87 research outputs found

    Gal-3 deficiency suppresses novosphyngobium aromaticivoransinflammasome activation and IL-17 driven autoimmune cholangitis in mice

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    © 2019 Arsenijevic, Milovanovic, Stojanovic, Djordjevic, Stanojevic, Jankovic, Vojvodic, Arsenijevic, Lukic and Milovanovic. Gal-3 has the role in multiple inflammatory pathways. Multiple-hit etiology of primary biliary cholangitis (PBC) and evolving immune response at various stages of the disease includes involvement of Gal-3 in PBC pathogenesis. In this study we aimed to clarify the role of Gal-3 in Novosphingobium aromaticivorans (N. aromaticivorans) induced biliary disease. Autoimmune cholangitis was induced in mice by two intra-peritoneal injections of N. aromaticivorans within 2 weeks. The role of Gal-3 was evaluated by using Lgals3-/-mice and mice treated with Gal-3 inhibitor. The histological and serological parameters of disease, phenotype of dendritic, NK, NKT, and T cells and inflammasome expression were evaluated. Marked attenuation of the disease in Lgals3-/-and Gal-3 inhibitor, DAVANAT®, treated mice is manifested by the absence of bile duct damage, granulomas and fibrosis. Liver infiltrates of N. aromaticivorans infected wild type mice had higher incidence of pro-inflammatory macrophages, dendritic cells, NK, NKT, and T cells. Lgals3 deletion and treatment with Gal-3 inhibitor reduced inflammatory mononuclear cell infiltrate, expression of NLRP3 inflammasome in the liver infiltrates and interleukin-1β (IL-1β) production in the livers of N. aromaticivorans infected mice. In vitro stimulation of wild type peritoneal macrophages with N. aromaticivorans caused increased NLRP3 expression, caspase-1 activity and IL-1β production compared with Lgals3-/-cells. Our data highlight the importance of Gal-3 in promotion of inflammation in N. aromaticivorans induced PBC by enhancing the activation of NLRP3 inflammasome and production of IL-1β and indicate Gal-3 as possible therapeutical target in autoimmune cholangitis. Galectin-3 appears involved in inflammatory response to gut commensal leading to PBC

    Diagnostic value of VEGF in peri-implantitis and its correlation with titanium particles: A controlled clinical study

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    OBJECTIVES VEGF is prototypic marker of neovascularization, repeatedly proposed as intrinsic characteristic of peri-implantitis. This study aimed to assess pattern of VEGF in peri-implantitis, its correlation with titanium particles (TPs) and capacity as respective biomarker. MATERIAL AND METHODS Pathological specificity of VEGF was assessed in peri-implant granulations using immunohistochemistry, periodontal granulations represented Ti-free positive controls. VEGF was correlated to TPs, identified using scanning electron microscopy coupled with dispersive x-ray spectrometry. Diagnostic accuracy, sensitivity and specificity of VEGF were estimated in PICF specimens from peri-implantitis, peri-implant mucositis (PIM) and healthy peri-implant tissues (HI) using machine learning algorithms. RESULTS Peri-implantitis exhibited rich neovascular network with expressed density in contact zones toward neutrophil infiltrates without specific pattern variations around TPs, identified in all peri-implantitis specimens (mean particle size 8.9 ± 24.8 µm2; Ti-mass (%) 0.380 ± 0.163). VEGF was significantly more expressed in peri-implantitis (47,065 ± 24.2) compared to periodontitis (31,14 ± 9.15), and positively correlated with its soluble concentrations in PICF (p = 0.01). VEGF was positively correlated to all clinical endpoints and significantly increased in peri-implantitis compared to both PIM and HI, but despite high specificity (96%), its overall diagnostic capacity was average. Two patient clusters were identified in peri-implantitis, one with 8-fold higher VEGF values compared to HI, and second with lower values comparable to PIM. SIGNIFICANCE VEGF accurately reflects neovascularization in peri-implantitis that was expressed in contact zones toward implant surface without specific histopathological patter variation around TPs. VEGF answered requests for biomarker of peri-implantitis but further research is necessary to decrypt its exact underlying cause

    Periodontology for Geriatric Patients

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    International audiencePurpose of ReviewElderly population represents the fastest growing population segment and target group of many expert organizations developing strategies for successful aging. The substantial increase in man’s lifespan together with implementation of preventive dental programs resulted in decreased tooth loss and increased prevalence of periodontal disease. Hence, the present review focused on positioning periodontal health within aging process, characteristic of the senescent periodontium, periodontitis-aging interplay, clinical characteristics, and implications for periodontal care in geriatric patients.Recent FindingsThe senescent periodontium undergoes degenerative changes that are unrelated to progressive destruction in lack of inflammation. The pathological interplay periodontitis-systemic aging is evidenced. Geriatric patients demonstrate comparable treatment outcomes to those of patients ≤ 60 years regarding non-surgical and surgical periodontal treatment and implant therapy as well.SummaryAdequate oral hygiene and appropriate control of risk factors represent the key pre-conditions for successful periodontal and systemic aging

    The simple isocratic HPLC-UV method for the simultaneous determination of reduced and oxidized glutathione in animal tissue

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    The aim of our work was to optimize and apply simple high-performance liquid chromatography method with ultraviolet detection (HPLC-UV) for simultaneous determination of reduced (GSH) and oxidized (GSSG) glutathione in biological matrix (specifically, the rat liver tissue was used herein), since the ratio between oxidized and reduced glutathione forms (GSSG-GSH) has been recognized as an important biological marker of oxidatively depleted GSH in oxidative stress (OS)-associated diseases and poisonings. An isocratic chromatographic separation of GSH and GSSG (2.8 min and 6.3 min, respectively) was performed with the mobile phase consisted of sodium perchlorate solution (pH adjusted to 2.8) at flow rate of 1 mL min(-1), detection set at 215 nm, and column temperature of 40 degrees C. The method offers short run time, linearity in the range of 0.01-200 mu M concentration for both compounds (R-2 = 1), low limits of detection and quantification (GSH: 0.18 mu M and 0.56 mu M, GSSG: 0.52 mu M and 1.58 mu M, respectively), precision, accuracy (bias <2%), and high reproducibility. Through suitable sample handling, an overestimation of GSSG was prevented. High recovery (>99%) was achieved. The method was successfully applied for the analysis of GSH and GSSG in liver homogenates of Wistar rats intraperitoneally exposed to cadmium (Cd) (1 mg kg(-1) CdCl2/21 days). Regardless of other Cd-mediated hepatotoxicity mechanisms, herein, we have exclusively interpreted/emphasized oxidative GSH depletion. The presented method is acceptable for a routine analysis of GSH and GSSG in biological matrix, while the calculated ratio GSSG-GSH is considered as a valuable OS marker

    Effect of dental caries on periodontal inflammatory status: A split-mouth study.

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    OBJECTIVE This controlled split-mouth study aimed to estimate the effect of caries and related treatment on concentrations of interleukin (IL)-2, interferon (IFN)-γ, IL-12, IL-17A, IL-13, IL-10, IL-6, IL-5, IL-4, IL-22, tumor necrosis factor (TNF)-α, and IL1-β in gingival crevicular fluid (GCF) of caries affected teeth before (B), 7 (7D) and 30 (30D) days post-treatment and to compare them with concentrations from healthy teeth. DESIGN Study population included 81 systemically and periodontally healthy non-smokers exhibiting at least one shallow occlusal/ inter-proximal caries and one healthy tooth from the same morphologic group at the contralateral position. Following clinical exam, the GCF samples were collected baseline as well as 7D and 30D, while the biomarker measurement was performed using multiplex flowcytometry. RESULTS Caries affected teeth exhibited significantly higher levels of IFN-γ, IL-1β, IL-2, IL-4 and IL-6 when compared to healthy teeth. Post-treatment cytokines levels showed general trend of increase when compared to baseline, that was significant for IL-22 and IL-17 at 7D, while IFN-γ was significantly increased at 7D compared to the healthy teeth. At 30D, IFN-γ, TNF-α, IL-17 and IL-4 levels were significantly increased when compared to healthy teeth, while IL-2 levels were significantly higher than baseline levels. CONCLUSION Considering significantly increased periodontal levels of inflammatory markers in caries affected teeth and in response to performed treatment, it seems that dental caries and related restorative treatment might contribute to periodontal inflammation via additive effects already in early-stage caries

    Chapter Парадоксальность Кроткой

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    A Gentle Creature’s Paradox. The aim of this article is to analyze a smile as a mimetic, nonverbal facial expression. Although a smile most often displays joy and pleasure, it sometimes expresses emotions such as sadness, cruelty, anger, etc. This analysis aims to focus on the paradoxical “mistrustful, silent, and evil smile” of A Gentle Creature. Her smile marks the beginning of her life with the Pawnbroker and it is her companion until the end of her life. The paradox of smile illuminates other paradoxes such as that of communication (verbal/nonverbal, communication/its negation), of death (suicide and the icon, destruction/resurrection, silence/birth of words), of the Pawnbroker’s story (author-narrator, narrative/story, fantastic/realistic, contradictions in the story), and of the event (real event/event in the narrator’s mind)

    The acute phase of inflammatory response involved in the wound-healing process after excimer laser treatment

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    Mirko Resan,1,2 Miroslav Vukosavljevic,1,2 Danilo Vojvodic,2,3 Brigitte Pajic-Eggspuehler,4 Bojan Pajic2,4&ndash;6 1Eye Clinic, Military Medical Academy, Belgrade, Serbia; 2Faculty of Medicine of the Military Medical Academy, University of Defense, Belgrade, Serbia; 3Department for Clinical and Experimental Immunology, Institute for Medical Research, Military Medical Academy, Belgrade, Serbia; 4Eye Clinic ORASIS, Swiss Eye Research Foundation, Reinach AG, Switzerland; 5Department of Physics, Faculty of Science, University of Novi Sad, Novi Sad, Serbia; 6Division of Ophthalmology, Department of Clinical Neurosciences, University Hospitals of Geneva, Switzerland Purpose: To evaluate the participation of proinflammatory cytokines in the acute phase of corneal wound-healing response after excimer laser treatment. Methods: The study included 68 myopic eyes up to -3.0 diopters divided into two groups: 1) eyes treated with laser in situ keratomileusis (LASIK) (n=31) and 2) eyes treated with photorefractive keratectomy (PRK) (n=37). Each group was then divided into three subgroups based on tear sampling times: before (0 hours), 1 hour after, and 24 hours after treatment. The tear fluid was sampled from lower lateral tear meniscus using a cellulose microsurgical sponge. The levels of tumor necrosis factor-&alpha; (TNF-&alpha;), interleukin (IL)-1&beta;, IL-6, and IL-8 in tear fluid were determined by flow cytometry method. Results: Statistical significance was observed in the concentrations of TNF-&alpha; (P=0.0421) and IL-1&beta; (P=0.0225) between samples collected 1 and 24 hours after PRK treatment in favor of samples collected 1 hour after treatment. IL-6 concentration changes showed a significant increase in the PRK group in both time intervals following treatment compared to pretreatment (0 hour/1 hour, P=0.0031; 0 hour/24 hours, P=0.0059). For IL-8 concentrations, significant differences were observed between control and experimental groups in samples collected 1 hour after LASIK and 1 hour after PRK treatment (P&lt;0.001 for both groups), and IL-8 concentrations between control and experimental groups in samples collected 24 hours after LASIK and 24 hours after PRK treatment were greater after PRK treatment (P=0.0005). Comparison of average concentration values of proinflammatory cytokines in all the tested samples between LASIK and PRK groups showed significantly higher levels of IL-1&beta; in the LASIK group 24 hours after treatment (P=0.0134), and of IL-6 in the PRK group 24 hours after treatment (P=0.0031). Conclusion: The acute phase of corneal wound healing after excimer laser treatment is defined by an intensive inflammatory response. After PRK treatment, there were increased concentrations of TNF-&alpha; and IL-1&beta; in tear samples 1 hour after treatment, IL-6, 1 and 24 hours after treatment, and IL-8, 1 and 24 hours after treatment. After LASIK treatment, there were increased concentrations of IL-8 in tear samples 1 hour after treatment and IL-1&beta;, 24 hours after treatment. Both PRK and LASIK methods are characterized with a significant inflammatory response. However, tear findings following PRK method showed more intensive inflammatory response than the findings after LASIK method. Keywords: LASIK, PRK, tears, proinflammatory cytokines, wound healin
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