Therapeutic Evaluation of Outpatient Submucosal Inferior Turbinate Surgery for Patients with Severe Allergic Rhinitis

BackgroundSurgical treatment for inferior turbinate (IT) is selected to treat severe allergic rhinitis (AR) that is unresponsive to conservative treatment. This study aimed to determine the clinical effects of outpatient sub- mucosal IT surgery (OSITS) on patients with severe AR.MethodsBetween January 2008 and August 2012, 95 patients with severe AR who underwent OSITS at the Department of Otolaryngology, Hyogo College of Medicine, were retrospectively analyzed. There were 53 men and 42 women. Their mean age was 27 years (11–75 years). OSITS was bilaterally performed using a bipolar radiofrequency electrocautery under local anesthesia. Symptoms, QOL, and physical findings were evaluated using scores from both pre- and postoperative periods (average: 12.4 months), according to Practical Guideline for the Management of AR in Japan 2009.ResultsIn perennial AR, all mean scores of nasal symptoms, QOL, and physical findings significantly improved after OSITS (p < 0.05, n = 83). Nasal obstruction, sleep problems, and IT congestion were the most strongly affected. Eye symptoms were not influenced by OSITS. OSITS also showed significant effects on nasal obstruction and IT congestion in seasonal AR (p < 0.05, n = 12), but not sneezing, nasal discharge, and QOL. In terms of the efficacy, OSITS was beneficial in 90% of perennial AR cases and 75% of seasonal AR cases. Epistaxis (1%), vestibulitis (1%), and IT atrophy (4%) were observed after OSITS.ConclusionsThese data indicate that OSITS using radiofrequency electrocautery could be a beneficial therapeutic option in patients with severe AR.     

Cytokine mucosal expression in ulcerative colitis,the relationship between cytokine release and disease activity

BackgroundUlcerative colitis (UC) is an inflammatory bowel disease with conflicting evidence from studies on the roles of TNFα, IL-8, TGFβ and other cytokines and characterised by neutrophil infiltration and tissue destruction.AimTo compare cytokine profiles of inflamed and non-inflamed mucosa in patients with distal UC, and matched controls.MethodsPatients were prospectively recruited, mucosal biopsies at flexible sigmoidoscopy (FS) were taken from UC patients within macroscopically inflamed and non-inflamed proximal mucosa, and from age–sex matched controls undergoing FS. Endoscopic and histological inflammation was graded. Quantitative cytokine analysis for IL-4, TNFα, IL-17A, IL-8, IL-10, TGFβ and IFNγ was carried out on tissue homogenates. Statistical comparison was by Wilcoxon signed rank pair analysis, Mann–Whitney U test and Spearman's correlation.Results69 active UC patients (54 paired non-inflamed/inflamed mucosa) and 69 controls were compared. In inflamed mucosa, elevation in IL-8 and reduction in TGFβ was measured compared with non-inflamed mucosa (p < 0.001; p < 0.02) and control mucosa (p < 0.001; p < 0.001); IL-8 was positively correlated (r_s = 0.481, p < 0.01) and TGFβ inversely correlated (r_s = 0.462; p < 0.01) with grade of inflammation. TNFα concentration was not significantly different. Comparisons of inflamed with non-inflamed mucosa also demonstrate significant reduction in concentration of IFNγ (p < 0.001), IL-4 (p < 0.005) and IL-17A (p < 0.002).ConclusionOur findings suggest that IL-8 is elevated and TGFβ is reduced in distal colitis. Lower concentration of IFNγ, IL-4 and IL-17A were also noted. TNFα levels were unchanged. These findings suggest that the inflammatory response in UC may predominantly involve IL-8 mediated neutrophil infiltration and failure of TGFβ mediated tissue healing.     

IL-17 in cutaneous lupus erythematosus

BackgroundLupus erythematosus (LE) is a heterogeneous disease with broad clinical spectrum from cutaneous to visceral and systemic inflammation. IL-17 isoforms (IL-17A and IL-17F) are proinflammatory cytokines with unclear implications in lupus erythematosus pathogenesis. In this study we focused upon IL-17 in normal and modified lupus skin with a correlative study between local and serological expression.Material and methods89 subjects were recruited and divided in 5 groups—10 patients with psoriasis (disease control group), 13 healthy controls, 26 with discoid chronic lupus (DLE), 23 with systemic lupus erythematosus (SLE) and 17 with subacute lupus erythematosus (SCLE). Blood samples and skin punched-biopsy specimens were performed. Serum IL-17A, IL-17F, and IL-23 concentrations were determined by ELISA. Skin IL-17A and CD4 expression were evaluated by immunohistochemistry.ResultsImmunohistochemical expression of IL-17A was higher in DLE, SCLE and SLE patients than in negative control subjects (all p < 0.05). Serum IL-17A concentrations were higher in DLE and SLE patients than in negative controls (p < 0.05). Serum IL-17A levels were similar in SCLE and negative controls (p > 0.05). Serum IL-17F concentrations were higher in DLE, SCLE and SLE patients than in healthy controls (all p < 0.05). In DLE, SCLE, SLE patients and healthy controls we observed comparable levels of IL-23 (p > 0.05). Serum anti Ro antibodies correlate with IL-17A+ lymphocytes from SCLE lesion and SLE normal skin (all p < 0.05).ConclusionIL-17 isoforms (IL-17A and IL-17F) are implicated in SLE but also in DLE and SCLE immunopathogenesis.     

Serum and urinary biomarkers that predict hepatorenal syndrome in patients with advanced cirrhosis

BackgroundPrediction of hepatorenal syndrome (HRS) remains difficult in advanced cirrhotic patients.AimsTo evaluate use of serum and urine biomarkers to predict HRS.MethodsWe prospectively recruited Child’s B or C cirrhotic patients with normal serum creatinine, and followed them for 12 weeks for the development of HRS. Serum Cystatin C (CysC), serum and urine Neutrophil Gelatinase-Associated Lipocalin (NGAL), serum and urine IL-18, serum N-acetyl-β-d glucosaminidase (NAG), urine kidney injury molecule-1 (KIM-1) and urine liver-type fatty acid binding protein (LFABP) were measured at recruitment (baseline), and their relationship with subsequent HRS investigated.Results43 patients were included. 12 (27.9%) developed HRS at 7.3 ± 5.1 weeks from baseline. Logistic regression analysis showed that baseline urinary NGAL and urinary KIM-1 were significantly associated with the development of HRS (RR 1.007, 95% CI 1.001–1.012, p = 0.014; RR 1.973, 95% CI 1.002–3.886, p = 0.049). The cut-off values for NGAL and KIM-1 to predict HRS were 18.72 ng/mL and 1.499 ng/mL respectively (AUCs 0.84, p = 0.005; and 0.78, p = 0.008).ConclusionUrinary NGAL and KIM-1 could serve as biomarkers to predict HRS in advanced cirrhotic patients.     

Effects of olopatadine hydrochloride on the release of thromboxane B2 and histamine from nasal mucosa after antigen–antibody reaction in guinea pigs

BackgroundVarious mediators, such as thromboxane (TX) A₂, peptide leukotrienes (P-LT) and histamine, are involved in allergic nasal obstruction. The aim of the present study was to investigate the mechanism whereby olopatadine hydrochloride, a novel anti-allergic drug, ameliorated the allergic nasal obstruction.MethodsThe levels of TXB₂, P-LT and histamine in nasal lavage fluid (NLF) were measured after intranasal antigen challenge in sensitized guinea pigs.ResultsHistamine and TXB₂ levels in the NLF increased eight- and threefold, respectively, 10 min after antigen challenge, whereas the P-LT level was under the detection limit. Oral administration of olopatadine at 0.1, 1 and 3 mg/kg significantly inhibited the increases in TXB₂ and histamine levels. At 3 mg/kg, olopatadine also ameliorated the nasal obstruction caused 10 min after antigen challenge, as determined by acoustic rhinometry.ConclusionsThese results suggest that the amelioration by olopatadine of the allergic nasal obstruction involves the inhibition of the release of TXA₂ and histamine.     

Local Induction of a Specific Th1 Immune Response by Allergen Linked Immunostimulatory DNA in the Nasal Explants of Ragweed- Allergic Subjects

BackgroundAllergen immunotherapy is effective in allergic individuals however efforts are being made to improve its safety, convenience, and efficacy. It has recently been demonstrated that allergen-linked immunostimulatory DNA (ISS) is effective in stimulating an allergen-specific Th1 response with decreased allergenicity. The objective of this study is to investigate whether ISS linked to purified ragweed allergen Amb-a-1 (AIC) can inhibit local allergen-specific Th2 and induce allergen-specific Th1 responses in explanted nasal mucosa of ragweed-sensitive subjects. In addition, we set out to determine whether AIC is more effective compared to stimulation with unlinked Amb a 1 and ISS.MethodsTissue from ragweed-sensitive patients (n = 12) was cultured with whole ragweed allergen (RW), Amb-a-1, AIC, Amb-a-1 and ISS (unlinked), or tetanus toxoid (TT) for 24 hours. IL-4, ? 5, ? 13, TNF-α and IFN-γ mRNA-positive cells were visualized by in situ hybridization and T cells, B cells and neutrophils were enumerated using immunocytochemistry.ResultsRW or Amb-a-1 increased the number of IL-4, IL-5, and IL-13 mRNA + cells in the tissue compared to medium alone. AIC had similar cytokine mRNA reactivity as control tissue. AIC and TT increased IFNγ-mRNA expression. Unlinked Amb-a-1 and ISS showed similar effects to AIC, however this response was weaker. The number of TNF mRNA + cells, T cells, B cells and neutrophils remained unchanged.ConclusionsAIC is effective in stimulating a local allergen-specific Th1- and abolishing Th2-cytokine mRNA reactivity in the nose and may be considered as a strong candidate for an improved approach to immunotherapy in ragweed-sensitive individuals.     

Increased level of interleukin-13, but not interleukin-4 and interferon-γ in chronic rhinosinusitis with nasal polyps

BackgroundThis study was performed to investigate the serum level of interleukin (IL)-13, IL-4, and interferon (IFN)-γ in chronic rhinosinusitis with nasal polyps (CRSwNP) and subsequent inflammation pattern and comorbidities including asthma and aspirin intolerance.MethodsA case–control study was conducted on 60 adult patients with CRSwNP with mean age of 37.7 ± 12.7 (ranging from 18 to 70) years, and on 20 healthy controls. Serum levels of IL-13, IL-4, and IFN-γ were assessed, using enzyme-linked immunosorbent assay to be compared between case and control groups. Serum level of total immunoglobulin (Ig) E was also assessed in the patients with CRSwNP.ResultsSerum level of IL-13 in the patients with CRSwNP was significantly higher than the controls (0.98 ± 1.56 vs. 0.34 ± 0.16 pg/ml, respectively, p = 0.002). IL-4 and IFN-γ did not differ significantly between the two groups. Total IgE level was significantly increased in the patients with CRSwNP, compared to the normal values (301.43 ± 516.54 IU/ml, p = 0.033). Among the patients with CRSwNP, 12/60 (20%) had aspirin intolerance and 44/60 (73.3%) had asthma. IgE was also higher in asthmatics than non-asthmatics patients (364.9 ± 586.6 vs. 126.7 ± 135.7, respectively, p = 0.015). Patients with aspirin intolerance had higher levels of IFN-γ (4.7 ± 1.4 vs. 4.1 ± 0.6, respectively, p = 0.022).ConclusionsIL-13 with high level of total IgE was observed in the patients with CRSwNP, which predisposes them to have concomitant asthma. IFN-γ seems to be down-regulated in the patients with CRSwNP, but could be over-expressed in the presence of aspirin intolerance.     

IL-17 is a key cytokine correlating with disease activity and clinical presentation of systemic lupus erythematosus

AimsTo determine the role of IL-17 cytokine in systemic lupus erythematosus (SLE) patients and its association with clinical presentation of the disease and disease activity.Methods72 SLE patients and 70 healthy age and sex matched controls were included in the study. SLE disease activity was assessed in all patients with SLE disease activity index (SLEDAI-2K) scores. Plasma levels of IL-6, and IL-17 were measured by enzyme-linked immunosorbent assay and correlated their levels with clinical manifestations of the disease and SLEDAI-2K.ResultsPlasma levels of IL-6 and IL-17 were significantly elevated in SLE patients than in control subjects (13.98 ± 6.95 versus 7.47 ± 1.23 pg/mL) and (19.47 ± 10.21 versus 9.93 ± 1.89 pg/mL), respectively. IL-6 and IL-17 were positively correlated with SLEDAI-2K scores (r = 0.684 at P < 0.001, r = 0.322 at P = 0.006), and lupus nephritis (r = 0.364 at P = 0.002, r = 0.474 at P < 0.001) respectively; similarly, the IL-17/IL-6 ratio was positively correlated with SLEDAI-2K (r = 0.243 at P = 0.039). Also, the level of both cytokines was positively correlated to each other during periods of disease activity (r = 0.755, P < 0.001) as well as during remission (r = 0.384, P = 0.040).ConclusionOver-expression of IL-17 correlates with disease activity of SLE. A longitudinal study in a larger cohort of SLE patients can help validate the results.     

Efficacy and Safety of Fluticasone Furoate Nasal Spray in Japanese Children with Perennial Allergic Rhinitis: A Multicentre,Randomized, Double-Blind,Placebo-Controlled Trial

Background:Fluticasone furoate nasal spray (FFNS) is a glucocorticoid developed for the treatment of allergic rhinitis (AR). This is the first randomized clinical trial to assess the efficacy and safety of FFNS in Japanese children with perennial AR (PAR).Methods:In this multicentre, randomized, double-blind, placebo-controlled, parallel-group, phase III study, 261 children aged 6 to < 15 years were treated with FFNS 55 μg, once daily or placebo for two weeks. Nasal and ocular symptoms were rated by parents/guardians/patients in the patient daily diary. The primary endpoint was the mean change from baseline in the three total nasal symptom score (3TNSS). In addition, rhinoscopic findings were rated by the investigators as an efficacy measure. As a safety measure, adverse events and clinical chemistry and hematology were evaluated.Results:Mean change from baseline over the entire treatment period in 3TNSS was greater in the FFNS 55 μg group compared with placebo, and the difference was statistically significant (p < 0.001). Significant improvements in rhinoscopic findings of swelling of inferior turbinate mucosa and quantity of nasal discharge were also observed. The total ocular symptom score (TOSS) was reduced significantly in the FFNS 55 μg group, compared with placebo, in the second week in a subgroup of patients with baseline TOSS > 0. The incidence of adverse events was similar between FFNS 55 μg (18%) and placebo (19%).Conclusions:Two-week treatment with FFNS 55 μg, once daily is effective and tolerable in Japanese children aged 6 to < 15 years with PAR.     

Correlation between nasal eosinophils and nasal airflows in children with asthma and/or rhinitis monosensitised to house dust mites

BackgroundAllergic rhinitis and asthma due to mite sensitisation are diseases which are frequently associated and characterised by persistent inflammation. In the present study, we aimed to investigate the relationship between nasal airflows and nasal eosinophils in patients with asthma and/or rhinitis due to house dust mite sensitisation.MethodsTwenty-four children with both rhinitis and asthma (R + A), 13 children with rhinitis and no asthma (R) and 10 non-allergic healthy children were evaluated prospectively. The patients belonging to the first two groups had moderate–severe grade of nasal obstruction. Total nasal symptom scores, peak nasal inspiratory flows (PNIFs) obtained by anterior rhinomanometry, skin prick tests, nasal eosinophils and FEV1 values were all assessed.ResultsPercentages of nasal eosinophils and PNIFs in patients with R + A and R (r = −0.415, p = 0.04) were found to be statistically significant and to have an inverse correlation. Skin prick tests were also significantly correlated with nasal eosinophils and PNIFs (r = 0.372, p = 0.01 and r = −0.306, p = 0.04, respectively). Both PNIFs and nasal eosinophils of patients with R + A were significantly correlated with FEV1 values (r = −0.641, p = 0.001 and r = 0.548, p = 0.007, respectively).ConclusionIn this study, a close relationship was demonstrated between eosinophil infiltration and nasal airflows in children having asthma and/or rhinitis monosensitised to mites. Additionally, the significant association found between FEV1 values and nasal eosinophils or PNIFs supported the close link of upper and lower airways.     

Serum cystatin C in advanced liver cirrhosis and different stages of the hepatorenal syndrome

Background and study aimsThe hepatorenal syndrome (HRS) is classified into two types (HRS-2 and HRS-1) based on mild or high serum creatinine elevations. Although it has been identified as an early marker of renal dysfunction, data are lacking about cystatin C across the wide range of renal changes in end-stage liver disease. This study investigates serum cystatin C and creatinine in patients with advanced liver cirrhosis and classic HRS throughout its whole spectrum.Patients and methodsSerum cystatin C immunonephelometric measurements were obtained from 65 Child–Pugh C patients: 32 with normal creatinine, 17 with HRS-2 and 16 with HRS-1. The glomerular filtration rate (GFR) was estimated according to modification of diet in renal disease (MDRD) and the Hoek formulae (creatinine- and cystatin C-based, respectively) with staging of renal dysfunction severity into an increasing order from 1 to 5.ResultsEarly HRS was identified by the raised cystatin C in 56.3% of patients having normal creatinine. Cystatin C correlated significantly with creatinine in HRS-2 (r = 0.74; p < 0.001) and showed a significantly lower multiplication ratio (folds of rise) compared to creatinine in HRS-1 patients (p < 0.01). There was no satisfactory agreement between MDRD and Hoek GFR staging (k = 0.29).ConclusionsThe ‘early’ HRS identified by a rise in cystatin C in cases with advanced cirrhosis was found to be common and can be added to the already classified two types, as type-3 HRS. Compared to creatinine, cystatin C provides no better information in HRS-2, and underestimates the renal deterioration in HRS-1. Further studies are required to determine the course of the early HRS.     

Relation between serum IL-17 level and risk of osteoporotic fracture in premenopausal rheumatoid arthritis patients: Clinical,radiological and laboratory studies

IntroductionOsteoporosis is a main extra-articular complication of rheumatoid arthritis (RA) which may lead to fractures. Interleukin-17 (IL-17) is one of the cytokines which plays a significant role in RA pathogenesis and promotion of osteoporosis.Aim of the workTo study the relation between serum IL-17 levels and the risk of osteoporotic fractures in pre-menopausal RA patients.Patients and methodsTwenty-five premenopausal RA patients and 20 matched healthy controls were included in this study. All patients were subjected to detailed history taking, thorough clinical examination, disease activity assessment using the disease activity score-28 (DAS-28) and disability was assessed using Health Assessment Questionnaire–Disability Index (HAQ-DI). Bone mineral density and serum IL-17 levels were measured in patients and the control. Fracture Risk Assessment Tool (FRAX index) was also calculated.ResultsThe mean age of RA patients was 38.8 ± 7.6 years. The BMD was significantly reduced in patients compared to the control at the femur neck (p = 0.008), wrist (p = 0.046) and at the lumbar spine (p = 0.005). The Z score was below the expected range for age in 36% compared to 5% in the control (p = 0.03). Serum IL-17 concentrations were significantly higher in patients (5.99 ± 1.22 pg/ml) compared to the control (3.73 ± 2.15 pg/ml) (p < 0.001). Serum IL-17 levels showed a significant correlation with FRAX scores. Z-score interpretation showed a strong positive significant correlation with FRAX index; major osteoporotic fractures and hip fracture (p = 0.005 and p = 0.013, respectively) in patients.ConclusionThe premenopausal Rheumatoid arthritis patients showed a high fracture probability. Interleukin-17 serum level is associated with higher liability to fractures among rheumatoid patients.     

Assessment of nasal obstruction: Correlation between subjective and objective techniques

BackgroundNasal sensation of airflow describes the perception of the passage of air through the nose. Nasal obstruction can be assessed using subjective techniques (symptom scores and visual analogue scales [VAS]) and objective techniques (anterior rhinomanometry [RMN], acoustic rhinometry [AR], and peak nasal inspiratory flow [PNIF]). Few studies have evaluated the correlation between these techniques.ObjectiveThe primary objective of our study was to determine the degree of correlation between subjective and objective techniques to assess nasal obstruction.Materials and methodsNasal obstruction was assessed using a symptom score, VAS, RMN, AR (minimal cross-sectional area [MCSA] and volume), and PNIF in 184 volunteer physicians. Spearman's rho was recorded. Correlations were considered weak if r ≤ 0.4, moderate if 0.4 < r < 0.8, and strong if r > 0.8.ResultsMean (SD) age was 37.1 (6.9) years (range, 25–56 years); 61% were women. We found a strong correlation (r > 0.8; p = 0.001) between the different parameters of RMN and a moderate correlation between symptom score and VAS (r = 0.686; p = 0.001) and between MCSA and RMN (resistance) (r = 0.496; p = 0.001) and PNIF (r = 0.459; p = 0.001). The correlations were weak or non-significant for the remaining comparisons.ConclusionNasal obstruction can be assessed using subjective and objective approaches. The correlations between objective techniques were moderate to strong. In addition, between subjective techniques we reported a moderate correlation. Finally, the correlations between the subjective and objective techniques were weak and absent. These findings suggest that each of the techniques assesses different aspects of nasal obstruction, thus making them complementary.     

Does active Crohn's disease have decreased intestinal antioxidant capacity?

Background and aimsOxidative stress is presumed to play an important role in Crohn's disease (CD) pathogenesis. Nevertheless, the evaluation of the intestinal antioxidant capacity through the analysis of glutathione peroxidase activity in CD remains to be determined.Methods20 CD outpatients and 16 volunteers going through colonic cancer screening were enrolled. Colonoscopy with biopsies was performed in all individuals. Samples from inflamed and non-inflamed mucosa were taken when there was CD endoscopic activity. Spectrophotometric assays were performed to measure tissue glutathione peroxidase (GPx) activity, and total (GSH_T) and oxidized (GSSG) glutathione in all samples. Demographics and clinical characteristics were collected from clinical charts.ResultsInflamed CD mucosa presented reduced GPx activity compared to non-inflamed CD mucosa (42.94 mU/mg protein vs 79.62 mU/mg protein, P < 0.05) and control mucosa (42.94 mU/mg protein vs 95.08 mU/mg protein, P < 0.001). GSH_T concentration was reduced in inflamed mucosa when compared to non-inflamed CD mucosa (0.78 μmol/g vs 1.98 μmol/g, P < 0.01) and the control group (0.78 μmol/g vs 2.11 μmol/g, P < 0.001). A significant correlation was detected between GPx activity and GSSG (r = − 0.599), disease duration (r = 0.546), and thiopurine treatment (r = − 0.480) in non-inflamed CD mucosa.ConclusionOur findings suggest that reduced GPx activity is present in inflamed CD mucosa. In addition, endoscopic activity, disease duration and thiopurine therapy could be associated with mucosal decreased antioxidant activity.     

Influence of adipocytokines and IL-6 on ankylosing spondylitis disease activity and functional status

Aim of the workThis study aimed to assess serum levels of some adipocytokines (leptin, adiponectin and resistin) and IL-6 in patients with ankylosing spondylitis (AS) to evaluate their relationship to disease activity and functional capacity.Patient and methodTwenty-five AS patients were enrolled. Body mass index (BMI), Bath AS Disease Activity Index (BASDAI), Bath AS Functional Index (BASFI) and acute phase reactants, such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels, were assessed. Serum leptin, adiponectin, resistin and interleukin (IL)-6 levels were determined using enzyme-linked immunosorbent assay (ELISA).ResultsThe mean levels of leptin (9.1 ± 3.9 ng/ml), resistin (2.27 ± 1.15 ng/ml) and IL-6 (9.2 ± 5.8 pg/ml); were significantly elevated in patients with AS compared to the controls (p = 0.000, p = 0.0028 and p = 0.000, respectively). Only serum leptin levels correlated significantly with IL-6 (p = 0.004), and both serum leptin and IL-6 levels correlated significantly with BASDAI (p = 0.02 and p = 0.005, respectively), ESR (p = 0.04) and CRP (p = 0.01 and p = 0.006, respectively) in AS patients. Serum resistin did not correlate with any of the AS disease parameters, whereas, serum adiponectin neither significantly elevated nor correlated with any of these parameters.ConclusionThe associations of significantly increased levels of serum leptin and IL-6 with AS disease activity parameters give clues to their role in the inflammatory process of the disease. Failure to find any correlation between high serum resistin levels and AS disease activity parameters is suggestive of its role in the pathogenesis rather than disease activity.     

Progresión y predictores de insuficiencia valvular neoaórtica y dilatación de la raíz neoaórtica en adultos jóvenes tras cirugía de switch arterial

Introduction and objectivesThere are limited data on the long-term development of neoaortic root dilatation (NRD) and neoaortic valve regurgitation (AR) after arterial switch operation (ASO) for transposition of the great arteries during adult life.MethodsWe performed a retrospective longitudinal analysis of 152 patients older than 15 years who underwent ASO for transposition of the great arteries and who were followed-up for 4.9 ± 3.3 years in 2 referral centers. Sequential changes in body surface-adjusted aortic root dimensions and progression to moderate/severe AR were determined in patients with 2 or more echocardiographic examinations. Risk factors for dilatation were tested by Cox regression to identify predictors of AR progression.ResultsAt baseline, moderate AR was present in 9 patients (5.9%) and severe AR in 4 (2.6%), of whom 3 had required aortic valve surgery. Initially, the median neoaortic root dimension was 20.05 ± 2.4 mm/m², which increased significantly to 20.73 ± 2.8 mm/m² (P < .001) at the end of follow-up. The mean change over time was 0.14 mm/m²/y (95%CI, 0.07-0.2). Progressive AR was observed in 20 patients (13.5%) and 6 patients (4%) required aortic valve surgery. Progressive AR was associated with bicuspid valve, AR at baseline, NRD at baseline, and neoaortic root enlargement. Independent predictors were bicuspid valve (HR, 3.3; 95%CI, 1.1-15.2; P = .037), AR at baseline (HR, 5.9; 95%CI, 1.6-59.2; P = .006) and increase in NRD (HR, 4.1 95%CI, 2-13.5; P = .023).ConclusionsIn adult life, NRD and AR progress over time after ASO. Predictors of progressive AR are bicuspid valve, AR at baseline, and increase in NRD.     

Curcumin induces M2 macrophage polarization by secretion IL-4 and/or IL-13

AimsTo address the underlying mechanisms by which curcumin facilitates M2 phenotype polarization of macrophages and its roles in the protective effects during experimental autoimmune myocarditis (EAM).Methods and resultsThe expression of classic M2 markers, including macrophage mannose receptor (MMR), arginase-1 (Arg-1) and peroxisome proliferator-activated receptor-γ (PPAR-γ) was upregulated in curcumin-treated Raw264.7 macrophages. Curcumin increased interleukin-4 (IL-4) and interleukin-13 (IL-13) mRNA expression and protein secretion. Curcumin notably increased STAT6 phosphorylation. Leflunomide, a STAT6 inhibitor, and IL-4 and/or IL-13 neutralizing antibodies antagonized the induction of MMR, Arg-1 and PPAR-γ by curcumin in Raw264.7 cells. In vivo, 6-week old male Lewis rats were used to induce EAM and orally administrated with curcumin or corn oil for 3 weeks after myosin injection. Cardiac functional parameters, including left ventricular fractional shortening (LVFS), ejection fraction (EF), left ventricular end-systolic diameter (LVEDs) and heart rate (HR) were significantly improved by curcumin treatment. Curcumin also reduced the inflammatory cell infiltration and myocardial mRNA levels of interleukin-1β (IL-1β) and inducible nitric oxide synthase (iNOS). Meanwhile, the myocardial mRNA levels of MMR and Arg-1 were markedly up-regulated by curcumin. Immunofluorescence assay showed that the number of CD68 ⁺ MMR ⁺ and CD68 ⁺ Arg-1 ⁺ double positive macrophages in curcumin-treated myocardial tissue was significantly higher than untreated control. The number of CD68 ⁺ iNOS ⁺ double positive macrophages was increased obviously in EAM group, but decreased markedly by curcumin treatment.ConclusionsTaken together, these results show that curcumin induces macrophage M2 polarization by secretion of IL-4 and/or IL-13. Curcumin ameliorates EAM by reducing infiltration inflammatory macrophages and by polarizing M0 and M1 macrophages to M2 phenotype.     

Th-17 cells and serum IL-17 in rheumatoid arthritis patients: Correlation with disease activity and severity

Aim of the workTo investigate the role of T-helper 17 (Th17) cells in peripheral blood and serum interleukin-17 (IL-17) in rheumatoid arthritis (RA) patients, and their correlation with disease activity and joint destruction.Patients and methodsThis study included forty RA patients and twenty matched healthy controls. Disease activity score in 28 joints (DAS-28), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), rheumatoid factor (RF), anti-CCP, tumor necrosis factor alpha (TNF-α), serum IL-17 and Th17 cells in peripheral blood were measured. Radiological assessment using modified Sharp/van der Heijde (mSvH) score for hand and feet in addition to MRI score for the wrist and metacarpophalangeal (MCP) joints were performed for detection of synovitis and bone erosion.ResultsThe patients were 38 females and 2 males with a mean of 41.15 ± 5.85 years and disease duration of 15.6 ± 4.62 years. Serum IL-17 and Th17 cells in peripheral blood were found to be significantly increased in RA patients (204.1 ± 33.8 pg/ml and 4.62 ± 1.13%) than in controls (25.36 ± 5.39 pg/ml and 0.7 ± 0.021%) (p < 0.001). Th17 cells significantly correlated with serum IL-17 (r 0.88, p < 0.001). Both Th17 cells and serum IL-17 significantly correlated with DAS-28, ESR, CRP, TNF-α, Van der Heijde modification score and MRI scores for wrist and MCP joints for synovitis and bone erosion (all with a p < 0.001).ConclusionThis study demonstrates an important role for Th-17 cells and serum IL-17 in the pathogenesis of the inflammatory and destructive pattern characteristic of RA.     

Determination of urine tumor necrosis factor,IL-6, IL-8, and serum IL-6 in patients with hemorrhagic fever with renal syndrome

ObjectiveThe aim of this study was to explore the role of cytokines in the pathogenesis of hemorrhagic fever with renal syndrome (HFRS).MethodsDouble-antibody sandwich ELISA was used to determine serum interleukin (IL)-6, urine tumor necrosis factor (TNF), IL-6, and IL-8 levels in 56 patients with HFRS.ResultsSerum IL-6, urine TNF, IL-6, and IL-8 concentrations in HFRS patients were significantly higher than those in the control group (p < 0.001). The concentrations increased at fever stage, then continued to increase during the hypotension stage and peaked at the oliguria stage. The concentrations of serum IL-6, urine TNF, IL-6, and IL-8 increased according to the severity of the disease, and differed greatly among different types of the disease. Serum IL-6 had remarkable relationships with serum specific antibodies. It was positively related to serum β2-microglobulin (β2-MG), blood ureanitrogen (BUN), and creatinine (Cr). Significant positive relationships were also found both between urine IL-6 and TNF, and between IL-6 and IL-8 (r = 0.5768, p < 0.05; r = 0.3760, p < 0.01).ConclusionTNF, IL-6, and IL-8 were activated during the course of the disease. IL-6 was associated with the immunopathological lesions caused by the hyperfunction of the humoral immune response. IL-6, IL-8 and TNF were involved in renal immune impairment. Determining them might, to a certain extent, be useful in predicting the prognosis and outcome of patients with HFRS.