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Effect of ß-glucan on serum levels of IL-12, hs-CRP, and clinical outcomes in multiple-trauma patients: a prospective randomized study.
Fazilaty, Z, Chenari, H, Shariatpanahi, ZV
Ulusal travma ve acil cerrahi dergisi = Turkish journal of trauma & emergency surgery : TJTES. 2018;(4):287-293
Abstract
BACKGROUND Trauma is associated with a profound immunological dysfunction. This predisposes patients to infections and adverse outcomes. ß-glucan has been implicated in the initiation of anti-microbial immune response. The present study aimed to evaluate the effects of an enteral diet containing ß-glucan on serum levels of IL-12 and highly-sensitive C-reactive protein (hs-CRP), occurrence of infection, and clinical outcomes in critically ill multiple-trauma patients. METHODS Forty multiple trauma patients requiring enteral nutrition for at least 10 days were randomly assigned to the intervention group (n=20) or the placebo group (n=20). The intervention group received a high-protein enteral diet providing 3 g ß-glucan, and the control group received a similar diet, except for 3 g of maltodextrin as a placebo. Serum levels of IL-12 and hs-CRP were measured on days 0, 10, and 21. RESULTS The ß-glucan group showed significantly higher serum levels of IL-12 on day 21 compared to the control group. Infection frequency and duration of mechanical ventilation were significantly lower in the ß-glucan group. A significant difference was found in the Sequential Organ Failure Assessment (SOFA) score in favor of the ß-glucan group. No difference was found in the serum levels of hs-CRP, length of ICU stay, occurrence of infection, and mortality rates between the two groups. CONCLUSION ß-glucan may increase serum levels of IL-12, shorten the duration of mechanical ventilation, and reduce organ failure in critically ill multiple-trauma patients.
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Particulate metal exposures induce plasma metabolome changes in a commuter panel study.
Ladva, CN, Golan, R, Liang, D, Greenwald, R, Walker, DI, Uppal, K, Raysoni, AU, Tran, V, Yu, T, Flanders, WD, et al
PloS one. 2018;(9):e0203468
Abstract
INTRODUCTION Advances in liquid chromatography-mass spectrometry (LC-MS) have enabled high-resolution metabolomics (HRM) to emerge as a sensitive tool for measuring environmental exposures and corresponding biological response. Using measurements collected as part of a large, panel-based study of car commuters, the current analysis examines in-vehicle air pollution concentrations, targeted inflammatory biomarker levels, and metabolomic profiles to trace potential metabolic perturbations associated with on-road traffic exposures. METHODS A 60-person panel of adults participated in a crossover study, where each participant conducted a highway commute and randomized to either a side-street commute or clinic exposure session. In addition to in-vehicle exposure characterizations, participants contributed pre- and post-exposure dried blood spots for 2-hr changes in targeted proinflammatory and vascular injury biomarkers and 10-hr changes in the plasma metabolome. Samples were analyzed on a Thermo QExactive MS system in positive and negative electrospray ionization (ESI) mode. Data were processed and analyzed in R using apLCMS, xMSanalyzer, and limma. Features associated with environmental exposures or biological endpoints were identified with a linear mixed effects model and annotated through human metabolic pathway analysis in mummichog. RESULTS HRM detected 10-hr perturbations in 110 features associated with in-vehicle, particulate metal exposures (Al, Pb, and Fe) which reflect changes in arachidonic acid, leukotriene, and tryptophan metabolism. Two-hour changes in proinflammatory biomarkers hs-CRP, IL-6, IL-8, and IL-1β were also associated with 10-hr changes in the plasma metabolome, suggesting diverse amino acid, leukotriene, and antioxidant metabolism effects. A putatively identified metabolite, 20-OH-LTB4, decreased after in-vehicle exposure to particulate metals, suggesting a subclinical immune response. CONCLUSIONS Acute exposures to traffic-related air pollutants are associated with broad inflammatory response, including several traditional markers of inflammation.
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Effect of memantine on C-reactive protein and lipid profiles in bipolar disorder.
Chang, HH, Chen, PS, Wang, TY, Lee, SY, Chen, SL, Huang, SY, Hong, JS, Yang, YK, Lu, RB
Journal of affective disorders. 2017;:151-157
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Abstract
BACKGROUND Balance in the immune system plays roles in bipolar disorder (BD) and its metabolic co-morbidities. Memantine is an NMDA receptor antagonist with anti-inflammatory effects. However, the effects of memantine adjunct treatment on metabolic status of BD are unclear. METHODS During the 12 weeks period, a total of 191 BD patients were enrolled and split into valproate (VPA) + placebo and VPA + memantine (5mg/day) arms. The fasting plasma levels of high-sensitivity C-reactive protein (CRP) and metabolic indices were assessed. BD patients were stratified according to their initial CRP level. RESULTS A cut-off value of initial CRP level of 2322ng/mL discriminated the waist circumference in these BD patients after 12-week VPA treatment. In the high CRP (> 2322ng/mL) group, patients in the VPA + memantine arm had a significantly decreased in their CRP (p= 0.009), total cholesterol (p= 0.002), LDL (p= 0.002) levels, BMI (p= 0.001), and waist circumference (p< 0.001), compared to those in the VPA + placebo arm. However, analysis of the low CRP group did not showed the effect. LIMITATIONS We recruited BD patients in depressed states and the sample size was relative small. The effects of the fixed dose of memantine on metabolic indices were 12-week follow up in BD patients treated with VPA. CONCLUSIONS BD patients with high initial CRP levels receiving memantine adjunct treatment have a reduced risk of inflammation and metabolic imbalance. Prospective studies are needed to confirm the long-term outcome for memantine adjunct therapy in BD patients.
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Plasma Ferritin and Hepcidin Are Lower at 4 Months Postpartum among Women with Elevated C-Reactive Protein or α1-Acid Glycoprotein.
Jorgensen, JM, Yang, Z, Lönnerdal, B, Chantry, CJ, Dewey, KG
The Journal of nutrition. 2017;(6):1194-1199
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Background: Ferritin and hepcidin are markers of iron status that typically increase during inflammation or infection. The postpartum period is a physiologically unique life stage in which the relations between these proteins and other markers of inflammation have not been extensively studied.Objective: We aimed to determine whether 2 markers of inflammation [high-sensitivity C-reactive protein (CRP) and α1-acid glycoprotein (AGP)] were associated with ferritin or hepcidin in postpartum women in California.Methods: This is a secondary analysis of a randomized controlled iron-intervention trial. Plasma CRP, AGP, ferritin, and hepcidin were analyzed at 2 and 17 wk postpartum in 114 lactating women. We examined Pearson correlation coefficients between all biomarkers at both time points and differences in mean values of ferritin and hepcidin between those with and without elevated CRP and/or AGP.Results: At 2 and 17 wk postpartum, 58% and 26% of women had CRP >5 mg/L and 78% and 29% had AGP >1 g/L, respectively. Neither CRP nor AGP was significantly correlated with ferritin (r = 0.07 and -0.06; n = 114 at 2 wk; -0.14 and -0.14; n = 95 at 17 wk) or hepcidin (r = 0.18 and -0.03 at 2 wk; -0.05 and -0.14 at 17 wk; P > 0.05 for all). At 2 wk, geometric mean plasma ferritin and hepcidin concentrations did not differ between women with and without elevated CRP or AGP (P > 0.5), but at 17 wk women with elevated CRP or AGP had lower mean (95% CI) ferritin and hepcidin than did women without either elevated CRP or AGP [ferritin: 30.3 ng/mL (23.4, 39.1 ng/mL) compared with 40.2 ng/mL (32.9, 49.2 ng/mL); P < 0.01; hepcidin: 44.3 ng/mL (32.3, 60.9 ng/mL) compared with 67.6 ng/mL (56.1, 81.5 ng/mL); P = 0.02].Conclusion: Lower ferritin and hepcidin among women with elevated CRP or AGP at 17 wk postpartum suggests that these markers of iron status react differently to physiologic immune activation than to pathologic inflammatory states.
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Surgical Stress Reduction in Elderly Patients Undergoing Elective Colorectal Laparoscopic Surgery within an ERAS Protocol.
Mari, G, Costanzi, A, Crippa, J, Falbo, R, Miranda, A, Rossi, M, Berardi, V, Maggioni, D, ,
Chirurgia (Bucharest, Romania : 1990). 2016;(6):476-480
Abstract
ERAS program applied to colorectal laparoscopic surgery is well known to reduce hospitalization improving short terms outcomes and minimizing the Surgical Stress Response. However its effectiveness in elderly population is yet to be demonstrated. The primary aim of this study is to compare the level of immune and nutritional serum indexes across surgery in patients aged over 70 years old undergoing elective colorectal laparoscopic surgery within an ERAS protocol or according to a Standard program. 83 patients undergoing colorectal laparoscopic surgery were enrolled and randomized in two groups (ERAS Group 40, Standard Group 43) within a larger randomized trial on a general population. Surgical stress parameters were collected preoperatively, 1, 3 and 5 days after surgery. Nutritional parameters were collected preoperatively, 1 and 5 days after surgery. Short Term Outcomes were also prospectively assessed. IL-6 levels were lower in the EG on 1, 3, and 5 days post-operatively (p 0.05). IL-6 levels in the Enhanced group returned to pre operative level 3 days after surgery. C-reactive protein level was lower in the Enhanced group on day 1, 3, and 5 (p 0.05). There was no difference in Cortisol and Prolactin levels between groups. Prealbumin serum level was higher on day 5 (p 0.05) compared to standard group. Postoperative outcomes in terms of normal bowel function and length of hospital stay were significantly improved in the ERAS group. Colorectal laparoscopic surgery within an ERAS prototcol in elderly patients affects Surgical Stress Response, decreasing IL-6 and CRP levels postoperatively and improving Prealbumin post operative synthesis.
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Biomarkers of necrotising soft tissue infections: aspects of the innate immune response and effects of hyperbaric oxygenation-the protocol of the prospective cohort BIONEC study.
Hansen, MB, Simonsen, U, Garred, P, Hyldegaard, O
BMJ open. 2015;(5):e006995
Abstract
INTRODUCTION The mortality and amputation rates are still high in patients with necrotising soft tissue infections (NSTIs). It would be ideal to have a set of biomarkers that enables the clinician to identify high-risk patients with NSTI on admission. The objectives of this study are to evaluate inflammatory and vasoactive biomarkers as prognostic markers of severity and mortality in patients with NSTI and to investigate whether hyperbaric oxygen treatment (HBOT) is able to modulate these biomarkers. The overall hypothesis is that plasma biomarkers can be used as prognostic markers of severity and mortality in patients with NSTI and that HBOT reduces the inflammatory response. METHODS AND ANALYSIS This is a prospective, observational study being conducted in a tertiary referral centre. Biomarkers will be measured in 114 patients who have been operatively diagnosed with NSTI. On admission, baseline blood values will be obtained. Following surgery and HBOT, daily blood samples for measuring regular inflammatory and vasoactive biomarkers (pentraxin-3, interleukin-6 and nitrite) will be acquired. Samples will be analysed using validated ELISA assays, chemiluminescence and Griess reaction. Clinical data will be obtained during admission in the intensive care unit for a maximum of 7 days. The primary analysis will focus on pentraxin-3, interleukin-6 and nitrite as early markers of disease severity in patients with NSTI. ETHICS AND DISSEMINATION The study has been approved by the Regional Scientific Ethical Committee of Copenhagen (H-2-2014-071) and the Danish Data Protection Agency (J. no. 30-0900 and J. no. 30-1282). Results will be presented at national and international conferences and published in peer-reviewed scientific journals. TRIAL REGISTRATION NCT02180906.
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Vitamin D and C-Reactive Protein: A Mendelian Randomization Study.
Liefaard, MC, Ligthart, S, Vitezova, A, Hofman, A, Uitterlinden, AG, Kiefte-de Jong, JC, Franco, OH, Zillikens, MC, Dehghan, A
PloS one. 2015;(7):e0131740
Abstract
Vitamin D deficiency is widely prevalent and has been associated with many diseases. It has been suggested that vitamin D has effects on the immune system and inhibits inflammation. The aim of our study was to investigate whether vitamin D has an inhibitory effect on systemic inflammation by assessing the association between serum levels of vitamin D and C-reactive protein. We studied the association between serum 25-hydroxyvitamin D and C-reactive protein through linear regression in 9,649 participants of the Rotterdam Study, an observational, prospective population-based cohort study. We used genetic variants related to vitamin D and CRP to compute a genetic risk score and perform bi-directional Mendelian randomization analysis. In linear regression adjusted for age, sex, cohort and other confounders, natural log-transformed CRP decreased with 0.06 (95% CI: -0.08, -0.03) unit per standard deviation increase in 25-hydroxyvitamin D. Bi-directional Mendelian randomization analyses showed no association between the vitamin D genetic risk score and lnCRP (Beta per SD = -0.018; p = 0.082) or the CRP genetic risk score and 25-hydroxyvitamin D (Beta per SD = 0.001; p = 0.998). In conclusion, higher levels of Vitamin D are associated with lower levels of C-reactive protein. In this study we did not find evidence for this to be the result of a causal relationship.
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HELP LDL apheresis reduces plasma pentraxin 3 in familial hypercholesterolemia.
Zanetti, M, Zenti, M, Barazzoni, R, Zardi, F, Semolic, A, Messa, MG, Mearelli, F, Russi, G, Fonda, M, Scarano, L, et al
PloS one. 2014;(7):e101290
Abstract
BACKGROUND Pentraxin 3 (PTX3), a key component of the humoral arm of innate immunity, is secreted by vascular cells in response to injury, possibly aiming at tuning arterial activation associated with vascular damage. Severe hypercholesterolemia as in familial hypercholesterolemia (FH) promotes vascular inflammation and atherosclerosis; low-density lipoprotein (LDL) apheresis is currently the treatment of choice to reduce plasma lipids in FH. HELP LDL apheresis affects pro- and antiinflammatory biomarkers, however its effects on PTX3 levels are unknown. We assessed the impact of FH and of LDL removal by HELP apheresis on PTX3. METHODS Plasma lipids, PTX3, and CRP were measured in 19 patients with FH undergoing chronic HELP LDL apheresis before and after treatment and in 20 control subjects. In the patients assessment of inflammation and oxidative stress markers included also plasma TNFα, fibrinogen and TBARS. RESULTS At baseline, FH patients had higher (p = 0.0002) plasma PTX3 than matched control subjects. In FH PTX3 correlated positively (p≤0.05) with age, gender and CRP and negatively (p = 0.01) with HELP LDL apheresis vintage. The latter association was confirmed after correction for age, gender and CRP. HELP LDL apheresis acutely reduced (p≤0.04) plasma PTX3, CRP, fibrinogen, TBARS and lipids, but not TNFα. No association was observed between mean decrease in PTX3 and in LDL cholesterol. PTX3 paralleled lipids, oxidative stress and inflammation markers in time-course study. CONCLUSION FH is associated with increased plasma PTX3, which is acutely reduced by HELP LDL apheresis independently of LDL cholesterol, as reflected by the lack of association between change in PTX3 and in LDL levels. These results, together with the finding of a negative relationship between PTX3 and duration of treatment suggest that HELP LDL apheresis may influence both acutely and chronically cardiovascular outcomes in FH by modulating PTX3.
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Relationship between vitamin D and inflammatory markers in older individuals.
De Vita, F, Lauretani, F, Bauer, J, Bautmans, I, Shardell, M, Cherubini, A, Bondi, G, Zuliani, G, Bandinelli, S, Pedrazzoni, M, et al
Age (Dordrecht, Netherlands). 2014;(4):9694
Abstract
In older persons, vitamin D insufficiency and a subclinical chronic inflammatory status frequently coexist. Vitamin D has immune-modulatory and in vitro anti-inflammatory properties. However, there is inconclusive evidence about the anti-inflammatory role of vitamin D in older subjects. Thus, we investigated the hypothesis of an inverse relationship between 25-hydroxyvitamin D (25(OH)D) and inflammatory markers in a population-based study of older individuals. After excluding participants with high-sensitivity C-reactive protein (hsCRP) ≥ 10 mg/dl and those who were on chronic anti-inflammatory treatment, we evaluated 867 older adults ≥65 years from the InCHIANTI Study. Participants had complete data on serum concentrations of 25(OH)D, hsCRP, tumor necrosis factor (TNF)-α, soluble TNF-α receptors 1 and 2, interleukin (IL)-1β, IL-1 receptor antagonist, IL-10, IL-18, IL-6, and soluble IL-6 receptors (sIL6r and sgp130). Two general linear models were fit (model 1-adjusted for age, sex, and parathyroid hormone (PTH); model 2-including covariates of model 1 plus dietary and smoking habits, physical activity, ADL disability, season, osteoporosis, depressive status, and comorbidities). The mean age was 75.1 ± 17.1 years ± SD. In model 1, log(25OH-D) was significantly and inversely associated with log(IL-6) (β ± SE = -0.11 ± 0.03, p = <0.0001) and log (hsCRP) (β ± SE = -0.04 ± 0.02, p = 0.04) and positively associated with log(sIL6r) (β ± SE = 0.11 ± 0.04, p = 0.003) but not with other inflammatory markers. In model 2, log (25OH-D) remained negatively associated with log (IL-6) (β ± SE = -0.10 ± 0.03, p = 0.0001) and positively associated with log(sIL6r) (β ± SE = 0.11 ± 0.03, p = 0.004) but not with log(hsCRP) (β ± SE = -0.01 ± 0.03, p = 0.07). 25(OH)D is independently and inversely associated with IL-6 and positively with sIL6r, suggesting a potential anti-inflammatory role for vitamin D in older individuals.
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Metabolic syndrome and C-reactive protein in patients with depressive disorder on antidepressive medication.
Stanojević, A, Popović, I, Nenadović, M, Ravanić, D, Paunović-Milosavljević, G
Srpski arhiv za celokupno lekarstvo. 2013;(7-8):511-5
Abstract
INTRODUCTION Recurrent depression is a psychiatric disorder of which etiology and pathogenesis might be related to immune response. Metabolic Syndrome (MetS) and its components are also strongly associated with elevated inflammatory indicators, as so as the body mass index (BMI) and total cholesterol levels. OBJECTIVE Objective of this study was to investigate if there was any difference in C-reactive protein (CRP) levels in patients with recurrent depressive disorder, treated with antidepressants, compared to a healthy control group of subjects and if there was an association between increased CRP levels and the presence of MetS in these two groups. METHODS Sixty subjects entered the study; of these 35 patients with the diagnosis of recurrent depressive disorder, while the healthy control group included 25 subjects. MetS was defined according to the NCEP ATP III criteria. The cut-off point for CRP was set at > 5 mg/L. RESULTS There was no statistically significant difference in the prevalence of MetS and CRP values between the studied groups. Waist circumference and total cholesterol levels were significantly higher in the experimental group. Patients that fulfilled the criteria for MetS showed significantly higher values of central obesity and arterial hypertension in the experimental group as well. The elevated CRP levels were associated with increased frequency of MetS in depressed patients. CONCLUSION Both CRP levels and metabolic risk profile screening, according to the international criteria, may be beneficial in order to obtain better assessment for depressive long-term medicated patients.