Changes of progesterone-induced blocking factor in patients after kidney transplantation.

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.

Incidence of nonmelanoma skin cancer after human organ transplantation: single-center experience in Hungary.

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.

Changes in oxidative stress in patients screened for skin cancer after solid-organ transplantation.

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.

Influence of pituitary adenylate cyclase-activating polypeptide on the activation of mitogen activated protein kinases following small bowel cold preservation.

Cold preservation prior to small bowel transplantation can moderate tissue oxidative injury. This stress triggers several intracellular pathways via mitogen activated protein (MAP) kinases. MAP kinases include the extracellular signal related kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 MAP kinase. Pituitary adenylate cyclase-activating polypeptide (PACAP) plays a central role in intestinal physiology. We sought to investigate the effect of PACAP on the activation of MAP kinases during cold preservation of the small bowel. Total orthotopic intestinal autotransplantation was performed on 40 Wistar rats. Perfused grafts were stored in University of Wisconsin (UW) solution for 1 (GI), 2 (GII), 3 (GIII), or 6 hours (GIV) without or with 30 PACAP, namely 1 (GV), 2 (GVI), 3 (GVII), or 6 hours (GVIII). After 3 hours of reperfusion in all groups, the activation of MAP kinases were measured using immunocytochemistry of small bowel tissue. Among the UW preserved grafts (GI-GIV), phosphorylated ERK1/2 level were decreased, while phosphorylated JNK1/2 and p38 MAP kinase activation were elevated compared with control levels. In GV-GVIII PACAP we observed enhanced phospho-ERK1/2 appearance with decreased JNK and p38 MAP kinase activity at the end of the reperfusion periods. We concluded that cold preservation decreased phosphorylated ERK1/2 levels and increased JNK1/2 and p38 MAP kinase activities, which meant that cold storage triggered apoptotic cell death. In contrast, PACAP treatment induced signalling pathways protective against oxidative injury by MAP kinases in bowel tissue.

Changes and effect of PACAP-38 on intestinal ischemia-reperfusion and autotransplantation.

Tissue injury caused by cold preservation and reperfusion during small bowel transplantation remains an unsolved problem. Increasing evidence suggests that pituitary adenylate cyclase-activating polypeptide (PACAP) has protective effects in several ischemia-reperfusion (I/R) models. This study investigated the effect of PACAP-38 on oxidative stress in autotransplanted intestine. We established sham-operated, I/R, and autotransplanted groups in Wistar rats (n = 55). We applied ischemia for 1 (GI), 2 (GII), or 3 hours (GIII). In autotransplanted groups, we performed total orthotopic intestinal autotransplantation. Grafts were preserved in University of Wisconsin (UW) solution for 1 (GIV), 2 (GV), 3 (GVI), or 6 (GVII) hours and in PACAP-38-containing UW for 1 (GVIII), 2 (GIX), 3 (GX), or 6 (GXI) hours. Reperfusion lasted 3 hours in each group. Endogenous PACAP-38 values were measured by radioimmunoassay. Oxidative stress parameters malondialdehyde (MDA), reduced glutathione (GSH), and superoxide dismutase (SOD) were measured in tissue homogenates. Concentration of endogenous PACAP-38 significantly decreased in GI to GIII compared with the sham-operated animals following I/R periods (P < .05). Cold preservation in UW and reperfusion of the intestine increased the level of tissue MDA in GIV to GVII, which correlated with the duration of cold storage. The content of GSH decreased in GIV to GVII to levels that were significantly different between GIV and GVIII and between GVII and GXI. SOD activity decreased dramatically in GIV to GVII with significantly higher activity in GIX to GXI. Our findings confirmed that I/R decreased endogenous PACAP-38 concentration. Administration of PACAP-38 to UW solution mitigated the oxidative injury during intestinal autotransplantation.

Threshold level of NF-kB activation in small bowel ischemic preconditioning procedure.

Ischemic preconditioning (IPC), which is obtained by exposure to brief periods of vascular occlusion, improves organ tolerance to prolonged ischemia. The aim of this study was to evaluate the threshold level of NF-kB activation in small intestine during an IPC procedure. Various intestinal IPC were performed on 20 Wistar rats in seven groups: group I (GI, nonpreconditioned); group II (GII, 1-minute ischemia and 1-minute reperfusion); group III (GIII, two cycles of 1-minute ischemia and 1-minute reperfusion); group IV (GIV, 2-minutes ischemia and 2-minutes reperfusion); group V (GV, two cycles of 2-minute ischemia and 2-minute reperfusion); group VI (GVI, 5-minute ischemia and 10-minute reperfusion); group VII (GVII, two cycles of 5-minute ischemia and 10-minute reperfusion). Bowel biopsies were collected after laparotomy (control) as well as at 30, 60, and 120 minutes following IPC. We determined the cytoplasmic and nuclear NF-kB by a chemiluminescence-based ELISA method. Our results showed low, constant NF-kB levels in GI. In the preconditioned groups (GII-GVII), NF-kB was significantly elevated at 30 minutes following IPC (P < .05 vs control). After 1 hour, NF-kB activity decreased to the control level. However, 2 hours after IPC both forms of NF-kB were elevated significantly again, which was independent of the number of IPC cycles (P < .05 vs control). Our experiments revealed that one cycle of 1-minute ischemia and 1-minute reperfusion is a critical threshold level for NF-kB activation during small bowel IPC. Longer and more IPC cycles did not result in further elevation of NF-kB activation.

Mitigation of oxidative injury by classic and delayed ischemic preconditioning prior to small bowel autotransplantation.

Ischemic preconditioning (IPC) has been defined as short periods of ischemia with intermittent reperfusion. IPC induces two phases of protection. We sought to investigate the effects of classic and delayed preconditioning on oxidative stress markers prior to autotransplantation. Total orthotopic intestinal autotransplantation was performed on 18 mongrel dogs in three groups: group I (GI, nonpreconditioned), group II (GII, classic preconditioned), and group III (GIII, delayed preconditioned). In GI 3-hour cold preservation in University of Wisconsin solution was followed by 1 hour of reperfusion. In GII before this procedure the intestine was preconditioned by occlusion of the mesenteric artery with four cycles each of 5 minutes of ischemia and 10 minutes of reperfusion (IPC protocol). In GIII on day 1 the animals underwent the IPC protocol, and autotransplantation was performed on day 2. Oxidative stress parameters included malondialdehyde (MDA), reduced glutathione (GSH), and superoxide dismutase (SOD) measurements in tissue samples. Our results showed increased lipid peroxidation with decreased GSH level and SOD activity in GI (control: 254.38 +/- 18.32 IU/g; reperfused: 55.01 +/- 26.40 IU/g; P <.05). In GII MDA was slightly elevated, and the GSH concentration was increased markedly. Furthermore, better preservation of SOD activity was observed at the end of the reperfusion. Meanwhile, in GIII GSH was significantly increased, indicating the activation of the endogenous antioxidant protective system (control: 382.13 +/- 24.22 micromol/L per gram; reperfused: 515.25 +/- 26.36 micromol/L per gram; P <.05). Moreover, SOD surpassed the control activity. Our findings confirmed that both forms of preconditioning mitigate the severity of oxidative stress prior to preservation and autotransplantation. Delayed preconditioning is more effective to protect bowel tissue against oxidative injury.

[Monitoring of oxidative stress after experimental small bowel autotransplantation]. / Az oxidatív stressz monitorozása kísérletesen létrehozott vékonybél autotranszplantációt követóen.

The difficulty at transplanting the small bowel mainly is caused by the biology of the intestine. It is highly immunogenic, is one of the most sensitive tissues to ischemia-reperfusion injury. Our aims were to investigate changes of oxygen free radical mediated reactions after autotransplantation at different preservation times and perfusion fluids. Our results prove that this model is feasible to examine ischemia-reperfusion injury in the small intestine. Euro Collins (EC) is a suitable preserving solution for small bowel transplantation. There was no significant lipid peroxidation within the first 6 hours of graft preservation. However superoxide dismutase (SOD) activity was dramatically reduced during reperfusion in the tissues samples. Significant increase of reduced glutathione at the same time can be explained by compensatory mechanism to neutralize increased free radical production.

Liver and pancreas transplantation in Europe--and in Hungary.

Liver transplantation (LT) is the sole treatment modality of most of diffuse liver diseases. Simultaneous-pancreas-kidney (SPK) transplantation is also a life saving operation for IDDM patients. Both procedures are established treatment options in the European Community (EC) and in the US. These procedures are performed in a significantly smaller number in Hungary. Having a larger demand for LT than the supply of cadaver donors alternative solutions are sought to increase the number of transplantable livers. In Hungary partly the shortage of donors and the shortage of recipients are the factors rendering the number of LTs and SPKs low. These factors can be changed by better organisation and good survival data that make the two procedures accepted by the community of physicians.

[Aorto-bifemoral bypass through retroperitoneal "mini"-incision (preliminary report)]. / Aorto-bifemoralis bypass mtét retroperitoneális "mini" feltárásból (Elözetes közlemény).

The large vertical midline or transverse transperitoneal approaches used to the conventional aortoiliac reconstruction are accompanied with a relatively high postoperative morbidity and mortality rate (2% to 5%) even in patients who are good risks undergoing aortic surgery. The purpose of this study was develop a new technique for aorto-bifemoral bypass operation to minimize the operative stress on these patients. The recommended left paramedian retroperitoneal approach using 5-6 cm skin-incision and a special retractor with three dimensional vision and using modified surgical instruments directly with eye control, offers the possibility to decrease the operative stress significantly and the sufficient control of the serious bleeding might occur. If it is necessary this exposure can be immediately converted to a conventional approach by simply enlargement of the incision. In our first case the functional results were very good and consequently hospitalization time and the convalescence period were short. This minimal access approach appears to diminish the catabolic response and is hopefully associated with accelerated recovery and virtual abolition of large wound-related complications. It could become the procedure of choice for selected patients with obstructive or aneurysmal aorto-iliac disease.

[Characteristics of cellular infiltration in rejected renal grafts]. / A sejtes infiltráció jellemzése a kilöködö vesetransplantatumban.

The composition of the cellular infiltrate in 42 needle and wedge biopsies of transplanted kidneys was investigated immunohistochemically. The various inflammatory cell populations were examined in different rejection types and cyclosporin-A nephrotoxicity (CsAN) as well as in different locations in the graft (perivascular and intertubular area, tubular epithelium, glomeruli) separately. There was generally a Th cell predominance except the most unfavorable rejection type, the acute vascular rejection (AVR), where the Tc cells outnumbered all other infiltrating cell populations. The most macrophages too were detected in AVR. The high proportion of plasma cells in chronic rejection indicate an important role of the humoral immune response in this type of rejection, and could also be used as a differential diagnostic sign versus CsAN.

[Significance of plasma cells in the rejection of kidney grafts]. / A plasmasejtek jelentösége vesetranszplantátumok kilöködésében.

Authors studied with immunohistochemical methods the immunoglobulin content of plasma cells during the rejection of renal grafts, in different rejections, in Cyclosporin-A nephro-toxicity and in chronic interstitial nephritis, as a comparison. By far the most plasma cells occurred in chronic rejection, containing more than 80% IgG. Whereas great majority of plasma cells were IgG positive in chronic interstitial nephritis. Probably, in chronic rejection a special, secondary type humoral immune reaction has a significant role in addition to cellular immune mechanisms.

[Accurate detection of hemangioma of the liver by SPECT]. / Májhaemangioma specifikus kimutatása SPECT-tel.

The hemangioma cavernosum is a frequent, benign tumor of the liver. Generally the hemangioma becomes suspected during the US examination as a secondary result. From the point of view of the differential diagnostics the three-phase blood-pool scintigraphy, a new very sensitive isotope diagnostic method, has a great importance in these cases. The images taken at the beginning, the early and the late-phase show the kind of alteration unambiguously. Since the conventional planar scintigraphy is not always able to detect the small (1-2 cm in diameter) lesions and the lesions surrounded by intact parenchyma, the SPECT has big advantage increasing the resolution of images and introducing the three-dimensional imaging. The authors illustrate the possibility of specific detection of liver hemangioma in a case by SPECT.