H. Verdievel

Concentrations of 5-ASA and Ac-5-ASA in human ileocolonic biopsy homogenates after oral 5-ASA preparations.

Intramucosal 5-aminosalicylic acid (5-ASA) and acetylated 5-ASA (Ac-5-ASA) concentrations were determined in ileocolonic biopsy specimens from 61 patients with irritable bowel syndrome treated for one week with near equimolar doses of different slow release preparations of 5-ASA (Claversal, Asacol, or Pentasa) or azo-bound drugs (Salazopyrin, Dipentum). The transit time in these patients was accelerated by a laxative, metoclopramide, and colonic lavage. The presence of 5-ASA in the mucosa was confirmed by autofluorescence. The highest concentrations of 5-ASA were obtained after Asacol (mean (SEM), 298.5 (37.3) ng/mg wet wt), followed by Claversal 500 mg (108.8 (11.7) ng/mg wet wt) and Pentasa (25.7 (2.2) ng/mg wet wt). Very low concentrations only were observed after Claversal 250 mg (0.3 (0.03) ng/mg wet wt), Salazopyrine (1.2 (0.1) ng/mg wet wt), and Dipentum (11.0 (3.2) ng/mg wet wt). The results for Ac-5-ASA were similar but the concentrations were generally lower. Serum concentration-time curves over eight hours were obtained from 34 healthy volunteers after a single oral dose of 400 to 500 mg of the different drugs. For the slow release forms, an apparently inverse relationship was found between the area under the curve of the serum concentrations and the intramucosal concentrations, supporting the importance of the local availability of the drug. This inverse relationship was absent for the azo-bound drugs. Colonic washout induced mechanical removal of intraluminal 5-ASA with a secondary disturbance in absorption resulting in a rapid decline in the serum concentrations. However, only for Dipentum did this result in significantly lower 5-ASA mucosal concentrations. This is the first reported attempt to evaluate the mucosal availability of 5-ASA after different oral preparations. It shows that where transit time is accelerated higher mucosal concentrations occur after slow release preparations (except for Claversal 250 mg) than after azo-bound drugs. Additional studies are necessary to correlate these concentrations with clinical effects.

High-performance liquid chromatographic assay for the determination of 5-aminosalicylic acid and acetyl-5-aminosalicylic acid concentrations in endoscopic intestinal biopsy in humans.

A high-performance liquid chromatographic method for the simultaneous determination of 5-amino-salicylic acid (5-ASA) and N-acetyl-5-ASA (Ac-5-ASA) concentrations in endoscopic mucosal biopsy homogenates is presented. The mean recoveries of 5-ASA and Ac-5-ASA from spiked blank biopsy homogenates ranged from 95.9 to 120% and from 92.5 to 100%, respectively. The coefficients of variation for 5-ASA and Ac-5-ASA were 0.7-8.6% and 1.4-12.9%, respectively. This method is useful for direct determination of topical availability of 5-ASA and Ac-5-ASA and probably an accurate parameter of drug bioavailability.

Influence of Low-Dose Oral Contraceptives, Alcohol, and Grapefruit on [13C]Aminopyrine Breath Test

The aminopryine breath test (ABT) measures hepatic reserve in patients with acute and chronic liver disease and gives an assesment of the hepatic function in patients undergoing major liver surgery. Aminopyrine is metabolized by the mixed cytochrome P-450 system, which can be influenced by many foreign compounds and drugs. Whether these foreign compounds and drugs can influence the results of the ABT has seldomly been tested. We studied three groups: Healthy female volunteers, either normally menstruating or taking oral contraceptives, were asked to perform a [13C]ABT during the time of the menses and at midcylce. Healthy volunteers were asked to perform a ABT after consuming 30 g of alcohol. Healthy volunteers were asked to perform a ABT after consuming 250 ml of grapefruit juice. The 13C/12C ratio in expired air was measured by gas isotope ratio mass spectrometry.

Non-transferrin-bound iron in untreated and ribavirin-treated chronic hepatitis C patients.

Background : In patients with chronic hepatitis C, elevations in serum iron levels, hepatic iron content and oxidative stress‐related molecules have been reported. Treatment with ribavirin induces an increase in hepatic iron concentration. In situations of iron overload, non‐transferrin‐bound iron can appear. Therefore, we determined non‐transferrin‐bound iron levels in untreated chronic hepatitis C patients and in patients during interferon–ribavirin treatment.

WS16.3 Consecutive transient elastography measurements to detect cystic fibrosis liver disease

Background Cystic fibrosis (CF) related liver disease (CFLD) is diagnosed using a combination of criteria. Transient elastography (TE) (ultrasonographic method evaluating liver stiffness) differentiates CF patients with and without liver disease (CFnoLD) and identifies patients with an increased risk for portal hypertension. Aim: Detect evolving CFLD using TE measurements. Method Retrospective study (2007–2013) including all patients with TE measurements, performed by the same operator. Measurement was correlated to the presence or development of CFLD based on the medical files. Results 150 CF patients [median age 17 (9–24) years] were included, 118 with repeated TE: 20 (14%) had CFLD at the first TE measurement, 4 (3%) developed CFLD during follow-up. The median TE value in CFLD was 14 (8.7–32.2) compared to 5.3 (4.9–5.7) in CFnoLD (P = 0.0001). The intra-individual differences between 2 consecutive measurements [median interval between measurements 1 yr (1–2)] was 0.05 (–1, 1.2) in CFnoLD and 0.55 (–1.68, 1.53) in the CFLD patients. The area under the receiver operating curve for TE predicting CFLD was 0.985. TE measurements above 6.55 kPa predicted CFLD with a sensitivity of 94.7% and a specificity of 90.8% according to the AUROC. In CF Conclusion TE measurements progressively increased in CF patients developing CFLD. A prospective study is needed to evaluate whether TE will be able to detect CFLD before it becomes clinically apparent.

The 13C-octanoic-acid breath test: Validation of a new non-invasive method to measure gastric emptying in rats

Currently available rat models for measuring gastric emptying are hampered by the necessity to kill the animals at the end of each experiment, which makes repetitive testing impossible. We have developed and validated a noninvasive test model, adapted from the 13C-octanoic breath test in humans, for repetitive measurements of gastric emptying in rats. Male Wistar rats were trained on a fixed protocol to eat a piece of pancake doped with 1 microg 13C-octanoic acid after 12 h fasting, and to stay thereafter in cylindrical glass cages. Breath tests were performed by a fully automated system of computer-guided switching valves, which collected consecutive breath samples. All breath samples were analysed by gas chromatography and isotope mass spectrometry. The area under the curve (AUC) from the cumulative 13CO2 excretion from 0 to 6 h was determined by the trapezium method to calculate the gastric half-emptying times (t(1/2)). Inter-day variability was determined. The effect of subcutaneous or intraperitoneal injection of saline was studied. The test was further validated for pharmacological interventions by oral administration of cisapride and parenteral administration of atropine, to induce, respectively. acceleration and delay of gastric emptying. Mean gastric emptying times +/- SD of 24 rats were 119.3 +/- 28.2 min, 138.7 +/- 26.0 min, and 124.5 +/- 30.9 min on three different test days. The mean coefficient of variation of three repeated measurements in the same 24 rats was 17.5%. No significant differences were observed after subcutaneous or intraperitoneal injection of saline. In a second test series of eight rats, cisapride significantly accelerated gastric emptying (mean t(1/2) 112.7 +/- 33.1 min, P < 0.05), while atropine caused a significant delay (mean t(1/2) 205.9 +/- 24.9 min, P < 0.05) when compared to control test results (mean t(1/2) 140.7 +/- 16.7 min) in the same rats. We validated the 13C-octanoic breath test to study gastric emptying in rats. This test method obviates the necessity to kill laboratory animals and allows repetitive measurements of gastric emptying to study its physiology or pathophysiology as well as the effect of pharmacological agents.

Comparison of different permeability probes in patients with spondylarthropathy and noninflammatory rheumatic disease: What is the effect of NSAIDs?

relates to the presence of CagA. The evolution of 1-1. pylori related gastritis was studied in relation to cagA and to duration of follow-up, in patients with either persistent or cured H. pylori infection. Dyspeptic patients entered the study starting in 1984. H. pylori infection was assessed by culture and histopathology of antral biopsies. The grading of activity of gastritis, superficial epithelial damag e (SED), atrophy and intestinal metaplasia (IM) was based on the updated Sydney classification. CagA status was determined by specific serum IgG antibodies. H. pylori eradication was attempted with bismuth-, or ppi-antibiotic combination therapies. Results of 265 patients were available for analysis. The median follow up was 5.3 years (range 1.1-12.5). Group I consisted of 124 patients with persisting H. pylori infection. Group II consisted of 141 patients in whom H. pylori eradication was achieved. CagA results were available in 185/265 patients (94 of group I; 91 of group II) of whom 140 (76%) were infected with a CagA ÷ strain. Pretreatment degrees of activity, SED, atrophy and IM were similar (ns) in group I and II. Higher degree of activity and SED was found in CagA+ infected patients (p < 0.0001). The degree of activity, SED, atrophy and IM remained unchanged over the years in group I. After successful H. pylori eradication, the degree of activity and SED improved significantly (p < 0.001), irrespective of the CagA status. The degree of atrophy improved from 2.2 to 1.2 (p < 0.001) in CagA+infected patients, however, the degree of atrophy remained unaffected in CagA-neg infected patients (from 1.8-1.6; ns). The degree of IM remained unchanged after successful H. pylori eradication, irrespective of the CagA status. Mean degrees of gastritis in group I and II, after a follow-up period less than 4 years or more than 4 years, were similar (ns). In conclusion, atrophy is partially reversible in CagA+infected patients, but IM remains unchanged. In CagA-neg H. pylori infection, atrophy and IM appeared irreversible. The length of follow-up in this cohort did not influence the observed degrees of activity, SED, atrophy and IM. Whether partial reversibility of atrophy will lead to reduction in cancer risk requires further prolonged observation.