Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0037116 (silicosis)
 1,822 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

After successful animal studies since 1986, a single left lung transplantation was performed on a 35-year-old male patient with end-stage silicosis in July 1991. The surgical technique was similar to that used by the Toronto Transplant Group, except for some modification in bronchial anastomosis. The donor lung was preserved by simple surface cooling after the administration of heparin, methylprednisolone and PGE1. The ischemic time for the donor lung was 3.5 hours. A cardiopulmonary bypass through the femoral vessels was applied for a duration of 90 minutes. Immediate postoperative complications included massive bleeding, disseminated intravascular coagulation, adult respiratory distress syndrome and acute graft rejection. Fortunately, we overcame these complications through intensive care. Immunosuppression included antilymphocytic globulin, cyclosporine, azathioprine and corticosteroids. The results of this single lung transplantation were satisfactory. The patient was doing well and was able to satisfactorily breathe room air six weeks after the transplantation. Unfortunately, the patient died of opportunistic systemic aspergillosis six months after the transplantation. In conclusion, lung transplantation is an effective treatment for patients with end-stage lung diseases, and the results of this first single lung transplantation in Taiwan are encouraging and promising.
 ...
PMID:Single lung transplantation for end-stage silicosis: report of a case. Lung Transplant Group. 136 97

A murine model of experimental silicosis has been developed after the intratracheal injection of alpha-quartz crystals. Pulmonary inflammation was monitored by increases in wet lung weight and cell number and protein content of the lung lavage fluid; fibrosis was assessed by measuring increases in hydroxyproline content of the lungs. Acute pulmonary cellular inflammation occurred between weeks 1 and 2, followed by a chronic inflammatory response at week 12. Lung hydroxyproline content, an indication of collagen deposition, was initiated as early as 1 week after silica injection and continued to increase steadily over time. The inflammatory and fibrotic changes induced by silica appeared to be a specific effect of the injection of this toxic particulate and not the result of the introduction of a foreign body, because mice injected with silica crystals were found to have significantly greater increases in acute cellular inflammation and chronic collagen deposition than did mice injected with latex beads. A possible role for the immune system in modulating silica-induced damage was suggested by the variability in response of six different strains of mice (C3H/He, CBA/J, Balb/c, DBA/2, C57BL/6, C57BL/10), which differed at specific genetic loci. Both strains with high (DBA/2) and low (C3H/He) response demonstrated similar patterns of inflammation and fibrosis over a period of 12 weeks. This model demonstrates great potential in future studies for elucidating the role of the immune system in the development of pulmonary inflammation and fibrosis induced by toxic inorganic particulates.
 ...
PMID:Kinetics of inflammatory and fibrotic pulmonary changes in a murine model of silicosis. 298 21

The selection of an experimental model for silicosis requires a thorough understanding of many pulmonary parameters specific to the experimental animal (e.g., clearance time, penetration curves, anatomical differences), as well as the strain's sensitivity to different conditions. The pulmonary response of three rat strains (i.e., Fischer 344, Sprague-Dawley, and Wistar) to silica dust was compared using two methods of exposure: intratracheal injection and inhalation. The test period lasted 3 months for injection and 6 and 12 months for inhalation. The histological study of the lung revealed a distinct nodular reaction in Sprague-Dawley and Wistar strains. Intratracheal injections led to the development of fibrotic nodules in Wistar rats, whereas such silicotic nodules were infrequent in injected Fischer 344 rats, and almost absent when exposure was by inhalation. Sprague-Dawley and Fischer 344 rats showed frequent thickening and metaplasia of the alveolar walls near the terminal bronchioles. This tendency was particularly pronounced in rats exposed by inhalation (especially Fischer 344 rats). Macroscopic examination (wet lung weight) and biochemical dosing (lung silica, hydroxyproline, and lipid content) revealed an increase in the various parameters examined in Sprague-Dawley rats relative to the other two strains, regardless of the type of exposure. The histological examination, however, leads us to conclude that the Wistar rats offer the best experimental model for silicosis, because their pulmonary reaction is more characteristic of the human condition than that of the other two strains.
 ...
PMID:In vivo experimental model for silicosis. 1121 22

Multipotent mesenchymal stem cells (MSCs) possess regenerative properties and have been shown to improve outcomes and survival in acute and chronic lung diseases, but there have been some safety concerns raised related to MSC-based therapy. Subsequent studies have demonstrated that many of the regenerative effects of MSCs can be attributed to the MSC-derived secretome, which contains soluble factors and extracellular vesicles (EVs). MSC-derived extracellular vesicles (MSC-derived EVs) replicate many of the beneficial effects of MSCs and contain a variety of bioactive factors that are transferred to recipient cells, mediating downstream signaling. MSC-derived EV therapy holds promise as a safe and effective treatment for pulmonary disease, but there remain many scientific and clinical questions that will need to be addressed before EVs are widely applied as a therapy. To date, the use of MSC-derived EVs as a treatment for lung disease has been conducted primarily in in vitro or pre-clinical animal models. In this review, we will discuss the current published research investigating the use of EVs as a potential therapeutic for acute lung injury/acute respiratory distress syndrome (ALI/ARDS), bronchopulmonary dysplasia (BPD), idiopathic pulmonary fibrosis (IPF), pulmonary arterial hypertension (PAH), asthma, and silicosis.
 ...
PMID:Therapeutic Use of Extracellular Vesicles for Acute and Chronic Lung Disease. 3223 Aug 28