Cobalt use and regulation in horseracing: a review

Cobalt, atomic weight 58.9, is a metallic element and environmental substance found in the animal in microgram quantities, predominantly as vitamin B12, but is also a component of at least one mammalian enzyme unassociated with B12. Cobalt is a required trace mineral and has long been administered as a dietary supplement to humans and animals. Cobalt deficiency outside of its requirement in vitamin B12 has not been reported in humans. The administration of cobalt salts was once standard treatment for anaemia in humans, owing to its ability to stimulate red blood cell synthesis. Elemental cobalt acts by stabilising hypoxia inducible factor (HIF-1α), which activates the erythropoietin gene, which in turn increases haemoglobin/red blood cell synthesis, which had led to a presumption that cobalt may be performance enhancing in athletes. Administration of cobalt in amounts sufficient to significantly increase the haematocrit are associated with risk of toxicity in humans, and the only cobalt administration study in horses showed no effect on red blood cell parameters or toxicity. Because of the perception that cobalt administration may enhance athletic performance, racing regulators have recently begun to restrict cobalt use in horseracing which has led to the introduction of cobalt thresholds in several racing jurisdictions. The International Federation of Horseracing Authorities is considering an international regulatory threshold for cobalt of 100 ng/ml in urine, based on studies performed in five different countries. In the United States, the Racing Commissioners International has recently set a primary plasma threshold of 25 ng/ml and secondary threshold of 50 ng/ml. One New York and New Jersey racetrack owner has initiated testing for cobalt and has denied his facilities to trainers whose horses tested positive for excessive quantities of cobalt. This review seeks to summarise what is known about the use of cobalt in horse racing

Bovine Colostrum Supplementation Optimises Earnings, Performance and Recovery in Racing Thoroughbreds

Bovine colostrum (BC) is the first milk produced by cows after calving and contains numerous beneficial substances for the immunity and development of the newborn calf. Because of the growth and immune factors in BC, it has become an attractive supplement for use by athletes to support immunity and health during athletic performance. In order to evaluate the effects of oral BC supplementation on equine athletes, this study evaluated the earnings, performance, recovery and incidence of upper respiratory infections (URTI) in racing horses. The study design was a randomized cross-over racing performance study. 21 horses in race training were randomly assigned to train and compete with or without BC supplementation. After each horse competed in three races, it was crossed over to the other group, allowed a three week washout period, and then competed in three additional races. Horses in public training stables of 3 participating trainers were used. Race performance as determined by earnings, Bloodstock Research Information System (BRIS) speed figures, recovery as determined by number of days between races and incidence of upper respiratory tract disease was recorded. 11 horses completed the study. There was no effect of the order of BC supplementation on the measured variables. Horses on BC supplementation earned $ 2,088 more purse money per race, than when unsupplemented (P = 0.016), and ran an average of 5 BRIS speed points higher (P = 0.03). Horses returned to racing on average 7.5 days faster (16.9 days vs 24.4 days, P = 0.048). There were no URTI among the horses on BC supplementation and two infections while not on BC supplementation (z-test, P = 0.11). Statistical analysis showed that horses recovered more quickly, earned three times more money and raced better as judged by BRIS scores while competing with BC supplementation. BC supplemented horses also experienced fewer URTI, although this effect was not significant

Variability in plasma concentrations of methylprednisolone 6 days after intrasynovial injection of methylprednisolone acetate in racing horses: A field study

Background: Methylprednisolone (MP) acetate is a commonly used corticosteroid for suppression of inflammation in synovial structures in horses. Its use is often regulated in equine sports by plasma MP concentrations. Objectives: To describe variability in MP plasma concentrations after MP acetate injection in different synovial structures and with co-administration with hyaluronic acid (HA). Study design: Field study in actively racing horses in three disciplines (Thoroughbred, Standardbred and Quarter Horse). Methods: Seventy-six horses (15 Thoroughbreds, 20 Standardbreds and 41 Quarter Horses) were included in the study. Injection of any synovial structure with a total body dose of 100 mg MP acetate was permitted, data were grouped according to the synovial structure injected and coadministration with HA. Plasma was collected before injection and at 6 days post-injection. Per cent censored data (below the limit of quantification) for each synovial structure were determined, and summary statistics generated by Robust Regression on Order. Differences between synovial structures and co-administration with HA were identified by ANOVA with Tukey’s post hoc testing. Results: Metacarpophalangeal (MCP) plasma concentrations contained 86% censored data and could not be included in the statistical analysis. The carpal joints (CJO) group had a lower plasma MP concentration (P \u3c 0.05) than the distal tarsal joints (DTJ) or medial femorotibial (MFT), the no HA (NHA) group had a lower plasma MP concentration (P \u3c 0.05) than HA. Main limitations: The synovial structures injected varied by racing discipline, so this study was unable to identify any differences between disciplines. Conclusions: Practitioners should be aware that injection of DTJ, CS and MFT joints, and combining MP acetate with HA may prolong its clearance, and withdrawal times for competition in regulated equine sports

Dexamethasone serum concentrations after intravenous administration in horses during race training

Dexamethasone (DXM) sodium phosphate is a widely used corticosteroid for inflammatory conditions in horses, regulated in racing jurisdictions in the USA by a 0.005 ng/ml serum/plasma threshold. This study seeks to describe serum concentrations of DXM at 48 and 72 h after intravenous administration of 20 mg DXM sodium phosphate over 1 to 5 days, and to identify a possible source of DXM overages. 74 horses (39 Thoroughbreds, 13 Standardbreds, 22 Quarter Horses) in active race training received 20 mg DXM sodium phosphate. Serum was collected before injection, at 48 and 72 h post last injection, and analysed by LC/MS-MS (limit of quantification (LOQ) = 2.5 pg/ml). No differences were identified by ANOVA (P≤0.05) for racing breeds, age, gender or the number of days of DXM sodium phosphate administration, so data were pooled for each time point. The DXM serum concentration at 48 h (mean ± standard deviation, range) was 2.18±1.56 pg/ml (&&2.5 to 40 pg/ml). Summary statistics could not be derived for 72 h DXM serum concentration data owing to censored data, but ranged from &2.5 to 95.8 pg/ml. There was one extreme outlier (Tukey) at 48 h, and two extreme outliers at 72 h. A separate study was conducted using sedentary experimental horses to determine the likelihood that positive DXM samples could result from environmental transfer. Urine was collected from a mare 2 to 3 h post administration of 20 mg DXM. Hay with 100 ml of the DXM (17 ng/ml) containing urine was offered to each of six experimental horses and blood was collected at 0, 4, 8, 12, 16, 20 and 24 h. All six horses had plasma DXM concentration above the limit of detection and five of six had plasma DXM concentrations above the LOQ for at least one sample time

Dexamethasone serum concentrations after intravenous administration in horses during race training

Dexamethasone (DXM) sodium phosphate is a widely used corticosteroid for inflammatory conditions in horses, regulated in racing jurisdictions in the USA by a 0.005 ng/ml serum/plasma threshold. This study seeks to describe serum concentrations of DXM at 48 and 72 h after intravenous administration of 20 mg DXM sodium phosphate over 1 to 5 days, and to identify a possible source of DXM overages. 74 horses (39 Thoroughbreds, 13 Standardbreds, 22 Quarter Horses) in active race training received 20 mg DXM sodium phosphate. Serum was collected before injection, at 48 and 72 h post last injection, and analysed by LC/MS-MS (limit of quantification (LOQ) = 2.5 pg/ml). No differences were identified by ANOVA (P ≤ 0.05) for racing breeds, age, gender or the number of days of DXM sodium phosphate administration, so data were pooled for each time point. Summary statistics could not be derived for 72 h DXM serum concentration data owing to censored data, but ranged from \u3c 2.5 to 95.8 pg/ml. There was one extreme outlier (Tukey) at 48 h, and two extreme outliers at 72 h. A separate study was conducted using sedentary experimental horses to determine the likelihood that positive DXM samples could result from environmental transfer. Urine was collected from a mare 2 to 3 h post administration of 20 mg DXM. Hay with 100 ml of the DXM (17 ng/ml) containing urine was offered to each of six experimental horses and blood was collected at 0, 4, 8, 12, 16, 20 and 24 h. All six horses had plasma DXM concentration above the limit of detection and five of six had plasma DXM concentrations above the LOQ for at least one sample time

Комплексная эколого-геохимическая оценка состояния природной среды на территории г. Горняк (Алтайский край)

Объектом исследования является территория г. Горняк (Алтайский край). Предметом исследования являются компоненты природной среды (волосы, накипь, почва, материал хвостохранилищ и листья тополя). Цель работы – изучить элементный состав природной среды и организма человека на территории г. Горняк (Алтайский край).The object of the study is the territory of the town of Gornyak (Altai Territory). The subject of the study is the components of the natural environment (hair, scale, soil, tailings material and poplar leaves). The purpose of the work is to study the elemental composition of the natural environment and the human body in the city of Gornyak (Altai Territory)

S100A4 mRNA-protein relationship uncovered by measurement noise reduction

Intrinsic biological fluctuation and/or measurement error can obscure the association of gene expression patterns between RNA and protein levels. Appropriate normalization of reverse-transcription quantitative PCR (RT-qPCR) data can reduce technical noise in transcript measurement, thus uncovering such relationships. The accuracy of gene expression measurement is often challenged in the context of cancer due to the genetic instability and “splicing weakness” involved. Here, we sequenced the poly(A) cancer transcriptome of canine osteosarcoma using mRNA-Seq. Expressed sequences were resolved at the level of two consecutive exons to enable the design of exon-border spanning RT-qPCR assays and ranked for stability based on the coefficient of variation (CV). Using the same template type for RT-qPCR validation, i.e. poly(A) RNA, avoided skewing of stability assessment by circular RNAs (circRNAs) and/or rRNA deregulation. The strength of the relationship between mRNA expression of the tumour marker S100A4 and its proportion score of quantitative immunohistochemistry (qIHC) was introduced as an experimental readout to fine-tune the normalization choice. Together with the essential logit transformation of qIHC scores, this approach reduced the noise of measurement as demonstrated by uncovering a highly significant, strong association between mRNA and protein expressions of S100A4 (Spearman’s coefficient ρ = 0.72 (p = 0.006)).publishedVersio

Rewarding work : cross-national differences in benefits, volunteering during unemployment, well-being and mental health

Due to increasing labour market flexibilisation a growing number of people are likely to experience unemployment and, as a consequence, lower mental health and well-being. This article examines cross-national differences in well-being and mental health between unemployed people who engage in voluntary work and those who do not, using multilevel data from the European Quality of Life Survey on unemployed individuals in 29 European countries and other external sources. This article finds that, regardless of their voluntary activity, unemployed people have higher levels of well-being and mental health in countries with more generous unemployment benefits. Unexpectedly, the results also suggest that regular volunteering can actually be detrimental for mental health in countries with less generous unemployment benefits. This article concludes that individual agency exercised through voluntary work can partially improve well-being but the generosity of unemployment benefits is vital for alleviating the negative mental health effects of unemployment

TNF deficiency causes alterations in the spatial organization of neurogenic zones and alters the number of microglia and neurons in the cerebral cortex

•TNF deficiency alters the spatial organization of neurogenic zones.•TNF deficiency decreases WNT signaling-related proteins.•TNF deficiency alters neuronal and microglial numbers.•Long-term use of non-selective TNF inhibitors impairs learning and memory.•Long-term use of the soluble TNF selective inhibitor XPro1595 does not affect neurogenesis, learning and memory. Although tumor necrosis factor (TNF) inhibitors are used to treat chronic inflammatory diseases, there is little information about how long-term inhibition of TNF affects the homeostatic functions that TNF maintains in the intact CNS. To assess whether developmental TNF deficiency causes alterations in the naïve CNS, we estimated the number of proliferating cells, microglia, and neurons in the developing neocortex of E13.5, P7 and adult TNF knock out (TNF−/−) mice and wildtype (WT) littermates. We also measured changes in gene and protein expression and monoamine levels in adult WT and TNF−/− mice. To evaluate long-term effects of TNF inhibitors, we treated healthy adult C57BL/6 mice with either saline, the selective soluble TNF inhibitor XPro1595, or the nonselective TNF inhibitor etanercept. We estimated changes in cell number and protein expression after two months of treatment. We assessed the effects of TNF deficiency on cognition by testing adult WT and TNF−/− mice and mice treated with saline, XPro1595, or etanercept with specific behavioral tasks. TNF deficiency decreased the number of proliferating cells and microglia and increased the number of neurons. At the same time, TNF deficiency decreased the expression of WNT signaling-related proteins, specifically Collagen Triple Helix Repeat Containing 1 (CTHRC1) and Frizzled receptor 6 (FZD6). In contrast to XPro1595, long-term inhibition of TNF with etanercept in adult C57BL/6 mice decreased the number of BrdU+ cells in the granule cell layer of the dentate gyrus. Etanercept, but not XPro1595, also impaired spatial learning and memory in the Barnes maze memory test. TNF deficiency impacts the organization of neurogenic zones and alters the cell composition in brain. Long-term inhibition of TNF with the nonselective TNF inhibitor etanercept, but not the soluble TNF inhibitor XPro1595, decreases neurogenesis in the adult mouse hippocampus and impairs learning and memory after two months of treatment