scholarly journals Intradermal lipopolysaccharide challenge as an acute in vivo inflammatory model in healthy volunteers

Author(s):  
Thomas P. Buters ◽  
Pieter W. Hameeteman ◽  
Iris M. E. Jansen ◽  
Floris C. Hindevoort ◽  
Wouter Voorde ◽  
...  
2019 ◽  
Vol 130 ◽  
pp. 32-43 ◽  
Author(s):  
Elias Begas ◽  
Maria Bounitsi ◽  
Thomas Kilindris ◽  
Evangelos Kouvaras ◽  
Konstantinos Makaritsis ◽  
...  

2017 ◽  
Vol 51 (4) ◽  
pp. 410-418 ◽  
Author(s):  
Rupert S. Austin ◽  
Maisalamah Haji Taha ◽  
Frederic Festy ◽  
Richard Cook ◽  
Manoharan Andiappan ◽  
...  

Swept-source optical coherence tomography (SS-OCT) shows potential for the in vivo quantitative evaluation of micro-structural enamel surface phenomena occurring during early erosive demineralization. This randomized controlled single-blind cross-over clinical study aimed to evaluate the use of SS-OCT for detecting optical changes in the enamel of 30 healthy volunteers subjected to orange juice rinsing (erosive challenge) in comparison to mineral water rinsing (control), according to wiped and non-wiped enamel surface states. Participants were randomly allocated to 60 min of orange juice rinsing (pH 3.8) followed by 60 min of water rinsing (pH 6.7) and vice versa, with a 2-week wash-out period. In addition, the labial surfaces of the right or left maxillary incisors were wiped prior to SS-OCT imaging. An automated ImageJ algorithm was designed to analyse the back-scattered OCT signal intensity (D) after orange juice rinsing compared to after water rinsing. D was quantified as the OCT signal scattering from the 33 µm sub-surface enamel, normalised by the total OCT signal intensity entering the enamel. The back-scattered OCT signal intensity increased by 3.1% (95% CI 1.1-5.1%) in the wiped incisors and by 3.5% (95% CI 1.5-5.5%) in the unwiped incisors (p < 0.0001). Wiping reduced the back-scattered OCT signal intensity by 1.7% (95% CI -3.2 to -0.3%; p = 0.02) in comparison to the unwiped enamel surfaces for both rinsing solutions (p = 0.2). SS-OCT detected OCT signal changes in the superficial sub-surface enamel of maxillary central incisor teeth of healthy volunteers after orange juice rinsing.


Molecules ◽  
2021 ◽  
Vol 26 (12) ◽  
pp. 3602
Author(s):  
Elena Genova ◽  
Maura Apollonio ◽  
Giuliana Decorti ◽  
Alessandra Tesser ◽  
Alberto Tommasini ◽  
...  

Interferonopathies are rare genetic conditions defined by systemic inflammatory episodes caused by innate immune system activation in the absence of pathogens. Currently, no targeted drugs are authorized for clinical use in these diseases. In this work, we studied the contribution of sulforaphane (SFN), a cruciferous-derived bioactive molecule, in the modulation of interferon-driven inflammation in an immortalized human hepatocytes (IHH) line and in two healthy volunteers, focusing on STING, a key-component player in interferon pathway, interferon signature modulation, and GSTM1 expression and genotype, which contributes to SFN metabolism and excretion. In vitro, SFN exposure reduced STING expression as well as interferon signature in the presence of the pro-inflammatory stimulus cGAMP (cGAMP 3 h vs. SFN+cGAMP 3 h p value < 0.0001; cGAMP 6 h vs. SFN+cGAMP 6 h p < 0.001, one way ANOVA), restoring STING expression to the level of unstimulated cells. In preliminary experiments on healthy volunteers, no appreciable variations in interferon signature were identified after SFN assumption, while only in one of them, presenting the GSTM1 wild type genotype related to reduced SFN excretion, could a downregulation of STING be recorded. This study confirmed that SFN inhibits STING-mediated inflammation and interferon-stimulated genes expression in vitro. However, only a trend towards the downregulation of STING could be reproduced in vivo. Results obtained have to be confirmed in a larger group of healthy individuals and in patients with type I interferonopathies to define if the assumption of SFN could be useful as supportive therapy.


2019 ◽  
Vol 124 ◽  
pp. 6-18 ◽  
Author(s):  
Stephen C. Kanick ◽  
Peter A. Schneider ◽  
Bruce Klitzman ◽  
Natalie A. Wisniewski ◽  
Kerstin Rebrin

2000 ◽  
Vol 93 (5) ◽  
pp. 1184-1187 ◽  
Author(s):  
Jonathan H. Waters ◽  
Clifford A. Bernstein

Background The intent of this study was to evaluate the impact of the commonly used colloids-hetastarch and albumin-on in vivo acid-base balance. From this evaluation, a better understanding of the mechanism of dilutional acidosis was expected. Methods In a prospective, randomized fashion, 11 healthy volunteers were administered 15 ml/kg hetastarch solution, 6%, or 15 ml/kg albumin, 5%, intravenously over 30 min. Four weeks later, the study subjects were administered the other colloid. Arterial blood gas and electrolyte parameters were measured at baseline and at 30, 60, 90, 120, 210, and 300 min after colloid administration. Pre- and postlaboratory values were compared within groups using a paired t test and a Wilcoxon signed rank test and between groups using repeated-measures analysis of variance and a Wilcoxon rank sum test. Results Thirty min after infusion, subjects who were administered hetastarch showed statistically significant changes (P &lt; 0.05) in base excess (from 2.5 +/- 0.9 mEq/l to 0.7 +/- 1.1 mEq/l), HCO3- concentration (from 27 +/- 1.0 mEq/l to 25 +/- 1.3 mEq/l), Cl- concentration (from 108 +/- 2 mEq/l to 112 +/- 2 mEq/l), albumin concentration (from 4.4 +/- 0.2 g/dl to 3.5 +/- 0.5 g/dl), and arterial carbon dioxide tension (Paco2; from 40.8 +/- 2.3 mmHg to 39. 2 +/- 3.2 mmHg), whereas only the albumin concentration (from 4.4 +/- 0.2 g/dl to 4.8 +/- 0.6 g/dl) changed significantly in the albumin-treated group. Conclusions Decreases in base excess were observed for 210 min after hetastarch administration but not after albumin. The mechanism for this difference is discussed.


2004 ◽  
Vol 184 (5) ◽  
pp. 409-415 ◽  
Author(s):  
J. Eric Jensen ◽  
Jodi Miller ◽  
Peter C. Williamson ◽  
Richard W J. Neufeld ◽  
Ravi S. Menon ◽  
...  

BackgroundMembrane phospholipid and high-energy abnormalities measured with phosphorus magnetic resonance spectroscopy (31P-MRS) have been reported in patients with schizophrenia in several brain regions.AimsUsing improved imaging techniques, previously inaccessible brain regions were examined in patients with first-episode schizophrenia and healthy volunteers with 4.0 T 31P-MRS.MethodBrain spectra were collected in vivo from 15 patients with first-episode schizophrenia and 15 healthy volunteers from 15 cm3 effective voxels in the thalamus, cerebellum, hippocampus, anterior/posterior cingulate, prefrontal cortex and parieto-occipital cortex.ResultsPeople with first-episode schizophrenia showed increased levels of glycerophosphocholine in the anterior cingulate. Inorganic phosphate, phosphocreatine and adenosine triphosphate concentrations were also increased in the anterior cingulate in this group.ConclusionsThe increased phosphodiester and high-energy phosphate levels in the anterior cingulate of brains of people with first-episode schizophrenia may indicate neural overactivity in this region during the early stages of the illness, resulting in increased excitotoxic neural membrane breakdown.


2021 ◽  
pp. 2004149
Author(s):  
Sara Rolandsson Enes ◽  
Thomas H. Hampton ◽  
Jayita Barua ◽  
David H. McKenna ◽  
Claudia C. dos Santos ◽  
...  

BackgroundDespite increased interest in MSC-based cell therapies for the acute respiratory distress syndrome (ARDS), clinical investigations have not yet been successful and understanding of the potential in vivo mechanisms of MSC actions in ARDS remain limited. ARDS is driven by an acute severe innate immune dysregulation, often characterised by inflammation, coagulation, and cell injury. How this inflammatory microenvironment influences MSC functions remains to be determined.AimTo comparatively assess how the inflammatory environment present in ARDS lungs versus the lung environment present in healthy volunteers alters MSC behaviors.MethodsClinical grade human bone marrow-derived MSCs (hMSCs) were exposed to bronchoalveolar lavage fluid (BALF) samples obtained from ARDS patients or from healthy volunteers. Following exposure, hMSCs and their conditioned media were evaluated for a broad panel of relevant properties including viability, levels of expression of inflammatory cytokines, gene expression, cell surface HLA expression, and activation of coagulation and complement pathways.ResultsPro-inflammatory, pro-coagulant, and major histocompatibility complex (self recognition) related gene expression was markedly up-regulated in hMSCs exposed ex vivo to BALF obtained from healthy volunteers. In contrast, these changes were less apparent and often opposite in hMSCs exposed to ARDS BALF samples.ConclusionThese data provide new insights into how hMSCs behave in healthy versus inflamed lung environments strongly suggesting that the inflamed environment in ARDS induces hMSC responses potentially benefical for cell survival and actions. This further highlights the need to understand how different disease environments affect hMSC functions.


Spine ◽  
2009 ◽  
Vol 34 (22) ◽  
pp. E811-E817 ◽  
Author(s):  
Fiona E. Mellor ◽  
Jennifer M. Muggleton ◽  
Jeff Bagust ◽  
William Mason ◽  
Peter W. Thomas ◽  
...  

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