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1.
Analyst ; 134(2): 301-7, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-19173053

RESUMO

Matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS) is a recently developed technique that generates molecular profiles usually of peptide and protein signals directly from the surface of thin tissue sections and can be coupled with automation to generate two-dimensional ion density maps. This allows specific information to be obtained on the relative abundance and spatial distribution of the analytes of interest. The technique has potential for application in many diseases including cancer with respect to elucidating the molecular pathology and identifying potential biomarkers. In this proof-of-principle study we have evaluated inkjet printing of the sinapinic acid matrix used for MALDI-IMS directly onto the surface of human oral squamous cell carcinoma biopsy specimens. This MS profiling technique produced reproducible informative chemical images for clinical pathology. Analysis of the resulting protein profiles of highly expressed protein in squamous cell carcinoma of the tongue reveals spectral features at approximately 4500 and approximately 8360 Da.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma de Células Escamosas/química , Neoplasias Bucais/química , Proteínas de Neoplasias/análise , Carcinoma de Células Escamosas/diagnóstico , Humanos , Neoplasias Bucais/diagnóstico , Proteômica/métodos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/instrumentação , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos
2.
Analyst ; 133(12): 1707-13, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19082073

RESUMO

The release of active pharmaceutical ingredients (APIs) into the environment is an ecologically important topic for study because, whilst APIs have been designed to have a wide range of biological properties for the target of interest (usually in man), little information on potential ecological risks is currently available regarding their effects on the organisms that inhabit the environment. In this study, the algae Micrasterias hardyi was exposed to propranolol, metoprolol (beta-adrenergic receptor agonist drugs) and mefenamic acid (a non steroidal anti-inflammatory drug), at concentrations ranging between 0.002-0.2 mM. Initial studies showed that Fourier transform infrared (FT-IR) spectroscopy on algal homogenates illustrated that all three APIs had a quantitative effect on the metabolism of the organisms and it was possible to estimate the level of API exposure from the FT-IR metabolic fingerprints using partial least squares (PLS) regression. From the inspection of the PLS loadings matrices it was possible to elucidate that all drugs caused effects on protein and lipid levels. Most strikingly propranolol had significant effects on the lipid components of the cell. These were dramatically reduced possibly as a consequence of loss of membrane integrity. In order to investigate this further, FT-IR microspectroscopy was used to generate detailed metabolic fingerprinting maps. These chemical maps revealed that all the drugs had a dramatic effect on the distribution of various chemical species throughout the algae, and that all drugs had an affect on protein and lipid levels. In particular, as noted in the PLS analyses for propranolol treated cells, the lipid complement found in the lipid storage areas in the processes of M. hardyi was greatly reduced. This illustrates the power of spatial metabolic fingerprinting for investigating abiotic stresses on complex biological species.


Assuntos
Eucariotos/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Antagonistas Adrenérgicos beta/toxicidade , Anti-Inflamatórios não Esteroides/toxicidade , Ácido Mefenâmico/toxicidade , Metoprolol/toxicidade , Propranolol/toxicidade , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Testes de Toxicidade Aguda
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