RESUMEN
Purpose. EBER-1 (a non-coding RNA transcribed by EBV) expression was detected in most of Epstein-Barr virus (EBV)-positive nasopharyngeal carcinoma (NPC) patients. However, the relevance between EBER-1 expression and NPC clinical outcome has not been reported. This study aims to assess the possible correlations of EBER-1 expression and clinical parameters and its potential prognostic predictive ability in NPC patients outcomes. Methods. We examined EBER-1 mRNA expression in 301 NPC and 130 non-NPC tissues using in situ hybridization and did statistics. Results. EBER-1 expression was up-regulated in NPC tissues when compared to non-NPC tissues. A receiver operating characteristic analysis revealed that EBER-1 expression could distinguish non-cancerous patients from NPC patients (p < 0.001, sensitivity: 72.5 %, specificity: 83.5 %, AUC = 0.815). A survival analysis revealed that patients with high levels of EBER-1 expression had a significantly good prognosis (Disease-free survival: p = 0.019, overall survival: p = 0.006). Conclusion. These results indicated that EBER-1 expression is a potential prognosis factor of NPC and highly negative correlated with the progress of NPC (AU)
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Asunto(s)
Humanos , Masculino , Femenino , Carcinoma/patología , Carcinoma/genética , Neoplasias Nasofaríngeas/metabolismo , Neoplasias Nasofaríngeas/patología , Infecciones por Virus de Epstein-Barr/transmisión , Infecciones por Virus de Epstein-Barr/virología , Consentimiento Informado/psicología , Fenotipo , Apoptosis/genética , Ácido Gástrico/metabolismo , Carcinoma/complicaciones , Carcinoma/diagnóstico , Neoplasias Nasofaríngeas/complicaciones , Neoplasias Nasofaríngeas/diagnóstico , Infecciones por Virus de Epstein-Barr/metabolismo , Infecciones por Virus de Epstein-Barr/patología , Supervivencia sin Enfermedad , Consentimiento Informado/normas , Apoptosis/fisiología , Ácido Gástrico/enzimologíaRESUMEN
Aspartic proteinases in the gastric fluid of clawed lobsters Homarus americanus and Homarus gammarus were isolated to homogeneity by single-step pepstatin-A affinity chromatography; such enzymes have been previously identified as cathepsin D-like enzymes based on their deduced amino acid sequence. Here, we describe their biochemical characteristics; the properties of the lobster enzymes were compared with those of its homolog, bovine cathepsin D, and found to be unique in a number of ways. The lobster enzymes demonstrated hydrolytic activity against synthetic and natural substrates at a wider range of pH; they were more temperature-sensitive, showed no changes in the K(M) value at 4°C, 10°C, and 25°C, and had 20-fold higher k(cat)/K(M) values than bovine enzyme. The bovine enzyme was temperature-dependent. We propose that both properties arose from an increase in molecular flexibility required to compensate for the reduction of reaction rates at low habitat temperatures. This is supported by the fast denaturation rates induced by temperature.
Asunto(s)
Aclimatación/fisiología , Proteasas de Ácido Aspártico/metabolismo , Frío , Ácido Gástrico/enzimología , Nephropidae/enzimología , Animales , Proteasas de Ácido Aspártico/fisiología , Catepsina D/metabolismo , Bovinos , Cromatografía de Afinidad , Concentración de Iones de Hidrógeno , Nephropidae/fisiología , Pepstatinas , Especificidad de la EspecieRESUMEN
The Ca(2+) activated K(+) channel K(ca)3.1 is expressed in a variety of tissues. In the gastric gland it is expressed in the basolateral cell membrane. To determine the functional significance of K(ca)3.1 activity for gastric acid secretion, gastric acid secretion was determined in isolated glands from gene targeted mice lacking functional K(ca)3.1 (K(ca)3.1(-/-)) and from their wild type littermates (K(ca)3.1(+/+)). According to BCECF-fluorescence cytosolic pH in isolated gastric glands was similar in K(ca)3.1(-/-) and K(ca)3.1(+/+) mice. Na(ca)-independent pH recovery (ΔpH/min) following an ammonium pulse, a measure of H(ca)/K(ca) ATPase activity, was, however, significantly faster in K(ca)3.1(-/-) than in K(ca)3.1(+/+) mice. Accordingly, the luminal pH was significantly lower and the acid content significantly higher in K(ca)3.1(-/-) than in K(ca)3.1(+/+) mice. The abundance of mRNA encoding H(ca)/K(ca) ATPase and KCNQ1 was similar in both genotypes. Increase of extracellular K(ca) concentrations to 35 mM (replacing Na(ca)/NMDG) and treatment with histamine (100 µM) significantly increased ΔpH/min to a larger extent in K(ca)3.1(+/+) than in K(ca)3.1(-/-) mice and dissipated the differences between the genotypes. Carbachol (100 µM) increased ΔpH/min in both genotypes but did not abolish the difference between K(ca)3.1(-/-) and K(ca)3.1(+/+) mice. In K(ca)3.1(+/+) mice the K(ca)3.1 opener DCEBIO (100 µM) did not significantly alter basal ΔpH/min but significantly blunted ΔpH/min in the presence of carbachol. In conclusion, K(ca)3.1 activity suppresses carbachol stimulated gastric acid secretion.
Asunto(s)
Ácido Gástrico/enzimología , Mucosa Gástrica/fisiología , ATPasa Intercambiadora de Hidrógeno-Potásio/metabolismo , Concentración de Iones de Hidrógeno/efectos de los fármacos , Canales de Potasio de Conductancia Intermedia Activados por el Calcio , Canal de Potasio KCNQ1/metabolismo , Células Parietales Gástricas/fisiología , Amoníaco/farmacología , Animales , Transporte Biológico , Calcio/metabolismo , Carbacol/farmacología , Fluoresceínas/análisis , Ácido Gástrico/metabolismo , Determinación de la Acidez Gástrica , Mucosa Gástrica/efectos de los fármacos , ATPasa Intercambiadora de Hidrógeno-Potásio/genética , Histamina/farmacología , Canales de Potasio de Conductancia Intermedia Activados por el Calcio/genética , Canales de Potasio de Conductancia Intermedia Activados por el Calcio/metabolismo , Canal de Potasio KCNQ1/genética , Ratones , Ratones Noqueados , Omeprazol/farmacología , Técnicas de Cultivo de Órganos , Células Parietales Gástricas/efectos de los fármacos , Potasio/metabolismo , Protones , ARN Mensajero/análisisRESUMEN
Two types of beta-1,3-glucanases, AkLam36 and AkLam33 with the molecular masses of 36kDa and 33kDa, respectively, were isolated from the digestive fluid of the common sea hare Aplysia kurodai. AkLam36 was regarded as an endolytic enzyme (EC 3.2.1.6) degrading laminarin and laminarioligosaccharides to laminaritriose, laminaribiose, and glucose, while AkLam33 was regarded as an exolytic enzyme (EC 3.2.1.58) directly producing glucose from polymer laminarin. AkLam36 showed higher activity toward beta-1,3-glucans with a few beta-1,6-linked glucose branches such as Laminaria digitata laminarin (LLam) than highly branched beta-1,3-glucans such as Eisenia bicyclis laminarin (ELam). AkLam33 showed moderate activity toward both ELam and LLam and high activity toward smaller substrates such as laminaritetraose and laminaritriose. Although both enzymes did not degrade laminaribiose as a sole substrate, they were capable of degrading it via transglycosylation reaction with laminaritriose. The N-terminal amino-acid sequences of AkLam36 and AkLam33 indicated that both enzymes belong to the glycosyl hydrolase family 16 like other molluscan beta-1,3-glucanases.
Asunto(s)
Aplysia/enzimología , Glucano 1,3-beta-Glucosidasa/aislamiento & purificación , Glucano 1,3-beta-Glucosidasa/metabolismo , Secuencia de Aminoácidos , Animales , Ácido Gástrico/enzimología , Glucano 1,3-beta-Glucosidasa/química , Glucanos , Glicosilación , Datos de Secuencia Molecular , Polisacáridos/metabolismoRESUMEN
A new technique for intragastric pH-gram analysis during alkaline test is described. The technique is based on a mathematical model of the acid-alkaline balance in the body of stomach. The model provides intragastric pH-gram approximation by the least-squares method. This makes it possible to determine the specific rate of acid production in the stomach and accurately calculate the alkaline time. The structure of a hardware-software system for implementation of the new technique is developed. The suggested algorithms can be implemented on the basis of the Gastroscan-5M acidogastrometer.
Asunto(s)
Pruebas Diagnósticas de Rutina/métodos , Ácido Gástrico/química , Ácido Gástrico/enzimología , Modelos Teóricos , Algoritmos , Pruebas Diagnósticas de Rutina/instrumentación , Determinación de la Acidez Gástrica , Humanos , Concentración de Iones de HidrógenoRESUMEN
Las enzimas pancreáticas constituyen agentes terapéuticos de utilidad clínica dentro de un espectro mucho más amplio del que se acepta habitualmente. En este trabajo se trata de demostrar que ejercen una influencia benéfica en un variado grupo de entidades... y que la asociación de una mejora en el mecanismo del proceso digestivo, especialmente de los carbohidratos, y el consecutivo alivio de los fenómenos dispépticos fermentativos, ello en conjunción con una atenuación de la hipersensibilidad del sistema nervioso aferente, cambio muy ligado a una depresión liberadora sobre la CCK, explican el valor terapéutico innegable que poseen los fermentos pancreáticos en el enfoque terapéutico del colon irritable
Asunto(s)
Adulto , Humanos , Perros , Páncreas/metabolismo , Enfermedades Funcionales del Colon/enzimología , Ácido Gástrico/enzimología , Ácido Gástrico/metabolismo , EnzimasRESUMEN
Las enzimas pancreáticas constituyen agentes terapéuticos de utilidad clínica dentro de un espectro mucho más amplio del que se acepta habitualmente. En este trabajo se trata de demostrar que ejercen una influencia benéfica en un variado grupo de entidades... y que la asociación de una mejora en el mecanismo del proceso digestivo, especialmente de los carbohidratos, y el consecutivo alivio de los fenómenos dispépticos fermentativos, ello en conjunción con una atenuación de la hipersensibilidad del sistema nervioso aferente, cambio muy ligado a una depresión liberadora sobre la CCK, explican el valor terapéutico innegable que poseen los fermentos pancreáticos en el enfoque terapéutico del colon irritable
Asunto(s)
Adulto , Humanos , Perros , Ácido Gástrico/enzimología , Ácido Gástrico , Enfermedades Funcionales del Colon , Enzimas , PáncreasRESUMEN
BACKGROUND: Lansoprazole is a potent proton-pump inhibitor (PPI) of parietal cells, which reduces the secretion of gastric acid. Although human gastric lipase (HGL) is produced only by the chief cells of the stomach, the possibility that interactions may occur between lansoprazole and HGL has never been addressed so far in humans. The aim of this study was therefore to quantify the effects of lansoprazole on HGL secretion and intragastric lipolysis during the ingestion of test meals by healthy human volunteers. METHODS: Six healthy volunteers were intubated twice with a gastric and a duodenal tube, before ingesting a standard liquid test meal alone (-PPI experiments) and after 7 days of lansoprazole treatment (+PPI experiments). The HGL concentration was assessed in gastric and duodenal samples by measuring the lipase activity using a pH-stat, and the lipolysis products were quantified by performing thin layer chromatography. The level of intragastric lipolysis was defined as the percentage acyl chains released from the meal triglycerides. The pyloric outputs of HGL and lipolysis products were calculated, based on the use of a non-absorbable marker added to the meal. RESULTS: The pH of the gastric contents was significantly higher in the +PPI experiments than in the -PPI experiments (p < 0.05), since mean values of 4.3 +/- 2.5 and 2.2 +/- 1.6, respectively, were recorded at the end of the gastric emptying of the meal. The HGL concentrations recorded during the meal were found to be higher in the experiments with lansoprazole (p < 0.05) than in those without lansopra- zole, but the HGL secretion levels (-PPI: 15.4 +/- 8.0 mg; +PPI: 19.0 +/- 7.4 mg) and the intragastric lipolysis (-PPI: 24.0 +/- 8.0%; +PPI: 23.6 +/- 6.8%) were not significantly affected by lansoprazole (p > 0.05 in both cases). CONCLUSION: Lansoprazole affected neither the HGL secretion nor the intragastric lipolysis levels, although an increase was observed in the intragastric pH at the end of the gastric emptying of the meal. The HGL concentration increased, however, due to the decrease in the acid secretion process, resulting in less diluted gastric contents.
Asunto(s)
Inhibidores Enzimáticos/farmacología , Ácido Gástrico/enzimología , Lipasa/efectos de los fármacos , Lipasa/metabolismo , Lipólisis/efectos de los fármacos , Omeprazol/farmacología , 2-Piridinilmetilsulfinilbencimidazoles , Adulto , Estudios Cruzados , Femenino , Ácido Gástrico/metabolismo , Vaciamiento Gástrico/efectos de los fármacos , Vaciamiento Gástrico/fisiología , Humanos , Concentración de Iones de Hidrógeno/efectos de los fármacos , Hidrólisis/efectos de los fármacos , Lansoprazol , Masculino , Omeprazol/análogos & derivados , Valores de Referencia , Factores de TiempoRESUMEN
p38 belongs to the mitogen-activated protein kinase family and plays a crucial role in cellular responses to both cytokines and various stresses. We investigated the role of p38 in the healing of experimental gastric ulcers. Gastric ulcers were induced by submucosal injection of acetic acid solution into male rats. Western blotting and a kinase assay examined the p38 activity and phosphorylation state in ulcerated tisue. After orally administering FR167653 (p38 kinase inhibitor) for 3 to 14 days, the production level of cytokines and the protein-level expression of cyclooxygenase and inducible nitric oxide synthase were examined by enzyme-linked immunosorbent assay and Western blotting. Only in fibroblasts and macrophages/monocytes in ulcerated tissue, p38 was found to be phosphorylated with an elevated kinase activity level. FR 167653 inhibited the activity of p38, yet had no effect on its phosphorylation state. The drug significantly impaired ulcer healing (without affecting acid secretion) and angiogenesis in the ulcer base. The production of interleukin-1beta and tumor necrosis factor-alpha were significantly reduced after FR167653 treatment. In addition the expression of cyclooxygenase-2 and inducible nitric oxide synthase proteins increased PGE2 generation and NOx secretion in the ulcerated stomach were suppressed by FR167653. From these findings, we conclude that p38, activated by gastric ulceration, might play some role in the healing of gastic ulcers in rats.
Asunto(s)
Proteínas Quinasas Activadas por Mitógenos/biosíntesis , Úlcera Gástrica/enzimología , Animales , Antiinflamatorios no Esteroideos/farmacología , Ciclooxigenasa 1 , Citocinas/biosíntesis , Dinoprostona/biosíntesis , Fibroblastos/efectos de los fármacos , Fibroblastos/enzimología , Ácido Gástrico/enzimología , Ácido Gástrico/metabolismo , Isoenzimas/biosíntesis , Macrófagos/efectos de los fármacos , Macrófagos/enzimología , Masculino , Proteínas de la Membrana , Proteínas Quinasas Activadas por Mitógenos/antagonistas & inhibidores , Óxido Nítrico Sintasa/biosíntesis , Óxido Nítrico Sintasa de Tipo II , Prostaglandina-Endoperóxido Sintasas/biosíntesis , Pirazoles/farmacología , Piridinas/farmacología , Ratas , Úlcera Gástrica/patología , Proteínas Quinasas p38 Activadas por MitógenosRESUMEN
Gastric acid secretion is dependent on carbonic anhydrase (CA). To define the role of membrane-bound CA, we used biochemical, histochemical, and pharmacological approaches in the frog (Rana pipiens). CA activity and inhibition by membrane-permeant and -impermeant agents were studied in stomach homogenates and microsomal fractions. H(+) secretion in the histamine-stimulated isolated mucosa was measured before and after mucosal addition of a permeant CA inhibitor (methazolamide) and before and after mucosal or serosal addition of two impermeant CA inhibitors of differing molecular mass: a 3,500-kDa polymer linked to aminobenzolamide and p-fluorobenzyl-aminobenzolamide (molecular mass, 454 kDa). Total CA activity of frog gastric mucosa is 2,280 U/g, of which 10% is due to membrane-bound CA. Membrane-bound CA retains detectable activity below pH 4. Histochemically, there is membrane-associated CA in surface epithelial, oxynticopeptic, and capillary endothelial cells. Methazolamide reduced H(+) secretion by 100%, whereas the two impermeant inhibitors equally blocked secretion by 40% when applied to the mucosal side and by 55% when applied to the serosal side. The presence of membrane-bound CA in frog oxynticopeptic cells and its relative resistance to acid inactivation and inhibition by impermeant inhibitors demonstrate that it subserves acid secretion at both the apical and basolateral sides.
Asunto(s)
Anhidrasas Carbónicas/metabolismo , Ácido Gástrico/enzimología , Mucosa Gástrica/enzimología , para-Aminobenzoatos , Ácido 4-Aminobenzoico/farmacología , Animales , Inhibidores de Anhidrasa Carbónica/farmacología , Membrana Celular/enzimología , Permeabilidad de la Membrana Celular/efectos de los fármacos , Permeabilidad de la Membrana Celular/fisiología , Reactivos de Enlaces Cruzados , Citoplasma/enzimología , Ácido Gástrico/metabolismo , Mucosa Gástrica/citología , Mucosa Gástrica/metabolismo , Histocitoquímica , Concentración de Iones de Hidrógeno , Metazolamida/farmacología , Microsomas/enzimología , Polietilenglicoles/farmacología , Rana pipiens , Tiadiazoles/farmacologíaRESUMEN
The 9 widely used antacids were studied for antipepsic activity.
Asunto(s)
Antiácidos/farmacocinética , Ácido Gástrico/enzimología , Pepsina A/efectos de los fármacosRESUMEN
Coleus barbatus (Labiatae) Benth is popularly used in Brazil "for the healing of liver and stomach diseases". The water extract (WE 1 to 10 g/Kg, p.o.) of stem and leaves given to rats and mice did not induce signs of intoxication. Preveious treatment of mice with WE (1 g/kg, p.o.) shortened the sleeping time induced by pentobarbital (50 mg/Kg, i.p.) by 37 por cento, althoyugh the extract alone did not increase the spontaneous activity nor did it induce hyperexcitability. In mice WE (2 g/Kg, p.o.) increased the intestinal transit of charcoal by 30 por cento, while reduced gastric secretions ion rats treated with WE (2g/Kg intraduodenal) 3,9 ± 1.0 to 0.5 ± 0.2 ml/4h, respectively). The treatment also reduced the total acid secretion from 34.4 ± 11.0 to 2.7 ± 0.5 mEq/l and raisedgastric pH from 2.2 ± 0.3 to 6.5 ± 0.8. Treatment with WE (2g/Kg, p.o.) protected against gastric ulcers induced by stress (5.3 ± 1.6 and 1.5 ± 0.5 ulcers/cm²), but did nor protect against indonethacin induced ulcers. The results show that the water extract of C barbatus Benth produces mild stimulation of thecentral nervous system and increases intestinal movements. The extract also reduces gastric secretion indicating an antidyspeptic activity, and protects against gastric ulcers induced by stress.