The effects of exercise training on the lungs and cardiovascular function of animals exposed to diesel exhaust particles and gases.

Air pollution has been identified as one of the main environmental risks to health. Since exercise training seems to act as an anti-inflammatory modulator, our hypothesis is that exercise training prevents damage to respiratory and cardiovascular function caused by diesel exhaust particle (DEP) exposure. This study aimed to evaluate whether aerobic exercise training prior to DEP exposure prevents inflammatory processes in the pulmonary and cardiovascular systems. Therefore, BALB/C male mice were or were not submitted to a 10-week exercise training protocol (5×/week, 1 h/d), and after four weeks, they were exposed to DEP in a chamber with 24 µg/m3 PM2.5 or filtered air. Heart rate variability, lung mechanics and bronchoalveolar lavage fluid, cytokines and polymorphonuclear cells in the lung parenchyma were evaluated. Exposure to DEPs reduced heart rate variability and the elastance of the respiratory system and increased the number of cells in bronchoalveolar lavage fluid, as well as macrophages, neutrophils and lymphocytes, the density of polymorphonuclear cells and the proportion of collagen fibres in the lung parenchyma. Additionally, DEP-exposed animals showed increased expression of IL-23 and IL-12p40 (proinflammatory cytokines) and inducible nitric oxide synthase. Exercise training avoided the increases in all these inflammatory parameters, except the elastance of the respiratory system, the amount of collagen fibres and the expression of inducible nitric oxide synthase. Additionally, trained animals showed increased expression of the anti-inflammatory cytokine IL-1ra. Although our data showed a reduction in proinflammatory markers and an increase in markers of the anti-inflammatory pathway, these changes were not sufficient to prevent damage to the lung and cardiovascular function induced by DEPs. Based on these data, we propose that aerobic exercise training prevents the lung inflammatory process induced by DEPs, although it was not sufficient to avoid chronic damage, such as a loss of lung function or cardiovascular events.

Laringocele mixto. Reporte de caso / Mixed laryngocele. Case report

El laringocele es una afección benigna de laringe. Está relacionada con el desarrollo embriológico del sáculo y constituye una mal-formación congénita. Es más frecuente en el sexo masculino y sexta década de la vida. Suele tener diferentes presentaciones clínicas que generan diversas modalidades de tratamiento. Se presenta un caso clínico de paciente femenina con aumento de volumen cervical y en exploración clínica e imagenológica se diagnosticó un laringocele mixto que requirió tratamiento con cirugía de cuello

Laryngocele is a benign condition of the larynx. It is related to the embryological development of the saccule and constitutes a congenital malformation. It is more frequent in males and sixth decade of life. It usually has different clinical presentations that generate different treatment modalities. A clinical case of a female patient with an increase in cervical volume is presented, and a clinical and imaging examination diagnosed a mixed laryngocele that required treatment with neck surgery

Tumor de cavum: quiste de thornwaldt. Reporte de un caso / Cavum tumor: thornwaldt's cyst. Case report

El quiste de Thornwaldt es un tumor benigno de cavum, poco frecuente, generalmente asintomático, pero puede llegar a causar sintomatología significativa según su tamaño. Se genera a partir de un resto embrionario de la notocorda. Suele ser un hallazgo incidental en los estudios endoscópicos e imagenológicos y su tratamiento depende de su sintomatología. Presentamos el caso de una paciente de 27 años de edad quien acudió a nuestro servicio con sintomatología caracterizada por obstrucción nasal, rinolalia y disfagia de dos años de evolución, secundarios a una tumoración de cavum hallada en la faringoscopía, la cual requirió tratamiento quirúrgico para su resolución

Thornwaldt's cyst is a rare benign cavum tumor usually asymptomatic, but it can cause significant symptoms depending on its size. Its generated from an embryological rest of the notochord. It is usually an incidental finding in endoscopic and imaging studies and its treatment depends on the symptoms. We present the case of a 27-year-old female patient who came to our service with symp-toms characterized by nasal obstruction, rhinolalia and dysphagia of two years of evolution secondary to a cavum tumor found in pharyngoscopy, which required surgical treatment for resolution

Osteoma gigante fronto-etmoidal: presentación de caso / Fronto-ethmoidal giant osteoma: report case

El osteoma, es un tumor formador de hueso de etiología benigna, presenta un diámetro aproximado menor de 2 cm. Su localización más frecuente son los senos paranasales, bien sea endostal o parostal, su presentación clínica puede ser asintomática hasta producir dolor nocturno intenso en la zona afectada que a menudo simula un cuadro de rinosinusitis, el cual cede tras la administración de analgésicos. Los estudios por imagen, contribuyen en su diagnóstico y localización. La resección del mismo, permite mejorar la calidad de vida en los pacientes que lo padecen. Se presenta el caso clínico de una paciente femenina de 33 años de edad quien consulta por dolor en región paranasal de predominio nocturno que cede tras la administración de analgésicos. El estudio tomográfico confirmó la presencia de una lesión de densidad cálcica en región fronto-etmoidal, se realizó exéresis de la lesión y el estudio anatomopatológico confirmo su naturaleza

Osteoma, is a bone-forming tumor of benign etiology, has an approximate diameter of less than 2 cm. Its most frequent location is the paranasal sinuses, either endostal or parostal, it can be asymptomatic until it shows intense nocturnal pain in the affected area that often simulates a rhinosinusitis picture, which can manifest after the administration of analgesics. Imaging studies contribute to its diagnosis and location. The resection of the same, improves the quality of life in the patients who suffer it. We present the clinical case of a 33-year-old female patient who consulted for pain in the predominantly nocturnal paranasal region that subsided after analgesics were administered. The tomographic study confirmed the presence of a lesion of calcic density in the fronto-ethmoidal region, excision of the lesion was performed and the anatomopathological study confirmed its nature

Automated early detection of drops in commercial egg production using neural networks.

1. The purpose of this work was to support decision-making in poultry farms by performing automatic early detection of anomalies in egg production. 2. Unprocessed data were collected from a commercial egg farm on a daily basis over 7 years. Records from a total of 24 flocks, each with approximately 20 000 laying hens, were studied. 3. Other similar works have required a prior feature extraction by a poultry expert, and this method is dependent on time and expert knowledge. 4. The present approach reduces the dependency on time and expert knowledge because of the automatic selection of relevant features and the use of artificial neural networks capable of cost-sensitive learning. 5. The optimum configuration of features and parameters in the proposed model was evaluated on unseen test data obtained by a repeated cross-validation technique. 6. The accuracy, sensitivity, specificity and positive predictive value are presented and discussed at 5 forecasting intervals. The accuracy of the proposed model was 0.9896 for the day before a problem occurs.

Food allergy in breastfeeding babies. Hidden allergens in human milk.

BACKGORUND: Food allergy is a rare disorder among breastfeeding babies. OBJECTIVE: Our aim was to identify responsible allergens in human milk. METHODS: We studied babies developing allergic symptoms at the time they were breastfeeding. Skin prick tests (SPT) were performed with breast milk and food allergens. Specific IgE was assessed and IgE Immunoblotting experiments with breast milk were carried out to identify food allergens. Clinical evolution was evaluated after a maternal free diet. RESULTS: Five babies had confirmed breast milk allergy. Peanut, white egg and/or cow's milk were demonstrated as the hidden responsible allergens. No baby returned to develop symptoms once mother started a free diet. Three of these babies showed tolerance to other food allergens identified in human milk. CONCLUSION: A maternal free diet should be recommended only if food allergy is confirmed in breastfed babies.

Evaluation of metal mobility from copper mine tailings in northern Chile.

This work shows the results obtained on a copper mine tailing in the Antofagasta Region, Chile. The tailing was classified as saline-sodic with high concentrations of metals, especially Cu and Fe, with pH 8.4. Our objectives were to (1) compare the physicochemical properties of the tailing with surrounding soils of the mine under study, and (2) evaluate the effect of two amendments (CaCO3 and compost) and their mixtures on Cu(2+), Mn, Fe, Zn, Mg(2+), and K(+) and Ca(2+), SO4 (2-), NO3 (-), and PO4 (3-) leaching. The data obtained were submitted to variance and covariance analysis. The results from the comparison between both substrates showed that in general, the tailing presented greater content of metals. Regarding tailing leaching, pH, electrical conductivity (EC), and concentration of the elements of interest were measured. The statistical analysis showed that Cu(2+) leaching and immobilization of Fe occurred to the greatest extent with compost. The EC decreased throughout the experiment with irrigation and increased upon treatment with compost. The major interactions found among the chemical parameters were (1) tailings without treatment, Cu(2+)/Fe and NO3 (-)/SO4 (2-); (2) tailings treated with CaCO3, Cu(2+)/K(+); (3) tailings treated with compost, NO3 (-)/SO4 (-2) and EC/Cu(2+); and (4) tailings treated with both amendments, EC/Fe and Cu(2+)/Fe. The ANOVA showed that the number of irrigations and the amendments statistically significantly affected the copper mobility and the organic amendment significantly influenced the iron mobility.

Identification of the first nonsense CDSN mutation with expression of a truncated protein causing peeling skin syndrome type B.

BACKGROUND: Peeling skin disease (PSD), a generalized inflammatory form of peeling skin syndrome, is caused by autosomal recessive nonsense mutations in the corneodesmosin gene (CDSN). OBJECTIVES: To investigate a novel mutation in CDSN. METHODS: A 50-year-old white woman showed widespread peeling with erythema and elevated serum IgE. DNA sequencing, immunohistochemistry, Western blot and real-time polymerase chain reaction analyses of skin biopsies were performed in order to study the genetics and to characterize the molecular profile of the disease. RESULTS: Histology showed hyperkeratosis and acanthosis of the epidermis, and inflammatory infiltrates in the dermis. DNA sequencing revealed a homozygous mutation leading to a premature termination codon in CDSN: p.Gly142*. Protein analyses showed reduced expression of a 16-kDa corneodesmosin mutant in the upper epidermal layers, whereas the full-length protein was absent. CONCLUSIONS: These results are interesting regarding the genotype-phenotype correlations in diseases caused by CDSN mutations. The PSD-causing CDSN mutations identified heretofore result in total corneodesmosin loss, suggesting that PSD is due to full corneodesmosin deficiency. Here, we show for the first time that a mutant corneodesmosin can be stably expressed in some patients with PSD, and that this truncated protein is very probably nonfunctional.

Enfrentamiento de las vasculitis primarias / Clinical aspects of primary vasculitis

Las Vasculitis Primarias son enfermedades poco frecuentes, potencialmente fatales, sin causa etiológica conocida, que pueden comprometer a vasos sanguíneos de distinto tamaño, produciéndoles un proceso inflamatorio en la pared vascular, que conduce a la estrechez u obstrucción del vaso afectado, con consecuente isquemia o necrosis del tejido que irrigan. Sus manifestaciones clínicas pueden ser muy variadas, y frecuentemente inespecíficas. Sin embargo hay algunas que hacen sospechar el diagnóstico y que deben ser evaluadas con detalle. El estudio diagnóstico de las vasculitis primarias, implica varios aspectos que deben ser considerados. La actividad, la extensión, el daño visceral y el diagnóstico diferencial. En este sentido los exámenes bioquímicos; los exámenes funcionales organicos; los estudios de imágenes (radiológicos, tomografía computarizadas, resonancia magnética, radio isotópicas, y de Pet -CT); y la histopatología (biopsias de riñón, sistema nervioso periférico, pulmonar, etc.); y los estudios de autoanticuerpos (muy especialmente los ANCA, en vasculitis de pequeño vaso) ayudan a fundamentar el diagnóstico definitivo. Su tratamiento debe considerar dos etapas. Inicialmente la terapia de inducción de la remisión, y luego de lograrla, la de mantenimiento de la remisión. De la naturaleza de la vasculitis y del éxito que se logre con el tratamiento, dependerá su pronóstico. Las drogas tradicionales, más usadas en el tratamiento, y habitualmente más efectivas, son los corticoesteroides (orales o EV en bolos) y la ciclofosfamida (oral o preferentemente en bolos EV). Tambien se han usado la Azatioprina, el metotrexato, y el micofenolato mofetil, especialmente como mantenimiento de remisión. En los últimos años, se ha destacado el uso de terapia biológica, con anticuerpos monoclonales anti lifocitos B, el Rituximab, que resulta de gran utilidad, muy especialmente en las vasculitis de pequeño vaso ANCA positivo. El diagnóstico diferencial incluye patologías muy diversas; trombosis ateroesclerótica; embolias ateroescleróticas, embolias sépticas, el uso de drogas ilícitas, y la trombosis secundaria al Sindrome Antifosfolípido.

Primary vasculitis is an infrecuent desease, and may present in very different clinical pictures. Any size of blood vessels can be affected (aorta, large it; arteries, médium -size, and small), it may be produced by immunological tissue damage mechanisms. Classification of primary vasculitis usually consider both aspects. Histopathology includes, giant cells large vasculitis; granulomatous aortitis; systemic inflamatory necrotizing and segmentary médium size arterities; Granomalous necrotazing small vessel vasculitis, with or without eosinofilic infiltration; and leucocitoclastic small vessel vasculitis. Clinicians should be awared of this deseases in order to diagnose promptly and do a proper therapy.

Short-term exposure of mice to cigarette smoke and/or residual oil fly ash produces proximal airspace enlargements and airway epithelium remodeling

Chronic obstructive pulmonary disease (COPD) is associated with inflammatory cell reactions, tissue destruction and lung remodeling. Many signaling pathways for these phenomena are still to be identified. We developed a mouse model of COPD to evaluate some pathophysiological mechanisms acting during the initial stage of the disease. Forty-seven 6- to 8-week-old female C57/BL6 mice (approximately 22 g) were exposed for 2 months to cigarette smoke and/or residual oil fly ash (ROFA), a concentrate of air pollution. We measured lung mechanics, airspace enlargement, airway wall thickness, epithelial cell profile, elastic and collagen fiber deposition, and by immunohistochemistry transforming growth factor-β1 (TGF-β1), macrophage elastase (MMP12), neutrophils and macrophages. We observed regional airspace enlargements near terminal bronchioles associated with the exposure to smoke or ROFA. There were also increases in airway resistance and thickening of airway walls in animals exposed to smoke. In the epithelium, we noted a decrease in the ciliated cell area of animals exposed to smoke and an increase in the total cell area associated with exposure to both smoke and ROFA. There was also an increase in the expression of TGF-β1 both in the airways and parenchyma of animals exposed to smoke. However, we could not detect inflammatory cell recruitment, increases in MMP12 or elastic and collagen fiber deposition. After 2 months of exposure to cigarette smoke and/or ROFA, mice developed regional airspace enlargements and airway epithelium remodeling, although no inflammation or increases in fiber deposition were detected. Some of these phenomena may have been mediated by TGF-β1.

Short-term exposure of mice to cigarette smoke and/or residual oil fly ash produces proximal airspace enlargements and airway epithelium remodeling.

Chronic obstructive pulmonary disease (COPD) is associated with inflammatory cell reactions, tissue destruction and lung remodeling. Many signaling pathways for these phenomena are still to be identified. We developed a mouse model of COPD to evaluate some pathophysiological mechanisms acting during the initial stage of the disease. Forty-seven 6- to 8-week-old female C57/BL6 mice (approximately 22 g) were exposed for 2 months to cigarette smoke and/or residual oil fly ash (ROFA), a concentrate of air pollution. We measured lung mechanics, airspace enlargement, airway wall thickness, epithelial cell profile, elastic and collagen fiber deposition, and by immunohistochemistry transforming growth factor-ß1 (TGF-ß1), macrophage elastase (MMP12), neutrophils and macrophages. We observed regional airspace enlargements near terminal bronchioles associated with the exposure to smoke or ROFA. There were also increases in airway resistance and thickening of airway walls in animals exposed to smoke. In the epithelium, we noted a decrease in the ciliated cell area of animals exposed to smoke and an increase in the total cell area associated with exposure to both smoke and ROFA. There was also an increase in the expression of TGF-ß1 both in the airways and parenchyma of animals exposed to smoke. However, we could not detect inflammatory cell recruitment, increases in MMP12 or elastic and collagen fiber deposition. After 2 months of exposure to cigarette smoke and/or ROFA, mice developed regional airspace enlargements and airway epithelium remodeling, although no inflammation or increases in fiber deposition were detected. Some of these phenomena may have been mediated by TGF-ß1.

Outcome after steroid withdrawal in heart transplantation.

BACKGROUND: There is a lack of consensus and insufficient data to assess the impact of late steroid withdrawal after heart transplantation (HTx). The aim of the study was to investigate the security and feasibility of corticosteroid withdrawal at 1 year after transplantation. METHODS AND RESULTS: Steroid withdrawal was attempted after at least 12 months of treatment in 86 HTx patients who fulfilled the criteria. At 1 and 3 months after drug discontinuation, patients underwent 2 endomyocardial biopsies (EMB). After a mean follow-up of 25 +/- 13 months, 63% of the patients remained steroid free. In 30 patients (35%) corticosteroids were reinitiated, in 15 cases because of acute rejection (7%), 5 (6%) because of worsening renal function, 5 (6%) because of malignancy, 3 (4%) because of adverse effects of immunosuppressive drugs, and 2 because of severe allograft coronary artery disease. Four patients (5%) died after drug discontinuation. There was a significant decrease in total cholesterol (198 +/- 35 to 181 +/- 38 mg/dL; P < .001) and low-density lipoprotain (LDL) cholesterol levels (113 +/- 30 to 105 +/- 30 mg/dL; P < .001). There were no differences in mortality between patients with and without corticosteroids. CONCLUSION: Steroid withdrawal is feasible and safe in HTx patients. In our study, it was successfully maintained in 63% of the patients. EMB is helpful to identify patients with acute rejection at 1 and 3 months after withdrawal. Short- to mid-term metabolic benefits are significant reductions in serum total and LDL cholesterol.

Tracheal instillation of urban PM(2.5) suspension promotes acute cardiac polarization changes in rats.

The mechanisms by which PM(2.5) increases cardiovascular mortality are not fully identified. Autonomic alterations are the current main hypotheses. Our objective was to determine if PM(2.5) induces acute cardiac polarization alterations in healthy Wistar rats. PM(2.5) samples were collected on polycarbonate filters. Solutions containing 10, 20, and 50 microg PM(2.5) were administered by tracheal instillation. P wave duration decreased significantly at 20 microg (0.99 +/- 0.06, 0.95 +/- 0.06, and 0.96 +/- 0.07; P < 0.001), and 50 microg (0.98 +/- 0.06, 0.98 +/- 0.07, and 0.96 +/- 0.08; 60, 90 and 120 min, respectively) compared to blank filter solution (P < 0.001). PR interval duration decreased significantly at 20 microg (0.99 +/- 0.06, 0.98 +/- 0.07, and 0.97 +/- 0.08) and 50 microg (0.99 +/- 0.05, 0.97 +/- 0.0, and 0.95 +/- 0.05; 60, 90, and 120 min, respectively) compared to blank filter and 10 microg (P < 0.001). QRS interval duration decreased at 20 and 50 microg in relation to blank filter solution and 10 microg (P < 0.001). QT interval duration decreased significantly (P < 0.001) with time in animals receiving 20 microg (0.94 +/- 0.12, 0.88 +/- 0.14, and 0.88 +/- 0.11) and 50 microg (1.00 +/- 0.13; 0.97 +/- 0.11 and 0.98 +/- 0.16; 60, 90 and 120 min, respectively) compared to blank filter solution and 10 microg (P < 0.001). PM(2.5) induced reduced cardiac conduction time, within a short period, indicating that depolarization occurs more rapidly across ventricular tissue.

Tracheal instillation of urban PM2.5 suspension promotes acute cardiac polarization changes in rats

The mechanisms by which PM2.5 increases cardiovascular mortality are not fully identified. Autonomic alterations are the current main hypotheses. Our objective was to determine if PM2.5 induces acute cardiac polarization alterations in healthy Wistar rats. PM2.5 samples were collected on polycarbonate filters. Solutions containing 10, 20, and 50 µg PM2.5 were administered by tracheal instillation. P wave duration decreased significantly at 20 µg (0.99 ± 0.06, 0.95 ± 0.06, and 0.96 ± 0.07; P < 0.001), and 50 µg (0.98 ± 0.06, 0.98 ± 0.07, and 0.96 ± 0.08; 60, 90 and 120 min, respectively) compared to blank filter solution (P < 0.001). PR interval duration decreased significantly at 20 µg (0.99 ± 0.06, 0.98 ± 0.07, and 0.97 ± 0.08) and 50 µg (0.99 ± 0.05, 0.97 ± 0.0, and 0.95 ± 0.05; 60, 90, and 120 min, respectively) compared to blank filter and 10 µg (P < 0.001). QRS interval duration decreased at 20 and 50 µg in relation to blank filter solution and 10 µg (P < 0.001). QT interval duration decreased significantly (P < 0.001) with time in animals receiving 20 µg (0.94 ± 0.12, 0.88 ± 0.14, and 0.88 ± 0.11) and 50 µg (1.00 ± 0.13; 0.97 ± 0.11 and 0.98 ± 0.16; 60, 90 and 120 min, respectively) compared to blank filter solution and 10 µg (P < 0.001). PM2.5 induced reduced cardiac conduction time, within a short period, indicating that depolarization occurs more rapidly across ventricular tissue.

Acute pulmonary and hematological effects of two types of particle surrogates are influenced by their elemental composition.

Several epidemiological studies have consistently demonstrated significant associations between ambient levels of particulate matter and lung injury and cardiovascular events with increased morbidity and mortality. Particle surrogates (PS), such as residual oil fly ash (ROFA), have been widely used in experimental studies aimed at characterizing the mechanisms of particle toxicity. Since PS composition varies depending on its source, studies with different types of PS may provide clues about the relative toxicity of the components generated by high-temperature combustion process. In this work, we have studied the effects of nasal instillation of increasing doses of different PS in mice: saline, carbon, and two types of particle surrogates. PS type A (PSA) was the ROFA collected from the waste incinerator of our university hospital; PS type B (PSB) was collected from the electrostatic precipitator of a large steel company and thus had an elevated metal content. After 24h, we analyzed hematological parameters, fibrinogen, bronchoalveolar lavage, bone marrow, and pulmonary histology. Nasal instillation of the two types of PS-induced leucopenia. PSB elicited a greater elevation of plasma fibrinogen levels. Bone marrow and pulmonary inflammatory changes were more intense for PSA. We concluded that the PS composition modulates acute inflammatory changes more significantly than the mass for these two types of PS.

Urban air pollution induces micronuclei in peripheral erythrocytes of mice in vivo.

In this study, we explored the role of chronic exposure to urban air pollution in causing DNA damage (micronuclei frequency in peripheral erythrocytes) in rodents in vivo. Mice (n=20) were exposed to the urban atmosphere of São Paulo for 120 days (February to June 1999) and compared to animals (n=20) maintained in the countryside (Atibaia) for the same period. Daily levels of inhalable particles (PM10), CO, NO(2), and SO(2), were available for São Paulo. Occasional measurements of CO and O(3) were made in Atibaia, showing negligible levels of pollution in the area. The frequency of micronuclei (repeated-measures ANOVA) increased with aging, the highest values obtained for the 90th day of experiment (P<0.001). The exposure to urban air pollution elicited a significant (P=0.016) increase of micronuclei frequency, with no significant interaction with time of study. Associations (Spearman's correlation) between pollution levels of the week that precede blood sampling and micronuclei counts were observed in São Paulo. The associations between micronuclei counts and air pollution were particularly strong for pollutants associated with automotive emissions, such as CO (P=0.037), NO(2) (P<0.001), and PM10 (P<0.001). Our results support the concept that urban levels of air pollution may cause somatic mutations.