Polioencephalomalacia (PEM) was induced in calves by feeding a semipurified, low-roughage diet of variable copper and molybdenum composition. Two formulations resulting in Cu-insufficient and Cu-sufficient forms of the diet were fed (n = 10 and 4 calves, respectively); both diets induced PEM. Clinical signs of disease developed as early as 15 days after transition to the experimental diets and included impaired vision, decreased response to external stimuli, and abnormal gait. Grossly evident cerebrocortical lesions consisted of laminar areas of cavitation and/or autofluorescence seen under UV illumination. Hepatic Cu concentration was decreased in calves fed the Cu-insufficient diet, but not below normal range. During the course of feeding either diet, rumen pH decreased, rumen volatile fatty acid concentrations increased, rumen and blood lactic acid concentrations increased, and rumen and plasma thiamine concentrations increased. The thiamine pyrophosphate effect on erythrocyte transketolase activitywas unaltered in calves of either diet group. This nutritionally induced form of PEM does not appear to be related to Cu deficiency or reduction in plasmaor rumen thiamine concentration.

Biochemical changes in the small intestine during development of naturally acquired wheat-sensitive enteropathy of Irish Setters were investigated. To distinguish primary biochemical abnormalities from secondary effects of intestinal damage, progeny of affected dogs reared on a normal wheat-containing diet were compared with their own littermates reared on a cereal-free diet and with age-matched clinically normal Irish Setters fed the same wheat-containing diet. Peroral jejunal biopsy specimens were sequentially obtained between weaning and 1 year of age; specific activity and reorientating sucrose density-gradient distribution of organelle marker enzymes were determined. Major primary biochemical abnormalities were not detected in affected progeny. In affected dogs fed wheat, there was a selective, but secondary, loss of the brush border alkaline phosphatase and aminopeptidase N activities. This loss was associated with the development of partial villus atrophy, but represented a specific effect of dietary wheat on the brush border, not merely a nonspecific effect of mucosal damage, because other brush border enzymes, including disaccharidases, were not similarly affected. Increased soluble activities of lysosomal and peroxisomal marker enzymes late in the disease process may represent alterations in these 2 organelles as a secondary consequence of mucosal damage.

Heinz body formation was examined in kittens, in response to consumption of a variety of diets. A commercial salmon-based diet containing 16.5 mg of nitrite, 39 mg of histamine, and 210,000 IU of vitamin A/kg of diet (dry-matter basis) was found to induce Heinz body formation. Purified experimental diets--containing nitrite up to 405 mg/kg; histamine, 50 mg/kg; histamine, 50 mg/kg plus nitrite, 45 mg/kg; or vitamin A, 250,000 IU/kg--failed to induce Heinz body formation. The effect of propylene glycol (PG) on Heinz body formation was examined by giving groups of 6 kittens purified diets containing 5 or 10% PG for 12 weeks. Two additional kittens were fed a commercial soft-moist diet containing PG for 12 weeks. All kittens fed PG developed Heinz bodies, with peak values for erythrocytes containing Heinz bodies being: 28% for kittens of the 10% PG group; 20% for kittens of the 5% PG group; and 36% for kittens of the soft-moist diet group. Kittens did not develop anemia or methemoglobinemia. Heinz body percentage required 6 to 8 weeks to decrease to the pretreatment value of < 1% after diets containing PG were discontinued. 51Chromium-labeled erythrocytes were used to evaluate erythrocyte survival in 4 kittens of the 10% PG-fed group and in 4 control kittens. Kittens with Heinz body formation induced by 10% PG had significantly (P < 0.001) decreased erythrocyte survival, compared with that for controls, with half-life of 8.3 days for kittens of the PG group, compared with 12.6 days for kittens of the control group.

The influence of variable zinc content (29.1, 250, 1,000 and 2,000 mg/kg of dry weight) in a basic diet containing 7.7 mg of copper/kg on the ability of weanling foals to maintain normal copper balance was investigated. Serum copper and zinc concentrations were monitored, and terminal hepatic copper and zinc contents were measured in 4 weanling foals fed the basic diet containing 29.1 mg of zinc/kg and in 2 foals each fed the higher-zinc diets. Foals fed the lower-zinc diets (29.1 and 250 mg/kg) maintained normal serum copper and zinc concentrations for 14 to 15 weeks, whereas those fed the 2 higher-zinc diets became hypocupremic within 5 to 6 weeks and were lame within 6 weeks, owing to cartilaginous disease characteristic of osteochondritis dissecans. Serum zinc concentration in the foals fed the 2 higher-zinc diets increased to > 2 microgram/ml within 2 weeks. Foals fed the high-zinc diets became lame after serum copper concentration had remained at 0.3 microgram/ml for > 1 week. Serum copper concentration in these arthritic foals was less than or equal to 0.2 microgram/ml at the end of the study. In lame foals, fractures of the cartilage of the articular and growth physes occurred through the zone of hypertrophic cells, and varied from bilateral to unilateral and from small to large. Free masses and flaps of cartilage attached to one side were numerous.

Groups of male specific-pathogen-free cats were fed a basal, purified diet (A), with or without 0.45% added magnesium (MgCl2, diet B; MgO, diet C) or 1 of 2 commercial diets (D,E). Urine samples collected for 48 hours after 2 weeks of feeding were analyzed for calcium, magnesium, sodium, potassium, ammonium, sulfate, phosphate, oxalate, and citrate content. Concentrations were used to calculate the negative logarithm of the struvite activity product (pSAP), using a microcomputer-based program for calculation of supersaturation of the urine with crystal solutes. The pSAP value for all samples also was hand-calculated by use of an equation. Consumption of diet B caused a significant (P < 0.05) increase in urine calcium concentration. Total urine phosphate concentration was lower in urine from cats fed diets A, B, or C than in urine from cats fed diets D or E. For the various diets, urine PO4-3 was: 5.3 microM for diet A; 6.3 microM for diet C; 0.9 microM for diet E; 36 nM for diet D, and 0.5 nM for diet B. Consumption of diets B and C caused significant increases in urine magnesium concentration (53.1 nM and 49.1 mM, respectively). Ammonium ion concentration was highest in urine from cats fed diets B and D, 116.2 mM and 100.3 mM, respectively. When the pSAP, hand-calculated assuming ionic strength u = 0.2, was regressed on that calculated by use of the microcomputer program, the coefficient of determination was 0.96 (P less than or equal to 0.01).

Morphologic changes in the small intestine were investigated during development of naturally acquired wheat-sensitive enteropathy in Irish Setters. To distinguish underlying morphologic abnormalities from non-specific effects of intestinal damage, progeny of affected dogs reared on a normal wheat-containing diet were compared with their own littermates reared on a cereal-free diet and with age-matched clinically normal Irish Setters fed the same wheat-containing diet. Peroral jejunal biopsy specimens were taken sequentially between 4 months and 1 year of age. At 4 months of age, there were no differences in villus height, comparing the 3 groups, but increased numbers of intraepithelial lymphocytes and goblet cells were already present in biopsy specimens from the affected Irish Setters fed wheat. Dietary wheat resulted in a progressive reduction in virus height in the jejunum of affected Irish Setters from 6 months onward. Underlying morphologic abnormalities were not found, and the characteristic morphologic changes of this enteropathy were secondary to the presence of dietary wheat. However, development of partial villus atrophy was preceded by increased numbers of intraepithelial lymphocytes and goblet cells.