Marja Raekallio

Genome-Wide Analysis Reveals Selection for Important Traits in Domestic Horse Breeds

Intense selective pressures applied over short evolutionary time have resulted in homogeneity within, but substantial variation among, horse breeds. Utilizing this population structure, 744 individuals from 33 breeds, and a 54,000 SNP genotyping array, breed-specific targets of selection were identified using an FST-based statistic calculated in 500-kb windows across the genome. A 5.5-Mb region of ECA18, in which the myostatin (MSTN) gene was centered, contained the highest signature of selection in both the Paint and Quarter Horse. Gene sequencing and histological analysis of gluteal muscle biopsies showed a promoter variant and intronic SNP of MSTN were each significantly associated with higher Type 2B and lower Type 1 muscle fiber proportions in the Quarter Horse, demonstrating a functional consequence of selection at this locus. Signatures of selection on ECA23 in all gaited breeds in the sample led to the identification of a shared, 186-kb haplotype including two doublesex related mab transcription factor genes (DMRT2 and 3). The recent identification of a DMRT3 mutation within this haplotype, which appears necessary for the ability to perform alternative gaits, provides further evidence for selection at this locus. Finally, putative loci for the determination of size were identified in the draft breeds and the Miniature horse on ECA11, as well as when signatures of selection surrounding candidate genes at other loci were examined. This work provides further evidence of the importance of MSTN in racing breeds, provides strong evidence for selection upon gait and size, and illustrates the potential for population-based techniques to find genomic regions driving important phenotypes in the modern horse.

Pain alleviation in animals: attitudes and practices of Finnish veterinarians.

A questionnaire was sent to 911 Finnish veterinarians to assess their attitudes and practices to pain relief in animals. Responses to statements about recognition and treatment of pain were either to agree or to disagree. The pain caused by specified surgical and clinical conditions was rated. Inquiries were also posed about the number of analgesics available and their use in specific surgical procedures and clinical situations. The questionnaires were returned by 441 respondents. Women and younger veterinarians generally rated pain higher and treated it more frequently than men and older colleagues. Younger veterinarians and those in larger practices also had more analgesics available than older veterinarians and those in smaller practices. Respondents agreed with the statement that relieving pain is beneficial for animals. However, large differences were present in the frequency of use of pain alleviation between different animal species undergoing similar operations and between clinical conditions scored equally in the numerical rating of pain. The severity and clinical relevance of feline pain is probably often underestimated, as cats were less likely to receive analgesics than dogs after similar operations.

Genetic Diversity in the Modern Horse Illustrated from Genome-Wide SNP Data

Horses were domesticated from the Eurasian steppes 5,000–6,000 years ago. Since then, the use of horses for transportation, warfare, and agriculture, as well as selection for desired traits and fitness, has resulted in diverse populations distributed across the world, many of which have become or are in the process of becoming formally organized into closed, breeding populations (breeds). This report describes the use of a genome-wide set of autosomal SNPs and 814 horses from 36 breeds to provide the first detailed description of equine breed diversity. FST calculations, parsimony, and distance analysis demonstrated relationships among the breeds that largely reflect geographic origins and known breed histories. Low levels of population divergence were observed between breeds that are relatively early on in the process of breed development, and between those with high levels of within-breed diversity, whether due to large population size, ongoing outcrossing, or large within-breed phenotypic diversity. Populations with low within-breed diversity included those which have experienced population bottlenecks, have been under intense selective pressure, or are closed populations with long breed histories. These results provide new insights into the relationships among and the diversity within breeds of horses. In addition these results will facilitate future genome-wide association studies and investigations into genomic targets of selection.

The effects of L-659,066, a peripheral α2-adrenoceptor antagonist, on dexmedetomidine-induced sedation and bradycardia in dogs

OBJECTIVE To investigate the influence of L-659,066, a peripheral α2-adrenoceptor antagonist, on dexmedetomidine-induced sedation and reduction in pulse rate (PR) in dogs. STUDY DESIGN Randomized, cross-over. ANIMALS Six healthy laboratory Beagles. METHODS All animals received dexmedetomidine (5 μg kg-1 IV, DEX) alone or in combination with L-659,066 (250 μg kg-1 IV, DEX + L) with a 7-day rest period between treatments. Sedation was assessed using a composite sedation score and PRs were recorded. Atipamezole (50 μg kg-1 IM, ATI) was administered to reverse the sedation. Overnight Holter-monitoring was carried out to obtain a minimum heart rate (MHR) at rest. RESULTS Bioequivalence was shown for clinical sedation between DEX and DEX + L. Heart rate was significantly higher with DEX + L during the period of sedation. Bioequivalence was demonstrated between MHR and PR in the DEX + L group during the period of sedation. Recoveries after ATI were uneventful. CONCLUSIONS L-659,066 did not affect the quality of dexmedetomidine-induced sedation whilst it attenuated the reduction in PR. Thus, L-659,066 could prove a useful adjunct to reduce the peripheral cardiovascular effects attributed to dexmedetomidine in dogs. CLINICAL RELEVANCE The clinical safety of α2-adrenoceptor agonists could be markedly improved with less peripheral cardiovascular effects.OBJECTIVE To investigate the influence of L-659,066, a peripheral alpha2-adrenoceptor antagonist, on dexmedetomidine-induced sedation and reduction in pulse rate (PR) in dogs. STUDY DESIGN Randomized, cross-over. Animals Six healthy laboratory Beagles. METHODS All animals received dexmedetomidine (5 microg kg(-1) IV, DEX) alone or in combination with L-659,066 (250 microg kg(-1) IV, DEX + L) with a 7-day rest period between treatments. Sedation was assessed using a composite sedation score and PRs were recorded. Atipamezole (50 microg kg(-1) IM, ATI) was administered to reverse the sedation. Overnight Holter-monitoring was carried out to obtain a minimum heart rate (MHR) at rest. RESULTS Bioequivalence was shown for clinical sedation between DEX and DEX + L. Heart rate was significantly higher with DEX + L during the period of sedation. Bioequivalence was demonstrated between MHR and PR in the DEX + L group during the period of sedation. Recoveries after ATI were uneventful. CONCLUSIONS L-659,066 did not affect the quality of dexmedetomidine-induced sedation whilst it attenuated the reduction in PR. Thus, L-659,066 could prove a useful adjunct to reduce the peripheral cardiovascular effects attributed to dexmedetomidine in dogs. CLINICAL RELEVANCE The clinical safety of alpha2-adrenoceptor agonists could be markedly improved with less peripheral cardiovascular effects.

Abdominal radiography in monitoring the resolution of sand accumulations from the large colon of horses treated medically.

This retrospective study consisted of 14 horses (age 6 weeks-12 years) with radiographically evident sand accumulations cranioventrally in the abdomen and clinical signs suggestive of sand enteropathy. The horses were treated medically and resolution of sand was monitored radiographically. Routine treatment consisted of psyllium mucilloid, combined with magnesium sulphate and/or mineral oilif needed. Initially, the number, size and shape of the sand accumulations showed large variation and the response to therapy was not predictable based on the initial appearance of the accumulation. In 2 foals, some of the sand was passed and the rest was mixed with other intestinal contents within 2-4 days. Even large accumulations disappeared in 2-4 days with psyllium alone or combined with mineral oil in 4 horses. In another 4 horses, the size of the accumulations decreased but varying amounts remained approximately at the same site, despite treatment for 1-4 weeks, and all these horses also had either gastric or large colon impaction. Three horses had a limited response to psyllium treatment, but the accumulation resolved with repeated doses of magnesium sulphate, with or without mineral oil. One horse did not respond to prolonged laxative treatment but the accumulation resolved on pasture. Clinical improvement was not necessarily related to the resolution of sand. Radiography of the cranioventral abdomen was found to be a useful means for monitoring the resolution of sand and confirming the effect of medical treatment in removing sand from the large colon in the horse.

The effects of increasing doses of MK-467, a peripheral alpha2-adrenergic receptor antagonist, on the cardiopulmonary effects of intravenous dexmedetomidine in conscious dogs

Different doses of MK-467, a peripheral alpha(2)-adrenergic receptor antagonist, with or without dexmedetomidine were compared in conscious dogs. Eight animals received either dexmedetomidine (10 μg/kg [D]), MK-467 (250 μg/kg [M250] or dexmedetomidine (10 μg/kg) with increasing doses of MK-467 (250 μg/kg [DM250], 500 μg/kg [DM500] and 750 μg/kg [DM750], respectively). Treatments were given intravenously (i.v.) in a randomized, crossover design with a 14-day washout period. Systemic hemodynamics and arterial blood gas analyses were recorded at baseline and at intervals up to 90 min after drugs administration. Dexmedetomidine alone decreased heart rate, cardiac index and tissue oxygen delivery and increased mean arterial pressure and systemic vascular resistance 5 min after administration. DM250 did not completely prevent these early effects, while DM750 induced a decrease in mean arterial pressure. With DM500, systemic hemodynamics remained stable throughout the observational period. MK-467 alone increased cardiac index and tissue oxygen delivery and had no deleterious adverse effects. No differences in arterial blood gases were observed between treatments that included dexmedetomidine. It was concluded that MK-467 attenuated or prevented dexmedetomidines systemic hemodynamic effects in a dose-dependent manner when given simultaneously i.v. but had no effect on the pulmonary outcome in conscious dogs. A 50:1 dose ratio (MK-467:dexmedetomidine) induced the least alterations in cardiovascular function.

Oral ketoprofen is effective in the treatment of non-infectious lameness in sows.

The efficacy of ketoprofen in the treatment of non-infectious lameness in sows was examined in a double-blinded study. Two dose rates of oral ketoprofen were compared to placebo treatment over five consecutive days. Lameness was assessed with a five-grade scoring system prior to and on the last day of the treatment. The rate of treatment success was 54.3% for the ketoprofen 4mg/kg group (n=46), 53.2% for the ketoprofen 2mg/kg group (n=47) and 20.8% for the pigs in the placebo group (n=48). The difference between both ketoprofen groups and the placebo group was significant (P=0.001), but there was no difference between the two ketoprofen groups (P=0.78). Oral ketoprofen was well tolerated and no adverse events were observed. As lameness is a very common problem in sows, oral ketoprofen appeared to be a practical way to alleviate pain and improve the welfare of sows.

Evaluating Complementary Therapies for Canine Osteoarthritis Part I: Green-lipped Mussel (Perna canaliculus)

A green-lipped mussel (GLM) preparation was evaluated in a randomized, double-controlled and double-blinded clinical trial. It was hypothesized that the treatment effect would be less than that of the positive control (carprofen) but more than that of the negative control (placebo). Forty-five dogs with chronic pain and a radiographic diagnosis of osteoarthritis that were randomly allocated into one of three groups completed the study. All dogs were fed the test products or placebo for 8 weeks. The dogs were evaluated four times, at 4-week intervals. Six different variables were assessed: veterinary-assessed mobility index, two force plate variables, owner-evaluated chronic pain index and pain as well as locomotion visual analogue scales (VASs). Intake of extra carprofen was also evaluated. A chi-squared and a Mann–Whitney test were used to determine significance between groups. When changed to dichotomous variables, there were more dogs in the GLM than in the placebo group that improved, according to veterinary-assessed mobility, owner-evaluated chronic pain index and pain VAS (P = 0.031, P = 0.025, P = 0.011, respectively). For the same three, the odds ratio and their confidence interval were over one. The extent of improvement was significantly different between the GLM and the control in veterinary-assessed mobility (P = 0.012) and pain VAS (P = 0.004). In conclusion, GLM alleviated chronic orthopedic pain in dogs although it was not as effective as carprofen. As no side-effects were detected, GLM may be beneficial in dogs e.g. when non-steroidal anti-inflammatory drugs cannot be used.

The effects of L‐659,066, a peripheral α2‐adrenoceptor antagonist, and verapamil on the cardiovascular influences of dexmedetomidine in conscious sheep

We investigated whether administration of L-659,066, a peripheral α(2) -adrenoceptor antagonist, or verapamil, a calcium-channel antagonist, would prevent the cardiovascular effects of dexmedetomidine. Eleven sheep received three intravenous treatments with a randomized, cross-over design: dexmedetomidine (5 μg/kg, DEX); DEX with L-659,066 (250 μg/kg, DEX + L); and verapamil (0.05 mg/kg) 10 min prior to DEX (Ver + DEX). Haemodynamics were recorded at intervals upto 40 min. Acute increases in mean arterial pressure (MAP) (106 ± 10.7 to 120.8 ± 11.7 mmHg), central venous pressure (CVP) (3.3 ± 3.2 to 14.7 ± 5.0 mmHg) and systemic vascular resistance (SVR) (1579 ± 338 to 2301 ± 523 dyne s/cm(5) ), and decreases in cardiac output (CO) (5.36 ± 0.87 to 3.93 ± 1.30 L/min) and heart rate (HR) (88.6 ± 15.3 to 49.7 ± 5.5/min) were detected with DEX. The peak SVR remained lower after Ver + DEX (1835 ± 226 dyne s/cm(5) ) than DEX alone, but the other parameters did not significantly differ between these treatments. 2 min after drug delivery, differences between DEX and DEX + L were statistically significant for all measured haemodynamic parameters. With DEX + L, an early decrease in MAP (99.9 ± 6.8 to 89.3 ± 6.6 mmHg) was detected, and DEX + L induced a slight but significant increase in CVP and a decrease in HR at the end of the observation period, while SVR and CO did not significantly change. All animals were assessed as deeply sedated from 2-20 min with no differences between treatments. L-659,066 has great potential for clinical use to prevent the cardiovascular effects of dexmedetomidine mediated by peripheral α(2) -adrenoceptors, whereas the effects of verapamil were marginal.

Plasma glucose, insulin, free fatty acids, lactate and cortisol concentrations in dexmedetomidine-sedated dogs with or without MK-467: a peripheral α-2 adrenoceptor antagonist.

Six healthy laboratory Beagles were treated IV with 10 μg/kg dexmedetomidine (DEX) or 10 μg/kg dexmedetomidine combined with 500 μg/kg MK-467 in the same syringe (DMK) in a randomised cross-over design with a 14 day washout. Blood was collected immediately before treatment and 35, 60 and 120 min post-injection through a central venous catheter. The plasma concentrations of glucose, insulin, non-esterified free fatty acids (NEFAs), lactate and cortisol were determined. A repeated-measures ANOVA test was used to compare treatments and effects for each sample time point. Significant differences between treatments were found for plasma glucose (P=0.037) and insulin (P=0.009). DEX significantly increased plasma glucose at 120 min, but reduced plasma insulin at 35 and 60 min. NEFA decreased for both treatments at 35 min. This reduction was transient for DMK, whereas it persisted during the follow up period for DEX. Plasma lactate concentrations increased at 35 and 60 min with DEX. Neither treatment altered plasma cortisol concentrations. The addition of MK-467 to dexmedetomidine prevented or abolished most metabolic changes in healthy Beagles.