Markers Of Inflammation In Subjects Research Articles

Salivary concentrations of secretory leukocyte protease inhibitor and matrix metallopeptidase-9 following a single bout of exercise are associated with intensity and hydration status.

To investigate the effects of exercise on salivary concentrations of inflammatory markers by analyzing a panel of 25 inflammatory markers in subjects who had participated in bicycle ergometer tests varying in workload and hydration status. Fifteen healthy young men (20-35 years) had performed 4 different exercise protocols of 1 hour duration in a randomly assigned cross-over design, preceded by a rest protocol. Individual workloads depended on participant's pre-assessed individual maximum workload (Wmax): rest (protocol 1), 70% Wmax in hydrated (protocol 2) and dehydrated (protocol 3) state, 50% Wmax (protocol 4) and intermittent 85%/55% Wmax in 2 min blocks (protocol 5). Saliva samples were collected before (T0) and immediately after exercise (T1), and at several time points after exercise (2 hours (T3), 3 hours (T4), 6 hours (T5) and 24 hours (T6)). Secretory Leukocyte Protease Inhibitor (SLPI), Matrix Metallopeptidase-9 (MMP-9) and lactoferrin was analyzed using a commercial ELISA kit, a panel of 22 cytokines and chemokines were analyzed using a commercial multiplex immunoassay. Data was analyzed using a multilevel mixed linear model, with multiple test correction. Among a panel of 25 inflammatory markers, SLPI concentrations were significantly elevated immediately after exercise in all protocols compared to rest and higher concentrations reflected the intensity of exercise and hydration status. MMP-9 showed a significant increase in the 70% Wmax dehydrated, 50% Wmax and intermittent protocols. Salivary concentrations of SLPI and MMP-9 seem associated with exercise intensity and hydration status and may offer non-invasive biomarkers to study (local) inflammatory responses to different exercise intensities in human studies.

Abstract 14108: Eicosapentaenoic Acid and Docosahexaenoic Acid and Their Association With Oral Inflammatory Markers in Subjects With Clinical Coronary Artery Disease

Background: Our group previously reported that subjects with coronary artery disease (CAD) randomized to the omega-3 fatty acids, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), had lower levels of blood inflammatory markers and prevention of progression of non-calcified coronary plaque. Macrophage inhibitory protein (MIP)-1β is an inflammatory chemokine expressed by T cells in human plaques; circulating levels are increased in patients with atherosclerosis. The relation between EPA+DHA supplementation and oral inflammatory markers is unclear. Aim: To determine if EPA+DHA supplementation lowers levels of oral inflammatory markers. Methods: Subjects with clinical CAD were randomized to EPA+DHA, 3.36 g daily, or none for 30 months; 199 underwent a dental exam. Gingival crevicular fluid was collected at baseline and 30 months and analyzed for inflammatory markers. Results: MIP-1-β level was significantly lower in the EPA+DHA group compared to control at 30 months in the left upper quadrant of the mouth but not in the right upper quadrant (Table). This difference could potentially be explained by handedness. For example, Right-handed people tend to brush the left side of the mouth better whereas left-handed individuals and ambidextrous individuals have better brushing skills on the right side of the mouth. Other inflammatory markers (MCP, TNF-a, IL-1 and IL-6) were not different between groups on either side. Conclusions: Subjects with CAD randomized to EPA+DHA had reduced levels of the oral inflammatory marker, MIP-1β, at 30 months, suggesting that EPA+DHA can confer oral health benefits in addition to lowering systemic inflammation. For greatest benefit, brushing equally on both sides of the mouth should be encouraged, for which a powered toothbrush can help as it doesn’t rely on manual dexterity and handedness. Future research should examine whether the benefit of omega-3 fatty acids on oral health increases the benefit on coronary plaque.

A Balanced Dietary Ratio of n-6:n-3 Polyunsaturated Fatty Acids Exerts an Effect on Total Fatty Acid Profile in RBCs and Inflammatory Markers in Subjects with Obesity.

The n-3 polyunsaturated fatty acids (PUFAs) can reduce inflammatory markers and may therefore be useful in obesity management. The aim of this study was to analyze the effect of supplementation with n-3 PUFAs on total fatty acid profile in red blood cells (RBCs), as well as biochemical and inflammatory markers, in subjects with obesity. The study consisted in a randomized placebo-controlled, double-blind clinical trial involving 41 subjects with obesity during a 4-month follow-up. Individuals were randomly assigned to two groups: n-3 PUFA supplementation (1.5 g fish oil) and placebo (1.5 g sunflower oil). Anthropometric, biochemical, dietetic, cytokine and total fatty acid profiles in RBCs were measured. Both groups increased their PUFA intake and DHA incorporation in RBCs. However, the placebo group showed a reduction in serum IL-8 and MCP-1 at the end of the study. A multiple linear regression model adjusted by body fat mass and sex showed that an increase in DHA in RBCs decreased the serum IL-8 levels in both study groups at the end of the study. Our results highlight the role of dietary DHA and n-3 supplementation usefulness in exerting beneficial anti-inflammatory effects.

#3195 PATIENTS ON HD WITH CENTRAL CATHETERS LOCKED WITH TAUROLIDINE HAVE A SIMILAR INFLAMMATORY PROFILE TO SUBJECTS WITH NATIVE ARTERIOVENOUS FISTULA

Abstract Background and Aims Inflammation is a near-universal condition in haemodialysis (HD) patients, which contributes to increased complications, morbidity and mortality. The inflammatory profile is enhanced in subjects who need a central venous catheter (CVC) as vascular access in comparison with patients with native arteriovenous fistula (AVF), the optimal vascular access for HD. The aim of the present study was to analyse the inflammatory profile of HD patients according to their vascular access (CVC vs AVF), and to evaluate whether Taurolidine-citrate-heparin lock solution (TCH; taurolidine 1.35%, citrate 4% and heparin 500 IU) is able to modulate the inflammatory state of patients with CVC towards an inflammatory profile similar to that observed in subjects with AVF. Method A total of 109 patients with AVF or tunneled CVC under regular haemodialysis for more than 6 months were screened. Exclusion criteria included intercurrent infections in the previous 3 months, active inflammatory or immunologic diseases, and treatment with antibiotics or drugs affecting the immune system. Finally, 85 patients were included in the study and classified according to the vascular access: 25 patients with AVF and 60 with CVC. Subsequently, two subgroups were formed from the group of patients with tunneled CVC according to a heparin-containing catheter lock solution with (CVC-TCH) and without taurolidine-citrate (CVC-Hep). Subsequently, high sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-alpha) concentrations in serum and messenger ribonucleic acid (mRNA) gene expression levels of IL-6 and TNF-alpha in peripheral blood mononuclear cells (PBMC) were measured at inclusion and after three months follow-up. Results Altogether eighty-five subjects (42 males and 43 females; mean age 61 ± 9 yrs; 39% diabetics) were initially included in the study. In 25 subjects the vascular access was AVF, while the rest used tunneled CVC; of these 31 used standard CVC-Hep and 29 used CVC-TCH. Five patients dropped out the study and thus 80 patients completed the 3-month follow-up and were finally evaluated. At inclusion, patients with CVC had significantly higher serum and expression levels of inflammatory parameters compared to subjects with AVF. After 3 months, there were no significant changes in inflammatory markers in subjects with AVF compared to baseline, whereas in subjects with CVC-Hep a significant increase in serum and gene expression of IL-6 could be observed. On the contrary, subjects with CVC-TCH experienced a decrease of all parameters compared to baseline, of which differences in serum IL-6 and gene expression levels of IL-6 and TNF-alpha were significant. After 3 months of follow-up there was no significant difference in any inflammatory parameter when comparing patients with CVD-TCH with those with AVF (Table). Conclusion In patients under HD with cuffed tunneled CVC, the use of TCH lock solution after each HD session is associated with a significant improvement in the inflammatory serum and gene expression state. Thus, the inflammatory profile of patients with CVC using TCH does not differ from that of patients with native AVF after at least three months of CVC-TCH use.

The Influence of Probiotics Consumption on Management of Prediabetic State: A Systematic Review of Clinical Trials.

Prediabetes consists of the intermediary stage between normal glucose regulation and overt diabetes mellitus and develops when blood glucose levels are higher than normal but not high enough to confirm a type 2 diabetes mellitus diagnosis (T2DM). Recent evidence suggests that probiotics could be promising approaches to improve this state. In this study, we performed a systematic review to compile the results of clinical trials investigating the effects of pro-/pre-/synbiotics on prediabetes subjects from 2010 to 2020. The article search was carried out in Medline, Embase, Scopus, Web of Science, The Cochrane Library, Clinical trials.gov, ProQuest, Open Grey, and Google Scholar. Search filters were developed using 2 parameters: “prestate diabetes” and “probiotics.” Of the 418 studies that were screened, 15 original articles reached the inclusion criteria. Pooling data from these trials showed positive and significant effects of probiotics in the reduction of hyperglycemia, insulin concentration levels, lipid profile, and BMI (Body mass index). Administration of probiotics may provide beneficial and healthful effects in the clinical management of patients with prediabetes and metabolic syndrome. Different probiotics compositions have shown beneficial and noticeable effects on glucose homeostasis, lipid profiles, BMI, and inflammatory markers in subjects with prediabetes, metabolic syndrome, and healthy individuals and could be advantageous in recomposing the gut microbiota back into the normal state during the prediabetic state.

Systemic inflammatory markers of persistent cerebral edema after aneurysmal subarachnoid hemorrhage

BackgroundCerebral edema (CE) at admission is a surrogate marker of ‘early brain injury’ (EBI) after subarachnoid hemorrhage (SAH). Only recently has the focus on the changes in CE after SAH such as delayed resolution or newly developed CE been examined. Among several factors, an early systemic inflammatory response has been shown to be associated with CE. We investigate inflammatory markers in subjects with early CE which does not resolve, i.e., persistent CE after SAH.MethodsComputed tomography scans of SAH patients were graded at admission and at 7 days after SAH for CE using the 0–4 ‘subarachnoid hemorrhage early brain edema score’ (SEBES). SEBES ≤ 2 and SEBES ≥ 3 were considered good and poor grade, respectively. Serum samples from the same subject cohort were collected at 4 time periods (at < 24 h [T1], at 24 to 48 h [T2]. 3–5 days [T3] and 6–8 days [T4] post-admission) and concentration levels of 17 cytokines (implicated in peripheral inflammatory processes) were measured by multiplex immunoassay. Multivariable logistic regression analyses were step-wisely performed to identify cytokines independently associated with persistent CE adjusting for covariables including age, sex and past medical history (model 1), and additional inclusion of clinical and radiographic severity of SAH and treatment modality (model 2).ResultsOf the 135 patients enrolled in the study, 21 of 135 subjects (15.6%) showed a persistently poor SEBES grade. In multivariate model 1, higher Eotaxin (at T1 and T4), sCD40L (at T4), IL-6 (at T1 and T3) and TNF-α (at T4) were independently associated with persistent CE. In multivariate model 2, Eotaxin (at T4: odds ratio [OR] = 1.019, 95% confidence interval [CI] = 1.002–1.035) and possibly PDGF-AA (at T4), sCD40L (at T4), and TNF-α (at T4) was associated with persistent CE.ConclusionsWe identified serum cytokines at different time points that were independently associated with persistent CE. Specifically, persistent elevations of Eotaxin is associated with persistent CE after SAH.

The effect of Nigella sativa oil on vascular dysfunction assessed by flow-mediated dilation and vascular-related biomarkers in subject with cardiovascular disease risk factors: A randomized controlled trial.

Cardiovascular diseases (CVD) are the leading causes of mortality worldwide. Flow-mediated dilation (FMD) is a marker of vascular function. Beneficial cardiometabolic effects of Nigella sativa (N. sativa) have been observed. We evaluated the effect of N. sativa oil on FMD, plasma nitrite, and nitrate (NOx) as nitric oxide (NO) metabolites, and inflammatory markers in subjects with CVD risk factors. Fifty participants were randomly assigned to either the N. sativa (two capsules of 500 mg N. sativa oil) or the placebo group (two capsules of 500 mg mineral oil), for 2 months. The brachial FMD, plasma NOx, vascular cellular adhesion molecule-1 (VCAM-1), and intracellular adhesion molecule-1 (ICAM-1) were measured. FMD and plasma NOx levels was significantly increased in the N. sativa group compared to the placebo group (changes: 2.97 ± 2.11% vs. 0.71 ± 3.19%, p < 0.001 for FMD and 4.73 ± 7.25 μmol/L vs. 0.99 ± 5.37 μmol/L, p=0.036 for plasma NOx). However, there was no significant difference in ICAM-1 and VCAM-1 levels between groups. Therefore, N. sativa oil improves vascular NO and FMD in subjects with cardiovascular risk factors. However, more studies are warranted to confirm the beneficial impacts of the N. sativa oil on vascular inflammation.

Atrial electromechanical delay of patients with COPD in acute and stable periods

Background: The increased level of the airway and systemic inflammation, worsened clinical symptoms, and impaired lung functions are regarded as the characteristics of chronic obstructive pulmonary disease (COPD). The COPD may cause right/left ventricle dysfunction, pulmonary hypertension, and cor pulmonale. Objectives: The current study aimed to assess atrial electromechanical delay (AEMD) and echocardiographic changes and their relationship with inflammatory markers in subjects suffering from COPD during acute and stable periods. Methods: This prospective study was carried out on a total of 45 patients (including 22 and 23 female and male participants, respectively) suffering from COPD exacerbation. The stable phase of the participants was considered the control group. The first and second echocardiography was conducted in the first 24 h and following 3 months, respectively. Conventional and Tissue Doppler Imaging was utilized for the evaluation of atrial conduction times and systolic-diastolic functions of the right-left heart. The inflammatory markers, including the c-reactive protein-to-albumin ratio (CAR), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio, were also measured in this study. Results: In the stable period, there was a significant reduction in lateral/tricuspid, lateral/mitral, and septal AEMD. The evaluation of right ventricle basal, mid and vertical diameters, tricuspid annular plane systolic excursion, Amax tricuspid, tricuspid regurgitant velocity, systolic pulmonary arterial pressure, tricuspid annular systolic motion, left atrium diameter, left ventricle end-diastolic diameter, interventricular septum thickness, mitral early diastole/atrium systole ratio, systolic mitral motion, systolic septal motion, and heart rate showed significant differences after 3 months. In addition, there was a significant decrease in C-reactive protein, CAR, and NLR. Conclusion: In the stable period, a significant reduction was observed in AEMDs and there was an improvement in the systolic functions of the right-left heart. No correlation was observed between AEMDs and inflammatory markers.

The Effect of Supplementation with Low Doses of a Cod Protein Hydrolysate on Satiety Hormones and Inflammatory Biomarkers in Adults with Metabolic Syndrome: A Randomized, Double-Blind Study.

Metabolic syndrome (MetS) is characterised by metabolic abnormalities that increase the risk of developing type 2 diabetes mellitus and cardiovascular disease. Altered levels of circulating ghrelin, several adipokines and inflammatory markers secreted from adipose tissue, such as leptin, adiponectin, tumor necrosis factor alpha, are observed in overweight and obese individuals. We assessed the effect of supplementation with low doses of a cod protein hydrolysate (CPH) on fasting and postprandial levels of acylated ghrelin, as well as fasting levels of adiponectin, leptin and inflammatory markers in subjects with MetS. A multicentre, double-blinded, randomized controlled trial with a parallel group design was conducted. Subjects received a daily supplement of CPH (4 g protein, n = 15) or placebo (0 g protein, n = 15). We observed no effect on fasting or postprandial levels of acylated ghrelin, fasting levels of adiponectin (p = 0.089) or leptin (p = 0.967) after supplementation with CPH, compared to placebo. Overall, our study showed that 8 weeks supplementation with a low dose of CPH in subjects with MetS had no effect on satiety hormones or most of the inflammatory markers, but the levels of high-sensitivity C-reactive protein were statistically significantly different in the CPH-group compared to placebo group. The robustness and clinical relevance of these findings should be explored in future studies with a larger sample size.

Assessment of biochemical markers of inflammation in subjects with knee osteoarthritis undergoing low-level laser therapy

Background: It is a common experience that elderly population suffer from degenerative joint disease known as osteoarthritis (OA). There are several biochemical markers that are altered in this low-grade inflammation of knee joint as in OA. Low-level laser therapy (LLLT) is known to be safe and effective methods in the management of pain and inflammation in knee OA. Aim and Objective: This study aims to study the serum biomarkers to assess the inflammatory status in subjects with knee OA undergoing LLLT. Materials and Methods: The study subjects were in the age group of 45–75 years who had clinically diagnosed knee OA. The LLLT (810 nm, 10 mW) was given to the subjects for a total duration of 3 months with a periodicity of 3 times a week. Serum osteocalcin and prostaglandin E2 (PGE2) assay were done before and after therapy as well as in controls. Results: Mean PGE2 in the study subjects before the intervention and after laser therapy was 271.20 ± 128.30 pg/ml and 351.21 ± 98.92 pg/ml, respectively (P = 012). Mean osteocalcin (ng/ml) in the study subjects before the intervention and controls was 9.65 ± 7.90 ng/ml and 4.87 ± 3.23 ng/ml, respectively (P = 004). Conclusion: It can be concluded that LLLT had anti-inflammatory effects in subjects with knee osteoarthritis (KOA) as evident from significant increase in anti-inflammatory markers such as osteocalcin and PGE2.

Effect of semaglutide on liver enzymes and markers of inflammation in subjects with type 2 diabetes and/or obesity.

SummaryBackgroundObesity and type 2 diabetes are drivers of non‐alcoholic fatty liver disease (NAFLD). Glucagon‐like peptide‐1 analogues effectively treat obesity and type 2 diabetes and may offer potential for NAFLD treatment.AimTo evaluate the effect of the glucagon‐like peptide‐1 analogue, semaglutide, on alanine aminotransferase (ALT) and high‐sensitivity C‐reactive protein (hsCRP) in subjects at risk of NAFLD.MethodsData from a 104‐week cardiovascular outcomes trial in type 2 diabetes (semaglutide 0.5 or 1.0 mg/week) and a 52‐week weight management trial (semaglutide 0.05‐0.4 mg/day) were analysed. Treatment ratios vs placebo were estimated for ALT (both trials) and hsCRP (weight management trial only) using a mixed model for repeated measurements, with or without adjustment for change in body weight.ResultsElevated baseline ALT (men >30 IU/L; women >19 IU/L) was present in 52% (499/957) of weight management trial subjects. In this group with elevated ALT, end‐of‐treatment ALT reductions were 6%‐21% (P<0.05 for doses≥0.2 mg/day) and hsCRP reductions 25%‐43% vs placebo (P < 0.05 for 0.2 and 0.4 mg/day). Normalisation of elevated baseline ALT occurred in 25%‐46% of weight management trial subjects, vs 18% on placebo. Elevated baseline ALT was present in 41% (1325/3268) of cardiovascular outcomes trial subjects. In this group with elevated ALT, no significant ALT reduction was noted at end‐of‐treatment for 0.5 mg/week, while a 9% reduction vs placebo was seen for 1.0 mg/week (P = 0.0024). Treatment ratios for changes in ALT and hsCRP were not statistically significant after adjustment for weight change.ConclusionsSemaglutide significantly reduced ALT and hsCRP in clinical trials in subjects with obesity and/or type 2 diabetes.

Randomised clinical trial: emricasan versus placebo significantly decreases ALT and caspase 3/7 activation in subjects with non‐alcoholic fatty liver disease

SummaryBackgroundLipotoxicity leading to excessive caspase‐mediated apoptosis and inflammation is believed to drive liver damage in NAFLD. Emricasan is a pan‐caspase inhibitor that decreased serum ALT and apoptotic and inflammatory markers in subjects with chronic hepatitis.AimsTo assess whether 28 days of emricasan would reduce elevated levels of serum ALT, AST, cleaved cytokeratin‐18, full‐length cytokeratin‐18, and caspase 3/7 in subjects with NAFLD and raised aminotransferases.MethodsDouble‐blind, placebo‐controlled, office‐practice study assessed the efficacy, safety, and tolerability of emricasan in subjects with NAFLD and ALT levels ≥1.5 x ULN during screening. Subjects were randomised to emricasan 25 mg twice daily or matching placebo. Subjects with cirrhosis and other causes for raised aminotransferases were excluded. The primary endpoint was the change in ALT at day 28 in the emricasan group vs placebo.Results38 subjects were randomised, 19 each to emricasan or placebo. Baseline disease factors were well balanced except for lower median ALT values in emricasan subjects. Three subjects randomised to placebo discontinued prior to day 28. ALT values decreased significantly in emricasan‐treated subjects vs placebo at days 7 (P < 0.0001) and 28 (P = 0.02). cCK18 (day 7), flCK18 (days 7 and 28), and caspase 3/7 (day 7) were also significantly decreased in emricasan‐treated subjects vs placebo. Emricasan treatment was generally safe and well tolerated.ConclusionsEmricasan decreased ALT and biomarkers in subjects with NAFLD and raised aminotransferases after 28 days. These results support the further development of emricasan in patients with NAFLD. Trial registration: ClinicalTrials.gov, Identifier: NCT02077374.

The effects of vitamin D supplementation on proatherogenic inflammatory markers and carotid intima media thickness in subjects with metabolic syndrome: a randomized double-blind placebo-controlled clinical trial.

Metabolic syndrome may predispose to cardiovascular diseases. Since, in recent studies, vitamin D is advocated for cardioprotective roles, this study was designed to investigate the effects of vitamin D supplementation on proatherogenic inflammatory markers and common carotid intima media thickness in subjects with metabolic syndrome. This randomized double blind clinical trial was conducted in Tabriz, Iran. Eligible subjects (n = 80) with metabolic syndrome were recruited thorough advertisement and randomized to receive either vitamin D (50,000 IU/week) or matching placebo for 16 weeks. Interlukin-6, high sensitivity C-reactive protein, vascular cell adhesion molecule-1, E-selectin, and common carotid intima media thickness were measured at the beginning and end of the study. The study was registered at http://www.irct.ir (code: IRCT201409033140N14). Sixteen weeks supplementation with vitamin D increased median of serum 25-hydroxy vitamin D [25(OH)D] and mean calcium levels (p < 0.001) in the intervention group. There was also a significant difference in parathyroid hormone level at the end of the study (p < 0.001). Vitamin D treatment reduced IL-6 level after 16 weeks (p = 0.027). Compared to baseline, vascular cell adhesion molecule-1 and E-selectin levels decreased significantly in vitamin D treated subjects; however, there were no significant differences between two groups. No effect of vitamin D supplementation was observed in either common carotid intima media thickness or high sensitivity C-reactive protein concentrations at the end of the study (p > 0.05). Vitamin D supplementation improved some proatherogenic inflammatory markers in subjects with metabolic syndrome. No changes of high sensitivity C-reactive protein and carotid intima media thickness were shown after 16 weeks.

Markers of neuroinflammation associated with Alzheimer’s disease pathology in older adults

BackgroundIn vitro and animal studies have linked neuroinflammation to Alzheimer’s disease (AD) pathology. Studies on markers of inflammation in subjects with mild cognitive impairment or AD dementia provided inconsistent results. We hypothesized that distinct blood and cerebrospinal fluid (CSF) inflammatory markers are associated with biomarkers of amyloid and tau pathology in older adults without cognitive impairment or with beginning cognitive decline. ObjectiveTo identify blood-based and CSF neuroinflammation marker signatures associated with AD pathology (i.e. an AD CSF biomarker profile) and to investigate associations of inflammation markers with CSF biomarkers of amyloid, tau pathology, and neuronal injury. Design/methodsCross-sectional analysis was performed on data from 120 older community-dwelling adults with normal cognition (n=48) or with cognitive impairment (n=72). CSF Aβ1–42, tau and p-tau181, and a panel of 37 neuroinflammatory markers in both CSF and serum were quantified. Least absolute shrinkage and selection operator (LASSO) regression was applied to determine a reference model that best predicts an AD CSF biomarker profile defined a priori as p-tau181/Aβ1–42 ratio >0.0779. It was then compared to a second model that included the inflammatory markers from either serum or CSF. In addition, the correlations between inflammatory markers and CSF Aβ1–42, tau and p-tau181 levels were assessed. ResultsForty-two subjects met criteria for having an AD CSF biomarker profile. The best predictive models included 8 serum or 3 CSF neuroinflammatory markers related to cytokine mediated inflammation, vascular injury, and angiogenesis. Both models improved the accuracy to predict an AD biomarker profile when compared to the reference model. In analyses separately performed in the subgroup of participants with cognitive impairment, adding the serum or the CSF neuroinflammation markers also improved the accuracy of the diagnosis of AD pathology.None of the inflammatory markers correlated with the CSF Aβ1–42 levels. Six CSF markers (IL-15, MCP-1, VEGFR-1, sICAM1, sVCAM-1, and VEGF-D) correlated with the CSF tau and p-tau181 levels, and these associations remained significant after controlling for age, sex, cognitive impairment, and APOEε4 status. ConclusionsThe identified serum and CSF neuroinflammation biomarker signatures improve the accuracy of classification for AD pathology in older adults. Our results suggest that inflammation, vascular injury, and angiogenesis as reflected by CSF markers are closely related to cerebral tau pathology.

Functional Bowel Disorders Are Associated with a Central Immune Activation.

Background Subjects with depression and unexplained neurological symptoms have a high prevalence of gastrointestinal comorbidity probably related to the brain-gut communication. This study explored associations between functional gastrointestinal disorders (FGID) and inflammatory markers in subjects with these disorders. Methods The FGID, including irritable bowel syndrome (IBS), were classified according to the Rome III criteria, and degree of symptoms was assessed with IBS symptom severity score (IBS-SSS). A range of interleukins (IL), chemokines and growth factors, tryptophan, and kynurenine were analysed in serum and the cerebrospinal fluid (CSF), and short-chain fatty acids (SCFA) were analysed in the faeces. The results are reported as partial correlation (pc) and p values. Results Sixty-six subjects were included. IBS was associated with high levels of tryptophan (p = 0.048) and kynurenine (p = 0.019) and low level of IL-10 (p = 0.047) in the CSF. IBS-SSS was associated with high tumor necrosis factor and low IL-10 in the CSF; pc = 0.341 and p = 0.009 and pc = −0.299 and p = 0.023, respectively. Propionic minus butyric acid in faeces was negatively associated with IL-10 in the CSF (pc = −0.416, p = 0.005). Conclusions FGID were associated with a proinflammatory immune activation in the central nervous system and a disturbed tryptophan metabolism that could have been mediated by the faecal microbiota.

Physical Exercise on Inflammatory Markers in Type 2 Diabetes Patients: A Systematic Review of Randomized Controlled Trials.

Background. Type 2 diabetes mellitus (T2DM) is a serious disease associated with high morbidity and mortality. Scientific findings showed that physical exercise is an option for treatment of these patients. This study's objective is to investigate the effects of supervised aerobic and/or resistance physical training on inflammatory markers in subjects with T2DM. Methods. A systematic review was conducted on four databases, MEDLINE, CENTRAL, LILACS, and Scopus, and manual search from 21 to 30 November 2016. Randomized clinical trials involving individuals diagnosed with T2DM, who have undergone supervised training protocols, were selected in this study. Results. Eleven studies were included. Studies that evaluated control group versus aerobic exercise reported controversial results about the effectiveness of physical training in modifying C-reactive protein (CRP) and cytokine levels. The only variable analyzed by the six studies in comparison to the control group versus resistance exercise was CRP. This protein showed no significant difference between groups. Between the two modes of exercise (aerobic and resistance), only one study demonstrated that aerobic exercise was more effective in reducing CRP. Conclusion. The evidence was insufficient to prove that aerobic or resistance exercise improves systemic levels of inflammatory markers in patients with T2DM.

Differential expression of the inflammation marker IL12p40 in the at-risk mental state for psychosis: a predictor of transition to psychotic disorder?

BackgroundThe identification of biomarkers of transition from the at-risk mental state (ARMS) to psychotic disorder is important because early treatment of psychosis is associated with improved outcome. Increasing evidence points to an inflammatory contribution to psychosis.We questioned whether raised levels of plasma inflammatory markers predict transition from ARMS to psychotic disorder and whether any such predictors could be reduced by omega-3 (ω-3) polyunsaturated fatty acids (PUFAs).MethodsWe measured the levels of 40 neuroinflammation biomarkers using a commercially available immunoassay kit. Firstly, we compared inflammatory markers in subjects in the ARMS who transitioned to psychotic disorder (n = 11) compared to subjects who did not (n = 28). Then we compared inflammatory markers in all subjects before and after ω-3 PUFA treatment (n = 40).ResultsOur data provides preliminary evidence that elevations in the baseline plasma levels of the inflammatory marker IL12/IL23p40 are associated with transition from ARMS to psychotic disorder. IL12/IL23p40 levels did not change following 12 weeks administration of ω-3 PUFAs. These findings provide evidence that elevated plasma IL12/IL23p40 is a potential biomarker of increased risk for transition to psychotic disorder.ConclusionFurther studies are required to confirm and extend this finding. Our results do not provide support for the possibility that administration of ω-3 PUFAs act to reduced transition to psychotic disorder by reducing blood levels of IL12/IL23p40.Trial registrationClinicalTrials.gov, a service of the U.S. National Institutes of Health, Identifier: NCT00396643, last updated December 20, 2007. Retrospectively registered.

Relation of magnesium with insulin resistance and inflammatory markers in subjects with known Coronary artery disease

Background: Magnesium plays an important role in regulating insulin action and secretion. Dietary magnesium deficiency and hypomagnesemia have been associated with inflammation. There is paucity of data regarding this in Indian subjects. Hence, we studied the relation of serum and dietary magnesium with insulin resistance (IR) and inflammatory markers. Methods & Results: We studied the relation of serum high sensitive C-Reactive Protein (hsCRP), interlukin-6 (IL-6) and tumor Necrosis Factor (TNF-α) with cardiovascular risk factors in three hundred coronary artery disease patients. Nutrition assessment was done at the time of recruitment. Patients were evaluated for anthropometry, cardiovascular risk factors, and blood samples were collected. Patients were divided into three groups according to serum magnesium levels; ≤1.6 (Group 1), >1.6–2.6 (Group 2) and: >2.6 mg/dl (Group 3) and into two groups according to recommended dietary allowance (RDA) for magnesium (≤350 mg/day and >350 mg/day). More than half of patients (58.6%) were having hypomagnesemia and 62% were consuming magnesium below RDA. Insulin and IR was significantly higher and insulin sensitivity was significantly lower in group 1 compared to group 2 and 3. Insulin and IR was correlated negatively; and insulin sensitivity was correlated positively with serum magnesium. Similarly inflammatory markers were significantly higher in group1 when compared with group 2 and 3 and they were correlated negatively with serum magnesium. Dietary magnesium was positively correlated with serum magnesium. Insulin and IR were significantly higher and insulin sensitivity was significantly lower in subjects with low RDA for magnesium. Insulin and IR were correlated negatively and sensitivity was correlated positively with dietary magnesium. Inflammatory markers; IL-6, TNF-α, and hs CRP were significantly high in subjects with low RDA for magnesium and were correlated negatively with dietary magnesium. Conclusion: Hypomagnesemia and low dietary magnesium is associated with IR and inflammatory markers in patients with coronary artery disease. Key words: Inflammatory markers; Hypomagnesemia; C-reactive protein; Interleukin-6; Tumor necrosis factor–alpha; Coronary artery disease.

Association of dietary factors with insulin resistance and inflammatory markers in subjects with diabetes mellitus and coronary artery disease in Indian population

BackgroundInsulin resistance (IR) and inflammation have been implicated in pathogenesis of diabetes and cardiovascular disease. Dietary factors have been reported to be associated to insulin resistance and inflammation. Hence, we studied the association of dietary factors with IR and inflammation in known patients with diabetes mellitus and coronary artery disease with the hypothesis that carbohydrate and fat will be positively; and protein, fiber and mineral will be negatively associated with IR and inflammatory markers. MethodsThree hundred patients (M: 216; F: 84, age: 25–92) who had coronary disease on angiography were included in this study consecutively. All patients were evaluated for anthropometry and cardiovascular risk factors, and blood samples were collected for biochemical and inflammatory markers. Nutrition assessment was done once at the time of recruitment, based on 24h dietary recall. Results and ConclusionsDiabetic patients had significantly lower protein and total dietary fiber intake as compared to non diabetics. Diabetic patients had lower intake of vitamin A, riboflavin and vitamin B12. There was significantly lower intake of minerals by diabetic patients. Dietary carbohydrate and fat were positively, and protein and dietary fiber intakes were negatively correlated with HOMA-IR and IL-6. There was no correlation of individual amino acids with HOMA-IR but showed strong negative correlation with inflammatory markers (hsCRP; IL-6 and TNF-α). Intake of vitamins and minerals was negatively correlated with HOMA-IR and inflammatory markers. There is a strong correlation between dietary factors, insulin resistance and inflammatory markers.

The relationship between vitamin D status and markers of diabetes risk in individuals at risk for developing diabetes: preliminary data from the Evidence trial (1041.10)

Data from epidemiological studies show an inverse association between low levels of serum 25‐hydroxyvitamin D3 (25(OH)D3) and markers of diabetes risk including high blood glucose levels. The EVIDENCE trial is a randomized, double‐blind clinical trial which aims to examine the effect of vitamin D3 fortified cheese versus placebo on fasting and serum glucose 2h after consuming 75g of glucose (OGTT), insulin, glycated haemoglobin (HbA1c) and markers of inflammation in subjects with low serum 25(OH)D3 (蠄65nmol/ L) and who are at an increased risk for developing type 2 diabetes (T2D). Twenty‐one subjects (11M, 10F) with a mean age of 52 ± 12y enrolled in the EVIDENCE trial visited the laboratory after a 12hr overnight fast. Fasting blood samples were drawn from subjects and assayed for 25(OH)D3, glucose, HbA1c, triglycerides, total, LDL and HDL cholesterol. In this sample of participants enrolled in the EVIDENCE trial we observed a significant inverse association between 25(OH)D3 and triglycerides (r= ‐0.5413, p= 0.011) and waist circumference (r= ‐0.4427, p= 0.045). We also observed an moderate inverse association between serum 25(OH)D3 and HbA1c (r= ‐0.270), however it was not statistically significant. No significant associations were observed between 25(OH)D3 and glucose, total, LDL and HDL cholesterol which may be due to the small sample size. These preliminary data suggests that vitamin D status is inversely related to factors which increase an individual’s risk for developing diabetes.The results from the EVIDENCE trial will assist us in obtaining a better understanding of the potential role of vitamin D in modulating some of the risk factors associated with T2D.Grant Funding Source: Supported by Dairy Farmers of Canada