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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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Rosuvastatin improves impaired endothelial function, lowers high sensitivity CRP, complement and immuncomplex production in patients with systemic sclerosis--a prospective case-series study.
Timár, O, Szekanecz, Z, Kerekes, G, Végh, J, Oláh, AV, Nagy, G, Csiki, Z, Dankó, K, Szamosi, S, Németh, Á, et al
Arthritis research & therapy. 2013;(5):R105
Abstract
INTRODUCTION We studied the effect of rosuvastatin on endothelial and macrovascular function, cardiovascular risk factors and the complement pathway in patients with systemic sclerosis (SSc). METHODS Altogether 28 patients with SSc underwent laboratory and complex vascular assessments before and after six months of 20 mg rosuvastatin treatment. Flow-mediated dilation (FMD) of the brachial artery, as well as carotid artery intima-media thickness (ccIMT), carotid-femoral and aorto-femoral pulse wave-velocity (PWV) were analyzed by ECG-synchronized ultrasound. Ankle-brachial index (ABI) was determined by Doppler, and forearm skin microcirculation was assessed by Laser Doppler perfusion monitoring. RESULTS Brachial artery FMD significantly improved upon rosuvastatin therapy (2.2% ± 3.3% before versus 5.7% ± 3.9% after treatment, P = 0.0002). With regard to patient subsets, FMD significantly improved in the 21 lcSSc patients (from 2.1% to 5.6%, P = 0.001). In the seven dcSSc patients, we observed a tendency of improvement in FMD (from 3% to 6%, P = 0.25). Changes in PWV, ccIMT and ABI were not significant. Mean triglyceride (1.7 ± 0.97 versus 1.3 ± 0.46 mmol/l, P = 0.0004), total cholesterol (5.3 ± 1.6 mmol/l versus 4.2 ± 1.3 mmol/l, P = 0.0003), low density lipoprotein cholesterol (3.0 ± 1.3 versus 2.2 ± 1.0 mmol/l, P = 0.005) and C-reactive protein levels (CRP) (5.1 ± 5.2 versus 3.4 ± 2.7, P = 0.01) levels significantly decreased after rosuvastatin treatment. Mean C3, C4 and IC levels also decreased significantly as compared to pretreatment values. CONCLUSIONS Six-month rosuvastatin therapy improves endothelial function and lowers CRP, C3, C4 and IC levels indicating possible favourable effects of this statin on the cardiovascular and immune system in SSc.
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Effect of exercise training on C-reactive protein in postmenopausal breast cancer survivors: a randomized controlled trial.
Fairey, AS, Courneya, KS, Field, CJ, Bell, GJ, Jones, LW, Martin, BS, Mackey, JR
Brain, behavior, and immunity. 2005;(5):381-8
Abstract
The objective of this study was to determine the effects of exercise training on changes in C-reactive protein (CRP) and other cardiovascular risk factors in postmenopausal breast cancer survivors. Fifty-three postmenopausal breast cancer survivors were randomly assigned to an exercise (n = 25) or control group (n = 28). The exercise group trained on cycle ergometers 3 times per week for 15 weeks. The control group did not train. The primary end point was change in CRP between baseline and week 15. Secondary end points were changes in RHR, HRR, SBP, DBP, TC, LDL-C, HDL-C, TG, and TC:HDL-C ratio. Fifty-two participants completed the trial. Baseline values did not differ between groups except that TG (p = .007) and TC:HDL-C ratio (p = .023) were higher in the exercise group. Intention-to-treat analysis showed that CRP decreased by 1.39 mg/L in the exercise group whereas it increased by 0.10 mg/L in the control group (mean between group change, -1.49 mg/L; 95% CI, -3.09 to 0.10 mg/L; p = .066). Intention-to-treat analysis also showed a clinically and statistically significant difference between groups for change in HRR (mean change, +10.6 beats/min; 95% CI, +3.4 to +17.7 beats/min; p = .004) and clinically but not statistically significant differences between groups for change in RHR (mean change, -5.5 beats/min; 95% CI, -11.5 to +0.5 beats/min; p = .073), SBP (mean change, -5.5 mmHg; 95% CI, -14.5 to +3.4 mmHg; p = .218), DBP (mean change,-3.6 mmHg; 95% CI, -9.3 to +2.1 mmHg; p = .214), and HDL-C (mean change, +0.05 mmol/L; 95% CI, -0.03 to 0.14 mmol/L; p = .214). These data suggest that exercise training may have beneficial effects on CRP and other cardiovascular risk factors in postmenopausal breast cancer survivors. Larger randomized controlled trials are warranted.
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Effect of c-reactive protein and interleukins blood levels in postsurgery arginine-enhanced enteral nutrition in head and neck cancer patients.
de Luis, DA, Izaola, O, Cuellar, L, Terroba, MC, Arranz, M, Fernandez, N, Aller, R
European journal of clinical nutrition. 2003;(1):96-9
Abstract
OBJECTIVE It is known that the immune system is frequently affected in patients with head and neck cancer. Although immune dysfunction could be multifactorial, this immune system may be modulated by specific nutritional substrates, such as arginine. The aim of our study was to evaluate the effect of enteral nutrition supplemented with arginine on c-reactive protein (CRP), interleukin 6 (IL-6) and tumour necrosis factor (TNFalpha) in surgical head and neck cancer patients. DESIGN Randomized trial. SETTING Tertiary care. SUBJECTS A population of 36 patients with oral and laryngeal cancer were enrolled. INTERVENTIONS At surgery patients were randomly allocated to two groups: (a) patients receiving an enteral diet supplements with arginine and dietary fibre (group I, n=18); (b) patients receiving an isocaloric, isonitrogenous enteral formula (group II, n=18). Perioperatively and on postoperative day 5 the following parameters were evaluated: serum values of prealbumin, transferrin, albumin, total number of lymphocytes, interleukin 6, tumour necrosis factor alpha and c-reactive protein. RESULTS The mean age was 59.6+/-10.9 y (two females/34 males). No significant intergroup differences in the trend of the three plasma proteins and weight were detected. CRP decreased in both groups (group I: 152.9+/-76.9 vs 68.9+/-82.5 mg/dl; P<0.05; and group II: 105.9+/-92 vs 43.6+/-59.1 mg/dl; P<0.05). Interleukin 6 did not change (group I: 16.3+/-12.3 vs 35.6+/-83.4 pg/ml; NS; and group II: 22.8+/-40 vs 9.9+/-17.7 pg/ml; NS). TNFalpha did not show any differences (group I: 4.6+/-1.6 vs 5.1+/-1.5 pg/ml; NS; and group II: 8.8+/-6.1 vs 5.8+/-1.7 pg/ml; NS). Lymphocytes increased in both groups (group I: 1405.6+/-517 vs 1634+/-529 x 10(6)/ml; P<0.05; and group II: 1355+/-696 vs 1561+/-541 x 10(6)/ml; P<0.05). CONCLUSIONS Enhanced formula did not change IL6 and TNFalpha levels. Further studies are needed to determine whether route of nutrition or type of formula is the key in these patients.