Concentrations Of Inflammatory Markers Research Articles

Systematic Review of the Effects of Ultraviolet Radiation on Markers of Metabolic Dysfunction.

Emerging findings suggest that exposure to ultraviolet wavelengths of sunlight modulates metabolic function. Here we review the metabolic effects of exposure to ultraviolet radiation (UVR), focusing on the effects of phototherapies (that administer UVR), and advice to increase sun exposure in individuals enrolled in clinical trials and intervention studies. We identified 25 studies in which the effects of UVR on metabolic outcomes were examined, including: narrowband ultraviolet B phototherapy (nbUVB, n = 12); psoralen ultraviolet A phototherapy (n = 4); other types of UVR phototherapy (n = 5); and sun exposure advice (n = 5). Most studies recruited a small number of participants (≤100), who were middle-aged individuals undergoing treatment for psoriasis flare, with phototherapy or sun exposure advice administered for ≤12 weeks. Data obtained at baseline were usually compared with an endpoint following treatment with UVR, for a limited number of outcomes. There were few studies in which markers of glucose metabolism were assessed, with some beneficial effects of sun exposure (but not phototherapy) reported. LDL-cholesterol levels were lower in individuals receiving sun exposure advice, while treatment with nbUVB reduced blood concentrations of inflammatory markers (C-reactive protein and interleukin-6). Future studies should focus on determining whether the effects of these interventions change with time, and if they are dependent on the source of UVR (i.e. phototherapy or sun exposure) and wavelength(s) of light administered. Furthermore, studies need to measure a variety of (clinical) markers of glucose metabolism, adiposity and inflammation, control for factors such as skin type and sex, and stratify participants for metabolic disease diagnosis.

The effects of megestrol acetate on nutrition, inflammation and quality of life in elderly haemodialysis patients.

Malnutrition, inflammation and poor quality of life are prevalent among elderly haemodialysis patients. Megestrol acetate (MA) is a synthetic progestin that is widely used to increase appetite and weight in various clinical settings. MA has been indicated to be effective in improving quality of life in patients with cancers. The aim of the present study was to evaluate the efficacy and safety of MA in treating malnourished elderly haemodialysis patients. A randomized controlled study involving 46 hypoalbuminemia haemodialysis patients aged 70years or older was conducted. The patients in MA-treated group (n = 23) took 160mg of MA daily, while those in control group (n = 23) were enrolled without any intervention. Anthropometric parameters and laboratory results, including height, dry weight, body mass index, and modified subjective global assessment score as well as serum albumin, triglyceride, total cholesterol, hsCRP, IL-1b and IL-6 concentrations were measured in all patients before and after the intervention. Health-related quality of life was also evaluated using the KDQOL-SF 1.3. In the MA-treated group, a total of 18 patients finished the therapy over a 3-month period. Appetite was reported as improved by 15 patients, and a statistically significant increase was observed in dry weight (53.36 ± 6.15 vs. 54.24 ± 6.32, P < 0.01) and serum albumin concentration (29.05 ± 3.91 vs. 37.67 ± 4.88, P < 0.01) in the MA-treated group compared to those of the control group. The quality of life in both the physical domain (46.73 ± 18.17 vs. 63.37 ± 22.35, P < 0.01) and the mental domain (50.28 ± 20.36 vs. 68.02 ± 25.48, P < 0.01) was also improved in the same group. There was no significant change in the inflammatory marker concentrations after the intervention. No serious or unexpected adverse events were observed except that one patient who withdrew due to excessive fluid gain between haemodialysis sessions. Our data suggest that MA can be effective in improving nutritional status and quality of life by increasing appetite in elderly haemodialysis patients with acceptable side effects; however, MA might not ameliorate inflammation.

Genetic Variations in VDR could Modulate the Efficacy of Vitamin D3 Supplementation on Inflammatory Markers and Total Antioxidant Capacity among Breast Cancer Women: A Randomized Double Blind Controlled Trial.

Background:Low levels of vitamin D are found in a great part of breast cancer women. Study subjects using vitamin D3 supplement had lower rates of cancers and fewer markers of inflammation. Additionally, recent studies demonstrate the power of vitamin D supplementation to lower inflammation and oxidative stress biomarkers associate with VDR polymorphism to reduce inflammation. This study was aimed to assess the impact of vitamin D3 supplementation on the serum concentration of inflammatory markers and antioxidant capacity with regard to VDR polymorphism in the VDR gene in breast cancer women. Methods:A randomized, double-blind, placebo-controlled trial was conducted on 56 breast cancer women. Participants were assigned to 2 treatment arms: placebo and vitamin D3 for 2 months intervention. Supplementation group received 50,000 IU of vitamin weekly. Blood samples were collected at baseline and after the intervention to measure the 25(OH) D3, TNF-α, TGF- β and TAC. Genotyping was performed for FokI, BsmI, ApaI, and TaqI polymorphism. Results:After eight weeks supplementation, the intervention group showed a significant increase in the serum concentration of 25(OH) D3 (28±2.6 to 39±3.5; p=0.004 and TAC (48.9±13.3 to 63.5±13.3; p= 0.017). Changes in TNF-α, TGF- β1 were not significant. Serum TAC levels of participants with the TT/Tt, Ff genotypes were more responsive to supplementation. Conclusions:Supplementation with a vitamin D3 increased the TAC in breast cancer women, although it had no effect on inflammatory markers. Serum TAC in the TT/Tt, Ff were more responsive to vitamin D supplement compared with those with the FF/ff and tt genotypes.

Alterações no perfil das proteínas de fase aguda e leucograma em cordeiros Dorper durante os seis primeiros meses de vida

The first months in the life of mammals are marked by many challenges, such as acquisition of maternal antibodies, immunological maturity, environmental exposure and food adaptation. These challenges may lead to changes in the concentration of inflammatory markers, as the acute phase proteins (APPs) and leukocytes. The better understanding of these markers behavior in physiological conditions is fundamental for diagnosis, monitoring, and prognosis of diseases. Therefore, the aim of this study was to determine the changes in the APPs and leukogram profile in Dorper lambs from birth until the sixth month of life. Samples were collected from 12 clinically healthy lambs at 0, 6, 12, 24, 48 hours and then at 7, 15, 30, 60, 90, 120, 150 and 180 days of age. All lambs were born with a low concentration of haptoglobin and ceruloplasmin. Significant increases occurred in the 48th hour and on the 7th day of life (P&lt;0.05), respectively. The highest APPs concentration was observed on the 90th day. All leukogram cells varied throughout the experimental period. It was possible to characterize the changes in APPs and leukogram profile from birth to six months of life in Dorper lambs. This study offers new perspectives on the use of APPs in lambs during the first months of life.

Associations between Dietary Inflammatory Index Scores and Inflammatory Biomarkers among Older Adults in the Lothian Birth Cohort 1936 Study

ObjectivesChronic low-grade inflammation is a key underlying mechanism in several age-related chronic conditions and previous studies have shown that diet can modulate the inflammatory process. We investigated the ability of the Dietary Inflammatory Index (DII®), a summary measure of dietary inflammatory potential, to predict concentrations of plasma inflammatory markers in a sample of older people.DesignCross-sectional and 3-year follow-up analysis of Lothian Birth Cohort 1936 (LBC1936) study data.SettingBaseline data collection occurred between 2004 and 2007 in Edinburgh, Scotland. Participants: Men and women (n 928, age ∼70 at baseline) living in Edinburgh and surrounding regions who are surviving participants of the Scottish Mental Survey of 1947.MeasurementsEnergy-adjusted DII (E-DII) scores at age 70 (derived from a food-frequency questionnaire), plasma concentrations of inflammatory biomarkers at age 70 (C-reactive protein (CRP), fibrinogen) and age 73 (CRP, fibrinogen, hs-CRP, Interleukin-6 (IL-6)). Analyses were performed using multivariable logistic regression adjusting for age, sex, smoking, body mass index, physical activity, and hypercholesterolaemia.ResultsHigher E-DII scores (pro-inflammatory diet) were associated with increased odds of elevated CRP (>3mg/L) at age 70 (OR 1.12; 95% CI: 1.02, 1.24, P = 0.02), and elevated IL-6 (>1.6pg/ml) at age 73 (OR 1.11; 95% CI: 1.00, 1.23, P = 0.04), but not with fibrinogen.ConclusionThese results are consistent with the ability of the DII to predict inflammatory biomarker concentrations and suggest that diet plays a role in the regulation of inflammation, even after controlling for potential confounders. This validation study provides support for using the DII in research among older populations.

Systemic low-grade inflammation and subsequent depressive symptoms: Is there a mediating role of physical activity?

ObjectiveSystemic low-grade inflammation has been associated with the onset of depression, but the exact mechanisms underlying this relationship remain elusive. This study examined whether physical activity (PA) explained the association between elevated serum levels of inflammatory markers and subsequent depressive symptoms. DesignProspective cohort design. MethodThe sample consisted of 3809 non-depressed men and women (aged 50+) recruited from the English Longitudinal Study of Ageing (ELSA). Serum levels of inflammatory markers (C-reactive protein (CRP), fibrinogen) and covariates (age, sex, education, wealth, body mass index, smoking, cholesterol, triglycerides) were measured at baseline (wave 4, 2008/09). Self-reported weekly moderate/vigorous (high) PA versus no weekly moderate/vigorous (low) PA was examined at a four-year follow-up (wave 6, 2012/13), using a single-item question. Depressive symptoms were assessed at baseline, four years (wave 6, 2012/13) and six years post baseline (wave 7, 2014/15), using the 8-item version of the Centre for Epidemiological Studies Depression Scale (CES-D). ResultsParticipants with higher baseline concentrations of inflammatory markers were significantly more likely to report low PA levels four years later (CRP: OR: 1.25; 95% CI, 1.05–1.48; fibrinogen: OR: 1.18; 95% CI, 1.05–1.39). Moreover, low PA was associated with higher odds of elevated depressive symptoms at follow-up (OR: 1.59; 95% CI, 1.15–2.19). Mediation analyses revealed that low PA explained a total of 36.71% of the relationship between high CRP and elevated depressive symptoms, and 33.26% between higher levels of fibrinogen and elevated depressive symptoms six years later. No direct association was found between systemic low-grade inflammation and future depressive symptoms. ConclusionThese results suggest that low PA is a significant partial mediator of the relationship between systemic low-grade inflammation and subsequent elevated depressive symptoms in a nationally representative cohort of older adults.

Telmisartan and/or chlorogenic acid attenuates fructose-induced non-alcoholic fatty liver disease in rats: Implications of cross-talk between angiotensin, the sphingosine kinase/sphingoine-1-phosphate pathway, and TLR4 receptors

Renin-angiotensin-aldosterone system (RAS) has been implicated in non-alcoholic fatty liver disease (NAFLD); the most common cause of chronic liver diseases. There is accumulating evidence that altered TLR4 and Sphingosine kinase 1(SphK1)/sphingosine1phosphate (S1P) signaling pathways are key players in the pathogenesis of NAFLD. Cross talk of the sphingosine signaling pathway, toll-4 (TLR4) receptors, and angiotensin II was reported in various tissues. Therefore, the aim of this study was to define the contribution of these two pathways to the hepatoprotective effects of telmisartan and/or chlorogenic acid (CGA) in NAFLD. CGA is a strong antioxidant that was previously reported to inhibit angiotensin converting enzyme. Male Wistar rats were treated with either high-fructose, with or without telmisartan, CGA, telmisartan + CGA for 8 weeks. Untreated NAFL rats showed characteristics of NAFLD, as evidenced by significant increase in the body weight, insulin resistance, and serum hepatotoxicity markers (Alanine and Aspartate transaminases) and lipids as compared to the negative control group, in addition to characteristic histopathological alterations. Treatment with either telmisartan and/or CGA improved aforementioned parameters, in addition to upregulation of antioxidant enzymes (Superoxide dismutase and Glutathione peroxidase). Effect of inhibiting RAS on both sphingosine pathway and TLR4 was evident by the suppressing effect of telmisartan and/or CGA on high fructose-induced upregulation of hepatic SPK1 and S1P, in addition to concomitant up-regulation of Sphingosine-1-Phosphate receptor (S1PR)3 protein level and increased expression of S1PR1 and TLR4. As TLR4 and SPK/S1P signaling pathways play important roles in the progression of liver inflammation, the effect on sphingosine pathway and TLR4 was associated with decreased concentrations of inflammatory markers, enzyme kB kinase (IKK), nuclear factor-kB and tumor necrosis factor-α as compared to untreated NAFL group. In conclusion, the present data strongly suggests the cross-talk between angiotensin, the Sphingosine SPK/S1P Axis and TLR4 Receptors, and their role in the pathogenesis of fructose-induced NAFLD, and the protection afforded by drugs inhibiting RAS.

Combined Collagen-Induced Arthritis and Organic Dust-Induced Airway Inflammation to Model Inflammatory Lung Disease in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is characterized by extra-articular involvement including lung disease, yet the mechanisms linking the two conditions are poorly understood. The collagen-induced arthritis (CIA) model was combined with the organic dust extract (ODE) airway inflammatory model to assess bone/joint-lung inflammatory outcomes. DBA/1J mice were intranasally treated with saline or ODE daily for 5 weeks. CIA was induced on days 1 and 21. Treatment groups included sham (saline injection/saline inhalation), CIA (CIA/saline), ODE (saline/ODE), and CIA + ODE (CIA/ODE). Arthritis inflammatory scores, bones, bronchoalveolar lavage fluid, lung tissues, and serum were assessed. In DBA/1J male mice, arthritis was increased in CIA + ODE > CIA > ODE versus sham. Micro-computed tomography (µCT) demonstrated that loss of BMD and volume and deterioration of bone microarchitecture was greatest in CIA + ODE. However, ODE-induced airway neutrophil influx and inflammatory cytokine/chemokine levels in lavage fluids were increased in ODE > CIA + ODE versus sham. Activated lung CD11c+ CD11b+ macrophages were increased in ODE > CIA + ODE > CIA pattern, whereas lung hyaluronan, fibronectin, and amphiregulin levels were greatest in CIA + ODE. Serum autoantibody and inflammatory marker concentrations varied among experimental groups. Compared with male mice, female mice showed less articular and pulmonary disease. The interaction of inhalation-induced airway inflammation and arthritis induction resulted in compartmentalized responses with the greatest degree of arthritis and bone loss in male mice with combined exposures. Data also support suppression of the lung inflammatory response, but increases in extracellular matrix protein deposition/interstitial disease in the setting of arthritis. This coexposure model could be exploited to better understand and treat RA-lung disease. © 2019 American Society for Bone and Mineral Research.

Depression in adolescent girls: Relationship to serum vitamins a and E, immune response to heat shock protein 27 and systemic inflammation

Background: The inflammation and oxidative stress are thought to play an important role in the etiopathogenesis of some psychological disorders. We aimed to assess the potential relationships between serum fat soluble vitamins (Vitamins A and E), antibody titers to Hsp27 (anti-Hsp27) and hematological markers of inflammation, with mood disorders in a population of adolescent girls. Methods: A total of 563 adolescent girls (Age 12–18 years) were included in the study. The presence and severity of depression, insomnia and sleepiness were assessed using validated questionnaires. Serum vitamins A and E, anti-Hsp27 antibody titers, white blood cell, lymphocyte, neutrophil, platelet counts, and red blood cell distribution width (RDW), were also measured. Neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and RDW to platelet ratio (RPR) were calculated. Results: Serum anti-HSP27 antibody titers, PLR, and RPR values was significantly higher in subjects with a high depression score compared to normal individuals (p < 0.05). However, there was no association between serum inflammatory markers concentrations and sleep disorders; although individuals with insomnia had a lower vitamin E/HDL ratio compared to healthy adolescents. In multivariate logistic regression analyses adjusted for potential confounders, anti-HSP was an independent predictor of severe depression (OR = 5.0, 95% CI: 1.6–15.7, p < 0.05). Limitation: The cross-sectional design of study and the inclusion of only female adolescents participants are limitations. Conclusion: Our findings suggest that serum anti-HSP27 antibody titers may be useful biological marker in depressive patients. This finding may support a role of oxidative stress in the etiology of depression, and targeting this pathway may be of value in the treatment of depression.

Effects of Elastic Resistance Training on Functional Performance and Myokines in Older Women—A Randomized Controlled Trial

ObjectivesTo investigate the short- and long-term effects of elastic resistance training (ERT) on physical performance, inflammatory markers, and myokines in older women living in a nursing home. DesignA randomized controlled trial, with 12 weeks of ERT intervention. Setting and participantsNursing home. Twenty female nursing home residents (mean age = 84 ± 8 years) were randomized into 2 groups: the training group (n = 11), and the control group (n = 9). MeasuresMuscle mass was estimated with bioelectrical impedance, and the functional test Short Physical Performance Battery (SPPB) was performed, whereas handgrip strength and plasma concentration of myokines and inflammatory markers were measured before and after the intervention period. Additional blood samples were also taken after the fourth ERT session. A mixed model (group × time) analysis of variance was applied to determine the effect on primary and secondary outcomes. ResultsAfter 1 exercise session, the training group showed a significant increase in brain-derived neurotrophic factor (BDNF) (P = .04) and a decrease in interleukin (IL)-8 (P = .01) plasma concentration. After 12 weeks of intervention, the results showed a significant group × time effects for the SPPB total score (P < .01), as well as gait speed (P = .04), chair rise (P < .01), and BDNF concentration (P = .02). However, there were no significant interactions for grip strength, IL-15, IL-8, resistin, glucose, and C-reactive protein (P ≥ .06). Conclusions/ImplicationsThe present study emphasizes the clinical impact of moderate-intensity ERT on mobility and functional performance in older women. The results indicate that an increase in exercise-induced peripheral BDNF may have a protective role in the preservation of muscular function in older women. Incorporating ERT into nursing homes could be a feasible preventive strategy to counteract functional deterioration.

Propolis Supplementation Effects on Semen Parameters, Oxidative Stress, Inflammatory Biomarkers and Reproductive Hormones in Infertile Men with Asthenozoospermia; A Randomized Clinical Trial

Background and Aims: Decreased sperm motility and increased level of oxidative stress are major causes of male infertility. This study was designed to evaluate the effect of propolis supplementation on spermatogram and reproductive hormones in asthenozoospermic men. Materials and Methods: In this randomized, double-blind controlled clinical trial, 60 asthenozoospermic men attending an infertility clinic in Velayat Hospital in Qazvin, Iran, were randomly assigned to one of intervention and placebo groups (n=30 for each group). For 10 weeks each participant in the intervention group took 1500 mg of propolis daily, while in the placebo group they received daily placebo. Sperm parameters, total antioxidant capacity, concentrations of malondialdehyde of plasma, inflammatory markers and reproductive hormones were measured at the baseline and at the end of the interventions. Results: Out of 60 who participated in this study, 29 men in the intervention group and 28 men in the placebo group completed the study. After the intervention, concentration and percentage of motile sperms as well as total antioxidant capacity of plasma significantly increased while the concentration of plasma malondialdehyde and inflammatory markers significantly decreased in the intervention group compared to the placebo group (p&lt;0.05). Conclusions: Propolis supplementation led to increase in the concentration and motility of asthenozoospermic sperms and reduction of oxidative stress and inflammatory markers. Since increase in reactive oxygen species has been observed in abnormal sperms, oral intake of propolis may be one of the ways to deal with oxidative damage in spermatozoa of infertile men.

Abstract P292: Almond Consumption Increases Satiety Hormones Relative to a High-Carbohydrate Food but Has Minimal Impact on Body Composition: A Pilot Study in Black and Hispanic Adults

Epidemiological studies show that nut consumers have lower body weight than non-consumers. Individuals who consume more tree nuts have lower odds of obesity and metabolic syndrome than those who are low tree nut consumers. In clinical intervention studies, nut consumption has been shown to lower abdominal adiposity and improving weight loss relative to a low-fat/high-carbohydrate (LF/HC) control food. Those studies, however, have been conducted predominantly in White, non-Hispanic populations. Interestingly, minority adults, who have the highest prevalence of obesity and experience cardio-metabolic health disparities, have low nut intakes. The objective of this study was to evaluate the impact of almond consumption, relative to an energy-matched LF/HC control food, on weight status and adiposity in Blacks and Hispanics. We hypothesized that 24 wk of almond consumption would improve appetite regulation and body composition in Blacks and Hispanics. Twenty-nine adults (17 completers: 9 men and 8 women), BMI &gt;25 kg/m 2 , age 30-65 y, were recruited and randomized to consume either almonds or LF/HC cereal bars providing 17.5% of their estimated energy requirements. Outcome variables were measured at baseline, week 12, and endpoint. Peptide YY concentrations were higher in the almond group compared to LF/HC (time x treatment interaction at 12 wk, P&lt;0.001; 24 wk, P=0.13). Similarly, glucagon-like peptide 1 concentrations were higher in the almond group compared to LF/HC (time x treatment interaction at 12 wk, P=0.10; 24 wk, P=0.015). However, ghrelin levels decreased in LF/HC compared to the almond group at 12 wk but not 24 wk (time x treatment interaction at 12 wk, P=0.017; 24 wk, P=0.23). There was a slight trend for a time x treatment interaction on body weight (P=0.14; change in almond=0.6±1.8 kg; LF/HC=1.9±2.7 kg). There was a time x treatment interaction on inter-muscular adipose tissue (P=0.013; change in almond=-0.10±0.14 cm 3 ; LF/HC=0.04±0.07 cm 3 ). There was no effect of almond or LF/HC consumption on inflammatory markers concentrations (interleukin-6, C-reactive protein, and tumor necrosis factor; all p&gt;0.18). Daily almond intake for 24 wk, in the context of a usual diet, does not induce profound body composition changes, but may ameliorate appetite and ectopic fat deposition. More studies should be performed in minority population to determine the potential effects of specific foods for weight management in the context of a weight loss diet.

The use of telmisartan in patients with refractory arterial hypertension and obesity

Aim.To evaluate the effectiveness of telmisartan as a component of triple antihypertensive therapy in patients with obesity and refractory arterial hypertension.Material and methods.The study included 30 patients with obesity and refractory arterial hypertension. All patients received an angiotensin II receptor blocker (ARB) or an angiotensin-converting enzyme inhibitor (ACE inhibitor) in an adequate dosage as part of a triple antihypertensive therapy that also includes a calcium antagonist and thiazide diuretic. Participants were randomly divided into two equal groups. In the main group, telmisartan (Dr. Reddy’s Laboratories) was prescribed at a dosage of 80 mg/day instead of the previously taken ARB or ACE inhibitor. In the control group, patients continued to receive a previously prescribed ARB or an ACE inhibitor. The primary end point was a decrease in mean daily systolic and/or diastolic blood pressure (SBP and DBP) according to 24-hour blood pressure monitoring at 10 mm Hg and more than 20 weeks after the start of the study. The secondary end point was a decrease in the concentration of inflammatory markers and an increase in the level of adiponectin by 15%.Results.After 20 weeks, in the telmisartan group, we noted a significant decrease in the average daily SBP and DBP: in the main group from 145,9±5,4/95,6±4,8 mm Hg to 134,8±3,0/84,9±4,2 mm Hg, in the control group with 147,2±4,9/96,4±5,6 mm Hg to 142,4±4,3/96,9±62 mm Hg. We also determined an increase in the serum adiponectin concentration from 9,3±5,6 μg/ml to 13,4±6,6 μg/ml in the main group and a decrease from 8,8±5,2 μg/ml to 8,6±5,6 μg/ml in the control group, as well as a decrease in the concentration of highly sensitive C-reactive protein (main group from 8,8±3,0 to 6,0±2,8 mg/l and the control group from 7,4±3,8 to 6,9±4,9 mg/l) and interleukin-6 (main group from 16,2±6,1 to 12,3±2,8 pg/ml, control group from 22,5±4,2 to 19,9±5,2 pg/ml).Conclusion.Telmisartan can be considered as a drug of choice as part of multi-component therapy in the treatment of patients with obesity and refractor arterial hypertension.

Abstract WP169: Coated-platelets and Tumor Necrosis Factor Alpha Predict TIA/stroke at Twenty-one Months in Asymptomatic Carotid Stenosis

Background: The clinical spectrum of carotid atherosclerosis is well characterized, but the events leading to plaque instability and stroke are less understood. Evidence suggests that platelets serve as an interface among hemostasis, inflammation, and atherosclerosis. Coated-platelets, a subset of platelets with high procoagulant potential, are increased in asymptomatic carotid stenosis patients at high risk for stroke or TIA. We now examine the impact of other soluble mediators of inflammation, cell adhesion, angiogenesis and coagulation on the association between coated-platelets and TIA/stroke in asymptomatic carotid stenosis. Methods: Consecutive asymptomatic patients with ≥50% carotid stenosis were enrolled. Coated-platelet levels were assayed and plasma was obtained for measurement of 58 biomarkers. Patients were followed at 6-month intervals for intensive vascular risk reduction. Those with signs or symptoms of TIA/stroke underwent either brain CT or MRI. Rank order correlations between inflammatory marker concentrations, coated-platelet levels and TIA/stroke were determined using the Spearman correlation coefficient. Variables associated with TIA/stroke (p&lt;0.15) were included in multivariate analysis. Results: We enrolled 117 patients (97% male, average age 71, 94% on statins, 96% on antiplatelets, and 33% currently smoking, average HgA1c 6.6% and average LDL 86 mg/dL). There were 6 strokes and 2 TIA’s ipsilateral to carotid stenosis during a mean 21.3 ± 6.7 months of follow-up (incidence of 3.89/100 person-years). Stepwise logistic regression identified TNF alpha (OR=11.1, p=0.0300) and coated-platelet group (OR=14.1, p=0.0167) as predictors of TIA/stroke ipsilateral to stenosis. Cox Proportional Hazard analysis yielded a TIA/stroke HR of 11.8 for the high coated-platelet group (95% CI 1.4, 96.1, p=0.0215) and 8.0 (95% CI 0.97, 66.3, p=0.0529) for the high TNF alpha group. Discussion: Coated-platelets and TNF alpha predict TIA/stroke in asymptomatic carotid stenosis at 21 months. These findings expand on our previous work in coated-platelets and asymptomatic carotid stenosis and suggest that coated-platelets may represent a common link between hemostatic and inflammatory mechanisms of plaque instability.

Adipokine profiles in preeclampsia

Objectives: Hypertensive disorders of pregnancy (HDP), including preeclampsia (PE), are associated with short- and long-term maternal health complications, and obesity is a leading attributable risk factor for HDP. Yet, most women identified as obese [by body mass index (BMI) ≥ 30 kg/m2] do not develop HDP, indicating limited predictability of BMI alone. In nonpregnant populations, increased visceral fat mass (VFM) is an obesity-associated phenotype increasing the risk of developing hypertension. We sought to assess whether, in pregnancy, obese women with PE would have higher circulating levels of adipokines preferential to VFM compared to obese women without PE.Study Design: We performed a case-control study of women with and without PE, including obese (n = 65; BMI ≥ 30 kg/m2) and normal weight (n = 52; BMI 18.4–24.9 kg/m2) women. Plasma concentrations of adipokines preferential to VFM (visfatin, resistin), adipokines reflecting overall adiposity (leptin, adiponectin), and inflammatory cytokines were compared.Results: We found that among obese women, cases had significantly higher levels of VFM-associated adipokines and cytokines compared to controls [visfatin (p < .01, t = −3.8), resistin (p = .002, t = 1.12), IFN gamma (p = .04, t = −2.0), IL-6 (p < .01, t = −2.65), IL1-beta (p < .01, t = −4.1), IL-2 (p < .01, t = −3.9)]. Interestingly, however, obese and normal weight cases had similar VFM-adipokine and cytokine levels [visfatin (p = .34, t = −0.35), resistin (p = .55, t = −0.25)], and inflammatory marker concentrations [IFN gamma (p = .86, t = −0.76), IL-6 (p = .91, t = −0.53), IL-1beta (p = .67, t = 1.18), and IL-2 (p = .45, t = −1.16)]. These data possibly suggest an association between VFM and PE that is present independent of BMI.Conclusion: In summary, we demonstrated that, in normal-weight and obese women, PE was associated with higher concentrations of VFM-preferential adipokines compared to normal-weight and obese controls without PE.

The Effects of Probiotic Supplements on Blood Markers of Endotoxin and Lipid Peroxidation in Patients Undergoing Gastric Bypass Surgery; a Randomized, Double-Blind, Placebo-Controlled, Clinical Trial with 13Months Follow-Up.

The effect of probiotic supplements among subjects undergoing bariatric surgery indicates conflicting results. Moreover, whether these effects remain after ceasing the treatment remained to be elucidated. This study was conducted to assess the effect of probiotic supplements on blood markers of endotoxin (lipopolysaccharides-binding protein: LBP), inflammation and lipid peroxidation (malondialdehyde: MDA) in patients with morbid obesity undergoing the one-anastomosis gastric bypass (OAGB). This study is a placebo-controlled, double-blind, and randomized clinical trial and 9months of additional follow-up. Forty-six morbid obese patients undergoing OAGB were randomized to 4months of probiotic or placebo supplements. Anthropometric indices and blood concentration of LBP, inflammatory markers, MDA, vitamin D3, and B12 were measured at 0, 4, and 13months of study. Probiotic supplements could improve serum LBP (P = 0.039), TNF-α (P = 0.005), vitamin B12 (P = 0.03), vitamin D3 (P = 0.001), and weight loss (P = 0.01) at month 4 in comparison to placebo; however, only serum MDA concentrations decreased significantly in the probiotic group compared with those in the placebo group (P = 0.013) at the end of follow-up period. It was observed that 4months probiotic supplementation compared with placebo prohibited an elevation in the LBP levels and improved serum TNF-α and 25-OH vitamin D3 concentrations and weight loss in patients undergoing the OAGB surgery. However, these effects did not persist 9months after the cessation of the treatment. Further investigations are required to find how long supplementation and which dosage of it can benefit body status for the long-term. This study has been registered at Clinicaltrial.gov with registration number NCT02708589 .

Investigating the Impact of Selective Cox-2 and 5-Lox Blockers on Inflammatory Markers within Urinary Samples of Smoker Volunteers

Cyclooxygenase-2 (COX-2) and 5-lipoxygenase (5-LOX) consumed arachidonate for the production of eicosanoids which play a role in the inflammation (like COPD), carcinogenesis (like lung cancer), and cardiovascular diseases. This study was designed to introduce noninvasive biomarkers and therapies that aim to reduce the risk for individuals with greater risk of developing smoking-related lung diseases. During this prospective randomized clinical trial, urinary concentration of prostaglandin E metabolite (PGE-M) and leukotriene E4 (LTE4), as markers of COX and 5-LOX inflammatory process, was measured in former (arm A); current (arm B); and never smoker subjects at zero time. The effect of the three treatment groups: etoricoxib and zileuton as a selective COX-2 and 5-LOX inhibitors, respectively, and their combination on the concentrations of these inflammatory markers were evaluated in the current and former smoking population, after 4 weeks. Analysis of variance (ANOVA), chi-square, and paired t-test were applied to analyze our data. At zero time, concentrations of both inflammatory markers were high and significantly associated with status of smoking, which confirmed by measurement of cotinine levels (p<0.05). Treatment with etoricoxib alone and etoricoxib – zileuton combination significantly reduced urinary PGE-M levels, while zileuton alone significantly elevated this marker, in both former and current smokers, compared with their pretreatment values (p<0.05). In addition, treatment with zileuton alone and etoricoxib – zileuton combination significantly reduced urinary LTE4 levels, while etoricoxib alone significantly elevated this marker, in both former and current smokers, compared with their pretreatment values (p<0.05). Former and current smokers were well tolerated with these therapeutic regimens, with no reports of any serious adverse effects. One can conclude that a subclinical respiratory inflammation may associate with smoking people, reflected by elevated levels of PGE-M and LTE4 within urinary samples. Combining etoricoxib and zileuton was associated with inhibition of both COX-2 and 5-LOX pathways manifested by reduced levels of urinary PGE-M and LTE4, for both former and current smokers.

Cytokines, Oxidative Stress and Cellular Markers of Inflammation in Schizophrenia.

In this article, we review current evidence linking immune dysfunction in schizophrenia and related psychotic disorders focusing particularly on circulating cytokines, oxidative stress and cellular markers of inflammation in various stages on illness from drug-naïve first episode psychosis to chronic schizophrenia. Acute psychotic episode is associated with low-grade systemic inflammation in some patients, as reflected by increased concentrations of cytokines and other inflammatory markers in peripheral blood. Evidence from general population-based longitudinal cohort studies reporting an association between elevated inflammatory markers in childhood/adolescence and risk of schizophrenia and related psychosis subsequently in adulthood suggest that inflammation could be a causal risk factor for psychosis rather than simply be a consequence of illness. Mendelian randomization studies also suggest that associations between IL-6, CRP and schizophrenia are likely to be causal. In addition, we discuss evidence for disruptions in oxidative stress markers and CSF cytokine levels in schizophrenia, and potential reasons for reported trans-diagnostic associations for inflammatory cytokines including role of early-life adversity/maltreatment. We argue that low-grade inflammation is a clinically useful feature, because it is associated with poor response to antipsychotic medication in first episode psychosis. We discuss clinical implications for immunological understanding of schizophrenia including scope for clinical trials of anti-inflammatory agents and notable gaps in current knowledge, and offer suggestions for future research.

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.

Hemodynamic responses of patients with stable coronary artery disease to a comedy film: study protocol for a randomized controlled trial

Background and objective: Alternative and complementary interventions have been developed in an attempt to improve treatment and increase the survival of patients with coronary artery disease (CAD); one such intervention is laughter therapy. However, there is very little information on the effect of this therapeutic modality in patients with CAD. The present randomized controlled trial will compare the effect of 24 sessions of a comedy film and neutral documentary in patients with CAD. Subjects and methods: This is a randomized, parallel-design, examiner-blinded and controlled clinical trial. Patients with stable CAD of both sexes, aged ≥ 18 years, receiving regular follow-up at a public university hospital in Southern Brazil will be included in the trial. Subjects will be randomly allocated to an intervention group (will watch a 30-minute comedy film) or a control group (will watch a 30-minute neutral documentary). Patient recruitment will end in December 2019. Analysis of the primary outcome measure will be completed in December 2019. The current protocol version is 1.0. The study protocol was approved by the Institutional Review Board of Hospital de Clinicas de Porto Alegre (protocol No. 13-0124) on July 9, 2013. Outcome measures: The primary outcomes are the difference from baseline to the 2-month time point (corresponding to 24 sessions) in endothelial function, as assessed by brachial artery flow-mediated dilation measurement and peak oxygen consumption (peak VO2) on cardiopulmonary exercise testing. Secondary outcome measures include concentrations of inflammatory markers in blood, biochemical parameters, and quality of life. Discussion: This study will provide new evidence on the effect of an easy-to-use, inexpensive, readily deployable non pharmacological therapeutic intervention for patients with stable CAD. Trial registration: ClinicalTrials.gov identifier: NCT02824120. Date of registration: July 6, 2016.