RESUMEN
Initiation of intestinal Na(+)-glucose cotransport results in transient cell swelling and sustained increases in tight junction permeability. Since Na(+)/H(+) exchange has been implicated in volume regulation after physiological cell swelling, we hypothesized that Na(+)/H(+) exchange might also be required for Na(+)-glucose cotransport-dependent tight junction regulation. In Caco-2 monolayers with active Na(+)-glucose cotransport, inhibition of Na(+)/H(+) exchange with 200 microM 5-(N,N-dimethyl)- amiloride induced 36 +/- 2% increases in transepithelial resistance (TER). Evaluation using multiple Na(+)/H(+) exchange inhibitors showed that inhibition of the Na(+)/H(+) exchanger 3 (NHE3) isoform was most closely related to TER increases. TER increases due to NHE3 inhibition were related to cytoplasmic acidification because cytoplasmic alkalinization with 5 mM NH(4)Cl prevented both cytoplasmic acidification and TER increases. However, NHE3 inhibition did not affect TER when Na(+)-glucose cotransport was inhibited. Myosin II regulatory light chain (MLC) phosphorylation decreased up to 43 +/- 5% after inhibition of Na(+)/H(+) exchange, similar to previous studies that associate decreased MLC phosphorylation with increased TER after inhibition of Na(+)-glucose cotransport. However, NHE3 inhibitors did not diminish Na(+)-glucose cotransport. These data demonstrate that inhibition of NHE3 results in decreased MLC phosphorylation and increased TER and suggest that NHE3 may participate in the signaling pathway of Na(+)-glucose cotransport-dependent tight junction regulation.
Asunto(s)
Mucosa Intestinal/metabolismo , Intercambiadores de Sodio-Hidrógeno/metabolismo , Uniones Estrechas/metabolismo , Ácidos/metabolismo , Álcalis/metabolismo , Amilorida/farmacología , Animales , Antiulcerosos/farmacología , Antihipertensivos/farmacología , Transporte Biológico/efectos de los fármacos , Transporte Biológico/fisiología , Células CACO-2 , Cimetidina/farmacología , Clonidina/farmacología , Citoplasma/metabolismo , Diuréticos/farmacología , Impedancia Eléctrica , Electrofisiología , Células Epiteliales/citología , Células Epiteliales/metabolismo , Glucosa/metabolismo , Guanidinas/farmacología , Humanos , Concentración de Iones de Hidrógeno , Metacrilatos/farmacología , Microvellosidades/metabolismo , Cadenas Ligeras de Miosina/metabolismo , Quinasa de Cadena Ligera de Miosina/antagonistas & inhibidores , Quinasa de Cadena Ligera de Miosina/metabolismo , Fosforilación , Sodio/metabolismo , Intercambiador 3 de Sodio-Hidrógeno , Sulfonas/farmacologíaRESUMEN
Mitochondrial alterations are known to be constantly associated with Reye's syndrome. Fifty-eight liver specimens from 50 patients who fulfilled the clinical and pathologic criteria were examined by electron microscopy. The degree of mitochondrial injury was graded I, II, and III according to the severity of the alteration of mitochondrial matrix. The results correlated well with clinical parameters--specifically initial clinical stage, peak clinical stage, and clinical outcome. Electron microscopic examination of hepatic mitochondria is therefore potentially useful in evaluating Reye's syndrome patients.
Asunto(s)
Hígado/patología , Mitocondrias Hepáticas/ultraestructura , Síndrome de Reye/patología , Biopsia , Humanos , Hígado/ultraestructura , Microscopía Electrónica , Pronóstico , Síndrome de Reye/clasificaciónRESUMEN
Malacoplakia of the vagina was incidentally discovered in a 47-year-old white woman with a history of chronic active hepatitis and steroid hormone therapy. The relation between malacoplakia, liver disease, and steroid therapy is discussed.