RESUMEN
Proton pump inhibitors (PPIs) have been widely used in the treatment of gastroesophageal reflux disease and peptic ulcer disease. Although they have a potent acid suppressive effect and excellent efficacy in acid-related diseases, PPI-induced rhabdomyolysis has been reported. Here, we report the case of a patient with reflux esophagitis who developed rhabdomyolysis after esomeprazole treatment. A 67-year-old man with reflux esophagitis who had started esomeprazole treatment for the preceding 10 months complained of back and limb fatigue and myalgia. His serum creatinine kinase (CK) level was markedly elevated, and CK isozyme exhibited an MM pattern. He was diagnosed with rhabdomyolysis induced by esomeprazole. The cessation of esomeprazole rapidly improved his symptoms, and the serum CK level was normalized within 16 days. PPI-induced rhabdomyolysis is a rare complication. In most cases, PPI-induced rhabdomyolysis occurs within 3 months after starting PPIs. However, rhabdomyolysis occurred at 10 months after starting esomeprazole treatment in our patient. Early diagnosis of PPI-induced rhabdomyolysis is required even in long-term PPI users.
Asunto(s)
Esomeprazol/efectos adversos , Inhibidores de la Bomba de Protones/efectos adversos , Rabdomiólisis/diagnóstico , Anciano , Esomeprazol/uso terapéutico , Esofagitis Péptica , Reflujo Gastroesofágico , Humanos , Masculino , Inhibidores de la Bomba de Protones/uso terapéutico , Rabdomiólisis/inducido químicamente , Rabdomiólisis/terapia , Resultado del TratamientoRESUMEN
BACKGROUND AND AIM: Fas-associated phosphatase-1 (FAP-1) has been thought as an inhibitor in Fas-mediated apoptosis. Here, we investigated the role of FAP-1 in Fas-mediated apoptosis of human colon cancer cells. METHOD: The viability of four colon cancer cell lines treated with agonistic anti-Fas antibody was determined using WST-1 assay and cell death detection ELISA. pRc/CMV-FAP-1 was transfected to a FAP-1-negative, Fas-resistant colon cancer cell line SW480 by lipofection and the clones expressing FAP-1 protein were selected by limiting dilution. In the clones, expression of 550 genes was analyzed by cDNA microarrays. Protein expression of FAP-1 and molecules related to apoptosis was examined by western blot. RESULTS: We obtained two FAP-1 overexpressed clones which were much more susceptible to Fas-mediated apoptosis than control cells. In the clones, caspase 8 and caspase 3 were fully activated by agonistic anti-Fas antibody treatment. Bcl-2 family proteins were not related to the high susceptibility of these clones, because caspase 9 was not activated. Transfection of FAP-1 did not suppress the survival actions of insulin-like growth factor (IGF-1) which enhanced survival signal through Akt phosphorylation. Upregulation in 21 genes and downregulation in 29 genes was revealed by cDNA arrays. We confirmed protein expression of p21 and phosphorylated p21 were much more enhanced in the clones than in control cells. CONCLUSIONS: Overexpression of FAP-1 enhanced susceptibility to Fas-mediated apoptosis in SW480 and upregulation of p21 may contribute to this phenomenon. Our results indicate a novel function of FAP-1 in Fas-mediated apoptosis of human colon cancer cells.
Asunto(s)
Apoptosis , Neoplasias del Colon/metabolismo , Proteínas Tirosina Fosfatasas/metabolismo , Receptor fas/metabolismo , Anticuerpos , Proteínas Reguladoras de la Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/metabolismo , Caspasa 3/metabolismo , Caspasa 8/metabolismo , Línea Celular Tumoral , Supervivencia Celular , Neoplasias del Colon/genética , Neoplasias del Colon/patología , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Perfilación de la Expresión Génica , Humanos , Factor I del Crecimiento Similar a la Insulina/farmacología , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Análisis de Secuencia por Matrices de Oligonucleótidos , Fosforilación/efectos de los fármacos , Proteína Fosfatasa 1 , Proteína Tirosina Fosfatasa no Receptora Tipo 13 , Proteínas Tirosina Fosfatasas/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , ARN Mensajero/metabolismo , Transfección , Receptor fas/inmunologíaRESUMEN
BACKGROUND: This study examined whether targeted disruption of the genes for the prostacyclin receptor (IP) or the thromboxane A2 receptor (TP) confers a susceptibility to salt-dependent hypertension. METHODS AND RESULTS: Eight female IP- or TP-deficient mice were examined. Baseline systolic blood pressure (SBP) did not differ between TP(-/-) and TP(+/+), but was significantly lower in the IP(-/-) group than in the IP(+/+). With a high salt diet, SBP in IP(-/-) gradually increased. In contrast, SBP in the IP(+/+), TP(-/-), or TP(+/+) groups remained unchanged. CONCLUSIONS: The prostacyclin receptor may participate in the maintenance of baseline BP. With salt loading, BP adaptation may take place, at least in part, via IP mediated signals.
Asunto(s)
Receptores de Epoprostenol/deficiencia , Receptores de Epoprostenol/genética , Receptores de Tromboxano A2 y Prostaglandina H2/deficiencia , Receptores de Tromboxano A2 y Prostaglandina H2/genética , Sodio en la Dieta/farmacología , Animales , Presión Sanguínea/efectos de los fármacos , Peso Corporal , Femenino , Frecuencia Cardíaca , Heterocigoto , Homocigoto , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Tromboxano B2/orinaRESUMEN
BACKGROUND/AIMS: Human hepatoma cells have been reported to be resistant to Fas-mediated apoptosis. Sodium butyrate (SB) induced apoptosis of several cancer cells. We investigated the effects of SB on Fas-mediated apoptosis of hepatoma cells. METHODS: In hepatoma cells (HuH-6, HuH-7, Hep-G2, and PLC/PRF/5), susceptibility to Fas-mediated apoptosis and Fas expression were assessed. Caspase-3 activation and cell cycle progression were evaluated in HuH-6. A cDNA microarray assay was performed to screen the changes in the expression of mRNAs. RESULTS: Pretreatment with SB caused an enhancement of the sensitivity to anti-Fas-mediated cytotoxicity, though it did not increase the expression of Fas. The cDNA microarray assay revealed up-regulation of pro-apoptotic Bik, Bak, Bid and c-Jun N-terminal protein kinase-1, and down-regulation of anti-apoptotic Bag-1 and cellular Fas-associated death domain-like interleukin-1beta-converting enzyme inhibitor protein. In some molecules, expression of the proteins was confirmed by Western blotting. An increase in truncated-Bid accompanying the reduction in Bid was also observed. CONCLUSIONS: SB enhances the susceptibility of hepatoma cells to anti-Fas-mediated cytotoxicity by altering the mRNA and protein expression and/or the activation status of proteins that could be involved in the Fas signaling pathway. SB may have an important role in the elimination of hepatoma cells.