RESUMEN
BACKGROUND AND STUDY AIM: Endoscopic submucosal dissection (ESD) for colorectal tumors is not generally recommended because of the technical difficulties and complications, including perforation. These aspects of ESD are thoroughly analyzed in our retrospective study. PATIENTS AND METHODS: We studied 105 colorectal tumors, from 100 patients, that were treated by ESD at the Kyoto Prefectural University of Medicine or Nara City Hospital between 2005 and 2008. We analyzed tumor size, operation time, rate of en bloc resection, and complications. In addition, we thoroughly investigated the cases of perforation. RESULTS: The average tumor size was 30.4 mm; average operation time, 102 min; and rate of en bloc resection, 88.5 %. Perforation occurred in 10.4 % of the ESD procedures. Of the 11 perforations, 8 were detected during ESD and treated by clip closure during endoscopy, while 3 were evident only on subsequent routine computed tomography (CT); these were also managed conservatively. A case of postoperative hemorrhage was also observed. CONCLUSIONS: ESD effectively achieved a high rate of en bloc resection. However, the perforation rate was substantial; hence, improvement in the ESD method is required. The outcomes of ESD, especially for early colorectal malignancies, need to be assessed further.
Asunto(s)
Neoplasias del Colon/cirugía , Disección/métodos , Endoscopía Gastrointestinal/métodos , Neoplasias del Recto/cirugía , Anciano , Anciano de 80 o más Años , Endoscopía Gastrointestinal/efectos adversos , Femenino , Humanos , Perforación Intestinal/epidemiología , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Estudios RetrospectivosRESUMEN
The continuous intra-cortical infusion of a glia toxin, fluorocitrate, at the concentration of 1 mM caused a decrease in the cortical extracellular contents of an intrinsic coagonist for the N-methyl-D-aspartate (NMDA) type glutamate receptor, D-serine, by peaking at 40 min by -25% but produced an increase in those of glycine and L-serine. The attenuated glial activity by fluorocitrate was verified by a marked reduction in the extracellular glutamine contents. The present findings suggest that a group of glial cells such as a population of the protoplasmic astrocytes could, at least in part, participate differently in the regulation of the extracellular release of D-serine and another NMDA coagonist glycine in the medial frontal cortex of the rat.
Asunto(s)
Encéfalo/metabolismo , Líquido Extracelular/química , Líquido Extracelular/metabolismo , Neuroglía/metabolismo , Serina/metabolismo , Animales , Área Bajo la Curva , Encéfalo/efectos de los fármacos , Citratos/toxicidad , Glutamina/metabolismo , Masculino , Microdiálisis , Neuroglía/efectos de los fármacos , Ratas , Ratas Wistar , Serina/efectos de los fármacosRESUMEN
In rats, the subcutaneous injection of a dopamine uptake inhibitor, nomifensine (40 mg/kg), induced a significant increase in the c-fos mRNA levels in the neocortex on postnatal days 23 and 49, in the striatum on days 8, 14, 23 and 49, and in the hippocampus on day 23, when compared with saline administration. The repeated injection with nomifensine (40 mg/kg once daily) from postnatal days 49 to 53 and from 23 to 27, but not from days 8 to 12 and 14 to 18, resulted in an enhanced stereotypy response elicited by a subsequent challenge of the drug (5 mg/kg) 21 days after the last injection (behavioral sensitization). The present results suggest that the neuronal circuits regulated by nomifensine might undergo regionally-different developmental changes, which could be implicated in the development of behavioral expressions including nomifensine-induced stereotypy sensitization.
Asunto(s)
Encéfalo/crecimiento & desarrollo , Encéfalo/metabolismo , Inhibidores de Captación de Dopamina/farmacología , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Nomifensina/farmacología , Proteínas Proto-Oncogénicas c-fos/genética , Factores de Edad , Animales , Encéfalo/efectos de los fármacos , Estimulantes del Sistema Nervioso Central/farmacología , Dopamina/metabolismo , Hipocampo/efectos de los fármacos , Hipocampo/crecimiento & desarrollo , Hipocampo/metabolismo , Masculino , Neocórtex/efectos de los fármacos , Neocórtex/crecimiento & desarrollo , Neocórtex/metabolismo , Neostriado/efectos de los fármacos , Neostriado/crecimiento & desarrollo , Neostriado/metabolismo , ARN Mensajero/efectos de los fármacos , ARN Mensajero/metabolismo , Ratas , Ratas Wistar , Receptores Dopaminérgicos/efectos de los fármacos , Receptores Dopaminérgicos/metabolismo , Conducta Estereotipada/efectos de los fármacos , Conducta Estereotipada/fisiologíaRESUMEN
Approximately 50% of familial Alzheimer's disease (AD) cases are linked to the presenilin (PS) gene. This suggests that an altered function of mutated PSs accounts for a fundamental process leading to AD. Here we identify a new PS binding protein, PBP, which is highly expressed in cerebral cortex and hippocampus. immunohistochemical studies and cell fractionation analysis show that PBP redistributes from cytoplasm to membranes in the presence of PS. In addition, PBP is deficient in the soluble fraction of sporadic AD brains.
Asunto(s)
Proteínas Portadoras/análisis , Factores de Intercambio de Guanina Nucleótido , Proteínas de la Membrana/metabolismo , Proteínas del Tejido Nervioso , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismo , Secuencia de Aminoácidos , Animales , Northern Blotting , Western Blotting , Células COS , Proteínas Portadoras/química , Proteínas Portadoras/genética , Fraccionamiento Celular , Línea Celular , Membrana Celular/química , Corteza Cerebral/química , Corteza Cerebral/ultraestructura , Citoplasma/química , ADN Complementario , Hipocampo/química , Hipocampo/ultraestructura , Humanos , Inmunohistoquímica , Hibridación in Situ , Riñón , Ratones , Datos de Secuencia Molecular , Fragmentos de Péptidos/química , Presenilina-1 , Saccharomyces cerevisiae , TransfecciónRESUMEN
We have examined the effects of schizophrenomimetic drugs including phencyclidine (PCP) and methamphetamine (MAP) on cortical and striatal dopamine (DA) metabolism using an in vivo dialysis technique in the rat. An acute systemic injection of PCP (2.5-10 mg/kg, intraperitoneally (i.p.)) dramatically increased concentrations of DA, 3,4-dihydroxy-phenylacetic acid, and homovanillic acid in the dialysates from the medial frontal cortex in a dose-dependent fashion. However, PCP (2.5-10 mg/kg, i.p.) caused a much lower augmentation of extracellular DA release, with a significant decrease in dialysate DOPAC levels in the striatum. Moreover, continuous infusion of tetrodotoxin (TTX, 10(-5) M) into the prefrontal or striatal region through the microdialysis tube completely blocked the ability of PCP (10 mg/kg, i.p.) to alter the extracellular release of DA and its metabolites in the respective areas. In contrast, MAP (4.8 mg/kg, i.p.) elicited a marked and tetrodotoxin-resistant increase in DA levels with a significant loss of DOPAC contents in the extracellular space of both the frontal cortex and the striatum. The present results clearly demonstrate the differential effects of PCP on cortical and striatal DA transmission, suggesting that PCP may facilitate DA release in the medial frontal cortex by increasing impulse flow in the DA neurons projecting to the cortical area, whereas PCP-induced elevation of extracellular DA in the striatum may be caused mainly by reuptake inhibition of DA liberated by basal activity of the striatal DA neurons. The regional variation in PCP-induced DA release would be due to the combination of NMDA (N-methyl-D-aspartate) receptor blocking and DA reuptake inhibition by the drug. The uniform and TTX-resistant nature of MAP-induced changes in brain DA metabolism may result from the direct actions of MAP at DA nerve terminals.
Asunto(s)
Cuerpo Estriado/efectos de los fármacos , Dopamina/metabolismo , Lóbulo Frontal/efectos de los fármacos , Metanfetamina/farmacología , Fenciclidina/farmacología , Ácido 3,4-Dihidroxifenilacético/metabolismo , Animales , Relación Dosis-Respuesta a Droga , Masculino , Ratas , Ratas Wistar , Factores de TiempoRESUMEN
We have examined in the rat the effects of a selective non-competitive antagonist for the N-methyl-D-aspartate (NMDA) type excitatory amino acid receptor, dizocilpine (MK-801), on cortical dopamine (DA) metabolism using an in vivo dialysis technique. An acute intraperitoneal injection of MK-801 (0.4-1.25 mg/kg) dramatically increased the concentrations of dopamine, 3,4-dihydroxy-phenylacetic acid and homovanillic acid in the dialysates from the medial frontal cortex in a dose-dependent fashion. Moreover, MK-801 caused a delayed and small augmentation of the cortical extracellular release of 5-hydroxyindoleacetic acid. Continuous infusion of tetrodotoxin into the prefrontal region via the microdialysis tube completely blocked the ability of MK-801 (1.25 mg/kg, intraperitoneally) to augment the extracellular release of DA, its metabolites and the serotonin metabolite in the frontal cortex. The present results suggest that MK-801 facilitates DA release in the medial frontal cortex by increasing impulse flow in the DA neurons projecting to the cortical area adding further support to the view that the NMDA receptor may be involved in the tonic inhibition of frontal cortical DA neurons. It is also proposed that frontal serotonin neurons might be under regulation by excitatory amino acidergic transmission via the NMDA receptor.
Asunto(s)
Maleato de Dizocilpina/farmacología , Dopamina/metabolismo , Espacio Extracelular/metabolismo , Lóbulo Frontal/metabolismo , Tetrodotoxina/farmacología , Ácido 3,4-Dihidroxifenilacético/metabolismo , Animales , Ácido Homovanílico/metabolismo , Ácido Hidroxiindolacético/metabolismo , Masculino , Microdiálisis , Ratas , Ratas WistarRESUMEN
Using a brain microdialysis technique, we have shown in the rat that local infusion of a selective and competitive N-methyl-D-aspartate (NMDA) receptor antagonist, cis-4-phosphonomethyl-2-piperidine carboxylic acid (CGS-19755), into the medial frontal cortex via dialysis tubing caused a concentration-related increase in the extracellular release of dopamine, 3,4-dihydroxyphenylacetic acid, and homovanillic acid in the cortical region. Coinfusion of a sodium channel blocker, tetrodotoxin, completely inhibited the ability of the NMDA antagonist to augment frontal dopamine metabolism. These findings suggest that dopamine neurons projecting to the frontal cortex might be under a tonic transsynaptic inhibition exerted by excitatory amino acid neurotransmission via the NMDA receptor at the level of dopamine terminal fields.