Prospective randomized trial comparing relapse rates in dogs with steroid-responsive meningitis-arteritis treated with a 6-week or 6-month prednisolone protocol.

Background: Traditionally, 6-month courses of prednisolone are used to treat steroid-responsive meningitis-arteritis (SRMA), but this medication is associated with adverse effects that can lead to poor quality of life.

Hypothesis/objectives: Resolution of clinical signs and rate of relapse of SRMA would not be significantly different between a 6-month prednisolone protocol and a 6-week protocol.

Animals: Forty-four hospital cases from multiple referral centers in the United Kingdom (2015-2019).

Perry syndrome: Novel DCTN1 mutation in a large kindred and first observation of prodromal disease.

Introduction: Perry syndrome (PS) is a hereditary neurodegenerative disorder caused by mutations in the DCTN1 gene and characterized by TDP-43 pathology. As the diagnosis is usually made at the advanced stages of the disease, there are no studies on the asymptomatic mutation carriers and their conversion to overt disease.

Methods: We personally examined 27 members of the large kindred of 104 individuals with familial parkinsonism.

Organic cation transporter 3 and the dopamine transporter differentially regulate catecholamine uptake in the basolateral amygdala and nucleus accumbens.

Regional alterations in kinetics of catecholamine uptake are due in part to variations in clearance mechanisms. The rate of clearance is a critical determinant of the strength of catecholamine signaling. Catecholamine transmission in the nucleus accumbens core (NAcc) and basolateral amygdala (BLA) is of particular interest due to involvement of these regions in cognition and motivation.

Low frequency of pre-treatment and post-treatment haematological abnormalities in dogs with non-infectious meningoencephalitis treated with cytosine arabinoside and prednisolone.

Background: Cytosine arabinoside (CA) and prednisolone are drugs commonly used together in the management of canine non-infectious meningoencephalitis (NIME). The aim of this study was to report the haematological findings before and after CA and prednisolone treatment and identify any adverse haematological events in this clinical setting, following the veterinary cooperative oncology group established common terminology criteria for recording adverse events following administration of chemotherapy or biological antineoplastic therapy.

Results: While 48 patients with a presumptive diagnosis of NIME had pretreatment haematology results, only 12 patients met the inclusion criteria of also having post-treatment haematology results available for review after being treated with prednisolone and CA at a standard dose (200 mg/m) in a single referral hospital in the UK.

25-Hydroxy vitamin D3 serum concentration in dogs with acute polyradiculoneuritis compared to matched controls.

Objectives: To determine if dogs with acute polyradiculoneuritis have lower serum 25-hydroxy vitamin D3 concentration compared to a control group of dogs with idiopathic epilepsy.

Materials And Methods: Retrospective case-control study of 21 dogs with acute canine polyradiculoneuritis and 21 control dogs with idiopathic epilepsy matched for year and season of presentation from a referral hospital population in the UK. Serum concentration of 25-hydroxy vitamin D3 was compared between groups using Student's t-test.

An exploratory study into factors influencing development of acute canine polyradiculoneuritis in the UK.

Objectives: To investigate whether the development of acute canine polyradiculoneuritis is associated with various putative risk factors.

Materials And Methods: Retrospective case-control study with conditional logistic regression analysis from a referral hospital population in the UK where controls were matched for year of presentation.

Results: Forty-three cases were identified with acute canine polyradiculoneuritis and 86 controls were selected.

Prognostic Factors Associated with Recovery of Ambulation and Urinary Continence in Dogs with Acute Lumbosacral Spinal Cord Injury.

Background: Limited information is available about prognostic factors for recovery after spinal cord injury (SCI) to the L4-S3 segments. Previous research suggests that L4-S3 SCI does not have a worse prognosis than T3-L3 SCI.

Hypothesis/objectives: To elucidate prognostic factors for regaining urinary continence and ambulation in dogs with L4-S3 SCI and compare prognosis to T3-L3 SCI.

Effectiveness of manual bladder expression in paraplegic dogs.

OBJECTIVE To determine the effectiveness of manual bladder expression in paraplegic dogs by comparing urine volumes measured by use of intermittent catheterization and ultrasonography. ANIMALS 36 paraplegic dogs. PROCEDURES 93 measurements of bladder volume were collected for the 36 dogs.

Biased agonists of the kappa opioid receptor suppress pain and itch without causing sedation or dysphoria.

Agonists targeting the kappa opioid receptor (KOR) have been promising therapeutic candidates because of their efficacy for treating intractable itch and relieving pain. Unlike typical opioid narcotics, KOR agonists do not produce euphoria or lead to respiratory suppression or overdose. However, they do produce dysphoria and sedation, side effects that have precluded their clinical development as therapeutics.

Degenerative Encephalopathy in Nova Scotia Duck Tolling Retrievers Presenting with a Rapid Eye Movement Sleep Behavior Disorder.

Background: Neurodegenerative diseases are a heterogeneous group of disorders characterized by loss of neurons and are commonly associated with a genetic mutation.

Hypothesis/objectives: To characterize the clinical and histopathological features of a novel degenerative neurological disease affecting the brain of young adult Nova Scotia Duck Tolling Retrievers (NSDTRs).

Animals: Nine, young adult, related NSDTRs were evaluated for neurological dysfunction and rapid eye movement sleep behavior disorder.

Distinct Effects of Nalmefene on Dopamine Uptake Rates and Kappa Opioid Receptor Activity in the Nucleus Accumbens Following Chronic Intermittent Ethanol Exposure.

The development of pharmacotherapeutics that reduce relapse to alcohol drinking in patients with alcohol dependence is of considerable research interest. Preclinical data support a role for nucleus accumbens (NAc) κ opioid receptors (KOR) in chronic intermittent ethanol (CIE) exposure-induced increases in ethanol intake. Nalmefene, a high-affinity KOR partial agonist, reduces drinking in at-risk patients and relapse drinking in rodents, potentially due to its effects on NAc KORs.

Switch from excitatory to inhibitory actions of ethanol on dopamine levels after chronic exposure: Role of kappa opioid receptors.

Acute ethanol exposure is known to stimulate the dopamine system; however, chronic exposure has been shown to downregulate the dopamine system. In rodents, chronic intermittent exposure (CIE) to ethanol also increases negative affect during withdrawal, such as, increases in anxiety- and depressive-like behavior. Moreover, CIE exposure results in increased ethanol drinking and preference during withdrawal.

Cancer patient age and family caregiver bereavement outcomes.

Purpose: This study drew on life course theory to argue that the strains of cancer caregiving and bereavement are modified by the age of the patient. We expected that caregivers of middle-aged patients would be more distressed than caregivers of older patients.

Methods: This panel study conducted 199 interviews with family caregivers of advanced cancer patients; first following diagnosis and again shortly after the patient's death.

Early-Life Social Isolation Stress Increases Kappa Opioid Receptor Responsiveness and Downregulates the Dopamine System.

Chronic early-life stress increases vulnerability to alcoholism and anxiety disorders during adulthood. Similarly, rats reared in social isolation (SI) during adolescence exhibit augmented ethanol intake and anxiety-like behaviors compared with group housed (GH) rats. Prior studies suggest that disruption of dopamine (DA) signaling contributes to SI-associated behaviors, although the mechanisms underlying these alterations are not fully understood.

Supersensitive Kappa Opioid Receptors Promotes Ethanol Withdrawal-Related Behaviors and Reduce Dopamine Signaling in the Nucleus Accumbens.

Background: Chronic ethanol exposure reduces dopamine transmission in the nucleus accumbens, which may contribute to the negative affective symptoms associated with ethanol withdrawal. Kappa opioid receptors have been implicated in withdrawal-induced excessive drinking and anxiety-like behaviors and are known to inhibit dopamine release in the nucleus accumbens. The effects of chronic ethanol exposure on kappa opioid receptor-mediated changes in dopamine transmission at the level of the dopamine terminal and withdrawal-related behaviors were examined.

Effects of chronic ethanol exposure on neuronal function in the prefrontal cortex and extended amygdala.

Chronic alcohol consumption and withdrawal leads to anxiety, escalated alcohol drinking behavior, and alcohol dependence. Alterations in the function of key structures within the cortico-limbic neural circuit have been implicated in underlying the negative behavioral consequences of chronic alcohol exposure in both humans and rodents. Here, we used chronic intermittent ethanol vapor exposure (CIE) in male C57BL/6J mice to evaluate the effects of chronic alcohol exposure and withdrawal on anxiety-like behavior and basal synaptic function and neuronal excitability in prefrontal cortical and extended amygdala brain regions.

Grief and risk of depression in context: the emotional outcomes of bereaved cancer caregivers.

We investigated the relationships of grief and depression to cancer caregiving in early bereavement. We began with three expectations: (a) each outcome would reflect different situational predictors, (b) grief would be more directly related to such predictors, and (c) components of grief would relate differently to the caregiving context and depressed mood. We conducted telephone interviews with family caregivers of incurable cancer patients from two hospitals.

The longitudinal relationship between quality of life and survival in advanced stage cancer.

Objectives: Quality of Life (QoL) at baseline is frequently found to be a prognostic factor in cancer studies. However, little is known about the relationship of the trajectory of QoL and survival in patients with advanced cancer. This study evaluates the effects of both level and change of QoL on survival to explore the potential of utilizing longitudinal information of QoL for prognosis.

Chronic intermittent ethanol exposure reduces presynaptic dopamine neurotransmission in the mouse nucleus accumbens.

Background: Increasing evidence suggests that chronic ethanol exposure decreases dopamine (DA) neurotransmission in the nucleus accumbens (NAc), contributing to a hypodopaminergic state during withdrawal. However, few studies have investigated adaptations in presynaptic DA terminals after chronic intermittent ethanol (CIE) exposure. In monkeys and rats, chronic ethanol exposure paradigms have been shown to increase DA uptake and D2 autoreceptor sensitivity.

A Single Amphetamine Infusion Reverses Deficits in Dopamine Nerve-Terminal Function Caused by a History of Cocaine Self-Administration.

There are ∼ 1.6 million people who meet the criteria for cocaine addiction in the United States, and there are currently no FDA-approved pharmacotherapies. Amphetamine-based dopamine-releasing drugs have shown efficacy in reducing the motivation to self-administer cocaine and reducing intake in animals and humans.

Greater ethanol inhibition of presynaptic dopamine release in C57BL/6J than DBA/2J mice: Role of nicotinic acetylcholine receptors.

The mesolimbic dopamine system, originating in the ventral tegmental area (VTA) and projecting to the nucleus accumbens (NAc), has been heavily implicated in the reinforcing effects of ethanol. Recent slice voltammetry studies have shown that ethanol inhibits dopamine release selectively during high-frequency activity that elicits phasic dopamine release shown to be important for learning and reinforcement. Presently, we examined ethanol inhibition of electrically evoked NAc dopamine in two mouse strains with divergent dopamine responses to ethanol, C57BL/6 (C57) and DBA/2J (DBA) mice.

Dopamine transporters govern diurnal variation in extracellular dopamine tone.

The majority of neurotransmitter systems shows variations in state-dependent cell firing rates that are mechanistically linked to variations in extracellular levels, or tone, of their respective neurotransmitter. Diurnal variation in dopamine tone has also been demonstrated within the striatum, but this neurotransmitter is unique, in that variation in dopamine tone is likely not related to dopamine cell firing; this is largely because of the observation that midbrain dopamine neurons do not display diurnal fluctuations in firing rates. Therefore, we conducted a systematic investigation of possible mechanisms for the variation in extracellular dopamine tone.

The impact of demographic, social, and environmental factors on the development of steroid-responsive meningitis-arteritis (SRMA) in the United Kingdom.

Background: Steroid-responsive meningitis-arteritis (SRMA) is an inflammatory disease of dogs that is suspected to be immune-mediated. The development of other immune-mediated diseases has been linked to vaccinations, time of the year, geographic location, sex, neuter status, and breed.

Hypothesis/objectives: To identify if the development of SRMA is associated with time of year, vaccination, geographic location, sex, neuter status, and breed.

Screening diagnostics to identify triggers in 21 cases of steroid-responsive meningitis-arteritis.

Objectives: To evaluate whether screening tests used to identify infectious and neoplastic triggers for immune-mediated haemolytic anaemia, in particular a complete blood count and differential, serum biochemistry profile, urine analysis (including culture), abdominal ultrasound and thoracic radiographs, can identify triggers for steroid-responsive meningitis-arteritis.

Methods: Retrospective descriptive review.

Results: Twenty-one steroid-responsive meningitis-arteritis cases were identified in which all screening tests had been performed.