Histologic evidence that mast cells contribute to local tissue inflammation in peripheral spondyloarthritis by regulating interleukin-17A content

Rheumatology ◽  
2018 ◽  
Vol 58 (4) ◽  
pp. 617-627 ◽  
Author(s):  
Sijia Chen ◽  
Troy Noordenbos ◽  
Iris Blijdorp ◽  
Leonieke van Mens ◽  
Carmen A Ambarus ◽  
...  

Abstract Objectives Synovial mast cells contain IL-17A, a key driver of tissue inflammation in SpA. A recent in vitro study showed that tissue-derived mast cells can capture and release exogenous IL-17A. The present study aimed to investigate if this mechanism could contribute to tissue inflammation in SpA. Methods Potential activation of mast cells by IL-17A was assessed by gene expression analysis of the Laboratory of Allergic Diseases 2 (LAD2) mast cell line. The presence of IL-17A-positive mast cells was assessed by immunohistochemistry in synovial tissue obtained before and after secukinumab treatment, as well as in skin and gut tissues from SpA-related conditions. Results IL-17A did not induce a pro-inflammatory response in human LAD2 mast cells according to the canonical IL-17A signalling pathway. In SpA synovial tissue, the percentage of IL-17A-positive mast cells increased upon treatment with secukinumab. IL-17A-positive mast cells were also readily detectable in non-inflamed barrier tissues such as skin and gut. In non-inflamed dermis and gut submucosa, IL-17A-positive mast cells are the most prevalent IL-17A-positive cells in situ. Compared with non-inflamed tissues, both total mast cells and IL-17A-positive mast cells were increased in psoriatic skin dermis and in submucosa from inflammatory bowel disease gut. In contrast, the proportion of IL-17A-positive mast cells was strikingly lower in the inflamed compared with non-inflamed gut lamina propria. Conclusion IL-17A-positive mast cells are present across SpA target tissues and correlate inversely with inflammation, indicating that their IL-17A content can be regulated. Tissue-resident mast cells may act as IL-17A-loaded sentinel cells, which release IL-17A to amplify tissue inflammation.

2008 ◽  
Vol 100 (10) ◽  
pp. 693-698 ◽  
Author(s):  
Michael Buerke ◽  
Sebastian Schubert ◽  
Iris Reindl ◽  
Thomas Michel ◽  
Baerbel Hauroeder ◽  
...  

SummaryBivalirudin, a direct thrombin inhibitor binds specifically and reversibly to both fibrin-bound and unbound thrombin. Bivalirudin is approved for use as an anticoagulant in patients undergoing percutaneous coronary intervention. The OASIS-5 trial presented a significant increase in cardiac catheter thrombosis for the pentasaccharid fondaparinux compared to enoxaparin. Catheter thrombosis has never been reported in any trial using bivalirudin. Our study compared the development of catheter thrombosis for bivalirudin, enoxaparin, and unfractionated heparin in a controlled in-vitro environment. Ten healthy male volunteers were pretreated with aspirin 500 mg 2 hours before venesection of 50 ml of blood. The seven groups of anticoagulant combinations tested were:UFH, UFH + eptifibatide, enoxaparin, enoxaparin + eptifibatide, bivalirudin bolus, bivalirudin + eptifibatide, bivalirudin bolus + continuous infusion. The blood/anticoagulant mix continuously circulated through a cardiac guiding catheter for 60 minutes or until the catheter became blocked with thrombus. Thrombus development was assessed by weighing each catheter before and after the procedure. Electron microscopy was used to quantify the degree of erythrocyte, platelet and fibrin deposition. Following anticoagulation with bolus dose bivalirudin, the catheter was invariably occluded with thrombus after 33 minutes of circulation. However, a continuous infusion of Bivalirudin prevented the development of occlusive catheter thrombosis. In the bolus bivalirudin group the mean thrombus weight was significantly greater than in all other groups (p-value < 0.01 in all analyses). Bivalirudin given as a bolus was not sufficient to prevent cardiac catheter thrombosis in our in-vitro study. However, a continuous infusion of bivalirudin had similar anti-thrombotic efficacy compared to other treatment strategies.


Author(s):  
Teresa Al Haddad ◽  
Elie Khoury ◽  
Nada Farhat Mchayleh

Abstract Objectives The aim of the present in vitro study is to compare the remineralization brushing effect of three toothpastes and Aloe vera (AV) gel. Materials and Methods Forty sound extracted teeth were placed in a demineralizing solution for 4 days and randomly assigned to four groups: group A: 1,450-ppm fluoride toothpaste; group B: AV nonfluoridated toothpaste; group C: AV 1,000-ppm fluoridated toothpaste; and group D: AV gel. A 3-minute pH cycling was performed twice a day for each group for 12 days. Specimens were analyzed before and after by scanning electron microscope—energy dispersive X-ray. Statistical analysis The outcomes were analyzed by Kolmogorov–Smirnov’s tests, repeated-measures analyses of variance followed by univariate analyses, and Bonferroni’s multiple comparisons tests to compare the calcium-to-phosphorus (Ca:P) ratio within time among toothpaste groups. Results Following remineralization, the Ca:P ratio increased in all groups. The difference of the Ca:P ratio was not significant between groups C, D, and A. The mean ratio was significantly lower in group B (p-value = 0.026). Conclusions The AV gel demonstrated a remineralization capacity equal to that of the 1,450-ppm fluoride toothpaste. In contrast, fluoride-free AV toothpaste showed a lower remineralization efficiency. Further studies are required to understand its mechanism.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Noelle Zurmühl ◽  
Anna Schmitt ◽  
Ulrike Formentini ◽  
Johannes Weiss ◽  
Heike Appel ◽  
...  

Abstract Background Human plasmacytoid dendritic cells (pDC) have a dual role as interferon-producing and antigen-presenting cells. Their relevance for allergic diseases is controversial. and the impact of pDC on allergic immune responses is poorly understood. Methods This in vitro study on human pDC isolated from peripheral blood was designed to compare side by side the uptake of three clinically relevant representative allergens: fluorochrome-labeled house dust mite Der p 1, Bee venom extract from Apis mellifera (Api) and the food allergen OVA analyzed flow cytometry and confocal microscopy. Results We found that the internalization and its regulation by TLR9 ligation was significantly different between allergens in terms of time course and strength of uptake. Api and OVA uptake in pDC of healthy subjects was faster and reached higher levels than Der p 1 uptake. CpG ODN 2006 suppressed OVA uptake and to a lesser extent Der p 1, while Api internalization was not affected. All allergens colocalized with LAMP1 and EEA1, with Api being internalized particularly fast and reaching highest intracellular levels in pDC. Of note, we could not determine any specific differences in antigen uptake in allergic compared with healthy subjects. Conclusions To our knowledge this is the first study that directly compares uptake regulation of clinically relevant inhalative, injective and food allergens in pDC. Our findings may help to explain differences in the onset and severity of allergic reactions as well as in the efficiency of AIT.


2018 ◽  
Vol 77 (12) ◽  
pp. 1773-1781 ◽  
Author(s):  
Felice Rivellese ◽  
Daniele Mauro ◽  
Alessandra Nerviani ◽  
Sara Pagani ◽  
Liliane Fossati-Jimack ◽  
...  

ObjectivesMast cells (MCs) are involved in the pathogenesis of rheumatoid arthritis (RA). However, their contribution remains controversial. To establish their role in RA, we analysed their presence in the synovium of treatment-naïve patients with early RA and their association and functional relationship with histological features of synovitis.MethodsSynovial tissue was obtained by ultrasound-guided biopsy from treatment-naïve patients with early RA (n=99). Immune cells (CD3/CD20/CD138/CD68) and their relationship with CD117+MCs in synovial tissue were analysed by immunohistochemistry (IHC) and immunofluorescence (IF). The functional involvement of MCs in ectopic lymphoid structures (ELS) was investigated in vitro, by coculturing MCs with naïve B cells and anticitrullinated protein antibodies (ACPA)-producing B cell clones, and in vivo in interleukin-27 receptor alpha (IL27ra)-deficient and control mice during antigen-induced arthritis (AIA).ResultsHigh synovial MC counts are associated with local and systemic inflammation, autoantibody positivity and high disease activity. IHC/IF showed that MCs reside at the outer border of lymphoid aggregates. Furthermore, human MCs promote the activation and differentiation of naïve B cells and induce the production of ACPA, mainly via contact-dependent interactions. In AIA, synovial MC numbers increase in IL27ra deficient mice, in association with ELS and worse disease activity.ConclusionsSynovial MCs identify early RA patients with a severe clinical form of synovitis characterised by the presence of ELS.


2020 ◽  
pp. 1-14
Author(s):  
Daniel Erdwey ◽  
Hendrik Meyer-Lueckel ◽  
Marcella Esteves-Oliveira ◽  
Christian Apel ◽  
Richard Johannes Wierichs

<b><i>Objectives:</i></b> The aim of this in vitro study was to compare the demineralization inhibitory effect of gels/solutions used in combination with either standard or highly fluoridated dentifrices on sound dentin as well as on artificial dentin caries-like lesions. <b><i>Methods:</i></b> Bovine dentin specimens (<i>n</i> = 240) with two different surfaces each (sound [ST] and artificial caries lesion [DT]) were prepared and randomly allocated to twelve groups. Weekly interventions during pH-cycling (28 days, 6 × 120 min demineralization/day) were: the application of gels/solutions containing amine fluoride/sodium fluoride (12,500 ppm F [ppm]; pH = 4.4; AmF); NaF (12,500 ppm; pH = 6.6; NaF1); NaF (12,500 ppm; pH = 6.3; NaF2); silver diamine fluoride (14,200 ppm; pH = 8.7; SDF); acidulated phosphate fluoride (12,500 ppm; pH = 3.8; APF), and no intervention (standard control; S). Furthermore, half of the specimens in each group were brushed (10 s; twice per day) with dentifrice slurries containing either 1,450 ppm (e.g., AmF<sub>1450</sub>) or 5,000 ppm (e.g., AmF<sub>5000</sub>). Differences in integrated mineral loss (ΔΔZ) and lesion depth (ΔLD) were calculated between values before and after pH-cycling using transversal microradiography. <b><i>Results:</i></b> After pH-cycling Ss showed significantly increased ΔZ<sub>DT</sub> and LD<sub>DT</sub> values, indicating further demineralization. In contrast, except for one, all groups including fluoride gels/solutions showed significantly decreased ΔZ<sub>DT</sub> values. Additional use of most fluoride gels/solutions significantly enhanced mineral gain, mainly in the surface area; however, acidic gels/solutions seemed to have negative effects on lesion depths. <b><i>Significance:</i></b> Under the present pH-cycling conditions the highly fluoridated dentifrice significantly reduced caries progression and additional application of nearly all of the fluoride gels/solutions resulted in remineralization. However, there was no difference in the remineralizing capacity of fluoride gels/solutions when used in combination with either standard or highly fluoridated dentifrices.


Materials ◽  
2019 ◽  
Vol 12 (11) ◽  
pp. 1833 ◽  
Author(s):  
Rafael Delgado-Ruiz ◽  
Ana Nicolas Silvente ◽  
Georgios Romanos

Implant connections must resist surgical and prosthetic procedures without deformation. This study evaluated the deformation of different internal connections (IC) of narrow dental implants (NDI) after their insertion in artificial dense bone. Thirty NDI, with different IC geometries, Group A (internal hexagon), Group B (tri-channeled), and Group C (four-channeled), with the same length and similar narrow diameters, were inserted in type II density bone blocks. Drilling protocols for dense bone from each implant manufacturer were followed. The Insertion torque (IT), connection length, vertex angles, and wall deformations were analyzed before and after the insertion of the implants. ANOVA (Analysis of Variance) and Tukey post-test were used for statistical comparisons. IT values were higher for Group A, surface damage, and titanium particles were observed in the IC in all the groups. Angle deformations between 5 and 70 degrees were present in all the groups, and the walls of Group B connection were the most affected by deformations (p < 0.05). Within the limitations of this experiment, it can be concluded that narrow diameter implants will suffer deformation of the implant connection and will also experience surface damage and titanium particle release when inserted in type II bone density.


2020 ◽  
Vol 11 (2) ◽  
pp. 38
Author(s):  
Minh N. Luong ◽  
Laurie Huang ◽  
Daniel C. N. Chan ◽  
Alireza Sadr

Bioactive mineral-based dentin desensitizers that can quickly and effectively seal dentinal tubules and promote dentin mineralization are desired. This in vitro study evaluated a novel nanohydroxyapatite-based desensitizer, Predicta (PBD, Parkell), and its effect on bond strength of dental adhesives. Human dentin discs (2-mm thick) were subjected to 0.5 M EDTA to remove the smear layer and expose tubules, treated with PBD, and processed for surface and cross-sectional SEM examination before and after immersion in simulated body fluid (SBF) for four weeks (ISO 23317-2014). The effects of two dental desensitizers on the microshear bond strength of a universal adhesive and a two-step self-etch system were compared. SEM showed coverage and penetration of nanoparticles in wide tubules on the PBD-treated dentin at the baseline. After four weeks in SBF, untreated dentin showed amorphous mineral deposits while PBD-treated dentin disclosed a highly mineralized structure integrated with dentin. Desensitizers significantly reduced microshear bond strength test (MSBS) of adhesives by 15–20% on average, depending on the bonding protocol. In conclusion, PBD demonstrated effective immediate tubules sealing capability and promoted mineral crystal growth over dentin and into the tubules during SBF-storage. For bonding to desensitizer-treated dentin, a two-step self-etching adhesive or universal bond with phosphoric acid pretreatment are recommended.


Materials ◽  
2019 ◽  
Vol 12 (24) ◽  
pp. 4196
Author(s):  
Martina Eichenberger ◽  
Anna Iliadi ◽  
Despina Koletsi ◽  
George Eliades ◽  
Carlalberta Verna ◽  
...  

The aim of the present study was to quantitatively assess changes in enamel roughness parameters before and after lingual bracket debonding. The lingual surface of 25 sound premolars extracted for orthodontic reasons was studied by 3D optical interferometric profilometry before and after debonding of lingual brackets following enamel finishing (with fine diamond) and polishing (with 12- and 20-fluted carbide burs). The roughness parameters tested were the amplitude parameters Sa and Sz, the hybrid parameter Sdr, and the functional parameters Sc and Sv. The parameter differences (after debonding-reference) were calculated, and statistical analysis was performed via a Wilcoxon signed-rank test. Statistically significantly higher values were observed in all the surface roughness parameters of enamel surfaces after finishing and polishing, with the mostly affected parameter being the Sdr. Under the conditions of the present study, the finishing and polishing instruments used after debonding of lingual noncustomized brackets created a surface texture rougher than the control in all the tested roughness parameters.


2014 ◽  
Vol 08 (01) ◽  
pp. 001-008 ◽  
Author(s):  
Nicola Scotti ◽  
Allegra Comba ◽  
Alberto Gambino ◽  
Davide Salvatore Paolino ◽  
Mario Alovisi ◽  
...  

ABSTRACT Objective: The aim of this in vitro study was to evaluate the marginal sealing ability of a bulk fill flowable resin composite on both enamel and dentin substrates. Materials and Methods: 48 non-carious molars were selected and four Class-V cavities were prepared at the CEJ of each sample. Cavities were filled with Venus Diamond (Heraeus Kulzer); Venus Diamond Flow (Heraeus Kulzer) and Surefil SDR (Dentsply). Samples were divided into two groups: First group samples were immersed in a methylene blue solution for 30 min at 25°C. Second group samples were artificially aged and then treated with methylene blue. Samples were sectioned in the center of the restoration and observed with a 40x stereomicroscope, and the percentage of cavity infiltration was calculated. Results: Results were analyzed statistically by ANOVA (P < 0.05). The amount of infiltration was significantly lower for the enamel substrate compared with dentin (P = 0.0001) and in samples immediately immersed in methylene blue compared with those that were artificially aged (P = 0.011). The interaction between the composite material and the marginal substrate significantly affected dye penetration (P = 0.006). Conclusions: Bulk fill flowable resins provided significantly better marginal seal in dentin, both before and after artificial ageing. Nanohybrid resin composites and bulk fill flowable resins showed similar microleakage values at enamel margins. Bulk fills flowable resins provided significantly better marginal seal in dentin, both before and after artificial ageing. Nanohybrid resin composites and bulk fill flowable resins showed similar microleakage values at enamel margins.


1972 ◽  
Vol 20 (11) ◽  
pp. 917-922 ◽  
Author(s):  
DAVID I. WILKINSON ◽  
DAVID GLICK

In an attempt to clarify the question of whether histidine is stored in the mast cell for coversion to histamine or whether the rate of conversion is rapid enough to prevent accumulation of histidine so that the rate-limiting step is the histidine uptake, it was found that no histidine was demonstrable in rat peritoneal mast cells by either quantitative analysis or paper chromatographic detection. Microadaptation of Hassall's method, based on conversion of l-histidine by histidase to urocanic acid and measurement of the latter by its absorbance at 277 nm, was made to permit determination of histidine in nanogram amounts in the presence of histamine. This adaptation was found reliable when compared with the o-phthalaldehyde method in estimation of l-histidine in serum and in insulin hydrolysate, and then it was applied to analysis of mast cells before and after l-histidine uptake in vitro. The adaptation should be generally useful in microanalysis of l-histidine in histologically and cytologically defined samples.


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