Intercellular adhesion molecular-1, Fas, and Fas ligand as diagnostic biomarkers for acute allograft rejection of pancreaticoduodenal transplantation in pigs.

BACKGROUND: The early diagnosis of pancreas allograft dysfunction is crucial for the management and long-term survival of transplanted pancreases. We investigated whether intercellular adhesion molecular-1 (ICAM-1), Fas, and Fas ligand (FasL) can be used as novel biomarkers of acute pancreaticoduodenal allograft dysfunction in pigs. METHODS: Forty outbred landraces were randomly divided into three groups. In the control group (8 pigs), a sham operation was performed but no drugs were administered. In groups 1 and 2 (8 pairs each), pancreaticoduodenal transplantation was performed, with the latter administered immunosuppressive drugs and the former not administered drugs. The expression of ICAM-1, Fas, and FasL mRNA in the peripheral vein blood was assessed by flow cytometry and RT-PCR, pre-transplant and on days 1, 3, 5, and 7 after transplantation. Simultaneously, the levels of glucose, insulin, and glucagon in the serum of the recipients were evaluated. The allograft pancreas tissue was obtained to assess the pathological damage and the expression of Fas and FasL by immunohistochemistry. RESULTS: On the first 7 days after transplantation, ICAM-1, Fas, and FasL mRNA expression in the blood leukocytes of the recipient increased significantly in groups 1 and 2 compared with the control group (P < 0.01). However, the levels in group 2 were significantly lower than those in group 1 (P < 0.05). Interestingly, the FasL expression increased but the Fas expression decreased gradually in the graft pancreas tissue during the first week after transplantation in both groups 1 and 2 compared with the control group (P < 0.05). The levels of serous glucose, insulin, and glucagon in groups 1 and 2 obviously changed on day 1 after transplantation but returned to normal on day 2. The recipient's pancreas pathological sections did not exhibit any rejection changes on days 1 and 3 after transplantation but showed rejection damage on days 5 and 7. CONCLUSION: ICAM-1, Fas, and FasL were found to be sensitive biomarkers of acute pancreas allograft dysfunction after pancreaticoduodenal transplantation in pigs, and their monitoring could be used to evaluate the effectiveness of the immunosuppression therapy.

Association between gene polymorphisms of IRAK-M and the susceptibility of sepsis.

The aim of this study was to explore the association between the single-nucleotide polymorphisms of interleukin-1 receptor-associated kinase-M (IRAK-M) gene and the susceptibility of sepsis. The allele frequency and genotype distribution of IRAK-M gene polymorphisms were assessed in 118 controls and 82 sepsis patients by semiquantitative polymerase chain reaction and restriction fragment length polymorphism (RFLP) analysis. The plasma levels of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) were detected by enzyme-linked immunosorbent assay. Associations between IRAK-M polymorphisms and the susceptibility of sepsis were analyzed by Cox regression. Data were analyzed by the χ(2) test and the Student's t test, whenever appropriate. Statistical calculations were performed by using statistical package SPSS version 18.0. The genotype distribution of IRAK-M+22148 polymorphism significantly differed between the sepsis and control groups (P < 0.0001). The frequency of the G allele was remarkably more common in the sepsis group than that of the control group (P < 0.0001). However, the frequency of the A allele was significantly less common in the sepsis group than that of control group (P < 0.0001). Moreover, the plasma levels (in picograms per milliliter) of TNF-α and IL-6 in patients with G/G genotype were greatly higher than those with A/A genotype after lipopolysaccharide stimulation (P < 0.05). The genetic polymorphism of IRAK-M+22148 G>A is associated with the susceptibility of sepsis. The G/G genotype of IRAK-M increases the risk of developing sepsis, and the A/A genotype may play a protective role in the process of developing sepsis.

Pretreatment with erythropoietin reduces hepatic ischemia-reperfusion injury.

BACKGROUND: During hepatectomy, a period of ischemia and restoration of the blood supply can result in hepatic ischemia-reperfusion injury (IRI). Current research indicates that erythropoietin (EPO) has a protective effect in animal models of cerebral ischemia, myocardial infarction, and renal IRI. However there is lack of research into the role of EPO in hepatic IRI. This study aimed to explore the role of EPO in hepatic IRI and its possible mechanism of action. METHODS: Thirty male Sprague-Dawley rats were divided into three groups: (1) ten rats in the experimental group were given 1000 IU/kg EPO one day before the operation; (2) ten rats in a control group were given normal saline preoperatively as a placebo; and (3) ten rats served as a sham-operated group. Hepatic IRI was induced by occluding the hepatic arteries of the three cephalad hepatic segments and the portal vein for about 45 minutes, while in the sham-operated group only laparotomy was performed. The levels of ALT and AST were tested 24 hours pre- and post-operation. All rats were sacrificed 24 hours after the operation to assess the pathologic changes in the liver and measure the expression of heme oxygenase-1 (HO-1) through Western blotting and RT-PCR. RESULTS: Hepatic IRI was markedly mitigated in the experimental group as compared with the control group. Moreover, the expression of HO-1 at the level of both transcription and protein increased prominently (P<0.05) in the experimental group. CONCLUSION: These results demonstrate that EPO can up-regulate HO-1 in liver tissues and accordingly decrease hepatic injury through its anti-inflammatory property.

[Establishment of whole pancreaticoduodenal allotransplantation model with portal venous drainage and enteric drainage in pigs].

OBJECTIVE: To establish an porcine model of whole pancreaticoduodenal transplantation with portal venous drainage and enteric drainage for ensuring physiologically normal function without hyperinsulinemia and reducing postoperative complications. METHODS: Twenty sichuan native outbreding white pigs weighing 25-30 kg were divided equally into two groups to serve as the donors and recipients. Cooling of the grafts was accomplished with in situ flush with 4 degrees C UW preservation solution via an aortic cannula. A whole pancreatoduodenal graft with the segment of abdominal aorta and the portal vein was harvested from the donor pigs. Type I diabetes model was established by complete removal of the recipient pancreas. The whole pancreatoduodenal graft was preserved and shaped in UW solution, and the subphrenic abdominal aorta of the recipient was joined with the donor abdominal aorta via a side-to-end anastomosis, and venous reflux was reconstructed between the donor portal vein and the recipient superior mesenteric vein. Side-to-side intestinal anastomosis was performed between the donor duodenum and the recipient jejunum. RESULTS: Ten pancreaticoduodenal transplantations (PVE+ED style) were done, and pancreatic graft thrombosis and embolism occurred only in 1 pig 6 days after transplantation. CONCLUSION: The model of whole pancreaticoduodenal transplantation with portal venous drainage and enteric drainage is stable and reliable.