ABSTRACT
Age-related changes in the body's physiological responses play a critical role in systemic arterial hypertension (SAH) and type 2 Diabetes mellitus (T2DM). SAH and T2DM have clinically silent low-grade inflammation as a common risk factor. This inflammation has a relevant element, the excess of fatty tissue. In this scenario, little is known about how inflammatory markers interact with each other. Therefore, this work evaluated the interplay among anthropometric, biochemical, and inflammatory markers in the elderly with SAH and T2DM. Men aged 60-80 years old with SAH and T2DM were classified by body mass index (BMI) as eutrophic elderly (EE, 24 individuals) or overweight elderly (OE, 25 individuals). Body composition analysis was performed using bioimpedance. Blood samples were collected to perform inflammatory and biochemical evaluations. The cytokines IL-17A, IL-1ß, IFN-y, TNF-α, and IL-10, were evaluated by ELISA. Triglycerides, total and fractions of cholesterol, and glucose were measured by spectrophotometry. Overweight elderly men had a higher glycemic index and an increase in most anthropometric markers, as well as higher means for all pro-inflammatory cytokines analyzed (IL-17A, IL-1ß, IFN-y, and TNF-α) in comparison to their eutrophic elderly counterparts. However, there was a decrease in IL-10 anti-inflammatory cytokine and IL-10/IL-17A ratio compared to their eutrophic elderly counterparts. Although overweight elderly men have worsening inflammatory parameters, the magnitude of their correlations with anthropometric and biochemical parameters becomes less evident. The Bayesian networks highlight that in the eutrophic elderly, IL-17A and TNF-α are the cytokines most associated with interactions, and most of these interactions occur with biochemical parameters. It is worth highlighting the role of IFN-y in overweight elderly men. This cytokine influences IL-10 and TNF-α production, contributing to the inflammatory profile exacerbated in this group.
Subject(s)
Body Composition , Diabetes Mellitus, Type 2 , Hypertension , Inflammation , Aged , Aged, 80 and over , Humans , Male , Bayes Theorem , Biomarkers , Cytokines , Interleukin-10 , Interleukin-17 , Overweight/complications , Tumor Necrosis Factor-alpha , Middle AgedABSTRACT
Due to the inflammatory nature of type 2 diabetes mellitus (T2DM) and the increased cardiovascular risk, there is a growing need for innovative strategies to change our identification and treatment approach to avoid clinical complications. One approach would be the use of circulating biomarkers to track disease progression and management. Thus, this study aimed to evaluate the concentrations of inflammatory biomarkers in patients diagnosed with type 2 diabetes mellitus and systemic arterial hypertension, correlating inflammatory cytokines and disease severity. Initially, 259 individuals were stratified into different degrees of disease: low risk, moderate risk, high risk, and very high risk, according to the European Society of Cardiology, which correlates blood pressure values with the presence of cardiovascular risk factors. For this stratification, analysis of body composition, blood pressure measurement, and questionnaires were applied. Blood was collected for biochemical measurements and for ELISA to detect concentrations of cytokines IL-17, IL-1ß, IFN-Y, TNF-α, and IL-10. The findings suggest that inflammation is present, contributing to the worsening of systemic arterial hypertension and type 2 diabetes mellitus. Through Bayesian analysis, we found that hyperglycemia plays a role in fueling inflammation, contributing to the maintenance of the state of dysregulation and persistent inflammation, which can contribute to systemic damage. Our work correlates biochemical, glycemic, body composition, blood pressure and inflammatory profiles, showing how they participate together in worsening the prognosis of patients diagnosed with chronic non-communicable diseases. We have seen that all these parameters can be changed with the practice of physical activity, even in conditions of obesity, hyperglycemia or dyslipidemia, when patients do not control the changes with standard pharmacological treatment. Thus, the management measures of these chronic non-communicable diseases must take into account the crosstalk between the systems, and the dysregulation of just one of these systems is enough to generate consequences in all the other systems.
Subject(s)
Diabetes Mellitus, Type 2 , Hyperglycemia , Hypertension , Noncommunicable Diseases , Bayes Theorem , Biomarkers , Cytokines , Diabetes Mellitus, Type 2/complications , Humans , Hyperglycemia/diagnosis , Hypertension/complications , InflammationABSTRACT
We show that increased plasma superoxide dismutase 1 (SOD1) levels are statistically significant predictors of the failure of pentavalent antimony treatment for cutaneous leishmaniasis caused by Leishmania braziliensis. In Leishmania amazonensis-infected patients, host SOD1 levels can be used to discriminate between localized and drug-resistant diffuse cutaneous leishmaniasis. Using in situ transcriptomics (nCounter), we demonstrate a significant positive correlation between host SOD1 and interferon α/ß messenger RNA (mRNA) levels, as well as interkingdom correlation between host SOD1 and parasite SOD2/4 mRNA levels. In human macrophages, in vitro treatment with SOD1 increases the parasite burden and induces a diffuse cutaneous leishmaniasis-like morphology. Thus, SOD1 is a clinically relevant biomarker and a therapeutic target in both localized and diffuse cutaneous leishmaniasis.
Subject(s)
Antimony/therapeutic use , Antiprotozoal Agents/therapeutic use , Biomarkers/blood , Leishmania braziliensis/immunology , Leishmaniasis, Cutaneous/drug therapy , Leishmaniasis, Cutaneous/pathology , Superoxide Dismutase/blood , Adult , Cells, Cultured , Female , Gene Expression Profiling , Humans , Male , Superoxide Dismutase-1 , Treatment FailureABSTRACT
A expressão de Faz/FasL tem sido descrita como crucial para resistência à infecção por Leishmania, independente de uma resposta Th1, no modelo murino. Visto que esses dados na leishmaniose humana são ausentes, nós quantificamos a expressão de Fas (CD95) ex vivo em PBMC de pacientes com leishmaniose cutânea localizada e investigamos o polimorfismo 670 da região promotora do gene Apo-1/Fas por PCR-RFLP. Foram realizadas marcações com anti-CD95 e marcadores de linhagens (CD3, CD4, CD8, CD14, CD16, 16b, CD56 e CD49d) em PBMC separados pelo gradiente de densidade e análise por citometria de fluxo. Quarenta pacientes com leishmaniose cutânea localizada (oriundos da área endêmica de Jequié e Jequiriçá-Ba) foram incluídos após consentimento livre e esclarecido. Os resultados foram comparados com um grupo de 27 controles urbanos sadios e correlacionados com dados clínicos e demográficos (idade, IDRM, sorologia, tamanho de lesão, tempo da doença). As análises do polimorfismo na posição 670 do gene Fas demonstraram que o genótipo GG foi o mais freqüente entre os pacientes com LCL (45 por cento), com 35 por cento e 20 por cento de GA e AA, respectivamente. Em controles normais, a freqüência dos genótipos GA, AA e GG foram 51,9 por cento, 18,5 por cento e 29,6 por cento, respectivamente. A expressão de Fas em PBMC, dos pacientes comparados com os controles, foi aumentada em linfócitos e monócitos, mas um maior aumento foi observado em monócitos. A expressão de Fas em monócitos correlacionou negativamente (p=0,03, r=-0,53) com duração da doença. Nenhuma correlação foi observada entre a expressão de Fas e resposta imune humoral (IgG anti-Leishmania) ou celular (IDRM), sugerindo que a expressão de Fas e /ou apoptose poderia ser um terceiro parâmetro imune independente modificando a evolução da doença
