Micronucleus test for monitoring genotoxicity of polluted river water in Rana catesbeiana tadpoles.
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Animals↗
Biomedical subjects
P H Saldiva
Publications and source records attributed to P H Saldiva.
Health effects of air pollution exposure on children and adolescents in São Paulo, Brazil.
Children and adolescents have been considered more susceptible to the effects of air pollution than adults. In order to investigate the responses of children of different ages to air pollution exposure, daily records of hospital admissions for children in five age groups (equal or less than 2 years of age, 3-5, 6-13, 14-19, and all ages together, i.e., from 0-19 years of age) were obtained from January 1993 to November 1997 in São Paulo, Brazil, and were compared to daily records of PM10, O3, SO2, CO and NO2 concentrations in ambient air. For each age group a generalized additive Poisson regression was fitted controlling for smooth functions of time, temperature, humidity, and days of the week, with an additional indicator for holidays. Polynomial distributed lag models were used to estimate the 7-day cumulative effect of each pollutant. Children 2 years or less were the most susceptible to the effects of all five pollutants with an increase of 9.4% (95% CI: 7.9,10.9) in respiratory admissions associated with each interquartile range increase in PM10. The oldest group was the second most susceptible to air pollutants, with each interquartile range increase in PM10 associated with a 5.1% (95% CI: 0.3,9.8) increase in respiratory admissions. An interquartile range increase in CO was associated with an 11.3% (95% CI: 5.9,16.8) increase in respiratory hospitalizations. When a multipollutant model was used, the effect of PM10 on respiratory admissions for all ages together was unchanged, while the SO2 and the other pollutants effect was substantially reduced. This study showed that daily respiratory hospital admissions for children and adolescents in São Paulo increased with air pollution, and that the largest effects were found for the youngest (2 years or less) and oldest (14-19 years) age groups.
Adolescent↗
Tadpole epithelium test: potential use of Rana catesbeiana histopathologic epithelial changes to evaluate aquatic pollution.
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Animals↗
Simultaneous occurrence of lymphoepithelial cysts, cytomegalovirus and mycobacterial infections in the intraparotid lymph nodes of a patient with AIDS.
We report the unusual simultaneous occurrence of lymphoepithelial cysts, cytomegalovirus (CMV) and mycobacterial infections in the intraparotid lymph nodes of a 52-year-old AIDS patient who died of disseminated mycobacteriosis. Although cytomegalovirosis is a common finding in the salivary glands of HIV patients, the association of CMV inclusions with lymphoepithelial cyst (LC) has not been previously reported. Parotid mycobacterial infection is an uncommon finding, despite its usual disseminated presentation in HIV patients. These data emphasize that in immunosuppressed patients, simultaneous diseases of the parotid gland may occur and should be considered for diagnosis and treatment.
AIDS-Related Opportunistic Infections↗
A rat model of acute lung injury induced by cardiopulmonary bypass.
Impaired lung function is still a major complication after cardiac surgery with cardiopulmonary bypass. The purpose of the present study was to develop an experimental model of acute pulmonary injury induced by cardiopulmonary bypass in Wistar rats. Cardiopulmonary bypass was performed for 60 min using a non-pulsatile roller pump and a membrane oxygenator (n = 8 for cardiopulmonary bypass group and n = 7 for control rats). We measured tracheal pressure, airflow, and lung volume changes and obtained pulmonary resistance and dynamic elastance. After the cardiopulmonary bypass, lungs were submitted to a quick-freezing protocol and morphometric analysis was performed. There was a time-dependent increase in dynamic elastance, but not pulmonary resistance, only in the rats submitted to cardiopulmonary bypass (P = 0.005). Lungs from animals submitted to cardiopulmonary bypass showed significantly more alveolar hemorrhage (P = 0.025) and edema (P = 0.021), as well as perivascular edema (P = 0.003) when compared to control rats. In our experimental model, rats submitted to cardiopulmonary bypass developed acute pulmonary changes similar to the early phase of acute pulmonary distress syndrome. Cardiopulmonary bypass resulted in an increase in pulmonary elastance without changes in resistance. This experimental model is suitable for studies concerning the mechanisms of acute lung injury induced by cardiopulmonary bypass.
Animals↗
Effects of mannitol on the acute lung injury induced by oleic acid in rats.
Our purpose was to evaluate the pulmonary effects of mannitol infusion in a rat model of acute lung injury induced by oleic acid (OA) to compare the effects of mannitol to those of another diuretic, furosemide (FUR), and to assess if mannitol effects remained after correction of the volume depletion induced by this agent. Acute lung injury was induced in Wistar rats by intravenous administration of 100 mg/kg of OA. Mannitol (1 mL of a 20% solution) was infused either 15 min before or 2 h after OA infusion. FUR was infused intravenously in a dose (1 mg/kg) that induced a similar amount of diuresis compared to mannitol. We also studied rats that received NaCl 0.9% infusion to correct for volume losses induced by mannitol. The severity of the acute lung injury was evaluated by morphometric studies of the lungs 4 h after OA infusion. The amount of intraalveolar fluid accumulation and the intensity of alveolar distention and collapse were evaluated. Mannitol infusion either 15 min before or 2 h after OA administration resulted in a significant decrease in the amount of intraalveolar edema and alveolar distention and collapse (P < 0.001). FUR administration before OA infusion had an effect similar to mannitol. We did not observe any significant effect of mannitol when the rats received saline infusion to correct for diuresis induced by mannitol. We conclude that mannitol decreases the severity of pulmonary injury induced by OA in rats. This effect is mainly due to its diuretic properties.
Animals↗
Air pollution and child mortality: a time-series study in São Paulo, Brazil.
Although most available evidence relating air pollution and mortality was obtained for adults, pollution has been also associated with increased mortality in children, but in a significantly smaller number of studies. This study was designed to evaluate the association between child mortality and air pollution in the city of São Paulo, Brazil, from 1994 to 1997. Daily records of mortality due to respiratory diseases for children under 5 years of age were obtained from the municipal mortality information improvement program. Daily concentrations of sulfur dioxide (SO(2)), carbon monoxide (CO), inhalable particulate matter less than 10 microm in diameter (PM(10)), and ozone were obtained from the state air pollution controlling agency. Information on minimum daily temperature and on relative humidity were obtained from the Institute of Astronomy and Geophysics of the University of São Paulo. Statistical analysis was performed through generalized additive models considering a Poisson response distribution and a log link. Explanatory variables were time, temperature, humidity, and pollutant concentrations. The loess smoother was applied to time (in order to model seasonality) and temperature. Significant associations between mortality and concentrations of CO, SO(2), and PM(10) were detected. The coefficients (and standard errors) of these three pollutants were 0.0306 (0.0076), 0.0055 (0.0016), and 0.0014 (0.0006), respectively. The observed associations were dose dependent and quite evident after a short period of exposure (2 days). According to the proposed model and considering the mean of the pollutant concentration during the period of the study, the estimated proportions of respiratory deaths attributed to CO, SO(2), and PM(10), when considered individually, are around 15, 13, and 7%, respectively.
Air Pollution↗
Effects of bronchial transection and reanastomosis on mucociliary system.
STUDY OBJECTIVES: The mechanisms involved in the impairment of mucociliary function after lung transplantation are not completely understood. The purpose of the present study was to isolate the effects of unilateral bronchial transection and reanastomosis in a rat model. DESIGN: In situ bronchial mucociliary transport (MCT) was determined proximal and distal to the bronchial anastomosis, as well as in the right bronchus, in 48 rats classified into six groups: intact rats, and rats at 1 day, 2 days, 7 days, 15 days, and 30 days after bronchial transection and reanastomosis of the left main stem bronchus. In vitro mucus transportability and mucus contact angle were studied in another group of eight rats after 1 week of surgery. RESULTS: Distal to the anastomosis site, left bronchus in situ MCT (mean +/- SD) was 0.26 +/- 0.19 mm/min for the intact group, and 0.11 +/- 0.13 mm/min, 0.07 +/- 0.04 mm/min, 0.03 +/- 0.04 mm/min, 0.07 +/- 0.12 mm/min, and 0.05 +/- 0.06 mm/min for 1 day, 2 days, 7 days, 15 days, and 30 days after surgery, respectively (all significantly reduced, p < 0.05). No intergroup differences were found proximal to the anastomosis (p = 0.30). When comparing the left and right bronchi, differences were detected in both distal (p < 0.0001) and proximal sides (p = 0.0001). No significant differences in mucus transportability in vitro were found (p = 0.15). Mucus contact angle of the left bronchus (52.8 +/- 20.5 degrees ) was significantly greater than that of the mucus from the right bronchus (34.4 +/- 12.9 degrees; p < 0.05). CONCLUSIONS: We conclude that bronchial transection and reanastomosis lead to a marked impairment of MCT in distal airways, which can in part be explained by alterations in the surface properties of mucus.
Anastomosis, Surgical↗
Effects of formaldehyde on the frog's mucociliary epithelium as a surrogate to evaluate air pollution effects on the respiratory epithelium.
The increasing use of alcohol as an alternative fuel to gasoline or diesel can increase emission of formaldehyde, an organic gas that is irritant to the mucous membranes. The respiratory system is the major target of air pollutants and its major defense mechanism depends on the continuous activity of the cilia and the resulting constant transportation of mucous secretion. The present study was designed to evaluate the effects of formaldehyde on the ciliated epithelium through a relative large dose range around the threshold limit value adopted by the Brazilian legislation, namely 1.6 ppm (1.25 to 5 ppm). For this purpose, the isolated frog palate preparation was used as the target of toxic injury. Four groups of frog palates were exposed to diluted Ringer solution (control, N = 8) and formaldehyde diluted in Ringer solution at three different concentrations (1.25, 2.5 and 5.0 ppm, N = 10 for each group). Mucociliary clearance and ciliary beat frequency decreased significantly in contact with formaldehyde at the concentrations of 2.5 and 5.0 ppm after 60 min of exposure (P<0.05). We conclude that relatively low concentrations of formaldehyde, which is even below the Brazilian threshold limit value, are sufficient to cause short-term mucociliary impairment.
Air Pollutants↗
Morphometric differences in pulmonary lesions in primary and secondary ARDS. A preliminary study in autopsies.
The present study was undertaken in order to describe the morphological differences between pulmonary lesions in acute respiratory distress syndrome originating from direct pulmonary injury (ARDSp) and those originating from extrapulmonary injury (ARDSexp). We investigated a total of 38 ARDS-patients (27 males) ranging in age from 19 to 75 years, classified according to underlying disease in pulmonary (ARDSp) and extrapulmonary disease (ARDSexp). The extent of acute diffuse alveolar damage was assessed morphometrically on histologic gross sections in the upper and lower lobes of one lung. The lesions showed quantitative differences in extent and distribution according to underlying disease (primary pulmonary or secondary involvement). In pulmonary ARDS, a predominance of alveolar collapse (16.6%+/-12.3% versus 10.3%+/-11.9%, p = 0,03), fibrinous exudate (1.7%+/-3.2% versus 0.4%+/-1.1%, p = 0.01) and alveolar wall edema (11.2%+/-7.4% versus 6.6%+/-4.4%, p = 0,05) were found compared to extrapulmonary ARDS. We conclude that the morphology of acute diffuse alveolar damage (DAD) is mainly determined by underlying disease (pulmonary ARDS or extrapulmonary ARDS) differing in quantitative terms within the lung. Physiological, radiographic and respiratory system mechanics differences described in ARDSp and ARDSexp may therefore be due to morphometric differences in pulmonary lesions.
Adult↗
The effects of systemic hormonal replacement therapy on the skin of postmenopausal women.
OBJECTIVE: The aim of this study was to determine the effects of hormonal replacement therapy on the skin of postmenopausal women. METHOD: Forty-one postmenopausal women were randomly allocated to receive either hormonal replacement (valerate estradiol--2 mg/day for 21 days and cyproterone acetate--1 mg/day for 10 days) or placebo, both in a cyclic scheme for 6 months. Neither patients nor investigators were aware of the group allocation. Histologic changes were evaluated by skin biopsy of the left upper arm at baseline and after 6 months of treatment, utilizing computerized image analysis to assess the ratio area of epidermis/basement membrane length (AE/BML), ratio area of keratin/basement membrane length (AK/BML) and collagen and elastic fibers content. RESULT: Collagen content of the left upper arm increased after 6 months of treatment only in the hormonal group (+6.49%; P < 0.05). Other parameters did not present any significant alteration after treatment in both groups. CONCLUSION: Hormonal replacement for climacterics increases skin collagen content.
Collagen↗
Urban levels of air pollution modifies the progression of urethane-induced lung tumours in mice.
This paper investigates the effects of air pollution in urethane-induced lung tumours in mice by means of histological, morphometrical, and DNA ploidy. The experimental exposure was done in locations with different air pollution profiles: a polluted area (downtown São Paulo) and a "clean" environment. Swiss mice were employed and urethane (3 g/kg) was used as a carcinogenic substance. All the animals, whether exposed or not to air pollution, were sacrificed after 6 months, and the lung lesions were analysed. The results showed a significant effect of air pollution on tumour progression, observed by changes in the phenotype of the tumour cells as demonstrated by morphometry and DNA ploidy. We observed more atypical adenomas in the air pollution-exposed group (p = 0.02). Coherently, morphometric differences were also detected between the two groups. Neoplasms of exposed mice exhibited an increase in the nuclear fraction (p = 0.002) and in the nucleus/cytoplasm ratio (p = 0.011), as a decrease in the stromal fraction (p < 0.001). There was a higher risk of aneuploidy in the 6-months-of-air-pollution-exposure group (relative risk: 1.58; 95% of confidence interval: 1.007 to 2.403). These results indicate that urban air pollution accelerates the process of progression towards malignancy.
Adenoma↗
Lipid emulsion reduces subacute toxicity of amphotericin B: a histopathological study.
In previous work acute toxic effects of amphotericin B (AB) were reduced in both in vitro and in vivo tests when AB was associated with a triglyceride-rich emulsion (AB-emulsion). The present paper compares the severity of the histopathological alterations as determined by morphometry produced in the target tissues (kidneys, liver, and lungs) by AB-emulsion with those produced by the conventional formulation AB-deoxycholate (DOC) following subacute AB treatment. No morphological alterations were seen in the spleen and heart following both AB-DOC and AB-emulsion treatment. Although the alterations in the liver, kidneys and lungs are basically the same for both formulations, the intensity of the changes varies considerably. AB-emulsion always caused statistically decreased severity of morphologic alterations, compared to AB-DOC by stereological measurements, for the three treatment regimes of AB-administration. These three treatment regimens consisted of 1 mg AB/kg of body weight every 48 hours for 20 days, 2 mg AB/kg of body weight every 48 hours for 12 days, and 2 mg AB/kg of body weight for 4 consecutive days. Thus, these regimens consisted of total doses varying from 8-12 mg/kg of body weight. Specifically, these morphological changes included proximal and distal tubular edema, inflammation and tubular cell degeneration in the kidney and a moderate inflammation of the portal region in the liver. Vacuolization of hepatocytes only occurred for AB-DOC treatment. In addition, acute interstitial inflammation was observed in the lungs prior to interstitial and alveolar edema. The intensity of the histopathological damage increase with the dose and with the reduction in the time interval between AB administrations. Abnormal serum biochemical parameters were observed for serum urea which was higher for both treated AB-groups, as compared to control, and for iron which was lower for the AB-DOC group. In conclusion, the decreased severity of the morphological alterations in the kidneys, liver, and lungs following subacute treatment with AB-emulsion, as compared to AB-DOC formulation, confirms our previous results consisting of acute toxic effects induced by in vitro and in vivo tests with AB-emulsion treatment.
Amphotericin B↗
Prognostic values of stromal proportion and PCNA, Ki-67, and p53 proteins in patients with resected adenocarcinoma of the lung.
Data from 64 patients who underwent surgical resection of lung adenocarcinomas were studied to identify clinicopathologic markers that might provide prognostic information on the clinical behavior of this neoplasia Patient staging was performed in accordance with the tumor-node-metastasis system as follows: Stage I (n = 29), Stage II (n = 11), Stage IIIA (n = 21), and Stage IIIB (n = 3). Overall follow-up time corresponded to the follow-up time for patients who were alive and to the survival time for patients who had died, all of them expressed in months. Data included age, staging, histologic type, morphometric assessment of histologic features related to tumor (stroma and vascularization), and immunohistochemical detection of proliferation cell markers (Ki-67 protein and proliferating cell nuclear antigen) and p53 protein. The morphometric assessment was made by the point-counting procedure. Data analysis included Life Tables for Survival and Cox Regression models. Overall follow-up analysis showed that significant univariate predictors (P < .05) were T stage; N stage; tumor stromal proportion; and immunohistochemical indexes of proliferating cell nuclear antigen, Ki-67, and p53 proteins. Variables that presented independent predictive value for overall follow-up with the multivariate model (P < .05) were sex, T stage, N stage, tumor stromal proportion, and immunohistochemical detection of p53 protein. We conclude that tumor stromal proportion and immunohistochemical detection of p53 protein, controlled for sex, T stage, and N stage, may be of critical value in the evaluation of recurrence of lung adenocarcinoma, serving as indicators for a more accurate prognosis.
Adenocarcinoma↗
Uncommon histopathological findings in fatal measles infection: pancreatitis, sialoadenitis and thyroiditis.
AIMS: We report uncommon histopathological findings in fatal measles infection. METHODS AND RESULTS: We describe the autopsies of four patients who died during a measles outbreak in São Paulo, Brazil, in 1997. Two of the patients were children receiving chemotherapy for non-Hodgkin's lymphoma, one was an adult with acquired immunodeficiency syndrome (AIDS) and the fourth was an apparently healthy woman. All patients had their deaths attributed to measles pneumonia. The autopsies revealed extensive giant cell pneumonia and diffuse alveolar damage, severe acute pancreatitis, necrotizing sialoadenitis and thyroiditis due to measles. Measles antigen was detected in lung tissue using a monoclonal anti-measles antibody. CONCLUSIONS: : Pancreatitis, thyroiditis and sialoadenitis are not previously reported histopathological findings in measles infection. Pancreatitis is a potentially severe complication and should be considered when treating patients with atypical measles.
Adolescent↗
Architectural remodelling in acute and chronic interstitial lung disease: fibrosis or fibroelastosis?
AIMS: Pulmonary fibrosis in acute and chronic lung disease has been much investigated, but little attention has been directed at the elastic tissue in these situations. Our aim was to verify whether elastic deposition accompanies collagen deposition in the repairing process of acute and chronic lung injury. METHODS AND RESULTS: We measured, by image analysis, the content of fibres of the collagenous and elastic systems of the alveolar septum in histological slides sampled from autopsied lungs, using the picrosirius-polarization method and Weigert's resorcin-fuchsin stain, respectively. Five groups were studied: I, 10 normal patients; II, 10 patients with cardiogenic pulmonary oedema; III, 23 adult respiratory distress syndrome (ARDS) patients in the early phase; IV, 14 ARDS patients in the late fibroproliferative phase; and V, 10 idiopathic pulmonary fibrosis patients. The first two groups were used as controls. The content of fibres of the collagenous and elastic systems was significantly increased in groups IV and V as compared to the other groups. CONCLUSIONS: Our results indicate that deposition of elastic system fibres is present in the fibroproliferative phase of ARDS and in usual interstitial pneumonia and suggest that this event may contribute to the alveolar mechanical dysfunction and remodelling that occur in acute and chronic interstitial lung disease.
Acute Disease↗
Assessment of the effects of sugar cane plantation burning on daily counts of inhalation therapy.
This study was designed to evaluate the association between sugar cane plantation burning and hospital visits in Araraquara in the state of São Paulo, Brazil. From June 1 to August 31, 1995, the daily number of visits of patients who needed inhalation therapy in one of the main hospitals of the city was recorded and used as health impairment estimation. Sedimentation of particle mass (the amount of particles deposited on four containers filled with water) was measured daily. The association between the weight of the sediment and the number of visits was evaluated by means of Poisson regression models controlled for seasonality, temperature, day of the week, and rain. We found a significant and dose-dependent relationship between the number of visits and the amount of sediment. The relative risk of visit associated with an increase of 10 mg in the sediment weight was 1.09 (1-1.19), and the relative risk of an inhalation therapy was 1.20 (1.03-1.39) on the most polluted days (fourth quartile of sediment mass). These results indicate that sugar cane burning may cause deleterious health effects in the exposed population.
Agriculture↗
In situ monitoring of the mutagenic effects of the gaseous emissions of a solid waste incinerator in metropolitan São Paulo, Brazil, using the Tradescantia stamen-hair assay.
The present work was designed to determine the potential genotoxicity at the vicinity of a solid waste incinerator in the metropolitan area of São Paulo, using the Tradescantia stamen-hair bioassay. Experiments were carried out between December 1998 and April 1999 in four regions (40 pots of plants per site) selected on the basis of their pollution levels predicted by theoretical modeling of the dispersion of the incinerator's plume. The exposure sites were defined as follows: highest level (incinerator); a high level (museum) located 1.5 km from the emission point; a moderate level (school, at a distance of 3.5 km from the incinerator); and a control (at Jaguariúna countryside). The difference in genotoxicity among the groups was statistically significant (p < 0.001). The frequency of mutations observed in the countryside was significantly lower [2.25 +/- 1.55, mean +/- SD (standard deviation)] than that of the sites close to the incinerator. The frequency of mutations measured at the school (3.70 +/- 1.36) was significantly lower than that measured at both the museum (4.89 +/- 1.12) and the incinerator (5.69 +/- 1.34). In conclusion, we found a positive correlation between the spatial distribution of the emissions of the incinerator located in an urban area and the mutagenic events measured by the Tradescantia stamen-hair assay. The in situ approach employed in this study was simple, efficient, and of low cost. No air or chemical extraction of pollutants was necessary for genotoxicity testing as required by other assays.
Air Pollutants↗