Severity of acute pancreatitis: a multivariate analysis of oxidative stress markers and modified Glasgow criteria.

BACKGROUND: It is unknown whether measurement of markers of oxidative stress can improve the prediction of severity of acute pancreatitis. METHODS: Consecutive patients admitted with a diagnosis of acute pancreatitis were divided into mild (n = 62) and severe (n = 23) groups based on the Atlanta classification. Plasma oxidative stress markers were measured within 24 h of admission and included ascorbic acid (endogenous antioxidant), protein carbonyl (a marker of protein oxidation), thiobarbituric acid reactive substances (a marker of lipid peroxidation) and myeloperoxidase (a neutrophil enzyme that produces oxidants). Canonical correlation analysis was used to describe the relationship between these markers and the modified Glasgow criteria. Canonical variate analysis was used to define the best variables that could discriminate mild and severe pancreatitis. RESULTS: There was a significant correlation between markers of oxidative stress and the modified Glasgow criteria (first canonical correlation 0.69, P < 0.0001, Wilk's lambda test). Blood urea, serum albumin and white cell count were the best variables that discriminated mild and severe acute pancreatitis, and all were better than the oxidative stress markers. CONCLUSION: The markers of oxidative stress were highly correlated with the severity of pancreatitis. They are unlikely to be better than the modified Glasgow criteria in predicting it.

Early ascorbic acid depletion is related to the severity of acute pancreatitis.

BACKGROUND: Ascorbic acid (AA) is an important endogenous antioxidant in plasma and has been shown to be decreased at the time of hospital admission in patients with acute pancreatitis. The aim of this study was to determine whether plasma AA concentration continues to decrease after admission and whether the extent of decrease is related to the severity of pancreatitis. METHODS: Consecutive patients with mild (n = 62) and severe (n = 23) acute pancreatitis had plasma AA concentration measured on the day of recruitment and on days 2 and 5 by high-performance liquid chromatography. RESULTS: The plasma AA concentration in patients with acute pancreatitis was significantly less than that in normal volunteers on days 0, 2 and 5 (P < 0.0001) and this was more marked in those with severe disease. There was a decrease in plasma AA concentration from day 0 to day 2 in patients with mild (P < 0.0001) and severe (P = 0.0005) pancreatitis, and from day 2 to day 5 in patients with severe pancreatitis (P = 0.023). CONCLUSION: Endogenous plasma AA continues to decrease over the first 5 days in hospital and the extent is related to the severity of acute pancreatitis. Presented to a meeting of the Australasian Surgical Research Society, Auckland, New Zealand, August 1995 and published in abstract form as Aust N Z J Surg 1996; 66: 243

Plasma von Willebrand factor and intestinal ischaemia-reperfusion injury in rats.

The purpose of this study was to determine whether plasma von Willebrand factor concentrations are correlated with the degree of intestinal ischaemia-reperfusion injury. Forty-six anaesthetised adult Wistar rats were divided into five groups. The sham-operated group (S, n=10) had laparotomy and isolation of the superior mesenteric artery without clamping. Three ischaemia-reperfusion groups (n=10 in each) had clamping of the superior mesenteric artery for 15, 30, and 45 minutes, respectively, and reperfusion for 15 minutes. A control group (C, n=6) had direct puncture of the heart to sample blood. Mean arterial pressure was measured continuously. Blood was collected at the end of the study to measure von Willebrand factor. The small bowel injury was graded histologically. There was a significant systemic hypotension after declamping in all ischaemia-reperfusion groups, which had a high negative correlation with the histological score (R=-0.46, F=10.1, p<0.003, simple linear regression). Plasma von Willebrand factor was significantly elevated in the three ischaemia-reperfusion groups compared with the control group but not significantly different from the sham-operated group (mean von Willebrand factor concentration (SEM): 156 (29), 283 (29), 295 (25), 381 (44), and 366 (40)% in C, S, ischaemia-reperfusion 15, ischaemia-reperfusion 30, and ischaemia-reperfusion 45 groups, respectively). The concentration of von Willebrand factor was not correlated to the histological score (R=0.22, F=1.83, p<0.2) or the degree of hypotension after the removal of the clamp (R=-0.22, F=1.8, p<0.2, simple linear regression). This study shows that von Willebrand factor concentration does not correlate with the degree of intestinal ischaemia-reperfusion injury. It is unlikely that von Willebrand factor can be used as a predictor of disease severity.

Small bowel ischaemia-reperfusion increases plasma concentrations of oxidised proteins in rats.

OBJECTIVES: To find out whether plasma concentrations of protein carbonyl (a specific marker of oxidative damage of proteins) are increased during intestinal ischaemia-reperfusion and whether they are correlated with von Willebrand's factor (vWF, a marker of endothelial injury) or myeloperoxidase (a marker of neutrophil activation). DESIGN: Randomised experimental study. SETTING: University department of surgery, New Zealand. ANIMALS: Thirty anaesthetised adult Wistar rats. INTERVENTIONS: The sham operated group (n = 10) had laparotomy and isolation of the superior mesenteric artery without clamping. The ischaemia-reperfusion group (IR, n = 10) had the superior mesenteric artery clamped for 1 hour and reperfusion for 15 minutes. The control group (n = 10) had direct puncture of the heart to sample blood. MAIN OUTCOME MEASURES: Plasma concentrations of protein carbonyl, vWF, and myeloperoxidase. RESULTS: Plasma protein carbonyl concentrations were significantly higher in the IR group than in the sham group (p < 0.02, Mann-Whitney test, median (range) 0.187 (0.141-0.242) compared with 0.144 (0.121-0.185) nmol/mg) and in the control group (p < 0.01, Mann-Whitney test, median (range) 0.187 (0.141-0.242) compared with 0.136 (0.108-0.175) nmol/mg). There was a significant correlation between protein carbonyl and vWF concentrations (r = 0.54, F = 10.9, p < 0.003, linear regression) but not with those of myeloperoxidase. CONCLUSION: Intestinal ischaemia-reperfusion caused an increase in the plasma protein carbonyl concentration, which is possibly produced by endothelial cells.

Anti-inflammatory cytokine response and clinical outcome in acute pancreatitis.

OBJECTIVE: To test the hypothesis that elevated interleukin (IL)-10 plasma concentration relative to IL-6 and IL-8 in patients with acute pancreatitis is associated with improved clinical outcome. DESIGN: Case series. SETTING: University hospital surgical and intensive care unit. PATIENTS: Patients with mild (n = 18) and severe (n = 14) acute pancreatitis were recruited within 12 hrs of admission and studied for 5 days. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The plasma concentration of IL-10 was significantly elevated in patients with severe pancreatitis during the 5 days and especially so in those who died compared with survivors on day 5 (p <.03). The ratio of IL-10/IL-6 was decreased in patients with severe pancreatitis on day 5 (p < .01). There was a significant decrease in the ratio of IL-10/IL-8, but not of IL-10/IL-6, during the first 5 days (p < .014). CONCLUSIONS: The findings are consistent with the hypothesis that an increase in plasma IL-10 relative to IL-6 or IL-8 is associated with improved clinical outcome.

Intestinal ischaemia-reperfusion increases plasma amylin concentration in rats.

Intestinal ischaemia-reperfusion and hyperamylinaemia are both associated with severe acute pancreatitis. The aim of this study was to examine the relationship between intestinal-ischaemia reperfusion and plasma amylin in an experimental model. Wistar rats (n = 24, 400-450 g) were divided into three groups: (1) a sham (S)-operated group (n = 7) that underwent laparotomy and isolation (without clamping) of the superior mesenteric artery, (2) an ischaemia-reperfusion (IR) group (n = 7) that had clamping of the superior mesenteric artery for 60 min followed by 15 min reperfusion, and (3) a control (C) group (n = 10) that underwent no surgery. Amylin was significantly elevated in the IR group (median 39 pM, range 30-44) compared with the S group (19 pM, range 15-45; Mann-Whitney U, p < 0.05) and the C group (24 pM, range 15-55; p < 0. 01). Insulin was significantly elevated in the IR group (2,060 pM, range 1,000-4,650) compared with the S group (558 pM, range 424-2, 020; p < 0.01). There was a significant positive correlation between amylin and insulin (R = 0.82, F = 46.6, p < 0.0001), but not between amylin and glucose or insulin and glucose. Intestinal histology was consistent with an ischaemia-reperfusion injury, whereas pancreatic histology was normal. The unique finding that plasma amylin concentration is increased with intestinal ischaemia-reperfusion injury warrants further investigation.

Manganese superoxide dismutase: a marker of ischemia-reperfusion injury in acute pancreatitis?

Recent evidence has suggested that ischemia-reperfusion injury is fundamental to the pathogenesis of acute pancreatitis. This study was designed to determine whether acute pancreatitis is associated with elevated serum manganese superoxide dismutase (MnSOD), a key antioxidant enzyme, considered a marker of ischemia-reperfusion injury in myocardial infarction. Thirty-four patients with acute pancreatitis had measurements of MnSOD on days 0, 2, and 5 after recruitment. The patients were recruited within 12 h of admission to hospital and had measurements of MnSOD on days 0, 2, and 5. Patients with severe acute pancreatitis had significantly elevated serum MnSOD concentrations on days 2 and 5 compared with patients with mild acute pancreatitis, but not on the day of recruitment. Elevated serum MnSOD correlated with peripheral plasma markers of lipid peroxidation (malondialdehyde) and neutrophil activation (myeloperoxidase) and was associated with decreased plasma ascorbic acid concentrations. The serial measurement of serum MnSOD may prove useful as a marker of the effectiveness of treatment designed to limit ischemia-reperfusion injury in patients with severe acute pancreatitis.

Splanchnic mucosal ischemia: an unrecognized consequence of routine pneumoperitoneum.

The hemodynamic consequences of a pneumoperitoneum are well understood, but there have been no studies investigating its impact on splanchnic mucosal perfusion. By use of nasogastric tonometry, this study demonstrates that fit patients undergoing elective laparoscopic cholecystectomy at normal pneumoperitoneum pressures (12-15 mm Hg) develop significant splanchnic mucosal ischemia. This is a particular concern in patients with preexistent peripheral vascular disease undergoing prolonged laparoscopic procedures.

Gastric intramucosal pH predicts death in severe acute pancreatitis.

BACKGROUND: This study tested the hypothesis that gastric intramucosal pH (pHi) can predict death in severe acute pancreatitis. METHODS: Seventeen consecutive patients with predicted severe acute pancreatitis were studied prospectively. Four died from complications related to pancreatitis. Gastric pHi was measured by nasogastric tonometry at least every 12 h for the first 48 h after admission and then on a daily basis during the first week. RESULTS: The lowest pHi recorded during the first 48 h was significantly less in those admitted to the intensive care unit than that in those who remained on the surgical ward (P = 0.0015) and in nonsurvivors compared with the survivors (P = 0.009). A receiver-operator characteristic curve defined a pHi of 7.25 as the optimal cut-off point to predict death (sensitivity 100 per cent, specificity 77 per cent, overall predictive value 82 per cent). CONCLUSION: These results suggest that splanchnic ischaemia may be an important determinant of outcome in patients with severe acute pancreatitis.

Regulation of apoptosis induced by transforming growth factor-beta1 in nontumorigenic rat prostatic epithelial cell lines.

Transforming growth factor-beta1 (TGF-beta1), which is induced in the prostate following castration, has been speculated to mediate apoptosis of epithelial cells during prostatic involution. Here, we report the first evidence of a direct effect of TGF-beta on induction of apoptosis in prostatic epithelial cells in vitro, using NRP-152 nontumorigenic and NRP-154 tumorigenic rat prostatic epithelial cell lines. TGF-beta1 induces apoptosis of both cell lines within 24 h, as shown by a decrease in cell viability, in situ DNA nick-end labeling, and internucleosomal DNA fragmentation. Moreover, the ability of TGF-beta to induce apoptosis of NRP-152 is strictly dependent on culture conditions, because dexamethasone enhances while insulin and insulin-like growth factor-I specifically block apoptosis induced by TGF-beta. We suggest that TGF-betas are direct physiological regulators of apoptosis of prostatic epithelial cells.