Increased mucosal matrix metalloproteinase-1, -2, -3 and -9 activity in patients with inflammatory bowel disease and the relation with Crohn's disease phenotype.

BACKGROUND AND OBJECTIVE: Matrix metalloproteinases are associated with matrix turnover in both physiological and pathological conditions. We postulate an association between aberrant matrix metalloproteinases proteolytic activity and the intestinal tissue destruction, seen in patients with Crohn's disease and/or ulcerative colitis. MATERIALS AND METHODS: Surgically resected inflamed and non-inflamed ileum and colon with/without extensive fibrosis from 122 Crohn's disease, 20 ulcerative colitis and 62 control patients were homogenized. Protein levels of matrix metalloproteinases and tissue inhibitor of metalloproteinases were measured by enzyme-linked immunosorbent assays (ELISA), while matrix metalloproteinases and myeloperoxidase activity were measured by specific activity assays. RESULTS: Expression of total levels of matrix metalloproteinases-1, -2, -3 and -9 relative to tissue inhibitor of metalloproteinases-1 and -2 was increased in inflamed inflammatory bowel disease compared to non-inflamed inflammatory bowel disease and control intestinal mucosa. Also, net matrix metalloproteinases-1, -2, -3 and -9 activity in inflamed inflammatory bowel disease was increased, with similar expression profiles in Crohn's disease and ulcerative colitis. Within inflamed inflammatory bowel disease, a close correlation of matrix metalloproteinases with myeloperoxidase was observed. The expression of matrix metalloproteinases and tissue inhibitor of metalloproteinases was similar in inflamed Crohn's disease tissue with or without extensive fibrosis and not related to fistulizing disease. CONCLUSIONS: We have shown increased net matrix metalloproteinases activity in intestinal inflammatory bowel disease tissue, likely to contribute to the tissue damage and remodelling seen in inflammatory bowel disease.

Faecal elastase-I: helpful in analysing steatorrhoea?

BACKGROUND: The faecal elastase-1 test (FE-1) is considered easy to perform and sensitive to detect severe and moderate exocrine pancreatic insufficiency. However, little information is available on the specificity of this test in the analysis of steatorrhoea. Our aim was to evaluate the clinical value of FE-1 in the analysis of patients sent in for faecal fat determination. METHODS: Stool samples were collected over 24 hours in 40 healthy controls and 119 patients: 58 patients with chronic pancreatitis and 61 nonpancreatic disease patients with chronic diarrhoea. Faecal fat excretion was determined and FE-1 was measured using a commercially available ELISA kit, which employs two monoclonal antibodies to bind to two distinct epitopes of human pancreatic elastase-1. RESULTS: Faecal elastase-1 test shows good reproducibility. The test lacks sensitivity in detecting exocrine pancreatic insufficiency and chronic pancreatitis (68 and 59%, respectively). However, it is specific with respect to differentiating pancreatic from nonpancreatic causes in patients with steatorrhoea. CONCLUSION: FE-1 lacks sensitivity to detect chronic pancreatitis. It can serve as a simple, noninvasive method to determine the aetiology of steatorrhoea.

Effect of cortisol and ACTH on corticosteroid-suppressed peripheral blood natural killer cells from healthy volunteers and patients with Crohn's disease.

Recently, we have shown that administration of adrenocorticotropic hormone (ACTH) to corticosteroid-treated Crohn's disease (CD) patients increased the peripheral blood natural killer (NK) cell activity which was suppressed by the corticosteroids. To elucidate this observation we analysed the in vitro effect of budesonide, prednisolone, cortisol, and ACTH on NK cells of healthy volunteers and corticosteroid-treated CD patients. Incubation of peripheral blood mononuclear cells (PBMNC) from healthy volunteers during the cytotoxicity assay caused a dose-dependent inhibition of NK cell activity by the three corticosteroids, while ACTH had hardly any effect. Pre-incubation for 18 h with high and low inhibiting concentrations also showed a significant inhibiting effect on NK cell activity of the corticosteroids. The percentage of CD56+ NK cells tended to increase after pre-incubation with a high inhibiting concentration of budesonide, prednisolone, and cortisol. Incubation of budesonide- or prednisolone-suppressed PBMNC from healthy volunteers and CD patients, with ACTH and/or cortisol, to mimic the in vivo situation, did not restore the corticosteroid-induced suppression of NK cell activity. The increase of the budesonide- or prednisolone-suppressed NK cell activity after in vivo administration of ACTH to the CD patients is therefore probably not a direct effect of cortisol or ACTH. Presumably other factors like cytokines and/or neurohormones must be involved in the in vivo interaction between corticosteroids, ACTH, and NK cells.

Sexual arousal and the quality of semen produced by masturbation.

The influence of sexual arousal on the quality of semen produced by masturbation was investigated. One group of 29 patients referred to our andrology outpatient clinic (group A) and one group of 14 healthy potential sperm donors filled out a questionnaire after having produced two semen samples, at least 1 month apart, by masturbation. Changes in questionnaire scores between first and second visit were compared with changes in semen characteristics between those two occasions to identify statistically significant correlations. A second group of 23 subfertility patients (group B) were asked to produce a semen sample by masturbation in a designated room at the hospital without additional sexual stimulation, and a second sample while viewing a sexually explicit video. Differences in questionnaire scores and semen characteristics obtained with visual erotic stimulation (VES) and without VES were analysed. In group A, the change in sexual arousal and change in intensity of orgasm correlated with change in semen volume (r = 0.38, P < 0.05; r = 0.48, P < 0.01 respectively). In healthy donors and group B, however, no such correlation was found. With VES in group B, significantly higher scores were given for 'feeling at ease/relaxed' (P < 0.01), 'sexual arousal' (P < 0.001), 'quality of erection' (P = 0.01), 'intensity of orgasm' (P < 0.05), 'satisfaction after orgasm' (P < 0.05), and 'ease with which orgasm was achieved' (P < 0.001) with VES compared to without VES. There was no statistically significant improvement in semen quality with VES compared to without VES. It is concluded that sexual arousal has no significant influence on the quality of an ejaculate produced by masturbation. On the other hand, providing a patient with a sexually stimulating video is obviously a facilitative factor when the patient 'has to' produce a semen sample for analysis. The use of visual erotic stimulation is recommended when patients and donors have to produce a semen sample in the university surroundings of a fertility clinic.

c-Ha-ras oncogene transfection does not affect NK cell sensitivity of human colorectal carcinoma cell lines.

BACKGROUND, MATERIALS AND METHODS: To investigate whether a c-Ha-ras oncogene, pointmutated in codon 12, modulates NK sensitivity of human colorectal tumor cells, this oncogene was introduced in two colorectal carcinoma cell lines, i.e. CaCo2 and SW480. RESULTS: Although transfection with this oncogene increased the levels of c-Ha-ras mRNA (4- to 5-fold) and induced phenotypic and genotypic changes, respectively, in the CaCo2 and SW480 cell lines, the susceptibility to NK cell lysis was only marginally affected. However, CaCo2 and SW480 cell lines transfected with a plasmid containing the wild type of the c-Ha-ras gene were found to be more sensitive to NK cells. CONCLUSIONS: The present study suggests that the sensitivity of human colorectal carcinoma cells to NK cell activity in vitro depends only marginally on the expression of the c-Ha-ras oncogene.

Stress relaxation of the human cervix: a new tool for diagnosis of cervical incompetence.

A method is described for determination of the stress-relaxation characteristics of the cervix uteri of non-gravid women after almost stepwise dilatation of the cervical canal by a water-filled balloon. The stress relaxation is followed by measurement of the pressure decay in the same balloon. Application of this atraumatic technique to women with a normal cervix and women known to have an incompetent cervix yields diagnostic ranges of various parameters, in particular a time constant and the elastic ratio. The technique seems promising for easy detection of cervical incompetence, allowing suitable measures to be taken for prevention of immature deliveries. A mechanical model of the tissue of the ostium internum has further been developed on the basis of the measured characteristics.