Graft Protection Against Cold Ischemia Preservation: An Institute George Lopez 1 and Histidine-tryptophan-ketoglutarate Solution Appraisal.

Cold storage of organs in preservation solutions, such as Institute George Lopez 1 (IGL-1) or histidine-tryptophan-ketoglutarate (HTK), is a mandatory step for organ transplantation. This preservation leads to an ischemic injury that affects the outcome of the organ. This article studies the liver graft eluate after organ recovery using IGL-1 or HTK solutions. We explore the influence of the volume used for washing out the liver and the consequences in the graft preservation when both solutions are used. Livers were washed out with different volumes of HTK and IGL-1 according to manufacturers' instructions and then preserved in both solutions for 24 hours at 4°C. Tissue and eluates were collected for subsequent analyses. We measured transaminases (aspartate aminotransferase and alanine aminotransferase), histology by hematoxylin/eosin staining, and red blood cell and hemoglobin counts, respectively. After washing out and cold storage, the IGL-1 processed livers showed better preservation than those with HTK solution; however, in this latter case, an important accumulation of erythrocytes was found when compared to IGL-1. These data were consistent with the higher hemoglobin and red blood cell counts observed for IGL-1 eluates after 24 hours. The volume used for washing out the organ depends on the composition and properties of the organ preservation solutions (ie, IGL-1 and HTK); this is an important factor for the graft cold preservation. The total volume used for washing out the graft should be considered because it has a direct impact on the total cost for clinical transplantations.

PAP1 signaling involves MAPK signal transduction.

Pancreatitis-associated protein 1 (PAP1) belongs to the Reg family of secretory proteins. Several important biological roles have been attributed to PAP1 but the signaling pathways activated by this protein remain only partially understood. Here, we describe the intracellular pathways triggered by PAP1 in a pancreatic acinar cell line. Taking advantage of the fact that PAP1 induces its own transcription, we performed ChIP assays to analyze the recruitment of transcriptional factors on its promoter. Our results show that PAP1 increased the transactivation activity of pap1 and the binding on its promoter of the nuclear factors C/EBPbeta, P-CREB, P-ELK1, EGR1, STAT3, and ETS2, which are downstream targets of MAPK signaling. p44/42, p38, and JNK MAPKs activity increased after PAP1 treatment. In addition, pharmacological inhibition of these kinases markedly inhibited the induction of pap1 mRNA. Taken together, these results indicated that the mechanism of PAP1 action involves the activation of the MAPK superfamily.

Oxidised lipids present in ascitic fluid interfere with the regulation of the macrophages during acute pancreatitis, promoting an exacerbation of the inflammatory response.

BACKGROUND: Pancreatitis-associated ascitic fluid (PAAF) plays a critical role in the pathogenesis of acute pancreatitis. Taking into consideration that damaged pancreas exudes high concentrations of lipolytic enzymes in the peritoneal cavity, large amounts of lipid metabolism derived products could occur in PAAF. In this study, we have examined the involvement of the lipid fraction of PAAF generated in the early stages of experimental acute pancreatitis. METHODS: Pancreatitis was induced in rats by intraductal administration of 5% sodium taurocholate. After 3 h, PAAF was collected and its lipid fraction was obtained. Lipid composition and levels of lipid peroxidation were measured. Toxicity was evaluated by measuring the effects of the PAAF lipid fraction on cell viability of hepatic and macrophage cell lines. In vivo effects on the liver were also evaluated. Effects on the inflammatory response were determined by measuring the levels of nuclear factor kappa B (NF kappa B) activation, the effect on the inhibitory activity of 15-deoxy-PGJ(2) and the possible interference on PPAR gamma activation. RESULTS: High concentrations of oxidised free fatty acids were detected in PAAF. Besides the direct cell toxicity, the PAAF-derived lipid extract interfered with the anti-inflammatory pathway mediated by PPAR gamma. Addition of this lipid extract to macrophage cell cultures had no direct effect on the activation of NF kappa B, but abolished the inhibitory activity of endogenous PPAR gamma agonists such as 15-deoxy-PGJ(2). CONCLUSIONS: Oxidised free fatty acids present in PAAF interfere with the endogenous regulatory mechanism of the inflammatory response, thus promoting an exacerbation of macrophage activation in acute pancreatitis.

Importance of the liver in systemic complications associated with acute pancreatitis: the role of Kupffer cells.

Although its exact nature is still unknown, acute pancreatitis progresses with a local production of inflammatory mediators, eventually leading to systemic inflammatory response syndrome. Knowing that almost all pancreatic mediators released from the pancreas to the bloodstream may pass through the liver before their dilution in the systemic circulation, it would be reasonable to assume a determinant role for this organ in the development of the inflammatory response associated with acute pancreatitis. Thus, recent studies have shown the involvement of the liver in the complex network of events triggering the multiorgan dysfunction associated with the disease. Once pancreatic mediators reach the liver, they strongly activate Kupffer cells, the resident macrophages, greatly amplifying the release of cytokines into the bloodstream and thus contributing to the systemic manifestations of acute pancreatitis. Altogether, these results show that the pancreas is not the only source of mediators that trigger the deleterious effects of acute pancreatitis, but that the liver may orchestrate the final outcome of the disease. The purpose of this review is to discuss progress in understanding the function of the liver in the early stages of the development of systemic organ dysfunction secondary to acute pancreatitis.