Pharmacokinetic profiles of metamizole (dipyrone) active metabolites in goats and its residues in milk

Metamizole (dipyrone, MET) is a nonopioid analgesic drug commonly used in human and veterinary medicine. The aim of this study was to assess two major active metabolites of MET, 4‐methylaminoantipyrin (MAA) and 4‐aminoantipyrin (AA), in goat plasma after intravenous (IV) and intramuscular (IM) administration. In addition, metabolite concentration in milk was monitored after IM injection. Six healthy female goats received MET at a dose of 25 mg/kg by IV and IM routes in a crossover design study. The blood and milk samples were analyzed using HPLC coupled with ultraviolet detector and the plasma vs concentration curves analyzed by a noncompartmental model. In the goat, the MET rapidly converted into MAA and the mean maximum concentration was 183.97 μg/ml (at 0.08 hr) and 51.94 μg/ml (at 0.70 hr) after IV and IM administration, respectively. The area under the curve and mean residual time values were higher in the IM than the IV administered goats. The average concentration of AA was lower than MAA in both groups. Over 1 μg/ml of MAA was found in the milk (at 48 hr) after MET IM administration. In conclusion, IM is considered to be a better administration route in terms of its complete absorption with long persistence in the plasma. However, this therapeutic option should be considered in light of the likelihood of there being milk residue.     

Mouse bioassay to assess oestrogenic and anti-oestrogenic compounds: hydroxytamoxifen, diethylstilbestrol and genistein

Young intact and adult gonadectomized C3H male and female mice were utilized as bioassay models to detect endocrine disruption chemicals. Animals treated with oestradiol (E) or progesterone (Prog) or E plus Prog were used to assess steroid hormone agonist and antagonist activities of 4-OH-tamoxifen (TAM), diethylstilbestrol (DES) and genistein (GEN) by bioassay. The stimulation or inhibition of mammary growth by TAM depended on sex, the state of animal (intact or gonadectomized), hormonal treatment (Prog, E, E plus Prog) and dose of TAM. TAM stimulated mammary growth in untreated ovariectomized (OV-X) females and in Prog-treated intact males and OV-X females. In intact males, mammary growth was increased by TAM at dose 0.1-1 microg day(-1) and decreased at dose 10 microg day(-1). Mammary growth was inhibited by TAM in Prog-treated intact females and in E or E plus Prog-treated intact and gonadectomized males and females. Uterine weights were increased by TAM in both untreated and treated (E, Prog, E plus Prog) intact and OV-X females; however, seminal vesicle weights were decreased by TAM in both untreated and treated (E, Prog, E plus Prog) intact males. DES alone affected mammary growth (an inverted-U-shaped dose-response curve) both in male and female mice. DES increased uterine weights; however, seminal vesicle weights were decreased. GEN increased mammary and uterine growth in OV-X females, GEN plus Prog stimulated mammary growth in intact males. The results obtained in these studies show clearly that only a bioassay consisting of several endpoints reflective to the mechanism of oestrogen and anti-oestrogen action has the ability to evaluate activities of a molecule.     

Estimation of the total sulfur amino acid requirement and the effect of betaine in diets deficient in total sulfur amino acids for the weanling pig.

Four experiments were conducted to determine whether betaine (BET) could replace dietary methionine (MET) in diets for weanling pigs. Pigs in each experiment were allotted to treatments on the basis of weight in a randomized complete block design. Each treatment was replicated four (Exp. 4), five (Exp. 1 and 2), or six (Exp. 3) times with five or six pigs per replicate. In Exp. 1, pigs were fed a diet formulated to be deficient in total sulfur amino acids (TSAA) (negative control; NC) or the NC + 0.05 or 0.10% MET or BET during Phase 1 and 0.035 or 0.07% MET or BET during Phase 2. Growth performance was not affected (P > 0.10) by dietary treatments, indicating that the diets were not deficient in TSAA. In Exp. 2, graded levels of TSAA (0.74, 0.79, 0.84, 0.89, or 0.94%) were fed. Overall ADG was increased (0 vs added MET, P < 0.07) in pigs fed TSAA levels of 0.79% or greater, but gain:feed was not affected (P > 0.10) by diet. Overall ADFI was increased (linear, P < 0.08) and plasma urea N (PUN) was decreased (quadratic, P < 0.01) as the level of TSAA was increased. Most of the change in ADG, PUN, and ADFI occurred between 0.74 and 0.84% TSAA. Thus, the 0.74% TSAA diet was used in Exp. 3 as the NC. In Exp. 3, the diets included the following: 1) NC, 2) NC + 0.05% MET, 3) NC + 0.10% MET, 4) NC + 0.039% BET, or 5) NC + 0.078% BET. The addition of MET resulted in increased (linear, P < 0.10) ADG, ADFI, and gain:feed, but MET decreased PUN (linear, P < 0.05). Daily gain, ADFI, and TSAA intake were not different (P > 0.10) between pigs fed 0.05% MET or 0.039% BET, but gain:feed was decreased (P < 0.01) in pigs fed 0.039% BET compared with pigs fed 0.05% MET. In Exp. 4, a 2 x 2 x 2 factorial arrangement of treatments was used (MET, 0 or 0.072%; cystine, 0 or 0.059%; or BET, 0 or 0.057%). Overall ADG and gain:feed were increased (P < 0.10) in pigs fed MET. The intake of TSAA was increased (P < 0.05), and PUN was decreased (P < 0.10) in pigs fed MET or cystine. Overall ADFI was increased in pigs fed BET or MET independently but not affected when BET and MET were fed together (BET x MET, P < 0.10). The addition of BET to TSAA-deficient diets resulted in increased ADG, which was due to an increase in ADFI (TSAA intake). Thus, BET did not spare MET in this experiment.     

水貂不同赖氨酸、蛋氨酸水平颗粒饲料对营养物质消化代谢的影响

为确定水貂适宜氨基酸组成、降低饲料成本,试验选取成年健康公母水貂各60只,随机分成6组,采用2×3因子试验设计,即赖氨酸2个水平,分别为1.85%和1.7%,蛋氨酸3个水平分别为0.81%、0.99%和1.24%,对采食正常试验组水貂进行了消化代谢试验。结果表明:①日粮赖氨酸水平的变化对公母貂干物质摄入、排出及消化率影响不显著(P>0.05);蛋氨酸水平的变化对母貂干物质摄入、排出及消化率影响不显著(P>0.05),公貂粪干物质排出量蛋氨酸水平为0.99%组显著低于蛋氨酸水平为1.24%组(P<0.05),公貂干物质消化率蛋氨酸水平为0.99%组极显著地高于蛋氨酸水平为0.81%组和1.24%组(P<0.01)。②日粮赖氨酸水平的变化对公母貂有机物摄入、排出及消化率影响不显著(P>0.05);蛋氨酸水平的变化对公母貂有机物摄入、排出及母貂消化率影响不显著(P>0.05),公貂蛋氨酸水平为0.99%组有机物消化率显著高于蛋氨酸水平为0.81%组(P<0.05),与蛋氨酸水平为1.24%组差异不显著(P>0.05)。③公母貂蛋白质消化代谢受赖氨酸水平变化的影响不显著(P>0.05);公母貂蛋白质摄入及粪蛋白的排出受蛋氨酸水平变化影响不显著(P>0.05),蛋氨酸为1.24%时公貂尿蛋白排出显著高于0.99%水平组(P<0.05),与0.81%水平组尿蛋白排出差异不显著(P>0.05);公貂蛋白存留0.99%水平组极显著高于1.24%水平组(P<0.01);公貂蛋白质消化率0.99%水平组显著高于1.24%水平组(P<0.05),与0.81%水平组差异不显著(P>0.05);母貂蛋氨酸水平变化对各消化代谢率指标影响不显著(P>0.05)。④1.85%赖氨酸水平组公貂赖氨酸摄入、尿排出及消化代谢率均显著高于1.7%赖氨酸水平组(P<0.05),母貂间差异不显著(P>0.05),赖氨酸水平对公母貂蛋氨酸摄入、粪尿排出及消化代谢率无显著影响(P>0.05);蛋氨酸水平对公母貂赖氨酸摄入、粪尿排出无显著影响(P>0.05),蛋氨酸0.99%水平公貂赖氨酸消化代谢率均极显著高于蛋氨酸1.24%水平和0.81%水平公貂(P<0.01),蛋氨酸水平对母貂间赖氨酸消化代谢率无显著影响(P>0.05);蛋氨酸水平对公母貂蛋氨酸摄入、粪尿排出及消化代谢率均有显著影响(P<0.05),随着蛋氨酸水平的降低,蛋氨酸的摄入逐渐降低,而尿排出蛋氨酸1.24%组显著高于0.99%和0.81%水平组(P<0.05);蛋氨酸0.99%和1.24%水平组公母貂蛋氨酸的消化代谢率均极显著高于0.81%水平组(P<0.01),蛋氨酸0.99%和1.24%水平组公母貂蛋氨酸的消化代谢率无显著差异(P>0.05)。     

Lysine and methionine transport by bovine jejunal and ileal brush border membrane vesicles

Lysine (LYS) and methionine (MET) transport were studied using brush border membrane vesicles from bovine jejunal and ileal tissues. Total transport of LYS and MET was divided into mediated and diffusion components. Mediated uptake was further divided into sodium (Na)-dependent and Na-independent systems. Total LYS and MET uptake by ileal brush border (BB) vesicles tended to be higher than that by jejunal BB vesicles at all concentrations evaluated but differences were significant (P less than .05) at 2.5 and 7.5 mM for LYS and 5, 12.5 and 15 mM for MET. The greater capacity of ileal BB vesicles appeared to be due to the Na-dependent component of LYS uptake and the diffusion component of MET uptake. Transporters had less affinity but higher capacity than for LYS transport in both ileal and jejunal tissue. Methionine transport was greater (P less than .05) than LYS transport in both ileal and jejunal BB vesicles when the initial amino acid concentration was 7.5 mM. But when the initial amino acid concentration was 1.25 mM, MET uptake was greater (P less than .13) than LYS uptake in jejunal, but not in ileal, BB vesicles. The relative contribution of mediated and diffusion uptake systems to total MET and LYS uptake was found to be dependent on substrate concentration. Both intestinal site and substrate concentration influenced the contributions of Na-dependent, Na-independent and diffusion systems to total methionine and lysine uptake.     

Responses of organic housed laying hens to dietary methionine and energy during a summer and winter season

1. The main dietary challenge in organic laying hen production is to fulfil the digestible methionine (MET) requirement in a diet consisting of ingredients of organic origin only.

2. The aim of the present experiment was to determine the response of organic housed laying hens (26–34 weeks of age) to dietary energy and MET during a summer and winter trial. Per trial, a total of 128 17-week-old Brown Nick hens were allotted to 16 pens, which were connected to an outdoor run. Each experiment comprised 8 dietary treatments according to a 4 × 2 factorial design. The factors were AFD MET level (2.3, 2.7, 3.1 and 3.5 g/kg) and energy content (10.9 and 12.1 MJ).

3. Dietary energy content did not affect energy intake (1361 kJ/d) in summer, whereas energy intake in winter was increased in hens that were fed on the 12.1-MJ diets (1514 vs. 1421 kJ/d). Maximal egg mass in summer was achieved if a diet with 3.5 g/kg MET was given, corresponding to a digestible MET intake of 421 mg/d. During winter, maximal egg mass was achieved with a digestible MET intake of 360 mg/d, which was already realised with a MET content of 2.7 g/kg.

4. Because digestible MET content for maximal egg performance differed between the summer and winter trial, dietary energy to MET ratio might be adjusted to seasonal conditions.

     

Comparison of the cardio‐respiratory effects of methadone and morphine in conscious dogs††

The effects of methadone and morphine were compared in conscious dogs. Six animals received morphine sulfate (1 mg/kg) or methadone hydrochloride (0.5 mg/kg [MET0.5] or 1.0 mg/kg [MET1.0]) intravenously (i.v.) in a randomized complete block design. Cardiopulmonary variables were recorded before (baseline), and for 120 min after drug administration. One outlier was not included in the statistical analysis for hemodynamic data. Morphine decreased heart rate (HR) compared to baseline from 30 to 120 min (?15% to ?26%), while cardiac index (CI) was reduced only at 120 min (?19%). Greater and more prolonged reductions in HR (?32% to ?46%) and in CI (?24% to ?52%) were observed after MET1.0, while intermediate reductions were recorded after MET0.5 (?19 to ?28% for HR and ?17% to ?27% for CI). The systemic vascular resistance index (SVRI) was increased after methadone; MET1.0 produced higher SVRI values than MET0.5 (maximum increases: 57% and 165% for MET0.5 and MET1.0, respectively). Compared to morphine, oxygen partial pressure (PaO₂) was lower (?12% to ?13%) at 5 min of methadone (0.5 and 1.0 mg/kg), while carbon dioxide partial pressure (PaCO₂) did not change significantly. It was concluded that methadone induces cardiovascular changes that are dose‐related and is a more potent cardiovascular depressant agent than morphine in conscious dogs.     

Unique hemagglutination activity of an isolate of Newcastle disease virus

The MET95 strain of a lentogenic Newcastle disease virus (NDV) isolated from a broiler in Japan, showed unique hemagglutination (HA) activity. The MET95 strain failed to show HA when examined by rapid glass plate method although they showed HA titer of 1:1,024 by micro-plate method. This unique HA was also observed after the MET95 strain was passaged ten times in chickens. The failure of HA by rapid glass plate method was not shown in any other NDVs examined.     

Field report from large-scale killing of ducks

An outbreak of avian influenza in August 2007 resulted in the culling of hundreds of thousands of Peking ducks. An earlier tutorial had shown that whole house gassing with carbon dioxide to kill waterfowl has to be refused because of interference with animal welfare. Culling by electrocution is a reliable method that fulfils animal welfare requirements. Stationary electrocution lines for slaughtering should be preferred if suitable for the killing of the birds. Mobile electrocution lines (MET) are a good alternative or supplementation with a capacity of circa 2,500 animals per hour. MET are suitable for killing Peking ducks with a weight of approximately 500 g. At least two veterinarians are required per MET for the supervision of animal welfare during culling. When following German animal welfare laws, killing in mobile gas containers filled with carbon dioxide is an alternative with a capacity comparable to that of MET. The problem of looking into the containers for controlled stunning and killing can be solved by installing observation windows. Manpower requirements are comparable to those of MET, while requirements for material and transportation are unlikely higher. This method is suitable for birds which are too small to be killed by electrocution.     

Bioavailability of methionine-hydroxy-analog free acid and S-methyl-methionine in the growing rat.

The biological utilization of DL-methionine (MET), DL-methionine-hydroxy-analog and DL-S-methyl-methionine-sulphonium-chloride (SMM) was tested in rat growth assay. Weight gain, feed efficiency, protein efficiency ratio (PER), net protein ratio (NPR) and net protein utilization (NPU) were applied as criteria. A test diet containing soybean meal as sole protein source was fortified with MET, MHA or SMM at 1.5 and 3.0 g/kg levels, respectively. All fortifications had a significant (p < 0.05) positive influence on weight gain, feed conversion and protein utilization. SMM showed the highest activity. MET and MHA were almost equally well utilized at 3.0 g/kg fortification level, however MHA proved slightly less efficient at 1.5 g/kg level than MET.     

Bayesian estimates of genetic parameters for metritis, retained placenta, milk fever, and clinical mastitis in Holstein dairy cows via Gibbs sampling

The objective of this study was to estimate heritability and genetic correlations between the liabilities of clinical mastitis (CM), milk fever (MF), metritis (MET), and retained placenta (RP) within the first three lactations of Holstein dairy cows. The records of 57,301 dairy cows from 20 large dairy herds in Iran between January 2005 and June 2009 were analysed with univariate and bivariate threshold animal models, using Gibbs sampling methodology. The final model included the fixed class effects of herd-year, season of calving, parity of dam, the linear covariate effect of age at calving, and the random direct genetic effect of animal. Posterior means of heritability for liabilities in first, second, and third lactations were 0.06, 0.08, and 0.09, respectively, for CM; 0.10, 0.12, and 0.11, respectively, for MF; 0.09, 0.07, and 0.10, respectively, for MET, and 0.07, 0.08, and 0.08, respectively, for RP. Posterior means of genetic correlations between disease liabilities were low or moderate (from −0.01 to 0.26). The results of this study indicated the importance of health traits for considering in the selection index of Iranian Holstein dairy cows.     

Influence of DL-methionine supplementation on growth, ruminal fermentation and dilution rates in heifers

A 3 X 3 replicated Latin square design was used to evaluate three isonitrogenous supplements designed to supply 250 g crude protein (CP) daily. Measurements included in situ dry matter (DM) and neutral detergent fiber (NDF) fermentation and ruminal dilution rates. Supplements contained beet pulp plus DL-methionine and urea (MET), ammonium sulfate and urea (U) or soybean meal (SBM). Six mature, ruminally cannulated crossbred beef cows were individually fed supplement and a mixture (63% NDF and 6.1% CP) of chopped 75% grass hay and 25% barley straw in ad libitum. Fermentation rate of DM was increased (P less than .05) by 30% with MET in comparison to SBM or U (9.54 vs 7.28% and 7.74%/h for MET, SBM and U, respectively). Even though MET improved fermentation rate by 30%, particle dilution rate was more important in affecting ruminal digestibility than fermentation rate. Two 90-d heifer growth trials were conducted to evaluate similar supplements. Supplements similar to those used in the in situ trial were mixed with roughage to provide a complete diet balanced for .3 kg daily gain. Heifers consumed 112% of the National Research Council CP requirement. Weight gain, intake and feed conversion were similar (P greater than .10) for all treatments. In heifer trial 2, 90% of the National Research Council CP requirement was fed. The heifers supplemented with MET and SBM had faster (P less than .05) weight gains than heifers receiving U. These studies show that feeding DL-methionine with urea, as compared with feeding an isonitrogenous supplement containing SBM, increased the fermentation rate of DM.(ABSTRACT TRUNCATED AT 250 WORDS)     

Tamoxifen advances puberty in the White Leghorn hen.

1. Tamoxifen (TAM) administration advances puberty in cockerels. In the present study the effect of TAM administration on the sexual development of White Leghorn hens was studied. 2. Two-week-old White Leghorn females were injected intramuscularly with TAM on alternate days at doses of 0.1 mg (0.1 TM), 1 mg (1TM), 5 mg (5TM) and 10 mg/kg body weight (10TM) respectively, while the controls were injected with maize oil (vehicle). The experiment was terminated at 23 weeks of age, when all the control hens laid eggs. Sample autopsies were made on chicks of 6, 14 and 23 weeks of age. 3. Body growth was not affected by any of the treatments. 4. Comb growth was accelerated by all doses of TAM, while hematocrit increased in the 1TM, 5TM and 10TM hens. 5. Egg laying advanced in the 0.1TM and 1TM birds, was delayed in 5TM hens and did not occur at all in the 10TM females. 6. TAM caused a precocious increase in plasma oestrogen and androgen, suppressed adiposity in a dose-related manner and, at low doses, advanced the development of the gonadal system. 7. At 23 weeks of age, when the gonadal system of the controls was fully active, TAM caused a dose-related depression in abdominal fat, liver, ovary, and oviduct weights, plasma total lipids and calcium concentrations and a dose-related increase in plasma oestrogen and androgen titres, and comb weight. 8. It seems that TAM increased gonadotropic activity and its androgen stimulating action, but suppressed peripheral signs of the elevated plasma oestrogen titres. Low doses of TAM enhanced gonadotropic activity and egg laying but the antioestrogenic effect depressed development of the gonadal system, suppressing egg production when high doses were administered. It therefore seems that oestrogens are necessary for normal ovarian development in hens.     

Effect of marinade containing thyme and orange oils on broiler breast fillet and whole wing aerobic bacteria during refrigerated storage

Raw meat typically hosts spoilage organisms and sometimes hosts pathogens; to combat this, natural antimicrobial interventions have gained interest among consumers. In a previous study a marinade containing a thyme-orange essential oils combination (TOC) at the 0.5% level was found to inhibit Salmonella and Campylobacter species. The objective of the current study was to evaluate the effect of a salt-phosphate marinade solution with 0.5% TOC (treatment) or without TOC (control) applied by vacuum tumbling on the shelf life of broiler breast fillets and whole wings. The total aerobic and facultative mesophiles (TAM) occurring naturally on these products during refrigerated storage for 14 d (at 1, 7, 10, and 14 d) were enumerated. A total of 48 (24 for each trial) skinless breast fillets and 48 (24 for each trial) whole wings were used for the 2 trials. For each trial, 12 of the 24 breast fillets or wings were marinated using the control marinade solution and the remaining 12 were marinated in the treatment marinade solution. On d 1, 7, 10, and 14, 3 treatment and 3 control breast fillets and wings were randomly selected for TAM enumeration. Sample rinsates were plated in duplicate and incubated at 35°C for 48 h. Thyme-orange combination marinade significantly reduced TAM numbers on d 1, 7, and 10 compared with the controls. Log reductions of 0.3, 0.9, and 1.1 were recorded on d 1, 7, and 10, respectively. The difference in TAM between the treated and untreated whole wings was not significant. Therefore, 0.5% TOC in marinade can be used as a natural antimicrobial to reduce TAM on skinless breast fillets; however, a higher concentration may be required for skin-on products.     

Precocious puberty in tamoxifen‐treated cockerels: Hypothalamic gonadotrophin‐releasing hormone‐I and plasma luteinising hormone,prolactin, growth hormone and testosterone

1. The administration of the anti‐oestrogen, tamoxifen (TAM) to juvenile chicks results in precocious puberty. In the present study the effects of TAM administration (1 mg/kg body weight on alternate days from 12 d of age) on testicular function, hypothalamic chicken gonadotropin‐re‐leasing hormone (cGn‐RH‐I), plasma luteinising hormone (LH), growth hormone (GH), prolactin (PRL) and testosterone were studied in juvenile White Leghorn cockerels.

2. The increase in hypothalamic GnRH‐I content which occurs during sexual development was advanced in TAM‐treated birds, in association with precocious testicular development, an early rise of plasma testosterone content and enhanced comb growth.

3. Plasma LH concentrations behaved similarly and were higher in the TAM‐treated than in control birds, during most of the experimental period. Plasma PRL concentration, which is high at hatching, decreased more quickly in TAM‐treated than in control birds; plasma GH values were not consistently affected by TAM treatment.

4. Both the growth and the involution of the bursa of Fabricius in the TAM‐treated cockerels preceded that in the control chicks.

5. It is concluded that TAM treatment induces precocious puberty in the cockerel by blocking the negative feedback action of aromatised testicular androgens on the hypothalamus.     

Effect of increasing taurine and methionine supplementation on urinary taurine excretion in a model insectivore,the giant anteater (Myrmecophaga tridactyla)

The giant anteater (Mymercophaga tridactyla) is a highly specialized insectivore for which nutrient requirements are not clearly established, making diet formulation challenging for this species. Multiple clinical reports suggest anteaters have an obligate dietary taurine (TAU) requirement. Sulphur amino acid (SAA) metabolism in adult anteaters was evaluated using noninvasive methods to measure TAU synthesis potential from dietary methionine (MET) and a basal diet containing on a dry matter (DM) basis 1.7 mg TAU/kg DM and 6.9 g MET/kg DM. Urinary equilibrium times for TAU excretion were determined by feeding the basal diet with or without 1.5 g/kg DM supplemental TAU (crossover design; n = 4). Effects of supplemental dietary TAU (1.7, 2.0, 2.4, 2.7, 3.0, 3.3 g/kg DM) or MET (6.9, 9.0, 11.2 g/kg DM) on urinary TAU were evaluated (randomized block trials; n = 5 or 4 respectively). All urinary values (TAU, MET, unbound inorganic sulphate) were normalized to creatinine (CRT). Results indicate urinary TAU equilibrium in anteaters requires at least 2 weeks of feeding. Urinary ratio of TAU to CRT (TAU:CRT) increased as dietary TAU content increased from 1.7 to 3.0 g/kg DM, consistent with renal homoeostatic modulation of TAU excretion. Our data indicate that TAU needs were met by TAU in the basal diet or by de novo synthesis. Supplemental MET resulted in ~five‐ to eightfold increases in urinary TAU:CRT excretion, further supporting existence of mechanisms for TAU synthesis from dietary SAA in anteaters. Adult anteaters appear able to synthesize TAU when diets contain adequate SAA, but dietary TAU may be critical if protein intakes are low or of poor quality. This study may provide guidance on choice of domestic canids vs. felids as suitable physiologic models for improved nutrition in giant anteaters, and also outlines a noninvasive method for assessing TAU status/metabolism that may be useful across species.     

Response of nitrogen metabolism in preparturient dairy cows to methionine supplementation

Three multiparous Holstein cows (607 kg of BW) were surgically prepared with an elevated carotid artery and indwelling catheters in the hepatic, portal, and two mesenteric veins to study the effects of methionine supplementation on amino acid metabolism during the last 2 wk of pregnancy. The study began 15 d before the expected calving date. Dietary treatments were Control (1.53 Mcal NE(l)/kg, 15.6% CP, and 40% ruminally undegradable protein) and Control supplemented with 60 g/d of ruminally protected methionine (MET, supplying 39 g/d of DL-methionine and approximately 18 g/d of methionine available for intestinal absorption). Each cow received both dietary treatments in a crossover design. Cows were fed once daily. After 5 d on treatment, a blood flow marker (para-aminohippurate) was infused into a mesenteric vein, and arterial, portal, and hepatic blood samples were obtained at 0, 2, 6, 12, and 18 h after feeding. Net flux of methionine was calculated as the plasma arteriovenous difference multiplied by plasma flow. Dry matter intake (10.8 kg/d) and portal (824 L/h) and hepatic (995 L/h) plasma flows were not affected (P > .10) by treatment. Arterial plasma concentration of methionine was greater (P = .10) with MET (27.67 microM) than with Control (16.42 microM). Net portal absorption of methionine increased (P = .10) with MET (26.2 g/d) compared with Control (9.5 g/d). The net portal methionine flux was negatively correlated (r = -.59; P < .001) with arterial urea concentrations. Net flux of methionine across splanchnic tissues shifted (P = .06) from a net uptake with Control (4 g/d) to a net output with MET (11 g/d). Therefore, MET increased by 15 g/d the methionine supply to the rest of the body. The net uptake of methionine by splanchnic tissues observed with Control indicated a net mobilization of methionine by peripheral tissues. Results indicate that methionine was the limiting amino acid with Control and that MET was beneficial because it increased methionine supply to peripheral tissues and reduced arterial urea concentrations.     

Cardiorespiratory effects of a cardioselective muscarinic antagonist in anesthetized horses

Treatment of bradycardia in horses has been historically ignored because of the motility depressant effects of nonselective antimuscarinics. This study evaluated the cardiopulmonary effects of a cardioselective (M2) muscarinic antagonist, methoctramine (MET), in anesthetized horses. In a previous in vitro study, we determined that supraphysiological doses of MET were necessary to inhibit acetylcholine‐induced longitudinal jejunal smooth muscle contractions in this species. Six adult horses were allocated to two treatments in a randomized complete block design. Anesthesia was induced with xylazine/ketamine, and maintained with halothane (1% end‐tidal) and a constant infusion of xylazine (1 mg kg^?1 hour^?1) under mechanical ventilation. Invasive hemodynamic variables were monitored at baseline (approximately 45 minutes after induction) and for 120 minutes after MET or saline (control) had been injected. MET was titrated at 10‐minute intervals (10 µg kg^?1 IV) until the heart rate (HR) increased at least 30% above the baseline, or a maximum cumulative dose of 30 µg kg^?1 had been injected. A person blinded to the treatment evaluated recovery scores and monitored intestinal auscultation until 24 hours after the end of anesthesia using previously published methods. Cardiovascular parameters were analyzed by anova followed by a Dunnet's test, and nonparametrical data were analyzed by a Mann–Whitney U‐test (p < 0.05). Values were mean ± SEM unless otherwise stated. MET significantly increased HR from baseline to 120 minutes post‐injection (from 29 ± 1 to 36 ± 2 beats minute^?1 at 20 minutes). Thermodilution cardiac output (CO) and mean arterial pressure (MAP) were increased from baseline to 75 minutes post‐MET injection (from 13.9 ± 0.8 to 19.4 ± 2.0 L minute^?1 for CO at 20 minutes, and from 82 ± 3 to 103 ± 5 mm Hg for MAP at 20 minutes). Recovery characteristics and bowel auscultation scores did not differ among the groups. The return to at least 75% of the maximum auscultation score occurred at 10 (8–18) hours [median (range)] for controls and at 9 (8–12) hours for MET. It was concluded that MET increased HR and improved hemodynamic function during halothane/xylazine anesthesia with no apparent effect on return to full‐bowel motility, as assessed by auscultation. Accordingly, M2 muscarinic antagonists might be represented as a safer alternative to treat intraoperative bradycardia in horse.     

Antinociceptive and Behavioral Effects of Methadone Alone or in Combination with Detomidine in Conscious Horses

The antinociceptive and behavioral effects of methadone (MET) alone or combined with detomidine (DET) were studied in horses. Intravenous treatments were randomly administered in a two-phase crossover study. In phase 1, six horses were treated with saline (control) or 0.2 or 0.5 mg/kg methadone (MET_0.2; MET_0.5, respectively). In phase 2, six horses were treated with 0.01 mg/kg DET alone or with DET combined with 0.2 mg/kg MET (DET/MET_0.2). Thermal nociceptive threshold (TNT) and electrical nociceptive thresholds (ENT) were recorded by using a heat projection lamp and electrodes placed in the coronary band of the thoracic limbs, respectively. Spontaneous locomotor activity (SLA) was studied by movement sensors in the stall (phase 1). Chin-to-floor distance was assessed in phase 2. In phase 1, the TNT increased significantly for 30 minute after MET_0.5 but not after saline or MET_0.2. Hyperesthesia and ataxia were observed in 2 of 6 and 6 of 6 horses after MET_0.2 and MET_0.5, respectively. SLA increased significantly for 120 minutes after MET in a dose-dependent way, but not after placebo. In phase 2, DET and DET/MET_0.2 significantly increased the TNT and ENT above baseline for 15 and 30 minutes, respectively; thresholds were significantly higher with DET/MET_0.2 than with DET at the same times. Chin-to-floor distance decreased significantly from baseline for 30 minutes, and no excitatory behavior was observed in both treatments. Although the higher dose of MET induced short-acting antinociception, the associated adverse effects may contraindicate its clinical use. The lower dose of MET potentiated DET-induced antinociception without adverse effects, which might be useful under clinical circumstances.     

Characterization of a lentogenic Newcastle disease virus isolated from broiler chickens in Japan

Newcastle disease virus (NDV), named MET95, was isolated from a non-vaccinated broiler flock in Japan in 1995. The MET95 strain was determined to be a lentogenic NDV. The strain has the properties of eluting rapidly at 4 C and has low thermostability in hemagglutinating activity with chicken erythrocytes. In these studies, no difference could be found between the MET95 strain and the Hitcher B1 vaccine strain. However, the chickens inoculated with the MET95 strain, as well as chickens that they were in contact with, had a much higher hemagglutination-inhibition antibody response than those inoculated with the B1 strain. Accordingly, the MET95 strain is thought to be a promising candidate as a live ND vaccine strain. In Japan, this is the first report on the isolation of lentogenic NDV from chickens since the paper on the Ishii strain isolated in 1966.