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.
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A Colonies on MEA after one week, B conidial head x920, C atypical reduced conidial head x920, D conidial head x 920.
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A case of onychomycosis associated with Aspergillus ochraceopetaliformis as described in Med Mycol. 2009 Mar 9:1-5, 2009,Brasch J, Varga J, Jensen JM, Egberts F & Tintelnot K
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Histology of the infected nail (PAS stain) showing thick fungal elements and septate hyphae within nail material.
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culture and identified in a case of onychomycosis – Culture at higher magnification.
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culture and identified in a case of onychomycosis – Culture of Aspergillus ochraceopetaliformis on Sabouraud agar with cycloheximide at 26C
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This patient with chronic cavitary pulmonary aspergillosis was treated with itraconazole, with some success, but considerable gastrointestinal disturbance (diarrhoea, flatulence and uncomfortable feeling in his abdomen). He also developed a facial rash. Itraconazole was stopped and he reverted to voriconazole which he was unable to take because of a severe feeling of being generally unwell. His facial rash resolved. Application was made for funding posaconazole. He started this and after 6 weeks an almost identical facial rash to that seen with itraconazole appeared. He tolerated posaconazole well in other respects, and his chronic cavitary pulmonary aspergillosis is now significantly better (symptomatically and serologically). July 2007
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This patient with ABPA and chronic cavitary pulmonary aspergillosis has been stabilized on voriconazole treatment for >5 years. She had a degree of photosensitivity most of that time, noticed early in the course of voriconazole treatment. She is oxygen and wheelchair dependent and doesn’t go outside very much, so most of her light exposure has been indoor light. She developed rough scaly patches over her face, neck and lower arms. Dermatological review indicated multiple solar keratoses”. Skin biopsy from the right forearm confirmed this clinical diagnosis – “skin showing hyperkeratosis with a little parakeratosis and acanthosis. The keratinocytes have a glassy appearance but show nuclear atypia with dyskeratotic cells, and occasional suprabasal mitoses. The intraepidermal sweat ducts are spared. Appearances suggest an actinic keratosis with moderate to severe dysplasia.” These features are characteristic of a low grade premalignant change.
She was treated with local 5-fluorouracil cream (Efudix) (3 cycles) to the affected lesions. These photos were taken at the apogee of inflammation. The inflammation resolved after discontinuing the cream. This reaction is expected with application of this mild chemotherapy agent. Alternative or supplementary treatments include cryotherapy, curettage and cautery, if necessary. Following treatment her skin was much softer and considerably improved. Voriconazole has been stopped, and posaconazole substituted.
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