RESUMO
In designing a study to evaluate the inhalation biopersistence of a chrysotile asbestos that was used as a component of a joint-compound, a feasibility study was initiated to evaluate the short-term biopersistence of the chrysotile alone and of the chrysotile in combination with the sanded reformulated joint-compound. Two groups of Wistar rats were exposed to either 7RF3 chrysotile (Group 2) or to 7RF3 chrysotile combined with aerosolized sanded joint-compound (Group 3). In addition, a control group was exposed to filtered-air. The chrysotile used in the Ready Mix joint compound is rapidly removed from the lung. The chrysotile alone exposure group had a clearance half-time of fibers L > 20 microm of 2.2 days; in the chrysotile plus sanded exposure group the clearance half-time of fibers L > 20 microm was 2.8 days. However, across all size ranges there was approximately an order of magnitude decrease in the mean number of fibers remaining in the lungs of Group 3 as compared to Group 2 despite similiar aerosol exposures. Histopathological examination showed that the chrysotile exposed lungs had the same appearance as the filtered-air controls. This study uniquely illustrates that additional concurrent exposure to an aerosol of the sanded joint-compound, with large numbers of fine-particles depositing in the lungs, accelerates the recruitment of macrophages, resulting in a tenfold decrease in the number of fibers remaining in the lung. The increased number of macrophages in the chrysotile/sanded joint exposure group was confirmed histologically, with this being the only exposure-related histological finding reported.
Assuntos
Asbestos Serpentinas/farmacocinética , Materiais de Construção , Pulmão/metabolismo , Material Particulado/farmacocinética , Aerossóis , Animais , Asbestos Serpentinas/toxicidade , Câmaras de Exposição Atmosférica , Carga Corporal (Radioterapia) , Materiais de Construção/toxicidade , Estudos de Viabilidade , Exposição por Inalação , Pulmão/efeitos dos fármacos , Pulmão/patologia , Macrófagos/efeitos dos fármacos , Macrófagos/patologia , Masculino , Fibras Minerais , Tamanho da Partícula , Material Particulado/toxicidade , Ratos , Ratos Wistar , Reprodutibilidade dos Testes , Fatores de TempoRESUMO
Neurocognitive involvement in multiple sclerosis (MS) is heterogeneous with some authors suggesting a frontal pattern in patients with predominantly frontal lesions. To assess the relationship between the distribution of lesions and two cognitive components (visual N2, auditory P3a) of the event-related brain potential (ERP) receiving contributions from frontal lobe structures, we performed a combined ERP and magnetic resonance imaging (MRI) study. Thirty-four MS patients were assigned to "low lesion volume, (LLV)"(n = 12),"high lesion volume,(HLV)"(n = 12) and"frontal lesion volume, (FLV)" (n = 10) groups according to lesion volume and distribution on T2-weighted MRI-scans of the brain. ERPs in visual and auditory classification tasks as well as neuropsychological tests were carried out in patients and control subjects (n = 15). The index for automatic feature registration, the N2 component with its mainly frontal contribution in the visual task, was significantly reduced in amplitude in the FLV and HLV groups (both p < 0.01 vs. controls). Moreover its amplitude correlated with lesion volume (r=0.64, p < 0.001). In contrast neither P3a nor P3b subcomponents with a multiple generator nature in the auditory task varied systematically with lesion volume or distribution. Total lesion volume rather than predominant lesion arrangement appears to be the most important factor in neurocognitive changes in MS. This is most consistent with the view that MS lesions lead to partial disconnections within widespread cortical networks which in turn produce a pattern of neuropsychological deficits that reflect total lesion load more than lesion distribution.