Pharmacokinetic properties of abamectin after oral administration in dogs.

As the introduction of concentrated cattle pour-on products containing abamectin, there have been veterinary reports of both fatal and non-fatal poisoning in New Zealand working dogs. Because these products are highly palatable to dogs, a toxic dose is readily ingested. The pharmacokinetic properties of abamectin in dogs are not published in the public domain. This information is important in understanding the processes of absorption and elimination when treating poisoned dogs and is useful in determining an appropriate treatment for poisoned dogs. The pharmacokinetic properties of abamectin administered orally to six healthy dogs (3 male and 3 female) at a dose of 0.2 mg/kg were established. Plasma concentrations of abamectin were determined by high-performance liquid chromatography (HPLC) coupled with a fluorescence detector. The maximum plasma concentration (Cmax ) for abamectin was 135.52 ± 38.6 ng/ml at 3.16 ± 0.75 h. The elimination half-life (T1/2 elim (h)) was 26.51 ± 6.86 h. The area under the curve (AUC 0-∞) was 3723.50 ± 1213.08 ng h/ml. The mean residence time (MRT) was 38.82 ± 8.93 h. These pharmacokinetic data provide helpful information regarding the treatment of poisoned dogs.

Pharmacokinetics, efficacy and convulsive dose of articaine hydrochloride in goat kids.

OBJECTIVE: To investigate the pharmacokinetics, efficacy and convulsive dose of articaine hydrochloride in goat kids. STUDY DESIGN: Experimental prospective study. ANIMALS: A total of 18 (n = 6 animals per experiment) male Saanen goat kids (2-4 weeks old). METHODS: The study consisted of three experiments. The first determined the pharmacokinetics of articaine following intravenous administration of articaine hydrochloride (8 mg kg-1). The second experiment investigated the anaesthetic efficacy and pharmacokinetics following cornual nerve block using 1.5% articaine hydrochloride. Anaesthesia of horn buds was evaluated using the response to pinprick test. Non-compartmental analysis was used. The final experiment determined the convulsive dose of articaine and its corresponding plasma concentration following intravenous infusion of articaine hydrochloride (4 mg kg-1 minute-1). Data are shown as mean ± standard deviation. RESULTS: The mean terminal half-life (t1/2λz), mean volume of distribution at steady state (Vdss) and mean plasma clearance (CL) of articaine following intravenous administration were 0.66 hour, 3.81 L kg-1 and 5.33 L hour-1 kg-1, respectively. After cornual nerve block, the mean maximum plasma concentration of articaine was 587 ng mL-1 at 0.22 hour and its mean t1/2λz was 1.26 hours. Anaesthesia of horn buds was observed within 4 minutes following cornual nerve block. The mean dose required to produce convulsions was 16.24 mg kg-1 and mean convulsive plasma concentrations of articaine and articainic acid were 9905 and 1517 ng mL-1, respectively. CONCLUSIONS: Intravenous administration of 8 mg kg-1 of articaine hydrochloride did not cause any adverse effects. Pharmacokinetic data suggest that articaine was rapidly eliminated and cleared. Cornual nerve block using 1.5% articaine hydrochloride alleviated the response to the acute nociceptive stimulus during disbudding. CLINICAL RELEVANCE: Articaine hydrochloride appears to be a safe and effective local anaesthetic for disbudding in goat kids.

Analgesic effects of morphine and butorphanol in broiler chickens.

OBJECTIVE: To evaluate analgesic efficacies of morphine and butorphanol in lame broiler chickens. STUDY DESIGN: Double blind, randomized, controlled experimental study. ANIMALS: In study 1, 36 lame and 36 sound chickens. In study 2, 48 lame and 48 sound chickens. METHODS: Sound and lame chickens were gait scored and randomly assigned into four groups: sound-drug, sound-placebo, lame-drug, and lame-placebo in study 1. In study 2, an additional lame and sound handling control group was included. Chickens in drug groups were injected with either morphine or butorphanol 2 mg kg-1 intravenously. Chickens in placebo groups were injected with an equal volume of normal saline. All birds underwent an obstacle course (OC) and latency-to-lie (LTL) test before injection and at 30 minutes and 2 hours after injection, to assess their walking ability and their standing ability. The time taken to finish the OC and the standing time in the LTL test were recorded. Friedman tests with Dunn's correction were used to identify significant differences. RESULTS: Lame chickens finished the OC faster (mean ± standard deviation 36 ± 8 c.f. 69 ± 18 seconds) after the injection of butorphanol. Morphine caused sedation with an increase in time taken to finish the OC, even in sound chickens. In the lame handling control and placebo groups the OC times increased and the LTL times decreased with each observation. CONCLUSION: Intravenous butorphanol (2 mg kg-1) may be analgesic in chickens for up to 2 hours. Morphine caused sedation.

Effect of choline chloride premedication on xylazine-induced hypoxaemia in sheep.

OBJECTIVE: To determine the anti-inflammatory efficacy of choline in vivo and in vitro and to investigate the anti-inflammatory mechanisms of choline. STUDY DESIGN: Randomized, controlled studies. ANIMALS: In vivo trials used 16 Romney sheep. In vitro experiments utilized RAW 264.7 mouse macrophage cells. METHODS: Hypoxaemia induced in 16 sheep by intravenous (IV) injection of 50 µg kg-1 xylazine, an α-2 agonist, was measured in sheep at 0, 1 and 4 minutes using arterial blood gas analysis with and without 50 mg kg-1 IV choline chloride premedication. Cell culture studies used enzyme-linked immunosorbent assay to measure the release of tumour necrosis factor (TNF-α) from lipopolysaccharide (LPS) stimulated macrophages with and without choline chloride premedication. TNF-α release was compared to thalidomide suppressed and untreated cells. RESULTS: Choline premedication in sheep mitigated a reduction in arterial partial pressure of oxygen (PaO2) but did not prevent development of clinically significant hypoxaemia. Decrease in mean PaO2 of choline treated sheep was 6.36 kPa (47.7 mmHg) compared to 9.81 kPa (73.6 mmHg) in control sheep. In vitro studies demonstrate that choline administered concurrent with LPS activation did not significantly suppress TNF-α expression but that treatment of cells with choline 10 minutes prior to LPS activation did significantly suppress TNF-α expression. Choline pretreated cells expressed 23.99 ± 4.52 ng mg-1 TNF-α while LPS only control cells expressed 33.83 ± 3.20 ng mg-1. CONCLUSIONS: Choline is able to prevent macrophage activation in vitro when administered prior to LPS activation and may reduce hypoxaemia in sheep developing pulmonary oedema after xylazine administration. This effect requires premedication with choline. CLINICAL RELEVANCE: Pharmacological manipulation of autonomic inflammatory responses holds promise for the treatment of inflammation. However, the complex cellular mechanisms involved in this reflex means that an adequate therapy should approach multiple pathways and mechanisms of the inflammatory response.

A novel endoscopic marker for radiological localization and image-guided radiotherapy in esophageal and gastric cancers (with video).

BACKGROUND AND AIMS: Radiotherapy is an accepted modality in the treatment of esophageal cancers and is currently being evaluated in conjunction with chemotherapy for the neoadjuvant treatment of gastric cancers. Our aim was to assess whether a novel endoscopically inserted marker can be used to improve radiological assessment of the primary cancer and allow for image-guided radiotherapy. METHODS: A phase II feasibility study was conducted at a tertiary-care center. Twenty-six consecutive adult patients with esophagogastric cancers underwent endoscopic marking of the tumor margins with a novel radiopaque marker (mixture of lipiodol and n-butyl 2-cyanoacrylate). The main outcome measure was the successful insertion of the marker based on a combination of radiological, endoscopic, and histological assessment. RESULTS: A total of 92 markers were inserted in 26 patients. Twenty-two (88%) had follow-up imaging to assess the 81 markers inserted, 79 of which (97.5%) were visible. There were no postprocedural adverse events noted in our cohort. Radiological assessment of tumor size improved such that it was in line with the endoscopic evaluation after marker placement in 18 of 21 patients (85.7%) who had appropriate follow-up radiology imaging. Ten patients (38.5%) from our cohort underwent image-guided radiotherapy (IGRT) by using the endoscopically inserted markers. CONCLUSION: Within the limitations of our small pilot study, endoscopic placement of our novel marker was successful in the majority of our cohort without significant adverse events. Marker placement resulted in improved radiological localization in the majority of our cohort and allowed for IGRT. (Australian New Zealand Clinical Trials Registry: ACTRN12613000239763.).

Minimizing pain in deer antler removal: Local anaesthetics in ZnO nanoparticle based collagen dressings as a promising solution.

Antler removal in deer is a common practice for various purposes, including meat production and traditional medicine. However, the current industry practice using lidocaine as a local anesthetic has limitations, such as short duration of action and the potential for postoperative infections. In this study, we investigated the performance of a ZnO collagen nanocomposites loaded with local anesthetics to improve wound management and alleviate pain associated with antler removal in red deer. The research involved the preparation of collagen nanocomposites with local anesthetics and testing the drug release rates using in vitro drug release tests. Pharmacokinetic analysis was performed to evaluate the total drug release from the collagen matrix in red deer after velvet removal. Additionally, the analgesic efficacy of these collagen nanocomposite dressings was assessed after antler removal in red deer. Functionalized ZnO nanoparticles were incorporated into collagen fibers to enhance their mechanical stability and prolong drug release. The developed collagen nanocomposites aimed to slowly release local anesthetics and promote wound healing. The findings of this research could have significant implications for improving the pain management and wound healing associated with antler removal in deer. The results obtained from the in vitro drug release tests, pharmacokinetic analysis, and analgesic efficacy evaluations provide valuable insights into the understanding and development of novel approaches for antler removal procedures in red deer. The findings contribute to the advancement of knowledge in this field and lay the foundation for future implementation of improved techniques and protocols for antler removal.

Pharmacokinetics and Pharmacodynamics of Butorphanol and Dexmedetomidine after Intranasal Administration in Broiler Chickens (Gallus gallus domesticus).

Butorphanol and dexmedetomidine (DXM) can produce analgesia in birds. Intranasal (IN) route of drug administration is easier, and free of risks such as pain and tissue damage compared with intravenous, intramuscular or subcutaneous routes in bird species, including wild birds. Although previous studies have demonstrated the use of IN route for producing sedation, no studies are available on the pharmacokinetics and pharmacodynamics of IN drugs in birds. This study analyzed the pharmacokinetics and sedative-analgesic efficacy of intranasal butorphanol (2 mg/kg), dexmedetomidine (80 µg/kg) and their combination (butorphanol, 2 mg/kg; DXM, 80 µg/kg) in healthy, male, Ross broiler chickens (n = 6/group) aged between 6 and 8 weeks. Maximum plasma concentration (Cmax, p = 0.01), area under the plasma concentration-time curve from time zero to 120 min (AUC0 to 120, p = 0.02) and apparent volume of distribution at steady state (Vss, p = 0.02) of DXM were significantly higher than that of DXM co-administered with butorphanol. The mechanical nociceptive thresholds and the sedation scores of DXM group were significantly higher than the baseline value. Dexmedetomidine (80 µg/kg, IN) was effective in chickens, and the drug absorption was more rapid than that of DXM with butorphanol. However, the duration of action of DXM was short. Lower value of Cmax and nociceptive thresholds showed the nonsignificant efficacy of butorphanol at a dose of 2 mg/kg after IN administration in broiler chickens.

Pharmacokinetics and efficacy of a novel long-acting bupivacaine formulation for cornual nerve block in calves.

Local anesthetics are commonly used in farm animals to provide analgesia for painful procedures but can cause adverse effects at high systemic concentrations. The pharmacokinetics and efficacy of a long-acting sucrose acetate isobutyrate (SAIB) bupivacaine formulation following cornual nerve block in calves were compared to lidocaine. Fourteen calves were randomly assigned to one of the treatment groups (i) 5% Bupivacaine-SAIB (BUP-SAIB), n = 7; or (ii) 2% lidocaine (LID), n = 7. Cornual nerve block was performed, and duration of effective analgesia was evaluated by nociceptive threshold testing using a hand-held pressure algometer. Blood samples were collected at various time points and plasma concentrations were analyzed by HPLC. Pharmacokinetic parameters were calculated using a non-compartmental model. The mechanical nociceptive thresholds showed that the novel formulation could desensitize the skin around the horn bud for 18.77 ± 8.88 h (range 8-36 h), compared to 0.79 ± 0.34 h (range 0.5-1.5 h) with lidocaine. The mean maximum plasma concentration (Cmax) of bupivacaine was 152.03 (SD 37.34) ng/mL and its Tmax was 0.39 (SD 0.13) h. The half-life of elimination was 32.79 ± 11.00 h and the rate of clearance was 0.12 ± 0.03 L h-1. No toxicity signs were seen after treatment in either group. The novel formulation produced long-lasting analgesia of several times greater duration than that produced by lidocaine. This study showed that the safety and efficacy of the SAIB formulation justifies further studies in a larger population of animals.

Atypical presentation of oncocytic parathyroid adenoma masquerading as metastatic carcinoma.

Parathyroid carcinoma is the rarest endocrine malignancy. Definitive diagnosis is challenging as it is difficult to distinguish malignant from benign disease. A 71-year-old man presented with weight loss and hypercalcaemia. CT scans revealed multiple lung nodules and lytic bone lesions that were consistent with metastatic dissemination. Technetium-99m-sestamibi-single-photon emission computed tomography scan showed an abnormal uptake in the right thyroid lobe. Fine-needle aspiration (FNA) was performed on three occasions. The patient underwent parathyroidectomy with ipsilateral hemithyroidectomy without postoperative complications. Microscopic examination showed a parathyroid neoplasm with fibrosis and intravascular tumour on a background of unremarkable thyroid parenchyma. This resulted in an initial impression of parathyroid carcinoma. Further review by two independent pathologists provided a final diagnosis of oncocytic parathyroid adenoma. This case highlights the subjectivity and interobserver variation with endocrine histological examination. FNA can induce changes that mimic parathyroid carcinoma on histology. An index of suspicion for benign parathyroid adenomas should be maintained.

QC-Automator: Deep Learning-Based Automated Quality Control for Diffusion MR Images.

Quality assessment of diffusion MRI (dMRI) data is essential prior to any analysis, so that appropriate pre-processing can be used to improve data quality and ensure that the presence of MRI artifacts do not affect the results of subsequent image analysis. Manual quality assessment of the data is subjective, possibly error-prone, and infeasible, especially considering the growing number of consortium-like studies, underlining the need for automation of the process. In this paper, we have developed a deep-learning-based automated quality control (QC) tool, QC-Automator, for dMRI data, that can handle a variety of artifacts such as motion, multiband interleaving, ghosting, susceptibility, herringbone, and chemical shifts. QC-Automator uses convolutional neural networks along with transfer learning to train the automated artifact detection on a labeled dataset of ∼332,000 slices of dMRI data, from 155 unique subjects and 5 scanners with different dMRI acquisitions, achieving a 98% accuracy in detecting artifacts. The method is fast and paves the way for efficient and effective artifact detection in large datasets. It is also demonstrated to be replicable on other datasets with different acquisition parameters.

Wired for musical rhythm? A diffusion MRI-based study of individual differences in music perception.

Music perceptual abilities are subjective and exhibit high inter-individual variability. Twenty-nine participants with varying degrees of musical training were tested for musical perception ability with the Profile of Music Perception Skills (PROMS) and brain structural measures obtained via diffusion tensor imaging. Controlling for the period of training, TBSS results showed that individuals with better musical perception abilities showed increased deviations from linear anisotropy in the corpus callosum. Specifically, mode of anisotropy in the genu and body of the corpus callosum was negatively correlated with music perception score suggesting the presence of crossing fibers. A multi-compartment model of crossing fibers revealed a significant positive relation for partial volumes of secondary fiber populations with timing aspects of music perception. Our results suggest that inter-hemispheric connectivity differences in the anterior parts of the corpus callosum may reflect innate differences in the processing of the rhythmic aspects of music.

Tuberculous infection of thyroid gland: a case report.

Introduction. Tuberculosis is one of the leading causes of morbidity and mortality and almost one-third of the world is infected with this disease. Tuberculosis has been reported in many parts of the human body. But thyroid gland involvement is extremely rare and its true incidence is unknown. Case Presentation. We present the case of a 26-year-old woman who presented with a thyroid cyst which turned out to be a primary mycobacterium tuberculosis infection. Conclusion. The correct diagnosis of thyroid tuberculosis is important because of the availability of medical treatment and the limited role of surgery.