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Altered Regulation of Fibrinolysis in Scleroderma and Potential for Thrombolytic Therapy
Published in Pia Glas-Greenwalt, Fibrinolysis in Disease Molecular and Hemovascular Aspects of Fibrinolysis, 2019
Marvin J. Fritzler, David A. Hart
Lung involvement occurs in approximately 75% of patients.31 However, progressive lung disease leading to respiratory failure is surprisingly uncommon.32-34 A pattern of restrictive ventilatory defects and a reduced diffusing capacity for carbon monoxide is the most common finding.35-37 Early in the course of lung disease, an inflammatory component is present.38-40 This may be manifest as an alveolitis with large numbers of macrophages, lymphocytes, neutrophils, and eosinophils in bronchoalveolar aspirates.39-43 At autopsy, diffuse alveolar, interstitial, and pleural fibrosis are commonly observed. Pulmonary hypertension of varying severity brought on by gradual obliteration of the pulmonary vascular bed is typically observed in patients with widespread skin involvement.1 By comparison, approximately 5% of patients with the limited form of cutaneous disease develop severe pulmonary arterial hypertension with cor pulmonale that typically occurs in the relative absence of pulmonary fibrosis.1,44 This form of pulmonary disease is characterized by subintimal proliferative changes and medial hypertrophy of small pulmonary arteries.45
Pathogenic role of antigen-antibody complexes
Published in Gabriel Virella, Medical Immunology, 2019
Gabriel Virella, George C. Tsokos
The clinical expression of IC disease depends on the target organs where the deposition of IC predominates: The kidney is very frequently affected (SLE, mixed cryoglobulinemia, chronic infections, poststreptococcal glomerulonephritis, purpura hypergammaglobulinemia, serum sickness, etc.), usually with glomerulonephritis as the prevailing feature.The joints are predominantly affected in rheumatoid arthritis.The skin is affected in cases of serum sickness, mixed cryoglobulinemia, purpura, and vasculitis.The large vessels are affected by the subendothelial formation of antigen-antibody complexes containing oxidized LDL and the corresponding antibodies, leading to the development or progression of atherosclerosis.The lungs are affected in extrinsic alveolitis.
The Interstitial Pneumonias
Published in Lourdes R. Laraya-Cuasay, Walter T. Hughes, Interstitial Lung Diseases in Children, 2019
Organization of the inflammatory infiltrate with deposition of collagen and fibroblastic proliferation follows.1,2 Resolution can be partial or complete. The inflammatory cells of the alveolitis can destroy connective tissue. The neutrophil and alveolar macrophage can produce significant amounts of collagenase, elastase, and glycosaminoglycans which attack connective tissue macromolecules.11 Destruction of connective tissue can also occur by alteration in the antiprotease system. Several of these enzymes have been obtained from bronchoalveolar lavage specimens from patients with idiopathic pulmonary fibrosis.12 This increase in connective tissue in the lung leads to fibrosis when incompletely resolved. Thereafter, chronic respiratory failure can ensue and progress gradually to ultimate death.
Pulmonary toxicity and gene expression changes in response to whole-body inhalation exposure to multi-walled carbon nanotubes in rats
Published in Inhalation Toxicology, 2022
Tina M. Sager, Christina M. Umbright, Gul Mehnaz Mustafa, Jenny R. Roberts, Marlene S. Orandle, Jared L. Cumpston, Walter G. McKinney, Theresa Boots, Michael L. Kashon, Pius Joseph
The 45 (mg/m3)h cumulative dose group of rats had minimal histological changes, i.e., small areas of focal alveolitis and airway epithelial hyperplasia in less than 25% of the MWCNT-7 exposed rats (Figure 3(B)). No granulomatous lesions were detected in this group of rats. Intra-alveolar macrophages were elevated in all exposed rats but at a much less prominent level compared with the higher dose groups of rats. Small focal areas of alveolitis with slightly increased cellularity and alveolar thickness was seen sporadically in some of the control, air exposed rats which is considered as background lesions (Figure 3(A)). The lung histology of the rats exposed to the lowest, 22.5 (mg/m3)h cumulative dose of MWCNT-7, was similar to that of the control, air exposed rats (micrograph not presented).
Protective and anti-inflammatory effect of selenium nano-particles against bleomycin-induced pulmonary injury in male rats
Published in Drug and Chemical Toxicology, 2021
Rana Shahabi, Ali Anissian, Seyed Ali Javadmoosavi, Farinaz Nasirinezhad
The right lung fixed for one week in 10% (w/v) buffered formaldehyde solution at room temperature; the tissue was dried in graded ethanol and fixed in paraffin. The paraffin-embedded tissues were cut to 4-μm thicknesses with a microtome. Stained with hematoxylin and eosin (H&E) for evaluation of histopathological changes, and Masson’s trichrome staining was performed to identify the density of the accumulated collagen fibers. All slides were examined by a certified histologist (blinded manner) using an LX400 light microscope (LaboMed, Fremont, CA) at 400 magnifications. The degree of alveolitis and inflammation was reviewed by the method suggested by Szapiel et al. (1979) (Table 2). A total of 10 fields in each slide and 10 slides in each rat were examined. The mean score of all fields in each section was considered as the inflammatory score.
Scleroderma-related interstitial lung disease: principles of management
Published in Expert Review of Respiratory Medicine, 2019
Aparna Das, Anupam Kumar, Andrea Valeria Arrossi, Subha Ghosh, Kristin B. Highland
Systemic corticosteroids have to be used cautiously and sparingly in patients with SSc-ILD due to increased risk for development of scleroderma renal crisis [32]. The majority of studies of corticosteroids in SSc are for treatment of musculoskeletal symptoms and use low doses. Hoyles et al. utilized low dose prednisolone in their study that compared cyclophosphamide followed by azathioprine, versus placebo [20]. A statistical trend towards improvement was noted in the treatment arm, but cannot be deciphered to be a corticosteroid effect. Other smaller studies have demonstrated efficacy of higher doses of steroids in patients with active alveolitis (presence of ground glass opacities) [33]. In all of these studies, steroids were used as combination or adjuvant therapy with other immunosuppression, confounding the results [33,34]. Despite the lack of data favoring its use, corticosteroids are widely used in the treatment of SSc-ILD [35]. However, expert opinion recommends that the use of corticosteroids should be avoided due to the concern for triggering scleroderma renal crisis. Low dose corticosteroids could be considered for patients with extensive ground glass opacities in the lungs (with clinical suspicion of active alveolitis or flare of underlying ILD), only in combination with another immunosuppressant agent, but never as monotherapy. Patients need to be carefully monitored for the development of scleroderma renal crisis.