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Vyhledávání a hodnocení závažnosti endoteliální dysfunkce u dětí s chronickým autoimunitním onemocněním / Searching for and Evaluating the Severity of Endothelial Dysfunction in Children with Chronic Autoimmune DiseaseSýkorová, Aneta January 2019 (has links)
We aimed to evaluate the endothelial function by combining RHI measurements and specific biochemical markers in the children with possible risk of premature manifestation of atherosclerosis and in the control group of healthy children. In all, 124 children (of which 106 patients divided into five groups according to diagnosis - type 1 diabetes mellitus, Crohn's disease, cystic fibrosis, familial hypercholesterolemia and acute lymphoblastic leukemia and 18 healthy controls) were enrolled in the study. During the study, we measured RHI using a new plethysmographic method and further evaluated biochemical markers of endothelial dysfunction (ADMA, E-selectin, hsCRP and VCAM) and lipidogram in individual groups of children. The primary objective of our study was the determination of RHI and biochemical parameters in healthy subjects and in selected risk groups of children (type 1 diabetes mellitus, Crohn's disease, cystic fibrosis, familial hypercholesterolemia and children after successful treatment of acute lymphoblastic leukemia). At the same time, we compared patients from individual groups with the control group. We found significantly elevated RHI values in groups of children with type 1 diabetes, Crohn's disease, cystic fibrosis, and children after successful treatment of acute lymphoblastic leukemia....
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"Clonagem e caracterização de genes regulados por glicose em ilhotas pancreáticas humanas" / Cloning and characterization of glucose-regulated genes in human pancreatic isletsAita, Carlos Alberto Mayora 16 December 2002 (has links)
O Diabetes mellitus (DM) do tipo 1 é uma doença causada pela destruição, por mecanismo auto-imune, das células beta das ilhotas pancreáticas, produtoras de insulina. O tratamento convencional da doença é realizado por meio de injeções diárias de insulina exógena. O transplante de ilhotas pancreáticas inclui-se, atualmente, como uma das alternativas terapêuticas à insulinoterapia. Entretanto, para atingir a insulino-independência, é necessário transplantar um grande número de ilhotas por paciente. O conhecimento do mecanismo de proliferação das células beta pode possibilitar a realização do transplante a partir da expansão celular ex vivo. A glicose é um dos principais indutores da proliferação de células beta. Neste trabalho, foi estabelecida e executada a tecnologia de isolamento e purificação de ilhotas pancreáticas humanas, visando sua estimulação com glicose. Para identificar genes regulados por glicose nestas ilhotas, foi utilizada a técnica de hibridização subtrativa SSH, associada ao rastreamento da biblioteca através de macroarranjos de DNA. Num primeiro rastreamento, foram identificados dois fragmentos gênicos induzidos pela glicose. Um destes apresentou homologia com uma proteína hipotética humana de função desconhecida e o segundo com o receptor de polipetídeo pancreático. Este trabalho permitiu a identificação de novos genes regulados pela glicose em ilhotas pancreáticas humanas, os quais podem estar relacionados à proliferação celular deste tecido. / Type 1 Diabetes mellitus (T1DM) is caused by autoimmune destruction of the insulin-producing pancreatic islet b-cells. Treatment is generally approached by daily subcutaneous injections of exogenous insulin. Nowadays, pancreatic islet transplantation is considered as an effective alternative treatment to insulin therapy. However, in order to reach insulin-independence, a large number of islets is required for each patient. Knowledge of the mechanisms regulating islet b-cell proliferation may allow ex-vivo b-cell expansion prior to transplant. Glucose is considered one of the main inducers of islet b-cells proliferation. We established and executed the technology of human islet isolation and purification. The islets were then stimulated in culture with glucose. In order to identify glucose-regulated genes in cultured human islets, we utilized the suppression subtractive hybridization (SSH) method, followed by cDNA library screening by DNA macroarrays. Preliminary screening allowed us to isolate two cDNAs displaying glucose regulation, one of which is similar to a human hypothetical protein of unknown function and the other shows similarity to the pancreatic polypeptide receptor. This work allowed identification of glucose-regulated genes in human pancreatic islets, which may be related to cell proliferation in this tissue.
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Diabetes Mellitus tipo 1: controle glicêmico e fatores de risco cardiovasculares em adultos / Type 1 Diabetes Mellitus: glycemic control and cardiovascular risk factors in adultsGONÇALVES, Alessandra Rocha 29 June 2012 (has links)
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Previous issue date: 2012-06-29 / Objective: To evaluate the nutritional status, the glycemic control and the prevalence
of cardiovascular risk factors in patients with type 1 diabetes mellitus (T1DM),
attended at the nutrition and endocrinology outpatient clinic of the Goiânia Geral
Hospital (GGH). Methodology: a cross-sectional study conducted from March to
August/2011, with the following inclusion criteria: consolidated diagnosis of the
disease for at least six months, age ranging from 19 to 60 years. Fifty-two patients
were selected and interviewed, and 44 came to the clinic for collection of biological
material. Personal, socioeconomic and biochemical data were collected. Fasting
glucose (FG), glycated hemoglobin (HbA1c), lipid profile and microalbuminuria (MA)
were determined. MA and HbA1c were determined by immunoturbidimetry and FG
and lipid profile by the enzymatic colorimetric method using a Labmax Plenno
apparatus. After collecting the material, physical assessment was performed by three
trained interviewers who collected measurements of weight, height, waist
circumference and blood pressure measurement, following recommendations from
the literature. The following risk factors were evaluated: hypertension, dyslipidemia,
general obesity (BMI- body mass index), abdominal obesity (WC- waist
circumference), glycated hemoglobin, microalbuminuria, family history of type 2
diabetes, and smoking. The cutoffs recommended by the American Diabetes
Association (ADA) were adopted. Statistical analysis was performed using the
Statistical Package for the Social Sciences SPSS 18.0. Results: The average age
of patients was 30.6 ± 7.4 years, the time of diagnosis was 9.9 ± 7.1 years and
median education was 12 years. The HbA1c was inadequate in 90.9% of the
patients and 38.6% of the patients were found to be overweight (n=17). Most cases
of inadequacy of BMI, WC and total cholesterol (TC) involved females. The
prevalence of hypertension was 38.6% (n=17) and the prevalence of dyslipidemia
was 63.6% (n=28). The prevalence of inappropriate LDL, HDL, cholesterol and
triglyceride levels was 39.5%, 25%, 22.7%, and 22.7%, respectively. The prevalence
of MA was 72%. Conclusion: most patients presented unsatisfactory glucose
control. The prevalence of overweight and hypertension, of altered lipid profile, and
microalbuminuria was high. / Objetivo: Avaliar o estado nutricional, o controle glicêmico e a prevalência dos
fatores de risco cardiovasculares em pacientes adultos com diabetes mellitus tipo 1
(DM1), atendidos no ambulatório de nutrição e endocrinologia do Hospital Geral de
Goiânia (HGG). Metodologia: Estudo transversal, realizado entre março e
agosto/2011, cujos critérios de inclusão foram: diagnóstico consolidado da doença
há pelo menos seis meses, idade maior ou igual a dezenove anos e menor que
sessenta anos. Foram selecionados e entrevistados 52 pacientes, dos quais 44
compareceram para coleta de material biológico. Coletou-se dados clínicos,
socioeconômicos e bioquímicos. Foram realizados exames de glicemia de jejum
(GJ), hemoglobina glicada (HbA1c), perfil lipídico e microalbuminúria (MA). O
método utilizado para dosar HbA1c E MA foi a Imunoturbidimetria, realizada no
aparelho Labmax Plenno. Os exames de glicemia de jejum e lipidograma também
foram realizados no mesmo equipamento, pelo método enzimático-colorimétrico
(oxidase/ peroxidase). Após a coleta de material, foi realizada avaliação física por
três entrevistadores treinados que coletaram medidas de peso, altura, circunferência
da cintura e aferição da pressão arterial, seguindo recomendações da literatura.
Foram avaliados os seguintes fatores de risco cardiovasculares: hipertensão arterial,
dislipidemia, obesidade geral (IMC- Índice de massa corporal), obesidade abdominal
(CC- circunferência da cintura), hemoglobina glicada, microalbuminúria, história
familiar de diabetes tipo 2 e tabagismo. Foram adotados os pontos de corte
recomendados pela American Diabetes Association (ADA). A análise estatística foi
realizada no programa Statistical Package for the Social Sciences- SPSS 18.0.
Resultados: A idade média dos pacientes foi de 30,6±7,4 anos, o tempo de
diagnóstico foi de 9,9 ±7,1 anos e a mediana da escolaridade foi de 12 anos. A
HbA1c estava inadequada em 90,9% dos pacientes. O excesso de peso foi
observado em 38,6% dos pacientes (n=17). A maior prevalência de inadequação do
IMC, CC e colesterol total (CT) foi associada ao sexo feminino. A prevalência de
hipertensão arterial foi de 38,6% (n=17) e de dislipidemia foi de 63,6% (n=28) dos
pacientes. As prevalências de inadequação do LDL, HDL, colesterol e triglicerídeos
foram de 38,6%, 25%, 22,7%, 22,7%, respectivamente. A prevalência de MA foi de
72%. Conclusão: A maioria dos pacientes apresentou controle glicêmico
insatisfatório. Foi alta a prevalência de excesso de peso e de inadequação da
pressão arterial, do perfil lipídico, e microalbuminúria.
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Associação dos polimorfismos -318C/T, CT60 e A49G do gene CTLA4, R620W do gene PTPN22 e A946T do gene IFIH1 em pacientes pediátricos com doença autoimune tireoidiana e diabetes mellitus tipo 1 / Association of -318C/T, A49G and CT60 polymorphisms of CTLA4 gene, R620W of PTPN22 gene, and A946T of IFIH1 gene in pediatric patients with autoimmune thyroid disease and type 1 diabetes mellitusMárcia Regina Bedin 12 July 2013 (has links)
As doenças autoimunes da tireoide (DAIT) representadas, principalmente pela doença de Graves (DG) e tireoidite de Hashimoto (TH), apresentam causas multifatoriais, incluindo fatores genéticos e ambientais. Diversos genes estão envolvidos, entre eles CTLA4, PTPN22 e mais recentemente IFIH1, principalmente quando associados a diabetes mellitus tipo 1 (DM1). OBJETIVOS: Determinar a frequência alélica e genotípica dos polimorfismos: -318C/T, A49G e CT60 do CTLA4, R620W do PTPN22 e A946T do IFIH1 em pacientes pediátricos portadores de DG, TH e DM1 associado a TH e em uma população controle normal, e determinar a associação com características clínicas e laboratoriais. MATERIAL E MÉTODOS: Foram estudados 142 pacientes menores de 21 anos ao diagnóstico. Os dados clínicos e laboratoriais foram obtidos em prontuário. A genotipagem foi realizada por PCR em tempo real de todos os polimorfismos. Dados clínicos e laboratoriais como sexo, idade de início, bócio, anticorpos anti-GAD, IA2 e IAA e níveis de TRAb e anti-TPO foram analisados. RESULTADOS: Sessenta e dois pacientes foram diagnosticados com DG, com idade média ao diagnóstico (IMD) de 10,8 ± 4,4 anos, sendo 43 do sexo feminino; TH esteve presente em 44 pacientes, sendo 37 meninas, com IMD de 10,3 (± 2,9 anos); e 36 pacientes com DM1 associado a TH, sendo 21 meninas, com IMD de 6,2 (± 4,0 anos) no momento do diagnóstico de DM1 e de 11,6 (± 4,6 anos) ao diagnóstico de TH. O grupo controle foi constituído por 81 indivíduos sem diabetes, função tireoidiana normal e ausência de anticorpos antitireoidianos. Todos os polimorfismos estavam em equilíbrio de Hardy-Weinberg. O polimorfismo -318C/T não esteve associado com nenhum dos grupos. O alelo de risco G do polimorfismo A49G foi mais frequente em pacientes com TH (p=0,047) e o genótipo patogênico (AG e GG) foi mais frequente em pacientes com DG (p=0,049). O alelo de risco G do polimorfismo CT60 foi mais frequente apenas em pacientes com DG (p=0,035). O alelo de risco T do polimorfismo R620W foi mais frequente em pacientes com DM1 associado a TH (p=0,043). O alelo de risco T do polimorfismo A946T foi mais frequente em pacientes com DM1 associado a TH (p=0,009), assim como o genótipo patogênico (CT e TT) quando comparado ao grupo controle (p=0,007). Quando agrupamos todas as DAIT, observamos associação com A49G (p=0,024) e R620W (p=0,047). Quando agrupamos apenas pacientes com TH, encontramos diferença no A49G (p=0,018) e no A946T (p=0,041). O polimorfismo CT60 foi associado com menor duração da terapia medicamentosa no grupo DG (p=0,004), mas não com os níveis de TRAb ou presença de bócio. No DM1 com HT, o alelo de risco do A49G foi mais frequentemente encontrado no sexo masculino (p=0,04); R620W foi relacionado com a presença de bócio (p=0,03), enquanto A946T foi associado com níveis de anti-TPO mais baixos (p=0,047). Os níveis de anti-GAD, IA2 e Resumo IAA não foram associados aos polimorfismos. CONCLUSÃO: Encontramos associações genéticas diferentes entre os pacientes com DAIT, sugerindo que as crianças possuem provavelmente padrões genéticos distintos, apesar do menor tempo de exposição a fatores ambientais / Autoimmune thyroid diseases (AITD) represented by Graves\' disease (GD) and Hashimoto\'s thyroiditis (HT), have multifactorial causes, including genetic and environmental factors. Several genes are involved, including CTLA4, PTPN22 and more recently IFIH1, especially when associated with type 1 diabetes (T1D). OBJECTIVES: To determine the allelic and genotypic frequencies of the polymorphisms: -318C/T, A49G and CT60 of CTLA4, R620W of PTPN22 and A946T of IFIH1 in pediatric patients with GD, HT and T1D associated with HT and in a control population and determine association with clinical and laboratory features. MATERIAL AND METHODS: We studied 142 patients under 21 years at diagnosis. Clinical and laboratory data were obtained from medical records. Genotyping was performed by real time PCR for all polymorphisms. Clinical and laboratory data were analyzed, such as gender, age of onset, goiter, anti-GAD, IA2 and IAA levels and TRAb and anti-TPO levels. RESULTS: Sixty-two patients were diagnosed with GD, with mean age at diagnosis (MAD) of 10.8 ± 4.4 years, 43 females; HT was present in 44 patients, 37 girls, MAD 10.3 (± 2.9 years) and type 1 diabetes associated with HT was present in 36 patients, 21 girls, MAD 6.2 (± 4.0 years) at diagnosis of T1D and 11.6 (± 4.6 years) at diagnosis of HT. Control group consisted of 81 subjects without diabetes, normal thyroid function and absence of antithyroid antibodies. All polymorphisms were in Hardy-Weinberg equilibrium. The polymorphism -318C/T was not associated with any of the groups. The risk allele G of A49G polymorphism was more frequent in patients with HT (p=0.047) and the pathogenic genotype (AG and GG) was more frequent in patients with GD (p=0.049). The risk allele G of CT60 polymorphism was more frequent only in patients with GD (p=0.035). The risk allele T of R620W polymorphism was more frequent in patients with T1D associated with HT (p=0.043). The risk allele T of A946T polymorphism was more frequent in patients with T1D associated with HT (p=0.009), as well as the pathogenic genotype (CT and TT) compared to control group (p=0.007). When all AITD is grouped, we observed association with A49G (p=0.024) and R620W (p=0.047). Only when patients with HT are grouped, we found differences in A49G (p=0.018) and A946T (p=0.041). CT60 polymorphism was associated with a shorter duration of drug therapy on GD group (p=0.004), but no association with TRAb levels or presence of goiter were found. In T1D with HT, the risk allele of A49G was more often found in males (p=0.04); R620W was associated with presence of goiter (p=0.03), while A946T was associated with anti-TPO levels (p=0.047). The anti-GAD, IAA and IA2 levels were not associated with any polymorphisms. CONCLUSION: We found different genetic associations among patients with AITD, suggesting that children are likely to have distinct genetic background, despite shorter exposure to environmental factors
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Análise da expressão gênica global de células estromais mesenquimais e de células tronco hematopoéticas isoladas da medula óssea de pacientes com diabetes mellitus do tipo 1 / Global gene expression analysis of mesenchymal stromal cells and hematopoietic stem cells isolated from bone marrow of type 1 diabetes patientsKalil William Alves de Lima 25 February 2013 (has links)
O diabetes mellitus do tipo 1 (T1D) é uma doença autoimune mediada por células T e caracterizada pela destruição seletiva das células ? pancreáticas produtoras de insulina. Células estromais mesenquimais (MSCs) e células tronco hematopoéticas (HSCs) são os principais componentes do nicho hematopoético na medula óssea. Estas células vêm sendo utilizadas nos últimos anos em transplantes autólogos para tratamento do T1D. O objetivo geral do presente trabalho foi avaliar o perfil de expressão gênica global de MSCs e HSCs de pacientes com T1D e compará-lo com células isoladas de indivíduos saudáveis através da técnica de microarray e programas específicos de bioinformática. As MSCs e HSCs foram isoladas da medula óssea de pacientes com T1D antes e após o tratamento com imunossupressão em altas doses seguida pelo transplante autólogo de células tronco hematopoéticas (AHSCT). As MSCs apresentaram valor elevado de expressão absoluta de diversas moléculas potencialmente relacionadas com suas funções de suporte à hematopoese. MSCs de pacientes diabéticos apresentaram perfil de expressão gênica global distinto das isoladas de indivíduos saudáveis, com hiper-regulação da sinalização via proteína G e hiporregulação da atividade transcricional. O receptor ?3 adrenérgico, assim como a sinalização simpática, foram hiper-expressos nas células dos pacientes. Genes que codificam moléculas que suportam a hematopoese e regulados pelo sistema nervoso simpático, VCAM1 e CXCL12, foram hiporregulados em nossa análise. Após o AHSCT, houve atenuação do perfil de expressão diferencial das MSCs dos pacientes, entretanto elas permaneceram com hiperatividade da sinalização via proteína G e déficit da atividade transcricional. As HSCs apresentaram altos níveis de expressão absoluta de diversas integrinas e receptores de citocinas e fatores de crescimento, potencialmente relacionados com funções na hematopoese. HSCs de pacientes com T1D apresentaram perfil de expressão gênica global distinto das de indivíduos saudáveis, com hiper-regulação de genes associados com a atividade transcricional. Os fatores de transcrição TCFL2 e p53, que têm papel fundamental na regulação do ciclo celular das HSCs, foram diferencialmente expressos entre as HSCs de pacientes diabéticos e controles. Assim, nossos resultados de expressão gênica global apontaram alterações intrínsecas nas HSCs e MSCs de pacientes diabéticos que podem estar relacionadas com a falha terapêutica dos transplantes autólogos. A implicação dessas alterações no desenvolvimento e patogênese do T1D permanece desconhecida e a realização de ensaios funcionais poderá esclarecer o significado biológico das mesmas. / Type 1 diabetes mellitus (T1D) is a T cell-mediated autoimmune disease, characterized by selective destruction of insulin-producing pancreatic ? cells. Mesenchymal stromal cells (MSCs) and hematopoietic stem cells (HSCs) are the main components of hematopoietic niches. In the last years, these cells are being used in autologous transplantation settings for T1D treatment. The main goal of this study was to evaluate the global gene expression profile of MSCs and HSCs from T1D patients, by using microarrays and bioinformatics specific programs. MSCs and HSCs were isolated from bone marrow of T1D patients before and after treatment with high dose immunossupression followed by hematopoietic stem cell transplantation. MSCs showed high absolute expression values of several molecules potentially related to their function of hematopoiesis support. MSCs from T1D patients exhibited distinct gene expression profile from control MSCs and presented up-regulation of the G protein-coupled receptor signaling pathway and down-regulation of transcriptional activity. The ?3 adrenergic receptor, as well the sympathetic nervous system signaling were up-regulated on patient´s cells. Genes that codify molecules which support hematopoeisis and are regulated by the symphatic nervous system, VCAM1 and CXCL12, were downregulated on our analysis. After AHSCT, there was an attenuation of the differential expression profile of MSCs from T1D patients, however they remained with G proteincoupled receptor signaling pathway hyperactivity and transcriptional activity deficit. HSCs exhibited high absolute expression values of integrins, cytokine receptors and growth factors, molecules potencially related to hematopoietic functions. HSCs from T1D patients showed distinct expression profile from control HSCs and demonstrated up-regulation of genes related to transcriptional activity. The transcription factors TCFL2 and p53, which have important role in regulating HSC cycle, were differentially expressed between HSCs from T1D patients and controls. Thus, our global gene expression analysis has revealed intrinsic alterations on MSCs and HSCs from T1D patients that could be related to the autologous transplant therapeutic failures. The implications of these alterations on the development and pathogenesis of T1D remain unknown and functional assays could unravel their biological meaning.
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Efeito do tratamento periodontal básico no controle glicêmico e da inflamação de pacientes com Diabetes Mellitus tipo 1 e tipo 2: Ensaio Clínico Controlado / Effect of basic periodontal treatment on glycemic control and inflammation in patients with diabetes mellitus type 1 and type 2: Controlled Clinical TrialLopes, Claudia Camila Peruzzo 06 April 2016 (has links)
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Previous issue date: 2016-04-06 / Periodontitis is often associated with diabetes mellitus (DM) and can be
considered a chronic complications. Growing evidences suggests that periodontal
disease has an adverse effect on glycemic control and an active role in the
pathophysiology of complications related to DM, as in type 1 diabetes mellitus as
in type 2 diabetes mellitus. Objective: Compare the response of basic periodontal
therapy in diabetes patients with diabetes type 1 and type 2. Methodology: We
selected 70 patients with periodontitis, these were divided into three groups:
Control group (systemically healthy patients); Group test 1 (patients with type 1
diabetes mellitus); Group test 2 (patients with type 2 diabetes mellitus). The
groups received basic periodontal treatment after clinical examination. The
analyzis were performed at 0, 3 and 6 months, clinical parameters including
periodontal and gingival crevicular amount of fluid. They were measured glycated
hemoglobin (HbA1c) and prostaglandin E2 concentration. Results: There was an
improvement in all clinical periodontal parameters evaluated in both groups as well
as the amount of gingival crevicular fluid. It occurred more significant decrease
(p<0,05) in HbA1c and PGE2 expression in group test 1, after 6 months.
Conclusion: The basic periodontal treatment was more effective for glycemic
control in patients with type 1 diabetes mellitus / A periodontite é frequentemente associada com diabetes mellitus (DM) e pode ser
considerada uma das complicações crônicas da doença. Crescentes evidências
apontam que a doença periodontal (DP) tem um efeito adverso sobre o controle
glicêmico e uma participação ativa na fisiopatologia das complicações
relacionadas ao DM, tanto no diabetes mellitus tipo 1(DM1) quanto no diabetes
mellitus tipo 2 (DM2). Objetivo: Comparar a resposta do tratamento periodontal
básico em pacientes portadores de diabetes mellitus tipo 1 e tipo 2. Metodologia:
Foram selecionados 70 pacientes com periodontite, estes foram divididos em três
grupos: Grupo controle (pacientes sistemicamente saudáveis); Grupo teste 1
(pacientes portadores de diabetes mellitus tipo 1); Grupo teste 2 (pacientes
portadores de diabetes mellitus tipo 2). Os grupos receberam tratamento
periodontal básico, após exame clínico. As análises foram realizadas aos 0, 3 e 6
meses, incluindo parâmetros clínicos periodontais e a quantidade de fluido
crevicular gengival (GCF). Foram dosadas a hemoglobina glicada (HbA1c) e a
concentração de prostaglandina E2 (PGE2) no GCF. Resultados: Houve melhora
de todos os parâmetros clínicos periodontais avaliados em todos os grupos, bem
como na quantidade de fluido crevicular gengival. Ocorreu diminuição mais
expressiva (p<0,05) da HbA1c e da expressão de PGE2 no grupo teste 1, após 6
meses. Conclusão: O tratamento periodontal básico mostrou-se mais eficaz para
o controle glicêmico dos pacientes portadores de diabetes mellitus tipo 1.
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Prevention of type 1 diabetes mellitus in experimental studiesHolstad, Maria January 2001 (has links)
The aim of the study was to examine the immune response and different immunoprotective strategies in experimental type 1 diabetes mellitus. The autoimmune destruction of the insulin-producing pancreatic β-cells that leads to type 1 diabetes is complex and incompletely understood. Activated immune cells infiltrate the pancreatic islets at an early stage of the disease, and they produce and release cytokines, which may contribute to β-cell dysfunction and death. Several immunomodulatory agents with different mechanisms have recently been developed in order to suppress cytokine function such as MDL 201, 449A, a novel transcriptional inhibitor of TNF-α. At least in rodent β-cells, many of the toxic actions of cytokines depend on the synthesis of nitric oxide (NO). Aminoguanidine (AG), an inhibitor of NO formation, might therefore be an interesting compound for prevention of type 1 diabetes. Another substance that could influence the course of events leading to this disease is the pituitary hormone prolactin (PRL), since it has the ability to activate different immune cells. We have studied the effects of AG, PRL and MDL 201, 449A on the development of hyperglycaemia and pancreatic insulitis in multiple low dose streptozotocin induced autoimmune diabetes in mice. The natural course after syngeneic islet transplantation of pancreatic islets in NOD mice, a model of type 1 diabetes mellitus was also investigated. AG and PRL were also studied in vitro on cultured isolated rodent pancreatic islets. We suggest that the insulin-producing cells are specifically targeted by the inflammatory response after syngeneic islet transplantation in type 1 diabetic mice. Our data do not exclude a role for NO in type 1 diabetes, but it raises concerns about the use of AG as a therapeutic agent since an increased mortality and no decline in diabetes frequency was observed. AG did not seem to be directly harmful to β-cell function, but it could affect pancreatic and islet blood flows. PRL and MDL 201, 449A could both counteract hyperglycaemia and insulitis in the early phase of autoimmune diabetes.
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Mapping genetic diseases in northern SwedenEinarsdottir, Elisabet January 2005 (has links)
The population of northern Sweden has previously been shown to be well suited for the mapping of monogenic diseases. In this thesis we have tested the hypothesis that this population could also be used for efficient identification of risk genes for common diseases. In Paper I we have hypothesised that despite the admixture of Swedish, Finnish and Sami, the northern Swedish population consists of sub-populations geographically restricted by the main river valleys running through the region. This geographic isolation, in combination with founder effects and genetic drift, could represent a unique resource for genetic studies. On the other hand, it also underlines the importance of accounting for this e.g. in genetic association studies. To test this hypothesis, we studied the patterns of marriage within and between river valley regions and compared allelic frequencies of genetic markers between these regions. The tendency to find a spouse and live in the river valley where one was born is strong, and allelic frequencies of genetic markers vary significantly between adjacent regions. These data support our hypothesis that the river valleys are home to distinct sub-populations and that this is likely to affect mapping of genetic diseases in these populations. In Paper II, we tested the applicability of the population in mapping HSAN V, a monogenic disease. This disease was identified in only three consanguineous individuals suffering from a severe loss of deep pain perception and an impaired perception of heat. A genome-wide scan combined with sequencing of candidate genes resulted in the identification of a causative point mutation in the nerve growth factor beta (NGFB) gene. In Paper III, a large family with multiple members affected by familial forms of type 1 diabetes mellitus (T1DM) and autoimmune thyroiditis (AITD) was studied. This syndrome was mapped to the IDDM12 region on 2q33, giving positive lodscores when conditioning on HLA haplotype. The linkage to HLA and to the IDDM12 region thus confirmed previous reports of linkage and/or association of T1DM and AITD to these loci and provided evidence that the same genetic factors may be mediating these diseases. This also supported the feasibility of mapping complex diseases in northern Sweden by the use of familial forms of these diseases. In Paper IV, we applied the same approach to study type 2 diabetes mellitus (T2DM). A non-parametric genome-wide scan was carried out on a family material from northern Sweden, and linkage was found to the calpain-10 locus, a previously described T2DM-susceptibility gene on 2q37. Together, these findings demonstrate that selecting for familial forms of even complex diseases, and choosing families from the same geographical region can efficiently reduce the genetic heterogeneity of the disease and facilitate the identification of risk genes for the disease.
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Early arterial disease of the lower extremities in diabetes diagnostic evaluation and risk markers /Sahli, David, January 2009 (has links)
Diss. (sammanfattning) Umeå : Umeå universitet, 2009. / Härtill 4 uppsatser. Även tryckt utgåva.
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Body composition in adolescents with type 1 diabetes : aspects of glycaemic control and insulin sensitivity /Särnblad, Stefan, January 2004 (has links)
Diss. (sammanfattning) Uppsala : Univ., 2004. / Härtill 5 uppsatser.
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