Healing effect of warfarin in the course of cerulein-induced acute pancreatitis in rats.

Acute pancreatitis (AP) is the most common gastrointestinal disease leading to hospitalizations and unexpected deaths. The development of AP leads to damage of the pancreatic microcirculation with a cascade of subsequent events resulting, among others, in coagulopathy. Previous research showed that anticoagulants can be important therapeutic agents. Heparin and acenocoumarol can alleviate the course of AP, as well as accelerate healing and post-inflammatory regeneration of the pancreas. The aim of this study was to determine whether warfarin, a drug with more stable effects than acenocoumarol, affects the healing and regeneration of the pancreas in the cerulein-induced AP. AP was evoked in Wistar male rats by intraperitoneal administration of cerulein. The first dose of warfarin (45, 90 or 180 µg/kg) was administered 24 hours after the first dose of cerulein and the doses of warfarin were repeated once a day in subsequent 10 days. The severity of AP was assessed immediately after the last dose of cerulein, as well as at days 1, 2, 3, 5, and 10 after AP induction. Treatment with warfarin dose-dependently increased international normalized ratio (INR) and attenuated the severity of pancreatitis in histological examination and accelerated pancreatic recovery. These effects were accompanied with a faster reduction in the AP-evoked increase in serum activity of amylase and lipase, the serum concentration of pro-inflammatory interleukin-1ß, and the plasma level of D-Dimer. In addition, treatment with warfarin decreased pancreatic weight (an index of pancreatic edema) and improved pancreatic blood flow in rats with AP. The therapeutic effect was particularly pronounced after the administration of warfarin at a dose of 90 µg/kg. We conclude that treatment with warfarin accelerated regeneration of the pancreas and recovery in the course of cerulein-induced mild-edematous acute pancreatitis.

Markers of Antioxidant Defense in Patients with Type 2 Diabetes.

AIMS: Diabetes is considered a state of increased oxidative stress. This study evaluates blood concentrations of selected markers of antioxidant defense in patients with type 2 diabetes. METHODS: The study included 80 type 2 diabetes patients and 79 apparently healthy controls. Measured markers included ferric reducing ability of plasma (FRAP), reduced glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GR), γ-glutamyltransferase (GGT) and uric acid serum, and plasma and/or hemolysate levels. RESULTS: FRAP, uric acid, CRP, and GGT levels were significantly higher in patients with diabetes. Plasma and hemolysate GR was significantly higher whereas GPx activity was significantly lower in patients with diabetes. There were no significant differences in antioxidant defense markers between patients with and without chronic diabetes complications. Fasting serum glucose correlated with plasma GPx, plasma and hemolysate GR, FRAP, and serum GGT, and HbA1c correlated with serum GGT. Only FRAP and serum uric acid were significantly higher in obese (BMI > 30 kg/m(2)) patients with diabetes than in nonobese patients. CONCLUSIONS: Some components of antioxidant defense such as GR, uric acid, and GGT are increased in patients with type 2 diabetes. However, the whole system cannot compensate for an enhanced production of ROS as reflected by the trend toward decreased erythrocytes GSH.

Correlation of peripheral blood monocyte and neutrophil direct counts with plasma inflammatory cytokines and TNF-alpha soluble receptors in the initial phase of acute pancreatitis.

MATERIAL: The relationship between direct count of peripheral blood leucocyte populations and plasma concentrations of IL-6, IL-8, sTNFR-55 and sTNFR-75 during five initial days of acute pancreatitis was studied. RESULTS: Most significant relationship was found for monocytes, which correlated with sTNFR-55 (R = 0.38, p < 0.05) and sTNFR-75 (R = 0.41, p < 0.05 and R = 0.55, p < 0.01 during 1st and 2nd day, respectively). Later, in days 2, 3 and 4 an interrelation between monocytes and IL-6 (R = 0.49 to R = 0.41, p < 0.01) was observed. Monocytes also correlated with IL-8 in days 2 and 3 (R = 0.41, p < 0.05 and R = 0.43, p < 0.01, respectively). Neutrophil count correlated with IL-6 in days 3 and 4 (R = 0.34, p < 0.05 and R = 0.56, p < 0.01, respectively) and with IL-8 in the 4th day only (R = 0.39, p < 0.05). No significant correlations of lymphocyte, eosinophil and basophil direct counts with cytokines and receptors during the initial 5 days of AP were found. CONCLUSIONS: Observed relationships between monocyte direct counts and plasma cytokine levels reflect monocytes involvement in the development of acute pancreatitis.