Relationship of irisin expression with metabolic alterations and cardiovascular risk in type 2 diabetes mellitus: a preliminary study.

OBJECTIVE: The aim of this study was to investigate the role of irisin in type 2 diabetes mellitus and its association with metabolic alterations and obesity. METHODS: A cross-sectional case-control study was conducted on participants treated at Centro Universitário FMABC between August 2018 and July 2019, by comparing a control group (n=14) with type 2 diabetes mellitus patients (n=16). The control group consisted of participants aged above 21 years with no chronic diseases, diabetes, smoking, or illicit drug use. The type 2 diabetes mellitus group included patients aged above 21 years, who were diagnosed with type 2 diabetes for at least 5 years (glycated hemoglobin>7%). Exclusion criteria were not willing to continue, recent hospitalization, and failure to meet inclusion criteria. Biochemical parameters included blood glucose, glycated hemoglobin, plasma irisin levels, and irisin gene expression in peripheral blood. RESULTS: Type 2 diabetes mellitus patients exhibited significantly higher plasma glucose levels [143 (40) vs. 92 (13) mg/dL, *p<0.05] and glycated hemoglobin levels [7.1% (1.6) vs. 5.6% (0.5), *p<0.05] compared to the control group. Irisin gene expression in type 2 diabetes mellitus patients was lower 0.02288 (0.08050) than the control group 8.506e-006 (1.412e-005) (p=0.06). Correlation analysis revealed a positive association between irisin expression and body mass index in type 2 diabetes mellitus (Rho=0.5221, 95%CI -0.058 to 0.838, p=0.06), while plasma irisin showed a negative correlation with body mass index (Rho=-0.656, 95%CI -0.836 to 0.215, p=0.03). No significant correlations were found between plasma glucose or glycated hemoglobin levels and irisin expression. CONCLUSION: The data suggests that body mass index directly influences plasma irisin levels and the regulation of irisin gene expression, possibly linking irisin to adiposity changes observed in obesity-related type 2 diabetes mellitus.

Relationship of irisin expression with metabolic alterations and cardiovascular risk in type 2 diabetes mellitus: a preliminary study

SUMMARY OBJECTIVE: The aim of this study was to investigate the role of irisin in type 2 diabetes mellitus and its association with metabolic alterations and obesity. METHODS: A cross-sectional case-control study was conducted on participants treated at Centro Universitário FMABC between August 2018 and July 2019, by comparing a control group (n=14) with type 2 diabetes mellitus patients (n=16). The control group consisted of participants aged above 21 years with no chronic diseases, diabetes, smoking, or illicit drug use. The type 2 diabetes mellitus group included patients aged above 21 years, who were diagnosed with type 2 diabetes for at least 5 years (glycated hemoglobin>7%). Exclusion criteria were not willing to continue, recent hospitalization, and failure to meet inclusion criteria. Biochemical parameters included blood glucose, glycated hemoglobin, plasma irisin levels, and irisin gene expression in peripheral blood. RESULTS: Type 2 diabetes mellitus patients exhibited significantly higher plasma glucose levels [143 (40) vs. 92 (13) mg/dL, *p<0.05] and glycated hemoglobin levels [7.1% (1.6) vs. 5.6% (0.5), *p<0.05] compared to the control group. Irisin gene expression in type 2 diabetes mellitus patients was lower 0.02288 (0.08050) than the control group 8.506e-006 (1.412e-005) (p=0.06). Correlation analysis revealed a positive association between irisin expression and body mass index in type 2 diabetes mellitus (Rho=0.5221, 95%CI -0.058 to 0.838, p=0.06), while plasma irisin showed a negative correlation with body mass index (Rho=-0.656, 95%CI -0.836 to 0.215, p=0.03). No significant correlations were found between plasma glucose or glycated hemoglobin levels and irisin expression. CONCLUSION: The data suggests that body mass index directly influences plasma irisin levels and the regulation of irisin gene expression, possibly linking irisin to adiposity changes observed in obesity-related type 2 diabetes mellitus.

Kidney Diseases: The Age of Molecular Markers.

Kidney diseases are conditions that increase the morbidity and mortality of those afflicted. Diagnosis of these conditions is based on parameters such as the glomerular filtration rate (GFR), measurement of serum and urinary creatinine levels and equations derived from these measurements (Wasung, Chawla, Madero. Clin Chim Acta 438:350-357, 2015). However, serum creatinine as a marker for measuring renal dysfunction has its limitations since it is altered in several other physiological situations, such as in patients with muscle loss, after intense physical exercise or in people on a high protein diet (Riley, Powers, Welch. Res Q Exerc Sport 52(3):339-347, 1981; Juraschek, Appel, Anderson, Miller. Am J Kidney Dis 61(4):547-554, 2013). Besides the fact that serum creatinine is a marker that indicates glomerular damage, it is necessary the discovery of new biomarkers that reflect not only glomerular damage but also tubular impairment. Recent advances in Molecular Biology have led to the generation or identification of new biomarkers for kidney diseases such as: Acute Kidney Failure (AKI), chronic kidney disease (CKD), nephritis or nephrotic syndrome. There are recent markers that have been used to aid in diagnosis and have been shown to be more sensitive and specific than classical markers, such as neutrophil gelatinase associated lipocalin (NGAL) or kidney injury molecule-1 (KIM-1) (Wasung, Chawla, Madero. Clin Chim Acta 438:350-357, 2015; George, Gounden. Adv Clin Chem 88:91-119, 2019; Han, Bailly, Abichandani, Thadhani, Bonventre. Kidney Int 62(1):237-244, 2002; Fontanilla, Han. Expert Opin Med Diagn 5(2):161-173, 2011). However, early diagnostic biomarkers are still necessary to assist the intervention and monitor of the progression of these conditions.

NGAL and SMAD1 gene expression in the early detection of diabetic nephropathy by liquid biopsy.

INTRODUCTION: Diabetic nephropathy (DN) is a disease that progresses with the slow and progressive decline of the glomerular filtration rate (GFR); the installation of this pathology is silent and one of the major causes of death in patients with diabetes. AIMS: To identify new molecular biomarkers for early identification of the onset of DN in patients with type II diabetes mellitus (DM2). We studied the expression profile of the genes; suppressor of mothers against decapentaplegic type 1 (SMAD1), neutrophil gelatinase-associated lipocalin (NGAL) and type IV collagen (COLIV1A) in peripheral blood and urine sediment samples. METHODS: Ninety volunteers, 51 with DM2 and 39 healthy, were recruited from the Faculdade de Medicina do ABC outpatient clinic. We conducted an interview and collected anthropometric data, as well as blood and urine samples for biochemical evaluation and real-time PCR amplification of the genes of interest. RESULTS: Gene expression data: peripheral blood NGAL (DM2 0.09758±0.1914 vs CTL 0.02293±0.04578), SMAD1 (blood: DM2 0.01102±0.04059* vs CTL 0.0001317±0.0003609; urine: DM2 0.7195±2.344* vs CTL 0.09812±0.4755), there was no significant expression of COLIV1A. These genes demonstrated good sensitivity and specificity in the receiving operating characteristic curve evaluation. CONCLUSION: Our data suggest the potential use of NGAL and SMAD1 gene expression in peripheral blood and urine samples as early biomarkers of DN.

Irisin and troponin I expression in dialysis patients submitted to remote ischemic preconditioning: a pilot study / Expressão de irisina e troponina I em pacientes em diálise submetidos a pré-condicionamento isquêmico remoto: um estudo piloto

ABSTRACT Background: Renal replacement therapy continues to be related to high hospitalization rates and poor quality of life. All-cause morbidity and mortality in renal replacement therapy in greater than 20% per year, being 44 times greater when diabetes is present, and over 10 times that of the general population. Regardless of treatment, the 5-year survival is 40%, surpassing many types of cancers. Irisin is a hormone that converts white adipose tissue into beige adipose tissue, aggregating positive effects like fat mass control, glucose tolerance, insulin resistance, prevention of muscle loss, and reduction in systemic inflammation. Objectives: To determine the serum levels of troponin I in hemodialysis patients submitted to remote ischemic preconditioning (RIPC) associated with irisin expression. Methods: This was a prospective, randomized, double-blind clinical trial with patients with chronic kidney disease submitted to hemodialysis for a 6-month period. Troponin I, IL-6, urea, TNF-α, and creatinine levels were determined from blood samples. The expressions of irisin, thioredoxin, Nf-kb, GPX4, selenoprotein and GADPH were also evaluated by RT-PCR. Results: Samples from 14 hypertensive patients were analyzed, 9 (64.3%) of whom were type 2 diabetics, aged 44-64 years, and 50% of each sex. The difference between pre- and post-intervention levels of troponin I was not significant. No differences were verified between the RIPC and control groups, except for IL-6, although a significant correlation was observed between irisin and troponin I. Conclusion: Remote ischemic preconditioning did not modify irisin or troponin I expression, independent of the time of collection.

RESUMO Introdução: A terapia de substituição renal continua associada a altas taxas de hospitalização e baixa qualidade de vida. A morbimortalidade por todas as causas na terapia de substituição renal é superior a 20% ao ano, sendo 44 vezes maior quando a diabetes está presente e mais de 10 vezes a da população em geral. Independentemente do tratamento, a sobrevida em 5 anos é de 40%, superando muitos tipos de câncer. A irisina é um hormônio que converte tecido adiposo branco em tecido adiposo bege, agregando efeitos positivos como o controle de massa gorda, tolerância à glicose, resistência à insulina, prevenção de perda muscular e redução da inflamação sistêmica. Objetivos: Determinar os níveis séricos de troponina I em pacientes em hemodiálise submetidos ao pré-condicionamento isquêmico remoto (PCIR) associado à expressão da irisina. Métodos: Estudo clínico prospectivo, randomizado, duplo-cego, com pacientes com doença renal crônica submetidos à hemodiálise por um período de 6 meses. Os níveis de troponina I, IL-6, uréia, TNF-α e creatinina foram determinados a partir de amostras de sangue. As expressões de irisina, tioredoxina, Nf-kb, GPX4, selenoproteína e GADPH foram também avaliadas por RT-PCR. Resultados: Foram analisadas amostras de 14 pacientes hipertensos, 9 (64,3%) dos quais eram diabéticos tipo 2, com idades entre 44 e 64 anos e 50% de cada gênero. A diferença entre os níveis pré e pós-intervenção de troponina I não foi significativa. Não houve diferenças entre os grupos PCIR e controle, exceto pela IL-6, embora tenha sido observada correlação significativa entre irisina e troponina I. Conclusão: O pré-condicionamento isquêmico remoto não modificou a expressão de irisina ou troponina I, independentemente do tempo de coleta.

Irisin and troponin I expression in dialysis patients submitted to remote ischemic preconditioning: a pilot study.

BACKGROUND: Renal replacement therapy continues to be related to high hospitalization rates and poor quality of life. All-cause morbidity and mortality in renal replacement therapy in greater than 20% per year, being 44 times greater when diabetes is present, and over 10 times that of the general population. Regardless of treatment, the 5-year survival is 40%, surpassing many types of cancers. Irisin is a hormone that converts white adipose tissue into beige adipose tissue, aggregating positive effects like fat mass control, glucose tolerance, insulin resistance, prevention of muscle loss, and reduction in systemic inflammation. OBJECTIVES: To determine the serum levels of troponin I in hemodialysis patients submitted to remote ischemic preconditioning (RIPC) associated with irisin expression. METHODS: This was a prospective, randomized, double-blind clinical trial with patients with chronic kidney disease submitted to hemodialysis for a 6-month period. Troponin I, IL-6, urea, TNF-α, and creatinine levels were determined from blood samples. The expressions of irisin, thioredoxin, Nf-kb, GPX4, selenoprotein and GADPH were also evaluated by RT-PCR. RESULTS: Samples from 14 hypertensive patients were analyzed, 9 (64.3%) of whom were type 2 diabetics, aged 44-64 years, and 50% of each sex. The difference between pre- and post-intervention levels of troponin I was not significant. No differences were verified between the RIPC and control groups, except for IL-6, although a significant correlation was observed between irisin and troponin I. CONCLUSION: Remote ischemic preconditioning did not modify irisin or troponin I expression, independent of the time of collection.

Obstructive sleep apnea syndrome and sleep quality in hypertensive patients / Síndrome da apneia obstrutiva do sono e qualidade do sono em hipertensos

Summary Introduction: Obstructive sleep apnea and hypopnea syndrome (OSAHS) is one of the developmental factors of high blood pressure (HBP), a relevant global public health problem. OSAHS is characterized by the reduction or complete cessation of respiratory airflow due to intermittent airway collapse. Additionally, significant changes in sleep rhythm and pattern are observed in these patients. Objective: To evaluate the association between OSAHS and sleep quality in essential and resistant hypertensives. Method: A cross-sectional, observational study evaluated 43 hypertensive patients treated at the outpatient clinics of the Faculdade de Medicina do ABC (FMABC) who were medicated with two or more antihypertensive drugs and divided into nonresistant or resistant to treatment. Results: Group I (using up to two antihypertensive agents - 60.47% of the sample) presented mean systolic blood pressure (SBP) of 127.5±6.4 mmHg, mean diastolic blood pressure (DBP) of 79.6±5.2 mmHg, mean body mass index (BMI) of 27.2±5.3 kg/m2 and mean age of 51.2±15.1 years. Group II (using more than two antihypertensive drugs - 37.2% of the sample) presented mean SBP of 132.1±9.3 mmHg, mean DBP of 84.5±5.8 mmHg, mean BMI of 27.2±7.2 kg/m2 and mean age of 55.5±13.4 years. The patients presented low quality of sleep/sleep disorder evaluated by the Pittsburgh Sleep Quality Index (PSQI), which represents a preponderant factor for OSAHS. Conclusion: Patients at high risk for OSAHS had poor sleep quality and high levels of DBP, suggesting a causal relation between these parameters. However, they did not present a higher prevalence of resistant high blood pressure (RHBP).

Resumo Introdução: A síndrome da apneia e a hipopneia obstrutiva do sono (SAHOS) estão inseridas entre os fatores de desenvolvimento da hipertensão arterial sistêmica (HAS), um relevante problema de saúde pública mundial. A SAHOS é caracterizada pela redução ou cessação completa do fluxo aéreo respiratório, decorrente do colapso intermitente das vias respiratórias. Adicionalmente, observam-se nos pacientes importantes alterações no ritmo e padrão do sono. Objetivo: Avaliar a associação entre SAHOS e qualidade de sono em hipertensos essenciais e resistentes. Método: Estudo observacional, transversal avaliou 43 pacientes hipertensos provenientes dos ambulatórios da Faculdade de Medicina do ABC (FMABC) medicados com dois ou mais anti-hipertensivos, divididos em não resistentes ou resistentes ao tratamento. Resultados: Grupo I (que utilizava até dois anti-hipertensivos - 60,47% da amostra) apresentou pressão arterial sistêmica (PAS) média de 127,5±6,4 mmHg, pressão arterial diastólica (PAD) média de 79,6±5,2 mmHg, índice de massa corpórea (IMC) médio de 27,2± 5,3 kg/m2 e idade média de 51,2±15,1 anos. Grupo II (que utilizava mais que dois anti-hipertensivos - 37,2% da amostra) apresentou PAS média de 132,1±9,3 mmHg, PAD média de 84,5±5,8 mmHg, IMC médio de 27,2±7,2 kg/m2 e idade média de 55,5±13,4 anos. Os pacientes apresentaram baixa qualidade de sono/distúrbio do sono avaliada pelo PSQI, o que representa um fator preponderante para SAHOS. Conclusão: Os pacientes com alto risco para SAHOS tiveram pior qualidade de sono e elevados níveis de PAD, sugerindo uma relação causal entre esses parâmetros. Contudo, não apresentaram maior prevalência de hipertensão arterial resistente.

Predominance of STEMI and severity of coronary artery disease in a cohort of patients hospitalized with acute coronary syndrome: a report from ABC Medical School.

INTRODUCTION: acute coronary syndromes (ACS) represent a widely prevalent health issue with high mortality in Brazil and worldwide. The severity of ACS is not known in patients in the city of São Bernardo do Campo a municipality contiguous and adjacent to the city of São Paulo. OBJECTIVES: to study the profile of coronary disease in patients hospitalized with ACS who underwent coronary angiography in the emergency room between 2012 and 2013. METHODS: this is an observational study that included consecutive patients with ACS admitted to the emergency room of a hospital. Data collection was performed using medical records with the following variables: sex, age, risk factors for cardiovascular disease, coronary angiography. RESULTS: the sample in this period included 131 patients, of which 64.8% were men. The most prevalent diagnosis was ST-elevation myocardial infarction (STEMI) (57.2%) followed by non-ST-elevation myocardial infarction (NSTEMI) (22.1%) and unstable angina (UA) (20.6%). There were no significant differences in the epidemiology and risk factors between the diagnoses, except that heart failure was more prevalent in patients with UA. DISCUSSION: there were no differences between groups regarding the coronaries involved; however, STEMI patients showed similar numbers of multi- and singlevessel lesions, NSTEMI patients showed more multivessel lesions, and UA patients showed more multivessel lesions or lesion-free arteries. Although multivessel lesions were prevalent in all groups, STEMI patients showed a significantly higher number of single-vessel lesions compared with the other acute coronary syndromes. CONCLUSION: the study demonstrated a predominance of STEMI in the studied population, which differs from the usual results in ACS.

Predominance of STEMI and severity of coronary artery disease in a cohort of patients hospitalized with acute coronary syndrome: a report from ABC Medical School / Predomínio de infarto agudo do miocárdio com supra ST e gravidade da doença arterial coronariana em uma coorte de pacientes internados com síndrome coronariana aguda: relato da Faculdade de Medicina do ABC.

Summary Introduction: acute coronary syndromes (ACS) represent a widely prevalent health issue with high mortality in Brazil and worldwide. The severity of ACS is not known in patients in the city of São Bernardo do Campo a municipality contiguous and adjacent to the city of São Paulo. Objectives: to study the profile of coronary disease in patients hospitalized with ACS who underwent coronary angiography in the emergency room between 2012 and 2013. Methods: this is an observational study that included consecutive patients with ACS admitted to the emergency room of a hospital. Data collection was performed using medical records with the following variables: sex, age, risk factors for cardiovascular disease, coronary angiography. Results: the sample in this period included 131 patients, of which 64.8% were men. The most prevalent diagnosis was ST-elevation myocardial infarction (STEMI) (57.2%) followed by non-ST-elevation myocardial infarction (NSTEMI) (22.1%) and unstable angina (UA) (20.6%). There were no significant differences in the epidemiology and risk factors between the diagnoses, except that heart failure was more prevalent in patients with UA. Discussion: there were no differences between groups regarding the coronaries involved; however, STEMI patients showed similar numbers of multi- and singlevessel lesions, NSTEMI patients showed more multivessel lesions, and UA patients showed more multivessel lesions or lesion-free arteries. Although multivessel lesions were prevalent in all groups, STEMI patients showed a significantly higher number of single-vessel lesions compared with the other acute coronary syndromes. Conclusion: the study demonstrated a predominance of STEMI in the studied population, which differs from the usual results in ACS. .

Resumo Introdução: a síndrome coronariana aguda (SCA) é uma das principais causas de morbidade e mortalidade no Brasil e no mundo. A gravidade da coronariopatia em pacientes atendidos na cidade de São Bernardo do Campo não é conhecida. Objetivo: estudar o perfil da doença coronariana em pacientes internados com SCA e submetidos à cineangiocoronariografia entre 2012 e 2013. Métodos trata-se de estudo descritivo no qual se incluíram pacientes com SCA admitidos no setor de emergência do hospital. Houve consulta aos prontuários das seguintes variáveis: sexo, idade, fatores de risco para doença cardiovascular, diagnóstico e lesões coronárias. O erro alfa estabelecido foi de 5%. Resultados: a amostra neste período foi de 131 pacientes, sendo 64,8% homens. O diagnóstico mais prevalente foi o infarto agudo do miocárdio com supradesnível do segmento ST (IAMCST) (57,2%), seguido de infarto agudo do miocárdio sem supradesnível do segmento ST (IAMSST) (22,1%) e angina instável (AI) (20,6%). Não houve diferenças significativas quanto ao perfil epidemiológico e a fatores de risco entre os diagnósticos, com exceção da presença de insuficiência cardíaca, mais prevalente nos pacientes com AI. Discussão: as coronárias acometidas não diferiram entre os grupos; porém, enquanto o grupo IAMCST apresentou proporção de lesões multi e uniarteriais similares, o grupo IAMSST apresentou mais lesões multiarteriais, e o grupo AI, mais lesões multiarteriais ou artérias livres de lesões. Apesar das lesões multiarteriais serem prevalentes em todos os grupos, os pacientes com IAMCST apresentaram um número significativamente maior de lesões uniarteriais em comparação a pacientes com outras síndromes coronárias agudas. Conclusão: o estudo demonstrou um predomínio de IAMCST na população estudada, o que difere dos resultados habituais na SCA. .

Inflammatory biomarker kinetics after mechanical and bioprosthetic valve replacement.

INTRODUCTION: valve disease is an important cause of heart failure. There is a direct relationship between valve deterioration and the patient's inflammatory status and cytokines: interleukin-6, interleukin-1, tumor necrosis factor, and C-reactive protein, involved in this major state of inflammation. OBJECTIVE: to report a series of cases of valve replacement, using a bioprosthetic or mechanical valve, and the inflammatory profile of them. METHODS: patients older than 18 years and with bioprosthetic or mechanical valve placed for a minimum of 6 months and maximum of 2 years were included. In addition to the demographic characteristics of each patient, inflammatory markers were measured and a comparison was made of echocardiographic results before (based on medical records) and after surgery. A total of 46 patients were enrolled, 23 with mechanical valve and 23 with bioprosthetic valve. RESULTS: of the 46 patients, 20 presented complete data were included, 12 with bioprosthetic and 8 with mechanical valve. There was no difference between types of prosthesis or implant site for the values of inflammatory markers although they were all above reference range. DISCUSSION: patients undergoing aortic mechanical valve implant benefited more than those undergoing bioprosthetic implant and both with much better results than those of valve replacements performed on mitral valve. In short, there was no difference in relation to inflammatory biomarkers.

Inflammatory biomarker kinetics after mechanical and bioprosthetic valve replacement / Cinética dos marcadores inflamatórios após troca valvar protética mecânica e bioprótese: série de casos

Introduction: valve disease is an important cause of heart failure. There is a direct relationship between valve deterioration and the patient’s inflammatory status and cytokines: interleukin-6, interleukin-1, tumor necrosis factor, and C-reactive protein, involved in this major state of inflammation. Objective: to report a series of cases of valve replacement, using a bioprosthetic or mechanical valve, and the inflammatory profile of them. Methods: patients older than 18 years and with bioprosthetic or mechanical valve placed for a minimum of 6 months and maximum of 2 years were included. In addition to the demographic characteristics of each patient, inflammatory markers were measured and a comparison was made of echocardiographic results before (based on medical records) and after surgery. A total of 46 patients were enrolled, 23 with mechanical valve and 23 with bioprosthetic valve. Results: of the 46 patients, 20 presented complete data were included, 12 with bioprosthetic and 8 with mechanical valve. There was no difference between types of prosthesis or implant site for the values of inflammatory markers although they were all above reference range. Discussion: patients undergoing aortic mechanical valve implant benefited more than those undergoing bioprosthetic implant and both with much better results than those of valve replacements performed on mitral valve. In short, there was no difference in relation to inflammatory biomarkers. .

Introdução: doença valvar é importante causa de insuficiência cardíaca. Existe relação direta entre a deterioração valvar e o estado inflamatório do paciente, sendo as citocinas interleucina-6, interleucina-1, fator de necrose tumoral e a proteína C reativa as principais envolvidas nesse estado de estimulação. Objetivo: relatar uma série de casos de troca valvar, bioprótese ou mecânica e seu perfil inflamatório. Métodos: pacientes maiores de 18 anos e portadores de bioprótese ou protética mecânica, com período mínimo de 6 meses e máximo de 2 anos, foram incluídos. Além das características demográficas de cada paciente, colheram-se os marcadores inflamatórios e comparou-se o ecocardiograma conforme registro de prontuário antes e depois da cirurgia. Um total de 46 pacientes foi incluído, tendo sido 23 com valva mecânica e 23 de bioprótese. Resultados: dos 46 pacientes, chegamos ao total de 20 pacientes com dados completos, sendo 12 com bioprótese e 8 com protética mecânica. Não houve diferença entre tipo de prótese ou local de implante para os valores dos marcadores inflamatórios, contudo, na média, seus valores estavam aumentados. Discussão: pacientes submetidos ao implante de valva protética mecânica aórtica beneficiaram-se mais do que os submetidos ao implante de bioprótese e ambos com resultado bem superior às trocas realizadas na valva mitral. Não houve diferença em relação aos biomarcadores inflamatórios. .

Hipertensão, diabetes e dislipidemia ­ mecanismos envolvidos / Hypertension, diabetes and dyslipidemia ­ mechanisms involved

As doenças cardiovasculares (DCV) são as principais causas de morbidade e mortalidade no Brasil. Consubstanciam-se a hipertensão (HAS), a diabetes mellitus (DM), a dislipidemia (DLP) e o tabagismo como fatores de risco cardiovasculares de maior importância. Indaga-se a relação entre a fisiopatologia da aterosclerose e os principais fatores de risco. A HAS, em sua fisiopatologia, relaciona-se com a DM; intrinsecamente, HAS e DM atuam na resistência vascular periférica (RVP). A obesidade, avaliada pelo índice de massa corpórea, têm relação linear com a ingestão de gorduras, que promove hiperinsulinemia, aumentando o risco de DM (principalmente em mulheres); a obesidade visceral, avaliada pela cintura abdominal, aumenta o risco de desenvolver a HAS, principalmente em homens. Afisiopatologia da HAS, relativa a esses marcadores, é descrita também por sua ação no sistema nervoso central (SNC) com hiperatividade simpática, atuando nos receptores tipo1 da angiotensina II e no acometimento na doença microvascular na DM principalmente com proteinúria. O endotélio, na gênese e formação da aterosclerose, modifica-se tanto na HAS quanto na DM, com o efeito vasodilatador (mediado pelo óxido nítrico). Aação antiaterogênica da insulina usualmente se dá por meio da liberação de oxido nítrico e pela via de ativação da proteína cinase (AKT). No entanto, na presença da resistência insulínica, ocorre a ativação da via da proteína ativada-rasmitogênio (ras-MAP cinase), consubstanciando-se a via pró-aterogênica. Embora esses mecanismos, intrinsecamente ligados, se sobreponham em pacientes com HAS, DM e DLP, o adequado controle de um desses fatores de risco, mesmo em menor escala, promoverá redução da morbimortalidade e, consequentemente, a adesão ao tratamento.

The cardiovascular diseases (CVD) are major causes of morbidity and mortality in Brazil. The major cardiovascular risk factors are hypertension (HYS), diabetes mellitus(DM), dyslipidemia (DYS) and smoking. There are inquires between the pathophysiology of atherosclerosis and the major risk factors. The HYS, in its pathophysiology, is related to DM; both of them inherently act in peripheral vascular resistance (RVP). Obesity, evaluated by body mass index, have linear relation to fat intake, which promotes hyperinsulinemia, increasing the risk of DM (mostly in women); the visceral obesity evaluated by waist circumference, increases the risk of developing HYS, mainly in men. The HYS pathophysiology, related to these markers, is also described by its action on the central nervous system (CNS) with sympathetic hyperactivity, acting on the angiotensin II type 1 receptor and in the involvement of DM microvascular disease, mostly with proteinuria. The endothelium in the genesis and formation of atherosclerosis is modified in HYS and DM, with a vasodilatation effect (mediated by nitric oxide). The antiatherogenic action of insulin usually takes place through releasing nitric oxide and via activation of protein kinase (AKT). Nevertheless, in the occurrence of insulin resistance, the protein-activated rasmitogen (ras-MAP kinase) is activated, resulting in the pro-atherogenic route. Even though these mechanisms intrinsically linked overlap in patients with HYS, DM and DYS, the appropriate control of these risk factors, even on a smaller scale, shall promote reduction of morbidity and mortality, and, consequently, treatment adherence.

A randomized trial of the topical effect of antifibrinolytic epsilon aminocaproic Acid on coronary artery bypass surgery without cardiopulmonary bypass.

We assessed the effect of the topical application of epsilon-aminocaproic antifibrinolytic acid (EACA) on the pericardium of patients submitted to coronary artery bypass graft (CABG) without the use of cardiopulmonary bypass (CPB). This is a prospective, randomized, and double-blind study. We evaluated 26 patients with chronic coronary heart disease indicated for CABG without CPB (EACA and placebo groups). The analysis of the postoperative hematological results showed no difference between groups in hemoglobin and hematocrit. There was no difference between the groups regarding the postoperative bleeding through the drains in the first 24 hours, 48 hours, and accumulated loss until removal of drains. The use of EACA in patients undergoing CABG without CPB presented no difference in the reduction of the amount of bleeding and the need for blood transfusions.

Prior exercise training does not prevent acute cardiac alterations after myocardial infarction in female rats.

OBJECTIVE: This study aimed to investigate whether previous exercise training could prevent or attenuate acute cardiac alterations after myocardial infarction. METHODS: Female rats were submitted to swim training (1 h/day; 5 days/week) or allowed to remain sedentary for 8 weeks. Afterwards, they were randomly assigned to left coronary artery occlusion or sham surgery. After this procedure, the rats remained sedentary for one week until euthanasia. Cardiac structural and functional analyses were performed using Doppler echocardiography. The rats that had a moderate or large infarct size were included in the evaluations. The data (mean ± SEM) were analyzed using a two-way ANOVA model followed by Tukey's post-hoc test. RESULTS: After the surgery, no significant difference between the exercise and sedentary groups was observed in the left ventricular infarct sizes (34.58 ± 3.04 vs. 37.59 ± 3.07). In another group of rats evaluated with Evans blue 1 h after myocardial infarction, no siginificant difference in the area at risk was observed between the exercised and sedentary rats (49.73 ± 1.52 vs. 45.48 ± 3.49). The changes in the left ventricular fractional areas for the exercised and sedentary myocardial infarction groups (36 ± 2% and 39 ± 3%, respectively) were smaller than those for the exercise sham surgery (ES, 67 ± 1%) and sedentary sham surgery (SS, 69 ± 2%) groups. The E/A was higher in the sedentary myocardial infarction (4.4 ± 0.3) and exercised myocardial infarction (5.5 ± 0.3) rats than in the SS (2.4 ± 0.1) and ES (2.2 ± 0.1) rats. CONCLUSION: Previous swim training of female rats does not attenuate systolic and diastolic function alterations after myocardial infarction induced by left coronary artery occlusion, suggesting that cardioprotection cannot be provided by exercise training in this experimental model.

Prior exercise training does not prevent acute cardiac alterations after myocardial infarction in female rats

OBJECTIVE: This study aimed to investigate whether previous exercise training could prevent or attenuate acute cardiac alterations after myocardial infarction. METHODS: Female rats were submitted to swim training (1 h/day; 5 days/week) or allowed to remain sedentary for 8 weeks. Afterwards, they were randomly assigned to left coronary artery occlusion or sham surgery. After this procedure, the rats remained sedentary for one week until euthanasia. Cardiac structural and functional analyses were performed using Doppler echocardiography. The rats that had a moderate or large infarct size were included in the evaluations. The data (mean + SEM) were analyzed using a two-way ANOVA model followed byTukey's post-hoc test. RESULTS: After the surgery, no significant difference between the exercise and sedentary groups was observed in the left ventricular infarct sizes (34.58 + 3.04 vs. 37.59 + 3.07). In another group of rats evaluated with Evans blue 1 h after myocardial infarction, no siginificant difference in the area at risk was observed between the exercised and sedentary rats (49.73 + 1.52 vs. 45.48 + 3.49). The changes in the left ventricular fractional areas for the exercised and sedentary myocardial infarction groups (36 + 2 percent and 39 + 3 percent, respectively) were smaller than those for the exercise sham surgery (ES, 67+1 percent) and sedentary sham surgery (SS, 69 + 2 percent) groups. The E/A was higher in the sedentary myocardial infarction (4.4 + 0.3) and exercised myocardial infarction (5.5 + 0.3) rats than in the SS (2.4 + 0.1) and ES (2.2 + 0.1) rats. CONCLUSION: Previous swim training of female rats does not attenuate systolic and diastolic function alterations after myocardial infarction induced by left coronary artery occlusion, suggesting that cardioprotection cannot be provided by exercise training in this experimental model.

Insuficiência cardíaca e atividade física: o aumento de enzimas antioxidantes e a melhora da atividade nervosa simpática: [revisão] / Heart failure and physical activity: the increase in antioxidant enzymes and improvement of sympathetic nerve activity: [review]

A insuficiência cardíaca vem se tornando um problema cada vez maior em saúde pública, e uma das principais causas de internações hospitalares em todo o mundo. Mesmo com os progressos médicos e os avanços tecnológicos atuais, a prevalência da doença aumentou nas últimas cinco décadas. Estudos recentes com animais mostraram que existe uma relação entre hiperatividade simpática na insuficiência cardíaca e aumento do estresse oxidativo sistêmico e central. Este trabalho tem como objetivo analisar, por meio de revisão bibliográfica, os benefícios produzidos pela atividade física em pacientes portadores de insuficiência cardíaca. Foram revisados estudos relacionados ao estresse oxidativo, controle neural da circulação, insuficiência cardíaca e exercício físico entre outubro de 2009 e abril de 2010 nas bases de dados: Medline, Pubmed e Lilacs. As referências eram datadas de 1986 a 2010. Utilizaram-se os seguintes termos: ?Oxidative Stress?, ?Chronic Heart Failure?, ?Baroreflex?, ?Nervous System? and ?Exercise?. Ratos com insuficiência cardíaca induzida possuem um aumento de espécies reativas de oxigênio na região rostroventrolateral do bulbo, assim como comprometimento na atividade simpática. Alguns estudos sugerem que a atividade física normaliza a atividade simpática por meio de seus mecanismos antioxidantes em seres humanos. Outro aspecto interessante é que a atividade física reduz os níveis plasmáticos de angiotensina II, regula a disfunção do baroreflexo arterial e promove o aumento de enzimas antioxidantes no músculo esquelético de pacientes com insuficiência cardíaca. Portanto, conclui-se que a atividade física é um regime terapêutico não-farmacológico de extrema importância para pacientes com insuficiência cardíaca.

Heart failure is an increasing problem in public health, and a major cause of hospitalization worldwide. Even with the medical progress and technological advances in the present, the prevalence of the disease increased in the last five decades. Recent animal studies have shown that there is a relationship between sympathetic hyperactivity in heart failure and increased oxidative stress, systemic and central. This paper aims to examine, through literature review, the benefits of physical activity in patients with heart failure. We reviewed studies related to oxidative stress, neural control of circulation, heart failure and exercise between October 2009 and April 2010, on the databases: Medline, Pubmed e Lilacs. The references dated from 1986 to 2010, and we used the following terms: ?oxidative stress?, ?chronic heart failure?, ?baroreflex?, ?nervous system? and ?exercise?. Rats with induced heart failure have an increase of reactive oxygen species in the rostroventrolateral medula, and impairment of sympathetic activity. Some studies suggest that physical activity normalizes the sympathetic activity through its antioxidant mechanisms in the rostroventrolateral medulla. Some studies suggest that physical activity normalizes sympathetic activity through its antioxidant mechanisms in humans. Another interesting aspect is that physical activity reduces plasma levels of angiotensin II, regulates the baroreflex dysfunction of the blood and promotes the increase of antioxidant enzymes in skeletal muscle of patients with heart failure. We concluded that physical activity is anm extremely important non-pharmacological treatment for patients with heart failure.

Electric countershock and cold stress effects on liver and adrenal gland

OBJECTIVES: Cold exposure induces glycogen and lipid depletion in the liver and the adrenal gland, respectively. However, no previous study has determined the effects of electrical countershock on those tissues. We aimed to evaluate the effects of electrical countershock on lipid depletion in the adrenal gland and on glycogen depletion in the liver. METHODS: We used 40 male Wistar rats divided into four groups: the control group, in which the animals were subjected to a resting period of seven days; the electrical discharge group, in which the animals were subjected to a resting period followed by administration of ten 300-mV electrical discharges; the electrical post-discharge group, in which the animals received ten electrical shocks (300 mV) followed by rest for seven consecutive days; and the cold stress group, in which the animals were subjected to a resting period and were then exposed to -8ºC temperatures for four hours. All animals underwent a laparotomy after treatment. The lipid and glycogen depletions are presented using intensity levels (where + = low intensity and ++++ = high intensity, with intermediate levels in between). RESULTS: The rats exposed to the cold stress presented the highest glycogen and lipid depletion in the liver and the adrenal gland, respectively. Furthermore, we noted that the electrical countershock significantly increased lipid depletion in the adrenal gland and glycogen depletion in the liver. One week after the electrical countershock, the liver and adrenal gland profiles were similar to that of the control group. CONCLUSION: Electrical countershock immediately increased the glycogen depletion in the liver and the lipid depletion in the adrenal gland of rats.

Anti-hypertensive drugs have different effects on ventricular hypertrophy regression: [review]

OBJECTIVES: There is a direct relationship between the regression of left ventricular hypertrophy (LVH) and a decreased risk of mortality. This investigation aimed to describe the effects of anti-hypertensive drugs on cardiac hypertrophy through a meta-analysis of the literature. METHODS: The Medline (via PubMed), Lilacs and Scielo databases were searched using the subject keywords cardiac hypertrophy, antihypertensive and mortality. We aimed to analyze the effect of anti-hypertensive drugs on ventricle hypertrophy. RESULTS: The main drugs we described were enalapril, verapamil, nifedipine, indapamina, losartan, angiotensin-converting enzyme inhibitors and atenolol. These drugs are usually used in follow up programs, however, the studies we investigated used different protocols. Enalapril (angiotensin-converting enzyme inhibitor) and verapamil (Ca++ channel blocker) caused hypertrophy to regress in LVH rats. The effects of enalapril and nifedipine (Ca++ channel blocker) were similar. Indapamina (diuretic) had a stronger effect than enalapril, and losartan (angiotensin II receptor type 1 (AT1) receptor antagonist) produced better results than atenolol (selective â1 receptor antagonist) with respect to LVH regression. CONCLUSION: The anti-hypertensive drugs induced various degrees of hypertrophic regression.

Fluoxetine effects on mitochondrial ultrastructure of right ventricle in rats exposed to cold stress / Efeitos da fluoxetina sobre a ultraestrutura mitocondrial no ventrículo direito de ratos expostos ao estresse pelo frio

OBJECTIVE: To assess fluoxetine effects on mitochondrial structure of the right ventricle in rats exposed to cold stress. METHODS: The experimental study procedures were performed in 250-300g male EPM-Wistar rats. Rats (n=40) were divided into four groups: 1) Control group (CON); 2) Fluoxetine (FLU); 3) Induced hypothermia (IH) and; 4) Induced hypothermia treated with fluoxetine (IHF). Animals of FLU group were treated by the administration of gavages containing 0.75 mg/kg/day fluoxetine during 40 days. The induced hypothermia was obtained by maintaining the groups 3 and 4 in a freezer at -8ºC for 4 hours. The animals were sacrificed and fragments of the right ventricle (RV) were removed and processed prior to performing electron microscopic analysis. RESULTS: The ultrastructural changes in cardiomyocytes were quantified through the number of mitochondrial cristae pattern (cristolysis). The CON (3.85 percent), FLU (4.47 percent) and IHF (8.4 percent) groups showed a normal cellular structure aspect with preserved cardiomyocytes cytoarchitecture and continuous sarcoplasmic membrane integrity. On the other hand, the IH (34.4 percent) group showed mitochondrial edema and lysis in cristae. CONCLUSION: The ultrastructural analysis revealed that fluoxetine strongly prevents mitochondrial cristolysis in rat heart, suggesting a protector effect under cold stress condition.

OBJETIVO: Analisar os efeitos da fluoxetina sobre a estrutura mitocondrial do ventrículo direito de ratos expostos ao estresse pelo frio. MÉTODOS: Os procedimentos do estudo foram realizados em ratos Wistar-EPM (250-300g) machos. Os ratos (n=40) foram divididos em quatro grupos: 1) Controle (CON); 2) Fluoxetina (FLU); 3) Induzidos à hipotermia (IH) e; 4) Induzidos à hipotermia tratados com fluoxetina (IHF). O grupo FLU foi tratado com gavagem contendo 0,75 mg/kg/dia de fluoxetina durante 40 dias. O estresse induzido pelo frio foi realizado mantendo os grupos 3 e 4 em um freezer (-8ºC) por quatro horas. Os animais foram sacrificados e fragmentos do ventrículo direito (VD) foram removidos e processados antes de serem conduzidos para a microscopia eletrônica. RESULTADOS: As alterações ultraestruturais dos cardiomiócitos foram quantificadas pelo número padrão de cristas mitocondriais (cristólises). Os grupos CON (3,85 por cento), FLU (4,47 por cento) e IHF (8,4 por cento) mostraram aspecto normal de suas estruturas celulares com a citoarquitetura dos cardiomiócitos preservada com integridade sarcoplasmática contínua. Por outro lado, o grupo IH (34,4 por cento) apresentou edema mitocondrial e lise nas cristas. CONCLUSÃO: A análise ultraestrutural revelou que a fluoxetina previne fortemente cristólises mitocondriais em miocárdio de ratos, sugerindo possível efeito protetor na condição de estresse induzido pelo frio.