Trichothecenes treatment

Some microorganisms are also able to transform trichothecenes into less toxic compounds. For example, rumenal bacteria, bacteria from the large intestine of chickens, and bacterial populations from soil samples, were capable of transforming deoxynivalenol into 3-acetyldeoxynivalenol or 3-keto-4-deoxynivalenol (Binder et ah, 2000 Swanson et ah, 1987 He et ah, 1993 Shima et ah, 1997). Therefore, it seems likely that the development of wheat crops with the capability of eliminating this mycotoxin or bio-treatments could possibly be developed as a feasible strategy. 

Respiratory, skin, and eye protection is required for personnel working with trichothecenes. There are no specific therapies for trichothecene toxicoses. Neither vaccines nor specific antidotes are readily available. Treatment in people and animals is symptomatic and supportive, and the only known prophylactic measure is avoidance of exposure (Fricke and Poppenga, 1989 National Academy of Science, 1983). T-2 toxin is stable in the environment, and resistant to heat and ultraviolet light. 

Several woikers have observed differences in the stereoselectivity of the reactions of (1) and (2) with ketones related to the trichothecene family of natural products (Scheme 4). Reaction of ketone (12) with (1) stereoselectively led to epoxide (13), whereas ylide (2) gave (14) instead. Very high dia-stereoselection was obtained in the late stages of a synthesis of (+)-phyllanthocin treatment of ketone... 

The defined geometry of these steps has permitted the synthesis of some cycloheptane acids related to terpenoid natural products. The key reaction was the rearrangement of a suitably substituted bicy-clo[4.2.0]octane. Thus the photoaddition of ethylene to 3-methylcyclohexenone gave the ketone (42), which was converted to the alcohol (43). On treatment with HgO and HBF4 this gave the unstable hydroxy aldehyde (44), which was readily oxidized to the dicarboxylic acid (45 Scheme 17).- Ring expansion methodology was also used in an approach to the synthesis of the trichothecenes (see Scheme 18).32... 

In all these cases the responses observed in plants are, upon treatment with the trichothecenes, very similar to those seen in plants. Among those genera that have been claimed to produce trichothecenes are Acremonium (11), Cylindrocarpon (11), Dendrostilbella (12), Fusarium (11), Myrothecium (11), TrichoTerma (11), Trichothecium (11), and of these Cylindrocarpon, Fusarium, Myrothecium, and Trichothecium are plant pathogens ... 

Many trichothecenes contain ester groups, whereas others contain alcoholic 0-H groups. The ester part of trichothecenes is hydrolyzed to alcohols when heated with dilute alkalies. Treatment with concentrated acid or rigorous boiling in water can open up the epoxy ring. 

In contrast to treatment for exposure to any of the other toxins, simply washing the skin with soap and water within 1 to 3 hours after exposure to the trichothecene mycotoxins will eliminate or greatly reduce the risk of illness or injury. 

In areas that have experienced a yellow rain attack, environmental assays have been in the range of 1 to 150 parts per million (ppm) and blood samples in the range of 1 to 296 parts per billion (ppb).8"1016 22 In the laboratory, at 10 and 50 minutes after an intramuscular exposure to 0.4 mg/kg of T-2 toxin in the dog, plasma concentrations of T-2 toxin were 150 and 25 ppb, and for HT-2 toxin were 50 and 75 ppb, respectively.60 Thus, any screening procedure for trichothecene mycotoxins in biomedical samples must have detection limits of 1 to 100 ppb. Most of the analytical procedures require extraction and cleanup treatment to remove interfering substances.73... 

No specific therapy for trichothecene-induced mycotoxicosis is known or is presently under experimental evaluation. Several therapeutic approaches have been evaluated in animal models. It is perhaps significant, however, that although experimental procedures for treatment of systemic exposure have been successful in reducing mortality in animal models, they have not been tested in primates. Thus, these treatments are not available for field use for humans exposed to trichothecene mycotoxins. 

Symptomatic measures for the treatment of exposure to trichothecene mycotoxins are modeled after the care of casualties of mustard poisoning.85 Irrigation of the eyes with large volumes of isotonic saline may assist in the mechanical removal of trichothecene mycotoxins, but would have limited useful therapeutic effects. After the skin has been decontaminated, some erythema may appear, accompanied by burning and itching. Most casualties whose skin has been treated with soap and water within 12 hours of exposure will have mild dermal effects these should be relieved by calamine and other lotion or cream, such as 0.25% camphor and methanol. 

Prophylactic induction of enzymes involved in the conjugation of xenobiotics reduced or prevented the acute toxic effects of T-2 toxin in the rat, while inhibition of these enzymes resulted in a higher toxicity for this trichothecene.96 Pretreatment with flavonoids,97 ascorbic acid,98 vitamin E," selenium,100 or chemoprotective compounds such as emetine101 that block trichothecene-cell association all reduce acute toxicity of these mycotoxins. However, none of these chemoprotective treatments have undergone extensive efficacy studies to evaluate their ability to protect against an aerosol or dermal exposure to trichothecene mycotoxins. 

Capillary Columns for SFC-MS. At present, the major limitation to broad application of capillary SFC technology is related to the availability of columns compatible with supercritical fluid mobile phases. The fused silica capillary columns used in this work were deactivated and coated with crosslinked and surface-bonded stationary phases using techniques similar to those reported by Lee and coworkers (40,41). Columns from less than 1 m to more than 20 m in length and with inner diameters of 10 to 200 ym have been examined. Colvimn deactivation was achieved by purging with a dry nitrogen flow at 350 C for several hours followed by silylation with a polymethylhydrosiloxane. Any unreacted groups on the hydro-siloxane were capped by treatment with chlorotrimethylsilane at 250 C. After deactivation, the columns were coated with approximately a 0.15-.25 ym film of SE-54 (5Z phenyl polymethylphenyl-siloxane) or other polysiloxane stationary phases. The coated stationary phases were crosslinked and bonded to the deactivation layer by extensive crosslinking with azo-t-butane (41). The importance of deactivation procedures for elution of more polar compounds, such as the trichothecenes, has been demonstrated elsewhere (42). 

No specific therapy for trichothecene mycotoxin poisoning is currently available. Skin decontamination with soap and water or the hypochlorite- (M258A1) or resin-based (M291) military decontamination kits can effectively remove toxin up to six hours after exposure, although none of them neutralize the toxin. Treatment of respiratory, dermal, and GI effects currently must be symptom based and supportive in nature. Superactive activated charcoal, for example, a common treatment for many orally taken poisons, has been shown to bind 0.48 mg T-2/gm charcoal in mice and improve survival rates significantly. 

In 1986, Kraus [129], Gilbert [130] and VanMiddlesworth [131] all reported application of the Ireland-Claisen rearrangement in syntheses of the trichothecenes trichodiene and bazzanene. In each case the diastereoselectivity of the rearrangement was minimal as a result of a lack of stereoselectivity in the enolization of the ester. The Kraus synthesis is illustrative (Scheme 4.136). Treatment of the cyclo-... 

The preparation of the branched C-pyranoside 27, which is structurally related to trichothecenes, has been carried out by treatment of the thionoformate 28 (prepared in several steps from 2,3,4,6-tetra-0-acetyl-2-hydroxy-D-glucal) with tributyltin hydride. Also described are the tricyclic compounds 29, prepared from an intermediate used for the synthesis of 27. 

Roridin E, roridin A and myrotoxin A+B all produced necrotic spots on detached leaves of muskmelon (Fig ire 2B). Necrosis first appeared 24 hr after inoculation in all treatments except the control but the rate of subsequent chlorotic lesion development surrounding the necrotic spots differed for each trichothecene roridin A induced larger lesion sizes than roridin E, while myrotoxin A+B induced the smallest lesions. All muskmelon genotypes responded similarly to roridin A and myrotoxin A+B but had differential responses to roridin E these responses to roridin E were also highly correlated (r=0.99, P=0.01) with genotype responses... 

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