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1.
Am J Physiol Lung Cell Mol Physiol ; 318(5): L1084-L1096, 2020 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-32209025

RESUMO

Alveolar epithelial cell (AEC) apoptosis, arising from mitochondrial dysfunction and mitophagy defects, is important in mediating idiopathic pulmonary fibrosis (IPF). Our group established a role for the mitochondrial (mt) DNA base excision repair enzyme, 8-oxoguanine-DNA glycosylase 1 (mtOGG1), in preventing oxidant-induced AEC mtDNA damage and apoptosis and showed that OGG1-deficient mice have increased lung fibrosis. Herein, we determined whether mice overexpressing the mtOGG1 transgene (mtOgg1tg) are protected against lung fibrosis and whether AEC mtOGG1 preservation of mtDNA integrity mitigates phosphatase and tensin homolog-induced putative kinase 1 (PINK1) deficiency and apoptosis. Compared with wild type (WT), mtOgg1tg mice have diminished asbestos- and bleomycin-induced pulmonary fibrosis that was accompanied by reduced lung and AEC mtDNA damage and apoptosis. Asbestos and H2O2 promote the MLE-12 cell PINK1 deficiency, as assessed by reductions in the expression of PINK1 mRNA and mitochondrial protein expression. Compared with WT, Pink1-knockout (Pink1-KO) mice are more susceptible to asbestos-induced lung fibrosis and have increased lung and alveolar type II (AT2) cell mtDNA damage and apoptosis. AT2 cells from Pink1-KO mice and PINK1-silenced (siRNA) MLE-12 cells have increased mtDNA damage that is augmented by oxidative stress. Interestingly, mtOGG1 overexpression attenuates oxidant-induced MLE-12 cell mtDNA damage and apoptosis despite PINK1 silencing. mtDNA damage is increased in the lungs of patients with IPF as compared with controls. Collectively, these findings suggest that mtOGG1 maintenance of AEC mtDNA is crucial for preventing PINK1 deficiency that promotes apoptosis and lung fibrosis. Given the key role of AEC apoptosis in pulmonary fibrosis, strategies aimed at preserving AT2 cell mtDNA integrity may be an innovative target.


Assuntos
Células Epiteliais Alveolares/efeitos dos fármacos , Asbestose/genética , DNA Glicosilases/genética , Pulmão/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Proteínas Quinases/genética , Fibrose Pulmonar/genética , Células Epiteliais Alveolares/metabolismo , Células Epiteliais Alveolares/patologia , Animais , Apoptose/efeitos dos fármacos , Apoptose/genética , Asbestos/administração & dosagem , Asbestose/etiologia , Asbestose/metabolismo , Asbestose/patologia , Bleomicina/administração & dosagem , Dano ao DNA , DNA Glicosilases/deficiência , DNA Mitocondrial/genética , DNA Mitocondrial/metabolismo , Feminino , Regulação da Expressão Gênica , Peróxido de Hidrogênio/farmacologia , Pulmão/metabolismo , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mitocôndrias/metabolismo , Cultura Primária de Células , Proteínas Quinases/metabolismo , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/metabolismo , Fibrose Pulmonar/patologia , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Titânio/administração & dosagem
2.
Laeknabladid ; 105(7): 327-334, 2019.
Artigo em Islandês | MEDLINE | ID: mdl-31411568

RESUMO

Asbestos are crystallized silicate minerals that form fibers with different structures and characteristics. Asbestos fibers are very durable and can tolerate very high temperatures. Therefore it was common to use asbestos as a fire retardants, heat insulation and where high temperature is used. Asbestos has been banned in Iceland from 1983 but can still be found in large amounts in buildings, ships and hot water pipes. Large amounts of asbestos were imported in the years before the ban but diminished soon to almost nothing today. Needle or filamentous shaped dust is released when working with asbestos. It is this dust that is dangerous for health. The latent time from exposure to disease can be up to forty years. Asbestos reaches the lungs via inhalation and can cause asbestosis that is a form of lung fibrosis with slow progression. Asbestos can also cause benign pleural effusions, pleural plaques and diffuse pleural thickening. Asbestos is a carcinogen. Lung cancer is most common but asbestos is also a risk factor for cancers of other organs. Mesothelioma is most common in the pleura but can be seen in other membranes. The incidence of these tumors is high in Iceland and is still increasing among males. Of all the European countries mortality is highest in Iceland. It is important for physicians to include asbestos exposure in the differential diagnosis of lung diseases and when lung cancer is diagnosed.


Assuntos
Asbestos/efeitos adversos , Asbestose/epidemiologia , Materiais de Construção/efeitos adversos , Exposição Ambiental/efeitos adversos , Neoplasias Pulmonares/epidemiologia , Mesotelioma/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Asbestose/diagnóstico por imagem , Asbestose/patologia , Feminino , Humanos , Islândia/epidemiologia , Incidência , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Masculino , Mesotelioma/diagnóstico , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco , Distribuição por Sexo , Fatores de Tempo
3.
Occup Environ Med ; 76(10): 765-771, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31331950

RESUMO

OBJECTIVES: To determine cell differential counts and the number of asbestos bodies (ABs) in bronchoalveolar lavage (BAL) fluid obtained from patients with asbestosis, and to correlate the results with their survival. METHODS: The BAL cell differential counts and ABs from 91 patients with asbestosis were determined. The BAL cell differential counts were analysed in relation to smoking status. BAL cell differential counts and the number of ABs were correlated with the patients' survivals. RESULTS: A neutrophilic cell pattern was observed independently of smoking habits with both Papanicolau (8.4%) and May-Grunwald-Giemsa (6.5%) staining. Smoking and a high number of ABs (>2 AB/mL) were associated with high total cell counts and high macrophage and low lymphocyte differential counts. The median survival of the patients was 131.8 months. Shortened survival was associated with high numbers of ABs (78 vs 165 months; p=0.042) and low lymphocyte (77 vs 179 months; p=0.005), high neutrophil (102 vs 180 months; p=0.016) and high eosinophil (104 vs170 months; p=0.007) differential counts. CONCLUSION: A neutrophilic cell pattern was evident in BAL from patients with asbestosis. Smoking and ABs both affected the total cell count and the macrophage and lymphocyte differential counts. Several BAL parameters associated with patient survival, suggesting that BAL cell count analyses could be used in the estimation of the prognosis of patients with asbestosis.


Assuntos
Asbestos/análise , Asbestose/patologia , Líquido da Lavagem Broncoalveolar/citologia , Análise de Sobrevida , Idoso , Contagem de Células , Feminino , Finlândia , Humanos , Linfócitos/patologia , Macrófagos/patologia , Masculino , Neutrófilos/patologia , Fumar/efeitos adversos
4.
Histopathology ; 73(1): 29-37, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29464753

RESUMO

AIMS: To confirm whether or not grade 4 asbestosis progresses from the respiratory bronchiole to the peripheral lung. METHODS AND RESULTS: We examined retrospectively the autopsy or lobectomy specimens from 31 cases (29 males; mean age 64 years) satisfying the pathological criteria of grade 4 asbestosis. Asbestos bodies (ABs) were quantified in samples of dissolved lung and in tissue preparations on glass slides. Respiratory bronchiolar lesions were graded as 0, 1 and ≥2. Grade 4 asbestosis was subdivided into an atelectatic induration (AI) and usual interstitial pneumonia pattern (UIP pattern). Five, 10, and 16 cases had grades 0, 1 or ≥2 lesions, respectively, with mean respective numbers of ABs in dissolved lung of 117 000/g dry lung, 468 000/g and 968 000/g; and in specimens on glass slides of seven ABs/cm2 of tissue slice, 34 ABs /cm2 and 195 ABs /cm2 . The differences were significant. Fifteen and 16 cases showed AI and UIP patterns, respectively, with mean respective numbers of ABs in dissolved lung of 1 006 000/g dry lung and 354 000/g, and 186 and 56 ABs/cm2 on glass slides. The differences were significant. AI patterns originated in subpleural lobules or subpleural zonal areas and UIP patterns originated in subpleural, peripheral lobules. CONCLUSIONS: Grade 4 asbestosis does not start in the respiratory bronchiole. The presence of a grade 1 lesion is not required for the diagnosis of grade 4 asbestosis.


Assuntos
Asbestose/patologia , Bronquíolos/patologia , Idoso , Feminino , Humanos , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
5.
Int J Occup Med Environ Health ; 31(3): 293-305, 2018 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-29099505

RESUMO

OBJECTIVES: This study has researched the significance of histologically raised findings and lung dust analyses in the context of claiming the recognition of and thus compensation for an asbestos-associated occupational disease. MATERIAL AND METHODS: For this approach, all findings from the German Mesothelioma Register in 2015 that included lung dust analyses were evaluated and were compared with information on asbestos fiber exposure at work based on fiber years, and with the results of radiological findings. RESULTS: For 68 insured persons, recognition of an asbestos-induced lung disease according to Section 4104 of the German Ordinance on Occupational Diseases (Berufskrankheitenverordnung - BKV) could be recommended solely on the basis of the histological examinations of lung tissues and complementary lung dust analyses. Neither did the calculation of the cumulative asbestos dust exposure at work yield 25 fiber years, nor could bridge findings (e.g., plaques) be identified. In addition, the autopsies of 12 patients revealed plaques that had not been diagnosed during radiological examinations. These results show that - irrespective of the prescribed working techniques and radiological diagnosis - pathological/anatomical and histological diagnostics are often the only way for the insureds to demonstrate the causal connection between asbestos and their disease. Even after long intervals of up to 40 years post last exposure, the asbestos fibers would still be easily detectable in the lung tissues evaluated. CONCLUSIONS: Whenever suitable tissue is available, it should be examined for mild asbestosis with the aid of a lung dust analysis. Otherwise there is a risk that an occupational disease is wrongfully rejected. In the context of health insurance, the lung dust analysis and the resulting proof of the presence of asbestosis often constitute one option of providing evidence of an occupational disease. Int J Occup Med Environ Health 2018;31(3):293-305.


Assuntos
Asbestos/análise , Asbestose/diagnóstico , Pneumopatias/diagnóstico , Doenças Profissionais/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Asbestose/diagnóstico por imagem , Asbestose/patologia , Poeira/análise , Alemanha , Técnicas Histológicas , Humanos , Pneumopatias/patologia , Pessoa de Meia-Idade , Doenças Profissionais/patologia , Exposição Ocupacional/estatística & dados numéricos , Doenças Pleurais/diagnóstico , Doenças Pleurais/patologia , Indenização aos Trabalhadores
6.
Inhal Toxicol ; 29(9): 404-413, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-29039215

RESUMO

During its days of operation (1920s-1990), the world's largest source of vermiculite was extracted from a mine located near Libby, Montana. The material mined at this site was shipped for various commercial applications to numerous sites in the United States. There was a "fibrous" component with toxic potential within the vermiculite deposit that has resulted in "asbestos-like" diseases/deaths being reported in numerous studies involving miners as well as residents of the town of Libby. The present case involves the clinical assessments of an individual who worked at the mine from 1969 to 1990. He had no other known occupational exposures to fibrous materials. He developed a clinical picture that included "asbestos-like" pathological features and eventually an adenocarcinoma. The clinical assessment including radiographic features will be presented. The evaluation will also include the analytical evaluation of the fibrous/ferruginous body composition of the lung tissue. This is to our knowledge the first time such an extensive evaluation has been conducted in a vermiculite miner from Libby, Montana.


Assuntos
Silicatos de Alumínio , Amiantos Anfibólicos/análise , Pulmão/química , Exposição Ocupacional , Idoso , Asbestose/patologia , Humanos , Pulmão/patologia , Masculino , Mineração , Montana , Fibrose Pulmonar
7.
Dis Markers ; 2017: 9645940, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28757678

RESUMO

BACKGROUND: The identification of diagnostic/prognostic biomarkers for asbestos-related diseases is relevant for early diagnosis and patient survival and may contribute to understanding the molecular mechanisms underlying the disease development and progression. AIMS: To identify a pattern of miRNAs as possible diagnostic biomarkers for patients with malignant pleural mesothelioma (MPM) and asbestosis (ASB) and as prognostic biomarkers for MPM patients. METHODS: miRNA-16, miRNA-17, miRNA-126, and miRNA-486 were quantified in plasma and formalin-fixed paraffin-embedded samples to evaluate their diagnostic and prognostic roles compared to patients with other noncancerous pulmonary diseases (controls). Results. The expression of all the miRNAs was significantly lower in patients with MPM and ASB than that in controls. miRNA-16, miRNA-17, and miRNA-486 in plasma and tissue of MPM patients were significantly correlated. Furthermore, the expression of miRNA-16 in plasma and tissue, and miRNA-486 only in tissue, was positively related with cumulative survival in MPM patients. CONCLUSIONS: All the miRNA levels were decreased in patients with MPM or ASB, supporting the role of circulating miRNAs as a potential tool for diseases associated with exposure to asbestos fibers. miRNA-16 was directly related to MPM patient prognosis, suggesting its possible use as a prognostic marker in MPM patients.


Assuntos
Asbestose/sangue , Neoplasias Pulmonares/sangue , Mesotelioma/sangue , MicroRNAs/sangue , Idoso , Asbestose/metabolismo , Asbestose/patologia , Estudos de Casos e Controles , Feminino , Humanos , Pulmão/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Mesotelioma/metabolismo , Mesotelioma/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Projetos Piloto
8.
Lung ; 195(5): 671-677, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-28791466

RESUMO

INTRODUCTION: This study aimed to characterize, for the first time in Spain, the type of asbestos fibres (AF) in the lungs of exposed and non-exposed populations. MATERIALS AND METHODS: Lung samples from 38 subjects living in Barcelona and Ferrol, Spain, were studied, which were divided into three groups: Group A-five subjects without known respiratory disease; Group B-20 ex-shipyard workers and Group C-13 patients with lung cancer. After eliminating the organic material, the inorganic residue was analysed using electronic microscopy (EM). To identify the type of fibre, the samples were analysed by scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDX). RESULTS: All the fibres identified corresponded to amphiboles (crocidolite 45%, anthophyllite 22%, tremolite 16%, amosite 15% and actinolite 3%). In 14 patients (37%), a single type of asbestos was found in the lungs (amosite in two, actinolite in one, anthophyllite in four, crocidolite in five and tremolite in two). Forty-six percent of the AF analysed had a length > 5 µm and a diameter < 0.2 µm. CONCLUSIONS: The results of this study provide the first data on the type of asbestos retained in the lung of Spanish population. A particularly striking finding is the exclusive retention of amphiboles, which suggests that chrysotile is eliminated after inhalation. Our findings support estimations considering Spain and other southern European countries with similar asbestos imports and consumption at a high risk to develop asbestos-related diseases in the years to come.


Assuntos
Amiantos Anfibólicos , Asbestose/patologia , Neoplasias Pulmonares/patologia , Pulmão , Mesotelioma/patologia , Exposição Ocupacional , Neoplasias Pleurais/patologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Feminino , Humanos , Neoplasias Pulmonares/cirurgia , Masculino , Microscopia Eletrônica , Microscopia Eletrônica de Varredura , Pessoa de Meia-Idade , Fibras Minerais , Espanha , Espectrometria por Raios X
9.
Ultrastruct Pathol ; 41(5): 309-311, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28805487

RESUMO

The nanopathological diagnostics (ND) is an ultra-specialized branch of pathological anatomy aimed to identify the nanoparticles of metallic, semimetallic, or nonmetallic elements in the inorganic particulate matter present inside pathological tissues, even on the nanometer scale. ND exploits an environmental scanning electron microscope, connected to an X-ray microprobe mounted on an energy-dispersive spectrometer. The searching of nanoparticles can be performed on paraffin-embedded material, omitting emissions of black overlay and plating procedures. The technique is highly sensitive and specific, reproducible and rapid, covering an entire operating cycle in few hours. Nowadays, ND finds many applications: (I) intratumor detection of heavy metals and endocrine metal disruptors; (II) identification of pathogenic nanoparticles in medical or veterinary drugs and devices, cosmetics, household products, and foodstuffs; (III) differential diagnosis of sarcoid-type granulomas (berylliosis, baritosis) and foreign body granulomas (prosthetic, iatrogenic); (IV) attestation of occupational disease correlating the datum with the occupational risk (anthracosis, asbestosis, bauxite fibrosis, byssinosis, chalicosis, siderosis, silicosis, stannosis, talcosis); and (V) forensic investigations to ascertain a causal link between disease and environmental, military, or work exposure. In addition to filling a knowledge gap, ND offers to the pathologist a current research field, with particular reference to the impact of occupational and environmental pollution on the human health and cancer.


Assuntos
Asbestose/patologia , Pulmão/patologia , Microscopia Eletrônica de Varredura , Neoplasias/diagnóstico , Neoplasias/patologia , Animais , Asbestose/diagnóstico , Humanos , Microscopia Eletrônica de Varredura/métodos , Pneumoconiose/diagnóstico , Pneumoconiose/patologia , Espectrometria por Raios X/métodos
10.
Sci Rep ; 7: 44862, 2017 03 23.
Artigo em Inglês | MEDLINE | ID: mdl-28332562

RESUMO

Once penetrated into the lungs of exposed people, asbestos induces an in vivo biomineralisation process that leads to the formation of a ferruginous coating embedding the fibres. The ensemble of the fibre and the coating is referred to as asbestos body and is believed to be responsible for the high toxicological outcome of asbestos. Lung tissue of two individuals subjected to prolonged occupational exposure to crocidolite asbestos was investigated using synchrotron radiation micro-probe tools. The distribution of K and of elements heavier than Fe (Zn, Cu, As, and Ba) in the asbestos bodies was observed for the first time. Elemental quantification, also reported for the first time, confirmed that the coating is highly enriched in Fe (~20% w/w), and x-ray absorption spectroscopy indicated that Fe is in the 3+ oxidation state and that it is present in the form of ferritin or hemosiderin. Comparison of the results obtained studying the asbestos bodies upon removing the biological tissue by chemical digestion and those embedded in histological sections, allowed unambiguously distinguishing the composition of the asbestos bodies, and understanding to what extent the digestion procedure altered their chemical composition. A speculative model is proposed to explain the observed distribution of Fe.


Assuntos
Asbestos/efeitos adversos , Asbestose/etiologia , Asbestose/patologia , Calcinose/metabolismo , Fibras Minerais/efeitos adversos , Exposição Ocupacional/efeitos adversos , Idoso de 80 Anos ou mais , Biópsia , Feminino , Humanos , Ferro , Pulmão/metabolismo , Pulmão/patologia , Masculino , Metais Pesados , Oligoelementos
11.
Med Pr ; 68(2): 247-258, 2017 Mar 24.
Artigo em Polonês | MEDLINE | ID: mdl-28345684

RESUMO

BACKGROUND: The adverse health effects of occupational exposure to asbestos dust may occur several years after first exposure. The objective of the study was to assess the relationship between lesions in the respiratory system and the factors contributing to occupational exposure to asbestos described in the first medical examination as well as to analyze the factors responsible for the progression of these changes in further medical tests. MATERIAL AND METHODS: The study group comprised 591 former workers of asbestos processing plant "Gambit" in Lubawka. The results of medical examinations carried out in 2001-2012 were assessed. Statistical inference was performed based on bilateral significance tests at the 0.05 level of significance. RESULTS: A higher risk of interstitial lung changes along with an increase in the cumulative concentration of asbestos was indicated; for the employees with the highest exposure, the adjusted odds ratio (OR) was 1.63 (95% confidence interval (CI): 0.99-2.71), while for changes with the severity degree qualifying for asbestosis diagnosis, the risk was significantly increased, over fivefold higher, compared to subjects employed in the lowest exposure. The analysis of the relationship between the progression of interstitial changes and the exposure to asbestos dust showed a fourfold higher risk of the progression in workers employed in the highest exposure. Mean values of FEV1 (forced expiratory volume in 1 s), FVC (forced vital capacity), FEV1/FVC (forced expiratory volume in 1 s to forced vital capacity) were significantly lower in the subjects working in a higher asbestos exposure. The effect of tobacco smoking on the occurrence of interstitial lung changes and their progression was also confirmed. CONCLUSIONS: The results of prophylactic medical examinations of the health status of workers formerly employed in the plants using chrysotile indicate the importance andthe need for a long-term clinical follow-up and the promotion of anti-smoking prevention in this group of former employees. Med Pr 2017;68(2):247-258.


Assuntos
Asbestos Serpentinas/efeitos adversos , Asbestose/patologia , Pulmão/patologia , Exposição Ocupacional/efeitos adversos , Ventilação Pulmonar , Adulto , Idoso , Idoso de 80 Anos ou mais , Asbestose/diagnóstico por imagem , Asbestose/epidemiologia , Asbestose/fisiopatologia , Poeira , Feminino , Humanos , Pulmão/diagnóstico por imagem , Pulmão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Polônia , Radiografia Torácica
12.
Respir Res ; 18(1): 38, 2017 02 21.
Artigo em Inglês | MEDLINE | ID: mdl-28222740

RESUMO

BACKGROUND: Myofibroblasts play a major role in the synthesis of extracellular matrix (ECM) and the stimulation of these cells is thought to play an important role in the development of silicosis. The present study was undertaken to investigate the anti-fibrotic effects of dibutyryl-cAMP (db-cAMP) on rats induced by silica. METHODS: A HOPE MED 8050 exposure control apparatus was used to create the silicosis model. Rats were randomly divided into 4 groups: 1)controls for 16 w; 2)silicosis for 16 w; 3)db-cAMP pre-treatment; 4) db-cAMP post-treatment. Rat pulmonary fibroblasts were cultured in vitro and divided into 4 groups as follows: 1) controls; 2) 10-7mol/L angiotensin II (Ang II); 3) Ang II +10-4 mol/L db-cAMP; and 4) Ang II + db-cAMP+ 10-6 mol/L H89. Hematoxylin-eosin (HE), Van Gieson staining and immunohistochemistry (IHC) were performed to observe the histomorphology of lung tissue. The levels of cAMP were detected by enzyme immunoassay. Double-labeling for α-SMA with Gαi3, protein kinase A (PKA), phosphorylated cAMP-response element-binding protein (p-CREB), and p-Smad2/3 was identified by immunofluorescence staining. Protein levels were detected by Western blot analysis. The interaction between CREB-binding protein (CBP) and Smad2/3 and p-CREB were measured by co-immunoprecipitation (Co-IP). RESULTS: Db-cAMP treatment reduced the number and size of silicosis nodules, inhibited myofibroblast differentiation, and extracellular matrix deposition in vitro and in vivo. In addition, db-cAMP regulated Gαs protein and inhibited expression of Gαi protein, which increased endogenous cAMP. Db-cAMP increased phosphorylated cAMP-response element-binding protein (p-CREB) via protein kinase A (PKA) signaling, and decreased nuclear p-Smad2/3 binding with CREB binding protein (CBP), which reduced activation of p-Smads in fibroblasts induced by Ang II. CONCLUSIONS: This study showed an anti-silicotic effect of db-cAMP that was mediated via PKA/p-CREB/CBP signaling. Furthermore, the findings offer novel insight into the potential use of cAMP signaling for therapeutic strategies to treat silicosis.


Assuntos
Asbestose/tratamento farmacológico , Asbestose/metabolismo , Proteína de Ligação a CREB/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , CMP Cíclico/análogos & derivados , Proteínas de Membrana/metabolismo , Miofibroblastos/efeitos dos fármacos , Fosfoproteínas/metabolismo , Animais , Asbestose/patologia , Diferenciação Celular/efeitos dos fármacos , CMP Cíclico/administração & dosagem , Masculino , Miofibroblastos/patologia , Ratos , Ratos Wistar , Transdução de Sinais/efeitos dos fármacos , Resultado do Tratamento
13.
Arch Bronconeumol ; 53(6): 318-323, 2017 Jun.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-27914752

RESUMO

INTRODUCTION: Bronchoalveolar lavage (BAL) analysis has been proposed as an objective technique for confirming asbestos exposure. However, the reliability and diagnostic yield of this procedure has not been studied in Spain. The aim of this study was to assess the usefulness of the analysis of asbestos bodies (AB) in bronchoalveolar lavage (BAL) for the diagnosis of asbestos-related diseases (ARD). METHODS: BAL samples from 72 patients (66 male, mean age 66 years) undergoing bronchoscopy were analyzed. Lung tissue from 23 of these patients was also analyzed. Asbestos exposure was assessed by anamnesis and a review of the patient's medical records. BAL and lung samples were processed and AB count was determined by light microscopy. The accepted threshold value to diagnose asbestos-related diseases was 1 AB/ml BAL or 1000 AB/gr dry tissue. RESULTS: Thirty-nine patients reported exposure to asbestos. Of these, 13 (33%) presented AB values above 1 AB/ml BAL. In the 33 non-exposed patients, 5 (15%) presented AB values above 1 AB/ml BAL. There was a significant difference between the AB levels of exposed and non-exposed patients (P=.006). The ROC curve showed that a value of 0.5 AB/ml BAL achieved the most satisfactory sensitivity, 46%, and a specificity of 83%. The correlation between AB levels in BAL and lung was 0.633 (P=.002). CONCLUSIONS: BAL study provides objective evidence of exposure to asbestos. The good correlation between the AB counts in BAL and lung tissue indicates that both techniques are valid for the analysis of asbestos content.


Assuntos
Asbestos/análise , Líquido da Lavagem Broncoalveolar/química , Pneumopatias/etiologia , Fibras Minerais/análise , Idoso , Asbestos/efeitos adversos , Asbestose/diagnóstico , Asbestose/etiologia , Asbestose/patologia , Broncoscopia , Carcinoma/química , Carcinoma/diagnóstico , Carcinoma/etiologia , Carcinoma/patologia , Feminino , Humanos , Pneumopatias/diagnóstico , Pneumopatias/patologia , Neoplasias Pulmonares/química , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/patologia , Masculino , Mesotelioma/química , Mesotelioma/diagnóstico , Mesotelioma/etiologia , Mesotelioma/patologia , Pessoa de Meia-Idade , Ocupações , Neoplasias Pleurais/química , Neoplasias Pleurais/diagnóstico , Neoplasias Pleurais/etiologia , Neoplasias Pleurais/patologia , Valor Preditivo dos Testes , Curva ROC , Estudos Retrospectivos , Sensibilidade e Especificidade
14.
Rom J Morphol Embryol ; 57(3): 1171-1174, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28002541

RESUMO

Asbestos is a mineral-mined form the rocks, consisting in amosite (brown asbestos), crocidolite (blue asbestos) and÷or chrysotile (white asbestos) used in many industries. Researches about the exposure to asbestos dust and asbestosis related diseases started almost a century ago. The first case report of fatal asbestosis disease was published in 1906, in England, by Dr. Hubert Montague Murray. A decade after, asbestos "curious bodies" were firstly described in the lung tissue by Cooke (1926) and McDonald (1927). Occupational exposure to asbestos is now regulated in Romania, but past exposure is still a cause of asbestosis-related diseases (ARDs), including lung cancer. A peculiar association between a lung adenocarcinoma, a previously healed pulmonary tuberculosis (PTB) disease, is reported in a 61-year-old nonsmoker white man, a former factory worker with 29 years of occupational exposure history to cement and asbestos fibers. The positive diagnosis of asbestos exposure was facilitated by asbestos bodies determined in bronchoalveolar lavage fluid. The main purpose of this case report is to describe the development of a right pleural effusion which was not revelatory for a mesothelioma but for an adenocarcinoma of the lung. An accurate morphologic and immunohistochemistry assessment of a pleural biopsy sample excluded mesothelioma and was crucial in the positive diagnosis of adenocarcinoma. In conclusion, unilateral paraneoplastic pleural effusion in a nonsmoker male with occupational exposure to asbestosis fibers was suggestive for adenocarcinoma related asbestosis of the lung. Lung cancer and malignant pleural exudate developed after a long latency cumulative retention time of asbestos fibers.


Assuntos
Adenocarcinoma/imunologia , Líquido da Lavagem Broncoalveolar/citologia , Neoplasias Pulmonares/imunologia , Mesotelioma/imunologia , Adenocarcinoma/patologia , Adenocarcinoma de Pulmão , Asbestose/patologia , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/patologia , Masculino , Mesotelioma/patologia , Pessoa de Meia-Idade
15.
Eur J Radiol ; 85(9): 1594-600, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27501894

RESUMO

OBJECTIVE: To elucidate differences in the level and localization of pleural irregularities in early malignant pleural mesothelioma (eMPM) and benign asbestos pleural effusion (BAPE) using CT. STUDY DESIGN: Retrospective assessment of CT findings of consecutive patients with BAPE at a single centre and patients with eMPM reported in Japanese vital statistics. METHODOLOGY: Thirty-six patients with confirmed diagnoses of BAPE and sixty-six patients with confirmed diagnoses of eMPM (mesothelioma stages T1 or T2) were included. Informed consent, CT scans, and clinical and pathologic details were obtained for all patients and were reviewed by one radiologist, two pathologists, and two pulmonologists. Asbestosis, pleural plaque, rounded atelectasis, and diffuse pleural thickening were assessed in all patients. RESULTS: Prevalence of asbestosis, pleural plaque, rounded atelectasis, and diffuse pleural thickening was significantly higher in the BAPE group. Low-level irregularity was more common in the BAPE group (p<0.001), whereas high-level irregularity, mediastinal localization, and interlobar fissure were more prevalent in the eMPM group (p<0.001). Interlobar pleural irregularity was not observed in any patients in the BAPE group, although 55% of patients in the eMPM group showed interlobar pleural irregularity. Mediastinal pleural involvement was observed in 74% of patients in the eMPM group and had a positive predictive value of 89%. CONCLUSION: This study demonstrates that the level and localization of plural irregularities significantly differed between patients with BAPE and eMPM. Large-scale prospective studies are needed to fully establish the diagnostic utility of such differences.


Assuntos
Asbestose/patologia , Neoplasias Pulmonares/patologia , Mediastino/patologia , Mesotelioma/patologia , Pleura/patologia , Derrame Pleural/patologia , Tomografia Computadorizada por Raios X , Idoso , Asbestose/diagnóstico por imagem , Feminino , Humanos , Japão , Neoplasias Pulmonares/diagnóstico por imagem , Masculino , Mesotelioma/diagnóstico por imagem , Pessoa de Meia-Idade , Pleura/diagnóstico por imagem , Derrame Pleural/diagnóstico por imagem , Estudos Retrospectivos
18.
Med Lav ; 107(2): 141-7, 2016 Mar 24.
Artigo em Italiano | MEDLINE | ID: mdl-27015029

RESUMO

BACKGROUND: Malignant mesothelioma cases among primary school teachers are usually linked with asbestos exposure due to the mineral contained in the building structure. Among the approximately 12,000 cases of mesothelioma described in the fourth report of the National Mesothelioma Register, 11 cases of primary school teachers are reported, in spite of the fact that the "catalogue of asbestos use" does not describe circumstances of asbestos exposure other than or different to that due to asbestos contained in the buildings. Four cases in the Brescia Provincial Mesothelioma Register are identified as teachers, without this circumstance of exposure. OBJECTIVES: To characterize the asbestos concentration and fibre type retained in the lungs of a teacher reported as a new mesothelioma case and preliminarily classified as of unknown asbestos exposure. METHODS: The mesothelioma case presented here was diagnosed at age 78 and malignant mesothelioma was confirmed at autopsy; the patient was interviewed directly for occupational history. Samples of lung parenchyma from necropsies were collected, stored and analyzed by scanning electron microscope (SEM) and samples of DAS paste were analyzed by SEM to detect asbestos fibre content. RESULTS: It was possible to confirm past exposure to DAS paste in forming and finishing dry items and toys during school recreational activity almost every day from the mid-60s to about the mid-70s. Subsequent SEM analysis showed: i) chrysotile fibres were found in an old and unused pack of DAS paste; ii) a lung burden of 1,400 asbestos bodies, 310.000 total asbestos fibres (33% chrysotile, 67% amphibole) and 210.000 talc fibre per gr/dry lung tissue was detected from necropsies performed on the subject. These results seem to be in agreement with an occupational exposure to asbestos due to past use of DAS paste. After the investigation, this case was reclassified from "unknowun" to " sure" occupational asbestos exposure. The occupational origin of the tumour was recognized by the Italian Workers' Compensation Authority (INAIL). CONCLUSION: This case suggests i) the need to carry out any possible detailed studies of the circumstances and exposure sources whenever any mesothelioma case is classified as "asbestos exposure unknown", according to the guidelines of the National Mesothelioma Register, ii) handling of DAS paste can be considered as sure asbestos exposure and iii) it should be borne in mind that mesothelioma cases can occur even after cumulative low, occupational exposure, even only to chrysotile.


Assuntos
Asbestos Serpentinas/efeitos adversos , Asbestose/complicações , Docentes , Neoplasias Pulmonares/etiologia , Mesotelioma/etiologia , Exposição Ocupacional/efeitos adversos , Jogos e Brinquedos , Neoplasias Pleurais/etiologia , Idoso , Amiantos Anfibólicos/efeitos adversos , Asbestose/etiologia , Asbestose/patologia , Autopsia , Feminino , Humanos , Itália , Neoplasias Pulmonares/patologia , Mesotelioma/patologia , Neoplasias Pleurais/patologia
20.
Histopathology ; 69(3): 492-8, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26864248

RESUMO

AIMS: To determine whether usual interstitial pneumonia (UIP) pattern fibrosis is seen in asbestosis. METHODS AND RESULTS: The occurrence of UIP pattern fibrosis was studied in four asbestos cohorts systematically referred following postmortem to the UK Pneumoconiosis Unit, Cardiff. The combined exposed workforce comprised >25 000 persons. Over the 17-year period, 233 subjects were identified; 210 had degrees of interstitial fibrosis with a fibrotic non-specific interstitial pneumonia pattern and subpleural accentuation, and three showed UIP pattern fibrosis. All three of these cases showed grade 4 fibrosis (honeycombing) with no asbestos fibre dose-response correlation. A Poisson distribution of probability analysis indicated that the observed cases of UIP in this workforce could be wholly accounted for by the prevalence of idiopathic pulmonary fibrosis (IPF) in the population. CONCLUSIONS: UIP pattern fibrosis is rarely observed in asbestos-exposed subjects, and shows no dose-response correlation with asbestos fibres on mineral analysis; this points to an alternative disease, such as IPF. The results indicate that UIP pattern fibrosis should not be regarded as genuine asbestosis, irrespective of the status of asbestos biomarkers, and this impacts upon the postmortem handling of asbestos-related deaths.


Assuntos
Asbestose/patologia , Fibrose Pulmonar Idiopática/patologia , Asbestose/complicações , Humanos , Fibrose Pulmonar Idiopática/epidemiologia , Fibrose Pulmonar Idiopática/etiologia , Incidência , Estudos Retrospectivos
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