Pharmacokinetic and Phase I Evaluation of Carboplatin in Dogs

Thirty dogs with spontaneously occurring malignant neoplasms were treated monthly with carboplatin (CBDCA) given as a 30-minute intravenous infusion in a dose escalation study. Twenty-eight dogs were considered evaluable for toxicity. The maximally tolerated dose of CBDCA was conceptually defined as that dose, determined by logistic regression analyses of toxicity data, resulting in a 50% incidence of moderate toxicity (MOD₅₀) or a 5% incidence of severe toxicity (SEV₅). Each designated maximally tolerated dose was calculated for the first course of treatment only and for the first and second courses of treatment combined to estimate cumulative drug toxicity. The MOD₅₀ and SEV₅ for the first treatment course were 340 and 278 mg/M², respectively. MOD₅₀ and SEV₅ values for the first plus second treatment courses were 327 and 231 mg/M², respectively. The nadir of neutrophil and platelet counts occurred approximately 14 days after treatment. The mean neutrophil and platelet values for all dogs experiencing myelosuppression during the first two treatment courses were 1541/μL and 62,600/μL, respectively. Nonparametric pharmacokinetic analysis of plasma CBDCA values suggested that half-life (T_1/2), area-under-the-curve and total body clearance (CL_b) were not dose dependent. Volume of distribution (VD_ss) significantly increased with dose only between 100 and 150 mg/M², not between 150 and 300 mg/M². Dose-independent serum CBDCA pharmacokinetic disposition indicates that detailed investigation of tissue CBDCA distribution would be warranted and may identify novel dosing strategies that could improve the therapeutic index of CBDCA by minimizing toxicity. (Journal of Veterinary Internal Medicine 1993; 7:235–240. Copyright © 1993 by the American College of Veterinary Internal Medicine.)     

Correlated responses from selection for income minus food cost in pullets on traits in older hens

1. After 5 generations of selection on income minus food cost between 21 and 40 weeks of age (SECR), a correlated genetic improvement of 14.5% and 16.3% of the base population mean could be observed for income minus food cost between 41 and 60 weeks (IF60) in two lines of laying hens. The total responses up to 60 weeks amounted to 17.2% and 17.3% of the base population mean. A heritability of 0.30 for IF60 and a genetic correlation of 0.61 between SECR and IF60 were estimated.

2. The correlated relative genetic responses for 5 traits of the period between 41 and 60 weeks of age for the two lines were: 4.3% and 5.2% in egg number, 5.8% and 7.4% in egg weight, 8.4% and 10.8% in egg mass, ‐2.7% and ‐0.6% in body weight at 60 weeks, and ‐5.2% and ‐6.3% in food efficiency.

3. The estimated heritabilities of these 5 traits from the whole data set were 0.36, 0.75, 0.34, 0.71 and 0.17. The estimated genetic correlations between SECR and the same 5 traits were 0.30, 0.46, 0.61, ‐0.22 and ‐0.49.

4. A high genetic correlation of income minus food cost with egg weight and a low one with egg number were found in pullets, but the relationships were reversed in older hens.     

Influence of site and variety on starch,hemicellulose and cellulose composition of wheats and their digestibilities by adult cockerels

1. It has been shown that both the variety of wheat and the environment under which growth took place influenced the quantities of starch and cell wall carbohydrate contents of wheat.

2. The different varieties of wheat investigated contained different proportions of water‐soluble to water‐insoluble hemicelluloses.

3. By comparison of the arabinose to xylose ratios it was concluded that water‐soluble and insoluble arabinoxylans of wheat were branched to the same degree.

4. Starch from six wheat varieties grown in the U.K. was very well digested by adult cockerels and true metabolisable energy values of the wheats were high.

5. Small amounts of cell wall carbohydrates were digested by adult cockerels.     

Effects of an induced pause in egg production and supplementation of the diet with iron on egg shell colour,quality and performance of brown egg layers

1. A pause in egg production was induced in brown‐egg laying hens, aged 68 weeks, by feeding them whole oats for 7 d. Subsequently, these hens, together with control groups, were given laying diets with either 400 or 600 mg/kg iron. The 200 mg/kg of supplemental iron was added in the form of either ferrous sulphate or iron proteinate (chelated iron).

2. The feeding of whole oats halted egg production in 5.7 ±0.22 d and the duration of the pause was 8.3 ±0.78 d.

3. The induction of a pause improved the subsequent rate of egg production, egg output, efficiency of food utilisation, albumen quality, egg specific gravity and shell colour. It also increased food intake and body weight gain but neither egg weight nor the rate of mortality were affected.

4. Neither supplementation of the diet with iron nor its source had any significant effect on laying performance, egg quality or shell colour.     

Studies on acid oils and fatty acids for chickens. III. Effect of chemical composition on metabolisable energy of by‐products of vegetable oil refining

1. Fourteen by‐products of oil refining, selected for their variability in free fatty acid and unsaponifiable contents, were analysed chemically with the objective of relating the determined ME values of the products to chemical composition by means of multiple linear regression analysis. Refined sunflower oil was included as a reference fat.

2. Twenty‐one 2‐week‐old chicks were used to determine fat digestibilities and AMEn values of diets, using the total collection method. Fats were included in a wheat‐soyabean meal diet at 100 g/kg. Multiple linear regression analysis was used to express the ME values of fats as functions of the parameters measured (moisture, gross energy, impurities, unsaponifiables, non eluted material, free fatty acid content, unsaturated: saturated ratio, peroxide value, TBA test).

3. The ME of the fat products lay in the range 12.62 to 24.35 MJ/kg, and 29.26 MJ/kg for refined sunflower oil. Free fatty acid content of the fats was shown to be a poor predictor of their ME values, whereas non eluted material (NEM) of the fat products showed a good correlation with their ME. A regression equation could be derived (R² = 0.6548; SEE = 2–0064) with the unsaturated: saturated ratio (U:S) and NEM. An ME prediction equation based on the U:S, NEM and unsaponifiable content is also proposed (R² = 0–7168; SEE= 1.9058).     

Effects of cultivar,pelleting and enzyme addition on nutritive value of barley in poultry diets

1. The effect of pelleting process and Trichoderma viride enzymes (TVE) addition on apparent metabolisable energy, corrected for nitrogen balance (AMEn) and on productive value of practical diets containing 40 and 45% of three different barley cultivars and one wheat were studied in poultry.

2. The effect of the pelleting process on AMEn was inconsistent and was dependent on the cereal included and the addition of enzyme.

3. The growth trial showed a significant effect of enzyme addition to pelleted diets over the whole growth period (0 to 42 d). Addition of TVE improved weight gain and food efficiency by 1.3% and 2.9%, respectively and decreased food intake by 1.6% between 0 and 22 d. In the finisher period (23 to 42 d) TVE improved efficiency by 2.8% and reduced food intake by 2.9%.

4. The incidence of sticky droppings was related to the viscosity of barley used, and enzyme supplementation reduced it. Both pelleting and enzyme addition increased dry matter content of excreta.

5. At the end of the experiment, 14 animals per treatment were slaughtered and carcass yield, viscera weight and abdominal fat were determined.     

Rapeseed meal and egg taint: Treatment of rapeseed meal to reduce tainting potential

1. Treatment of rapeseed meal with calcium hydroxide suspension decreased the sinapine content by up to 90%. Smaller decreases were obtained by autolysis, steaming and treatment with ammonia.

2. When this treated meal was fed to susceptible ("tainting") hens the concentration of trimethylamine in the eggs was decreased to much less than that required to cause taint.     

Effect of injecting amino acids into the egg on embryonic and subsequent growth in the domestic fowl

1. The growing embryo uses about 1% of the total protein available in the egg during the first week of incubation.

2. Injecting the growing embryo with amino acids equivalent to the amount of protein used resulted in higher weight of chicks at all stages up to 56 d.     

Cellular changes in the granulosa layer of the maturing ovarian follicle of the domestic fowl

1. The relationships between length, width and height of the maturing ovarian follicle of the domestic fowl (Gallus domesticus) are shown.

2. During the rapid‐growth phase (yolk deposition) of the oocyte, i.e. an increase in size from about 9 mm diameter to 35 mm diameter, there is about a 15‐fold increase in its surface area. During this time the number of granulosa cells adjacent to the oocyte increases by about 5‐fold.

3. The granulosa cells become flatter during the growth period of the follicle, consequently increasing their surface area adjacent to the oocyte by about 3‐fold.

4. Together the change in shape of the granulosa cells and the increase in their number account for the increase in area of the granulosa layer during follicular growth.

5. Measurement of the DNA content of the granulosa layer indicated a progressive decrease in the cellular content of DNA as the follicle matures.