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Biomedical subjects

R H Dowling

Publications and source records attributed to R H Dowling.

At least 19 recordsLinked to original sources
PubMed1992

Nuclear magnetic resonance spectroscopy to determine the micellar cholesterol in human bile.

The cholesterol of gallstones comes from the vesicular rather than the micellar phase of bile. Progress in this field has been limited because conventional analytical methods disturb the distribution of cholesterol between the two phases. The resonance of the cholesterol C6 proton occurs at a chemical shift of 5.4 ppm, to be shown by 2D NMR to be specific for biliary cholesterol, and arises only from the micellar mode. Thus integration of the C6 proton resonance peak area provides a direct non-invasive determination of the cholesterol distribution in human bile.

Bile↗
PubMed1992

Calcium and carbonate ion concentrations in gallbladder and hepatic bile.

Calcium carbonate is a major component of gallstones, but there are few data on calcium and carbonate (CO3(2-)) concentrations in human bile. Therefore, in patients undergoing cholecystectomy for gallstones, total [CaTOT] and free ionized [Ca2+] calcium concentrations, pH, PCO2, and total [CO2] were measured and [CO3(2-)] was derived in gallbladder and hepatic bile (aspirated anaerobically at surgery or from T tubes). Gallbladder bile had lower pH (6.96 vs. 7.30) and total [CO2] (14.1 vs. 21.6 mmol/L), higher PCO2 (53.8 vs. 40.2 mm Hg), lower [CO3(2-)] (2.52 vs. 6.11 x 10(5) mol/L) and lower [Ca2+] x [CO3(2-)] ion product (1.88 vs. 4.74 x 10(-8) mol/L) than did hepatic bile. Gallbladder bile pH correlated positively with total [CO2], [CO3(2-)], and [Ca2+] x [CO3(2-)] but negatively with PCO2. Patients with surface gallstone calcification had similar gallbladder bile [CaTOT] and [Ca2+] but higher gallbladder bile pH (7.30 vs. 6.90), lower PCO2 (42.9 vs. 57.2 mm Hg), higher [CO3(2-)] (7.29 vs. 1.84 x 10(-5) mol/L), and higher [Ca2+] x [CO3(2-)] ion product [4.73 vs. 1.45 x 10(-8) (mol/L)2] than those with radiolucent gallstones. There were no differences in these parameters between patients with cholesterol stones and those with pigment stones. These data suggest that the human gallbladder acidifies bile by secreting hydrogen ion and that impairment of this secretion is one cause of calcified gallstone formation in humans.

Adult↗
PubMed1992

Gallstones during octreotide therapy.

Gallbladder stones (GBS) are found in up to 50% of patients receiving octreotide, but the reported prevalence of cholecystolithiasis in patients treated with octreotide is variable and little is known about gallstone incidence, composition, pathogenetic mechanisms, dissolvability, and primary prevention. Octreotide treatment apart, in industrialised societies most GBS are mixed in composition, cholesterol-rich (arbitrarily greater than 70% cholesterol by weight), radiolucent (70%), and, given a patent cystic duct (70%), dissolvable in bile rendered unsaturated in cholesterol by oral ursodeoxycholic (UDCA) +/- chenodeoxycholic (CDCA) acid treatment. They form when (1) GB bile becomes supersaturated with cholesterol (as the molar ratio of cholesterol to phospholipids in biliary vesicles approaches 1:1, the vesicles become unstable); (2) there is an imbalance between pro- and anti-nucleating factors, which favors cholesterol crystal precipitation; and (3) there is stasis within the GB as a result of altered motor function and/or excess mucus that traps the crystals. These changes may be associated with altered (4) biliary bile acid composition (more DCA and less CDCA than normal), and/or (5) phospholipid fatty acid composition (arachidonyl-rich lecithin acting as a substrate for mucosal prostaglandin synthesis which, in turn, may influence both gallbladder motility, and mucus glycoprotein synthesis and secretion). During octreotide treatment, meal-stimulated cholecystokinin (CCK) release is impaired leading to GB hypomotility, but little is known about the effects of octreotide on biliary cholesterol saturation, crystal nucleation time, mucus glycoprotein concentration, bile acid or phospholipid fatty acid composition. Most, but not all, reports suggest that the prevalence of GBS in octreotide-treated patients is considerably greater than that in age-, sex-, and weight-matched controls, but proof (by pre-treatment and on-treatment ultrasound) that the GBS were absent before, but developed during, therapy is not always available. Furthermore, there are few data on analysis of GBS composition in patients developing stones during treatment, although initial reports suggest that octreotide-associated GBS are also radiolucent, cholesterol-rich, and dissolve with oral bile acid treatment. Maximum GBS attenuation values, measured in Hounsfield Units (HU) by localized computerized tomography scanning of the GB, predict stone composition and dissolvability: GBS with scores of less than 100 HU are cholesterol-rich and dissolve well with oral bile acid treatment. However, preliminary results in 11 acromegalic patients treated with 200 to 600 micrograms octreotide/d for 29 to 68 months show that the HU scores range from 23 to 490 (mean +/- SEM, 116 +/- 41), suggesting that at least four of these 11 patients have non-cholesterol stones.(ABSTRACT TRUNCATED AT 400 WORDS)

Acromegaly↗
PubMed1992

Combination therapy with oral ursodeoxycholic and chenodeoxycholic acids: pretreatment computed tomography of the gall bladder improves gall stone dissolution efficacy.

In a five year study, 55 patients with radiolucent gall stones were treated with the combination of 7.5 mg chenodeoxycholic acid (CDCA) and 5.0 mg ursodeoxycholic acid (UDCA)/kg/day--that is, half the monotherapeutic doses. Side effects were few but four patients could not tolerate the prescribed bile acids because of diarrhoea or nausea. Analysis of fasting duodenal bile confirmed that CDCA+UDCA converted supersaturated into unsaturated bile but the saturation indices did not predict the dissolution response. By actuarial analysis, the confirmed (by ultrasound x2) complete gall stone dissolution rates in all 55 patients were mean (SEM) 29 (7)% at 12 and 44 (8)% at 24 months. The advent of routine computed tomography before treatment enabled comparison of dissolution efficacy in those screened by computed tomography (n = 24), whose maximum gall stone attenuation was less than 100 Hounsfield units, with that in those not screened (n = 29). Although stone size and number were comparable, patients screened by computed tomography had significantly better dissolution rates (p less than 0.025) than those not screened in this way. At 12 months, partial or complete gall stone dissolution rates were 93 (7)% in the screened and 55 (11)% in the non-screened patients. At 18 months, complete dissolution rates were 64 (12%) and 20 (9)% respectively. Computed tomography before treatment is cost effective in selecting those patients likely to achieve gall stone dissolution on treatment with UDCA+CDCA.

Adult↗
PubMed1992

Inhibition of human gall bladder mucus synthesis in patients undergoing cholecystectomy.

Hypersection of gall bladder mucus is associated with gall stone formation in animal models. Aspirin inhibits both mucus synthesis and secretion, prevents gall stone formation in animals and reduces gall stone recurrence in man after dissolution therapy. Mucus biosynthesis in human gall bladder mucosal explants is inhibited by aspirin in vitro. We have studied the effects of aspirin in vivo. Fifty five patients with functioning gall bladder and stones have been randomised, 27 to group 1 (aspirin EC 300 mg once daily for seven days before cholecystectomy) and 28 to group 2 (controls). Gall bladder bile composition was analysed and mucus synthesis rates measured using 3H-glucosamine incorporation into mucosal explants cultured for 24 hours. Patient age, sex, and gall bladder histology were similar in both groups. There were no differences in stone composition, gall bladder bile calcium concentration, cholesterol saturation and cholesterol nucleation time. The mean 3H-glucosamine incorporation in aspirin treated patients was 1347 fmol/g wet weight as compared with 2008 fmol/g wet weight in controls (95% confidence interval 222-1100, p<0.005, unpaired t test). This reduction in biosynthesis was associated with gall bladder bile mucus concentrations of 7.6 mg/ml in patients and 7.1 mg/ml in controls (ns). Treatment with aspirin led to a significant reduction in mucus biosynthesis by the gall bladder mucosa. This action is consistent with a role for aspirin in the prevention of gall stones.

Adult↗
PubMed1992

Gallbladder stones--dissolve, blast, or extract? Laparoscopic cholecystectomy versus 'the rest'.

This article reviews selected aspects of the non-surgical/minimally invasive treatments of gallbladder stones (GBS) and discusses briefly the residual role of these treatments in the era of laparoscopic cholecystectomy. In patients with specific, gallstone-related symptoms who wish to retain their 'functioning' gallbladders, there are at least six different management options. They range from rapid but invasive to slow but safe: i) the rotary lithotrite; ii) percutaneous cholecystolithotomy; iii) percutaneous transhepatic or iv) endoscopic retrograde cannulation of the gallbladder followed by instillation (manual or pump-assisted) of contact solvents; v) extracorporeal shock-wave lithotripsy + adjuvant bile acids and; vi) oral bile acids alone. The recommended investigation sequence is i) ultrasound (to diagnose the presence of GBS), followed by ii) oral cholecystography (to assess cystic duct patency, gallbladder anatomy and GBS size, number, lucency, buoyancy, and contour), and iii) regional computed tomography scanning of the gallbladder (to predict stone composition and dissolvability and to plan routes of access to the gallbladder). The decision-making steps are i) choice of some form of active treatment versus no treatment (other than observation); ii) in those with specific symptoms and a patent cystic duct who opt for active treatment, to choose between removing versus retaining the gallbladder; and iii) in those who wish to retain their 'functioning' gallbladder, to offer and select the most appropriate of the alternative options. In conclusion, despite the excellence of laparoscopic cholecystectomy, there remains a place for the non-surgical/minimally invasive approaches in a carefully selected minority of symptomatic GBS patients. Although GBS may recur in approximately 50% of patients, the recurrent stones are often asymptomatic, can be detected 'early' by follow-up ultrasound, and are easily treated. Ultimately, the aim of gallstone research must be to prevent not only recurrent but also primary GBS formation, which would obviate the need for both medical and surgical treatment.

Administration, Oral↗
PubMed1992

Cellular and molecular basis of intestinal and pancreatic adaptation.

This article reviews the structural and functional changes which develop in the intestine and pancreas in response to a variety of stimuli and which characterise adaptive hyper- or hypo-plasia. It then discusses the principal physiological mechanisms controlling this adaptive growth. In the gut, these include luminal nutrition, endocrine, autocrine and paracrine hormonal influences, growth factors, enterotrophic components of pancreatico-biliary secretions, neural factors, changes in blood flow and mesenchyme-epithelial interactions. The cell biology of adaptive growth involves cell membrane receptors (first messengers) and a cascade of intracellular second messengers, the best studied of which is changes in polyamine metabolism and in related enzymes. The effects of ornithine decarboxylase (ODC) blockade with difluoromethyl ornithine (DFMO) and of diamine oxidase (DAO) blockade with aminoguanidine, are described. In general, DFMO inhibits or prevents adaptive hyperplasia while in the small bowel, aminoguanidine treatment induces 'supranormal' adaptation. However, both the gut and the pancreas transport 'exogenous' (ingested in food and circulating in the blood stream) polyamines across their apical and basolateral membranes. The influence of this exogenous polyamine transport on 'endogenous' (enzyme-regulated) intracellular polyamine concentrations, is largely unknown. Finally, the molecular biology of adaptive growth is described briefly--as illustrated by the use of a growth hormone transgenic model in which mice develop marked intestinal mucosal hyperplasia and increases in the relative abundance of insulin-like growth factor-I (IGF-I) mRNA in the intestine.

Adaptation, Physiological↗
PubMed1991

Gall bladder emptying patterns in response to a normal meal in healthy subjects and patients with gall stones: ultrasound study.

In this study gall bladder emptying patterns in response to a solid meal were studied using ultrasound. A similar triphasic pattern was seen in eight healthy control subjects and eight patients with gall stones, with 'early' and 'late' net emptying phases separated by a period of net refilling with peak postprandial gall bladder volumes occurring at (mean (SD)) 33.1 (17.9) minutes and 27.4 (18.8) minutes in control subjects and patients, respectively. A phase of slower net emptying followed, which was complete at 146 (33) minutes in control subjects and 125 (33) minutes in the gall stone patients (not significant). Superimposed upon this overall triphasic pattern, postprandial gall bladder emptying was punctuated by repeated short lived episodes of filling and emptying. The mean (SD) estimated postprandial bile outputs were 0.83 (0.34) ml/min in four control subjects and 1.2 (1.1) ml/min in seven patients with gall stones. We propose a 'washout' model to reconcile this large turnover of bile with the concentrating and storage functions of the gall bladder and predict that the extent rather than the rate of gall bladder emptying is important in determining stasis of bile in the gall bladder.

Adult↗
PubMed1991

Gastric carcinogenesis in the rat induced by duodenogastric reflux without carcinogens: morphology, mucin histochemistry, polyamine metabolism, and labelling index.

Chronic duodenogastric reflux induces gastric adenocarcinomas in the rat without the use of carcinogens. Altogether, 186 male Wistar rats were randomised to undergo either a simple gastrojejunostomy or a gastrotomy and sacrificed at eight weekly intervals for 56 weeks. No control animals developed dysplasia or carcinoma. All rats subjected to a gastrojejunostomy showed hyperplasia of the proliferative neck zone, with increased sulphomucin production adjacent to the scar. Low grade dysplasia was found at 16 weeks, and carcinoma was first seen at 32 weeks. Most carcinomas were well differentiated mucin secreting adenocarcinomas of the expanding type, which secreted a mixture of sialomucins and sulphomucins. Duodenogastric reflux was associated with a 100% increase in labelling index (assessed autoradiographically with tritiated thymidine) in the gastric mucosa when compared with corresponding tissue adjacent to a gastrotomy scar. This increase was significant at eight weeks and persisted for 56 weeks after surgery. This study supports the theory that, in this model, hyperplasia precedes the development of carcinoma.

Animals↗
PubMed1991

Molecular differences between human and experimental pancreaticobiliary diversion-induced rat pancreatic neoplasia.

A series of molecular changes are now known to be seen in human pancreatic neoplasia, including the very frequent mutational activation of Kirsten ras oncogene at codon 12, overexpression of the epidermal growth factor receptor, and abnormalities of c-erbB-2 expression. In order to determine whether similar changes can be seen in animal models of pancreatic cancer a molecular analysis of tumours induced in rats by pancreaticobiliary diversion was performed. The polymerase chain reaction was used to amplify portions of the rat Kirsten ras gene and sequence specific oligonucleotide hybridisation was used to define whether sequences were wild type or mutant. No evidence of mutation was found in the Kirsten ras gene at codons 12 or 61, where activating mutations are known to occur. In addition immunohistochemical methods were used to investigate expression of c-erB-2 and the epidermal growth factor receptor but no evidence of abnormal expression was found. We conclude that there are major molecular differences between human and experimental rat pancreatic cancer.

Amino Acid Sequence↗
PubMed1990

Postheparin plasma diamine oxidase in health and intestinal disease.

In animals, the distribution of the enzyme diamine oxidase is confined, almost exclusively, to the small bowel mucosa. In humans, plasma diamine oxidase is at or below assay detection limits but can be liberated into the circulation from binding sites in the intestine by i.v. heparin. Therefore, the authors wished to see if diamine oxidase could be released by a low and safe dose of heparin (5000 U) and if the resultant area under the concentration-time curve would provide a noninvasive marker of segmental intestinal disease. In 17 control subjects, the mean area under the curve (following administration of 5000 U i.v. heparin) was 35.9 +/- 5.0 (SEM) mU.L-1.2 h-1; in 6 individuals studied on two separate occasions, postheparin plasma diamine oxidase profiles were reproducible (r = 0.98; p less than 0.001). The longitudinal distribution of diamine oxidase in the gastrointestinal tract, measured in 12 gastric, 16 jejunal, 6 ileal, and 18 colonic biopsies, was similar in humans to that found in animals. In patients with normal peroral biopsies, there was a linear relationship between jejunal mucosal and postheparin plasma diamine oxidase activities (r = 0.84; p less than 0.01). The areas under the curve in controls were then compared with those in patients with segmental intestinal diseases: 21 with ileal disease with or without colonic Crohn's disease (10 unoperated and 11 with ileal resection), 7 with non-Crohn's ileal resection, 8 with ulcerative colitis, 10 with untreated and 7 with treated celiac disease (6 studied before and after a gluten-free diet), and 5 studied during total parenteral nutrition and again after resumption of oral feeding. The results in the 18 ileectomized patients were subdivided into those with major (arbitrarily greater than 75 cm) and minor (less than 75 cm) resections. Areas under the curve were markedly reduced in nonresected Crohn's patients (6.0 +/- 1.79 mU.L-1.2 h-1; p less than 0.001 vs. controls), correlating inversely, in a first-order relationship, with disease activity (r = 0.82; p less than 0.001) and returning toward normal in 4 patients achieving disease remission. Low areas under the curve in total parenteral nutrition patients (4.5 +/- 0.9; p less than 0.001) were also reversible on resumption of oral feeding. However, areas under the curve were not significantly lower in patients with limited ileal resection (less than or equal to 75 cm), with celiac disease (untreated and treated), or ulcerative colitis than in controls.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗
PubMed1990

Recurrent urticaria and reduced diamine oxidase activity.

An abnormal metabolism of histamine has been suspected in urticaria and the role of diamine oxidase (DAO: histaminase) is therefore of interest. We have studied DAO activity in plasma and jejunal biopsy material and have measured the post-heparin DAO release in 11 control subjects and nine with recurrent urticaria, three of whom had had concurrent episodes of abdominal pain. Two of the nine urticaria subjects had only a minimal rise in plasma DAO activity after heparin, three had a response which was at the lower end of the normal range, and four were normal. In four out of five cases in which jejunal biopsy activity was obtained, there was concordance between mucosal DAO activity and the post-heparin plasma DAO response. Those with abdominal symptoms had abnormally low mucosal DAO activity and the subject who was most severely affected had proven episodes of small bowel oedema.

Adult↗
PubMed1990

Effect of intestinal diamine oxidase (DAO) depletion by heparin on mucosal polyamine metabolism.

The aim of this study was to examine the relative importance of the enzymes ornithine decarboxylase (ODC) and diamine oxidase (DAO) in intestinal polyamine metabolism in normal rats. To study this we measured jejunal and ileal DAO and ODC activities and polyamine levels 2 h after injecting, in non-fasting male Wistar rats, either normal saline (controls) or a large dose of i.v. heparin to deplete intestinal mucosal DAO stores. We found that heparin significantly reduced mean DAO activity (p less than 0.001). As a result putrescine levels increased significantly in both jejunum (p less than 0.02) and ileum (p less than 0.01). Heparin-induced DAO depletion had no significant effect on spermine and spermidine levels at either site. The increased putrescine was associated with reduced ODC activity in both jejunum (p less than 0.01) and ileum (p less than 0.05). ODC activity correlated negatively with putrescine (p less than 0.001). These results suggest that (i) in normal rats, DAO is more important than ODC in regulating mucosal putrescine levels and (ii) putrescine exerts feedback inhibition of ODC.

Amine Oxidase (Copper-Containing)↗
PubMed1990

Role of polyamines in the early adaptive response to jejunectomy in the rat: effect of DFMO on the ileal villus:crypt axis.

To study the role of the polyamines putrescine, spermidine and spermine and of the enzymes controlling their synthesis (ornithine decarboxylase; ODC) and degradation (diamine oxidase; DAO) along the villus:crypt axis at the crucial early stage of the ileal adaptive response to jejunectomy, we measured polyamine concentrations and the activities of ODC, DAO and alkaline phosphatase (a marker of enterocyte maturity) in epithelial cells isolated by the Weiser technique from villus tips, mid villi, lower villi and crypts 4 days after surgery in transected control (TRC) and jejunectomised rats untreated or given the specific ODC blocker, alpha-difluoromethyl ornithine (DFMO, 2% in drinking water beginning 3 days before surgery). In the TRCs, there was a diminishing villus tip-to-crypt gradient not only in alkaline phosphatase but also in ODC and DAO activities. After jejunectomy, there were up to 93% increases in mean enterocyte ODC activity when compared with the corresponding cell fractions from the TRCs, but in both the control and jejunectomised rats, DFMO treatment markedly inhibited ODC activity (p less than 0.05-0.01) and reduced spermidine and particularly putrescine concentrations (p less than 0.005-0.001) in all four cell fractions. Only 4 days post-operation, jejunectomy stimulated a significant increase in ileal wet weight but DFMO treatment completely prevented this adaptive response and significantly reduced segmental intestinal weight (mg/cm) in the TRCs. These results (i) extend our knowledge of polyamines and related enzymes along the villus:crypt gradient in the normal intestine, (ii) provides the first data on these variables after resection, and (iii) lend further support to the hypothesis that changes in enterocyte ODC activity and in putrescine and spermidine concentrations play an important role in initiating the ileal adaptive response to proximal small bowel resection in the rat.

Adaptation, Physiological↗
PubMed1990

Effect of fasting and feeding on polyamines and related enzymes along the villus: crypt axis.

Fasting and feeding have profound effects on crypt cell production and small bowel mucosal growth but the mechanism whereby food stimulates villus tip enterocytes to influence crypt cell production is unknown. We therefore measured the activities of ornithine decarboxylase (ODC), diamine oxidase (DAO) and alkaline phosphatase (ALP--a marker of enterocyte maturity) and polyamine concentrations in epithelial cells from villus tips, mid villi, lower villi and crypts of small intestine in non-fasted controls and 18-24 h fasted rats. Fasting reduced crypt cell production and caused villus hyperplasia, DAO activity (mU/g) increased in control villus tips from 9.6 +/- (SEM) 0.8 to 12.3 +/- 1.5 after fasting (NS), from 7.6 +/- 0.4 to 13.9 +/- 3.0 in mid villi (p less than 0.01), from 5.7 +/- 1.0 to 10.4 +/- 7.4 in lower villi (p less than 0.01) and from 5.4 +/- 0.9 to 12.8 +/- 1.5 in the crypts (p less than 0.001). ALP showed a similar pattern of results. In contrast, fasting lowered ODC activity (pmol/mg protein/h) dramatically from 319 +/- 82 in control villus tips to 16.7 +/- 3.0 during fasting, from 297 +/- 59 to 10.7 +/- 3.6 in mid villi, from 224 +/- 45 to 6.3 +/- 2.8 in lower villi and from 150 +/- 31 to 5.8 +/- 3.3 in the crypts. Fasting reduced putrescine concentrations in all fractions but particularly in the crypts and in general was associated with increases in spermidine and spermine concentrations. The role of DAO in the maintenance of low putrescine concentrations during fasting is unclear.

Alkaline Phosphatase↗
PubMed1990

Is the intestine the sole source of heparin-stimulated plasma diamine oxidase? Acute effects of jejunectomy, ileectomy and total enterectomy.

The assumption that the intestine is the sole/major source of post-heparin diamine oxidase (DAO) has been tested only once by Kobayashi et al. in 1969. In this study we tested whether the intestine is indeed the sole/major source of post-heparin plasma DAO and furthermore we studied the relative contribution of jejunum and ileum to post-heparin plasma DAO. We measured non-fasting plasma DAO before and every 15 min for 2 h after i.v. heparin (4,000 U/kg BW) and compared the resultant areas under the concentration-time curves (AUCs: mU/l X 2 h) in unoperated controls, jejunectomised, ileectomised and totally enterectomised (from gastro-oesophageal to colorectal junctions) male Wistar rats. Total enterectomy virtually abolished the post-heparin rise in plasma DAO, the mean AUC falling from 55.3 +/- (SEM) 10.2 in controls to 2.1 +/- 1.1 after enterectomy (p less than 0.001). The mean AUCs after jejunectomy and ileectomy were 25.6 +/- 5.5 and 10.75 +/- 2.42, respectively. Therefore in acute jejunal and ileal resection the AUCs were 2.1 and 5.4 times, respectively, lower than those seen in the controls (p less than 0.02 and p less than 0.001). The difference in mean AUC values between jejunectomy and ileectomy groups was also statistically significant (p less than 0.05). We conclude that total enterectomy abolishes the post-heparin rise in circulating DAO activity, confirming that the intestine is the major source of post-heparin plasma DAO. The ileum contributes more than the jejunum to this post-heparin rise in plasma enzyme activity.

Amine Oxidase (Copper-Containing)↗
PubMed1990

Aminoguanidine blocks intestinal diamine oxidase (DAO) activity and enhances the intestinal adaptive response to resection in the rat.

The aim of this study was to assess the effect inhibiting diamine oxidase (DAO) activity on intestinal adaptation after 80% proximal small bowel resection in the rat. Aminoguanidine (AG), a DAO inhibitor, was administered subcutaneously (25 mg kg-1 day-1) to rats for 11 days after small bowel transection (n = 6) or resection (n = 6). Two additional groups of animals (n = 6) served as transection or resection controls and received normal saline subcutaneously for the same period. On day 12 after operation, the animals were sacrificed, mucosal homogenates prepared from the ileal remnants (or from the control ileum), analysed for DAO and ornithine decarboxylase (ODC) activities, and the concentrations of the polyamines putrescine, spermidine, spermine, and the indices of mucosal mass (wet weight, protein and DNA) measured. The results were expressed both per unit length intestine and per milligram mucosal DNA. AG treatment completely inhibited DAO activity in both the transection control and resected rats. In the AG-treated resection group, inhibition of DAO activity was accompanied by increases (p less than 0.005) in all three indices of mucosal mass (wet weight, protein and DNA per centimetre intestine), putrescine concentrations (p less than 0.05) and ODC activity per centimetre intestine (p less than 0.001) when compared with the saline-treated resection controls. The results of this study suggest that inhibition of the putrescine-degrading enzyme, DAO, enhances the adaptive response to intestinal resection. Therefore, DAO may play a major role in regulating adaptive intestinal mucosal growth. Furthermore, inhibition of DAO activity could be important therapeutically in patients with the short bowel syndrome.

Adaptation, Physiological↗