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At least 1,297 records · Page 72Linked to original sources
PubMed2007

The physiology of a local renin-angiotensin system in the pancreas.

The systemic renin-angiotensin system (RAS) plays an important role in regulating blood pressure, electrolyte and fluid homeostasis. However, local RASs also exist in diverse tissues and organs, where they play a multitude of autocrine, paracrine and intracrine physiological roles. The existence of a local RAS is now recognized in pancreatic acinar, islet, duct, endothelial and stellate cells, the expression of which is modulated in response to physiological and pathophysiological stimuli such as hypoxia, pancreatitis, islet transplantation, hyperglycaemia, and diabetes mellitus. This pancreatic RAS has been proposed to have important endocrine and exocrine roles in the pancreas, regulating local blood flow, duct cell sodium bicarbonate secretion, acinar cell digestive enzyme secretion, islet beta-cell (pro)insulin biosynthesis, and thus, glucose-stimulated insulin release, delta-cell somatostatin secretion, and pancreatic cell proliferation and differentiation. It may further mediate oxidative stress-induced cell inflammation, apoptosis and fibrosis. Further exploration of this system would probably offer new insights into the pathogenesis of pancreatitis, diabetes, cystic fibrosis and pancreatic cancer formation. New therapeutic targets and strategies might thus be suggested.

Animals↗
PubMed1992

Effects of chronic and in utero treatment with diuretics on mouse exocrine cells studied by X-ray microanalysis.

In an attempt to develop an animal model for the disease cystic fibrosis, mice were chronically treated with diuretics. In addition, pregnant mice were treated with diuretics and the effect of this treatment in utero on the newborn mice was studied. Pancreas and submandibular gland acinar cells were investigated by X-ray microanalysis and transmission electron microscopy. Long-term treatment with furosemide (up to 13 months) caused transient changes in the elemental content of the pancreatic acinar cells: a decrease in chloride and sulfur, and an increase in phosphorus, potassium and magnesium. All changes normalized with prolonged treatment. Some morphological changes were found in the zymogen granules. Treatment with amiloride or furosemide in utero caused a decrease in cellular sodium and chloride levels, indicative of inhibition of transepithelial ion and fluid transport. Also treatment of adult animals for two months with amiloride caused lower intracellular sodium and chloride levels. In adult animals only minor effects of diuretic treatment on submandibular gland acinar cells were noted. In utero treatment with amiloride caused an increase in sodium and chloride content indicative of cell damage.

Amiloride↗
PubMed1956

Intestinal obstruction in the newborn.

Any newborn who continues to vomit in the first few days of life, particularly if the vomitus contains bile and if the abdomen is distended, should have immediate investigation because intestinal obstruction in the newborn is a fatal condition unless promptly recognized and surgically corrected. The most common cause of obstruction at this age is atresia and the simplest possible surgical procedure which adequately corrects this deformity should be done. It is also possible to successfully correct the obstruction caused by other congenital deformities such as annular pancreas and meconium ileus. Although prematurity is a definite factor in the outcome, intestinal obstruction in the newborn can be corrected with a surprisingly low mortality. Occasionally unusual methods are needed to tide these infants over the critical period of postoperative care.

Child↗
PubMed2000

Islet autoantibodies and insulin dependent diabetes mellitus in cystic fibrosis.

Cystic fibrosis-related diabetes mellitus (CF-DM) is thought to be secondary to beta-cell destruction by fibrous tissue replacing the exocrine pancreas. The aim of this study was to investigate the hypothesis that other factors may also be responsible. Glutamic acid decarboxylase (GAD) and islet cell (IA-2) antibodies were measured by quantitative ELISA in a group of patients with CF (n=30) in comparison to a group of newly diagnosed DM type 1 (IDDM) patients (n=30) and normal subjects (n=30). GAD antibodies were positive (>32 ng/ml) in 50% of the CF, 93% of the IDDM and 0% of the control group. IA-2 antibodies were detected (>0.9 U/ml) in 40% of the CF, 93% of the IDDM and 0% of the control group. Among the fifteen CF patients with positive GAD and IA-2 antibodies, four already had IDDM and another five abnormally low (<45 mU/l) first phase insulin response (FPIR) indicating a prediabetic state. We conclude that factors other than mechanical may be involved in the development of CFDM. The presence of autoantibodies predicting IDDM supports the hypothesis that CF-DM may have a multifactorial pathogenesis.

Adolescent↗
PubMedDate not supplied

Review of the abdominal manifestations of cystic fibrosis in the adult patient.

Cystic fibrosis is a common inherited fatal disease. As the life expectancy of affected individuals continues to increase with advances in disease management, this disease is no longer limited to the pediatric population. Currently, 40% of patients with cystic fibrosis are adults. In addition, patients may not present until adulthood and frequently have extrapulmonary symptoms. Abdominal manifestations are common and affect multiple organ systems. Hepatobiliary manifestations include fatty infiltration of the liver, gallbladder abnormalities, bile duct abnormalities, focal biliary fibrosis, and multinodular cirrhosis. Manifestations in the pancreas include acute pancreatitis, fatty replacement, calcifications, cysts, duct abnormalities, and carcinoma. Gastrointestinal manifestations include gastroesophageal reflux, peptic ulceration of the gastric and duodenal mucosa, distal intestinal obstruction syndrome, intussusception, appendicitis, fibrosing colonopathy, pneumatosis intestinalis, rectal mucosal prolapse, malignancies, and pseudomembranous colitis. Renal manifestations include nephrolithiasis, as well as secondary renal complications such as interstitial nephritis due to antibiotic therapy and amyloidosis. Awareness of these manifestations is important to successfully guide management of cystic fibrosis in adult patients.

Abdomen↗
PubMed1991

Expression of the cystic fibrosis gene in human development.

The specialised epithelia lining the respiratory tract, pancreatic ducts, male genital ducts and sweat gland ducts are defective in the severe inherited disease, cystic fibrosis (CF). We have looked at the expression of the CF gene in human fetal tissues to throw light on the development of function in specialised ductal epithelia and to determine the age of onset of the CF disease process. The CF gene is already seen to be transcribed in mid-trimester fetal lung, pancreas and male genital ducts. Hence, by this developmental stage, and before they are fully differentiated, these epithelia have the capability to perform important transport functions. Epithelial cell cultures derived from fetal pancreas and male genital ducts maintain expression of the CF gene in vitro and so form good models for analysing CF gene function and differentiation of these specialised epithelia.

Blotting, Northern↗
PubMed1991

Alterations of amylase secretion in the chronically reserpinized rat: an acetylcholine-mediated phenomenon.

Chronic reserpine treatment of animals, an experimental model for cystic fibrosis (CF), results in generalized exocrinopathy, impaired secretion, and decreased pancreatic content of amylase. However, the mechanisms of altered acinar pancreatic function in both CF patients and reserpine-treated rats are still unknown. The present study was designed to investigate the secretory response of the rat pancreas after reserpine treatment. Rats were given reserpine (1 mg kg-1 day-1 ip) or vehicle, and killed 2, 4, or 7 days later. To distinguish between specific effects of reserpine and those related to secondary malnutrition caused by the drug, secretory response of a group of pair-fed animals to reserpine was also investigated. During reserpine treatment, body weight and food intake were significantly reduced from the 2nd day on. Amylase release from dispersed pancreatic acini, prepared from control pair-fed and from reserpine-treated rats were used to evaluate functional secretory capacity. After 7 days, both chronic reserpine and pair-feeding significantly decreased pancreatic amylase concentration to 75 and 50% of controls, respectively. Reserpine caused desensitization of the pancreatic acini secretory response to carbamylcholine, without altering maximal amylase release. Desensitization occurred gradually and reached a maximum after 7 days. Secretory responses to caerulein and to the phorbol ester 12.0-tetradecanoyl phorbol-13 acetate (TPA) were not altered. These findings indicate that desensitization of amylase release after reserpine was specific to this muscarinic agonist. It may result from increased endogenous acetylcholine release in the course of treatment.

Acetylcholine↗
PubMed1985

Effects of product formulation on in vitro activity of pancreatic enzymes.

The lipase activity of two enteric-coated and two uncoated pancreatic enzyme formulations was evaluated in vitro at different pH values and compared with postprandial duodenal pH data in cystic fibrosis patients. Lipase activity was measured over a pH range of 4-8 in four formulations: Viokase tablets and Viokase powder (Viobin), Cotazym-S (Organon), and Pancrease enteric-coated spherules (McNeil). A pH-stat technique was used in which the amount of hydroxyl ion that must be added to maintain a preset pH value is measured to determine the amount of lipase substrate (tributyrin) that is split into butyric acid. At least three determinations of activity were made at each pH. Six capsules of each enteric-coated formulation were subjected to disintegration testing at various pH values. These data were then compared with data available for postprandial duodenal pH in patients with cystic fibrosis. The lipase activity of all formulations studied decreased when pH decreased, especially when the pH was below 5.75. At a pH value between 5 and 5.5, which represents the postprandial duodenal pH in cystic fibrosis patients, activity was reduced 50% or more for all formulations tested. The two enteric-coated products displayed no activity at pH 5.5 and below because the coating did not dissolve in this pH range. Lipase activity in enteric-coated pancreatic enzyme preparations is limited because the enteric coating of these products dissolves slowly in the duodenal pH range (5-5.75) that is found in patients with cystic fibrosis.

Buffers↗
PubMed1991

Severe deficiency of cystic fibrosis transmembrane conductance regulator messenger RNA carrying nonsense mutations R553X and W1316X in respiratory epithelial cells of patients with cystic fibrosis.

Cystic fibrosis (CF) is the most common, lethal inherited disorder in the Caucasian population. We have recently reported two African-American patients with nonsense mutations in each CF gene and severe pancreatic disease, but mild pulmonary disease. In order to examine the effect of these nonsense mutations on CF gene expression, bronchial and nasal epithelial cells were obtained from one of these patients (no. 246), a compound heterozygote for nonsense mutations R553X and W1316X; a healthy normal individual; a patient (no. 528) homozygous for the common CF mutation (delta F508); and a CF patient (no. 272) who carries the R553X mutation and a missense mutation, S549N. When mRNA from bronchial cells of the normal individual, the delta F508 homozygote, and the S549N/R553X compound heterozygote was reverse transcribed and amplified by polymerase chain reaction using primers derived from the CF gene, DNA fragments of the predicted size were observed. However, patient no. 246 with nonsense mutations in each CF gene has no detectable cystic fibrosis transmembrane conductance regulator (CFTR) messenger RNA, and therefore should have severely diminished, and possibly absent, CFTR protein. Furthermore, less than 2% of the CFTR transcripts in nasal epithelial cells from patient no. 272 (S549N/R553X) were derived from the gene with the nonsense mutation. We conclude that severe reduction in CFTR mRNA causes CF, but can have different consequences in the lung and pancreas.

Adolescent↗
PubMed2001

Cholesterol esterase activities in commercial pancreatic enzyme preparations and implications for use in pancreatic insufficient cystic fibrosis.

BACKGROUND: Although clinical symptoms in pancreatic insufficiency are often dramatically improved by pancreatic preparations, these often fail to normalize biochemical indicators of malabsorption. It seemed relevant, therefore, to investigate the amounts of cholesterol esterase in these preparations and, using in-vitro methods, some of the activities of this enzyme. The enzyme is just as physiologically important as lipase in accomplishing lipid digestion and absorption. METHODS: Cholesterol esterase was assayed in commercial pancreatic extract preparations, lyophilized pig pancreas and human duodenal fluid. The in-vitro activities of the enzyme were also investigated on single and mixed dietary substrates. RESULTS: Other than Creon, the commercial preparations showed negligible cholesterol esterase activities, whereas considerable activities were found in pancreatic tissue and duodenal fluids. In-vitro, pig cholesterol esterase was confirmed to be dependent on 3-hydroxy bile salt concentration for hydrolysis and synthesis and that the rate for hydrolysis greatly exceeds that of synthesis in normal concentrations of bile salts. However, with mixed lipid substrates, no bile salt concentration was found at which hydrolysis or synthesis predominates. CONCLUSIONS: When pancreatic or hepato-biliary function is compromised, optimum lipid hydrolysis may not be achieved in therapeutic use, and the pig enzyme may perform differently to the human enzyme. In-vivo trials may reveal whether augmentation of the commercial products with this enzyme would be worthwhile.

Absorption↗
PubMed1996

Regulation of the CFTR chloride channel from humans and sharks.

The cystic fibrosis transmembrane conductance regulator (CFTR) in an ATP-dependent channel which mediates cAMP-stimulated chloride secretion by epithelia, particularly those of the pancreas, airways, and intestine. CFTR homologues have been found in all higher vertebrates examined to date and also in some lower vertebrates, although only the human, shark, and Xenopus genes have been heterologously expressed and shown to generate protein kinase A-activated Cl channels. Once phosphorylated, CFTR channels require hydrolyzable nucleotides to be active, but they can be locked in an open burst state when exposed to mixtures of ATP and its hydrolysis-resistant analogue AMP-PNP. This locking requires low-level phosphorylation at unidentified sites that are not among the ten "strong" (dibasic) PKA consensus sequences on CFTR. Mutagenesis of the dibasic PKA sites, which reduces in vitro phosphorylation by > 98%, reduces open probability (Po) by about 50% whilst having no effect on burst duration. Thus, incremental phosphorylation of these sites under normal conditions does not increase Po by slowing down ATP hydrolysis and stabilizing the open burst state, although locking does strictly require low-level phosphorylation at one or more cryptic sites. In addition to serving as a Cl channel, there is compelling evidence that CFTR inhibits the amiloride-sensitive, epithelial sodium channel (ENaC). The mechanism of coupling is not known but most likely involves physical interactions between the channels, perhaps mediated by an intermediate protein that impinges on other transport proteins. CFTR does not function as a conductive channel for ATP; however, extracellular ATP does regulate epithelial channels through activation of P2U purinergic receptors and, after being hydrolyzed extracellularly, through activation of adenosine receptors which elevate cAMP.

Adenosine Triphosphate↗
PubMed1950

Meconium ileus.

Explore the source record for details and available documents.

Cystic Fibrosis↗
PubMed1990

Duodenal pH in cystic fibrosis and its relationship to fat malabsorption.

To investigate the relationship between duodenal pH levels and supplemental pancreatic enzyme function in cystic fibrosis, 18 children with this condition had pH recordings performed from the second and fourth part of the duodenum. Compared to age-matched controls, patients with cystic fibrosis had significantly longer periods below a pH of 4.0 in the postprandial period and significantly less time above pH 5.8. These values correspond to the pH levels at which lipase is irreversibly destroyed (pH 4.0) and enteric coating of enzyme supplements dissolves (pH 5.8). A significant relationship was found between the pH recordings from the fourth part of the duodenum and the degree of residual fat malabsorption while taking enteric-coated enzyme supplements. Four patients with an excessively acidic duodenum and residual fat malabsorption despite high-dose enzyme supplementation were treated with misoprostol (Searle), a known acid-reducing agent. There were significant improvements in both duodenal pH values and fat absorption. We conclude that there is a wide range of duodenal pH values found in patients with cystic fibrosis and that the efficiency with which enzyme supplements work is closely related to these pH levels. Administration of misoprostol to those patients with excessively acidic duodenal pH levels as well as residual malabsorption appears to be of benefit in improving both the excessively acidic pH levels and the fat malabsorption.

Acid-Base Equilibrium↗
PubMed1993

High dose Nutrizym 22 in cystic fibrosis.

New high dose pancreatic enzyme preparations could be potentially helpful to cystic fibrosis (CF) patients. The purpose of this study was to compare the efficacy of the new high dose pancreatic enzyme preparation, Nutrizym 22 with the standard preparation Nutrizym GR. Twenty-five CF children (aged 7-16 years) entered the study and 22 completed it; 3 did not, due to non-compliance. All were taking Nutrizym GR for at least 2 weeks before entering the study. A randomised double blind, crossover method using standard Nutrizym GR or double strength Nutrizym 22 capsules was carried out over two consecutive 14-day periods. Crossover analyses of variance showed no statistically significant differences in actual weight gain, appetite, abdominal pain, stool consistency or faecal fat during the prestudy and study periods. It is concluded that half the capsule numbers of the high strength preparation are just as effective as the standard capsule dosage.

Adolescent↗