Publications by authors named "Monique Matsuda"

21 Publications

  • Page 1 of 1

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

Chemosphere 2020 Sep 18;254:126817. Epub 2020 Apr 18.

Endurance Performance Research Group (GEDAE-USP), School of Physical Education and Sport, University of São Paulo, São Paulo, SP, Brazil.

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.
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http://dx.doi.org/10.1016/j.chemosphere.2020.126817DOI Listing
September 2020

Nrf2 positively regulates autophagy antioxidant response in human bronchial epithelial cells exposed to diesel exhaust particles.

Sci Rep 2020 02 28;10(1):3704. Epub 2020 Feb 28.

Laboratory of Experimental Air Pollution (LIM-05), Department of Pathology, School of Medicine, University of São Paulo, Av. Dr. Arnaldo 455, São Paulo, Brazil.

Diesel exhaust particles (DEP) are known to generate reactive oxygen species in the respiratory system, triggering cells to activate antioxidant defence mechanisms, such as Keap1-Nrf2 signalling and autophagy. The aim of this study was to investigate the relationship between the Keap1-Nrf2 signalling and autophagy pathways after DEP exposure. BEAS-2B cells were transfected with silencing RNA (siRNA) specific to Nrf2 and exposed to DEP. The relative levels of mRNA for Nrf2, NQO1, HO-1, LC3B, p62 and Atg5 were determined using RT-PCR, while the levels of LCB3, Nrf2, and p62 protein were determined using Western blotting. The autophagy inhibitor bafilomycin caused a significant decrease in the production of Nrf2, HO-1 and NQO1 compared to DEPs treatment, whereas the Nrf2 activator sulforaphane increased the LC3B (p = 0.020) levels. BEAS-2B cells exposed to DEP at a concentration of 50 μg/mL for 2 h showed a significant increase in the expression of LC3B (p = 0.001), p62 (p = 0.008), Nrf2 (p = 0.003), HO-1 (p = 0.001) and NQO1 (p = 0.015) genes compared to control. In siRNA-transfected cells, the LC3B (p < 0.001), p62 (p = 0.001) and Atg5 (p = 0.024) mRNA levels and the p62 and LC3II protein levels were decreased, indicating that Nrf2 modulated the expression of autophagy markers (R < 1). These results imply that, in bronchial cells exposed to DEP, the Nrf2 system positively regulates autophagy to maintain cellular homeostasis.
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http://dx.doi.org/10.1038/s41598-020-59930-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7048799PMC
February 2020

Occupational effect of sugarcane biomass burning on the conjunctival mucin profile of harvest workers and residents of an adjacent town - A Brazilian panel study.

Exp Eye Res 2020 01 1;190:107889. Epub 2019 Dec 1.

Pulmonary Division - Heart Institute (InCor), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Av. Dr. Enéas de Carvalho Aguiar 44, 8th Floor, São Paulo, SP, Brazil.

Pre-harvest burning of sugarcane fields produces large amounts of air pollutants which are known to cause health problems, including ocular surface abnormalities. In this study, we evaluated the effect of biomass burning on mucus quality and mucin gene expression (MUC1, MUC5AC, MUC16) in the conjunctiva of sugarcane workers (SWs) and residents of an adjacent town (RTs). Impression cytology samples of the inferior tarsal and bulbar conjunctiva of 78 SWs and 32 RTs were collected before (T1) and immediately after (T2) a 6-month harvest period. The neutral, acid and total mucus content of goblet cells was determined by PAS and AB staining. The levels of MUC5AC, MUC1 and MUC16 mRNA in the conjunctiva were measured by real-time PCR. Compared to RTs, SWs had higher levels of bulbar acid mucus and MUC16 mRNA and tarsal MUC5AC mRNA at T2 and lower levels of neutral mucus at T1 and T2. In the SW group, MUC1 mRNA levels were higher at T2 than at T1, but the levels of neutral and acid mucus were similar. In the RT group, acid mucus decreased and neutral mucus increased in the bulbar and tarsal conjunctiva at T2. In conclusion, our findings show that sugarcane harvesting is associated with abnormalities in mucus quality and content and changes in mucin mRNA levels on the ocular surface. This may help explain the ocular inflammatory signs and symptoms observed in subjects exposed to air pollutants and high temperatures from sugarcane biomass burning.
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http://dx.doi.org/10.1016/j.exer.2019.107889DOI Listing
January 2020

Workers of São Paulo city, Brazil, exposed to air pollution: Assessment of genotoxicity.

Mutat Res Genet Toxicol Environ Mutagen 2018 Oct 6;834:18-24. Epub 2018 Aug 6.

Experimental Air Pollution Laboratory of Pathology Department, University of São Paulo, Rua Dr. Arnaldo, 455, 01246-903, São Paulo, SP, Brazil. Electronic address:

Air pollution affects all major urban centers, particularly megacities with populations greater than 10 million people. Vehicular and industrial emissions are among the most important sources of air pollutants in these cities. Air pollution composition, dose, and time of exposure can cause differential effects on human health. We have evaluated the genotoxic effects of air pollution (PM and NO) on São Paulo city workers. Fifty-seven male individuals, 28-66 years old, with occupational exposure to air pollution, participated in this study; all worked daily outdoor shifts in São Paulo. Participants were recruited from three occupations: traffic controllers (n = 18); taxi drivers (n = 21); and workers at the Forestry Institute (n = 18). These workers were classified into two groups based on their workplace locations: Downtown Group (DT): traffic controllers and taxi drivers; Outskirts of Town Group (OT): workers at the Forestry Institute. Individual samplers of air pollution (Harvard air impactor) were used to collect PM and NO pollutants. Genotoxicity analysis (micronucleus test) was performed on buccal mucosa epithelial cells and peripheral blood lymphocytes. PM concentrations were significantly different between the groups (DT = 32.92 μg m, OT = 25.77 μg m; p = 0.03); however, no difference was observed in NO concentrations. Micronucleus frequencies in both buccal mucosa (DT = 2.78%, OT = 1.16%; p < 0.0001) and in peripheral lymphocytes (DT = 1.51%, OT = 0.73%; p < 0.0001) were significantly different between the groups. We observed a direct correlation between the individual dose of PM and micronucleus frequency in the buccal mucosa (p = 0.0021). Our results indicate that workers in the most urban areas of São Paulo are exposed to higher concentrations of PM and showed higher micronucleus frequencies in both buccal mucosa and lymphocytes.
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http://dx.doi.org/10.1016/j.mrgentox.2018.08.002DOI Listing
October 2018

Exercising in Air Pollution: The Cleanest versus Dirtiest Cities Challenge.

Int J Environ Res Public Health 2018 07 17;15(7). Epub 2018 Jul 17.

Endurance Performance Research Group (GEDAE-USP), School of Physical Education and Sport, University of São Paulo, São Paulo 05508030, Brazil.

: Aerobic exercise is recommended to improve health. However, the increased ventilation might increase the doses of inhaled air pollutants, negating the health benefits in highly polluted areas. Our objective was to estimate the inhaled dose of air pollutants during two simulated exercise sessions at cleanest and dirtiest cities reported by World Health Organization (WHO) considering air quality. : Minute ventilation data were extracted from laboratory-based exercise of 116 incremental running tests and used to calculate total ventilation of a hypothetical 30-min moderate continuous exercise routine. Afterwards, total ventilation values were combined with particulate matter (PM) data reported by the WHO for the 10 cleanest and 10 dirtiest cities, to calculate inhaled doses and the relative risk of all-cause mortality by exercising in different air pollution concentrations. : The dirtiest cities are located at less developed countries compared to cleanest cities. The inhaled dose of PM and PM were significantly higher in the dirtiest cities compared to the cleanest cities at rest and exercise, and significantly higher during exercise compared to the rest at dirtiest cities. The relative risk of all-cause mortality analysis showed that, while exercise in the cleanest cities improved health benefits throughout up to 90 min, there were no further health benefits after 15 min of exercise in the dirtiest cities, and the air pollution health risks surpassed the exercise benefits after 75 min. : Our findings suggest that a traditional 30-min of moderate aerobic exercise session might induce inhalation of high levels of pollutants when performed at dirtiest cities. Considering several adverse health effects from air pollutants inhalation, so the results suggest that the air pollution levels of the cities should be taken into account for physical exercise recommendations.
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http://dx.doi.org/10.3390/ijerph15071502DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6069042PMC
July 2018

Phototoxic assessment of a sunscreen formulation and its excipients: An in vivo and in vitro study.

J Photochem Photobiol B 2017 Aug 29;173:545-550. Epub 2017 Jun 29.

Programa de Biologia Celular e do Desenvolvimento, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro Federal, Rio de Janeiro, Brazil. Electronic address:

Background: Cosmetic preservatives are used to protect cosmetic formulations and improve its shelf-life. However, these substances may exert phototoxic effects when used under sunlight.

Objective: To assess safety, efficacy and putative phototoxic effects of a sunscreen formulation SPF 30 and its excipients.

Materials/methods: Irradiation was performed with solar simulated light (SSL) and the sunscreen from the School of Pharmacy/UFRJ/Brazil. We used albino hairless mice in different groups (control (G1), only irradiated (G2), sunscreen plus irradiation (G3) and vehicle plus irradiation (G4) for morphological assessment and immunefluorescence detection to OKL38. In vitro analyses were with a Saccharomyces cerevisiae (SC) strain plus SSL in the presence of methylparaben, propylparaben, imidazolidinyl urea, aminomethyl propanol and their association.

Results: G3 and G4 displayed photosensitization leading to thickening of the epidermis and increased dermal cellularity. G4 displayed strong OKL38 labeling when compared with other groups. Aminomethyl propanol, methylparaben and propylparaben are endowed with phototoxic activity against SC. Propylparaben displayed the highest phototoxic effect, followed by excipients association.

Conclusions: The sunscreen's vehicle is endowed with phototoxic activity. Propylparaben was the most phototoxic agent, increasing the overall phototoxicity of excipient association, pointing to a critical concern regarding vehicle associations intended to cosmetic purposes.
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http://dx.doi.org/10.1016/j.jphotobiol.2017.06.043DOI Listing
August 2017

Cellular stress response in human Müller cells (MIO-M1) after bevacizumab treatment.

Exp Eye Res 2017 07 15;160:1-10. Epub 2017 Apr 15.

Program of Cell and Developmental Biology, Institute of Biomedical Sciences, Federal University of Rio de Janeiro (UFRJ), Brazil.

Bevacizumab, an anti-vascular endothelial growth factor (VEGF) agent, is widely used in the treatment of retinal vascular diseases. However, due to the essential role Müller cell derived-VEGF plays in the maintenance of retinal neurons and glial cells, cell viability is likely to be affected by VEGF inhibition. We therefore evaluated the effect of bevacizumab-induced VEGF inhibition on Müller cells (MIO-M1) in vitro. MIO-M1 cells were cultured for 12 or 24 h in media containing bevacizumab at 0.25 or 0.5 mg/mL. Controls were cultured in medium only. Cell viability was determined with the trypan blue exclusion test and MTT assay. Caspase-3, beclin-1, glial fibrillary acidic protein (GFAP) and vimentin content were quantified by immunohistochemistry. Gene expression was evaluated by real-time quantitative PCR. Treatment with bevacizumab did not reduce MIO-M1 cell viability, but increased metabolic activity at 24 h (0.5 mg/mL) and induced apoptosis and autophagy, as shown by the increased caspase-3 levels at 12 h (0.25 and 0.5 mg/mL) and the increased beclin levels at 24 h (0.5 mg/mL). Caspase-3 mRNA was upregulated at 12 h and downregulated at 24 h in cells treated with bevacizumab at 0.25 mg/mL. Bevacizumab treatment was also associated with structural protein abnormalities, with decreased GFAP and vimentin content and upregulated GFAP and vimentin mRNA expression. Although bevacizumab did not significantly affect MIO-M1 cell viability, it led to metabolic and molecular changes (apoptosis, autophagy and structural abnormalities) suggestive of significant cellular toxicity.
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http://dx.doi.org/10.1016/j.exer.2017.04.005DOI Listing
July 2017

Human bronchial epithelial cells exposed in vitro to diesel exhaust particles exhibit alterations in cell rheology and cytotoxicity associated with decrease in antioxidant defenses and imbalance in pro- and anti-apoptotic gene expression.

Environ Sci Pollut Res Int 2016 May 9;23(10):9862-70. Epub 2016 Feb 9.

Laboratory of Experimental Air Pollution (LIM05), Department of Pathology, School of Medicine, University of São Paulo, Av. Dr. Arnaldo 455, 1°andar, sala 1150, Cerqueira César, São Paulo, SP, CEP:01246-903, Brazil.

Diesel exhaust particles (DEPs) from diesel engines produce adverse alterations in cells of the airways by activating intracellular signaling pathways and apoptotic gene overexpression, and also by influencing metabolism and cytoskeleton changes. This study used human bronchial epithelium cells (BEAS-2B) in culture and evaluates their exposure to DEPs (15ug/mL for 1 and 2 h) in order to determine changes to cell rheology (viscoelasticity) and gene expression of the enzymes involved in oxidative stress, apoptosis, and cytotoxicity. BEAS-2B cells exposed to DEPs were found to have a significant loss in stiffness, membrane stability, and mitochondrial activity. The genes involved in apoptosis [B cell lymphoma 2 (BCL-2 and caspase-3)] presented inversely proportional expressions (p = 0.05, p = 0.01, respectively), low expression of the genes involved in antioxidant responses [SOD1 (superoxide dismutase 1); SOD2 (superoxide dismutase 2), and GPx (glutathione peroxidase) (p = 0.01)], along with an increase in cytochrome P450, family 1, subfamily A, polypeptide 1 (CYP1A1) (p = 0.01). These results suggest that alterations in cell rheology and cytotoxicity could be associated with oxidative stress and imbalance between pro- and anti-apoptotic genes.
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http://dx.doi.org/10.1007/s11356-016-6228-xDOI Listing
May 2016

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

PLoS One 2015 20;10(11):e0143131. Epub 2015 Nov 20.

Laboratory for investigation in Ophthalmology (LIM-33), University of Sao Paulo Medical School, Sao Paulo, SP, Brazil.

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.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0143131PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4654582PMC
June 2016

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

Ann Hum Biol 2016 May 6;43(3):255-60. Epub 2015 Jul 6.

a Endurance Performance Research Group (GEDAE-USP), School of Physical Education and Sport .

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.
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http://dx.doi.org/10.3109/03014460.2015.1050065DOI Listing
May 2016

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

J Sports Sci 2016 5;34(2):163-70. Epub 2015 May 5.

a Endurance Performance Research Group, School of Physical Education and Sport , University of São Paulo , São Paulo , SP , Brazil.

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.
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http://dx.doi.org/10.1080/02640414.2015.1040823DOI Listing
September 2016

Is the COL5A1 rs12722 gene polymorphism associated with running economy?

PLoS One 2014 4;9(9):e106581. Epub 2014 Sep 4.

Laboratory of Experimental Air Pollution, Department of Pathology, School of Medicine, University of São Paulo, São Paulo, Brazil.

The COL5A1 rs12722 polymorphism is considered to be a novel genetic marker for endurance running performance. It has been postulated that COL5A1 rs12722 may influence the elasticity of tendons and the energetic cost of running. To date, there are no experimental data in the literature supporting the relationship between range of motion, running economy, and the COL5A1 rs12722 gene polymorphism. Therefore, the main purpose of the current study was to analyze the influence of the COL5A1rs12722 polymorphism on running economy and range of motion. One hundred and fifty (n = 150) physically active young men performed the following tests: a) a maximal incremental treadmill test, b) two constant-speed running tests (10 km · h(-1)) and 12 km · h(-1)) to determine the running economy, and c) a sit-and-reach test to determine the range of motion. All of the subjects were genotyped for the COL5A1 rs12722 single-nucleotide polymorphism. The genotype frequencies were TT = 27.9%, CT = 55.8%, and CC = 16.3%. There were no significant differences between COL5A1 genotypes for running economy measured at 10 km · h(-1) (p = 0.232) and 12 km · h(-1) (p = 0.259). Similarly, there were no significant differences between COL5A1 genotypes for range of motion (p = 0.337). These findings suggest that the previous relationship reported between COL5A1 rs12722 genotypes and running endurance performance might not be mediated by the energetic cost of running.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0106581PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4154741PMC
May 2015

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

Invest Ophthalmol Vis Sci 2014 Jul 24;55(8):5109-15. Epub 2014 Jul 24.

Laboratory of investigation in Ophthalmology (LIM-33), University of São Paulo Medical School, São Paulo, Brazil.

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.
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http://dx.doi.org/10.1167/iovs.14-14466DOI Listing
July 2014

Effects of ambient levels of traffic-derived air pollution on the ocular surface: analysis of symptoms, conjunctival goblet cell count and mucin 5AC gene expression.

Environ Res 2014 May 20;131:59-63. Epub 2014 Mar 20.

Division of Ophthalmology and the Laboratory for Investigation in Ophthalmology (LIM-33), University of São Paulo Medical School, Av. Dr. Arnaldo 455, 5th floor, 01246-903 São Paulo, Brazil.

Purpose: To quantify ocular symptoms, goblet cells (GC) and mucin 5AC (MUC5AC) gene expression on the conjunctiva of healthy subjects exposed to ambient levels of traffic-derived air pollution and to estimate its correlation with NO2 and particulate matter smaller than 2.5 μm (PM2.5) levels.

Methods: Twenty-one taxi drivers or traffic controllers were assessed with the Ocular Surface Disease Index (OSDI) questionnaire and conjunctival impression cytology. MUC5AC mRNA levels were determined based on the cytology of the right eye, and GC density was assessed based on the cytology of the left eye. Mean individual levels of 24-h NO2 and PM2.5 exposure were assessed the day before examination. Possible associations between NO2 or PM2.5 levels, OSDI scores, GC densities and MUC5AC mRNA levels were verified.

Results: The subjects were exposed to mean PM2.5 levels of 35±12 μg/m(3) and mean NO2 levels of 189±47 μg/m(3). OSDI scores were low (7.4±8) and GC densities were 521±257 and 782±322 cell/mm(2) on the bulbar and tarsal conjunctivas, respectively. The mean GC-derived MUC5AC mRNA expression was 14±7 fM/μg of total RNA. A significant and positive correlation was observed between MUC5AC mRNA levels and tarsal GC density (p=0.018). A trend toward association between PM2.5 levels and tarsal GC cell density (p=0.052) was found.

Conclusion: Exposure to ambient levels of air pollution impacts conjunctival GC density. An increase in MUC5AC mRNA levels may be part of an adaptive ocular surface response to long-term exposure to air pollution.
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http://dx.doi.org/10.1016/j.envres.2014.02.014DOI Listing
May 2014

Diesel exhaust particles selectively induce both proinflammatory cytokines and mucin production in cornea and conjunctiva human cell lines.

Invest Ophthalmol Vis Sci 2013 Jul 16;54(7):4759-65. Epub 2013 Jul 16.

Laboratorio de Investigaciones Oculares, Departamento de Patologí, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.

Purpose: To evaluate the effect of diesel exhaust particles (DEP) on the viability, proliferation, apoptosis, secretion of cytokines (IL-6, IL-8, and TNF-α), and mucin gene transcription (MUC1, MUC5AC, and MUC16) in human epithelial cells of the cornea (HCLE) and conjunctiva (IOBA-NHC).

Methods: HCLE and IOBA-NHC cells were incubated with DEP (10-500 μg/mL) for 24 hours. Cell proliferation was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Apoptotic cells were measured by an annexin V-FITC and propidium iodide kit for flow cytometry. Proinflammatory cytokines were determined by an ELISA kit. Mucin gene transcription was quantified by real-time PCR.

Results: DEP significantly decreased the viability, proliferation, and secretion of IL-8, but increased the secretion of IL-6 on both HCLE and IOBA-NHC cell lines in a dose-dependent manner. Neither cornea nor conjunctiva cells incubated with DEP released TNF-α. DEP induced a significant increase in the percentage of apoptotic cells in IOBA-NHC, whereas no changes were observed in HCLE. Finally, DEP significantly decreased the transcription levels of MUC1 and MUC16 in HCLE, but increased the transcription levels of MUC1, MUC5AC, and MUC16 in IOBA-NHC.

Conclusions: These findings suggest that human corneal and conjunctival epithelial cells incubated with DEP showed cytotoxicity and an inflammatory response mediated by IL-6, not by TNF-α or IL-8. Also, the decrease in mucin expression in the cornea cells might leave exposed areas in the cornea for contact with DEP. Finally, the increase in mucin expression in the conjunctiva cells might be involved at least in the clearance of DEP to protect the ocular epithelium.
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http://dx.doi.org/10.1167/iovs.12-10541DOI Listing
July 2013

In vitro effects of bevacizumab treatment on newborn rat retinal cell proliferation, death, and differentiation.

Invest Ophthalmol Vis Sci 2012 Nov 29;53(12):7904-11. Epub 2012 Nov 29.

Programa de Biologia Celular e do Desenvolvimento, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.

Purpose: Vascular endothelial growth factor (VEGF) is an important signal protein in vertebrate nervous development, promoting neurogenesis, neuronal patterning, and glial cell growth. Bevacizumab, an anti-VEGF agent, has been extensively used for controlling pathological retinal neovascularization 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 cell death, proliferation, and differentiation 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 2 days. Immunohistochemical staining was assessed against proliferating cell nuclear antigen (PCNA, to detect cell proliferation); caspase-3 and beclin-1 (to investigate cell death); and vimentin and glial fibrillary acidic protein (GFAP, markers of glial cells). Gene expressions were quantified by real-time reverse-transcription polymerase chain reaction. Results from treatment and control groups were compared.

Results: No significant difference in the staining intensity (on immunohistochemistry) of PCNA, caspase-3, beclin-1, and GFAP, or in the levels of PCNA, caspase-3, beclin-1, and vimentin mRNA was observed between the groups. However, a significant increase in vimentin levels and a significant decrease in GFAP mRNA expression were observed in bevacizumab-treated retinal explants compared with controls.

Conclusions: Bevacizumab did not affect cell death or proliferation in early developing rat retina but appeared to interfere with glial cell maturation by increasing vimentin levels and downregulating GFAP gene expression. Thus, we suggest anti-VEGF agents be used with caution in developing retinal tissue.
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http://dx.doi.org/10.1167/iovs.12-10283DOI Listing
November 2012

Correlation between signs and symptoms of ocular surface dysfunction and tear osmolarity with ambient levels of air pollution in a large metropolitan area.

Cornea 2013 Apr;32(4):e11-5

Department of Ophthalmology, Laboratory for Investigation in Ophthalmology (LIM-33), University of São Paulo Medical School, São Paulo, Brazil.

Purpose: To evaluate the effect of high levels of environmental air pollution on tear osmolarity and its possible correlation with clinical signs and symptoms.

Methods: This was a panel study involving 71 taxi drivers and traffic controllers from São Paulo, Brazil. Mean individual levels of 24-hour exposure to nitrogen dioxide (NO2) and particulate matter smaller than 2.5 μm (PM2.5) were assessed on 4 different occasions. On the first and third visits, subjects were submitted to clinical evaluations including the administration of the Ocular Surface Disease Index questionnaire, slit-lamp examination, estimation of tear breakup time (BUT), the Schirmer test, and vital staining of the cornea and conjunctiva. On the second and fourth visits, tear samples were collected for osmolarity assays. Statistical analysis was performed using generalized estimating equations.

Results: Although the taxi drivers and traffic controllers in our sample were exposed to high levels of NO2 and PM2.5, few symptoms were reported on the Ocular Surface Disease Index questionnaire. BUT values were reduced, whereas vital staining and Schirmer test mean results were within normal limits, despite considerable variability. A significant and negative correlation was found between PM2.5 levels and tear film osmolarity levels (P < 0.05). An increase of 10 μg/m(3) in PM2.5 was associated with a 10.9 mOsm/kg decrease in tear osmolarity. There also was a negative correlation, although not statistically significant, between NO2 and tear osmolarity.

Conclusions: Exposure to air pollution reduces tear film stability and influences tear film osmolarity. Combining clinical examination with the assessment of tear osmolarity may help understand ocular surface response to high levels of air pollution.
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http://dx.doi.org/10.1097/ICO.0b013e31825e845dDOI Listing
April 2013

Ocular surface adverse effects of ambient levels of air pollution.

Arq Bras Oftalmol 2011 Sep-Oct;74(5):377-81

Division of Ophthalmology Laboratory for Investigation in Ophthalmology, Universidade de São Paulo, Brazil.

It is widely recognized today that outdoor air pollution can affect human health. Various chemical components that are present in ambient pollution may have an irritant effect on the mucous membranes of the body, particularly those of the respiratory tract. Much less attention has been focused on the adverse effect on the ocular surface, despite the fact that this structure is even more exposed to air pollution than the respiratory mucosa since only a very thin tear film separates the corneal and conjunctival epithelia from the air pollutants. So far, clinical data are the more widespread tools used by ophthalmologists for assessing possible aggression to the ocular surface; however, clinical findings alone appears not to correlate properly with the complaints presented by the patients pointing out the need for further clinical and laboratory studies on the subject. The purpose of this study is to review signs and symptoms associated with chronic long-term exposure to environmental air pollutants on the ocular structures currently defined as the ocular surface and to review clinical and laboratory tests used to investigate the adverse effects of air pollutants on such structures. We also review previous studies that investigated the adverse effects of air pollution on the ocular surface and discuss the need for further investigation on the subject.
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http://dx.doi.org/10.1590/s0004-27492011000500016DOI Listing
September 2012

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

Cardiovasc Diabetol 2011 Apr 25;10:35. Epub 2011 Apr 25.

Heart Institute, University of São Paulo Medical School, São Paulo 05403-000, Brazil.

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.
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http://dx.doi.org/10.1186/1475-2840-10-35DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3100243PMC
April 2011

The effects of chronic exposure to traffic derived air pollution on the ocular surface.

Environ Res 2010 May 24;110(4):372-4. Epub 2010 Mar 24.

Laboratório de Investigação em Oftalmologia, Faculdade de Medicina, Universidade de São Paulo, Av. Dr. Arnaldo 455, 5th Floor, 01246-903 São Paulo, Brazil.

Objectives: The purpose of this study was to explore the clinical relevance of chronic exposure to ambient levels of traffic derived air pollution on the ocular surface.

Methods: A panel study involving 55 volunteers was carried out in São Paulo, Brazil. We measured the mean individual levels of nitrogen dioxide (NO(2)) exposure for 7 days. All subjects answered the Ocular Symptom Disease Index (OSDI) and a symptoms inventory. Subsequently, subjects underwent Schirmer I test, biomicroscopy, vital staining and tear breakup time (TBUT) assessment. Subject's mean daily exposure to NO(2) was categorized in quartiles. Statistical analysis was performed using one-way ANOVA, Tukey HSD and Chi-Square tests.

Results: A dose-response pattern was detected between OSDI scores and NO(2) quartiles (p<0.05). There was a significant association between NO(2) quartiles and reported ocular irritation (Chi(2)=9.2, p<0.05) and a significant negative association between TBUT and NO(2) exposure (p<0.05, R=-0.316, Spearman's correlation). There was a significant increase in the frequency of meibomitis in subjects exposed to higher levels of NO(2) (p<0.05).

Conclusions: Subjects exposed to higher levels of traffic derived air pollution reported more ocular discomfort symptoms and presented greater tear film instability, suggesting that the ocular discomfort symptoms and tear breakup time could be used as convenient bioindicators of the adverse health effects of traffic derived air pollution exposure.
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http://dx.doi.org/10.1016/j.envres.2010.03.003DOI Listing
May 2010

Ambient levels of air pollution induce goblet-cell hyperplasia in human conjunctival epithelium.

Environ Health Perspect 2007 Dec;115(12):1753-6

Laboratório de Investigação em Oftalmologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brasil.

Background: Ocular mucosa is exposed constantly to the external environment, and chronic exposure to air pollution may affect the ocular surface.

Objective: We assessed the effect of air pollution on the ocular surface by combining determinations of individual exposure and conjunctival impression cytology.

Methods: A panel study was conducted with 29 volunteers recruited in two locations with different pollution levels: São Paulo (n = 13) and Divinolândia (n = 16). We assessed mean individual levels of nitrogen dioxide (NO2) exposure for 7 days, using a passive sampler. Impression cytology samples were obtained from inferior tarsal conjunctiva. Comparisons between the two groups in terms of NO2 exposure and goblet-cell counts were performed using the Student t-test. Correlations between goblet-cells counts and corresponding individual NO2 exposure levels were determined using Spearman's correlation.

Results: Individuals living in São Paulo received a significantly (p = 0.005) higher dose of NO2 (mean 32.47; SD 9.83) than those living in Divinolândia (mean 19.33; SD 5.24). There was a steady increase in goblet-cell counts, proportional to NO2 exposure (Spearman's correlation = 0.566, p = 0.001), with a dose-response pattern.

Conclusions: A positive and significant association between exposure to air pollution and goblet-cell hyperplasia in human conjunctiva was detected. The combination of simple measurements of exposure and impression cytology was an effective and noninvasive approach for characterizing human response to ambient levels of air pollution.
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http://dx.doi.org/10.1289/ehp.10363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2137119PMC
December 2007