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Biomedical subjects

A L Widdison

Publications and source records attributed to A L Widdison.

At least 37 records · Page 2Linked to original sources
PubMed1993

Assay of trypsinogen activation in the cat experimental model of acute pancreatitis.

An enzyme-linked immunosorbent assay for trypsinogen activation peptide (TAP) was used to measure urinary TAP levels in standard feline models of acute oedematous pancreatitis and acute haemorrhagic pancreatitis. It has been shown that the extent of pancreatic damage as assessed histologically is significantly greater in the model of acute haemorrhagic pancreatitis. This increase in damage has been found to be associated with a significantly greater increase in the excretion of urinary TAP.

Acute Disease↗
PubMed1993

Differential effects of experimentally induced chronic pancreatitis on neuropeptide immunoreactivities in the feline pancreas.

The distribution and concentration of calcitonin gene-related peptide (CGRP), substance P (SP), vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY), and gastrin-releasing peptide (GRP) immunoreactivities in the pancreas of cats with experimentally induced chronic pancreatitis and of age- and sex-matched controls were investigated. By narrowing the main pancreatic duct between the head and the body to approximately 25% of its normal diameter, we induced within 5 weeks chronic pancreatitis restricted to the body and tail. In control animals, peptide immunoreactive nerves were distributed to the islets, acini, and ducts; the latter were predominantly innervated by fibers immunoreactive for NPY, VIP, or CGRP. The vasculature received an abundant supply of NPY-, CGRP-, and, to a lesser extent, SP-containing axons. Within intrapancreatic ganglia, peptide immunoreactivities were identified in fibers and ganglion cells, with the exception of CGRP and SP immunostaining, which could be visualized only in fibers. In animals with chronic pancreatitis, the innervation pattern of each peptidergic system was comparable to that described in controls. However, there was a remarkable increase in the density and staining intensity of VIP and NPY immunoreactive fibers in the exocrine parenchyma and fibrous septa of the body and tail, where chronic pancreatitis developed. Fibers immunoreactive for CGRP and SP also were moderately denser than in controls, whereas those containing GRP immunoreactivity did not show any detectable changes. In addition, a marked increase of the immunostaining for VIP and, to a much lesser extent, for NPY and GRP, was observed in neurites supplying the head of the pancreas, which appeared devoid of histologically detectable pathological alterations. Radioimmunoassay analysis confirmed the immunohistochemical observations. The increased density of distinct peptidergic nerves in the pancreas with induced chronic pancreatitis might be the result of compensatory phenomena in response to the inflammatory process.

Animals↗
PubMed1992

Species differences in the immunoreactive patterns of calcitonin gene-related peptide in the pancreas.

In the pancreas, calcitonin gene-related peptide (CGRP) immunoreactivity has been described in nerve fibers and in distinct types of islet cells. This unique, apparently species-specific cell-type expression prompted the present investigation to clarify further the pattern of CGRP immunoreactivity in different mammalian species (i.e., different strains of rats, mice, guinea pigs, rabbits, cats, dogs, pigs, and humans) commonly used for functional and anatomical studies of the pancreas by means of immunohistochemistry using three different CGRP antibodies. In each species, CGRP-immunoreactive neurites innervate the exocrine and endocrine compartments, the vasculature, and the intrapancreatic ganglia, where they form dense networks encircling unstained cell bodies. The only exception is the pig pancreas, where the islets appear to be devoid of immunoreactive fibers. The overall density of immunoreactive pancreatic axons in different species is as follows: rat, mouse, and rabbit greater than guinea pig greater than or equal to pig and cat much greater than dog and human. CGRP-immunoreactive endocrine cells appear to be restricted to the rat pancreas, where they form a subpopulation of somatostatin-containing D cells. In contrast, in mouse, guinea pig, cat, dog, and human pancreas, a homogeneous staining of the core of the islets, where insulin-producing B cells are located, was visualized in sections incubated with the rabbit CGRP antiserum at 4 degrees C, but not at 37 degrees C (an incubation temperature that does not affect the islet cell staining in the rat nor the fiber labeling in any species). Furthermore, the staining of islet B cells was not reproducible with all the CGRP antibodies used, all of which comparably stain nerve fibers in each species, and islet D cells in the rat. Immunoreactive islet cells were not visualized in pig and rabbit pancreas. These results are consistent with the hypothesis that the expression of CGRP in nerve fibers is a common feature of mammalian pancreas, whereas its expression in endocrine cells appears to be restricted to the D cells of the rat pancreas.

Animals↗
PubMed1992

Pancreatic ductal and interstitial pressures in cats with chronic pancreatitis.

We investigated the etiology of interstitial hypertension in chronic pancreatitis by examining the relationship between pancreatic ductal and interstitial pressures in cats. The main pancreatic duct was cannulated in the tail of the gland and perfused at 1, 2, or 5 ml/hr, to simulate pancreatic secretion. Intraductal and interstitial pressures were measured in four groups of animals: (1) normal cats; (2) normal cats after acutely narrowing the main duct to 25% of its original diameter; (3) normal cats after encasing the body and tail in a rigid latex capsule; and (4) cats with chronic pancreatitis created by narrowing the main duct five weeks earlier. Duct perfusion increased intraductal pressure in all of the cats, but significantly more in groups 2, 3, and 4 compared to group 1. Pancreatic interstitial pressure was unchanged by duct perfusion in groups 1 and 2, but increased in groups 3 and 4. We concluded that the compliant tissue of the normal pancreas expanded to effectively dissipate the increase in duct pressure associated with duct perfusion. In chronic pancreatitis, the inelastic parenchyma and capsule limited the distensibility of the gland, which resulted in elevated interstitial pressures during duct perfusion.

Animals↗
PubMed1992

Influence of levamisole on pancreatic infection in acute pancreatitis.

We investigated the effect of levamisole on pancreatic infection in a model of acute pancreatitis (AP) in cats. Animals with and without AP received Escherichia coli intravenously. Blood was then taken at intervals for culture. AP reduced phagocytic function by 28% as measured by the rate of bacterial disappearance from the blood (p less than 0.03). In other cats, AP was induced, and E. coli were placed into the pancreatic duct. Levamisole was given orally in some cats; the remainder were untreated. Control cats (neither AP nor levamisole) also received E. coli. Seven days later, pancreases from all control cats were sterile. In AP cats, the pancreatic infection rate was 73%. Levamisole reduced the rate of infection to 22% (p less than 0.03). We concluded that phagocytic function was impaired in cats with AP. Levamisole reduced the rate of pancreatic infection.

Animals↗
PubMed1992

Patterns of innervation of vasoactive intestinal polypeptide, neuropeptide Y, and gastrin-releasing peptide immunoreactive nerves in the feline pancreas.

In this study, we performed a detailed analysis of the immunoreactive (IR) patterns and tissue distribution of vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY), and gastrin-releasing peptide (GRP) in the feline pancreas by means of immunohistochemical and radioimmunological techniques. Immunoreactivity for each peptide is localized to varicose nerve fibers distributed throughout the exocrine and endocrine pancreas, with some differences in the density and pattern of fiber distribution. In the acinar and stromal compartments, VIP-IR processes have a higher density than NPY- and GRP-containing fibers, the latter being the least abundant. The vasculature receives a particularly prominent NPY innervation, while GRP- and VIP-IR fibers are found occasionally in association with blood vessels. Around ducts, NPY- and VIP-IR nerves are more numerous than those positive for GRP-IR, which are quite sparse. One of the most interesting findings of the present work is the visualization of all peptide-IRs both in neuronal cell bodies and fibers within the intrapancreatic ganglia. VIP-IR is observed in virtually all ganglion cells, while GRP- and NPY-IRs are seen in a few neuronal cells. VIP and NPY tissue levels are much higher than GRP concentrations in all regions of the pancreas. VIP content in the head and body is greater than in the tail. The morphological relationship of VIP-, NPY-, and GRP-IR fibers with different pancreatic structures is consistent with specific peptidergic neural inputs in the regulation of pancreatic functions.

Animals↗
PubMed1992

The low-pressure duct perfusion model of acute pancreatitis.

The low-pressure duct perfusion model reliably produces acute pancreatitis in cats. The main pancreatic duct is made permeable in one of several ways: the perfusion of glycodeoxycholic acid along the main pancreatic duct, the administration of intragastric ethanol, the stimulation of pancreatic secretion into an obstructed duct, or the creation of acute hypercalcemia. Active pancreatic enzymes are then perfused through the main pancreatic duct via a catheter inserted into the duct in the tail of the gland, and acute edematous pancreatitis results. Simultaneous infusion of 16,16-dimethylprostaglandin E2 converts acute edematous into acute hemorrhagic pancreatitis. Histologically, the characteristic changes of human acute pancreatitis are manifest 24 h later: necrosis, polymorphonuclear leukocyte infiltrate, hemorrhage and edema.

Acute Disease↗
PubMed1992

Pancreatic blood flow in cats with chronic pancreatitis.

Pancreatic blood flow and its relationship to pancreatic interstitial pressure were investigated in a model of chronic pancreatitis in cats using a hydrogen gas-clearance technique with an intraductal electrode. The intraductal technique correlated well with blood flow measurements made using gamma-labeled microspheres (r = 0.88, P less than 0.001). In control cats, the basal blood flow of 69.1 +/- 9.5 mL.min-1.100 g-1 increased by 25% to 86.2 +/- 11 mL.min-1.100 g-1 with secretory stimulation (P less than 0.05). Interstitial pressure was -0.02 +/- 0.3 mm Hg and did not change significantly with stimulation. In cats with chronic pancreatitis, basal interstitial pressure was 1.8 +/- 0.5 mm Hg and basal blood flow 39.9 +/- 4 mL.min-1.100 g-1 (P less than 0.05). Stimulation of the chronic pancreatitis gland increased the pressure to 3.0 +/- 0.4 mm Hg (P less than 0.01) and reduced flow 15% to 34.2 +/- 4 mL.min-1.100 g-1 (P less than 0.05). Papaverine increased blood flow in control and chronic pancreatitis cats without altering tissue pressure, suggesting that despite the reduced basal blood flow, the ability to increase blood flow was preserved in chronic pancreatitis. The increased interstitial pressure associated with secretion appeared to limit the gland's normal hyperemic response in this model of chronic pancreatitis.

Animals↗
PubMed1992

The influence of ethanol on pancreatic blood flow in cats with chronic pancreatitis.

BACKGROUND: The mechanism by which ethanol predisposes to acute pancreatitis, especially in established chronic pancreatitis, is not known. Here we studied the effects of acute ethanol ingestion on pancreatic blood flow in chronic pancreatitis, a setting characterized by diminished basal blood flow to the pancreas. METHODS: Obstructive pancreatitis was created by partial duct ligation for 3 weeks in nine cats. Controls (n = 8) were not operated on. Blood flow was measured in anesthetized animals with a hydrogen gas clearance technique and an intraductal electrode. Pancreatic interstitial pressure, systemic and portal blood pressures, and serum ethanol levels were recorded, and pancreatic vascular resistance was calculated. Measurements were made before and for 2 hours after 20 cc of 40% (wt/vol) ethanol was instilled into the stomach. RESULTS: Basal flow was reduced in the obstructed pancreas to 51% of normal. Both groups showed an acute decrease in blood flow when ethanol was given. A more steep (50% of baseline) and a more prolonged (120 minutes) fall was observed in the pancreatitis group than in controls (31% and 60 minutes, respectively). The decline in blood flow correlated with increases in interstitial pressure and vascular resistance. CONCLUSIONS: Acute ethanol ingestion sharply reduces pancreatic blood flow, especially in glands with chronic pancreatitis.

Animals↗
PubMed1991

A study of the time course of conversion of edematous to hemorrhagic pancreatitis.

We studied the conversion of acute edematous pancreatitis (AEP) to acute hemorrhagic pancreatitis (AHP) in an experimental model in cats. In the model, 16,16 dimethyl PgE2 effects this conversion by increasing microvascular permeability. First, we induced AEP in cats and then gave PgE2 at increasing intervals after the induction of AEP to see how long an interval would still allow conversion. In 6 groups of cats, PgE2 was administered for 2 h, starting at 2, 4, 6, 8, 10, or 12 h after the creation of AEP. Twelve h later, the cats were sacrificed and the pancreases were graded for inflammation and hemorrhage. Significant pancreatic hemorrhage did not occur when the PgE2 was administered at 12 h compared to 2 h. Next, we determined that PgE2 still retained its ability to increase pancreatic vascular permeability when administered 12 h after the creation of AEP. This was done by perfusing a marker molecule through the MPD (fluorescein isothiocyanate labeled dextran: FITC-D, mol wt 20,000) and then finding it in portal venous blood (PVB). The presence of FITC-D in PVB signified increased vascular permeability, since normally none was present. We concluded that conversion of AEP to AHP was possible during the first 12 h after induction of AEP. Lack of conversion at 12 h was not caused by a lack of vascular reactivity at that time.

16,16-Dimethylprostaglandin E2↗
PubMed1991

The antiinflammatory effect of dopamine in alcoholic hemorrhagic pancreatitis in cats. Studies on the receptors and mechanisms of action.

Hemorrhagic pancreatitis was induced in cats by perfusing pancreatic enzymes through a pancreatic duct after the administration of intragastric ethanol. Dimethyl prostaglandin E2 was administered concurrently. In the first study, dopamine's antiinflammatory effect on the pancreas was determined in the presence of haloperidol, propranolol, or both. Next, dopamine's effects on blood flow in the normal and inflamed pancreas were compared using a hydrogen gas-clearance technique. In the final study, the effect of dopamine on fluorescein isothiocyanate-labeled dextran leakage from the pancreatic duct to portal venous blood was investigated. It was found that blockade of either dopamine or beta-adrenergic receptors reduced, and blockade of both receptors completely eliminated, the antiinflammatory effect. Dopamine had no effect on pancreatic blood flow in normal cats. In pancreatitis, although dopamine transiently reduced blood flow, after an hour flow had returned to normal. Dopamine reversed the leakage of fluorescein isothiocyanate-labeled dextran from the pancreatic duct caused by ethanol and by ethanol and prostaglandin E2. It was concluded that dopamine ameliorated pancreatitis by reducing pancreatic ductal and/or microvascular permeability rather than by altering pancreatic blood flow. The antiinflammatory effect was mediated by both dopamine and beta-adrenergic receptors.

Acute Disease↗
PubMed1991

New perspectives in the surgical management of chronic pancreatitis.

Although the etiology of pain in chronic pancreatitis remains uncertain, that symptom remains the most common indication for surgery in these patients. Current endoscopic and imaging techniques now permit accurate definition of the morphology of the disease. Thus, surgical intervention can be more selectively applied to address specific abnormalities. Pancreaticojejunostomy should be the first line of surgical therapy if the ductal system is dilated. When, in addition, the head of the pancreas is enlarged and inflamed, the operation should include a localized resection of the head, preserving the stomach and duodenum. If the duct is not dilated, some form of pancreatic resection is indicated. The resection should be limited to the most severely diseased part of the pancreas. Efforts should be made to preserve as much pancreatic tissue as possible, while maintaining normal gastrointestinal continuity. In this way, the nutritional and metabolic consequences of pancreatic resection will be minimized.

Chronic Disease↗