RESUMO
BACKGROUND: Delivery of a pharmacologically effective drug dosage to a target tissue is critical. Barrett's epithelia are a unique challenge for drug delivery of orally administered zinc due to rapid transit down the esophageal lumen, incomplete absorptive differentiation of these epithelia, and the use of proton-pump inhibitor drugs abrogating intestinal uptake of supplemental zinc. METHODS: Barrett's esophagus patients were administered oral zinc gluconate (26 mg zinc twice daily) for 14 days prior to biopsy procurement. Barrett's biopsies were analyzed for total zinc content by atomic absorption spectroscopy and by western immunoblot for cellular proteins known to be regulated by zinc. RESULTS: Cellular levels of both the Znt-1 transport protein and the alpha isoform of PKC were over 50% lower in the zinc treatment group. CONCLUSION: Oral zinc administration can result in effective delivery of zinc to Barrett's epithelia with resulting effects on intracellular signal transduction.
Assuntos
Esôfago de Barrett/tratamento farmacológico , Suplementos Nutricionais , Sistemas de Liberação de Medicamentos , Esôfago/efeitos dos fármacos , Gluconatos/administração & dosagem , Administração Oral , Adulto , Idoso , Esôfago de Barrett/metabolismo , Esôfago de Barrett/patologia , Biópsia , Western Blotting , Proteínas de Transporte de Cátions/efeitos dos fármacos , Proteínas de Transporte de Cátions/metabolismo , Esôfago/metabolismo , Esôfago/patologia , Feminino , Gluconatos/farmacocinética , Humanos , Masculino , Metaplasia , Pessoa de Meia-Idade , Proteína Quinase C-alfa/metabolismo , Transdução de Sinais/efeitos dos fármacos , Espectrofotometria Atômica , Fatores de Tempo , Resultado do TratamentoAssuntos
Colite Isquêmica/genética , Mutação , Protrombina/genética , Adulto , Colite Isquêmica/patologia , Análise Mutacional de DNA , Feminino , Humanos , Recidiva , RiscoRESUMO
Colorectal cancer (CRC) is one of the most common cancers in the western world. Early screening and detection could be highly preventative and therefore reduce mortality. Tight junctions (TJ) are well known for their function in controlling paracellular traffic of ions and molecules. It has become increasingly evident that TJs play a crucial role in maintaining cell-cell integrity, and the loss of cell junctional sealing could involve itself in the processes of carcinoma and cancer metastasis. If correlations between altered TJ proteins and CRC presence or invasiveness could be established, they may serve as important markers and guidelines for prophylactic and prognostic purposes, along with other screening methods. This review will present recent data from clinical and animal studies showing how altered TJ protein expression is a feature of certain CRCs. The up-regulation of claudin-1 in many CRCs is especially noteworthy. The focus of this article is simply on the association - however imperfect - between CRC and the major TJ transmembrane barrier proteins, namely claudins and occludin. Any causal relationship between TJ protein change and neoplasia remains conclusively unproven at present.