Feeding saponin-containing Yucca schidigera and Quillaja saponaria to decrease enteric methane production in dairy cows.

An experiment was conducted in vitro to determine whether the addition of saponin-containing Yucca schidigera or Quillaja saponaria reduces methane production without impairing ruminal fermentation or fiber digestion. A slightly lower dose of saponin was then fed to lactating dairy cows to evaluate effects on ruminal fermentation, methane production, total-tract nutrient digestibility, and milk production and composition. A 24-h batch culture in vitro incubation was conducted in a completely randomized design with a control (no additive, CON) and 3 doses of either saponin source [15, 30, and 45 g/kg of substrate dry matter (DM)] using buffered ruminal fluid from 3 dairy cows. The in vivo study was conducted as a crossover design with 2 groups of cows, 3 treatments, and three 28-d periods. Six ruminally cannulated cows were used in group 1 and 6 intact cows in group 2 (627 +/- 55 kg of body weight and 155 +/- 28 d in milk). The treatments were 1) early lactation total mixed ration, no additive (control; CON); 2) CON diet supplemented with whole-plant Y. schidigera powder at 10 g/kg of DM (YS); and 3) CON diet supplemented with whole-plant Q. saponaria powder at 10 g/kg of DM (QS). Methane production was measured in environmental chambers and with the sulfur hexafluoride (SF(6)) tracer technique. In vitro, increasing levels of both saponin sources decreased methane concentration in the headspace and increased the proportion of propionate in the buffered rumen fluid. Concentration of ammonia-N, acetate proportion, and the acetate:propionate ratio in the buffered rumen fluid as well as 24-h digestible neutral detergent fiber were reduced compared with the CON treatment. Medium and high saponin levels decreased DM digestibility compared with the CON treatment. A lower feeding rate of both saponin sources (10 g/kg of DM) was used in vivo in an attempt to avoid potentially negative effects of higher saponin levels on feed digestibility. Feeding saponin did not affect milk production, total-tract nutrient digestibility, rumen fermentation, or methane production. However, DM intake was greater for cows fed YS and QS than for CON cows, with a tendency for greater DM intake for cows fed YS compared with those fed QS. Consequently, efficiency of milk production (kg of milk/kg of DM intake) was lower for cows fed saponin compared with controls. The results show that although saponin from Y. schidigera and Q. saponaria lowered methane production in vitro, the reduction was largely due to reduced ruminal fermentation and feed digestion. Feeding a lower dose of saponin to lactating dairy cows avoided potentially negative effects on ruminal fermentation and feed digestion, but methane production was not reduced. Lower efficiency of milk production of cows fed saponin, and potential reductions in feed digestion at high supplementation rates may make saponin supplements an unattractive option for lowering methane production in vivo.

Anti-inflammatory and anti-arthritic effects of Yucca schidigera: a review.

Yucca schidigera is a medicinal plant native to Mexico. According to folk medicine, yucca extracts have anti-arthritic and anti-inflammatory effects. The plant contains several physiologically active phytochemicals. It is a rich source of steroidal saponins, and is used commercially as a saponin source. Saponins have diverse biological effects, including anti-protozoal activity. It has been postulated that saponins may have anti-arthritic properties by suppressing intestinal protozoa which may have a role in joint inflammation. Yucca is also a rich source of polyphenolics, including resveratrol and a number of other stilbenes (yuccaols A, B, C, D and E). These phenolics have anti-inflammatory activity. They are inhibitors of the nuclear transcription factor NFkappaB. NFkB stimulates synthesis of inducible nitric oxide synthase (iNOS), which causes formation of the inflammatory agent nitric oxide. Yucca phenolics are also anti-oxidants and free-radical scavengers, which may aid in suppressing reactive oxygen species that stimulate inflammatory responses. Based on these findings, further studies on the anti-arthritic effects of Yucca schidigera are warranted.

Studies on the use of Yucca schidigera to control giardiosis.

The potential anti-giardial activity of a powdered preparation of Yucca schidigera (yucca powder) was investigated in vitro, in a modified adherence inhibition assay, and in vivo, by enumeration of trophozoites (intestinal) or cysts (fecal) in experimentally infected gerbils and lambs receiving oral doses of whole or butanol-extracted yucca powder. Yucca powder, butanol-, acetone- and chloroform-extracted powder, and the butanol-insoluble fraction of the powder were required in concentrations of 22, 15, 62, 135 and 250 microg/ml, respectively, to reduce in vitro trophozoite adherence by 50%. Ethyl ether extract exhibited no anti-giardial activity. Virtually no trophozoites were tolerant of butanol extract at >or=90 microg/ml. Butanol extract at 1500 microg/ml exerted effects on trophozoites similar to the nitroimidazole, metronidazole, at 40 microg/ml during a 27-h incubation. Reducing trophozoite adherence to 50% of the controls required 5-10h of exposure to butanol extract or metronidazole. Oral administration of butanol extract (6.1mg) or metronidazole (1mg) once daily for 3 days reduced the number of trophozoites in the small intestine of infected gerbils, significantly (P<0.05) in the jejunum and ileum, and numerically (P>0.05) in the duodenum (n=8). Oral dosing of 50mg of butanol extract in eight doses over 3 days reduced (P<0.05) trophozoites in the duodenum and jejunum, and eliminated them from the ileum. Including 4.5% (w/w) yucca powder in the diet did not alter Giardia trophozoite recovery from the duodenum or jejunum of infected gerbils, but trophozoite reduction (P=0.051) was observed in the ileum (n=9). Jejunum gut loop data were inconclusive, possibly due to insufficient duration of exposure of trophozoites to butanol extract. Compared to controls (0g yucca powder per day) lambs receiving 10g of yucca powder per day in their diet shed fewer (P<0.05) Giardia cysts in their feces after 5, 9, 12 and 19 days of treatment, but a corresponding decline in the prevalence of infection was not observed (n=10). After 26 days, Giardia infections persisted in 90% of the lambs in both treatment groups. At the dosing levels studied in vivo, yucca powder did not affect the extent of cyst shedding by experimentally infected lambs, but further purification and concentration of the saponin fraction from Y. schidigera may provide the anti-giardial effects observed in vitro and in dosing trials.

Effect of steroidal saponin from Yucca schidigera extract on ruminal microbes.

The effects of steroidal saponins (SAP) isolated from Yucca schidigera extract on ruminal bacteria and fungi were investigated in pure culture studies. Prevotella bryantii, Ruminobacter amylophilus, Selenomonas ruminantium and Streptococcus bovis were cultured through ten 24-h transfers in ruminal fluid medium containing 0 or 25 microg SAP ml-1 (measured as smilagenin equivalents). The four strains, each non-exposed or pre-exposed to SAP, were then inoculated into medium containing 0 or 250 microgram smilagenin equivalents ml-1 and 24-h growth curves were determined. The cellulolytic ruminal bacteria Ruminococcus flavefaciens, Fibrobacter succinogenes and Rc. albus were cultured for 72 h on Whatman no. 1 filter paper in medium containing 0, 9, 90 or 180 microgram SAP ml-1 for the determination of filter paper digestion and endoglucanase activity. The ruminal bacteria differed in their responses to SAP. Steroidal saponins in the medium reduced the growth of Strep. bovis (P < 0.01 at 2, 3, 4, 5, 6 and 8 h), P. bryantii (P < 0.05 at 4, 5, 6, 8, 10 and 24 h) and Rb. amylophilus (P < 0.05 at 14 and 24 h), but the growth of S. ruminantium was enhanced (P < 0.05) at 10, 14 and 24 h. The growth curves of all four non-cellulolytic species were similar (P > 0.05) between pre-exposed and non-exposed cultures and the concentrations of total SAP and soluble (deglycosylated) SAP in the liquid fraction were unchanged (P > 0.05) over time. Steroidal saponins inhibited the digestion of filter paper by all three cellulolytic bacteria, but F. succinogenes was less (P < 0.05) sensitive to SAP and more (P < 0. 05) effective at deglycosylating SAP than were Rc. flavefaciens or Rc. albus. Transmission electron microscopy revealed that SAP altered the cell walls of the SAP-inhibited non-cellulolytic bacteria. The ruminal fungi, Neocallimastix frontalis and Piromyces rhizinflata, were cultured on filter paper in medium containing 0, 0. 45, 2.25 or 4.5 microgram SAP ml-1. Filter paper digestion by both fungi was completely inhibited by 2.25 microgram SAP ml-1. Steroidal saponins from Y. schidigera inhibit cellulolytic ruminal bacteria and fungi, but their effects on amylolytic bacteria are species dependent and similar to the effects of ionophores. As such, SAP may be useful in nutritional applications targeting starch-digesting ruminal micro-organisms.

Effect of Yucca schidigera on ruminal fermentation and nutrient digestion in heifers.

In a replicated 3 x 3 Latin square experiment, six heifers (443 +/- 6.1 kg) fed a 61% barley grain:39% alfalfa silage diet (DM basis) were given intraruminal doses of powdered Yucca schidigera (YS). Doses of 0 (control), 20, or 60 g/d were given at 0800 daily. Ruminal content was sampled 0, 2, 4, and 6 h after dosing. Acidity, concentrations of reducing sugars, free amino acids, and peptides in the rumen were not affected (P > .05) by YS. Relative to control, ruminal ammonia concentration was reduced (P < .05) 2 h after YS dosing. Ruminal propionate concentration was increased (P < .05) by YS. Protozoal numbers in the rumen were lower (P < .05) with YS than without. Yucca did not affect (P > .05) rate or extent of in situ DM degradability. Fibrolytic, amylolytic, and proteolytic activities in ruminal contents were similar among treatments (P > .05). Dry matter intake, apparent digestibilities of DM, NDF, and CP, nitrogen balance, and microbial protein synthesis in the rumen were not affected (P > .05) by treatment. The effect of YS on ruminal ammonia concentration likely resulted from a decreased concentration of protozoa and, presumably, from ammonia binding by YS. The effect on ruminal propionate was probably a result of a selective inhibitory effect of YS on rumen microbial species.

Shrinking membership in the American Society of Animal Science: does the discipline of poultry science give us some clues?

Concerns have been expressed by the American Society of Animal Science (ASAS) leadership about the declining membership in ASAS. I present the viewpoint that the history of the Poultry Science Association (PSA) membership and the elimination of poultry science departments from many land grant universities could be an indication of what the future holds for animal science. I suggest that the industrialization of poultry production has led to a decline in the demand for traditionally trained poultry scientists. Industrialization of swine production is proceeding rapidly, with other animal-based industries showing the same trend. If maintaining a large ASAS membership is indeed a priority, new opportunities must be developed. Equine and companion animal programs offer such possibilities, tapping into a high level of student interest.

Interactions in sheep between tall fescue ergot alkaloids and hepatotoxic carbon tetrachloride and Senecio pyrrolizidine alkaloids.

The interaction between ergot alkaloids in endophyte-infected (E+) tall fescue (Festuca arundinacea) seed and pyrrolizidine alkaloids (PA) in tansy ragwort (TR; Senecio jacobaea) when simultaneously fed to sheep was investigated. Because of the hepatogenic effects of prolactin (PRL), it was hypothesized that low serum PRL induced by ergot alkaloids would increase the susceptibility of sheep to hepatotoxicity induced by PA. Sheep are normally resistant to PA-induced hepatotoxicity. Twenty-four wether lambs weighing 34.1 +/- 2.3 kg were used after being randomly assigned to 1 of 6 treatments of 4 wethers each. The diets offered were a control basal diet containing endophyte-free (E-) tall fescue seed, control + carbon tetrachloride (CCL4), E+ tall fescue basal diet, E+2CCl4, E(-)+TR, or E+2TR. The diets were composed of 50% alfalfa meal, 34.5% rolled barley, 5% soybean meal, 4% cane molasses, 0.5% trace mineralized salt and 6% tall fescue (E- or E+) seed. In the 2 TR treatments 25% of the alfalfa was replaced by TR. Interaction between ergot alkaloids in E+ tall fescue and PA in TR was assessed by gamma glutamyl transferase (GGTP) activity and/or sulfobromophthalein (BSP) clearance rate, both of which measure liver function. Serum GGTP activity was measured on days 14 and 28; plasma BSP clearance was monitored on days 28 and 70 by collection of blood at 4, 8 and 16 min after i.v. BSP injection. Serum PRL assays were performed on days 14, 70 and 84. Serum GGTP activity was elevated by CCl4 drenching on days 14 and 28. On day 28 TR feeding reduced GGTP activity, but there was no difference between the 2 TR treatments. There was no difference in the mean BSP half-times (t1/2) and % BSP retentions on day 28 among any of the 6 treatments. On day 70, there was no difference in the t1/2 or % BSP retention 4 min after BSP injection among any of the treatments. At 8 min after BSP injection, however, % BSP retention was significantly higher for the control +CCl4 than for the E+2CCl4 treatment. At 16 min after BSP injection, the E+ treatment had a higher mean % BSP retention value than the E+2CCl4 treatment; there were no differences among the other treatments. Serum PRL levels were reduced by E+ or CCl4 on all 3 dates of PRL evaluation. The lack of interaction between ergot alkaloids in E+ tall fescue seed and PA in TR as assessed by GGTP activity and/or BSP clearance in sheep may imply that the target sites o the 2 alkaloids are metabolically different. The low serum PRL with E+ did not increase susceptibility of sheep to CCl4 or PA.

Species differences in the hepatic microsomal enzyme metabolism of the pyrrolizidine alkaloids.

Species differences in pyrrolic metabolites and senecionine (SN) N-oxide formation among eight animal species (sheep, cattle, gerbils, rabbits, hamsters, Japanese quail, chickens, rats) varying in susceptibility to pyrrolizidine alkaloid (PA) intoxication were measured in vitro by hepatic microsomal incubations. The results suggested that there is not a strong correlation between the production of pyrrolic metabolites and susceptibility of animals to PA toxicity. The rate of PA activation in hamsters, a resistant species, measured by formation of (+/-)6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP) far exceeded the rate of SN N-oxide formation (detoxification) (DHP/N-oxide = 2.29). In contrast, SN N-oxide was the major metabolite in sheep, another resistant species, with much lower production of DHP (DHP/N-oxide = 0.26). The roles of cytochrome P450s and flavin-containing monooxygenases (FMO) in bioactivation and detoxification of pyrrolizidine alkaloids (PA) were studied in vitro using sheep and hamster hepatic microsomes. Chemical and immunochemical inhibition data suggested that the conversion of SN to DHP is catalyzed mainly by cytochrome P450s (68-82%), whereas the formation of SN N-oxide is carried out largely by FMO (55-71%). There also appeared to be a high rate of glutathione-DHP conjugation in hamster (63%) and sheep (79%) liver microsomal incubation mixtures. Therefore, low rates of pyrrole metabolite production coupled with glutathione conjugation in sheep may explain the resistance of sheep to SN, whereas the high rate of GSH-DHP conjugation may be one of the factors contributing to the resistance of hamsters to intoxication by this PA.

Do domestic animals have minds and the ability to think? A provisional sample of opinions on the question.

Faculty, staff, and graduate students in a number of departments, students in an undergraduate course, and some groups outside the university were polled to obtain their perceptions about whether domestic animals have minds, the ability to think, and differing degrees of intelligence (the surveys focused only on horses, cows, sheep, dogs, chickens, pigs, cats, and turkeys). A clear majority of all groups surveyed (except the Department of Zoology) said yes, they believe animals have minds, but a substantial number of those in animal sciences and zoology (17 to 25%) said no. A number of others in animal sciences, zoology, and philosophy (11 to 37%) refused to answer the question because the concept of mind was not defined. From 80 to 100% of respondents in other groups said yes to the question of minds. From 67 to 100% of all participants said yes, they perceive that animals have the ability to think, but a substantial number of animal scientists, zoologists, veterinarians, and English faculty said no, animals don't think (6 to 33%). On the question Do domestic animals differ in relative intelligence?, the responses varied from 88% in animal sciences to 100%. Surprisingly, when asked to rank different animal species by intelligence, there was a remarkable degree of similarity across all groups regardless of background; the overall ranking from highest intelligence to lowest was dog, cat, pig, horse, cow, sheep, chicken, and turkey. Most of the respondents believed that the possession of minds, thought, and intelligence were relevant factors in how animals should be treated and the prevalent concept was that we should not be cruel to animals, but should treat them humanely.

The roles of CYP3A and CYP2B isoforms in hepatic bioactivation and detoxification of the pyrrolizidine alkaloid senecionine in sheep and hamsters.

The roles of cytochrome CYP3A and CYP2B isozymes in the bioactivation and detoxification of the pyrrolizidine alkaloid (PA) senecionine (SN) have been investigated in vitro with sheep and hamster hepatic microsomes. Our results show that the rate of SN activation measured by (+/-)-6, 7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP) formation greatly exceeded the rate of SN N-oxide formation (detoxification) in hamsters. In contrast, SN N-oxide, a detoxification product, was the major metabolite in sheep with much lower DHP production. Immunoinhibition studies with anti-sheep CYP3A and CYP2B antibodies show that members of CYP3A subfamily play the major role in the conversion of PA to pyrrolic metabolites in both species (over 90% in sheep; 68% in hamster). These enzymes also contribute 38.8 and 41. 3% of SN N-oxidation in sheep and hamsters, respectively. In contrast, CYP2B isoforms have a limited capacity toward DHP formation in both species (47% in sheep; 32% in hamster), while these enzymes catalyzed only 24.6 and 35.4% SN N-oxidation in sheep and hamster, respectively. Using triacetyloleandomycin (TAO) and gestodene, two highly selective chemical inhibitors of CYP3A isoforms, our data show that 90% of DHP formation was inhibited by either inhibitor in sheep. Gestodene appeared to be more efficient than TAO in the inhibition of DHP production in hamsters. Testosterone 6beta-hydroxylase activity, a functional marker of CYP3A, was significantly inhibited by TAO and gestodene in sheep liver microsomes and by gestodene (100 microM) in hamster liver microsomes. These results suggest that CYP3A isozymes have important roles in bioactivation and detoxification of PA in both species, whereas CYP2B subfamily members are less efficient in biotransformation of PA.

Protein kinase C isoforms in muscle cells and their regulation by phorbol ester and calpain.

Objectives were to identify the PKC isoforms in cultured muscle cells, to examine roles of Ca(2+)-dependent proteinases (calpains) in processing of various muscle PKC isozymes and to obtain a mechanistic description of the processing of PKCs by examining the temporal relationships between phorbol ester-dependent translocation of muscle PKCs and calpains between cytosolic and membrane compartments. Using six isoform (alpha, beta, gamma, delta, epsilon, zeta)-specific polyclonal antibodies, PKC alpha, delta and zeta were detected in rat skeletal muscle and in L8 myoblasts and myotubes. PKC alpha and zeta were primarily localized in the cytosolic fraction of L8 myotubes whereas PKC delta was more abundant in the membrane fraction. Phorbol ester (TPA) caused rapid depletion of myotube PKC alpha and PKC alpha and PKC delta isoforms from the cytosolic compartment and rapid appearance of these isoforms in the membrane fraction. However, long-term exposure of myotubes to TPA eventually caused down-regulation of PKCs in the membrane compartment. Down-regulation of PKCs in the membrane fraction was partially blocked by calpain inhibitor II. However, the rapid TPA-dependent cytosolic depletion of PKCs was unaffected by calpain inhibitor. This suggests that calpains may be responsible for membrane-associated down-regulation of PKCs but not for cytosolic depletion. In the final study we assessed the effects of phorbol ester on compartmentation of m-calpain with PKCs in muscle cells. Like the PKCs, TPA caused rapid association of m-calpain with the membrane fraction followed by down-regulation. This demonstrates that phorbol esters cause translocation of both PKCs and calpains to membranes where processing of PKCs may occur via the limited proteolysis exerted by calpains.

Endogenous toxins and mycotoxins in forage grasses and their effects on livestock.

Plant toxins are the chemical defenses of plants against herbivory. Grasses have relatively few intrinsic toxins, relying more on growth habit to survive defoliation and endophytic fungal toxins as chemical defenses. Forage grasses that contain intrinsic toxins include Phalaris spp. (tryptamine and carboline alkaloids), sorghums (cyanogenic glycosides), and tropical grasses containing oxalates and saponins. Toxic effects of these grasses include neurological damage (Phalaris staggers), hypoxia (sudangrass), saponin-induced photosensitization (Brachiaria and Panicum spp.), and bone demineralization (oxalate-containing grasses). Endophytic toxins in grasses include ergot alkaloids in tall fescue and tremorgens (e.g., lolitrem B) in perennial ryegrass. Lolitrems cause neurological effects, producing the ryegrass staggers syndrome. Annual ryegrass toxicosis is caused by corynetoxins, which are chemically similar to tunicamycin antibiotics. Corynetoxins are produced by Clavibacter bacteria that parasitize a nematode, Anguina agrostis, that may infect annual ryegrass. Corynetoxins inhibit glycoprotein synthesis, causing defective formation of various blood components of the reticulo-endothelial system. Another mycotoxin in ryegrass is sporidesmin, which causes liver damage and secondary photosensitization (facial eczema). Fusarium toxins such as zearalenone and trichothecenes also occur in forage grasses. Kikuyugrass poisoning results in severe damage to the ruminal epithelium and omasal mucosa, and neurological signs. The causative agent, which may be associated with army worm predation of the grass, has not been identified. The properties and significance of these toxins are reviewed.

A review of the functional and evolutionary roles of the liver in the detoxification of poisonous plants, with special reference to pyrrolizidine alkaloids.

Coevolutionary relationships between herbivores and poisonous plants are described. Hepatic detoxification reactions (Phase I and Phase II) are discussed in the context of susceptibility and resistance to poisonous plants. Animal species differences in susceptibility to poisonous plants are discussed, with a comparison of liver vs rumen microbe detoxification pathways. It is concluded, especially with regard to pyrrolizidine alkaloids, that species differences are due to differences in hepatic metabolism rather than to rumen microbes. Linkages between hepatic detoxification abilities and feeding behavior are proposed, as an evolutionary strategy allowing animals resistant to particular toxins to evolve feeding responses to exploit food resources containing toxins to which the animal is resistant.

Dietary pyrrolizidine (Senecio) alkaloids and tissue distribution of copper and vitamin A in broiler chickens.

The effect of feeding a diet containing 5% tansy ragwort (TR) (Senecio jacobaea), a poisonous plant containing pyrrolizidine alkaloids (PA), on the blood and liver levels of copper, zinc, iron and vitamin A in broiler chicks was examined. Serum and liver copper and liver iron concentrations were increased in chicks fed a diet with 5% TR, while serum and liver zinc and vitamin A decreased. When PA were removed from the diet, partial restoration of normal serum vitamin A level occurred, indicating that the ability to mobilize liver vitamin A is not irreversibly inhibited by PA. The decline in serum vitamin A occurred by 8 days of TR feeding with a concurrent decline in growth rate. When chicks were fed a diet high in vitamin A (25,000 IU/kg), followed by a basal diet containing TR, serum vitamin A levels were significantly (P < 0.01) decreased, while liver vitamin A level increased. This indicates that mobilization of previously stored vitamin A from the liver is impaired by PA. Prior feeding of a high vitamin A level resulted in protective effects against PA toxicity, as assessed by histopathology. This study shows that a dietary source of PA modifies metabolism and tissue distribution of minerals and vitamin A.

Prediction and causation of litter market traits from preweaning and weaning characteristics in commercial meat rabbits.

Market data on 1,315 rabbits from 201 litters from Californian (CAL), New Zealand White (NZW), CAL X NZW and NZW X CAL dams bred to CAL, NZW and Flemish Giant sires were subjected to multiple regression and path analyses. Market traits observed in litters at 56 d included average kit weight (A56W), litter size (LS56), total litter weight (L56W) and within-litter uniformity in individual weights (LCV). Preweaning variables as covariates included in the model were dam metabolic body weight (DMW), litter born (LSB), litter birth weight (LBW), milk yield from 1 to 21 d (MY) and feed intake from 1 to 28 d of the dam and litter (FI). Results from multiple regression analyses indicated linear and quadratic effects (P less than .20) due to LSB and MY for all four market characters. The LBW influenced (P less than .05) LS56 and L56W, and FI affected (P less than .05) LS56, L56W and LCV. Separate analyses were conducted involving 28-d weaning and feed intake variables as covariates: litter size weaned (LSW), litter weaning weight (LWW) and litter feed intake from 28 to 56 d (LFI). The three weaning covariates were important (P less than .05) for all market traits except LS56 (LWW was not significant). The most accurate regression equations were obtained from the weaning model for prediction of L56W and LS56 (R2 = .68 and .78). Path analyses revealed that preweaning covariates generally had direct rather than indirect effects on market traits. Both direct and indirect effects of weaning covariates were important for market traits. Results suggest that litter market traits of size and weight can be predicted with a reasonable degree of accuracy.

Effects of cimaterol on rabbit growth and myofibrillar protein degradation and on calcium-dependent proteinase and calpastatin activities in skeletal muscle.

The objectives of this study were to examine effects of a beta-adrenergic agonist (cimaterol) on growth and muscle development in rabbits and to examine cimaterol's effects on myofibrillar protein degradation (MPD) and on activities of several proteolytic enzymes including the calcium-dependent proteinases (CDP). Twelve New Zealand White rabbits were assigned to either control diets or to diets containing cimaterol for 35 d, after which they were killed and effects on performance and tissue weight gains were determined. Urine was collected from d 21 through 28 from each rabbit for assessment of N tau-methylhistidine (NMH) excretion. Cimaterol increased rates of gain, efficiency of gain and skeletal muscle weights. Enhancement in muscle weight was associated with an increase in total DNA and with a reduction in NMH. Cimaterol did not affect activities of cathepsin B, cathepsin D or neutral serine proteinase, but it reduced activities of the millimolar and micromolar forms of the CDP by 58 and 57%, respectively, and it reduced activity of the inhibitor of the CDP (calpastatin) by 52%. Cimaterol-dependent myofibrillar protein accretion was likely mediated, at least in part, by a reduction in MPD. The change in MPD was associated with a reduction in muscle CDP activities. Cimaterol-dependent muscle hypertrophy therefore may involve changes in calcium-dependent proteolysis of myofibrillar proteins. The significance of the effects of cimaterol on calpastatin activity is not known.

Effects of dietary pyrrolizidine (Senecio) alkaloids on vitamin A metabolism in rats.

In two experiments, the effect of feeding the pyrrolizidine alkaloid (PA)-containing plant tansy ragwort (Senecio jacobaea) on the metabolism of vitamin A in rats was examined. In Experiment 1, dietary levels of 0, 5 and 10% tansy ragwort and 0, 25,000 and 100,000 IU supplementary vitamin A/kg diet were used. In rats fed tansy ragwort, both plasma and liver concentrations of vitamin A were depressed (P less than 0.05). Plasma values were decreased to about 50% of control values. In Experiment 2, rats fed 5% tansy ragwort had depressed plasma and liver vitamin A concentrations 48 h after oral dosing with vitamin A. Fecal excretion of vitamin A was decreased in tansy ragwort-fed rats. In control rats, most fecal vitamin A was excreted in the first 24 h post-dosing, while in tansy ragwort-fed animals, the excretion was delayed, suggesting a possible effect of PA on gut motility. The results indicate that PA causes reductions in liver and plasma vitamin A concentrations. Postulated mechanisms include an effect of PA on hepatic retinol-binding protein synthesis, and impaired biliary excretion depressing vitamin A absorption.

Toxicity and metabolism of pyrrolizidine alkaloids.

Pyrrolizidine alkaloids (PA) are found mainly in plants of three families: boraginaceae, Compositae and Leguminosae. In North America, PA poisoning of livestock is caused primarily by consumption of Senecio and Crotalaria spp. The PA of Senecio spp. cause irreversible hepatic damage; toxicity signs are a consequence of impaired liver function. Crotalaria intoxication leads to pulmonary damage as a primary effect; hepatic effects are less prominent. Large species differences exist in susceptibility to PA toxicosis. Small herbivores such as sheep, goats, rabbits, guinea pigs and other herbivorous laboratory animals are highly resistant to PA toxicity, associated with a low rate of hepatic production of reactive metabolites (pyrroles) and(or) a high rate of activity of detoxifying enzymes. Diester PA common to Heliotropium and Echium spp. are metabolized in the ovine rumen to 1-methyl metabolites, whereas the macrocyclic ester PA of Senecio spp. are not. Exposure to PA results in high concentrations of liver Cu, reduced liver Zn, and abnormal Fe metabolism with hematopoiesis markedly impaired. Pyrrolizidine alkaloid toxicity alters vitamin A metabolism in rats, depressing plasma and liver levels of vitamin A. Synthetic antioxidants in the diet confer protective activity in laboratory animals (e.g., rats, mice) against PA toxicoses. The PA and their metabolites are secreted in the milk of lactating animals, but this probably does not represent a significant human health hazard.