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1.
Eur J Clin Microbiol Infect Dis ; 33(7): 1173-80, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24487911

RESUMO

Pneumocystis pneumonia (PcP) is a major HIV-related illness caused by Pneumocystis jirovecii. Definitive diagnosis of PcP requires microscopic detection of P. jirovecii in pulmonary specimens. The objective of this study was to evaluate the usefulness of two serum markers in the diagnosis of PcP. Serum levels of (1-3)-beta-d-glucan (BG) and lactate dehydrogenase (LDH) were investigated in 100 HIV-positive adult patients and 50 healthy blood donors. PcP cases were confirmed using indirect immunofluorescence with monoclonal anti-Pneumocystis antibodies and nested-PCR to amplify the large subunit mitochondrial rRNA gene of P. jirovecii in pulmonary specimens. BG and LDH levels in serum were measured using quantitative microplate-based assays. BG and LDH positive sera were statistically associated with PcP cases (P ≤ 0.001). Sensitivity, specificity, positive/negative predictive values (PPV/NPV), and positive/negative likelihood ratios (PLR/NLR) were 91.3 %, 61.3 %, 85.1 %, 79.2 %, 2.359, and 0.142, respectively, for the BG kit assay, and 91.3 %, 35.5 %, 75.9 %, 64.7 %, 1.415 and 0.245, respectively, for the LDH test. Serologic markers levels combined with the clinical diagnostic criteria for PcP were evaluated for their usefulness in diagnosis of PcP. The most promising cutoff levels for diagnosis of PcP were determined to be 400 pg/ml of BG and 350 U/l of LDH, which combined with clinical data presented 92.8 % sensitivity, 83.9 % specificity, 92.8 % PPV, 83.9 % NPV, 5.764 PLR and 0.086 NLR (P < 0.001). This study confirmed that BG is a reliable indicator for detecting P. jirovecii infection. The combination between BG/LDH levels and clinical data is a promising alternative approach for PcP diagnosis.


Assuntos
Biomarcadores/sangue , L-Lactato Desidrogenase/sangue , Pneumonia por Pneumocystis/diagnóstico , beta-Glucanas/sangue , Adulto , Idoso , Feminino , Infecções por HIV/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Proteoglicanas , Sensibilidade e Especificidade , Soro/química , Adulto Jovem
2.
Mutat Res ; 724(1-2): 28-34, 2011 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-21640195

RESUMO

Doxorubicin (Dox) is a widely used drug in oncology with a broad spectrum of interactions with various cellular components; therefore, it is likely to act through different mechanisms. In clinical practice there is inter-individual variability in cytotoxic drug response and in the occurrence of adverse reactions. Glutathione S-transferases (GSTM1, GSTT1 and GSTP1) are thought to be involved in the detoxification of endogenous and exogenous genotoxicants. The aim of this work is the assessment of a possible influence of polymorphisms in GSTs on the levels of genetic damage induced in vitro by Dox in cultured human lymphocytes. For this purpose, whole blood cultures from individuals with different genotypes for GSTM1, GSTT1 and GSTP1 were exposed to Dox and the cytokinesis-blocked micronucleus (CBMN) assay was used as the endpoint for chromosomal damage in the lymphocytes. Genotyping of GSTM1 and GSTT1 was carried out by multiplex PCR and the GSTP1-Ile105Val polymorphism was determined by PCR/RFLP. The total number of micronuclei present in 1000 binucleated cells and the frequency of micronucleated binucleated lymphocytes in the different individuals were analyzed considering the GSTM1, GSTT1 and GSTP1 genotypes. The results obtained suggest that GSTM1 and GSTT1 deletion polymorphisms do not modify significantly the genotoxic potential of Dox. However, the GSTP1 Ile105Val polymorphism was associated with an increase of micronucleated binucleated cells induced by Dox. Lymphocytes from homozygous individuals for the variant form (Val/Val) presented a significant increase in micronucleated binucleated cells (approximately 1.5-fold; p<0.05) when compared with individuals with at least one wild-type allele. These results suggest a possible role for GSTP1 on the modulation of the genotoxicity induced by Dox, which may be considered in cancer therapy.


Assuntos
Antibióticos Antineoplásicos/toxicidade , Doxorrubicina/toxicidade , Glutationa Transferase/genética , Polimorfismo Genético , Adulto , Divisão Celular/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Feminino , Genótipo , Humanos , Linfócitos/efeitos dos fármacos , Masculino , Testes para Micronúcleos/métodos , Adulto Jovem
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