The relationship between measures of reproductive soundness, behavior, and hair testosterone concentrations during performance testing of bulls

Cattle temperament strongly impacts handlers’ safety, and testosterone is associated with cattle docility. Measuring hair testosterone may provide a non-invasive way to evaluate hormone concentrations. This study aimed to analyze chronic hair testosterone concentrations as a method of assessing relationships between endocrine, production, behavioral, and reproductive traits in bulls. Bulls (n=30) were separated into 3 pens for 84 days. Hair, serum, and data were collected at 28-day intervals. Dataloggers on each bull tracked total steps taken, total lying time, number of lying bouts, and lying bout duration from d 0-28 and d 56-84. Reproductive evaluation and carcass ultrasound took place on d 85. Correlation analyses were performed in SAS 9.3. Hair testosterone positively correlated with serum testosterone on d 0 (r=0.50,

The relationship between measures of reproductive soundness, behavior, and hair testosterone concentrations during performance testing of bulls

Cattle temperament strongly impacts handlers’ safety, and testosterone is associated with cattle docility. Measuring hair testosterone may provide a non-invasive way to evaluate hormone concentrations. This study aimed to analyze chronic hair testosterone concentrations as a method of assessing relationships between endocrine, production, behavioral, and reproductive traits in bulls. Bulls (n=30) were separated into 3 pens for 84 days. Hair, serum, and data were collected at 28-day intervals. Dataloggers on each bull tracked total steps taken, total lying time, number of lying bouts, and lying bout duration from d 0-28 and d 56-84. Reproductive evaluation and carcass ultrasound took place on d 85. Correlation analyses were performed in SAS 9.3. Hair testosterone positively correlated with serum testosterone on d 0 (r=0.50,

Theatrical Medicine: Aboriginal Performance, Ritual and Commemoration (for Vanessa Lee Buckner)

The paper begins by discussing some Aboriginal teachings offering the author’s working definition of Medicine based on the teachings that elders have shared. These cultural traditions reflect a belief in the power of performance and the possibility of performance as medicinal. The paper applies some of these teachings about Medicine to suggest that the form and experience of these theatrical events can be understood as contemporary good Medicine. These performances and plays by Aboriginal people bring balance to the witnesses through honouring the deceased by way of naming rituals, they bring balance to communities by showing the humanity of Aboriginal women, and they provide a cathartic ritual or ceremony for the release of trauma. Résumé Cet article commence par présenter un certain nombre d’enseignements et de cérémonies de la tradition autochtone, pour ensuite proposer une définition de la médecine fondée sur les enseignements des Anciens. Ces traditions culturelles reflètent une croyance dans le pouvoir de la performance et dans ses possibilités médicinales. L’article étudie quelques enseignements sur la médecine et décèle dans la forme et l’expérience de ces événements théâtraux des propriétés médicinales contemporaines. Les performances et les pièces d’artistes autochtones contribuent au mieux-être des témoins qui rendent hommage aux femmes décédées par une lecture rituelle de leurs noms; elles contribuent au mieux-être des communautés en montrant l’humanité des femmes autochtones et elles fournissent un rituel ou une cérémonie cathartique qui permet d’évacuer le traumatisme

Sex Differences in Kappa Opioid Receptor Agonist Mediated Attenuation of Chemotherapy-Induced Neuropathic Pain in Mice

Chemotherapy-induced neuropathic pain is a common side effect for cancer patients which has limited effective treatment options. Kappa opioid receptor (KOR) agonists are a promising alternative to currently available opioid drugs due to their low abuse potential. In the current study, we have investigated the effects of Salvinorin A (SalA) analogues, 16-Ethynyl SalA, 16-Bromo SalA and ethyoxymethyl ether (EOM) SalB, and in a preclinical model of paclitaxel-induced neuropathic pain in male and female C57BL/6J mice. Using an acute dose-response procedure, we showed that compared to morphine, 16-Ethynyl SalA was more potent at reducing mechanical allodynia; and SalA, 16-Ethynyl SalA, and EOM SalB were more potent at reducing cold allodynia. In the mechanical allodynia testing, U50,488 was more potent in males and SalA was more potent in females. There were no sex differences in the acute cold allodynia testing. In the chronic administration model, treatment with U50,488 (10 mg/kg) reduced the mechanical and cold allodynia responses to healthy levels over 23 days of treatment. Overall, we have shown that KOR agonists are effective in a model of chemotherapy-induced neuropathic pain, indicating that KOR agonists could be further developed to treat this debilitating condition

Nalfurafine Reduces Neuroinflammation and Drives Remyelination in Models of CNS Demyelinating Disease

Objectives: Multiple sclerosis (MS) is a neurodegenerative disease characterised by inflammation and damage to the myelin sheath, resulting in physical and cognitive disability. There is currently no cure for MS, and finding effective treatments to prevent disease progression has been challenging. Recent evidence suggests that activating kappa opioid receptors (KOR) has a beneficial effect on the progression of MS. Although many KOR agonists like U50,488 are not suitable for clinical use because of a poor side-effect profile, nalfurafine is a potent, clinically used KOR agonist with a favorable side-effect profile. Methods: Using the experimental autoimmune encephalomyelitis (EAE) model, the effect of therapeutically administered nalfurafine or U50,488 on remyelination, CNS infiltration and peripheral immune responses were compared. Additionally, the cuprizone model was used to compare the effects on non-immune demyelination. Results: Nalfurafine enabled recovery and remyelination during EAE. Additionally, it was more effective than U50,488 and promoted disease reduction when administered after chronic demyelination. Blocking KOR with the antagonist, nor‐BNI, impaired full recovery by nalfurafine, indicating that nalfurafine mediates recovery from EAE in a KOR‐dependent fashion. Furthermore, nalfurafine treatment reduced CNS infiltration (especially CD4+ and CD8+ T cells) and promoted a more immunoregulatory environment by decreasing Th17 responses. Finally, nalfurafine was able to promote remyelination in the cuprizone demyelination model, supporting the direct effect on remyelination in the absence of peripheral immune cell invasion. Conclusions: Overall, our findings support the potential of nalfurafine to promote recovery and remyelination and highlight its promise for clinical use in MS

Evaluation of Biased and Balanced Salvinorin A Analogs in Preclinical Models of Pain

This work is licensed under a Creative Commons Attribution 4.0 International License.In the search for safer, non-addictive analgesics, kappa opioid receptor (KOPr) agonists are a potential target, as unlike mu-opioid analgesics, they do not have abuse potential. Salvinorin A (SalA) is a potent and selective KOPr agonist, however, clinical utility is limited by the short duration of action and aversive side effects. Biasing KOPr signaling toward G-protein activation has been highlighted as a key cellular mechanism to reduce the side effects of KOPr agonists. The present study investigated KOPr signaling bias and the acute antinociceptive effects and side effects of two novel analogs of SalA, 16-Bromo SalA and 16-Ethynyl SalA. 16-Bromo SalA showed G-protein signaling bias, whereas 16-Ethynyl SalA displayed balanced signaling properties. In the dose-response tail-withdrawal assay, SalA, 16-Ethynyl SalA and 16-Bromo SalA were more potent than the traditional KOPr agonist U50,488, and 16-Ethynyl SalA was more efficacious. 16-Ethynyl SalA and 16-Bromo SalA both had a longer duration of action in the warm water tail-withdrawal assay, and 16-Ethynyl had greater antinociceptive effect in the hot-plate assay, compared to SalA. In the intraplantar 2% formaldehyde test, 16-Ethynyl SalA and 16-Bromo SalA significantly reduced both nociceptive and inflammatory pain-related behaviors. Moreover, 16-Ethynyl SalA and 16-Bromo SalA had no anxiogenic effects in the marble burying task, and 16-Bromo SalA did not alter behavior in the elevated zero maze. Overall, 16-Ethynyl SalA significantly attenuated acute pain-related behaviors in multiple preclinical models, while the biased KOPr agonist, 16-Bromo SalA, displayed modest antinociceptive effects, and lacked anxiogenic effects.Health Research Council – Explorer grant (16/646)National Institute on Drug Abuse (DA018151)Victoria University of Wellington doctoral scholarshi

Human helminth therapy to treat inflammatory disorders - where do we stand?

Parasitic helminths have evolved together with the mammalian immune system over many millennia and as such they have become remarkably efficient modulators in order to promote their own survival. Their ability to alter and/or suppress immune responses could be beneficial to the host by helping control excessive inflammatory responses and animal models and pre-clinical trials have all suggested a beneficial effect of helminth infections on inflammatory bowel conditions, MS, asthma and atopy. Thus, helminth therapy has been suggested as a possible treatment method for autoimmune and other inflammatory disorders in humans

In vitro antigen presenting cell-derived IL-10 and IL-6 correlate with Trichuris muris isolate-specific survival

Trichuris muris, the mouse whipworm, is used as a laboratory model of the human parasite T. trichiura. Three laboratory isolates of T. muris exist — the E, J and S isolates. Previous data have shown that the S isolate survives to chronicity in C57BL/6 mice unlike the E and J isolates, which are expelled. The ability of the S isolate to persist is thought to be due to it secreting unique excretory/secretory antigens, which interact with APCs such that protective T cell responses do not develop. To determine whether APCs respond differently to E/S antigens from the three isolates we cultured isolate-specific E/S with bone marrow-derived macrophages (BMMΦ) and dendritic cells (BMDCs) in vitro. Markers of co-stimulation and levels of MHC-II were analysed by FACS and cytokine levels in supernatants quantified. E/S antigens from the S isolate consistently stimulated significantly higher levels of IL-10 and IL-6 from both macrophages (F4/80+CD11b+CD11c−) and dendritic cells (CD11c+CD11b+F4/80−) compared to J and E isolate E/S. If these in vitro differences in APC-derived cytokines, particularly IL-10, are biologically significant in vivo, they may contribute to the S isolate survival, by creating a regulatory cytokine environment in which protective immune responses are less effective