Cystic ovary disease impairs transport speed, smooth muscle contraction, and epithelial ion transport in the bovine oviduct.

Cystic ovary disease (COD) is a common cause of bovine infertility but the impact of this disease on the oviduct is unknown. The aim of this study was to analyze the effects of COD on particle transport speed (PTS), ciliary beat frequency, myosalpinx contraction, and epithelial ion transport. Oviducts were obtained from cows affected by COD and compared with those of healthy, mid-diestrus cows. PTS and CBF were examined using live-cell imaging. Smooth muscle contraction and epithelial ion transport were investigated using organ baths and Ussing chambers. Our results showed that muscarinic receptors are involved in cholinergic signaling in the oviduct and that forskolin-induced cyclic AMP production is involved in active ion transport in the oviductal epithelium. Oviducts from cows with luteal cysts revealed significantly decreased PTS (p = 0.02). Further to that, in the oviducts of COD cows, the cholinergic regulation of smooth muscle contractions and active epithelial ion transport were significantly diminished (p < 0.0001). These results imply that in COD cows, oviductal transport is compromised by decreased fluid flow speed and reduced cholinergic regulation of smooth muscle contraction and ion transport. This knowledge contributes to a more comprehensive understanding of COD supporting the development of novel therapeutic concepts for infertility treatment.

Competence perceptions of veterinary nursing students and registered veterinary nurses in Ireland: a mixed methods explanatory study.

BACKGROUND: Veterinary regulators require veterinary nursing students to demonstrate clinical competence prior to registration and practice as a veterinary nurse. However, in common with other medical professions, there is no one broadly accepted definition of competence. Studies in nursing have revealed that practicing nurses may view newly qualified colleagues as lacking competence, leading to disillusionment with nursing training programmes. Similar studies are lacking in veterinary nursing, despite the profession having recently undergone a similar transition from workplace-based training to undergraduate education. METHODS: A mixed methods explanatory study surveyed 66 Irish registered veterinary nurses and 31 first year veterinary nursing students at two Irish third level institutions to obtain their views on what constitutes veterinary nursing competence and when veterinary nurses develop it. The surveys were followed by student focus groups and semi-structured one-on-one interviews with registered veterinary nurses. Content analysis was employed to analyse the surveys, while the focus groups and interview transcripts underwent thematic analysis. RESULTS: Students perceived competence primarily as the ability to provide patient care, and they expected it to develop close to the time of graduation. RVNs held a broader definition of competence, incorporating leadership skills and confidence as well as patient care provision. RVNs expected it to take approximately two years of workplace-based experience post-graduation for a veterinary nurse to develop competence. In addition, RVNs recognised that anxiety felt by many newly qualified veterinary nurses during this period could be attenuated by mentorship from more experienced colleagues. CONCLUSIONS: Irish RVNs and veterinary nursing students perceive competence differently, similar to previous findings from the nursing profession. Educators and regulators should provide explicit descriptions of terms such as 'competence' to avoid confusion and possible disillusionment amongst veterinary nursing stakeholders.

Translating Pharmacogenetics and Pharmacogenomics to the Clinic: Progress in Human and Veterinary Medicine.

As targeted personalized therapy becomes more widely used in human medicine, clients will expect the veterinary clinician to be able to implement an evidence-based strategy regarding both the prescribing of medicines and also recognition of the potential for adverse drug reactions (ADR) for their pet, at breed and individual level. This review aims to provide an overview of current developments and challenges in pharmacogenetics in medicine for a veterinary audience and to map these to developments in veterinary pharmacogenetics. Pharmacogenetics has been in development over the past 100 years but has been revolutionized following the publication of the human, and then veterinary species genomes. Genetic biomarkers called pharmacogenes have been identified as specific genetic loci on chromosomes which are associated with either positive or adverse drug responses. Pharmacogene variation may be classified according to the associated drug response, such as a change in (1) the pharmacokinetics; (2) the pharmacodynamics; (3) genes in the downstream pathway of the drug or (4) the effect of "off-target" genes resulting in a response that is unrelated to the intended target. There are many barriers to translation of pharmacogenetic information to the clinic, however, in human medicine, international initiatives are promising real change in the delivery of personalized medicine by 2025. We argue that for effective translation into the veterinary clinic, clinicians, international experts, and stakeholders must collaborate to ensure quality assurance and genetic test validation so that animals may also benefit from this genomics revolution.

Evaluation of a coaching workshop for the management of veterinary nursing students' OSCE-associated test anxiety.

BACKGROUND: High stress levels amongst undergraduates (particularly in relation to assessment) and efforts to improve mental wellbeing have been increasingly reported in the veterinary educational literature. However reports to date have primarily focused on the experiences of students of veterinary medicine, rather than veterinary nursing students. METHODS: The purpose of this mixed method sequential explanatory study was to establish the "Big-five" personality traits and quantify the level of test anxiety associated with objective structured clinical examinations (OSCEs) amongst a cohort of 23 final year veterinary nursing students at an Irish third level college. The 12 item Brief FRIEDBEN Test Anxiety Scale (B-FTAS) and the 20 item mini International Personality Item Pool (mini-IPIP) were used to identify test anxiety levels and personality traits in this cohort. Focus groups were then employed to examine the effectiveness of a coaching intervention in ameliorating this test anxiety. RESULTS: The initial, quantitative, phase found these students to have higher levels of test anxiety than previously reported for undergraduates sitting written examinations. No association was found between test anxiety and neurotic personality traits in this student cohort. In the qualitative follow up phase the coaching intervention was reported to have been helpful in equipping the students to better manage test anxiety. The OSCE stressors identified in this study closely resembled those previously reported by nursing and midwifery students. CONCLUSIONS: The shared experience of the coaching intervention and formative OSCE was reported to have been helpful in empowering the students to manage assessment-associated anxiety. Implications and recommendations for educators were identified.

Motivation and Prior Animal Experience of Newly Enrolled Veterinary Nursing Students at two Irish Third-Level Institutions.

Veterinary nurses report an intrinsic desire to work with animals. However, this motivation may be eroded by poor working conditions and low pay, resulting in the exit of experienced veterinary nurses from clinical practice. This study sought to quantify the level of animal-handling experience students possessed at the start of their training and to explore the factors motivating them to enter veterinary nurse training in two Irish third-level institutions. The authors had noted a tendency for veterinary nursing students to possess limited animal-handling skills, despite their obvious motivation to work with animals. The study explores possible reasons for this, as it mirrors previous reports in relation to students of veterinary medicine. First-year veterinary nursing students at Dundalk Institute of Technology and University College Dublin were surveyed and a focus group was held in each institution to explore student motivations for choosing this career and their prior animal-handling experience and workplace exposure. The results show that veterinary nursing students are highly intrinsically motivated to work with and care for animals. The majority had spent time in the veterinary workplace before starting their studies but they had limited animal-handling experience beyond that of family pets, primarily dogs. The study also revealed potential tensions between the veterinary nursing and veterinary medical students at University College Dublin: a hitherto unexposed aspect of the hidden curriculum in this institution. The results of this study highlight the need for ongoing investment in practical animal-handling training for veterinary nursing students.

A comparison of the effects of lindane and FeCl3/ADP on spontaneous contractions in isolated rat or human term myometrium.

Oxidative stress affects the contractile behavior of smooth muscle resulting in complications during labor. Toxicants such as lindane and ferric chloride (FeCl3)/adenosine diphosphate (ADP) cause oxidative stress and have previously been shown to inhibit smooth muscle contraction. In this study we examined the effects of the oxygen species scavengers, ascorbic acid and N-acetylcysteine on lindane and FeCl3/ADP's inhibition of spontaneous myometrial contractions in rat and human myometrium. Lindane and FeCl3/ADP gave rise to concentration-dependent reductions in rat (EC50 11.8×10-6M and 0.9×10-3M) and human myometrial contractions (EC50 16.3×10-6M and 1.1×10-3M, respectively). Pre-treatment with N-acetylcysteine significantly increased the EC50 for the effects of lindane on motility index of human tissue and reduced the maximum inhibitory effect of FeCl3/ADP on contractions in both rat and human myometrium. Ascorbic acid reduced the effects of FeCl3/ADP in rat tissue only. In conclusion pre-treatment with specific antioxidants may protect both rat and human myometrium from the inhibitory effects of lindane and FeCl3/ADP.

Occupational stress and the importance of self-care and resilience: focus on veterinary nursing.

BACKGROUND: Burnout and compassion fatigue are frequently mentioned in relation to veterinary work. Veterinary nursing is a caring profession and those who seek a career within this field do so because of a natural empathetic desire to care for animals. However it is the individuals who are the most caring and empathetic towards others that will be most at risk of experiencing occupational stress when they are confronted with psychologically demanding workplace roles and working environments. MAIN BODY: Burnout is considered an 'unintentional end point' for certain individuals who are exposed to chronic stress within their working environment. When suffering burnout, a person may experience emotional exhaustion, may become more cynical or they may have a reduced sense of personal accomplishment in regards to their own work. Signs of burnout can include increased levels of absenteeism at work, or the working standards of that staff member may decline below that of what would normally be expected of them. This could directly impact on patient care in the veterinary practice. Working in a role that places emotional demands on staff, such as a need to show compassion and empathy towards clients who are emotionally distressed, puts staff at risk from experiencing compassion fatigue. Workplace supports may include appropriate debriefing sessions among willing participants, particularly after an emotionally stressful encounter with a client. Taking personal responsibility for care of one's own mental and physical health is just as important as taking care of the patient's health. Personal strategies may include lifestyle changes, adopting a healthier lifestyle, reduction of working hours, and ensuring adequate sleep. Adopting healthy self-care strategies can promote characteristics of "resilience" - personal qualities or traits such as optimism, self-confidence, level headedness, hardiness, and having the ability to be resourceful during times of adversity. CONCLUSION: All veterinary staff may be better prepared to deal with occupational stress related conditions if they gain better insight and ability to recognise the condition in self and others, and if provided with the toolkits to develop coping strategies and resilience.

A Role for Adrenergic Receptors in the Uterotonic Effects of Ergometrine in Isolated Human Term Nonlaboring Myometrium.

BACKGROUND: Ergometrine is a uterotonic agent that is recommended in the prevention and management of postpartum hemorrhage. Despite its long-standing use, the mechanism by which it acts in humans has never been elucidated fully. The objective of this study was to investigate the role of adrenoreceptors in ergometrine's mechanism of action in human myometrium. The study examined the hypothesis that α-adrenoreceptor antagonism would result in the reversal of the uterotonic effects of ergometrine. METHODS: Myometrial samples were obtained from women undergoing elective cesarean delivery. The samples were then dissected into strips and mounted in organ bath chambers. After the generation of an ergometrine concentration-response curve (10 to 10 M), strips were treated with increasing concentrations of ergometrine (10 to 10 M) alone and ergometrine (10 to 10 M) in the presence of phentolamine (10 M), prazosin (10 M), propranolol (10 M), or yohimbine (10 M). The effects of adding ergometrine and the effect of drug combinations were analyzed using linear mixed effects models with measures of amplitude (g), frequency (contractions/10 min), and motility index (g×contractions/10 min). RESULTS: A total of 157 experiments were completed on samples obtained from 33 women. There was a significant increase in the motility index (adding 0.342 g × counts/10 min/µM; 95% confidence interval [CI], 0.253-0.431, P < .001), amplitude (0.078 g/µM; 95% CI, 0.0344-0.121, P = 5e-04), and frequency (0.051 counts/10 min/µM; 95% CI, 0.038-0.063, P < .001) in the presence of ergometrine. The α-adrenergic antagonist phentolamine and the more selective α1-adrenergic antagonist prazosin inhibited the ergometrine mediated increase in motility index, amplitude, and frequency (-1.63 g × counts/10 min/µM and -16.70 g × counts/10 min/µM for motility index, respectively). CONCLUSIONS: These results provide novel evidence for a role for α-adrenergic signaling mechanisms in the action of ergometrine on human myometrial smooth muscle in the in vitro setting. Information that sheds light on the mechanism of action of ergometrine may have implications for the development of further uterotonic agents.

Opioid mediated activity and expression of mu and delta opioid receptors in isolated human term non-labouring myometrium.

The existence of opioid receptors in mammalian myometrial tissue is now widely accepted. Previously enkephalin degrading enzymes have been shown to be elevated in pregnant rat uterus and a met-enkephalin analogue has been shown to alter spontaneous contractility of rat myometrium. Here we have undertaken studies to determine the effects of met-enkephalin on in vitro human myometrial contractility and investigate the expression of opioid receptors in pregnant myometrium. Myometrial biopsies were taken from women undergoing elective caesarean delivery at term. Organ bath experiments were used to investigate the effect of the met-enkephalin analogue [d-Ala 2, d-met 5] enkephalin (DAMEA) on spontaneous contractility. A confocal immunofluorescent technique and real time PCR were used to determine the expression of protein and mRNA, respectively for two opioid receptor subtypes, mu and delta. DAMEA had a concentration dependent inhibitory effect on contractile activity (1 × 10(-7)M-1 × 10(-4)M; 54% reduction in contractile activity, P<0.001 at 1 × 10(-4)M concentration). Mu and delta opioid receptor protein sub-types and their respective mRNA were identified in all tissues sampled. This is the first report of opioid receptor expression and of an opioid mediated uterorelaxant action in term human non-labouring myometrium in vitro.

Chloride-led disruption of the intestinal mucous layer impedes Salmonella invasion: evidence for an 'enteric tear' mechanism.

METHODS: The intestinal epithelial layer can switch from a net absorptive state to one of net secretion in the presence of luminal toxins and pathogens. This suggests an innate defence role for regulated secretion of mucus, electrolytes and water. We hypothesised that chloride-led fluid secretion across the mucus-covered intestinal epithelium alters barrier properties by influencing the overlying mucous-gel layer. RESULTS: We demonstrated that chloride-led disruption of the epithelial-associated mucus-gel covering HT29-MTX-E12 (E12) human colonic epithelial monolayers, a goblet-cell like line derived from parental HT29 cells, resulted in reduction of associated mucus as well as a reduction in mucous-gel density and barrier properties. Changes in epithelial secretory state were accompanied by increased water transport, and the resulting loss of gel integrity reduced Salmonella typhimurium invasion of epithelia in both E12 monolayers and of isolated rat ileal mucosae. However, neither chloride secretion nor mucus disruption altered numbers of adhering bacteria. CONCLUSION: These data suggest a role for chloride led fluid secretion in the shedding of the adherent mucous-gel layer, possibly as a rate-limiting innate defence mechanism, and offer evidence for "enteric tears" in intestinal host defence.

The dynamic influence of the DRB1*1101 allele on the resistance of sheep to experimental Teladorsagia circumcincta infection.

Suffolk sheep carrying the DRB1*1101 (previously referred to as-DRB1*0203 or G2) allele have been reported to show increased resistance to natural Teladorsagia circumcincta infection compared to non-carriers. The objective of this study was to compare the biochemical and physiological responses of DRB1*1101 carrier and non-carrier twin lambs to an experimental infection with 3 × 10(4) L3 Teladorsagia circumcincta. The variables studied included worm burden, faecal egg count, abomasal mast cells, IgA, IgE, IgG1 plus IgG2 and haematological parameters at 0, 3, 7, 21 and 35 days post infection (dpi), and duodenal smooth muscle contractility at 0 and 35 dpi. DRB1*1101 carrier lambs had significantly lower worm burden, higher mast cell and plasma platelet counts than the DRB1*1101 non-carriers (P < 0.05). Before infection, the non-carrier lambs exhibited significantly higher mucosal levels of all antibody isotypes measured compared to the carriers; these levels remained relatively stable over the course of infection in the non-carriers while there was a slow build up of these antibodies in the carriers up to day 21 post infection (pi). The DRB1*1101 non-carrier lambs had a significantly higher plasma lymphocyte count, and produced greater duodenal contractile force relative to the carrier lambs (P < 0.05). There was no significant difference between genotypes in the level of plasma eosinophils, monocytes, neutrophils or FEC. This evidence suggests that resistance conferred by DRB1*1101 is acquired rather than innate, depends on worm expulsion rather than fecundity and is dependent on mucosal mast cell proliferation, platelet activation, and IgA and IgE antibody responses.

Peripheral and gastrointestinal immune systems of healthy cattle raised outdoors at pasture or indoors on a concentrate-based ration.

BACKGROUND: Despite an increasing preference of consumers for beef produced from more extensive pasture-based production systems and potential human health benefits from the consumption of such beef, data regarding the health status of animals raised on pasture are limited. The objective of this study was to characterise specific aspects of the bovine peripheral and the gastrointestinal muscosal immune systems of cattle raised on an outdoor pasture system in comparison to animals raised on a conventional intensive indoor concentrate-based system. RESULTS: A number of in vitro functional tests of immune cells suggested subtle differences between the animals on the outdoor versus indoor production systems. There was a decrease in the number of neutrophils and monocytes engaged in phagocytosis in outdoor cattle (P < 0.01 and P < 0.05, respectively) in comparison to those indoors. Following mitogen stimulation, a lower level of interferon-gamma was produced in leukocytes from the outdoor animals (P < 0.05). There was evidence of a gastrointestinal nematode infection in the outdoor animals with elevated levels of serum pepsinogen (P < 0.001), a higher number of eosinophils (P < 0.05) and a higher level of interleukin-4 and stem cell factor mRNA expression (P < 0.05) in the outdoor animals in comparison to the indoor animals. Lower levels of copper and iodine were measured in the outdoor animals in comparison to indoor animals (P < 0.001). CONCLUSION: Despite distinctly contrasting production systems, only subtle differences were identified in the peripheral immune parameters measured between cattle raised at pasture in comparison to animals raised on a conventional intensive indoor concentrate-based production system.

A comparison of the inhibitory effects of bupivacaine and levobupivacaine on isolated human pregnant myometrium contractility.

BACKGROUND: Epidural analgesia with levobupivacaine and bupivacaine is a common and effective method of labor pain relief. However, its use is associated with an increased instrumental delivery rate. One of the mechanisms postulated to account for this unwanted effect is the direct effect of local anesthetics on myometrial contractility. We determined the effects of bupivacaine and levobupivacaine on the amplitude and frequency of contractions of human term myometrium. METHODS: Uterine specimens were obtained from nonlaboring parturients scheduled for elective lower-segment cesarean delivery at term. Longitudinal muscle strips were prepared and mounted vertically in tissue chambers, and changes in the amplitude (peak force) and the frequency of contractions were recorded. Spontaneous contractions commenced after a period of application of 1 g (9.81 mN) of tension to the myometrial strips. No uterotonic drugs were used. The muscle strips were then exposed to cumulative concentrations of bupivacaine and levobupivacaine and dose-response curves were generated. RESULTS: Both bupivacaine and levobupivacaine decreased the amplitude of contractions in human myometrium in a concentration-dependent manner, reaching significance at 1x10(-4) M for both bupivacaine and levobupivacaine compared with the internal control amplitude. With both drugs, the decrease in amplitude was accompanied by an increase in the frequency of contractions reaching significance at 3x10(-5) M for both bupivacaine and levobupivacaine compared with the internal control frequency. CONCLUSIONS: The concentrations required for the effects on amplitude are much higher (33 fold) than the clinically relevant plasma concentrations of these drugs after epidural administration, and are unlikely to be significant in the setting of low-dose epidural analgesia in labor.

Rat, ovine and bovine Peyer's patches mounted in horizontal diffusion chambers display sampling function.

Freshly excised rat, ovine and bovine ileal Peyer's patch (PP) and non-Peyer's patch tissues (NPP) were mounted in modified horizontal polyethylene diffusion chambers with a range of window areas. Rat tissue was initially used to establish that barrier function and histology were maintained for up to 60 min. Horse-radish peroxidase (HRP) fluxes and S. Typhimurium adherence and invasion were significantly higher in rat PP over NPP. Particle uptake was shown to be a rapid, energy-, time-, and size-dependent process, occurring more readily in PP than NPP tissue in each species. In a kinetic analysis, particles were localized initially in the follicle-associated epithelium and then in the dome region. For NPP uptake, particles were initially localized to villous epithelium, and were then detected in the crypts and lamina propria. Electrophysiological parameters including pharmacologically-stimulated inward short-circuit current responses were determined in isolated PP and NPP from each species mounted under identical conditions in Ussing chambers. In conclusion, comparative functional and histological characteristics of PP from several species were demonstrated in horizontal diffusion chambers. Horizontal diffusion chambers are therefore a useful in vitro model in which a range of functions including transport of particulate formulations by PP may be examined.

Oral delivery of pathogens from the intestine to the nervous system.

Most therapeutic agents are delivered orally. Consequently, the major classes of therapeutically useful chemicals are partially lipophilic, small molecular weight compounds. They have reasonable permeability coefficient values across cell membranes, including those of intestinal epithelia and vascular endothelia. In contrast, large molecular weight biotechnology compounds have limited usefulness by non-injected routes as a consequence of their low membrane permeability and variable solubility. However, a wide range of infectious agents have developed strategies or have hijacked physiological routings in order to enter the host by the oral route. Efforts to address such issues have refreshed interest in mechanisms by which different types of payloads (including particulates and microorganisms) translocate across gut epithelia and then distribute to target tissues. Special attention is given to the potential role of the enteric nervous system and its plasticity.

Reflex cardiorespiratory effects of nociceptive oesophageal distension in the decerebrate rat.

It is well established that painful distension of hollow viscera such as the oesophagus can evoke a reflex tachycardia and pressor response; however, the nature of the oesophageal afferent pathway(s) remains controversial. This study investigated the afferent arc which mediates these reflex cardiovascular changes in the decerebrate rat. In addition, the effect of oesophageal distension on the respiratory activity of the costal diaphragm was studied. Focal distension of the oesophagus (volume of 0.3 ml applied for 10 s) just above the diaphragmatic hiatus evoked a reproducible pressor response and tachycardia in the decerebrate rat. Respiration was transiently inhibited at the beginning of oesophageal distension and prior to the rise in blood pressure. Neuromuscular blockade with the nicotinic acetylcholine receptor blocker alpha-bungarotoxin (140 microg bolus) had no effect on the magnitude of the cardiovascular response. Therefore the efferent supply to the striated muscle of the rat oesophagus was not essential in mediating this reflex. Signal averaging of the mean blood pressure response showed that neither selective ablation of oesophageal spinal afferents nor bilateral vagotomy altered the early trajectory of the pressure response. Bilateral vagotomy reduced the peak magnitude of the response to sustained oesophageal distension. In contrast, selective removal of spinal afferents had no effect on the response. Ablation of both neural pathways was essential to abolish the reflex cardiovascular and respiratory responses. It can be concluded that both vagal and spinal afferent pathways are utilised in the reflex cardiorespiratory response to painful oesophageal distension. Although ablation of one neural pathway had no effect on the response it was still implicated in the reflex, since ablation of both pathways was necessary to prevent the cardiorespiratory changes. This study emphasises the need for caution when inferences are made concerning single selective ablations of multiply innervated organs.