International Journal of Pancreatology

The effect of complete Freund’s adjuvant (CFA), in combination with streptozotocin (STZ), on pancreatic insulin content, plasma glucose, and pancreatic histopathology were studied in male Balb/c mice. One injection of CFA, followed 24 h later by a single dose of 100 mg/kg of STZ (group I), produced a 92% (p<0.01) reduction in pancreatic insulin, a 54% (p<0.01) increase in glucagon content, and severe hyperglycemia. The depletion of pancreatic insulin was associated with degranulation, necrosis of beta cells, and reduction of the apparent islet size. Focal pancreatitis, without apparent islet inflammation, occurred in all animals in this group. After treatment with STZ alone (group II), pancreatic insulin content decreased 73% (p<0.01), whereas plasma glucose levels, even though being in the hyperglycemic range, were significantly lower (p<0.02) than the mice in group I. Although pyknotic and hypertrophic cell nuclei could be observed in several islets of mice from group II, major histopathological changes, such as pancreatitis and extensive beta cell necrosis seen in group I, were absent. The results show that in the Balb/c mouse strain, a nonspecific insult by CFA prior to a cell-specific cytotoxic insult markedly enhanced destruction of beta cells and the development of hyperglycemia.

Superoxide dismutase (SOD) is a free-radical scavenger present in B cells. It is thought to be responsible for protection against the autoimmune processes that characterize type I diabetes mellitus. Streptozocin (STZ) has been used as a low-dose treatment (LDS) to induce diabetes in animal models. The aim of this study was to follow the islet SOD levels in a day-to-day study after an LDS treatment with STZ, 40 mg/kg body wt/d in C57BL6/J mice. Results reveal a progressive SOD decrease in pancreatic islets with increasing periods from the LDS treatment. This SOD decrease starts from the end of the STZ administration (d 5). In addition, it was noticed that glycemia starts to rise when SOD values have already reached their lowest levels. This indicates that a reduction of free-radical defense is a prerequisite for further cellular injuries. Furthermore, a difference was noticed between males and females: only 40% of female mice underwent a SOD decrement and an increase in glycemia, indicating an androgendependent mechanism.

The aim of the present study was to determine the role of endogenous nitric oxide (NO) in pancreatic secretion in vivo and amylase release from pancreatic acini in vitro and in caerulein-induced acute pancreatitis in rats. Blockade of NO synthase byN G-nitro-L-arginine (L-NNA) (2.5 mg/kg iv) significantly reduced basal pancreatic protein secretion and that induced by the infusion of CCK (0.5 μg/kg-h), feeding, and the diversion of pancreatic juice in rats with pancreatic fistula. This inhibitory effect was partially reversed when L-arginine (50 mg/kg-h iv) was added to L-NNA. L-Arginine alone (50 mg/kg iv) did not affect basal or caerulein-induced pancreatic secretion. L-NNA, L-arginine, or their combination added in various concentrations to the incubation medium of dispersed acini failed to affect basal or secretagogue (caerulein or urecholine) stimulated amylase release. Infusion of caerulein (5 μg/kg-h) for 5 h produced histological changes of acute edematous pancreatitis accompanied by a marked increase in pancreatic protein content and about 50% reduction in tissue blood flow. L-NNA alone also reduced the pancreatic blood flow and caused a significant increase in pancreatic weight and protein content. L-NNA significantly potentiated the inflammatory changes in the pancreas caused by caerulein. Addition of L-arginine enhanced the pancreatic blood flow and ameliorated the pancreatitis induced by caerulein alone or that combined with L-NNA. We conclude that NO is involved in the stimulation of pancreatic secretion in vivo and exhibits a beneficial effect on pancreatitis, probably by improving the pancreatic blood flow.

These results provide morphological evidence for an alcohol-induced selective intrapancreatic nerve degeneration. This affected mainly the nerve fibers that are inhibitory of the exocrine pancreas, and might represent the morphological background of hypersectory state of the pancreas in chronic alcoholism. Intrapancreatic intrinsic nerves were studied by immunohistochemistry and electron microscopy after 4 mo of alcohol consumption and compared with control mice. A dense entwork of nerve fibers was observed in the normal mouse pancreas around the blood vessels and ending on the exocrine cells. The presence of VIP, NPY, PP, SP, and serotonin in these nerves was demonstrated by immunohistochemistry. Four months of alcohol consumption did, not result in apparent morphological, changes of the pancreas. However, the majority of periacinar nerve terminals showed degenerative changes. Synaptic vesicles were diminished in number in some other nerve processes, whereas the perivascular nerve fibers were relatively well preserved. A slight decrease was found in the intensity of VIP and SP immunoreactivity, and the PP fibers almost disappeared.

Lymphogenous as well as hematogenous metastases were significantly less frequent in the elderly group of patients, although local invasion was comparable. Survival was comparable between both groups although palliative therapy alone was significantly more frequent in the elderly. The relative and absolute numbers of elderly patients continue to increase, as does the incidence of pancreatic carcinoma. To determine the optimal therapy for elderly patients with pancreatic carcinoma, we examined their clinicopathological features. The clinical and histopathological features of pancreatic carcinoma in patients 70 yr of age or older (n=89) were compared with those in patients aged 69 yr or less (n=184). A total of 273 patients showed histologically tubular adenocarcinomas and their major variants. The male: female ratio peaked at 1∶0.3 in patients under 49 yr old but gradually decreased to 1∶1.2 in those aged over 80 yr. There were no significant differences between the two groups in the resectability, prognosis, location, or histology of the tumor. Hematogenous and lymphogeneous metastases were detected at autopsy in 68 and 61% of patients older than 70, and in 82 and 80% of the younger group.