RESUMEN
BACKGROUND: We previously reported that a faecal cyclooxygenase-2 (COX-2) mRNA assay was useful for identifying colorectal cancer (CRC). This study sought to investigate the factors that contribute to faecal COX-2 mRNA expression in subjects with CRC. METHODS: The study cohort comprised 78 patients with CRC and 36 control subjects. The expressions of COX-2, beta-2-microglobulin (B2M), carcinoembryonic antigen (CEA), E-cadherin (E-cad), and CD45 mRNA in faeces and COX-2 mRNA expression in tissue were determined by quantitative real-time RT-PCR. RESULTS: The level of faecal expression of COX-2 mRNA in CRC was significantly higher than that in controls. A significant correlation was found between faecal COX-2 mRNA expression and faecal B2M, CEA, E-cad, or CD45 mRNAs, markers of exfoliated total cells, colonocytes, and leukocytes, respectively. A significant correlation was found between the expression of COX-2 mRNA in faeces and tumour surface area, COX-2 mRNA expression in primary tumour. There was no difference in faecal COX-2 mRNA expression between proximal CRC and distal CRC. CONCLUSION: COX-2 mRNA expression in faeces seems to originate from tumour lesion and to be affected by factors such as the number of exfoliated cells, exfoliation of inflammatory cells, COX-2 mRNA expression in tumour, and tumour size.
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Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Ciclooxigenasa 2/genética , Heces/química , ARN Mensajero/genética , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/metabolismo , Cadherinas/genética , Cadherinas/metabolismo , Antígeno Carcinoembrionario/genética , Antígeno Carcinoembrionario/metabolismo , Estudios de Casos y Controles , Estudios de Cohortes , Colon/metabolismo , Colon/patología , Neoplasias Colorrectales/metabolismo , Ciclooxigenasa 2/metabolismo , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , ARN Mensajero/metabolismo , Recto/metabolismo , Recto/patología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Tasa de Supervivencia , Adulto Joven , Microglobulina beta-2/genética , Microglobulina beta-2/metabolismoRESUMEN
BACKGROUND: (13)CO(2) is produced on metabolism of (13)C-labelled-pantoprazole ([(13)C]-pantoprazole) by CYP2C19. AIM: To investigate whether the [(13)C]-pantoprazole breath test can predict CYP2C19 status and efficacy of proton pump inhibitors (PPIs) in Japanese. METHODS: We classified 110 healthy volunteers as rapid metabolizers (RM), intermediate metabolizers (IM) or poor metabolizers (PM) of CYP2C19 by genotyping. Breath samples were collected at 10-min intervals for 60 min after dosing with 100 mg [(13)C]-pantoprazole. Changes in the carbon isotope ratios ((13)CO(2)/(12)CO(2)) in carbon dioxide in breath samples were measured and expressed as a delta-over-baseline (DOB) ratio ( per thousand). Of the 110 subjects, twenty-two randomly selected subjects underwent intragastric pH monitoring on day 7 of dosing with 30 mg of lansoprazole. RESULTS: The DOB values of RMs were the highest and those of PMs the lowest of the three groups. Statistically significant differences were observed in the area-under-the-curve (AUC)(20-60 min) of DOB among the three groups. The mean 24-h intragastric pHs attained by lansoprazole 30 mg for 7 days were inversely correlated with the AUC(20-60 min) of DOB. CONCLUSIONS: [(13)C]-pantoprazole breath test can easily estimate the individual activity of CYP2C19 and predict the efficacy of a PPI (i.e. lansoprazole). This test would be useful for individualized medicine with a PPI.
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2-Piridinilmetilsulfinilbencimidazoles/farmacología , Hidrocarburo de Aril Hidroxilasas/metabolismo , Inhibidores Enzimáticos/farmacología , Inhibidores de la Bomba de Protones/farmacología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antiulcerosos , Área Bajo la Curva , Pruebas Respiratorias , Citocromo P-450 CYP2C19 , Femenino , Humanos , Lansoprazol , Masculino , Persona de Mediana Edad , Pantoprazol , Adulto JovenRESUMEN
BACKGROUND AND AIMS: Chromosomal instability (CIN) is recognised as a hallmark of cancer and is caused by a spindle assembly checkpoint disorder or chromosome mis-segregation during mitosis. Although the recent identification of human shugoshin (hSgo1), an important player in proper chromosome segregation, has suggested the involvement of hSgo1 in colorectal tumourigenesis, little is known about how it is involved. The aim of this study was to obtain information about the status of hSgo1 in human colorectal cancer. METHOD AND RESULTS: Among the 46 colorectal cancer cases, hSgo1 mRNA expression was decreased in the tumour tissue in comparison with the corresponding normal tissue (p = 0.032). Human Sgo1-downregulated tumours (tumour to normal mucosa ratio<0.5) had preferential location on the left side large bowel rather than on the right side (p = 0.012), and a higher variation of centromere numbers revealed by fluorescence in situ hybridisation (FISH). To assess the effects of hSgo1 downregulation, hSgo1 knockdown was performed by transfecting the diploid HCT116 cell line with a short hairpin RNA expression vector. hSgo1 knockdown cells proliferated slowly because of both G(2)/M arrest and apoptosis (p<0.001), and markers of CIN in the form of aneuploidy (p<0.001) and micronuclei (p<0.005) were later observed in hSgo1 knockdown cells. Increased centrosome amplification (p<0.05), the presence of binucleated cells and mitotic catastrophes were also noted in hSgo1 knockdown cells. CONCLUSIONS: These findings suggest that hSgo1-downregulated colorectal cancers have a clinicopathological character of CIN, and hSgo1 downregulation leads to CIN in colorectal cancer cells.
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Carcinoma/genética , Proteínas de Ciclo Celular/metabolismo , Inestabilidad Cromosómica , Neoplasias Colorrectales/genética , Regulación hacia Abajo , Regulación Neoplásica de la Expresión Génica , Anciano , Anciano de 80 o más Años , Aneuploidia , Biomarcadores/análisis , Western Blotting/métodos , Carcinoma/metabolismo , Carcinoma/patología , Proteínas de Ciclo Celular/análisis , Proteínas de Ciclo Celular/genética , Centrosoma/ultraestructura , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Femenino , Células HCT116 , Humanos , Inmunohistoquímica , Hibridación Fluorescente in Situ , Antígeno Ki-67/análisis , Pérdida de Heterocigocidad , Masculino , Persona de Mediana Edad , ARN Interferente Pequeño , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Transfección/métodosRESUMEN
BACKGROUND: Polymorphism in MDR1 is associated with variation in the plasma level of a proton pump inhibitor. AIM: To investigate whether MDR1 polymorphism is associated with eradication rates of Helicobacter pylori by a triple therapy with lansoprazole, amoxicillin and clarithromycin in relation to CYP2C19 genotype status and bacterial susceptibility to clarithromycin. METHODS: A total of 313 patients infected with H. pylori completed the treatment with lansoprazole 30 mg b.d., clarithromycin 200 mg b.d. and amoxicillin 750 mg b.d. for 1 week. MDR1 C3435T polymorphism and CYP2C19 genotypes of patients and sensitivity of H. pylori to clarithromycin were determined. RESULTS: Logistic regression analysis revealed that the MDR1 polymorphism as well as CYP2C19 genotypes of patients and clarithromycin-resistance of H. pylori were significantly associated with successful eradication. Eradication rates for H. pylori were 82% (83/101: 95% CI = 73-89), 81% (112/139: CI = 73-87), and 67% (44/73: CI = 48-72) in patients with the MDR1 3435 C/C, C/T and T/T genotype, respectively (P = 0.001). CONCLUSIONS: Polymorphism of MDR1 is one of the determinants of successful eradication of H. pylori by the triple therapy with lansoprazole, amoxicillin and clarithromycin, together with CYP2C19 genotype and bacterial susceptibility to clarithromycin.
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Antibacterianos/uso terapéutico , Antiulcerosos/uso terapéutico , Hidrocarburo de Aril Hidroxilasas/genética , Infecciones por Helicobacter/tratamiento farmacológico , Helicobacter pylori/genética , Oxigenasas de Función Mixta/genética , Polimorfismo de Longitud del Fragmento de Restricción , 2-Piridinilmetilsulfinilbencimidazoles/uso terapéutico , Amoxicilina/uso terapéutico , Claritromicina/uso terapéutico , Citocromo P-450 CYP2C19 , Quimioterapia Combinada , Femenino , Genotipo , Humanos , Lansoprazol , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
OBJECTIVES: To elucidate the prenatal and postnatal course of fetal congenital atrioventricular block (CAVB) during the past decade in the Japanese population. DESIGN: Retrospective multicentre study. All fetuses with CAVB in 10 Japanese institutions in the period from January 1990 to August 2001 were included. PATIENTS: Of the 48 fetuses with CAVB, 17 had a congenital heart defect (CHD) (14 with left atrial isomerism) and 31 had a structurally normal heart (22 with positive maternal autoantibodies). Gestational age at diagnosis was 15 to 38 (median 26) weeks. RESULTS: Of the 17 fetuses with a CHD, three were aborted, one died before birth, and eight died after birth (three in the neonatal period and five after the neonatal period). Of the 31 fetuses without a CHD, two died before birth and two died after birth. CHD (p = 0.005) and the presence of fetal hydrops (p = 0.05) were significant risk factors for death. However, fetal ventricular and atrial heart rates, gestational age at delivery, and birth weight were not related to death. Transplacental medication of sympathomimetics increased the fetal heart rate in five of eight fetuses treated. Dexamethasone did not improve the degree of heart block in any of the six fetuses treated. Postnatally, pacemakers were implanted in 30 of 40 babies. Four fetuses with maternal autoantibodies had decreased cardiac function. CONCLUSIONS: CHD and fetal hydrops are risk factors for prenatal and postnatal death. The fetal ventricular rate of 55 beats/min did not appear to be a threshold value by which to predict fetal hydrops. Patients with CAVB should be subjected to close long term follow up to check for the need for pacemaker implantation or for late onset cardiac dysfunction.
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Bloqueo Cardíaco/congénito , Antiarrítmicos/uso terapéutico , Autoanticuerpos/análisis , Femenino , Edad Gestacional , Bloqueo Cardíaco/diagnóstico , Bloqueo Cardíaco/tratamiento farmacológico , Cardiopatías Congénitas/complicaciones , Frecuencia Cardíaca Fetal/fisiología , Humanos , Hidropesía Fetal/etiología , Japón , Embarazo , Resultado del Embarazo , Atención Prenatal/métodos , Diagnóstico Prenatal , Estudios RetrospectivosRESUMEN
The traditional paradigm of colonic fluid and electrolyte transport includes a spatial separation of absorptive and secretory processes to surface and crypt cells, respectively. Recent studies of isolated microperfused colonic crypts revealed constitutive Na-dependent fluid absorption while secretion is regulated by one or more neurohumoral agonists. One obvious reason for the difference found in microdissected crypts is their separation from the lamina propria milieu. While it has been shown that isolated crypts are devoid of obvious lamina propria elements, including pericryptal fibroblasts, detailed morphologic information of the content of isolated crypts has been lacking. To characterize the morphology of the isolated crypt, we performed transmission electron microscopy (TEM) and immunofluorescence on microdissected and Ca2+ chelated crypts. Crypt cell type analysis was carried out separately on intact rat colon using light microscopy. TEM revealed a complete lack of either lamina propria cells or extracellular material in crypts isolated by either technique. TEM also revealed a subtle difference between the two isolation methods, with intact basal membranes in microdissected crypts but focal disruption of basal membranes in Ca2+- chelated crypts. Immunofluorescent stains for two basement membrane components (laminin and collagen type IV) revealed the presence of adherent basement membrane only on microdissected crypts; evidence that the plane of separation differs in these two preparations. Crypt cell type analysis on intact rat colon revealed an equal proportion of goblet cells in the right and left colon (approximately 50%) when measuring the middle 70% of the crypts - the area studied during crypt microperfusion. This morphologic analysis will increase our understanding of the observed physiology of isolated colonic crypts.
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Colágeno/química , Colon/citología , Células Caliciformes/ultraestructura , Laminina/química , Animales , Membrana Basal/ultraestructura , Separación Celular , Colágeno/inmunología , Técnica del Anticuerpo Fluorescente/métodos , Laminina/inmunología , Masculino , Microscopía Electrónica/instrumentación , Microscopía Electrónica/métodos , Ratas , Ratas Sprague-DawleyRESUMEN
ATP-binding cassette (ABC) transporters bind and hydrolyze ATP. In the cystic fibrosis transmembrane conductance regulator Cl(-) channel, this interaction with ATP generates a gating cycle between a closed (C) and two open (O1 and O2) conformations. To understand better how ATP controls channel activity, we examined gating transitions from the C to the O1 and O2 states and from these open states to the C conformation. We made three main observations. First, we found that the channel can open into either the O1 or O2 state, that the frequency of transitions to both states was increased by ATP concentration, and that ATP increased the relative proportion of openings into O1 vs. O2. These results indicate that ATP can interact with the closed state to open the channel in at least two ways, which may involve binding to nucleotide-binding domains (NBDs) NBD1 and NBD2. Second, ATP prolonged the burst duration and altered the way in which the channel closed. These data suggest that ATP also interacts with the open channel. Third, the channel showed runs of specific types of open-closed transitions. This finding suggests a mechanism with more than one cycle of gating transitions. These data suggest models to explain how ATP influences conformational transitions in cystic fibrosis transmembrane conductance regulator and perhaps other ABC transporters.
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Adenosina Trifosfato/fisiología , Regulador de Conductancia de Transmembrana de Fibrosis Quística/fisiología , Fibrosis Quística/fisiopatología , Activación del Canal Iónico/fisiología , Adenosina Trifosfato/metabolismo , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Células HeLa , Humanos , Probabilidad , Factores de TiempoRESUMEN
Opening and closing of the cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel is regulated by the interaction of ATP with its two cytoplasmic nucleotide-binding domains (NBD). Although ATP hydrolysis by the NBDs is required for normal gating, the influence of ATP binding versus hydrolysis on specific steps in the gating cycle remains uncertain. Earlier work showed that the absence of Mg(2+) prevents hydrolysis. We found that even in the absence of Mg(2+), ATP could support channel activity, albeit at a reduced level compared with the presence of Mg(2+). Application of ATP with a divalent cation, including the poorly hydrolyzed CaATP complex, increased the rate of opening. Moreover, in CFTR variants with mutations that disrupt hydrolysis, ATP alone opened the channel and Mg(2+) further enhanced ATP-dependent opening. These data suggest that ATP alone can open the channel and that divalent cations increase ATP binding. Consistent with this conclusion, when we mutated an aspartate thought to bind Mg(2+), divalent cations failed to increase activity compared with ATP alone. Two observations suggested that divalent cations also stabilize the open state. In wild-type CFTR, CaATP generated a long duration open state, whereas ATP alone did not. With a CFTR variant in which hydrolysis was disrupted, MgATP, but not ATP alone, produced long openings. These results suggest a gating cycle for CFTR in which ATP binding opens the channel and either hydrolysis or dissociation leads to channel closure. In addition, the data suggest that ATP binding and hydrolysis by either NBD can gate the channel.
Asunto(s)
Adenosina Trifosfato/metabolismo , Regulador de Conductancia de Transmembrana de Fibrosis Quística/fisiología , Activación del Canal Iónico/fisiología , Ácido Aspártico/genética , Ácido Aspártico/metabolismo , Calcio/metabolismo , Calcio/farmacología , Cationes Bivalentes , Medios de Cultivo , Regulador de Conductancia de Transmembrana de Fibrosis Quística/efectos de los fármacos , Regulador de Conductancia de Transmembrana de Fibrosis Quística/genética , Regulador de Conductancia de Transmembrana de Fibrosis Quística/metabolismo , Células HeLa , Humanos , Hidrólisis , Activación del Canal Iónico/efectos de los fármacos , Magnesio/metabolismo , Magnesio/farmacología , Mutagénesis , Técnicas de Placa-ClampRESUMEN
Acidosis is associated with inflammation and ischemia and activates cation channels in sensory neurons. Inflammation also induces expression of FMRFamidelike neuropeptides, which modulate pain. We found that neuropeptide FF (Phe-Leu-Phe-Gln-Pro-Gln-Arg-Phe amide) and FMRFamide (Phe-Met-Arg-Phe amide) generated no current on their own but potentiated H+-gated currents from cultured sensory neurons and heterologously expressed ASIC and DRASIC channels. The neuropeptides slowed inactivation and induced sustained currents during acidification. The effects were specific; different channels showed distinct responses to the various peptides. These results suggest that acid-sensing ion channels may integrate multiple extracellular signals to modify sensory perception.
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Potenciales de Acción/efectos de los fármacos , FMRFamida/farmacología , Ganglios Espinales/efectos de los fármacos , Canales Iónicos/efectos de los fármacos , Proteínas del Tejido Nervioso/efectos de los fármacos , Neuropéptidos/farmacología , Oligopéptidos/farmacología , Canales Iónicos Sensibles al Ácido , Potenciales de Acción/fisiología , Animales , Células Cultivadas , Canales de Sodio Degenerina , Canales Epiteliales de Sodio , FMRFamida/fisiología , Ganglios Espinales/fisiología , Humanos , Canales Iónicos/fisiología , Proteínas del Tejido Nervioso/fisiología , Neuropéptidos/fisiología , Oligopéptidos/fisiología , Ratas , XenopusRESUMEN
Dietary sodium depletion has multiple diverse effects on ion transport in the rat colon, including both the induction and inhibition of electroneutral NaCl absorption in proximal and distal colon of rat, respectively. To establish the mechanism of the differential regulation of Na+ absorption by sodium depletion, this study utilized 1) HOE-694, a dose-dependent inhibitor of Na+/H+ exchanger (NHE) isoforms, in studies of proton gradient-driven 22Na uptake (i.e., Na+/H+ exchange) by apical membrane vesicles (AMV); 2) Northern blot analyses of NHE isoform-specific mRNA abundance; and 3) Western blot analyses of NHE isoform-specific protein expression. HOE-694 inhibition studies establish that 25 microM HOE-694-sensitive (NHE2) and 25 microM HOE-694-insensitive (NHE3) Na+/H+ exchange activities are present in AMV of both proximal and distal colon of normal rats. In proximal colon, dietary sodium depletion enhanced both NHE2 and NHE3 isoform-specific Na+/H+ exchange activities, protein expression, and mRNA abundance. In contrast, in distal colon both NHE2 and NHE3 isoform-specific Na+/H+ exchange activities, protein expression, and mRNA abundance were inhibited by sodium depletion. NHE1 isoform-specific mRNA abundance in proximal or distal colon was not altered by sodium depletion. Differential effects by sodium depletion on Na+/H+ exchange in rat colon are tissue specific and isoform specific; sodium depletion both induces and inhibits apical Na+/H+ exchange at a pretranslational level.
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Colon/metabolismo , Intercambiadores de Sodio-Hidrógeno/metabolismo , Sodio/deficiencia , Animales , Northern Blotting , Western Blotting , Masculino , Ratas , Ratas Sprague-Dawley , Sodio/farmacocinética , Intercambiador 3 de Sodio-Hidrógeno , Distribución TisularRESUMEN
An apical membrane ouabain-sensitive H-K exchange and a barium-sensitive basolateral membrane potassium channel are present in colonic crypt cells and may play a role in both K absorption and intracellular pH (pHi) regulation. To examine the possible interrelationship between apical membrane H-K exchange and basolateral membrane K movement in rat distal colon in the regulation of pHi, experiments were designed to assess whether changes in extracellular potassium can alter pHi. pHi in isolated rat crypts was determined using microspectrofluorimetric measurements of the pH-sensitive dye BCECF-AM (2', 7'-bis(carboxyethyl-5(6)-carboxy-fluorescein acetoxy methylester). After loading with the dye, crypts were superfused with a Na-free solution which resulted in a rapid and reversible fall in pHi (7.36 +/- 0.02 to 6.98 +/- 0.03). Following an increase in extracellular [K] to 20 mm, in the continued absence of Na, there was a further decrease in pHi (0.20 +/- 0.02, P < 0.01). K-induced acidification was blocked both by 2 mm bath barium, a K channel blocker, and by 0. 5 mm lumen ouabain. K-induced acidification was also observed when intracellular acidification was induced by a NH4Cl prepulse. These observations suggest that increased basolateral K movement increases intracellular [K] resulting in a decrease in pHi that is mediated by a ouabain-sensitive apical membrane H,K-ATPase. Our results demonstrate an interrelationship between basolateral K movement and apical H-K exchange in the regulation of pHi and apical K entry in rat distal colon.
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Antiportadores/metabolismo , Colon/citología , ATPasa Intercambiadora de Hidrógeno-Potásio/metabolismo , Concentración de Iones de Hidrógeno , Mucosa Intestinal/citología , Transporte Iónico , Canales de Potasio/metabolismo , Potasio/metabolismo , Animales , Antiportadores/efectos de los fármacos , Bario/farmacología , Polaridad Celular , Colon/metabolismo , Células Epiteliales/efectos de los fármacos , Células Epiteliales/metabolismo , ATPasa Intercambiadora de Hidrógeno-Potásio/efectos de los fármacos , Homeostasis , Mucosa Intestinal/metabolismo , Líquido Intracelular/metabolismo , Masculino , Ouabaína/farmacología , Potasio/farmacología , Canales de Potasio/efectos de los fármacos , Antiportadores de Potasio-Hidrógeno , Ratas , Ratas Sprague-Dawley , ATPasa Intercambiadora de Sodio-Potasio/efectos de los fármacos , ATPasa Intercambiadora de Sodio-Potasio/metabolismoRESUMEN
We examined the effect of soluble corn bran hemicellulose (CBH, 10 g/day) on glucose control and serum insulin in three groups: patients with impaired glucose tolerance (IGT) with (20 subjects) or without (8 subjects) obesity and with healthy non-obese controls (10 subjects). Long-term supplementation (6 months) with CBH decreased the post oGTT curve for patients with impaired mild Type II diabetes, but not that for the controls. Hemoglobin A1c decreased significantly during CBH supplementation in the obese patients, while the fasting glucose level decreased in all three groups, although not significantly. A decreased serum insulin response by oGTT was found in those patients with IGT. The improved oGTT result was associated with improved insulin release and perhaps with peripheral insulin sensitivity. These findings suggest that CBH at a low dose might contribute to glycemic control and would play a useful role in treating Type II diabetes patients.
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Fibras de la Dieta/farmacología , Glucosa/metabolismo , Resistencia a la Insulina/fisiología , Obesidad/metabolismo , Polisacáridos/farmacología , Zea mays , Adulto , Anciano , Diabetes Mellitus Tipo 2/metabolismo , Dieta , Metabolismo Energético/efectos de los fármacos , Femenino , Prueba de Tolerancia a la Glucosa , Hemoglobina Glucada/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Encuestas NutricionalesRESUMEN
Jejunal villus cells from young-adult (6 months) and senescent (24 months) male Wistar rats were studied to evaluate the effect of aging on intracellular pH (pHi) regulation. pHi was measured by quantitative fluorescence microscopy by using BCECF-AM [2',7'-bis(carboxyethyl)-5(6)-carboxy-fluorescein acetoxy methylester] under basal conditions and after inducing cytoplasmic acidification with pulsed NH4Cl. In the senescent rats, the recovery rate from the acidified levels was significantly lower than that in the young-adult rats (.208 +/- .005 vs .255 +/- .004 pH units/min). The relationship between pHi recovery and external Na+ concentration followed Michaelis-Menten type kinetics, the maximum velocity (Vmax) of alkalinization being significantly lower in the senescent rats than in the young-adult rats (.227 +/- .033 vs .297 +/- .024 pH units/min). These results indicate that the recovery of pHi from an acidic level was slower in the senescent rats, due to the reduced activity of Na+/H+ exchange as revealed by the decreased Vmax value.
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Envejecimiento/metabolismo , Yeyuno/metabolismo , Amilorida/farmacología , Cloruro de Amonio/farmacología , Animales , Fluoresceínas , Concentración de Iones de Hidrógeno , Técnicas In Vitro , Yeyuno/citología , Masculino , Microscopía Fluorescente , Ratas , Ratas Wistar , Sodio/farmacologíaRESUMEN
The acidic microclimate layer in the vicinity of the cell surface of mammalian jejunum is important for absorption of some nutrients, such as small peptides and folate. The present study was undertaken to investigate the effect of aging on the cell surface pH (microclimate pH) of the jejunum of rats. The microclimate pH was measured in vitro in superfused preparations using single-barreled pH-sensitive microelectrodes filled with a liquid ion exchanger. The thickness of the microclimate layer was estimated by reading the distance of microelectrode advancements. The existence of a microclimate pH in the jejunum was confirmed in the senescent rats, but the value of the microclimate pH was significantly higher in the senescent (24 mo) rats (6.52 +/- 0.02) than in the young-adult (6 mo) rats (6.09 +/- 0.01) (P < 0.01). Na+ removal from the perfusate or the addition of amiloride elevated the pH in the senescent rats as well as in the young-adult rats. The microclimate layer was slightly thinner in the senescent rats than in the young-adult rats. The acidity of the microclimate layer of intestinal surface is lower in senescent animals than in the young-adult ones. One of reasons for this is the thinner mucus layer in senescent animals.
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Envejecimiento/fisiología , Concentración de Iones de Hidrógeno , Absorción Intestinal , Mucosa Intestinal/fisiología , Yeyuno/fisiología , Alanina/farmacología , Amilorida/farmacología , Animales , Bucladesina/farmacología , Membrana Celular/efectos de los fármacos , Membrana Celular/fisiología , GMP Dibutiril Cíclico/farmacología , Dipéptidos/farmacología , Ditiotreitol/farmacología , Glicina/farmacología , Mucosa Intestinal/crecimiento & desarrollo , Yeyuno/crecimiento & desarrollo , Cinética , Masculino , Microelectrodos , Monosacáridos/farmacología , Ratas , Ratas Wistar , Sodio/farmacología , Factores de TiempoRESUMEN
A 38-year-old female was admitted for investigation of the cause of hypergastrinemia, hypercalcemia and an elevated plasma parathyroid hormone (PTH) level. Her siblings, elder brother and sister who had duodenal carcinoid tumor with hypergastrinemia and parathyroid adenomas, were diagnosed as multiple endocrine neoplasia (MEN) type 1. In the present patient, endoscopic examination showed a carcinoid tumor of the duodenum, but examinations by computed tomography (CT) and ultrasonography of the abdomen failed to reveal pancreatic lesions. Serum gastrin levels of this patient and her siblings improved to the normal level after resection of carcinoid tumors. The hypergastrinemia accompanying MEN type 1 in these cases might be due to carcinoid tumor of the duodenum.
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Tumor Carcinoide/genética , Neoplasias Duodenales/genética , Gastrinas/sangre , Neoplasia Endocrina Múltiple Tipo 1/genética , Adulto , Tumor Carcinoide/sangre , Neoplasias Duodenales/sangre , Femenino , Humanos , Masculino , Neoplasia Endocrina Múltiple Tipo 1/sangre , LinajeRESUMEN
Nineteen monoclonal antibodies (MAbs), reactive in enzyme-linked immunosorbent assay (ELISA), with porcine transmissible gastroenteritis (TGE) virus TO-163 were obtained. Of these MAbs, 5 showed neutralizing (NT) activity (x 3,200 to 25,600) against TO-163. One of the MAbs which had NT activity showed hemagglutination inhibition activity (x 5,120) too. 14 hybridomas of polypeptide specificity against TO-163 strain were developed from which 11, 2, and 1 were specific for protein E2, N, and E1, respectively. Immunofluorescence staining patterns in TGE virus-infected cells reacted with MAbs were divided into three groups (types I, II and III). The fluorescence staining of E2 specific MAbs having NT activity were limited to the perinuclear area. All MAbs having NT activity showed the same fluorescence staining pattern.
Asunto(s)
Anticuerpos Monoclonales/inmunología , Antígenos Virales/análisis , Virus de la Gastroenteritis Transmisible/inmunología , Animales , Especificidad de Anticuerpos , Línea Celular , Hibridomas , PorcinosRESUMEN
The severity of isolated pulmonary valvular stenosis (PS) was evaluated noninvasively and quantitatively using two-dimensional pulsed Doppler echocardiography (2D-PDE). The subjects consisted of 17 patients with PS diagnosed by cardiac catheterization (3 to 15-year-old with a mean age of 7.9 years) and 28 healthy children (3 to 12-year-old with a mean age of 7.2 years). Flow signals by 2D-PDE were recorded in the right ventricular outflow tract just below the pulmonary valve and in the main pulmonary artery. The following three parameters were measured from the flow signals in the right ventricular outflow tract: the right ventricular pre-ejection period (RPEP) from the onset of the QRS in the electrocardiogram to the beginning of RV ejection in 2D-PDE, the acceleration time from the onset of RV ejection to peak velocity (AcT), and the right ventricular ejection time (RET) from the onset to the end of right ventricular (RV) ejection. Acceleration time index (AcT/RET), and systolic time intervals including RPEP/RET, RPEP/square root RR and RET/square root RR in PS were compared with those of the controls. The correlations between the above-mentioned parameters and pressure gradients and RV systolic pressures in PS were examined. Data were expressed as mean value +/- SD. AcT/RET ranged from 0.37 to 0.53 (0.45 +/- 0.04) in the controls and from 0.54 to 0.76 (0.62 +/- 0.07) in PS. The mean AcT/RET was significantly greater in PS than in the controls (p less than 0.001). There was a highly positive correlation of AcT/RET with pressure gradients (r = 0.94) and RV systolic pressures (r = 0.93). RPEP/RET ranged from 0.32 to 0.47 (0.37 +/- 0.04) in the controls and from 0.24 to 0.35 (0.29 +/- 0.03) in PS, and the mean was significantly lower in PS than in the controls (p less than 0.001), and this was caused by the short RPEP and prolonged RET. RPEP/square root RR ranged from 102 to 160 msec (122 +/- 16 msec) in the controls and from 86 to 136 msec (107 +/- 16 msec) in PS, and the mean was significantly shorter in PS (p less than 0.05). RET/square root RR ranged from 300 to 345 msec (323 +/- 13 msec) in the controls and from 308 to 417 msec (363 +/- 27 msec) in PS, and the mean was significantly longer in PS (p less than 0.001). The pressure gradient and RV systolic pressure in PS did not correlate with RPEP/RET, RPEP/square root RR and RET/ square root RR.4+ 102 to 160 msec (122 +/- 16 msec) in the controls and from 86 to 136 msec (107 +/- 16 msec) in PS, and the mean was significantly shorter in PS (p less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)