor\'s plasma LDL pool for measuring at 234 nm both the lag time for LDL oxidation (LAG) and the maximal rate of conjugated diene formation (MCD) on CuSO4 (10 µmol/mL) at 37°C, for 4 h. Total cholesterol, triglycerides, apolipoprotein A-I and phospholipids were measured in HDL2 and HDL3. TBARS, total antioxidant status and paraoxonase-1 activity were determined in plasma or serum. Results: VO2 peak increased similarly in C and in DM 2 after AET. In the basal period and after AET, both DM 2 and C did not differ according to TG, HDL-c, insulin and HOMA index. HbA1c and glycemia were higher in DM 2 before and after AET. Before AET TC and LDL-c was lower in DM 2 than in C. After AET, TC and LDL-c was similar between C and DM 2. In the presence of HDL3 lag time and MCD was similar in C and DM 2, but only in DM 2 AET improved lag time and reduce MCD. HDL3 composition was similar in DM 2 and C after AET. In the presence HDL2 lag time was lower in DM 2 than in C in the basal period, but did not differ after AET. MCD was lower in DM 2 after AET. HDL2 had less total and free cholesterol in DM 2 than in C but differences vanished after AET. After training plasma TBARS concentration was reduced in DM 2 alone. Training did not modify the total antioxidant status and serum paraoxonase-1 activity in both groups. AET reduces lipid peroxides in plasma, corrects the HDL2 and improves the HDL3 antioxidant effects in DM 2 subjects. These events were independent of changes in insulin resistance and plasma HDL concentration and composition

When researchers began addressing the electrophysiology of conscious error awareness more than a decade ago, the role of the error-related negativity (ERN), alongside the subsequently occurring error positivity (Pe), was an obvious locus of attention given the fact that they are taken as indices of cortical error processing. In contrast to the clear-cut findings that link the amplitude of the Pe to error awareness, the association between the ERN amplitude and error awareness is vastly unclear, with a range of studies reporting significant differences in the ERN amplitude with respect to error awareness, while others observing no modulation of the ERN amplitude. One problem in the studies obtaining null findings is the fact that conclusions are drawn based on small sample sizes, increasing the probability of type II error, especially given the fact that the ERN elicited using various error awareness paradigms tends to be small. The aim of the present study was to therefore address the issue of type II error in order to draw more certain conclusions about the modulation of the ERN amplitude by conscious error awareness. Forty participants performed a manual response inhibition task optimised to examine error awareness. While the early and late Pe amplitudes showed the expected sensitivity to error awareness, the ERN results depicted a more complex picture. The ERN amplitude for unaware errors appeared more negative than that of aware errors, both numerically and on the grand average ERP. The unexpected findings were explained in terms of (a) latency issues in the present data, (b) characteristics of the manual response inhibition task used and the possibility that it elicits variation in neurocognitive processing, and (c), in relation to possible contamination by the contingent negative variation (CNV), an ERP component elicited during response preparation. Suggestions for future research on how to address the issues raised in the present paper are also discussed.

Abstract Type 2 diabetes can be prevented if the impaired glucose tolerance is found. Oral glucose tolerance test is needed in clinical practise for that but it is expensive and inconvenient. Obesity, hypertension, dyslipidemia and hypertension in pregnancy are factors often found in persons with type 2 diabetes. When there are more than one factor in same person the risk of type 2 diabetes multiplies. The purpose of this study was to investigate the prevalence of abnormal glucose metabolism and risk factors of type 2 diabetes in middle aged Finnish population in Savitaipale municipality and develop a method to screen abnormal glucose metabolism in primary health care. It was also studied the correlation of blood pressure and body mass index during pregnancy and abnormal glucose metabolism in later life. The study population was 1561 people born 1933–1956. 77,5% participated and 1097 people of them not having known abnormal glucose metabolism were taken to the cross-sectional study to develop the screening method. All 325 women who have had childbirth and files of that were taken to the prospective pregnancy cohort study. Information was collected with interview, measurements, laboratory research and from childbirth files. According the World Health Organisation criteria 1999 the prevalence of diabetes was 8,7% in men and 7,4% in women, previously undiagnosed 3,9% and 3,1%. Every fourth had abnormal glucose metabolism (men 23,2%, women 23,5%). The prevalence of obesity, hypertension, use of long-term antihypertensive medication and dyslipidemia (only in women) was higher among those, who had abnormal glucose metabolism. Logistic models were made for the classified risk factors. The model (AUC 0.718 for men, 0.761 for women) containing age, gender, waist circumference, systolic blood pressure and use of long-term antihypertensive medication was as good as model containing in addition family history of diabetes, smoking habits, serum lipids and long-term use of lipid lowering medication. Risk score tables were made from classified risk factors to evaluate the probability of the abnormal glucose metabolism. The blood pressure level and body mass index in pregnancy correlated independently with abnormal glucose metabolism in later life, blood pressure also adjusted with body mass index. Hypertension in pregnancy or after delivery correlated with abnormal glucose metabolism adjusted with body mass index. Hypertension in pregnancy doubled the risk of abnormal glucose metabolism in later life adjusted for body mass index in pregnancy and hypertension in later life. This information is important in prevention of type 2 diabetes. / Tiivistelmä Tyypin 2 diabetesta voidaan estää, mikäli heikentynyt glukoosinsieto tunnistetaan. Siihen tarvitaan glukoosirasituskoetta, jota on pidetty kalliina ja hankalana toteuttaa. Lihavuus, kohonnut verenpaine, dyslipidemia ja raskausdiabetes ovat tyypin 2 diabeteksen riskitekijöitä ja niiden ryvästyminen samaan henkilöön lisää diabetekseen sairastumisen todennäköisyyttä. Tyypin 2 diabeteksen riskitekijöiden ja poikkeavan glukoosiaineenvaihdunnan määrää ja raskauden aikaisen verenpaineen yhteyttä myöhemmin ilmaantuvaan poikkeavaan glukoosiaineenvaihduntaan tutkittiin 1933–1956 syntyneessä savitaipalelaisessa väestössä. Tavoitteena oli kehittää perusterveydenhuoltoon soveltuva poikkeavan glukoosiaineenvaihdunnan seulontamenetelmä. Kohdejoukosta (n = 1561) osallistui 77,5 %, joista 1097:llä henkilöllä ei tiedetty olevan diabetesta. Heistä kerättiin tietoa haastattelulla, mittauksilla ja laboratoriotutkimuksilla sekä äitiysneuvolakorteista. Raskausaineistoon ja takenevaan kohorttitutkimukseen otettiin kaikki ne 325 naista, myös diabeetikot, joista raskaudesta oli tiedot käytettävissä. Diabetesta sairasti 8,7 % miehistä ja 7,4 % naisista, aiemmin diagnosoimattomia oli 3,9 % ja 3,1 %. Poikkeava glukoosiaineenvaihdunta oli joka neljännellä. Lihavuutta, kohonnutta verenpainetta, verenpainelääkkeen käyttöä ja naisilla dyslipidemiaa oli enemmän niillä, joilla oli poikkeava glukoosiaineenvaihdunta. Tutkimuksessa luotiin luokitelluista muuttujista logistisia malleja. Malli, johon muuttujiksi valittiin ikä, sukupuoli, vyötärön ympärys, systolinen verenpaine ja verenpainelääkkeen käyttö, todettiin yhtä hyväksi (miesten ROC -käyrän AUC 0.718, naisten 0.761) ennustamaan heikentynyt glukoosinsieto ja diabetes kuin malli, johon lisäksi valittiin suvun diabetes, tupakointi, rasva-arvoja ja lipidilääkityksen käyttö. Muuttujista tehtiin taulut, joista voi nähdä poikkeavan glukoosiaineenvaihdunnan todennäköisyyden. Raskauden aikainen verenpaine ja painoindeksi olivat yhteydessä myöhemmin ilmaantuvaan poikkeavaan glukoosiaineenvaihduntaan, samoin loppuraskauden verenpaine painoindeksillä vakioituna. Raskaudessa todettu kohonnut verenpaine oli, mutta raskauden aiheuttama kohonnut verenpaine ei ollut, yhteydessä myöhemmin ilmaantuvaan poikkeavaan glukoosiaineenvaihduntaan painoindeksistä riippumatta, samoin loppuraskauden diastolinen verenpaine seulonnan diastolisesta verenpaineesta riippumatta. Raskaudessa tai sen jälkeen todettu kohonnut verenpaine kaksinkertaisti poikkeavan glukoosiaineenvaihdunnan riskin loppuraskauden painoindeksistä tai seulonnassa todetusta kohonneesta verenpaineesta riippumatta. Kahdella helposti mitattavalla muuttujalla voidaan päätellä glukoosirasituskokeen tarve. Diabetesta ehkäistäessä on tärkeä tietää, että raskauden kohonnut verenpaine ja ylipaino lisäävät myöhempää poikkeavaa glukoosiaineenvaihduntaa.

Magister Scientiae - MSc / Obesity is a globally increasing disease particularly in developing countries and among children. It is mainly caused by intake of diets high in fat and the lack of physical activity. Obesity is a risk factor for diseases such as type II diabetes, high blood pressure, high cholesterol and certain cancers. Prediabetes is a condition where blood glucose levels are above normal but have not reached those of diabetes. It is difficult to diagnose, as there are no signs or symptoms. Some type II diabetes patients bear no symptoms at all and the disease is discovered late. Proteomics is a field that can provide opportunities for early diagnosis of diseases through biomarker discovery. The early diagnosis of diabetes can assist in the prevention and treatment of diabetes. Therefore there is a need for the early diagnosis of diabetes. Twenty Wistar rats were used. The rats were initially fed a CHOW diet, which is the standard balanced diet for rats, for 4 weeks. The rats were then divided into 2 groups of 10 where 1 group was fed CHOW and another was fed a high fat (HF) diet in order to induce obesity. The two groups were fed their respective diets for 18 weeks. Rats were weighed. Rats were placed in metabolic chambers and 24 hour urine samples were collected. Ketone levels were measured by Ketostix. Urine proteins were precipitated by acetone, quantified and separated on both the 1D SDS-PAGE and the 2D SDS-PAGE. Protein expression changes between CHOW and HF fed rats were determined and identified using MALDI-TOF mass spectrometry. Protein spots intensities increased and decreased between the CHOW and HF fed rats. Transducin (beta)-like 3 was identified as the only differentially expressed protein, which might serve as a potential biomarker for prediabetes. / South Africa