Hard metal lung disease: a case series / Doença pulmonar por metal duro: uma série de casos

ABSTRACT Objective: To describe diagnostic and treatment aspects of hard metal lung disease (HMLD) and to review the current literature on the topic. Methods: This was a retrospective study based on the medical records of patients treated at the Occupational Respiratory Diseases Clinic of the Instituto do Coração, in the city of São Paulo, Brazil, between 2010 and 2013. Results: Of 320 patients treated during the study period, 5 (1.56%) were diagnosed with HMLD. All of those 5 patients were male (mean age, 42.0 ± 13.6 years; mean duration of exposure to hard metals, 11.4 ± 8.0 years). Occupational histories were taken, after which the patients underwent clinical evaluation, chest HRCT, pulmonary function tests, bronchoscopy, BAL, and lung biopsy. Restrictive lung disease was found in all subjects. The most common chest HRCT finding was ground glass opacities (in 80%). In 4 patients, BALF revealed multinucleated giant cells. In 3 patients, lung biopsy revealed giant cell interstitial pneumonia. One patient was diagnosed with desquamative interstitial pneumonia associated with cellular bronchiolitis, and another was diagnosed with a hypersensitivity pneumonitis pattern. All patients were withdrawn from exposure and treated with corticosteroid. Clinical improvement occurred in 2 patients, whereas the disease progressed in 3. Conclusions: Although HMLD is a rare entity, it should always be included in the differential diagnosis of respiratory dysfunction in workers with a high occupational risk of exposure to hard metal particles. A relevant history (clinical and occupational) accompanied by chest HRCT and BAL findings suggestive of the disease might be sufficient for the diagnosis.

RESUMO Objetivo: Descrever aspectos relacionados ao diagnóstico e tratamento de pacientes com doença pulmonar por metal duro (DPMD) e realizar uma revisão da literatura. Métodos: Estudo retrospectivo dos prontuários médicos de pacientes atendidos no Serviço de Doenças Respiratórias Ocupacionais do Instituto do Coração, localizado na cidade de São Paulo, entre 2010 e 2013. Resultados: Entre 320 pacientes atendidos no período do estudo, 5 (1,56%) foram diagnosticados com DPMD. Todos os pacientes eram do sexo masculino, com média de idade de 42,0 ± 13,6 anos e média de tempo de exposição a metal duro de 11,4 ± 8,0 anos. Os pacientes foram submetidos a avaliação clinica, história ocupacional, TCAR de tórax, prova de função pulmonar, broncoscopia com LBA e biópsia pulmonar. Todos apresentaram distúrbio ventilatório restritivo. O achado de imagem à TCAR de tórax mais frequente foi de opacidades em vidro fosco (em 80%). Em 4 pacientes, o LBA revelou presença de células gigantes multinucleadas. Em 3, foi diagnosticada pneumonia intersticial por células gigantes na biópsia pulmonar. Houve o diagnóstico de pneumonia intersticial descamativa associada à bronquiolite celular em 1 paciente e de pneumonite de hipersensibilidade em 1. Todos foram afastados da exposição e tratados com corticoide. Houve melhora em 2 pacientes e progressão da doença em 3. Conclusões: Apesar de ser uma entidade rara, a DPMD deve ser sempre considerada em trabalhadores com risco ocupacional elevado de exposição a metais duros. A história clínica e ocupacional associada a achados em TCAR de tórax e LBA sugestivos da doença podem ser suficientes para o diagnóstico.

Cobalt oxide nanoparticles aggravate DNA damage and cell death in eggplant via mitochondrial swelling and NO signaling pathway

BACKGROUND: Despite manifold benefits of nanoparticles (NPs), less information on the risks of NPs to human health and environment has been studied. Cobalt oxide nanoparticles (Co3O4-NPs) have been reported to cause toxicity in several organisms. In this study, we have investigated the role of Co3O4-NPs in inducing phytotoxicity, cellular DNA damage and apoptosis in eggplant (Solanum melongena L. cv. Violetta lunga 2). To the best of our knowledge, this is the first report on Co3O4-NPs showing phytotoxicity in eggplant. RESULTS: The data revealed that eggplant seeds treated with Co3O4-NPs for 2 h at a concentration of 1.0 mg/ml retarded root length by 81.5 % upon 7 days incubation in a moist chamber. Ultrastructural analysis by transmission electron microscopy (TEM) demonstrated the uptake and translocation of Co3O4-NPs into the cytoplasm. Intracellular presence of Co3O4-NPs triggered subcellular changes such as degeneration of mitochondrial cristae, abundance of peroxisomes and excessive vacuolization. Flow cytometric analysis of Co3O4-NPs (1.0 mg/ml) treated root protoplasts revealed 157, 282 and 178 % increase in reactive oxygen species (ROS), membrane potential (APm) and nitric oxide (NO), respectively. Besides, the esterase activity in treated protoplasts was also found compromised. About 2.4-fold greater level of DNA damage, as compared to untreated control was observed in Comet assay, and 73.2 % of Co3O4-NPs treated cells appeared apoptotic in flow cytometry based cell cycle analysis. CONCLUSION: This study demonstrate the phytotoxic potential of Co3O4-NPs in terms of reduction in seed germination, root growth, greater level of DNA and mitochondrial damage, oxidative stress and cell death in eggplant. The data generated from this study will provide a strong background to draw attention on Co3O4-NPs environmental hazards to vegetable crops.

Hip-implant related chorio-retinal cobalt toxicity.

A 39-year-old female with elevated serum cobalt levels from her bilateral hip prostheses presented with a 3-week history of blurred vision in her left eye. Optical coherence tomography revealed patchy degeneration of the photoreceptor-retinal pigment epithelium (RPE) complex. The lesions were hypofluorescent on indocyanine green angiography. We postulate that this is a case of implant-related chorio-retinal cobalt toxicity.

Pneumoconiose por exposição a metal duro com pneumotórax bilateral espontâneo / Hard metal pneumoconiosis with spontaneous bilateral pneumothorax

A pneumoconiose por metal duro, descrita pela primeira vez em 1964, é uma doença difusa causada por inalação de partículas de cobalto. A doença pode se manifestar de três formas diferentes: asma ocupacional, doença intersticial e alveolite alérgica. Relata-se um caso de um jovem do sexo masculino, afiador de ferramentas, com quadro de tosse seca e dispnéia progressiva há um ano, apresentando-se à admissão com pneumotórax espontâneo bilateral. O diagnóstico foi confirmado através de biópsia pulmonar a céu aberto.

Hard metal pneumoconiosis, first described in 1964, is a diffuse disease caused by the inhalation of cobalt particles. The disease can manifest as occupational asthma, interstitial disease or allergic alveolitis. We report the case of a young male, working as a tool sharpener, who presented with dry cough and progressive dyspnea for one year, as well as with spontaneous bilateral pneumothorax at admission. The diagnosis was confirmed by open lung biopsy.

Doença pulmonar por metal duro em trabalhador da indústria petrolífera / Hard metal lung disease in an oil industry worker

A doença pulmonar por metal duro é uma pneumonia intersticial por células gigantes relacionada com a exposição à poeira composta por metais duros. Neste artigo é relatado o caso de um profissional da indústria petrolífera, diagnosticado com doença pulmonar por metal duro com base na documentação clínica, radiológica, funcional pulmonar e anatomopatológica.

Hard metal lung disease, which manifests as giant cell interstitial pneumonia, is caused by exposure to hard metal dust. We report the case of an oil industry worker diagnosed with hard metal lung disease. The diagnosis was based on the clinical, radiological and anatomopathological analysis, as well as on pulmonary function testing.

Efectos del cloruro de cobalto sobre el epitelio de unión y epitelio reducido del esmalte del primer molar superior de rata / Effects of cobalt chloride in junctional epithelium and reduced enamel epithelium of the rat maxillary first molar

El cobalto es uno de los principales componentes de las aleaciones metálicas fundidas, usadas frecuentemente en odontología. El metal es el constituyente de 45 a 70 por ciento de los trabajos protéticos. En virtud de la existencia de evidencias que elementos metálicos pueden causar toxicidad sistémica y local, este trabajo tuvo como objetivo evaluar los efectos del cobalto sobre el epitelio de unión y el epitelio del esmalte del primer molar superior de rata, durante la lactancia. Con esa finalidad fueron usadas ratas con 1 día de vida postnatal, cuyas madres recibieron 300 mg de cloruro de cobalto por litro de agua destilada en el bebedero, durante a la lactancia. Al cabo de 21 días, las crías fueron sacrificadas con sobredosis anestésica. Las cabezas fueron separadas, fijadas en "alfac", descalcificadas e incluidas en parafina. Fueron utilizados cortes frontales seriados teñidos con hematoxilina y eosina. Fueron estimados los siguientes parámetros nucleares: diámetros mayor, menor y geométrico medio, relación entre diámetros, perímetro, área, volumen, relación entre volumen y área, excentricidad, coeficiente de forma e índice de contorno. Mediante métodos estereológicos fueron evaluados: relación núcleo/citoplasma, volumen celular, densidad numérica celular, relación superficie externa/camada basal, espesor de las camadas epiteliales y densidad de superficie. Todos los datos obtenidos fueron sometidos a análisis estadístico mediante la prueba no-paramétrica de Wilcoxon-Mann-Whitney. Los núcleos de los tejidos estudiados mostraron valores menores para diámetros, perímetro, área, volumen y relación volumen/área. Estereológicamente, fue posible observar en el epitelio de unión y en el epitelio reducido del esmalte, células menores con citoplasma más escaso, lo que se refleja en mayor número de células por mm3 de tejido. En este estudio, el cobalto ocasionó un cuadro de atrofia epitelial, sugiriendo una acción directa sobre los epitelios de unión y del esmalte.

Cobalt is one of the main components of cast metal alloys broadly used in dentistry. It is the constituent of 45 to 70 percent of numerous prosthetic works. There are evidences that metal elements cause systemic and local toxicity. The purpose of the present study was to evaluate the effects of cobalt on the junctional epithelium and reduced enamel epithelium of the first superior molar in rats, during lactation. To do this, 1-day old rats were used, whose mothers received 300mg of cobalt chloride per liter of distilled water in the drinker, during lactation. After 21 days, the rat pups were killed with an anesthetic overdose. The heads were separated, fixed in "alfac", decalcified and embedded in paraffin. Frontal sections stained with hematoxylin and eosin were employed. Karyometric methods allowed to estimate the following parameters: biggest, smallest and mean diameters, D/d ratio, perimeter, area, volume, volume/area ratio, eccentricity, form coefficient and contour index. Stereologic methods allow to evaluate: cytoplasm/nucleus ratio, cell and cytoplasm volume, cell number density, external surface/basal membrane ratio, thickness of the epithelial layers and surface density. All the collected data were subjected to statistic analysis by the non-parametric Wilcoxon-Mann-Whitney test. The nuclei of the studied tissues showed smaller values after karyometry for: diameters; perimeter, area, volume and volume/area ratio. Stereologically, it was observed, in the junctional epithelium and in the reduced enamel epithelium, smaller cells with scarce cytoplasm, reflected in the greater number of cells per mm3 of tissue. In this study, cobalt caused epithelial atrophy, indicating a direct action on the junctional and enamel epithelium.

The effects of Co2+ and Zn2+ on the contents of protein, abscisic acid, proline and chlorophyll in bean (Phaseolus vulgaris cv. Strike) seedlings.

17-day-old bean plants (Phaseolus vulgaris cv. Strike) were used to analyze the effects of Co2+ and Zn2+ on the time course of proline, total protein, chlorophyll and abscisic acid (ABA) levels in leaves. Controls, Co2+ and Zn2+-treated plants were grown for 8 days in Hoagland solution. Samples were taken at 2 day intervals. Proline, chlorophyll (a+b) and total protein contents of 17 day old primary leaves were determined by a spectrophotometer. ABA contents in roots and leaves of the seedlings were measured by high-pressure liquid chromatography. The presence of Zn2+ and Co2+ significantly increased the ABA contents in roots and leaves (p < 0.05 or p < 0.01). The increase of the abscisic acid content in the leaves was related to the content of the roots. This was further substantiated by enhanced accumulation of proline in the leaves of seedlings exposed to zinc and cobalt. The contents of chlorophyll (a+b) and total protein decreased with the concentration of both metals (p < 0.05 or p < 0.01). Cobalt proved to be comparatively more toxic than zinc.

Result of standard patch test in patients suspected of having allergic contact dermatitis.

Contact dermatitis is a common skin disease. Disease was diagnosed by a history of contact substance together with geographic distribution of lesion. Up till now, standard patch test is one of the most reliable test to identify and confirm causative agent of allergic contact dermatitis. To determine the rate of positive standard patch test and to identify the common allergen of contact dermatitis in Thailand, we performed the standard patch test in 129 patients, suspected having allergic contact dermatitis at Department of Dermatology, King Chulalongkorn Memorial Hospital, Thailand from June 1, 2003 to September 1, 2004. The rate of positive standard patch test is 59.7% (n = 77/129). The most 3 common positive allergens were nickel sulfate (18.60%), cobalt chloride (17.05%) and fragrance mix (14.73%), respectively. The chance of positive standard patch test significantly correlated with sex (woman), initial diagnosis as contact dermatitis and history of house-worker (p = 0.017, p = 0.005 and p = 0.023, respectively). Whereas, there were no significant correlation between the chance of positive standard patch test and age of patient, location of lesion, history of recurrence, history of atopy, history of drug and food allergy. In addition, history of metal allergy significantly correlated with the chance of positive nickel sulfate or cobalt chloride in standard patch test (p = 0.017). In conclusion, this study demonstrated the prevalence of causative allergen of contact dermatitis in Thai patients using that standard patch test. Moreover, our data shown that the chance positive standard patch test was greater in patient, who were women or initial diagnosed as contact dermatitis or had history of houseworker or history of metal allergy.

Reaçöes aos metais utilizados em ortodontia / Hypersensibility to orthodontic metals appliance

Estudo clínico e experimental da incidência de hipersensibilidade a metais dos aparelhos ortodônticos e das consequências morfológicas da absorçäo do níquel. Realizaram-se testes de contato, antes e dois meses após a colocaçäo de aparelhos, em 38 pacientes, utilizando-se como antígenos o cloreto e cobalto, sulfato de cobre, bicromato de potássio, sulfato de ferro, cloreto de manganês, sal de molibdênio, sulfato de níquel e óxido de titânio. Concluiu-se que: manganês, cromo e níquel apresentaram positividade, estatisticamente significativa, com prevalência de 21,1 por cento para os dois últimos matais. Näo houve diferença estatisticamente significativa no resultado do teste de contato em relaçäo ao sexo e ao aparelho (antes ou depois). Avaliou-se, através de espectroscopia de absorçäo atômica, a quantidade de níquel na urina de 21 pacientes, nestes dois momentos, constatando-se aumento da mesma após a montagem do aparelho, näo havendo diferença estatística entre os sexos. A avaliaçäo experimental foi realizada em 26 camundongos (Swiss webster), divididos em dois grupos controle (C14 e C45) e dois grupos níquel (N14 e N15), que receberam aplicaçäo subcutânea de sulfato de níquel, sendo sacrificados após 15 e 46 dias. Constatou-se, no grupo experimental, aumento de peso total e de alguns órgäos, lesäo microscópica em órgäos hematopoiéticos, coraçäo, fígado e rins, mais evidente em N45. Nefrotoxicidade foi evidenciada por modificaçäo no padräo de ligaçäo às lectinas. No fígado, a análise estereológica demonstrou aumento do volume dos hepatócitos e de seus núcleos. Näo se dectou quantidades mensuráveis de níquel ao micrscópio eletrônico de varredura com raios X por energia dispersa (EDS)

COPP/ABV chemotherapy followed by radiotherapy for patients with hodgkin's disease

The aim of this trial was to evaluate efficacy and toxicity of COPP/ABV combined with reduced radiotherapy in patients with stage I-III Hodgkin's disease [HD]. Forty-three patients were prospectively treated with 4 cycles [stage I and II patients] or six cycles [stage III patients] of COPP/ABV [cyclophosphamide, vincristine, procarbazine, prednisone/adriamycin, bleomycin, vinblastine] followed by radiotherapy; 25 Gy to areas of initial involvement. In sites of bulky disease >/= 5 cm, the radiotherapy dose was raised to 40 Gy. The complete remission [CR] rate was 83.7%. The 5-year progression free survival [PFS] was 64% and the 5-year overall survival [OS] was 77%. Prognostic factors that could significantly affect the CR rate and the PFS were age [< vs >/= 40 years], stage of disease [I and II vs III] and the presence of bulky disease >/= 5 cm. Treatment was well tolerated with acceptable early and late toxicity. It is concluded that COPP/ABV combined with reduced radiotherapy for patients with stage I-III HD is a safe and effective approach. Further research is needed with treatment strategies being tailored according to prognostic factors

Experimental dilating cardiomyopathy and myocardial ionic changes in mice.

This study was designed to examine the myocardial ionic changes in experimental animal models of dilating cardiomyopathy induced by treating male balb-c mice either with cobalt chloride [2 mg/ kg, i.p] or tyramine HC1 [5 mg/kg i.p] once daily for 5 and 10 days. Age and weight matched mice were treated with distilled water served as controls. Our results showed that cobalt chloride and tyramine HC1 produced an increase in cardiac mass and non specific histopathological changes of congestive cardiomyopathy. The induction of cardiomyopathy was associated with significant alterations in myocardial ions which is related to the inducing agent. We conclude that the similarity and discrepency in myocardial ions levels in experimental dilating [congestive] cardiomyopathy is a part related to the causative agent

Cobalt-induced inhibition of growth in cyanobacteria Anabaena doliolum and Anacystis nidulans: interaction with sulphur containing amino acids.

Cobalt, above 1 microM concentration was growth inhibitory for both A. doliolum and A. nidulans. Its toxicity was mitigated by sulphur containing amino acids (cystine and cysteine), however, methionine could not mitigate the cobalt toxicity at all.

Sobre los compuestos de coordinación como agentes antitumorales: III: efectos electrónico-estructurales / On coordination compounds as antitumorigenic agents: III: electronic and structural effects

Se reportan los valores de toxicidad in vitro, en la linea celular Kb, de 28 tiosemicarbazonas y sus correspondientes compuestos de coordinación con cobalto, níquel, cobre y cinc. A partir de estos valores se hacen consideraciones sobre qué influencia pueden tener sobre esta propiedad los efectos electrónicos y estructurales, y se concluye que los primeros resultan ser los determinantes

Retinal toxicity of trace elements.

Acute toxicity of lead, nickel and cobalt on rabbit retina was studied. It was found that all these metals produced similar photoreceptor degenerative changes, but lead produced extensive degenerative changes at ganglion cell layer also. Electroretinographically nickel group showed statistically (by analysis of variance) significant prolongation of 'b' wave implicit time as seen in autosomal dominant retinitis pigmentosa.