RESUMEN
The prediction of graft rejection can play an important part in graft survival. Analysis of immune reactions has shown that graft rejection shares mechanisms with recurrent abortions during pregnancy. Progesterone-induced blocking factor (PIBF), a mediator of progesterone that blocks natural killer cell activity in peripheral blood, produces antiabortive effects. The aim of this study was to examine the PIBF concentration in the urine of transplanted recipients. The study included 116 white adults (70 men and 46 women) of median age 49.3 years, who had undergone kidney transplantations. The median duration after transplantation was 3.46 years. The average period between renal disease and our measurement was 12.3 years, and the median interval between graft rejection and our study was 1.75 years. Urine samples were used to measure PIBF concentrations by an enzyme-linked immunsorbent assay. PIBF urinary concentrations decreased significantly in patients who experienced ≥1 rejection episode (31.8±2.2 ng/mL) compared with those without any episode (22.7±1.2 ng/ml; P<.01). Moreover, the urinary PIBF level was significantly lower among patients who had increased creatinine and urea nitrogen levels in blood samples (P<.05 and P<.01, respectively). Decreased PIBF values in kidney transplant patients followed previous rejection episodes. A close negative correlation was observed between urinary PIBF concentrations and blood levels of creatinine and urea nitrogen. These findings suggested that PIBF detection may predict graft rejection in transplant recipients.
Asunto(s)
Rechazo de Injerto/etiología , Trasplante de Riñón/efectos adversos , Proteínas Gestacionales/orina , Factores Supresores Inmunológicos/orina , Biomarcadores/sangre , Biomarcadores/orina , Nitrógeno de la Urea Sanguínea , Creatinina/sangre , Ensayo de Inmunoadsorción Enzimática , Femenino , Rechazo de Injerto/orina , Humanos , Hungría , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Curva ROC , Factores de Tiempo , Resultado del TratamientoRESUMEN
Ischemia/reperfusion (I/R) injury is a serious condition that results from some surgical procedures, including intestinal transplantation. Ischemic postconditioning is defined as brief periods of reperfusion alternating with reocclusion applied during the early minutes after reperfusion. The objective of this study was to investigate the effect of ischemic postconditioning before small bowel autotransplantation. Total orthotopic intestinal autotransplantation was performed in 30 white domestic pigs. Grafts were stored in cold University of Wisconsin solution for 1, 3, or 6 hours. Duration of reperfusion was 3 hours in all grafts. Before reperfusion, the intestine was postconditioned via 3 cycles of ischemia for 30 seconds and reperfusion for 30 seconds (ischemic postconditioning protocol). Tissue from the small intestine was obtained after laparotomy (control group) and at the end of reperfusion periods. To monitor oxidative stress, tissue concentrations of malondialdehyde and reduced glutathione, and activity of superoxide dismutase were determined at spectrophotometry. Tissue damage on sections stained with hematoxylin- eosin was evaluated using a quantitative method (Scion Image software; Scion Corp, Frederick, Maryland). Our results demonstrated that ischemic postconditioning significantly decreased the reperfusion-ended lipid peroxidation value (mean +/- SEM, 142.0 +/- 7.1 micromol/g vs 125.0 +/- 2.1 micromol/g; P < .05). Moreover, the capacity and activity of endogenous antioxidant protective systems (glutathione 789+/-8.0 micromol/g vs 934 +/- 5.7 micromol/g, and superoxide dismutase 110 +/- 9 IU/g vs 126 +/- 4 IU/g; P < .05) remained higher in the ischemic postconditioning groups compared with tissues without ischemic postconditioning. At quantitative analysis, tissue injury was increased by the duration of cold preservation. The greatest injury was observed in the mucosal and submucosal layers and in the depth of crypts after 6 hours of preservation. Ischemic postconditioning significantly decreased intestinal wall injury in each group (P < .05). It was concluded that ischemic postconditioning before reperfusion mitigated oxidative stress and histologic damage during small bowel autotransplantation.
Asunto(s)
Intestino Delgado/trasplante , Poscondicionamiento Isquémico/métodos , Animales , Frío , Glutatión/metabolismo , Mucosa Intestinal/metabolismo , Intestino Delgado/irrigación sanguínea , Intestino Delgado/metabolismo , Peroxidación de Lípido , Malondialdehído/metabolismo , Músculo Liso/metabolismo , Preservación de Órganos/métodos , Superóxido Dismutasa/metabolismo , Porcinos , Trasplante AutólogoRESUMEN
Tissue injury caused by cold preservation remains a problem in small intestinal transplantation. Pituitary adenylate cyclase-activating polypeptide (PACAP) has a central role in intestinal physiology. The objective of the present study was to compare the effects of cold ischemia injury in PACAP-38 knockout and wild-type mice after cold storage of small bowel. Cold ischemia was produced using small bowel preservation in University of Wisconsin solution at 4 degrees C in 20 PACAP-38 wild-type mice for 1, 3, and 6 hours (groups 1, 2, and 3, respectively) and 20 PACAP-38 knockout mice for 1, 3, and 6 hours (groups 4, 5, and 6, respectively). Biopsy samples of small bowel were obtained after laparotomy (control) and at the end of preservation periods. To determine oxidative stress, malondialdehyde, reduced glutathione, and superoxide dismutase concentrations were measured. Tissue damage was assessed using a quantitative method on sections stained with hematoxylin-eosin. After 6 hours, tissue lipid peroxidation was increased significantly in PACAP-38 knockout mice (mean +/- SD, 153.04 +/- 7.2 micromol/g) compared with sham-operated mice (110.44 +/- 5.5 micromol/g) and wild-type mice (120.0 +/- 1.1 micromol/g) (P < .05). The capacity and activity of the endogenous antioxidant system decreased significantly after 3 and 6 hours of preservation (reduced glutathione, 808.7 +/- 5.2 micromol/g and 720.4 +/- 8.7 micromol/g; and superoxide dismutase, 125.1 +/- 1.4 IU/g and 103.3 +/- 1.9 IU/g vs 212.11 +/- 5.8 IU/g; P < .05). Quantitative histologic analysis demonstrated destruction of mucosal and submucosal layers and crypts in knockout mice compared with wild-type mice. These processes depended on duration of cold preservation. These findings demonstrate that PACAP-38 has a key role in protection against intestinal cold preservation injury.
Asunto(s)
Polipéptido Hipofisario Activador de la Adenilato-Ciclasa/deficiencia , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa/metabolismo , Adenosina , Alopurinol , Animales , Antioxidantes/metabolismo , Criopreservación/métodos , Glutatión/metabolismo , Insulina , Intestino Delgado/metabolismo , Peroxidación de Lípido , Malondialdehído/metabolismo , Ratones , Ratones Noqueados , Preservación de Órganos/métodos , Soluciones Preservantes de Órganos , Polipéptido Hipofisario Activador de la Adenilato-Ciclasa/genética , Rafinosa , Superóxido Dismutasa/metabolismoRESUMEN
There is increasing evidence that nonmelanoma skin cancers (NMSCs) are the most frequently observed tumors in transplant recipients. The incidence of posttransplantation NMSC was determined using our dermatologic screening program. Included in the study were 116 white adults (70 men and 46 women; median age, 49.3 years) who had undergone kidney or combined kidney-pancreas transplantation, with follow-up from September 2008 to December 2009. All patients underwent a full skin examination for NMSC, and completed a standardized questionnaire. Screening resulted in detection of 16 NMSCs in 11 patients out of 116 (9.5%). Lesions were equally distributed by sex, and were detected at a median of 4.1 years posttransplantation. Histologic analysis verified 13 basal cell carcinomas and 3 squamous cell carcinomas (ratio, 4:1). The incidence of NMSC was significantly greater in patients who received cyclosporine immunosuppression therapy (16 vs 1; P < .05), had experienced 2 or more painful sunburns before transplantation (10 vs 11), or worked outdoors (10 vs 11). These data indicate the relevance of skin cancer surveillance in transplant recipients. Our results correspond to international statistics except for the ratio of basal cell carcinoma to squamous cell carcinoma. Further studies are needed to elucidate the reasons for this difference.
Asunto(s)
Trasplante de Órganos/efectos adversos , Neoplasias Cutáneas/epidemiología , Carcinoma Basocelular/epidemiología , Carcinoma de Células Escamosas/epidemiología , Femenino , Estudios de Seguimiento , Humanos , Hungría/epidemiología , Trasplante de Riñón/efectos adversos , Masculino , Persona de Mediana Edad , Trasplante de Páncreas/efectos adversos , Piel/patología , Neoplasias Cutáneas/clasificación , Encuestas y Cuestionarios , Factores de TiempoRESUMEN
Transplant recipients are at high risk of nonmelanoma skin cancer (NMSC). Ultraviolet radiation can generate oxygen free radicals (OFRs), leading to oxidative stress and carcinogenesis, primarily during immunosuppression therapy. In the present study, changes in oxidative stress were examined in transplant recipients with and without NMSC. The study included 116 white adults who had undergone kidney or combined kidney-pancreas transplantation. Dermatologic follow-up revealed 16 NMSCs (13.8%). To monitor oxidative stress, peripheral blood samples were used to measure malondialdehyde (MDA), reduced glutathione, sulfhydryl (-SH) groups, OFRs, and activity of myeloperoxidase, superoxide dismutase, and catalase. The mean (SD) plasma MDA concentration was significantly greater in patients without NMSC compared with healthy control individuals (0.48+/-0.05 nmol/mL; P < .05), whereas MDA concentration in hemolysate was slightly increased. In peripheral blood samples, the MDA concentration in both plasma (0.71+/-0.03 nmol/mL) and hemolysate (87.74+/-1.25 nmol/mL) was significantly increased in the NMSC group compared with the healthy control group (0.24+/-0.05 nmol/mL vs 75.87+/-2.8 nmol/mL; P < .05) or patients without NMSC (0.48+/-0.04 nmol/mL vs 79.62+/-2.77 nmol/mL; P < .05). The reduced glutathione concentration was significantly decreased in the -SH groups compared with the healthy control group (P < .05). Antioxidant activity of myeloperoxidase (0.78+/-0.05 IU/mL) and catalase (1855.8+/-45.41 IU/mL) was significantly increased in the group without NMSC compared with the healthy control group (0.41+/-0.1 IU/mL vs 1642.07+/-82.96 IU/mL) and the NMSC group (0.93+/-0.03 IU/mL vs 2180.5+/-15.03 IU/mL). The superoxide dismutase activity was decreased slightly but not significantly. Total production of OFRs was significantly greater in the NMSC group compared with the non-NMSC group or the healthy control group (P < .05). These findings suggest that an imbalance exists between pro-oxidant and antioxidant status in transplant recipients, with a significant difference in patients with vs without NMSC.