High-mobility group box protein-1 seems to act as a late cytokine mediator in the pathogenesis of severe acute pancreatitis. Pyrrolidine dithiocarbamate might inhibit the activation of nuclear factor-kappaB to blockade tumor necrosis factor-alpha, thereby indirectly suppressing the high-mobility group box protein-1 and reducing pancreatic tissue damage in rats with severe acute pancreatitis.

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AimTo investigate the therapeutic effects of fluorouracil (5-Fu) and octreotide (Oct) continuous regional arterial infusion (CRAI,) alone or in combination, was administered in a canine model of severe acute pancreatitis (SAP).Materials and MethodsThe animals were divided into five groups; group A (Sham), group B (SAP), group C (SAP and 5-Fu), group D (SAP and Oct), and group E (SAP and 5-Fu + Oct). Levels of amylase, α-tumor necrosis factor (TNF-α), blood urea nitrogen (BUN), creatinine, thromboxane B2 and 6-keto- prostaglandin F1α were measured both before and after the induction of SAP. Pathologic examination of the pancreas and kidneys was performed after termination of the study.ResultsPathologic changes noted in the pancreas in SAP significantly improved following CRAI with either single or combined administration of 5-Fu and Oct, where combination therapy demonstrated the lowest injury score. All treatment groups had significantly lower levels of serum TNF-α and amylase activity (P<0.05), though only groups D and E had a lower BUN level as compared to group B. The plasma thromboxane B2 level increased in SAP, but the ratio of thromboxane B2/6-keto- prostaglandin F1α decreased in the treatment groups, with the combination therapy (group E) demonstrating the lowest ratio as compared to the other 3 experimental groups (P<0.05).ConclusionsThe findings in the present study demonstrate an attenuation of SAP in a canine model following CRAI administration with 5-Fu or Oct, alone or in combination.

Aim: To investigate the therapeutic effects of fluorouracil (5-Fu) and octreotide (Oct) continuous regional arterial infusion (CRAI,) alone or in combination, was administered in a canine model of severe acute pancreatitis (SAP). Materials and Methods:The animals were divided into five groups; group A (Sham), group B (SAP), group C (SAP and 5-Fu), group D (SAP and Oct), and group E (SAP and 5-Fu + Oct). Levels of amylase, a-tumor necrosis factor (TNF-a), blood urea nitrogen (BUN), creatinine, thromboxane B2 and 6-keto-prostaglandin F1a were measured both before and after the induction of SAP. Pathologic examination of the pancreas and kidneys was performed after termination of the study.Results: Pathologic changes noted in the pancreas in SAP significantly improved following CRAI with either single or combined administration of 5-Fu and Oct, where combination therapy demonstrated the lowest injury score. All treatment groups had significantly lower levels of serum TNF-a and amylase activity (P,0.05), though only groups D and E had a lower BUN level as compared to group B. The plasma thromboxane B 2 level increased in SAP, but the ratio of thromboxane B 2 /6keto-prostaglandin F 1a decreased in the treatment groups, with the combination therapy (group E) demonstrating the lowest ratio as compared to the other 3 experimental groups (P,0.05). Conclusions:The findings in the present study demonstrate an attenuation of SAP in a canine model following CRAI administration with 5-Fu or Oct, alone or in combination.