Oksana Sokhatska

Differential responses of adiposity, inflammation and autonomic function to aerobic versus resistance training in older adults

BACKGROUND Increased body fat, autonomic dysfunction and low-grade chronic inflammation are interrelated risk factors implicated in the etiology of several chronic conditions normally presented by older adults. OBJECTIVE This study aims to assess the effectiveness of different training protocols on reducing body fat, improving autonomic function, and decreasing low-grade systemic inflammation in community-dwelling elderly adults. METHODS Fifty participants (11 men, 68±5.5years) were randomly allocated into resistance or aerobic training or control groups. Evaluations were done at baseline and following the 8-month intervention period on their body composition (assessed by DXA), inflammatory biomarkers (high-sensitivity C-reactive protein [hs-CRP], tumor necrosis-alpha [TNF-α], interferon-gamma [IFN-γ], interleukins-6 and -10 [IL-6, IL-10]), lipoproteic profile, fasting glycemia, blood pressure, heart rate variability (HRV; frequency and time domains) and aerobic fitness (assessed by six-minute walk distance [6MWD]). A paired t-test was used to detect changes (%Δ=[(post-test score-pretest score)/pre-test score]×100) within groups, while between-group differences were analyzed using the one-way ANOVA or General Linear Models. RESULTS A significant change (Δ%) both in total (-5.4±6.3% and -3.3±2.9%, respectively) and central body fat (8.9±11.3% and -4.8±4.5%) was observed in resistance and aerobic training groups, respectively; along with a change in resting systolic and diastolic blood pressures (-9.2±9.8% and -8.5±9.6%), heart rate (-4.6±6.5%), hs-CRP (-18.6±60.6%), and 6MWD (9.5±6.9%) in response to aerobic training. CONCLUSIONS The present findings provide further evidence for the benefits of aerobic and resistance training on reducing body fat. Aerobic training was demonstrated to reduce hs-CRP and blood pressure in community-dwelling elderly participants with no serious medical conditions.

Substance P antagonist improves both obesity and asthma in a mouse model

Evidence suggests a causal relationship between obesity and asthma; however, the underlying mechanisms remain unknown. Substance P (SP), involved in neurogenic inflammation by acting through its receptor NK1‐R, seems to participate in obese–asthma phenotype in mice.

Increased circulating platelet microparticles as a potential biomarker in asthma.

Endothelial (EMPs) and platelet microparticles (PMPs) have been studied as biomarkers in several inflammatory diseases and as central players in intercellular communication.

Neurogenic inflammation in allergen-challenged obese mice: a missing link in the obesity-asthma association?

ABSTRACT Aim: A number of studies have shown an association between obesity and asthma. Controversy remains on the mechanisms supporting this association. In this study we aimed to assess neurogenic inflammation in a model of diet-induced obesity and allergen-challenged mice. Methods: High fat diet-induced (HFD) obese Balb/c mice were sensitized and challenged with ovalbumin (OVA). Glucose, insulin, OVA-specific IgE and substance P (SP), and the main tachykinin involved in neurogenic inflammation, were quantified in sera. Cell counts were performed in bronchoalveolar lavage fluid (BALF). The extent of peribronchial infiltrates was estimated on lung tissue sections and inflammation was score based on inflammatory cell counts surrounding the bronchi. Results: Obesity per se and allergen-sensitization per se increased serum SP (P = .027, P = .004, respectively). Further increased was observed in obese-sensitized mice (P = .007). Obese-sensitized mice also showed higher insulin (P = .0016), OVA-specific IgE (P = .016), peribronchial inflammatory score (P = .045), and tendency for higher glycemia. The interaction of obesity and asthma on SP levels was confirmed (P = .005, R2 = 0.710). SP was positively correlated with metabolic (glycemia, r = 0.539, P = .007) and allergic inflammation parameters (BALF eosinophils, r = 0.445, P = 0.033; BALF mast cells, r = 0.574, P = .004; peribronchial inflammation score, r = 0.661, P < .001; and OVA-specific IgE, r = 0.714, P < .001). Conclusions: Our findings provide support to the neurogenic inflammation link between obesity and asthma in mice. These two conditions independently increased SP and the presence of both pathologies further increased this level. Neurogenic inflammation may be a previously unrecognized mechanism beyond the obese-asthma phenotype. Further studies are need to confirm this role of SP in human obesity-asthma association.

Chitosan Coated Textiles May Improve Atopic Dermatitis Severity by Modulating Skin Staphylococcal Profile: A Randomized Controlled Trial.

Background Atopic dermatitis (AD) patients may benefit from using textiles coated with skin microbiome–modulating compounds. Chitosan, a natural biopolymer with immunomodulatory and antimicrobial properties, has been considered potentially useful. Objective This randomized controlled trial assessed the clinical utility of chitosan-coated garment use in AD. Methods Of the 102 patients screened, 78 adult and adolescents were randomly allocated to overnight use of chitosan-coated or uncoated cotton long-sleeved pyjama tops and pants for 8 weeks. The primary outcome was change in disease severity assessed by Scoring Atopic dermatitis index (SCORAD). Other outcomes were changes in quality of life, pruritus and sleep loss, days with need for rescue medication, number of flares and controlled weeks, and adverse events. Changes in total staphylococci and Staphylococcus aureus skin counts were also assessed. Comparisons were made using analysis of variance supplemented by repeated measures analysis for the primary outcome. Interaction term between time and intervention was used to compare time trends between groups. Results Chitosan group improved SCORAD from baseline in 43.8%, (95%CI: 30.9 to 55.9), P = 0.01, placebo group in 16.5% (-21.6 to 54.6); P = 0.02 with no significant differences between groups; Dermatology Quality of life Index Score significantly improved in chitosan group (P = 0.02) and a significant increase of skin Coagulase negative Staphylococci (P = 0.02) was seen. Conclusions Chitosan coated textiles may impact on disease severity by modulating skin staphylococcal profile. Moreover, a potential effect in quality of life may be considered. Trial Registration ClinicalTrials.gov NCT01597817

Meal-exercise challenge and physical activity reduction impact on immunity and inflammation (MERIIT trial)

Background The effect of a pre-exercise meal as countermeasure to exercise induced immunodepression is poorly known. Also, sedentary behavior is associated with increased cardiometabolic risk but studies on immune changes are lacking. Therefore, we aimed to assess: 1) the impact of a pre-exercise Mediterranean meal (MdM) compared with a fast-food type meal (FFM) on exercise-induced immunological changes and 2) the impact of an induced acute period of sedentary behavior on neuro-immune-endocrine status. Methods /Design: This is a two steps clinical trial including: (a) randomized crossover clinical trial, comparing the effect a high-fat/low-nutrient dense meal, FFM, with an isoenergetic similar high-nutrient dense meal, MdM, in the immune response to an exercise challenge (EC) and (b) a pilot trial assessing the neuro-immune-endocrine change induced by acute decreasing by half the usual physical activity level. Results A total of 46 participants (26 females), median aged 25 years were included. Of those 39-completed protocol, including overweight, physical active and inactive and participants with asthma. There were no differences in the EC between interventions. Dietary factors and physical activity were closely monitored during interventions and kept similar. During physical inactivity induction, 31% reached the target of 50% reduction in mean step number and 77% reached a 30% reduction. Conclusion The use of a pre-exercise meal to modulate immune response and the understanding of the immunological impact of physical inactivity might help to establish future recommendations on how to practice exercise in a safer way and to recognize the potential impact of inactivity.

Evaluation of interrelationships between thyroid function, autoimmunity, insulin resistance and lipid profile in Graves' disease

Introduction: Thyroid hormones modulate the lipoprotein and glucose metabolisms. In hyperthyroidism, insulin resistance is a frequent finding. The aim of our study was to assess the interrelationships between thyroid function, autoimmunity, lipid profile, glucose metabolism and other cardiovascular risk factors in patients with Graves’ disease. Material & Methods: We recorded free T3, free T4, TSH, TSH receptor antibodies, parameters of the lipid profile, glucose metabolism (including insulin resistance markers like homeostasis model assessment for insulin resistance - HOMA-IR), C reactive protein and homocysteine in 126 patients with Graves’ disease in the first cycle of treatment with methimazole (92.9% females, mean age 44.9 ± 15.2 years). Patients were divided in subgroups according to: TSH receptor antibodies [positive (n = 57) or negative (n = 69)] and thyroid function [euthyroidism (n = 74), subclinical (n = 29) or clinical hyperthyroidism (n = 22)]. Spearman correlations, t-tests and Mann-Whitney tests were performed for statistical analysis. Results: Comparing the positive and negative TSH receptor antibodies groups, significantly lower apolipoprotein B (80.3 ± 23.9 vs 89.7 ± 23.8 mg/dL; p = 0.047) and TSH [0.180 (0.002-1.080) vs 1.020 (0.235-2.055) μUI/mL; p < 0.001] were found in the positive TSH receptor antibodies group. Comparing with the normal thyroid function group, patients in the clinical hyperthyroid group presented significantly lower apolipoprotein B (70.9 ± 25.8 vs 89.8 ± 24.0 mg/dL; p = 0.007] and higher fasting glucose (96.0 ± 24.4 vs 86.4 ± 10.0 mg/dL; p = 0.019), insulin [10.4 (6.2-15.8) vs 7.5 (4.8-9.7) μUI/mL; p = 0.021], HOMA-IR [2.09 (1.29-4.53) vs 1.55 (0.96-2.13); p = 0.023] and C reactive protein [0.57 (0.20-0.93) vs 0.20 (0.07-0.38) mg/L; p = 0.005]. No significant differences were found between the subclinical hyperthyroid and the normal groups. There was a negative correlation between TSH and the TSH receptor antibodies (r = -0.386; p < 0.001). Apolipoprotein B was positively correlated with TSH (r = 0.236; p = 0.016), and negatively with the TSH receptor antibodies (r = -0.211; p = 0.030). Both free T3 and free T4 were positively correlated with fasting insulin (r = 0.268; p = 0.008 and r = 0.226; p = 0.025, respectively) and HOMA-IR (r = 0.258; p = 0.010 and r = 0.259; p = 0.010, respectively). Free T4 was also positively correlated with fasting glucose (r = 0.269; p = 0.008). Conclusion: In patients with Graves’ disease, the interrelationships between thyroid function, autoimmunity, insulin resistance and lipid profile may contribute to the increased cardiovascular risk. The lipid profile suggests a hypolipidemic effect.

Cardiovascular risk factors in patients with autoimmune thyroiditis

Introduction: Thyroid dysfunction has been related to an increased cardiovascular risk resulting from alterations in lipid profile, insulin resistance, homocysteine levels and low grade systemic inflammation. The impact of normal TSH levels and subclinical hypothyroidism and autoimmunity in the increased cardiovascular risk remains controversial. Our objective was to evaluate the interrelations between thyroid function, thyroid autoimmunity and cardiovascular risk factors, in patients with autoimmune thyroiditis. Methods: 353 subjects with autoimmune thyroiditis were evaluated. We defined three groups based on TSH levels: TSH 0.5-2.5 μUI/mL, TSH 2.5-5.0 μUI/mL and TSH 5.0-10.0 μUI/mL. We recorded thyroid function tests, thyroid autoimmunity, insulin resistance markers including HOMA-IR (Homeostasis Model Assessment for Insulin Resistance), lipid profile, homocysteine, high-sensitivity C-reactive protein (hs-CRP) and vitamin B12 levels. Statistical analysis was performed using KruskalWallis test and Spearman correlations. Results: Our sample comprised 94% females with a mean age of 47.0 ± 16.3 years. The group TSH 5.0-10.0 μUI/mL presented higher levels of HOMA-IR when compared to the other two groups [2.96 (1.76-4.59) in TSH 5.0-10.0 μUI/mL vs 1.86 (0.97-2.56) in TSH 2.5-5.0 μUI/mL and 1.58 (1.06-2.46) in TSH 0.5-2.5 μUI/mL, p = 0.002]. In the total group we observed positive correlations between free T3 and both HDL (r = 0.118, p = 0.028) and apolipoprotein A-I (Apo A-I) (r = 0.129, p = 0.024); TSH was positively correlated with HOMA-IR (r = 0.146, p = 0.018) while free T4 was negatively correlated with homocysteine (r = -0.119, p = 0.041). In the group TSH 0.5-2.5 μUI/mL, positive correlations were found between TSH and both HDL (r = 0.136, p = 0.031) and homocysteine (r = 0.147, p = 0.028), between free T4 and CRP (r = 0.136, p = 0.037) and between anti-thyroglobulin antibodies and apolipoprotein B (r = 0.165, p = 0.013); anti-thyroglobulin antibodies were negatively correlated with homocysteine (r = -0.186, p = 0.006). Negative correlations between anti-thyroglobulin antibodies, total cholesterol (r = 0.371, p = 0.004), LDL (r = -0.325, p = 0.011), apolipoprotein B (r = -0.342, p = 0.022) and lipoprotein(a) (r = -0.470, p = 0.001) were revealed in the group TSH 2.5-5.0 μUI/mL. Regarding the group TSH 5.0-10.0 μUI/mL, we found positive correlations between free T3 and HDL (r = 0.358, p = 0.030), vitamin B12 (r = 0.398, p = 0.024) and HOMA-IR (r = 0.424, p = 0.031), and between anti-thyroglobulin and homocysteine (r = 0.383, p = 0.033). Conclusion: We observed significant correlations between thyroid function, thyroid autoimmunity, insulin resistance, lipid profile and homocysteine that may contribute to an increased cardiovascular risk in patients with autoimmune thyroiditis.

Subclinical hypothyroidism, autoimmune thyroiditis, and cardiovascular risk factors

Background and objectives: There is increasing evidence that subclinical hypothyroidism is related with an increased cardiovascular risk. The objective is to evaluate the relationship between autoimmune thyroiditis, subclinical hypothyroidism and cardiovascular risk factors. Methods: We recorded thyroid function tests, anti-TPO and antithyroglobulin antibodies, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, apolipoproteinA1, apolipoproteinB, lipoprotein(a), homocysteine, high sensitivity CRP, folic acid, vitamin B12, HOMA-IR, HOMA-β, QUICKI, HISI, WBISI, IGI in 185 subjects with autoimmune thyroiditis and in euthyroid state and in 69 subjects with autoimmune thyroiditis and subclinical hypothyroidism. Statistical analysis was performed with Mann-Whitney test, logistic regression and Spearman correlations. The results were adjusted for age and body mass index. Statistical significance was considered for a bilateral value of p<0.05. Results: 94% of subjects were female. The median age was significantly higher in the euthyroid group. Patients with higher levels of total cholesterol (OR=1.008; p=0.034), CRP (OR=1.684; p=0.041) or anti-thyroglobulin antibodies (OR=1.002; p=0.021) had an increased likelihood of having subclinical hypothyroidism. In the total group of patients, we observed positive correlations between TSH, CRP and HOMA-IR, between free T3 and HDLcholesterol and between free T4 and IGI. TSH levels correlated negatively with QUICKI, HISI and WBISI. In the group with subclinical hypothyroidism, we found negative correlations between free T3 and homocysteine and between free T4 and anti-TPO antibodies.