RESUMEN
The viscosity obtained from pressure-flow characteristics of an oxygenator may help to detect factors that change oxygenator resistance. The objective of this study was to model pressure-flow characteristics of a membrane oxygenator with an integrated arterial filter and to quantify their influence on apparent viscosity of non-Newtonian fluids. One Newtonian fluid (glycerin solution) and two non-Newtonian fluids (whole bovine blood and a human red blood cell suspension) were perfused through an oxygenator and their pressure-flow characteristics examined systematically. Four resistance parameters for the pressure gradient characteristics approximation equation were obtained by the least squares method from the relational expression of pressure-flow characteristics and viscosity. For all three fluids, a non-linear flow to pressure change was observed with a coefficient of determination of almost 1 by exponential approximation. The glycerin solution had a higher pressure gradient (10-70%) than the other fluids; the apparent viscosity of the non-Newtonian fluids was around 35% lower than the static one measured by a torsional oscillation viscometer. Overall, our study demonstrated that the influence on the apparent viscosity of non-Newtonian fluids can be quantified by pressure gradient differences in a membrane oxygenator with an integrated arterial filter.
Asunto(s)
Presión Sanguínea , Viscosidad Sanguínea , Oxigenación por Membrana Extracorpórea , Modelos Cardiovasculares , Oxigenadores de Membrana , Animales , Bovinos , HumanosRESUMEN
Monitoring the blood pump and the oxygen gas flow meter are important maneuvers at the initiation of cardiopulmonary bypass (CPB). We present a novel system, designed to improve safety in the heart-lung machine by linking the control of blood flow and the oxygen gas flow meter. This system uses a mass flow controller to provide and control oxygen flow based on the ventilation-perfusion (V/Q) ratio, using the electronic signal of the blood flow. We tested the system, in vitro and in vivo, and examined the resulting level of blood oxygenation. When extracorporeal circulation was initiated, the oxygen flow was instantly linked to the circulating blood flow, providing an adequate V/Q ratio; the partial pressure of oxygen in the blood was maintained at a normal level. Although we have yet to confirm the safety of this system in clinical trials, the new safety assist device can automatically supply oxygen to the oxygenator at the beginning of CPB.
Asunto(s)
Puente Cardiopulmonar/instrumentación , Máquina Corazón-Pulmón , Hemodinámica , Oxígeno/sangre , Oxigenadores , Animales , Análisis de los Gases de la Sangre , Diseño de Equipo , PorcinosRESUMEN
BACKGROUND AND STUDY AIMS: Growing evidence suggests that esophageal stricture frequently develops after endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD) in early esophageal cancer patients, with an incidence proportional to the greater extent of mucosal defects resulting from improved EMR/ESD techniques. There seems to be a potential risk of perforation during bougienage in such patients. PATIENTS AND METHODS: 648 stricture dilations for 78 lesions in 76 patients were consecutively included. The outcomes after combined use of Maloney and Savary wire-guided bougienage for esophageal strictures after EMR/ESD were analyzed in a single-institute retrospective case series study. The perforation rate was determined and risk factors for perforation were identified. RESULTS: Patients underwent a median of 5.0 dilation procedures performed over a median 3.0 months for post-EMR/ESD strictures. Initial dilation was done a median 14 days following endoscopic resection. Perforations developed in seven patients (7/648 dilation procedures, 1.1%), all in the lower esophagus, and bleeding occurred in one patient (0.1% dilations). Two independent risk factors for development of perforation during dilation therapy for post-EMR/ESD stricture were identified: multiple dilations (odds ratio [OR] 1.2; P=0.012), and lower site of stricture (OR 12.8; P=0.043). Dysphagia was ameliorated by the dilations, and no patient required surgery. CONCLUSIONS: A specific emerging risk of perforation in dilation therapy for post-EMR/ESD strictures was identified. Carefully planned treatment is necessary in patients with severe post-EMR/ESD strictures especially strictures requiring multiple dilations or located in the lower esophagus.
Asunto(s)
Carcinoma de Células Escamosas/cirugía , Dilatación/efectos adversos , Neoplasias Esofágicas/cirugía , Perforación del Esófago/epidemiología , Perforación del Esófago/etiología , Estenosis Esofágica/terapia , Esofagoscopía/efectos adversos , Esófago/cirugía , Membrana Mucosa/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Dilatación/instrumentación , Estenosis Esofágica/etiología , Esófago/patología , Humanos , Masculino , Persona de Mediana Edad , Membrana Mucosa/patología , Estudios Retrospectivos , Factores de Riesgo , Resultado del TratamientoRESUMEN
Extracellular matrix dynamics, crucial for tissue remodelling, are highly regulated by a cascade of matrix metalloproteinases (MMPs) during inflammation and wound healing processes in inflammatory bowel disease (IBD). Contrary to expectations, there are limited reports to date that MMP inhibitors have some beneficial therapeutic effects in experimental colitis models. Furthermore, clinical trials of MMP inhibitors against certain tumours have failed to show any therapeutic benefit. One major reason for this lack of success may be the apparent uncertainty about the precise spectrum of inhibitory activity required. Since tumour necrosis factor alpha (TNFalpha), a key mediator in colonic inflammation, promotes MMP production in a dose-dependent manner, the therapeutic success of anti-TNFalpha agents against IBD motivated us to re-evaluate the therapeutic potential of MMP inhibition. First, using a quantitative polymerase chain reaction (PCR), western blotting, and zymography, we determined which MMPs were relevant to experimental colitis induced in mice by dextran sulphate sodium. Next, we examined a distinct role for MAPK and NFkappaB signalling pathways in the regulation of the expression of these MMP genes. Finally, we examined whether transcriptional regulation of these MMPs, either indirectly using inhibitors of MAPK and/or NFkappaB signalling pathways or directly using siRNA directed against these MMPs, contributes to the prevention of colitis. Changes in the expression level of colonic MMP-3 and MMP-10 preceded the clinical course of colitis. Colitis improved in mice that received these signal inhibitors, together with suppression of MMP expression. Moreover, siRNA that targeted MMP-3 and MMP-10 effectively reduced both the transcription of these MMPs and the severity of colitis. We conclude that MMP-3 and MMP-10 play a causal role in excess tissue destruction in colitis. Specific inhibition of these MMPs should provide novel therapeutics against IBD.
Asunto(s)
Colitis/prevención & control , Inhibidores Enzimáticos/uso terapéutico , Inhibidores de la Metaloproteinasa de la Matriz , Animales , Colitis/inducido químicamente , Colitis/enzimología , Sulfato de Dextran , Modelos Animales de Enfermedad , Activación Enzimática/efectos de los fármacos , Femenino , Imidazoles/uso terapéutico , Enfermedades Inflamatorias del Intestino/inducido químicamente , Enfermedades Inflamatorias del Intestino/enzimología , Enfermedades Inflamatorias del Intestino/prevención & control , Metaloproteinasa 10 de la Matriz , Metaloproteinasa 3 de la Matriz/genética , Metaloproteinasa 3 de la Matriz/metabolismo , Metaloproteinasas de la Matriz/metabolismo , Metaloproteinasas de la Matriz/fisiología , Metaloendopeptidasas/genética , Metaloendopeptidasas/metabolismo , Ratones , Ratones Endogámicos BALB C , Quinasas de Proteína Quinasa Activadas por Mitógenos/metabolismo , FN-kappa B/metabolismo , Piridinas/uso terapéutico , ARN Interferente Pequeño/genética , Transducción de Señal , Factor de Necrosis Tumoral alfa/farmacologíaRESUMEN
BACKGROUND: Most array analyses of ulcerative colitis have focused on identifying susceptibility genes for ulcerative colitis. AIM: To clarify the changes in gene expression during inflammation in ulcerative colitis colon mucosa using cDNA macroarray. METHODS: From 23 ulcerative colitis patients, 16 each of inflamed and non-inflamed specimens (total 32 samples for individual analysis) were obtained by colonoscopic biopsy. Eighteen of the 32 samples, used for pairwise analysis, consisted of nine sample pairs, each pair being from the same patient. We examined expression profiles of approximately 1300 genes with cDNA macroarray. Comparisons were made using two kinds of statistics, t-test and significance analysis of microarray in both analyses. The reproducibility of significant genes from the macroarray analysis was confirmed by real-time ploymerase chain reaction. RESULTS: We detected five upregulated genes, categorized into proinflammatory genes (MRP14, GRO gamma and SAA1) and anti-inflammatory genes (TIMP1 and Elafin) in inflamed mucosa, and one upregulated gene (L-FABP) in non-inflamed mucosa. CONCLUSIONS: As the cDNA macroarray analysis in this study exactly reflects the total profile of gene expression in the clinical setting of ulcerative colitis, the genes identified will be directly applicable to diagnostics or as novel therapeutic targets in active ulcerative colitis.
Asunto(s)
Colitis Ulcerosa/genética , ADN Complementario/análisis , Genes/genética , Acrosoma , Adulto , Antígenos/genética , Calgranulina B/genética , Proteínas Portadoras/genética , Quimiocina CXCL1 , Quimiocinas CXC/genética , ADN Complementario/genética , Proteínas de Unión a Ácidos Grasos , Humanos , Inflamación/genética , Péptidos y Proteínas de Señalización Intercelular/genética , Isoantígenos , Análisis de Secuencia por Matrices de Oligonucleótidos , Proteínas Inhibidoras de Proteinasas Secretoras , Proteínas/genética , ARN/análisis , ARN/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa/métodos , Proteínas de Plasma Seminal , Inhibidor Tisular de Metaloproteinasa-1/genética , Regulación hacia Arriba/genéticaRESUMEN
PURPOSE: The purpose of this study was to investigate the mechanism of the regulation of histamine synthesis in enterochromaffin-like cells, chemically and structurally, by treatment with omeprazole and pirenzepine. METHODS: The ultrastructures of enterochromaffin-like cells and parietal cells were examined in rats treated with oral omeprazole (20 mg/kg) or intraperitoneal pirenzepine (1 mg/kg) administration. Serum gastrin concentrations, mRNA levels of H+-K+-ATPase and histidine decarboxylase, and the fundic concentrations of somatostatin and histamine were determined. RESULTS: Pirenzepine treatment suppressed omeprazole-induced increases in serum gastrin levels and mRNA levels of H+-K+-ATPase and histidine decarboxylase. Pirenzepine also decreased omeprazole-induced increases of histamine concentration in fundic mucosa. Pirenzepine elevated somatostatin mRNA level, previously decreased by omeprazole treatment, in fundic mucosa. In the cytoplasm of enterochromaffin-like cells, omeprazole markedly reduced the numbers of vesicles and granules, but significantly increased their diameters, whereas pirenzepine treatment changed neither of these features. The densities and diameters of both vesicles and granules produced by treatment with omeprazole and pirenzepine were between those produced by treatment with omeprazole alone and pirenzepine alone. CONCLUSIONS: Omeprazole-induced hypergastrinemia and pirenzepine-induced somatostatin synthesis play important roles not only in histamine synthesis but also in ultrastructural changes in enterochromaffin-like cells.
Asunto(s)
Antiulcerosos/uso terapéutico , Células Similares a las Enterocromafines/efectos de los fármacos , Omeprazol/uso terapéutico , Células Parietales Gástricas/efectos de los fármacos , Estómago/citología , Estómago/efectos de los fármacos , Animales , Northern Blotting , Quimioterapia Combinada , ATPasa Intercambiadora de Hidrógeno-Potásio/efectos de los fármacos , Histamina/sangre , Concentración de Iones de Hidrógeno/efectos de los fármacos , Masculino , Pirenzepina/uso terapéutico , ARN Mensajero/efectos de los fármacos , Ratas , Ratas Wistar , Estómago/químicaRESUMEN
We examined the role of capsaicin-sensitive afferent neurons in pH-dependent gastrin secretion in the rat stomach. The change in serum gastrin levels relative to changes in luminal pH (using omeprazole for luminal alkalization or 0.1 N HCl for luminal acidification) was studied after oral administration of 4% lidocaine or capsaicin-induced ablation of afferent neurons. The increase of serum gastrin levels by luminal alkalization was significantly inhibited (50%) after administration of 4% lidocaine. Capsaicin pretreatment (125 mg/kg subcutaneously over two days) inhibited the change in serum gastrin levels both the luminal alkalization (38%) and acidification (66%). Antral gastrin contents, somatostatin contents, gastrin mRNA expression, and somatostatin mRNA expression were not significantly affected by capsaicin pretreatment. Our results indicate that capsaicin-sensitive afferent neurons participate in the secretion of gastrin by luminal alkalization and inhibition of gastrin by luminal acidification.