Thyroid hormones and metabolic rate during induction of Vitamin B12 deficiency in goats

Vitamin B12 deficiency was induced in 15 small East African goats by feeding cobalt deficient Chloris gayana hay (containing 0.02 mg of Co/kg dry matter) over a 25 week experimental period. Cobalt was supplemented as an oral drench to supply 0.3 g of Co/goat/week to 15 treated goats. At intervals of 3-4 weeks, serum concentrations of Vitamin B12 , total thyroxine (TT4), free tetra-iodothyronine (FT4) and free tri-iodothyronine (FT3) were determined by radioimmunoassay, while the rate of resting metabolism was determined by measuring the goats' rate of oxygen consumption. Serum Vitamin B12 concentration was significantly higher (p<0.01) in cobalt-treated (289.6 +/- 40.76 pg/ml) than in control (142.8 +/- 28.27 pg/ml) goats. The mean serum TT4 concentration was significantly (p<0.01) higher in control (59.0 +/- 1.70 nmol/l) than in cobalt-treated (51.6 +/- 2.45 nmol/l) goats. However, the levels of FT4, FT3 and the rate of resting metabolism were unaffected by the goats' cobalt status. Furthermore, the goats did not lose weight or become anaemic.     

Assessment of dose and time responses to TRH and thyrotropin in healthy dogs

Changes in total thyroxine (T₄ [TT₄]), free T₄(FT₄) and total tri-iodothyronine (T₃ [TT₃]) in serum after the intravenous administration of different doses of thyrotropin (TSH) and thy-rotropin-releasing hormone (TRH) were measured in six healthy beagles. Significant (P<0·05) elevations in serum TT₄, FT₄ and TT₃ were observed at each sampling time (two, four, five, six, seven, eight and 10 hours) after administration of 1, 3 or 5 iu (total dose) TSH and peak mean responses were observed six to eight hours after injection. At six hours after injection the mean TT₄, FT₄ and TT₃ levels were approximately 2·6, 3·9 and 1·5 times basal levels, respectively, and there were no significant differences between the three doses of TSH. Significant (P<0·05) elevations in serum TT₄ and FT₄ but not TT₃ were observed at each sampling time (two, four, five, six, seven and eight hours) after the administration of TRH. Peak mean responses were observed at four hours after injection at which time TT₄ and FT₄ levels were approximately 1·7 and 1·9 times basal levels, respectively. No significant differences were observed between the four doses of TRH used (100, 200, 300 and 600 μg total dose). Concentrations of TT₄, FT₄ and TT₃ were significantly (P<0·05) higher following the administration of TSH compared with TRH, and the response to TRH showed greater individual variation.     

Absence of a weight gain response to Vitamin B12 supplementation in weaned dairy heifers grazing pastures of marginal cobalt content

Aim. To obtain information on serum and liver vitamin B₁₂ and urinary methylmalonic acid concentrations as diagnostic tests to predict a weight gain response to supplementation with vitamin B₁₂ in young dairy cattle when grazing pasture of low cobalt content.

Methodology. Forty dairy cattle (12 Friesian, 14 Friesian × Jersey and 14 Jersey) were allocated to two equal sized groups, treated and untreated, based on liveweight. At monthly intervals for 14 months, all animals were weighed, their serum and urine sampled, their liver biopsied and the pasture sampled from the paddocks they were grazing and going to graze. Serum and liver were assayed for Vitamin B₁₂ concentrations. For the first 5 months of the trial, urine was assayed for methylmalonic acid concentrations. Both washed and unwashed pasture samples were assayed for cobalt concentrations.

Results. No weight gain response occurred to Vitamin B₁₂ supplementation in young growing cattle grazing pasture with a cobalt concentration of 0.04-0.06 mg/kg DM. For 5 months of the trial, liver Vitamin B₁₂ concentrations from untreated calves were in the range 75-220 nmol/kg and serum vitamin B₁₂ concentrations were as low as 72 pmol/1. There was no associated growth response to supplementation.

Conclusion. Further trials involving young cattle grazing pastures with cobalt concentrations less than 0.04 mg/kg DM are required to reliably determine liver and serum Vitamin B₁₂ concentrations at which growth responses to Vitamin B₁₂ or cobalt supplementation are likely under New Zealand pastoral grazing conditions.     

Total Thyroxine and Free Thyroxine Index in Plasma of Dairy Cows in Relation To Strength of Heat

Total thyroxine (TT₄) and free thyroxine index (FT₄I) were measured in peripheral plasma of cows. The samples were collected at the time of insemination from 66 cows showing pronounced signs of the heat and from 56 cows showing weak or silent heat. Neither TT₄ or FT₄I in plasma differed significantly between the two categories of oestrous cows.     

Growth response to increasing doses of microencapsulated vitamin B12 and related changes in tissue vitamin B12 concentrations in cobalt-de cient lambs

AIM: To investigate growth responses of cobalt-deficient lambs to increasing doses of microencapsulated vitamin B₁₂, and to measure associated changes in serum and liver vitamin B₁₂ concentrations over 243 days.

METHODS: From a flock grazing pastures that had low cobalt (Co) levels (about 0.06 mg Co/kg dry matter), 4-6-week-old lambs (n=137) were assigned to four groups and received either no treatment or a subcutaneous injection of 3.0, 4.5 or 6.0 mg of microencapsulated vitamin B₁₂ on Day 1. At approximately monthly intervals, all lambs were weighed and blood samples were collected from a selection (n=10) of monitor animals, up to Day 243. Liver biopsies were also carried out on the monitor lambs (n=8) on Days 1, 124 and 215.

RESULTS: The vitamin B₁₂-treated lambs grew significantly faster (p<0.001) than untreated animals. Liveweights after 243 days were 28, 45, 45 and 47 kg for the untreated, 3.0, 4.5 and 6.0 mg vitamin B₁₂-treated lambs, respectively. Of the initial group of untreated lambs, 68% had to be removed before the end of the trial because of substantial weight loss, but none of the treated animals were similarly afflicted. Serum vitamin B₁₂ concentrations increased in all vitamin B₁₂-treated lambs, reaching a peak at Day 25, and those of the 4.5 and 6.0 mg vitamin B₁₂-treated lambs remained significantly higher (except at Day 124) than the untreated lambs to Day 187. However, at Day 124, but not Day 215, the liver vitamin B₁₂ concentrations of treated lambs were two to three times higher than those of controls.

CONCLUSIONS: The growth rates of Co-deficient lambs were markedly improved by injection of 3.0, 4.5 or 6.0 mg of microencapsulated vitamin B₁₂, and liveweights were maintained for at least 243 days. Serum vitamin B₁₂ concentrations were related to this growth response; concentrations of <220 pmol vitamin B₁₂/l were associated with a 95% probability that lambs were Co-deficient and would thus respond to Co/vitamin B₁₂ supplementation. Based on these data, the current New Zealand reference criteria for Co deficiency should be reviewed.

CLINICAL SIGNIFICANCE: An injection of 3 mg microencapsulated vitamin B₁₂2 given to lambs at tailing will treat Co deficiency and will increase and maintain liveweights in a flock for up to 8 months.     

Ovarian and Hormonal Responses to Follicular Phase Administration of Investigational Metastin/Kisspeptin Analog,TAK‐683, in Goats

This study evaluated the effects of follicular phase administration of TAK‐683, an investigational metastin/kisspeptin analog, on follicular growth, ovulation, luteal function and reproductive hormones in goats. After confirmation of ovulation by transrectal ultrasonography (Day 0), PGF_2α (2 mg/head of dinoprost) was administered intramuscularly on Day 10 to induce luteal regression. At 12 h after PGF_2α administration, intravenous administration of vehicle or 35 nmol (50 μg)/head of TAK‐683 was performed in control (n = 4) and treatment (n = 4) groups, respectively. Blood samples were collected at 6‐h intervals for 96 h and then daily until the detection of subsequent ovulation (second ovulation). After the second ovulation, ultrasound examinations and blood sampling were performed every other day or daily until the subsequent ovulation (third ovulation). Mean concentrations of LH and FSH in the treatment group were significantly higher 6 h after TAK‐683 treatment than those in the control group (12.0 ± 10.7 vs 1.0 ± 0.7 ng/ml for LH, 47.5 ± 28.2 vs 15.1 ± 3.4 ng/ml for FSH, p < 0.05), whereas mean concentrations of oestradiol in the treatment group decreased immediately after treatment (p < 0.05) as compared with the control group. Ovulation tended to be delayed (n = 2) or occurred early (n = 1) in the treatment group as compared with the control group. For the second ovulation, ovulatory follicles in the treatment group were significantly smaller in maximal diameter than in the control group (3.8 ± 0.5 vs 5.4 ± 0.2 mm, p < 0.05, n = 3). Administration of TAK‐683 in the follicular phase stimulates gonadotropin secretion and may have resulted in ovulation of premature follicles in goats.     

Genetic phylogeography and maternal lineages of 18 Chinese black goat breeds

To understand the origin and genetic phylogeography of Chinese black goats, variations of mitochondrial DNA were characterised with 394 goats from 18 breeds, including 91 new individuals from regions poorly studied until now. Comparison of a 481-bp segment revealed a total of 192 haplotypes with 141 variable sites. The haplotype and nucleotide diversities ranged from 0.782?±?0.079 to 1.000?±?0.020 and from 0.009?±?0.001 to 0.045?±?0.006, respectively, indicating a relatively high genetic diversity in Chinese black goats. Phylogenetic analyses identified five haplogroups (A, B₁, B₂, C and D). The dominant haplogroups A, B₁ and B₂ were distributed in most of breeds, while the haplogroups C and D were only presented in the breeds located in north or northwest of China. Analysis of molecular variance and multidimensional scaling plot of F _ST analyses indicated no obvious geographic structure among breeds. Furthermore, the migration rates revealed that a wide range of gene flow or gene exchange occurred among breeds, which may result in the weak geographic structure of Chinese black goats. Population expansion analysis based on mismatch distribution indicated that two expansion events in Chinese black goats occurred at 10 and 28 mutational time units. Finally, our findings indicate the multiple maternal origins of Chinese black goats and more gene flow (female-mediated) which occurred during their domestic and breeding histories.     

Effect of eCG dose on ovarian haemodynamics,hormonal profiles and prolificacy rate when oestrus was induced during low-breeding season in Beetal goats

The objectives of the experiment were to determine the effect of two doses of equine chorionic gonadotropin (eCG) in a standard synchronization protocol based on a short-term progesterone (P₄) priming on ovarian structures and haemodynamics, concentrations of steroid hormones and prolificacy rate when oestrus was induced during low-breeding season (LBS) in Beetal dairy goats. We hypothesized that inclusion of eCG in a short-term P₄ priming-based synchronization protocol would increase the blood perfusion to ovarian structures leading to enhance oestrous and ovulatory responses and prolificacy rate in goats. Forty-two multiparous acyclic goats were blocked by body condition and, within block, assigned randomly to receive saline as control (CON), low eCG (L-eCG; 300 IU) or high eCG (H-eCG; 600 IU) dose. Initially, a controlled internal drug release (CIDR) device was placed in the anterior vagina on d −8, followed by removal of CIDR on d −3, concurrent with the administration of PGF_2α and eCG according to their respective treatments. Goats were monitored for oestrous response. B-mode and Doppler ultrasonography was performed with 12-h interval, starting from day −3 until natural breeding (day 0), and then on days 5, 10, 15 and 20 post-breeding to monitor follicular and luteal dynamics and blood flow, respectively. Blood was sampled at 0, 12, 24, 36 and 60 h after CIDR removal to quantify plasma concentrations of estradiol-17β (E₂), whereas plasma concentrations of P₄ were assayed at days 5, 10, 15 and 20 after breeding. Pregnancy and prolificacy rates were determined at day 30 and 150 after breeding, respectively. Data were analysed with mixed-effects models, and orthogonal contrasts were used to evaluate the effect of treatment [Con vs. (½ L-eCG + ½ H-eCG)] and dose of eCG (L-eCG vs. H-eCG). Data are presented in sequence as CON, L-eCG, H-eCG (LSM ± SEM). The oestrous intensity score (152.9 vs. 182.7 vs. 186.5 ± 15.1; p = .02) was greater in eCG-treated goats as compared to CON. Administration of eCG reduced the intervals to standing oestrus (66.2 vs. 41.8 vs. 48.9 h ± 5.5; p = .05), breeding (70.2 vs. 44.4 vs. 45.4 h ± 4.5; p = .03) and ovulation (84.5 vs. 61.2 vs. 63.4 h ± 6.2; p = .05) compared with CON goats. The mean growth rate of pre-ovulatory follicle was greater (1.11 vs. 1.49 vs. 1.45 mm ± 0.08; p = .01) in eCG-treated goats resulting in an increased diameter of pre-ovulatory follicle (6.27 vs. 7.20 vs. 7.31 mm ± 0.07; p < .01) and corpora lutea (6.75 vs. 8.26 vs. 8.07 mm ± 0.42; p = .04) than CON. The mean follicular blood flow did not differ among treatments; however, the mean luteal blood flow was greater in L-eCG-treated goats (0.81 vs. 1.61 vs. 1.07 cm² ± 0.12; p = .001). The mean concentrations of E₂ (4.03 vs. 5.21 vs. 4.78 pg/ml ± 0.42; p = .04) and P₄ (4.85 vs. 6.39 vs. 6.22 ng/ml ± 0.34; p = .04) were greater in eCG-treated goats. The twinning rate did not differ between treatments; nevertheless, prolificacy rate was greater (p = .04) in L-eCG-treated goats. Collectively, our data suggest that the administration of eCG improves the induction of oestrous and ovarian dynamics. Administration of L-eCG enhances prolificacy rate, therefore, a low dose of eCG might be practically beneficial to improve reproduction during LBS in acyclic Beetal dairy goats.     

Reduction of the prevalence of footrot on New Zealand farms by vaccination

AIM: To compare serum analyses of vitamin B₁₂ and methylmalonic acid (MMA) as indices of cobalt/vitamin B₁₂ deficiency in lambs around weaning.

METHODS: Lambs on five properties, considered to be cobalt- deficient, were supplemented with either cobalt bullets, or short- or long-acting vitamin B₁₂ preparations. Blood samples, and in some cases liver biopsies, and liveweights were obtained at monthly intervals. Serum samples were assayed for vitamin B₁₂ and MMA and liver for vitamin B₁₂ concentrations. Pasture cobalt concentrations were measured on three of the properties.

RESULTS: Pasture cobalt concentrations were generally maintained below 0.07 μg/g dry matter (DM) on the properties sampled. Growth responses to supplementation were observed on only 2/5 properties, despite serum vitamin B12 concentrations being within the currently used ’marginal‘ reference range (336–499 pmol/L) for at least 3 months on all properties and in the deficient reference range (0–335 pmol/L) for at least 2 months on all farms except one. Serum MMA concentrations in supplemented lambs were <2 μmol/L, except in those animals sampled 1 month after receiving treatment with a short-acting vitamin B12 injection. Serum MMA concentrations in unsupplemented animals on properties on which no growth response to supplementation occurred generally reached peak levels of between 4 and 7 μmol/L at the nadir of serum vitamin B12 concentration. When a growth response was observed, differences in weight gain between supplemented and unsupplemented lambs occurred as mean serum MMA concentrations increased from 9 to 14 μmol/L. On one property where supplementation commenced before weaning, normal growth rates were maintained despite serum vitamin B12 concentrations of 140 pmol/L and serum MMA concentrations in excess of 40 μmol/L serum.

CONCLUSIONS: The possibility that current serum vitamin B₁₂ references ranges for diagnosis of cobalt deficiency are set too high and lead to over-diagnosis of responsiveness to cobalt/ vitamin B₁₂ supplementation is discussed. The suggestion is made that serum MMA concentrations in excess of 9–14 μmol/L will provide a more reliable diagnostic test for cobalt deficiency. However, there was sufficient variation between properties in the relationships between cobalt concentrations of pasture and serum vitamin B₁₂ or MMA concentrations to require more rigorous testing of the reliability of using serum MMA concentration for this purpose. The possibility that differences in rumen fermentation and therefore propionate and vitamin B₁₂ production could be involved is discussed. The measurement of serum MMA and vitamin B₁₂ appears to be of little value whilst the lamb is still suckling.

CLINICAL SIGNIFICANCE: Serum MMA concentration may offer advantages over serum vitamin B₁₂ concentrations in the diagnosis of a cobalt/vitamin B₁₂ responsiveness in weaned lambs.     

Detomidine-Butorphanol-Propofol for Carotid Artery Translocation and Castration or Ovariectomy in Goats

Objective—To determine the safety and efficacy of propofol, after detomidine-butorphanol premedication, for induction and anesthetic maintenance for carotid artery translocation and castration or ovariectomy in goats. Study Design—Case series. Animals—Nine 4-month-old Spanish goats (17.1 ± 2.6 kg) were used to evaluate propofol anesthesia for carotid artery translocation and castration or ovariectomy. Methods—Goats were premedicated with detomidine (10 μg/kg intramuscularly [IM]) and butorphanol (0.1 mg/kg IM) and induced with an initial bolus of propofol (3 to 4 mg/kg intravenously [IV]). If necessary for intubation, additional propofol was given in 5-mg (IV) increments. Propofol infusion (0.3 mg/kg/min IV) was used to maintain anesthesia, and oxygen was insufflated (5 L/min). The infusion rate was adjusted to maintain an acceptable anesthetic plane as determined by movement, muscle relaxation, ocular signs, response to surgery, and cardiopulmonary responses. Systolic (SAP), mean (MAP) and diastolic (DAP) arterial pressures, heart rate (HR), ECG, respiratory rate (RR), Spo₂, and rectal temperature (T) were recorded every 5 minutes postinduction; arterial blood gas samples were collected every 15 minutes. Normally distributed data are represented as mean ± SD; other data are medians (range). Results—Propofol (4.3 ± 0.9 mg/kg IV) produced smooth, rapid (15.2 ± 6 sec) sternal recumbency. Propofol infusion (0.52 ± 0.11 mg/kg/min IV) maintained anesthesia. Mean anesthesia time was 83 ± 15 minutes. Muscle relaxation was good; eye signs indicated surgical anesthesia; two goats moved before surgery began; one goat moved twice during laparotomy. Means are reported over the course of the data collection period. Means during the anesthesia for pH_a (arterial PH), P_aco₂, P_ao₂, HCO₃, and BE (base excess) ranged from 7.233 ± 0.067 to 7.319 ± 0.026, 54.1 ± 4.6 to 65.3 ± 12.0 mm Hg, 133.1 ± 45.4 to 183.8 ± 75.1 mm Hg, 26.9 ± 2.6 to 28.2 ± 2.1 mEq/L, and -0.8 ± 2.9 to 1.4 ± 2.2 mEq/L. Means over time for MAP were 53 ± 12 to 85 ± 21 mm Hg. Mean HR varied over time from 81 ± 6 to 91 ± 11 beats/minute; mean RR, from 9 ± 8 to 15 ± 5 breaths/minute; S_po₂, from 97 ± 3% to 98 ± 3%; mean T, from 36.0 ± 0.6±C to 39.1 ± 0.7±C. Over time, S_po₂ and S_ao₂ did not change significantly; HR, RR, T, and P_aco₂ decreased significantly; SAP, DAP, MAP, pH_a, P_ao₂, and BE increased significantly. HCO₃ concentrations increased significantly, peaking at 45 minutes. Recoveries were smooth and rapid; the time from the end of propofol infusion to extubation was 7.3 ± 3 minutes, to sternal was 9.2 ± 5 minutes, and to standing was 17.7 ± 4 minutes. Median number of attempts to stand was two (range of one to four). Postoperative pain was mild to moderate. Conclusions—Detomidine-butorphanol-propofol provided good anesthesia for carotid artery translocation and neutering in goats. Clinical Relevance—Detomidine-butorphanol-propofol anesthesia with oxygen insufflation may be safely used for surgical intervention in healthy goats.     

Cobalt metabolism in horse. Serum level and biosynthesis of vitamin B12.

The levels of serum vitamin B₁₂ were determined on 16 mature partly warm-blooded, partly Finnish rural-race horses by the radioisotopic competitive inhibition assay method. The mean value from three samplings carried out in dupli- or triplicate was 1.54 ± 0.16 ng/ml. The utilization of serum inorganic cobalt for cyanocobalamin synthesis was studied on two geldings, which received a dose of 200 µCi ⁵⁸CoGl₂ i.v. A Sephadex G-100 gel filtration was carried out with the serum proteins from serial blood samplings at different time intervals 15 min. to 48 hrs. after administration. The gel filtration showed the presence of two labelled proteins in the serum, one of them appearing some time after administration and disappearing almost completely towards the end of the experimental period. The two elution peaks are considered to represent inorganic ⁵⁸Co and ⁵⁸Co labelled vitamin B₁₂. The appearance of labelling in serum vitamin B₁₂ indicates the passing of cobalt into the intestine, and reabsorption into blood in the form of vitamin B₁₂.     

Analysis of serum proteins in clinically healthy goats (Capra hircus) using agarose gel electrophoresis

Background: Electrophoretic patterns of serum proteins provide useful information on pathological conditions in ruminants. Their reference values, however, are dissimilar to those of other species. Reference values for goats using agarose gel as the supporting matrix have not been reported. Objective: The aim of this study was to evaluate serum concentrations of total protein and protein fractions (albumin and globulins) by means of agarose gel electrophoresis (AGE) in goats in order to establish electrophoretic reference intervals and to evaluate potential changes associated with aging. Methods: Blood was collected from 105 clinically healthy Girgentana goats by means of jugular venipuncture. Serum protein concentrations were assessed by AGE. Three age groups were compared: 1–1.5 years, 2–4 years, and 5–12 years. Results: Values (mean ± SD) were determined for concentrations of total protein (72.26 ± 6.40 g/L), albumin (31.80 ± 4.00 g/L), α‐globulins (6.40 ± 1.23 g/L), β₁‐globulins (10.50 ± 2.58 g/L), β₂‐globulins (5.18 ± 1.60 g/L), and γ‐globulins (18.65 ± 5.90 g/L) and for albumin/globulin (A/G) ratio (0.82 ± 0.20). One‐way ANOVA showed statistically significant age‐related differences for total protein and α‐globulin concentrations and A/G ratios. Age influenced protein concentrations with the 5–12‐year‐old group having higher total protein and α‐globulin concentrations and lower albumin concentration and A/G ratios than the 2–4‐year‐old group. Conclusions: This study provides reference values for total protein concentrations and protein fractions obtained by AGE in goats. Some values vary with age. Age‐specific reference intervals are reported in order to provide clinicians with an additional diagnostic aid.     

EVALUATING THE CLINICAL AND PHYSIOLOGICAL EFFECTS OF LONG-TERM ULTRAVIOLET B RADIATION ON RABBITS (ORYCTOLAGUS CUNICULUS)

Vitamin D is an essential hormone in vertebrates. Most animals acquire this hormone through their diet and/or exposure to ultraviolet B (UVB) radiation. The objectives for this research were to evaluate the clinical and physiologic effects of artificial UVB light supplementation on rabbits (Oryctolagus cuniculus) and to evaluate the long-term safety of artificial UVB light supplementation over a 6-month period. Twelve New Zealand white rabbits were randomly assigned to one of two treatment groups: Group A was exposed to 12 hours of artificial UVB radiation daily and Group B received ambient fluorescent light with no UVB supplementation for 12 hours daily. All animals were offered the same diet and housed under the same conditions. Blood samples were collected every 3 weeks over 6 months to measure blood chemistry values, parathyroid hormone, ionized calcium, and serum 25-hydroxyvitamin D₃ (25-OHD₃) levels. Serial ophthalmologic examinations were performed at the beginning of the study and every 2 months thereafter. At the end of the study the animals were euthanized and necropsied. Mean ± SD serum 25-OHD₃ concentrations differed significantly (P = 0.003) between animals provided supplemental UVB radiation (83.12 ± 22.44 nmol/L) and those not provided UVB radiation (39.33 ± 26.07 nmol/L). There were no apparent negative clinical or pathologic side effects noted between the groups. This study found that exposing rabbits to UVB radiation long term significantly increased their circulating serum 25-OHD₃ levels, which was sustainable over time.     

Pharmacokinetics of tulathromycin in plasma and milk samples after a single subcutaneous injection in lactating goats (Capra hircus)

Eight adult female dairy goats received one subcutaneous administration of tulathromycin at a dosage of 2.5 mg/kg body weight. Blood and milk samples were assayed for tulathromycin and the common fragment of tulathromycin, respectively, using liquid chromatography/mass spectrometry. Pharmacokinetic disposition of tulathromycin was analyzed by a noncompartmental approach. Mean plasma pharmacokinetic parameters (±SD) following single‐dose administration of tulathromycin were as follows: C_max (121.54 ± 19.01 ng/mL); T_max (12 ± 12–24 h); area under the curve AUC_0→∞ (8324.54 ± 1706.56 ng·h/mL); terminal‐phase rate constant λz (0.01 ± 0.002 h⁻¹); and terminal‐phase rate constant half‐life t_1/2λz (67.20 h; harmonic). Mean milk pharmacokinetic parameters (±SD) following 45 days of sampling were as follows: C_max (1594 ± 379.23 ng/mL); T_max (12 ± 12–36 h); AUC_0→∞ (72,250.51 ± 18,909.57 ng·h/mL); λz (0.005 ± 0.001 h⁻¹); and t_1/2λz (155.28 h; harmonic). All goats had injection‐site reactions that diminished in size over time. The conclusions from this study were that tulathromycin residues are detectable in milk samples from adult goats for at least 45 days following subcutaneous administration, this therapeutic option should be reserved for cases where other treatment options have failed, and goat milk should be withheld from the human food chain for at least 45 days following tulathromycin administration.     

A comparison of vitamin B12 levels in the liver and serum of sheep receiving treatments used to correct cobalt deficiency

The efficacies of four methods, used for the prophylaxis of cobalt deficiency in sheep as measured by the elevation of liver and serum vitamin B₁₂ levels, were compared in marginally deficient sheep over 14 weeks. The methods used were weekly drenches of either cobalt sulphate or cobalt chelate (EDTA); three-weekly injections of hydroxocobalamin, and ruminal cobalt pellets.

On the basis of elevated liver and serum vitamin B₁₂ levels, chelated cobalt was shown to be available to rumen microflora for the synthesis of vitamin B12. However, at no stage were liver and serum vitamin B₁₂ levels of sheep receiving the chelate significantly different from those receiving the same amount of cobalt as the sulphate.

After five, three-weekly injections of hydroxocabalamin liver vitamin B₁₂ levels were significantly higher (p < 0.01) than for the other treatments, with the exception of cobalt sulphate.

Cobalt pellets led to an initial rapid and significant rise in serum vitamin B₁₂ when compared with the other treatments. However, at four weeks there was no significant difference between treatment groups for serum vitamin B₁₂. Fourteen weeks after the administration of cobalt pellets, serum and liver. vitamin B₁₂ levels in this group were not significantly different from those of untreated sheep. At this time, three out of 12 sheep had lost their pellets.     

Pharmacokinetic–pharmacodynamic modelling of meperidine in goats (I): pharmacokinetics

Qiao, G.-L., Fung, K.-F. Pharmacokinetic-pharmacodynamic modelling of meperidine in goats (I): pharmacokinetics. J. vet. Pharmacol. Therap. 16 , 426–437. Plasma and cerebrospinal fluid (CSF) pharmacokinetics of meperidine were investigated after intramuscular (i.m.) or intravenous (i.v.) administration at a dose of 5 mg/kg in adult goats. After i.m. dosing, the plasma profile was best described by a one-compartment open model. In healthy (n = 16) and postoperative (n = 16) goats, the parameters were, respectively: /_max 8.3 ± 3.9 and 9.2 ± 5.5 min, V_d 2.763 ±1.231 and 3.929 ±2.101 1/kg, Cl_b 0.125 ± 0.036 and 0.087 ± 0.025 1/kg/min, K_c 0.0563 ± 0.0358 and 0.0271 ± 0.0136 min^-1. The plasma profile was best fitted by a two-compartment open model following i.v. injection. In this case, the parameters for healthy (n= 7) and post-operative (n= 13) goats were, respectively: V_d 5.212 ± 1.992 and 5.085 ± 2.288 1/kg, Cl_b 0.096 ± 0.028 and 0.075 ± 0.026 1/kg/min, P 0.0211 ± 0.0093 and 0.0160 ± 0.0052 min.^-1. There were, however, a few individuals with a prolonged elimination phase. Bioavailability of i.m. meperidine was 66.5 ± 15.8% in healthy (n= 6) goats, but much higher in postoperative (n = 10) ones at 94.6 ± 30.0%. Meperidine diffused into and out of CSF according to a first-order rate process. The time-course of CSF drug concentration was simulated by a biexponential function. CSF kinetic parameters of i.m. meperidine for healthy (n = 7) and postoperative (n = 13) goats were: elimination rate constant (K_ei) 0.0269 ± 0.0131 and 0.0305 ± 0.0177 min“¹, peak CSF concentration time (T_naxl) 15.9 ± 5.0 and 17.0 ± 6.9 min. For the i.v. dosed healthy (n = 6) and postoperative (n = 8) animals, K_el was 0.0408 ± 0.0107, 0.0414 ± 0.0123 min^-1 and 7_maxt was 10.0 ± 5.0 and 7.7 ± 2.5 min, respectively. It was demonstrated that an obviously lower peak concentration can be reached significantly later in CSF than in plasma, and the kinetic behaviour of meperidine in plasma is different from that in the CSF, indicating meperidine analgesia might not be predicted by simple extrapolation from the kinetic data.     

Estrus induction in anestrous mixed-breed goats using the “female-to-female effect”

A trial was conducted during the anestrous period in female goats to determine: (a) whether estrus can be induced in anestrous goats by administration of equine chorionic gonadotropic hormone (eCG) and PGF_2α under pen conditions and (b) whether these sexually active female goats can elicit sexual arousal in sexually inactive bucks. One hundred and fifteen pluriparous, nonlactating mixed-breed female goats were randomly assigned to one of four treatment groups: (1) administration of a single dose of 240 IU of eCG, 50 μg PGF_2α i.m., and 25 mg progesterone (P₄) (eCG; n?=?30); (2) administration of P₄ and exposure to female goats treated with eCG–PGF_2α (P₄; n?=?39); (3) administration of 0.5 ml saline and P₄ (Sal; n?=?23); and (4) P₄ plus exposure to female goats treated with saline (Con; n?=?23). After hormone administration, all goats were put together with adult sexually inactive bucks for 15 days. The percentage of goats in estrus during these 15 days was similar in eCG-treated animals and untreated animals exposed to the eCG animals (97 and 95 %). Pregnancy rate was also similar (63 vs. 64 %) between these two groups. eCG-treated goats exhibited estrus earlier (P?<?0.05) than the treated goats in contact with the eCG goats. Furthermore, eCG-treated goats had larger litters (1.9?±?0.2 vs. 1.6?±?0.1, P?<?0.05) than the untreated goats in contact with the eCG goats. These results show that fertile estrus can be induced in anestrous female goats by exposing them to female goats induced to estrus with eCG. This female–female interaction triggers the stimulation cycle leading to the sexual arousal of bucks.     

A critical evaluation of serum methylmalonic acid and vitamin B12 for the assessment of cobalt deficiency of growing lambs in New Zealand

AIM: To derive reference ranges for serum methylmalonic acid (MMA) for the diagnosis of cobalt/vitamin B₁₂-responsiveness in lambs and critique existing serum vitamin B₁₂ reference ranges.

METHODS: Individual animal data from earlier supplementation trials, involving 225 ewes, 106 suckling lambs, 301 lambs during the suckling and post-weaning periods and 414 weaned lambs, for which weight gain to supplementation was observed, were used to derive relationships between serum vitamin B₁₂ and MMA, and liveweight gain.

RESULTS: Serum MMA concentrations were rarely elevated above the norm of <2 µmol/L when serum vitamin B₁₂ concentrations were >375 pmol/L, and not elevated into the range where a liveweight response to supplementation occurred (>10 µmol/L) unless serum vitamin B₁₂ concentrations were below 200 pmol/L. Suckling lambs were able to maintain high growth rates despite elevated serum MMA concentrations (>20 µmol/L).

CONCLUSIONS: The current reference ranges used in New Zealand for serum vitamin B₁₂ are set conservatively high. Serum MMA concentrations appear to allow better differentiation of a responsive condition than vitamin B₁₂ concentrations. Serum MMA concentrations <13 µmol/L indicate responsiveness to supplementation whilst concentrations <7 µmol/L indicate unresponsiveness. In the range 7–13 µmol/L, variation in response was observed and predictability of response is less certain, but supplementation is advisable.

CLINICAL RELEVANCE: The current reference ranges for vitamin B₁₂ responsiveness are conservatively high and lead to over-diagnosis of vitamin B₁₂ deficiency in ill-thriftiness of sheep.     

Secretory Profiles of Pregnancy-Associated Glycoproteins at Different Stages of Pregnancy in the Goat

Plasma concentrations of pregnancy‐associated glycoproteins (PAG) were determined in goats during pregnancy by two homologous radioimmunoassays that employed caprine PAG₅₅₊₆₂ (caPAG₅₅₊₆₂) and caprine PAG₅₅₊₅₉ (caPAG₅₅₊₅₉) and their specific antisera. The effects of fetal number on PAG concentrations were analysed. The concentrations of caPAG₅₅₊₆₂ were higher than that of caPAG₅₅₊₅₉ throughout pregnancy (p <0.05). Both caPAG₅₅₊₆₂ and caPAG₅₅₊₅₉ reached maximal levels in week 8 (48.6 ± 5.0 and 30.4 ± 4.3 ng/ml, respectively), decreased between weeks 12 and 14 (45.5 ± 2.5 to 31.9 ± 2.7 ng/ml and 30.6 ± 2.1 to 15.8 ± 2.8 ng/ml, respectively, p <0.01) and remained relatively constant until parturition. Twin‐bearing goats had higher PAG concentrations than single‐bearing animals, but the difference was only significant in week 4 (52.3 ± 3.7 versus 30.9 ± 3.9 ng/ml and 18.9 ± 1.7 versus 12.6 ± 2.0 ng/ml, for caPAG₅₅₊₆₂ and caPAG₅₅₊₅₉, respectively, p <.,0.05). This is the first study of PAG concentrations in goat throughout pregnancy by a homologous radioimmunoassay system. The profiles of caPAG₅₅₊₆₂ and caPAG₅₅₊₅₉ were closely parallel. Concentrations of PAG were lower than those obtained by a heterologous radioimmunoassay and their patterns were also different, due to a different specificity of the antisera used in heterologous system. Goats that delivered twins had higher PAG concentrations at the time of implantation than those that delivered a single fetus, indicating that PAG concentrations provide a useful measure of the trophoblast secretory activity.