Gülen Arslan

Relationship between Intestinal Permeability and Calprotectin Concentration in Gut Lavage Fluid

BACKGROUND Calprotectin is released from neutrophils and monocytes, and increased calprotectin levels in stool may serve as a marker of intestinal inflammation. Intestinal permeability is increased in inflammatory bowel diseases, especially in Crohn disease. We studied the relationship between intestinal permeability and calprotectin concentration in intestinal lavage fluid in patients with known or suspected inflammatory bowel disease (IBD). METHODS Thirty-eight patients were examined; 17 had Crohn disease; 3, ulcerative colitis; and 18, irritable bowel syndrome. Intestinal lavage was performed by means of a nasojejunal tube positioned by gastroduodenoscopy. By means of a peristaltic pump 2 l isotonic polyethylene glycol solution (MW, 3350) containing 50 microCi 51Cr-labelled ethylenediaminetetraacetic acid (EDTA) were administered through the tube over a period of 40 min. The first clear fluid passed per rectum was collected and analysed for calprotectin levels with an enzyme-linked immunosorbent assay method. Urine was collected for 5 h and analysed for gamma radioactivity. 51Cr-EDTA excretion in urine was expressed as percentage of dose administered (that is, intestinal permeability). RESULTS Both intestinal permeability and calprotectin concentration were significantly higher in patients with IBD than in patients with functional conditions. In Crohn disease the values depended on disease activity but not on whether the disease was located in the small or in the large bowel. There was a highly significant correlation between calprotectin concentration in gut lavage fluid and intestinal permeability (r=0.79, P<0.0001). CONCLUSION The significant correlation between calprotectin concentration in gut lavage fluid and intestinal permeability supports the view that increased intestinal permeability in IBD might, at least in part, be a consequence of increased transepithelial migration of neutrophils.Background: Calprotectin is released from neutrophils and monocytes, and increased calprotectin levels in stool may serve as a marker of intestinal inflammation. Intestinal permeability is increased in inflammatory bowel diseases, especially in Crohn disease. We studied the relationship between intestinal permeability and calprotectin concentration in intestinal lavage fluid in patients with known or suspected inflammatory bowel disease (IBD). Methods: Thirty-eight patients were examined; 17 had Crohn disease; 3, ulcerative colitis; and 18, irritable bowel syndrome. Intestinal lavage was performed by means of a nasojejunal tube positioned by gastroduodenoscopy. By means of a peristaltic pump 2 l isotonic polyethylene glycol solution (MW, 3350) containing 50 mCi Cr-labelled ethylenediaminetetraacetic acid (EDTA) were administered through the tube over a period of 40 min. The first clear fluid passed per rectum was collected and analysed for calprotectin levels with an enzyme-linked immunosorbent assay method. Urine was collected for 5 h and analysed for gamma radioactivity. Cr-EDTA excretion in urine was expressed as percentage of dose administered (that is, intestinal permeability). Results: Both intestinal permeability and calprotectin concentration were significantly higher in patients with IBD than in patients with functional conditions. In Crohn disease the values depended on disease activity but not on whether the disease was located in the small or in the large bowel. There was a highly significant correlation between calprotectin concentration in gut lavage fluid and intestinal permeability ( r = 0.79, P< 0.0001). Conclusion: The significant correlation between calprotectin concentration in gut lavage fluid and intestinal permeability supports the view that increased intestinal permeability in IBD might, at least in part, be a consequence of increased transepithelial migration of neutrophils.

Quality of life in patients with subjective food hypersensitivity: Applicability of the 10-item short form of the Nepean Dyspepsia Index

The aim of this study was to investigate quality of life and applicability of the 10-item short form of the Nepean Dyspepsia Index (SF-NDI) in patients with subjective food hypersensitivity. Fifty-two adult patients and 120 controls were examined using three questionnaires: Quality of life Nepean Dyspepsia Index (NDI), Gastrointestinal Symptom Rating Scale (GSRS), and Ulcer Esophagitis Subjective Symptoms Scale (UESS). To document psychometric properties, 20 of the patients filled in the SF-NDI questionnaire once more 4 weeks later. Patients had poor quality of life compared with controls from health care workers or general population (P < 0.001). Scores on SF-NDI were significantly correlated with scores on the GSRS (r = 0.34, P = 0.02) and UESS (r = 0.41, P = 0.003). The SF-NDI performed very satisfactorily, with a high reliability, construct validity, and responsiveness. Patients with subjective food hypersensitivity have considerably reduced quality of life. The SF-NDI provides reliable, responsive, and clinically valid measures of quality of life in these patients.

Subjective Health Complaints and Modern Health Worries in Patients with Subjective Food Hypersensitivity

Perceived food hypersensitivity is much more common than food allergy as medically verified. Unexplained symptoms and wrong attribution are typical in subjective health complaints. We hypothesize that subjective health complaints and worries are abnormally prevalent among patients with subjective food hypersensitivity. Forty-six patients with subjective food hypersensitivity and two control groups, one formed by 50 health care workers and one by 70 sex- and age-matched volunteers from the general population, were included in our study. All filled in two questionnaires: Subjective Health Complaints Inventory and Modern Health Worries Scale. None of the patients had IgE-mediated food allergy. The patients scored significantly higher than the controls on sum scores for four domains of subjective health complaints, including gastrointestinal complaints (P < 0.001), musculoskeletal complaints (P < 0.01), “pseudoneurology” (P < 0.001), and allergy (P < 0.001). Sum scores on modern health worries did not differ significantly between groups. The results support our hypothesis of an association between subjective food hypersensitivity and subjective health complaints, corroborating the view that, in the absence of food allergy, the conditions are sharing pathogenetic mechanisms.

Low‐dose oral ferrous fumarate aggravated intestinal inflammation in rats with dss‐induced colitis

Background: Oral ferrous iron therapy may reinforce intestinal inflammation. One possible mechanism is by catalyzing the production of reactive oxygen species. We studied the effects of low‐dose oral ferrous fumarate on intestinal inflammation and plasma redox status in dextran sulfate sodium (DSS)‐induced colitis in rats. Methods: Forty male Wistar rats were divided into 5 groups: no intervention, sham gavage (distilled water), ferrous fumarate, DSS, and ferrous fumarate + DSS. Ferrous fumarate was dissolved in distilled water (0.60 mg Fe2+/kg per day) and administered by gavage on days 1 to 14. All rats were fed a standard diet. Colitis was induced by 5% DSS in drinking water on days 8 to 14. Rats were killed on day 16. Histologic colitis scores, fecal granulocyte marker protein, plasma malondialdehyde, plasma antioxidant vitamins, and plasma aminothiols were measured. Results: DSS significantly increased histologic colitis scores (P < 0.001) and fecal granulocyte marker protein (P < 0.01). Ferrous fumarate further increased histologic colitis scores (P < 0.01) in DSS‐induced colitis. DSS + ferrous fumarate decreased plasma vitamin A compared with controls (P < 0.01). Otherwise, no changes were seen in plasma malondialdehyde, plasma antioxidant vitamins, or plasma aminothiols. Conclusion: Low‐dose oral ferrous iron enhanced intestinal inflammation in DSS‐induced colitis in rats.

Effects of duodenal seal oil administration in patients with inflammatory bowel disease.

Long-chain n-3 PUFA in fish oil have modulating effects on inflammatory responses. The aim of this open pilot study was to investigate whether duodenal seal oil administration would benefit patients with inflammatory bowel disease (IBD). Seal oil (10 mL) was administered three times a day directly into the distal part of the duodenum via a nasoduodenal feeding tube for 10 d in 10 patients, 5 of whom had Crohn’s disease and 5 ulcerative colitis. Nine of the 10 patients suffered from IBD-associated joint pain. Various parameters of disease activity and FA incorporation in tissues were analyzed before and after treatment. Following seal oil therapy, joint pain index, disease activity, and serum cholesterol level were significantly decreased, whereas the n-3 to n-6 ratio both in intestinal biopsies and blood was significantly increased. Measures of calprotectin concentration in gut lavage fluid, intestinal permeability, and lipid peroxidation were not significantly changed. The results suggest positive effects of seal oil in patients with IBD, especially on IBD-associated joint pain. Further controlled studies are warranted.

Patients with subjective food hypersensitivity: the value of analyzing intestinal permeability and inflammation markers in gut lavage fluid.

Background/Aim: Subjective food hypersensitivity is prevalent in the general population. The aim of this study was to seek objective evidence of food hypersensitivity by analyzing intestinal permeability and inflammation markers in gut lavage fluid. Methods: Fifty-two patients with abdominal complaints self-attributed to food hypersensitivity were examined by skin prick test, serum IgE analysis, double-blind, placebo-controlled food challenge (DBPCFC), and intestinal lavage. The results were compared with those of 44 patients without food hypersensitivity. Neither the patients nor the controls had organic diseases that could explain their symptoms. Intestinal lavage was performed by administering 2 liters of isotonic polyethylene glycol (molecular weight 3,350 daltons) solution containing 50 µCi of [51Cr]EDTA through a nasoduodenal tube. The first clear fluid passed per rectum was collected and analyzed for histamine, eosinophilic cationic protein (ECP), tryptase, and calprotectin. The intestinal permeability was assessed by determining the 5-hour urinary excretion of [51Cr]EDTA. Calprotectin was also analyzed in native faecal samples. Results: The ECP concentration in gut lavage fluid was significantly higher in the patients than in the controls (p = 0.007), but the overlap between groups was large. Food hypersensitivity was confirmed by positive DBPCFC in only 4 patients. On average, histamine and ECP concentrations were high in these patients. Tryptase, intestinal permeability, and faecal and lavage calprotectin levels were normal. Conclusions: Very few patients had objective evidence of food hypersensitivity. Analyzing intestinal permeability and inflammation markers in gut lavage fluid did not contribute to the diagnosis, but further studies on histamine and ECP are warranted.

Effects of short-term oral administration of dietary marine oils in patients with inflammatory bowel disease and joint pain: A pilot study comparing seal oil and cod liver oil

BACKGROUND Very long chain n-3 polyunsaturated fatty acids have modulating effects on inflammatory mechanisms. Seal and fish oils are rich in n-3 polyunsaturated fatty acids, and possibly therefore high doses of nasoduodenally administered seal oil rapidly relieved inflammatory bowel disease (IBD)-associated joint pain in two recent studies. In the present study, we compared the effects of short-term oral administration of seal oil and cod liver oil on IBD-related joint pain, leucotriene B(4) level, serum fatty acid profile and IBD activity. METHODS Thirty-eight patients with IBD-related joint pain were included in the study; 21 had Crohns disease and 17 ulcerative colitis. Ten milliters of seal oil (n=18) or cod liver oil (n=20) was self-administered orally 3 times a day for 14 days before meals in a double-blind setting. RESULTS There were no significant differences between the two intervention groups or between Crohns disease and ulcerative colitis patients. There was a tendency toward improvement in several joint pain parameters after both seal oil and cod liver oil administration. Further, plasma leucotriene B(4) concentration, serum Sigma n-6 to Sigma n-3, and arachidonic acid (20:4n-6) to eicosapentaenoic acid (20:5n-3) ratios were similarly reduced after administration of seal oil and cod liver oil. CONCLUSION No significant differences in the two treatment groups were seen; in both groups, the changes in several joint pain parameters, leucotriene B(4) level of plasma, and serum fatty acid profile were putatively favourable.

Response to intestinal provocation monitored by transabdominal ultrasound in patients with food hypersensitivity.

Objective Owing to lack of objective measures, the diagnosis of food hypersensitivity may be difficult. The aim of this study was to investigate whether the intestinal response to direct provocation in patients with food hypersensitivity could be recognized by ultrasound. Material and methods Thirty-two patients with chronic abdominal complaints, self-attributed to food hypersensitivity/allergy were included in the study. Via a nasoduodenal tube, the duodenal mucosa was challenged with the suspected food item dissolved in 10 ml water or saline. Using external ultrasound, the sonographic features (wall thickness and diameter of the duodenal bulb and jejunum, peristalsis activity and luminal fluid) were recorded before and during one hour after challenge. Results Sonographic changes were observed after challenge in 14 (44%) of the 32 patients. A positive sonographic response (increased wall thickness, diameter, peristalsis and/or luminal fluid) was significantly related to a positive skin prick test (p=0.008) and a positive double-blind placebo-controlled food challenge (p=0.03). A significant correlation was found between provocation-induced symptoms and wall thickness of the duodenal bulb (r=0.50, p=0.004) or the jejunum (r=0.42, p=0.02). Intra- and interobserver variation of the tracing procedure showed low values. Conclusions Responses of the proximal small intestines to direct provocation (swelling of the wall and exudation of fluid into the lumen) could be visualized by transabdominal ultrasound. This new provocation test could be helpful in the evaluation of patients with food hypersensitivity.

Food allergy and intolerance: response to intestinal provocation monitored by endosonography

OBJECTIVE Objective assessment of adverse reactions to food is a long-felt want. We report our preliminary experience with a new endosonographic allergen provocation test. METHODS Twenty patients were examined, seven patients having food allergy and 13 having food intolerance. The duodenal mucosa was challenged with allergen extracts via a nasoduodenal tube. The responses were recorded using a miniprobe for endosonography through the tube. Thereafter, intestinal lavage was performed by giving 2 l PEG solution containing micro Ci (51)CrEDTA. The gut lavage fluid and urine for 5 h were collected. RESULTS Increased mucosal thickness in response to provocation was recorded in 11 patients, but not more often or pronounced in the allergic than in the intolerance group. Interestingly, increased mucosal thickness associated with a new echogenic layer was seen in two patients and a sustained duodenal contraction, lasting 15-20 min associated with pain, in another two. Intestinal permeability and inflammatory mediators were not significantly different in the two groups. CONCLUSION In patients with self-reported adverse reactions to food abnormal responses to duodenal provocation may be recognised by endosonography. However, neither endosonography nor intestinal permeability or faecal calprotectin responses were able to distinguish between food allergy and intolerance. Sustained duodenal contractions in response to food might be a cause of abdominal pain.

Short-term duodenal seal oil administration normalised n-6 to n-3 fatty acid ratio in rectal mucosa and ameliorated bodily pain in patients with inflammatory bowel disease

BackgroundA high dietary intake of n-6 compared to n-3 fatty acids (FAs) may promote the production of pro-inflammatory eicosanoids and cytokines. In two recent studies, short-term (10-day) duodenal administration of n-3 polyunsaturated fatty acid rich seal oil ameliorated joint pain in patients with inflammatory bowel disease (IBD). Using unpublished data from these two studies we here investigated whether normalisation of the n-6 to n-3 FA ratio in blood and tissues by seal oil administration was associated with improved health related quality of life (HRQOL) as assessed by the generic short-form 36 (SF-36) questionnaire.ResultsIn the first pilot study, baseline n-6 to n-3 FA ratio in rectal mucosal biopsies from 10 patients with IBD (9 of those had joint pain) was significantly increased compared with that in 10 control patients without IBD or joint pain. Following seal oil administration, the n-6 to n-3 FA ratio of the IBD-patients was significantly lowered to the level seen in untreated controls. In the subsequent, randomized controlled study (n = 19), seal oil administration reduced the n-6 to n-3 FA ratio in blood similarly and also the SF-36 assessed bodily pain, while n-6 FA rich soy oil administration had no such effect.ConclusionIn these two separate studies, short-term duodenal administration of seal oil normalised the n-6 to n-3 FA ratio in rectal mucosa and improved the bodily pain dimension of HRQOL of patients with IBD-related joint pain. The possibility of a causal relationship between n-6 to n-3 FA ratio in rectal mucosa and bodily pain in IBD-patients warrants further investigations.