The potential of FT-IR spectroscopy for improving healthcare in sepsis - An animal model study.

Fourier Transform-Infrared (FT-IR) absorption spectroscopy has been used to investigate pathophysiological changes caused by sepsis. Sepsis has been defined as a potentially fatal organic dysfunction caused by a dysregulated host response to infection and can lead a patient to risk of death. This study used samples consisting of the blood plasma of mice which were induced to sepsis state, compared to a healthy group using FT-IR associated with attenuated total reflectance (ATR) spectroscopy. For statistical analysis, principal components analysis (PCA) and linear discriminant analysis (LDA) were applied, independently, to the second derivative spectra of both the fingerprint (900-1800 cm-1) and the high wavenumber (2800-3100 cm-1) regions. The technique efficiently differentiated the blood plasma of the two groups, sepsis and healthy mice, the analysis indicating that fatty acids and lipids in the blood samples could be an important biomarker of sepsis.

Cell-free DNA as an obesity biomarker.

Obesity is a disease that affects about 13 % of the world population (2016) (Who 2018). This condition generates a process of systemic inflammation that may contribute to the release of cell-free DNA (cfDNA) into the bloodstream. cfDNA has been considered a potential biomarker to monitor several physiological and pathological conditions, such as tumors, exercise intensity and obesity. Therefore, the objective of this study was to evaluate the association of cfDNA levels with the amount of weight and fat mass lost six months after bariatric surgery. Thirty-eight subjects classified as obese (BMI, 43.5+/-6.2; BFP, 46.6+/-4.8) were evaluated anthropometrically and underwent bariatric surgery. Weight, BMI, body fat percentage (BFP), waist circumference, C-Reactive Protein (CRP) and cfDNA levels were evaluated before and six months after surgery; furthermore, a correlation was performed between cfDNA levels and BFP and CRP. Decrease in total body weight and CRP were observed after bariatric surgery; however, the cfDNA levels remained unchanged. There was a weak correlation between cfDNA levels and BFP before the bariatric surgery, and a moderate correlation between cfDNA and CRP. Obese subjects who underwent bariatric surgery, the decrease in body fat percentage did not result in changes in cfDNA levels six months after surgery.

Cardiovascular Adaptations Induced by Resistance Training in Animal Models.

In the last 10 years the number of studies showing the benefits of resistance training (RT) to the cardiovascular system, have grown. In comparison to aerobic training, RT-induced favorable adaptations to the cardiovascular system have been ignored for many years, thus the mechanisms of the RT-induced cardiovascular adaptations are still uncovered. The lack of animal models with comparable protocols to the RT performed by humans hampers the knowledge. We have used squat-exercise model, which is widely used by many others laboratories. However, to a lesser extent, other models are also employed to investigate the cardiovascular adaptations. In the subsequent sections we will review the information regarding cardiac morphological adaptations, signaling pathway of the cardiac cell, cardiac function and the vascular adaptation induced by RT using this animal model developed by Tamaki et al. in 1992. Furthermore, we also describe cardiovascular findings observed using other animal models of RT.

Cardiac AT(1) receptor-dependent and IGF1 receptor-independent signaling is activated by a single bout of resistance exercise.

AT(1) receptor (AT1R) blockade prevents physiological cardiac hypertrophy induced by resistance training. Also, our group showed that a single bout of resistance exercise (RE) activates the AKT/mTOR which was also inhibited by AT1R blocker. Here, we investigated whether IGF1-receptor (IGF1-R) and MAPKs were also activated after a single bout of RE. Wistar rats were divided into Sedentary (Sed), Sedentary treated with losartan (Sed+LOS), Exercise (EX), and Exercise treated with losartan (EX+LOS). Cardiac tissue was obtained 5 and 30 min after 4 sets of 12 repetitions of squat exercise (80 % 1RM). We demonstrated that a single bout of RE did not induce IGF1-R tyrosine phosphorylation. ERK1/2 and P38 phosphorylation levels were elevated in the EX 5min and EX 30min groups however, only ERK1/2 was inhibited by losartan treatment (AT1R blocker). Next, we showed that beta-arrestin-2 expression increased 28 % in trained animals compared to sedentary group. Altogether, our results demonstrate that AT1R, but not IGF1-R, may exert the hypertrophic cardiac stimulus RE-induced. Also, activation of AKT/mTOR and ERK1/2 pathways may occur through the beta-arrestin-dependent pathway.

Resistance training attenuates salt overload-induced cardiac remodeling and diastolic dysfunction in normotensive rats.

Elevated salt intake induces changes in the extracellular matrix collagen, leading to myocardial stiffness and impaired relaxation. Resistance training (RT) has been used as a remarkably successful strategy in the treatment of heart disease. Therefore, the aim of this study was to investigate the effects of RT on preventing pathological adaptation of the left ventricle (LV) induced by salt overload. Male Wistar rats (10 weeks old) were distributed into four groups (n=8/group): control (CO), control+1% salt (CO+SALT), RT and RT+1% salt (RT+SALT). The RT protocol consisted of 4×12 bouts of squat training, 5/week for 8 weeks, with 80% of one repetition maximum (1RM). Echocardiographs were analyzed and interstitial collagen volume fraction (CVF) was determined in the LV. The 1RM tests in the RT and RT+SALT groups increased 145 and 137%, respectively, compared with the test performed before the training program. LV weight-to-body weight ratio and LV weight-to-tibia length ratio were greater in the RT and RT+SALT groups, respectively, compared with the CO group. Although there was no difference in the systolic function between groups, diastolic function decreased 25% in the CO+SALT group compared with the CO group measured by E/A wave ratio. RT partially prevented this decrease in diastolic function compared with the CO+SALT group. A 1% salt overload increased CVF more than 2.4-fold in the CO+SALT group compared with the CO group and RT prevented this increase. In conclusion, RT prevented interstitial collagen deposition in LV rats subjected to 1% NaCl and attenuated diastolic dysfunction induced by salt overload independent of alterations in blood pressure.

Soy milk versus simvastatin for preventing atherosclerosis and left ventricle remodeling in LDL receptor knockout mice.

Functional food intake has been highlighted as a strategy for the prevention of cardiovascular diseases by reducing risk factors. In this study, we compared the effects of oral treatment with soy milk and simvastatin on dyslipidemia, left ventricle remodeling and atherosclerotic lesion of LDL receptor knockout mice (LDLr-/-) fed a hyperlipidic diet. Forty 3-month old male LDLr-/- mice were distributed into four groups: control group (C), in which animals received standard diet; HL group, in which animals were fed a hyperlipidic diet; HL+SM or HL+S groups, in which animals were submitted to a hyperlipidic diet plus soy milk or simvastatin, respectively. After 60 days, both soy milk and simvastatin treatment prevented dyslipidemia, atherosclerotic lesion progression and left ventricle hypertrophy in LDLr-/- mice. These beneficial effects of soy milk and simvastatin were associated with reduced oxidative stress and inflammatory state in the heart and aorta caused by the hyperlipidic diet. Treatment with soy milk was more effective in preventing HDLc reduction and triacylglycerol and VLDLc increase. On the other hand, simvastatin was more effective in preventing an increase in total cholesterol, LDLc and superoxide production in aorta, as well as CD40L both in aorta and left ventricle of LDLr-/-. In conclusion, our results suggest a cardioprotective effect of soy milk in LDLr-/- mice comparable to the well-known effects of simvastatin.

Combined p19Arf and interferon-beta gene transfer enhances cell death of B16 melanoma in vitro and in vivo.

Approximately 90% of melanomas retain wild-type p53, a characteristic that may help shape the development of novel treatment strategies. Here, we employed an adenoviral vector where transgene expression is controlled by p53 to deliver the p19 alternate reading frame (Arf) and interferon-ß (IFNß) complementary DNAs in the B16 mouse model of melanoma. In vitro, cell death was enhanced by combined gene transfer (63.82±15.30% sub-G0 cells); yet introduction of a single gene resulted in significantly fewer hypoploid cells (37.73±7.3% or 36.96±11.58%, p19Arf or IFNß, respectively, P<0.05). Annexin V staining and caspase-3 cleavage indicate a cell death mechanism consistent with apoptosis. Using reverse transcriptase quantitative PCR, we show that key transcriptional targets of p53 were upregulated in the presence of p19Arf, although treatment with IFNß did not alter expression of the genes studied. In situ gene therapy revealed significant inhibition of subcutaneous tumors by IFNß (571±25 mm3) or the combination of p19Arf and IFNß (489±124 mm3) as compared with the LacZ control (1875±33 mm3, P<0.001), whereas p19Arf yielded an intermediate result (1053±169 mm3, P<0.01 vs control). However, only the combination was associated with increased cell death and prolonged survival (P<0.01). As shown here, the combined transfer of p19Arf and IFNß using p53-responsive vectors enhanced cell death both in vitro and in vivo.

The renin-angiotensin system is modulated by swimming training depending on the age of spontaneously hypertensive rats.

AIM: To investigate the effects of swimming training on the renin-angiotensin system (RAS) during the development of hypertensive disease. MAIN METHODS: Male spontaneously hypertensive rats (SHR) were randomized into: sedentary young (SY), trained young (TY), sedentary adult (SA), and trained adult (TA) groups. Swimming was performed 5 times/wk/8wks. KEY FINDINGS: Trained young and adult rats showed both decreased systolic and mean blood pressure, and bradycardia after the training protocol. The left ventricular hypertrophy (LVH) was observed only in the TA group (12.7%), but there was no increase on the collagen volume fraction. Regarding the components of the RAS, TY showed lower activity and gene expression of angiotensinogen (AGT) compared to SY. The TA group showed lower activity of circulatory RAS components, such as decreased serum ACE activity and plasma renin activity compared to SA. However, depending on the age, although there were marked differences in the modulation of the RAS by training, both trained groups showed a reduction in circulating angiotensin II levels which may explain the lower blood pressure in both groups after swimming training. SIGNIFICANCE: Swimming training regulates the RAS differently in adult and young SHR rats. Decreased local cardiac RAS may have prevented the LVH exercise-induced in the TY group. Both groups decreased serum angiotensin II content, which may, at least in part, contribute to the lowering blood pressure effect of exercise training.