A previous study by our group showed that regular exercise training (ET) attenuated pulmonary injury in an experimental model of chronic exposure to cigarette smoke (CS) in mice, but the time-course ...effects of the mechanisms involved in this protection remain poorly understood. We evaluated the temporal effects of regular ET in an experimental model of chronic CS exposure. Male C57BL/6 mice were divided into four groups: Control (sedentary + air), Exercise (aerobic training + air), Smoke (sedentary + smoke), and Smoke + Exercise (aerobic training + smoke). Mice were exposed to CS and ET for 4, 8, or 12 wk. Exercise protected mice exposed to CS from emphysema and reductions in tissue damping and tissue elastance after 12 wk (
< 0.01). The total number of inflammatory cells in the bronchoalveolar lavage increased in the Smoke group, mainly due to the recruitment of macrophages after 4 wk, neutrophils and lymphocytes after 8 wk, and lymphocytes and macrophages after 12 wk (
< 0.01). Exercise attenuated this increase in mice exposed to CS. The protection conferred by exercise was mainly observed after exercise adaptation. Exercise increased IL-6 and IL-10 in the quadriceps and lungs (
< 0.05) after 12 wk. Total antioxidant capacity and SOD was increased and TNF-α and oxidants decreased in lungs of mice exposed to CS after 12 wk (
< 0.05). The protective effects of exercise against lung injury induced by cigarette smoke exposure suggests that anti-inflammatory mediators and antioxidant enzymes play important roles in chronic obstructive pulmonary disease development mainly after the exercise adaptation.
These experiments investigated for the first time the temporal effects of regular moderate exercise training in cigarette smoke-induced chronic obstructive pulmonary disease. We demonstrate that aerobic conditioning had a protective effect in emphysema development induced by cigarette smoke exposure. This effect was most likely secondary to an effect of exercise on oxidant-antioxidant balance and anti-inflammatory mediators.
Nicotinic α‐7 acetylcholine receptor (nAChRα7) is a critical regulator of cholinergic anti‐inflammatory actions in several diseases, including acute respiratory distress syndrome(ARDS). Given the ...potential importance of α7nAChR as a therapeutic target, we evaluated whether PNU‐282987, an α7nAChR agonist, is effective in protecting the lung against inflammation. We performed intratracheal instillation of LPS to generate acute lung injury (ALI) in C57BL/6 mice. PNU‐282987 treatment, either before or after ALI induction, reduced neutrophil recruitment and IL‐ 1β, TNF‐α, IL‐6, keratinocyte chemoattractant (KC), and IL‐10 cytokine levels in the bronchoalveolar lavage fluid (P> 0.05). In addition, lung NF‐κB phosphorylation decreased, along with collagen fiber deposition and the number of matrix metalloproteinase‐9+ and −2+ cells, whereas the number of tissue inhibitor of metalloproteinase‐1+ cells increased (P < 0.05). PNU‐282987 treatment also reduced lung mRNA levels and the frequency of M1 macrophages, whereas cells expressing the M2‐related markers CD206 and IL‐10 increased, suggesting changes in the macrophage profile. Finally, PNU‐282987 improved lung function in LPS‐treated animals. The collective results suggest that PNU‐282987, anagonist of α7nAChR, reducesLPS‐induced experimental ALI, thus supporting the notion that drugs that act on α7nAChRs should be explored for ARDS treatment in humans.—Pinheiro, N. M., Santana, F. P. R., Almeida, R. R., Guerreiro, M., Martins, M.A., Caperuto, L.C., Câmara, N.O.S., Wensing, L.A., Prado, V. F., Tibério, I. F. L. C., Prado, M.A.M., Prado, C. M. Acute lung injury is reduced by the α7nAChR agonist PNU‐282987 through changes in the macrophage profile. FASEB J. 31, 320–332 (2017) www.fasebj.org
Glycol methacrylate (GMA), a water and ethanol miscible plastic resin, is a medium handy to use for light microscopy embedding that has a number of advantages than paraffin embedding. The GMA ...improves the histological, morphometrical, and immunohistochemical evaluations, mainly due to the accurate assessment of cytological details. This chapter focuses on our experience in the GMA processing and describes in detail the fixation, embedding, and staining methods that we have been using for testes evaluations.
•For the first time, plant stability and memory were associated using experimental data.•The overall stability (OSt) considers homeostasis and resistence against drought.•Leaf CO2 assimilation and ...stomatal conductance were robust traits for evaluating drought memory in sugarcane.
Stability is a key trait for plant growth and development in a changing environment, involving homeostasis and resilience. While homeostasis refers to the maintenance of the internal structural and functional plant integrity, resilience is associated with the plant ability in returning to the initial conditions after a given disturbance. Such concepts are especially relevant for perennial and semi-perennial plants facing seasonal and frequent stress conditions. Although plant memory is closely associated with plant performance under recurrent stresses, to date, there is no study evaluating how stress memory is linked to stability under varying water conditions. Herein, we evaluated the association between drought stability and memory in sugarcane plants and proposed a new stability index to evaluate plant memory. Two datasets were analyzed, the first deals with leaf gas exchange and photochemistry of sugarcane plants grown in nutrient solution and exposed to one, two or three water deficit cycles. The second takes into account the physiological performance of sugarcane propagules obtained by vegetative propagation from plants that faced drought. To quantify sugarcane stability, we estimated the drought impact, the disturbance rate (DR), drought perturbation, and recovery rate (RR) for plants from both datasets. Drought memory – given by improved performance after previous stress events or when origin material faced drought – was detected in both datasets, changing either DR or RR. Based on these indices, we proposed the overall stability (OSt), defined as the ratio between RR and DR. While DR is associated to plant homeostasis, RR is a measure of plant resilience. Sugarcane plants exposed to three cycles of water deficit or those propagules originated from stressed plants presented the highest OSt values, showing higher RR and/or lower DR when compared to well-watered plants or to propagules from well-watered plants. Regarding the physiological traits evaluated, leaf CO2 assimilation and stomatal conductance were the most consistent variables in revealing drought stability and memory. Concluding, OSt revealed consistently patterns of response associated with plant memory, besides quantifying plant stability under stressful conditions.
•Eighteen cases of Chagas disease were confirmed serologically in the semiarid region of Rio Grande do Norte state, Brazil, with two deaths reported.•Only 7.5% of residents in the outbreak area ...admitted knowledge that Chagas disease can also be acquired orally;.•Twelve percent of dwellings were found to be suitable for triatomine colonization;.•Thirteen percent of people reported they may have been bitten by triatomines in the last three years;.•The physical proximity between humans and triatomine populations with high trypanosoma cruzi prevalence represents a risk factor to further oral/vector contaminations.
Chagas disease is a neglected tropical disease strongly associated with low socioeconomic status, affecting nearly 8 million people – mainly Latin Americans. The current infection risk is based on acute case reports, most of which are typically associated with oral transmissions. In the semi-arid region of Northeastern Brazil, serious outbreaks of this transmission type have surged in the last years. One of those occurred in 2016 in the state of Rio Grande do Norte. Rural residents of four municipalities surrounding Marcelino Vieira ingested sugar cane juice – which was probably ground with Trypanosoma cruzi-infected insects. Eighteen cases of Chagas disease were confirmed serologically, with two deaths reported. Socioeconomic information, schooling of residents and the structure of peridomestic and domestic environments in the rural area of Marcelino Vieira, along with entomological indicators, were investigated to understand better the factors related to the outbreaks in this region. We found triatomines (mainly Triatoma brasiliensis) in 35% (24/67) of domiciliary units and all rocky outcrops inspected (n = 7). Overall, 25% (91/357) of examined T. brasiliensis were infected by T. cruzi in artificial ecotopes, with almost the same prevalence in the sylvatic environment (22%; 35/154). Among all ecotopes investigated, wood/tile/brick piles were the ones linked to high insect infestations and triatomine T. cruzi infection prevalence. Ninety-five percent of people interviewed recognized the triatomines and knew the classic route of transmission of disease – triatomine bite-dependent. However, only 7.5% admitted knowledge that Chagas disease can also be acquired orally – which poses a risk this transmission route currently recognized. Here, we highlight the physical proximity between humans and triatomine populations with high T. cruzi infection prevalence as an additional risk factor to oral/vector contaminations. In sum, residents have low income, low level of education, and/or a willful disregard for the routes of Chagas disease transmission (specifically oral transmission), a combination of factors that may have favored the Chagas disease outbreak. We here provide recommendations to avoid further outbreaks.
Both oxidative/nitrosative stress and alterations in DNA methylation are observed during carcinogenesis of different tumor types, but no clear correlation between these events has been demonstrated ...until now. Melanoma cell lines were previously established after submitting the nontumorigenic melanocyte lineage, melan-a, to cycles of anchorage blockade. In this work, increased intracellular oxidative species and nitric oxide levels, as well as alterations in the DNA methylation, were observed after melan-a detachment, which were also associated with a decrease in intracellular homocysteine (Hey), an element in the methionine (universal methyl donor) cycle. This alteration was accompanied by increase in glutathione (GSH) levels and methylated DNA content. Furthermore, a significant increase in dnmti and 3b expression was identified along melan-a anchorage blockade. LG-Nitro-L-arginine methyl esther (L-NAME), known as a nitric oxide synthase (NOS) inhibitor, and N-acetyl-L-cysteine (NAC) prevented the increase in global DNA methylation, as well as the increase in dnmti and 3b expression, observed during melan-a detachment. Interestingly, both L-NAME and NAC did not inhibit nitric oxide (NO) production in these cells, but abrogated superoxide anion production during anchorage blockade. In conclusion, oxidative stress observed during melanocyte anchorage blockade seems to modulate DNA methylation levels and may directly contribute to the acquisition of an anoikis-resistant phenotype through an epigenetic mechanism.
The aim of this study was to compare clinical and biomechanical features of scars resulting from the treatment of burn contractures using different acellular dermal matrices (ADM).
Extensive burns ...often lead to severe sequelae, such as skin contractures, that can be treated using ADM to improve the quality of these scars.
A prospective, randomized and controlled clinical trial was performed including patients with burn contractures at least 1-year post-burn, treated using split-thickness skin graft (STSG). These patients were randomized into 4 groups: control (received only STSG without ADM), Integra (ADM + STSG), Matriderm (ADM + STSG), and Pelnac (ADM + STSG). Exclusion criteria were loss of follow-up and graft integration failure. The evaluation was performed using the Vancouver Scar Scale (VSS), the durom-eter, and the cutometer in areas of normal skin, hypertrophic scar, and surgical scar, at least 1 year after the surgery.
In the VSS, durometer, and cutometer evaluation, there was no difference in the comparison of surgical scars among groups. Analyzing each group, with an intraindividual evaluation comparing areas of normal skin with surgical scars, the results suggested a possibility of a surgical scar hardness closer to normal skin for Integra and Matriderm groups measured with the durometer. In the cutometer evaluation, surgical scars were not comparable to areas of normal skin.
This study suggests that there is no difference in the quality of scar assessed through the analysis of clinical and biomechanical features comparing acellular dermal matrices (Integra, Matriderm, and Pelnac) and only split-thickness skin graft without a dermal matrix.
Phospholipase A2 toxins present in snake venoms interact with biological membranes and serve as structural models for the design of small peptides with anticancer, antibacterial and antiparasitic ...properties. Oligoarginine peptides are capable of increasing cell membrane permeability (cell penetrating peptides), and for this reason are interesting delivery systems for compounds of pharmacological interest. Inspired by these two families of bioactive molecules, we have synthesized two 13-mer peptides as potential antileishmanial leads gaining insights into structural features useful for the future design of more potent peptides. The peptides included p-Acl, reproducing a natural segment of a Lys49 PLA2 from Agkistrodon contortrix laticinctus snake venom, and its p-AclR7 analogue where all seven lysine residues were replaced by arginines. Both peptides were active against promastigote and amastigote forms of Leishmania (L.) amazonensis and L. (L.) infantum, while displaying low cytotoxicity for primary murine macrophages. Spectrofluorimetric studies suggest that permeabilization of the parasite's cell membrane is the probable mechanism of action of these biomolecules. Relevantly, the engineered peptide p-AclR7 was more active in both life stages of Leishmania and induced higher rates of ethidium bromide incorporation than its native template p-Acl. Taken together, the results suggest that short peptides based on phospholipase toxins are potential scaffolds for development of antileishmanial candidates. Moreover, specific amino acid substitutions, such those herein employed, may enhance the antiparasitic action of these cationic peptides, encouraging their future biomedical applications.
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•13-mer peptides based on phospholipase and oligoarginine sequences are promising leishmanicidal compounds.•Arginine may confer better antileishmanial activity to cationic peptides than lysine residues.•13-mer leishmanicidal peptides interfere with cell membrane permeabilization.•13-mer peptides showed low toxicity to mammalian cells.
The objective of this study was to determine the utility of nasoendoscopy of the upper airway as a predictor of the efficacy of oral appliance treatment in obstructive sleep apnoea (OSA).A total of ...61 consecutive patients with moderate-to-severe polysomnographically diagnosed OSA were recruited for this study. Using nasoendoscopy, we prospectively assessed the velopharynx and oro/hypopharynx in each patient while awake and in the supine position. We measured cross-sectional area (CSA), and anteroposterior and lateral diameters of the airway before and after mandibular advancement, and expressed the changes in dimensions as expansion ratios (after/before). We then compared the measurements of responders and nonresponders with oral appliance treatment.The expansion ratio (median (interquartile range)) for the CSA was greater in responders compared with nonresponders in the velopharynx (2.9 (2.3-5.0) versus 1.7 (1.5-1.9), p<0.001) and in the oro/hypopharynx (3.4 (2.5-5.6) versus 2.4 (1.8-3.7), p<0.05). Baseline apnoea-hypopnoea index and the CSA expansion ratio of the velopharynx were independent predictors of oral appliance treatment outcome based on a multivariate logistic regression analysis. The estimated area under the receiver operator characteristic curve was 0.87 and the cut-off value of the expansion ratio was 2.00.These results indicate that nasoendoscopy may have significant clinical utility in predicting the success of oral appliance treatment.
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