Made available in DSpace on 2014-06-11T19:23:35Z (GMT). No. of bitstreams: 0 Previous issue date: 2013-01-29Bitstream added on 2014-06-13T18:09:51Z : No. of bitstreams: 1 barbosa_egmm_me_arafcf.pdf: 437958 bytes, checksum: 3c5ca7946a683a97660f6cc74c0cab06 (MD5) / A potência e a eficácia das terapias antirretrovirais (TARV) aumentaram a expectativa de vida dos pacientes infectados pelo vírus da imunodeficiência humana. Entretanto, resultados de vários estudos sugerem que estas terapias também podem produzir modificações metabólicas, tais como as doenças ósseas. O objetivo do presente estudo foi avaliar a qualidade óssea e marcadores de formação e reabsorção óssea em pacientes infectados pelo HIV em uso ou não da TARV. Foi realizado um estudo transversal, com 50 homens adultos, em tratamento ou não com antirretrovirais. Foram aplicados métodos de avaliação do consumo alimentar, medidas antropométricas e avaliação da composição corporal e óssea utilizando a dual energy x-ray absorptiometry (DXA). Para a avaliação bioquímica foram utilizados os marcadores: hormônio do folículo estimulante (FSH), hormônio luteinizante (LH), paratormônio (PTH), testosterona, cálcio total, fósforo, magnésio, albumina, cálcio 24h, creatinina, uréia, fator 1 de crescimento semelhante a insulina (IGF-I), 25 hidroxivitamina D, osteocalcina e deoxipiridinolina urinária. Os resultados obtidos foram escritos na forma de artigo científico, sendo que o primeiro abordou a influência do tempo de uso da TARV na densidade mineral óssea e mostrou uma redução na massa óssea na maioria dos participantes avaliados e o consumo de cálcio foi adequado apenas no Grupo B1 em tratamento há mais de dois anos com antirretrovirais. O segundo artigo abordou o impacto da TARV nos marcadores do metabolismo ósseo e mineral e mostrou valor aumentado no marcador de reabsorção óssea em todos os grupos do estudo. Concluímos que a maioria dos participantes apresentou uma desmineralização óssea, principalmente com maior tempo de uso da TARV da classe de inibidores de transcriptase reversa... / The potency and efficacy of antiretroviral therapies (ART) have increased the life expectancy of HIV-infected patients. However, the results of various studies suggest that these therapies may also produce metabolic modifications such as bone diseases. The objective of the present study was to evaluate the bone quality and the markers of bone formation and reabsorption in HIV-seropositive patients using or not ART. A cross-sectional study was conducted on 50 adult men treated or not with ART. Methods for the evaluation of food consumption were applied, as well as anthropometric measurements and the evaluation of body and bone composition using dual energy x-ray absorptiometry (DXA). The following markers were used for biochemical evaluation: follicle stimulating hormone (FSH), luteinizing hormone (LH), parathormone (PTH), testosterone, total calcium, phosphorus, magnesium, albumin, 24h calcium, creatinine, urea, insulin-like growth factor 1 (IGF-I), 25 hydroxyvitamin D, osteocalcin, and urinary deoxypyridinoline. The results obtained were presented in the form of scientific articles. The first concerned the influence of the time of ART use on bone mineral density and showed a reduction of bone mass in most of the participants evaluated, with calcium consumption being adequate only in Group B1 under treatment with ARVs for more than two years. The second concerned the impact of ART on the markers of bone and mineral metabolism and showed an increase in the bone resorption marker in all study groups. We conclude that most of the volunteers presented bone demineralization, especially after a longer time of use of ART of the nucleoside reverse transcriptase inhibitor class. The increased bone remodeling indicates a greater... (Complete abstract click electronic access below)

Please read the abstract in the section 00front of this document / Thesis (DPhil (Medical Immunology))--University of Pretoria, 2007. / Immunology / unrestricted

Orientador: Anderson Marliere Navarro / Banca: Alcyone Artioli Machado / Banca: Flavia Queiroga de Almeida / Resumo: A potência e a eficácia das terapias antirretrovirais (TARV) aumentaram a expectativa de vida dos pacientes infectados pelo vírus da imunodeficiência humana. Entretanto, resultados de vários estudos sugerem que estas terapias também podem produzir modificações metabólicas, tais como as doenças ósseas. O objetivo do presente estudo foi avaliar a qualidade óssea e marcadores de formação e reabsorção óssea em pacientes infectados pelo HIV em uso ou não da TARV. Foi realizado um estudo transversal, com 50 homens adultos, em tratamento ou não com antirretrovirais. Foram aplicados métodos de avaliação do consumo alimentar, medidas antropométricas e avaliação da composição corporal e óssea utilizando a dual energy x-ray absorptiometry (DXA). Para a avaliação bioquímica foram utilizados os marcadores: hormônio do folículo estimulante (FSH), hormônio luteinizante (LH), paratormônio (PTH), testosterona, cálcio total, fósforo, magnésio, albumina, cálcio 24h, creatinina, uréia, fator 1 de crescimento semelhante a insulina (IGF-I), 25 hidroxivitamina D, osteocalcina e deoxipiridinolina urinária. Os resultados obtidos foram escritos na forma de artigo científico, sendo que o primeiro abordou a influência do tempo de uso da TARV na densidade mineral óssea e mostrou uma redução na massa óssea na maioria dos participantes avaliados e o consumo de cálcio foi adequado apenas no Grupo B1 em tratamento há mais de dois anos com antirretrovirais. O segundo artigo abordou o impacto da TARV nos marcadores do metabolismo ósseo e mineral e mostrou valor aumentado no marcador de reabsorção óssea em todos os grupos do estudo. Concluímos que a maioria dos participantes apresentou uma desmineralização óssea, principalmente com maior tempo de uso da TARV da classe de inibidores de transcriptase reversa... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The potency and efficacy of antiretroviral therapies (ART) have increased the life expectancy of HIV-infected patients. However, the results of various studies suggest that these therapies may also produce metabolic modifications such as bone diseases. The objective of the present study was to evaluate the bone quality and the markers of bone formation and reabsorption in HIV-seropositive patients using or not ART. A cross-sectional study was conducted on 50 adult men treated or not with ART. Methods for the evaluation of food consumption were applied, as well as anthropometric measurements and the evaluation of body and bone composition using dual energy x-ray absorptiometry (DXA). The following markers were used for biochemical evaluation: follicle stimulating hormone (FSH), luteinizing hormone (LH), parathormone (PTH), testosterone, total calcium, phosphorus, magnesium, albumin, 24h calcium, creatinine, urea, insulin-like growth factor 1 (IGF-I), 25 hydroxyvitamin D, osteocalcin, and urinary deoxypyridinoline. The results obtained were presented in the form of scientific articles. The first concerned the influence of the time of ART use on bone mineral density and showed a reduction of bone mass in most of the participants evaluated, with calcium consumption being adequate only in Group B1 under treatment with ARVs for more than two years. The second concerned the impact of ART on the markers of bone and mineral metabolism and showed an increase in the bone resorption marker in all study groups. We conclude that most of the volunteers presented bone demineralization, especially after a longer time of use of ART of the nucleoside reverse transcriptase inhibitor class. The increased bone remodeling indicates a greater... (Complete abstract click electronic access below) / Mestre

Twenty Holsteins, ten pregnant heifers and ten pregnant cows (third or greater pregnancy) were subdivided and fed either a low calcium (Ca) or Ca-supplemented ration for four weeks prepartum to determine the influence of age and prepartum Ca intake on hormonal control of peripartum Ca homeostasis. Jugular blood samples were taken on a fixed schedule from 21 days prepartum through 21 days postpartum for parathyroid hormone (PTH), calcitonin (CT), Ca, magnesium (Mg), and phosphorus (P) analysis. Heifers and cows receiving the high Ca ration prepartum tended to have higher prepartum serum Ca. Cows fed the high Ca ration prepartum (hi-Ca cows) exhibited severe hypocalcemia (6.1 mg/dl) at parturition and remained hypocalcemic for three days. Serum PTH concentration increased prepartum (-5 to -3 days) and at parturition, followed by an increase in CT, in all groups except high-Ca cows. Circulating CT was lower in high-Ca cows throughout the experiment. Serum concentrations of PTH and Mg increased from 7 to 21 days in all except high-Ca cows. Feed intake corrected for metabolic bodyweight was similar for both dietary treatments and ages. Milk production was greater for the first week in cows fed low Ca prepartum. There was no correlation between hypocalcemia and increased milk Ca concentration. In conclusion, heifers were able to achieve calcium homeostasis despite the high Ca ration, while high-Ca cows exhibited subclinical milk fever. / M.S.

by Warren Tak-keung Lee. / Thesis (Ph.D.)--Chinese University of Hong Kong, 1995. / Includes bibliographical references (leaves 161-186). / Chapter CHAPTER 1: --- INTRODUCTION --- p.1 / Chapter 1.1 --- Background --- p.1 / Chapter 1.2 --- Objectives --- p.3 / Chapter CHAPTER 2: --- LITERATURE REVIEW --- p.4 / Chapter 2.1 --- Calcium intakes of Hong Kong Chinese: past and present --- p.4 / Chapter 2.1.1 --- Adults --- p.4 / Chapter 2.1.2 --- Children --- p.5 / Chapter 2.2 --- Calcium Metabolism --- p.6 / Chapter 2.2.1 --- Calcium and bone mass --- p.9 / Chapter 2.2.2 --- Ethnicity and bone mass --- p.9 / Chapter 2.2.3 --- Physical activity and bone mass --- p.10 / Chapter 2.2.4 --- Hormonal control of calcium metabolism --- p.11 / Chapter 2.2.5 --- Intestinal calcium absorption --- p.14 / Chapter (1) --- Calcium transport across the intestine / Chapter (2) --- Active Calcium Transport / Chapter (3) --- Passive calcium transport / Chapter (4) --- Age and calcium absorption / Chapter 2.2.6 --- Dietary components in relation to calcium bioavailability and absorption --- p.17 / Chapter (1) --- Habitual calcium intake / Chapter (2) --- Vitamin D nutritional status / Chapter (3) --- Protein / Chapter (4) --- Phosphorous and Ca:P ratio / Chapter (5) --- Sodium / Chapter (6) --- Lactose / Chapter (7) --- Glucose and Glucose Polymers / Chapter (8) --- Phytate / Chapter (9) --- Oxalate / Chapter (10) --- Plant estrogen (phyto-estrogen) / Chapter 2.2.7 --- Bioavailability from calcium salts --- p.23 / Chapter 2.3 --- Calcium intakes and requirements --- p.25 / Chapter 2.3.1 --- Calcium requirements in adulthood --- p.28 / Chapter 2.3.2 --- Calcium requirements in childhood --- p.29 / Chapter 2.3.3 --- Manifestation of calcium deficiency in children --- p.30 / Chapter 2.4 --- Assessment of Dietary Intakes --- p.32 / Chapter 2.4.1 --- Food weighing method --- p.32 / Chapter 2.4.2 --- Food Recording method --- p.34 / Chapter 2.4.3 --- 24-hour dietary recall --- p.35 / Chapter 2.4.4 --- Food frequency method --- p.36 / Chapter 2.4.5 --- Dietary history method --- p.38 / Chapter 2.4.6 --- Chemical analysis of duplicate meals --- p.39 / Chapter 2.4.7 --- Photographic method --- p.40 / Chapter 2.4.8 --- Selecting suitable methods for the present study --- p.40 / Chapter 2.5 --- Food composition database --- p.41 / Chapter 2.6 --- Evaluation of bone mass in vivo --- p.43 / Chapter 2.6.1 --- Single photon absorptiometry --- p.44 / Chapter 2.6.2 --- Dual photon absorptiometry --- p.46 / Chapter 2.6.3 --- Dual energy X-ray absorptiometry --- p.47 / Chapter 2.6.4 --- Quantitative computerized tomography --- p.47 / Chapter 2.6.5 --- The techniques selected to quantify bone mass in the present study --- p.48 / Chapter 2.7 --- Measurement of intestinal calcium absorption --- p.49 / Chapter 2.7.1 --- Metabolic balance study --- p.49 / Chapter 2.7.2 --- Isotopic techniques (radioisotope or stable isotope) --- p.50 / Chapter (1) --- Radio isotope vs stable isotope / Chapter (2) --- The single-label isotope technique / Chapter (3) --- The double-label isotope technique / Chapter (4) --- "Preparation of stable isotopes for human study, and determination of stable isotopes in body fluids" / Chapter (I) --- Dosage considerations / Chapter (II) --- Intrinsic or Extrinsic labelling / Chapter (III) --- Oral and intravenous administration of isotopes / Chapter 2.7.3 --- The technique selected to determine calcium absorption in the present study --- p.60 / Chapter 2.8 --- Mass spectrometry --- p.60 / Chapter 2.8.1 --- Thermal ionization mass spectrometry --- p.60 / Chapter 2.8.2 --- Fast atom bombardment mass spectrometry --- p.61 / Chapter 2.8.3 --- Inductively coupled plasma mass spectrometry --- p.61 / Chapter 2.8.4 --- Electron impact mass spectrometry and Gas chromatography mass spectrometry --- p.62 / Chapter 2.8.5 --- Neutron activation analysis --- p.62 / Chapter 2.8.6 --- The type of mass spectrometry used to determine stable isotopic ratios in the present study --- p.63 / Chapter 2.9 --- Assessment of physical activity in children --- p.63 / Chapter 2.9.1 --- Activity questionnaire or record --- p.64 / Chapter 2.9.2 --- Direct measurement of physical activity --- p.65 / Chapter (1) --- Accelerometer / Chapter (2) --- Pedometer / Chapter (3) --- Actometer / Chapter (4) --- Video-recording / Chapter (5) --- Heart-rate recording / Chapter 2.9.3 --- Selection of a suitable physical activity assessment method --- p.67 / Chapter CHAPTER 3 --- RANDOMIZED DOUBLE-BLIND CONTROLLED CALCIUM SUPPLEMENTATON TRIALS IN RELATION TO BONE AND HEIGHT ACQUISITION IN 7-YEAR OLD CHINESE CHILDREN FROM JIANGMEN (CHINA) AND HONG KONG --- p.71 / Chapter 3.1 --- Chapter summary --- p.71 / Chapter 3.2 --- Chapter Introduction --- p.72 / PART I --- p.73 / Chapter 3.3 --- Double-blind Controlled Randomized Calcium Supplementation and Bone and Height Acquisition in Chinese Children Accustomed to Mean Calcium Intake at About 300mg/d --- p.73 / Chapter 3.3.1 --- Introduction --- p.73 / Chapter 3.3.2 --- Objectives --- p.74 / Chapter 3.3.3 --- Subject and Methods --- p.74 / Chapter 3.3.4 --- Results --- p.81 / Chapter 3.3.5 --- Discussions --- p.83 / Chapter 3.3.6 --- Conclusion --- p.84 / PART II --- p.84 / Chapter 3.4 --- Randomized double-blind controlled calcium supplementation in relation to bone mineral accretion and height increment of Hong Kong Chinese children --- p.84 / Chapter 3.4.1 --- Introduction --- p.84 / Chapter 3.4.2 --- Objectives --- p.85 / Chapter 3.4.3 --- Subjects and Methods --- p.85 / Chapter 3.3.4 --- Results --- p.91 / Chapter 3.4.5 --- Discussions --- p.95 / Chapter 3.4.6 --- Conclusion --- p.97 / Chapter 3.5 --- Comparisons of the two calcium supplementation trials from Jiangmen and Hong Kong --- p.97 / Chapter 3.6 --- Chapter Discussions --- p.99 / Chapter 3.7 --- Chapter Conclusion --- p.103 / Chapter CHAPTER 4 --- TRUE FRACTIONAL CALCIUM ABSORPTION OF CHINESE CHILDREN AND THE EFFECTS OF DOUBLE-BLIND CONTROLLED CALCIUM SUPPLEMENTATION ON CALCIUM ABSORPTION IN CHILDREN MEASURED WITH STABLE ISOTOPES (42Ca and 44Ca) --- p.117 / Chapter 4.1 --- Chapter summary --- p.117 / Chapter 4.2 --- Chapter introduction --- p.118 / PART I --- p.119 / Chapter 4.3 --- True fractional calcium absorption in Chinese children measured with stable isotopes (42Ca and 44Ca) --- p.119 / Chapter 4.3.1 --- Introduction --- p.119 / Chapter 4.3.2 --- Objectives --- p.120 / Chapter 4.3.3 --- "Subjects, Materials and Methods" --- p.120 / Chapter 4.3.4 --- Results --- p.127 / Chapter 4.3.5 --- Discussions & Conclusion --- p.131 / Part II --- p.131 / Chapter 4.4 --- Effects of double-blind controlled calcium supplementation on calcium absorption in Chinese children measured with stable isotopes (42Ca and 44Ca) --- p.131 / Chapter 4.4.1 --- Introduction --- p.131 / Chapter 4.4.2 --- Objective --- p.132 / Chapter 4.4.3 --- "Subjects, Materials and Methods" --- p.132 / Chapter 4.4.4 --- Results --- p.135 / Chapter 4.4.5 --- Discussions --- p.137 / Chapter 4.4.6 --- Conclusion --- p.139 / Chapter 4.5 --- Chapter Conclusion and Discussions --- p.140 / Chapter CHAPTER 5 --- GENERAL DISCUSSIONS AND RECOMMENDATIONS FOR FURTHER STUDY --- p.156 / Chapter 5.1 --- Ethnic differences in bone acquisition and calcium absorption --- p.156 / Chapter 5.2 --- Calcium requirements for Chinese children --- p.157 / Chapter 5.3 --- Indications for further studies --- p.158 / REFERENCES --- p.161 / APPENDIXES / PUBLICATIONS

O infarto agudo do miocárdio (IAM) é um evento que acomete milhares de pessoas ao redor do mundo. Após o IAM são desencadeados diversos processos, como alterações na expressão de proteínas envolvidas na contratilidade cardíaca e no remodelamento cardíaco após o IAM, bem como o desequilíbrio no estado redox da célula, que podem levar a um grave prognóstico. A utilização dos hormônios da tireoide vem sendo amplamente estudada na tentativa de desenvolver um método terapêutico eficiente para o tratamento do IAM. Desta forma, o objetivo deste estudo foi verificar os efeitos da tiroxina (T4) sobre a expressão e a concentração de antioxidantes e pró-oxidantes e sobre a expressão de proteínas relacionadas ao metabolismo do cálcio, e suas possíveis relações com a melhora na função cardíaca após o IAM. Foram utilizados ratos Wistar, divididos nos seguintes grupos experimentais: SHAM, infartado (IAM) e infartado e tratado com T4 nas doses de 1,2, 2,4 e 6,0 mg/L de água de beber. O tratamento foi iniciado 24 horas após a indução do IAM e após 14 dias foram coletados dados morfométricos e ecocardiográficos, além de analisadas as expressões das proteínas cálcio ATPase do retículo sarcoplasmático (SERCA2a), fosfolambam (PLB), fator nuclear eritroide do tipo 2 (Nrf2) e hemeoxigenase 1 (HO-1). Também foram quantificadas as concentrações de peróxido de hidrogênio (H2O2) e de glutationa total em homogeneizado de tecido cardíaco. Os animais infartados, tratados ou não, apresentaram hipertrofia cardíaca independente da dose do tratamento. O IAM provocou uma redução da função cardíaca, e o tratamento com T4 não foi capaz de reverter esses efeitos. A expressão das proteínas PLB e Nrf2 diminuiu após o IAM. Os animais tratados com T4 em suas doses mais altas apresentaram valores da expressão da proteína Nrf2 semelhantes aos animais do grupo SHAM. Os grupos infartado e tratado com T4 nas doses de 2,4 e 6,0 mg/L apresentaram valores de expressão da SERCA2a maiores quando comparados com o grupo SHAM. As concentrações de H2O2 e de glutationa total não foram alteradas após o IAM, e o tratamento com T4 também não alterou estes parâmetros. Em suma, uma vez que a dose de T4 de 6,0 mg/L modulou a expressão do Nrf2, uma proteína importante para o estado redox da célula, sugerimos que poderia estar ocorrendo uma adaptação de sistemas antioxidantes distintos dos analisados neste estudo e que também são regulados por este fator de transcrição. / The acute myocardial infarction (AMI) is an event that affects thousands of people around the world. After AMI are triggered several processes, such as changes in expression of proteins involved in cardiac contractility and cardiac remodeling, as well as the cell redox state imbalance, which can lead to serious prognosis. The use of thyroid hormones has been widely studied in an attempt to develop an efficient therapeutic method for treatment of AMI. Thus, the objective of this study was to investigate the effects of thyroxine (T4) on expression and concentration of antioxidant and pro-oxidants and the expression of proteins related to calcium metabolism, and their possible relationships with improvement in cardiac function after AMI. Wistar rats were divided into the following groups: SHAM, myocardial infarction (AMI) and myocardial infarction and treated with T4 at doses of 1,2, 2,4 and 6,0 mg / L of drinking water. Treatment was initiated 24 hours after induction of AMI and after 14 days were collected morphometric and echocardiographic data, and analyzed protein expression of sarcoplasmic reticulum calcium ATPase (SERCA2a), phospholamban (PLB), nuclear factor erythroid type 2 (Nrf2) and hemeoxygenase 1 (HO-1). Also were quantitated concentrations of hydrogen peroxide (H2O2) and total glutathione in homogenized of cardiac tissue. The infarcted animals, treated or not, showed cardiac hypertrophy, independent of the dose of treatment. The AMI has caused a decline in cardiac function parameters, and treatment with T4 was not able to reverse these effects. The protein expression of PLB and Nrf2 decreased after AMI. Animals treated with T4 in their higher doses had values of Nrf2 protein expression similar to those animals of the SHAM group. The infarcted groups and treated with T4 at doses of 2.4 and 6.0 mg / L had higher SERCA2a expression when compared to the sham group. The concentrations of H2O2 and total glutathione were not altered after AMI, and treatment with T4 did not alter these parameters. In short, since the treatment dose of 6.0 mg / L modulates the expression of Nrf2, an important protein for the redox state of the cell, we suggest what might be going on an adaptation of antioxidant systems distinct from those analyzed in this study and are also regulated by this transcription factor.

O infarto agudo do miocárdio (IAM) é um evento que acomete milhares de pessoas ao redor do mundo. Após o IAM são desencadeados diversos processos, como alterações na expressão de proteínas envolvidas na contratilidade cardíaca e no remodelamento cardíaco após o IAM, bem como o desequilíbrio no estado redox da célula, que podem levar a um grave prognóstico. A utilização dos hormônios da tireoide vem sendo amplamente estudada na tentativa de desenvolver um método terapêutico eficiente para o tratamento do IAM. Desta forma, o objetivo deste estudo foi verificar os efeitos da tiroxina (T4) sobre a expressão e a concentração de antioxidantes e pró-oxidantes e sobre a expressão de proteínas relacionadas ao metabolismo do cálcio, e suas possíveis relações com a melhora na função cardíaca após o IAM. Foram utilizados ratos Wistar, divididos nos seguintes grupos experimentais: SHAM, infartado (IAM) e infartado e tratado com T4 nas doses de 1,2, 2,4 e 6,0 mg/L de água de beber. O tratamento foi iniciado 24 horas após a indução do IAM e após 14 dias foram coletados dados morfométricos e ecocardiográficos, além de analisadas as expressões das proteínas cálcio ATPase do retículo sarcoplasmático (SERCA2a), fosfolambam (PLB), fator nuclear eritroide do tipo 2 (Nrf2) e hemeoxigenase 1 (HO-1). Também foram quantificadas as concentrações de peróxido de hidrogênio (H2O2) e de glutationa total em homogeneizado de tecido cardíaco. Os animais infartados, tratados ou não, apresentaram hipertrofia cardíaca independente da dose do tratamento. O IAM provocou uma redução da função cardíaca, e o tratamento com T4 não foi capaz de reverter esses efeitos. A expressão das proteínas PLB e Nrf2 diminuiu após o IAM. Os animais tratados com T4 em suas doses mais altas apresentaram valores da expressão da proteína Nrf2 semelhantes aos animais do grupo SHAM. Os grupos infartado e tratado com T4 nas doses de 2,4 e 6,0 mg/L apresentaram valores de expressão da SERCA2a maiores quando comparados com o grupo SHAM. As concentrações de H2O2 e de glutationa total não foram alteradas após o IAM, e o tratamento com T4 também não alterou estes parâmetros. Em suma, uma vez que a dose de T4 de 6,0 mg/L modulou a expressão do Nrf2, uma proteína importante para o estado redox da célula, sugerimos que poderia estar ocorrendo uma adaptação de sistemas antioxidantes distintos dos analisados neste estudo e que também são regulados por este fator de transcrição. / The acute myocardial infarction (AMI) is an event that affects thousands of people around the world. After AMI are triggered several processes, such as changes in expression of proteins involved in cardiac contractility and cardiac remodeling, as well as the cell redox state imbalance, which can lead to serious prognosis. The use of thyroid hormones has been widely studied in an attempt to develop an efficient therapeutic method for treatment of AMI. Thus, the objective of this study was to investigate the effects of thyroxine (T4) on expression and concentration of antioxidant and pro-oxidants and the expression of proteins related to calcium metabolism, and their possible relationships with improvement in cardiac function after AMI. Wistar rats were divided into the following groups: SHAM, myocardial infarction (AMI) and myocardial infarction and treated with T4 at doses of 1,2, 2,4 and 6,0 mg / L of drinking water. Treatment was initiated 24 hours after induction of AMI and after 14 days were collected morphometric and echocardiographic data, and analyzed protein expression of sarcoplasmic reticulum calcium ATPase (SERCA2a), phospholamban (PLB), nuclear factor erythroid type 2 (Nrf2) and hemeoxygenase 1 (HO-1). Also were quantitated concentrations of hydrogen peroxide (H2O2) and total glutathione in homogenized of cardiac tissue. The infarcted animals, treated or not, showed cardiac hypertrophy, independent of the dose of treatment. The AMI has caused a decline in cardiac function parameters, and treatment with T4 was not able to reverse these effects. The protein expression of PLB and Nrf2 decreased after AMI. Animals treated with T4 in their higher doses had values of Nrf2 protein expression similar to those animals of the SHAM group. The infarcted groups and treated with T4 at doses of 2.4 and 6.0 mg / L had higher SERCA2a expression when compared to the sham group. The concentrations of H2O2 and total glutathione were not altered after AMI, and treatment with T4 did not alter these parameters. In short, since the treatment dose of 6.0 mg / L modulates the expression of Nrf2, an important protein for the redox state of the cell, we suggest what might be going on an adaptation of antioxidant systems distinct from those analyzed in this study and are also regulated by this transcription factor.

O infarto agudo do miocárdio (IAM) é um evento que acomete milhares de pessoas ao redor do mundo. Após o IAM são desencadeados diversos processos, como alterações na expressão de proteínas envolvidas na contratilidade cardíaca e no remodelamento cardíaco após o IAM, bem como o desequilíbrio no estado redox da célula, que podem levar a um grave prognóstico. A utilização dos hormônios da tireoide vem sendo amplamente estudada na tentativa de desenvolver um método terapêutico eficiente para o tratamento do IAM. Desta forma, o objetivo deste estudo foi verificar os efeitos da tiroxina (T4) sobre a expressão e a concentração de antioxidantes e pró-oxidantes e sobre a expressão de proteínas relacionadas ao metabolismo do cálcio, e suas possíveis relações com a melhora na função cardíaca após o IAM. Foram utilizados ratos Wistar, divididos nos seguintes grupos experimentais: SHAM, infartado (IAM) e infartado e tratado com T4 nas doses de 1,2, 2,4 e 6,0 mg/L de água de beber. O tratamento foi iniciado 24 horas após a indução do IAM e após 14 dias foram coletados dados morfométricos e ecocardiográficos, além de analisadas as expressões das proteínas cálcio ATPase do retículo sarcoplasmático (SERCA2a), fosfolambam (PLB), fator nuclear eritroide do tipo 2 (Nrf2) e hemeoxigenase 1 (HO-1). Também foram quantificadas as concentrações de peróxido de hidrogênio (H2O2) e de glutationa total em homogeneizado de tecido cardíaco. Os animais infartados, tratados ou não, apresentaram hipertrofia cardíaca independente da dose do tratamento. O IAM provocou uma redução da função cardíaca, e o tratamento com T4 não foi capaz de reverter esses efeitos. A expressão das proteínas PLB e Nrf2 diminuiu após o IAM. Os animais tratados com T4 em suas doses mais altas apresentaram valores da expressão da proteína Nrf2 semelhantes aos animais do grupo SHAM. Os grupos infartado e tratado com T4 nas doses de 2,4 e 6,0 mg/L apresentaram valores de expressão da SERCA2a maiores quando comparados com o grupo SHAM. As concentrações de H2O2 e de glutationa total não foram alteradas após o IAM, e o tratamento com T4 também não alterou estes parâmetros. Em suma, uma vez que a dose de T4 de 6,0 mg/L modulou a expressão do Nrf2, uma proteína importante para o estado redox da célula, sugerimos que poderia estar ocorrendo uma adaptação de sistemas antioxidantes distintos dos analisados neste estudo e que também são regulados por este fator de transcrição. / The acute myocardial infarction (AMI) is an event that affects thousands of people around the world. After AMI are triggered several processes, such as changes in expression of proteins involved in cardiac contractility and cardiac remodeling, as well as the cell redox state imbalance, which can lead to serious prognosis. The use of thyroid hormones has been widely studied in an attempt to develop an efficient therapeutic method for treatment of AMI. Thus, the objective of this study was to investigate the effects of thyroxine (T4) on expression and concentration of antioxidant and pro-oxidants and the expression of proteins related to calcium metabolism, and their possible relationships with improvement in cardiac function after AMI. Wistar rats were divided into the following groups: SHAM, myocardial infarction (AMI) and myocardial infarction and treated with T4 at doses of 1,2, 2,4 and 6,0 mg / L of drinking water. Treatment was initiated 24 hours after induction of AMI and after 14 days were collected morphometric and echocardiographic data, and analyzed protein expression of sarcoplasmic reticulum calcium ATPase (SERCA2a), phospholamban (PLB), nuclear factor erythroid type 2 (Nrf2) and hemeoxygenase 1 (HO-1). Also were quantitated concentrations of hydrogen peroxide (H2O2) and total glutathione in homogenized of cardiac tissue. The infarcted animals, treated or not, showed cardiac hypertrophy, independent of the dose of treatment. The AMI has caused a decline in cardiac function parameters, and treatment with T4 was not able to reverse these effects. The protein expression of PLB and Nrf2 decreased after AMI. Animals treated with T4 in their higher doses had values of Nrf2 protein expression similar to those animals of the SHAM group. The infarcted groups and treated with T4 at doses of 2.4 and 6.0 mg / L had higher SERCA2a expression when compared to the sham group. The concentrations of H2O2 and total glutathione were not altered after AMI, and treatment with T4 did not alter these parameters. In short, since the treatment dose of 6.0 mg / L modulates the expression of Nrf2, an important protein for the redox state of the cell, we suggest what might be going on an adaptation of antioxidant systems distinct from those analyzed in this study and are also regulated by this transcription factor.

Doctorat en Sciences médicales / info:eu-repo/semantics/nonPublished

Please read the abstract in the front section of this document / Dissertation (MSc (Physiology))--University of Pretoria, 2007. / Physiology / unrestricted