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The trichothecenes, simple and Macrocyclic (3–4 rings to which an ethylene oxide ring is attached), are secondary metabolities of a group of fungi, which cause severe toxicoses via damage to eukaryotic cells by interfering with ribosomal structure and/or activity. In the sample trichothecenes, the ethylene oxide ring is protected against premature opening, i.e. against inactivation, by a bridge between the oxygen in ring B and the hydroxyl group at position 3 in ring C. If the latter is absent, as in certain macrocyclics, the trichothecenes are of little toxicity, but in the toxic members of the Macrocyclic series a different, still unknown protective mechanisms is involved.

AbstractThe trichothecene mycotoxins are secondary metabolites, produced by a variety of species of fungi, and are contaminating various agricultural commodities. The toxicity of the trichothecenes has been tested by several methods of systemic applications. The toxic effects of trichothecenes, introduced directly into the rat brain, are much more selective and specific than the toxic actions, evoked by peripheral applications. In vitro, the enzymatic conversion of T-2 toxin by brain homogenate is largely restricted, as compared to the metabolic changes in the mammalian body as a whole. In vivo, slight modifications of the substituents, attached to the fundamental ring system A-C of the trichothecenes, cause marked variations in cerebral toxicity. This is particularly noteworthy for the macrocyclic trichothecenes, where relatively small changes in the large ring D cause more than a hundred fold variation in toxicity.

1. Electrical stimulation in the posterior medulla of the unanesthetised rabbit shows diffuse distribution and intermingling of pressor and depressor points.2. Transverse transections, caudally of the hypothalamus, convert the majority of bulbar pressor responses into depressor reactions. This effect is similar to the barbiturate-induced reversal of hypertensise responses.3. It is assumed that medullary pressor neurons act mainly through higher brain centers, while the bulbar depressor elements have chiefly descending connections to the spinal cord, in addition to some ascending links.

1. Blood pressure changes, evoked by stimulation of peripheral nerves, decline if the frequency of stimulation passes beyond the optimal range. Instability of a response develops progressively and is ascribed to the increasing influence of inhibitory components in a given circuit.2. Unstable reactions can be converted into sustained responses by two methods: a by intermittent stimulation, which prevents the inhibitory effects to summate to their threshold value; and b by application of barbiturate, which produces selective block of inhibitory transmission.3. With graded doses of nembutal, a double reversal of the blood pressure response to sciatic stimulation can be produced. This phenomenon is interpreted on the basis of the complex composition of the nerve, which sends fibres to autonomic centres in the hypothalamus and the medulla.