Terapia alternativa para o treinamento dos músculos respiratórios utilizando o breath stacking / Alternative therapy for respiratory muscle training using breath stacking

Objetivo: Avaliar a efetividade da técnica de breath-stacking como método de treinamento dos músculos ventilatórios. Métodos: Trinta e oito jovens saudáveis foram incluídos no estudo. A pressão respiratória máxima foi avaliada em cmH2O em um manovacuômetro digital. O sistema de breath-stacking (máscara facial conectada a um tubo T acoplado a uma válvula unidirecional inspiratória) foi o método utilizado para gerar a sobrecarga ao longo de 12 sessões do programa de treinamento da muscular (4 sessões/semana). Resultados: Ambas pressões inspiratórias e expiratórias máximas aumentaram significativamente após o treino dos músculos ventilatórios. O pico de pressão positiva aumentou significativamente ao final do programa. Conclusão: O breath-stacking gera sobrecarga suficiente para os músculos ventilatórios promovendo aumento consistente das pressões respiratórias máximas quando utilizado em um protocolo de treino da musculatura ventilatória. A técnica foi bem tolerada, mas permanece a necessidade de testes em situações clínicas que envolvam fraqueza muscular e outras disfunções orgânicas.

Effect of inspiratory muscle training associated or not to physical rehabilitation in preoperative anatomic pulmonary resection: a systematic review and meta-analysis.

OBJECTIVE: The aim of this study is to systematically review the effect of inspiratory muscle training (IMT) associated or not with physical rehabilitation in the preoperative period of anatomical pulmonary resection. METHODS: Search in the databases: MEDLINE, Cochrane CENTRAL, EMBASE, LILACS and PEDro up to November 2019. Randomized clinical trials (RCTs) were included in adults in the preoperative period of pulmonary resection. The selection of studies and data extraction was performed by two independent reviewers. The risk of bias assessed with RoB 2.0 and the quality of evidence with GRADE. PROSPERO: CRD42018105859. RESULTS: Six RCTs were included; patients who underwent IMT in the preoperative period showed a significant improvement in functional capacity assessed by the 6-min walk test (6WT) (MD 28,93 [IC 95% 0,28; 57,58], p = 0,04, I2 = 0%) and significantly reduced the length of hospital stay (MD -3,63 [IC 95% -4,96; -2,29], p = 0,00, I2 = 0%). There was no significant difference between groups regarding pulmonary function, in postoperative complications such as pneumonia (RR 0,56 [IC 95% 0,29; 1,10], p = 0,09, I2 = 0%), atelectasis (RR 0,81 [IC 95% 0,24; 2,69], p = 0,72, I2 = 0%), mechanical ventilation > 48 h (RR 0,43 [IC 95% 0,12; 1,58], p = 0,20, I2 = 0%), in mortality (RR 0,33 [IC 95% 0,04; 3,12], p = 0,33, I2 = 0%), and quality of life. CONCLUSION: IMT associated with physical exercise in the preoperative period of pulmonary resection improves functional capacity and reduces the length of hospital stay in the postoperative period.

Effect of physical exercise on the functional capacity of children and adolescents submitted to transplantation of hematopoietic stem cells-A systematic review with meta-analysis.

Previous studies have shown beneficial effects of physical exercise (PE) in adults submitted to hematopoietic stem cell transplantation (HSCT). Conduct a systematic review about the effects of PE on the functional capacity of children and adolescents submitted to HSCT. The studies were searched in the databases MEDLINE (via PubMed), Central Register of Controlled Trials (Cochrane CENTRAL), EMBASE, LILACS, and Evidence Database in Physical Therapy (PEDro) (CRD42018080093). Two independent reviewers performed the article selection, data extraction, and methodological quality assessment. Randomized and nonrandomized clinical trials comparing PE with usual treatment in children and adolescents aged 3-18 years were included. The risk of bias was assessed using the Cochrane Collaboration tool and ROBINS-I tool, and the overall quality of the evidence was determined by the GRADE system. We included three studies with 91 patients. PE improved the functional capacity assessed by the timed up and down stairs test (MD -1.23 [95% CI, 2.27 to -.20, I2 = 0%]), but there was no significant effect in the six-minute walk test (MD 44.63 [95% CI, -20.86 to 110.13, I2 = 83%]). The benefits regarding quality of life and peripheral muscle strength of these individuals were not clearly demonstrated, but positive responses were observed in relation to the analyzed data. None of the studies evaluated the fatigue. The limitations found were the high heterogeneity between studies, as well as the sample size and the low methodological rigor. PE might be favorable to improve the functional capacity of children and adolescents treated with HSCT. However, further studies are needed to clarify the best PE program.

Low-intensity pulsed ultrasound (LIPUS) stimulates mineralization of MC3T3-E1 cells through calcium and phosphate uptake.

The present study aimed to evaluate the effect of low-intensity pulsed ultrasound (LIPUS) on pre-osteoblast mineralization using in vitro bioassays. Pre-osteoblastic MC3T3-E1 cells were exposed to LIPUS at 1 MHz frequency, 0.2 W/cm2 intensity and 20% duty cycle for 30 min. The analyses were carried out up to 336 h (14 days) after exposure. The concentration of collagen, phosphate, alkaline phosphatase, calcium and transforming growth factor beta 1 (TGF-ß1) in cell supernatant and the presence of calcium deposits in the cells were analyzed. Our results showed that LIPUS promotes mineralized nodules formation. Collagen, phosphate, and calcium levels were decreased in cell supernatant at 192 h after LIPUS exposure. However, alkaline phosphatase and TGF-ß1 concentrations remained unchanged. Therapeutic pulsed ultrasound is capable of stimulating differentiation and mineralization of pre-osteoblastic MC3T3-E1 cells by calcium and phosphate uptake with consequent hydroxyapatite formation.

Fructose-1,6-bisphosphate reverts iron-induced phenotype of hepatic stellate cells by chelating ferrous ions.

Hepatic fibrosis is an extracellular matrix deposition by hepatic stellate cells (HSC). Fibrosis can be caused by iron, which will lead to hydroxyl radical production and cell damage. Fructose-1,6-bisphosphate (FBP) has been shown to deliver therapeutic effects in many pathological situations. In this work, we aimed to test the effects of FBP in HSC cell line, GRX, exposed to an excess of iron (Fe). The Fe-treatment increased cell proliferation and FBP reversed this effect, which was not due to increased necrosis, apoptosis or changes in cell cycle. Oil Red-O staining showed that FBP successfully increased lipid content and lead GRX cells to present characteristics of quiescent HSC. Fe-treatment decreased PPAR-γ expression and increased Col-1 expression. Both effects were reversed by FBP which also decreased TGF-ß1 levels in comparison to both control and Fe groups. FBP, also, did not present scavenger activity in the DPPH assay. The treatment with FBP resulted in decreased proliferation rate, Col-1 expression and TGF-ß1 release by HSC cells. Furthermore, activated PPAR-γ and increased lipid droplets induce cells to become quiescent, which is a key event to reversion of hepatic fibrosis. FBP also chelates iron showing potential to improve Cell redox state.

Fructose-1,6-bisphosphate decreases IL-8 levels and increases the activity of pro-apoptotic proteins in HepG2 cells.

Hepatocellular carcinoma (HCC) is the most prevalent primary liver tumor that affects the world population. Liver cancer inevitably causes great harms and its treatment is extremely difficult. Its development is related to the existence of chronic liver injury, such as in cirrhosis. Cancer is a disease related to the process of inflammation so, research with anti-inflammatory agents has been performed for the development of anti-tumor drugs. Fructose-1,6-bisphosphate (FBP), a metabolite of the glycolytic route, has shown anti-inflammatory actions. The purpose of this study is to investigate the effect of FBP on HepG2 cells growth and inflammatory parameters. Results showed that FBP decreased the proliferation of HepG2 cells through trypan blue assay, without causing necrosis, shown by the intracellular release of LDH. By flow cytometry, we observed a significant IL-8 decrease which is closely related to the tumoral progression and chemotherapeutic resistance, especially in HCC. Then, we found, by RT-PCR, a high expression level of pro-apoptotic protein, such as Bax and p53, and decreased the expression levels of anti-apoptotic proteins, like Bcl-2 suggesting apoptosis. Finally, our results showed that FBP can be a potential therapeutic agent to slow the progress of HCC.

Gallic acid reduces cell growth by induction of apoptosis and reduction of IL-8 in HepG2 cells.

Hepatocellular carcinoma is the most prevalent primary liver tumor and is among the top ten cancer that affect the world population. Its development is related, in most cases, to the existence of chronic liver injury, such as in cirrhosis. The knowledge about the correlation between chronic inflammation and cancer has driven new researches with anti-inflammatory agents that have potential for the development of antitumor drugs. Gallic acid is a phenolic acid found in many natural products and have shown anti-inflammatory, anti-tumor, anti-mutagenic and antioxidant actions. The purpose of this study was to investigate the effect of gallic acid on acute and chronic cell proliferation and inflammatory parameters of hepatocellular carcinoma cells (HepG2), as well as to investigate the mechanisms involved. Results showed that the gallic acid decreased the proliferation of HepG2 cells in a dose-dependent manner (Trypan blue exclusion assay), without causing necrosis (LDH assay). We observed a significant increase in the percentage of small and regular nuclei (Nuclear Morphometric Analysis assay), a significant induction of apoptosis by Annexin V-FITC and PI assay and no interference with the cell cycle using the FITC BrdU Flow Kit. We observed a significant reduction in the levels of IL-8 and increased levels of IL-10 and IL-12 (Cytometric Bead Array Human Inflammation Assay). Furthermore, gallic acid caused no cancer cells regrowth at a long term (Cumulative Population Doubling assay). According to these results, gallic acid showed a strong potential as an anti-tumor agent in hepatocellular carcinoma cells.

Gallic acid reduces the effect of LPS on apoptosis and inhibits the formation of neutrophil extracellular traps.

Apoptosis and NETosis of neutrophils are two major mechanisms of programmed cell death that differ in their morphological characteristics and effects on the immune system. Apoptosis can be delayed by the presence of pathogens or chemical components such as lipopolysaccharide (LPS). Neutrophils have other antimicrobial strategy, called neutrophil extracellular traps (NETs), which contributes to the elimination and control of the pathogen. NETosis is induced by infection, inflammation or trauma and represents an innate immune activation mechanism. The objective of this study was to evaluate the effect of gallic acid (GA) in the modulation of apoptosis and NETs release. The results show that GA decreased the anti-apoptotic effect of LPS, blocked the induction of NETs and prevented the formation of free radicals induced by LPS. These findings demonstrate that the GA is a novel therapeutic agent for decreasing the exacerbated response of the body against an infectious agent.

Effects of neonatal inflammation on the inflammatory and oxidative profile during experimental sepsis in adult life.

The present study aimed to evaluate the long-term effects of neonatal inflammation on the inflammatory and oxidative profile during experimental sepsis in adult life. Neonatal Balb/c mice received different treatments on day 10: LPS i.p. injection (100g/kg) (nLPS) or saline i.p. injection (nSal). As adults, fear/anxiety behavior was evaluated in the elevated plus maze. The following week, saline solution or LPS was administered and, after 12h, serum (inflammatory cytokines), liver (mitochondrial complexes and oxidative stress) and adrenal gland samples (angiotensin II type 1 and 2 receptors) were collected. There was an increase in the fear/anxiety behavior in the nLPS group. Neonatal administration of LPS increased the mRNA expression of the AT1 receptor and decreased the mRNA expression of the AT2 receptor in the adrenal glands of males. The complexes II and II-III increased in the nLPS saline male group when compared to control. The LPS administration in adult females, regardless of the neonatal treatment, induced a decrease of the glutathione enzyme activity. There were no differences in the inflammatory cytokines. The results showed that neonatal inflammation influenced mitochondrial respiratory chain metabolism and angiotensin II receptors in a sex-dependent manner. Balb/c mice fear and anxiety behaviors in adulthood were programmed by early life inflammatory stress.