摘要:

During the last few years, considerable progress has been made in the dissection of cellular and molecular mechanisms of hepatic fibrogenesis. The disease, initiated by hepatocellular damage and perpetuated by inflammatory reactions, results not only in an overall increase in extracellular matrix (ECM) but also in molecular and histological rearrangement of virtually all matrix molecules including collagens, structural glycoproteins, proteoglycans and hyaluronan. These alterations of ECM cause severe clinical (e.g. hemodynamic) complications and further metabolic changes in the whole organ. Perisinusoidal fat (retinoid)-storing cells have been identified as the (precursor) cell type mainly responsible for matrix production in the diseased liver. However, these cells have to be activated, i.e. stimulated to proliferate, to transform phenotypically to myofibroblasts and to express matrix genes before full competency for fibrogenesis is reached. Multiple cell interactions with Kupffer cells, platelets, endothelial cells and hepatocytes mediated by various cytokines and growth factors (e.g. TGF-β1, TGF-α, PDGF, FGF, IGF-1) are involved in the mechanism of fat-storing cell activation which is the common and central pathogenetic mechanism in fibrogenesis. A three-step cascade model of fat-storing cell activation is proposed, which offers target mechanisms for possible anti-fibrotic intervention

ISSN:0012-2823    

DOI:10.1159/000201257

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Manifestations of esophageal disease are present in up to 60% of patients with Zollinger-Ellison syndrome (ZES), although esophageal function has been studied in only a few patients and the prevalence of Barrett’s mucosa is unknown in these patients. It is unclear whether the high prevalence of esophageal disease is related to gastric acid hypersecretion alone or to abnormalities of esophageal motility or lower esophageal sphincter (LES) function in addition. To address these issues in the present study esophageal function was evaluated prospectively in 92 consecutive patients with ZES (66 with active disease, 26 disease-free after curative resection) seen during a 1-year period after controlling acid hypersecretion. In the patients with active disease the mean basal acid output (BAO) was 33 ± 3.0 mEq/h, the maximal acid output (MAO) was 56 ± 4.0 mEq/h, fasting serum gastrin was 8,736 ± 4,813 pg/ml and duration of disease prior to study was 12.5 ± 2.0 years. At the time of manometry, gastric acid secretion was controlled in all patients and no patient had evidence of gastroesophageal reflux disease at upper gastrointestinal endoscopy. Esophageal manometry revealed normal motility in 85% of patients. Eleven percent had low LES pressures, and only 1 % of patients had an elevated LES pressure. The frequency of Barrett’s mucosa (3%) was similar to that found in the general population but much less than that reported in patients with idiopathic GERD. No correlation was noted between LES pressures or manometric abnormalities and the fasting serum gastrin, BAO, MAO or the presence or absence of multiple endocrine neoplasia type I or previous vagotomy. Esophageal manometric results and LES pressure were similar in disease-free patients and those with active ZES. In conclusion, these results suggest that hypergastrinemia or other disease-specific abnormalities are not contributing to the high incidence of esophageal disease in patients with ZES because esophageal function in patients with ZES is similar to normals. Specifically, motility disorders in patients with ZES occur in similar frequency to normals, and LES pressure is normal in most patients. Despite the high levels of acid secretion and prominence of symptoms, the occurrence of Barrett’s mucosa was uncommon (3%) raising the possibility of additional protective mechanisms in patients

ISSN:0012-2823    

DOI:10.1159/000201258

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

We examined the effects of nonsteroidal anti-inflammatory drugs (NSAIDs) on mucosal ulceration in isolated bullfrog stomachs and investigated the roles of endogenous prostaglandins (PGs) and nutrient HCO-3 in the mucosal protection in vitro. Gastric sacs were prepared by separation from the muscle layer and incubation for 1-8 h in HCOs”-Ringer’s solution gassed with 95% O2/5% CO2 or PO34---Ringer’s solution gassed with 100% O2 in the presence of histamine (1 × 10-4M). Under these conditions, multiple ulcers developed in the mucosa only when the gastric sacs were incubated in HCO-3-free nutrient solution; both the number and severity of ulcers increased with time and reached a maximum after 6 h of incubation. Luminal pH was decreased because of stimulation of acid secretion by histamine, irrespective of whether the mucosa was bathed in Ringer’s solution with or without HCO3, while gastric potential difference was reduced only in the mucosa bathed in HC03-free nutrient solution. 16,16-Dimethyl PGE2 added to the nutrient side significantly reduced the number of ulcers developed in the mucosa bathed in HCOrfree nutrient solution. In contrast, indomethacin and aspirin, but not salicylate, caused ulceration even in the mucosa bathed in HCO-3-nutrient solution. Histamine-induced acid secretion was reduced by 16,16-dimethyl PGE2 but not affected by these NSAIDs. In conclusion, ulceration of the isolated gastric mucosa in the presence of acid depends upon either a deficiency of endogenous PGs or a lack of nutrient HCO-3/CO

ISSN:0012-2823    

DOI:10.1159/000201259

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Indomethacin induces gastric ulcerations and decreases cell proliferation in the gastric ulcer margin. Since epithelial cell proliferation is under control of epidermal growth factor (EGF), we studied whether indomethacin may affect specific binding of [125I]-EGF to its receptors in cultured human gastric KATO III cells. To assess effects of EGF, indomethacin and their combination on cell proliferation, KATO III cells were incubated for 24 h with either (a) vehicle, (b) indomethacin (doses from 10-5 to 10-3M), (c) EGF (doses 0.01, 0.05 or 0.1 μg/ml) or (d) a combination of b and c, and the bromodeoxyuridine labeling index was determined. Indomethacin in a dose which did not affect cell viability significantly (by 21.5%) decreased [125I]-EGF binding to the KATO III cells and decreased the bromodeoxyuridine labeling index. Epidermal growth factor significantly increased cell proliferation and increased the labeling index from 28.9 ± 0.6% in the vehicle group to 36.2 ± 0.5%. Co-treatment with indomethacin significantly reduced the proliferative response of KATO III cells to EGF. In conclusion, indomethacin, in a dose which does not affect cell viability, decreased binding of EGF to cultured gastric KATO III cells and decreased their proliferative response to E

ISSN:0012-2823    

DOI:10.1159/000201260

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Patients with ulcerative colitis are usually non- or ex-smokers in contrast to Crohn’s disease where smoking is common. Abnormalities of quantity and quality of intestinal mucus have been postulated in the pathogenesis of these diseases. It is possible that smoking habit may exert its effects via changes in mucus in inflammatory bowel disease. We have therefore studied incorporation of N-acetylglucosamine into synthesized colonic mucin in explants from 85 controls with normal colonoscopic appearances and histology, including 27 smokers and 58 nonsmokers, 36 patients with ulcerative colitis and 19 with ileocolonic Crohn’s disease over 24 h in tissue culture. Incorporation of N-acetylglucosamine into normal explants was 31.3 ± (SD) 7.1 dpm/μg biopsy protein, incorporation was increased in patients with active Crohn’s disease (mean 41.2 ± (SD) 10.4 dpm/μg biopsy protein, p = 0.003), decreased in inactive ulcerative colitis (mean 24.1 ± 7.8 dpm/μg biopsy protein, p = 0.0006) but normal in active ulcerative colitis (mean 35.0 ± 13.8 dpm/μg biopsy protein, p = 0.44). No significant relationship was found between cigarette smoking habits and mucus synthesis in controls with normal mucosa (nonsmokers, n =58, mean 31.0 ± (SD) 7.52 dpm/μg biopsy protein; smokers, n = 27, mean 31.8 ± (SD) 6.1 dpm/μg biopsy protein, p = 0.9). This study shows that mucus glycoprotein synthesis is reduced in inactive ulcerative colitis, rising to normal levels in active disease and that synthesis is increased in Crohn’s disease. There is no effect of smoking on mucus synthesis by control biopsies suggesting that the differences seen in inflammatory bowel disease are not related t

ISSN:0012-2823    

DOI:10.1159/000201261

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

To assess the feasibility of a prospective incidence study of inflammatory bowel disease (IBD), the registration methods and incidence figures during 1990 were evaluated. The study was a collaboration between 14 hospitals in an area of close to one million inhabitants. Common diagnostic criteria for ulcerative colitis (UC), Crohn’s disease (CD) and indeterminate colitis (IND) were established prior to the start of the study. There was an overall incidence rate for IBD of 19.3 per 105 inhabitants, with 10.6 for UC, 5.1 for CD and 3.6 for IND.The age-specific incidence rates showed a peak between 25 and 34 years for UC and between 15 and 25 for CD. There was a male predominance for UC and a female preponderance for CD. These results are comparable with the previous registrations in western and northern areas of Norwa

ISSN:0012-2823    

DOI:10.1159/000201262

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Ursodeoxycholic acid (UDCA) is a nontoxic bile acid currently used in the treatment of different cholestatic diseases. This bile acid is also considered to be a ‘hypercholeretic bile acid’. The effects of daily administration of UDCA on bile flow and the bile acid secretion rate in man are not fully known. The aim of this study was to explore the effects by UDCA on bile flow and its different fractions. The biliary clearances of polyethylene glycol 900 (PEG 900) and mannitol were measured simultaneously in patients with an indwelling T tube after cholecystectomy. One group (n = 6) were given UDCA (10 mg/kg/day) for at least 14 days before the investigation and a control group (n = 8) received no bile acid treatment. The bile secretion was studied in acute experiments where bile was drained for 6 h. The bile plasma ratio for PEG 900 was 31 and that for mannitol was 0.7 which corresponds well with the results obtained in different animal species. The relationship between bile flow and the bile salt secretion rate, as expressed by linear regression analysis, showed no difference between the 2 groups (control y = 0.22 + 0.012x, r = 0.61, p < 0.001; UDCAy = 0.20 + 0.016x, r = 0.88, p < 0.001). The relationship between the biliary clearance of PEG 900 and the bile salt secretion rate, as expressed with linear regression analysis, showed a significantly steeper slope for the UDCA-treated patients (control y = 8.1 + 0.34x, r = 0.41, p < 0.05; UDCA y = 5 + 1.58x, r = 0.78, p < 0.001). No difference in the biliary clearance of mannitol was noted. Daily administration of UDCA did not increase bile flow or the bile salt secretion rate, but clearly enhanced the biliary clearance of PEG 900. One possible explanation for this finding is that UDCA increases the canalicular influx of water due to cholehepatic shunting of this bile a

ISSN:0012-2823    

DOI:10.1159/000201263

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

The purpose of this study was to investigate the utility of repeated applications of ceruletid to reduce gallbladder volume and its feasibility as a means of prophylaxis of acute acalculous cholecystitis in intensive care patients. First, a dose-response curve of ceruletid was obtained in 20 mechanically ventilated patients of a surgical intensive care unit (SICU) not receiving enteral nutrition. An effective dose of ceruletid, defined by a 50% reduction of gallbladder volume was established and subsequently studied in 40 mechanically ventilated SICU patients on total parenteral nutrition in a prospective, randomized, controlled, triple-blind trial. Gallbladder volume, sludge formation and side effects were evaluated. A dose of 1.5 μg/kg body weight ceruletid was established as the effective dose, causing 50% reduction of gallbladder volume in all patients studied and reduction of gallbladder sludge in 95%. In 67.5% of patients side effects were observed, requiring therapeutic intervention in 68%. It is concluded that ceruletid is effective in stimulating gallbladder contraction and reducing sludge formation in severely ill patients on intensive care units. Its routine use as prophylaxis of acute acalculous cholecystitis, however, may be limited by the nature, severity and frequency of side effects

ISSN:0012-2823    

DOI:10.1159/000201264

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

Fasting gallbladder volume and fasting gallbladder roundness index (ratio of anteroposterior diameter to gallbladder length) were estimated by ultrasonography in 182 normal subjects and 43 patients with gallstones and correlated to body size indices. In 20 of the normal subjects, gallbladder emptying was assessed and correlated to gallbladder roundness index. Gallstone patients had a larger fasting gallbladder volume as compared to normals (42 ± 10 vs. 22 ± 7 (SD) ml, p < 0.001). Gallbladder fasting volume was found to be significantly related to roundness index (p < 0.001) and body surface area (p 0.3 showed a less-complete gallbladder emptying as compared to those with a roundness index < 0.3 (p < 0.01). It is concluded that increased body size, but not obesity alone, is associated with an increased gallbladder fasting volume, and that a rounder gallbladder tends to empty less completel

ISSN:0012-2823    

DOI:10.1159/000201265

出版商:S. Karger AG    

年代:1995

数据来源: Karger

摘要:

The polyamines are involved in repair processes after intestinal ischemia. Arginine and ornithine, both precursors of polyamines were therefore expected to exert beneficial effects on mucosal barrier dysfunction. Arginine may also generate NO and there is support for the view that NO may be beneficial after an ischemic insult. Male Wistar rats were given, by gavage, isonitrogenous solutions of L-arginine (0.5 g/kg) or L-ornithine (0.7 g/kg) 17 and 2 h before ischemia. Controls received an isonitrogenous solution of casein hydrolysate (1 g/kg). Transient intestinal ischemia was produced in anesthetized rats by occluding the superior mesenteric artery for 90 min. Intestinal morphology, hydrolase activities, polyamine and cGMP contents, and cell proliferation rates were determined 4 h after reperfusion. Administration of arginine or ornithine did not prevent ischemic damage but accelerated morphological repair, enhanced cell proliferation, and polyamine content was observed. Arginine was significantly more effective than ornithine. Formation of cGMP was enhanced after arginine administration. NG-nitroarginine methylester, an inhibitor of NO synthase, prevented the arginine effects on mucosal repair. We conclude that arginine-derived NO is an important mediator in the restitution of intestinal mucosa by minimizing cell injury during reperfusion.

ISSN:0012-2823    

DOI:10.1159/000201266

出版商:S. Karger AG    

年代:1995

数据来源: Karger