Plasma Concentrations Of Inflammatory Markers Research Articles

Involvement of circulating microRNAs in the pathogenesis of atherosclerosis in young patients with obesity.

Obesity is considered an important factor contributing to the development of atherosclerosis. Inflammation plays a key role in endothelial dysfunction (ED), an initial stage of the atherosclerotic process. Several microRNAs (miRNAs) may play an important role in the inflammatory process, but there is a lack of information about their participation in the early stages of atherosclerosis development in patients with obesity. We aimed to assess the relations between plasma concentration of selected miRNAs, ED evaluated by reactive hyperemia index (RHI), inflammatory markers and other factors involved in the pathogenesis of atherosclerosis in adolescents and young adults with obesity. Participants (30 males, 30 females; aged 15 25 years) were divided into two groups: those with overweight/obesity (OW/O) (20 males, 20 females) and controls (C) (10 males, 10 females). The plasma concentrations of inflammatory markers, cytokines, adipocytokines, markers of lipid profile and glucose metabolism and selected miRNAs (miR 92, 126, -146a, -155) were analyzed. No significant differences in any of the miRNAs were found between the groups. MiR-146a correlated positively with RHI. Dividing the group by sex showed more significant associations between miRNA and analyzed parameters (IL-6, fasting glycemia) in men. Several observed correlations indicate a potential role of miRNAs in inflammation, the atherosclerotic process and glycemic control, primarily in male subjects with obesity. The relatively low number of observed associations between assessed parameters related to obesity and the pathogenesis of its complications could be attributed to the early stage of the atherosclerotic process in young subjects with obesity, where only subtle abnormalities are expectedly found. Key words Endothelial dysfunction, Atherosclerosis, Obesity, MicroRNA, Reactive hyperemia index.

Increased TMEM166 Level in Patients with Postoperative Stroke after Carotid Endarterectomy

Postoperative stroke is a challenging and potentially devastating complication after elective carotid endarterectomy (CEA). We previously demonstrated that transmembrane protein 166 (TMEM166) levels were directly related to neuronal damage after cerebral ischemia–reperfusion injury in rats. In this subsequent clinical study, we aimed to evaluate the prognostic value of TMEM166 in patients suffering from post-CEA strokes. Thirty-five patients undergoing uncomplicated elective CEA and 8 patients who suffered ischemic strokes after CEA were recruited. We evaluated the protein level and expression of TMEM166 in patients diagnosed with postoperative strokes and compared it to those in patients who underwent uncomplicated elective CEA. Blood samples and carotid artery plaques were collected and analyzed. High expressions of TMEM166 were detected by immunofluorescence staining and Western Blot in carotid artery plaques of all patients who underwent CEA. Furthermore, circulating TMEM166 concentrations were statistically higher in post-CEA stroke patients than in patients allocated to the control group. Mean plasma concentrations of inflammatory markers, including interleukin 6 (IL-6) and C-reactive protein (CRP), were also elevated in patients with postoperative strokes. Therefore, based on these findings, we hypothesize that elevated TMEM166 levels, accompanied by a strong inflammatory response, serve as a useful biomarker for risk assessment of postoperative stroke following CEA.

Biomarkers Reflecting the Severity of Bronchial Asthma in Children.

Bronchial asthma, the most prevalent chronic inflammatory airway disease in children, exhibits a concerning rise in both incidence and prevalence. Asthma biomarkers hold promise for stratifying patients into distinct clinical phenotypes, paving the way for targeted and personalized treatment approaches. This study aimed to evaluate the association between novel and non-established semi-invasive circulating and well-known exhaled inflammatory biomarkers in two distinct pediatric asthma populations stratified by disease severity. Forty-four asthmatic children aged 8-12 years meeting inclusion criteria were recruited from hospitalized patients. The first group (n=15, mean age 9.8 years) consisted of patients with mild persistent asthma who did not require regular inhaled corticosteroids (ICS). The second group (n=29, mean age 9.8 years) consisted of children with moderate to persistent asthma who received regular ICS treatment. Serum levels of interleukins (IL-13, IL-1β), eosinophil-derived neurotoxin (EDN), and surfactant protein D (SPD) were measured by ELISA in all participants. In addition, exhaled nitric oxide (FeNO) and blood eosinophil counts were evaluated. No significant differences were observed in the baseline plasma concentrations of inflammatory markers (IL-13, IL-1β, SPD, and EDN) or exhaled FeNO between the ICS-treated and non-ICS-treated groups. Further inter-individual analysis confirmed significant positive correlations between IL-13, SPD, and IL-1β (Pearson's r = 0.591-0.781) in both groups of patients. Interestingly, the ICS-treated group compared to the nontreated group showed an exclusive moderate negative correlation between FeNO and IL-1β. In contrast, FeNO exhibited a positive correlation with EDN and a strong association with eosinophil count in all the study groups. Our findings highlight the complex and unresolved role of asthma biomarkers in routine clinical practice for the management of childhood asthma, particularly in predicting exacerbations. By comparing the relationships of carefully selected biomarkers, we can achieve a greater clinical predictive value.

Longitudinal associations of circadian eating patterns with sleep quality, fatigue and inflammation in colorectal cancer survivors up to 24 months post-treatment.

Fatigue and insomnia, potentially induced by inflammation, are distressing symptoms experienced by colorectal cancer (CRC) survivors. Emerging evidence suggests that besides the nutritional quality and quantity, also the timing, frequency and regularity of dietary intake (chrono-nutrition) could be important for alleviating these symptoms. We investigated longitudinal associations of circadian eating patterns with sleep quality, fatigue and inflammation in CRC survivors. In a prospective cohort of 459 stage I-III CRC survivors, four repeated measurements were performed between 6 weeks and 24 months post-treatment. Chrono-nutrition variables included meal energy contribution, frequency (a maximum of six meals could be reported each day), irregularity and time window (TW) of energetic intake, operationalised based on 7-d dietary records. Outcomes included sleep quality, fatigue and plasma concentrations of inflammatory markers. Longitudinal associations of chrono-nutrition variables with outcomes from 6 weeks until 24 months post-treatment were analysed by confounder-adjusted linear mixed models, including hybrid models to disentangle intra-individual changes from inter-individual differences over time. An hour longer TW of energetic intake between individuals was associated with less fatigue (β: -6·1; 95 % CI (-8·8, -3·3)) and insomnia (β: -4·8; 95 % CI (-7·4, -2·1)). A higher meal frequency of on average 0·6 meals/d between individuals was associated with less fatigue (β: -3·7; 95 % CI (-6·6, -0·8)). An hour increase in TW of energetic intake within individuals was associated with less insomnia (β: -3·0; 95 % CI (-5·2, -0·8)) and inflammation (β: -0·1; 95 % CI (-0·1, 0·0)). Our results suggest that longer TWs of energetic intake and higher meal frequencies may be associated with less fatigue, insomnia and inflammation among CRC survivors. Future studies with larger contrasts in chrono-nutrition variables are needed to confirm these findings.

No Observed Difference in Inflammatory and Coagulation Markers Following Diets Rich in n-6 Polyunsaturated Fat vs Monounsaturated Fat in Adults With Untreated Hypercholesterolemia: A Randomized Trial

BackgroundInflammatory and prothrombotic responses are hallmark to the progression of cardiovascular disease and may be influenced by the type of dietary fat. Cottonseed oil (CSO) is rich in n-6 polyunsaturated fats and improves traditional cardiovascular disease risk factors such as cholesterol profiles. However, some clinicians are still hesitant to promote n-6 polyunsaturated fats consumption despite growing evidence suggesting they may not be independently pro-inflammatory. ObjectiveTo investigate the inflammatory and coagulation marker responses to an 8-week diet intervention rich in either CSO or olive oil (OO) (OO is rich in monounsaturated fat) in adults with untreated hypercholesterolemia. DesignThis was a secondary analysis of a parallel-arm randomized clinical trial with the main outcome of cholesterol measures. Participants/settingParticipants included in this analysis were 42 sedentary adults aged 30 to 75 years (62% women) in the Athens, GA, area, between May 2018 and June 2021, with untreated hypercholesterolemia or elevated blood lipids and body mass index >18.5. Hypercholesterolemia was defined as at least two blood lipid levels in a borderline undesirable/at risk range (total cholesterol level ≥180 mg/dL, low-density lipoprotein cholesterol level ≥110 mg/dL, high-density lipoprotein cholesterol level <50 mg/dL, or triglyceride level ≥130 mg/dL), or at least one in an undesirable range (total cholesterol level ≥240 mg/dL, low-density lipoprotein cholesterol level ≥160 mg/dL, high-density lipoprotein cholesterol level <40 mg/dL, or triglyceride level ≥200 mg/dL). InterventionParticipants were randomly assigned to either the CSO or OO group in a partial outpatient feeding trial. Meals from the study provided approximately 60% of their energy needs with 30% of energy needs from either CSO or OO for 8 weeks. Participants fulfilled their remaining energy needs with meals of their choosing. Main outcome measuresFasting plasma concentrations of inflammatory markers, including C-reactive protein, tumor necrosis factor-α, interleukin-6, and interleukin-1β were measured at baseline and 8 weeks. Markers of coagulation potential, including plasminogen activator inhibitor-1, and tissue factor were measured at the same time points. Statistical analyses performedRepeated measures linear mixed models were used with treatment and visit in the model for analyses of all biochemical markers. ResultsThere were no significant differences in fasting C-reactive protein (P = 0.70), tumor necrosis factor-α (P = 0.98), interleukin-6 (P = 0.21), interleukin-1β (P = 0.13), plasminogen activator inhibitor-1 (P = 0.29), or tissue factor (P = 0.29) between groups across the intervention. ConclusionsInflammation and coagulation marker responses to diets rich in CSO vs OO were not significantly different between groups, and neither group showed changes in these markers in adults with untreated hypercholesterolemia. This provides additional evidence suggesting that dietary n-6 polyunsaturated fats may not promote inflammation compared with monounsaturated fatty acids, even in adults at increased risk for cardiovascular disease.

Red Blood Cell Membrane Fatty Acid Composition, Dietary Fatty Acid Intake and Diet Quality as Predictors of Inflammation in a Group of Australian Adults.

Evidence suggests that diet can play a role in modulating systemic inflammation. This study aims to examine the relationship between fatty acids (FAs) (self-reported dietary intake and red blood cell (RBC) membrane fatty acid concentrations), three diet quality scores, and the plasma concentrations of inflammatory markers (interleukin-6, IL-6; tumour necrosis factor alpha, TNF-α; and C-reactive protein, CRP) in a group of Australian adults (n = 92). Data were collected on their demographic characteristics, health status, supplement intake, dietary intake, RBC-FAs and plasma inflammatory markers over a nine-month period. Mixed-effects models were used to determine the relationship between RBC-FAs, dietary intake of FAs, diet quality scores and inflammatory markers to determine which variable most strongly predicted systemic inflammation. A significant association was identified between dietary saturated fat intake and TNF-α (β = 0.01, p < 0.05). An association was also identified between RBC membrane saturated fatty acids (SFA) and CRP (β = 0.55, p < 0.05). Inverse associations were identified between RBC membrane monounsaturated fatty acids (MUFAs) (β = -0.88, p < 0.01), dietary polyunsaturated fatty acids (PUFAs) (β = -0.21, p < 0.05) and CRP, and the Australian Eating Survey Modified Mediterranean Diet (AES-MED) score and IL-6 (β = -0.21, p < 0.05). In summary, using both objective and subjective measures of fat intake and diet quality, our study has confirmed a positive association between saturated fat and inflammation, while inverse associations were observed between MUFAs, PUFAs, the Mediterranean diet, and inflammation. Our results provide further evidence that manipulating diet quality, in particular fatty acid intake, may be useful for reducing chronic systemic inflammation.

Successful Treatment of COVID-19 Patient on ECMO Using Mesenchymal Stromal Cells (MSC)-Derived Exosomes: A Case Report

IntroductionThe use of mesenchymal stromal cells (MSC) was recently proposed as a promising intervention for COVID-19 related respiratory failure (RF). Prior studies have suggested that its larger size might lead to entrapment in extracorporeal membrane oxygenation (ECMO), affect circuit function, and attenuate its efficacy. We present a successful case of a severe COVID-19 patient treated with MSC-derived exosomes while receiving veno-venous (VV) ECMO support.Case Report41-year-old unvaccinated obese White male with no past medical history presenting with shortness of breath and a +COVID-19 nasopharyngeal test was admitted receiving high-flow nasal cannula (HFNC), remdesivir, and dexamethasone (Day 1), followed by intubation (day 5), and a peripheral VV ECMO insertion (day 10) due to worsening RF. We used bivalirudin for post-ECMO anticoagulation. Subsequently, he received the first cycle of MSC-derived exosomes on alternative days (day 1, 3, & 5) between days 13-17, followed by the second cycle between days 34-38. After administration of exosomes, the plasma concentration of inflammatory markers reduced, including a decrease of 77% for ferritin, 74% for CRP, and 62% for procalcitonin in approximately one week, along with consistent improvement of PaO2/FiO2 ratio. ECMO membrane oxygenator was exchanged on day 23 at the time of tracheostomy. After successful weaning, ECMO decannulation was performed on day 47, and the patient was discharged home on day 61.SummaryECMO has emerged as a supportive strategy for patients with severe COVID-19 related RF. The patient's inflammatory response has been implicated in the pathophysiology of lung failure. Multiple pharmacological methods are employed to control the severity of this inflammatory response, thus preventing progression to the fibrotic stage of the disease. In our experience, MSC-derived exosomes neither resulted in any side effects nor impaired the function of ECMO and might have enhanced the recovery of the patient.

The association of plasma inflammatory markers with omega-3 fatty acids and their mediating role in psychotic symptoms and functioning: An analysis of the NEURAPRO clinical trial

BackgroundThere is increasing evidence that dysregulation of polyunsaturated fatty acids (FAs) mediated membrane function plays a role in the pathophysiology of schizophrenia. Even though preclinical findings have supported the anti-inflammatory properties of omega-3 FAs on brain health, their biological roles as anti-inflammatory agents and their therapeutic role on clinical symptoms of psychosis risk are not well understood. In the current study, we investigated the relationship of erythrocyte omega-3 FAs with plasma immune markers in a clinical high risk for psychosis (CHR) sample. In addition, a mediation analysis was performed to examine whether previously reported associations between omega-3 FAs and clinical outcomes were mediated via plasma immune markers. Clinical outcomes for CHR participants in the NEURAPRO clinical trial were measured using the Brief Psychiatric Rating Scale (BPRS), Schedule for the Scale of Assessment of Negative Symptoms (SANS) and Social and Occupational Functioning Assessment Scale (SOFAS) scales. The erythrocyte omega-3 index [eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA)] and plasma concentrations of inflammatory markers were quantified at baseline (n = 268) and 6 month follow-up (n = 146) by gas chromatography and multiplex immunoassay, respectively. In linear regression models, the baseline plasma concentrations of Interleukin (IL)-15, Intercellular adhesion molecule (ICAM)-1 and Vascular cell adhesion molecule (VCAM)-1 were negatively associated with baseline omega-3 index. In addition, 6-month change in IL-12p40 and TNF-α showed a negative association with change in omega-3 index. In longitudinal analyses, the baseline and 6 month change in omega-3 index was negatively associated with VCAM-1 and TNF-α respectively at follow-up. Mediation analyses provided little evidence for mediating effects of plasma immune markers on the relationship between omega-3 FAs and clinical outcomes (psychotic symptoms and functioning) in CHR participants. Our results indicate a predominantly anti-inflammatory relationship of omega-3 FAs on plasma inflammatory status in CHR individuals, but this did not appear to convey clinical benefits at 6 month and 12 month follow-up. Both immune and non-immune biological effects of omega-3 FAs would be resourceful in understanding the clinical benefits of omega-3 FAs in CHR papulation.

Self-Reported Cannabis Use and Markers of Inflammation in Men Who Have Sex With Men With and Without HIV.

Background: Chronic inflammation contributes to aging and organ dysfunction in the general population, and is a particularly important determinant of morbidity and mortality among people with HIV (PWH). The effect of cannabis use on chronic inflammation is not well understood among PWH, who use cannabis more frequently than the general population. Materials and Methods: We evaluated participants in the Multicenter AIDS Cohort Study (MACS) beginning in 2004 with available data on cannabis use and inflammatory biomarkers. Associations of current cannabis use with plasma concentrations of inflammatory markers were adjusted for hepatitis C, tobacco smoking, and comorbidities. Markers were analyzed individually and in exploratory factor analysis (EFA). Results: We included 1352 men within the MACS. Twenty-seven percent of HIV-negative men, 41% of HIV viremic men, and 35% of virologically suppressed men reported cannabis use at baseline. Among cannabis users, 20-25% in all groups defined by HIV serostatus were daily users, and the same proportion reported weekly use. The remaining ∼50% of users in all groups reported monthly or less frequent use. Four biomarker groupings were identified by EFA: Factor 1: immune activation markers; Factor 2: proinflammatory cytokines; Factor 3: Th1- and Th2-promoting cytokines; and Factor 4: inflammatory chemokines. In EFA, daily users had 30% higher levels of Factor 2 biomarkers than nonusers (p=0.03); this was the only statistically significant difference by cannabis use status. Among individual markers, concentrations of IL-1β, IL-2, IL-6, and IL-8 (Factor 2); IL-10 (Factor 3); and BAFF (Factor 1) were higher (p<0.05) among daily cannabis users than among nonusers, after adjusting for HIV serostatus and other covariates. Discussion: Associations between daily cannabis use and proinflammatory biomarker levels did not differ by HIV serostatus. Further prospective studies with measured cannabis components are needed to clarify the impact of these compounds on inflammation. Our findings can facilitate for hypothesis generation and selection of biomarkers to include in such studies.

1914-P: Prolonged (12-Hour) Glucagon Infusion Stimulates Adipocyte Lipolysis and Inflammation In Vivo in Humans

Hyperglucagonemia is a characteristic feature of T2DM and contributes to the metabolic disturbances. Although some rodent studies have suggested that glucagon stimulates lipolysis in adipocytes, the long-term effect of hyperglucagonemia on adipose tissue metabolism and glucose homeostasis in vivo in humans is unclear. The aim of the present study was to examine the effect of 12-hour glucagon infusion on hepatic glucose production (HGP) and adipocyte metabolism in healthy individuals. 8 NGT subjects (5M/3F, age=35±5, BMI = 24±1) received a 12-hour (6PM to 6AM) glucagon infusion (6ng/kg/min) with 3-3H-glucose infusion followed by subcutaneous adipose tissue biopsy at 6AM. On a different day the subjects returned for a repeat study with infusion (6PM to 6AM) of normal saline. Plasma glucagon increased from 57±3 to 219±21 pg/ml. Plasma glucose increased transiently after the start of glucagon and declined to baseline levels at 6AM. Plasma insulin levels increased significantly following glucagon compared to saline (20±7 vs. 8±3 mU/L, p&amp;lt;0.05) and remained elevated at 6AM. Basal HGP (3.2±0.1 vs. 2.9±0.1 mg/kg/min, p&amp;lt;0.01) and fasting plasma FFA concentrations (0.70±0.1 vs. 0.39±0.1 mM, p&amp;lt;0.01) were increased after 12-hour glucagon infusion despite increased plasma insulin levels, indicating severe hepatic and adipocyte insulin resistance. Lipolysis-related gene expression in adipose tissue biopsy were upregulated following 12-hour glucagon infusion (ATGL, 1.14±0.07 vs. 0.77±0.03; HSL, 1.17±0.03 vs. 0.9±0.13; MGL, 1.2±0.04 vs. 0.82±0.2, all p&amp;lt;0.05). Plasma concentration of inflammatory markers were also increased after 12-hour glucagon infusion (IL-1β, 0.65±0.05 vs. 0.49±0.05 pg/mL; TNF-α, 2.03±0.23 vs. 1.75±0.17 pg/mL, both p&amp;lt;0.05). Overall, these results demonstrate that prolonged physiologic hyperglucagonemia causes marked hepatic and adipocyte insulin resistances, stimulates lipolysis and increases plasma FFA, and induces adipocyte and systemic inflammation. Disclosure D. Tripathy: None. M. Fourcaudot: None. L. Norton: None. R.A. DeFronzo: None. X. Chen: None.

Stability of plasma indices of inflammation/coagulation and homeostasis after fatty and non-fatty meals in treated people with HIV

ObjectivesThe relationship between lipid levels in plasma and inflammatory indices is complex and fatty meals alter plasma inflammatory markers in people with diabetes. There is interest in monitoring the effects of interventions on plasma inflammatory and coagulation elements in people with HIV, as they have been linked to risk for morbid outcomes and HIV persistence. Understanding the effects of feeding and time of specimen acquisition is important for the correct scheduling of clinical sampling. MethodsWe examined the effects of feeding on plasma inflammatory, coagulation and homeostatic indices among 24 non-diabetic people with HIV, with controlled viraemia and on antiretroviral therapy after fasting and then 1, 3 and 6 hours after ingesting a fatty meal, and also approximately 1 week later after fasting and after an isocaloric non-fatty meal. Plasma levels of IL-6, IL-7, IP-10, sCD14, sCD163, sTNFrII and D-dimer were monitored by immunoassay. ResultsFasting levels of all markers obtained approximately 1 week apart were significantly correlated (P<0.001). Mild alterations in plasma concentrations of inflammatory markers were observed after feeding but geometric means varied more than 10% from baseline for only IL-6 and IL-7. Meal type was differentially associated with changes in plasma levels for IL-7 only. Antiretroviral treatment regimen, body mass index and changes in plasma triglyceride levels were not linked to post-feeding changes in these biomarkers. ConclusionsThese plasma inflammatory, coagulation and homeostatic indices are relatively stable at fasting and are only minimally affected by feeding or time of day. These findings will aid in the monitoring of inflammatory and homeostatic indices that may contribute to control of HIV expression and its persistence.

High Visceral to Subcutaneous Fat Ratio Is Associated with Increased Postoperative Inflammatory Response after Colorectal Resection in Inflammatory Bowel Disease.

Aim Excessive postoperative inflammatory response, which is characterized by overproduction of cytokines, often leads to complications after colorectal surgery. However, the impact of body composition on postoperative inflammatory response is largely unknown. The aim of this study is to elucidate whether body fat amount and its distribution affects postoperative inflammation after colorectal surgery in IBD patients. Methods Eighty-six patients undergoing colorectal resection for IBD from June 2014 to Jan 2017 were enrolled. Abdominal CT images within one week prior to surgery were assessed for visceral fat, subcutaneous fat, and muscle mass. Postoperative inflammatory response was evaluated using serum CRP, PCT, and IL-6 levels on postoperative days 1, 3, and 5. Univariate analysis was conducted to identify risk factors for infectious complications. The correlation between body composition and postoperative plasma concentration of inflammatory markers was analyzed using a linear regression model. ROC curve was applied to analyze the effect of different body composition parameters on postoperative infectious complications and to determine the relationship between inflammatory markers and infectious complications. Results Neither volume of fat or muscle was related to postoperative plasma concentrations of CRP, IL-6, and PCT. However, visceral to subcutaneous fat ratio was associated with PCT levels on postoperative days (POD) 1, 3, and 5, with the highest regression coefficient on POD1 (β = 0.360; 95% CI, 0.089–0.631; P = 0.010). Body composition did not predict postoperative infectious complications, while CRP on POD 3 was predictive of infectious complications. Conclusion Increased visceral to subcutaneous fat ratio was associated with postoperative inflammatory response in IBD patients undergoing colorectal resection. This may partly explain the increased incidence of postoperative complications in patients with visceral obesity.

Long-Term Immunomodulatory Effects of a Mediterranean Diet in Adults at High Risk of Cardiovascular Disease in the PREvención con DIeta MEDiterránea (PREDIMED) Randomized Controlled Trial

Background: The Mediterranean diet (MedDiet) has demonstrated short-term anti-inflammatory effects, but little is known about its long-term immunomodulatory properties.Objective: Our goal was to assess the long-term effects of the MedDiet on inflammatory markers related to atherogenesis in adults at high risk of cardiovascular disease (CVD) compared with the effects of a low-fat diet (LFD).Methods: We randomly assigned 165 high-risk participants (one-half men; mean age: 66 y) without overt CVD to 1 of 3 diets: a MedDiet supplemented with extra-virgin olive oil, a MedDiet supplemented with nuts, or an LFD. Follow-up data were collected at 3 and 5 y. Repeated-measures ANOVA, adjusted for potential confounding variables, was used to evaluate changes in diet adherence, CVD risk factors, and inflammatory variables.Results: The 2 MedDiet groups achieved a high degree of adherence to the intervention, and the LFD group had reduced energy intake from fat by 13% by 5 y. Compared with baseline, at 3 and 5 y, both MedDiet groups had significant reductions of ≥16% in plasma concentrations of high-sensitivity C-reactive protein, interleukin-6, tumor necrosis factor α, and monocyte chemoattractant protein 1 (P ≤ 0.04), whereas there were no significant changes in the LFD group. The reductions in CD49d and CD40 expressions in T lymphocytes and monocytes at 3 y were ≥16% greater in both MedDiet groups than were the changes in the LFD group (P < 0.001) at 3 y. Compared with baseline, at 3 y, the MedDiet groups had increased HDL-cholesterol (≥8%) and decreased blood pressure (>4%) and total cholesterol, LDL-cholesterol, and triglyceride (≥8%) concentrations. At 5 y, concentrations of glucose (13%) and glycated hemoglobin (8%) had increased with the LFD.Conclusions: The MedDiet participants had lower cellular and plasma concentrations of inflammatory markers related to atherosclerosis at 3 and 5 y. This anti-inflammatory role of the MedDiet could explain in part the long-term cardioprotective effect of the MedDiet against CVD. This trial was registered at controlled-trials.com as ISRCTN35739639.

Long-term effects of angiotensin II blockade with irbesartan on inflammatory markers in hemodialysis patients: A randomized double blind placebo controlled trial (SAFIR study).

Low-grade chronic inflammation is common in hemodialysis (HD) patients. Previous studies suggest an anti-inflammatory effect of angiotensin II receptor blocker (ARB) treatment. The aim of this study was to compare the effect of ARB vs. placebo on plasma concentrations of inflammatory markers in HD patients. Adult HD patients were randomized for double-blind treatment with the ARB irbesartan 150-300 mg/day or placebo. At baseline, 1 week, 3, 6, 9, and 12 months plasma high sensitivity C-reactive protein (hsCRP), interleukin (IL)-1β, IL-6, IL-8, IL-18, and transforming growth factor-β (TGF-β) were measured using Luminex and enzyme-linked immunosorbent assay (ELISA) technology. Eighty-two patients were randomized (placebo/ARB: 41/41). The groups did not differ in initial levels of any of the inflammatory markers (placebo/ARB median(range)): hsCRP 3.3(0.2-23.4)/2.7(0.2-29.6) μg/mL; IL-1β 1.1(0.0-45.9)/1.1(0.0-7.2) pg/mL; IL-6 10(1-90)/12(1-84) pg/mL; IL-8 31(9-134)/34(5-192) pg/mL; IL-18 364(188-1343)/377(213-832) pg/mL; TGF-β 3.2(0.8-13.9)/3.6(1.3-3.8) ng/mL. Overall, there was no significant difference in hsCRP, IL-6, IL-8, and TGF-β between placebo and ARB-treated patients during the study period, and hsCRP, IL-6, IL-8, and TGF-β were relatively stable during the study period (P ≥ 0.18 in all tests for parallel curves, equal levels, and constant levels). The IL-1β level was slightly different in the two groups over time, but not significantly (P = 0.09 in test for parallel curves) and it was also relatively stable during the study period (P ≥ 0.49 in tests for equal levels and constant level). IL-18 was the only inflammatory marker which was not constant during the study period (P = 0.001 in test for constant level), but there was no significant difference between placebo and ARB-treated (P ≥ 0.51 in tests for parallel curves and equal levels). Inflammatory biomarkers were neither acutely, nor in the long-term significantly affected by the ARB irbesartan. Our findings suggest that ARB treatment in HD patients does not offer protective anti-inflammatory effects.

Non-soya legume-based therapeutic lifestyle change diet reduces inflammatory status in diabetic patients: a randomised cross-over clinical trial.

The present randomised cross-over clinical trial investigated the effects of two intervention diets (non-soya legume-based therapeutic lifestyle change (TLC) diet v. isoenergetic legume-free TLC diet) on inflammatory biomarkers among type 2 diabetic patients. A group of thirty-one participants (twenty-four women and seven men; weight 74.5 (SD 7.0) kg; age 58.1 (SD 6.0) years) were randomly assigned to one of the two following intervention diets for 8 weeks: legume-free TLC diet or non-soya legume-based TLC diet. The latter diet was the same as the legume-free TLC diet, except that two servings of red meat were replaced with different types of cooked non-soya legumes such as lentils, chickpeas, peas and beans over a period of 3 d per week. The intervention period was followed by a washout period of 4 weeks, after which the groups followed the alternate treatment for 8 weeks. Concentrations of inflammatory markers were measured at baseline and after the intervention periods. Compared with the legume-free TLC diet, the non-soya legume-based TLC diet significantly decreased high-sensitivity C-reactive protein, IL-6 and TNF-α in overweight diabetic patients. The replacement of two servings of red meat by non-soya legumes in the isoenergetic TLC diet for a period of 3 d per week reduced the plasma concentrations of inflammatory markers among overweight diabetic patients, independent of weight change.

P.5.f.007 Self-perception of medical residents' ability to predict and deal with patients with suicide risk

Simão AP, Avelar NC, Tossige-Gomes R, Neves CD, Mendonça VA, Miranda AS, Teixeira MM, Teixeira AL, Andrade AP, Coimbra CC, Lacerda AC. Functional performance and inflammatory cytokines after squat exercises and whole-body vibration in elderly individuals with knee osteoarthritis.To investigate the effects of squat exercises combined with whole-body vibration on the plasma concentration of inflammatory markers and the functional performance of elderly individuals with knee osteoarthritis (OA).Clinical, prospective, randomized, single-blinded study.Exercise physiology laboratory.Elderly subjects with knee OA (N=32) were divided into 3 groups: (1) squat exercises on a vibratory platform (platform group, n=11); (2) squat exercises without vibration (squat group, n=10); and (3) the control group (n=11).The structured program of squat exercises in the platform and squat groups was conducted 3 times per week, on alternate days, for 12 weeks.Plasma soluble tumor necrosis factor-α receptors 1 (sTNFR1) and 2 (sTNFR2) were measured using immunoassays (the enzyme-linked immunosorbent assay method). The Western Ontario and McMaster Universities Osteoarthritis Index questionnaire was used to evaluate self-reported physical function, pain, and stiffness. The 6-minute walk test, the Berg Balance Scale, and gait speed were used to evaluate physical function.In the platform group, there were significant reductions in the plasma concentrations of the inflammatory markers sTNFR1 and sTNFR2 (P<.001 and P<.05, respectively) and self-reported pain (P<.05) compared with the control group, and there was an increase in balance (P<.05) and speed and distance walked (P<.05 and P<.001, respectively). In addition, the platform group walked faster than the squat group (P<.01).The results suggest that whole-body vibration training improves self-perception of pain, balance, gait quality, and inflammatory markers in elderly subjects with knee OA.

Effect of High Pressure-Volume and Low Pressure-Volume Mechanical Ventilation on Plasma Concentrations of Inflammatory Markers in Horses during General Anaesthesia

Systemic changes of interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), neutrophil elastase (ELT) and myeloperoxidase (MPO) during mechanical ventilation (MV) in horses anaesthetized for surgery are evaluated. Thirty-four client-owned ASA I-II horses randomly received mechanical ventilation (MV) with either a peak inspiratory pressure (PIP) of 30 cm H2O and tidal volume (VT)>10 mL kg-1 (high pressure-volume MV) or PIP of 15 cm H2O and VT ≤ 10 mL kg-1 (low pressure-volume MV) in dorsal or lateral recumbency. Horses were premedicated with acepromazine (0.1 mg kg-1 IM) and xylazine (0.6 mg kg-1 IV), induced with midazolam (0.06 mg kg-1 IV) and ketamine (2.2 mg kg-1 IV) and maintained with isoflurane in oxygen 70% plus ketamine-midazolam infusion (1 and 0.02 mg kg-1 h-1, respectively). Anti-inflammatory drug and antibiotics were administered before surgery. Plasmatic proinflammatory mediator concentrations were estimated by ELISA at the beginning (T0) and after 60 minutes (T1) of MV. Mean plasmatic TNF-α, MPO, and ELT concentrations at T1 were significantly (p<0.05) lower than T0. Mean plasmatic concentration of IL-6 did not significantly change with time. The reduction in plasmatic concentration of proinflammatory mediators at T1 was not linked to ventilation strategy or recumbency. None of the ventilation protocols enhanced systemic inflammatory response during surgery after 1 hour of MV. The anti-inflammatory properties of drugs included in the anaesthesia protocol may have contributed to the overall decreased systemic inflammatory mediator concentrations, despite MV and surgery.

Изучение роли факторов роста фибробластов (β-FGF, TGFβ1), маркеров воспаления (IL-6, TNF-α, СRP) и конечных продуктов гликирования (AGE, RAGE) у пациентов с ишемической болезнью сердца и сахарным диабетом 2 типа

Aims. To evaluate plasma levels of transforming growth factor beta (TGFbeta1), basic fibroblast growth factor (bFGF), markers for nonspecific inflammatory process (interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-alpha), C-reactive protein (CRP)) and their putative correlation with advanced glycation end-products relative to diabetes compensation in patients with ischemic heart disease (IHD). Materials and Methods. 87 patients with IHD were enrolled in this study. All subjects underwent standard clinical examination, including laboratory assessment of glycemic parameters, lipid panel and renal function, with echocardiography, supplemented with coronary angiography. Analyses for study parameters were performed on samples obtained from aorta and, separately, from cubital vein during coronary angiography. Results. Diabetes mellitus in patients with IHD is firmly associated with TGFbeta1, IL-6 and CRP elevation in both arterial and venous plasma. TGFbeta1 positively correlates with lipid profile parameters. Plasma concentration of inflammatory markers and advanced glycation end-products positively correlates with the extent of coronary lesions in relation to the presence of diabetes mellitus. Conclusion. Our data suggests the interplay between connective tissue growth factors and lipid metabolism in the atherosclerotic process.

The effect of exercise on plasma concentrations of inflammatory markers in normal and previously laminitic ponies

The mechanisms underlying predisposition to pasture-associated laminitis remain unclear; chronic inflammation is implicated, and this may be exacerbated by physical inactivity. To determine whether exercise affects the inflammatory profile of normal and previously laminitic ponies. Prospective case-control study. The short (1 day) and longer term (14 days) effects of low intensity (10 min walking and 5 min trotting) exercise on plasma inflammatory marker concentrations in normal (NL) and previously laminitic (PL) nonobese ponies (n = 6/group) was determined. Plasma concentrations of TNF-α, serum amyloid A (SAA), haptoglobin, insulin, adiponectin and fibrinogen were assayed by validated/standard methods. Data were analysed using a linear mixed effects model. Before exercise, plasma [adiponectin] was significantly (P = 0.0001) lower in PL (mean ± s.d. 2.4 ± 0.1 ng/l) than in NL (4.03 ± 0.2 ng/l), but exercise had no effect. Previous laminitis and exercise had no effect on plasma [TNF-α] or [fibrinogen]. Serum amyloid A concentrations in all ponies were significantly (P = 0.00001) reduced after longer term exercise compared to Day 1 values. Plasma [haptoglobin] was significantly (P = 0.00001) higher in PL compared to NL on Day 1. This difference was no longer apparent after longer term exercise, such that [haptoglobin] in PL had decreased to concentrations similar to NL. Following short-term exercise, all ponies had an initial decrease in serum [insulin] immediately after exercise, followed by an increase peaking 10 min after exercise cessation, before returning to pre-exercise values. On Day 14 these fluctuations were significantly (P = 0.001) reduced in all ponies. Fourteen days of low intensity exercise significantly decreased [SAA] in all ponies and plasma [haptoglobin] in PL such that it was no longer increased compared to NL. Regular low intensity exercise appears to have an anti-inflammatory effect, which is possibly greater in PL and so may be beneficial in reducing this putative risk factor in pasture-associated laminitis.

Plasma concentrations of inflammatory markers in previously laminitic ponies

The mechanisms underlying individual animal predisposition to pasture-associated laminitis remain unclear; however, chronic inflammation is implicated. To identify differences in the inflammatory profile of a group of previously laminitic ponies compared with control animals at pasture in late spring and winter. Previously laminitic (PL; n = 38 and 42) and nonlaminitic control ponies (NL; n = 41 and 39) were sampled in late spring and winter. Body condition score, height, weight and crest height and thickness were measured. Plasma concentrations of tumour necrosis factor-α, serum amyloid A, haptoglobin, insulin, adiponectin, triglyceride, fibrinogen, interleukin-17, interleukin-4 and interferon-γ were assayed by validated/standard methods. Factors independently associated with each cytokine were determined by multivariate analysis. Plasma [adiponectin] was significantly influenced by laminitis status, being lower in PL (median [interquartile range] 2.1[1.4-3.2] μg/l) than in NL ponies (3.4 [2.6-4.1] μg/l; P<0.0001). No other cytokines or inflammatory markers were associated with laminitis status. Plasma fibrinogen and serum amyloid A concentrations were significantly (P = 0.04 and P = 0.01) higher in geldings (3.5 [3.0-4.0] g/l; 2.2 [0.5-3.6] mg/l) than in mares (3.0 [3.0-4.0] g/l; 1.5 [0.4-2.1] mg/l) and significantly (P = 0.04 and P<0.001) higher in winter (3.5 [3.0-4.0] g/l; 2.5 [0.9-3.6] mg/l) than in late spring (3.0 [3.0-3.5] g/l; 1.1 [0.3-1.9] mg/l). Serum haptoglobin concentration showed the same significant (P<0.001) seasonal difference (winter 2.1 [1.6-2.6 g/l; late spring 1.8 1.4-2.4 g/l) and was significantly (P = 0.01) inversely associated with weight. Serum interleukin-4 concentration was significantly (P<0.0001) higher in winter (2.0 [1.2-3.0] ng/l) than in late spring (0.0 [0.0-0.0] ng/l). Serum insulin concentration was significantly (P = 0.02) influenced by season (winter 31.7 [9.6-43.5] miu/l; late spring 84.0 [7.0-131.0] miu/l). Plasma triglyceride concentration was significantly (P = 0.02) higher in PL (0.5 [0.3-0.7] mmol/l) than in NL ponies (0.4 [0.2-0.5] mmol/l). There were significant effects of season, gender and bodyweight on a number of proinflammatory mediators or markers of inflammation. The only marker influenced by laminitis status was adiponectin, and concentrations of this anti-inflammatory marker were lower in previously laminitic animals. Recurrent laminitis may be associated with reduced anti-inflammatory capacity rather than a proinflammatory state.