Genotoxicity assessment using micronuclei assay in rheumatoid arthritis patients.

OBJECTIVES: This study investigated whether: (i) rheumatoid arthritis (RA) patients have more micronuclei (MN) than healthy controls; (ii) methotrexate (MTX) treated RA patients have more MN than those not using MTX, and (iii) folic acid supplementation decreases the number of MN in MTX treated patients. METHODS: MN assays were performed in oral mucosa sweeps of 50 consecutive MTX treated RA patients, 30 consecutive RA patients not receiving MTX and 39 healthy controls. MTX treated RA patients were then randomly placed in a cross-over design to receive folic acid supplementation, and MN assays were repeated after 6 weeks. RESULTS: The MTX-RA patients had a mean age of 46 +/- 10 yrs and a mean disease duration of 12 +/- 9 yrs; 80% were women. The MTX dose range was 8.7 +/- 1.5 mg/week and the mean duration of use was 16 +/- 18 months. In the non-MTX RA group, the mean age was 48 +/- 14 yrs, the mean disease duration was 13 +/- 9 yrs, and 87% were women. At baseline, the number of MN were significantly higher in RA patients as compared with controls (3.31 +/- 2.3 vs 0.8 +/- 0.8, p <0.001). No difference in MN numbers was observed between users and non-users of MTX. Folic acid supplementation did not decrease the MN number in the MTX treated RA patients. CONCLUSIONS: Genotoxicity, as assessed by the MN assay, is increased in RA patients. These results suggest that genotoxicity is associated with RA itself and not with MTX use. Folic acid supplementation had no effect on the number of MN.

Cell proliferation in nasal respiratory epithelium of people exposed to urban pollution.

The nasal passages are a common portal of entry and are a prime site for toxicant-induced pathology. Sustained increases in regenerative cell proliferation can be a significant driving force in chemical carcinogenesis. The atmosphere in Mexico City contains a complex mixture of air pollutants and its residents are exposed chronically and sequentially to numerous toxicants and potential carcinogens. We were concerned that exposure to Mexico City's atmosphere might induce cytotoxicity and increase nasal respiratory epithelial cell proliferation. Nasal biopsies were obtained for DNA cell cycle analysis from 195 volunteers. The control population consisted of 16 adults and 27 children that were residents in a Caribbean island with low pollution. The exposed Mexico City population consisted of 109 adults and 43 children. Sixty-one of the adult subjects were newly arrived in Mexico City and were followed for 25 days from their arrival. Control children, control adult and exposed Mexico City children all had similar percentages of cells in the replicative DNA synthesis phase (S phase) of the cell cycle (%S). A significant increase in %S in nasal epithelial cells was seen in exposed adult residents in Mexico City biopsied at three different dates compared with control adults. Newly arrived adults exhibited a control level of cell turnover at day 2 after coming to the city. However, at days 7, 14 and 25 they exhibited significant increases in %S. These data demonstrate an increased and sustained nasal cell turnover rate in the adult population observable in as little as 1 week of residence in Mexico City. This increase in cell proliferation is in agreement with other reports of induced pathological changes in the nasal passages of Mexico City dwellers. These observations suggest an increased potential risk factor of developing nasal neoplasms for residents of large cities with heavy pollution.

Revascularización coronaria sin circulación extracorpórea. UNa alternativa terapéutica. (Reporte preliminar) / Coronary evascularization without extracorporeal circulation. A therapeutic alternative

La cirugía de revascularización coronaria directa ha tenido gran auge desde sus inicios, ya que al paso de los años ha demostrado sus beneficios a corto y largo plazo. Rutinariamente hemos considerado que este procedimiento debe realizarse en asistolia y mediante el apoyo transoperatorio de la bomba de circulación extracorpórea. Las ventajas que la circulación extracorpórea proporciona durante el procedimiento son indudables; sin embargo, al paso de los años se han identificado diversas complicaciones íntimamente asociadas con dicho dispositivo. Es por ello que la revascularización coronaria sin apoyo de circulación extracorpórea, en casos bien seleccionados, ha encontrado un campo donde instalarse. En el presente artículo presentamos nuestra serie preliminar de cinco casos y nuestros resultados inmediatos, a la vez que revisamos las indicaciones y contraindicaciones, así como la técnica actual para realizar dicho procedimiento

Nasal inflammatory responses in children exposed to a polluted urban atmosphere.

Southwest Metropolitan Mexico City (SWMMC) preadolescent children have been exposed to a highly polluted urban atmosphere most of their lives. The main objective of this study was to determine by nasal lavage (NAL) the acute inflammatory nasal influx elicited in these children upon exposure to three different polluted days. Ozone, the main criteria pollutant for SWMMC, varied both in the number of hours above the National Ambient Air Quality Standard (NAAQS), which is 0.12 ppm as a 1-h maximum concentration not to be exceeded more than once per year, and in the maximal concentrations in the preceding three NAL sampling dates. Nasal neutrophilic influx, the surface expression of the B2 integrin CD11b on the nasal polymorphonuclear leukocytes (PMNs), rhinoscopic findings, respiratory symptoms, and nasal cytologies were evaluated in the 38 exposed children and in the 28 control children living in a nonpolluted Pacific coast port. SWMMC children had an average daily outdoor exposure of 7.7 h and complained of nasal mucus secretion, epistaxis, intermittent nasal obstruction, diurnal cough episodes, and chest discomfort. Nasal mucosal atrophy by rhinoscopy was present in 37/38, and all children had an abnormal nasal cytology. Exposed children had significantly higher nasal PMNs and nasal PMN-CD11b expression than controls. PMN median values in exposed children were higher than controls on all sampling dates (November 12, p < .001; November 17, p < .001; and November 24, p < .00001). Interestingly, a lower nasal neutrophilic response (p < .0004) was recorded in the SWMMC children 18 h after exposure to the highest O3 concentrations (up to 0.307 ppm) and the largest number of hours with O3 > 0.12 ppm (7 h). The question of a competing inflammatory response at the bronchioalveolar level with structural damage is raised. These NAL findings underscore the need to restrict outdoor activity in SWMMC children during the months of greater potential exposure to ozone.

Human nasal mucosal changes after exposure to urban pollution.

Millions of people worldwide are living in areas where ozone (O3) concentrations exceed health standards (an hourly average of 235 micrograms/m3/0.12 ppm, not to be exceeded more than once per year). Ozone induces acute nasal inflammatory responses and significant epithelial lesions in experimental animals and humans. To determine the nasal effects of a 15-day exposure to an urban polluted atmosphere with O3 as the main pollutant, we studied a population of healthy, young males newly arrived to southwest metropolitan Mexico City (SWMMC). The study included 49 non-smoking residents in an unpolluted port, Veracruz City; 14 subjects stayed in the port and served as controls, while 35 subjects traveled to SWMMC and had serial nasal lavages at different times after arriving in SWMMC. Subjects had exposures to ambient O3 an average of 10.2 hr/day, with a total cumulative O3 exposure of 10.644 ppm.hr. Nasal inflammatory responses, polymorphonuclear leukocyte PMN-CD11b surface expression, rhinoscopic changes, and respiratory symptoms were evaluated. Exposed subjects had massive nasal epithelial shedding and significant responses in PMN nasal influx (p < 0.00001) and in PMN-CD11b expression (p < 0.05). Cumulative O3 exposure correlated with respiratory symptoms, PMNs (rs = 0.2374, p < 0.01), and CD11b (rs = 0.3094, p < 0.01); 94% of exposed subjects experienced respiratory symptoms, and 97% left the city with an abnormal nasal mucosa by rhinoscopy. Nasal epithelial changes persisted 2 weeks after the exposed subjects returned to their nonpolluted environment. Exposure to an urban polluted atmosphere induces significant and persistent nasal epithelial alterations in healthy subjects.(ABSTRACT TRUNCATED AT 250 WORDS)