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

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

Synthesis and Characterization of \u3cem\u3ed\u3c/em\u3e\u3csub\u3e5\u3c/sub\u3e-Barbarin for Use in Barbarin-Related Research

Based on structural similarities and equine administration experiments, Barbarin, 5-phenyl-2-oxazolidinethione from Brassicaceae plants, is a possible source of equine urinary identifications of aminorex, (R,S)-5-phenyl-4,5-dihydro-1,3-oxazol-2-amine, an amphetamine-related US Drug Enforcement Administration (DEA) controlled substance considered illegal in sport horses. We now report the synthesis and certification of d5-barbarin to facilitate research on the relationship between plant barbarin and such aminorex identifications. D5-barbarin synthesis commenced with production of d5-2-oxo-2-phenylacetaldehyde oxime (d5-oxime) from d5-acetophenone via butylnitrite in an ethoxide/ethanol solution. This d5-oxime was then reduced with lithium aluminum hydride (LiAlH4) to produce the corresponding d5-2-amino-1-phenylethan-1-ol (d5-phenylethanolamine). Final ring closure of the d5-phenylethanolamine was performed by the addition of carbon disulfide (CS2) with pyridine. The reaction product was purified by recrystallization and presented as a stable white crystalline powder. Proton NMR spectroscopy revealed a triplet at 5.88 ppm for one proton, a double doublet at 3.71 ppm for one proton, and double doublet at 4.11 ppm for one proton, confirming d5-barbarin as the product. Further characterization by high resolution mass spectrometry supports the successful synthesis of d5-barbarin. Purity of the recrystallized product was ascertained by High Performance Liquid Chromatography (HPLC) to be greater than 98%. Together, we have developed the synthesis and full characterization of d5-barbarin for use as an internal standard in barbarin-related and equine forensic research

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

Generation of Facial Composites

A system for generating facial composites, comprises a processor for processing facial composite data and a display for displaying images constructed from facial composite data. The processor is adapted to implement an interface in which a plurality of facial images are presented to a user, and in response to a user input, including the selection of one best match facial image of the plurality of faces, a further plurality of facial images is presented to the user. A mutation algorithm is used for generating the further plurality of facial images, and which generates facial images corresponding to facial composites which vary from the facial composite of the best match facial image in dependence on a random control parameter. The facial composite comprises a vector having a plurality of terms, and each term is assigned a probability of mutating. The random control parameter determines which vector terms are altered. This provides an efficient representation of multiple choice facial images

Recent developments in modeling of the stress derivative of magnetization in ferromagnetic materials

The effect of changing stress on the magnetization of ferromagnetic materials leads to behavior in which the magnetization may increase, or decrease, when exposed to the same stress under the same external conditions. A simple empirical law seems to govern the behavior when the magnetization begins from a major hysteresis loop. The application of the law of approach, in which the derivative of the magnetization with respect to the elastic energy supplied dM/dW is proportional to the magnetization displacement M an−M, is discussed

Salvage radiotherapy for patients with PSA relapse after radical prostatectomy: a single institution experience

<p>Abstract</p> <p>Background</p> <p>To assess the efficacy of salvage radiotherapy (RT) for persistent or rising PSA after radical prostatectomy and to determine prognostic factors identifying patients who may benefit from salvage RT.</p> <p>Methods</p> <p>Between 1990 and 2003, 59 patients underwent RT for PSA recurrence after radical prostatectomy. Patients received a median of 66 Gy to the prostate bed with 3D or 2D RT. The main end point was biochemical failure after salvage RT, defined as an increase of the serum PSA value >0.2 ng/ml confirmed by a second elevation.</p> <p>Results</p> <p>Median follow-up was 38 months. The 3-year and 5-year bDFS rates were 56.1% and 41.2% respectively. According to multivariate analysis, only preRT PSA ≥1 ng/ml was associated with biochemical relapse.</p> <p>Conclusion</p> <p>When delivered early, RT is an effective treatment after radical prostatectomy. Only preRT PSA ≥1 ng/ml predicted relapse.</p

Immune-escape mutations and stop-codons in HBsAg develop in a large proportion of patients with chronic HBV infection exposed to anti-HBV drugs in Europe

Background: HBsAg immune-escape mutations can favor HBV-transmission also in vaccinated individuals, promote immunosuppression-driven HBV-reactivation, and increase fitness of drug-resistant strains. Stop-codons can enhance HBV oncogenic-properties. Furthermore, as a consequence of the overlapping structure of HBV genome, some immune-escape mutations or stop-codons in HBsAg can derive from drug-resistance mutations in RT. This study is aimed at gaining insight in prevalence and characteristics of immune-associated escape mutations, and stop-codons in HBsAg in chronically HBV-infected patients experiencing nucleos(t)ide analogues (NA) in Europe. Methods: This study analyzed 828 chronically HBV-infected European patients exposed to ≥ 1 NA, with detectable HBV-DNA and with an available HBsAg-sequence. The immune-associated escape mutations and the NA-induced immune-escape mutations sI195M, sI196S, and sE164D (resulting from drug-resistance mutation rtM204 V, rtM204I, and rtV173L) were retrieved from literature and examined. Mutations were defined as an aminoacid substitution with respect to a genotype A or D reference sequence. Results: At least one immune-associated escape mutation was detected in 22.1% of patients with rising temporal-trend. By multivariable-analysis, genotype-D correlated with higher selection of ≥ 1 immune-associated escape mutation (OR[95%CI]:2.20[1.32-3.67], P = 0.002). In genotype-D, the presence of ≥ 1 immune-associated escape mutations was significantly higher in drug-exposed patients with drug-resistant strains than with wild-type virus (29.5% vs 20.3% P = 0.012). Result confirmed by ana