Intermediary syndrome

In cases of attempted suicide, often fatal intoxications occur where, in spite of early hospitalization, patients are beyond remedy. Initially, signs of recovery may be observed, but after 2-3 days patients relapse with a measurable increase in OP plasma concentrations. This phenomenon is called intermediary syndrome (IMS), first described by Senananyake et al. in 1987, and is possibly a consequence of a severe intoxication with permanent depolarization of the neuromuscular end-plates and constant excitation of the nicotinic acetylcholine receptors in the CNS of the patient. The IMS is clinically characterized by acute respiratory paresis, weakness of facial, palatal, external ocular, nuchal and proximal limb muscles and depressed tendon reflexes. Some authors propose that an insufficient therapy with oximes or atropine (see Section 9.2.5) and inadequate artificial respiration in the early stages of intoxication may cause the occurrence of an IMS. It is further remarkable that only some distinct OP agents (e.g. fenthion, dimethoate, monocrotophos and methamidophos) seem capable of producing the IMS. 

Abbreviations CBP, CREB binding protein CREB, cAMP response element binding protein FAT, factor acetyltransferase HAT, histone acetyltransferase MEL, mixed lineage leukaemia protein MORE, MOZ related factor MOZ, monocytic leukaemia zinc finger protein PHD, plant homeodomain RTS, Rubinstein-Taybi syndrome, TIE, transcription intermediary factor... 

In addition to altering the activities of enzymes from the MFO system in the liver, 2,3,7,8-TCDD also alters the activities of some key liver enzymes of the intermediary metabolism. These effects are intimately related with the wasting syndrome as discussed below (see Body Weight Effects). For example, 2,3,7,8-TCDD decreased the activities of hepatic PEPCK and G-6-Pase (key enzymes of gluconeogenesis) in mice and rats (Fan and Rozman 1995 Li and Rozman 1995 Viluksela et al. 1994 Weber et al. 1995) and also reduced the activity of TdO (key enzyme of tryptophan metabolism) in rats (Li and Rozman 1995 Viluksela et al. 1994), but not in mice (Weber et al. 1995). 

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