Importance of intracellular S-adenosylmethionine decarboxylase activity for the regulation of camostate-induced pancreatic polyamine metabolism and growth: in vivo effect of two novel S-adenosylmethionine decarboxylase inhibitors.

The present study was designed to investigate the inhibitory potency of the two novel S-adenosylmethionine decarboxylase (SAM-DC) inhibitors MDL 73811 and CGP 48664 on the camostate-induced pancreatic polyamine metabolism and especially intracellular spermidine accumulation as well as pancreatic growth in vivo. Male Wistar rats (180 g) were either treated with (1) the synthetic trypsin inhibitor camostate (200 mg/kg b.w.

Relaxant effect of xenin on rat ileum is mediated by apamin-sensitive neurotensin-type receptors.

The action of xenin, a novel 25-residue peptide of the neurotensin (NT)/xenopsin family, was investigated in isolated rat ileal muscle strips and in dispersed longitudinal smooth muscle cells of rat small intestine in vitro. Xenin relaxes KCl-precontracted ileal strips dose dependently (1 nM-3 microM). The order of potency of the investigated peptides was as follows: xenopsin = NT = xenin > neuromedin N.

Identification of novel growth-related genes linked to the mitogenic effect of PACAP on the rat pancreatic acinar cell line, AR4-2J.

The mRNA differential display technique was employed in order to identify novel growth-related genes linked to the mitogenic effect of PACAP on AR4-2J cells. Hereby, three differentially expressed and PACAP-inducible genes were found, one of these being homologous to a recently discovered putative growth-related early response gene in mice. In AR4-2J cells, mRNA levels of this novel rat gene are increased by PACAP in a rapid and transient fashion.

Pituitary adenylate-cyclase-activating polypeptide stimulates proto-oncogene expression and activates the AP-1 (c-Fos/c-Jun) transcription factor in AR4-2J pancreatic carcinoma cells.

Pituitary adenylate-cyclase-activating polypeptide (PACAP) has been shown to possess mitogenic activity in various tumor cells. The present study was designed to investigate signal transduction mechanisms and expression of the proto-oncogenes c-fos and c-jun linked to the mitogenic effect of PACAP in the pancreatic carcinoma cell line AR4-2J. PACAP-(1-27)-peptide and PACAP-(1-38)-peptide, but not the structurally related vasoactive intestinal polypeptide (VIP), potently stimulated [3H]thymidine incorporation and cell number at doses of 0.

Dissimilar activation patterns of the carcinogen dimethylhydrazine (DMH) on intracellular polyamine metabolism in various organs.

Weekly administrations of the potent carcinogen 1,2-dimethylhydrazine (DMH) predominantly induce carcinoma of the colon by nearly 100% after six months' treatment in rats. Polyamines, and especially the key enzyme of polyamine de novo synthesis ornithine decarboxylase (ODC) are well-known to play an important role in cell growth and tumor carcinogenesis. Male Wistar rats were s.

Faecal elastase 1: a novel, highly sensitive, and specific tubeless pancreatic function test.

Background: Indirect pancreatic function tests available today are unreliable for clinical practice in early chronic pancreatitis due to their low sensitivity in mild and moderate exocrine pancreatic insufficiency.

Aim: To evaluate the sensitivity, specificity, and practicability of faecal elastase 1 determination in patients with mild, moderate, and severe exocrine pancreatic insufficiency categorised according to the secretin-caerulein test as "gold standard'.

Patients And Methods: Faecal and duodenal elastase 1 concentration (commercial enzyme linked immunosorbent assay (ELISA)), faecal chymotrypsin activity, faecal fat analysis, and the secretin-caerulein test were performed on 44 patients with mild (n = 8), moderate (n = 14), and severe (n = 22) exocrine pancreatic insufficiency and 35 patients with gastrointestinal diseases of non-pancreatic origin.

Chylous cardiac tamponade in acute pancreatitis.

A 47-year-old woman with acute necrotizing pancreatitis developed sudden cardiorespiratory arrest and needed resuscitation. A pericardial effusion was found, and 350 ml of a white nontransparent milky fluid was aspirated that contained 1020 mg triglycerides/100 ml. The diagnosis of chylous cardiac tamponade was made.

Does high pancreatic duct pressure compromise the duct mucosal barrier function to pancreatic exocrine proteins?

The effect of duct pressure on the barrier function of the pancreatic duct mucosa to both activated and nonactivated pancreatic exocrine enzymes was studied in a feline model. The cat main pancreatic duct was perfused from the tail to the head of the gland with rat pancreatic juice at high duct pressure (40 cm H2O). In a first experiment, nonactivated pancreatic juice was perfused.

Self-expanding metallic coil stents for palliation of esophageal carcinoma: two cases of decisive stent dysfunction.

Two cases of different dysfunctions of self-expanding nickel-titanium coil stents are described here. In the first case, a metallic coil stent was placed in a 8-cm circular rigid stenosis of the mid-esophagus caused by a squamous-cell carcinoma (T3 N1 M1), and seven weeks later, the stent lumen was completely occluded by massive tumor ingrowth through inadequtely adapted single coil wires. In the second case, the caudal and cranial ends of the stent became increasingly invaginated after initially adequate stent expansion, resulting in a shortening of the stent to about two-thirds of its intended size, with subsequent complete luminal obstruction at both ends of the stent due to tumor overgrowth.

Diazepam binding inhibitor is a potent cholecystokinin-releasing peptide in the intestine.

Pancreatic proteases in the duodenum inhibit the release of cholecystokinin (CCK) and thus exert feedback control of pancreatic exocrine secretion. Exclusion of proteases from the duodenum either by the diversion of bile-pancreatic juice or by the addition of protease inhibitors stimulates exocrine pancreatic secretion. The mechanism by which pancreatic proteases in the duodenum regulate CCK secretion is unknown.

Inhibitory transmission in guinea pig stomach mediated by distinct receptors for pituitary adenylate cyclase-activating peptide.

Previous studies have shown that inhibitory transmission in guinea pig stomach involves an interplay between vasoactive intestinal peptide (VIP) and nitric oxide (NO). The present study examined the contribution of pituitary adenylate cyclase-activating peptide (PACAP), a homologous peptide present in gastric and intestinal myenteric neurons. VIP, PACAP-27 and PACAP-38 induced concentration-dependent relaxation that was partly inhibited by the antagonists VIP10-28 and PACAP6-38 and the NO synthase inhibitor NG-nitro-L-arginine (L-NNA).

PRG1: a novel early-response gene transcriptionally induced by pituitary adenylate cyclase activating polypeptide in a pancreatic carcinoma cell line.

The rat pancreatic carcinoma cell line AR4-2J was screened for growth-associated genes linked to the mitogenic effect of the novel gut brain hormone, pituitary adenylate cyclase activating polypeptide (PACAP). Using the mRNA differential display technique, we identified and sequenced an unknown rat gene, PACAP-responsive gene 1 (PRG1), which is highly homologous to gly96, a novel murine gene of unknown function. The PRG1 cDNA sequence of 1.

GLP-1/GIP chimeric peptides define the structural requirements for specific ligand-receptor interaction of GLP-1.

The gastrointestinal hormones glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP) strongly stimulate insulin release. Despite their high N-terminal sequence similarity, GLP-1 does not bind to the GIP receptor and vice versa. To characterize the domains required for interaction of the peptide ligands with their specific receptors, we performed displacement studies with various synthetic GLP-1/GIP hybrid peptides on RINm5F insulinoma cells.

Human galanin modulates human colonic motility in vitro. Characterization of structural requirements.

Background: Human galanin (hGal) is a 30-residue non-amidated gut-brain peptide that shows considerable sequence divergence compared with galanin (Gal) forms of other species. Conflicting results have been reported with regard to the structural requirements for its modulatory action on gut motility.

Methods: We investigated the effect of human and rat Gal and substituted analogues of Gal on the contractility of longitudinal muscle strips of the human colon in vitro.

Secretin-pancreozymin test (SPT) and endoscopic retrograde cholangiopancreatography (ERCP): both are necessary for diagnosing or excluding chronic pancreatitis.

Results of the SPT and the ERCP staged for their severity were compared in 202 patients. The correlation between both investigations was significant (p < 0.001); however, ERCP showed significantly more severe changes (p = 0.

Influence of density and viscosity of fluids on extracorporeal shock wave lithotripsy of gallstones in vitro.

Background: It is hitherto still questionable which of the physical properties of the bile fluid influence the outcome of extracorporeal shock wave lithotripsy (ESWL).

Methods: In this study the influence of the density and viscosity of bile simulating fluid on ESWL was tested in vitro by applying CsCl solutions of densities 1.0, 1.

Urgent ERCP in all cases of acute biliary pancreatitis? A prospective randomized multicenter study.

In this prospective multicenter study, the effect of early ERCP within 72 hours after the beginning of symptoms in the treatment of acute biliary pancreatitis was investigated. 100 patients with acute biliary pancreatitis but without biliary sepsis or obstructive jaundice were randomized in this trial. 48 patients of the invasive group received urgent ERCP within 72 hours after the beginning of pain.

[Differential therapy of exocrine pancreatic insufficiency--current aspects and future prospects of substitution therapy with pancreatic enzymes].

The indication for initiation of a replacement therapy with pancreatic enzymes in the course of ongoing exocrine pancreatic insufficiency is clinically given with the appearance of loss of body weight, steatorrhea with stool fat excretion of more than 15 g per day, dyspeptic symptoms with strong meteorism, diarrhoea, and subjective misbehaviour caused by chronic pancreatitis, in rare cases with the appearance of maldigestion of proteins and carbohydrates and--under certain circumstances--for the treatment of pain in chronic pancreatitis. Due to the increase of chronic pancreatitis in recent years, the number of patients who necessarily have to be treated with enzyme replacement therapy has increased, too. The adequate replacement therapy with pancreatic enzymes, especially in patients with severe exocrine pancreatic insufficiency, is still a serious problem--requiring sufficient knowledge of the individual pathophysiological circumstances of the patient as well as the various pharmacological aspects of the different types of enzyme drugs.

Effect of neurotensin on pancreatic growth and pancreatic polyamine metabolism in rats.

The neuropeptide neurotensin is known to play a role in the regulation of exocrine pancreatic secretion, but actually there are conflicting results as to whether or not neurotensin exerts a trophic response on the pancreas and there are no data concerning its effect on pancreatic polyamine metabolism. In the present study, acute and long-term effects of various intraperitoneal dosages of neurotensin that resulted in mildly supraphysiological and even unphysiological high plasma concentrations of neurotensin were studied. Furthermore, neurotensin was simultaneously administered with cholecystokinin (1 microgram CCK-8/kg body wt ip every 8 h) for five days.

Clinical experience with acarbose as first line therapy in NIDDM.

The treatment of non-insulin-dependent diabetes mellitus (NIDDM) is based on dietary and oral hypoglycemic therapy. Present therapy includes diet and exercise, sulfonylureas, biguanides, and, if these measures fail, incremental doses of insulin. Current therapeutic strategies include the combination of different agents in an attempt to optimize glycemic control.