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Modélisation de la trajectoire des patients avec une insuffisance rénale chronique terminale / Modeling treatment trajectories of patients with end stage renal diseaseCouchoud Heyer, Cécile Gabriella 28 March 2014 (has links)
Afin de mieux connaitre puis d'optimiser les trajectoires suivies par les patients arrivés au stade terminal de leur insuffisance rénale chronique, il a été nécessaire de mettre au point des outils permettant de modéliser ces trajectoires complexes. Les différentes modalités de traitement n'ont pas été comparées une à une mais une approche globale a été privilégiée tenant compte d'une vision intégrée où les modalités de traitement sont considérées comme complémentaires et non concurrentielles. Ce travail de modélisation a utilisé des modèles à compartiments avec prise en compte de risque concurrents et un modèle de mélange pour données de survie avec fraction non à risque. Les paramètres des modèles ont été estimés à partir des données du registre du Réseau Épidémiologie et Information en Néphrologie (REIN). L'outil de prédiction développé a également pu être alimenté par les données de remboursement de l'assurance maladie (SNIIRAM) sur l'année 2009. Cette première version de l'outil a permis d'évaluer les conséquences en termes d'espérance de vie restreinte à 15 ans et de coût moyen par mois de différentes stratégies simulées de prise en charge des patients en IRCT dans le cadre d'une analyse médico-économique, en partenariat avec la Haute Autorité de Santé. L'objectif final de ce travail sera de proposer des outils d'aide à la décision reposant sur des stratégies de prise en charge les mieux adaptées aux besoins des patients. A terme, les outils développés lors de ce travail pourraient également servir de base à une plateforme de simulation afin d'accompagner les décideurs publics lors de la réflexion sur les schémas d'organisation sanitaire / In order to better understand and then optimize the trajectories followed by end-stage renal disease patients, it was necessary to develop tools to model these complex trajectories. The different treatment modalities were not compared but a comprehensive approach was preferred taking into account an integrated vision where treatment modalities are considered complementary and non-competitive. We used compartments models which took into account competitive risk and a mixture model for survival with fraction not at risk. The model parameters were estimated from the data from the Renal Epidemiology and Information Network registry. Reimbursement data from the national health insurance (SNIIRAM) were also used. The prediction tool developed was used to evaluate the consequences in terms of expected 15- years restricted lifetime and average cost per month for different strategies in a medicoeconomic analysis, in partnership with the Haute Autorité de Santé. The final aim of this work is to offer decision support tools based on strategies best adapted to patients’ needs. The tools developed in this work could also serve as a basis for a simulation platform to accompany public decision-makers in their reflection on health organization
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Le retransqol : une échelle de mesure de la qualité de vie spécifique aux patients porteurs d'un greffon rénal fonctionnel. : Développement, adaptation et application / The ReTransQol : a specific questionnaire to assess the health-related quality of life of renal transplant recipient : Development, adaptation and application.Beauger, Davy 08 December 2014 (has links)
La prise en compte de la notion de la qualité de vie (QDV) du patient est révélatrice d'un changement profond dans la pratique médicale, notamment en néphrologie, pour les patients atteints d'insuffisance rénale chronique terminale (IRCT). Compte tenu de la prévalence, de l'incidence et de la mortalité de cette maladie en France, il paraissait important de pouvoir mesurer de façon pertinente et cohérente la QDV des patients atteints d'IRCT. La QDV liée à la santé constitue un indicateur pour apprécier les conséquences de cette maladie. En 2007, après une étude de revue de la littérature concernant les outils de mesure de la QDV des IRCT, il a été mis en évidence un manque de questionnaires spécifiques validés en langue française. Il existait donc un besoin réel d'évaluer la QDV de ces patients, et plus particulièrement celle des patients porteurs d'un greffon rénal fonctionnel.En 2008, une échelle spécifique a donc été développée et validée pour mesurer la QDV des patients greffés rénaux : le ReTransQol (ou RTQ). Après 5 années d'utilisation du RTQ dans diverses études nationales, cet outil a été amélioré et une nouvelle version a vu le jour: le RTQ V2. Après de nombreuses analyses, cette échelle présente actuellement de bonnes propriétés psychométriques et est validée auprès de diverses populations d'études. Le RTQ V2 sera d'ailleurs utilisé dans des études internationales (Brésil, Allemagne, Canada...), et une validation transculturelle est prévue. Le RTQ V2 est donc un outil de mesure spécifique de la QDV adapté pour une utilisation en routine auprès des patients porteurs d'un greffon rénal fonctionnel. / The inclusion of the concept of quality of life (QOL) is indicative of a profound change in the way of practicing medicine, particularly in the field of nephrology for patients with end stage renal disease (ESRD). Given the prevalence, incidence and mortality of this disease in France, it seemed important, even essential, to measure properly, appropriately and consistently, the QOL of patients with ESRD. Health related quality of life (HRQOL) is therefore an important indicator of results to evaluate the consequences of this disease, the effect of medical procedures, treatment effects, or the impact of health policies.In 2007, after a study of literature concerning the assessment of QOL's scales of patients with ESRD, it was revealed a certain lack, quantitative or qualitative, of specific questionnaires for measuring QOL for ESRD patients validated in French, especially for patients with a functioning kidney transplant.In 2008, a specific scale has been developed and validated to measure the QOL of renal transplant recipients: the ReTransQol (Renal Transplant Quality of life questionnaire). After 5 years of use and application of ReTransQol in different national studies, this tool has been improved and a new version was created: the ReTransQol V2 (or RTQ V2). After lots of analysis, this scale has currently good psychometric properties and has been validated in various populations. The RTQ V2 is also used in international studies (Brazil, Germany, Canada ...), and a cross-cultural validation of the scale is planned.The ReTransQol V2 is a specific tool to assess the HRQOL and is suitable for a routine use among renal transplant recipients.
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Avaliação da qualidade de vida do paciente renal crônico submetido à hemodiálise e sua adesão ao tratamento farmacológico de uso diário / Evaluation of the quality of life of end-stage renal patients submitted to hemodialysis and their adhesion to daily pharmacologic treatment.Terra, Fábio de Souza 23 March 2007 (has links)
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Previous issue date: 2007-03-23 / Coordenacao de Aperfeicoamento de Pessoal de Nïvel Superior / This study evaluated the QL of end-stage renal patients submitted to hemodialysis and their adhesion to daily pharmacologic treatment knowing their life expectancy and the main complications presented during HD It is an epidemiologic descriptive tranversal and quantitative research carried out at a hemodialysis clinic of a university hospital of Alfenas State of Minas Gerais Brazil with the participation of all the 30 dialysis patients in the period of the collection of data A questionnaire was used for the obtainment of data about the participants' characterization adhesion to pharmacologic treatment and life expectation QL was analyzed through the instrument WHOQOL-bref of the World Health Organization The data were tabulated in the statistical program SPSS version 10.0 and analyzed by means of the medium score with application of the following tests Qui-square Coefficient of Correlation of Pearson Test of Wilcoxon Student s t test Cronbach s Alpha Coefficient The results showed that most of the interviewees referred that HD interfered in their professional activities and in leisure and recreation but 53.33% were calm during the permanence in the clinic The most frequent complications were the arterial hypotension vomit and dizziness All the patients take medicines mainly antihypertensives With regard to knowledge of the indication of the medicines 40% of the dialysis patients know all the drugs that they take Thirty patients informed to take the medicines daily but 16.66% have already interrupted the treatment on their own account due to adverse reactions The average scores of QL were General QL 3.26 physical domain 3.10 psychological domain 3.58 social relationships 4.19 and environment 3.54 Therefore the participants of the study classified their QL as being above "neither bad, nor good" while the domain social relationships was evaluated between "good" and "very good" The variables did not interfere in the patients' QL in other words they did not present any correlation with the domains of WHOQOL-bref Through the reproducibility it was verified that the interviewees' QL was stable between the "test" and the "retest" having satisfactory reliability while the internal consistency of WHOQOL-bref was acceptable for the facets and domains indicating a homogeneity in the appraised items The main expectation of the patients' life is receiving a renal transplantation 82.35% are in the waiting list and 47.06% encountered the refusal of their relatives in donating the organ It can be verified that the instrument WHOQOL-bref showed to be effective to evaluate QL of end-stage renal patients submitted to HD thus being a reliable instrument for such a measure Finally dialysis patients will have a better QL when they are informed about their disease and treatment when cared for in a solid supportive system and rehabilitation in order to make them capable to lead an active productive and self-sufficient life / Este estudo avaliou a QV dos nefropatas crônicos submetidos à hemodiálise e sua adesão ao tratamento farmacológico de uso diário conhecer a expectativa de vida dessa população com relação ao futuro e as principais complicações apresentadas durante a HD Trata-se de uma pesquisa epidemiológica descritiva transversal e quantitativa realizada em uma clínica de hemodiálise de um hospital universitário de Alfenas-MG com todos os 30 pacientes submetidos à HD no período da coleta de dados Utilizou-se para a coleta um questionário com dados sobre a caracterização dos participantes adesão ao tratamento farmacológico e expectativa de vida e a QV foi analisada por meio do instrumento WHOQOL-bref da Organização Mundial da Saúde Os dados foram tabulados no programa estatístico SPSS versão 10.0 e analisados por meio do escore médio com aplicação dos seguintes testes Qui-quadrado Coeficiente de Correlação de Pearson Teste de Wilcoxon Teste t de Student Coeficiente Alfa de Cronbach Os resultados mostraram que a maioria dos entrevistados referiram que a HD interferiu em suas atividades profissionais e de lazer e recreação mas 53,33% se sentem tranqüilos durante a permanência na clínica As complicações de maior ocorrência foram a hipotensão arterial vômito e tontura Todos os pacientes fazem uso de medicamentos sendo os antihipertensivos os mais utilizados Quanto ao conhecimento da indicação dos medicamentos 40% dos renais crônicos conhecem todos os fármacos que usam Os 30 pacientes estudados informaram tomar os medicamentos diariamente mas 16,66% já interromperam o uso por conta própria devido a reações adversas Os escores médios referentes à QV foram QV geral 3,26 domínio físico 3,10 psicológico 3,58 relações sociais 4,19 e meio ambiente 3,54 Assim os participantes do estudo classificaram a QV como sendo acima do nem ruim nem boa enquanto o domínio relações sociais foi avaliado entre boa e muito boa As variáveis estudadas não interferiram na QV dos pacientes ou seja elas não apresentaram correlação com os domínios do WHOQOL-bref Por meio da reprodutibilidade verificou-se que a QV dos entrevistados foi estável entre o teste e o reteste tendo uma confiabilidade satisfatória enquanto a consistência interna do WHOQOL-bref foi aceitável para as facetas e domínios indicando uma homogeneidade nos itens avaliados A principal expectativa de vida dos pacientes é a realização do transplante renal sendo que 82,35% estão na lista de espera e 47,06% se depararam com a recusa dos familiares em doar o órgão Pode-se verificar que o instrumento WHOQOL-bref mostrou-se eficaz para avaliar a QV de renais crônicos submetidos à HD sendo confiável para essa medida Por fim o paciente submetido à HD terá uma melhor QV quando ele for informado acerca de sua doença e tratamento quando existir um sólido sistema de suporte e reabilitação e ser capaz de levar uma vida ativa produtiva e autosuficiente
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Velikost jednotlivých lipoproteinových částic u různých patologických stavů / The size of individual lipoproteins in various pathological conditionsDušejovská, Magdaléna January 2017 (has links)
Metabolic syndrome (MS) and end-stage renal disease (ESRD) represent two clinical- pathologic states with increased risk of atherosclerotic cardiovascular complications with considerable impact on the quality of life of the patients. The knowledge about the changes in distribution of individual lipoprotein subfractions could countribute to the estimation of risk of atherosclerosis development. The studies presented in this thesis aimed at analyses of subfractions of LDL and HDL in the abovementioned pathologic states; moreover, we tried to elucidate the associations of changes in lipoprotein subfractions with clinical as well as biochemical alterations. The Study I was a placebo controlled study observing the effect of polyunsaturated fatty acids of n-3 family (PUFA n-3) administration to patients with MS who were divided to statin-treated ones (36 patients), and those without statin therapy (24 probands). The Study II comprised of 57 patients with ESRD on high volume haemodiafiltration (HV-HDF). In this Study, the parameters after 5-year follow-up were compared with baseline characteristics. Also, we included comparisons with the control group of 50 age and sex matched patients without the signs of ESRD. In Study I, we observed lowering of triacylglycerol and cholesterol content in VLDL...
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Urinary Analysis of 8-Oxoguanine, 8-Oxoguanosine, Fapy-Guanine and 8-Oxo-2′-Deoxyguanosine by High-Performance Liquid Chromatography-Electrospray Tandem Mass Spectrometry as a Measure of Oxidative StressMalayappan, Bhaskar, Garrett, Timothy J., Segal, Mark, Leeuwenburgh, Christiaan 05 October 2007 (has links)
A sensitive and specific assay aimed at measuring the oxidized nucleic acids, 8-oxoguanine (8-oxoGua), fapy-guanine (Fapy-Gua), 8-oxoguanosine (8-oxoGuo), 8-oxo-2′-deoxyguanosine (8-oxodG) has been developed by coupling reversed phase liquid chromatography (HPLC) with electrospray tandem mass spectrometry detection (MS/MS) and isotope dilution. The HPLC-MS/MS approach with multiple reaction monitoring (MRM) allowed for the sensitive determination of 8-oxoGua, Fapy-Gua, 8-oxoGuo, and 8-oxodG in human urine samples. There is no sample preparation needed except for the addition of buffer and 13C- and 15N-labeled internal standards to the urine prior to sample injection into the HPLC-MS/MS system. This method was tested in urine samples from non-smokers, smokers, non-smokers with chronic kidney disease (CKD) and smokers with CKD, to assess the level of oxidative damage to nucleic acids. Markers of both RNA and DNA damage were significantly increased in the smokers with and without CKD compared to their respective control subjects. These findings suggest that a highly specific and sensitive analytical method such as isotope dilution HPLC-MS/MS may represent a valuable tool for the measurement of oxidative stress in human subjects.
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Vliv pohybové a nutriční a nutriční intervence na fyzickou zdatnost a QŽ jedinců v prvním roce po transplantaci ledviny / The effect of physical activity and nutrition interventions on physical fitness and quality of life during the first year after kidney transplantationŠvagrová, Klára January 2013 (has links)
UNIVERZITA KARLOVA V PRAZE FAKULTA TĚLESNÉ VÝCHOVY A SPORTU The effect of physical activity and nutrition interventions on physical fitness and quality of life during the first year after kidney transplantation Abstract of disertation Zpracovala: Mgr. Klára Švagrová Školitel: Prof. Ing. Václav Bunc, CSc. Školící pracoviště: Laboratoř sportovní motoriky Praha, 2012 ABSTRACT Kidney transplantation is the best known treatment of chronic kidney failure. However, it is often accompanied by a number of health complications. The transplantation itself positively affects both physical fitness and quality of life during the first year after the transplant surgery which are seriously diminished when compared to the healthy population. This improvement can be even enhanced by appropriate physical activity and nutrition interventions otherwise both the physical fitness and quality of life would start declining after the first post-transplant year again. The aim of this study was to confirm a positive effect of a long-term physical activity and nutrition interventions on health-related physical fitness and health-related quality of life in a representative sample of individuals in the first year after the kidney transplantation. At the same time it was fundamental to verify that the experimental trial can be...
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Avaliação dos eventos envolvidos na evolução crônica da lesão renal aguda pós isquêmica em ratos com deficiência de vitamina D / Assessment of the events involved in chronic evolution of acute kidney injury in a murine ischemia/reperfusion model after vitamin D deficiencyGonçalves, Janaína Garcia 08 August 2014 (has links)
Na maioria dos países, a incidência e prevalência da doença renal crônica (DRC) vem aumentando ao longo dos anos. Embora tenha havido uma melhora significativa no manejo da DRC com os inibidores do sistema renina-angiotensina-aldosterona, a doença ainda é progressiva, levando a necessidade do surgimento de novas estratégias protetoras. A fibrose renal progressiva está presente na DRC e envolve a participação de várias citocinas, com destaque para o fator Transforming growth factor- beta1 (TGF-beta1). Tem sido demonstrado que a mortalidade de pacientes com DRC está diretamente relacionada à função renal e está associada a riscos tradicionais como cardiovasculares e infecções. Entretanto, esses riscos tradicionais explicam apenas metade das causas de mortalidade nesses pacientes. Evidências crescentes mostram que o status de vitamina D pode ser um fator de risco não tradicional para a evolução da DRC. Tendo em vista o importante papel da vitamina D na manutenção das funções fisiológicas essenciais e a observação da queda dos níveis deste hormônio na DRC, torna-se relevante o estudo da deficiência de vitamina D nos eventos envolvidos na evolução crônica da lesão renal aguda em modelo experimental de isquemia/reperfusão renal. Ratos Wistar foram divididos em quatro grupos: controle, animais que receberam dieta padrão; dVD, animais que receberam dieta depletada em vitamina D; Isq, animais que receberam dieta padrão e foram submetidos ao insulto de isquemia/reperfusão renal bilateral no 28º dia; Isq+dVD, animais que receberam dieta depletada em vitamina D e foram submetidos ao insulto de isquemia/reperfusão bilateral no 28º dia. Ao final dos 90 dias do protocolo, os animais foram submetidos à eutanásia, amostras de sangue, urina e o tecido renal foram coletados para a análise dos mecanismos de lesão renal. Os animais submetidos ao insulto de isquemia/reperfusão renal apresentaram hipertrofia renal, aumento dos níveis de pressão arterial média, colesterol e de PTH plasmático. Além disso, foi observada expansão da área intersticial, aumento do infiltrado de macrófagos/monócitos, da expressão de colágeno IV, fibronectina, vimentina e alfa-actina e redução da expressão da proteína Klotho. A deficiência de vitamina D contribuiu para a elevação dos níveis plasmáticos de PTH e aumento da proteinúria assim como para as alterações túbulo-intersticiais crônicas importantes (fibrose e infiltrado inflamatório do interstício, dilatação e atrofia tubular), aumento da expressão da citocina TGF-beta1 expressão do receptor de vitamina D (VDR) e da proteína Klotho, observados nos animais deficientes em vitamina D submetidos ao insulto de isquemia/reperfusão renal. Portanto, através de vias inflamatórias e com participação do fator de crescimento TGF-beta1 ê um fator agravante para o dano túbulo-intersticial e formação de fibrose intersticial nesse modelo experimental de isquemia/reperfusão renal / In most countries, the incidence and prevalence of chronic kidney disease (CKD) has been increasing over the years. Although there was a significant improvement in the management of CKD with renin-angiotensin-system inhibitors, the disease is still progressive, leading to the need of emergence of new protective strategies. The progressive renal fibrosis is present in CKD and involves the participation of several cytokines, especially the Transforming growth factor-beta1 (TGF-beta1). It has been shown that the mortality of patients with CKD is directly related to renal function, which is associated to traditional risk factors such as cardiovascular diseases and infections. However, these traditional risk factors explain only half of the causes of mortality in these patients. Growing evidence shows that vitamin D status may be a non-traditional risk factor for the progression of CKD. Considering the important role of vitamin D in the maintenance of essential physiological functions and the observation of low levels of this hormone in CKD, the study of vitamin D deficiency in the events involved in chronic evolution of acute kidney injury in an experimental model of ischemia/reperfusion becomes relevant. Wistar rats were divided into four groups : control, animals received a standard diet ; dVD, animals received a vitamin D-depleted diet ; Isq, animals received a standard diet and were subjected to bilateral renal ischemia/reperfusion injury on day 28; Isq +dVD, animals received a vitamin D-depleted diet and were subjected to bilateral renal ischemia/reperfusion injury on day 28 . At the end of the 90 days of the protocol, the animals were euthanized and samples of blood, urine and kidney tissue were collected for analysis of the mechanisms of renal injury. The animals subjected to the insult of ischemia/ reperfusion showed renal hypertrophy, increased levels of mean blood pressure, cholesterol and plasma PTH. Furthermore, expansion of the interstitial area, increased infiltration of macrophages/monocytes, increased expression of collagen IV, fibronectin, vimentin and alpha-actin, and reduced expression of Klotho protein were observed. The vitamin D deficiency contributed to the elevation of plasma PTH levels and increased proteinuria as well as for important chronic tubulo-interstitial changes (fibrosis and inflammatory infiltration of the interstitium, tubular dilation and atrophy), increased expression of cytokine TGF-beta1 vitamin D receptor (VDR) and Klotho protein observed in vitamin D-deficient animals subjected to the insult of renal ischemia/reperfusion. Therefore, through inflammatory pathways and involvement of TGF-beta1 w y aggravating factor in tubulointerstitial damage and formation of interstitial fibrosis in this experimental model of renal ischemia/reperfusion
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Der Einfluss von Interleukin-1 und des Interleukin-1-Rezeptorantagonisten (Anakinra) auf die epithelial-mesenchymale Transition von Tubulusepithelzellen in vitro / The effect of interleukin-1 and interleukin-1-receptor antagonist (Anakinra) on epithelial-mesenchymal transition of tubular epithelial cells in vitroTakes, Julia 26 October 2011 (has links)
No description available.
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Efeito da metformina no remodelamento miocárdico e renal em ratos obesos com resistência à insulina / Effect of metformin on myocardial and renal remodeling in obese rats with insulin resistanceAdriana Burlá Klajman 03 June 2011 (has links)
Diversas evidências comprovam que a obesidade está associada a alterações estruturais e funcionais do coração em modelos humanos e animais. Outros estudos recentes também demonstram que a obesidade humana está associada com alterações na função e na estrutura vascular, especialmente em grandes e médias artérias. Estudos epidemiológicos têm confirmado que a obesidade é um fator de risco significativo para o aparecimento de proteinúria e de doença renal terminal em uma população normal. Com o objetivo de determinar as alterações morfológicas relacionadas ao remodelamento cardíaco, vascular e renal em um modelo experimental de obesidade induzida pelo glutamato monossódico (MSG) e os efeitos da metformina sobre estes achados, foram estudados 25 ratos divididos em cinco grupos: controle com 16 e 22 semanas (CON-16 e CON-22); obeso com 16 e 22 semanas (MSG-16 e MSG-22) e obeso + metformina (MET-22) 300mg/Kg/dia por via oral. A caracterização da resistência à insulina foi feita através da medida da insulina plasmática e cálculo do índice de HOMA-IR. As análises morfológicas e quantificação do colágeno miocárdico foram feitos pelo sistema de imagem Image Pro Plus analysis. A pressão arterial sistólica foi levemente maior no grupo MSG-22, adquirindo significância estatística quando comparada com o grupo MSG-16 (1222 vs 1082 mmHg, p<0,05). Por outro lado, o grupo MET-22 mostrou níveis mais baixos de pressão arterial (1181 mmHg), sem alcançar diferença significativa. No grupo de animais obesos, foi observado aumento na relação média-lumen com 16 semanas (39,93,7 vs 30,22,0 %, p<0,05) e com 22 semanas (39,81,3 vs 29,51,2%, p<0,05), que foi reduzida com o uso da metformina (31,50,9%). O depósito de colágeno na área perivascular no ventrículo esquerdo foi significativamente maior no grupo MSG-22 (1,390,06 vs 0,830,06 % no CON-22, p<0,01), sendo atenuado pela metformina (1,020,04%). No rim, a área seccional transversa das arteríolas intrarrenais foi semelhante entre os grupos (18,52,2 no CON-16; 19,93,7 no MSG-16; 18,93,1 no CON-22; 21,81,5 no MSG-22; 20,21,4 no MET-22). Foi observado aumento da área glomerular no grupo MSG-22 (141,34,5 vs 129,50,5 m2), mas sem significância estatística. Em conclusão, nos ratos com obesidade induzida pelo MSG, com resistência à insulina, as alterações cardíacas foram mais proeminentes do que as alterações renais. No coração foram observados sinais de remodelamento vascular hipertrófico nas pequenas artérias intramiocárdicas e evidências de fibrose miocárdica mais proeminente na área perivascular, alterações que foram, pelo menos parcialmente, atenuadas com o uso de metformina durante seis semanas, mostrando que esta droga pode ser benéfica na prevenção de complicações cardíacas, vasculares e renais associadas com a obesidade. / Many evidences show that obesity is associated to structural and functional changes in the heart of human and animal models. Recent studies also show that human obesity is associated with vascular structural and functional modifications, specially at large and medium-sized arteries. Epidemiological studies have confirmed that obesity is a significant risk factor for the development of proteinuria and end-stage renal disease in a normal population. With the objective to determinate morphological changes related to cardiac, vascular and renal remodeling in an experimental model of monosodium glutamate (MSG)-induced obesity and the effect of metformin at this finding. Twenty five rats were studied and divided into five groups: control with 16 e 22 weeks (CON-16 and CON-22); obese with 16 and 22 weeks (MSG-16 e MSG-22), and obese + metformin (MET-22) 300mg/Kg/day per oral. The characterization of insulin resistance was done through measurement of plasma insulin and calculation of HOMA-IR index. The morphological analysis and the quantification of myocardial collagen were carried out by Image Pro Plus analysis system. The systolic blood pressure was slightly higher in MSG-22 group, reaching statistical significance when compared to MSG-16 group (1222 vs 1082 mmHg, p<0.05). On the other hand, the MET-22 group demonstrated lower blood pressure levels (1181 mmHg), without reaching statistical difference. The obese animals presented increase in media-to-lumen ratio with 16 weeks (39.93.7 vs 30.22.0 %, p<0.05) and with 22 weeks (39.81.3 vs 29.51.2%, p<0.05), which was reduced with use of metformin (31.50.9%). The collagen deposition in perivascular area of left ventricle was significantly greater in MSG-22 group (1.390.06 vs 0.830.06 % in CON-22, p<0.01), and attenuated by metformin (1.020.04%). In the kidney, the media cross-sectional area of intrarenal arterioles was similar among the groups (18.52.2 in CON-16; 19.93.7 in MSG-16; 18.93.1 in CON-22; 21.81.5 in MSG-22; 20.21.4 in MET-22). An increase of glomerular area was observed in MSG-22 group (141.34.5 vs 129.50.5 m2), but without statistical significance. In conclusion, rats with MSG-induced obesity and insulin resistance presented more pronounced cardiac changes than renal alterations. In the heart, there were evidences of hypertrophic vascular remodeling were observed in intramyocardial small arteries and perivascular fibrosis. These findings were, at least partially, attenuated by metformin for six weeks, suggesting that this drug may be beneficial for prevention of cardiac, vascular and renal complications associated with obesity.
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Efeito da metformina no remodelamento miocárdico e renal em ratos obesos com resistência à insulina / Effect of metformin on myocardial and renal remodeling in obese rats with insulin resistanceAdriana Burlá Klajman 03 June 2011 (has links)
Diversas evidências comprovam que a obesidade está associada a alterações estruturais e funcionais do coração em modelos humanos e animais. Outros estudos recentes também demonstram que a obesidade humana está associada com alterações na função e na estrutura vascular, especialmente em grandes e médias artérias. Estudos epidemiológicos têm confirmado que a obesidade é um fator de risco significativo para o aparecimento de proteinúria e de doença renal terminal em uma população normal. Com o objetivo de determinar as alterações morfológicas relacionadas ao remodelamento cardíaco, vascular e renal em um modelo experimental de obesidade induzida pelo glutamato monossódico (MSG) e os efeitos da metformina sobre estes achados, foram estudados 25 ratos divididos em cinco grupos: controle com 16 e 22 semanas (CON-16 e CON-22); obeso com 16 e 22 semanas (MSG-16 e MSG-22) e obeso + metformina (MET-22) 300mg/Kg/dia por via oral. A caracterização da resistência à insulina foi feita através da medida da insulina plasmática e cálculo do índice de HOMA-IR. As análises morfológicas e quantificação do colágeno miocárdico foram feitos pelo sistema de imagem Image Pro Plus analysis. A pressão arterial sistólica foi levemente maior no grupo MSG-22, adquirindo significância estatística quando comparada com o grupo MSG-16 (1222 vs 1082 mmHg, p<0,05). Por outro lado, o grupo MET-22 mostrou níveis mais baixos de pressão arterial (1181 mmHg), sem alcançar diferença significativa. No grupo de animais obesos, foi observado aumento na relação média-lumen com 16 semanas (39,93,7 vs 30,22,0 %, p<0,05) e com 22 semanas (39,81,3 vs 29,51,2%, p<0,05), que foi reduzida com o uso da metformina (31,50,9%). O depósito de colágeno na área perivascular no ventrículo esquerdo foi significativamente maior no grupo MSG-22 (1,390,06 vs 0,830,06 % no CON-22, p<0,01), sendo atenuado pela metformina (1,020,04%). No rim, a área seccional transversa das arteríolas intrarrenais foi semelhante entre os grupos (18,52,2 no CON-16; 19,93,7 no MSG-16; 18,93,1 no CON-22; 21,81,5 no MSG-22; 20,21,4 no MET-22). Foi observado aumento da área glomerular no grupo MSG-22 (141,34,5 vs 129,50,5 m2), mas sem significância estatística. Em conclusão, nos ratos com obesidade induzida pelo MSG, com resistência à insulina, as alterações cardíacas foram mais proeminentes do que as alterações renais. No coração foram observados sinais de remodelamento vascular hipertrófico nas pequenas artérias intramiocárdicas e evidências de fibrose miocárdica mais proeminente na área perivascular, alterações que foram, pelo menos parcialmente, atenuadas com o uso de metformina durante seis semanas, mostrando que esta droga pode ser benéfica na prevenção de complicações cardíacas, vasculares e renais associadas com a obesidade. / Many evidences show that obesity is associated to structural and functional changes in the heart of human and animal models. Recent studies also show that human obesity is associated with vascular structural and functional modifications, specially at large and medium-sized arteries. Epidemiological studies have confirmed that obesity is a significant risk factor for the development of proteinuria and end-stage renal disease in a normal population. With the objective to determinate morphological changes related to cardiac, vascular and renal remodeling in an experimental model of monosodium glutamate (MSG)-induced obesity and the effect of metformin at this finding. Twenty five rats were studied and divided into five groups: control with 16 e 22 weeks (CON-16 and CON-22); obese with 16 and 22 weeks (MSG-16 e MSG-22), and obese + metformin (MET-22) 300mg/Kg/day per oral. The characterization of insulin resistance was done through measurement of plasma insulin and calculation of HOMA-IR index. The morphological analysis and the quantification of myocardial collagen were carried out by Image Pro Plus analysis system. The systolic blood pressure was slightly higher in MSG-22 group, reaching statistical significance when compared to MSG-16 group (1222 vs 1082 mmHg, p<0.05). On the other hand, the MET-22 group demonstrated lower blood pressure levels (1181 mmHg), without reaching statistical difference. The obese animals presented increase in media-to-lumen ratio with 16 weeks (39.93.7 vs 30.22.0 %, p<0.05) and with 22 weeks (39.81.3 vs 29.51.2%, p<0.05), which was reduced with use of metformin (31.50.9%). The collagen deposition in perivascular area of left ventricle was significantly greater in MSG-22 group (1.390.06 vs 0.830.06 % in CON-22, p<0.01), and attenuated by metformin (1.020.04%). In the kidney, the media cross-sectional area of intrarenal arterioles was similar among the groups (18.52.2 in CON-16; 19.93.7 in MSG-16; 18.93.1 in CON-22; 21.81.5 in MSG-22; 20.21.4 in MET-22). An increase of glomerular area was observed in MSG-22 group (141.34.5 vs 129.50.5 m2), but without statistical significance. In conclusion, rats with MSG-induced obesity and insulin resistance presented more pronounced cardiac changes than renal alterations. In the heart, there were evidences of hypertrophic vascular remodeling were observed in intramyocardial small arteries and perivascular fibrosis. These findings were, at least partially, attenuated by metformin for six weeks, suggesting that this drug may be beneficial for prevention of cardiac, vascular and renal complications associated with obesity.
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