Acute hepatic steatosis: a helpful diagnostic feature in metallic phosphide-poisoned horses.

Metal phosphides, particularly zinc and aluminum phosphide, occasionally poison horses and other equids following their use as rodenticides and insecticides. Grain-based aluminum phosphide baits are used to control rodents such as prairie dogs. The clinical course in intoxicated horses is short (<24-48 h), and animals may be found dead. Hepatic lesions caused by phosphine poisoning are not well described. Laboratory confirmation depends on detecting phosphine gas in gastric contents. Eight horses and a mule were exposed to zinc phosphide used to control prairie dogs on a Wyoming ranch. Three of 9 exposed equids developed some combination of sweating, ataxia, anxiety, and colic; 2 died acutely, and 1 recovered. A diagnosis of zinc phosphide was made by detecting phosphine in stomach contents from a horse and a mule. The liver was pale and swollen in the affected horse, which died after a clinical course of ~12 h. Other changes were generalized congestion and edema, pulmonary edema, and acute cerebrocortical edema. There was diffuse hepatocellular microvesicular steatosis. Similar histologic lesions were present in 7 equine livers from 2 previously published episodes of metallic phosphide poisoning. Older lesions (>24 h of clinical signs) had centrilobular hepatic necrosis with congestion and a mixture of microvesicular and macrovesicular steatosis. Phosphine poisoning should be considered in horses that die acutely and are found to have steatosis, either with or without hepatocellular necrosis.

Amyloid Precursor Protein Haploinsufficiency Preferentially Mediates Brain Iron Accumulation in Mice Transgenic for The Huntington's Disease Mutation.

BACKGROUND: Huntington's disease (HD) is an autosomal dominant disorder caused by a CAG expansion in the huntingtin gene that results in expression of mutant huntingtin protein. Iron accumulates in HD brain neurons. Amyloid precursor protein (APP) promotes neuronal iron export. However, the role of APP in brain iron accumulation in HD is unclear. OBJECTIVE: To determine the effects of APP insufficiency on HD in YAC128 mice. METHODS: We crossed APP hemizygous mice (APP+/-) with YAC128 mice that are transgenic (Tg) for human mutant huntingtin (hmHTT) to generate APP+/+ hmHTT-/-, APP+/- hmHTT-/-, APP+/+ hmHTT+/- and APP+/- hmHTT+/- progeny. Mice were evaluated for behavioral, biochemical and neuropathology HD outcomes at 2-12 months of age. RESULTS: APP heterozygosity decreased cortical APP 25% and 60% in non-Tg and Tg mice, respectively. Cerebral and striatal iron levels were increased by APP knockdown in Tg mice only. Nest-building behavior was decreased in Tg mice; APP knockdown decreased nest building in non-Tg but not Tg mice. Rota-rod endurance was decreased in Tg mice. APP+/- hHTT+/- mice demonstrated additional decreases in rota-rod endurance from 4-10 months of age. Tg mice had smaller striatal volumes and fewer striatal neurons but were not affected by APP knockdown. CONCLUSIONS: APP heterozygosity results in greater decreases of cortical APP in Tg versus non-Tg mice. Mutant huntingtin transgenic mice develop brain iron accumulation as a result of greater suppression of APP levels. Elevated brain iron in Tg mice was associated with a decline in motor endurance consistent with a disease promoting effect of iron in the YAC128 model of human HD.