Oxidative stress and interleukin-6 secretion during the progression of type 1 diabetes.

OBJECTIVE: To evaluate inflammatory, oxidizing, and reducing responses during the progression of type 1 diabetes mellitus (T1DM) in patients without chronic complications. SUBJECTS AND METHODS: Plasma antioxidant status, reactive oxygen species (ROS), and interleukin-6 (IL-6) were measured in 42 patients with T1DM and in 24 healthy subjects. RESULTS: Significant increases were detected in the median values of ROS and IL-6 in patients with T1DM compared with healthy subjects (ROS ~ 4,836 vs. 2,036 RLU/min, respectively; P < .05: IL-6 ~ 14.2 vs. 9.7 pg/mL, respectively; P = .002). No significant between-group differences (P > 0.05) were observed in oxidizing responses or in IL-6 concentrations when diabetic patients were grouped according to time after diagnosis (0 - 10, 10 - 20 and > 20 years). Plasma antioxidant responses were similar in patients with T1DM and in healthy subjects. CONCLUSIONS: Our results demonstrate that oxidizing and inflammatory responses are increased at the onset of T1DM, but remain unchanged during disease progression. These findings suggest that functional changes involved in diabetic complications may commence in the first years after diagnosis.

Oxidative stress and interleukin-6 secretion during the progression of type 1 diabetes / Estresse oxidativo e secreção de interleucina-6 durante a progressão do diabetes tipo 1

OBJECTIVE: To evaluate inflammatory, oxidizing, and reducing responses during the progression of type 1 diabetes mellitus (T1DM) in patients without chronic complications. SUBJECTS AND METHODS: Plasma antioxidant status, reactive oxygen species (ROS), and interleukin-6 (IL-6) were measured in 42 patients with T1DM and in 24 healthy subjects. RESULTS: Significant increases were detected in the median values of ROS and IL-6 in patients with T1DM compared with healthy subjects (ROS ~ 4,836 vs. 2,036 RLU/min, respectively; P < .05: IL-6 ~ 14.2 vs. 9.7 pg/mL, respectively; P = .002). No significant between-group differences (P > 0.05) were observed in oxidizing responses or in IL-6 concentrations when diabetic patients were grouped according to time after diagnosis (0 - 10, 10 - 20 and > 20 years). Plasma antioxidant responses were similar in patients with T1DM and in healthy subjects. CONCLUSIONS: Our results demonstrate that oxidizing and inflammatory responses are increased at the onset of T1DM, but remain unchanged during disease progression. These findings suggest that functional changes involved in diabetic complications may commence in the first years after diagnosis.

OBJETIVO: Avaliar as respostas inflamatória, oxidativa e redutora na progressão do diabetes melito tipo 1 (DM1) em pacientes sem complicações crônicas. SUJEITOS E MÉTODOS: Capacidade antioxidante do plasma, espécies reativas de oxigênio (ROS) e interleucina-6 (IL-6) foram avaliadas em 42 pacientes com DM1 e 24 indivíduos saudáveis. RESULTADOS: Aumentos significativos foram detectados nas medianas de ROS e IL-6 em pacientes com DM1 comparados com indivíduos saudáveis (ROS ~ 4.836 vs. 2.036 RLU/min, respectivamente, P < 0,05: IL-6 ~ 14,2 vs. 9,7 pg/mL, respectivamente, P = 0,002). Diferenças não significativas (P > 0,05) foram observadas na resposta oxidante e IL-6 quando os diabéticos foram agrupados de acordo com o tempo após o diagnóstico (0-10, 10-20 e > 20 anos). A resposta antioxidante do plasma foi semelhante em pacientes com DM1 e em indivíduos saudáveis. CONCLUSÕES: Nossos resultados demonstram que as respostas oxidante e inflamatória estão aumentadas desde o início do DM1, mas mantêm-se inalteradas durante a progressão da doença, sugerindo que as mudanças funcionais envolvidas nas complicações diabéticas podem começar nos primeiros anos após o diagnóstico.

Aspectos epidemiológicos de pacientes traqueostomizados em unidade de terapia intensiva adulto de um hospital de referência ao Sistema Único de Saúde em Belo Horizonte / Epidemiological profile of patients with tracheotomy in a referral public hospital intensive care unit in Belo Horizonte

OBJETIVOS: A traqueostomia é frequentemente realizada com a finalidade de favorecer o desmame da ventilação mecânica. No entanto, não se conhece o real impacto da traqueostomia nos diversos grupos de pacientes em nosso meio. O objetivo deste trabalho foi avaliar características epidemiológicas dos pacientes submetidos à traqueostomia na unidade de terapia intensiva da Santa Casa de Belo Horizonte e traçar paralelos com outros estudos semelhantes. MÉTODOS: Estudo descritivo, retrospectivo, através de revisão de prontuários e banco de dados do sistema "QuaTI" (Qualidade em Terapia Intensiva) de 87 pacientes traqueostomizados no ano de 2007. RESULTADOS: A análise dos 87 pacientes estudados mostrou média de idade de 58 ± 17 anos, média do APACHE II de 18 ± 6, tempo médio de intubação orotraqueal de 11,17 ± 4,78 dias, mortalidade na unidade de terapia intensiva de 40,2 por cento e mortalidade hospitalar geral de 62,1 por cento. A média de idade dos pacientes que faleceram na unidade de terapia intensiva (65 ± 17 anos) foi maior que a daqueles que receberam alta (53 ± 16 anos)p = 0,003. A média de idade dos indivíduos que faleceram no hospital (62 ± 17anos) foi maior que a dos sobreviventes (52 ± 16 anos) p = 0,008. A senilidade (idade maior ou igual a 65 anos) constituiu fator relacionado a mortalidade na unidade de terapia intensiva (OR 2,874, IC 1,165 a 7,088 p = 0,020) e à mortalidade hospitalar geral (OR 3,202, IC 1,188 a 8,628 p = 0,019). Não foram observadas outras variáveis associados a mortalidade. CONCLUSÕES: O perfil epidemiológico de pacientes traqueostomizados na unidade de terapia intensiva deste estudo revelou elevada taxa de mortalidade ao se comparar com estudos internacionais. A senilidade esteve relacionada a pior desfecho nestes pacientes. Não foram identificados outros aspectos relacionados a mortalidade no grupo estudado.

OBJECTIVES: Tracheostomy is a common procedure in intensive care unit to promote mechanical ventilation weaning. Despite tracheostomy is increasingly used there is no agreement of actual clinical practice of tracheostomy in different groups of patients in our environment. Objective of this study was to evaluate the epidemiological profile and outcomes of patients with tracheostomy at a clinical-surgical intensive care unit and compare this profile with the current literature. METHODS: Retrospective descriptive study through review of medical records and quality control database of "QuaTI" (Qualidade em Terapia Intensiva) of 87 patients with tracheostomy at Santa Casa de Belo Horizonte intensive care unit in 2007. We studied variables related to evolution aspects. RESULTS: The clinical and epidemiological analysis of the 87 patients showed: mean age 58 ± 17 years, mean Acute Physiology and Chronic Health Evaluation - APACHE II 18 ± 6, mean time of orotracheal intubation before tracheostomy of 11.17 ± 4.78 days. Intensive care unit mortality was 40.2 percent (35/87 patients), ward mortality was 36.5 percent (19/52) and overall hospital mortality 62.1 percent (54/87). Mean age of patients who died at intensive care unit (65 + 17 years) was greater than who were discharged to ward (53 ± 16 years) p = 0.003. Mean age of who died in hospital (intensive care unit and ward) (62 ± 17 years) was also higher than survivors (52 ± 16 years) p = 0.008. Old age (> 65 years) was related to intensive care unit mortality (OR 2.874, CI 1.165 a 7.088 p = 0.020) and also related to the overall hospital mortality (OR 3.202, CI 1.188 a 8.628 p = 0.019). There were not others variables related to mortality in this sample. CONCLUSIONS: The epidemiological profile of patients who underwent tracheotomy in the intensive care unit showed high mortality rate when compared to international series. Senility was related to worse...

Epidemiological profile of patients with tracheotomy in a referral public hospital intensive care unit in Belo Horizonte. / Aspectos epidemiológicos de pacientes traqueostomizados em unidade de terapia intensiva adulto de um hospital de referência ao Sistema Único de Saúde em Belo Horizonte.

OBJECTIVES: Tracheostomy is a common procedure in intensive care unit to promote mechanical ventilation weaning. Despite tracheostomy is increasingly used there is no agreement of actual clinical practice of tracheostomy in different groups of patients in our environment. Objective of this study was to evaluate the epidemiological profile and outcomes of patients with tracheostomy at a clinical-surgical intensive care unit and compare this profile with the current literature. METHODS: Retrospective descriptive study through review of medical records and quality control database of "QuaTI" (Qualidade em Terapia Intensiva) of 87 patients with tracheostomy at Santa Casa de Belo Horizonte intensive care unit in 2007. We studied variables related to evolution aspects. RESULTS: The clinical and epidemiological analysis of the 87 patients showed: mean age 58 ± 17 years, mean Acute Physiology and Chronic Health Evaluation - APACHE II 18 ± 6, mean time of orotracheal intubation before tracheostomy of 11.17 ± 4.78 days. Intensive care unit mortality was 40.2% (35/87 patients), ward mortality was 36.5% (19/52) and overall hospital mortality 62.1% (54/87). Mean age of patients who died at intensive care unit (65 + 17 years) was greater than who were discharged to ward (53 ± 16 years) p = 0.003. Mean age of who died in hospital (intensive care unit and ward) (62 ± 17 years) was also higher than survivors (52 ± 16 years) p = 0.008. Old age (> 65 years) was related to intensive care unit mortality (OR 2.874, CI 1.165 a 7.088 p = 0.020) and also related to the overall hospital mortality (OR 3.202, CI 1.188 a 8.628 p = 0.019). There were not others variables related to mortality in this sample. CONCLUSIONS: The epidemiological profile of patients who underwent tracheotomy in the intensive care unit showed high mortality rate when compared to international series. Senility was related to worse outcome in these patients. Other issues were not related mortality in this group.

cAMP activates the generation of reactive oxygen species and inhibits the secretion of IL-6 in peripheral blood mononuclear cells from type 2 diabetic patients.

Peripheral blood mononuclear cells (PBMNC) from patients with type 2 diabetes (DM2) have generated higher levels of reactive oxygen species (ROS) that were higher than those in cells from healthy individuals. In the presence of a cAMP-elevating agent, ROS production was significantly activated in PBMNC from DM2 patients but it was inhibited in cells from healthy subjects. Higher levels of IL-6 has been detected in the supernatant of PBMNC cultures from DM2 patients in comparison with healthy controls. When cells were cultured in the presence of a cAMP-elevating agent, the level of IL-6 decreased has by 46% in the supernatant of PBMNC from DM2 patients but it remained unaltered in controls. No correlations between ROS and IL-6 levels in PBMNC from DM2 patients or controls have been observed. Secretions of IL-4 or IFNgamma by PBMNC from patients or controls have not been affected by the elevation of cAMP. cAMP elevating agents have activated the production of harmful reactive oxidant down modulated IL-6 secretion by these cells from DM2 patients, suggesting an alteration in the metabolic response possibly due to hyperglicemia. The results suggest that cAMP may play an important role in the pathogenesis of diabetes.

Determination of the antioxidant status of plasma from type 2 diabetic patients.

An increase in oxidizing response above a certain threshold produces, in the absence of a concomitant rise in antioxidant/reducing response, oxidative stress that is associated with complications in diabetes. A simple technique involving reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) dye has been developed in order to determine quantitatively the antioxidant status of plasma. MTT (50microL; 5.0mg/mL in PBS) was incubated with plasma (100microL) in PBS for 30, 60 or 120min at 37 degrees C, the reaction terminated by addition of 1.0mL of 0.04M hydrochloric acid in isopropanol and the absorbance measured at 570nm. The modulation by plasma of the generation of reactive oxygen species (ROS) in 12,13-phorbol dibutyrate (PDB)-stimulated granulocytes was evaluated using a chemiluminescence luminol-dependent assay. Plasma from healthy subjects (n=15) showed significantly higher antioxidant status (p<0.05) over all time periods studied compared with plasma from diabetic patients (n=27). MTT was directly reduced by plasma although platelets were not involved. Moreover, the reduction of MTT by bovine serum albumin at levels equivalent to the concentration of human serum albumin in plasma was much lower. The antioxidant status of plasma, as evaluated by MTT dye reduction, may reflect an antioxidant response since ROS generation in PDB-stimulated granulocytes was rapidly down-regulated by the presence of plasma (3.3-fold in diabetic patients and 5.8-fold in healthy subjects) confirming the lower antioxidant activity of plasma from diabetic patients. The results demonstrate that extracellular reduction of MTT by plasma may occur via enzymatic and non-enzymatic processes.