RESUMEN
BACKGROUND: The number of deceased organ donors has decreased slightly over the past 4 years. Although the pool of intestinal transplantation candidates is relatively small, donor allocation is challenging because of the inability to maintain the donor in a good condition and the complexities involved in making a suitable weight match between donors and recipients. Our goal was to analyze the epidemiologic profile of potential donors based on the organs offered by the regional Organ Procurement Organization from Hospital das Clinicas-USP (OPO/HC-USP) and attempt to estimate possible matches and program viability. METHODS: We retrospectively analyzed information from the OPO/HC-USP database regarding organs offered over the past 7 years as well as patients listed in our program. Data were collected regarding donor characteristics (eg, sex, age, race, body mass index, blood type, cause of death) and medical care details (eg, intensive care unit stay, use of vasopressor agents and antibiotics). RESULTS: In this time period, there were 18,103 brain death notifications in the state of São Paulo; 5,202 (35%) became viable donors, resulting in 5,201 (99%) effectively used livers and kidneys. Most potential donors were male, in their 40s, white, and had blood type O. Only 3 potential donors from OPO/HC-USP would have reached the established minimum criteria for intestinal donation over these 7 years.
Asunto(s)
Muerte Encefálica , Intestinos/trasplante , Donantes de Tejidos/provisión & distribución , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Brasil , Niño , Preescolar , Femenino , Hospitales , Humanos , Lactante , Unidades de Cuidados Intensivos , Masculino , Persona de Mediana Edad , Nutrición Parenteral/estadística & datos numéricos , Estudios Retrospectivos , Adulto JovenRESUMEN
BACKGROUND: Different abnormalities of T cell effector function distinguish Crohn's disease (CD) from ulcerative colitis (UC). Because cell cycling determines effector function, pathogenic events in CD and UC may depend on cell cycle changes unique to each condition. METHODS: Cell cycle kinetics, cycle regulatory molecule expression, apoptosis, caspase and telomerase activity, and cellular expansion were evaluated in CD2 and CD3 activated control, CD, and UC lamina propria T cells. RESULTS: Compared with normal cells, CD T cells cycle faster, express increased phosphorylated Rb and decreased phosphorylated p53 levels, display less caspase activity but more telomerase activity, die less, and undergo vigorous cellular expansion. In contrast, UC T cells cycle slower, express normal levels of phosphorylated Rb and p53, display more caspase activity but have no telomerase activity, die more, and have a limited capacity to expand. CONCLUSIONS: T cell cycle abnormalities in CD indicate a state of hyperreactivity compatible with loss of tolerance, but a hyporeactive state compatible with anergy in UC. Thus distinct and divergent T cell cycle characteristics underlie the pathogenesis of the two main forms of inflammatory bowel disease.
Asunto(s)
Colitis Ulcerosa/inmunología , Enfermedad de Crohn/inmunología , Mucosa Intestinal/inmunología , Linfocitos T/patología , Adolescente , Adulto , Anciano , Apoptosis/inmunología , Ciclo Celular/fisiología , Proteínas de Ciclo Celular/metabolismo , División Celular/inmunología , Células Cultivadas , Colitis Ulcerosa/metabolismo , Colitis Ulcerosa/patología , Enfermedad de Crohn/metabolismo , Enfermedad de Crohn/patología , Femenino , Citometría de Flujo/métodos , Humanos , Inmunidad Mucosa , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patología , Activación de Linfocitos/inmunología , Masculino , Persona de Mediana Edad , Linfocitos T/inmunologíaRESUMEN
The pathogenesis of nonsteroidal anti-inflammatory drug (NSAID) enteropathy is a complex process involving the uncoupling of mitochondrial oxidative phosphorylation and inhibition of cyclooxygenase (COX). Rofecoxib, a selective inhibitor of COX-2, has shown less gastric damage, but the same beneficial effect is not clear in the case of the small bowel. Fifty-seven male Wistar rats (250-350 g) were divided into three groups (N=19 each) to evaluate the effect of this NSAID on the rat intestine. The groups received 2.5 mg/kg rofecoxib, 7.5 mg/kg indomethacin or water with 5% DMSO (control) given as a single dose by gavage 24 h before the beginning of the experiment. A macroscopic score was used to quantify intestinal lesions and intestinal permeability was measured using [51Cr]-ethylenediaminetetraacetic acid ([51Cr]-EDTA). The extent of intestinal lesion, indicated by a macroscopic score, was significantly lower when rofecoxib was administered compared to indomethacin (rofecoxib=0.0 vs indomethacin=63.6 +/- 25.9; P<0.05) and did not differ from control. The intestinal permeability to [51Cr]-EDTA was significantly increased after indomethacin (control=1.82 +/- 0.4 vs indomethacin=9.12 +/- 0.8%; P<0.0001), but not after rofecoxib, whose effect did not differ significantly from control (control=1.82 +/- 0.4 vs rofecoxib=2.17 +/- 0.4%; ns), but was significantly different from indomethacin (indomethacin=9.12 +/- 0.8 vs rofecoxib=2.17 +/- 0.4%; P<0.001). In conclusion, the present data show that rofecoxib is safer than indomethacin in rats because it does not induce macroscopic intestinal damage or increased intestinal permeability.
Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Inhibidores de la Ciclooxigenasa/farmacología , Indometacina/farmacología , Intestino Delgado/efectos de los fármacos , Isoenzimas/antagonistas & inhibidores , Lactonas/farmacología , Animales , Antiinflamatorios no Esteroideos/efectos adversos , Ciclooxigenasa 2 , Inhibidores de la Ciclooxigenasa 2 , Inhibidores de la Ciclooxigenasa/efectos adversos , Indometacina/efectos adversos , Mucosa Intestinal/efectos de los fármacos , Lactonas/efectos adversos , Masculino , Permeabilidad/efectos de los fármacos , Prostaglandina-Endoperóxido Sintasas , Ratas , Ratas Wistar , SulfonasRESUMEN
The pathogenesis of nonsteroidal anti-inflammatory drug (NSAID) enteropathy is a complex process involving the uncoupling of mitochondrial oxidative phosphorylation and inhibition of cyclooxygenase (COX). Rofecoxib, a selective inhibitor of COX-2, has shown less gastric damage, but the same beneficial effect is not clear in the case of the small bowel. Fifty-seven male Wistar rats (250-350 g) were divided into three groups (N = 19 each) to evaluate the effect of this NSAID on the rat intestine. The groups received 2.5 mg/kg rofecoxib, 7.5 mg/kg indomethacin or water with 5 percent DMSO (control) given as a single dose by gavage 24 h before the beginning of the experiment. A macroscopic score was used to quantify intestinal lesions and intestinal permeability was measured using [51Cr]-ethylenediaminetetraacetic acid ([51Cr]-EDTA). The extent of intestinal lesion, indicated by a macroscopic score, was significantly lower when rofecoxib was administered compared to indomethacin (rofecoxib = 0.0 vs indomethacin = 63.6 ± 25.9; P < 0.05) and did not differ from control. The intestinal permeability to [51Cr]-EDTA was significantly increased after indomethacin (control = 1.82 ± 0.4 vs indomethacin = 9.12 ± 0.8 percent; P < 0.0001), but not after rofecoxib, whose effect did not differ significantly from control (control = 1.82 ± 0.4 vs rofecoxib = 2.17 ± 0.4 percent; ns), but was significantly different from indomethacin (indomethacin = 9.12 ± 0.8 vs rofecoxib = 2.17 ± 0.4 percent; P < 0.001). In conclusion, the present data show that rofecoxib is safer than indomethacin in rats because it does not induce macroscopic intestinal damage or increased intestinal permeability.