70 research outputs found

    Resveratrol Induces Erythroid Maturation by Activating FOXO3 and Improves in Vivo Erythropoiesis in Normal and Beta -Thalassemic Mice

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    Resveratrol is a polyphenolic stilbene with anti-oxidant, anti-inflammatory and anti-tumoral bioactivities . High concentrations of resveratrol (50 \u3bcM) have been reported to induce HbF synthesis in an in vitro model of normal and beta-thalassemic erythropoiesis (Fibach E. Int J Mol Med 2012; Rodrigue CM. BJH 2001) and to improve erythropoiesis in a mouse model for Fanconi Anemia (Zhang Q. Blood 2010). Beta thalassemia (b-thal) is characterized by ineffective erythropoiesis and increased cellular oxidative stress. We studied the effects of resveratrol (5 \ub5M) on erythropoiesis in vitro from peripheral CD34+ cells of healthy and b-thal subjects. Erythroid maturation was evaluated at 7, 9, 11 and 14 days of culture by cytofluorimetric analysis using the CD71-GPA-CD36 strategy that allows to separate CFU-E, Pro-E, Int-E and Late-Erythroblasts (Merryweather-Clarke AT. Blood 2011). Resveratrol reduced cell growth in both cell types, with a reduction of CFU-E, increased Int-E at day 7 and 9, and increased Int-E and Late-E at 11 and 14 days. The early maturation of erythroid progenitors was confirmed by morphological analysis of the cells. We sorted CFU-E cells (at 7 days) from resveratrol treated and untreated cells and analyzed the cell cycle, cyclinD1 and p21 expression. In both cell types resveratrol induced increased frequency of S-G2/M cells compared to untreated cells with increased p21 levels, suggesting decreased cycling of CFU-E with increased maturation of erythroblasts. No changes of gamma chain mRNA levels were present in cells treated with resveratrol (5 \ub5M). Since FOXO3 is a key regulator of erythroid redox required for normal erythroid maturation (Marinkovic D. JCI 2007), FOXO3 expression and activity was assessed in sorted CFU (7day) and Int-E (11 day) with and without resveratrol. FOXO3a mRNA levels were increased in resveratrol treated cells in both sorted cell populations. We used nuclear localization as a surrogate assay for FOXO3a activity and found resveratrol increased the overall expression of FOXO3 protein in the nucleus without impacting significantly the nuclear/cytoplasmic ratio. Interestingly, resveratrol did not appear to modify FOXO1 expression or subcellular localization. These results suggest that resveratrol enhances specifically expression of FOXO3 in human erythroblasts. Dietary resveratrol supplementation (2.4 mg/Kg) was studied in wild-type and Hbb3th+/- mice (2 months of age) for 6 months. In resveratrol Hbb3th+/- treated mice increased Hb levels (8.3\ub10.6 vs 10.3\ub10.5 g/dL, n=12; P<0.05) and decreased reticulocyte count (33.9\ub10.8 vs 23.7\ub1 8.2 %, n=12; P<0.05) were observed. Significant increased MCV (34.6\ub10.6 vs 41.6\ub1 5.4 fL, n=12; P<0.05) and MCH ( 9.7\ub1 0.6 vs 12.8 \ub1 2.1 pg, n=12; P<0.05) were also noted. Flow cytometric evidence of decreased ineffective erythropoiesis and reduced spleen/ body weight ratio were also observed. These data indicate that resveratrol affects erythroid maturation both in vitro and in vivo, and that these effects have possible therapeutic relevance for the treatment of thalassemias

    Effect of interferents on the performance of direct-reading organic vapor monitors

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    <div><p>Direct-reading organic vapor monitors are often used to measure volatile organic compound concentrations in complex chemical gas mixtures. However, there is a paucity of data on the impact of multiple gases on monitor performance, even though it is known that monitor sensitivity may vary by chemical. This study investigated the effects of interferents on the performance of the MIRAN SapphIRe Portable Ambient Air Analyzer (SAP) and Century Portable Toxic Vapor Analyzer (TVA-1000) when sampling a specific agent of interest (cyclohexane). The TVA-1000 contained a dual detector: a photoionization detector (PID) and a flame ionization detector (FID). Three devices of each monitor were challenged with different combinations of cyclohexane and potential interferent vapors (hexane, methyl ethyl ketone, trichloroethylene, and toluene) at 21°C and 90% relative humidity (RH), an extreme environmental condition. Five replicates at four target concentrations were tested: 30, 150, 300, and 475 ppm. Multiple proportions of cyclohexane to interferent enabled the determination of the interferent effect on monitor performance. The monitor concentrations were compared to reference concentrations measured using NIOSH Method 1500. Three scenarios were investigated: no response factor, cyclohexane response factor, and weighted-mixed response factor applied. False negatives occurred more frequently for PID (21.1%), followed by FID (4.8%) and SAP (0.2%). Measurements from all monitors generally had a positive bias compared to the reference measurements. Some monitor measurements exceeded twice the reference concentrations: PID (36.8%), SAP (19.8%), and FID (6.3%). Evaluation of the 95% confidence intervals indicated that performance of all monitors varied by concentration. In addition, the performance of the PID and SAP varied by presence of an interfering compound, especially toluene and hexane for the PID and trichloroethylene for the SAP. Variability and bias associated with all these monitors preclude supplanting traditional sorbent-based tube methods for measuring volatile organic compounds (VOCs), especially for compliance monitoring.</p><p>Implications: <i>Industrial hygienists need to use care when using any of the three monitor detection types to measure the concentration of unknown chemical mixtures. Monitor performance is affected by the presence of interferents. Application of manufacturer recommended response factors may not adequately scale measurements to minimize monitor bias when compared to standard reference methods. Users should calibrate their monitors to a known reference method prior to use, if possible. Each of the monitors has its own limitations, which should be considered to ensure quality measurements are reported.</i></p></div

    Volatile organic compounds mixtures in hospital environment: the common exposure scenario

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    EXPOsE—Establishing protocols to assess occupational exposure to microbiota in clinical settings (02/SAICT/2016 - Project nº 23222).Chemical contamination is a reality in the hospital environment but unfortunately is rarely studied. However, if we consider that healthcare workers use a high diversity of products such as disinfectants, sterilizers, anesthetic gases, and much other is easy to recognize that workers and patients can be exposed to a complex mixture of chemicals. The aim of this study was to determine, through a review, the presence of volatile organic compounds (VOCs) mixtures in a hospital environment. Results showed that a complex mixture of VOCs is normally present and this aspect should be reflected in the risk assessment process. Future research work must be developed related to the possible health effects caused by exposure to complex mixtures of chemicals.info:eu-repo/semantics/publishedVersio

    In vitro toxicological evaluation of surgical smoke from human tissue

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    Abstract Background Operating room personnel have the potential to be exposed to surgical smoke, the by-product of using electrocautery or laser surgical device, on a daily basis. Surgical smoke is made up of both biological by-products and chemical pollutants that have been shown to cause eye, skin and pulmonary irritation. Methods In this study, surgical smoke was collected in real time in cell culture media by using an electrocautery surgical device to cut and coagulate human breast tissues. Airborne particle number concentration and particle distribution were determined by direct reading instruments. Airborne concentration of selected volatile organic compounds (VOCs) were determined by evacuated canisters. Head space analysis was conducted to quantify dissolved VOCs in cell culture medium. Human small airway epithelial cells (SAEC) and RAW 264.7 mouse macrophages (RAW) were exposed to surgical smoke in culture media for 24 h and then assayed for cell viability, lactate dehydrogenase (LDH) and superoxide production. Results Our results demonstrated that surgical smoke-generated from human breast tissues induced cytotoxicity and LDH increases in both the SAEC and RAW. However, surgical smoke did not induce superoxide production in the SAEC or RAW. Conclusion These data suggest that the surgical smoke is cytotoxic in vitro and support the previously published data that the surgical smoke may be an occupational hazard to healthcare workers

    Multi-instrument assessment of fine and ultrafine titanium dioxide aerosols

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    The measurement of fine (diameter: 100 nanometers–2.5 micrometers) and ultrafine (UF: 2) particles is instrument dependent. Differences in measurements exist between toxicological and field investigations for the same exposure metric such as mass, number, or surface area because of variations in instruments used, operating parameters, or particle-size measurement ranges. Without appropriate comparison, instrument measurements create a disconnect between toxicological and field investigations for a given exposure metric. Our objective was to compare a variety of instruments including multiple metrics including mass, number, and surface area (SA) concentrations for assessing different concentrations of separately aerosolized fine and UF TiO2 particles. The instruments studied were (1) DustTrak™ DRX, (2) personal DataRAMs™ (PDR), (3) GRIMMTM, and (4) diffusion charger (DC). Two devices of each field-study instrument (DRX, PDR, GRIMM, and DC) were used to measure various metrics while adjusting for gravimetric mass concentrations of fine and UF TiO2 particles in controlled chamber tests. An analysis of variance (ANOVA) was used to apportion the variance to inter-instrument (between different instrument-types), inter-device (within instrument), and intra-device components. Performance of each instrument-device was calculated using root mean squared error compared to reference methods: close-faced cassette and gravimetric analysis for mass and scanning mobility particle sizer (SMPS) real-time monitoring for number and SA concentrations. Generally, inter-instrument variability accounted for the greatest (62.6% or more) source of variance for mass, and SA-based concentrations of fine and UF TiO2 particles. However, higher intra-device variability (53.7%) was observed for number concentrations measurements with fine particles compared to inter-instrument variability (40.8%). Inter-device variance range(0.5–5.5%) was similar for all exposure metrics. DRX performed better in measuring mass closer to gravimetric than PDRs for fine and UF TiO2. Number concentrations measured by GRIMMs and SA measurements by DCs were considerably (40.8–86.9%) different from the reference (SMPS) method for comparable size ranges of fine and UF TiO2. This information may serve to aid in interpreting assessments in risk models, epidemiologic studies, and development of occupational exposure limits, relating to health effect endpoints identified in toxicological studies considering similar instruments evaluated in this study.</p
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