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11. Osmotic swelling-provoked release of organic osmolytes in human intestinal epithelial cells

Author

Tomasen, Sebastian F.B., Fekkes, Durk, de Jonge, Hugo R., and Tilly, Ben C.

Subjects
Chloride channels -- Research, Protein kinases -- Research, Biological sciences
Abstract

Osmotic swelling-provoked release of organic osmolytes in human intestinal epithelial cells. Am J Physiol Cell Physiol 286: C1417-C1422, 2004. First published February 11, 2004; 10.1152/ajpcell.00468.2003.--Human Intestine 407 cells respond to osmotic cell swelling by the activation of [Cl.sup.-] and [K.sup.+] -selective ionic channels, as well as by stimulating an organic osmolyte release pathway readily permeable to taurine and phosphocholine. Unlike the activation of volume-regulated anion channels (VRAC), activation of the organic osmolyte release pathway shows a lag time of ~30-60 s, and its activity persists for at least 8-12 min. In contrast to VRAC activation, stimulation of organic osmolyte release did not require protein tyrosine phosphorylation, active p[21.sup.rho], or phosphatidylinositol 3-kinase activity and was insensitive to [Cl.sup.-] channel blockers. Treatment of the cells with putative organic anion transporter inhibitors reduced the release of taurine only partially or was found to be ineffective. The efflux was blocked by a subclass of organic cation transporter (OCT) inhibitors (cyanine-863 and decynium-22) but not by other OCT inhibitors (cimetidine, quinine, and verapamil). Brief treatment of the cells with phorbol esters potentiated the cell swelling-induced taurine efflux, whereas addition of the protein kinase C (PKC) inhibitor GF109203X largely inhibited the response, suggesting that PKC is involved. Increasing the level of intracellular [Ca.sup.2+] by using A-23187-or [Ca.sup.2+]-mobilizing hormones, however, did not affect the magnitude of the response. Taken together, the results indicate that the hypotonicity-induced efflux of organic osmolytes is independent of VRAC and involves a PKC-dependent step. regulatory volume decrease; taurine; volume-regulated anion channels; chloride channel; protein kinase C

Published
2004

20. Trait anxiety, coping with stress, and norharman

Author

Verheij, Rene, Timmerman, Leo, Passchier, Jan, Fekkes, Durk, and Pepplinkhuizen, Lolke

Subjects
Anxiety -- Physiological aspects, Adjustment (Psychology) -- Physiological aspects, Psychotropic drugs -- Psychological aspects, Psychology and mental health
Abstract

Plasma levels of the [Beta]-carboline norharman, concentration of platelet 5-HT, trait measures of anxiety, and measures of coping and defense mechanisms were compared for 15 patients with panic disorder and 24 healthy volunteers. Patients indicated that they made less use of the defense mechanism of principalization than control subjects. No other differences between patients and controls were significant. Platelet 5-HT concentration was positively correlated with the subjectively reported anxiety. Plasma norharman concentration was negatively correlated with the defense mechanisms of principalization and repression and positively correlated with coping strategies involving palliation. The positive correlations of norharman levels with projection and self-comforting fell short of significance and existed in the patient group only. No correlation was apparent between levels of plasma norharman and scores on anxiety. It was concluded that norharman is not a marker for panic disorder or trait anxiety, but that it might reflect intrapsychic and coping processes.

Published
1997

25. Differences in potential biomarkers of delirium between acutely ill medical and elective cardiac surgery patients

Author

Egberts, Angelique, Osse, Robert J, Fekkes, Durk, Tulen, Joke H M, van der Cammen, Tischa J M, and Mattace-Raso, Francesco U S

Subjects
Aged, 80 and over, Male, renal function, Delirium, Homovanillic Acid, Middle Aged, Neopterin, Oxidative Stress, C-Reactive Protein, immune system diseases, inflammation, Elective Surgical Procedures, Clinical Interventions in Aging, Linear Models, Humans, Female, Amino Acids, Cardiac Surgical Procedures, Biomarkers, Original Research, Aged
Abstract

Angelique Egberts,1 Robert J Osse,2 Durk Fekkes,2,3 Joke HM Tulen,2 Tischa JM van der Cammen,1 Francesco US Mattace-Raso1 1Section of Geriatric Medicine, Department of Internal Medicine, Erasmus MC University Medical Center, Rotterdam, the Netherlands; 2Department of Psychiatry, Erasmus MC University Medical Center, Rotterdam, the Netherlands; 3Department of Clinical Chemistry, Erasmus MC University Medical Center, Rotterdam, the Netherlands Background/aims: The pathophysiology of delirium is poorly understood. Increasing evidence suggests that different pathways might be involved in the pathophysiology depending on the population studied. The aim of the present study was to investigate potential differences in mean plasma levels of neopterin, amino acids, amino acid ratios and homovanillic acid between two groups of patients with delirium.Methods: Data from acutely ill medical patients aged 65 years and older, and patients aged 70 years and older undergoing elective cardiac surgery, were used. Differences in biomarker levels between the groups were investigated using univariate ANOVA with adjustments for age, sex, comorbidities, C-reactive protein (CRP) and the estimated glomerular filtration rate (eGFR), where appropriate. Linear regression analysis was used to identify potential determinants of the investigated biochemical markers.Results: Eighty patients with delirium were included (23 acutely ill medical patients and 57 elective cardiac surgery patients). After adjustment, higher mean neopterin levels (93.1 vs 47.3 nmol/L, P=0.001) and higher phenylalanine/tyrosine ratios (1.39 vs 1.15, P=0.032) were found in acutely ill medical patients when compared to elective cardiac surgery patients. CRP levels were positively correlated with neopterin levels in acutely ill medical patients, explaining 28.4% of the variance in neopterin levels. eGFR was negatively correlated with neopterin in elective cardiac surgery patients, explaining 53.7% of the variance in neopterin levels.Conclusion: In this study, we found differences in mean neopterin levels and phenylalanine/tyrosine ratios between acutely ill medical and elective cardiac surgery patients with delirium. Moreover, our findings may suggest that in acutely ill medical patients, neopterin levels are mainly determined by inflammation/oxidative stress whereas in elective cardiac surgery patients, neopterin levels are mainly driven by renal function/fluid status. These findings suggest that the markers and pathways that might be involved in the pathophysiology of delirium may differ between specific groups of patients. Keywords: delirium, inflammation, neopterin, oxidative stress, renal function

Published
2019

27. Differences in potential biomarkers of delirium between acutely ill medical and elective cardiac surgery patients

Author

Egberts,Angelique, Osse,Robert J., Fekkes,Durk, Tulen,Joke H.M., van der Cammen,Tischa J.M., Mattace-Raso,Francesco U.S., Egberts,Angelique, Osse,Robert J., Fekkes,Durk, Tulen,Joke H.M., van der Cammen,Tischa J.M., and Mattace-Raso,Francesco U.S.

Abstract

Angelique Egberts,1 Robert J Osse,2 Durk Fekkes,2,3 Joke HM Tulen,2 Tischa JM van der Cammen,1 Francesco US Mattace-Raso1 1Section of Geriatric Medicine, Department of Internal Medicine, Erasmus MC University Medical Center, Rotterdam, the Netherlands; 2Department of Psychiatry, Erasmus MC University Medical Center, Rotterdam, the Netherlands; 3Department of Clinical Chemistry, Erasmus MC University Medical Center, Rotterdam, the Netherlands Background/aims: The pathophysiology of delirium is poorly understood. Increasing evidence suggests that different pathways might be involved in the pathophysiology depending on the population studied. The aim of the present study was to investigate potential differences in mean plasma levels of neopterin, amino acids, amino acid ratios and homovanillic acid between two groups of patients with delirium.Methods: Data from acutely ill medical patients aged 65 years and older, and patients aged 70 years and older undergoing elective cardiac surgery, were used. Differences in biomarker levels between the groups were investigated using univariate ANOVA with adjustments for age, sex, comorbidities, C-reactive protein (CRP) and the estimated glomerular filtration rate (eGFR), where appropriate. Linear regression analysis was used to identify potential determinants of the investigated biochemical markers.Results: Eighty patients with delirium were included (23 acutely ill medical patients and 57 elective cardiac surgery patients). After adjustment, higher mean neopterin levels (93.1 vs 47.3 nmol/L, P=0.001) and higher phenylalanine/tyrosine ratios (1.39 vs 1.15, P=0.032) were found in acutely ill medical patients when compared to elective cardiac surgery patients. CRP levels were positively correlated with neopterin levels in acutely ill medical patients, explaining 28.4% of the variance in neopterin levels. eGFR was negatively correlated with neopterin in elective cardiac surgery patients, explaining 53.7% of the variance in neopterin

Published
2019

30. The relation between plasma tyrosine concentration and fatigue in primary biliary cirrhosis and primary sclerosing cholangitis

Author

Vrolijk Jan, Fekkes Durk, ter Borg Pieter CJ, and van Buuren Henk R

Subjects
Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Abstract Background In primary biliary cirrhosis (PBC) and primary sclerosing cholangitis (PSC) fatigue is a major clinical problem. Abnormal amino acid (AA) patterns have been implicated in the development of fatigue in several non-hepatological conditions but for PBC and PSC no data are available. This study aimed to identify abnormalities in AA patterns and to define their relation with fatigue. Methods Plasma concentrations of tyrosine, tryptophan, phenylalanine, valine, leucine and isoleucine were determined in plasma of patients with PBC (n = 45), PSC (n = 27), chronic hepatitis C (n = 22) and healthy controls (n = 73). Fatigue and quality of life were quantified using the Fisk fatigue severity scale, a visual analogue scale and the SF-36. Results Valine, isoleucine, leucine were significantly decreased in PBC and PSC. Tyrosine and phenylalanine were increased (p < 0.0002) and tryptophan decreased (p < 0.0001) in PBC. In PBC, but not in PSC, a significant inverse relation between tyrosine concentrations and fatigue and quality of life was found. Patients without fatigue and with good quality of life had increased tyrosine concentrations compared to fatigued patients. Multivariate analysis indicated that this relation was independent from disease activity or severity or presence of cirrhosis. Conclusion In patients with PBC and PSC, marked abnormalities in plasma AA patterns occur. Normal tyrosine concentrations, compared to increased concentrations, may be associated with fatigue and diminished quality of life.

Published
2005
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32. The effects of high-dose and low-dose tryptophan depletion on mood and cognitive functions of remitted depressed patients

Author

Booij, Linda, Van der Does, A.J. Willem, Haffmans, P.M. Judith, Riedel, Wim J., Fekkes, Durk, and Blom, Marc J.B.

Subjects
Drug therapy, Care and treatment, Methods, Mood disorders -- Care and treatment -- Drug therapy, Patient care -- Methods, Patients -- Care and treatment, Affective disorders -- Care and treatment -- Drug therapy
Abstract

It has frequently been demonstrated that acute tryptophan depletion (ATD) induces a transient depressed mood in some patients who are in remission from depression. However, the effects of ATD on [...]

Published
2005

33. Anesthesia With Propofol Does Not Reduce Interleukin-6 Release in Response to Abdominal Surgery of Varying Severity

Author

Fekkes, Durk, Hol, Jaap, Stolker, Robert jan, Fekkes, Durk, Hol, Jaap, and Stolker, Robert jan

Abstract

Background: Data on whether anesthesia with propofol promotes or attenuates interleukin-6 (IL-6) production are conflicting. The purpose of this study was to investigate the effect of different doses of propofol, but similar doses of opiates, on plasma concentrations of IL-6 in patients undergoing two distinct operations of different severity and duration. Methods: This study was a prospective, single-center, two-armed observational study. Blood samples were collected in 28 patients undergoing abdominal hysterectomy (H) or vulvectomy (V). IL-6 was measured 24 hours preoperatively, prior to induction, at the end of the operation, and at 24 and 96 hours postoperatively. We tested the effect of propofol on IL-6 levels with linear regression. Results: IL-6 concentrations at the end of surgery were significantly higher in group H than in group V (38.6 (31.3) pg/mL vs. 3.7 (2.7) pg/mL, P < 0.001). Peak levels of IL-6 were seen in group H at the end of operation, while maximum levels in group V were attained 24 hours after surgery. No relationship between administered amount of propofol and IL-6 release could be identified. However, peak levels of IL-6 were significantly correlated to surgery duration in both group H and group V (r = 0.773, P = 0.002 vs. r = 0.568, P = 0.034). Conclusions: Propofol does not diminish perioperative levels of IL-6 in patients undergoing abdominal hysterectomy or vulvectomy. The results also suggest that surgery duration is the main determinant of IL-6 response in both patient groups. Our findings indicate that there may be a clinical benefit to reduce the duration of surgery.

Published
2016

35. Cycloid psychoses in the psychosis spectrum: evidence for biochemical differences with schizophrenia

Author

van de Kerkhof,Noortje, Fekkes,Durk, van der Heijden,Frank, Hoogendijk,Witte, Stöber,Gerald, Egger,Jos, Verhoeven,Willem, van de Kerkhof,Noortje, Fekkes,Durk, van der Heijden,Frank, Hoogendijk,Witte, Stöber,Gerald, Egger,Jos, and Verhoeven,Willem

Abstract

Nora WA van de Kerkhof,1,2 Durk Fekkes,2,3 Frank MMA van der Heijden,1 Witte JG Hoogendijk,2 Gerald Stöber,4 Jos IM Egger,1,5,6 Willem MA Verhoeven1,2 1Vincent van Gogh Institute for Psychiatry, Centre of Excellence for Neuropsychiatry, Venray, 2Department of Psychiatry, 3Department of Clinical Chemistry, Erasmus University Medical Center, Rotterdam, The Netherlands; 4Department of Psychiatry, Psychosomatics and Psychotherapy, University of Würzburg, Würzburg, Germany; 5Behavioural Science Institute, 6Donders Institute for Brain, Cognition and Behaviour, Radboud University Nijmegen, Nijmegen, The Netherlands Abstract: Cycloid psychoses (CP) differ from schizophrenia regarding symptom profile, course, and prognosis and over many decades they were thought to be a separate entity within the psychosis spectrum. As to schizophrenia, research into the pathophysiology has focused on dopamine, brain-derived neurotrophic factor, and glutamate signaling in which, concerning the latter, the N-methyl-d-aspartate receptor plays a crucial role. The present study aims to determine whether CP can biochemically be delineated from schizophrenia. Eighty patients referred for psychotic disorders were assessed with the Comprehensive Assessment of Symptoms and History, and (both at inclusion and after 6 weeks of antipsychotic treatment) with the Positive and Negative Syndrome Scale and Clinical Global Impression. From 58 completers, 33 patients were diagnosed with schizophrenia and ten with CP according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and Leonhard criteria, respectively. Fifteen patients were diagnosed with other disorders within the psychosis spectrum. At both time points, blood levels of the dopamine metabolite homovanillic acid, brain-derived neurotrophic factor, and amino acids related to glutamate neurotransmission were measured and compared with a matched control sample. Patients with CP showed a sign

Published
2016

42. The bovine protein [Alpha]-lactalbumin increases the plasma ratio of tryptophan to the other large neutral amino acids, and in vulnerable subjects raises brain serotonin activity, reduces cortisol concentration, and improves mood under stress

Author

Markus, C Rob, Olivier, Berend, Panhuysen, Geert EM, Van der Gugten, Jan, Alles, Martine S, Tuiten, Adriaan, Westenberg, Herman GM, Fekkes, Durk, Koppeschaar, Hans F, and de Haan, Edward EHF

Subjects
High-tryptophan diet -- Psychological aspects, Stress management -- Health aspects, Whey -- Health aspects, Food/cooking/nutrition, Health
Abstract

Background: Increased brain serotonin may improve the ability to cope with stress, whereas a decline in serotonin activity is involved in depressive mood. The uptake of the serotonin precursor, tryptophan, into the brain is dependent on nutrients that influence the cerebral availability of tryptophan via a change in the ratio of plasma tryptophan to the sum of the other large neutral amino acids (Trp-LNAA ratio). Therefore, a diet-induced increase in tryptophan availability may increase brain serotonin synthesis and improve coping and mood, particularly in stress-vulnerable subjects. Objective: We tested whether [Alpha]-lactalbumin, a whey protein with a high tryptophan content, may increase the plasma Trp-LNAA ratio and reduce depressive mood and cortisol concentrations in stress-vulnerable subjects under acute stress. Design: Twenty-nine highly stress-vulnerable subjects and 29 relatively stress-invulnerable subjects participated in a double-blind, placebo-controlled study. Subjects were exposed to experimental stress after the intake of a diet enriched with either [Alpha]-lactalbumin or sodium-caseinate. Diet-induced changes in the plasma Trp-LNAA ratio and prolactin were measured. Changes in mood, pulse rate, skin conductance, and cortisol concentrations were assessed before and after the stressor. Results: The plasma Trp-LNAA ratio was 48% higher after the [Alpha]-lactalbumin diet than after the casein diet (P = 0.0001). In stress-vulnerable subjects this was accompanied by higher prolactin concentrations (P = 0.001), a decrease in cortisol (P = 0.036), and reduced depressive feelings (P = 0.007) under stress. Conclusions: Consumption of a dietary protein enriched in tryptophan increased the plasma Trp-LNAA ratio and, in stress-vulnerable subjects, improved coping ability, probably through alterations in brain serotonin. Am J Clin Nutr 2000;71:1536-44. KEY WORDS Tryptophan, [Alpha]-lactalbumin, serotonin, prolactin, cortisol, stress, mood

Published
2000

43. Disturbed Serotonergic Neurotransmission and Oxidative Stress in Elderly Patients with Delirium

Author

Egberts, Angelique, Fekkes, Durk, Wijnbeld, Eline, Ploeg, Milly, Saase, Jan, Ziere, Bert, van der Cammen, T.J.M., Mattace Raso, F.U.S., Egberts, Angelique, Fekkes, Durk, Wijnbeld, Eline, Ploeg, Milly, Saase, Jan, Ziere, Bert, van der Cammen, T.J.M., and Mattace Raso, F.U.S.

Abstract

Background: Oxidative stress and disturbances in serotonergic and dopaminergic neurotransmission may play a role in the pathophysiology of delirium. Aims: In this study, we investigated levels of amino acids, amino acid ratios and levels of homovanillic acid (HVA) as indicators for oxidative stress and disturbances in neurotransmission. Methods: Plasma levels of amino acids, amino acid ratios and HVA were determined in acutely ill patients aged >= 65 years admitted to the wards of Internal Medicine and Geriatrics of the Erasmus University Medical Center and the ward of Geriatrics of the Havenziekenhuis, Rotterdam, The Netherlands. Differences in the biochemical parameters between patients with and without delirium were investigated by analysis of variance in models adjusted for age, gender and comorbidities. Results: Of the 86 patients included, 23 had delirium. In adjusted models, higher mean phenylalanine/tyrosine ratios (1.34 vs. 1.14, p = 0.028), lower mean tryptophan/large neutral amino acids ratios (4.90 vs. 6.12, p = 0.021) and lower mean arginine levels (34.8 vs. 45.2 mu mol/l, p = 0.022) were found in patients with delirium when compared to those without. No differences were found in HVA levels between patients with and without delirium. Conclusion: The findings of this study suggest disturbed serotonergic neurotransmission and an increased status of oxidative stress in patients with delirium. (C) 2015 S. Karger AG, Basel

Published
2015

45. Neurotoxic and neuroprotective metabolites of kynurenine in patients with renal cell carcinoma treated with interferon-alpha: Course and relationship with psychiatric status

Author

van Gool, Arthur R., Verkerk, Robert, Fekkes, Durk, Bannink, Marjolein, Sleijfer, Stefan, Kruit, Wim H.J., van der Holt, Bronno, Scharpe, Simon, Eggermont, Alexander M.M., Stoter, Gerrit, Hengeveld, Michiel W., Psychiatry, Neurosciences, Medical Oncology, Hematology, and Surgery

Subjects
Human medicine
Abstract

Aims: Immunotherapy with interferon-alpha (IFN-alpha) is associated with psychiatric side-effects, including depression. One of the putative pathways underlying these psychiatric side-effects involves tryptophan (TRP) metabolism. Cytokines including IFN-alpha induce the enzyme indoleamine 2,3-dioxygenase (IDO), which converts TRP to kynurenine (KYN), leading to a shortage of serotonin (5-HT). In addition, the production of neurotoxic metabolites of KYN such as 3-hydroxykynurenine and quinolinic acid (QA) might increase and contribute to IFN-alpha-induced psychopathology. In contrast, other catabolites of KYN, such as kynurenic acid (KA), are thought to have neuroprotective properties. Methods: In a group of 24 patients treated with standard IFN-alpha for metastatic renal cell carcinoma (RCC), combined psychiatric and laboratory assessments were performed at baseline, 4 and 8 weeks, and at 6 months. Results: No psychopathology was observed, despite an increase in neurotoxic challenge as reflected in indices for the balance between neurotoxic and neuroprotective metabolites of KYN. Conclusions: The present hypothesis that a shift in the balance between neurotoxic and neuroprotective metabolites of KYN underlies the neuropsychiatric side-effects of IFN-alpha-based immunotherapy, is neither supported nor rejected.

Published
2008

46. Increased plasma glutamate, glycine, and arginine levels in complex regional pain syndrome type 1

Author

Wesseldijk, Feikje, Fekkes, Durk, Huygen, Frank, Mulder, Marieke, Zijlstra, Freek, Anesthesiology, Psychiatry, and Neurosciences

Abstract

Background: Various inflammatory mediators have been identified as potential contributors to complex regional pain syndrome type 1 (CRPS1), but these mediators do not entirely explain certain manifestations of the syndrome, such as pain. The objective of this study was to investigate the role of amino acids in the pathogenesis of CRPS1. Methods: We used HPLC to determine plasma concentrations of 16 amino acids, especially those related to the NMDA receptor (e.g., glutamate and glycine) and nitric oxide (NO) synthesis (e.g., arginine and citrulline) in patients with CRPS1 (n=64) and age- and sex-matched healthy controls (n=51). Patients rated pain intensity (visual analog scale) and the subjective experience of pain intensity (McGill Pain Questionnaire). Psychological dysfunction was assessed using the SCL-90. Results: Relative to controls, in CRPS1 patients, plasma levels of glutamate, arginine, taurine, and glycine were increased, and plasma levels of glutamine and the ratio of citrulline to arginine were decreased. Remarkably, in CRPS1 patients there was a highly significant inverse correlation between glutamine and glutamate, although the sum of molar concentrations of glutamate and glutamine remains unchanged. Subjective measures of pain and indicators of psychoneuroticism and emotional instability did not correlate with amino acid levels. Conclusion: This study shows for the first time a pronounced increase in amino acid levels in this chronic pain syndrome. The marked differences in glutamate, glutamine, glycine, taurine and arginine levels between patients and controls suggest the involvement of both the NDMA receptor and the endothelium-dependent arginine-NO system in CRPS1.

Published
2008

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