Numerous outbreaks of porcine focal symmetrical poliomyelomalacia (PFSP) of unknown etiology have been described. This syndrome is characterized neuropathologically by bilateral necrosis of the neurons and supporting structure in the anterior horns of the cervical and lumbar/sacral intumescens and various brain stem nuclei. Australian workers, sparked by the similarity of the neuropathological lesion in 6 widely separated outbreaks of PFSP in their country to neuropathological lesions induced in experimental animals with 6-aminonicontinamide (6-AN), experimentally injected swine with 6-AN and produced PFSP. They concluded that their previous field cases were caused by acute niacin deficiency. The Pennsylvania State University workers reported one large outbreak of PFSP, identical to those of the Australians. High dietary levels of selenium (Se) were incriminated as the etiologic agent. The Pennsylvania State University workers reproduced PFSP with neuropathological lesions identical to those of the Australians, with standard swine growing rations supplemented with 50 ppm Se. The identical nature of the neurological lesions has suggested to us a possible antagonist role for Se in niacin metabolism. High dietary Se levels administered to produce PFSP will be evaluated as a niacin antagonist by measuring specific niacin urinary metabolites. Stimulation of the Se detoxification pathway might be expected to disrupt niacin metabolites which are biochemically processed a similar manner. The administration of high Se levels in pigs selectively damages the anterior horn cells of the cervical and lumber/sacral intumescens. We propose to obtain in-depth information on the neuropathological lesions produced by Se toxicity. In addition, we will obtain important biochemical data on the interraction of Se and niacin in the production of PFSP, especially niacin metabolites. Se, at present, is an aggressively studied micronutrient and has wide ranging implications in comparative medicine, especially its anticarcinogenic potential. It has been recently established that Se toxicity in the U.S. has been associated with the increased use of vitamin and mineral supplements. Presently little current information is available on Se toxicity. Our data should add invaluable information relevant to Se toxicity.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS019841-02
Application #
3399932
Study Section
Toxicology Study Section (TOX)
Project Start
1985-07-01
Project End
1987-12-31
Budget Start
1986-07-01
Budget End
1987-12-31
Support Year
2
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Pennsylvania State University
Department
Type
Earth Sciences/Resources
DUNS #
City
University Park
State
PA
Country
United States
Zip Code
16802
Wilson, T M; Cramer, P G; Owen, R L et al. (1989) Porcine focal symmetrical poliomyelomalacia: test for an interaction between dietary selenium and niacin. Can J Vet Res 53:454-61
Wilson, T M; Hammerstedt, R H; Palmer, I S et al. (1988) Porcine focal symmetrical poliomyelomalacia: experimental reproduction with oral doses of encapsulated sodium selenite. Can J Vet Res 52:83-8