Soluble Immune Complexes Shift the TLR-Induced Cytokine Production of Distinct Polarized Human Macrophage Subsets towards IL-10

Contains fulltext : 109563.pdf (publisher's version ) (Open Access)BACKGROUND: Costimulation of murine macrophages with immune complexes (ICs) and TLR ligands leads to alternative activation. Studies on human myeloid cells, however, indicate that ICs induce an increased pro-inflammatory cytokine production. This study aimed to clarify the effect of ICs on the pro- versus anti-inflammatory profile of human polarized macrophages. MATERIALS AND METHODS: Monocytes isolated from peripheral blood of healthy donors were polarized for four days with IFN-gamma, IL-4, IL-10, GM-CSF, M-CSF, or LPS, in the presence or absence of heat aggregated gamma-globulins (HAGGs). Phenotypic polarization markers were measured by flow cytometry. Polarized macrophages were stimulated with HAGGs or immobilized IgG alone or in combination with TLR ligands. TNF, IL-6, IL-10, IL-12, and IL-23 were measured by Luminex and/or RT-qPCR. RESULTS: HAGGs did not modulate the phenotypic polarization and the cytokine production of macrophages. However, HAGGs significantly altered the TLR-induced cytokine production of all polarized macrophage subsets, with the exception of MPhi(IL-4). In particular, HAGGs consistently enhanced the TLR-induced IL-10 production in both classically and alternatively polarized macrophages (M1 and M2). The effect of HAGGs on TNF and IL-6 production was less pronounced and depended on the polarization status, while IL-23p19 and IL-12p35 expression was not affected. In contrast with HAGGs, immobilized IgG induced a strong upregulation of not only IL-10, but also TNF and IL-6. CONCLUSION: HAGGs alone do not alter the phenotype and cytokine production of in vitro polarized human macrophages. In combination with TLR-ligands, however, HAGGs but not immobilized IgG shift the cytokine production of distinct macrophage subsets toward IL-10

Impact of clinical phenotypes on management and outcomes in European atrial fibrillation patients: a report from the ESC-EHRA EURObservational Research Programme in AF (EORP-AF) General Long-Term Registry

Background: Epidemiological studies in atrial fibrillation (AF) illustrate that clinical complexity increase the risk of major adverse outcomes. We aimed to describe European AF patients\u2019 clinical phenotypes and analyse the differential clinical course. Methods: We performed a hierarchical cluster analysis based on Ward\u2019s Method and Squared Euclidean Distance using 22 clinical binary variables, identifying the optimal number of clusters. We investigated differences in clinical management, use of healthcare resources and outcomes in a cohort of European AF patients from a Europe-wide observational registry. Results: A total of 9363 were available for this analysis. We identified three clusters: Cluster 1 (n = 3634; 38.8%) characterized by older patients and prevalent non-cardiac comorbidities; Cluster 2 (n = 2774; 29.6%) characterized by younger patients with low prevalence of comorbidities; Cluster 3 (n = 2955;31.6%) characterized by patients\u2019 prevalent cardiovascular risk factors/comorbidities. Over a mean follow-up of 22.5 months, Cluster 3 had the highest rate of cardiovascular events, all-cause death, and the composite outcome (combining the previous two) compared to Cluster 1 and Cluster 2 (all P <.001). An adjusted Cox regression showed that compared to Cluster 2, Cluster 3 (hazard ratio (HR) 2.87, 95% confidence interval (CI) 2.27\u20133.62; HR 3.42, 95%CI 2.72\u20134.31; HR 2.79, 95%CI 2.32\u20133.35), and Cluster 1 (HR 1.88, 95%CI 1.48\u20132.38; HR 2.50, 95%CI 1.98\u20133.15; HR 2.09, 95%CI 1.74\u20132.51) reported a higher risk for the three outcomes respectively. Conclusions: In European AF patients, three main clusters were identified, differentiated by differential presence of comorbidities. Both non-cardiac and cardiac comorbidities clusters were found to be associated with an increased risk of major adverse outcomes

Micromorphological and Anatomical Characteristics of the Genus Chrysophthalmum Schultz Bip. (Asteraceae) Growing in Turkey

The genus Chrysophthalmum (Asteraceae) is represented by five species in the world. Three species of this genus are naturally grown in Turkey. The species growing in Turkey are C. montanum (DC.) Boiss., C. dichotomum Boiss. and Heldr. and C. gueneri Aytac and Anderb. Except C. montanum; the other species are endemic for Turkey. In the present study, micromorphological and anatomical characteristics of these species by using light microscopy (LM) and scanning electronmicroscopy (SEM) have been comparatively presented for the first time. Themicromorphological studies are related to trichomes and cypsela. In anatomical studies, crosssections of the stem, and leaf have been examined. In addition, to show stomatal distribution and anatomy on adaxial and abaxial leaves, surface sections of the leaves have been taken and stomatal index calculated. The features of stems, leaves, trichomes and cypsela have been found to be significant to distinguish the species. Mesophyll structure, number of vascular bundles in midrib, presence or absence of sclerenchymatous fibers in leaf, trichome types, presence or absence of pappus in cypsela, presence or absence of hair on cypsela surface are important diagnostic characters. A diagnostic key based on combined leaf, trichome and cypsela characteristics of the Chrysophthalmum species has been given

Efficacy of three different alpha 1-adrenergic blockers and hyoscine N-butylbromide for distal ureteral stones

PURPOSE: To evaluate hyoscine N-butyl bromide (HBB) and three different alpha-1 blockers in the treatment of distal ureteral stones. MATERIALS AND METHODS: A total of 140 patients with stones located in the distal tract of the ureter with stone diameters of 5 to 10mm were enrolled in the present study and were randomized into 4 equal groups. Group 1 received HBB, Group 2 received alfuzosin, Group 3 received doxazosin and Group 4 received terazosin. The subjects were prescribed diclofenac injection (75 mg) intramuscularly on demand for pain relief and were followed-up after two weeks with x-rays of the kidneys, ureters, bladder and urinary ultrasonography every week. The number of pain episodes, analgesic dosage and the number of days of spontaneous passage of the calculi through the ureter were also recorded. RESULTS: The average stone size for groups 1, 2, 3 and 4 was comparable (6.13, 5.83, 5.59 and 5.48 mm respectively). Stone expulsion was observed in 11%, 52.9%, 62%, and 46% in groups 1, 2, 3 and 4 respectively. The average time to expulsion was 10.55 ± 6.21 days in group 1, 7.38 ± 5.55 days in group 2, 7.85 ± 5.11 days in group 3 and 7.45 ± 5.32 days in group 4. Alpha blockers were found to be superior to HBB (p < 0.05). CONCLUSIONS: Medical treatment of distal ureteral calculi with alfuzosin, doxazosin and terazosin resulted in a signi?cantly increased stone-expulsion rate and decreased expulsion time when compared with HBB. HBB seems to have a negative effect on stone-expulsion rate