Melatonin prevents oxidative stress, inflammatory activity, and DNA damage in cirrhotic rats.

BACKGROUND: Cirrhosis is an important health problem characterized by a significant change in liver parenchyma. In animals, this can be reproduced by an experimental model of bile duct ligation (BDL). Melatonin (MLT) is a physiological hormone synthesized from serotonin that has been studied for its beneficial properties, including its antioxidant potential. AIM: To evaluate MLT's effects on oxidative stress, the inflammatory process, and DNA damage in an experimental model of secondary biliary cirrhosis. METHODS: Male Wistar rats were divided into 4 groups: Control (CO), CO + MLT, BDL, and BDL + MLT. MLT was administered (20 mg/kg) daily beginning on day 15 after biliary obstruction. On day 29 the animals were killed. Blood samples, liver tissue, and bone marrow were collected for further analysis. RESULTS: BDL caused changes in biochemical and histological parameters and markers of inflammatory process. Thiobarbituric acid (0.46 ± 0.01) reactive substance levels, superoxide dismutase activity (2.30 ± 0.07) and nitric oxide levels (2.48 ± 0.36) were significantly lower (P < 0.001) n the groups that received MLT. DNA damage was also lower (P < 0.001) in MLT-treated groups (171.6 ± 32.9) than the BDL-only group (295.5 ± 34.8). Tissue damage and the expression of nuclear factor kappa B, interleukin-1ß, Nrf2, NQO1 and Hsp70 were significantly lower in animals treated with MLT (P < 0.001). CONCLUSION: When administered to rats with BDL-induced secondary biliary cirrhosis, MLT effectively restored the evaluated parameters.

Effect of therapeutic ultrasound on the quadriceps muscle injury in rats - evaluation of oxidative stress and inflammatory process.

Muscle injuries are frequent, both in sports and work, and may be caused by stretching, distension, repetitive effort or bruising. Such lesions can lead to the generation of free radicals, triggering oxidative stress and the release of some inflammatory mediators. Therapeutic ultrasound (UST) is one of the most used electrotherapy resources in the physiotherapist's clinical practice. Our aim was to evaluate the use of therapeutic ultrasound on oxidative stress and inflammatory process in an experimental model of single quadriceps muscle injury in Wistar rats. We used a total of 28 male rats, weighing between 250-300 grams, randomly divided into four groups. In the right quadriceps, a simple impact of contusion was induced by means of a press. The animals were submitted to a daily UST treatment for a total of seven consecutive applications for three minutes each, that started 24 hours after the trauma induction. The results in the Trauma + Therapeutic ultrasound group at TBARS levels and in the enzymatic activity of SOD and GPx presented a significant difference. In the histological analysis of the Trauma + Therapeutic ultrasound group presented a reorganization of the fiber's structure and a reduction of the presence of inflammatory infiltrate. In the results of the immunohistochemistry of iNOS, TNF-α and NF-κB in muscle tissue, we observed that the group treated with ultrasound showed a reduction in the expression of the proteins. The use of UST was effective in protecting muscle tissue from oxidative stress, inflammatory process and in the rearrangement of muscle fibers.

Antifibrogenic effect of melatonin in rats with experimental liver cirrhosis induced by carbon tetrachloride.

BACKGROUND AND AIM: Liver diseases are a major public health problem, accounting for a significant number of hospital visits and admissions and an increasing mortality rate. Melatonin (MLT) is a powerful antioxidant molecule that has been shown to be beneficial under various conditions. The objective was to evaluate the effect of MLT on experimental liver cirrhosis induced by carbon tetrachloride (CCl4) in rats. METHODS: Twenty male Wistar rats (230-250 g) were divided into four groups. I: control group (CO); II: CO + MLT; III: CCl4; and IV: CCl4 + MLT. CCl4 was administered intraperitoneally (i.p.) as follows: 10 doses every 5 days, 10 doses every 4 days, and 7 doses every 3 days. MLT was administered i.p. at a dose of 20 mg/kg from the 10th week to the end of the experiment (16th week). RESULTS: In the CCl4 + MLT group, we found that MLT caused a decrease in the level of F2-isoprostanes and NQO1 expression. We also found that MLT reduced the inflammatory process as shown by decreased expressions of NF-KB/p65 and inducible nitric oxide synthase (iNOS) and a smaller amount of inflammatory infiltrate. MLT reduced the expression of transforming growth factor beta1 (TGF-ß1), alpha-smooth muscle actin (α-SMA), and vascular endothelial growth factor (VEGF). Picrosirius staining showed that MLT decreases fibrosis. CONCLUSION: MLT has a potent antifibrogenic effect, modulating the parameters of oxidative stress, angiogenesis, and inflammation.

Effects of resistance training on neuromuscular parameters in elderly with type 2 diabetes mellitus: A randomized clinical trial.

This study is a randomized controlled clinical trial that verified the resistance training efficacy on neuromuscular parameters, with muscle quality as primary outcome. Forty-four elderly with diabetes type 2 (69.7 ±â€¯6.9 years; 26 men) were randomly allocated to a 12-weeks resistance training group (RTG, 3 times a week), or an active control group with stretching classes (CG, once a week). Primary and secondary outcomes were assessed at baseline and after 12 weeks, as follow: quadriceps muscle thickness and rectus femoris muscle quality, maximal knee extension strength, rapid strength, functional performance, visceral adipose tissue, glycemic control, lipid profile and quality of life. Generalized estimating equations were used to analyses based on intention-to-treat and per-protocol approaches, which showed the same results. Among all outcomes measured there were improvements in the knee extension strength (P < 0.001) and quadriceps muscle thickness (P < 0.001) for RTG. The muscle quality did not improve for both groups (P = 0.98). For the secondary outcomes there were no improvements for functional performance, rapid strength, glycemic control, quality of life, visceral adipose tissue and lipid profile in both groups, with exception of triglyceride level reduction for RTG (P = 0.04).The resistance training program is an efficacious strategy for improve the neuromuscular health in elderly with T2DM, considering increases in lower limb strength and muscle mass, but the same was not found for muscle quality, rapid strength, functional performance and quality of life. Furthermore, the training program did not induce significant reduction in glycated hemoglobin values of patients who already had suitable glycemic control.

Comparison of Mechanical Insufflation-Exsufflation and Endotracheal Suctioning in Mechanically Ventilated Patients: Effects on Respiratory Mechanics, Hemodynamics, and Volume of Secretions.

CONTEXT: Cough assist (CA) is a device to improve bronchial hygiene of patients with secretion in the airways and ineffective cough. AIMS: To compare the physiological effects and the volume of secretion of mechanical insufflation-exsufflation (CA device) with isolated endotracheal suctioning in mechanically ventilated patients. SETTINGS AND DESIGN: Randomized crossover trial. MATERIALS AND METHODS: The patients were randomly allocated to the first technique, then the following technique was performed in the next day. We collected the variables related to oxygen saturation, hemodynamics (heart rate, systolic blood pressure, diastolic blood pressure, and mean arterial pressure [MAP]), and respiratory mechanics (tidal volume, minute volume, respiratory rate, and lung compliance and resistance), pre- and postimplementation (immediately and after 15 and 30 min), and the aspirated volume of secretion. STATISTICAL ANALYSIS USED: We used two-way analysis of variance followed by the Student-Newman-Keuls t-test to compare the variables at different time points. Student's t-test was used to compare secretion volumes. All data were stored and analyzed in SPSS for Windows Version 19.0. The significance level was set at 5%. RESULTS: Forty-three patients were included in the study. When we compared the results before and after the application of the techniques, we observed no significant difference in lung compliance, pulmonary resistance, MAP, peripheral oxygen saturation, and secretion volume in both groups. CONCLUSIONS: The mechanical insufflation-exsufflation does not alter respiratory mechanics and hemodynamic stability, and it does not improve airway clearance in mechanically ventilated patients.

T-cell profile and systemic cytokine levels in overweight-obese patients with moderate to very-severe COPD.

This study aimed to evaluate the immune profile of lean and overweight-obese COPD patients. Forty patients with moderate to very severe COPD were divided into lean group (n=20; aged 62.00±8.91years; BMI 22.26±1.65kg/m2) or overweight-obese group (n=20; aged 65.40±6.69years; BMI 29.19±3.55kg/m2). The cytokine profile (IL-2, IL-4, IL-6, IL-10, INF-γ, and TNF-α) was evaluated through the Cytometric Bead Array technique, and the expression of CD4, CD8, CD25, CD45ra, CD45ro, CD69, CD195(CCr5) and HLA-DR were evaluated in CD3+ T-cells. Overweight-obese COPD group had lower levels of IL-2 (p=0.01) and higher INF-γ levels (p=0.02) and IL-6 (p=0.003) than lean COPD. Lean COPD patients had higher CD25+ (p=0.01), CCr5 (p=0.04) and HLA-DR (p=0.007) expression on T cell surface compared to overweight-obese COPD participants. These changes are related to immune dysfunction of obesity, and excess of fat mass in COPD can be a key factor to low T-cells activation.

Use of neuromuscular electrical stimulation to preserve the thickness of abdominal and chest muscles of critically ill patients: A randomized clinical trial.

OBJECTIVE: To evaluate and compare the effects of neuromuscular electrical stimulation combined with conventional physical therapy on muscle thickness in critically ill patients. DESIGN: Double-blind, randomized controlled trial. PATIENTS: Twenty-five patients participated in the study. METHODS: Patients on mechanical ventilation for 24-48 h were randomized to an intervention group (neuromuscular electrical stimulation + conventional physical therapy) or a conventional group (sham neuromuscular electrical stimulation + conventional physical therapy). Primary outcome was thickness of the rectus abdominis and chest muscles, determined on cross-sectional ultrasound images before and after the intervention. RESULTS: Eleven patients were included in the intervention group and 14 in the conventional group. After neuromuscular electrical stimulation, rectus abdominis muscle thickness and chest muscle thickness were preserved in the intervention group, whereas there was a significant reduction in thickness in the conventional group, with a significant difference between groups. There was a significant difference between groups in length of stay in the intensive care unit, with shorter length of stay in the intervention group. CONCLUSION: There was no change in rectus abdominis and chest muscle thickness in the intervention group. A significant decrease was found in these measures in the conventional group.

Functional status, respiratory muscle strength, and quality of life in patients with cirrhosis.

BACKGROUND: Liver diseases are responsible for metabolic disorders and loss of muscle mass and function that affect functional status and quality of life (QoL). OBJECTIVE: To compare exercise capacity, respiratory muscle strength, and QoL in liver transplant candidates with cirrhosis of the following etiologies: hepatitis C virus (HCV), hepatitis B virus (HBV), and alcoholic cirrhosis (AC). METHODS: Cross-sectional study comprising 86 patients divided into three groups: HCV (40 patients), HBV (14 patients), and AC (32 patients). Patients were evaluated using the Six-Minute Walk Test (6MWT), manometry, and the QoL questionnaire SF-36. RESULTS: The AC group showed the lowest performance in the 6MWT (meters) compared to the HBV and HCV groups (373.50 ± 50.48, 464.16 ± 32, and 475.94 ± 27.84, respectively, p=0.001). In the domains of the SF-36, the AC group had lower scores for functional capacity and physical limitations when compared to the HBV and HCV groups (p=0.001). In the comparison of respiratory muscle strength, the AC group had lower MIP (cmH2O) compared to the HBV and HCV groups (-65.54 ± 11.28, -71.61 ± 6.96, -82.44 ± 13.71, respectively, p=0.001). The MEP (cmH2O) in the AC group was also lower than in the HBV and HCV groups (65.13 ± 10.74, 82.44 ± 13.87, 83.44 ± 12.20, respectively, p=0.001). CONCLUSION: The AC group showed worse exercise capacity, respiratory muscle strength, and QoL compared to patients with HCV and HBV.

Condição funcional, força muscular respiratória e qualidade de vida em pacientes cirróticos / Functional status, respiratory muscle strength, and quality of life in patients with cirrhosis

CONTEXTUALIZAÇÃO: As doenças hepáticas são responsáveis pelas alterações metabólicas, perda da massa e função muscular que interferem na condição funcional e na qualidade de vida (QV). OBJETIVO: Comparar a capacidade ao exercício, a força muscular respiratória e a QV entre os pacientes com cirrose hepática, candidatos ao transplante de fígado, com as seguintes etiologias: hepatite vírus C (HCV), hepatite vírus B (HBV) e cirrose alcoólica (CA). MÉTODOS: Estudo transversal, composto por 86 pacientes, divididos em três grupos: HCV (40 pacientes), HBV (14 pacientes) e CA (32 pacientes). Os pacientes foram avaliados por meio do teste da caminhada de seis minutos (TC6min), manovacuometria e QV pelo questionário SF-36. RESULTADOS: O grupo CA apresentou menor distância percorrida no TC6min (metros) quando comparado com os grupos HBV e HCV (373,50±50,48; 464,16±32 e 475,94±27,84, respectivamente, p=0,001). Nos domínios do SF-36, o grupo CA apresentou menores escores na capacidade funcional e limitações por aspectos físicos quando comparado com os grupos HBV e HCV (p=0,001). Na comparação da força dos músculos respiratórios, o grupo CA apresentou menor PImáx (cmH2O) quando comparado com os grupos HBV e HCV (-65,54±11,28; -71,61±6,96; -82,44±13,71, respectivamente, p=0,001). A PEmáx (cmH2O) no grupo CA foi menor do que nos grupos HBV e HCV (65,13±10,74; 82,44±13,87; 83,44±12,20, respectivamente, p=0,001). CONCLUSÃO: O grupo CA demonstrou pior capacidade ao exercício, força muscular respiratória e QV quando comparado aos pacientes com HCV e HBV.

BACKGROUND: Liver diseases are responsible for metabolic disorders and loss of muscle mass and function that affect functional status and quality of life (QoL). OBJECTIVE: To compare exercise capacity, respiratory muscle strength, and QoL in liver transplant candidates with cirrhosis of the following etiologies: hepatitis C virus (HCV), hepatitis B virus (HBV), and alcoholic cirrhosis (AC). METHODS: Cross-sectional study comprising 86 patients divided into three groups: HCV (40 patients), HBV (14 patients), and AC (32 patients). Patients were evaluated using the Six-Minute Walk Test (6MWT), manometry, and the QoL questionnaire SF-36. RESULTS: The AC group showed the lowest performance in the 6MWT (meters) compared to the HBV and HCV groups (373.50±50.48, 464.16±32, and 475.94±27.84, respectively, p=0.001). In the domains of the SF-36, the AC group had lower scores for functional capacity and physical limitations when compared to the HBV and HCV groups (p=0.001). In the comparison of respiratory muscle strength, the AC group had lower MIP (cmH2O) compared to the HBV and HCV groups (-65.54±11.28, -71.61±6.96, -82.44±13.71, respectively, p=0.001). The MEP (cmH2O) in the AC group was also lower than in the HBV and HCV groups (65.13±10.74, 82.44±13.87, 83.44±12.20, respectively, p=0.001). CONCLUSION: The AC group showed worse exercise capacity, respiratory muscle strength, and QoL compared to patients with HCV and HBV.