Delayed functional disability in dystrophic chickens receiving chemotherapy

Abstract

Line 413 early-onset, genetically homozygous dystrophic chickens were given twice-daily intraperitoneal injections of the antiserotoninergic drug cinanserin, alone or in combination with methysergide. Other trials consisted of penicillamine treatment in combination with either methysergide or cyproheptadine. Chemotherapy significantly prolonged the righting ability of treated dystrophic chickens, as measured by a periodic standardized flip-test procedure. Plasma creatine kinase activities were not affected by any of the various drug treatments. However, the blood serotonin levels of the dystrophic chickens (grand mean 1.47 microgram serotonin/ml blood) were found to be significantly higher (p less than 0.001) than those in the corresponding normal chickens (0.99 microgram/ml). This finding may partially account for the antiserotoninergic drug enhancement in righting ability that was demonstrated in the drug-treated dystrophic chickens.

In Vivo Effects of Protease Inhibitors on Chickens with Hereditary Muscular Dystrophy

“…1). As seen here, and has been reported extensively elsewhere (19)(20)(21), the untreated dystrophic control Line 413 chickens reached an optimal FN around day 30 ex ovo and subsequently declined. However, leupeptin-treated chickens maintained a perfect FN of five for 2 additional wk before decreasing in righting ability.…”

“…The incubation conditions and subsequent care and maintenance of the mostly female chicks were as previously described (18)(19)(20)(21).…”

“…The functional assessment ofmuscle strength was measured with the extensively described flip test procedure (18)(19)(20)(21). In brief, each drug-treated and untreated control chicken was given a standardized test for righting from the supine position every 5 d between 1300 and 1500 h. The number of successful attempts to regain an upright position scored out of five consecutive opportunities was defined as the flip number (FN).…”

“…As previously described (20), each muscle sample was excised, weighed, and placed in an isometric clamp before immersion in 4% paraformaldehyde, fixed for 18-24 h, and embedded in paraffin. 4-6-,um sections were stained with hematoxylin, eosin, and Masson's trichrome.…”

“…The purpose of the present study was to investigate further the effects in vivo of individual protease inhibitors on the genetically dystrophic Line 413 chicken within an established, standardized, drug screening program (18)(19)(20)(21). Reported here is new evidence for limited degrees of drug-related improvements in a functional test for righting ability and plasma CPK levels, and in muscle mass and histology.…”