Avaliamos a função cardíaca frente a Isquemia e reperfusão, em corações isolados de ratas intactas, com hipotireoidismo (Hipo), hipotireoidismo subclínico (HTS), redução dos níveis de hormônios ovarianos (OO) e a ambas condições (HTS+OO). Na estabilização, a Pressão Desenvolvida pelo Ventrículo Esquerdo (LVDP), Pressão Diastólica Final (EDP) e Pressão de Perfusão não diferiram. Porém, a Primeira Derivada Positiva das Pressões (+dP/dt), Primeira Derivada Negativa das Pressões (-dP/dt) e frequência cardíaca foram menores no grupo Hipo. Na reperfusão, os corações Hipo tiveram EDP, +dP/dt e -dP/dt semelhantes a estabilização. Assim, sugere-se que o HTS, a OO e o HTS + OO não alteraram a recuperação cardíaca após a isquemia. E que o Hipo é resistente à lesão por isquemia, apesar da função cardíaca deprimida. / We evaluate the cardiac function in relation to an ischemia and reperfusion event in hearts isolated from intact rats, With hypothyroidism (Hypo), subclinical hypothyroidism (HTS), decreased levels of ovarian hormones (OO) and both conditions (HTS + OO). At etabilization the Left Ventricle Developed Pressure (LVDP), Final Diastolic Pressure (EDP) and Perfusion Pressure did not differ. However, the First Positive Pressure Derivative (+ dP / dt), First Negative Pressure Derivative (-dP / dt) and heart rate were lower in the Hypo group. On reperfusion the hypothyroid hearts presented EDP, + dP / dt and -dP / dt Similar to stabilization. Thus, it is suggested that HTS, a OO e o HTS + OO Did not change cardiac recovery after ischemia.Is that hipo is resistant to ischemia injury, despite depressed cardiac function.

Elevated Thyroid-Stimulating Hormone (TSH) is associated with an increased risk of cardiovascular disease (CVD). We hypothesized that TSH-stimulated FA release from adipocytes contributes to macrophage inflammation. 3T3-L1 and human subcutaneous differentiated adipocytes were treated with TSH for 4 hours under various conditions and lipolysis assessed via glycerol secretion. Optimal conditions were determined and protein expression of ATGL, HSL and perilipin remained stable. TSH-stimulated 3T3-L1 or human adipocyte-conditioned medium (T-ACM) was placed on murine J774 or human THP-1 macrophages, respectively, and macrophage cytokine mRNA levels (IL-1β, IL-6, MCP-1, and TNFα) were measured by real-time RT-PCR. T-ACM did not change cytokine mRNA expression in J774 macrophages or THP-1 macrophages when compared to ACM. Absence of BSA in the medium may have hindered release of FA from differentiated adipocytes into the medium, BSA may be required to permit adequate FA accumulation in the medium to then evaluate the effect of T-ACM on macrophages. Further investigation is required to determine the effect of FA on J774 and THP-1 inflammatory response.

Elevated Thyroid-Stimulating Hormone (TSH) is associated with an increased risk of cardiovascular disease (CVD). We hypothesized that TSH-stimulated FA release from adipocytes contributes to macrophage inflammation. 3T3-L1 and human subcutaneous differentiated adipocytes were treated with TSH for 4 hours under various conditions and lipolysis assessed via glycerol secretion. Optimal conditions were determined and protein expression of ATGL, HSL and perilipin remained stable. TSH-stimulated 3T3-L1 or human adipocyte-conditioned medium (T-ACM) was placed on murine J774 or human THP-1 macrophages, respectively, and macrophage cytokine mRNA levels (IL-1β, IL-6, MCP-1, and TNFα) were measured by real-time RT-PCR. T-ACM did not change cytokine mRNA expression in J774 macrophages or THP-1 macrophages when compared to ACM. Absence of BSA in the medium may have hindered release of FA from differentiated adipocytes into the medium, BSA may be required to permit adequate FA accumulation in the medium to then evaluate the effect of T-ACM on macrophages. Further investigation is required to determine the effect of FA on J774 and THP-1 inflammatory response.

Elevated Thyroid-Stimulating Hormone (TSH) is associated with an increased risk of cardiovascular disease (CVD). We hypothesized that TSH-stimulated FA release from adipocytes contributes to macrophage inflammation. 3T3-L1 and human subcutaneous differentiated adipocytes were treated with TSH for 4 hours under various conditions and lipolysis assessed via glycerol secretion. Optimal conditions were determined and protein expression of ATGL, HSL and perilipin remained stable. TSH-stimulated 3T3-L1 or human adipocyte-conditioned medium (T-ACM) was placed on murine J774 or human THP-1 macrophages, respectively, and macrophage cytokine mRNA levels (IL-1β, IL-6, MCP-1, and TNFα) were measured by real-time RT-PCR. T-ACM did not change cytokine mRNA expression in J774 macrophages or THP-1 macrophages when compared to ACM. Absence of BSA in the medium may have hindered release of FA from differentiated adipocytes into the medium, BSA may be required to permit adequate FA accumulation in the medium to then evaluate the effect of T-ACM on macrophages. Further investigation is required to determine the effect of FA on J774 and THP-1 inflammatory response.

Several studies have associated subclinical hypothyroidism with risk factors for atherosclerotic disease, but its correlation with a decreased tolerance to the physical effort has been little studied. In this context, the hormonal replacement with L-thyroxine for the treatment of these patients remains controversial. The present study aimed to analyze the effect of sodium L-thyroxine on the tolerance to the physical effort and the lipidic profile of patients with subclinical hypothyroidism. Seven female volunteers aged between 40 and 60 years, without clinical signs of hypothyroidism and with TSH > 4.4 mU/dL, total T3 and free T4 in the plasma were selected. The plasmatic lipidic profile was evaluated before and after treatment of all patients. For the evaluation of tolerance to the physical effort, all patients were submitted to a progressive effort test. Levels of blood lactate before and after treatment were analyzed as parameters of effort. There was a significant improvement in tolerance to the lactate and consequently, in tolerance to the effort after treatment with thyroxine. The results demonstrated a significant decrease of LDL-c and triglycerides after the normalization of TSH levels with the hormonal replacement. Significant differences were not observed in the levels of HDL, VLDL and total cholesterol. / Vários estudos associam o hipotireoidismo subclínico a fatores de risco para doença aterosclerótica, mas poucos correlacionam este distúrbio à diminuição da tolerância ao esforço físico. Neste contexto, a reposição hormonal com o emprego da L-tiroxina no tratamento destes pacientes permanece controvertida. O presente estudo teve como objetivo analisar o efeito da Ltiroxina sódica na tolerância ao esforço físico e no perfil lipídico de pacientes com hipotireoidismo subclínico. Foram selecionados sete voluntárias, com idade entre 40 e 60 anos, TSH acima de 4,4mU/dl, T3 total e T4 livre no plasma, sem sinais clínicos de hipotireoidismo. Avaliou-se o perfil lipídico plasmático no pré e pós tratamento de todas as pacientes. Para avaliação da tolerância ao esforço, todas as pacientes foram submetidas a um teste de esforço progressivo. Como parâmetro de esforço foram analisados os níveis de lactato sangüíneo no pré e no pós tratamento. Houve melhora significativa na tolerância ao lactato e consequentemente, na tolerância ao esforço após tratamento com tiroxina. Os resultados demonstraram diminuição significativa do LDL-c e dos triglicérides após normalização dos níveis de TSH com a reposição hormonal. Não foi observada diferença significativa nos níveis de HDL, VLDL e colesterol total. / Mestre em Ciências da Saúde

Submitted by Renata Lopes (renatasil82@gmail.com) on 2017-06-22T15:01:31Z No. of bitstreams: 1 rafaelapinheirolacerda.pdf: 2532354 bytes, checksum: a9f84d4aefdf273756887ac76d89cfa7 (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2017-08-07T19:22:32Z (GMT) No. of bitstreams: 1 rafaelapinheirolacerda.pdf: 2532354 bytes, checksum: a9f84d4aefdf273756887ac76d89cfa7 (MD5) / Made available in DSpace on 2017-08-07T19:22:32Z (GMT). No. of bitstreams: 1 rafaelapinheirolacerda.pdf: 2532354 bytes, checksum: a9f84d4aefdf273756887ac76d89cfa7 (MD5) Previous issue date: 2014-01-28 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / INTRODUÇÃO: Pacientes com hipotireoidismo subclínico (HSC) podem apresentar alterações no sistema cardiovascular. Dessa forma, o objetivo desse estudo foi avaliar a integridade do reflexo pressor do exercício físico em mulheres com HSC. MÉTODOS: Foram avaliadas dezoito mulheres com HSC (Grupo HSC) e vinte mulheres eutiroidianas (Grupo Controle), pareadas por idade (37 ± 11 vs. 38 ± 11 anos, p=0,907, respectivamente), índice de massa corporal (26 ± 5 vs. 24 ± 4 kg/m2, p=0,221, respectivamente) e nível de atividade física (6,93 ± 0,81 vs. 7,66 ± 1,14, p=0,063, respectivamente). A pressão arterial foi medida minuto a minuto pelo método oscilométrico (DIXTAL2023®), a frequência cardíaca medida continuamente pelo eletrocardiograma (DIXTAL2023®) e o fluxo sanguíneo do antebraço pela técnica de pletismografia de oclusão venosa (Hokanson®). A condutância vascular do antebraço foi calculada pela divisão do fluxo sanguíneo do antebraço pela pressão arterial média, multiplicada por 100. Registrando essas variáveis por 3 minutos de basal seguidos de 3 minutos de exercício físico, foram realizados os protocolos de exercício físico passivo, exercício físico isométrico a 10% da contração voluntária máxima do antebraço, exercício físico a 30% da contração voluntária máxima do antebraço e por 2 minutos oclusão circulatória pós-exercício físico isométrico a 30%. ANOVA de dois fatores foi utilizada para testar as diferenças, adotando significativo p<0,05. RESULTADOS: Durante o exercício físico passivo, a pressão arterial sistólica, diastólica e média sofreram diminuição significativa, porém semelhante entre os grupos HSC e Controle. A frequência cardíaca, o fluxo sanguíneo do antebraço e a condutância vascular do antebraço não apresentaram modificações ao longo do protocolo de exercício físico passivo. Durante o exercício físico de leve intensidade a pressão arterial sistólica não sofreu nenhuma alteração, a pressão arterial diastólica foi significativamente diferente entre os grupos HSC e Controle. Os valores da pressão arterial média, frequência cardíaca, fluxo sanguíneo do antebraço e condutância vascular do antebraço apresentaram aumento significativo e se comportaram similarmente. Durante o exercício físico de moderada intensidade os valores de pressão arterial sistólica, diastólica, média, fluxo sanguíneo do antebraço e condutância vascular do antebraço aumentaram significativamente e similarmente entre os grupos HSC e Controle. Entretanto a frequência cardíaca apresentou comportamento significativamente diferente entre os grupos HSC e Controle, porém, ambos os grupos apresentaram aumento significativo da frequência cardíaca em relação aos valores basais. Para a oclusão circulatória, os grupos sofreram aumento da pressão arterial sistólica, diastólica e média, porém com comportamento similar. CONCLUSÃO: Mulheres com HSC apresentam reflexo pressor do exercício físico íntegro. / INTRODUCTION: Patients with subclinical hypothyroidism (SCH) may show changes in the cardiovascular system. Thus, the aim of this study was to evaluate the integrity of the pressor reflex exercise in women with SCH. METHODS: Were evaluated eighteen women with SCH (Group SCH) and twenty euthyroid women (Group Control), matched for age (37 ± 11 vs. 38 ± 11 years; p=0.907, respectively), body mass index (26 ± 5 vs. 24 ± 4 kg/m2; p=0.221, respectively) and level of physical activity (6,93 ± 0,81 vs. 7,66 ± 1,14, p=0,063, respectively). Blood pressure was measured every minute by oscillometry (DIXTAL2023®), heart rate measured continuously by electrocardiogram (DIXTAL2023®) and forearm blood flow by the technique of venous occlusion plethysmography (Hokanson®). In forearm vascular conductance was calculated by dividing the forearm blood flow by the mean arterial pressure multiplied by 100. Registering these variables from baseline for 3 minutes followed by 3 minutes of exercise, the protocols of passive exercise, isometric exercise at 10% of maximal voluntary contraction of forearm exercise at 30% maximal voluntary contraction of the forearm were performed and circulatory occlusion for 2 minutes post-isometric physical exercise to 30%. Two-factor ANOVA was used to test differences, significant considering p< 0.05. RESULTS: During the passive exercise, systolic blood pressure, diastolic and mean suffered significant decline, but similar between SCH and Control groups. The heart rate, forearm blood flow and vascular conductance of the forearm showed no change during the protocol of passive exercise. During mild exercise systolic blood pressure did not undergo any changes, diastolic blood pressure was significantly different between the SCH and Control groups. The values of mean arterial pressure, heart rate, forearm blood flow and vascular conductance of the forearm showed a significant increase and behaved similarly. During exercise of moderate intensity values of systolic, diastolic, mean, forearm blood flow and vascular conductance of the forearm increased significantly and similarly between SCH and Control groups. However, the heart rate behavior was significantly different between the SCH and Control groups, however, both groups showed a significant increase in heart rate from baseline. To circulatory occlusion groups had an increase in systolic blood pressure, diastolic and mean, but with similar behavior. CONCLUSION: Women with SCH have pressor reflex upright exercise.

Elevated Thyroid-Stimulating Hormone (TSH) is associated with an increased risk of cardiovascular disease (CVD). We hypothesized that TSH-stimulated FA release from adipocytes contributes to macrophage inflammation. 3T3-L1 and human subcutaneous differentiated adipocytes were treated with TSH for 4 hours under various conditions and lipolysis assessed via glycerol secretion. Optimal conditions were determined and protein expression of ATGL, HSL and perilipin remained stable. TSH-stimulated 3T3-L1 or human adipocyte-conditioned medium (T-ACM) was placed on murine J774 or human THP-1 macrophages, respectively, and macrophage cytokine mRNA levels (IL-1β, IL-6, MCP-1, and TNFα) were measured by real-time RT-PCR. T-ACM did not change cytokine mRNA expression in J774 macrophages or THP-1 macrophages when compared to ACM. Absence of BSA in the medium may have hindered release of FA from differentiated adipocytes into the medium, BSA may be required to permit adequate FA accumulation in the medium to then evaluate the effect of T-ACM on macrophages. Further investigation is required to determine the effect of FA on J774 and THP-1 inflammatory response.

In subclinical hypothyroidism (SH), high levels of circulating thyroid stimulating hormone (TSH) maintain normal thyroid hormone levels, despite mild thyroid failure. SH is associated with cardiovascular disease and insulin resistance, although the underlying pathophysiology is not fully understood. We hypothesized that TSH may inhibit insulin action in adipocytes. To investigate this relationship, we studied primary human differentiated adipocytes. Abdominal subcutaneous adipose tissue samples were obtained (approved by OHSN-REB) from 16 weight-stable patients undergoing elective abdominal surgery. We stimulated adipocytes differentiated from stromal preadipocytes with 5 mU/ml TSH and/or 100 nM insulin, and assessed acute insulin signaling, lipogenesis and glucose uptake. Immunoblot analysis revealed that TSH suppressed insulin-stimulated Akt phosphorylation by 45% (n=5; p = 0.01). When adipocytes were pre-incubated with conventional protein kinase C (cPKC) inhibitor Gö6976, TSH inhibition was blocked. Our data indicate that TSH inhibits insulin-stimulated lipogenesis (up to 37%), but depends on BMI. Insulin-stimulated glucose uptake was enhanced by 36% and also correlated with BMI. This data suggests that TSH can modulate adipocyte insulin signaling.

Objetivo: Valorar si existe asociación entre el hipotiroidismo subclínico y la resistencia a la insulina en pacientes no diabéticos de una clínica privada de Lima. Materiales y métodos: Se realizó un estudio observacional analítico de corte transversal. Se incluyeron como participantes a adultos que acudieron a consulta ambulatoria de endocrinología de una clínica privada de Lima en los años 2012 a 2018. Se excluyeron a los pacientes que previamente habían sido diagnosticados de diabetes o patologías tiroideas, que recibían alguna terapia con corticoides sistémicos o hipolipemiantes, o que estaban gestando. Las variables de estudio principales fueron hipotiroidismo subclínico y resistencia a la insulina, las cuales se trabajaron como variables categóricas. Para definir la variable hipotiroidismo subclínico se utilizaron los valores de TSH mayor o igual a 4.5 mU/L, y T4L en valores normales, mientras que la variable resistencia a la insulina se definió utilizando el valor de HOMA-IR mayor a 2.79. Asimismo, también se estudiaron otras variables como IMC, porcentaje de grasa corporal y sexo. Para valorar la asociación entre el hipotiroidismo subclínico y la resistencia a la insulina, se llevó a cabo un modelo lineal generalizado de la familia Poisson con varianza robusta crudo y ajustado. Se presentó como media de asociación a la razón de prevalencia (RP) con su intervalo de confianza al 95% Resultados: Se analizó 1389 pacientes, el promedio de edad fue 39.56 (13.54) años (SD) y el porcentaje de varones fue 25.87%. La prevalencia de HSC fue 13.17% (n=183) y la prevalencia de RI fue 40.4% en el grupo con HSC, y 46.2% en el grupo de eutiroideos. En el modelo de regresión crudo se encontró que los pacientes con HSC tenían un 12% menos probabilidades de tener RI en el análisis crudo (PR 0.876 IC 95%: 0.727-1.055) y 7% menos en el ajustado (PR 0.927, IC 95%: 0.792-1.084); no obstante, ninguno obtuvo una significancia estadística. Secundariamente, se encontró asociaciones entre RI con el IMC, porcentaje de grasa corporal y el sexo masculino. Conclusiones: En nuestra población de estudio no se encontró asociación entre hipotiroidismo subclínico y resistencia a la insulina. / Objective: To assess whether there is an association between subclinical hypothyroidism and insulin resistance in non-diabetic patients at a private clinic in Lima. Materials and methods: An analytical observational cross-sectional study was carried out. Participants were adults who attended the endocrinology outpatient clinic of a private clinic in Lima in the years 2012 to 2018. Patients who were previously diagnosed with diabetes or thyroid diseases, who received systemic corticosteroids, who took lipid-lowering drugs, were excluded. or that they were brewing. The main variables were subclinical hypothyroidism and insulin resistance, which were worked as categorical variables. To define the subclinical hypothyroidism variable, TSH values ​​greater than or equal to 4.5 mU / L and T4L were used in normal values, while the variable insulin resistance was defined using the HOMA-IR value greater than 2.79. Likewise, other variables such as BMI, percentage of body fat and sex were also studied. To assess the association between subclinical hypothyroidism and insulin resistance, a generalized linear model of the Poisson family with crude and adjusted robust variance was carried out. It was presented as an association measure to the prevalence ratio (PR) with its 95% confidence interval. Results: We analyzed 1389 patients, the average age was 39.56 (13.54) years (SD) and the % of men was 27.87%. The prevalence of HSC was 13.17% (n = 183) and the prevalence of IR was 40.4% in the HSC group and 46.2% in the non-HSC group. In the crude regression model, it was found that patients with HSC had a 12% lower probability of having IR in the crude analysis (PR 0.876 IC 95%: 0.727-1.055) and 7% less in the adjusted one (PR 0.927, IC 95%: 0.792-1.084); however, none obtained statistical significance. Secondarily, associations were found in IR with the IMC, percentage of body fat and male sex. Conclusions: In our study population there was no association between subclinical hypothyroidism and insulin resistance. / Tesis