Giant fibrovascular polyp of the esophagus.

Fibrovascular polyps of the esophagus are benign, pedunculated tumors that consist mostly of connective tissue and can reach impressive sizes. They arise from the upper third of the esophagus and may produce symptoms of dysphagia, progressive weight loss and regurgitation. The most serious clinical presentation is asphyxia secondary to laryngeal obstruction. Despite their size, diagnosis may be difficult. The location of the stalk and the vascularity makes surgical resection the preferred mode of removal of these unusual polyps.

Time-trends in the epidemiology of peptic ulcer bleeding.

OBJECTIVE: Despite the introduction of effective medical treatment of peptic ulcer disease, bleeding is still a frequent complication. The aim of this study was to investigate whether the incidence and the risk profile of peptic ulcer haemorrhage have changed within a 10-year period. MATERIAL AND METHODS: In a prospective epidemiological and observational study the incidence and risk profile of peptic ulcer haemorrhage in Düsseldorf, Germany were compared between two time periods (period A: 1.3.89-28.2.90 and period B: 1.4.99-31.3.2000), involving nine hospitals with both surgical and medical departments. Patients with proven peptic ulcer haemorrhage at endoscopy or operation were included in the study; those with bleeding under defined severe stress conditions were excluded. RESULTS: No differences in bleeding ulcer incidence were observed between periods A and B (51.4 per 100,000 person-years versus 48.7), or for duodenal ulcer (24.9 versus 25.7) or for gastric ulcer bleeding (26.5 versus 23.0). A marked increase in incidence rates was observed with increasing age. In period B, patients with bleeding ulcers were older (56% versus 41% 70 years or older), were usually taking non-steroidal anti-inflammatory drugs (NSAIDs) (45% versus 27%) and were less likely to have a history of ulcer (25% versus 59%) compared with patients in period A. CONCLUSIONS: The persisting high incidence of peptic ulcer disease is a superimposing of two trends: a higher incidence in the growing population of elderly patient with a higher intake of NSAIDs and a lower incidence among younger patients due to a decrease in incidence and improved medical treatment.

Increased protein glycation in cirrhosis and therapeutic strategies to prevent it.

Glycation of liver proteins by reactive aldehydes formed from the metabolism of ethanol and lipid peroxidation has been implicated in the development of both alcoholic and nonalcoholic liver cirrhosis. Modified proteins are targeted to the proteasome for proteolysis. Release of glycation-free adducts into the circulation may provide a diagnostic "signature" of hepatic protein damage. We quantitatively screened protein glycation, oxidation, and nitrosation adduct residues and free adducts in portal, hepatic, and peripheral venous blood plasma of cirrhotic patients; we also screened the hepatic and peripheral venous blood plasma of control subjects by liquid chromatography-mass spectrometry. There was a remarkable 14-16-fold increase of glyoxal-derived, hydroimidazolone-free adduct in portal and hepatic venous plasma of cirrhotic patients with respect to normal controls. There was only a twofold increase of glycation adduct residues in plasma proteins in cirrhotic patients, which was attributed mainly to decreased albumin turnover. Therapeutic strategies to decrease dicarbonyl compounds may be beneficial, such as dicarbonyl scavengers, glutathione repleting agents, and high-dose thiamine therapy.

Processing of protein glycation, oxidation and nitrosation adducts in the liver and the effect of cirrhosis.

BACKGROUND/AIMS: Plasma proteins are modified non-enzymatically in vivo by glycation, oxidation and nitrosation processes. Hepatic extraction of albumin glycated in vitro was reported but it is not clear if plasma proteins glycated in vivo also undergo hepatic extraction. We investigated the hepatic extraction of glycated, oxidised and nitrosated proteins in vivo. METHODS: Protein glycation, oxidation and nitrosation marker residues and free adducts were determined in portal, hepatic and peripheral venous blood plasma of cirrhotic patients and hepatic and peripheral venous blood plasma (as a surrogate of portal venous blood) of control subjects by liquid chromatography-mass spectrometry. RESULTS: There was no evidence for extraction of glycated, oxidised or nitrosated proteins or related free adducts by the liver in control subjects. There was limited extraction of methylglyoxal-modified proteins in cirrhotic patients and twofold increases in the concentrations of fructosyl-lysine and advanced glycation endproduct residues of plasma protein, with respect to controls. Remarkably, glyoxal-derived hydroimidazolone free adduct was increased 14-16-fold probably as a consequence of hepatic lipid peroxidation. CONCLUSIONS: We found no evidence for hepatic extraction of glycated, oxidised and nitrosated proteins or related free adducts in subjects with normal liver function and limited extraction of methylglyoxal-modified protein in cirrhotic subjects.

Disruption of paracellular sealing is an early event in acute caerulein-pancreatitis.

Caerulein-induced pancreatitis is a widely used experimental model for studies on acute pancreatitis, however, the molecular mechanisms underlying pancreatitis in response to caerulein hyperstimulation are incompletely understood. We therefore studied early effects of caerulein on tight junctional integrity. Mice were injected with the cholecystokinin analogue caerulein (50microg/kg BW/h) to induce pancreatitis. In pancreatic tissue occludin, claudin 1, zonula occludens protein 1 (ZO-1) were stained immunohistochemically and F-actin was visualized with phalloidin-TRITC. Stained sections and isolated acini were studied by confocal laser scanning microscopy. Under control conditions occludin, claudin1, ZO-1, and F-actin showed a linear staining pattern delineating the apical membranes of intralobular duct cells and of acinar cells. While in vitro caerulein hyperstimulation induced within 10 minutes disassembly of both occludin and ZO-1, in vivo caerulein hyperstimulation induced disassembly of occludin and claudin1 but not of ZO-1 from the tight junctions. Subsequent progressive disruption of ZO-1 was detected in a time dependent manner. Disruption of the transmembrane tight junction proteins occludin and claudin1 is an early event of caerulein hyperstimulation and may allow evasion of noxious luminal content into the interstitium, which may augment edema formation in acute pancreatitis.

Production and effects of endothelin-1 in rat pancreatic stellate cells.

INTRODUCTION: Proliferation and matrix synthesis of activated pancreatic stellate cells (PSCs) participate in the development of chronic pancreatitis. Besides other substances, endothelin-1 (ET-1) may influence the activation process of PSCs. Until now, ET-1 has not been studied in this particular cell type. AIMS: To characterize PSCs in rat pancreas with respect to expression of ET(A)-receptors, production of ET-1, and physiological effects induced by ET-1 during PSC activation. METHODOLOGY: Immunocytochemical and ELISA techniques and cDNA microarray analysis were used. Physiologic effects were characterized by single cell measurements of free cytosolic Ca2+-concentration and of PSC contractility on collagen lattices. RESULTS: Activation of PSCs in vitro, as assessed by alpha-smooth muscle actin expression, was accompanied by the de novo expression of ET(A)-receptors and synthesis of ET-1 mRNA and protein. Cytosolic Ca2+-concentration was increased upon ET-1 stimulation in activated but not in quiescent PSCs. Contractility of activated PSCs was significantly reduced by the selective ET(A)-receptor antagonist BQ123 but not by the ET(B)-receptor antagonist IRL-1038. CONCLUSIONS: The results suggest that ET-1 may act as a paracrine and autocrine factor for activated PSCs and may mediate contractions of activated, but not quiescent, PSCs.

Improvement of sonographic needle visibility in cirrhotic livers during transjugular intrahepatic portosystemic stent-shunt procedures with use of real-time compound imaging.

The visibility of a transjugular intrahepatic portosystemic stent-shunt (TIPS) puncture needle was assessed with use of real-time compound imaging and single-line ultrasonography (US). In vitro and in vivo, needle-tissue contrast was calculated. With an increasing angle of incidence, the decrease in needle visibility was more pronounced for single-line US than for compound imaging. At angles of incidence of more than 30 degrees, the needle was barely visible with either technique. Subjective evaluation during TIPS procedures in 10 patients proved that the needle tip was significantly better seen with compound imaging. Therefore, real-time compound imaging significantly improved contrast and subjective visibility of the needle.

Apoptosis in activated rat pancreatic stellate cells.

Proliferation and matrix synthesis by activated pancreatic stellate cells (PSC) participate in the development of chronic pancreatitis. Apoptosis of PSC may terminate this process but has not yet been studied in this particular cell type and was the aim of the present study. PSC were isolated from rat pancreas and characterized for expression of glial fibrillary acidic protein, alpha-smooth muscle actin, CD95, and tumor necrosis factor-alpha-related apoptosis-inducing ligand (TRAIL) receptors. Apoptosis was determined by TdT-UTP nick end-labeling reaction, annexin V binding, and caspase-8 activation. Both CD95L and TRAIL induced apoptosis in PSC. The apoptotic response was minor in PSC cultured for 7 days but increased markedly thereafter. Sensitization of PSC with culture duration was accompanied by increased expression of CD95 and TRAIL receptor 2 and no alterations of Flip expression or protein kinase B phosphorylation but was paralleled by the appearance of a COOH-terminal cleavage product of receptor-interacting protein. PSC apoptosis was also induced by PK-11195, a ligand of the peripheral benzodiazepine receptor. PSC apoptosis may be important in terminating the wound-healing response after pancreas injury and exhibits features distinct from apoptosis induction in hepatic stellate cells.

Glutathione might exert an important function in caerulein-stimulated amylase release in isolated rat pancreatic acini.

AIMS: The effect of different modes of thiol depletion on pancreatic exocrine secretory function and potential mechanisms of interference with the secretory process in pancreatic acinar cells were investigated. METHODOLOGY: After incubation with three thiol-modulating agents (L-buthionine sulfoximine, ethacrynic acid, and diamide) for 30 minutes, caerulein-stimulated amylase release and cholecystokinin (CCK) receptor binding characteristics were assessed in isolated rat pancreatic acini. The level of thiol groups (glutathione and protein thiols) and cytosolic-free calcium were measured in pancreatic acinar cells. RESULTS: All three thiol-modulating agents decreased caerulein (10(-10)M)-stimulated amylase release and the level of pancreatic acinar glutathione in a dose-dependent fashion without a marked increase in cell damage. Diamide also diminished the level of protein thiols. Ethacrynic acid and diamide, but not L-buthionine sulfoximine, inhibited the caerulein (10(-9)M)-induced Ca(2+) mobilization in pancreatic acinar cells. None of the three thiol-modulating agents altered the CCK receptor binding characteristics. CONCLUSION: The present findings strongly suggest an important role of glutathione in the secretory process in pancreatic acinar cells and in the secretory blockade observed in acute pancreatitis. A decrease in caerulein-induced Ca(2+) mobilization might participate in the inhibition of amylase release by some oxidative agents, but it is not the prominent cause in general.