Serum Free Thiols Are Superior to Fecal Calprotectin in Reflecting Endoscopic Disease Activity in Inflammatory Bowel Disease

Oxidative stress plays a pivotal role in the pathogenesis of inflammatory bowel diseases (IBD). Serum free thiols (R-SH) reliably reflect systemic oxidative stress, since they are readily oxidized by reactive species. Here, we aimed to establish concentrations of serum free thiols in IBD and assessed their discriminating capacity regarding endoscopic disease activity. Albumin-adjusted serum free thiol concentrations were measured in 78 IBD patients (31 Crohn’s disease (CD) and 47 ulcerative colitis (UC) patients) and 50 healthy controls and analyzed for associations with disease parameters and their discriminative value regarding endoscopic disease activity (n = 54) or fecal calprotectin (n = 36) in patients for which those data were available. Mean serum free thiol concentrations were significantly lower in both CD and UC as compared to healthy controls (19.4 ± 3.1 and 17.8 ± 3.4 vs. 21.1 ± 1.9 µmol/g albumin, P < 0.001). Free thiols highly accurately discriminated between mild and moderate-to-severe disease activity, better than fecal calprotectin (FC) levels (AUC = 0.87, P < 0.001 vs. AUC = 0.76, P < 0.05, respectively) and this was maintained after cross-validation (AUC = 0.89, P < 0.001). Serum free thiols are reduced in IBD as compared to healthy controls and strongly correlate with the degree of endoscopic disease activity. Quantifying systemic redox status in IBD may be a promising, minimally invasive strategy to monitor IBD disease activity.

Download Full-text

Mild Coronavirus Disease 2019 (COVID-19) Is Marked by Systemic Oxidative Stress: A Pilot Study

Antioxidants ◽

10.3390/antiox10122022 ◽

2021 ◽

Vol 10 (12) ◽

pp. 2022

Author(s):

Larissa E. van Eijk ◽

Adriana Tami ◽

Jan-Luuk Hillebrands ◽

Wilfred F. A. den Dunnen ◽

Martin H. de Borst ◽

...

Keyword(s):

Oxidative Stress ◽

Treatment Options ◽

Critical Role ◽

Healthy Controls ◽

Serum Samples ◽

Discriminative Ability ◽

Discriminative Performance ◽

Serum Free ◽

Free Thiol ◽

Systemic Oxidative Stress

Oxidative stress has been implicated to play a critical role in the pathophysiology of coronavirus disease 2019 (COVID-19) and may therefore be considered as a relevant therapeutic target. Serum free thiols (R-SH, sulfhydryl groups) comprise a robust marker of systemic oxidative stress, since they are readily oxidized by reactive oxygen species (ROS). In this study, serum free thiol concentrations were measured in hospitalized and non-hospitalized patients with COVID-19 and healthy controls and their associations with relevant clinical parameters were examined. Serum free thiol concentrations were measured colorimetrically (Ellman’s method) in 29 non-hospitalized COVID-19 subjects and 30 age-, sex-, and body-mass index (BMI)-matched healthy controls and analyzed for associations with clinical and biochemical disease parameters. Additional free thiol measurements were performed on seven serum samples from COVID-19 subjects who required hospitalization to examine their correlation with disease severity. Non-hospitalized subjects with COVID-19 had significantly lower concentrations of serum free thiols compared to healthy controls (p = 0.014), indicating oxidative stress. Serum free thiols were positively associated with albumin (St. β = 0.710, p < 0.001) and inversely associated with CRP (St. β = −0.434, p = 0.027), and showed significant discriminative ability to differentiate subjects with COVID-19 from healthy controls (AUC = 0.69, p = 0.011), which was slightly higher than the discriminative performance of CRP concentrations regarding COVID-19 diagnosis (AUC = 0.66, p = 0.042). This study concludes that systemic oxidative stress is increased in patients with COVID-19 compared with healthy controls. This opens an avenue of treatment options since free thiols are amenable to therapeutic modulation.

Download Full-text

Systemic Oxidative Stress Is Increased in Postmenopausal Women and Independently Associates with Homocysteine Levels

International Journal of Molecular Sciences ◽

10.3390/ijms21010314 ◽

2020 ◽

Vol 21 (1) ◽

pp. 314

Author(s):

Arno R. Bourgonje ◽

Amaal Eman Abdulle ◽

Areej M. Al-Rawas ◽

Muna Al-Maqbali ◽

Mohsin Al-Saleh ◽

...

Keyword(s):

Oxidative Stress ◽

Postmenopausal Women ◽

Biochemical Parameters ◽

Premenopausal Women ◽

Serum Levels ◽

Inverse Association ◽

Serum Free ◽

Free Thiol ◽

Systemic Oxidative Stress ◽

Increased Risk

Oxidative stress plays a pivotal role in the pathogenesis of cardiovascular diseases (CVD). Postmenopausal women have an increased risk of developing CVD due to decreased estrogen availability, which is accompanied by increased oxidative stress. Serum free thiols (R-SH) provide a robust and powerful read-out of systemic oxidative stress. In this study, we aimed to establish serum levels of free thiols and explore associations between free thiols and demographic, clinical, and biochemical parameters related to obesity and the risk for developing CVD in both pre- and postmenopausal women. Serum free thiols were measured in a cohort consisting of healthy pre- (n = 223) and postmenopausal (n = 118) Omani women. Postmenopausal women had significantly lower levels of serum free thiols as compared to premenopausal women (762.9 ± 85.3 vs. 780 ± 80.9 μM, age-adjusted p < 0.001). Women′s age was positively associated with serum free thiol levels in premenopausal women (β = 0.36, p = 0.002), whereas an inverse association was observed in postmenopausal women (β = −0.29, p = 0.002). Homocysteine levels were significantly inversely associated with serum free thiol levels in both pre- (β = −0.19, p = 0.005) and postmenopausal (β = −0.20, p = 0.032) women, independent from known cardiovascular risk factors. In this study, we show that postmenopausal women are affected by increased systemic oxidative stress, which independently associates with homocysteine levels.

Download Full-text

Plasma thiol redox status as indicator of acute kidney injury

10.21203/rs.3.rs-52235/v1 ◽

2020 ◽

Author(s):

Lisanne Boekhoud ◽

Jacqueline Koeze ◽

Elisabeth C. van der Slikke ◽

Arno R. Bourgonje ◽

Jill Moser ◽

...

Keyword(s):

Oxidative Stress ◽

Acute Kidney Injury ◽

Kidney Injury ◽

Redox Status ◽

Lower Serum ◽

Neutrophil Gelatinase Associated Lipocalin ◽

Free Thiol ◽

Systemic Oxidative Stress ◽

Thiol Redox ◽

Neutrophil Gelatinase

Abstract Introduction: Acute kidney injury (AKI) is associated with the abrupt loss of kidney function resulting in increased morbidity and mortality. Oxidative stress plays an important role in the pathophysiology of AKI. Free thiols (R-SH, sulfhydryl groups) are crucial components of the extracellular antioxidant machinery and reliably reflect systemic oxidative stress. Lower levels of thiols represent higher levels of oxidative stress. In this study, we hypothesized that plasma free thiols are associated with AKI upon admission to the intensive care unit (ICU). Methods: In this study, 301 critically ill patients were included for analysis. Plasma samples were taken upon admission. Plasma levels of albumin-adjusted plasma free thiols were determined and correlated with AKI stage upon ICU admission. Results: Albumin-adjusted plasma free thiols were significantly lower in patients with AKI (n=43, median [interquartile range] 7.28 µmol/g [3.52,8.95]) compared to patients without AKI (8.50 µmol/g [5.82, 11.28]; p < 0.05) upon admission to the ICU. Higher age (B = -0.72, p < 0.001), higher levels of neutrophil gelatinase-associated lipocalin (B = -0.002, p < 0.05), creatinine (B = -0.01, p < 0.05) and lower serum albumin (B = 0.47, p < 0.001) were associated with lower free thiol levels. Further, albumin-adjusted free thiol levels were significantly reduced in patients with sepsis (8.30 [5.52-10.64] µmol/g) compared to patients without sepsis (6.95 [3.72-8.92] µmol/g; p < 0.05). Conclusion: Albumin-adjusted plasma free thiols were significantly reduced in patients with AKI and patients with sepsis compared with patients without AKI and sepsis. Together, these data suggest that free thiol levels are mainly reduced in sepsis-associated AKI.

Download Full-text

Systemic Oxidative Stress, Aging and the Risk of Cardiovascular Events in the General Female Population

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.630543 ◽

2021 ◽

Vol 8 ◽

Author(s):

Martin F. Bourgonje ◽

Arno R. Bourgonje ◽

Amaal E. Abdulle ◽

Lyanne M. Kieneker ◽

Sacha la Bastide-van Gemert ◽

...

Keyword(s):

Oxidative Stress ◽

Cardiovascular Risk ◽

Postmenopausal Women ◽

Menopausal Status ◽

Female Population ◽

Serum Free ◽

Free Thiol ◽

Systemic Oxidative Stress ◽

Stage Disease ◽

End Stage

Introduction: Menopause is associated with increased cardiovascular risk, in which oxidative stress plays a pivotal role. Systemic oxidative stress is reflected by decreased levels of free thiols (R-SH, sulfhydryl groups), which are key components of the extracellular antioxidant machinery. In this study, we investigated the relation between serum free thiols as marker of oxidative stress and the female cardiovascular phenotype, as well as potential associations with the risk of cardiovascular (CV) events in pre- and postmenopausal women from the general population.Methods: Female participants (n = 2,980) of the Prevention of REnal and Vascular ENd-stage Disease (PREVEND) cohort study were included. Serum free thiol concentrations were analyzed for associations with demographic, clinical, biochemical, and gynecological parameters, as well as with menopausal status and, prospectively, with the risk of CV events.Results: Postmenopausal women had significantly reduced levels of serum free thiols (4.8 ± 1.0 vs. 5.2 ± 1.0 μmol/g, P < 0.001) compared to reproductive women. In multivariable analyses, serum free thiols were significantly associated with menopausal status (OR 0.70 [0.49–0.98], P = 0.039), even when adjusted for potential confounding factors, except for age (P = 0.550). Prospectively, serum free thiols were significantly associated with the risk of CV events (HR 0.52 [0.27–0.97], P = 0.040), even with covariate adjustment, although this disappeared when correcting for age.Conclusion: In this study, we revealed serum free thiols to be strongly associated with the female cardiovascular phenotype as well as with female risk of CV events, where the influence of age itself seemed to outweigh that of female menopause. Future studies are warranted to further unravel the clinical utility of serum free thiol levels in the context of female cardiovascular risk management.

Download Full-text

Home monitoring of disease activity and fecal calprotectin in adult patients with inflammatory bowel disease – interim analysis of 68 patients

10.26226/morressier.59a6b343d462b80290b5443a ◽

2017 ◽

Author(s):

Dorit Ankersen

Keyword(s):

Inflammatory Bowel Disease ◽

Disease Activity ◽

Bowel Disease ◽

Interim Analysis ◽

Home Monitoring ◽

Fecal Calprotectin ◽

Adult Patients ◽

Inflammatory Bowel

Download Full-text

Leucine-rich alpha-2 glycoprotein is a potential biomarker to monitor disease activity in inflammatory bowel disease receiving adalimumab: PLANET study

Journal of Gastroenterology ◽

10.1007/s00535-021-01793-0 ◽

2021 ◽

Author(s):

Shinichiro Shinzaki ◽

Katsuyoshi Matsuoka ◽

Hiroki Tanaka ◽

Fuminao Takeshima ◽

Shingo Kato ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Crohn’S Disease ◽

Crohn's Disease ◽

Disease Activity ◽

Bowel Disease ◽

Fecal Calprotectin ◽

Potential Biomarker ◽

Adalimumab Therapy ◽

Adalimumab Treatment ◽

Inflammatory Bowel

Abstract Background This multicenter prospective study (UMIN000019958) aimed to evaluate the usefulness of serum leucin-rich alpha-2 glycoprotein (LRG) levels in monitoring disease activity in inflammatory bowel disease (IBD). Methods Patients with moderate-to-severe IBD initiated on adalimumab therapy were enrolled herein. Serum LRG, C-reactive protein (CRP), and fecal calprotectin (fCal) levels were measured at week 0, 12, 24, and 52. Colonoscopy was performed at week 0, 12, and 52 for ulcerative colitis (UC), and at week 0, 24, and 52 for Crohn’s disease (CD). Endoscopic activity was assessed using the Simple Endoscopic Score for Crohn’s Disease (SES-CD) for CD and the Mayo endoscopic subscore (MES) for UC. Results A total of 81 patients was enrolled. Serum LRG levels decreased along with improvements in clinical and endoscopic outcomes upon adalimumab treatment (27.4 ± 12.6 μg/ml at week 0, 15.5 ± 7.7 μg/ml at week 12, 15.7 ± 9.6 μg/ml at week 24, and 14.5 ± 6.8 μg/ml at week 52), being correlated with endoscopic activity at each time point (SES-CD: r = 0.391 at week 0, r = 0.563 at week 24, r = 0.697 at week 52; MES: r = 0.534 at week 0, r = 0.429 at week 12, r = 0.335 at week 52). Endoscopic activity better correlated with LRG compared to CRP and fCal on pooled analysis at all time points (SES-CD: LRG: r = 0.636, CRP: r = 0.402, fCal: r = 0.435; MES: LRG: r = 0.568, CRP: 0.389, fCal: r = 0.426). Conclusions Serum LRG is a useful biomarker of endoscopic activity both in CD and UC during the adalimumab treatment.

Download Full-text

AB0702 THE FREQUENCY OF INFLAMMATORY BOWEL DISEASES IN PATIENTS WITH ANKYLOSING SPONDYLITIS

Annals of the Rheumatic Diseases ◽

10.1136/annrheumdis-2020-eular.3798 ◽

2020 ◽

Vol 79 (Suppl 1) ◽

pp. 1647.2-1647

Author(s):

G. Lukina ◽

P. Kulakova ◽

N. Savenkova ◽

E. Volnukhin ◽

A. Kovshik ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Longitudinal Study ◽

Ankylosing Spondylitis ◽

Disease Activity ◽

Bowel Disease ◽

Rapid Test ◽

Neutrophil Infiltration ◽

Fecal Calprotectin ◽

High Disease Activity ◽

Inflammatory Bowel

Background:Аnkylosing Spondylitis (AS) is closely associated with inflammatory bowel disease (IBD). About 6-46% of patients with IBD have various lesions of the musculoskeletal system [1]. 5-10% of patients with spondylarthritis (SpA) eventually develop IBD, with Crohn’s disease (CD) being more common than Ulcerative colitis (UC) [2]. Determining the level of fecal calprotectin (FC) is a study that allows to diagnose IBD. The concentration of FC directly depends on the neutrophil infiltration of the intestinal mucosa and has a direct connection with the activity of the inflammatory process [3]. It is known that level of FC increases in 2/3 of patients with AS and is closely related to parameters reflecting higher disease activity [4].Objectives:The aim of this study was to evaluate the frequency of IBD in patients with AS using an assessment of FC level.Methods:In the analysis were included 40 patients with AS, fulfilling the modified New York criteria, among them man -26 (65%), woman -14 (35%), mean age of patients was 41.2 ±10.5, mean disease duration - 13±8.8 years. All patients were examined with ESR, CRP, esophagogastroduodenoscopy, colonoscopy and quantitative analysis of the fecal calprotectin levels using the method of lateral immunochromatography with the BUHLMANN Quantum Blue rapid test. Standart range: 100-1800 µg /g.Results:All patients had a high disease activity, mean BASDAI was 5.2 ± 1.7, mean ASDAS CRP 3.8 ± 1.1. 35 patients (87.5 %) had FC level more than 100 µg / g, the remaining 5 patients (12.5%) less than 100 µg /g. 12 patients (30 %) had FC level more than 1,800 µg / g, 23 (57.5 %) from 101 µg / g to 1800 µg / g. All patients with FC levels more than 100 µg / g showed an increase CRP (mean 28.4 mg / l) and ESR (mean 36.3 mm\h) levels. IBD were diagnosed in 9 cases (22.5%): 5 patients (12.5 %) with CD and 4 patients (10 %) - UC, in the remaining cases (77.5%) was no intestinal pathology.Conclusion:The results showed high frequency of IBD in patients with AS. Patients with high FC levels (more than 100 μg/g) had high disease activity (AS). In most cases, inflammatory bowel disease were diagnosed in patients with FC levels more than 100 µg/g.References:[1] Bernstein CN, Blanchard JF, Rawsthorne P, Yu N. The prevalence of extraintestinal diseases in inflammatory bowel disease: a population-based study. Am J Gastroenterol. 2001 Apr;96(4):1116-22.[2] Klingberg, E., Strid, H., Stahl, A.et al. A longitudinal study of fecal calprotectin and the development of inflammatory bowel disease in ankylosing spondylitis. A longitudinal study of fecal calprotectin and the development of inflammatory bowel disease in ankylosing spondylitis. Arthritis Res Ther 2017. 19(1):21[3] Cypers H, Varkas G, Beeckman S, et al. Elevated calprotectin levels reveal bowel inflammation in spondyloarthritis. Annals of the Rheumatic Diseases. 2016. 75:1357-1362[4] Arzu Duran, Senol Kobak, Nazime Sen, et al. Fecal calprotectin is associated with disease activity in patients with ankylosing spondylitis. Bosnian Journal of Basic Medical Sciences. 2016. 16 (1):71-4Disclosure of Interests:Galina Lukina Speakers bureau: Novartis, Pfizer, UCB, Abbvie, Biocad, MSD, Roche, Polina Kulakova: None declared, Nadezhda Savenkova: None declared, Evgeniy Volnukhin: None declared, Anton Kovshik: None declared, Elena Alexandrova: None declared, Alexandr Novikov: None declared

Download Full-text

Effect of Cognitive Behavioral Therapy on Clinical Disease Course in Adolescents and Young Adults With Inflammatory Bowel Disease and Subclinical Anxiety and/or Depression: Results of a Randomized Trial

Inflammatory Bowel Diseases ◽

10.1093/ibd/izz073 ◽

2019 ◽

Vol 25 (12) ◽

pp. 1945-1956 ◽

Cited By ~ 3

Author(s):

Gertrude van den Brink ◽

Luuk Stapersma ◽

Anna Sophia Bom ◽

Dimitris Rizopolous ◽

C Janneke van der Woude ◽

...

Keyword(s):

Inflammatory Bowel Disease ◽

Cognitive Behavioral Therapy ◽

Disease Activity ◽

Bowel Disease ◽

Behavioral Therapy ◽

Fecal Calprotectin ◽

Clinical Disease ◽

Disease Course ◽

First Relapse ◽

Inflammatory Bowel

Abstract Background Anxiety and depressive symptoms are prevalent in patients with inflammatory bowel disease (IBD) and may negatively influence disease course. Disease activity could be affected positively by treatment of psychological symptoms. We investigated the effect of cognitive behavioral therapy (CBT) on clinical disease course in 10–25-year-old IBD patients experiencing subclinical anxiety and/or depression. Methods In this multicenter parallel group randomized controlled trial, IBD patients were randomized to disease-specific CBT in addition to standard medical care (CBT + care us usual [CAU]) or CAU only. The primary outcome was time to first relapse in the first 12 months. Secondary outcomes were clinical disease activity, fecal calprotectin, and C-reactive protein (CRP). Survival analyses and linear mixed models were performed to compare groups. Results Seventy patients were randomized (CBT+CAU = 37, CAU = 33), with a mean age of 18.3 years (±50% < 18 y, 31.4% male, 51.4% Crohn’s disease, 93% in remission). Time to first relapse did not differ between patients in the CBT+CAU group vs the CAU group (n = 65, P = 0.915). Furthermore, clinical disease activity, fecal calprotectin, and CRP did not significantly change over time between/within both groups. Exploratory analyses in 10–18-year-old patients showed a 9% increase per month of fecal calprotectin and a 7% increase per month of serum CRP in the CAU group, which was not seen in the CAU+CBT group. Conclusions CBT did not influence time to relapse in young IBD patients with subclinical anxiety and/or depression. However, exploratory analyses may suggest a beneficial effect of CBT on inflammatory markers in children.

Download Full-text

Sequential Analysis of Oxidative Stress Markers and Vitamin C Status in Acute Bacterial Osteomyelitis

Mediators of Inflammation ◽

10.1155/2014/975061 ◽

2014 ◽

Vol 2014 ◽

pp. 1-7 ◽

Cited By ~ 1

Author(s):

Rade Grbic ◽

Dijana J Miric ◽

Bojana Kisic ◽

Ljiljana Popovic ◽

Vojkan Nestorovic ◽

...

Keyword(s):

Oxidative Stress ◽

Vitamin C ◽

Sequential Analysis ◽

Bone Cells ◽

Redox Status ◽

Oxidative Stress Markers ◽

Total Vitamin ◽

Baseline Serum ◽

Stress Markers ◽

Systemic Oxidative Stress

In bacterial bone infections, excessively formed oxidants may result in local and systemic oxidative stress. Vitamin C is the major extracellular nonenzymatic antioxidant, also implicated in bone cells metabolism and viability. The physiological functions of vitamin C largely depend on its redox status. We sequentially assessed oxidative stress markers, hydroperoxides and malondialdehyde (MDA), total antioxidant activity (AOA), total vitamin C, ascorbic acid (Asc), and oxidized/reduced vitamin C ratio in 137 patients with acute osteomyelitis (OM). Compared to 52 healthy controls, in OM group baseline serum hydroperoxides, MDA and oxidized/reduced vitamin C ratio were higher whilst Asc and AOA were lower (P < 0.05, resp.). On the other side, total vitamin C levels in patients and controls were similar(P > 0.05), thereby suggesting a relative rather than absolute vitamin C deficiency in OM. During the follow-up, oxidative stress markers, AOA, and oxidizedreduced vitamin C ratio were gradually returned to normal, while there was no apparent change of total vitamin C concentrations. Persistently high values of oxidized/reduced vitamin C ratio and serum MDA were found in subacute OM. In conclusion, acute OM was associated with enhanced systemic oxidative stress and the shift of vitamin C redox status towards oxidized forms.

Download Full-text