Side effects of selection for growth in laboratory animalsEffets secondaires de la selection pour la croissance chez les animaux de laboratoireUnerwünschte Nebenwirkungen der Selektion auf Wachstum bei Labortieren

Correlated responses are examined from a biological rather than from a biometrical point of view. Selection for increased body weight in laboratory animals usually, though not always, leads to increases in food intake, gross efficiency and fat deposition, while some aspects of fertility are usually impaired. Increases in fatness are more pronounced in older animals, possibly because selection for early growth requires a high food intake which is not correspondingly reduced as the accretion of lean tissue slows down. Further, fat deposition may be an alternative to heat output, which explains why increases in both fat deposition and in gross efficiency may not be incompatible. It is concluded that many of the adverse side effects of selection for growth are the physiological consequences of increased fatness. In terms of applications to domestic livestock, it is suggested that the undesirable side effects should be controlled managementally by restricting food intake, on the grounds that the simultaneous avoidance of deleterious effects would unduly impair the efficiency of selection for increased growth.     

Luteinizing hormone concentrations in serum of postpartum beef cows injected with microencapsulated luteinizing hormone-releasing hormone analog

Twenty-five cows were divided equally into five groups to determine whether [D-Trp6]-luteinizing hormone releasing hormone (LHRH-A) microencapsulated in poly (DL-lactide co-glycolide) would increase basal serum concentrations of LH during the postpartum period. On d 5 postpartum, cows were injected i.m. with 2 ml of vehicle alone (Group 1) or vehicle containing microcapsules calculated to release .4, 1.6, 6.4 or 25.6 micrograms LHRH-A per day for approximately 30 d (Groups 2, 3, 4 and 5, respectively). Cows were bled every 15 min for 4 h immediately before and after injection and every 15 min for 4 h at weekly intervals for the next 4 wk to evaluate serum profiles of LH. Estrus was determined by twice daily observations and confirmed by serum progesterone. More cows in Groups 2, 3, 4 and 5 exhibited pulsatile patterns of LH after LHRH-A injection than in Group 1 (P less than .06). More pulses of LH were observed after LHRH-A injection in Groups 4 and 5 than in Group 1 (P less than .01). Mean concentrations of LH within treatment groups did not change during the initial injection, except in Group 5. All cows in Group 5 had a surge of LH immediately after injection. The induced surge of LH in two cows in Group 5 cows resulted in progesterone profiles similar to those during a normal luteal phase. Days to first postpartum estrus were not different among the five treatment groups. Microencapsulated LHRH-A given at a dose estimated to release 25 micrograms LHRH-A/d was effective in elevating LH concentrations following injection. However, effectiveness of this hormonal treatment in shortening postpartum anestrus was not substantiated.     

Pulmonary epithelial lining fluid and plasma ascorbic acid concentrations in horses affected by recurrent airway obstruction

OBJECTIVE: To determine the pulmonary epithelial lining fluid (ELF) concentrations and degree of oxidation of ascorbic acid in horses affected by recurrent airway obstruction (RAO) in the presence and absence of neutrophilic airway inflammation. ANIMALS: 6 RAO-affected horses and 8 healthy control horses. PROCEDURE: Nonenzymatic antioxidant concentrations were determined in RBC, plasma, and ELF samples of control horses and RAO-affected horses in the presence and absence of airway inflammation. RESULTS: ELF ascorbic acid concentration was decreased in RAO-affected horses with airway inflammation (median, 0.06 mmol/L; 25th and 75th percentiles, 0.0 and 0.4 mmol/L), compared with RAO-affected horses without airway inflammation (1.0 mmol/L; 0.7 and 1.5 mmol/L) and control horses (2.2 mmol/L; 1.4 and 2.2 mmol/L). Epithelial lining fluid ascorbic acid remained significantly lower in RAO-affected horses without airway inflammation than in control horses. Moreover, the ELF ascorbic acid redox ratio (ie, ratio of the concentrations of dehydroascorbate to total ascorbic acid) was higher in RAO-affected horses with airway inflammation (median, 0.85; 25th and 75th percentiles, 0.25 and 1.00), compared with RAO-affected horses without airway inflammation (0.04; 0.02 and 0.22). The number of neutrophils in bronchoalveolar lavage fluid was inversely related to the ELF ascorbic acid concentration (r = -0.81) and positively correlated with the ascorbic acid redox ratio (r = 0.65). CONCLUSIONS AND CLINICAL RELEVANCE: Neutrophilic inflammation in horses affected by RAO is associated with a reduction in the ELF ascorbic acid pool. Nutritional supplementation with ascorbic acid derivatives in horses affected by RAO is an area for further investigation.     

Effect of thalidomide on growth and metastasis of canine osteosarcoma cells after xenotransplantation in athymic mice

OBJECTIVE: To determine whether thalidomide inhibits the growth of primary and pulmonary metastatic canine osteosarcoma in mice after xenotransplantation. ANIMALS: Athymic nude mice. PROCEDURE: Canine osteosarcoma cells were injected SC in 50 mice. Mice were randomly placed into the following groups: control group (n = 13; DMSO [drug vehicle] alone [0.1 mL/d, IP]); low-dose group (12; thalidomide [100 mg/kg, IP]), mid-dose group (13; thalidomide [200 mg/kg, IP]); and high-dose group (12; thalidomide [400 mg/kg, IP]). Starting on day 8, treatments were administered daily and tumor measurements were performed for 20 days. On day 28, mice were euthanatized and primary tumors were weighed. Lungs were examined histologically to determine the number of mice with metastasis and tumor emboli. Mean area of the pulmonary micrometastatic foci was determined for mice from each group. RESULTS: Primary tumor size and weight were not significantly different among groups. The number of mice in the mid-dose (200 mg/kg) and high-dose (400 mg/kg) groups with micrometastasis was significantly less than the number of control group mice; however, the number of mice with tumor emboli was not affected by thalidomide treatment. Size of micrometastasis lesions was not affected by thalidomide treatment. CONCLUSIONS AND CLINICAL RELEVANCE: Mean area of micrometastases was not affected by treatment; however, growth of micrometastases had not yet reached an angiogenesis-dependent size. Although thalidomide did not affect growth of primary tumors in mice after xenotransplantation of canine osteosarcoma cells, our findings indicate that thalidomide may interfere with the ability of embolic tumor cells to complete the metastatic process within the lungs.     

Effect of increasing levels of undegradable intake protein on metabolic and endocrine factors in estrous cycling beef heifers

To determine the influence of three levels of undegradable intake protein (UIP) supplementation on metabolic and endocrine factors that influence reproduction, 23 yearling crossbred heifers (body condition score = 4.5 +/- 0.5; initial BW = 362 +/- 12 kg) were stratified by BW and assigned randomly to one of three supplements: 1) low UIP (1,135 g x heifer(-1) x d(-1); 30% CP, 115 g UIP, n = 7); 2) mid UIP (1,135 g x heifer(-1) x d(-1); 38% CP, 216 g UIP, n = 8); or 3) high UIP (1,135 g x heifer(-1) x d(-1); 46% CP, 321 g UIP, n = 8). Heifers were estrually synchronized before initiation of supplementation. Supplement was individually fed daily for 30 to 32 d, at which time heifers were slaughtered (d 12 to 14 of the estrous cycle) and tissues collected. Heifers were fed a basal diet of sudan grass hay (6.0% CP) ad libitum. On d 28 of supplementation (d 10 of the estrous cycle), no differences were observed (P > 0.10) in serum insulin or IGF-I among treatments. At slaughter (d 10 to 12 of the estrous cycle), treatments did not influence corpus luteum weight, cerebral spinal fluid leptin, or IGFBP; serum estradiol-17beta, progesterone, leptin, IGF-I, and IGFBP; or anterior pituitary content of IGFBP (P > 0.10). Follicular fluid IGFBP-2 and IGFBP-4 were greater in high-UIP heifers than low- or mid-UIP heifers on d 12 to 14 of the estrous cycle (P < 0.05). Basal serum LH concentrations and LH area under the curve (every 15 min for 240 min) did not differ (P > 0.10) following 28 d of supplementation (d 10 of the estrous cycle); however, basal serum FSH concentrations were greater (P = 0.06) in low- and mid- vs. high-UIP heifers (5.2 and 5.2 vs. 4.6 ng/mL, respectively), and FSH area under the curve was greater (P = 0.03) in low- vs. high-UIP heifers. At slaughter (d 12 to 14 of the estrous cycle), anterior pituitary LH and FSH content and steady-state mRNA encoding alpha, LHbeta, and GnRH receptor did not differ (P > 0.10) among treatments. However, FSHbeta mRNA was increased approximately twofold (P = 0.03) in mid vs. low UIP. In summary, low and mid levels of UIP supplements fed to estrous cycling beef heifers seemed to enhance pituitary expression and/or secretion of FSH relative to high levels of UIP. Moreover, high-UIP supplementation was associated with increased low-molecular-weight IGFBP compared with supplementation of low and mid levels of UIP. These data suggest that differing levels of UIP supplementation may alter pituitary and ovarian function, thereby influencing reproductive performance in beef heifers.     

Pesticide residues in food--acute dietary exposure

Consumer risk assessment is a crucial step in the regulatory approval of pesticide use on food crops. Recently, an additional hurdle has been added to the formal consumer risk assessment process with the introduction of short-term intake or exposure assessment and a comparable short-term toxicity reference, the acute reference dose. Exposure to residues during one meal or over one day is important for short-term or acute intake. Exposure in the short term can be substantially higher than average because the consumption of a food on a single occasion can be very large compared with typical long-term or mean consumption and the food may have a much larger residue than average. Furthermore, the residue level in a single unit of a fruit or vegetable may be higher by a factor (defined as the variability factor, which we have shown to be typically x3 for the 97.5th percentile unit) than the average residue in the lot. Available marketplace data and supervised residue trial data are examined in an investigation of the variability of residues in units of fruit and vegetables. A method is described for estimating the 97.5th percentile value from sets of unit residue data. Variability appears to be generally independent of the pesticide, the crop, crop unit size and the residue level. The deposition of pesticide on the individual unit during application is probably the most significant factor. The diets used in the calculations ideally come from individual and household surveys with enough consumers of each specific food to determine large portion sizes. The diets should distinguish the different forms of a food consumed, eg canned, frozen or fresh, because the residue levels associated with the different forms may be quite different. Dietary intakes may be calculated by a deterministic method or a probabilistic method. In the deterministic method the intake is estimated with the assumptions of large portion consumption of a 'high residue' food (high residue in the sense that the pesticide was used at the highest recommended label rate, the crop was harvested at the smallest interval after treatment and the residue in the edible portion was the highest found in any of the supervised trials in line with these use conditions). The deterministic calculation also includes a variability factor for those foods consumed as units (eg apples, carrots) to allow for the elevated residue in some single units which may not be seen in composited samples. In the probabilistic method the distribution of dietary consumption and the distribution of possible residues are combined in repeated probabilistic calculations to yield a distribution of possible residue intakes. Additional information such as percentage commodity treated and combination of residues from multiple commodities may be incorporated into probabilistic calculations. The IUPAC Advisory Committee on Crop Protection Chemistry has made 11 recommendations relating to acute dietary exposure.