Date: 26 November 2013
Secondary metabolites, structure diagram: Trivial name – gliotoxin
Copyright: n/a
Notes:
Species: A. flavus, A. fumigatus, A. niger, A. terreus, Eurotium chevalieri, Neosartorya pseudofischeriSystematic name: 10H-3,10a-Epidithiopyrazino[1,2-a]indole-1,4-dione, 2,3,5a,6-tetrahydro-6-hydroxy-3-(hydroxymethyl)-2-methyl-, (3R,5aS,6S,10aR)-Molecular formulae: C13H14N2O4S2Molecular weight: 326.393Chemical abstracts number: 67-99-2Selected references: Larsen TO, Smedsgaard J, Nielsen KF, Hansen MA, Samson RA, Frisvad JC. Production of mycotoxins by Aspergillus lentulus and other medically important and closely related species in section Fumigati. Med Mycol. 2007 May;45(3):225-32. Belkacemi, L.; Barton, R. C.; Hopwood, V.; Evans, E. G. V. (CORPORATE SOURCE PHLS Mycology Reference Laboratory, Department of Microbiology, University of Leeds, Leeds, UK). SOURCE Med. Mycol., 37(4), 227-233 (English) 1999 Blackwell Science Ltd. Lewis RE, Wiederhold NP, Lionakis MS, Prince RA, Kontoyiannis DP.J Clin Microbiol. 2005 Dec;43(12):6120-2. Frequency and species distribution of gliotoxin-producing Aspergillus isolates recovered from patients at a tertiary-care cancer center.Toxicity: Gliotoxin posseses a spectrum of biological activities including antibacterial and antiviral activities, and it is also a potent immunomodulating agent. Gliotoxin is also an inducer of apoptotic cell death in a number of cell types, and it has been found to be associated with some diseases attributed directly or indirectly to fungal infections. It is a secondary metabolite produced by a number of Aspergillus and Penicillium species.It is a potent immunosuppressive metabolite and brings about apoptosis in cells. Because of its effects on the immune system it may have a place in transplant surgery. There is limited evidence for its occurrence in moulded cereals. A. fumigatus is a potent pathogen which can colonise the lungs and other body tissues after ingestion of spores. There is some limited evidence that gliotoxin may be formed in situ in such circumstances. hamster LDLo oral 25mg/kg (25mg/kg) Veterinary and Human Toxicology. Vol. 32(Suppl), Pg. 63, 1990.mouse LD50 intraperitoneal 32mg/kg (32mg/kg) Chemotherapia. Vol. 10, Pg. 12, 1965. mouse LD50 intravenous 7800ug/kg (7.8mg/kg) Chemotherapia. Vol. 10, Pg. 12, 1965. mouse LD50 oral 67mg/kg (67mg/kg) Chemotherapia. Vol. 10, Pg. 12, 1965. mouse LD50 subcutaneous 25mg/kg (25mg/kg) Chemotherapia. Vol. 10, Pg. 12, 1965. rabbit LDLo intravenous 45mg/kg (45mg/kg) VASCULAR: BP LOWERING NOT CHARACTERIZED IN AUTONOMIC SECTION. GASTROINTESTINAL: HYPERMOTILITY, DIARRHEA Journal of the American Chemical Society. Vol. 65, Pg. 2005, 1943. rat LDLo intravenous 45mg/kg (45mg/kg) Veterinary and Human Toxicology. Vol. 32(Suppl), Pg. 63, 1990.rat LDLo unreported 50mg/kg (50mg/kg) BEHAVIORAL: ALTERED SLEEP TIME (INCLUDING CHANGE IN RIGHTING REFLEX) Journal of the American Chemical Society. Vol. 65, Pg. 2005, 1943.
Images library
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This 24-year-old male with AML on chemotherapy developed recent onset fever and cough. B- Representative section of High Resolution CT shows centri-lobular nodules, ‘tree-in-bud’ appearance consistent with bronchogenic spread of disease.
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This 24-year-old male with AML on chemotherapy developed recent onset fever and cough. A: Chest radiograph showing patchy air space consolidation involving both lungs.
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This man with severe chronic fibrosing alveolitis underwent a single left lung transplant at the end of November 2004. Postoperatively he developed reperfusion pulmonary oedema and was difficult to ventilate. He also developed acute renal failure requiring haemodialysis/haemofiltration which corrected his fluid overload and rising creatinine.Rejection was prevented with cyclosporin, mycophenolate and a decreasing dose of methylprednisolone. Cardiovascular problems identified mild pulmonary anastomostic stenosis with a 5% pressure gradient. He had a tracheostomy about 12 days post transplant. He then developed episodes of hypoxia and increased ventilatory pressures. Several bronchoscopies showed mucus plugging in the trachea and major bronchi. These were aspirated, with improvement of oxygenation. Cultures of one of these plugs grew A. fumigatus. These images show a bronchoscopy view of the trachea and anastomosis. Major obstruction of the airway is visible (70%) distal to the anastomosis which looks healthy. Some evidence of tracheal inflammation is visible.
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The chest x-ray shows a patient who had a left lung transplanted in May 2003 for cryptogenic fibrosing alveolitis, which was diagnosed post-transplant as sarcoidosis.
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Tracheal aspergillosis. Bronchoscopic views of the trachea showing nodules in the trachea that revealed Aspergillus on biopsy. The patient had chronic lymphocytic leukaemia treated with fludarabine and corticosteroids and presented with wheezing and bilateral alveolar shadows.
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Tracheal aspergillosis, Bronchoscopic views of the trachea showing nodules in the trachea that revealed Aspergillus on biopsy. The patient had chronic lymphocytic leukaemia treated with fludarabine and corticosteroids and presented with wheezing and bilateral alveolar shadows.
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Tracheal aspergillosis. Bronchoscopic views of the trachea showing nodules in the trachea that revealed Aspergillus on biopsy. The patient had chronic lymphocytic leukaemia treated with fludarabine and corticosteroids and presented with wheezing and bilateral alveolar shadows.
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Tracheal aspergillosis. Bronchoscopic views of the trachea showing nodules in the trachea that revealed Aspergillus on biopsy. The patient had chronic lymphocytic leukaemia treated with fludarabine and corticosteroids and presented with wheezing and bilateral alveolar shadows.
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Aspergillus tracheobronchitis in a normal child. This figure, drawn in 1890, illustrates the appearances of the trachea and main bronchi at autopsy in a 3 year old child. She had little else wrong at autopsy other than a minor degree of tuberculosis. She is the first recorded case of Aspergillus tracheobronchitis in the literature and illustrates well that this disease can affect previously well non-inimmunocompromised people. The full case is reported in Wheaton SW.
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pt FT. Normal chest radiograph of patient with extensive pseudomembranous Aspergillus tracheobronchitis, 4 days before death.
