The effect of the treatment of denture related stomatitis on peripheral T cells and monocytes

Purpose: Systemic immune activation has been recently linked to chronic inflammatory disorders of the oral cavity, particularly to periodontitis. The purpose of this study was to determine whether treatment of a fungus-induced oral inflammation, namely denture-related stomatitis (DRS), can affect the activation of the systemic immune response. Materials and Methods: Peripheral blood from patients with denture-related stomatitis caused by Candida albicans infection (n = 15) was collected at three time points: before treatment with nystatin, at the end of therapy and 2 months after finishing therapy. Activation of T cells and monocytes was assessed by flow cytometry. Results: The percentages of peripheral lymphocytes, T cells and their subpopulations, as well as monocytes were similar before, immediately following and two months after nystatin treatment. Cells expressing early activation marker CD69 and RANTES C-C chemokine receptor type 5 significantly increased immediately after treatment and returned to baseline levels after two months. Th17 cells, which have been implicated in the pathogenesis of DRS, remained unchanged. Central memory CD4+ subset and intermediate subset of monocytes were lower after therapy and this effect was sustained for two months. Conclusion: Treatment of denture-related stomatitis does not seem to affect the general state of the cellular components of the immune system. The results suggest a potential proinflammatory effect of the antifungal agent, nystatin. Although transient and not intense, this effect might be of particular clinical importance, because of relationships between inflammation and certain diseases. Further studies are required to clarify this aspect

Th17 responses are not altered by natural exposure to seasonal allergens in pollen-sensitive patients

Background: Allergic rhinitis affects 10–30 % of the global population and this number is likely to increase in the forthcoming years. Moreover, it commonly co-exists with allergic asthma as a chronic allergic respiratory syndrome. While the involvement of Th2 cells in allergy is well understood, alterations of pro-inflammatory Th17 responses remain poorly characterized. The aim of our study was to determine whether natural seasonal allergen exposure causes changes in T cell subset characteristics in patients with allergic rhinitis and asthma. Methods: Sixteen patients with allergic rhinitis/atopic asthma (9M, 7F; age 31.8 ± 12.1) and 16 healthy controls were recruited into the study (9M, 7F; age 31.2 ± 5.3). Blood samples were collected from the patients 1–3 months before pollen season (visit 1), within 7 days of the appearance of pollen/initiation of allergic symptoms (visit 2) and 2 weeks after visit 2 following the introduction of symptomatic treatment with antihistamines (visit 3). Flow cytometry was used to assess major T cell subsets (naïve, central memory, effector memory and CD45RA+ effector) and key T cell cytokine production (IFNγ, IL-17A, TNF and IL-4) using intracellular staining. Data were analyzed using repeated measures ANOVA and paired t test. Results: As expected, an increase in the percentage of IL‐4+ CD4+ cells was observed during natural pollen exposure in patients with allergic respiratory syndrome. No significant changes were observed in the production of other cytokines, including Th17 cells, which tended to be lower than in the control population but unchanged during pollen exposure. Introduction of antihistamine treatment led to only moderate changes in cytokine production from CD4 and CD8 T cells. Selective changes in CD8+ T cells were observed during natural pollen exposure including a decrease in transient cells (with features of CD45RA+ and CD45RO+ cells) and a decrease in the percentage of central memory cells in the peripheral circulation. Within the CD4 cell group the total percentage of CD45RA positive CD4 cells was increased during pollen exposure. Conclusions: Th1 and Th17 responses are not altered during pollen season but allergen exposure affects T cell activation and memory cell status in patients with allergic respiratory syndrome

Association of Body Composition with Curve Severity in Children and Adolescents with Idiopathic Scoliosis (IS)

The link between scoliotic deformity and body composition assessed with bioimpedance (BIA) has not been well researched. The objective of this study was to correlate the extent of scoliotic-curve severity with the anthropometrical status of patients with idiopathic scoliosis (IS) based on standard anthropometric measurements and BIA. The study encompassed 279 IS patients (224 girls/55 boys), aged 14.21 ± 2.75 years. Scoliotic curve severity assessed by Cobb’s angle was categorized as moderate (10°–39°) or severe (≥40°). Corrected height, weight, waist and hip circumferences were measured and body mass index (BMI), corrected height z-score, BMI Z-score, waist/height ratio (WHtR) and waist/hip ratio (WHR) were calculated for the entire group. Body composition parameters: fat mass (FAT), fat-free mass (FFM) and predicted muscle mass (PMM) were determined using a bioelectrical impedance analyzer. The mean Cobb angle was 19.96° ± 7.92° in the moderate group and 52.36° ± 12.54° in the severe group. The corrected body heights, body weights and BMIs were significantly higher in the severe IS group than in the moderate group (p < 0.05). Significantly higher FAT and lower FFM and PMM were observed in the severe IS group (p < 0.05). The corrected heights and weights were significantly higher in patients with severe IS and normal weight (p < 0.01). Normal and overweight patients with a severe IS had significantly higher adiposity levels assessed by FAT, FFM and PMM for normal and BMI, BMI z-score, WHtR, FAT and PMM for overweight, respectively. Overweight IS patients were significantly younger and taller than underweight and normal weight patients. The scoliotic curve severity is significantly related to the degree of adiposity in IS patients. BMI z-score, WHtR and BIA seem to be useful tools for determining baseline anthropometric characteristics of IS children

Body Composition in Multiple Sclerosis Patients and Its Relationship to the Disability Level, Disease Duration and Glucocorticoid Therapy

Background: Patients with multiple sclerosis (MS) have many potential factors (spasticity, immobilization, glucocorticoids use) for the deterioration of body composition. Aim: To assess the nutritional status (by classical anthropometry and by bioelectrical impedance analysis (BIA)) in MS patients and to correlate it with clinical state, MS duration time and the presence of glucocorticoid therapy in anamnesis (ever used). Methods: Anthropometrical (BMI and waist and hip circumferences, waist-to-height ratio (W/HtR), and waist-to-hip ratio (WHR)) and body composition (BIA) data were evaluated in 176 patients with MS. Fat mass (FM), and fat-free mass (FFM) were expressed as kilograms (kg), percentage (%) and indexes (FMI: fat mass index, FFMI: fat-free mass index) expressed in kg/m2. The median Expanded Disability Status Scale score was 4.5. Patients were then divided according to EDSS score as mild (EDSS 1.0–4.0) or moderate (EDSS 4.5–6.5) disability subgroup. Results: Waist c., WHtR, WHR, and FM% were significantly higher in the moderate MS group (p < 0.01; p < 0.001; p < 0.001; and p < 0.05, respectively). Whilst, FFM% was significantly lower (p < 0.05). BMI did not correlate significantly with any disability status score and MS time. Significant correlations were observed between EDSS, ΔEDSS and MS time and Waist c., WHtR, WHR, FM% and FFM%. WHtR had the strongest significance (p < 0.0001 vs. EDSS; p < 0.0001 vs. ΔEDSS; and p < 0.01 vs. MS time, respectively). After the adjustment to the MS time, only FM% was no longer significantly related to both EDSS and ΔEDSS. MS duration time, EDSS, ΔEDSS, WHtR, FM(kg), FM%, and FMI were significantly higher in the patients with a positive history of glucocorticoid therapy (all p < 0.05). Whilst, FFM% was significantly lower in MS patients treated with glucocorticoids (p < 0.01). Conclusions: Greater disability in MS patients is strongly related to lower fat-free mass and higher fat mass, especially with the abdominal distribution, irrespective of the duration time of the disease. Oral glucocorticoid therapy seems to have a negative impact on the body composition of MS patients. However, further prospective multifactorial studies in this field have to be done. For the proper assessment of nutritional status in MS patients, Waist c., WHtR, WHR, or body composition parameters seem to be of greater use than BMI

Association between Bone Turnover Markers, Leptin, and Nutritional Status in Girls with Adolescent Idiopathic Scoliosis (AIS)

The link between scoliotic deformity and bone metabolism in adolescent idiopathic scoliosis (AIS) has not been well researched. Moreover, the data concerning the cross-talk between fat tissue content/hormonal activity and bone markers in this group of patients are lacking. The aim of the study was to assess whether there exists a significant relationship between the severity of AIS and bone turnover markers and leptin levels. The study group was consisted of 77 AIS girls, aged 14.7 ± 2.17 years. Scoliotic curve severity assessed by Cobb’s angle was categorized as mild (10–19°), moderate (20–39°), or severe (≥40°). Corrected height, weight, and waist and hip circumferences were measured and body mass index (BMI), corrected height Z-score, BMI Z-score, and waist/height ratio (WHtR) were calculated for the entire group. Body composition parameters: fat mass (FAT), fat-free mass (FFM), and predicted muscle mass (PMM) were determined using a bioelectrical impedance analyzer. Bone turnover markers (osteocalcin (OC) and amino terminal of collagen cross-links (NTx) and leptin levels were assessed in serum. Multiple regression analysis showed that, OC, NTx (negatively with p < 0.05), and leptin (positively with p < 0.01) were significantly associated with curve severity in AIS girls. Moreover, Cobb’s angle was positively correlated with W/HtR (p < 0.01) and FAT (p < 0.05). One-way analysis of variance (ANOVA) revealed significant differences in leptin (p < 0.05 vs. mild only), OC (p < 0.05 vs. mild and moderate), and W/HtR (p < 0.01 and p < 0.05 vs. mild and moderate, respectively) between the three AIS severity subgroups. OC was significantly lower in the severe AIS subgroup, while leptin and W/HtR were significantly higher. Significant correlations between leptin and anthropometrical parameters as BMI z-score and W/HtR were shown. Leptin level correlated also significantly with BMI z score (p < 0.001), W/HtR (p < 0.0001), and body composition parameters (p < 0.000001). Moreover, there was a significant negative correlation between NTx and leptin level (p < 0.05). Bone metabolism in AIS girls seems to be altered and significantly related to the scoliotic curve severity. Leptin may be a crucial link in the cross-talk between bone turnover and body composition in this group of patients. Further studies concerning interrelationship between nutritional status and bone metabolism in patients with AIS are warranted

Vitamin D Deficiency in Obese Children Is Associated with Some Metabolic Syndrome Components, but Not with Metabolic Syndrome Itself

Vitamin D deficiency in children is a common nutritional issue in many populations worldwide, associated not only with skeletal malformations but, as recent studies suggest, also with the development of obesity and metabolic syndrome. The aim of this observational study was to assess the nutritional status of vitamin D in a group of Polish children with obesity and different grades of metabolic syndrome, with a consequent analysis of the correlation between vitamin D levels and the components of metabolic syndrome. For that purpose, the group of 78 participants (mean age: 14.18 ± 2.67 years) was recruited and further grouped in relation to vitamin D status into two groups of children with and without vitamin D deficiency. The biochemical parameters associated with obesity as well as anthropometric measures were assessed and analysed in search of significant differences between the groups. In the current group of children with obesity and vitamin D deficiency, HDL (45.00 ± 9.29) and adiponectin (7.21 ± 1.64) were found to be significantly lower than in their peers without vitamin D deficiency, whereas W/HtR (0.60 ± 0.04) and TG (171.31 ± 80.75) levels proved to be significantly higher. Body composition analysis using bioelectrical impedance returned no significant findings. The above findings suggest that vitamin D deficiency may influence lipid and glucose metabolism in children, leading to the development of abnormalities characteristic of the metabolic syndrome. A W/HtR parameter was shown to be a sensitive marker of abdominal obesity, which might provide an important means of assessing the correlation between vitamin D and this type of obesity. Independently, vitamin D deficiency may also influence the endocrinological function of adipose tissue, leading to lower concentrations of adiponectin. These in turn presented a linear correlation with the high results of the OGTT in the second hour of the test, hinting at its potential role in the pathophysiology of insulin resistance

Predictive Value of Adiposity Level, Metabolic Syndrome, and Insulin Resistance for the Risk of Nonalcoholic Fatty Liver Disease Diagnosis in Obese Children

Background. Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in obese children. Early diagnosis and treatment are essential for curing or slowing down the disease progression. The aim of the study was to assess the prevalence of NAFLD in this population and to identify anthropometrical and metabolic risk factors for NAFLD prediction and its development. Material and Methods. The study included 108 obese children. Anthropometric measurements, NAFLD diagnosis (based on ALT level and/or liver ultrasound), and metabolic syndrome (MS) components were assessed in all patients. Patients were divided into groups with and without NAFLD. Results. NAFLD was diagnosed in 49 (45%) patients with similar prevalence in boys (27; 55.10%) and girls [22 (44.9%), p=0.089]. NAFLD patients had significantly greater waist circumference, WHR, and WHtR and significantly higher total cholesterol, triglyceride, and fasting insulin concentrations as well as higher glucose and insulin concentrations in 120 minutes of OGTT and higher HOMA-IR levels compared to group of patients without NAFLD. In NAFLD patients, MS was significantly more likely to be diagnosed than in group without NAFLD (40.82% versus 22.81%,  p=0.04), but among the MS components only hypertriglyceridemia was significantly more frequently diagnosed in the group with NAFLD (p=0.002). Among analysed parameters the best independent risk factor for NAFLD was fasting insulin concentration with the cut-off point = 18,9 uIU/ml (AUC = 0.829). Conclusions. NAFLD is a very common disease in obese children. NAFLD predictive risk factors include increased waist circumference, elevated WHR and WHtR, and elevated total cholesterol, triglycerides, and fasting insulin as well as elevated glucose and insulin concentration in the OGTT and HOMA-IR index. NAFLD increases the risk of potential cardiovascular complications expressed by diagnosis of metabolic syndrome. The best independent predictive risk factor for diagnosing NAFLD in obese children is fasting insulin > 18.9 uIU/ml

Do we know enough about the immune pathogenesis of acute coronary syndromes to improve clinical practice?

Morbidities related to atherosclerosis, such as acute coronary syndromes (ACS) including unstable angina and myocardial infarction, remain leading causes of mortality. Unstable plaques are inflamed and infiltrated with macrophages and T lymphocytes. Activated dendritic cells interact with T cells, yielding predominantly Th1 responses involving interferon-gamma (IFN-γ) and tumour necrosis factor-alpha (TNF-α), while the role of interleukin 17 (IL-17) is questionable. The expansion of CD28nullCD4 or CD8 T cells as well as pattern recognition receptors activation (especially Toll-like receptors; TLR2 and TLR4) is characteristic for unstable plaque. Inflammation modifies platelet and fibrin clot characteristics, which are critical for ACS. Understanding of the inflammatory mechanisms of atherothrombosis, bridging inflammation, oxidative stress and immune regulation, will allow for the detection of subjects at risk, through the use of novel biomarkers and imaging techniques including intravascular ultrasound, molecular targeting, magnetic resonance imaging (MRI) and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET). Moreover, understanding the specific inflammatory pathways of plaque rupture and atherothrombosis may allow for immunomodulation of ACS. Statins and anti-platelet drugs are anti-inflammatory, but importance of immune events in ACS warrants the introduction of novel, specific treatments directed either on cytokines, TLRs or inflammasomes. While the prime time for the introduction of immunologically inspired diagnostic tests and treatments for atherosclerosis have not come yet, we are closer than ever before to finally being able to benefit from this vast body of experimental and clinical evidence. This paper provides a comprehensive review of the role of the immune system and inflammation in ACS