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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X-Rays -Allergic Bronchopulmonary Aspergillosis (ABPA) with 3 relapses.
A female patient JO (50 yrs) with right middle lobe collapse. The patient presented with a 6 month history of cough which has persisted despite antibiotics and both steroid and salbutamol inhalers. She then developed acute breathlessness with coughing and wheezing. There was no history of asthma. Bronchoscopy (Image K) showed a mucous plug obstructing the right upper lobe bronchus.
Images D – G are X rays showing relapse in 1998 and recovery
Images H – J are X rays showing relapse in 2003
Image K. Bronchoscopy appearance of mucous impaction of the bronchus intermedius – pt JO (50yrs). There was a long mucous plug in the anterior segment of the RUL. Half of this was aspirated and sent for microscopy and culture. The second half “fell into” the bronchus intermedius (which feeds the right middle lobe) and was only partially aspirated.
Images L – O: High resolution CT scan of thorax in pt JO, post bronchoscopy. 1.5mm sections at 1 cm intervals of whole lung. There is collapse and consolidation in the right middle lobe with dilation of the right middle lobe bronchi. There is also minor bronchiectasis in the right upperlobe with a little patchy air space shadowing . There is no mediastinal lymphadenopathy or any interstitial fibrosis.
Image P & Q: Histology: Mucous plug (3x 0.5x 0.5cm) containing numerous inflammatory cells, including eosinophils and nuclear debris.GMS staining reveals occasional fungal hyphae with septa and dichotomous branching. These appearances support the diagnosis of bronchopulmonary Aspergillosis. Bronchioalveolar lavage fluid was negative on microscopy and no fungi were grown. A year later Aspergillus fumigatus was grown from her sputum.
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