scholarly journals Accelerating Inflammation Resolution to Counteract Chemical Cutaneous Injury

2019 ◽  
Author(s):  
Satyanarayana Achanta ◽  
Narendranath Reddy Chintagari ◽  
Shrilatha Balakrishna ◽  
Boyi Liu ◽  
Sven-Eric Jordt
Keyword(s):  
Sulfur Mustard ◽  
Chemical Exposure ◽  
Punch Biopsy ◽  
Resolvin D1 ◽  
Cutaneous Injury ◽  
Tear Gas ◽  
Inflammation Resolution ◽  
Riot Control ◽  
Further Development ◽  
Medical Countermeasures

AbstractChemical exposure to vesicants such as sulfur mustard (SM), and electrophilic riot control agents such as 2-chlorobenzalmalononitrile (CS) tear gas agent, cause strong cutaneous inflammation. Classical anti-inflammatory treatments have focused on interference with target initiation and maintenance of inflammation, with mixed outcomes. Inflammation is broadly classified into three temporal phases, initiation, amplification and maintenance, and resolution. Resolution of inflammation was thought to be a passive process but the recent body of literature shows that resolution is an active process and is mediated by fatty acid-derived mediators (specialized pro-resolving mediators, SPMs). We hypothesized that accelerating resolution phase of inflammation may attenuate the exaggerated inflammatory response following chemical threat exposure, leading to decreased morbidity and improved recovery. In this study, SPMs, such as Resolvin D1 (RvD1) and Resolvin D2 (RvD2), were administered to mice at nanogram doses post-exposure to an SM analog, 2-chloroethyl-ethyl-sulfide (CEES) or CS tear gas agent. SPMs decreased edema (ear thickness and punch biopsy weights), pro-inflammatory cytokines (IL-1β, CXCL1/KC, MIP2) and protease marker (MMP-9), and vascular leakage (determined by IRDye 800 CW PEG) while improving histopathology in cutaneous chemical injury mouse models. These results support our hypothesis and pave the way for SPMs for further development as potential medical countermeasures for chemical threat agents-induced skin injuries.

Role of the Specialized Pro-resolving Mediator Resolvin D1 in Hashimotoʼs Thyroiditis

2021 ◽  
Author(s):  
Jing Song ◽  
Rongxin Sun ◽  
Yuanyuan Zhang ◽  
Ying Fu ◽  
Dong Zhao
Keyword(s):  
Thyroid Autoimmunity ◽  
Thyroid Stimulating Hormone ◽  
Inflammatory Factors ◽  
Thyroid Peroxidase ◽  
Sensitivity Index ◽  
Resolvin D1 ◽  
Thyroid Peroxidase Antibody ◽  
Thyroglobulin Antibody ◽  
Inflammation Resolution

Abstract Objective Resolvins are produced by the catabolism of polyunsaturated fatty acids (PUFAs) and play vital roles in inflammation resolution. Resolvins have been associated with autoimmune disorders. This study aimed to measure the level of Resolvin D1 (RVD1) in the serum of Hashimoto's thyroiditis (HT) patients and healthy controls (HCs) and to further analyse its correlation with thyroid autoantibodies and inflammatory factors. Methods Sixty-three participants were recruited, namely, 30 untreated HT patients and 33 sex- and age-matched HCs. Serum RVD1 and inflammatory chemokine (MCP-1 and IP-10) levels were measured by ELISA according to the manufacturer’s protocol. Serum total T3 (TT3), TT4, free T3 (FT3), FT4, thyroglobulin antibody (TgAb), thyroid peroxidase antibody (TPOAb) and thyroid-stimulating hormone (TSH) levels were measured using an electrochemiluminescence immunoassay. Thyroid homeostasis parameters, including the thyroid secretory capacity (SPINA-GT), the total deiodinase activity (SPINA-GD), Jostel’s TSH index (TSHI) and the thyrotroph thyroid hormone sensitivity index (TTSI), were calculated. Results Serum RVD1 levels in HT patients (134.76, 85.35–201.36 pg/mL) were significantly lower than those in HCs (187.64, 131.01–326.85 pg/mL) (P=0.004). As the TPOAb level increased, the RVD1 level showed a decreasing trend (P for trend=0.002). Both multinomial and ordinal logistics analyses revealed that serum RVD1 levels were negatively correlated with TPOAb levels in the adjusted models. Moreover, RVD1 showed a negative correlation with the inflammatory chemokine IP-1 0 (r=–0.276, P=0.034), TSHI (r=–0.269, P=0.036) and TTSI (r=–0.277, P=0.031). Conclusions Thyroid autoimmunity may be associated with low levels of RVD1. Decreased RVD1 levels indicate impaired resolution of inflammation in HT patients.

Therapeutic approaches to dermatotoxicity by sulfur mustard I. Modulation of sulfur mustard-induced cutaneous injury in the mouse ear vesicant model†**

2001 ◽  
Vol 20 (S1) ◽  
pp. S145-S151 ◽  
Author(s):  
Robert P. Casillas ◽  
Robyn C. Kiser ◽  
Jean A. Truxall ◽  
Al W. Singer ◽  
Shawn M. Shumaker ◽  
...  
Keyword(s):  
Sulfur Mustard ◽  
Therapeutic Approaches ◽  
Cutaneous Injury ◽  
Mouse Ear

scholarly journals The Time Course of Inflammatory Biomarkers Following a One-Hour Exercise Bout in Canines: A Pilot Study

Animals ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 486
Author(s):  
Wendy Pearson ◽  
Julia Guazzelli Pezzali ◽  
Renan Antunes Donadelli ◽  
Ashley Wagner ◽  
Preston Buff
Keyword(s):  
Pilot Study ◽  
Time Course ◽  
Venous Blood ◽  
Exercise Bout ◽  
Exercise Stress ◽  
Moderate Intensity ◽  
Resolvin D1 ◽  
Moderate Intensity Exercise ◽  
Hunting Dogs ◽  
Inflammation Resolution

There is little information available to describe the inflammatory consequences of and recovery from moderate-intensity exercise bouts in hunting dogs. The purpose of the current study is to generate pilot data on the appearance and disappearance of biomarkers of inflammation and inflammation resolution following a typical one-hour exercise bout in basset hounds. Four hounds were set out to find a scent and freely adopted running or walking over wooded terrain for approximately one hour. Venous blood samples were obtained before the exercise and at 1, 2, 4, 6, and 10 h following cessation of exercise and were analyzed for biomarkers of inflammation (prostaglandin E2 (PGE2), nitric oxide (NO), interleukin 1β (IL-1β)) tumour necrosis factor-α (TNF-α)), and inflammation resolution (resolvin D1 (RvD1)). There was an increase in inflammation one hour after the exercise, shown by a significant increase in PGE2. Following this peak, PGE2 steadily declined at the same time as RvD1 increased, with RvD1 peaking at six hours. This pilot study provides evidence that dogs that undergo an hour of hunt exercise experience transient inflammation that peaks one hour after the end of exercise; inflammation resolution peaks six hours after the end of exercise. Future studies should seek to further understand the distinct and combined roles of PGE2 and RvD1 in dog adaptation to exercise stress.

scholarly journals The inflammation-resolution promoting molecule resolvin-D1 prevents atrial proarrhythmic remodelling in experimental right heart disease

2020 ◽  
Author(s):  
Roddy Hiram ◽  
Feng Xiong ◽  
Patrice Naud ◽  
Jiening Xiao ◽  
Martin Sirois ◽  
...  
Keyword(s):  
Gene Expression ◽  
Heart Disease ◽  
M2 Macrophages ◽  
Gene Microarray ◽  
Resolvin D1 ◽  
Right Heart ◽  
M1 Macrophages ◽  
Anti Inflammatory ◽  
Inflammation Resolution ◽  
Inflammatory Signalling

Abstract Aims Inflammation plays a role in atrial fibrillation (AF), but classical anti-inflammatory molecules are ineffective. Recent evidence suggests that failure of inflammation-resolution causes persistent inflammatory signalling and that a novel drug-family called resolvins promotes inflammation-resolution. Right heart disease (RHD) is associated with AF; experimental RHD shows signs of atrial inflammatory-pathway activation. Here, we evaluated resolvin-therapy effects on atrial arrhythmogenic remodelling in experimental RHD. Methods and results Pulmonary hypertension and RHD were induced in rats with an intraperitoneal injection of 60 mg/kg monocrotaline (MCT). An intervention group received daily resolvin-D1 (RvD1), starting 1 day before MCT administration. Right atrial (RA) conduction and gene-expression were analysed respectively by optical mapping and qPCR/gene-microarray. RvD1 had no or minimal effects on MCT-induced pulmonary artery or right ventricular remodelling. Nevertheless, in vivo transoesophageal pacing induced atrial tachyarrhythmias in no CTRL rats vs. 100% MCT-only rats, and only 33% RvD1-treated MCT rats (P < 0.001 vs. MCT-only). Conduction velocity was significantly decreased by MCT, an effect prevented by RvD1. RHD caused RA dilation and fibrosis. RvD1 strongly attenuated RA fibrosis but had no effect on RA dilation. MCT increased RA expression of inflammation- and fibrosis-related gene-expression pathways on gene-microarray transcriptomic analysis, effects significantly attenuated by RvD1 (334 pathways enriched in MCT-rats vs. control; only 177 dysregulated by MCT with RvD1 treatment). MCT significantly increased RA content of type 1 (proinflammatory) CD68-positive M1 macrophages without affecting type 2 (anti-inflammatory) M2 macrophages. RvD1-treated MCT-rat RA showed significant reductions in proinflammatory M1 macrophages and increases in anti-inflammatory M2 macrophages vs. MCT-only. MCT caused statistically significant increases in protein-expression (western blot) of COL3A1, ASC, CASP1, CASP8, IL1β, TGFβ3, CXCL1, and CXCL2, and decreases in MMP2, vs. control. RvD1-treatment suppressed all these MCT-induced protein-expression changes. Conclusion The inflammation-resolution enhancing molecule RvD1 prevents AF-promoting RA remodelling, while suppressing inflammatory changes and fibrotic/electrical remodelling, in RHD. Resolvins show potential promise in combating atrial arrhythmogenic remodelling by suppressing ongoing inflammatory signalling.

scholarly journals Harnessing lipid signaling pathways to target specialized pro-angiogenic neutrophil subsets for regenerative immunotherapy

2020 ◽  
Vol 6 (44) ◽  
pp. eaba7702
Author(s):  
T. C. Turner ◽  
M. C. P. Sok ◽  
L. A. Hymel ◽  
F. S. Pittman ◽  
W. Y. York ◽  
...  
Keyword(s):  
Single Cell ◽  
Neutrophil Infiltration ◽  
Sterile Inflammation ◽  
Lipid Mediator ◽  
Cell Phenotype ◽  
Resolvin D1 ◽  
Flow Cytometry Data ◽  
Cell Flow Cytometry ◽  
Inflammation Resolution ◽  
Window Chamber

To gain insights into neutrophil heterogeneity dynamics in the context of sterile inflammation and wound healing, we performed a pseudotime analysis of single-cell flow cytometry data using the spanning-tree progression analysis of density-normalized events algorithm. This enables us to view neutrophil transitional subsets along a pseudotime trajectory and identify distinct VEGFR1, VEGFR2, and CXCR4 high-expressing pro-angiogenic neutrophils. While the proresolving lipid mediator aspirin-triggered resolvin D1 (AT-RvD1) has a known ability to limit neutrophil infiltration, our analysis uncovers a mode of action in which AT-RvD1 leads to inflammation resolution through the selective reprogramming toward a therapeutic neutrophil subset. This accumulation leads to enhanced vascular remodeling in the skinfold window chamber and a proregenerative shift in macrophage and dendritic cell phenotype, resulting in improved wound closure after skin transplantation. As the targeting of functional immune subsets becomes the key to regenerative immunotherapies, single-cell pseudotime analysis tools will be vital in this field.

scholarly journals The resolvin D1 receptor GPR32 transduces inflammation-resolution and atheroprotection

2021 ◽  
Author(s):  
Hildur Arnardottir ◽  
Silke Thul ◽  
Sven-Christian Pawelzik ◽  
Glykeria Karadimou ◽  
Gonzalo Artiach ◽  
...  
Keyword(s):  
D1 Receptor ◽  
Resolvin D1 ◽  
Inflammation Resolution

scholarly journals Chemical Safety Concerns of Sulfur Mustard Analog, 2-Chloroethyl Ethyl Sulfide, in Laboratory Study

2022 ◽  
Vol 19 (4) ◽  
Author(s):  
Feng Ye ◽  
Yan Sai ◽  
Zhongmin Zou
Keyword(s):  
Experimental Data ◽  
Laboratory Study ◽  
Sulfur Mustard ◽  
Chemical Weapon ◽  
Severe Damage ◽  
Chemical Safety ◽  
Safety Concerns ◽  
Toxicological Effects ◽  
Working Procedure ◽  
Medical Countermeasures

: Sulfur mustard (SM), a classic chemical weapon in the vesicant category, can induce severe damage, for which the therapy is still limited even today. Laboratory work is essential in unveiling toxicological effects and developing medical countermeasures. Sulfur mustard analog 2-chloroethyl ethyl sulfide (CEES), is employed in the lab for less toxicity. However, due to its similar characteristics to SM (being oily, hydrophobic, and volatile), the manipulation of CEES still needs special attention to avoid personnel injury and laboratory pollution. Here, to clear the chemical safety concerns in the laboratory study of CEES, the working procedure and experimental data are summarized, which might help educate new researchers to be skilled and professional.

Contingency Medical Countermeasures for Mass Nerve-Agent Exposure: Use of Pharmaceutical Alternatives to Community Stockpiled Antidotes

2018 ◽  
Vol 13 (03) ◽  
pp. 605-612 ◽  
Author(s):  
Michael D. Schwartz ◽  
Mark E. Sutter ◽  
Derek Eisnor ◽  
Mark A. Kirk
Keyword(s):  
Public Health ◽  
Drug Administration ◽  
Homeland Security ◽  
Food And Drug Administration ◽  
Medical Toxicology ◽  
Chemical Exposure ◽  
Nerve Agent ◽  
Government Procurement ◽  
Gamma Aminobutyric Acid ◽  
Medical Countermeasures

ABSTRACTHaving sufficient medical countermeasures (MCMs) available for the treatment of acetylcholinesterase-inhibiting nerve agent poisoned patients following a mass chemical exposure is a challenge for communities. After stockpiles containing auto-injectors are exhausted, communities need to be aware of alternative pharmaceutical options. The Department of Homeland Security Chemical Defense Program convened a federal interagency working group consisting of first responders, clinicians, and experts from the fields of medical toxicology, pharmacology, and emergency management. A literature review of pharmaceutical alternatives for treating nerve agent toxicity was performed. Pharmaceuticals that met the federal Public Health Emergency Medical Countermeasures Enterprise Product Specific Requirements were prioritized. Food and Drug Administration approval for one indication, market availability, and alignment to government procurement strategy were considered. This article summarizes the literature on comparative pharmacokinetics and efficacy against nerve agents (where available) of Food and Drug Administration approved drugs with muscarinic acetylcholine receptor antagonist and gamma-aminobutyric acid receptor agonist effects. This work is intended to serve as a resource of pharmaceutical options that may be available to communities (ie, emergency managers, planners, clinicians, and poison centers) when faced with a mass human exposure to a nerve agent and inadequate supplies of MCMs. (Disaster Med Public Health Preparedness. 2019;13:605-612)

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