Cytokine Profiles of Chronic Urticaria Patients and The Effect of Omalizumab Treatment.

INTRODUCTION: Cytokines are key mediators in immunological and inflammatory conditions, including chronic spontaneous urticaria (CSU). OBJECTIVES: To investigate Th1, Th2, and Th17 cytokine profiles in CSU and to evaluate the possible effect of omalizumab treatment. METHODS: Patients who were followed up for CSU, as well as healthy volunteers, were included in the study. To assess urticaria activity, the 7-day-Urticaria Activity Score (UAS-7), the Urticaria Control Test (UCT), and the Chronic Urticaria Quality of Life Questionnaire (CU-QoL) were filled. Serum levels of IL-6, IL-17, IL-31, eotaxin, RANTES, TNF-α, and TSLP were analyzed by ELISA and compared in CSU and control groups. The patients were analyzed in two groups as the omalizumab group and the non-omalizumab group based on their treatment status. RESULTS: Total IgE, ESR, CRP, RANTES, and TNF-a were significantly different in the overall comparison of the three groups: CSU-receiving omalizumab, CSU-not receiving omalizumab, and control groups (P <0.01, 0.015, <0.01, <0.01 and <0.01 respectively). Total IgE, CRP, RANTES, and TNF-α values were similar in those who received and did not receive omalizumab, yet these biomarkers were significantly higher in both groups than in the control group (P < 0.05). Statistical significance in ESR was observed only between the CSU-receiving omalizumab group and the control group (P = 0.01). Within the CSU patients, there was a slight but significant correlation between UCT and TNF-α (P = 0.008, r = 0.32) and IL-17 (P = 0.06, r = 0.33) levels. CONCLUSIONS: The investigated cytokine profile in CSU patients may differ from healthy controls, particularly with the higher levels of RANTES and TNF-α, and omalizumab treatment does not seem to affect that profile in CSU patients.

Oxidative stress stimulation leads to cell-specific oxidant and antioxidant responses in airway resident and inflammatory cells.

AIMS: The imbalance between reactive oxygen species (ROS) and the antioxidant response has been linked to various airway diseases, including asthma. However, knowledge on cell-specific responses of the airway resident and inflammatory cells against increased oxidant stress is very limited. We aim to better understand the cell-specific antioxidant response that contributes to the pathophysiology of lung disease in response to oxidative stress. MATERIALS AND METHODS: The human cell lines of epithelial, fibroblast, endothelial, monocyte, eosinophil and neutrophil were incubated with tert-butyl hydroperoxide (tBHP) or cigarette smoke condensate (CSC). Following stimulation, cell viability, total oxidant and antioxidant activity were assessed in both residential and inflammatory cells. Human Oxidative Stress Plus RT2 Profiler PCR array was used to determine 84 gene expression differences in oxidant and antioxidant pathways following oxidant stimulus in all cells. KEY FINDINGS: We showed that various cell types respond differently to oxidative stress inducers, with distinct gene expression and oxidant-antioxidant generation. Most importantly, eosinophils increased the activity of all main antioxidant enzymes in response to both oxidants. Monocytes, on the other hand, showed no change in response to each stimulation, whereas neutrophils only increased their CAT activity in response to both stimuli. The increase in NRF2-regulated genes HSPA1A, HMOX1 and DUSP1 after both tBHP and CSC in epithelial cells and fibroblasts indicates Nfr2 pathway activation. SIGNIFICANCE: This study advances our knowledge of the molecular and cellular mechanisms of cell-specific antioxidant response upon exposure to oxidative stress. Additionally, our observations imply that the eosinophils' distinct biological response may be utilized for endotype-based cell-targeted antioxidant therapy.

Smell Sensitivity in Primary Open-angle Glaucoma and Pseudoexfoliation Glaucoma.

PRCIS: This cross-sectional study of 20 patients with primary open-angle glaucoma (POAG), 20 with exfoliative glaucoma (XFG), 20 with exfoliation syndrome (XS) showed that exfoliative group had a significantly lower smell identification level as compared with the control groups. PURPOSE: To investigate smell sensitivity in POAG, XFG, and XFS in comparison with healthy controls. MATERIALS AND METHODS: This prospective, cross-sectional study included 20 patients with POAG, 20 with XFG, and 20 with XFS. The control group consisted of 20 age-matched and sex-matched healthy subjects with no evidence of ocular disease. The Sniffin' Sticks smell test was used to determine the, threshold values, and to assess the ability of smell identification, and differentiation in all patients One eye per patient was included for statistical purposes. One-way analysis of variance was used to compare the differences between the groups. Tukey honestly significant difference was used as a post hoc test when significant differences were detected among the 3 groups. RESULTS: The XFG, POAG, and control groups showed a significant difference in the odor discrimination, odor identification, and threshold discrimination identification scores. The median (minimum-maximum) smell threshold levels for the POAG, XFG, and XFS groups and healthy controls were 4.5 (0 to 7.5), 4 (0 to 7.5), 5 (4.5 to 6), and 5.5 (4 to 7.5), respectively. The smell differentiation values for the POAG, XFG, and XFS groups and healthy controls were 12 (2 to 14), 8 (0 to 13), 11 (10 to 13), and 12 (9 to 14), respectively. Smell sensitivity for the POAG, XFG, and XFS groups and healthy controls were 26 (4 to 30.5), 19 (0 to 29.5), 28.3 (22.8 to 30.5), and 29 (26.5 to 32), respectively. The smell sensitivity and differentiation were significantly different among the groups (P<0.001). The XFG group had a significantly lower smell identification level than the POAG, XFS, and control groups. CONCLUSION: Patients with XFS and XFG revealed reduced smell sensitivity and identification compared with patients with POAG and those without glaucoma. These findings provide new insights into neural degeneration and pseudoexfoliation.

Are They Careful Enough? Testing Consumers' Perception of Alternative Processing Technologies on the Quality of Organic Food.

Given the increasing public interest in how ingredients are processed and the growing demand for organic food products, it is critical to understand consumers' expectations about the process-related quality of organic products. Consumers perceive organic food to be nutritious, healthy and either natural or less processed, as they are afraid of the loss of nutritional, organoleptic and sensory properties of the food products. However, alternative food processing technologies might generate healthy and safe food options with nutritional quality properties. Simplified communication schemes might help to overcome this barrier for the consumer. The main objective of this study is to propose a working definition of "careful processing" for organic products and test its consistency through an experiment, while being used to rate different processing methods by consumers. Results show that the proposed definition allows the consumer to consistently rate alternative processing technologies. Consumers tend to score alternative processing technologies such as pulsed electric fields and microwaves as less careful, supporting the idea that organic consumers want as little man-made interference in their food products as possible. Results show that a simple but effective definition of careful processing may help consumers to distinguish more organic food products from conventional ones, no matter which communication scheme is used.

The Effects of Selective Inhibition of Histone Deacetylase 1 and 3 in Huntington's Disease Mice.

Huntington's disease (HD) is an autosomal dominant neurodegenerative disease characterized by a late clinical onset of psychiatric, cognitive, and motor symptoms. Transcriptional dysregulation is an early and central disease mechanism which is accompanied by epigenetic alterations in HD. Previous studies demonstrated that targeting transcriptional changes by inhibition of histone deacetylases (HDACs), especially the class I HDACs, provides therapeutic effects. Yet, their exact mechanisms of action and the features of HD pathology, on which these inhibitors act remain to be elucidated. Here, using transcriptional profiling, we found that selective inhibition of HDAC1 and HDAC3 by RGFP109 alleviated transcriptional dysregulation of a number of genes, including the transcription factor genes Neurod2 and Nr4a2, and gene sets and programs, especially those that are associated to insulin-like growth factor pathway, in the striatum of R6/1 mice. RGFP109 treatment led to a modest improvement of the motor skill learning and coordination deficit on the RotaRod test, while it did not alter the locomotor and anxiety-like phenotypes in R6/1 animals. We also found, by volumetric MRI, a widespread brain atrophy in the R6/1 mice at the symptomatic disease stage, on which RGFP109 showed no significant effects. Collectively, our combined work suggests that specific HDAC1 and HDAC3 inhibition may offer benefits for alleviating the motor phenotypic deficits and transcriptional dysregulation in HD.