Physiological reactivity to spontaneously occurring seizure activity in dogs with epilepsy and their carers

There is a complex bidirectional relationship between stress and epilepsy. Stressful stimuli and subsequent cortisol release act as a trigger for seizure activity in some individuals with epilepsy, and seizure activity itself may act as a stressor to the affected individual. Epilepsy is the most common chronic neurological condition in domestic dogs and requires chronic management by their human carers, impacting upon the quality of life of both dog and carer. Seizures occur unpredictably and may be stressful for carers to witness and manage. In the present study we investigated the role of seizure activity as a stressor, measuring the effect of spontaneously occurring seizure activity in dogs with epilepsy upon their own cortisol levels and that of their carers. Furthermore, we tested whether individual differences in HPA reactivity were associated with owner personality characteristics and the quality of the dog carer relationship. Saliva samples were obtained from sixteen dog carer dyads in the home setting 20 and 40 minute post-seizure, and at time-matched points on the following (non-seizure) day. Significant differences in cortisol levels were found in dogs at 40 minute post-seizure (265.1% increase), and at 20 minute post-seizure in their carers (40.5% increase). No associations were found between cortisol reactivity and the strength of the dog-carer bond. Carers with higher neuroticism scores exhibited higher cortisol levels at both post-seizure sampling points. As there was a gender bias in the carer sample (15/16 were female), and there are known sex differences in cortisol reactivity in response to psychological stress, the conclusions of this study may be limited to female carers. These findings are the first to objectively demonstrate the acutely stressful effects of seizures in dogs with epilepsy and their carers

Feline hypersomatotropism and acromegaly tumorigenesis: a potential role for the AIP gene

Acromegaly in humans is usually sporadic, however up to 20% of familial isolated pituitary adenomas are caused by germline sequence variants of the aryl-hydrocarbon-receptor interacting protein (AIP) gene. Feline acromegaly has similarities to human acromegalic families with AIP mutations. The aim of this study was to sequence the feline AIP gene, identify sequence variants and compare the AIP gene sequence between feline acromegalic and control cats, and in acromegalic siblings. The feline AIP gene was amplified through PCR using whole blood genomic DNA from 10 acromegalic and 10 control cats, and 3 sibling pairs affected by acromegaly. PCR products were sequenced and compared with the published predicted feline AIP gene. A single nonsynonymous SNP was identified in exon 1 (AIP:c.9T > G) of two acromegalic cats and none of the control cats, as well as both members of one sibling pair. The region of this SNP is considered essential for the interaction of the AIP protein with its receptor. This sequence variant has not previously been reported in humans. Two additional synonymous sequence variants were identified (AIP:c.481C > T and AIP:c.826C > T). This is the first molecular study to investigate a potential genetic cause of feline acromegaly and identified a nonsynonymous AIP single nucleotide polymorphism in 20% of the acromegalic cat population evaluated, as well as in one of the sibling pairs evaluated

Hormonal Regulation of Glucocorticoid Inactivation and Reactivation in aT3-1 and LßT2 Gonadotroph Cells

The regulation of reproductive function by glucocorticoids occurs at all levels of the hypothalamo-pituitary-gonadal axis. Within the pituitary, glucocorticoids have been shown to directly alter gene expression in gonadotrophs, indicating that these cell types are sensitive to regulation by the glucocorticoid receptor. Whilst the major glucocorticoid metabolising enzymes, 11β-hydroxysteroid dehydrogenase (11βHSD; HSD11B1 and HSD11B2), have been described in human pituitary adenomas, the activity of these enzymes within different pituitary cell types has not been reported. Radiometric conversion assays were performed in αT3-1, LβT2 (gonadotrophs), AtT-20 (corticotrophs) and GH3 (somatolactotrophs) anterior pituitary cell lines, using tritiated cortisol, corticosterone, cortisone or 11-dehydrocorticosterone as substrates. The net oxidation of cortisol/corticosterone and net reduction of cortisone/11-dehydrocorticosterone were significantly higher in the two gonadotroph cells lines compared with the AtT-20 and GH3 cells after 4 h. Whilst these enzyme activities remained the same in αT3-1 and LβT2 cells over a 24 h period, there was a significant increase in glucocorticoid metabolism in both AtT-20 and GH3 cells over this same period, suggesting cell-type specific activity of the 11βHSD enzyme(s). Stimulation of both gonadotroph cell lines with either 100 nM GnRH or PACAP (known physiological regulators of gonadotrophs) resulted in significantly increased 11β-dehydrogenase (11βDH) and 11-ketosteroid reductase (11KSR) activities, over both 4 and 24 h. These data reveal that gonadotroph 11βHSD enzyme activity can act to regulate local glucocorticoid availability to mediate the influence of the HPA axis on gonadotroph function

Minimally Invasive Markers of Stress and Production Parameters in Dairy Cows before and after the Installation of a Voluntary Milking System

Automatic milking systems (AMS) are a low-labour alternative to conventional parlours, with previous studies demonstrating that cows vary in their ability to cope with the change to AMS. Cortisol expression can be combined with other measures to assess stress: saliva and hair have the advantage of requiring minimally invasive sampling. No work has investigated the long-term impact of introduction of AMS. The aims of the study were to assess short-term and chronic stress associated with a change in milking system by measuring salivary and hair cortisol levels and to assess the impact on health and production parameters. Cows from one farm changing their milking system were recruited to the study and sampled for saliva (n = 10) and hair (n = 12) before and after installation. Cortisol levels were measured using a salivary cortisol enzyme immunoassay kit. Body condition, lameness and milk parameters of the whole herd were regularly assessed. Salivary cortisol showed no diurnal pattern but was affected by lameness and gestation. Non-lame cows showed a reduction in salivary cortisol after AMS introduction (p < 0.001). Hair cortisol levels increased after AMS, but it was unclear if this change was seasonal. Milk yield increased by 13% and somatic cell count reduced by 28%. Body condition score was consistently good, but lameness remained high throughout the study. Production values alone do not represent high welfare. The high lameness and associated cortisol levels suggest that cow stress requires consideration when changing milking systems

C-Type Natriuretic Peptide (CNP) Inhibition of Interferon-γ-Mediated Gene Expression in Human Endothelial Cells In Vitro

Cardiovascular diseases, including atherosclerosis, now account for more deaths in the Western world than from any other cause. Atherosclerosis has a chronic inflammatory component involving Th1 pro-inflammatory cytokines such as IFN-γ, which is known to induce endothelial cell inflammatory responses. On the other hand CNP, which acts via its receptors to elevate intracellular cGMP, is produced by endothelium and endocardium and is upregulated in atherosclerosis. It is believed to be protective, however its role in vascular inflammation is not well understood. The aim of this study was to investigate the effects of CNP on human endothelial cell inflammatory responses following IFN-γ stimulation. Human umbilical vein endothelial cells were treated with either IFN-γ (10 ng/mL) or CNP (100 nm), or both in combination, followed by analysis by flow cytometry for expression of MHC class I and ICAM-1. IFN-γ significantly increased expression of both molecules, which was significantly inhibited by CNP or the cGMP donor 8-Bromoguanosine 3’,5’-cyclic monophosphate (1 µm). CNP also reduced IFN-γ mediated kynurenine generation by the IFN-γ regulated enzyme indoleamine-2,3-deoxygenase (IDO). We conclude that CNP downmodulates IFN-γ induced pro-inflammatory gene expression in human endothelial cells via a cGMP-mediated pathway. Thus, CNP may have a protective role in vascular inflammation and novel therapeutic strategies for CVD based on upregulation of endothelial CNP expression could reduce chronic EC inflammation

Serum anti-Müllerian hormone concentrations before and after treatment of an ovarian granulosa cell tumour in a cat

Case summary A 15-year-old female cat was presented for investigation of progressive behavioural changes, polyuria, polydipsia and periuria. An ovarian granulosa cell tumour was identified and the cat underwent therapeutic ovariohysterectomy (OHE). The cat’s clinical signs resolved, but 6 months later it was diagnosed as having an anaplastic astrocytoma and was euthanased. Serum anti-Müllerian hormone (AMH) concentration prior to OHE was increased vs a control group of entire and neutered female cats. Following OHE, serum AMH concentration decreased to <1% of the original value. Relevance and novel information Serum AMH measurement may represent a novel diagnostic and monitoring tool for functional ovarian neoplasms in cats

Microwave Analysis of the Damped Detuned Accelerator Structure

Damped and detuned accelerating structures (DDS), designed to minimize the effects of long range wakefields excited by bunchtrains, are presently under investigations at SLAC. The authors report the first studies of beam-induced microwave signals in a prototype DDS. The DDS is a 206 cell, nearly constant gradient structure, employing Gaussian detuning, and four symmetrically placed waveguide manifolds to damp the first-band dipole modes. They describe the manifold and output coupler design, bench measurements, and measurements with beam during the ASSET experiment. Dipole mode signals have been used to steer the beam to the structure center and minimize the wakefield kick

Pilot study assessing the use of cabergoline for the treatment of cats with hypersomatotropism and diabetes mellitus

Abstract Objectives An affordable and effective treatment is needed to manage feline hypersomatotropism. The aim of this study was to assess whether treatment with oral cabergoline for 90 days in cats with hypersomatotropism and diabetes mellitus improved diabetic and insulin-like growth factor 1 (IGF-1) control. Methods This was a prospective cohort non-blinded pilot study enrolling client-owned cats with spontaneously occurring diabetes mellitus and hypersomatotropism. Cats received oral cabergoline (5–10 µg/kg q24h) for 90 consecutive days. Serum IGF-1 and fructosamine concentrations were measured on days 1, 30 and 90. Quality of life was determined using the DIAQoL-pet questionnaire on days 1 and 90. Results Nine cats were enrolled and eight completed the study. There was no significant change in the following: IGF-1 (day 1 median 2001 ng/ml [range 890–2001 ng/ml]; day 30 median 2001 ng/ml [range 929–2001 ng/ml]; day 90 median 1828 ng/ml [range 1035–2001 ng/ml]; χ2(2) = 0.667, P = 0.805); fructosamine (day 1 median 499 µmol/l [range 330–887 µmol/l], day 30 median 551 µmol/l [range 288–722 µmol/l], day 90 median 503 [range 315–851 µmol/l]; χ2(2) = 0.581, P = 0.764); or DIAQoL-pet score (median on day 1 –2.79 (range –4.62 to –0.28], median on day 90 –3.24 [range –4.41 to –0.28]; P = 0.715). There was a significant change of insulin dose (χ2(2) = 8.667, P = 0.008) with cats receiving higher insulin doses at day 90 compared with day 1 (median on day 1 was 0.98 [range 0.63–1.49] and median on day 90 was 1.56 [range 0.49–2.55] units/kg q12h; P = 0.026). Conclusions and relevance Cabergoline did not improve diabetic control or normalise insulin-like growth factor concentration, or improve patient quality of life

Modeling Micro-Porous Surfaces for Secondary Electron Emission Control to Suppress Multipactor

This work seeks to understand how the topography of a surface can be engineered to control secondary electron emission (SEE) for multipactor suppression. Two unique, semi-empirical models for the secondary electron yield (SEY) of a micro-porous surface are derived and compared. The first model is based on a two-dimensional (2D) pore geometry. The second model is based on a three-dimensional (3D) pore geometry. The SEY of both models is shown to depend on two categories of surface parameters: chemistry and topography. An important parameter in these models is the probability of electron emissions to escape the surface pores. This probability is shown by both models to depend exclusively on the aspect ratio of the pore (the ratio of the pore height to the pore diameter). The increased accuracy of the 3D model (compared to the 2D model) results in lower electron escape probabilities with the greatest reductions occurring for aspect ratios less than two. In order to validate these models, a variety of micro-porous gold surfaces were designed and fabricated using photolithography and electroplating processes. The use of an additive metal-deposition process (instead of the more commonly used subtractive metal-etch process) provided geometrically ideal pores which were necessary to accurately assess the 2D and 3D models. Comparison of the experimentally measured SEY data with model predictions from both the 2D and 3D models illustrates the improved accuracy of the 3D model. For a micro-porous gold surface consisting of pores with aspect ratios of two and a 50% pore density, the 3D model predicts that the maximum total SEY will be one. This provides optimal engineered surface design objectives to pursue for multipactor suppression using gold surfaces