Repetitive self-limited acute pancreatitis induces pancreatic fibrogenesis in the mouse.

The role of repetitive acute injury in the pathogenesis of chronic pancreatitis remains unknown. To determine if repetitive injury induced by pancreatic hyperstimulation would reproduce the characteristic features of human chronic pancreatitis, acute reversible pancreatic injury was induced in mice by twice weekly cerulein treatment, 50 microg/kg/hr x 6 hr, for 10 weeks. Procollagen alpha1(I) mRNA was markedly increased by week 2. Sirius red staining of interstitial collagen demonstrated progressive accumulation of extracellular matrix surrounding acinar units and in interlobular spaces. Atrophy, transdifferentiation of acinar units to ductlike tubular complexes, and dilatation of intraacinar lumina also developed. Electron microscopy demonstrated the presence of stromal cells in areas of fibrosis with morphologic characteristics of pancreatic stellate cells. These findings demonstrate that, in a murine model, repetitive acute injury to the pancreas by hyperstimulation can reproduce the major morphological characteristics of human chronic pancreatitis.

Role of Mycobacterium paratuberculosis in Crohn's disease: a prospective, controlled study using polymerase chain reaction.

PURPOSE: Mycobacterium paratuberculosis has been proposed as a causative agent in patients with Crohn's disease. The purpose of this study was to determine whether M. paratuberculosis was present in tissue from patients with Crohn's disease in a defined geographic area. METHODS: We prospectively evaluated, using polymerase chain reaction and culture, whether M. paratuberculosis was present in 44 specimens (37 from intestinal mucosal biopsies and 7 from surgical resections) from patients with Crohn's disease, ulcerative colitis, or normal colonic mucosa. RESULTS: Of the 25 specimens tested from the 21 Crohn's patients, only 1 positive specimen was noted, whereas the 8 specimens from the 5 ulcerative colitis patients and the 11 specimens from the 11 control patients failed to demonstrate a positive result with polymerase chain reaction. Cultures of all specimens revealed no growth of M. paratuberculosis. CONCLUSION: M. paratuberculosis was only rarely detected in biopsy or surgical specimens from patients with Crohn's disease. These results do not support a common causative role of M. paratuberculosis in Crohn's disease.

Effect of octreotide on stimulated insulin release from pancreatic tissue slices.

This study was designed to investigate a possible mechanism of action by which octreotide acetate causes insulin suppression in the denervated pancreas. Canine tissue slices were placed in a pH-adjusted medium with varying concentrations of glucose and octreotide acetate: Experiment 1, 30 min in basal medium with 0.6 mg/ml glucose; Experiment 2, addition of 6.0 mg/ml glucose; Experiment 3, addition of 4 microg octreotide acetate/70 ml (comparable to 100 microg/25 kg body weight); Experiment 4, addition of 16 microg octreotide acetate/70 ml; Experiment 5, incubation with 6.0 mg glucose/ml and 4 microg octreotide acetate/70 ml; Experiment 6, incubation with 6.0 mg glucose/ml and 16 microg octreotide acetate/70 ml; Experiment 7, preincubation with 4 microg octreotide acetate/70 ml, then with 6.0 mg glucose/ml; and Experiment 8, preincubation with 16 microg octreotide acetate/70 ml, then with 6.0 mg glucose/ml. Medium levels of insulin, glucagon, and amylase were collected at intervals during the incubation periods. There was an appropriate increase in the rate of insulin release to glucose stimulation in the high-glucose (6.0 mg/ml) group. There was no significant inhibition of basal or glucose-stimulated insulin release with either simultaneous or pretreatment of the canine pancreatic tissue slices with either concentration of octreotide acetate. These studies support an indirect mechanism by which octreotide acetate exerts its inhibitory effect on endocrine and exocrine function in the canine pancreas transplant model.

Glutathione synthesis in the exocrine pancreas.

Glutathione is essential for cellular cytoprotection, and in the exocrine pancreas, it is required for digestive enzyme synthesis. The purpose of these studies was to measure the capacity of the exocrine pancreas to synthesize glutathione, determine whether the pancreatic transsulfuration pathway has a role in providing cysteine needed for glutathione synthesis, and determine whether the glutathione synthetic capacity of the pancreas responds to pathologically relevant stresses. The activity of gamma-glutamylcysteine synthetase, the key regulatory enzyme for glutathione synthesis, was 3.56 +/- 0.29 mU/mg protein in the pancreas of fed rats, compared to 31 +/- 4 in the liver and 116 +/- 5 in the kidney. Studies using dispersed rat pancreatic acinar cells showed that the exocrine pancreas synthesizes glutathione from precursor amino acids and that the transsulfuration pathway is functionally intact in the pancreas and may serve as an important source of pancreatic cysteine. In mice, pancreatic gamma-glutamylcysteine synthetase activity was induced 37% by corn oil, 77% by ethanol, and 88% by both treatments. Thus, the glutathione synthetic capacity of the pancreas is quantitatively less than that of the kidney or liver, but its key regulatory enzyme responds dynamically to pathologically relevant metabolic stresses, suggesting that glutathione is a key pancreatic cytoprotectant.

Presentation and management of lymphatic cyst of the colon: report of a case.

PURPOSE: We report a case of lymphatic cyst of the colon in a 43-year-old white female previously treated with chemotherapy for a B cell lymphoma. METHODS: Radiographic, endoscopic, and pathologic evaluation of the cyst is presented. Surgical resection of this lesion was undertaken because of the size of the lesion, risk of obstruction, and history of an underlying malignancy. A recent review of the literature in relation to clinical symptoms, signs, diagnosis, and treatment of lymphatic cysts is presented. CONCLUSION: Lymphatic cysts of the colon are benign submucosal lesions that are being recognized with increasing frequency. Treatment options include endoscopic polypectomy for lesions smaller than 2 cm and surgical resection for larger lesions if there is a threat of obstruction or question of an underlying colorectal malignancy.

Effect of somatostatin and octreotide acetate on OP-CCK-stimulated exocrine secretion in the denervated canine pancreas.

Somatostatin and its analogue, octreotide acetate (Sandostatin), have been demonstrated to suppress exocrine secretion in a denervated canine pancreatic autograft model. To help define this inhibitory mechanism, the effect of these agents on cholecystokinin (CCK)-stimulated acinar cell secretion was evaluated. In vitro assessment evaluated the effect of somatostatin on octapeptide (OP)-CCK-stimulated amylase release of pancreatic tissue slices. In vivo assessment employed animals with pancreatic autografts and pancreaticocystostomies, evaluating the effect of a bolus intravenous injection of 100 micrograms of octreotide acetate on the basal and OP-CCK-stimulated (125 ng/kg/h) secretion of urinary (autograft) amylase and bicarbonate. Incubation of tissue slices with 0.16, 0.24, or 0.32 microgram/ml somatostatin had no significant effect on in vitro OP-CCK-simulated amylase release. Intravenous octreotide acetate resulted in a significant decrease in the basal rate of amylase secretion but had no significant effect on OP-CCK-stimulated autograft amylase or bicarbonate release. These studies demonstrate that octreotide acetate has an in vivo inhibitory effect on basal amylase release of pancreatic autografts but cannot counteract maximal stimulation with exogenous OP-CCK. Also, somatostatin does not inhibit OP-CCK-stimulated acinar cell secretion of pancreatic tissue slices. These results indicate that the exocrine inhibition produced by somatostatin analogues in the grafted pancreas occurs via an indirect mechanism.

Effect of L-364,718 on pancreatic endocrine function following partial pancreatectomy.

This study was designed to determine the effect of a potent cholecystokinin antagonist, L-364,718, on canine pancreatic endocrine function following partial pancreatectomy. Plasma glucose, insulin, and glucagon were determined over a 2-hr interval following an intravenous bolus of 0.5 g/kg glucose in a 50% solution. The following groups were established: normal animals (group A, n = 5), normal animals pretreated with 20 nmole/kg L-364,178 (group B, n = 5), partially pancreatectomized animals (group C, n = 5), and partially pancreatectomized animals pretreated with 20 nmole/kg L-364,178 (group D, n = 5). In contrast to animals with an intact pancreas, pretreatment with L-364,718 following partial pancreatectomy resulted in a significant decrease in peak insulin (group C = 132.8 +/- 13.0 microU/ml vs Group D = 90.4 +/- 16.1 microU/ml, P < 0.05) and the basal-to-peak insulin difference (group C = 111.9 +/- 11.5 microU/ml vs group D = 77.5 +/- 16.6 microU/ml, P < 0.05). Despite this, the rate of glucose utilization (K value) was significantly increased in the partially pancreatectomized animals given the antagonist (group C = -1.22 +/- 0.22%/min vs group D = -2.79 +/- 0.427%/min) and there were no significant differences in basal or peak glucose when comparing the groups given L-364,718 with the groups given placebo (group A vs B and group C vs D). Thus, the CCK antagonist L-364,718 significantly decreases peak insulin in partially pancreatectomized animals but not in nonoperative control animals. There is a paradoxical increase in the rate of glucose utilization but no effect on glucose homeostasis. The effect of this antagonist in other models of reduced islet cell reserve (i.e., pancreas transplantation) remains to be determined.

Nafcillin-associated hepatotoxicity. Report of a case and review of the literature.

Nafcillin is a semisynthetic penicillin that is generally well tolerated with few side effects. Hepatic complications are rare but have a potential for serious liver dysfunction. This unusual complication causes a predominantly cholestatic injury, which can persist for prolonged periods even after discontinuing the medication. The pathophysiology may include direct cytotoxicity or an immune-mediate hypersensitivity. Treatment is generally supportive, except for severely symptomatic patients who may require steroids. We report a case of nafcillin-associated hepatotoxicity and review the literature of this disorder.

Receptor antagonists for gastrointestinal peptides.

Receptors for gastrointestinal peptides are all G protein-coupled receptors. Since the discovery that dibutyryl guanosine 3',5'-cyclic monophosphate was a cholecystokinin-receptor antagonist, a variety of receptor antagonists have been developed for a number of different gastrointestinal peptides. These antagonists have been useful in classifying receptors for gastrointestinal peptides and in elucidating complex regulation of gastrointestinal function. Some antagonists also have therapeutic potential. Based on the receptors with which they interact, gastrointestinal peptides can be grouped into families, and, in general, a given receptor antagonist is specific for a given family. This review covers the different families of gastrointestinal peptides and the major antagonists that exist for each family.

Hypersensitivity reactions to human seminal plasma.

A rare but serious allergic reaction has been described. Human seminal plasma hypersensitivity predominantly occurs in young women possibly as a result of altered immune status involving the reproductive organs. The patients generally have a history of atopy and, in typical cases, immunologic tests corroborate a reaginic humoral mechanism. Fortunately, there is considerable evidence that selected patients can be successfully treated with selective immunotherapy. Alternatively, the application of topical cromolyn holds promise for successful prevention of symptoms.

Comparison of glucose, LCT, and LCT plus MCT as calorie sources for parenterally nourished rats.

Protein and fat metabolism were studied in fed and protein-depleted rats. The rats were given one of three isocaloric, isonitrogenous nutrient mixes parenterally. The nutritional regimens differed in the source of nonprotein calories: i) glucose, ii) an emulsion containing long-chain fatty acid triglyceride esters (LCT), and iii) an emulsion containing both LCTs and medium-chain fatty acid triglycerides (MCT). Nitrogen balance, protein synthesis and breakdown, fat deposition in the liver, and the periuterine fat pads were measured using [15N]glycine as the tracer for the protein metabolism and deuterium for the lipid studies. Results are as follows. i) Nitrogen retention and protein synthesis were greater in the fed rats treated with glucose than with LCT. ii) Nitrogen fluxes were lower with LCT than with glucose. iii) Extensive lipogenesis in the liver was only found with the glucose-treated rats. iv) None of the caloric regimens promoted lipogenesis in the periuterine fat pads. v) With the two lipid-containing regimens there was a relative depletion of the depot fat in the periuterine fat pads relative to their glucose-treated counterparts. v) Although the MCT-containing emulsion did not cause hepatomegaly, its apparent caloric effectiveness was lower than that of either glucose or LCT. vi) Chain elongation is not a major pathway for MCT metabolism in parenterally nourished rats.