Sergio Márquez-Gamiño

CYP2E1 epigenetic regulation in chronic, low-level toluene exposure: Relationship with oxidative stress and smoking habit.

BACKGROUND CYP2E1 is a versatile phase I drug-metabolizing enzyme responsible for the biotransformation of most volatile organic compounds, including toluene. Human toluene exposure increases CYP2E1 mRNA and modifies its activity in leucocytes; however, epigenetic implications of this interaction have not been investigated. GOAL To determine promoter methylation of CYP2E1 and other genes known to be affected by toluene exposure. METHODS We obtained venous blood from 24 tannery workers exposed to toluene (mean levels: 10.86+/-7mg/m(3)) and 24 administrative workers (reference group, mean levels 0.21+/-0.02mg/m(3)) all of them from the city of León, Guanajuato, México. After DNA extraction and bisulfite treatment, we performed PCR-pyrosequencing in order to measure methylation levels at promoter region of 13 genes. RESULTS In exposed group we found significant correlations between toluene airborne levels and CYP2E1 promoter methylation (r=-.36, p<0.05), as well as for IL6 promoter methylation levels (r=.44, p<0.05). Moreover, CYP2E1 promoter methylation levels where higher in toluene-exposed smokers compared to nonsmokers (p=0.009). We also observed significant correlations for CYP2E1 promoter methylation with GSTP1 and SOD1 promoter methylation levels (r=-.37, p<0.05 and r=-.34, p<0.05 respectively). CONCLUSION These results highlight the importance of considering CYP2E1 epigenetic modifications, as well as its interactions with other genes, as key factors for unraveling the sub cellular mechanisms of toxicity exerted by oxidative stress, which can initiate disease process in chronic, low-level toluene exposure. People co-exposed to toluene and tobacco smoke are in higher risk due to a possible CYP2E1 repression.

CYP2E1 phenotype in Mexican workers occupationally exposed to low levels of toluene

UNLABELLED CYP2E1, an inducible enzyme present in different human tissues, metabolizes several potentially toxic substances including many volatile organic compounds (VOCs). One indirect way to monitor exposure to VOCs may be, therefore, the assessment of CYP2E1 activity in vivo using the chlorzoxazone (CHZ) test. GOAL To compare CYP2E1 activity in two groups of workers: one with a known occupational exposure to VOCs (exposed group) and the other employed in administrative tasks at two universities (control group) from the city of León, Guanajuato, México. MATERIAL AND METHODS (1) Passive diffusion monitors were used to evaluate individual levels of exposure to toluene, benzene and ethylbenzene in 48 persons (24 tannery workers and 24 administrative controls) during a 8h work shift; (2) after 12h fasting 500mg CHZ, a selective probe for assessing CYP2E1 activity, was orally administered and, after 2h, a venous blood sample was collected for HPLC plasmatic quantitative determination of CHZ and its mean metabolite 6-hydroxychlorzoxazone. RESULTS Toluene mean exposure levels were higher in the exposed group (2.86±2ppm vs. 0.05±0.005ppm; p<0.001). Also, in this group CYP2E1 activity was lower (p<0.05) and it decreased as the accumulated months of labor exposure increased (negative correlation, p<0.05). These results are in line with previous findings obtained from shoemakers exposed to various solvents but, interestingly, they are partly in contrast with those of another study in printers. CONCLUSION In spite of the relatively low levels of toluene exposure found for tannery workers, an effect on CYP2E1 activity was evident. Although the mechanism of this interaction is still unknown, the decrease in CYP2E1 activity per se might represent a health risk, considering that these workers may be less protected against other CYP2E1 substrates present in the labor setting or derived from an intentional exposure.

Overview of Sleep Disorders Among Latinos in the United States

Latinos are the fastest growing minority group in the United States. Factors such as sleep quality and sleep disorders that may impact the health of this segment of the U.S. population are important now, and will be increasingly meaningful in the future. This overview of sleep disorders among Latino youth and adults identifies gaps in the literature and serves as a springboard for future sleep promotion, prevention, and intervention studies for Latino populations in the United States. Language, culture care, and access to care issues that need to be addressed in research and in clinical practice for Latinos are also described. La poblacion latina es el grupo minoritario de crecimiento mas rapido en los Estados Unidos. Existen factores como la calidad del sueno y los trastornos del sueno que pueden afectar la salud de este segmento de rapido crecimiento de la poblacion de los Estados Unidos que son importantes ahora, y seran cada vez mas significativos en el futuro. Esta vision general de los trastornos del sueno entre los jovenes latinos y adultos senala las deficiencias en la literatura y sirve como un trampolin para futuros estudios de promocion, prevencion e intervencion del sueno en poblaciones latinas en los Estados Unidos. Asimismos se describen temas como el lenguaje, el cuidado cultural y el acceso a la atencion medica de los latinos que necesitan ser abordados en la investigacion y en la practica clinica.

0226 Affection in the auditory brainstem pathway associated with occupational, low-level exposure to ethylbenzene

Introduction Hearing loss in occupational exposure to a solvent mixture has been already reported; however, mixture in those reports did not contain ethylbenzene, a compound showing peripheral ototoxicity in animals exposed to high levels. In this work, we evaluated the auditory brainstem pathway in two samples of workers exposed to different levels of a solvent mixture where ethylbenzene was present, compared to a reference group. Material and methods Individual exposure levels for up to seven compounds were obtained in two groups: Exposed (n=21 gas station attendants, GS, and leather shoe factory workers, LS) and Non-exposed (n=21, administrative workers) all of them from the city of León Guanajuato, México. The click-evoked auditory brainstem response test was performed in both groups. Results Toluene, n-hexane, acetone, ethylbenzene, xylene and methyl ethyl ketone exposure levels were higher in LS (p<0.001). Only n-hexane exposure levels were above the permissible levels, while mean ethylbenzene exposure levels ranged 0.4–14.58 mg/m3. Wave V latency at four different points of stimulation for both ears was delayed in the exposed group, as well as the I-V and I-III interwave latencies at 70 dB (p<0.05). LS workers showed a delayed I-III interpeak interval compared to non-exposed group. Also in LS, ethylbenzene exposure levels showed a significant correlation with wave V latency at 40 dB (r=0.8, p=0.008). Conclusion Our results point out to a central affection in the auditory system caused by ethylbenzene in a dose response manner. Workers exposed to ethylbenzene levels far below the permissible exposure limit should be closely monitored for early ototoxicity effects.

Affection in the auditory brainstem pathway associated with occupational, low-level exposure to ethylbenzene

Introduction Hearing loss in occupational exposure to a solvent mixture has been already reported; however, mixture in those reports did not contain ethylbenzene, a compound showing peripheral ototoxicity in animals exposed to high levels. In this work, we evaluated the auditory brainstem pathway in two samples of workers exposed to different levels of a solvent mixture where ethylbenzene was present, compared to a reference group. Material and methods Individual exposure levels for up to seven compounds were obtained in two groups: Exposed (n=21 gas station attendants, GS, and leather shoe factory workers, LS) and Non-exposed (n=21, administrative workers) all of them from the city of León Guanajuato, México. The click-evoked auditory brainstem response test was performed in both groups. Results Toluene, n-hexane, acetone, ethylbenzene, xylene and methyl ethyl ketone exposure levels were higher in LS (p<0.001). Only n-hexane exposure levels were above the permissible levels, while mean ethylbenzene exposure levels ranged 0.4–14.58 mg/m3. Wave V latency at four different points of stimulation for both ears was delayed in the exposed group, as well as the I-V and I-III interwave latencies at 70 dB (p<0.05). LS workers showed a delayed I-III interpeak interval compared to non-exposed group. Also in LS, ethylbenzene exposure levels showed a significant correlation with wave V latency at 40 dB (r=0.8, p=0.008). Conclusion Our results point out to a central affection in the auditory system caused by ethylbenzene in a dose response manner. Workers exposed to ethylbenzene levels far below the permissible exposure limit should be closely monitored for early ototoxicity effects.

PEMF effects on chondrocyte cellularity and gene expression of the rat distal femoral metaphyseal articular cartilage

the purpose of the current study was to determine the effect of PEMF on the rat distal femoral joint cartilage, in terms of chondrocytic gene expression level and cellularity. 20 Wistar female rats from two litters were randomly distributed in two groups: 10 rats (Stimulated Group) received PEMF (1 Hz, 30 mT/30 min per day/20 days in a row); the other 10 animals (Control Group) received similar treatment, with the difference that the electromagnetic stimulation was turned off. After the experimental intervention, thin histological sections were analyzed under Clear Field Microscopy in order to quantify chondrocytic cellularity. In addition, specific chondrocyte proteins expression was measure. Statistically significant differences were found in joint cartilage cellularity when MS and Non-MS were compared (101.13 ± 25.61 vs. 69.66 ± 15.55 cells per optical field, respectively; p=0.001). Collagen XI, Sox6 and Aggrecan expression levels were also different in magnetically stimulated tissues relative to control. On the other hand RUNX2 and ALPL expressions showed no significant differences between groups (X-squared test p < 0.05). These results are evidence that in vivo PEMF stimulation increases the number of well differentiated knee joint cartilage cells in healthy young adult rats. The low gene expression of RUNX2 and ALPL supports that the chondrocytic response to PEMF do not correspond to a hypertrophic reaction. These results highlight the possible therapeutic future of PEMF in cartilage injuries, and on its ageing.

EMGs Analysis of Lumbar, Pelvic and Leg Muscles in Leg Length Discrepancy Adolescents

To evaluate differences in surface electromyography (EMGs) activity of lumbar, pelvic and leg muscles in adolescents with and without LLD. EMGs activity records were taken during rest and maximal isometric voluntary contractions (MIVC). Peak to peak amplitude (PPA), mean rectified voltage (MRV) and root mean square (RMS), were analyzed. Statistical differences between short and large sides of LLD adolescents, were found (p<0.05). Higher values occurred in shorter limb muscles. No significative differences were found between left and right legs of the control subjects. When EMGs values were compared between short and large sides of LLD subjects with ipsilateral sides of controls, selective, statistically different EMGs values were exhibited. It is suggested that adaptative behavior to secondary biomechanical and/or neural changes occurred, even when none clinical symptoms were reported. The observations were remarked by the absence of EMGs differences between right and left sides of control subjects.