Inhalation of tungsten metal particulates alters the lung and bone microenvironments following acute exposure

2021 ◽  
Author(s):  
Kara Miller ◽  
Charlotte M McVeigh ◽  
Edward B Barr ◽  
Guy W Herbert ◽  
Quiteria Jacquez ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Inflammatory Cytokines ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis ◽  
Whole Body ◽  
Oral Exposure ◽  
Post Exposure ◽  
Whole Body Inhalation ◽  
Pro Inflammatory Cytokines

Abstract Inhalation of tungsten particulates is a relevant route of exposure in occupational and military settings. Exposure to tungsten alloys is associated with increased incidence of lung pathologies, including interstitial lung disease and cancer. We have demonstrated, oral exposure to soluble tungsten enhances breast cancer metastasis to the lungs through changes in the surrounding microenvironment. However, more research is required to investigate if changes in the lung microenvironment, following tungsten particulate exposure, can drive tumorigenesis or metastasis to the lung niche. This study examined if inhalation to environmentally relevant concentrations of tungsten particulates caused acute damage to the microenvironment in the lungs and/or systemically using a whole-body inhalation system. Twenty-four female BALB/c mice were exposed to Filtered Air, 0.60 mg/m3, or 1.7 mg/m3 tungsten particulates (< 1 µm) for 4 h. Tissue samples were collected at day 1 and 7 post-exposure. Tungsten accumulation in the lungs persisted up to 7 days post-exposure and produced acute changes to the lung microenvironment including increased macrophage and neutrophil infiltration, increased levels of pro-inflammatory cytokines IL-1β and CXCL1, and an increased percentage of activated fibroblasts (α-SMA+). Exposure to tungsten also resulted in systemic effects on the bone, including tungsten deposition and transient increases in gene expression of pro-inflammatory cytokines. Taken together, acute whole-body inhalation of tungsten particulates, at levels commonly observed in occupational and military settings, resulted in changes to the lung and bone microenvironments that may promote tumorigenesis or metastasis and be important molecular drivers of other tungsten-associated lung pathologies such as interstitial lung disease.

scholarly journals Analysis of the physical activity effects and measurement of pro-inflammatory cytokines in irradiated lungs in rats

2012 ◽  
Vol 27 (3) ◽  
pp. 223-230 ◽  
Author(s):  
Renata Cristiane Gennari Bianchi ◽  
Eduardo Rochete Ropelle ◽  
Carlos Kiyoshi Katashima ◽  
José Barreto Campello Carvalheira ◽  
Luiz Roberto Lopes ◽  
...  
Keyword(s):  
Physical Activity ◽  
Western Blotting ◽  
Inflammatory Cytokines ◽  
Lower Lobe ◽  
Whole Body ◽  
Control Group ◽  
Western Blotting Analysis ◽  
Blotting Analysis ◽  
Tnf Α ◽  
Pro Inflammatory Cytokines

PURPOSE: To study if the pre-radiotherapy physical activity has radio-protective elements, by measuring the radio-induced activation of pro-inflammatory cytokines as interleukin-6 (il-6), transforming growth factor -β (tgf -β), tumor necrosis factor -α (tnf-α) and protein beta kinase β (ikkβ), through western blotting analysis. METHODS: A randomized study with 28 Wistar hannover rats, males, with a mean age of 90 days and weighing about 200 grams. The animals were divided into three groups: (GI, GII and GIII). GIII group were submitted to swimming for eight weeks (zero load, three times a week, about 30 minutes). Then, the groups (except the control group) were submitted to irradiation by cobalt therapy, single dose of 3.5 gray in the whole body. All animals were sacrificed by overdose of pentobarbital, according to the time for analysis of cytokines, and then a fragment of the lower lobe of the right lung went to western blotting analysis. RESULTS: The cytokines IKK β, TNF-α and IL-6 induced by radiation in the lung were lower in the exercised animals. However, exercise did not alter the radiation-induced increase in tgf-β. CONCLUSION: The results show a lower response in relation to inflammatory cytokines in the group that practiced the exercise pre-radiotherapy, showing that exercise can protect tissues from tissue damage due to irradiation.

scholarly journals Pulmonary function testing in children's interstitial lung disease

2020 ◽  
Vol 29 (157) ◽  
pp. 200019
Author(s):  
Astrid Madsen Ring ◽  
Julia Carlens ◽  
Andy Bush ◽  
Silvia Castillo-Corullón ◽  
Salvatore Fasola ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Pulmonary Function ◽  
Lung Disease ◽  
Pulmonary Function Tests ◽  
Clinical Care ◽  
Whole Body ◽  
Future Research ◽  
Exercise Tests ◽  
Multiple Breath Washout ◽  
Randomised Controlled

The use of pulmonary function tests (PFTs) has been widely described in airway diseases like asthma and cystic fibrosis, but for children's interstitial lung disease (chILD), which encompasses a broad spectrum of pathologies, the usefulness of PFTs is still undetermined, despite widespread use in adult interstitial lung disease. A literature review was initiated by the COST/Enter chILD working group aiming to describe published studies, to identify gaps in knowledge and to propose future research goals in regard to spirometry, whole-body plethysmography, infant and pre-school PFTs, measurement of diffusing capacity, multiple breath washout and cardiopulmonary exercise tests in chILD. The search revealed a limited number of papers published in the past three decades, of which the majority were descriptive and did not report pulmonary function as the main outcome.PFTs may be useful in different stages of management of children with suspected or confirmed chILD, but the chILD spectrum is diverse and includes a heterogeneous patient group in all ages. Research studies in well-defined patient cohorts are needed to establish which PFT and outcomes are most relevant for diagnosis, evaluation of disease severity and course, and monitoring individual conditions both for improvement in clinical care and as end-points in future randomised controlled trials.

scholarly journals OP0213 MYOFASCIA-DOMINANT: INFLAMMATION DETECTED ON WHOLE BODY MRI PREDICTS RAPIDLY PROGRESSIVE INTERSTITIAL LUNG DISEASE IN PATIENTS WITH DERMATOMYOSITIS

2019 ◽  
Author(s):  
Kohei Karino ◽  
Michihiro Kono ◽  
Michihito Kono ◽  
Yuichiro Fujieda ◽  
Masaru Kato ◽  
...  
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Whole Body ◽  
Whole Body Mri

THU0589  ‘KU FEVER’: A CASE REPORT

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 537.1-537
Author(s):  
N. Cernovschi-Feasey ◽  
D. Christidis ◽  
M. Lloyd ◽  
S. Melath ◽  
J. Wajed
Keyword(s):  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Connective Tissue Diseases ◽  
Lymph Node Biopsy ◽  
Axillary Node ◽  
Lower Limbs ◽  
Whole Body ◽  
Low Grade ◽  
Axillary Lymph ◽  
Normal Range

Background:Anti-Ku antibodies have been associated with various connective tissue diseases, including myositis, arthritis, interstitial lung disease and glomerulonephritis1.Objectives:We present a case of a woman initially diagnosed with biopsy proven Kikuchi-Fujimoto disease who later developed a rapidly progressive myositis in association with anti-Ku antibodies.Methods:A 47 year-old woman, originally from Myanmar, presented with lymphadenopathy, myalgia, fatigue, livedo reticularis and low-grade fever for the previous 6 months. This was initially diagnosed as a viral infection. Her myalgia progressed with proximal muscle weakness in both legs and associated rise in creatine kinase levels to 349U/L (normal range 25-200). She also developed dyspnoea, an erythematous rash, mouth ulcers and unintentional weight loss.Blood tests show a lymphopenia and progressively rising CK, with a maximum level of 516 U/L. MRI whole body confirmed a widespread diffuse myositis in her upper and lower limbs, with an unusual ‘speckled’ pattern. High resolution CT Chest was normal. C3 0.40 g/l (normal range 0.75-1.65) and C4 0.12 g/l (0.14-0.54) were low, with a positive ANA (1:160) and Ro-60 antibody. dsDNA, antiphospholipid screen and virology screens were all negative. Extended myositis panel revealed positive anti-Ku antibodies. Axillary lymph node biopsy confirmed necrotising lymphadenitis, consistent with Kikuchi-Fujimoto disease.Results:She was initially treated with low dose Prednisolone and Hydroxychloroquine, with a limited response. Due to progressive myositis, pulsed IV Methylprednisolone 1g was provided over 3 days and mycophenolate mofetil (MMF) was started.An inpatient stay was needed after developing an axillary node abscess and a chest infection. This was treated with intravenous antibiotics and repeated aspirations. Due to progressive myositis on a background of sepsis, intravenous immunoglobulin (IVIG) was administered over 5 days. Our patient made a good recovery, with normalization of CK levels and resolution of the myositis noted on repeat MRI scan. She remains on MMF as maintenance therapy.Conclusion:Anti Ku antibodies appear to be associated with 2 spectrums of disease – elevated CK levels with interstitial lung disease and renal disease associated with anti-dsDNA antibodies1To our knowledge this is the first report in association with Kikuchi-Fujimoto disease. The combination of MMF and IVIG appears to have been effective treatment and her renal function remains stable, although we are monitoring the patient carefully for the possible development of interstitial lung disease.References:[1]Spielmann L, Nespola B, Séverac F, et al. Anti-Ku syndrome with elevated CK and anti-Ku syndrome with anti-dsDNA are two distinct entities with different outcomes. Annals of the Rheumatic Diseases 2019;78:1101-1106.Disclosure of Interests:None declared

scholarly journals COVID-19 Disease and Dermatomyositis: A Mini-Review

2022 ◽  
Vol 12 ◽  
Author(s):  
Jie Qian ◽  
Hui Xu
Keyword(s):  
Immune System ◽  
Interstitial Lung Disease ◽  
Inflammatory Response ◽  
Lung Disease ◽  
Inflammatory Cytokines ◽  
Early Identification ◽  
Poor Prognosis ◽  
Clinical Manifestations ◽  
Immunosuppressive Drugs ◽  
Interstitial Pulmonary Disease

The pandemic of coronavirus disease 2019 (COVID-19) caused by SARS-CoV-2 has caused a large number of deaths, and there is still no effective treatment. COVID-19 can induce a systemic inflammatory response, and its clinical manifestations are diverse. Recently, it has been reported that COVID-19 patients may develop myositis and interstitial pulmonary disease similar to dermatomyositis (DM). This condition is similar to the rapidly progressive interstitial lung disease associated with MDA5+ DM that has a poor prognosis and high mortality, and this poses a challenge for an early identification. Suppression of the immune system can protect COVID-19 patients by preventing the production of inflammatory cytokines. This article attempts to explore the possibility of a relationship between COVID-19 and DM in terms of the potential pathogenesis and clinical features and to analyze the therapeutic effect of the immunosuppressive drugs that are commonly used for the treatment of both DM and COVID-19.

scholarly journals Dietary choline supplementation attenuated high-fat diet-induced inflammation through regulation of lipid metabolism and suppression of NFκB activation in juvenile black seabream (Acanthopagrus schlegelii)

2019 ◽  
Vol 8 ◽  
Author(s):  
Min Jin ◽  
Tingting Pan ◽  
Douglas R. Tocher ◽  
Mónica B. Betancor ◽  
Óscar Monroig ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Inflammatory Cytokines ◽  
High Fat Diet ◽  
Sea Bream ◽  
Lipid Lowering ◽  
Whole Body ◽  
High Fat ◽  
Acanthopagrus Schlegelii ◽  
Dietary Choline ◽  
Pro Inflammatory Cytokines

Abstract The present study aimed to investigate whether dietary choline can regulate lipid metabolism and suppress NFκB activation and, consequently, attenuate inflammation induced by a high-fat diet in black sea bream (Acanthopagrus schlegelii). An 8-week feeding trial was conducted on fish with an initial weight of 8·16 ± 0·01 g. Five diets were formulated: control, low-fat diet (11 %); HFD, high-fat diet (17 %); and HFD supplemented with graded levels of choline (3, 6 or 12 g/kg) termed HFD + C1, HFD + C2 and HFD + C3, respectively. Dietary choline decreased lipid content in whole body and tissues. Highest TAG and cholesterol concentrations in serum and liver were recorded in fish fed the HFD. Similarly, compared with fish fed the HFD, dietary choline reduced vacuolar fat drops and ameliorated HFD-induced pathological changes in liver. Expression of genes of lipolysis pathways were up-regulated, and genes of lipogenesis down-regulated, by dietary choline compared with fish fed the HFD. Expression of nfκb and pro-inflammatory cytokines in liver and intestine was suppressed by choline supplementation, whereas expression of anti-inflammatory cytokines was promoted in fish fed choline-supplemented diets. In fish that received lipopolysaccharide to stimulate inflammatory responses, the expression of nfκb and pro-inflammatory cytokines in liver, intestine and kidney were all down-regulated by dietary choline compared with the HFD. Overall, the present study indicated that dietary choline had a lipid-lowering effect, which could protect the liver by regulating intrahepatic lipid metabolism, reducing lipid droplet accumulation and suppressing NFκB activation, consequently attenuating HFD-induced inflammation in A. schlegelii.

scholarly journals miR181b is induced by the chemopreventive polyphenol curcumin and inhibits breast cancer metastasis via down-regulation of the inflammatory cytokines CXCL1 and -2

2014 ◽  
Vol 8 (3) ◽  
pp. 581-595 ◽  
Author(s):  
Emanuel Kronski ◽  
Micol E. Fiori ◽  
Ottavia Barbieri ◽  
Simonetta Astigiano ◽  
Valentina Mirisola ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Inflammatory Cytokines ◽  
Cancer Metastasis ◽  
Breast Cancer Metastasis ◽  
Down Regulation

Myofascia-dominant involvement on whole-body MRI as a risk factor for rapidly progressive interstitial lung disease in dermatomyositis

Rheumatology ◽  
2020 ◽  
Vol 59 (7) ◽  
pp. 1734-1742
Author(s):  
Kohei Karino ◽  
Michihiro Kono ◽  
Michihito Kono ◽  
Keita Sakamoto ◽  
Yuichiro Fujieda ◽  
...  
Keyword(s):  
Risk Factors ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Respiratory Symptoms ◽  
Serum Creatine Kinase ◽  
Whole Body ◽  
Abnormal Signal ◽  
Whole Body Mri ◽  
Abnormal Signal Intensity ◽  
Independent Risk Factors

Abstract Objective Rapidly progressive interstitial lung disease (RPILD) is a major cause of death in patients with DM. Although clinically amyopathic DM (CADM) represents risk for RPILD, the incidence rate of RPILD in patients with CADM varies widely. Whole-body (WB) MRI can reveal involvement of systemic muscle and myofascia. The objective of this study was to explore the risk factors for RPILD in patients with DM using WB-MRI. Methods This retrospective study comprised 41 patients with DM who underwent WB-MRI before the initiation of treatment in our hospital. Muscular and myofascial signals were scored on 42 muscular groups. The myofascia/muscle ratio was calculated and used to define the relevance of myofascia-dominant involvement. RPILD was defined as worsening of dyspnoea, hypoxaemia and radiographic ILD/fibrosis within 3 months from the onset of respiratory symptoms. Results Among the 41 patients, 17 had CADM and 30 had ILD, including 10 patients with RPILD. All patients including those with CADM showed abnormal signal intensity in both muscle and myofascia (median score: 15 and 23, respectively). Muscle signal scores positively correlated with the serum creatine kinase level (r = 0.714; P< 0.001). Patients with RPILD showed a significantly higher myofascia/muscle ratio than those without RPILD (1.929 vs 1.200; P= 0.027). Logistic regression analysis identified higher myofascia/muscle ratio as independent risk factors for developing RPILD. Conclusion Myofascia-dominant involvement was defined and appreciated in patients with DM using WB-MRI. This may be one of the risk factors for RPILD.

Cytokine synergy, collagenases and cartilage collagen breakdown

2003 ◽  
Vol 70 ◽  
pp. 125-133 ◽  
Author(s):  
Tim E. Cawston ◽  
Jenny M. Milner ◽  
Jon B. Catterall ◽  
Andrew D. Rowan
Keyword(s):  
Matrix Metalloproteinases ◽  
Inflammatory Cytokines ◽  
Activator Protein 1 ◽  
Activator Protein ◽  
And Cartilage ◽  
Pro Inflammatory Cytokines

We have investigated proteinases that degrade cartilage collagen. We show that pro-inflammatory cytokines act synergistically with oncastatin M to promote cartilage collagen resorption by the up-regulation and activation of matrix metalloproteinases (MMPs). The precise mechanisms are not known, but involve the up-regulation of c-fos, which binds to MMP promoters at a proximal activator protein-1 (AP-1) site. This markedly up-regulates transcription and leads to higher levels of active MMP proteins.

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