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1.
Neurogastroenterol Motil ; 24(12): 1134-e572, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22963673

ABSTRACT

BACKGROUND: We previously showed that colonic mucosal biopsy supernatants from patients with irritable bowel syndrome (IBS) activate neurons of the human submucous plexus, an area with densely packed immune cells. Based on the concept that mucosa-nerve signaling is altered in IBS, we tested in this study whether the nerve sensitizing effect of IBS mucosal biopsy supernatants is more prominent in the submucous than myenteric plexus. METHODS: Fast neuroimaging with the voltage-sensitive dye Di-8-ANEPPS was used to record activity of guinea-pig submucous and myenteric neurons after application of constipation (C)- and diarrhea (D)-IBS supernatants (three each) and four supernatants from healthy control subjects. Results are based on recordings from 4731 neurons. KEY RESULTS: Control supernatants did not evoke significant responses in submucous or myenteric neurons. In contrast, all IBS supernatants evoked a significant spike discharge (median 3.6 Hz) in 46% of submucous neurons. This activation was significantly stronger than in the myenteric plexus where even twice the amount of supernatants evoked a lower spike frequency (median 2.1Hz) in only 8.5% of neurons. Pharmacological studies revealed serotonin, histamine, and proteases as components mediating neuronal activation. Individual application of these components revealed that only serotonin evoked a significantly stronger activation of submucous compared with myenteric neurons. CONCLUSIONS & INFERENCES: Direct neuronal activation by IBS mucosal biopsy supernatants is primarily a feature of submucous rather than myenteric neurons. This is associated with a stronger excitation of submucous neurons by serotonin. The plexus-specific effects support the concept that altered mucosa-nerve signaling underlies disturbances in IBS.


Subject(s)
Culture Media, Conditioned/pharmacology , Intestinal Mucosa/metabolism , Irritable Bowel Syndrome/metabolism , Neurons/drug effects , Submucous Plexus/drug effects , Action Potentials/drug effects , Adult , Animals , Biopsy , Electrophysiology , Female , Guinea Pigs , Humans , Male , Middle Aged , Myenteric Plexus/drug effects , Young Adult
2.
Eur J Clin Nutr ; 66(10): 1116-9, 2012 Oct.
Article in English | MEDLINE | ID: mdl-22872031

ABSTRACT

BACKGROUND/OBJECTIVE: Malnutrition is a prominent feature in liver cirrhosis, with deleterious impact on clinical outcome. The objective of this study is to investigate whether malnutrition is associated with increased gastrointestinal permeability in liver cirrhosis reflected by altered urinary excretion of non-metabolizable sugar probes. SUBJECTS/METHODS: Patients with advanced liver cirrhosis (Child Pugh Score B or C) were recruited. Nutritional status was determined according to the Subjective Global Assessment. Intestinal permeability was assessed by measuring the urinary excretion of orally administered, non-metabolized sugar probe molecules. The lactulose/mannitol ratio served as marker for intestinal permeability and reflects non-carrier-mediated transcellular and paracellular transport of the small intestine during the first 5 h. Sucrose recovery in urine within the first 5 h reflects gastroduodenal permeability; sucralose recovery in urine 5-26 h after consumption reflects colonic permeability. RESULTS: Sixty-four patients (56.7±10.8 years; 33% female) were included in the study. Twenty-one patients were considered well nourished according to the Subjective Global Assessment, 23 moderately nourished and 20 patients severely malnourished; 74% had alcoholic liver disease and 67% had cirrhosis stage Child C. Gastroduodenal and colonic permeability was significantly increased in patients with liver cirrhosis compared with 63 healthy controls (0.23±0.22 and 1.37±1.42% vs 0.14±0.10 and 0.41±0.72% in controls), but not different between well and malnourished subjects. Small intestinal permeability (lactulose/mannitol ratio) was increased in all patients (0.069±0.055%) and further increased in malnourished patients (0.048±0.031% vs 0.084±0.061%, P=0.004) due to decreased mannitol recovery only. CONCLUSIONS: Gastric, small intestinal and even colonic permeability was altogether increased in liver cirrhosis, and malnutrition was associated with further increased small intestinal permeability indicative of villous atrophy.


Subject(s)
Gastric Mucosa/metabolism , Intestinal Mucosa/metabolism , Liver Cirrhosis/metabolism , Malnutrition/metabolism , Aged , Atrophy , Dietary Sucrose/administration & dosage , Dietary Sucrose/urine , Female , Gastric Mucosa/pathology , Gastrointestinal Tract/metabolism , Gastrointestinal Tract/pathology , Humans , Intestinal Mucosa/pathology , Lactulose/administration & dosage , Lactulose/urine , Liver Cirrhosis/complications , Liver Cirrhosis/pathology , Liver Cirrhosis/physiopathology , Liver Cirrhosis, Alcoholic/complications , Liver Cirrhosis, Alcoholic/metabolism , Liver Cirrhosis, Alcoholic/pathology , Liver Cirrhosis, Alcoholic/physiopathology , Male , Malnutrition/complications , Malnutrition/pathology , Malnutrition/physiopathology , Mannitol/administration & dosage , Mannitol/urine , Middle Aged , Nutrition Assessment , Organ Specificity , Permeability , Severity of Illness Index
3.
Br J Anaesth ; 103(4): 511-7, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19648157

ABSTRACT

BACKGROUND: Cardiopulmonary bypass (CPB) impairs intestinal barrier function and induces systemic inflammation after cardiac surgery. The objective of this study was to evaluate the effect of profound haemodilution (haematocrit 19-21%) during normothermic CPB on gastrointestinal permeability and cytokine release in comparison with a standard haemodilution (haematocrit 24-26%). METHODS: This was a prospective, controlled, randomized pilot trial of 60 patients without gastrointestinal disease undergoing normothermic CPB (35.5-36 degrees C) for coronary artery bypass graft surgery. Gastrointestinal permeability was measured by the triple-sugar technique (sucrose, lactulose, and mannitol excretion in urine) before and after CPB. Interleukin (IL)-6, IL-10, and tumour necrosis factor alpha (TNFalpha) were quantified using enzyme-linked immunosorbent assays. RESULTS: Data from 59 patients (19-21% haematocrit, n=28; 24-26% haematocrit, n=31) were analysed. Data on gastrointestinal permeability were available for 47 patients (19-21% haematocrit, n=23; 24-26% haematocrit, n=24), blood samples for cytokine analysis from 59 patients. Mannitol excretion was normal before and after surgery without significant differences between the groups (after operation: 5.4% vs 2.9%, P=0.193). Lactulose and sucrose excretion was within a normal range before surgery and increased afterwards without differences between the groups. IL-6, IL-10, and TNFalpha were elevated after surgery, but there was no difference between the groups [IL-6 (P=0.78), IL-10 (P=0.74), and TNFalpha (P=0.67)]. CONCLUSIONS: Profound haemodilution during normothermic CPB brought about significant changes neither in intestinal permeability nor in cytokine release. It may be concluded that a haematocrit of 19-21% during normothermic CPB does not impair intestinal barrier function and cytokine response in patients without gastrointestinal comorbidity.


Subject(s)
Cardiopulmonary Bypass/methods , Coronary Artery Bypass/methods , Cytokines/biosynthesis , Gastrointestinal Tract/physiopathology , Hemodilution/methods , Aged , Body Temperature , Disaccharides , Female , Hematocrit , Humans , Intestinal Absorption , Intraoperative Care/methods , Male , Middle Aged , Permeability , Pilot Projects , Prospective Studies
4.
Neurogastroenterol Motil ; 21(11): 1203-e110, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19210628

ABSTRACT

There is growing evidence that STW 5 (Iberogast), fixed combination of hydroethanolic herbal extracts), besides being effective in functional dyspepsia, also improves symptoms in irritable bowel syndrome (IBS). Clinical data indicate that modulation of mucosal secretion is a promising approach to treat intestinal disorders associated with IBS. We therefore explored the effect of STW 5 on secretion in the human intestine and the mechanisms by which it acts. The Ussing chamber technique was used to measure mucosal secretion in human intestinal mucosa/submucosa preparations and in human epithelial cell line T84. In addition, we recorded STW 5 effects on human enteric neurons with voltage sensitive dye imaging. In human tissue and T84 cells STW 5 induced a dose-dependent increase in ion secretion that was significantly reduced by the Na-K-Cl cotransporter blocker bumetanide, the adenylate cyclase inhibitor MDL-12 330, the non-specific and selective cystic fibrosis transmembrane conductance regulator (CFTR) inhibitors glibenclamide and CFTR(inh)-172, respectively, and the blocker of calcium dependent Cl(-) channels (ClCa) SITS (4-acetamido-4-isothiocyanatostilbene-2,2-disulphonic acid). It was unaffected by amiloride, a blocker of epithelial Na(+) channels. In human tissue, the nerve blocker tetrodotoxin significantly suppressed the STW 5 response. STW 5 evoked an increased spike discharge in 51% of human submucous neurons. Results suggest that STW 5 is a secretogogue in the human intestine by direct epithelial actions and through activation of enteric neurons. The prosecretory effect is due to increased epithelial Cl(-) fluxes via CFTR and Ca-dependent ClCa channels. STW 5 may be a novel option to treat secretory disorders associated with IBS and constipation.


Subject(s)
Intestinal Mucosa/drug effects , Intestinal Mucosa/metabolism , Plant Extracts/pharmacology , Aged , Aged, 80 and over , Cell Line , Epithelial Cells/cytology , Epithelial Cells/drug effects , Epithelial Cells/metabolism , Female , Humans , Intestinal Mucosa/innervation , Ion Channel Gating/drug effects , Male , Middle Aged , Neurons/metabolism
5.
Eur J Clin Invest ; 39(2): 139-44, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19200167

ABSTRACT

BACKGROUND: Gastroduodenal and small intestinal permeability are increased in patients with Crohn's disease (CD) and intensive care patients. The relevance of colonic permeability has not yet been adequately investigated. The aim of this study was to investigate the clinical value of sucralose excretion as indicator for colonic permeability in these patient groups. DESIGN: After oral administration of four sugars and subsequent analysis of urinary excretion, gastroduodenal and intestinal permeability were calculated from saccharose excretion and lactulose/mannitol (L/M) ratio over 5 h, and sucralose excretion from 5 to 26 h in 100 healthy controls, 29 CD and 35 patients after coronary surgery (CABG). RESULTS: In controls, sucralose excretion was highly variable (0.67+/-0.92%) and not related to small intestinal permeability. In CD and CABG, L/M ratio was increased (0.054+/-0.060; 0.323+/-0.253 vs. 0.018+/-0.001 in controls). Sucralose excretion was increased in 77% of CABG but only in 7% of CD. There was an association between gastroduodenal and intestinal permeability in CD and CABG (r=0.72, and r=0.51), but sucralose excretion was not related to either one of these two parameters. Other than a weak association between sucralose and length of stay in intensive care in CABG patients (P=0.099), sucralose excretion was not related to clinical outcome. CONCLUSIONS: The proposed cut-off for normal sucralose excretion is 2.11%, but its high variability and lack of association to gastrointestinal permeability or clinical outcome leave it open, if it can provide information beyond established permeability tests.


Subject(s)
Colon/metabolism , Crohn Disease/urine , Intestine, Small/metabolism , Adolescent , Adult , Aged , Case-Control Studies , Female , Gastrointestinal Agents/urine , Humans , Lactulose/urine , Male , Mannitol/urine , Middle Aged , Permeability , Sucrose/urine , Sweetening Agents/metabolism , Young Adult
6.
Rheumatology (Oxford) ; 47(8): 1223-7, 2008 Aug.
Article in English | MEDLINE | ID: mdl-18540025

ABSTRACT

OBJECTIVES: The pain intensity of patients with FM has recently been reported to be correlated with the degree of small intestinal bacterial overgrowth (SIBO). SIBO is often associated with an increased intestinal permeability (IP). Increased IP, if shown in FM, may have pathogenetic relevance because it leads to the exposure of immune cells to luminal antigens and consequent immune modulation. It is currently unknown whether IP is altered in FM. We therefore examined the IP in a group of patients with primary FM and in two control groups, healthy volunteers and patients with an unrelated chronic pain syndrome, complex regional pain syndrome (CRPS). We hypothesized that patients with FM, but not volunteers or those patients with CRPS, would have altered IP. METHODS: Both gastroduodenal and small IP were assessed using an established three-sugar test, where urinary disaccharide excretion reflecting intestinal uptake was measured using HPLC. RESULTS: Forty patients with primary FM, 57 age- and sex-matched volunteers and 17 patients with CRPS were enrolled in this study. In the FM group, 13 patients had raised gastroduodenal permeability and 15 patients had raised small intestinal permeability, but only one volunteer had increased gastroduodenal permeability (P < 0.0001, chi-square test for the three groups). The IP values were significantly increased in the patient groups (P < 0.0003 for all comparisons, one-way analysis of variance). CONCLUSIONS: The IPs in primary FM and, unexpectedly, CRPS are increased. This study should stimulate further research to determine the implication of altered IP in the disease pathophysiology of FM and CRPS.


Subject(s)
Complex Regional Pain Syndromes/physiopathology , Fibromyalgia/physiopathology , Intestinal Absorption , Adult , Female , Gastric Mucosa/metabolism , Humans , Intestine, Small/metabolism , Male , Middle Aged , Pain Measurement/methods , Permeability
7.
Aliment Pharmacol Ther ; 26(7): 1025-33, 2007 Oct 01.
Article in English | MEDLINE | ID: mdl-17877509

ABSTRACT

BACKGROUND: A recent study reported that a non-synonymous single nucleotide polymorphism (rs11209026, p.Arg381Gln) located in the IL23R gene is a protective marker for inflammatory bowel disease. AIM: To analyse the frequency of p.Arg381Gln in three independent European inflammatory bowel disease cohorts and to evaluate how this variant influences disease behaviour. METHODS: We assessed a European cohort of 919 inflammatory bowel disease patients and compared the IL23R p.Arg381Gln genotype frequency with 845 healthy controls. Inflammatory bowel disease patients originated from Germany [Crohn's disease (CD): n = 318; ulcerative colitis (UC): n = 178], Hungary (CD: n = 148; UC: n = 118) and the Netherlands (CD: n = 157). Ethnically matched controls were included. We performed subtyping analysis in respect to CARD15 alterations and clinical characteristics. RESULTS: The frequency of the glutamine allele of p.Arg381Gln was significantly lower in inflammatory bowel disease patients compared with controls in a pooled analysis of all three cohorts (P < 0.000001) as well as in the individual cohorts (Germany: P = 0.001, Hungary: P = 0.02 and the Netherlands: P = 0.0002). The p.Arg381Gln genotype distribution was similar between CD and UC. We did not observe either statistical interactions between p.Arg381Gln and CARD15 variants or any significant associations between p.Arg381Gln genotype and subphenotypes. CONCLUSIONS: The p.Arg381Gln IL23R variant confers a protective effect against both CD and UC, but does not determine disease phenotype.


Subject(s)
Colitis, Ulcerative/genetics , Colonic Neoplasms/prevention & control , Crohn Disease/genetics , Nod2 Signaling Adaptor Protein/genetics , Polymorphism, Single Nucleotide/genetics , Receptors, Interleukin/genetics , Adult , Cohort Studies , Female , Genetic Carrier Screening/methods , Genotype , Humans , Male , Phenotype , Receptors, Interleukin/analysis
8.
J Int Med Res ; 35(1): 72-83, 2007.
Article in English | MEDLINE | ID: mdl-17408057

ABSTRACT

We studied the influence of sequential involvement of the gastrointestinal (GI) tract on the development of multiple organ dysfunction (MOD) after cardiopulmonary bypass (CPB). One hundred and forty-six patients undergoing elective cardiac surgery were included in this prospective observational study. Standardized oral inert-sugar tests (sucrose, lactulose, mannitol, sucralose) were performed before and after CPB in different patients. Enzyme-linked immunosorbent assay of plasma levels of endotoxin core antibodies (EndoCAb) were performed peri-operatively. The functional mucosal surface was calculated from the amount of mannitol absorbed from the GI tract. Lower urine concentrations of absorbed mannitol were observed pre-operatively in patients developing MOD. In binary logistic regression this was an independent parameter. Decreased plasma concentrations of EndoCAb after surgery were seen in every patient, but were more significant in patients developing MOD. A reduced pre-operative functional mucosal surface may predict the early occurrence of MOD after surgery.


Subject(s)
Cardiopulmonary Bypass , Gastrointestinal Tract/physiology , Multiple Organ Failure/physiopathology , Aged , Female , Humans , Male
9.
Gut ; 55(3): 342-7, 2006 Mar.
Article in English | MEDLINE | ID: mdl-16000642

ABSTRACT

BACKGROUND AND AIMS: A genetically impaired intestinal barrier function has long been suspected to be a predisposing factor for Crohn's disease (CD). Recently, mutations of the capsase recruitment domain family, member 15 (CARD15) gene have been identified and associated with CD. We hypothesise that a CARD15 mutation may be associated with an impaired intestinal barrier. METHODS: We studied 128 patients with quiescent CD, 129 first degree relatives (CD-R), 66 non-related household members (CD-NR), and 96 healthy controls. The three most common CARD15 polymorphisms (R702W, G908R, and 3020insC) were analysed and intestinal permeability was determined by the lactulose/mannitol ratio. RESULTS: Intestinal permeability was significantly increased in CD and CD-R groups compared with CD-NR and controls. Values above the normal range were seen in 44% of CD and 26% of CD-R but only in 6% of CD-NR, and in none of the controls. A household community with CD patients, representing a common environment, was not associated with increased intestinal permeability in family members. However, 40% of CD first degree relatives carrying a CARD15 3020insC mutation and 75% (3/4) of those CD-R with combined 3020insC and R702W mutations had increased intestinal permeability compared with only 15% of wild-types, indicating a genetic influence on barrier function. R702W and G908R mutations were not associated with high permeability. CONCLUSIONS: In healthy first degree relatives, high mucosal permeability is associated with the presence of a CARD15 3020insC mutation. This indicates that genetic factors may be involved in impairment of intestinal barrier function in families with IBD.


Subject(s)
Crohn Disease/genetics , Intestinal Absorption/genetics , Intracellular Signaling Peptides and Proteins/genetics , Mutation , Adolescent , Adult , Aged , Crohn Disease/physiopathology , Female , Genetic Predisposition to Disease , Humans , Intracellular Signaling Peptides and Proteins/physiology , Male , Middle Aged , Nod2 Signaling Adaptor Protein , Permeability , Polymorphism, Genetic
10.
Allergy ; 59(10): 1118-23, 2004 Oct.
Article in English | MEDLINE | ID: mdl-15355472

ABSTRACT

BACKGROUND: In a subgroup of patients with chronic urticaria (CU) the disease is caused by pseudoallergic reactions to food. The aim of this study was to investigate whether disturbances of the gastrointestinal barrier function play a role in the pathomechanism of the disease. METHODS: In 55 patients with CU gastrointestinal permeability was measured with an in vivo triple-sugar-test before and after 24 days of a diet low in pseudoallergens. Sucrose served as marker for gastroduodenal permeability, lactulose/mannitol ratio for intestinal permeability. RESULTS: Basal gastroduodenal and intestinal permeability were significantly higher in patients with urticaria as compared to controls. In 29 of the 55 patients skin symptoms decreased or completely disappeared during the diet (responders). Compared to nonresponders (n = 26), responders had a significantly higher gastroduodenal permeability before treatment (0.36 +/- 0.04 vs 0.15 +/- 0.01% sucrose; P < 0.001), which decreased after the diet (0.17 +/- 0.02; P < 0.001). The number of patients with Helicobacter pylori infections did not differ between the two groups. CONCLUSIONS: The results indicate that in a subgroup of patients with CU and pseudoallergy an impaired gastroduodenal barrier function may be of pathophysiological importance. The underlying mechanisms seem to be independent of H. pylori infection.


Subject(s)
Food Hypersensitivity/physiopathology , Gastric Mucosa/metabolism , Intestinal Absorption/physiology , Intestinal Mucosa/metabolism , Urticaria/physiopathology , Adult , Chronic Disease , Duodenum , Female , Food Hypersensitivity/immunology , Humans , Intestinal Absorption/immunology , Male , Middle Aged , Permeability , Stomach , Urticaria/immunology
11.
Aliment Pharmacol Ther ; 19(10): 1073-8, 2004 May 15.
Article in English | MEDLINE | ID: mdl-15142196

ABSTRACT

BACKGROUND: Mutations within the NOD2/CARD15 gene have recently been shown to be associated with Crohn's disease. AIMS: To investigate the clinical impact of the three common NOD2/CARD15 mutations in patients with Crohn's disease. METHODS: We investigated the prevalence of the three common NOD2/CARD15 mutations (Arg702Trp, Gly908Arg, 3020insC) in 180 patients with Crohn's disease, 70 patients with ulcerative colitis and 97 controls. In patients with Crohn's disease, prevalence of NOD2/CARD15 mutations were correlated to clinical and demographical parameters. RESULTS: In Crohn's disease patients, 35.6% carried at least one mutant allele of NOD2/CARD15 mutations compared with 14.3% of patients with ulcerative colitis (P = 0.006) and to 15.5% of controls (P = 0.0001). Genotype phenotype analyses revealed that NOD2/CARD15 mutations determined younger age at disease diagnosis (P = 0.03), ileal disease location (P = 0.01) and ileocecal resections (P = 0.0002). Interestingly, reoperation with resection of the anastomosis was significantly more frequent in patients with NOD2/CARD15 mutations (P = 0.01). CONCLUSIONS: Our investigations support the current hypothesis that NOD2/CARD15 mutations are associated with a phenotype of Crohn's disease with younger age at diagnosis, ileal involvement, ileocecal resections and a high risk of postoperative relapse and reoperation. NOD2/CARD15 mutations might therefore be used to identify high risk patients for relapse prevention strategies.


Subject(s)
Carrier Proteins/genetics , Crohn Disease/genetics , Intracellular Signaling Peptides and Proteins , Mutation/genetics , Adolescent , Adult , Female , Genotype , Humans , Male , Middle Aged , Nod2 Signaling Adaptor Protein , Phenotype , Polymerase Chain Reaction/methods , Polymorphism, Single Nucleotide
13.
Dig Dis Sci ; 40(2): 338-45, 1995 Feb.
Article in English | MEDLINE | ID: mdl-7851199

ABSTRACT

In this study the effects of partially hydrogenated chemically processed fats (CPF) and non-CPF on the ileal chyme fat and the fatty acid (FA) profile of the ileal mucosa and the subcutaneous tissue were analyzed. Samples were collected via an ileocutaneous fistula. For three months pigs were fed a control meal or diets containing either non-CPF high on 16:0, non-CPF high on 18:2 n6, CPF with 50% trans-18:1 or 20% trans-18:1. The latter fat was used after heat treatment. With both CPF diets, the fat content in the ileal chyme was three times higher than with non-CPF. In contrast to subcutaneous tissue reflecting dietary composition, changes in FA profile of ileal mucosa were restricted. Each non-CPF resulted in an increase of the characteristic major dietary FA. Both CPF increased the mucosal trans-FA percentage from 0 to 12% on average, although dietary composition was different. This study suggests: (1) less effects of trans-FA on the regulation of intraluminal fat load compared to saturated and cis-polyunsaturated FA, and (2) higher mucosal incorporation of trans-FA with heated CPF. This may play a role in the development of epithelial lesions in the ileum, which are known following ingestion of these fats.


Subject(s)
Dietary Fats/administration & dosage , Fatty Acids/analysis , Gastrointestinal Contents/drug effects , Ileum/drug effects , Intestinal Mucosa/drug effects , Animals , Biopsy , Dietary Fats/analysis , Gastrointestinal Contents/chemistry , Hot Temperature , Hydrogenation , Ileum/chemistry , Ileum/pathology , Intestinal Mucosa/chemistry , Intestinal Mucosa/pathology , Random Allocation , Swine , Time Factors
14.
Gut ; 35(10): 1424-8, 1994 Oct.
Article in English | MEDLINE | ID: mdl-7959199

ABSTRACT

In patients with active Crohn's disease and in a control group the fatty acid profiles in the whole lipid fraction of ileal and colonic mucosal biopsy specimens were determined by capillary gas chromatography. The biopsy specimens in Crohn's disease patients were taken from the inflamed terminal ileum as well as from the inflamed and macroscopically normal colon. Compared with controls the fatty acid distribution in the inflamed ileal mucosa was significantly characterised by (a) a decrease of 18:2 n6 and 18:3 n3 accompanied by a substantial increase of the highly polyunsaturated fatty acids 20:4 n6, 22:4 n6, and 22:6 n3 and (b) a higher unsaturation index of total fatty acids compared with controls. These changes were similar in the inflamed colon. Additionally, both the inflamed and the macroscopically normal colonic mucosa showed an increase of saturated (18:0) and a decrease of monounsaturated fatty acids (18:1 n9). Fatty acid profiles of ileum and colon showed side variations in controls, but not in the Crohn's disease group. These data suggest that in Crohn's disease changes in the distribution of polyunsaturated fatty acids seem to be the general feature of inflamed mucosa in small and large intestine. Results further suggest that colonic fatty acid metabolism in Crohn's disease is altered by degrees, showing changes in saturated and monounsaturated fatty acids as an additional, primary event.


Subject(s)
Colon/chemistry , Crohn Disease , Fatty Acids/chemistry , Ileum/chemistry , Acute Disease , Adolescent , Adult , Aged , Biopsy , Crohn Disease/pathology , Fatty Acids, Omega-3/chemistry , Fatty Acids, Unsaturated/chemistry , Female , Humans , Intestinal Mucosa/chemistry , Male , Middle Aged
15.
Z Gastroenterol ; 31(12): 727-34, 1993 Dec.
Article in German | MEDLINE | ID: mdl-8310726

ABSTRACT

Experimental investigations have shown alterations of the ileal mucosal surface after specific fat diets resembling early changes in Crohn's disease. An animal experiment in pigs has been conducted. After creation of an anisoperistaltic segment these were fed either a specific fat diet containing chemically processed, partially hydrogenated fats or a low fat control diet over a period of 3 months. Defined areas of the ileal lamina propria were examined by transmission electron microscopy with the underlying question to what extent ultrastructural alterations could be compared to Crohn's disease. In comparison to the control group these areas were characterized by a dense infiltration of "inflammatory" cells like lymphocytes, histiocytes, macrophages and plasma cells indicating a hyperplasia and activation of lympho-plasmocytotic cells. Additionally, a focal prominent infiltration of mast cells with degranulation was observed as well as a dilatation of axons with depletion of axonal organelles in half of the animals after fat-feeding. Compared to patients with Crohn's disease the results show obvious similarities. It is concluded, that chemically processed fats could cause direct stimulation of immunologically-specific and non-specific cells in the lamina propria mucosae or directly injure the intestinal mucosa with secondary infiltration of inflammatory cells into the lamina propria.


Subject(s)
Crohn Disease/pathology , Dietary Fats/adverse effects , Ileum/pathology , Animals , Dietary Fats/administration & dosage , Eosinophils/pathology , Female , Gastrointestinal Transit/physiology , Humans , Intestinal Mucosa/pathology , Lymphocytes/pathology , Macrophages/pathology , Mast Cells/pathology , Microscopy, Electron , Neutrophils/pathology , Plasma Cells/pathology , Swine
16.
Z Gastroenterol ; 30(6): 403-10, 1992 Jun.
Article in German | MEDLINE | ID: mdl-1636272

ABSTRACT

Regarding the unknown pathogenesis of Crohn's disease repeatedly the importance of diet has been accentuated. Epidemiological, biochemical and animal experimental results have focused on a possible relationship between the consumption of chemically processed, partial hydrogenated fats and the development of regional enteritis. In this context an experimental animal model in pigs was designed to analyze, whether transmission electron microscopic alterations of ileal mucosa could be induced by forage of chemically processed fats. By creation of a retroperistaltic ileal segment the contact time between chyme and intestinal mucosa was prolonged. Our underlying question was to what extent disorders of the intestinal barrier function could be compared to Crohn's disease. Present study concentrates on the epithelial-cell-layer. It was shown that in comparison to the control animals the lamina epithelialis mucosae of all animals after fat-feeding was characterized by: sublethal lesion of the enterocytes/crypt-epithelial cells (shortening and alteration of the microvilli, degeneration of mitochondria, formation of autophagocytic vacuoles); goblet cell hyperplasia and increased production of mucus; focal appearance of intraepithelial lymphocytes as well as presence of polymorphonuclear granulocytes in the epithelium; widening of the intercellular-space locally up to total loss of the functional structure of the epithelial-cell-layer. In total the picture can be evaluated as an inflammatory process of the ileal mucosa. It can be concluded, that chemically processed fats as used in the described experimental conditions could induce this process. The feature of mucosal damage shows obvious similarities to ultrastructural findings in Crohn's disease if compared.


Subject(s)
Crohn Disease/pathology , Dietary Fats/adverse effects , Intestinal Mucosa/pathology , Animals , Cytoplasmic Granules/ultrastructure , Epithelium/pathology , Female , Granulocytes/pathology , Ileum/pathology , Intercellular Junctions/ultrastructure , Lymphocytes/pathology , Microscopy, Electron , Swine
17.
Can J Physiol Pharmacol ; 68(12): 1495-502, 1990 Dec.
Article in English | MEDLINE | ID: mdl-2085795

ABSTRACT

The aim of the study was to clarify whether 5-hydroxytryptophan (5-HTP) stimulates the postprandial motor pattern of the duodenum in a similar way as that of the adjacent jejunal segment in dogs. Computerized analysis of motor patterns recorded by closely spaced strain gauges focused on the temporal and spatial distribution of the contractions. Results indicate that 5-HTP increased the incidence and the length of the spread of contraction waves after both an acaloric and a nutrient meal in the duodenum as well as in the adjacent jejunal segment. Effects were more pronounced after the nutrient than after the acaloric meal. After the nutrient meal, but not after the acaloric meal, 5-HTP additionally enhanced the number of both duodenal and jejunal contractions per minute and increased the force of duodenal contractions. The acaloric meal induced significant differences in the motor patterns between the duodenum and the adjacent jejunum. 5-HTP abolished these differences owing to a relatively stronger stimulation of duodenal motility. 5-HTP did not affect gastric emptying of both meals. We conclude (i) that 5-HTP is a potent stimulator of propagated contractions both in the duodenum and the adjacent jejunal segment and (ii) that intestinal motor patterns can be regulated independently of gastric emptying.


Subject(s)
5-Hydroxytryptophan/pharmacology , Eating/physiology , Gastrointestinal Motility/drug effects , Intestine, Small/drug effects , Animals , Dogs , Duodenum/drug effects , Gastric Emptying/drug effects , Jejunum/drug effects
18.
Am J Physiol ; 258(5 Pt 1): G738-44, 1990 May.
Article in English | MEDLINE | ID: mdl-2334000

ABSTRACT

This study was performed to clarify in detail the behavior of the propagation velocities and frequencies of contractions along the canine small intestine. In conscious dogs, duodenal, jejunal, and ileal contractions were recorded by multiple, closely spaced strain gauges and analyzed by a computerized method. During both the interdigestive and postprandial states, the propagation velocity increased from the duodenal bulb to the distal duodenum and declined aborally within the jejunum, reaching rather constant values in the ileum. The decrease was steepest in the proximal part of the jejunum. In contrast to the propagation velocities, the contraction frequencies were almost constant in the upper small intestine. In the ileum, the contraction frequencies were markedly lower than in the upper small intestine, indicating that the aboral decrease in frequency occurred in the distal parts of the jejunum. We conclude that both the propagation velocities and the frequencies of contractions decline aborally in a nonlinear fashion. However, the nonlinear patterns of the frequency and the propagation velocity gradients are different.


Subject(s)
Intestine, Small/physiology , Muscle Contraction , Muscle, Smooth/physiology , Animals , Dogs , Duodenum/physiology , Fluoroscopy , Ileum/physiology , Jejunum/physiology , Time Factors , Video Recording
19.
Dig Dis Sci ; 34(12): 1873-81, 1989 Dec.
Article in English | MEDLINE | ID: mdl-2598755

ABSTRACT

In this study special attention was paid to the characteristics of duodenal motility under the influence of various test meals. Closely spaced strain gauge transducers and a computerized method were used to analyze motor patterns of the duodenum and the adjacent jejunum. Compared with an acaloric meal, nutrients shortened the length of contraction spread in the duodenum from 5.2 +/- 1.0 to 3.8 +/- 0.5-2.8 +/- 0.6 cm and in the jejunum from 10.5 +/- 3.0 to 7.4 +/- 1.3-5.2 +/- 0.8 cm. Additionally, contraction frequency was reduced. Basic differences were found between duodenal and jejunal motility. They were most marked in absence of nutrients. The duodenal motor pattern was characterized by a lower contraction frequency (8.0 +/- 2.2 vs 11.1 +/- 1.8/min), a shorter length of contraction spread (5.2 +/- 1.0 vs 10.5 +/- 3.0 cm), and a higher incidence of stationary contractions (50% vs 34%). On the duodenal bulb 72% of contractions represented contraction waves, whereas in the mid-duodenum the predominant feature was stationary contractions (57%) promoting the mixing of chyme with secretions. The characteristic duodenal motor patterns might be related to special functions of the duodenum for transport and digestion.


Subject(s)
Duodenum/physiology , Food , Gastrointestinal Motility/physiology , Animals , Dogs , Eating , Energy Intake , Female , Gastric Emptying/physiology , Jejunum/physiology , Time Factors , Transducers, Pressure
20.
Can J Physiol Pharmacol ; 67(12): 1534-9, 1989 Dec.
Article in English | MEDLINE | ID: mdl-2627690

ABSTRACT

The aim of this study was to clarify if small doses of neurotensin (2.5 and 5.0 pmol.kg-1.min-1, i.v.) in dogs alter the postprandial motor pattern of the duodenum in comparison with the adjacent jejunum. The intestinal motor patterns were quantified by means of closely spaced strain gauge transducers and a computerized method. An acaloric viscous meal of cellulose was used to induce postprandial motility. Gastric emptying was measured radiographically. During intravenous control infusion of saline, the characteristics of duodenal and jejunal motor pattern were significantly different. The duodenum contracted at a lower rate and showed a higher incidence of stationary contractions. The lower dose (2.5 pmol.kg-1.min-1) of neurotensin showed no significant effects, whereas the higher dose (5 pmol.kg-1.min-1) significantly slowed gastric emptying and altered the motor pattern of both intestinal segments in a similar manner. It reduced the number of contractions, shortened the contraction spread, increased the incidence of stationary contractions, and decreased the incidence of propagated contractions. The alterations of motility caused enhanced mixing of luminal contents. The differences in motor patterns seen in the control state between both intestinal segments were diminished during neurotensin. Data revealed no differences in sensitivity of the duodenum and jejunum to neurotensin. Results suggest that neurotensin is one of the gastrointestinal peptides involved in regulating intestinal contractile patterns.


Subject(s)
Muscle, Smooth/drug effects , Neurotensin/pharmacology , Animals , Dogs , Duodenum/drug effects , Gastric Emptying , Gastrointestinal Motility , Jejunum/drug effects , Muscle Contraction/drug effects
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