scholarly journals Minimally Invasive Embedding of Saturated MSU Induces Persistent Gouty Arthritis in Modified Rat Model

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Han-Lin Xu ◽  
Sheng-Kun Li ◽  
Xiao-Ao Xue ◽  
Zi-Yi Chen ◽  
Ying-Hui Hua
Keyword(s):  
Minimally Invasive ◽  
Rat Model ◽  
Gouty Arthritis ◽  
Inflammatory Cells ◽  
Tnf Α ◽  
Quantitative Immunofluorescence ◽  
Invasive Method ◽  
Reproducible Method ◽  
Mechanical Pain Threshold

Introduction. Animal models are valid for in vivo research on the pathophysiological process and drug screening of gout arthritis. Intra-articular injection of monosodium urate (MSU) is the most common method, while stable MSU deposition enveloped by inflammatory cells was rarely reported. Objective. To develop a modified gouty arthritis rat model characterized by intra-articular MSU deposition and continuous joint pain with a minimally invasive method. Method. A total of twenty-four rats were randomly allocated into six groups. Three intervention groups of rats received intra-articular MSU embedment. Sham groups received pseudosurgeries with equal normal saline (NS). Gross parameters and pathological features of synovium harvested from anterior capsule were estimated. Mechanical pain threshold tests were conducted over a 96-hour period postoperatively. Moreover, quantitative immunofluorescence was conducted to assess tissue inflammation. Result. After MSU embedding, rats got more persistent arthritic symptoms as well as tissue MSU deposition. More significant synovial swelling was detected in the MSU group compared to sham groups ( P < 0.025 ). Behavioral tests showed that the embedding of MSU resulted in prolonged mechanical hyperalgesia during 2 hours to 96 hours postoperatively ( P < 0.05 ). MSU depositions enveloped by inflammatory cells that express IL-1β and TNF-α were detected in embedding groups. Quantitative immunofluorescence suggested that the frequencies of MSU interventions upregulated expression of proinflammatory factors including IL-1β and TNF-α ( P < 0.05 ). Conclusion. A minimally invasive method was developed to establish modified rat model of intra-articular MSU deposition. This model was proved to be a simple reproducible method to mimic the pathological characteristics of persistent gouty arthritis.

A Novel Rat Model of Persistent Gouty Arthritis by Minimally Invasive Saturated Msu Embedding 

2020 ◽  
Author(s):  
Hanlin Xu ◽  
ShengKun Li ◽  
XiaoAo Xue ◽  
ZiYi Chen ◽  
Yinghui Hua
Keyword(s):  
Minimally Invasive ◽  
Rat Model ◽  
Gouty Arthritis ◽  
The Novel ◽  
Minimally Invasive Surgical ◽  
Crystal Arthritis ◽  
Tnf Α ◽  
Quantitative Immunofluorescence ◽  
Reproducible Method

Abstract Background: Animal models are valid for in vivo research on the pathophysiological process and drug screening of gout arthritis. Intra-articular injection of monosodium urate (MSU) is commonly used to establish animal model at present, while stable MSU deposition and tophi formation were rarely reported. Method: A total of twenty-four rats were randomly allocated into six groups. Three intervention groups of rats received MSU embedment for 3-5 times, respectively. Sham groups received pseudo surgeries with normal saline (NS). Gross parameters and pathological features of synovium harvested from anterior capsule. Mechanical pain threshold tests of rats were conducted over a 96-hour period postoperatively. Result: Significant synovial swelling was detected in the MSU group compared to the sham group(P<0.05). Behavioral tests showed that the embedding of MSU resulted in prolonged mechanical hyperalgesia (P<0.05 during 2 hours to 96 hours postoperatively). MSU depositions enveloped by neutrophil extracellular traps (NETs) were detected where the IL-1β and TNF-α were co-expressed in embedding groups. Quantitative immunofluorescence suggested that the frequencies of MSU interventions promoted expression of proinflammatory factors (P<0.05).Conclusion: A minimally invasive surgical method was developed to establish the novel rat model of intra-articular MSU deposition. This model was proved to be a simple reproducible method to mimic the pathological characteristics of intra-articular crystal arthritis.

scholarly journals The Anti-Inflammatory Effects of Angiogenin in an Endotoxin Induced Uveitis in Rats

2020 ◽  
Vol 21 (2) ◽  
pp. 413
Author(s):  
Jihae Park ◽  
Jee Taek Kim ◽  
Soo Jin Lee ◽  
Jae Chan Kim
Keyword(s):  
Western Blot ◽  
Inflammatory Cytokines ◽  
Aqueous Humor ◽  
Rat Model ◽  
Inflammatory Responses ◽  
Inflammatory Cells ◽  
Ocular Tissue ◽  
Tnf Α ◽  
Anti Inflammatory

Angiogenin (ANG) is involved in the innate immune system and inflammatory disease. The aim of this study is to evaluate the anti-inflammatory effects of ANG in an endotoxin induced uveitis (EIU) rat model and the pathways involved. EIU rats were treated with balanced salt solution (BSS), a non-functional mutant ANG (mANG), or wild-type ANG (ANG). The integrity of the blood-aqueous barrier was evaluated by the infiltrating cell and protein concentrations in aqueous humor. Histopathology, Western blot, and real-time qRT-PCR of aqueous humor and ocular tissue were performed to analyze inflammatory cytokines and transcription factors. EIU treated with ANG had decreased inflammatory cells and protein concentrations in the anterior chamber. Compared to BSS and mANG, ANG treatment showed reduced expression of IL-1β, IL-8, TNF-α, and Myd88, while the expression of IL-4 and IL-10 was increased. Western blot of ANG treatment showed decreased expression of IL-6, inducible nitric oxide synthase (iNOS), IL-1β, TNF-α, and phosphorylated NF-κB and increased expression of IL-10. In conclusion, ANG seems to reduce effectively immune mediated inflammation in the EIU rat model by reducing the expression of proinflammatory cytokines, while increasing the expression of anti-inflammatory cytokines through pathways related to NF-κB. Therefore, ANG shows potential for effectively suppressing immune-inflammatory responses in vivo.

Nonstressed rat model of acute endotoxemia that unmasks the endotoxin-induced TNF-α response

1999 ◽  
Vol 276 (2) ◽  
pp. H671-H678 ◽  
Author(s):  
David W. A. Beno ◽  
Robert E. Kimura
Keyword(s):  
Rat Model ◽  
Endotoxic Shock ◽  
Stress Hormones ◽  
Tnf Α ◽  
Baseline Concentrations ◽  
Experimental Protocols ◽  
Factor Α ◽  
Necrosis Factor

Previous investigators have demonstrated that the tumor necrosis factor-α (TNF-α) response to endotoxin is inhibited by exogenous corticosterone or catecholamines both in vitro and in vivo, whereas others have reported that surgical and nonsurgical stress increase the endogenous concentrations of these stress-induced hormones. We hypothesized that elevated endogenous stress hormones resultant from experimental protocols attenuated the endotoxin-induced TNF-α response. We used a chronically catheterized rat model to demonstrate that the endotoxin-induced TNF-α response is 10- to 50-fold greater in nonstressed (NS) rats compared with either surgical-stressed (SS, laparotomy) or nonsurgical-stressed (NSS, tail vein injection) models. Compared with the NS group, the SS and NSS groups demonstrated significantly lower mean peak TNF-α responses at 2 mg/kg and 6 μg/kg endotoxin [NS 111.8 ± 6.5 ng/ml and 64.3 ± 5.9 ng/ml, respectively, vs. SS 3.9 ± 1.1 ng/ml ( P < 0.01) and 1.3 ± 0.5 ng/ml ( P < 0.01) or NSS 5.2 ± 3.2 ng/ml ( P < 0.01) at 6 μg/kg]. Similarly, baseline concentrations of corticosterone and catecholamines were significantly lower in the NSS group [84.5 ± 16.5 ng/ml and 199.8 ± 26.2 pg/ml, respectively, vs. SS group 257.2 ± 35.7 ng/ml ( P< 0.01) and 467.5 ± 52.2 pg/ml ( P < 0.01) or NS group 168.6 ± 14.4 ng/ml ( P < 0.01) and 1,109.9 ± 140.7 pg/ml ( P < 0.01)]. These findings suggest that the surgical and nonsurgical stress inherent in experimental protocols increases baseline stress hormones, masking the endotoxin-induced TNF-α response. Subsequent studies of endotoxic shock should control for the effects of protocol-induced stress and should measure and report baseline concentrations of corticosterone and catecholamines.

Depletion of pulmonary intravascular macrophages inhibits acute lung inflammation

2004 ◽  
Vol 286 (2) ◽  
pp. L363-L372 ◽  
Author(s):  
Baljit Singh ◽  
Jacqueline W. Pearce ◽  
Lakshman N. Gamage ◽  
Kyathanahalli Janardhan ◽  
Sarah Caldwell
Keyword(s):  
Lung Inflammation ◽  
Acute Inflammation ◽  
Inflammatory Cells ◽  
Acute Lung Inflammation ◽  
Tnf Α ◽  
Highly Sensitive ◽  
In Vitro Exposure ◽  
Pulmonary Intravascular Macrophages

Pulmonary intravascular macrophages (PIMs) are present in ruminants and horses. These species are highly sensitive to acute lung inflammation compared with non-PIM-containing species such as rats and humans. There is evidence that rats and humans may also recruit PIMs under certain conditions. We investigated precise contributions of PIMs to acute lung inflammation in a calf model. First, PIMs were recognized with a combination of in vivo phagocytic tracer Monastral blue and postembedding immunohistology with anti-CD68 monoclonal antibody. Second, gadolinium chloride depleted PIMs within 48 h of treatment ( P < 0.05). Finally, PIMs contain TNF-α, and their depletion reduces cells positive for IL-8 ( P < 0.05) and TNF-α ( P < 0.05) and histopathological signs of acute lung inflammation in calves infected with Mannheimia hemolytica. The majority of IL-8-positive inflammatory cells in lung septa of infected calves were platelets. Platelets from normal cattle contained preformed IL-8 that was released upon in vitro exposure to thrombin ( P < 0.05). These novel data show that PIMs, as the source of TNF-α, promote recruitment of inflammatory cells including IL-8-containing platelets to stimulate acute inflammation and pathology in lungs. These data may also be relevant to humans due to our ability to recruit PIMs.

scholarly journals Regulation of eosinophilia and allergic airway inflammation by the glycan-binding protein galectin-1

2016 ◽  
Vol 113 (33) ◽  
pp. E4837-E4846 ◽  
Author(s):  
Xiao Na Ge ◽  
Sung Gil Ha ◽  
Yana G. Greenberg ◽  
Amrita Rao ◽  
Idil Bastan ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Binding Protein ◽  
Allergic Airway Inflammation ◽  
Inflammatory Cells ◽  
Cell Clustering ◽  
Tnf Α ◽  
Chemokine Receptor Ccr3 ◽  
Cell Adhesion Molecule 1

Galectin-1 (Gal-1), a glycan-binding protein with broad antiinflammatory activities, functions as a proresolving mediator in autoimmune and chronic inflammatory disorders. However, its role in allergic airway inflammation has not yet been elucidated. We evaluated the effects of Gal-1 on eosinophil function and its role in a mouse model of allergic asthma. Allergen exposure resulted in airway recruitment of Gal-1–expressing inflammatory cells, including eosinophils, as well as increased Gal-1 in extracellular spaces in the lungs. In vitro, extracellular Gal-1 exerted divergent effects on eosinophils that were N-glycan– and dose-dependent. At concentrations ≤0.25 µM, Gal-1 increased eosinophil adhesion to vascular cell adhesion molecule-1, caused redistribution of integrin CD49d to the periphery and cell clustering, but inhibited ERK(1/2) activation and eotaxin-1–induced migration. Exposure to concentrations ≥1 µM resulted in ERK(1/2)-dependent apoptosis and disruption of the F-actin cytoskeleton. At lower concentrations, Gal-1 did not alter expression of adhesion molecules (CD49d, CD18, CD11a, CD11b, L-selectin) or of the chemokine receptor CCR3, but decreased CD49d and CCR3 was observed in eosinophils treated with higher concentrations of this lectin. In vivo, allergen-challenged Gal-1–deficient mice exhibited increased recruitment of eosinophils and CD3+ T lymphocytes in the airways as well as elevated peripheral blood and bone marrow eosinophils relative to corresponding WT mice. Further, these mice had an increased propensity to develop airway hyperresponsiveness and displayed significantly elevated levels of TNF-α in lung tissue. This study suggests that Gal-1 can limit eosinophil recruitment to allergic airways and suppresses airway inflammation by inhibiting cell migration and promoting eosinophil apoptosis.

Two indole-2-carboxamide derivatives attenuate lipopolysaccharide-induced acute lung injury by inhibiting inflammatory response

2018 ◽  
Vol 96 (12) ◽  
pp. 1261-1267
Author(s):  
Wei Dai ◽  
Xiangting Ge ◽  
Tingting Xu ◽  
Chun Lu ◽  
Wangfeng Zhou ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Lung Tissue ◽  
Inflammatory Diseases ◽  
Inflammatory Cells ◽  
Genes Expression ◽  
Tnf Α ◽  
Induced Changes

Acute lung injury (ALI) is the leading cause of mortality in the intensive care unit. Currently, there is no effective pharmacological treatment for ALI. In our previous study, we reported that Lg25 and Lg26, two indole-2-carboxamide derivatives, inhibited the lipopolysaccharide (LPS)-induced inflammatory cytokines in vitro and attenuated LPS-induced sepsis in vivo. In the present study, we confirmed data from previous studies that LPS significantly induced pulmonary edema and pathological changes in lung tissue, increased protein concentration and number of inflammatory cells in bronchoalveolar lavage fluids (BALF), and increased inflammatory cytokine TNF-α expression in serum and BALF, pro-inflammatory genes expression, and macrophages infiltration in lung tissue. However, pretreatment with Lg25 and Lg26 significantly attenuated the LPS-induced changes in mice. Taken together, these data indicate that the newly discovered indole-2-carboxamide derivatives could be particularly useful in the treatment of inflammatory diseases such as ALI.

Subdural Electrocorticogram Measurement with a Minimally-Invasive Procedure Using an SMA-Manipulated Microelectrode Array

2011 ◽  
Vol 222 ◽  
pp. 313-317 ◽  
Author(s):  
Toshitaka Yamakawa ◽  
Takeshi Yamakawa ◽  
S. Aou ◽  
Satoru Ishizuka ◽  
M. Suzuki ◽  
...  
Keyword(s):  
Minimally Invasive Surgery ◽  
Minimally Invasive ◽  
Microelectrode Array ◽  
Evoked Potential ◽  
Electrode Array ◽  
Invasive Procedure ◽  
Minimally Invasive Procedure ◽  
Subdural Electrode ◽  
Invasive Method

We propose a subdural electrode array guided by a 0.3mm-diamter shape memory alloy guidewire for a minimally-invasive method of electrocorticogram recording. The measured electric characteristics showed that the proposed electrodes are compatible with the application of electrocorticogram recording. Somatosensory evoked potential was measured by the proposed method in the animal test in vivo. The results confirmed that the proposed electrode array is available for the electrocorticogram recording under a minimally-invasive surgery.

scholarly journals Anti-Gout Effects of the Medicinal Fungus Phellinus igniarius in Hyperuricaemia and Acute Gouty Arthritis Rat Models

2022 ◽  
Vol 12 ◽  
Author(s):  
Hongxing Li ◽  
Xinyue Zhang ◽  
Lili Gu ◽  
Qín Li ◽  
Yue Ju ◽  
...  
Keyword(s):  
Rat Model ◽  
Biological Activities ◽  
Chemical Constituents ◽  
Gouty Arthritis ◽  
Therapeutic Effects ◽  
Acute Gouty Arthritis ◽  
Rat Models ◽  
Phellinus Igniarius ◽  
Anti Inflammatory

Background:Phellinus igniarius (P. igniarius) is an important medicinal and edible fungus in China and other Southeast Asian countries and has diverse biological activities. This study was performed to comparatively investigate the therapeutic effects of wild and cultivated P. igniarius on hyperuricaemia and gouty arthritis in rat models.Methods: UPLC-ESI-qTOF-MS was used to identify the chemical constituents of polyphenols from wild P. igniarius (WPP) and cultivated P. igniarius (CPP). Furthermore, WPP and CPP were evaluated in an improved hyperuricaemia rat model induced by yeast extract, adenine and potassium oxonate, which was used to examine xanthine oxidase (XO) activity inhibition and anti-hyperuricemia activity. WPP and CPP therapies for acute gouty arthritis were also investigated in a monosodium urate (MSU)-induced ankle swelling model. UHPLC-QE-MS was used to explore the underlying metabolic mechanisms of P. igniarius in the treatment of gout.Results: The main active components of WPP and CPP included protocatechuic aldehyde, hispidin, davallialactone, phelligridimer A, hypholomine B and inoscavin A as identified by UPLC-ESI-qTOF-MS. Wild P. igniarius and cultivated P. igniarius showed similar activities in reducing uric acid levels through inhibiting XO activity and down-regulating the levels of UA, Cr and UN, and they had anti-inflammatory activities through down-regulating the secretions of ICAM-1, IL-1β and IL-6 in the hyperuricaemia rat model. The pathological progression of kidney damage was also reversed. The polyphenols from wild and cultivated P. igniarius also showed significant anti-inflammatory activity by suppressing the expression of ICAM-1, IL-1β and IL-6 and by reducing the ankle joint swelling degree in an MSU-induced acute gouty arthritis rat model. The results of metabolic pathway enrichment indicated that the anti-hyperuricemia effect of WPP was mainly related to the metabolic pathways of valine, leucine and isoleucine biosynthesis and histidine metabolism. Additionally, the anti-hyperuricemia effect of CPP was mainly related to nicotinate and nicotinamide metabolism and beta-alanine metabolism.Conclusions: Wild P. igniarius and cultivated P. igniarius both significantly affected the treatment of hyperuricaemia and acute gouty arthritis models in vivo and therefore may be used as potential active agents for the treatment of hyperuricaemia and acute gouty arthritis.

scholarly journals Phillygenin Alleviates Lipopolysaccharide-Induced Acute Pneumonia by Modulating the Tumor Necrosis Factor α Signaling Pathway

2021 ◽  
Author(s):  
Cong-jie Wang ◽  
Yu-jun Tan ◽  
Chang-jun Lv ◽  
Zhong Liu ◽  
Gui-min Zhang ◽  
...  
Keyword(s):  
Rat Model ◽  
A549 Cells ◽  
Pregnane X Receptor ◽  
Bioinformatic Analysis ◽  
Luciferase Reporter Assay ◽  
Luciferase Reporter ◽  
Reporter Assay ◽  
Tnf Α ◽  
Acute Pneumonia

Abstract Purpose: There is an urgent need to develop effective anti-pneumonia drugs. Phillygenin (PHI) is derived from Forsythia suspense and possesses anti-inflammation, anti-oxidant bioactivities. In the present study, we aimed to evaluate the therapeutic potential of phillygenin (PHI) on lipopolysaccharide (LPS)-induced acute pneumonia.Methods: The molecular target of PHI was predicted by bioinformatic analysis. Hollow fiber-based ligand fishing (HFLF) strategy and luciferase reporter assay were further used to identify the target of PHI. LPS-induced acute pneumonia rat model and A549 cells model were used to evaluate PHI function. TNF-α pathway and apoptosis associated proteins were detected by Western Blot, immunofluorescence and immunohistochemistry. Cell cycle and cytokines were determined by flow cytometry.Results: The bioinformatic analysis and luciferase reporter assay identified that the target protein of PHI was pregnane X receptor (PXR) PHI could directly bind to PXR protein and inhibit NF-κB P65 activity. PHI significantly decreased the expression of phosphorylated JNK, P38, Erk, P65 in acute pneumonia rat model. PHI also declined the expression of Bax, Caspase-3 and Caspase-9 and repressed lung epithelial cell apoptosis induced by LPS in vivo and in vitro. In addition, PHI inhibited inflammation cytokines production including TNF-α, IFN-γ, IL-6, IL-1β and IL-18.Conclusions: PHI significantly alleviated LPS-induced lung injury in vivo by exerting anti-inflammatory effects. This is the first study to demonstrate that PHI, a small molecule natural product, significantly alleviates LPS-induced acute pneumonia by binding to PXR. Thus, PHI can be a novel therapeutic agent for pneumonia.

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