Validation of a LC-MS/MS method to simultaneously quantify thiafentanil and naltrexone in plasma for pharmacokinetic studies in wildlife.

Thiafentanil is a popular opioid agonist that is fully reversed by administering naltrexone. This agonist-antagonist combination is administered to a wide variety of wildlife species for chemical immobilisation, however plasma concentrations for thiafentanil remain unreported. This report describes a method that was developed and validated using human plasma and cross-validated for the analysis of goat plasma. Samples were extracted using a simple protein precipitation and analysed using LC-MS/MS. The assay was validated over the calibration range 4.38 - 1120 ng/mL for thiafentanil and 15.63 - 4000 ng/mL for naltrexone. The mean inter-day accuracies for QCs prepared in human plasma (n = 18) ranged from 94.8 - 103.8 % for thiafentanil and 94.8 - 95.9 % for naltrexone with corresponding precisions of 3.4 - 7.9 % and 2.8 - 11.4 %, respectively. The mean accuracies for QCs prepared in goat plasma (n = 6) ranged from 89.0 - 100.5 % for thiafentanil and 89.0 - 98.0 % for naltrexone with the associated precisions ranging from 7.1 - 11.6 % and 4.8 - 12.3 %, respectively. Both analytes were stable on bench for six hours and for three freeze-thaw cycles. The impact of heat-inactivation, necessary for the inactivation of potential foot-and-mouth disease, on analyte stability, matrix effect and recovery were evaluated, and a correction factor was established to determine the original analyte concentrations. The method was applied to pharmacokinetic samples collected from goats. The use of goats as a model species provides the first insight into the plasma concentrations of thiafentanil.

A randomised control trial to evaluate the effectiveness of a commercial vaccine for pinkeye in Australian beef cattle.

Pinkeye (a generic term to describe infectious bovine keratoconjunctivitis) is a significant disease of cattle worldwide, impacting productivity and animal welfare. One commercial pinkeye vaccine, a systematically administered Moraxella bovis bacterin, has been available in Australia since 2007. This is the first field trial of the effectiveness of this vaccine for the prevention of naturally occurring disease in Australia. Extensively run beef herds in southwest Queensland that regularly experienced pinkeye were enrolled in the trial and animals were randomly allocated to vaccinated and control groups in different proportions in each herd. The subsequent incidence of clinical pinkeye between the two groups was compared for animals less than one-year-old. Data were analysed from 649 cattle from five herds over two pinkeye seasons: three herds of 390 calves from 1st November 2019 to 20th January 2020 and two herds of 259 calves from 23rd September 2020 to 21st April 2021. Pinkeye was common with 24% of all calves (156/649) contracting the disease during the trial. Univariable and multivariable binary logistic mixed-effect models were fitted to account for clustered data and potential residual confounding due to sex, weight, breed, coat colour, and periocular pigmentation. The incidence of pinkeye was not significantly different between vaccinated and control groups, both alone (p = 0.67) and after adjusting for sex and weight differences (p = 0.69). The vaccine was not protective against naturally occurring pinkeye under the field conditions.

A Retrospective Observational Study of Psychosocial Determinants and Psychiatric Diagnoses of Mass Shooters in the United States.

Our aim was to better understand the underlying psychiatric, psychosocial, and psychodynamic aspects of mass shootings in the United States (US). The Mother Jones database of 115 mass shootings from 1982-2019 was used to study retrospectively 55 shooters in the US. After developing a psychiatric-assessment questionnaire, psychiatric researchers gathered multiple psychosocial factors and determined diagnoses and treatment by evaluating the clinical evidence obtained by interviewing forensic psychiatrists, who had assessed the assailant, and/or by reviewing psychiatric evaluations conducted during the judicial proceedings. All 35 surviving-assailant cases were selected. Additionally, 20 cases where the assailant died at the time of the shootings were randomly selected from the remaining 80 cases. The majority of assailants (87.5%) had misdiagnosed and incorrectly treated or undiagnosed and untreated psychiatric illness. Most of the assailants also experienced profound estrangement not only from families, friends, and classmates but most importantly from themselves. Being marginalized and interpersonally shunned rendered them more vulnerable to their untreated psychiatric illness and to radicalization online, which fostered their violence. While there are complex reasons that a person is misdiagnosed or not diagnosed, there remains a vital need to decrease the stigma of mental illness to enable those with severe psychiatric illness to be more respected, less marginalized, and encouraged to receive effective psychotherapeutic and pharmacologic treatments.

Perceptions of Australian cattle farmers regarding the impact of pinkeye on farm productivity and animal welfare.

Pinkeye (infectious bovine keratoconjunctivitis, IBK) is an important disease of cattle worldwide. It has a substantial negative impact on farm productivity and is a major cost burden, but specific data on losses are lacking. This study was conducted to understand farmers' perceptions of the impact of pinkeye on farm productivity and animal welfare, and factors influencing the money farmers estimated spending on pinkeye in 2018. Data were collected by the first Australia-wide online survey on pinkeye. There were 1035 suitable responses analysed for impact on farm productivity. From these 82% of respondents represented farms in southern Australia, 58% reported cattle breeding as their main enterprise, and 89% bred animals on farm. Farmers were more likely to rank the impact of pinkeye on farm productivity as high if they had younger cattle, treated cattle with pinkeye more frequently, and as their herd size increased. Fewer farmers chose pinkeye as an animal welfare concern than as an economic and farm management issue, but overall animal welfare was rated by the greatest number of farmers as a high severity concern (n = 691), followed by decreased sale value and farm profits (n = 561). This suggests a shift in the equipoise between the economics of food animal production and animal welfare expectations. The median amount reportedly spent on pinkeye in 2018 by Australian farmers (n = 779) was $250.00 per farm. Farmers reported spending more money on pinkeye as herd size and number of cattle affected by pinkeye increased, their perception of pinkeye impact on farm productivity and animal welfare increased, if they treated pinkeye more frequently, reported higher fly worry, if their herds contained Angus cattle, if they bred on farm, and if they were located in southern Australian regions. Study findings should be used to better understand pinkeye, target expenditure, and improve outcomes for cattle and farmers.

The Australian 2019/2020 Black Summer Bushfires: Analysis of the Pathology, Treatment Strategies and Decision Making About Burnt Livestock.

In 2019/2020, Australia experienced a severe bushfire event, with many tens of thousands of livestock killed or euthanized. Little systematic research has occurred to understand livestock bushfire injuries, risk factors for injury, or how to make decisions about management of bushfire-injured livestock. Addressing this research gap is important as there is an increasing bushfire incidence globally. This paper presents qualitative research findings about bushfire-injured and killed livestock in the south-east of Australia after the 2019/2020 Australian bushfires. We describe observed pathology, treatments used, and risk factors for injury, then use thematic analysis to understand decision making about managing fire-injured livestock. Livestock injured by the fires showed pathology predominantly associated with the common integument (feet, hooves and skin) and signs of acute respiratory damage. It could take several days for the full extent of burns to become apparent, leaving prognostic doubt. Treatment strategies included immediate euthanasia, salvage slaughter, retention for later culling, treatment and recovery on farm, hospitalization and intensive treatment, or no intervention. Risk factors reported for livestock injury included lack of warnings about an impending fire, the type and amount of vegetation around livestock and the weather conditions on the day the fire reached livestock. Moving stock to an area with little vegetation before fire arrived was seen as protective. Decision making regarding injured livestock appeared influenced by three main themes: (1) observations on the severity of pathology, clinical signs and level of prognostic doubt, (2) pre-existing beliefs about animal welfare (responsibility to minimize unnecessary suffering) and (3) assumptions about the future. The management of livestock was largely appropriate due to the rapid provision of veterinary expertise. However, it is likely that some injured livestock were euthanized due to conservative veterinary advice driven by a lack of opportunity to re-assess stock, with impacts on farmers. In future, resourcing regular revisits of injured livestock to manage risks of gradual progression of burn pathology may facilitate more accurate prognostic assessment, provided injured animals can receive appropriate pain relief. In addition, a more comprehensive burns classification system linked to prognosis that can be rapidly applied in the field may assist assessments.

A Retrospective Observational Study of Psychosocial Determinants and Psychiatric Diagnoses of Mass Shooters in the United States.

Our aim was to better understand the underlying psychiatric, psychosocial, and psychodynamic aspects of mass shootings in the United States (US). The Mother Jones database of 115 mass shootings from 1982-20119 was used to study retrospectively 55 shooters in the US. After developing a psychiatric-assessment questionnaire, psychiatric researchers gathered multiple psychosocial factors and determined diagnoses and treatment by evaluating the clinical evidence obtained by interviewing forensic psychiatrists, who had assessed the assailant, and/or by reviewing psychiatric evaluations conducted during the judicial proceedings. All 35 surviving-assailant cases were selected. Additionally, 20 cases where the assailant died at the time of the shootings were randomly selected from the remaining 80 cases. The majority of assailants (87.5%) had misdiagnosed and incorrectly treated or undiagnosed and untreated psychiatric illness. Most of the assailants also experienced profound estrangement not only from families, friends, and classmates but most importantly from themselves. Being marginalized and interpersonally shunned rendered them more vulnerable to their untreated psychiatric illness and to radicalization online, which fostered their violence. While there are complex reasons that a person is misdiagnosed or not diagnosed, there remains a vital need to decrease the stigma of mental illness to enable those with severe psychiatric illness to be more respected, less marginalized, and encouraged to receive effective psychotherapeutic and pharmacologic treatments.

A Retrospective Observational Study of Psychosocial Determinants and Psychiatric Diagnoses of Mass Shooters in the United States.

Our aim was to better understand the underlying psychiatric, psychosocial, and psychodynamic aspects of mass shootings in the United States (US). The Mother Jones database of 115 mass shootings from 1982-2019 was used to study retrospectively 55 shooters in the US. After developing a psychiatric-assessment questionnaire, psychiatric researchers gathered multiple psychosocial factors and determined diagnoses and treatment by evaluating the clinical evidence obtained by interviewing forensic psychiatrists, who had assessed the assailant, and/or by reviewing psychiatric evaluations conducted during the judicial proceedings. All 35 surviving-assailant cases were selected. Additionally, 20 cases where the assailant died at the time of the shootings were randomly selected from the remaining 80 cases. The majority of assailants (87.5%) had misdiagnosed and incorrectly treated or undiagnosed and untreated psychiatric illness. Most of the assailants also experienced profound estrangement not only from families, friends, and classmates but most importantly from themselves. Being marginalized and interpersonally shunned rendered them more vulnerable to their untreated psychiatric illness and to radicalization online, which fostered their violence. While there are complex reasons that a person is misdiagnosed or not diagnosed, there remains a vital need to decrease the stigma of mental illness to enable those with severe psychiatric illness to be more respected, less marginalized, and encouraged to receive effective psychotherapeutic and pharmacologic treatments.

Perceptions and practices of Australian cattle farmers for the treatment of pinkeye (infectious bovine keratoconjunctivitis).

Pinkeye or infectious bovine keratoconjunctivitis is a globally significant disease and occurs in every state of Australia. Economic loss due to pinkeye can be considerable and it is a major welfare concern, but not all cattle with the disease are treated by farmers. This study was conducted to understand the perceptions and practices of Australian farmers regarding the treatment of pinkeye: factors influencing when farmers treat pinkeye, treatments used and considered effective, and reasons for not treating. Data were gathered using a custom designed online questionnaire. Farmer responses suitable for assessment (n = 985) were analysed using descriptive analyses along with univariable and multivariable ordinal logistic regression models to evaluate the association of 15 explanatory variables with the outcome "when do you treat pinkeye?". Results revealed three variables, farm size, times yarded and ranking of the pain caused by pinkeye, were significantly associated with the frequency of pinkeye treatment. Specifically, farmers with smaller farm sizes were more likely to treat their cattle for pinkeye more frequently. So too were those who yarded their cattle more, and those that rated pinkeye as highly painful. The most used treatments for pinkeye in Australia were pinkeye ointments (n = 861), followed by eye patches (n = 637), pinkeye spray (n = 623), fly control (n = 507), and pinkeye powder (n = 408). Over half of those who had used subconjunctival injection, pinkeye ointments, eye patches, injectable antibiotics and veterinarians rated them as highly effective treatments. Kerosene is still used by some farmers (n = 106). The most common reason for not treating pinkeye was that it was 'too difficult to treat individuals'. These findings provide insight into the attitudes of Australian farmers to the treatment of pinkeye and should be used to improve pinkeye outcomes in cattle.

Japanese encephalitis in Bali, Indonesia: ecological and socio-cultural perspectives.

The increasing number of cases of acute encephalitis syndrome, a key presenting clinical sign of Japanese encephalitis infection in humans, along with increasing laboratory confirmed cases in Bali over recent years have led to the Indonesian government developing a national program of vaccination against Japanese encephalitis virus. In order to inform multidisciplinary management, a review was conducted to assess Japanese encephalitis virus-related cases in humans and animals including their determinants and detection in vectors. Along with published literature, key data from local authorized officers in Bali have been used to convey the recent situation of the disease. Related surveys detected up to 92% of the local children had antibodies against the virus with the annual incidence estimated to be 7.1 per 100,000 children. Additionally, reports on young and adult cases of infection within international travellers infected in Bali were documented with both non-fatal and fatal outcomes. Further seroprevalence surveys detected up to 90% with antibodies to the virus in animal reservoirs. The detection of the virus in certain Culex mosquito species and high levels of seropositivity may be associated with greater risk of the virus transmission to the human population. It was also highlighted that local sociocultural practices for agriculture and livestock were potentially associated with the high density of the vector and the reservoirs, which then may lead to the risk of the disease transmission in the ecology of Bali.

Risk factors associated with pinkeye in Australian cattle.

Pinkeye is the most important bovine ocular disease worldwide and a major welfare and economic concern to the Australian cattle industry. Pinkeye can occur in epidemic proportions, but severity and susceptibility vary within and between herds, indicating that the disease is multifactorial. This study was conducted to identify the on-farm risk factors associated with pinkeye disease in Australian cattle. Data were gathered from cattle farmers using a custom designed online questionnaire. Farmer responses suitable for assessment (n = 999) were analysed with descriptive, univariable and multivariable logistic regression to evaluate the association of 26 explanatory variables with pinkeye within-herd prevalence. Results revealed that farm location, farm grazing area, farmer-reported dust levels, fly levels, rain levels, animal zebu content and cattle age were significantly associated with pinkeye prevalence. More specifically, having a farm located in southern Australia, of smaller grazing area with cattle ≤ 2 years of age, was associated with a higher pinkeye prevalence. Pinkeye prevalence was also greater if respondents ranked their farms as having high fly levels compared to moderate and low fly levels, respectively and on farms ranked low for rainfall compared to moderate and high rainfall, respectively. Those that ranked their farms as having high dust levels had more pinkeye compared to moderate and low dust levels, but moderate dust levels were protective compared to low dust levels. The results confirm that pinkeye disease is multifactorial and is associated with a range of host and environmental factors. These findings should be used to assist in the control of the disease and improve pinkeye outcomes in Australian cattle.

Domestic Mass Shooters: The Association With Unmedicated and Untreated Psychiatric Illness.

BACKGROUND: Given the relative lack of psychiatric information and data on the perpetrators of US mass shootings, the aim of our study was to understand who these "mass shooters" were and whether they had a psychiatric illness. If so, were they competently diagnosed, and if so, were they treated with appropriate medication for their diagnoses before the violence? METHODS: Because a prospective study of diagnosis and treatment could not, for obvious reasons, be carried out, we designed a retrospective, observational study of mass shooters, defined as those who killed 4 or more people with firearms between 1982 and 2012 or who killed 3 or more people with firearms between 2013 and 2019 in the United States. We used the Mother Jones database-a database of 115 persons identified as committing a mass shooting in the United States between January 1982 and September 2019. In the vast majority of the incidents identified in the database, the perpetrator died either during or shortly after the crime, leaving little reliable information about their history-especially psychiatric history. We focused on the 35 mass shooters who survived and for which legal proceedings were instituted because these cases presented the most reliable psychiatric information. For each of these 35 mass shootings, we interviewed forensic psychiatrists and forensic psychologists who examined the perpetrator after the crime and/or collected the testimony and reports by psychiatrist(s) at trial or in the postconviction proceedings contained in the court record. In addition, we reviewed available information from the court proceedings, public records, a videotaped interview of assailant by law enforcement, social media postings of the assailant, and writings of the assailant. After collecting the clinical information from multiple sources on each case to make a Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, diagnosis, we also completed a Sheehan Diagnostic Scale. After this, 20 additional cases where the assailant died at the crime were randomly selected form the remaining 80, to determine whether there were differences in psychiatric diagnoses and treatment between such assailants and those who survived. RESULTS: Twenty-eight of 35 cases in which the assailant survived had a psychiatric diagnosis-18 with schizophrenia, 3 with bipolar I disorders, 2 with delusional disorders, persecutory type, 2 with personality disorders (1 paranoid and 1 borderline), 2 with substance-related disorders without other psychiatric diagnoses, and 1 with posttraumatic stress disorder. Four had no psychiatric diagnosis, and in 3, we did not have enough information to make a diagnosis.Of 15 of 20 cases in which the assailant died, 8 had schizophrenia. None of those diagnosed with psychiatric illnesses were treated with medication. CONCLUSIONS: A significant proportion of mass shooters experienced unmedicated and untreated psychiatric disorder.

Current incidence, treatment costs and seasonality of pinkeye in Australian cattle estimated from sales of three popular medications.

Pinkeye is an economically important ocular disease occurring in all cattle producing areas of Australia. This study was undertaken to estimate the frequency of occurrence of the disease in Australia and treatment costs of the disease to the cattle industry using the sales of popular pinkeye medications as a surrogate indicator. Monthly sales data for Orbenin® Eye Ointment, Opticlox® Eye Ointment and Terramycin® Pinkeye Aerosol were analysed. We first estimated the number of cattle that can be treated with a syringe or a can and then using the data of sales of these pinkeye medications and the total cattle population of Australia, estimated the incidence of pinkeye. Probability distributions were used to include uncertainty around the estimates. Costs to producers were estimated based on retail prices of these medications. The results indicated that 732,864 syringes of Orbenin® Eye Ointment, 134,800 syringes of Opticlox® Eye Ointment and 27,755 cans of Terramycin® Pinkeye Aerosol are sold in Australia per year. Based on some assumptions of the number of cases treated by these drugs and number of cases left untreated, the number of cattle affected by pinkeye each year in Australia was estimated to be 2.80 million (95 % PI: 1.76, 4.65) or 10.25 % (95 % PI: 6.43, 16.97) of the entire Australian cattle herd. The cattle industry is expected to lose AU$ 9.67 million (95 % PI: 8.56, 13.11) each year just considering the cost of these three drugs. The results suggest that losses due to pinkeye in the Australian cattle industry are considerably higher than previously thought and should be used to inform the development of disease prevention and control policies.

Comparison of some cardiopulmonary effects of etorphine and thiafentanil during the chemical immobilization of blesbok (Damaliscus pygargus phillipsi).

OBJECTIVE: To determine the cardiopulmonary effects of etorphine and thiafentanil for immobilization of blesbok. STUDY DESIGN: Blinded, randomized, two-way crossover study. ANIMALS: A group of eight adult female blesbok. METHODS: Animals were immobilized twice, once with etorphine (0.09 mg kg-1) and once with thiafentanil (0.09 mg kg-1) administered intramuscularly by dart. Immobilization quality was assessed and analysed by Wilcoxon signed-rank test. Time to final recumbency was compared between treatments by one-way analysis of variance. Cardiopulmonary effects including respiratory rate (ƒR), arterial blood pressures and arterial blood gases were measured. A linear mixed model was used to assess the effects of drug treatments over the 40 minute immobilization period. Significant differences between treatments, for treatment over time as well as effect of treatment by time on the variables, were analysed (p < 0.05). RESULTS: There was no statistical difference (p = 0.186) between treatments for time to recumbency. The mean ƒR was lower with etorphine (14 breaths minute-1) than with thiafentanil (19 breaths minute-1, p = 0.034). The overall mean PaCO2 was higher with etorphine [45 mmHg (6.0 kPa)] than with thiafentanil [41 mmHg (5.5 kPa), p = 0.025], whereas PaO2 was lower with etorphine [53 mmHg (7.1 kPa)] than with thiafentanil [64 mmHg (8.5 kPa), p < 0.001]. The systolic arterial pressure measured throughout all time points was higher with thiafentanil than with etorphine (p = 0.04). The difference varied from 30 mmHg at 20 minutes after recumbency to 14 mmHg (standard error difference 2.7 mmHg) at 40 minutes after recumbency. Mean and diastolic arterial pressures were significantly higher with thiafentanil at 20 and 25 minute measurement points only (p < 0.001). CONCLUSIONS: Both drugs caused clinically relevant hypoxaemia; however, it was less severe with thiafentanil. Ventilation was adequate. Hypertension was greater and immobilization scores were lower with thiafentanil.

Comparison of cardiopulmonary effects of etorphine and thiafentanil administered as sole agents for immobilization of impala (Aepyceros melampus).

OBJECTIVE: To compare the cardiopulmonary effects of the opioids etorphine and thiafentanil for immobilization of impala. STUDY DESIGN: Two-way crossover, randomized study. ANIMALS: A group of eight adult female impala. METHODS: Impala were given two treatments: 0.09 mg kg-1 etorphine or 0.09 mg kg-1 thiafentanil via remote dart injection. Time to recumbency, quality of immobilization and recovery were assessed. Respiratory rate, heart rate (HR), mean arterial blood pressure (MAP) and arterial blood gases were measured. A linear mixed model was used to analyse the effects of treatments, treatments over time and interactions of treatment and time (p < 0.05). RESULTS: Time to recumbency was significantly faster with thiafentanil (2.0 ± 0.8 minutes) than with etorphine (3.9 ± 1.6 minutes; p = 0.007). Both treatments produced bradypnoea, which was more severe at 5 minutes with thiafentanil (7 ± 4 breaths minute-1) than with etorphine (13 ± 12 breaths minute-1; p = 0.004). HR increased with both treatments but significantly decreased over time when etorphine (132 ± 17 to 82 ± 11 beats minute-1) was compared with thiafentanil (113 ± 22 to 107 ± 36 beats minute-1; p < 0.001). Both treatments caused hypertension which was more profound with thiafentanil (mean overall MAP = 140 ± 14 mmHg; p < 0.001). Hypoxaemia occurred with both treatments but was greater with thiafentanil [PaO2 37 ± 13 mmHg (4.9 kPa)] than with etorphine [45 ± 16 mmHg (6.0 kPa)] 5 minutes after recumbency (p < 0.001). After 30 minutes, PaO2 increased to 59 ± 10 mmHg (7.9 kPa) with both treatments (p < 0.001). CONCLUSIONS AND CLINICAL RELEVANCE: The shorter time to recumbency with thiafentanil may allow easier and faster retrieval in the field. However, thiafentanil caused greater hypertension, and ventilatory effects during the first 10 minutes, after administration.

Do potent immobilising-opioids induce different physiological effects in impala and blesbok?

Potent opioids are known to cause negative alterations to the physiology of immobilised antelope. How these effects differ between species has not been studied. This study aimed to compare time to recumbence and effects of opioid-based immobilisation on the physiology of impala (Aepyceros melampus) and blesbok (Damaliscus pygargus phillipsi). Eight animals of each species were immobilised, with 0.09 mg/kg etorphine and 0.09 mg/kg thiafentanil respectively, in a randomised two-way cross-over study. Variables measured and analysed by means of a linear mixed model included time to recumbence, heart rate, respiratory rate, arterial blood pressure, blood gases, lactate and glucose. In blesbok, mean time to recumbence was not significantly different with either drug (2.5 minutes and 2.2 min, respectively), but in impala thiafentanil achieved a shorter time to recumbence (2.0 min) than etorphine (3.9 min). Mean heart rates of immobilised impala were within reported physiological limits, but lower in immobilised blesbok when both opioids were used (35 beats/min to 44 beats/min vs. 104 ± 1.4 beats/min resting heart rate). Impala developed severe respiratory compromise and hypoxaemia from both opioids (overall mean PaO2 values ranged from 38 mmHg to 59 mmHg over 30 min). In contrast, blesbok developed only moderate compromise. Therefore, significantly different species-specific physiological responses to potent opioid drugs exist in blesbok and impala. Given that these different responses are clinically relevant, extrapolation of immobilising drug effects from one species of African ungulate to another is not recommended.

Dose-effect study of the serotonin agonist R-8-OH-DPAT on opioid-induced respiratory depression in blesbok (Damaliscus pygargus philipsi) and impala (Aepyceros melampus).

OBJECTIVE: To determine whether the R-enantiomer of 8-hydroxy-2-(di-n-propylamino) tetralin (R-8-OH-DPAT) alleviates respiratory depression in antelope species immobilized with etorphine. The experiment also aimed to establish the most clinically effective dose of this serotonin 5- HT1A receptor agonist. ANIMALS: A group of six female blesbok and six female impala. STUDY DESIGN: Each animal was subjected to four immobilization treatments in a prospective four-way crossover design-control treatment consisting of only etorphine at 0.09 mg kg-1 and three treatments consisting of etorphine at 0.09 mg kg-1 combined with 0.005, 0.02 and 0.07 mg kg-1 of R-8-OH-DPAT, respectively. Induction, quality of immobilization and recovery were monitored in each treatment. Physiological variables including heart rate, respiratory rate, arterial blood pressure and blood gases were measured for 35 minutes during immobilization. A linear mixed model was used to assess the effects of treatments over the recumbency period. RESULTS: R-8-OH-DPAT did not influence induction, immobilization or recovery scores. Respiratory rate in blesbok was increased in the medium- and high-dosage R-8-OH-DPAT treatment group. However, this increased respiratory rate did not translate into improvements of arterial partial pressure of oxygen (PaO2) values in the blesbok. The medium and higher dosages of R-8-OH-DPAT in impala led to an improved PaO2 as well as to decreased opioid-induced tachycardia during the first 10 minutes of immobilization. CONCLUSIONS AND CLINICAL RELEVANCE: Previous reports indicated that the racemic mixture of 8-OH-DPAT injected intravenously had a positive effect on blood-gas values in etorphine-treated hypoxemic goats. In this experiment, similar effects could be seen in impala at the higher dosage rates of R-8-OH-DPAT. However, failure to achieve an improvement of blood-gas values in blesbok was an unexpected result. It could be speculated that the dosage, species-specific differences of serotonin receptors or the use of the R-enantiomer of 8-OH-DPAT might play a role.

Pharmacokinetics and bioavailability after intramuscular injection of the 5-HT1A serotonin agonist R-8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) in domestic goats (Capra aegagrus hircus).

To determine the bioavailability and pharmacokinetic properties of the serotonin 5-HT1A receptor agonist R-8-OH-DPAT in goats, and 0.1 mg kg-1 R-8-OH-DPAT hydrobromide was administered intramuscularly (i.m.) and intravenously (i.v.) to six goats in a two-phase cross-over design experiment. Venous blood samples were collected from the jugular vein 2, 5, 10, 15, 20, 30, 40 and 60 min following treatment and analysed by liquid chromatography tandem mass spectrometry. Bioavailability and pharmacokinetic parameters were determined by a one-compartment analysis. Mean bioavailability of R-8-OH-DPAT when injected i.m. was 66%. The mean volume of distribution in the central compartment was 1.47 L kg-1 . The mean plasma body clearance was 0.056 L kg-1  min-1 . All goats injected i.v. and two of six goats injected i.m. showed signs of serotonin toxicity. In conclusion, R-8-OH-DPAT is well absorbed following i.m. injection and the observed pharmacokinetics suggest that administration via dart is feasible. Administration of R-8-OH-DPAT hydrobromide, at a dosage of 0.1 mg kg-1 , resulted in the observation of clinical signs of serotonin toxicity in the goats. It is suggested that dosages for the clinical use of the compound should be lower in order to achieve the desired clinical effect without causing serotonin toxicity.

Mitigation of electroencephalographic and cardiovascular responses to castration in Bos indicus bulls following the administration of either lidocaine or meloxicam.

OBJECTIVE: To investigate the mitigating effects of administration of local anaesthetic or systemic meloxicam on the electroencephalographic (EEG) and cardiovascular responses during surgical castration of Bos indicus bull calves. STUDY DESIGN: Prospective, randomized, experimental study. ANIMALS: Thirty-six 6-8 month-old Bos indicus bull calves, with a mean ± standard deviation weight of 237 ± 19 kg. METHODS: Animals were allocated randomly to three groups of 12 (group L, 260 mg of 2% lidocaine subcutaneously and intratesticularly 5 minutes prior to castration; group M, 0.5 mg kg-1 of meloxicam subcutaneously 30 minutes prior to castration; group C, no preoperative analgesia administered). Anaesthesia was induced and maintained with halothane (0.9-1.1%) in oxygen. Electroencephalogram, heart rate (HR) and mean blood pressure (MAP) were recorded for 300 seconds prior to (baseline, B) and from the start of surgery (first testicle removal, T1). HR and MAP were compared at 10 second intervals for 90 seconds from the start of T1. Median frequency (F50), spectral edge frequency (F95) and total power of the EEG (Ptot) were analysed using area under the curve comparing T1 to B. RESULTS: All EEG variables were significantly different between B and T1 (p ≤ 0.0001). No differences in F50 were found between groups during T1 (p = 0.6491). F95 and Ptot were significantly different between group L and groups C and M during T1 (p = 0.0005 and 0.0163, respectively). There were transient significant changes in HR and MAP in groups L and M compared to group C during the 20-50 second periods. CONCLUSIONS: The EEG changes indicate nociceptive responses in all three groups during surgical castration, greater in group L compared to groups C and M. Both analgesics attenuated the peracute cardiovascular response. Lidocaine and meloxicam administered prior to castration attenuated these responses in Bos indicus bull calves. CLINICAL RELEVANCE: These findings provide support for the preoperative administration of lidocaine and potentially meloxicam for castration in Bos indicus bull calves.

Objective Measures for the Assessment of Post-Operative Pain in Bos indicus Bull Calves Following Castration.

The aim of the study was to assess pain in Bos indicus bull calves following surgical castration. Forty-two animals were randomised to four groups: no castration (NC, n = 6); castration with pre-operative lidocaine (CL, n = 12); castration with pre-operative meloxicam (CM, n = 12); and, castration alone (C, n = 12). Bodyweight was measured regularly and pedometers provided data on activity and rest from day -7 (7 days prior to surgery) to 13. Blood was collected for the measurement of serum amyloid A (SAA), haptoglobin, fibrinogen, and iron on days 0, 3 and 6. Bodyweight and pedometry data were analysed with a mixed effect model. The blood results were analysed with repeated measure one-way analysis of variance (ANOVA). There was no treatment effect on bodyweight or activity. The duration of rest was greatest in the CM group and lowest in the C group. There was a significant increase in the concentrations of SAA, haptoglobin, and fibrinogen in all of the groups from day 0 to 3. Iron concentrations were not different at the time points it was measured. The results of this study suggest that animals rest for longer periods after the pre-operative administration of meloxicam. The other objective assessments measured in this study were not able to consistently differentiate between treatment groups.

Pregnant Sheep in a Farm Environment Did Not Develop Anaemia.

The aim of this study was to document the haematological profile of pregnant ewes throughout gestation. Sheep were divided into three groups (n = 8 per group): non-pregnant, singleton, or twin pregnancy. Blood samples were collected every 14 days from day 55 of gestation for haemoglobin concentration; packed cell volume; total protein; and albumin concentration. On days 55 and 125 of gestation blood was collected for trace element estimation: soluble copper and zinc; glutathione peroxidase (GSHPx); and methylmalonic acid (MMA). Pooled faecal samples were collected on days 55, 97, and 139 of gestation. Pasture cuts were collected on days 97 and 153 of gestation. The haematology and protein concentrations were not different between groups throughout the study. Copper concentration increased in all animals during the study (p < 0.0001). Zinc concentration was lowest in the singleton and twin pregnant sheep on day 55 of gestation (p = 0.04). GSHPx was not different between groups during the study. MMA decreased in all animals during the study (p < 0.0001), but was not different between groups. Faecal samples were consistently negative for strongyle and nematode eggs, and coccidian oocysts. The pasture was good quality. Pregnant sheep in a farm environment with normal trace element status, no parasites, and an adequate diet, did not develop anaemia (PCV < 0.27).