Aspects of protein metabolism and its controlAspects de la régulation du métabolisme des protéinesAspekte des Proteinstoffwechsels und seiner Kontrolle

Protein metabolism is a highly integrated process. The rates of deposition in a tissue depend on the balance between synthesis and degradation. While a lot is known about the factors controlling synthesis, e.g. amino acid supply, availability of messenger RNA, much less is known about the factors controlling degradation. Both these processes are markedly affected by hormones. When considering protein metabolism in the context of attempting to determine the factors controlling growth, it is essential to consider its integration between organs.     

Biliary secretion of 14C and identification of 5,6-dihydro-5,6-dihydroxycarbaryl glucuronide as a biliary metabolite of [14C]carbaryl in the rat

The biliary secretion of ¹⁴C was observed in conscious, bile-fistulated rats given single oral doses of [¹⁴C]carbaryl (1.5, 30, and 300 mg/kg). Over 94% of the ¹⁴C was absorbed after 12 hr. From 15 to 46% of the ¹⁴C was secreted in bile, 10–40% in urine, and less than 1% in feces 12 hr after dosing. Three metabolites were isolated from bile and identified by mass and/or NMR spectrometric methods. These metabolites were: 5,6-dihydro-5,6-dihydroxycarbaryl glucuronide (12–18% of the biliary ¹⁴C), a conjugate(s) of carbaryl (12% of the biliary ¹⁴C), and conjugated isomers of hydroxy-carbaryl (2% of the biliary ¹⁴C). The majority of the biliary ¹⁴C remains to be identified.     

Host association, on-host longevity and egg production of Ctenocephalides felis felis

Host association, on-host longevity and egg production of Ctenocephalides felis felis (Bouché) were evaluated using fleas from a commercial laboratory colony and first generation, laboratory-reared, native Indiana fleas. Fleas were placed on cats that were declawed, fitted with Elizabethan collars and housed in specially designed metabolic cages. An average of 85% of the female and 58% of the male fleas stayed continuously on the cats for at least 50 days, indicating that the cat flea is a permanent ectoparasite. The maximum longevity of the cat flea was not determined, but it was shown that it can survive and reproduce on the cat for at least 113 days. A female cat flea may produce up to 1745 eggs during a 50-day period.     

Differential activity of cythioate against female and male Ctenocephalides felis on cats.

A study was conducted to determine whether cythioate, a systemically active insecticide, has different activity against male and female Ctenocephalides felis, the cat flea. Eighteen cats were allotted equally to 1 control and 2 treatment groups and infested on day 0 with fixed ratios of male and female cat fleas. Cats in the untreated control group and treatment group 2 were infested with 50 fleas with a female-to-male ratio of approximately 2:1. Cats in treatment group 1 were infested with 50 fleas with a female-to-male ratio of 1:1. Cythioate was administered orally to cats in the treatment groups at the dosage of 3.6 mg/kg of body weight once daily on days 0 and 3. Fleas remaining after treatment were removed, sexed, and counted on day 5. The efficacy of cythioate after 2 dosings was 82.8 and 33.4% against female and male fleas, respectively. The greater activity against female fleas resulted in post-treatment female-to-male ratios in treatment groups 1 and 2 of 0.32:1 and 0.54:1, respectively. Fleas recovered from untreated control cats had a final female-to-male ratio of 2.27:1. Total population control efficacies for treatment groups 1 and 2 were 61.7 and 67.6%, respectively.     

The immunopathogenesis of flea allergy dermatitis in dogs, an experimental study

In this study, we investigated the development of clinical disease and immune responses in the development of an experimental model of flea allergy dermatitis. Dogs were randomly divided into four treatment groups and were infested with fleas on two different feeding schedules (continuous and episodic). Group 1 consisted of four non-exposed dogs (negative controls) and Group 2 consisted of six dogs exposed to fleas continually. Groups 3 and 4 consisted of 14 dogs each that were exposed to fleas on an episodic schedule (two consecutive days every other week for 12 weeks). Group 4 also received intraperitoneal injections of a low dose of lectin (ricin) with immunomodulatory properties. The purpose of Group 4 was to investigate the effects of ricin on enhancing the development of clinical signs, flea antigen-specific IgE levels and altering the number of CD4+ and CD8+ T cell subsets in peripheral blood. Clinical signs developed in all flea exposed dogs, however, the dermatology lesion scores were less and shorter in duration for continuously exposed dogs compared to episodic exposed dogs, independent of ricin treatment. Lesion development was concentrated in the flea triangle and consisted principally of erythema, followed by alopecia, excoriation, papules, and crusts. CD4+ and CD8+ lymphocyte subsets or IgE levels were not altered by ricin treatment. Flea antigen-specific IgE values were highest in dogs exposed to fleas on a continuous basis compared to those episodically exposed. A greater percentage of clinical responder dogs with negative flea-specific IgE titers or negative intradermal test (IDT) were present in the episodic exposure groups than in the continuous exposure group. IgE titers corresponded slightly better with clinical responders than the IDT. The agreement between the IgE titers and IDT was good (weighted K = 0.67). Histopathology of skin samples were consistent with a Type I hypersensitivity. In conclusion, we were able to develop a model of flea allergy dermatitis by experimentally exposing dogs to fleas on an episodic and continuous feeding schedule. In this study, continuously exposed dogs did not develop immunotolerance, and ricin did not enhance the development of FAD.     

Protein metabolism in animals treated with anabolic agents

One of the major factors controlling the deposition of protein in an animal is the activity of the hormones circulating in its blood. Many of the anabolic hormones interact with each other e.g. growth hormone and insulin and there is evidence for a direct interaction between catabolic and anabolic hormones e.g. testosterone and glucocorticoids. Exogenously administered hormone-like substances can have marked effects on animal growth. Diethyl stilbestrol acts like an oestrogen elevating plasma insulin and growth hormone concentration. Zeranol probably also acts in a similar way.Trenbolone acetate (TBA) an androgenic agent, is a very effective growth promotor especially in ruminants. Few changes of note in the endogenous plasma hormone concentrations in treated ruminants have been reported although the combined implant of TBA plus 17-oestradiol did depress plasma thyroxine in steers. We have used the rat as a model to test the effects of TBA on protein synthesis and protein degradation rate in the muscle of rats. Protein synthesis and protein degradation in the muscle of treated female rats was shown to be markedly reduced, the increased growth rate being brought about by a greater reduction in the rate of degradation than in the rate of synthesis. Cathepsin D activity in the muscle was also reduced. Attempts to demonstrate a direct action of TBA on muscle have been unsuccessful. The currently favoured hypothesis for the mode of action of TBA is that it interferes with catabolic action of glucocorticoids on muscle protein. This may not be the mode of action of all androgenic agents. Durabolin (nandrolone phenyl propionate) would appear to stimulate both protein synthesis and protein degradation, at least in the rat.