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Increased porphobilinogen deaminase activity in pre- and malignant tissue of the oesophagus
A36
Abstracts
/Netherlands
Journal
gastric juice and to dissolve in the alkaline duodenum. Fat is absorbed in the proximal jejunum and enzyme supplements need to be released in the distal duodenum. Slowly dissolving preparations, in combination with very high dosages (> 40000 U lipase/kg/day), raise the risk of colonic strictures, as reported recently (Lancet 1994;343:615-616). There are few objective data on dissolution times of ECM preparations at different pH levels. In healthy individuals, post-prandial pH in the distal duodenum is 5.67 (our observations). Intraluminal pH in the distal part of the duodenum of pancreatic-insufficient patients will be considerably lower than 5.6 because of low or absent pancreatic bicarbonate production. The aim of this study was to measure dissolution time in buffer solutions of different pH, for 5 ECM pancreatin preparations: 3 new high-strength and 2 regular strength preparations. Materials and methods: The following preparations were tested: Creon, Creon Forte (Solvay-Duphar), Pancrease, Pancrease-HL (Cilag) and Panzytrat (Knoll). Two capsules were placed in buffer solution at 37°C in a British Pharmacopeia (BP) dissolution testing apparatus. Fresh acetic acid/sodium acetate buffer solutions with pH between 4.0 and 6.0 (intervals of 0.2 pH units) were used. Solutions were stirred at 125 rpm and the rate of dissolution was monitored by taking 2-ml samples at regular intervals and measuring extinction at 280 nm, as described in BP. Measurements were repeated 6 times. Results: All preparations failed to dissolve at pH 4.0. Panzytrat and Pancrease-HL showed within 1 h: 40 and 55% dissolution at pH 5.0, rising to 67 and 79% dissolution at pH 5.2, and > 90% dissolution at pH 2 5.4. Creon and Creon Forte showed within 1 h: < 25% dissolution at pH I 5.2, with sharply rising rate of dissolution to > 90% dissolution at pH 5.4. Pancrease showed within 1 h: < 25% dissolution at pH I 5.2, rising to 55% within 1 h at pH 5.4, and > 90% at pH 2 5.6. All preparations dissolved completely ( > 90%) within 30 min at pH 6.0. Conclusions: (1) Pancreatic enzyme preparations that survive in gastric acid but dissolve rapidly at pH 5.2-5.6 are probably more effective. (2) Of the preparations tested, Panzytrat and Pancrease-HL best meet this criterion. Increased malignant Wilson *, Tilanus *. University
porphobilinogen deaminase activity in pre- and tissue of the oesophagus. P.D. Siersema ‘, J.H.P. A. Edixhoven-Bosdijk I, F.W.M. de Rooij ‘, H.W. Departments of ’ Internal Medicine Hospital, Rotterdam, Netherlands.
and
’ Surgery,
Administration of aminolevulinic acid (ALA) leads to porphyrin accumulation in some malignant turnours, and ALA has been used as a photosensitizer for photodynamic therapy. Porphyrin accumulation is due to an increased activity of porpohobilinogen deaminase (PBG-D) or a decreased activity of ferrochelatase or both. To determine whether ALA might be a photosensitizer of oesophageal turnours, we measured PBG-D and ferrochelatase in squamous-cell carcinoma and adenocarcinoma of the oesophagus, in normal squamous epithelium of the oesophagus and normal gastric mucosa and in metaplastic Barrett’s epithelium of the oesophagus, a premalignant condition. Tissue was obtained from patients undergoing oesophageal resection. Results are given in the table.
of Medicine
47 (1995)
AI -A42
Sq. cell ca. (n = 5) Adenoca. (n = 4) Barrett’s epith. (n = 3) Normal sq. epith. (n = 9) Gastric mucosa (n = 9)
PBGD (pmol/mg protein
Ferrochelatase (pmol/mg protein
43.1 f 9.9 * 44.9 + 9.5 l 39.0+ 9.2 * 21.6rtS.7 2l.lk5.9
485+ 174 3 447+218 3 373+207 3 301& 143 463 rtr220
’ p < 0.01, ‘p < 0.05 and 3p = NS compared to normal squamous epithelium. Conclusions: These results suggest that after ALA administration the increased PBG-D activity could result in greater accumulation of porphyrins in malignant tissue and in Barrett’s epithelium than in surrounding normal tissue. Our findings provide support for the concept of using ALA for photodynamic therapy of oesopheal cancer and Barrett’s epithelium.
Effect of gstrin on lower oesophageal sphincter characteristics and pstro-oesophageal reflux. J.W. Straathof, M. Coenraad, C.B.H.W Lamers, A.A.M. Masclee. Department of Gastroenterology-Hepatology, lands.
University
Hospital,
Leiden,
Nether-
Gastro-oesophageal reflux is common after meal ingestion. Intragastric nutrients potently stimulate gastrin release and gastric acid secretion. Little is known, however, about the role of gastrin in inducing postprandial gastro-oesophageal reflwc. We have therefore studied the effect of gastrin infusion leading to postprandial serum gastrin levels on lower oesophageal sphincter (LES) pressure, gastro-oesophageal reflux and reflux mechanisms, especially bn transient LES relaxations (TLESR), as the most important reflux mechanism. Ten healthy subjects (6M, 4F; age 22-29 yr) were studied with combined oesophageal pH-metry and manometry (Dentsleeve) for 180 min on 2 separate occasions in random order during (1) continuous intravenous infusion of gastrin-17 (15 pM. kg-‘. h-‘) or (2) saline (control). Serum gastrin levels (RIA) were determined at regular intervals. Results: Infusion of gastrin significantly (p < 0.01) increased serum gastrin from 27+4 to 74+ 8 rig/l, but in the control experiment no alterations in serum gastrin were observed. Infusion of gastrin significantly (p < 0.05) decreased LES pressure from 18 +3 mmHg (basal) to 12rt 2 mmHg (gastrin), in contrast to the control experiment (17*3 mmHg). The number of TLESR’s per hour was not significantly different between gastrin infusion and control: 3.1* 0.6 vs. 2.9 f 0.6 TLESR/h. However, the percentage of TLESR’s associated with reflux was significantly increased during gastrin infusion compared to control: 55&9 vs. 26+7% (p < 0.05). In addition, reflux time (% time pH below 4 in the distal oesophagus) during gastrin infusion was significantly increased over control: 3.8+0.7 vs. 0.6+0.3% (p < 0.05). Conclusions: In healthy subjects infusion of gastrin, leading to physiological postprandial serum levels: (1) significantly decreases LES pressure, (2) significantly increases gastro-
Abstracts
/Netherlands
Journal
gastric juice and to dissolve in the alkaline duodenum. Fat is absorbed in the proximal jejunum and enzyme supplements need to be released in the distal duodenum. Slowly dissolving preparations, in combination with very high dosages (> 40000 U lipase/kg/day), raise the risk of colonic strictures, as reported recently (Lancet 1994;343:615-616). There are few objective data on dissolution times of ECM preparations at different pH levels. In healthy individuals, post-prandial pH in the distal duodenum is 5.67 (our observations). Intraluminal pH in the distal part of the duodenum of pancreatic-insufficient patients will be considerably lower than 5.6 because of low or absent pancreatic bicarbonate production. The aim of this study was to measure dissolution time in buffer solutions of different pH, for 5 ECM pancreatin preparations: 3 new high-strength and 2 regular strength preparations. Materials and methods: The following preparations were tested: Creon, Creon Forte (Solvay-Duphar), Pancrease, Pancrease-HL (Cilag) and Panzytrat (Knoll). Two capsules were placed in buffer solution at 37°C in a British Pharmacopeia (BP) dissolution testing apparatus. Fresh acetic acid/sodium acetate buffer solutions with pH between 4.0 and 6.0 (intervals of 0.2 pH units) were used. Solutions were stirred at 125 rpm and the rate of dissolution was monitored by taking 2-ml samples at regular intervals and measuring extinction at 280 nm, as described in BP. Measurements were repeated 6 times. Results: All preparations failed to dissolve at pH 4.0. Panzytrat and Pancrease-HL showed within 1 h: 40 and 55% dissolution at pH 5.0, rising to 67 and 79% dissolution at pH 5.2, and > 90% dissolution at pH 2 5.4. Creon and Creon Forte showed within 1 h: < 25% dissolution at pH I 5.2, with sharply rising rate of dissolution to > 90% dissolution at pH 5.4. Pancrease showed within 1 h: < 25% dissolution at pH I 5.2, rising to 55% within 1 h at pH 5.4, and > 90% at pH 2 5.6. All preparations dissolved completely ( > 90%) within 30 min at pH 6.0. Conclusions: (1) Pancreatic enzyme preparations that survive in gastric acid but dissolve rapidly at pH 5.2-5.6 are probably more effective. (2) Of the preparations tested, Panzytrat and Pancrease-HL best meet this criterion. Increased malignant Wilson *, Tilanus *. University
porphobilinogen deaminase activity in pre- and tissue of the oesophagus. P.D. Siersema ‘, J.H.P. A. Edixhoven-Bosdijk I, F.W.M. de Rooij ‘, H.W. Departments of ’ Internal Medicine Hospital, Rotterdam, Netherlands.
and
’ Surgery,
Administration of aminolevulinic acid (ALA) leads to porphyrin accumulation in some malignant turnours, and ALA has been used as a photosensitizer for photodynamic therapy. Porphyrin accumulation is due to an increased activity of porpohobilinogen deaminase (PBG-D) or a decreased activity of ferrochelatase or both. To determine whether ALA might be a photosensitizer of oesophageal turnours, we measured PBG-D and ferrochelatase in squamous-cell carcinoma and adenocarcinoma of the oesophagus, in normal squamous epithelium of the oesophagus and normal gastric mucosa and in metaplastic Barrett’s epithelium of the oesophagus, a premalignant condition. Tissue was obtained from patients undergoing oesophageal resection. Results are given in the table.
of Medicine
47 (1995)
AI -A42
Sq. cell ca. (n = 5) Adenoca. (n = 4) Barrett’s epith. (n = 3) Normal sq. epith. (n = 9) Gastric mucosa (n = 9)
PBGD (pmol/mg protein
Ferrochelatase (pmol/mg protein
43.1 f 9.9 * 44.9 + 9.5 l 39.0+ 9.2 * 21.6rtS.7 2l.lk5.9
485+ 174 3 447+218 3 373+207 3 301& 143 463 rtr220
’ p < 0.01, ‘p < 0.05 and 3p = NS compared to normal squamous epithelium. Conclusions: These results suggest that after ALA administration the increased PBG-D activity could result in greater accumulation of porphyrins in malignant tissue and in Barrett’s epithelium than in surrounding normal tissue. Our findings provide support for the concept of using ALA for photodynamic therapy of oesopheal cancer and Barrett’s epithelium.
Effect of gstrin on lower oesophageal sphincter characteristics and pstro-oesophageal reflux. J.W. Straathof, M. Coenraad, C.B.H.W Lamers, A.A.M. Masclee. Department of Gastroenterology-Hepatology, lands.
University
Hospital,
Leiden,
Nether-
Gastro-oesophageal reflux is common after meal ingestion. Intragastric nutrients potently stimulate gastrin release and gastric acid secretion. Little is known, however, about the role of gastrin in inducing postprandial gastro-oesophageal reflwc. We have therefore studied the effect of gastrin infusion leading to postprandial serum gastrin levels on lower oesophageal sphincter (LES) pressure, gastro-oesophageal reflux and reflux mechanisms, especially bn transient LES relaxations (TLESR), as the most important reflux mechanism. Ten healthy subjects (6M, 4F; age 22-29 yr) were studied with combined oesophageal pH-metry and manometry (Dentsleeve) for 180 min on 2 separate occasions in random order during (1) continuous intravenous infusion of gastrin-17 (15 pM. kg-‘. h-‘) or (2) saline (control). Serum gastrin levels (RIA) were determined at regular intervals. Results: Infusion of gastrin significantly (p < 0.01) increased serum gastrin from 27+4 to 74+ 8 rig/l, but in the control experiment no alterations in serum gastrin were observed. Infusion of gastrin significantly (p < 0.05) decreased LES pressure from 18 +3 mmHg (basal) to 12rt 2 mmHg (gastrin), in contrast to the control experiment (17*3 mmHg). The number of TLESR’s per hour was not significantly different between gastrin infusion and control: 3.1* 0.6 vs. 2.9 f 0.6 TLESR/h. However, the percentage of TLESR’s associated with reflux was significantly increased during gastrin infusion compared to control: 55&9 vs. 26+7% (p < 0.05). In addition, reflux time (% time pH below 4 in the distal oesophagus) during gastrin infusion was significantly increased over control: 3.8+0.7 vs. 0.6+0.3% (p < 0.05). Conclusions: In healthy subjects infusion of gastrin, leading to physiological postprandial serum levels: (1) significantly decreases LES pressure, (2) significantly increases gastro-