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Circulating advanced glycation end products (AGE) and their receptor, RAGE, are increased after a myocardial infarction (MI) episode and seem to be associated with worse prognosis in patients. Despite the increasing importance of these molecules in the course of cardiac diseases, they have never been characterized in an animal model of MI. Thus, the aim of this study was to characterize AGE formation and RAGE expression in plasma and cardiac tissue during cardiac remodeling after MI in rats. Adult male Wistar rats were randomized to receive sham surgery (n = 15) or MI induction (n = 14) by left anterior descending coronary artery ligation. The MI group was stratified into two subgroups based on postoperative left ventricular ejection fraction: low (MIlowEF) and intermediate (MIintermEF). Echocardiography findings and plasma levels of AGEs, protein carbonyl, and free amines were assessed at baseline and 2, 30, and 120 days postoperatively. At the end of follow-up, the heart was harvested for AGE and RAGE evaluation. No differences were observed in AGE formation in plasma, except for a decrease in absorbance in MIlowEF at the end of follow-up. A decrease in yellowish-brown AGEs in heart homogenate was found, which was confirmed by immunodetection of N-ε-carboxymethyl-lysine. No differences could be seen in plasma RAGE levels among the groups, despite an increase in MI groups over the time. However, MI animals presented an increase of 50% in heart RAGE at the end of the follow-up. Despite the inflammatory and oxidative profile of experimental MI in rats, there was no increase in plasma AGE or RAGE levels. However, AGE levels in cardiac tissue declined. Thus, we suggest that the rat MI model should be employed with caution when studying the AGE-RAGE signaling axis or anti-AGE drugs for not reflecting previous clinical findings.

The glutathione system plays an essential role in antioxidant defense after surgery. We assessed the effects of intensive insulin treatment (IIT) on glutathione synthesis rate and redox balance in cancer patients, who had developed stress hyperglycemia after major surgery.We evaluated 10 non-diabetic cancer patients the day after radical abdominal surgery combined with intra-operative radiation therapy. In each patient, a 24-hr period of IIT, aimed at tight euglycemic control, was preceded, or followed, by a 24-hr period of conventional insulin treatment (CIT) (control regimen). Insulin was administered for 24 hours, during total parenteral nutrition, at a dosage to maintain a moderate hyperglycemia in CIT, and normoglycemic blood glucose levels in IIT (9.3±0.5 vs 6.5±0.3 mmol/L respectively, P

In this study, we investigated: i) the effects of bed rest and a subsequent physical training program on metabolic cost (Cw), mechanical work and efficiency during walking in older and young men; ii) the mechanisms underlying the higher Cw observed in older than young men.Twenty-three healthy male subjects (N = 16 older adults, age 59.6±3.4 years; N = 7 young, age: 23.1±2.9 years) participated in this study. The subjects underwent 14 days of bed rest followed by two weeks of physical training (6 sessions). Cw, mechanical work, efficiency, and co-contraction time of proximal muscles (vastus lateralis and biceps femoris) and distal muscles (gastrocnemius medialis and tibialis anterior) were measured during walking at 0.83, 1.11, 1.39, 1.67 m·s-1 before bed rest (pre-BR), after bed rest (post-BR) and after physical training (post-PT).No effects of bed rest and physical training were observed on the analysed parameters in either group. Older men showed higher Cw and lower efficiency at each speed (average +25.1 and -20.5%, P

Circulating levels of matrix metalloproteinase-2 (MMP-2) predict mortality and hospital admission in heart failure (HF) patients. However, the role of MMP-2 gene polymorphisms in the susceptibility and prognosis of HF remains elusive. In this study, 308 HF outpatients (216 Caucasian- and 92 African-Brazilians) and 333 healthy subjects (256 Caucasian- and 77 African-Brazilians) were genotyped for the -1575G>A (rs243866), -1059G>A (rs17859821), and -790G>T (rs243864) polymorphisms in the MMP-2 gene. Polymorphisms were analyzed individually and in combination (haplotype), and positive associations were adjusted for clinical covariates. Although allele frequencies were similar in HF patients and controls in both ethnic groups, homozygotes for the minor alleles were not found among African-Brazilian patients. After a median follow-up of 5.3 years, 124 patients (40.3%) died (54.8% of them for HF). In Caucasian-Brazilians, the TT genotype of the -790G>T polymorphism was associated with a decreased risk of HF-related death as compared with GT genotype (hazard ratio [HR] = 0.512, 95% confidence interval [CI] 0.285-0.920). However, this association was lost after adjusting for clinical covariates (HR = 0.703, 95% CI 0.365-1.353). Haplotype analysis revealed similar findings, as patients homozygous for the -1575G/-1059G/-790T haplotype had a lower rate of HF-related death than those with any other haplotype combination (12.9% versus 28.5%, respectively; P = 0.010). Again, this association did not remain after adjusting for clinical covariates (HR = 0.521, 95% CI 0.248-1.093). Our study does not exclude the possibility that polymorphisms in MMP-2 gene, particularly the -790G>T polymorphism, might be related to HF prognosis. However, due to the limitations of the study, our findings need to be confirmed in further larger studies.

BACKGROUND: MicroRNAs (miRs) are a class of small non-coding RNAs that regulate gene expression. Studies of transgenic mouse models have indicated that deregulation of a single miR can induce pathological cardiac hypertrophy and cardiac failure. The roles of miRs in the genesis of physiological left ventricular hypertrophy (LVH), however, are not well understood. OBJECTIVE: To evaluate the global miR expression in an experimental model of exercise-induced LVH. METHODS: Male Balb/c mice were divided into sedentary (SED) and exercise (EXE) groups. Voluntary exercise was performed on an odometer-monitored metal wheels for 35 days. Various tests were performed after 7 and 35 days of training, including a transthoracic echocardiography, a maximal exercise test, a miR microarray (miRBase v.16) and qRT-PCR analysis. RESULTS: The ratio between the left ventricular weight and body weight was increased by 7% in the EXE group at day 7 (p