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Biomedical subjects

A Gabryelewicz

Publications and source records attributed to A Gabryelewicz.

At least 19 recordsLinked to original sources
PubMed2001

Does chronic ethanol administration have influence on pancreatic regeneration in the course of caerulein induced acute pancreatitis in rats.

UNLABELLED: This study was undertaken in order to determine the influence of chronic ethanol administration on pancreatic regeneration during acute pancreatitis (AP). Rats were pair fed with isocaloric diet containing or not ethanol. After 8 weeks of such feeding AP was induced by s.c. injection of caerulein (Cae). 6 h, 24 h and 5 days after first Cae dose pancreatic weight, amylase, chymotrypsin, protein, RNA, DNA contents were determined and phosphatidic acid (PA) production in isolated pancreatic acini was measured. Proliferating cells were quantified by immunochemical staining of cells incorporating bromodeoxyuridine (BrdU). RESULTS: Pancreatic weight was significantly higher at 6 h after first Cae injection in both, ethanol fed (EF) and control groups (C), however at 24 h pancreatic weight did not differ from prior to AP induction in EF rats. Ethanol feeding (EF) did not influence significantly protein, chymotrypsin and amylase content in pancreatic tissue in groups with AP. In EF rats RNA content after 5 days of AP was higher than in control animals. Total DNA content in EF rats with AP was lower 6 h after AP induction, earlier than in control animals with AP. Immunochemistry showed higher labelling index for BrdU after 6 h, 24 h and 5 days of AP in EF rats. In contrast to this findings, in EF animals, AP induction was not able to stimulate further PA accumulation. CONCLUSION: We conclude that chronic ethanol feeding, while inhibiting PA accumulation in comparison to control group, does not impair pancreatic tissue regeneration during the early phase of Cae-induced AP. Stimulation of regenerative/reparative processes in EF rats during Cae-induced AP seems to be even more pronounced than in the control group.

Acute Disease↗
PubMed2000

Lysosomal activity of pulmonary alveolar macrophages in acute experimental pancreatitis in rats with reference to positive PAF-antagonist (BN 52021) effect.

The activation of pulmonary alveolar macrophages (PAM's), might play an important role in severe complications of acute pancreatitis. The aim of our study was to assess the labilization of macrophage lysosomal membranes and release of lysosomal cathepsin B (CB) and N-acetyl-beta-D-hexosaminidase (NAH) into bronchoalveolar lavage fluid (BALF) during taurocholate acute pancreatitis (AP) in rats treated with PAF-antagonist--BN 52021. Total activity of CB increased by 374% after 6 h and by 237% after 12 h of AP in lysosomal enriched fraction of PAM's. Fractional free activity of CB increased to 40% after 6 h and to 38% after 12 h of AP. Free activity of CB was increased 5 fold in the supernatant of macrophage homogenate, and 10 fold in the supernatant of BALF after 6 h of AP. The values of NAH activity roughly paralleled that of CB. Treatment with BN 52021 (5 mg x kg(-1) every 6 h i.v.) partially normalized the measured parameters. Our results indicate that the PAF-antagonist BN 52021 reduced the increase of total and free activity of lysosomal hydrolases of PAM's and partly prevented the labilization of their lysosomal membranes. Therefore, an important mechanism of BN 52021 beneficial effect in pulmonary complications of acute pancreatitis could be dependent on the stabilization of PAM's lysosomes.

Acute Disease↗
PubMed2000

Activation of mitogen-activated protein kinases in different models of pancreatic acinar cell damage.

UNLABELLED: Mitogen-activated protein kinase (MAPK) family members, namely MAPK, c-Jun NH2-terminal protein kinase (JNK), and p38MAPK, have been recently reported to have opposing effects on apoptosis. AIM: To determine the activity of MAPKs and the level of Bax, Bcl-2 and p53--proteins known to be involved in the regulation of apoptosis--in pancreatic acini subjected to stressful stimuli leading to cell death. METHODS AND RESULTS: Isolated pancreatic acini were irradiated for 30 min with ultraviolet B (UV-B) or stimulated with supraphysiological concentrations of cholecystokinin (CCK). As it was assessed by means of acridine orange/ethidium bromide staining, irradiation with UV-B induced predominantly apoptosis while necrosis predominated in CCK-stimulated acini. The activity of MAPK, JNK and p38MAPK was determined by means of Western-blotting, with the use of antibodies which recognize active, dually phosphorylated enzymes. Irradiation with UV-B induced a rapid, 3-fold increase in MAPK activity. It had a maximum at 30 min and then gradually declined to reach the normal level at 120 min. Concomitantly, early activation of p38-MAPK was found at 30 min. However, unlike MAPK, p38-MAPK activity was then gradually rising to reach a maximum (5-fold increase) at 180 min. UV-B-induced activation of both kinases was not affected by the pretreatment with antioxidant--N-acetylo-L-cysteine or protein kinase C inhibitor--GF-109203X. In UV-B-irradiated cells, we did not detect any significant JNK activation as well as any significant changes in Bax, Bcl-2 and p53 levels assessed by means of Western-blotting. CONCLUSION: It seems likely that a specific interaction between MAPK and p38MAPK signaling pathway may be involved in the determination of the cell death mechanism in pancreatic acini subjected to stressful stimuli.

Animals↗
PubMed2000

Reactive oxygen species activate mitogen-activated protein kinases in pancreatic acinar cells.

It has been recently reported that kinases that belong to the mitogen-activated protein kinase (MAPK) family are rapidly activated by cholecystokinin (CCK) in rat pancreas both in vitro and in vivo. It is known that reactive oxygen species (ROS) play an important role in the pathogenesis of acute pancreatitis induced by supraphysiologic stimulation with CCK analogue, cerulein. The aim of our study was to evaluate whether MAPKs are activated by ROS in pancreatic acini. The activity of MAPK, c-Jun amino-terminal kinase (JNK), and p38 MAPK was determined in isolated rat pancreatic acinar cells by means of Western blotting, with the use of specific antibody that recognizes active, dually phosphorylated kinases. Incubation of acini with ROS donors, hydrogen peroxide (H2O2) and/or menadione (MND), strongly activated all three kinases. Activation of these kinases by ROS, but not by CCK, was substantially inhibited by pretreatment of acini with antioxidant N-acetylo-L-cysteine (NAC). Whereas CCK-induced activation of MAPK or JNK was totally or partially blocked by protein kinase C (PKC) inhibitor GF-109203X, ROS-induced activation of MAPK, JNK, and p38 MAPK was PKC independent. In conclusion, ROS strongly activate MAPK, JNK, and p38 MAPK in pancreatic acinar cells. It may be of importance in acute pancreatitis, because ROS are involved in the pathogenesis of this disease.

Acetylcysteine↗
PubMed1999

Role of oxidative stress in the pathogenesis of caerulein-induced acute pancreatitis.

In the last decade, the role of oxidative stress has been extensively evaluated in different experimental models of acute pancreatitis. This review shows that there is strong evidence that this stress occurs as an early phenomenon in pancreatic tissue in the course of caerulein-induced acute pancreatitis. Oxidative stress was documented in pancreatic tissue by means of methods showing generation of reactive oxygen species (e.g., chemiluminescence) and accumulation of products of reactive oxygen species-mediated lipid peroxidation. with concomitant depletion of enzymatic and low molecular weight antioxidants. Features of acinar cell injury and inflammation, especially pancreatic edema, show a marked improvement following treatment with a broad spectrum of antioxidants, platelet activating factor antagonists, or donors of nitric oxide (NO). Unfortunately, in most cases these beneficial effects are temporary and generally restricted to an early phase of the disease. However, results of well-designed clinical trials should finally evaluate the importance of oxidative stress-oriented treatment in acute pancreatitis in humans.

Acute Disease↗
PubMed1999

Double-blind comparison [correction of Double-blind, placebo-controlled comparison] of rabeprazole 20 mg vs. omeprazole 20 mg in the treatment of erosive or ulcerative gastro-oesophageal reflux disease. The European Rabeprazole Study Group.

BACKGROUND: Rabeprazole sodium is the most recent member of a class of substituted benzimidazole molecules known as proton pump inhibitors. Other proton pump inhibitors have been shown to be effective in healing oesophagitis. METHODS: In this randomised, double-blind, multicentre study, conducted at 27 European sites, the efficacy and safety of rabeprazole and omeprazole were compared in patients with erosive or ulcerative gastro-oesophageal reflux disease (GERD).100 patients received rabeprazole 20 mg, and 102 patients omeprazole 20 mg once daily for 4 or 8 weeks, with healing monitored by endoscopy. RESULTS: Overall GERD healing rates observed and evaluated at weeks 4 and 8 were equivalent. Four-week healing rates for rabeprazole and omeprazole were 81%-81% and 92%-94% for 8-week healing. Rabeprazole-treated patients had similar relief of the frequency and intensity of heartburn to those treated with omeprazole. Both drugs were well tolerated over the 8-week treatment period. Mean changes in fasting serum gastrin were comparable. No significant differences in laboratory parameters were seen. Biopsies for argyrophil ECL cell histology at the end-point revealed a similar distributions of hyperplasia grades to those at baseline in both groups. Biopsies of body and antral mucosa for other parameters were similar between treatments for Helicobacter pylori colonization, presence or degree of inflammation, atrophy or intestinal metaplasia at the end-point. CONCLUSION: In this study, GERD healing rates following rabeprazole 20 mg once daily were equivalent to those obtained with omeprazole 20 mg once daily. Both treatments resulted in a comparable relief of the frequency and intensity of heartburn associated with this disease, and both were well tolerated.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1999

Comparison of rabeprazole 20 mg versus omeprazole 20 mg in the treatment of active duodenal ulcer: a European multicentre study.

BACKGROUND: Rabeprazole sodium is the newest member of a class of substituted benzimidazole molecules known as proton pump inhibitors. Other proton pump inhibitors have been shown to be effective in healing active duodenal ulcer. METHOD: This randomized, double-blind, multicentre study, conducted at 25 European sites, compared the efficacy and tolerability of rabeprazole and omeprazole in patients with active duodenal ulcers. One hundred and two patients with active duodenal ulcer received rabeprazole 20 mg and 103 patients omeprazole 20 mg once daily for 2 or 4 weeks, with ulcer healing monitored by endoscopy. RESULTS: After 2 weeks, complete ulcer healing was documented in 69% of patients given rabeprazole 20 mg and in 62% of patients given omeprazole 20 mg (N.S.). After 4 weeks, healing rates were 98% in the rabeprazole group and 93% in the omeprazole group (P = 0.083). Rabeprazole-treated patients had significantly greater improvement in daytime pain symptom relief than those treated with omeprazole at the conclusion of the study (P = 0.038). Both drugs were well tolerated over the 4-week treatment period. Mean changes from baseline to end-point in fasting serum gastrin were significantly greater in the rabeprazole group, but at end-point mean values were well within normal limits for both groups. No clinically meaningful changes or other between-group differences were observed in laboratory parameters. CONCLUSION: In this study, rabeprazole produced healing rates equivalent to omeprazole at weeks 2 and 4, and provided significantly greater improvement in daytime pain. Both treatments were well tolerated.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1999

The role of nitric oxide in caerulein-induced acute pancreatitis and the recovery process after inflammatory damage.

OBJECTIVES: Nitric oxide (NO) is involved in the control of pancreatic blood flow and secretion, and its role in the maintenance of pancreatic tissue has been suggested. The aim of our study was to evaluate the influence of NO on pancreatic trophic parameters during acute pancreatitis induction and the pancreas recovery process. DESIGN/METHODS: Acute pancreatitis was induced in rats by a supramaximal dose of caerulein. During acute pancreatitis induction, rats were treated with L-arginine (a substrate for NO synthesis), glyceryl trinitrate (NTG, NO donor), glycine, N(G)-nitro-L-arginine (L-NNA, NO synthase inhibitor), L-arginine + L-NNA, or saline. Pancreatic weight, total contents of RNA, DNA, protein, amylase and chymotrypsin as well as pancreas histology and the number of proliferating acinar cells were evaluated after pancreatitis induction in all groups and additionally after 7 and 14 days of recovery in untreated acute pancreatitis rats or those injected with L-NNA and/or L-arginine. RESULTS: Pancreas destruction after acute pancreatitis was evidenced by similar decreases of all parameters in untreated acute pancreatitis rats or those treated with L-NNA or glycine when compared to control healthy animals. The recovery process after acute pancreatitis was not affected by L-NNA injections; however, the increased cell proliferation occurred later than in untreated rats. NTG and especially L-arginine treatment resulted in significant attenuation of pancreas damage (partially prevented by L-NNA treatment) as evidenced by biochemical data with a slight improvement in morphology. Treatment with L-arginine alone or in combination with L-NNA resulted in augmented cell proliferation after acute pancreatitis induction followed by earlier recovery in comparison to untreated acute pancreatitis rats or the L-NNA-injected group. CONCLUSION: The present study suggests the involvement of NO in mild acute pancreatitis and in the recovery process after inflammatory damage.

Acute Disease↗
PubMed1999

Pancreatic regeneration after chronic ethanol feeding in rats.

UNLABELLED: Increase of phosphatidic acid (PA) accumulation in response to caerulein (Cae) and after subtotal pancreatectomy (SP) has been previously described and phospholipase D (PLD) derived PA involvement in pancreatic regeneration was suggested. We also described decrease of Cae stimulated PA accumulation after a single dose of ethanol (both in vitro and in vivo). The present study was undertaken in order to determine the influence of chronic ethanol feeding on basal and Cae stimulated PA accumulation and other parameters of pancreatic regeneration in control and ethanol feed rats. Male rats were pair fed ad libitum with an isocaloric liquid diet (Lieber De Carli) with or without ethanol. In vitro study: pair fed rats were killed after 2 or 6 weeks of feeding, pancreata were dissected out and weighted, dispersed pancreatic acini were then prepared and loaded with 3H myristic acid in order to label the phosphatidylcholine pool. Phosphatidic acid (3H PA) accumulation, in the presence of propranolol, was measured after stimulation with increasing doses of Cae. In vivo study: PA was measured 3 days after SP or sham operation in both groups of rats, and also after 1 h of Cae infusion (0.25 microg/kg/h). Pancreatic weight, amylase, protein, RNA and DNA content were established. RESULTS: In vitro study 1) Basal PLD activity expressed as PA accumulation was significantly elevated after 6 weeks of ethanol feeding in comparison to the control values (28%). 2) Cae in doses ranging from 100 pM to 5 nM was not able to stimulate PA accumulation in isolated pancreatic acini prepared from ethanol fed rats. In vivo study: 1) Body weight and pancreatic weight were similar in, both the ethanol fed and the control groups, after 2 and 6 weeks. 2) Ethanol feeding significantly decreased total amylase content in the pancreas, but did not change protein, RNA and DNA content. 3) in contrast to the control animals in which SP caused a 71.1% increase of PA accumulation over the sham operation, subtotal pancreatectomy was not able to stimulate PA in rats fed with ethanol. 4) Also Cae infusion did not stimulate PA accumulation in the ethanol fed animals in comparison to the controls. Since the involvement of PLD activation in the early stages of pancreatic regeneration was postulated, our results suggest that chronic ethanol feeding can influence this process by decrease of PA production, probably because of the inhibition of hydrolytic PLD activity in the presence of ethanol. This could be one of the mechanisms responsible for pancreatic injury after chronic ethanol consumption.

Amylases↗
PubMed1999

Effect of Helicobacter pylori infection, smoking and dietary habits on the occurrence of antrum intestinal metaplasia. Clinico-epidemiological study in Poland.

The purpose of the study was to assess risk factors for intestinal metaplasia arising from H. pylori-related chronic gastritis in a subset of the population referred to endoscopic examinations due to dyspeptic complaints. We aimed specifically to establish whether H. pylori itself may be responsible for the occurrence of intestinal metaplasia and to which extent the metaplasia may be associated with life style factors such as cigarette smoking, alcohol consumption or dietary habits. The study was carried out in a sample of 1290 outpatients referred for the first time to gastroenterologic outpatient clinics in 6 university centers in Poland. The study methods covered standardized health interviews, endoscopy and histology of gastric antral specimens taken at endoscopy. The interviews performed by trained interviewers sought information on tobacco and alcohol intake, diet, socioeconomic status, and other variables. In non-ulcer dyspepsia subjects there was 54.9% H. pylori related gastritis and 25.1% of non-H. pylori-related gastritis. The corresponding rates in the group of ulcer dyspepsia were 67.5% and 20.5%. The increased risk of chronic gastritis in antrum was associated with Helicobacter pylori infection (OR = 2.28; 95% CI:1.93-2.69), and with gastric peptic ulcer (OR = 1.88; 95% CI:1.20-2.94). In the non-ulcer dyspepsia the prevalence of metaplasia was 11.1% and in ulcer dyspepsia 19.7%. The risk of intestinal metaplasia within antrum depended greatly upon the presence of gastric peptic ulcer (OR = 3.85; 95% CI:2.35-6.32) and increased with age (OR = 1.05; 95% CI:1.04-1.07), smoking cigarettes currently or in the past (OR = 1.42; 95% CI:1.10-1.84), higher frequency of drinking vodka (OR = 1.32, 95% CI:1.01-1.75) and antral chronic gastritis (OR = 1.31; 95% CI:1.00-1.70), however, it was inversely related to daily consumption of fresh fruits or vegetables (OR = 0.59; 95% CI:0.38-0.93). The results of the study suggest that there is no sufficient evidence supporting the hypothesis about an association between H. pylori gastritis and intestinal metaplasia, however, the transition of gastritis to metaplasia depends greatly on life style factors such as cigarette smoking or vodka drinking and is impeded by daily consumption of fresh fruits or vegetables.

Alcohol Drinking↗
PubMed1998

Comparison of rabeprazole 20 mg vs. omeprazole 20 mg in the treatment of active gastric ulcer--a European multicentre study. The European Rabeprazole Study Group.

BACKGROUND: Rabeprazole sodium is the newest member of a class of substituted benzimidazole molecules known as proton pump inhibitors. Other proton pump inhibitors have been shown to be effective in healing active, benign gastric ulcers. METHODS: In this randomized, double-blind, multicentre study, conducted at 25 European sites, rabeprazole and omeprazole were compared in patients with active gastric ulcers. Two hundred and twenty-seven patients with active benign gastric ulcer were randomized to receive either rabeprazole 20 mg (n = 113) or omeprazole 20 mg (n = 114) once daily for 3 or 6 weeks, with healing monitored by endoscopy. RESULTS: After 3 weeks, complete healing (ITT analysis) was documented in 58% of patients given rabeprazole and 61% in patients given omeprazole (N.S.). After 6 weeks the healing rates were identical in both groups at 91%. Rabeprazole-treated patients had numerically greater symptom relief at all 12 points of comparison. The differences significantly favoured rabeprazole at week 3 for daytime pain improvement (P = 0.023) and at week 6 for pain frequency (P = 0.006) and complete resolution of night pain (P = 0.022). Both drugs were well-tolerated over the 6-week treatment course. Mean changes from baseline to end-point in fasting serum gastrin were comparable. No significant differences in laboratory parameters were seen. CONCLUSION: In this study, rabeprazole produced healing rates comparable to omeprazole at weeks 3 and 6, but provided more consistent and occasionally significantly superior symptom improvement. Both treatments were well-tolerated.

2-Pyridinylmethylsulfinylbenzimidazoles↗
PubMed1998

The role of epidermal growth factor in platelet-endothelium interactions.

The objective of this study was to determine whether endogenous EFG released after submaximal physical exercise, affects platelet-endothelium interactions. Sixteen healthy male volunteers, aged 23-26 years, were submitted to a submaximal bicycle ergometry test. Blood for determination of EGF concentrations, platelet function studies (concentrations of beta-TG, PF4 and TXB2) and endothelium activity (LTC4 and endothelin-1,2 concentrations) was taken via an intravenous catheter before starting exercise and 15, 30 and 60 min after. A similar scheme was followed to investigate changes in the same parameters induced by a slow intravenous infusion of 0.3 mg/kg b.w. phentolamine (an alpha-adrenergic blocker) before exercise. Plasma concentrations of EGF and the markers of platelet function-beta-TG and PF4 as well as LTC4 concentrations increased only 15 min following exercise. The concentrations of TXB2, and endothelium-1,2 were almost unchanged 15 min after the submaximal bicycle ergometry test. Phentolamine markedly decreased the EGF concentrations in plasma (15 min following exercise) while at 30 and 60 min after exercise it had no effect on this parameter. No significant changes in concentrations of beta-TG, PF6, LTC4 and endothelin-1,2 after phentolamine infusion were found. These results show that increase of plasma EGF following exercise was accompanied with increase of beta-TG, PF4 and LTC4 concentrations. Inhibition of alpha-adrenergic receptors with phentolamine abolished the exercise-induced increase in plasma EGF concentration. The findings suggest that endogenous EGF may affect the platelet function and changes the reactivity of the vascular endothelium.

Adult↗
PubMed1998

Oxidative stress as an early prognostic factor in acute pancreatitis (AP): its correlation with serum phospholipase A2 (PLA2) and plasma polymorphonuclear elastase (PMN-E) in different-severity forms of human AP.

The role of oxidative stress as an important pathogenetic factor in experimental AP is commonly accepted, but its role in human AP has still not been evaluated satisfactorily. In the present study we compared the parameters of oxidative stress to the level of PLA2 and PMN-E in patients with AP. The study was performed in 77 patients with mild (n = 31), moderate (n = 20), and severe (n = 26) AP (alcoholic and biliary) as assessed according to Ranson's and Balthazar's criteria. Serum and urine malondialdehyde (MDA) concentrations, as an index of oxidant-mediated lipid peroxidation, and sulfhydryl (SH) groups, a major nonenzymatic antioxidant, were measured along with serum PLA2 and plasma PMN-E at admission (day 0) and on days 2, 5, and 10 of the disease. The Serum MDA level in severe AP was elevated by 267% on day 0 and 230% after 10 days, in comparison to the control, by 104 and 105% in comparison to mild AP, and by 50 and 76% in comparison to moderate AP, respectively. This was accompanied by a decrease in serum SH groups by 23% on day 0 and 36% after 10 days, in comparison to the control, by 31 and 32% in comparison to mild AP, and by 20 and 11% (ns) in comparison to moderate AP, respectively. In all severity forms of AP, oxidative stress was proportionally accompanied by increased levels of PLA2 and plasma PMN-E. In conclusion, oxidative stress is an early phenomenon in patients with AP, and at the time of admission it is detectable in the serum and urine. The intensity of oxidative stress correlates with the severity of AP. Because of the significant correlation between MDA and PLA2 or PMN-E, we suppose that the parameters of oxidative stress may be useful as another early prognostic factor in human AP.

Acute Disease↗
PubMed1997

Does antecedent ethanol intake affect course of taurocholate pancreatitis in rats?

The pathogenic role of acute ethanol abuse in acute pancreatitis (AP) is still obscure. The aim of the study was to evaluate the effect of antecedent intake of a high dose of 40% ethanol (5 g/kg body wt.), on trypsinogen activation, pancreatic lysosomal membrane labilization, and activities of phospholipase A2 and lipase in taurocholate AP in rats. In 80 male Wistar rats, AP or sham operation (SO) was produced 6 hr after intragastric saline (S) or ethanol (E) administration, and animals were sacrificed after 6, 12, and 18 hr. Free active trypsin (FAT) and total potential trypsin (TPT) were assayed in the pancreatic homogenate. Percentage free activity (%F/T) of cathepsin B was determined as an index of lysosomal membrane fragility. The most evident activation of trypsin occured at 6 hr AP (11.6% of TPT in S group and 16.4% in E group). Antecedent ethanol increased FAT 18 hr after SO from 0.105 +/- 0.048 microg/g protein to 0.258 +/- 0.054 and AP lasting 18 hr from 0.331 +/- 0.072 to 0.695 +/- 0.110. The %F/T of cathepsin B was highest at 18 hr of AP, suggesting maximal labilization of lysosomal membranes at this time. This labilization occurred earlier (at 12 hr of AP) in E group. The increasing effect of antecedent E on lipolytic enzymes was evident after 6 hr of AP. In conclusion, the antecedent intake of high dose of ethanol significantly promoted the conversion of trypsinogen to trypsin in taurocholate acute pancreatitis, whereas its additional effect toward labilization of pancreatic lysosomal membranes and the increase of lipolytic enzymes activities was less evident. Therefore, the promoting impact of acute ethanol intake in the development of acute pancreatitis could be mainly dependent on its increasing effect on trypsinogen activation.

Acute Disease↗
PubMed1997

The effect of beta-thia-iminoprostacyclin in taurocholate acute pancreatitis in rats: the role of antecedent acute ethanol abuse.

The promoting effect of acute ethanol (E) abuse and protective effect of prostaglandin derivatives in acute pancreatitis (AP) remain obscure. The aim of this study was to assess the effect of previous intake of high-dose E on trypsinogen (Tn) activation and labilization of pancreatic lysosomal membranes (PLM), in taurocholate AP in rats, considering treatment with stable beta-thia-iminoprostacyclin (T). In 60 male Wistar rats taurocholate AP was induced or a sham operation was performed. Half of them received 40% E (5 g/kg body weight), 6 h earlier. T (0.3 mg/kg body weight i.g.) was applied before E or before the induction of AP. Free active (FAT) and total potential (TPT) trypsin, free (F) and total (T) cathepsin B, phospholipase A2 (PLA2), and lipase (L) activities were assayed. Percentage FAT/TPT was an index of Tn activation and fractional free (% F/T) activity of cathepsin B was an index of PLM fragility. FAT increased after 12 h of AP, and in E rats this increase was even more evident. Pretreatment and treatment with T partly prevented this increase, however, this effect was abolished or limited in rats previously given E-the changes were not effected by T. PLA2 and L activities in AP were not diminished after T. The promoting effect of acute E abuse prior to AP could be dependent on augmented activation of Tn and labilization of PLM. The protective effect of T seems to be dependent on the decrease in Tn activation in pancreatitic tissue. The potential therapeutic effect of this drug in AP could be limited by previous acute E intake, as evidenced by differences in histopathological changes.

Alcohol Drinking↗
PubMed1997

Role of endogenous nitric oxide in the control of exocrine and endocrine pancreatic secretion in humans.

BACKGROUND: Nitric oxide (NO) is an unstable vasodilator formed by NO synthetase (NOS) from L-arginine (L-Arg) in various cells but its role in the control of pancreatic secretion in humans has not been examined. AIMS: This study was designed to determine the role of endogenous NO in the control of exocrine and endocrine pancreas using NOS inhibitor, NG-monomethyl-L-Arg (L-NMMA). METHODS: Pancreatic secretion was stimulated by intravenous infusion of secretin (80 pmol/kg/h) plus caerulein (50 pmol/kg/h) and duodenal content was aspirated by gastroduodenal tube. Two series of tests with secretagogue infusion were performed, one, with addition of graded doses of L-NMMA and, another, with addition of a constant dose of L-Arg alone followed by L-NMMA alone and finally by a combination of L-Arg and L-NMMA. RESULTS: Addition of L-NMMA in graded doses (2-8 mumol/kg/h) reduced dose dependently the secretin-caerulein stimulated pancreatic enzyme secretion without alterations in the volume flow and bicarbonate outputs. The addition of L-Arg to L-NMMA reversed the inhibitory action of L-NMMA on protein enzyme response to secretin-caerulein in these subjects. Secretin-caerulein infusion caused significant increase in plasma insulin and pancreatic polypeptide levels but without changes in plasma glucagon or somatostatin levels. L-NMMA alone resulted in a significant fall in plasma insulin and pancreatic polypeptide levels, while L-Arg added to pancreatic secretagogue infusion caused a significant increase of plasma insulin and pancreatic polypeptide levels above those attained with secretagogues alone. After the addition of L-Arg to L-NMMA, both plasma insulin and pancreatic polypeptide levels rose significantly above the levels observed with L-NMMA plus secretin-CCK stimulation. CONCLUSION: This study provides evidence that the suppression of NOS reduces pancreatic enzyme secretion and the plasma insulin and pancreatic polypeptide levels suggesting that endogenous NO affects both exocrine and endocrine pancreatic secretion in humans.

Adult↗
PubMed1997

Comparison of the efficacy and safety of ebrotidine in the treatment of duodenal ulcer. A multicentre, double-blind, placebo-controlled phase II study.

Ebrotidine (N-[(E)-[[2-[[[2-[(diaminomethylene)amino]-4 -thiazoly]methyl]thio]ethyl]amino]methylene]-4-bromo-benzenesulfon amide, CAS 100981-43-9, FI-3542) is a new H2-receptor antagonist characterized by its high receptor affinity and gastroprotective effect. This Phase II study has been undertaken to establish the efficacy and safety of ebrotidine, administered in four dosages as a single evening dose versus placebo in the treatment of duodenal ulcer. A total of 110 duodenal ulcer patients were studied in a randomized, double-blind, placebo-controlled, multicentre clinical trial. The patients were assigned to 5 groups: placebo, 200 mg, 400 mg, 600 mg and 800 mg of ebrotidine once daily. Controls were performed at baseline and every two weeks at four follow-up visits unless ulcer healed before. Endoscopic examination was the main parameter for the assessment of treatment efficacy and ulcer healing rate. Vital signs and blood/ urine analysis were used to establish safety. The three groups treated with higher dosages (400 to 800 mg of ebrotidine daily) showed an endoscopic ulcer healing rate of 90-95%, significantly higher than 55% achieved with placebo (p < 0.05), whilst the differences between these three dosages of ebrotidine were not statistically significant. Healing rate in the group treated with 200 mg of ebrotidine daily was not significantly different from that in the placebo group. The development of symptoms, number of episodes of ulcer-related pain, total ulcerated surface area or subjective ratings by the patients and investigators also differed significantly between ebrotidine (400, 600 and 800 mg daily) and placebo, and again, no marked differences were found between these three doses of ebrotidine. As far as tolerance is concerned, no clinically or statistically significant changes were observed in vital signs and analytical parameters. The incidence of side effects was less than that presented by the placebo group, possibly due to a greater consumption of antacids in this group. Results showed that a daily dose of 400 mg ebrotidine is effective and safe in the treatment of duodenal ulcers.

Abdominal Pain↗