Correlation between faecal excretion of indium-111-labelled granulocytes and calprotectin, a granulocyte marker protein, in patients with inflammatory bowel disease.

BACKGROUND: Several studies have suggested that clinical indices of disease activity in inflammatory bowel disease (IBD) do not adequately reflect the degree of inflammation in most such patients. Faecal excretion of indium-111-labelled neutrophilic granulocytes has been suggested as the gold standard of disease activity, but its complexity and high cost and the exposure of patients to ionizing irradiation have limited the use of this technique. The aim of this study was to investigate the correlation between the faecal excretion of the granulocyte marker protein calprotectin and that of 111In-labelled granulocytes. METHODS: Calprotectin in stool extracts from 19 patients with Crohn's disease (CD), 10 with ulcerative colitis (UC), and 9 presumably healthy controls was assessed with a simple enzyme-linked immunosorbent assay. Simultaneously, the faecal excretion of autologous 111In-labelled granulocytes was measured. RESULTS: There was a strong correlation between the average daily excretion of calprotectin and that of the total 3-day excretion of 111In-labelled granulocytes (r = 0.87, P < 0.0001). Furthermore, the concentration of calprotectin, assessed in a small stool sample on day 1, also correlated well with the excretion 111In-labelled granulocytes (r = 0.80, P < 0.0001). CONCLUSION: The results suggest that faecal calprotectin reflects the granulocyte migration through the gut wall in patients with IBD and hence might serve as a simple, inexpensive alternative to the indium-111 technique.

Granulocyte marker protein is increased in stools from rats with azoxymethane-induced colon cancer.

BACKGROUND: We wanted to investigate the relationship between the fecal levels of granulocyte marker protein (GMP) and the presence of aberrant crypt foci (ACF) and colorectal cancer in rats given injections of azoxymethane (AOM) and fed either of two different diets, a basal diet plus 20% corn oil or 20% beef suet, respectively. METHODS: The rats received intraperitoneal injections of AOM, 15 mg/kg, once weekly for 6 weeks and were killed after 22 weeks. RESULTS: In the group fed beef suet 17 of 19 rats developed colon cancer, whereas in the group fed corn oil 4 of 14 rats developed cancer. None of the 20 control rats fed either the beef suet or corn oil diets developed cancer or aberrant crypts, and GMP remained unchanged. Surprisingly, the numbers of ACF were significantly higher (467 versus 295; P = 0.004) in the group fed corn oil than in the group fed beef suet. On the other hand, the size (crypts/focus) of the ACF was significantly higher (P = 0.03) in the beef suet group. Furthermore, fecal GMP was significantly higher in the beef suet group than in the corn oil group after 18 weeks, and this difference increased further toward the end of the study. GMP was greatly increased in all rats with colorectal cancer. CONCLUSIONS: Fecal GMP may have provided us with a valuable tool for further studies of the induction and progression of neoplasia in rats and, possibly, in mice, since the anti-GMP antibody cross-reacts with feces extracts from mice.

[Skiing over Greenland--physical and psychological changes]. / På ski over Grønland--fysiske og psykiske forandringer.

Three Norwegian physicians crossed the inland glacier of Greenland on skis without any support. Body weight, fat and lean body mass was measured by dual X-ray absorptiometry scanning. Maximal oxygen uptake, lung capacity measurements, and various blood tests were recorded. Subjective health-related well-being and four transistory arousal states were also recorded (GHQ-30 and AD ACL, short form). One participant lost 1 kilo body weight, while the others gained 1 and 4 kilos, respectively, during the trip. Overall, lean body mass increased (1.2-4.0 kg), while body fat was reduced (0.4-2.7 kg). These changes reversed after four weeks. Bone mass, lung function and blood tests did not vary throughout the study period. The level of energy and calmness were high at baseline and even higher towards the end of the expedition, while the scores were low and stable for tiredness and tension. Subjective well-being increased for all participants towards the second half of the trip. We conclude that expeditions involving physical and mental strain can produce positive psychological changes. Catabolic conditions are avoidable. Changes in body mass composition revert quickly.

NO-naproxen vs. naproxen: ulcerogenic, analgesic and anti-inflammatory effects.

BACKGROUND: A novel class of nitric oxide-releasing nonsteroidal anti-inflammatory drug (NO-NSAID) derivatives has recently been described which exert anti-inflammatory activities but produce significantly less gastrointestinal injury than the parent NSAID from which they are derived. The present studies were performed to determine if a nitroxybutylester derivative of naproxen was less ulcerogenic to the gastrointestinal tract than its parent NSAID, and if it exerted comparable analgesic and anti-inflammatory properties to the parent NSAID. METHODS: The two drugs were compared in an acute gastric injury model, an antral ulcer model and after twice-daily administration for 18 days (small intestinal damage model). Anti-inflammatory activity was examined in the carrageenan-induced paw oedema model, while analgesia was examined in the acetic acid-induced writhing model. The pharmacokinetic profiles of naproxen vs. NO-naproxen were compared by HPLC analysis. RESULTS: NO-naproxen was found to produce significantly less gastric damage despite inducing similar increases in plasma TNF alpha to naproxen. With chronic administration, small intestinal damage was markedly less with NO-naproxen than with the parent NSAID. However, NO-naproxen exerted superior analgesic and comparable anti-inflammatory effects to naproxen. NO-naproxen was not completely converted to naproxen, but the reduced plasma levels of the latter was not the underlying reason for reduced gastrointestinal toxicity of NO-naproxen. CONCLUSION: NO-naproxen represents a novel, gastrointestinal-sparing NSAID derivative with superior analgesic and comparable anti-inflammatory properties to naproxen.

Assessment of disease activity in ulcerative colitis by faecal calprotectin, a novel granulocyte marker protein.

This study comprised 62 outpatients with ulcerative colitis who underwent 64 colonoscopies. The disease activity was evaluated according to endoscopic and histological criteria. The results revealed a significant correlation between both the endoscopic as well as the histological gradings of disease activity and faecal calprotectin. The median faecal calprotectin levels in the control group (6 mg/l) and in the patients with no or low disease activity (11.5 mg/l) were significantly different (p < 0.0001). The median calprotectin level among patients with active disease was 68 mg/l which was significantly different from the latter group (p < 0.0001). Furthermore, we suggest that the degree of inflammation rather than the extent of the disease determined the faecal calprotectin levels. In conclusion, assessment of faecal calprotectin seems to be a marker of disease activity in patients with ulcerative colitis.

Faecal calprotectin: a novel test for the diagnosis of colorectal cancer?

Calprotectin, a prominent cytosol protein in neutrophil granulocytes, was present in increased concentrations in stools from 50 of 53 patients with colorectal cancer, 32 of 40 patients with colorectal polyps, and all of 18 patients with gastric cancer. After radical surgery, faecal calprotectin levels reverted to the normal range in all but one patient with colorectal cancer. Calprotectin determinations are simplified by the stability of this protein in stools. Reliable estimates can be obtained in samples of only 5 g. On the basis of data from the literature, the test for calprotectin seems better than that for occult blood for the detection of gastrointestinal neoplasms.

Assessment of the neutrophil dominating protein calprotectin in feces. A methodologic study.

This study describes methods for extraction and quantification of calprotectin (L1 protein) in feces by enzyme immunoassay. This protein is a prominent antimicrobial component of neutrophils, monocytes, macrophages, and squamous epithelia. Calprotectin was stable in feces during storage for 7 days at room temperature. Small fecal samples taken from a 24-h feces collection gave a reliable estimate of calprotectin. Within-assay precision was 1.9%, and between-assay precision 14.8%. In healthy subjects (n = 33) median fecal calprotectin was 2025 micrograms/l and in hospital controls (n = 40) 10,500 micrograms/l. Median values in patients with Crohn's disease (n = 21) was 43,000 micrograms/l and in ulcerative colitis (n = 17) 40,000 micrograms/l. Fecal calprotectin was significantly correlated to fecal alpha 1-antitrypsin in the patients with Crohn's disease. Ten of 11 patients with gastrointestinal carcinomas had calprotectin level above the suggested reference limit of 6740 micrograms/l.