Effects of air pollution exposure on inflammatory and endurance performance in recreationally trained cyclists adapted to traffic-related air pollution.

The aim of the present study was to analyze the effects of traffic-related air pollution (TRAP) on markers of inflammatory, neuroplasticity, and endurance performance-related parameters in recreationally trained cyclists who were adapted to TRAP during a 50-km cycling time trial (50-km cycling TT). Ten male cyclists performed a 50-km cycling TT inside an environmental chamber located in downtown Sao Paulo (Brazil), under TRAP or filtered air conditions. Blood samples were obtained before and after the 50-km cycling TT to measure markers of inflammatory [interleukin-6 (IL-6), C-reactive protein (CRP), interleukin-10 (IL-10), intercellular adhesion molecule-1 (ICAM-1)] and neuroplasticity [brain-derived neurotrophic factor (BDNF)]. Rating of perceived exertion (RPE), heart rate (HR), and power output (PO) were measured throughout the 50-km cycling TT. There were no significant differences between experimental conditions for responses of IL-6, CRP, and IL-10 (P > 0.05). When compared with exercise-induced changes in filtered air condition, TRAP provoked greater exercise-induced increase in BDNF levels (TRAP = 3.3 ± 2.4-fold change; Filtered = 1.3 ± 0.5-fold change; P = 0.04) and lower exercise-induced increase in ICAM-1 (Filtered = 1.1 ± 0.1-fold change; TRAP = 1.0 ± 0.1-fold change; P = 0.01). The endurance performance-related parameters (RPE, HR, PO, and time to complete the 50-km cycling TT) were not different between TRAP and filtered air conditions (P > 0.05). These findings suggest that the potential negative impacts of exposure to pollution on inflammatory, neuroplasticity, and performance-related parameters do not occur in recreationally trained cyclists who are adapted to TRAP.

Traffic-related air pollution and endurance exercise: Characterizing non-targeted serum metabolomics profiling.

Although the exposure to traffic-related air pollution (TRAP) has emerged as one of main problem worldwide to inhabitants' health in urban centers, its impact on metabolic responses during exercise is poorly understood. The aim of study was to characterize the profile of non-target serum metabolomics during prolonged exercise performed under TRAP conditions. Ten healthy men completed two 90 min constant-load cycling trials under conditions of either TRAP or filtered air. Experimental trials were performed in a chamber located on an avenue with a high volume of vehicle traffic. Blood samples were taken at 30 min, 60 min, and 90 min of exercise. Based on Nuclear Magnetic Resonance metabolomics, the non-target analysis was used to assess the metabolic profile. Twelve, 16 and 18 metabolites were identified as discriminants. These were: at 30 min of exercise, the coefficient of determination (R2) 0.98, the predictive relevance, (Q2) 0.12, and the area under the curve (AUC) 0.91. After 60 min of exercise: (R2: 0.99, Q2: 0.09, AUC: 0.94); and at 90 min of exercise (R2: 0.91, Q2: <0.01, AUC: 0.89), respectively. The discriminant metabolites were then considered for the target analysis, which demonstrated that the metabolic pathways of glycine and serine metabolism (p = 0.03) had been altered under TRAP conditions at 30 min of exercise; arginine and proline metabolism (p = 0.04) at 60 min of exercise; and glycolysis (p = 0.05) at 90 min of exercise. The present results suggest that exposure to TRAP during prolonged exercise leads to a significant change in metabolomics, characterized by a transitional pattern and lastly, impairs the glucose metabolism.

Exercising in the urban center: Inflammatory and cardiovascular effects of prolonged exercise under air pollution.

The aim of this study was to investigate, in a well-controlled experimental environment, whether air pollution from an urban center would affect inflammatory and cardiorespiratory responses during prolonged moderate exercise (i.e., 90 min). Ten healthy men performed two experimental trials under filtered and polluted air, inside an environmental chamber located in Sao Paulo downtown, Brazil. Blood samples were obtained at rest, 30, 60, and 90 min of the exercise to determine the serum cytokines concentration, while arterial pressure was recorded immediately after the exercise. The serum cytokines were not altered until 60 min of exercise for both conditions (P > 0.05). Otherwise, at 90 min of exercise, the IL-6 (P = 0.047) and vascular endothelial growth factor (VEGF) (P = 0.026) were significantly higher and IL-10 tended to decrease (P = 0.061) in polluted air condition compared to filtered air condition. In addition, both systolic (P = 0.031) and diastolic (P = 0.009) arterial pressure were higher in polluted air condition than filtered air condition. These findings demonstrate that the exercise of longer duration (i.e., 90 min), but not of shorter duration (i.e., <60 min), performed in vehicular air pollution condition results in pronounced pro-inflammatory and increased arterial pressure responses.

The genetics of human running: ACTN3 polymorphism as an evolutionary tool improving the energy economy during locomotion.

BACKGROUND: Covering long distances was an important trait to human evolution and continues to be highlighted for health and athletic status. This ability is benefitted by a low cost of locomotion (CoL), meaning that the individuals who are able to expend less energy would be able to cover longer distances. The CoL has been shown to be influenced by distinct and even 'opposite' factors, such as physiological and muscular characteristics, which are genetically inherited. In this way, DNA alterations could be important determinants of the characteristics associated with the CoL. A polymorphism in the ACTN3 gene (R577X) has been related to physical performance, associating the X allele with endurance and the R allele with strength/power abilities. AIM: To investigate the influence of ACTN3 genotypes on the CoL. SUBJECTS AND METHODS: One hundred and fifty healthy male individuals performed two constant speed tests (at 10 and 12 km/h) to determine the CoL. RESULTS: Interestingly, the results showed that heterozygous individuals (RX genotype) presented significantly lower CoL compared to RR and XX individuals. CONCLUSIONS: It is argued that RX genotype might generate an intermediate strength-to-endurance phenotype, leading to a better phenotypic profile for energy economy during running and, consequently, for long-term locomotion.

Influence of ACTN3 R577X polymorphism on ventilatory thresholds related to endurance performance.

The purpose of this study was to verify the association between ACTN3 polymorphism and physiological parameters related to endurance performance. A total of 150 healthy male volunteers performed a maximal incremental running test to determine the speeds corresponding to ventilatory threshold (VT) and respiratory compensation point (RCP). Participants were genotyped and divided into terciles based on the analysed variables. Genotype frequencies were compared through χ(2) test between lower and higher terciles, with the lowest or highest values of each analysed variable. ACTN3 XX genotype was over-represented in higher tercile for VT and RCP. Odds ratio also showed significantly higher chances of XX individuals to be in higher tercile compared to RR (7.3) and RR + RX (3.5) for VT and compared to RR genotype (8.1) and RR + RX (3.4) for RCP. Thus, XX individuals could attain the VT and RCP at higher speeds, suggesting that they are able to sustain higher running speeds in lower exercise intensity domains. It could result in higher lipid acids oxidation, saving muscle glycogen and delaying the fatigue during prolonged exercises, which could be the advantage mechanism of this genotype to endurance performance.

Lacrimal Cytokines Assessment in Subjects Exposed to Different Levels of Ambient Air Pollution in a Large Metropolitan Area.

BACKGROUND: Air pollution is one of the most environmental health concerns in the world and has serious impact on human health, particularly in the mucous membranes of the respiratory tract and eyes. However, ocular hazardous effects to air pollutants are scarcely found in the literature. DESIGN: Panel study to evaluate the effect of different levels of ambient air pollution on lacrimal film cytokine levels of outdoor workers from a large metropolitan area. METHODS: Thirty healthy male workers, among them nineteen professionals who work on streets (taxi drivers and traffic controllers, high pollutants exposure, Group 1) and eleven workers of a Forest Institute (Group 2, lower pollutants exposure compared to group 1) were evaluated twice, 15 days apart. Exposure to ambient PM2.5 (particulate matter equal or smaller than 2.5 µm) was 24 hour individually collected and the collection of tears was performed to measure interleukins (IL) 2, 4, 5 and 10 and interferon gamma (IFN-γ) levels. Data from both groups were compared using Student's t test or Mann- Whitney test for cytokines. Individual PM2.5 levels were categorized in tertiles (lower, middle and upper) and compared using one-way ANOVA. Relationship between PM2.5 and cytokine levels was evaluated using generalized estimating equations (GEE). RESULTS: PM2.5 levels in the three categories differed significantly (lower: ≤22 µg/m3; middle: 23-37.5 µg/m3; upper: >37.5 µg/m3; p<0.001). The subjects from the two groups were distributed unevenly in the lower category (Group 1 = 8%; Group 2 = 92%), the middle category (Group 1 = 89%; Group 2 = 11%) and the upper category (Group 1 = 100%). A significant relationship was found between IL-5 and IL-10 and PM2.5 levels of the group 1, with an average decrease of 1.65 pg/mL of IL-5 level and of 0.78 pg/mL of IL-10 level in tear samples for each increment of 50 µg/m3 of PM2.5 (p = 0.01 and p = 0.003, respectively). CONCLUSION: High levels of PM2.5 exposure is associated with decrease of IL-5 and IL-10 levels suggesting a possible modulatory action of ambient air pollution on ocular surface immune response.

Bevacizumab reduces neurocan content and gene expression in newborn rat retina in vitro.

PURPOSE: Extracellular matrix (ECM) and cellular membrane proteoglycans (PGs) play important roles in neural differentiation and cell adhesion. Vascular endothelial growth factor, an important signal protein in vascular and retinal neural cell development, is retained in the ECM due to its high affinity for PG. Bevacizumab, an anti-VEGF agent, has been extensively used for treating retinal diseases in adult and newborn patients, although its effect on the developing retina remains largely unknown. The purpose of this study was to investigate the effect of bevacizumab on neurocan, phosphacan, and syndecan-3 PG levels in newborn rat retina. METHODS: Retinal explants of sixty 2-day-old Lister hooded rats were obtained after eye enucleation and maintained in culture media with or without bevacizumab for 48 hours. Immunohistochemical staining was assessed against neurocan, phosphacan, and syndecan-3. Proteoglycan content was quantified based on the intensity of immunohistochemical labeling. Gene expressions were quantified by real-time reverse-transcription polymerase chain reaction. The results from the treatment and control groups were compared. RESULTS: No significant difference in the staining intensity and mRNA expression of phosphacan and syndecan-3 was observed between the groups. However, a significant decrease in neurocan content and mRNA expression was observed in bevacizumab-treated retinal explants compared with controls. CONCLUSIONS: Bevacizumab did not affect phosphacan and syndecan-3 levels but decreased neurocan content and gene expression. Therefore, it may interfere with early postnatal retinal cell differentiation. Although further studies are necessary to confirm our findings, we suggest anti-VEGF agents be used with caution in developing retinal tissue.

Changes in cardiac heparan sulfate proteoglycan expression and streptozotocin-induced diastolic dysfunction in rats.

BACKGROUND: Changes in the proteoglycans glypican and syndecan-4 have been reported in several pathological conditions, but little is known about their expression in the heart during diabetes. The aim of this study was to investigate in vivo heart function changes and alterations in mRNA expression and protein levels of glypican-1 and syndecan-4 in cardiac and skeletal muscles during streptozotocin (STZ)-induced diabetes. METHODS: Diabetes was induced in male Wistar rats by STZ administration. The rats were assigned to one of the following groups: control (sham injection), after 24 hours, 10 days, or 30 days of STZ administration. Echocardiography was performed in the control and STZ 10-day groups. Western and Northern blots were used to quantify protein and mRNA levels in all groups. Immunohistochemistry was performed in the control and 30-day groups to correlate the observed mRNA changes to the protein expression. RESULTS: In vivo cardiac functional analysis performed using echocardiography in the 10-day group showed diastolic dysfunction with alterations in the peak velocity of early (E) diastolic filling and isovolumic relaxation time (IVRT) indices. These functional alterations observed in the STZ 10-day group correlated with the concomitant increase in syndecan-4 and glypican-1 protein expression. Cardiac glypican-1 mRNA and skeletal syndecan-4 mRNA and protein levels increased in the STZ 30-day group. On the other hand, the amount of glypican in skeletal muscle was lower than that in the control group. The same results were obtained from immunohistochemistry analysis. CONCLUSION: Our data suggest that membrane proteoglycans participate in the sequence of events triggered by diabetes and inflicted on cardiac and skeletal muscles.

Gene expression of extracellular matrix proteoglycans in human cyclosporin-induced gingival overgrowth.

BACKGROUND: Gingival overgrowth is one of the side effects associated with the systemic use of cyclosporin A (CsA). In vitro studies on the extracellular matrix of gingival tissues have demonstrated an altered composition, particularly an accumulation of proteoglycans and collagen. We investigated the gene expression of extracellular matrix proteoglycans in CsA-induced gingival tissue alterations. METHODS: mRNA expression of the proteoglycans perlecan, decorin, biglycan, and versican was analyzed by reverse transcription polymerase chain reaction (RT-PCR) in gingival samples obtained from 12 individuals, six with CsA-induced gingival overgrowth (CsA group) and six with a normal gingiva (control group). The RT-PCR products were subjected to 1% agarose gel electrophoresis containing ethidium bromide and analyzed qualitatively and semiquantitatively by densitometry. Density values were normalized by determining the expression of the housekeeping gene beta-actin in the same sample. Groups were compared by the Student's t test. RESULTS: Perlecan expression showed a marked increase (54%) in the CsA group compared to the control group (P < 0.01), while no significant differences were observed for the other proteoglycans. CONCLUSION: CsA-induced gingival overgrowth seems to be associated with increased expression of perlecan, a typical basement membrane proteoglycan, but not decorin, biglycan, or versican.

Distribuição comparativa dos glicosaminoglicanos em artérias e veias de diferentes mamíferos / Comparative distribution of glycosaminoglycans in arteries and veins of different mammals

Foi realizada análise comparativa sobre a distribuição dos glicosaminoglicanos de artérias e veias em ratos, cachorros e humanos. Os nossos resultados demonstraram que dermatam sulfato foi o principal glicosaminoglicano encontrado tanto para as artérias quanto para as veias estudadas. Entretanto, a proporção de dermatam sulfato foi maior nas veias do que nas artérias nas três espécies analisadas. Este aumento pode estar associado às diferenças estruturais e funcionais encontradas na parede destes dois tipos de vasos sangüíneos (nas veias a pressão sangüínea é significativamente mais baixa). Além disso, a quantidade total dos glicosaminoglicanos foi maior nas artérias do que nas veias, sendo as maiores concentrações encontradas nas aortas independentemente da espécie animal estudada. Estes achados abrem perspectiva para o melhor conhecimento das alterações das macromoléculas que possam estar relacionadas ao processo degenerativo vascular, especialmente nas transformações estruturais que as veias safenas sofrem, quando empregadas como enxertos na revascularização do miocárdio