Low blood selenium concentration in Crohn disease.
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Biomedical subjects
Publications and source records attributed to K Loeschke.
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We compared the effects of various nitrates, sodium nitroprusside (SNP), molsidomine, and its bioactive metabolite SIN-1, on platelet aggregation and on the activity of soluble guanylate-cyclase from human platelets. SIN-1 and SNP proved to be potent inhibitors of platelet aggregation and activated soluble guanylate-cyclase in contrast to nitrates and molsidomine which produced weak inhibition of aggregation and failed to activate soluble guanylate-cyclase. These results suggest a correlation between these products' inhibitory effect on aggregation and activation of guanylate-cyclase.
Electrolyte transport was studied in rat cecum and colon adapting to 60% resection of the small intestine. Four weeks after surgery, the absorbing gross surface area, dry and wet weight, net absorption in vivo of sodium, chloride and volume, net potassium secretion, transmural electrical potential difference and mucosal Na-K-ATPase specific activity were determined. In the cecum, all tissue mass parameters were increased compared to sham-operated controls. Net transport was stimulated per organ but not per unit mass, and potential difference and Na-K-ATPase remained unaffected. In the colon, surface area and wet weight increased slightly while dry weight and electrolyte transport were not influenced. Thus, by enlargement without a change in cell function, the cecum but not the colon contributes to electrolyte homoeostasis after 60% jejunoilectomy in the rat. Na-K-ATPase specific activity and electrical potential difference were higher in the colon than the cecum, suggesting segmental heterogeneity of the larger bowel with respect to Na-K-ATPase-linked active sodium absorption.
Electrolyte transport was studied in rat colon adapting to 50% small intestinal resection with cecectomy. Four weeks after surgery, colonic gross surface area, dry and wet weight were increased compared to sham-operated controls. Net absorption in vivo of sodium, chloride and volume was stimulated per organ and per unit tissue mass, and net potassium secretion was diminished. The electrical potential difference, mucosal Na-K-ATPase specific activity and cAMP concentration remained unaffected. In vitro, measurements of unidirectional fluxes and electrical parameters across isolated mucosa indicated enhanced electrically neutral sodium chloride absorption in the proximal and possibly diminished bicarbonate secretion in the distal colon. Thus, removal of the cecum in addition to partial jejunoilectomy induces profound adaptive changes in the colon, involving not only mucosal growth but also a functional reaction of the individual epithelial cell.
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The effect of the diphenolic laxatives bisacodyl and deacetylbisacodyl on mucus secretion and fluid, sodium and potassium net transport was studied in rat colon perfused in vivo. Mucus output in the effluent was determined as total protein-bound hexose. Deacetylbisacodyl was more potent than the parent compound and was used to investigate dose-response relationships. At a low concentration (0.1 mg/dl), mucus and potassium secretion were stimulated whereas sodium and fluid absorption were inhibited, or converted to secretion, only at higher concentrations (0.5-3.0 mg/dl). All effects were dose-dependent and reversible within 1 h. With longer lasting perfusion of deacetylbisacodyl, mucus appeared in two peaks, one initial peak and another after 4 h. The late peak contained newly synthetized glycoproteins as indicated by the incorporation of intravenously injected [14C]galactose. It is concluded that stimulation of mucus secretion and synthesis contributes to the laxative action of bisacodyl. The effects of low versus high concentrations suggests that part of the potassium secretion is due to mucus release.
In the European Cooperative Crohn's Disease Study patients from 14 centers were included in whom diagnosis was made within 2 years before study entry on the basis of generally accepted radiological, endoscopical and/or histological criteria or a combination of all. Reasons for exclusion were: diagnosis older than 2 years in patients who did not require active treatment, age less than 18 years, duration of symptoms less than 3 months, presence of complications which potentially required emergency surgery. Data on clinical features were obtained in 633 patients, of whom 452 were eligible to participate in the study. In 110 patients randomized to placebo the natural course of Crohn's disease was studied. Patients with ileocolonic involvement were younger than patients with either colonic or small intestinal involvement only. Classic ileitis terminalis was present in 14% of the patients. 49% of the patients had combined involvement of both the small and large intestine. 30% of patients had only small intestinal involvement, and in 21% colonic disease was present. Small intestinal involvement was associated with a significantly lower Crohn's Disease Activity Index (CDAI) than other anatomical locations of the disease. Perianal disease was more often associated with colonic than with small intestinal involvement. 60% of placebo patients with active disease at entry achieved at least a transient remission within the initial 5 months of study. After 2 years, 23% of patients with active disease at entry and 68% of patients with quiescent disease had reached or maintained a remission, respectively. By stepwise multiple linear regression analysis long duration of disease between diagnosis and randomization, normal serum albumin and combined involvement of small intestine and colon were identified as predictors of a more favorable outcome of patients treated with placebo. In contrast, extensive small bowel disease, treatment with steroids and bowel resection prior to study entry correlated with a less favorable outcome. However, by life table analysis outcome of previously untreated and treated patients in the placebo group was similar.
A 26-year-old patient developed HBsAg-, HBeAg-positive chronic active hepatitis arising from an acute infection 6 months earlier. Treatment with adenine arabinoside (Ara-A), 15 mg/kg/day administered as overnight infusions for three weeks, resulted in clinical and complete biochemical remission with normalisation of aminotransferases, loss of HBsAg, HBeAg and DNA polymerase, and appearance of Anti-HBs during follow-up for 9 months. Treatment of chronic hepatitis B infection using Ara-A for several weeks may be especially effective when initiated early in the course of the disease.
The effect of loperamide on deoxycholic acid (DOC)-induced secretion was studied in ligated loops of the rat jejunum and colon in vivo. In controls, loperamide slightly augmented fluid absorption. 3 mmol DOC caused net fluid secretion. Loperamide reduced this secretion in the colon and reversed it to absorption in the jejunum. Na-K-ATPase specific activity and cAMP levels were measured in the jejunum, and [14C]erythritol clearance as an index of mucosal permeability in the colon. In the jejunum this opiate analogue affected neither basal or DOC-depressed Na-K-ATPase, nor mucosal cAMP. In the colon it reduced a large increase of the erythritol clearance caused by DOC. It is suggested that loperamide interferes with DOC-induced intestinal secretion in part by lowering mucosal permeability.
A toxin produced by Clostridium difficile has been implicated in the pathogenesis of antibiotic-associated colitis. It is not known how often the microorganism is encountered in Germany particularly in high risk patients. Therefore, following a lethal case of colitis, stool samples of 90 patients and 30 staff members of an intensive care unit were screened routinely for C. difficile over 2 months. The organism was found in 6 of 41 patients treated with antibiotics (14.6%); four of them apparently acquired C. difficile while in hospital whereas in 2 a pre-existing carrier state could not be excluded. Colitis developed in 3 of the 6 patients as judged from endoscopy or a positive cytotoxin assay; in 2 patients (not subjected to endoscopy) colitis was suspected on clinical grounds, and 1 patient became an asymptomatic carrier. C. difficile was not found in 49 patients without antibiotic medication, in the health personal and in 12 patients of a general ward. Patients harbouring C. difficile were clustered in certain bed sites of the unit. Environmental studies recovered the microorganism from bed pan washing machines of bedridden and from toilets of ambulant patients but not from other sites like the hands of the personal. These results suggest that chronic carriers of C. difficile, as far as they are identified by current bacteriological methods, are rare in Germany (not more than 2 out of 132 persons investigated, i.e. 1.5%). The frequent finding of C. difficile in patients treated in certain bed sites supports the view that the infection may be acquired from exogenous sources. Antibiotic-associated colitis should be considered more often when intensive care patients are treated with antibiotics.
The role of the adenylate cyclase (Ac)-cAMP system in mediating deoxycholic acid (DOC)-induced fluid secretion was studied in the rat jejunum and colon in vivo using the AC inhibitor, RMI 12 330 A. A potent inhibitory effect of RMI 12 330 A on fluid secretion induced by cholera toxin was demonstrated in ligated rat jejunal loops. On the contrary, the changes of fluid movement in jejunal and colonic loops caused by DOC could not be influenced by RMI 12 330 A, and mucosal cAMP levels of colonic loops were not increased. Colonic mucosal permeability estimated by the 14C-erythritol clearance increased significantly during a 45-min exposure to 3 mmol DOC, and was not affected by RMI 12 330 A. These results do not support the theory that the AC-cAMP system plays an important role in DOC-induced intestinal fluid secretion and suggest that an increase in mucosal permeability is the predominant factor responsible for the secretagogue effect.
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The effect of loperamide on net fluid transport and epithelial cAMP accumulation was tested in choleratoxin-exposed ligated colon loops of the rat in vivo. Purified choleratoxin (50 micrograms/ml saline, for 5 h) induced net secretion and doubled cAMP levels in comparison with saline-treated controls. Loperamide (4 mg/kg intragastrically) reduced this secretion by 75%, without diminishing cAMP accumulation; it had no effect on basal fluid transport or cAMP. The data suggest that the opiate analogue interferes with the secretory process at a point beyond the cAMP increase caused by activation of adenylate cyclase.
The studies deal with the influence of secretin and various ecbolic secretagogues on tissue levels of cAMP and cGMP in vivo and in the isolated perfused canine pancreas. The mutual behaviour of cellular cAMP and cGMP is observed and compared with the time course of the respective secretory events. Synthetic secretin as well as CCK, acetylcholine or Caerulein likewise elevate tissue cAMP and cGMP simultaneously. There exists no difference in the magnitude of increase and in the time course of changes in tissue cyclic nucleotide levels between hydrokinetic and ecbolic stimulation. The rise in cAMP and cGMP coincides with the onset of the respective secretory events and reaches peak values contemporarily to the excretory maxima. The following decrease in tissue cyclic nucleotides approximatively parallels juice or enzyme secretion in the isolated perfused pancreas but differs widely in vivo. Under this condition cAMP and cGMP rapidly fall to basal levels during undiminished excretory function and show a second rise after cessation of the latter. Secretin and various ecbolic secretagogues do not increase tissue content of cyclic nucleotides in the same dose-dependent manner as can be observed with pancreatic secretion. The behaviour of cAMP and cGMP after addition of secretin and CCK or acetylcholine remains widely unchanged during calcium-free perfusion in spite of an extensive excretory inhibition. The corresponding rise in cellular cAMP and cGMP in the sequence of hydrokinetic as well as of ecbolic stimulation points to an analogous intracellular mediation of various secretagogues in different target cells of the exocrine canine pancreas.