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1.
Differences in carotid atherosclerosis between patients with ankylosing spondylitis treated with tumor necrosis factor-α antagonists and healthy matched controls.
Zardi, EM, Pipita, ME, Giorgi, C, Lichinchi, D, Zardi, DM, Afeltra, A
Medicine. 2018;(27):e11250
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Abstract
An increased vascular risk is present in patients with ankylosing spondylitis (AS). In this report, we evaluate the presence and grade of atherosclerosis in patients with AS, uninterruptedly treated with tumor necrosis factor-α (TNF-α) antagonists for 2 years, in comparison to that in a nontreated group of healthy controls.Fourteen patients with AS and 14 healthy controls underwent carotid sonography to measure intima-media thickness (IMT) and to evaluate the presence of plaque. Bath Ankylosing Spondylitis Disease Activity Index, Bath Ankylosing Spondylitis Metrology Index, Bath Ankylosing Spondylitis Functional Index scores, erythrocyte sedimentation rate, C-reactive protein, glycemia, total cholesterol, and triglyceride levels were also recorded.Patients with AS showed significantly lower values of mean and maximum IMT at the level of the common carotid (P = .02 and .04, respectively) and the carotid bulb (P = .0006 and .0005, respectively) compared to those of healthy controls. They also had a number of carotid plaques significantly lower than that of healthy controls (P = .02). No differences were found in IMT values at the level of internal carotid between the 2 populations.The significantly lower carotid atherosclerosis found in patients with AS treated with TNF antagonists than in healthy controls shows the important complementary role of this treatment in reducing vascular disease progression probably by decreasing inflammation.
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Change in inflammatory parameters in prefrail and frail persons obtaining physical training and nutritional support provided by lay volunteers: A randomized controlled trial.
Haider, S, Grabovac, I, Winzer, E, Kapan, A, Schindler, KE, Lackinger, C, Titze, S, Dorner, TE
PloS one. 2017;(10):e0185879
Abstract
The aim of the study was to compare the effects of home visits with physical training and nutritional support on inflammatory parameters to home visits with social support alone within a randomized controlled trial. Prefrail and frail persons received home visits from lay volunteers twice a week for 12 weeks. Participants in the physical training and nutritional intervention group (PTN, n = 35) conducted two sets of six strength exercises and received nutritional support. The social support group (SoSu, n = 23) received visits only. TNF-α, IL-6, CRP, and total leukocyte count were assessed at baseline and after 12 weeks. Changes over time within groups were analyzed with paired t-tests; differences between groups were analyzed with ANCOVA for repeated measurements. In the PTN group, IL-6 and CRP remained stable, whereas in the SoSu group, IL-6 increased significantly from a median value of 2.6 pg/l (min-max = 2.0-10.2) to 3.0 pg/l (min-max = 2.0-20.8), and CRP rose from 0.2 mg/dl (min-max = 0.1-0.9) to 0.3 mg/dl (min-max = 0.1-3.0) after 12 weeks. In CRP, a significant difference between groups was found. TNF-α and total leukocyte count did not change in either the PTN group or the SoSu group. Persons showing an increase in physical performance (OR 4.54; 95% CI = 1.33-15.45) were more likely to have constant or decreased IL-6 values than persons who showed no improvement. In conclusion, in non-robust older adults, a physical training and nutritional support program provided by lay volunteers can delay a further increase in some inflammatory parameters.
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Golimumab for moderately to severely active ulcerative colitis.
Kedia, S, Ahuja, V, Makharia, GK
Expert review of clinical pharmacology. 2016;(10):1273-82
Abstract
INTRODUCTION Anti-TNF agents are the mainstay of therapy in patients with moderate to severe ulcerative colitis (UC) not responding to 5-aminosalisylic acid, corticosteroids, immunmodulators and for patients dependent on corticosteroids. There is a therapeutic gap of 30%- 60% with infliximab and adalimumab, which is required to be bridged by newer agents. The present review summarizes the literature on the role of golimumab, a new anti TNF agent, in ulcerative colitis. AREAS COVERED Literature search was done on PubMed using the search terms 'golimumab' AND 'ulcerative colitis' from inception till March 2016. Golimumab, a fully human monoclonal antibody against TNF-α, was approved by FDA for clinical use in UC in 2013. In vitro studies showed golimumab to be better than infliximab and adalimumab in terms of affinity and neutralization of TNF-α and its conformational stability. Golimumab was found to be effective and safe in inducing and maintaining clinical remission, clinical response and mucosal healing in patients with UC in the two registration trials. Expert commentary: Although there is no difference in terms of efficacy between golimumab, infliximab and adalimumab, golimumab is better than infliximab in terms of route of administration (subcutaneous vs intravenous) and better than adalimumab in terms of frequency of dosing (4 weeks vs 2 weeks).
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Impact of 24 months of anti-TNF therapy versus methotrexate on body weight in patients with rheumatoid arthritis: a prospective observational study.
Sfriso, P, Caso, F, Filardo, GS, Botsios, C, Costa, L, Scarpa, R, Todesco, S, Spinella, P, Oliviero, F, Punzi, L
Clinical rheumatology. 2016;(6):1615-8
Abstract
To evaluate the impact of anti-TNF-α therapy on the body weight of rheumatoid arthritis (RA) patients following 24 months of treatment. Data were collected on all RA patients included in the Veneto Region's Registry of Biological Therapy from January 2007 to July 2012. Inclusion criteria were: start of monotherapy with adalimumab, etanercept, or methotrexate, no previous use of biologic therapy, and at least 24 months of treatment. At baseline, 12, and 24 months, each patient completed a questionnaire about physical activity, smoking, alcohol, and food habits. One hundred and thirty-one RA patients in monotherapy with etanercept (n = 47), adalimumab (n = 44), and methotrexate (n = 40) were enrolled for this study. After 24 months of therapy, there was an increase of weight only in patients treated with anti-TNF-α. Patients on etanercept and adalimumab therapy showed a risk to gain weight six times greater compared to those on methotrexate therapy. The results of present study show that the use of anti-TNF-α in RA patients can be associated to a significant increase of body weight. This increase is not shown in patients under treatment with methotrexate. A more careful evaluation of weight changes needs to be considered in RA patients under anti-TNF-α treatment.
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Comparison of essential fatty acid intakes and serum levels of inflammatory factors between asthmatic and healthy adults: a case- control study.
Haidari, F, Mohammadshahi, M, Borsi, SH, Haghighizadeh, MH, Malgard, S
Iranian journal of allergy, asthma, and immunology. 2014;(5):335-42
Abstract
Dietary fatty acids play a critical role in modulation of airway inflammation in asthma. This study was conducted to compare dietary intakes of essential fatty acids and serum levels of inflammatory factors in asthmatic and healthy adults, and to examine the potential relationship between inflammatory markers and dietary fatty acids. In this case-control study, 47 asthmatic patients (26 males and 21 females) were compared with 47 controls (24 males and 23 females). Blood samples were taken from case and control groups and tumor necrosis factor-α (TNF-α), high sensitive C-reactive protein (hs-CRP), leptin and adiponectin were determined. Dietary intakes were assessed by semi-quantitative food frequency questionnaire (FFQ). Dietary intakes of omega-3 fatty acids were significantly lower in asthmatic patients compared to controls (p<0.05). Serum concentrations of TNF-α, hs-CRP and leptin were significantly higher in asthmatic patients. There was a significant negative relationship between adiponectin levels and saturated fatty acid intakes in both groups, but the relationship between adiponectin and mono-unsaturated fatty acid intakes was positive and significant only in asthmatic group. No significant correlation between other inflammatory factors and dietary intakes was found in this study. Higher intake of omega-3 and lower levels of inflammatory factors in the healthy control group compared to asthmatic group may explain the protective role of essential fatty acids in asthma. Further studies with larger sample size are needed in this regard.
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Polymorphism at the TNF-alpha gene interacts with Mediterranean diet to influence triglyceride metabolism and inflammation status in metabolic syndrome patients: From the CORDIOPREV clinical trial.
Gomez-Delgado, F, Alcala-Diaz, JF, Garcia-Rios, A, Delgado-Lista, J, Ortiz-Morales, A, Rangel-Zuñiga, O, Tinahones, FJ, Gonzalez-Guardia, L, Malagon, MM, Bellido-Muñoz, E, et al
Molecular nutrition & food research. 2014;(7):1519-27
Abstract
SCOPE To examine whether the consumption of a Mediterranean diet (MedDiet), compared with a low-fat diet, interacts with two single nucleotide polymorphisms at the tumor necrosis factor alpha gene (rs1800629, rs1799964) in order to improve triglycerides (TG), glycemic control, and inflammation markers. METHODS AND RESULTS Genotyping, biochemical measurements, dietary intervention, and oral fat load test meal were determined in 507 metabolic syndrome (MetS) patients selected from all the subjects included in CORDIOPREV clinical trial (n = 1002). At baseline, G/G subjects (n = 408) at the rs1800629 polymorphism, showed higher fasting and postprandial TG (p = 0.003 and p = 0.025, respectively), and high sensitivity C-reactive protein (hsCRP) (p = 0.003) plasma concentrations than carriers of the minor A-allele (G/A + A/A) (n = 99). After 12 months of MedDiet, baseline differences between genotypes disappeared. The decrease in TG and hsCRP was statistically significant in G/G subjects (n = 203) compared with carriers of the minor A-allele (p = 0.005 and p = 0.034, respectively) (n = 48). No other gene-diet interactions were observed in either diet. CONCLUSION These results suggest that the rs1800629 at the tumor necrosis factor alpha gene interacts with MedDiet to influence TG metabolism and inflammation status in MetS subjects. Understanding the role of gene-diet interactions may be the best strategy for personalized treatment of MetS.
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Perioperative levels of tumor necrosis factor-α correlate with outcomes in children and adults with tetralogy of Fallot undergoing corrective surgery.
Sethi, BS, Kapoor, PM, Chauhan, S, Chowdhury, UK, Kiran, U, Choudhury, M
World journal for pediatric & congenital heart surgery. 2014;(1):38-46
Abstract
BACKGROUND Previous studies reporting on tumor necrosis factor-α (TNF-α) as a marker of inflammatory response (IR) in patients with congenital heart disease were limited by small sample size and variability in diagnosis. We report perioperative changes in TNF-α levels and their correlation with preoperative factors and clinical outcomes in a large homogenous group of patients with tetralogy of Fallot (TOF) undergoing definitive repair at a tertiary care center. METHODS A total of 167 patients were divided into four groups on the basis of age. Group 1 included infants less than 1 year, group 2 included children between 1 and 12 years, group 3 included adolescents between 12 and 18 years, and group 4 included adults more than 18 years of age. Serum TNF-α levels were measured at three time points and correlated with perioperative variables. RESULTS The baseline TNF-α level correlated with patients' nutritional status and degree of cyanosis in all four groups. The magnitude of IR in the postcardiopulmonary bypass (post-CPB) period as measured by TNF-α level was much higher and correlated more consistently with adverse clinical outcomes in the younger age group (groups 1 and 2). On multivariable analysis; age at operation, preoperative degree of hypoxemia and TNF-α levels were found to be independent predictors of clinical outcomes. CONCLUSION We demonstrated a rise in serum TNF-α levels in patients with TOF undergoing definitive repair on CPB, which correlated with preoperative severity of cyanosis, nutritional status, and adverse clinical outcomes. The TNF-α levels may be monitored to identify cyanotic patients at an increased risk of exhibiting augmented IR to CPB.
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Role of G308 promoter variant of tumor necrosis factor alpha gene on weight loss and metabolic parameters after a high monounsaturated versus a high polyunsaturated fat hypocaloric diets.
de Luis, DA, Aller, R, Izaola, O, Gonzalez Sagrado, M, Conde, R
Medicina clinica. 2013;(5):189-93
Abstract
BACKGROUND AND OBJECTIVE The aim of our study was to investigate the influence of G-308 promoter variant of the tumor necrosis factor (TNF) alpha gene on metabolic changes and weight loss secondary to a high monounsaturated fat vs a high polyunsaturated fat hypocaloric diet in obese subjects. PATIENTS AND METHOD A sample of 261 obese subjects were enrolled in a consecutive prospective way, from May 2011 to July 2012 in a tertiary hospital. In the basal visit, patients were randomly allocated during 3 months to Diet M (high monounsaturated fat hypocaloric diet) and Diet P (high polyunsaturated fat hypocaloric diet). RESULTS One hundred and ninety seven patients (73.2%) had the genotype G-308G and 64 (26.8%) patients had the genotype G-308A. There were no significant differences between the effects (on weight, body mass index (BMI), waist circumference, fat mass) in either genotype group with both diets. With the diet type P and in genotype G-308G, glucose levels (-6.7(22.1)mg/dl vs -3.7(2.2)mg/dl: p = 0.02), HOMA-R (-0.6(2.1)units vs -0.26(3.1)units: p = 0.01), insulin levels (-1.7(6.6)UI/L vs -0.6(7.1)UI/L: p = 0.009), total cholesterol levels (-15.3(31.1)mg/dl vs -8.4(22.1)mg/dl: p = 0.01), LDL cholesterol levels (-10.7(28.1)mg/dl vs -3.8(21.1)mg/dl: p = 0.008) and triglycerides (-12.1(52.1)mg/dl vs -6.6(43.1)mg/dl: p = 0.02) decreased. CONCLUSION Carriers of the G-308G promoter variant of TNF alpha gene have a better metabolic response than A-308 obese with a high polyunsaturated fat hypocaloric diet.
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Divergent anti-inflammatory effects of different oil acute consumption on healthy individuals.
Papageorgiou, N, Tousoulis, D, Psaltopoulou, T, Giolis, A, Antoniades, C, Tsiamis, E, Miliou, A, Toutouzas, K, Siasos, G, Stefanadis, C
European journal of clinical nutrition. 2011;(4):514-9
Abstract
BACKGROUND/OBJECTIVES Inter-cellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1) and tumor necrosis factor-α (TNF-α), are implicated in atherogenesis. In addition, several types of oil as part of different types of diet are associated with the initiation of atherosclerosis and consequently with the risk of cardiovascular disease. However, the exact role of oil consumption on vascular inflammation remains unknown. In this parallel study, we assessed the acute effects of extra virgin olive oil, soy oil, corn oil and cod liver oil on circulating soluble(s) forms of adhesion molecules and TNF-α. SUBJECTS/METHODS In all, 67 healthy volunteers were randomized to receive 50 ml of oil. Soluble forms of VCAM-1, ICAM-1 and TNF-α were measured by enzyme-linked immunosorbent assay at baseline and at 3 h post oil consumption. RESULTS All types of oil had no significant effect on soluble VCAM-1 levels (P=nonsignificant (NS) for all). On the contrary, all oil types decreased ICAM-1 levels (P<0.01). Olive oil (P<0.05), soy oil and cod liver oil (P<0.01 for both) reduced TNF-α levels significantly, in contrast to corn oil, which induced a nonsignificant decrease (P=NS). Moreover, there was a significant correlation between the absolute change in ICAM-1 and TNF-α levels (ρ=0.379, P<0.05), but not between the absolute changes in VCAM-1 and TNF-α levels (ρ=0.019, P=NS). CONCLUSIONS Acute consumption of all types of oil decreased significantly ICAM-1 levels. In addition, olive oil, soy oil and cod liver oil decreased significantly TNF-α levels. Moreover, the absolute change in TNF-α levels was correlated with the absolute change in ICAM-1 levels. These findings indicate that acute consumption of specific types of oil is associated with specific significant anti-inflammatory effects.
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The effect of anti-TNF agent on oxidation status in patients with ankylosing spondylitis.
Karkucak, M, Capkin, E, Alver, A, Akyuz, A, Kiris, A, Ak, E, Topbas, M, Tosun, M
Clinical rheumatology. 2010;(3):303-7
Abstract
The aim of this study was to comparatively evaluate oxidative status of ankylosing spondylitis (AS) patients receiving anti-tumor necrosis factor (TNF) or non-steroid anti-inflammatory drugs (NSAID). Forty-seven patients with AS and 27 healthy controls were enrolled. Of these, 23 were on anti-TNF (group 1) and 24 on NSAIDs (group 2). Groups 1 and 2 were consisted of matched patients with respect to age, gender, body mass index, disease duration, C-reactive protein, erythrocyte sedimentation rate, total cholesterol, and Bath Ankylosing Spondylitis Disease Activity Index. Mean duration of treatment for patients in group 1 was 12.6 +/- 6.8 months. Serum total antioxidative status (TAS) and total oxidative status (TOS) levels were determined using new automated methods. Oxidative stress index (OSI) was calculated. The groups' carotid intima-media thicknesses (IMT-C) were also measured using ultrasonography. Group 1 had the highest TAS and lowest TOS levels. The TOS levels of group 1 was lower than the control, while group 2 being higher than controls. The difference in TOS levels between group 1 and group 2 was statistically significant (p = 0.040). OSI values were highest in group 2 and lowest in group 1. There was no significant correlation between oxidant/antioxidant parameters and IMT-C for group 1 (r = -0.30, p = 0.198 for OSI; r = 0.22, p = 0.366 for TAS; r = -0.22, p = 0.361 for TOS). This is the first study to evaluate total oxidative/antioxidative status in patients with AS on anti-TNF agent. These results clearly indicate positive effects of anti-TNF treatment on oxidative status of AS patients. The limited effects of NSAIDs compared with controls may be due to excess impaired oxidative status in the patients in this study.