Low-Level Laser Therapy Attenuates the Myeloperoxidase Activity and Inflammatory Mediator Generation in Lung Inflammation Induced By Gut Ischemia and Reperfusion: A Dose-Response Study

Introduction: Intestinal ischemia and reperfusion (i-I/R) is an insult associated with acute respiratory distress syndrome (ARDS). Herein we evaluate the dose-response effect of low-level laser therapy (LLLT) on lung inflammation induced by i-I/R.Methods: Mice were subjected to mesenteric artery occlusion (45 min) and killed after clamp release and intestinal reperfusion (2h). Increasing doses (1, 3, 5 and 7,5 J/cm2) of laser irradiation (660 nm) was carried out on the mice skin over the upper bronchus for 5 min after initiating reperfusion. Neutrophils activation was determined by myeloperoxidase (MPO) activity. The mRNA expression and protein concentration of inflammatory mediators IL-1β, IL-6, TNF and IL-10 in lung were measured by RT-PCR and ELISA, respectively.Results: With exception of 1J/cm2, LLLT reduced MPO activity as well as IL-1β levels in the lungs from inflamed mice. LLLT was also markedly effective in reducing both IL-6 and TNF expression and levels in the lungs from mice submitted to i-I/R in all laser doses studied. Otherwise, LLLT significantly increased the protein levels of IL-10 in inflamed mice by i-I/R; however only in the dose of 1J/cm2.Conclusion: We conclude that the LLLT is able to control the neutrophils activation and pro-inflammatory cytokines release into the lungs in a model of i-I/R in mice

Microwave versus Conventional Sintering of NiTi Alloys Processed by Mechanical Alloying

ABSTRACT: The present study shows a comparison between two sintering processes, microwave and conventional sintering, for the manufacture of NiTi porous specimens starting from powder mixtures of nickel and titanium hydrogenation-dehydrogenation (HDH) milled by mechanical alloying for a short time (25 min). The samples were sintered at 850 degrees C for 15 min and 120 min, respectively. Both samples exhibited porosity, and the pore size results are within the range of the human bone. The NiTi intermetallic compound (B2, R-phase, and B19 ') was detected in both sintered samples through X-ray diffraction (XRD) and electron backscattering diffraction (EBSD) on scanning electron microscopic (SEM). Two-step phase transformation occurred in both sintering processes with cooling and heating, the latter occurring with an overlap of the peaks, according to the differential scanning calorimetry (DSC) results. From scanning electron microscopy/electron backscatter diffraction, the R-phase and B2/B19 ' were detected in microwave and conventional sintering, respectively. The instrumented ultramicrohardness results show the highest elastic work values for the conventionally sintered sample. It was observed throughout this investigation that using mechanical alloying (MA) powders enabled, in both sintering processes, good results, such as intermetallic formation and densification in the range for biomedical applications.info:eu-repo/semantics/publishedVersio

Effects of creatine oral supplementation on the hepatic metabolism and morphology of rats

A creatina é uma amina nitrogenada e tem sido utilizada principalmente por atletas e praticantes de atividade física que desejam aumentar a massa muscular e o desempenho físico. Entretanto seu uso não está somente relacionado à prática esportiva, pois inúmeros trabalhos apresentam efeitos benéficos na prática médica. Alguns estudos demonstraram que a suplementação oral com creatina resulta em aumento da sua biodisponibilidade plasmática e também de seus estoques em inúmeros órgãos. Entretanto, estudos sobre possíveis efeitos tóxicos da suplementação com creatina são escassos. Portanto, o objetivo deste trabalho foi avaliar os possíveis efeitos tóxicos da suplementação oral com creatina sobre a função e morfologia hepáticas em ratos após 14 dias de suplementação oral com creatina na dose de 0.5 g/kg/dia. A função hepática foi avaliada através de testes bioquímicos e a estrutura hepática foi avaliada através da massa hepática relativa e da análise histológica. Os resultados demonstraram que 14 dias de suplementação com creatina não alteraram a função hepática quando comparado os grupos controle e suplementado: AST (39.5 x 44.4 U/L), ALT (18.6 x 30.8 U/L), ALP (38.5 x 31.4 U/L), GGT (134.8 x 143.8 U/L), proteínas totais (5.1 x 5.5 g/dl), triglicérides (141.0 x 141.0 mg/dl), colesterol total (130.1 x 126.2 mg/dl), colesterol LDL (36.1 x 36.1 mg/dl), colesterol HDL (65.6 x 62.4 mg/dl), colesterol VLDL (25.0 x 28.0 mg/dl), e também estrutura hepática, exceto nos níveis plasmáticos de albumina (3.0 x 3.5 mg/dl - p<0.02). Nossos resultados demonstraram claramente que, ao menos na dose utilizada, a suplementação oral com creatina não induziu a nenhum tipo de efeito tóxico sobre o fígado.Creatine is a nitrogenated amine and it has been used mainly by athletes and physical activity practitioners who wish to increase muscle mass and performance. However its use is not just related to sports practice, once several studies have shown beneficial effects on medical practice. Some studies have demonstrated that oral creatine supplementation increases its plasmatic bioavailability and also its concentration in several organs. However, studies about the possible toxic effects followed by creatine supplementation are scarce. Therefore, the aim of this work was to evaluate the hepatic structure and function in rats after 14 days of oral creatine supplementation at dose of 0.5g/kg/day. The hepatic function was evaluated through biochemical assays and the hepatic structure was analyzed through the relative hepatic mass and histological analysis. The results showed that 14 days of creatine supplementation did not alter the hepatic function and structure when compared with the control and supplemented groups, AST (39.5 x 44.4 U/L), ALT (18.6 x 30.8 U/L), ALP (38.5 x 31.4 U/L), GGT (134.8 x 143.8 U/L), total proteins (5.1 x 5.5 g/dl), triglycerides (141.0 x 141.0 mg/dl), total cholesterol (130.1 x 126.2 mg/dl), LDL cholesterol (36.1 x 36.1 mg/dl), HDL cholesterol (65.6 x 62.4 mg/dl), VLDL cholesterol (25.0 x 28.0 mg/dl), and also the hepatic structure, except for the albumin plasmatic levels (3.0 x 3.5 mg/dl - p<0.02). Our results clearly demonstrated that, at least at the used dosage, oral creatine supplementation did not induce any toxic effect on the liver

Exercise Prevents Diaphragm Wasting Induced by Cigarette Smoke through Modulation of Antioxidant Genes and Metalloproteinases

Background. The present study aimed to analyze the effects of physical training on an antioxidant canonical pathway and metalloproteinases activity in diaphragm muscle in a model of cigarette smoke-induced chronic obstructive pulmonary disease (COPD). Methods. Male mice were randomized into control, smoke, exercise, and exercise + smoke groups, which were maintained in trial period of 24 weeks. Gene expression of kelch-like ECH-associated protein 1nuclear factor erythroid-2 like 2and heme-oxygenase1 by polymerase chain reaction was performed. Metalloproteinases 2 and 9 activities were analyzed by zymography. Exercise capacity was evaluated by treadmill exercise test before and after the protocol. Results. Aerobic training inhibited diaphragm muscle wasting induced by cigarette smoke exposure. This inhibition was associated with improved aerobic capacity in those animals that were submitted to 24 weeks of aerobic training, when compared to the control and smoke groups, which were not submitted to training. The aerobic training also downregulated the increase of matrix metalloproteinases (MMP-2 and MMP-9) and upregulated antioxidant genes, such as nuclear factor erythroid-2 like 2 (NRF2) and heme-oxygenase1 (HMOX1), in exercise + smoke group compared to smoke group. Conclusions. Treadmill aerobic training protects diaphragm muscle wasting induced by cigarette smoke exposure involving upregulation of antioxidant genes and downregulation of matrix metalloproteinases.CAPES (Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior)Sao Paulo Research Foundation (FAPESP) Grant [2012/15165-2]Univ Brasilia, Phys Therapy Div, Brasilia, DF, BrazilUniv Paulista, Dept Phys Therapy, Brasilia, DF, BrazilUniv Sao Paulo, Sch Med, Dept Med LIM 20, Sao Paulo, SP, BrazilFed Univ Sao Paulo UNIFESP, Postgrad Program Sci Human Movement & Rehabil, Av Ana Costa 95, BR-11060001 Santos, SP, BrazilUniv Fed Sao Carlos, Dept Phys Therapy, Sao Carlos, SP, BrazilUniv Brasil, Postgrad Program Bioengn, Rua Carolina Fonseca 235, BR-08230030 Sao Paulo, SP, BrazilBrazilian Inst Teaching & Res Pulm & Exercise Imm, Rua Pedro Ernesto 240, BR-12245520 Sao Jose Dos Campos, SP, BrazilUniv Brasilia, Phys Therapy Div, Brasilia, DF, BrazilFed Univ Sao Paulo UNIFESP, Postgrad Program Sci Human Movement & Rehabil, Av Ana Costa 95, BR-11060001 Santos, SP, BrazilFAPESP [2012/15165-2]Web of Scienc

Aerobic Exercise Attenuated Bleomycin-Induced Lung Fibrosis in Th2-Dominant Mice

Introduction The aim of this study was to investigate the effect of aerobic exercise (AE) in reducing bleomycin- induced fibrosis in mice of a Th2-dominant immune background (BALB/c). Methods BALB/c mice were distributed into: sedentary, control (CON), Exercise-only (EX), sedentary, bleomycin-treated (BLEO) and bleomycin-treated+exercised (BLEO+EX);(n = 8/group). Following treadmill adaptation, 15 days following a single, oro-tracheal administration of bleomycin (1.5U/kg), AE was performed 5 days/week, 60min/day for 4 weeks at moderate intensity (60% of maximum velocity reached during a physical test) and assessed for pulmonary inflammation and remodeling, and cytokine levels in bronchoalveolar lavage (BAL). Results At 45 days post injury, compared to BLEO, BLEO+EX demonstrated reduced collagen deposition in the airways (p<0.001) and also in the lung parenchyma (p<0.001). In BAL, a decreased number of total leukocytes (p<0.01), eosinophils (p<0.001), lymphocytes (p<0.01), macrophages (p<0.01), and neutrophils (p<0.01), as well as reduced pro-inflammatory cytokines (CXCL-1;p<0.01), (IL-1 beta;p<0.001), (IL-5;p<0.01), (IL-6;p<0.001), (IL-13;p<0.01) and pro-fibrotic growth factor IGF-1 (p<0.001) were observed. Anti-inflammatory cytokine IL-10 was increased (p<0.001). Conclusion AE attenuated bleomycin-induced collagen deposition, inflammation and cytokines accumulation in the lungs of mice with a predominately Th2-background suggesting that therapeutic AE (15-44 days post injury) attenuates the pro-inflammatory, Th2 immune response and fibrosis in the bleomycin model

Effects of two different decellularization routes on the mechanical properties of decellularized lungs

Considering the limited number of available lung donors, lung bioengineering using whole lung scaffolds has been proposed as an alternative approach to obtain lungs suitable for transplantation. However, some decellularization protocols can cause alterations on the structure, composition, or mechanical properties of the lung extracellular matrix. Therefore, the aim of this study was to compare the acellular lung mechanical properties when using two different routes through the trachea and pulmonary artery for the decellularization process. This study was performed by using the lungs excised from 30 healthy male C57BL/6 mice, which were divided into 3 groups: tracheal decellularization (TDG), perfusion decellularization (PDG), and control groups (CG). Both decellularized groups were subjected to decellularization protocol with a solution of 1% sodium dodecyl sulfate. The behaviour of mechanical properties of the acellular lungs was measured after decellularization process. Static (Est) and dynamic (Edyn) elastances were obtained by the end-inspiratory occlusion method. TDG and PDG showed reduced Est and Edyn elastances after lung decellularization. Scanning electron microscopy showed no structural changes after lung decellularization of the TDG and PDG. In conclusion, was demonstrated that there is no significant difference in the behaviour of mechanical properties and extracellular matrix of the decellularized lungs by using two different routes through the trachea and pulmonary artery

Analytical validation of an ultraviolet–visible procedure for determining vitamin D3 in vitamin D3-loaded microparticles and toxigenetic studies for incorporation into food

Vitamin D is a water-insoluble compound presented in two main forms (D2 and D3), susceptible to environmental conditions. Microencapsulation is an alternative to supplements and preserve vitamin D properties in foods. Entrapment efficiency (EE) is the main property to evaluate the encapsulation effectiveness and therefore it is of interest the study of analytical methods for the identification and quantification of this compound within the particle. This paper describes a low cost UV–Vis methodology validation to the identification and quantification of vitamin D3 in microparticles produced by hot homogenization. The method was validated following the International Conference on Harmonization (ICH) guidelines. To guarantee safe application in foodstuff, microparticles toxigenicity was evaluated with Allium cepa L. in vivo model, showing no cytotoxic nor genotoxic potential. High entrapment efficiency was obtained, the results also demonstrated that the concentration of vitamin D3 in microparticles can be safely accessed by the validated method.This study was financed in part by the Coordenaç˜ao de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES) – Finance Code 001. The authors thank the Multiuser Laboratory of Federal University of Technology – Paraná – Campus Londrina, and the “Central Analítica Multiusuário da UTFPR Campo Mourão” (CAMulti-CM) for the analyses. Also, to CNPq for the financial support (Project n◦ 420055/2018-5) and scholarship.info:eu-repo/semantics/publishedVersio

P2Y6 Receptor Activation Promotes Inflammation and Tissue Remodeling in Pulmonary Fibrosis

Idiopathic pulmonary fibrosis (IPF) is a disease with a poor prognosis and very few available treatment options. The involvement of the purinergic receptor subtypes P2Y2 and P2X7 in fibrotic lung disease has been demonstrated recently. In this study, we investigated the role of P2Y6 receptors in the pathogenesis of IPF in humans and in the animal model of bleomycin-induced lung injury. P2Y6R expression was upregulated in lung structural cells but not in bronchoalveolar lavage (BAL) cells derived from IPF patients as well as in animals following bleomycin administration. Furthermore, BAL fluid levels of the P2Y6R agonist uridine-5′-diphosphate were elevated in animals with bleomycin-induced pulmonary fibrosis. Inflammation and fibrosis following bleomycin administration were reduced in P2Y6R-deficient compared to wild-type animals confirming the pathophysiological relevance of P2Y6R subtypes for fibrotic lung diseases. Experiments with bone marrow chimeras revealed the importance of P2Y6R expression on lung structural cells for pulmonary inflammation and fibrosis. Similar effects were obtained when animals were treated with the P2Y6R antagonist MRS2578. In vitro studies demonstrated that proliferation and secretion of the pro-inflammatory/pro-fibrotic cytokine IL-6 by lung fibroblasts are P2Y6R-mediated processes. In summary, our results clearly demonstrate the involvement of P2Y6R subtypes in the pathogenesis of pulmonary fibrosis. Thus, blocking pulmonary P2Y6 receptors might be a new target for the treatment of IPF

Aerobic exercise inhibits acute lung injury: from mouse to human evidence Exercise reduced lung injury markers in mouse and in cells

Acute respiratory distress syndrome (ARDS) is defined as hypoxemic respiratory failure with intense pulmonary inflammation, involving hyperactivation of endothelial cells and neutrophils. Given the anti-inflammatory effects of aerobic exercise (AE), this study investigated whether AE performed daily for 5 weeks would inhibit extra-pulmonary LPS-induced ARDS. C57Bl/6 mice were distributed into Control, Exercise, LPS and Exercise+ LPS groups. AE was performed on a treadmill for 5x/week for four weeks before LPS administration. 24hours after the final AE physical test, animals received 100ug of LPS intra-peritoneally. In addition, whole blood cell culture, neutrophils and human endothelial cells were pre-incubated with IL-10, an anti-inflammatory cytokine induced by exercise. AE reduced total protein levels (p<0.01) and neutrophil accumulation in bronchoalveolar lavage (BAL) (p<0.01) and lung parenchyma (p<0.01). AE reduced BAL inflammatory cytokines IL-1 beta, IL-6 and GM-CSF (p<0.001), CXCL1/KC, IL-17, TNF-alpha and IGF-1 (p<0.01). Systemically, AE reduced IL-1 beta, IL-6 and IFN-gamma (p<0.001), CXCL1/KC (p<0.01) and TNF-alpha (p<0.05). AE increased IL-10 levels in serum (p<0.001) and BAL (p<0.001). Furthermore, AE increased superoxide dismutase SOD (p<0.01) and decreased superoxide anion accumulation in the lungs (p<0.01). Lastly, pre-incubation with IL-10 significantly reduced LPS-induced activation of whole blood cells, neutrophils and HUVECs, as observed by reduced production of IL-1 beta, IL-6, IL-8 and TNF-alpha. Our data suggest that AE inhibited LPS-induced lung inflammation by attenuating inflammatory cytokines and oxidative stress markers in mice and human cell culture via enhanced IL-10 production.Sao Paulo Research Foundation (FAPESP) [2012/15165-2]Conselho Nacional de Pesquisa e Desenvolvimento (CNPq) [311335-2015-2]Comissao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES) [12804/13-4, 1303/13-9]FAPESP [2013/24076-6, 2014/23196-0, 2012/14604-8, 2012/25435-7, 2012/24880-7]CAPESNove Julho Univ, Sao Paulo, SP, BrazilBrazilian Inst Teaching & Res Pulm & Exercise Imm, Sao Jose Dos Campos, SP, BrazilFed Univ Sao Paulo UNIFESP, Postgrad Program Sci Human Movement & Rehabil, Santos, SP, BrazilUniv Brasil, Sao Paulo, SP, BrazilUniv Sao Paulo, Sch Med, Dept Pathol LIM 59, Sao Paulo, SP, BrazilUniv Fed Lavras UFLA, Sci Dept Hlth, Lavras, MG, BrazilFed Univ Sao Paulo UNIFESP, Campus Sao Paulo, Sao Paulo, SP, BrazilHarbor UCLA Med Ctr, Div Resp & Crit Care Physiol & Med, Los Angeles Biomed Res Inst, Torrance, CA 90509 USAUniv Tubingen, Inst Clin & Expt Transfus Med IKET, Tubingen, GermanyFed Univ Sao Paulo UNIFESP, Postgrad Program Sci Human Movement & Rehabil, Santos, SP, BrazilFed Univ Sao Paulo UNIFESP, Campus Sao Paulo, Sao Paulo, SP, BrazilFAPESP [2012/15165-2]CNPq [311335-2015-2]CAPES [12804/13-4, 1303/13-9]FAPESP [2013/24076-6, 2014/23196-0, 2012/14604-8, 2012/25435-7, 2012/24880-7]Web of Scienc