Concomitant 5-aminosalicylic acid treatment does not affect 6-thioguanine nucleotide levels in patients with inflammatory bowel disease on thiopurines.

Background: There are conflicting data as to whether co-treatment with 5-aminosalicylic acid (5-ASA) in patients with inflammatory bowel disease (IBD) under azathioprine (AZA) or 6-mercaptopurine (6-MP) therapy may influence 6-thioguanine nucleotide (6-TGN) concentrations, and whether this combination puts patients at risk of side-effects. The aim of the study was to determine 6-TGN levels in patients treated with AZA/6-MP, either alone or in combination with 5-ASA. Methods: Available blood samples from patients treated with AZA or 6-MP were retrieved from the Swiss IBD Cohort Study (SIBDCS). The eligible individuals were divided into 2 groups: those with vs. without 5-ASA co-medication. Levels of 6-TGN and 6-methylmercaptopurine ribonucleotides (6-MMPR) were determined and compared. Potential confounders were compared between the groups, and also evaluated as potential predictors for a multivariate regression model. Results: Of the 110 patients enrolled in this analysis, 40 received concomitant 5-ASA at the time of blood sampling. The median 6-TGN levels in patients with vs. those without 5-ASA co-treatment were 261 and 257 pmol/8×108 erythrocytes, respectively (P=0.97). Likewise, there were no significant differences in 6-MMPR levels (P=0.79). Through multivariate analysis, 6-TGN levels were found to be significantly higher in non-smokers, patients without prior surgery, and those without signs of stress-hyperarousal. Conclusions: Blood concentrations of 6-TGN and 6-MMPR did not differ between patients with vs. those without 5-ASA co-treatment. Our data warrant neither more frequent lab monitoring nor dose adaptation of AZA in patients receiving concomitant 5-ASA treatment.

Cortisol is significantly correlated with cardiovascular responses during high levels of stress in critical care personnel.

OBJECTIVE: Everyday stressors elicit adaptive changes in the hypothalamic-pituitary-adrenal (HPA) axis and the autonomic nervous system. Data on the relationship between these two systems under real-life conditions are sparse. We, therefore, sought to examine the association between HRV and salivary cortisol, which were recorded simultaneously in a stress-exposed, prospective, occupational cohort. METHODS: The study population comprised 88 nurses. We recorded heart rate (HR) and HRV during 301 working shifts. Participants provided salivary cortisol samples at the beginning of their work shift and every 2 hours thereafter. Samples were collected during three investigation periods spread over 9 months. Change scores for cortisol were calculated as deviations from the expected circadian baseline. Change scores from the grand diurnal mean in the time domain-based root mean square of successive differences served to index alterations in HRV. To account for the temporal delay between changes in HR/HRV and changes in salivary cortisol, the latter were compared with the changes in HR/HRV observed 15 minutes to 45 minutes before the cortisol sampling. RESULTS: During periods of high stress as indexed by high cortisol levels, we found significant associations between cortisol levels and HR (r = .48, p < .001) and HRV (r = -.28, p = .05). However, during low stress periods, these associations were attenuated and became nonsignificant. CONCLUSIONS: These data suggest a relative independence in the regulation of the HPA axis and the autonomic nervous system in response to everyday stressors but synchrony of both systems in highly stressful situations.