RESUMO
Cadmium (Cd) is a nephrotoxic environmental pollutant that causes insidious injury to the proximal tubule that results in severe polyuria and proteinuria. Cystatin C is a low molecular weight protein that is being evaluated as a serum and urinary biomarker for various types of ischemic and nephrotoxic renal injury. The objective of the present study was to determine if cystatin C might be a useful early biomarker of Cd nephrotoxicity. Male Sprague-Dawley rats were given daily injections of Cd for up to 12 weeks. At 3, 6, 9 and 12 weeks, urine samples were analyzed for cystatin C, protein, creatinine, ß2 microglobulin and kidney injury molecule-1. The results showed that Cd caused a significant increase in the urinary excretion of cystatin C that occurred 3-4 weeks before the onset of polyuria and proteinuria. Serum levels of cystatin C were not altered by Cd. Immunolabeling studies showed that Cd caused the relocalization of cystatin C from the cytoplasm to the apical surface of the epithelial cells of the proximal tubule. The Cd-induced changes in cystatin C labelling paralleled those of the brush border transport protein, megalin, which has been implicated as a mediator of cystatin C uptake in the proximal tubule. These results indicate that Cd increases the urinary excretion of cystatin C, and they suggest that this effect may involve disruption of megalin-mediated uptake of cystatin C by epithelial cells of the proximal tubule.
Assuntos
Biomarcadores/urina , Cádmio/toxicidade , Cistatina C/urina , Túbulos Renais Proximais/metabolismo , Animais , Biomarcadores/sangue , Cádmio/administração & dosagem , Moléculas de Adesão Celular/sangue , Creatinina/sangue , Cistatina C/sangue , Poluentes Ambientais , Humanos , Túbulos Renais Proximais/lesões , Túbulos Renais Proximais/patologia , Masculino , RatosRESUMO
BACKGROUND: Given the frequency with which many different strains of Staphylococcus aureus are found in various prehospital settings, this study sought to characterize S aureus isolates taken from one such environment. The objectives were to determine the frequency of S aureus in front-line, advanced life support (ALS) ambulances throughout the Chicago metropolitan area, and to generate antibiograms (antibiotic resistance profiles) for each S aureus isolate using 8 clinically relevant antibiotics. METHODS: Samples were obtained from 26 sites in 71 ambulances from 34 different Chicago-area municipalities. Selected colonies that demonstrated a growth pattern consistent with that of S aureus were subjected to a latex agglutination test specific for S aureus. Antibiograms and genetic analyses were performed on all latex agglutination test-positive isolates. RESULTS: At least one S aureus isolate was found in approximately 69% of all ambulances in the study. Of all isolates detected, 77% showed resistance to at least one antibiotic, and 34% displayed resistance to 2 or more antibiotics. Some level of oxacillin resistance was found in 21% of isolates; however, only slightly more than half of these oxacillin-resistant isolates were found to carry the methicillin-resistant S aureus-specific SCCmec cassette. Some 12% of all isolates were ultimately determined to be methicillin-resistant S aureus, whereas the remaining 88% were methicillin-sensitive S aureus with varying antibiograms. CONCLUSIONS: Antibiotic resistance appears to be prevalent in S aureus isolates detected in Chicago area ALS ambulances. Given the ease with which S aureus can survive on inanimate surfaces and exchange antibiotic resistance elements, a conscientious approach to the application of existing cleaning techniques, especially in key ambulance sites, is needed. Future work will include further characterizing isolates using multiple techniques, as well as follow-up studies with interested municipalities.