scholarly journals Evaluation of the pharmacokinetics and efficacy of transdermal flunixin for pain mitigation following castration in goats

2020 ◽  
Vol 4 (4) ◽  
Author(s):  
Meggan T Graves ◽  
Liesel Schneider ◽  
Sherry Cox ◽  
Marc Caldwell ◽  
Peter Krawczel ◽  
...  

Abstract The mitigation of pain associated with common management procedures is a rising concern among veterinarians, producers and consumers. Nonsteroidal anti-inflammatory drugs are vital compounds for this purpose due to their cost, convenience, and efficacy. A transdermal formulation of flunixin meglumine (FM) was approved for the treatment of pain in cattle; however, the efficacy has yet to be determined for small ruminants. The current study had two aims: 1) to determine the pharmacokinetics of transdermal flunixin meglumine (TD FM) in bucklings and 2) to evaluate pain mitigation by TD FM following castration. To evaluate pharmacokinetics, 12 male goats (mean age = 6 mo) received 2.2 mg/kg of FM IV (n = 6) or 3.3 mg/kg TD FM (n = 6). Plasma FM concentrations were measured. The mean Cmax, Tmax, and harmonic mean half-life for TD FM were 1.09 ± 0.65 μg/mL, 5.50 ± 2.95 h, and 7.16 ± 2.06 h, respectively. To evaluate the efficacy of pain mitigation, 18 goats were randomly assigned to three treatment groups: 1) TD FM and castration (FM CAST) (n = 6); 2) transdermal placebo and castration (PL CAST) (n = 6); and 3) TD FM and sham castration (SHAM) (n = 6). Plasma samples were collected at 0, 12, 24, 36, 48, 72, and 96 h to assess cortisol and prostaglandin E2 (PGE2). Daily dry matter intake (DMI) was recorded and body weight was measured at the beginning and end of the study. Thermography (IRT) images of the scrotum, as well as heart rate (HR), respiratory rate (RR), and rectal temperature, were taken twice daily. Separate mixed analysis of variance models were used to test the effects of treatment, time, and their interaction on mean body temperature, IRT, HR, and RR. Autoregressive covariance structure was utilized to account for repeated measures and individual goat DMI prior to the study was added as a covariate. There were no differences in vital parameters, IRT measurements, cortisol, or PGE2 in animals receiving either TD FM or placebo following castration (P > 0.05). DMI had a treatment by hour interaction and was significantly higher in FM CAST and SHAM groups than the PL CAST group (P = 0.04). Goats in the SHAM group gained weight throughout the study, whereas goats in all other groups lost weight (P = 0.02). Results indicate that TD FM may mitigate pain as demonstrated by increased DMI; however, a single dose may not be sufficient to reduce physiological indicators of pain associated with castration in goats.

Methodology ◽  
2017 ◽  
Vol 13 (1) ◽  
pp. 9-22 ◽  
Author(s):  
Pablo Livacic-Rojas ◽  
Guillermo Vallejo ◽  
Paula Fernández ◽  
Ellián Tuero-Herrero

Abstract. Low precision of the inferences of data analyzed with univariate or multivariate models of the Analysis of Variance (ANOVA) in repeated-measures design is associated to the absence of normality distribution of data, nonspherical covariance structures and free variation of the variance and covariance, the lack of knowledge of the error structure underlying the data, and the wrong choice of covariance structure from different selectors. In this study, levels of statistical power presented the Modified Brown Forsythe (MBF) and two procedures with the Mixed-Model Approaches (the Akaike’s Criterion, the Correctly Identified Model [CIM]) are compared. The data were analyzed using Monte Carlo simulation method with the statistical package SAS 9.2, a split-plot design, and considering six manipulated variables. The results show that the procedures exhibit high statistical power levels for within and interactional effects, and moderate and low levels for the between-groups effects under the different conditions analyzed. For the latter, only the Modified Brown Forsythe shows high level of power mainly for groups with 30 cases and Unstructured (UN) and Autoregressive Heterogeneity (ARH) matrices. For this reason, we recommend using this procedure since it exhibits higher levels of power for all effects and does not require a matrix type that underlies the structure of the data. Future research needs to be done in order to compare the power with corrected selectors using single-level and multilevel designs for fixed and random effects.


2020 ◽  
Vol 98 (Supplement_3) ◽  
pp. 5-5
Author(s):  
Katie J Heiderscheit ◽  
Erin Deters ◽  
Alyssa Freestone ◽  
Joshua Peschel ◽  
Stephanie L Hansen

Abstract The objective was to investigate effects of 18 h feed and water restriction or transit on cattle behavior. Angus-cross steers (36; 353 ± 33 kg) were housed in pens of 6 and assigned to treatments: control (CON), full access to feed and water; deprived (DEPR), no feed or water for 18 h; or transported (TRANS), trucked for 18 h. Individual BW (n = 12 steers/treatment) was recorded on d 0, 1, 3, 8, and 14, and individual dry matter intake (DMI) was determined via GrowSafe bunks. Bunk displacements on d 1 were recorded for each pen (n = 2 pens/treatment) by one trained observer continuously for 2 h in 10 min intervals via video analysis. Steer need preferences were assessed as time individuals took to perform behaviors (eat, drink, lay) after treatments ended on d 1. Data were analyzed using Proc Mixed of SAS with fixed effect of treatment; displacements, BW, and DMI were analyzed as repeated measures. Upon return to pens, time to eat or drink did not differ between DEPR and TRANS (P ≥ 0.17), but time to lay was 70.5 min for DEPR vs. 16.5 min for TRANS (P = 0.01). Displacements were greater for DEPR than CON or TRANS during the first 90 min after accessing feed, while CON displaced more frequently than TRANS for the first 30 min (treatment × time; P = 0.02). While DMI for TRANS was not recovered until d 2, DEPR and CON had similar DMI on d 1 (treatment × day; P < 0.01). Similarly, TRANS BW were, and DEPR tended to be, lesser than CON on d 1; however, BW among treatments were not different on other days (treatment × day; P < 0.01). Thus, restricting feed increases aggressive interactions at the bunk and cattle trucked long distances are quick to lay down when allowed. These behaviors should be considered when managing an unintentional feed restriction event or receiving cattle into the feedlot.


2020 ◽  
Vol 4 (4) ◽  
Author(s):  
Dalton Humphrey ◽  
Spenser Becker ◽  
Jason Lee ◽  
Keith Haydon ◽  
Laura Greiner

Abstract Four hundred and eighty (PIC 337 X 1050, PIC Genus, Hendersonville, TN) pigs were used to evaluate a novel threonine source (ThrPro, CJ America Bio, Fort Dodge, IA) for nursery pigs from approximately 7 to 20 kg body weight (BW). After weaning, pigs were sorted by sex and fed a common diet for 1 wk. Upon completion of the first week, pigs were sorted into randomized complete blocks, equalized by weight, within 16 replications. Pigs were allocated to one of three dietary treatments: positive control (POS)—standard ileal digestible threonine-to-lysine ratio (SID; Thr:Lys) 0.60, negative control (NEG)—SID Thr:Lys ≤0.46, and alternative Thr source (TEST)—SID Thr:Lys 0.60. The alternative Thr source included fermentative biomass and was assumed to contain 75% Thr and a digestibility coefficient of 100% based on the manufacturer’s specifications. All other nutrients met or exceeded the NRC recommendations. Growth and intake data were analyzed as repeated measures with a compound symmetry covariance structure using the MIXED procedure in SAS 9.4 (SAS Institute Inc., Cary, NC) with pen as the experimental unit. Treatment, phase, the interaction between treatment and phase, and block were included as fixed effects in the model. Differences in total removals were tested using Fisher’s Exact Test of PROC FREQ. Results were considered significant at P ≤ 0.05 and considered a trend at P > 0.05 and P ≤ 0.10. During the first 14 d, pigs fed TEST had decreased gain-to-feed ratio (G:F; 0.77 vs. 0.80, P = 0.022) compared to POS and increased G:F (0.77 vs. 0.73, P < 0.001) compared to NEG. Over days 14–28, pigs fed TEST had similar G:F (0.71 vs. 0.70, P = 0.112) compared to POS and increased G:F (0.71 vs. 0.63, P < 0.001) compared to NEG. Overall (days 0–28), pigs fed TEST had similar average daily gain (ADG; 0.47 vs. 0.47 kg/d, P = 0.982) and G:F (0.76 vs. 0.74, P = 0.395) compared to POS and increased ADG (0.47 vs. 0.43 kg/d, P < 0.001) and G:F (0.76 vs. 0.67, P < 0.001) compared to NEG. The average daily feed intake was not significantly different across treatments for the entirety of the study. In conclusion, the replacement of crystalline L-Thr with a novel Thr source resulted in similar growth performance in nursery pigs from approximately 7 to 20 kg.


Test ◽  
2017 ◽  
Vol 27 (2) ◽  
pp. 360-378 ◽  
Author(s):  
Ivan Žežula ◽  
Daniel Klein ◽  
Anuradha Roy

2019 ◽  
Vol 3 (2) ◽  
Author(s):  
E. Gubbels ◽  
R. R. Salverson ◽  
K. M. Cammack ◽  
J. K. Grubbs ◽  
K. R. Underwood ◽  
...  

ObjectivesThe objective of this study was to compare the influence of two low stress weaning methods with conventional weaning on post-weaning performance and carcass characteristics of beef steers.Materials and MethodsAngus × Simmental crossbred steer calves (n = 90) from a single source were stratified by body weight and dam age into three groups; one treatment was randomly assigned to each group: ABRUPT (calves isolated from dams on the day of weaning), FENCE (calves separated from dams via a barbed wire fence for 7 d prior to completely weaning), and NOSE (nose-flap inserted and calves remained with dams for 7 d prior to completely weaning). At d +7 post-weaning calves were transported to a commercial feedlot where they received standard step-up and finishing rations typical for a Northern Plains feedlot. To understand the influence of each weaning method on haptoglobin (an acute-phase protein), blood samples were collected via coccygeal venipuncture at d –7 (PreTreat), 0 (Weaning), and +7 (PostWean) from a subsample of calves (n = 10 per treatment) and analyzed using a bovine haptoglobin ELISA kit. Body weights (BW) were recorded on study d –34 (PreWean), –7 (PreTreat), 0 (Weaning), 7 (PostWean), 32 (Receiving), 175 (Ultrasound), and 253 (Final) and average daily gains (ADG) were calculated between each time period. On d 175 post-weaning BW were recorded, and ultrasound fat thickness and intramuscular fat were determined and utilized to project marketing dates. Carcass measurements were recorded at the time of harvest and included hot carcass weight, 12th rib backfat, ribeye area, USDA Yield Grade and Quality Grade, and marbling score. Haptoglobin, BW, and ADG data were analyzed as repeated measures using the ante-dependence covariance structure in the MIXED procedure of SAS (SAS Inst. Inc., Cary, NC) for effects of weaning treatment, day, and their interaction; birth weight was included as a covariate for ADG and BW. Carcass traits were analyzed for the effect of weaning treatment using the MIXED procedure. Separation of least-squares means was performed using LSD with a Tukey’s adjustment and assuming an α level of 0.05.ResultsWeaning method interacted (P < 0.0001) with time period for ADG and BW. Calf BW increased in all treatments until the PostWean period, wherein BW decreased (P < 0.0001) in ABRUPT and NOSE and was maintained (P > 0.05) in FENCE. From the Receiving to Final time periods BW increased similarly (P > 0.05) for all treatments. Calf ADG was greater (P < 0.01) in calves in the NOSE treatment at Weaning than ABRUPT or FENCE. In the PostWean period, the FENCE calves had ADG that was not different (P > 0.05) than zero but was greater (P < 0.0001) than the negative ADG of ABRUPT and NOSE calves. During the Receiving period ADG was greater (P < 0.05) for ABRUPT compared to NOSE and FENCE. Time influenced (P < 0.001) haptoglobin concentration. No difference in haptoglobin was observed between the PreTreat and Weaning or PostWean periods; however, haptoglobin concentration was greater (P < 0.001) at PostWean compared to Weaning. Weaning method did not influence (P > 0.05) carcass measurements.ConclusionCollectively these data suggest low stress weaning methods do not significantly improve post-weaning growth performance or carcass merit compared to calves weaned using conventional methods.


Author(s):  
Roberto Baldassarre ◽  
Cristian Ieno ◽  
Marco Bonifazi ◽  
Maria Francesca Piacentini

Purpose: The sensation of fatigue experienced at a certain point of the race is an important factor in the regulation of pacing. The rating of perceived exertion (RPE) is considered one of the main mediators utilized by athletes to modify pacing. The aim was to analyze the relationship between pacing and RPE of elite open water swimmers during national indoor pool championships. Methods: A total of 17 elite open water swimmers (males, n = 9; females, n = 8) agreed to provide RPE every 500 m during the finals of the national championships 5-km indoor pool race. Time splits, stroke rate, and RPE were collected every 500 m. The Hazard score was calculated by multiplying the momentary RPE by the remaining fraction of the race. Athletes were placed in one of two categories: medalists or nonmedalists. For all variables, separate mixed analysis of variances (P ≤ .05) with repeated measures were used considering the splits (ie, every 500 m) as within-subjects factor and the groups (ie, medalists and nonmedalists) as between-subjects factor. Results: Average swimming speed showed a significant main effect for split for both males and females (P < .001). A significant interaction was observed between average swimming speed and groups for females (P = .032). RPE increased in both groups (P < .001) with no difference observed between groups. However, the female nonmedalists showed a disproportionate nonlinear increase in RPE (5.20 [2.31]) halfway through the event that corresponded to the point where they started significantly decreasing speed. Conclusions: The results of the present study show different pacing strategies adopted by medalists and nonmedalists despite a similar RPE.


2019 ◽  
Vol 32 (4) ◽  
pp. 261-273 ◽  
Author(s):  
Lizbet K Gutiérrez-Prado ◽  
María T Sánchez-Torres-Esqueda ◽  
Teodulo Salinas-Rios ◽  
José L Figueroa-Velasco ◽  
José A Martínez-Aispuro ◽  
...  

Background: Coffee pulp has a high content of antioxidants capable of modifying the oxidative status in small ruminants. However, high amounts for a prolonged time can reduce fertility. Objective: To determine the effect of two inclusion levels of coffee pulp during estrous synchronization on reproductive variables and oxidative status of primiparous ewes. Methods: Sixty Suffolk x Dorset primiparous ewes were distributed into three treatments in a completely randomized design; T0: (n=20) 1.5 kg balanced diet, Tl: (n=20) 1.5 kg balanced diet and 5% coffee pulp, T2: (n=20) 1.5 kg balanced diet and 10% coffee pulp. Supplementation was given for 16 days before estrus synchronization and until the beginning of the breeding season. A progestogen (CIDR®) was inserted for ll days and a dose of PGF2a was applied two days prior to its withdrawal. Estrus detection started 12 hours after CIDR withdrawal. Blood samples were obtained during the supplementation period to measure oxidative status, antioxidant capacity, glucose and insulin, and up to 9 days after breeding to determine progesterone concentration. Pregnancy diagnosis was performed at 30 and 60 days post-breeding. An analysis of repeated measures of mixed effects and frequency analysis were carried out. Results: Inclusion of coffee pulp for a short period prior to breeding did not affect reproductive parameters, nor progesterone, glucose or insulin concentrations (p>0.05); however, antioxidant capacity increased, while lipid oxidation showed an opposite trend (p<0.05). Conclusion: Inclusion of up to 10% coffee pulp in the diet of ewe lambs for 16 days prior to breeding improves oxidative status without causing adverse effects on pregnancy, estrus or prolificacy.


2020 ◽  
pp. 1471082X2094331
Author(s):  
Wagner H. Bonat ◽  
Ricardo R. Petterle ◽  
Priscilla Balbinot ◽  
Alexandre Mansur ◽  
Ruth Graf

We propose a multivariate regression model to deal with multiple outcomes along with repeated measures in the context of longitudinal data analysis. Our model allows for flexible and interpretable modelling of the covariance structure within outcomes by using a linear combination of known matrices, while the generalized Kronecker product is employed to take into account the correlation between outcomes. We present maximum likelihood estimation along with extensions of the classical multivariate analysis of variance and multiple comparison hypothesis tests to deal with multivariate longitudinal data. The model and the associated multivariate hypothesis test are motivated by a prospective study conducted to compare three aesthetic eyelid surgery techniques, namely blepharoplasty, endoscopic forehead lift and endoscopic forehead lift associated with blepharoplasty. The effect of the techniques was assessed using measurements of a horizontal line through pupil centre and then three vertical lines, which go in direction to lateral canthus, middle pupil and medial canthus to the top of the brow. In this study, 30 female patients were randomly divided into three groups. Preoperative measurements were compared with postoperative measurements taken 30 days, 90 days and 10 years after the surgery. The presented multivariate model provided a better fit than its univariate counterpart. The results showed that the three surgery techniques tend to increase all considered outcomes in a long-term perspective, that is, from preoperative to 10 years postoperative evaluations. The only exception was for the outcome lateral eyebrow, for which the blepharoplasty had no significant effect.


2016 ◽  
Vol 28 (2) ◽  
pp. 259
Author(s):  
E. L. Gastal ◽  
S. T. Bashir ◽  
M. O. Gastal ◽  
S. G. S. de Tarso ◽  
S. P. Tazawa ◽  
...  

Mechanisms underlying the development of luteinized unruptured follicle (LUF) syndrome in mares were studied to provide a model for human anovulation. The aims of the present study were (1) to determine the effect of recombinant equine LH (reLH) and prostaglandin F2α (PGF2α) on LUF formation (Experiment 1), (2) to identify an optimal dose of COX-2 inhibitor (flunixin-meglumine; FM) required to experimentally induce LUF (Experiment 2), and (3) to evaluate the intrafollicular endocrine milieu in induced LUF (Experiment 3). In Experiment 1, mares (n = 30) were treated with reLH from Days 7 to 15 (Day 0 = ovulation), with PGF2α on Day 7 or in combination. In Experiment 2 (n = 18 mares), FM at doses of 2.0 or 3.0 mg kg–1 every 12 h and hCG (1500 IU) were administered after a follicle ≥32 mm was detected. In Experiment 3 (n = 23 mares), FM at a dose of 2.0 mg kg–1 every 12 h plus hCG was used to induce LUF and investigate the intrafollicular endocrine milieu. Shapiro-Wilk tests were used for analysing data for normal distribution, and data not normally distributed were transformed to ranks before any further analyses. For sequential data, mixed model repeated-measures ANOVA were used. For single-point data, Student’s t-tests were used. No LUF were induced in mares treated with reLH or PGF2α, in combination or separately. However, LUF were induced in 100% of mares using FM at the dose rate of 2.0 and 3.0 mg kg–1 of body weight in combination with 1500 IU of hCG. Intrafollicular PGF2α metabolite (PGFM), PGF2α, and prostaglandin E2 (PGE2) were lower, and the ratio of PGE2 : PGF2α was higher in induced LUF. Higher levels of intrafollicular growth hormone, cortisol, oestradiol, testosterone, and total primary sex steroids were observed in the induced LUF group; however, LH, prolactin, vascular endothelial growth factor-A, and nitric oxide did not differ between the control and induced LUF groups. In conclusion, COX-2 inhibitors used in conjunction with hCG can be used to pharmacologically induce LUF with 100% success in mares. This study revealed part of the intrafollicular endocrine milieu and the association of prostaglandins in LUF formation. We postulated that LUF result from decreased intrafollicular prostaglandin concentrations or altered prostaglandin synthesis, as indicated by disparity in PGE2 : PGF2α ratio. Increased intrafollicular oestradiol, testosterone, cortisol, and growth hormone were associated with LUF formation; however, further studies are necessary to ascertain the cause-effect relationship. The effect of LH on LUF formation remains unclear. This study further encourages the use of intrafollicular v. systemic biomarkers for evaluating ovulatory disorders. Finally, results from this study support the use of the mare as a model for investigating the poorly understood LUF syndrome in women.


2020 ◽  
Vol 32 (2) ◽  
pp. 214
Author(s):  
M. Peixer ◽  
P. Malard ◽  
J. Carvalho ◽  
M. Dode ◽  
J. Viana ◽  
...  

Cumulative tissue damage and chronic inflammation associated with frequent ovum pickup (OPU) may lead to a progressive reduction in the number and quality of the oocytes recovered, particularly in donors with a high antral follicle count. The aim of this study was to evaluate the effect of an intraovarian treatment with mesenchymal stem cells (MSC) on oocyte yield, quality, and development potential during invitro embryo production (IVEP) in cattle donors undergoing repeated OPU. Mesenchymal stem cells were previously isolated from adipose tissue, cultured in Dulbecco's modified Eagle medium until reaching 80% confluence, isolated with trypsin, and frozen in liquid N2 until use. Characterisation of MSC was carried out according to the guidelines of the International Society for Cellular Therapy. Nelore (Bos indicus) cows (n=5) were used in this study, with the ovaries as replicates. The cows underwent eight OPU sessions at 15-day intervals, and the oocytes recovered were graded and used for IVEP with the semen of a single sire and batch under similar invitro culture conditions. To ensure a high inflammatory response, immediately after the fourth OPU session all ovaries received 30 additional punctures, performed with a 16-gauge Jelco needle. Six hours later, the left ovary of each cow was injected with 500µL of Dulbecco's modified phosphate buffered saline (control ovary) and the right ovary received 500µL of Dulbecco's modified phosphate buffered saline with 2.5×106 allogenic MSC (treated ovary). Oocyte yield and embryo production before and after treatment were recorded for each ovary and donor. Grade I blastocysts produced from control and treated ovaries were used for gene expression evaluation. Data was analysed using the repeated-measures procedure of SAS (SAS Institute Inc.) to account for the effects of treatment, time, and interactions. There was no difference (P&gt;0.05) in any endpoint before treatment (sessions 1-4) between the right and left ovaries. Thus, differences between ovaries observed in OPU sessions 5-8 were assumed to be due to the treatment. After the injection of MSC, more total and viable oocytes were collected from the right ovaries compared with the left ovaries (15.3±2.2 vs. 8.7±1.2 (P&lt;0.02) and 13.6±2.1 vs. 7.1±1.0 (P&lt;0.01), respectively), resulting in more embryos produced invitro (7.6±1.2 vs. 3.6±0.6, respectively; P&lt;0.01) as well as more initial and expanded blastocysts (1.4±0.3 vs. 0.4±0.1 and 4.4±0.9 vs. 2.1±0.4, respectively; P&lt;0.04). The proportion of viable oocytes recovered from the right ovary after treatment was greater than that from the left ovary (89.1% vs. 81.5%; P&lt;0.05). However, blastocyst rates did not differ between ovaries before or after treatment (50.4% vs. 55.5%: P&gt;0.05). In the blastocysts produced from treated ovaries, SLC2A3 was overexpressed (P&lt;0.04), whereas there was no difference for the expression of KRT8, PLAC8, SLC2A1, CASP3, PRDX3, or SOD2 (P&gt;0.05), suggesting potential differences in glucose uptake and metabolism. In conclusion, intraovarian treatment with MSC improved oocyte yield and quality and may be an alternative to increase IVEP from donors under intensive OPU schedules. This research was supported by CNPq, CAPES, and Fazenda Grupo Esplanada.


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