Regional cerebral blood flow in dogs with congenital extrahepatic portosystemic shunts before surgery and six months after successful closure.

Previous studies both in humans and dogs with chronic liver diseases have shown that regional cerebral brain flow (rCBF) is altered. The current study aimed to assess abnormalities in rCBF in dogs with congenital extrahepatic portosystemic shunts (cEHPSS), both at diagnosis and after successful surgical attenuation. Furthermore, the influence of age at diagnosis, severity of hepatic encephalopathy (HE) and type of cEHPSS on rCBF were explored as a base for future research. Single photon emission computed tomography (SPECT) with 99mtechnetium-hexamethylpropylene amine oxime tracer was performed before surgical attenuation and six months postoperatively. Twenty-four dogs with cEHPSS had SPECT at time of diagnosis and 13 dogs with a confirmed closed cEHPSS had a second SPECT six months postoperatively. At diagnosis, dogs with cEHPSS had an altered rCBF distribution compared to healthy dogs. This altered rCBF distribution seemed to be most apparent in dogs ≥ one year and in dogs with overt HE at diagnosis. Six months postoperatively, only the rCBF distribution in the subcortical region decreased compared to pre-operatively. In conclusion, all dogs with cEHPSS had altered rCBF which did not seem to normalize completely six months after successful surgical attenuation. Dogs diagnosed at an older age seemed to have more distinct abnormalities in rCBF compared to younger dogs.

Low-dose xenogeneic mesenchymal stem cells target canine osteoarthritis through systemic immunomodulation and homing.

BACKGROUND: As current therapies for canine osteoarthritis (OA) provide mainly symptomatic improvement and fail to address the complex pathology of the disease, mesenchymal stem cells (MSCs) offer a promising biological approach to address both aspects of OA through their immunomodulatory properties. METHODS: This study aimed to investigate the safety and efficacy of xenogeneic MSCs in dogs with OA at different dose levels after intravenous injection. OA was surgically induced in the right stifle joint. Thirty-two male and female dogs were divided into three treatment groups and a control group. Regular general physical examinations; lameness, joint, radiographic, and animal caretaker assessments; pressure plate analyses; and blood analyses were performed over 42 days. At study end, joint tissues were evaluated regarding gross pathology, histopathology, and immunohistochemistry. In a follow-up study, the biodistribution of intravenously injected 99mTc-labeled equine peripheral blood-derived MSCs was evaluated over 24h in three dogs after the cruciate ligament section. RESULTS: The dose determination study showed the systemic administration of ePB-MSCs in a canine OA model resulted in an analgesic, anti-inflammatory, and joint tissue protective effect associated with improved clinical signs and improved cartilage structure, as well as a good safety profile. Furthermore, a clear dose effect was found with 0.3 × 106 ePB-MSCs as the most effective dose. In addition, this treatment was demonstrated to home specifically towards the injury zone in a biodistribution study. CONCLUSION: This model-based study is the first to confirm the efficacy and safety of systemically administered xenogeneic MSCs in dogs with OA. The systemic administration of a low dose of xenogeneic MSCs could offer a widely accessible, safe, and efficacious treatment to address the complex pathology of canine OA and potentially slow down the disease progression by its joint tissue protective effect.

Structural connectome alterations in anxious dogs: a DTI-based study.

Anxiety and fear are dysfunctional behaviors commonly observed in domesticated dogs. Although dogs and humans share psychopathological similarities, little is known about how dysfunctional fear behaviors are represented in brain networks in dogs diagnosed with anxiety disorders. A combination of diffusion tensor imaging (DTI) and graph theory was used to investigate the underlying structural connections of dysfunctional anxiety in anxious dogs and compared with healthy dogs with normal behavior. The degree of anxiety was assessed using the Canine Behavioral Assessment & Research Questionnaire (C-BARQ), a widely used, validated questionnaire for abnormal behaviors in dogs. Anxious dogs showed significantly decreased clustering coefficient ([Formula: see text]), decreased global efficiency ([Formula: see text]), and increased small-worldness (σ) when compared with healthy dogs. The nodal parameters that differed between the anxious dogs and healthy dogs were mainly located in the posterior part of the brain, including the occipital lobe, posterior cingulate gyrus, hippocampus, mesencephalon, and cerebellum. Furthermore, the nodal degree ([Formula: see text]) of the left cerebellum was significantly negatively correlated with "excitability" in the C-BARQ of anxious dogs. These findings could contribute to the understanding of a disrupted brain structural connectome underlying the pathological mechanisms of anxiety-related disorders in dogs.

Accelerated high frequency rTMS induces time-dependent dopaminergic alterations: a DaTSCAN brain imaging study in healthy beagle dogs.

Aim: The neurobiological effects of repetitive transcranial magnetic stimulation are believed to run in part through the dopaminergic system. Accelerated high frequency rTMS (aHF-rTMS), a new form of stimuli delivery, is currently being tested for its usefulness in treating human and canine mental disorders. However, the short-and long-term neurobiological effects are still unclear, including the effects on the dopaminergic system. In aHF-rTMS, multiple sessions are delivered within 1 day instead of one session per day, not only to accelerate the time to response but also to increase clinical efficacy. To gain more insight into the neurobiology of aHF-rTMS, we investigated whether applying five sessions in 1 day has direct and/or delayed effects on the dopamine transporter (DAT), and on dopamine metabolites of cerebrospinal fluid (CSF) in beagles. Materials and methods: Thirteen beagles were randomly divided into two groups: five active stimulation sessions (n = 9), and 5 sham stimulation sessions (n = 4). Using DaTSCAN, DAT binding indices (BI) were obtained at baseline, after 1 day, 1 month, and 3 months post stimulation. CSF samples were collected after each scan. Results: Active aHF-rTMS significantly reduced striatal DAT BI 1 day post-active stimulation session (p < 0.01), and the effect lasted to 1 month (p < 0.01). No significant DAT BI change was found in sham group. No significant changes in dopamine metabolites of CSF were found. Conclusion: Although no significant effects on CSF dopamine metabolites were observed, five sessions of active aHF-rTMS significantly decreased striatal DAT BI after 1 day and up to 1 month post stimulation, indicating immediate and delayed effects on the brain dopaminergic system. Our findings in healthy beagles further substantiate the assumption that (a)HF-rTMS affects the brain dopaminergic system and it may pave the way to apply (a)HF-rTMS treatment in behaviorally disturbed dogs.

Network analysis reveals abnormal functional brain circuitry in anxious dogs.

Anxiety is a common disease within human psychiatric disorders and has also been described as a frequently neuropsychiatric problem in dogs. Human neuroimaging studies showed abnormal functional brain networks might be involved in anxiety. In this study, we expected similar changes in network topology are also present in dogs. We performed resting-state functional MRI on 25 healthy dogs and 13 patients. The generic Canine Behavioral Assessment & Research Questionnaire was used to evaluate anxiety symptoms. We constructed functional brain networks and used graph theory to compare the differences between two groups. No significant differences in global network topology were found. However, focusing on the anxiety circuit, global efficiency and local efficiency were significantly higher, and characteristic path length was significantly lower in the amygdala in patients. We detected higher connectivity between amygdala-hippocampus, amygdala-mesencephalon, amygdala-thalamus, frontal lobe-hippocampus, frontal lobe-thalamus, and hippocampus-thalamus, all part of the anxiety circuit. Moreover, correlations between network metrics and anxiety symptoms were significant. Altered network measures in the amygdala were correlated with stranger-directed fear and excitability; altered degree in the hippocampus was related to attachment/attention seeking, trainability, and touch sensitivity; abnormal frontal lobe function was related to chasing and familiar dog aggression; attachment/attention seeking was correlated with functional connectivity between amygdala-hippocampus and amygdala-thalamus; familiar dog aggression was related to global network topology change. These findings may shed light on the aberrant topological organization of functional brain networks underlying anxiety in dogs.

Radioiodine treatment in hyperthyroid cats: insights into the characteristics of owners and their cats, and owner motivation and perceptions.

OBJECTIVES: Radioiodine (131I) therapy is the most appropriate treatment option for many hyperthyroid cats, as it is minimally invasive and often curative. Nevertheless, 131I treatment is not always pursued by owners. Hence, it is important to obtain more insight into owner satisfaction during and after 131I treatment, and their decision-making process. In this study, we describe the characteristics of owners and their hyperthyroid cats referred for 131I therapy, and determine owners' motivation and how they experienced the 131I treatment of their cat. METHODS: A survey was sent to owners whose cats underwent 131I therapy (n = 1071) between 2010 and 2017 at Ghent University. The survey contained 35 questions with tick-box or free-text answer options concerning family situation, pet insurance, previous therapy, comorbidities, motivation for 131I therapy and owner perception of this treatment. RESULTS: In total, 438 owners completed 94% or more of the questionnaire. Over half of the cats (55%) had received previous medical, dietary or surgical treatment. Motivations for changing the initial therapy to 131I therapy included difficulties in administering medication (31%), insufficient improvement in clinical signs (23%), side effects (16%) and following the referring veterinarian's advice (16%). Almost a fifth of owners (18%) were not informed about the existence of 131I therapy by their veterinarian and found information on 131I treatment online or through friends. Hospitalising their cat was very distressing for 17% of owners. Most owners (92%) were satisfied with the treatment. Reasons for dissatisfaction were insufficient communication, iatrogenic hypothyroidism, persistent hyperthyroidism and comorbidities post-treatment. CONCLUSIONS AND RELEVANCE: Our study stresses the importance of communication regarding the possible outcome of 131I treatment, the importance of managing underlying comorbidities before treatment and anticipating the stress of owners during their cat's hospitalisation period. The results of this study could help in improving client communication when advising on 131I treatment.

Homing of radiolabelled xenogeneic equine peripheral blood-derived MSCs towards a joint lesion in a dog.

Osteoarthritis (OA) is a highly prevalent condition in dogs, causing a substantial reduction in quality of life and welfare of the animals. Current disease management focusses on pain relief but does not stop the progression of the disease. Therefore, mesenchymal stem cells (MSCs) could offer a promising disease modifying alternative. However, little is known about the behavior and the mode of action of MSCs following their administration. In the current case report, 99mTechnetium labelled xenogeneic equine peripheral blood-derived MSCs were intravenously injected in a 9 year old dog suffering from a natural occurring cranial cruciate ligament rupture. The biodistribution of the MSCs was evaluated during a 6-h follow-up period, using a full body scintigraphy imaging technique. No clinical abnormalities or ectopic tissue formations were detected throughout the study. A radiopharmaceutical uptake was present in the liver, heart, lung, spleen, kidneys and bladder of the dog. Furthermore, homing of the radiolabelled MSCs to the injured joint was observed, with 40.61 % higher uptake in the affected joint in comparison with the healthy contralateral joint. Finally, a local radioactive hotspot was seen at a part of the tail of the dog that had been injured recently. The current study is the first to confirm the homing of xenogeneic MSCs to a naturally occurring joint lesion after IV administration.

The Impact of Accelerated HF-rTMS on Canine Brain Metabolism: An [18F]-FDG PET Study in Healthy Beagles.

Background: Repetitive transcranial magnetic stimulation (rTMS) has been proven to be a useful tool for the treatment of several severe neuropsychiatric disorders. Accelerated (a)rTMS protocols may have the potential to result in faster clinical improvements, but the effects of such accelerated paradigms on brain function remain to be elucidated. Objectives: This sham-controlled arTMS study aimed to evaluate the immediate and delayed effects of accelerated high frequency rTMS (aHF-rTMS) on glucose metabolism in healthy beagle dogs when applied over the left frontal cortex. Methods: Twenty-four dogs were randomly divided into four unequal groups: five active (n = 8)/ sham (n = 4) stimulation sessions (five sessions in 1 day), 20 active (n = 8)/ sham (n = 4) stimulation sessions (five sessions/ day for 4 days), respectively. [18F] FDG PET scans were obtained at baseline, 24 h poststimulation, after 1 and 3 months post the last stimulation session. We explicitly focused on four predefined regions of interest (left/right prefrontal cortex and left/right hippocampus). Results: One day of active aHF-rTMS- and not sham- significantly increased glucose metabolism 24 h post-active stimulation in the left frontal cortex only. Four days of active aHF-rTMS only resulted in a nearly significant metabolic decrease in the left hippocampus after 1 month. Conclusions: Like in human psychiatric disorders, active aHF-rTMS in healthy beagles modifies glucose metabolism, although differently immediately or after 1 month post stimulation. aHF-rTMS may be also a valid option to treat mentally disordered dogs.

Accelerated HF-rTMS Modifies SERT Availability in the Subgenual Anterior Cingulate Cortex: A Canine [11C]DASB Study on the Serotonergic System.

Repetitive transcranial magnetic stimulation (rTMS) is thought to partly exert its antidepressant action through the serotonergic system. Accelerated rTMS may have the potential to result in similar but faster onset of clinical improvement compared to the classical daily rTMS protocols, but given that delayed clinical responses have been reported, the neurobiological effects of accelerated paradigms remain to be elucidated including on this neurotransmitter system. This sham-controlled study aimed to evaluate the effects of accelerated high frequency rTMS (aHF-rTMS) over the left frontal cortex on the serotonin transporter (SERT) in healthy beagle dogs. A total of twenty-two dogs were randomly divided into three unequal groups: five active stimulation sessions (five sessions in one day, n = 10), 20 active stimulation sessions (five sessions/day for four days, n = 8), and 20 sham stimulation sessions (five sessions/day for four days, n = 4). The SERT binding index (BI) was obtained at baseline, 24 h post stimulation protocol, one month, and three months post stimulation by a [11C]DASB PET scan. It was found that one day of active aHF-rTMS (five sessions) did not result in significant SERT BI changes at any time point. For the 20 sessions of active aHF-rTMS, one month after stimulation the SERT BI attenuated in the sgACC. No significant SERT BI changes were found after 20 sessions of sham aHF-rTMS. A total of four days of active aHF-rTMS modified sgACC SERT BI one month post-stimulation, explaining to some extent the delayed clinical effects of accelerated rTMS paradigms found in human psychopathologies.

Scintigraphic tracking of 99mTechnetium-labelled equine peripheral blood-derived mesenchymal stem cells after intravenous, intramuscular, and subcutaneous injection in healthy dogs.

BACKGROUND: Mesenchymal stem cell treatments in dogs have been investigated as a potential innovative alternative to current conventional therapies for a variety of conditions. So far, the precise mode of action of the MSCs has yet to be determined. The aim of this study was to gain more insights into the pharmacokinetics of MSCs by evaluating their biodistribution in healthy dogs after different injection routes. METHODS: Three different studies were performed in healthy dogs to evaluate the biodistribution pattern of radiolabelled equine peripheral blood-derived mesenchymal stem cells following intravenous, intramuscular and subcutaneous administration in comparison with free 99mTechnetium. The labelling of the equine peripheral blood-derived mesenchymal stem cells was performed using stannous chloride as a reducing agent. Whole-body scans were obtained using a gamma camera during a 24-h follow-up. RESULTS: The labelling efficiency ranged between 59.58 and 83.82%. Free 99mTechnetium accumulation was predominantly observed in the stomach, thyroid, bladder and salivary glands, while following intravenous injection, the 99mTechnetium-labelled equine peripheral blood-derived mesenchymal stem cells majorly accumulated in the liver throughout the follow-up period. After intramuscular and subcutaneous injection, the injected dose percentage remained very high at the injection site. CONCLUSIONS: A distinct difference was noted in the biodistribution pattern of the radiolabelled equine peripheral blood-derived mesenchymal stem cells compared to free 99mTechnetium indicating equine peripheral blood-derived mesenchymal stem cells have a specific pharmacokinetic pattern after systemic administration in healthy dogs. Furthermore, the biodistribution pattern of the used xenogeneic equine peripheral blood-derived mesenchymal stem cells appeared to be different from previously reported experiments using different sources of mesenchymal stem cells.

Hostility in medication-resistant major depression and comorbid generalized anxiety disorder is related to increased hippocampal-amygdala 5-HT2A receptor density.

Major depressive disorder (MDD) and generalized anxiety disorder (GAD) are severe and difficult-to-treat psychiatric illnesses with high rates of comorbidity. Although both disorders are treated with serotonergic based psychotropic agents, little is known on the influence of the serotonergic neurotransmitter system on the occurrence of comorbid GAD when clinically depressed. To investigate this poorly understood clinical question, we examined the involvement of frontolimbic post-synaptic 5-HT2A receptors in 20 medication-resistant depressed (MRD) patients with half of them diagnosed with comorbid GAD with 123I-5-I-R91150 SPECT. To explore whether 5-HT2A receptor-binding indices (BI) associated with comorbid GAD could be related to distinct psychopathological symptoms, all were assessed with the symptom Checklist-90-Revised (SCL-90-R). MRD patients with comorbid GAD displayed significantly higher 5-HT2A receptor BI in the hippocampal-amygdala complex, compared to MRD patients without GAD. Correlation analyses revealed that the 5-HT2A receptor BI in these areas were significantly related to the SCL-90-R subscale hostility (HOS), especially for those MRD patients with comorbid GAD. Comorbid MRD-GAD may be characterized with increased hippocampal-amygdala 5-HT2A receptor BI which could represent enhanced levels in hostility in such kinds of patients. Adapted psychotherapeutic interventions may be warranted.

Planar and single-photon emission computed tomography imaging in dogs with thyroid tumors: 68 cases.

BACKGROUND: Information on scintigraphy findings in dogs with thyroid neoplasia is scarce. The use of single-photon emission computed tomography (SPECT) could improve detection of metastatic disease. HYPOTHESIS/OBJECTIVES: To describe planar and SPECT imaging findings in dogs with thyroid tumors, and to compare SPECT and thoracic radiography for metastasis detection. ANIMALS: Sixty-eight dogs with thyroid neoplasia. METHODS: Retrospective study, search of medical records for dogs with thyroid neoplasia (2008-2018). RESULTS: Thyroid scintigraphy was available from 68 dogs, of which 6 presented after surgical resection. Radionuclide uptake was increased in 56% of dogs, decreased in 24%, and comparable to that of the salivary glands in 13%. The remainder had multiple masses with variable uptake. A homogeneous uptake pattern was present in 16% and a heterogeneous uptake pattern in 73%. In 11% (all dogs with multiple masses), various uptake patterns were present. Thyroid tumors were well delineated in 55%. There was a significant association between hormone status and uptake pattern (P = .009), with a heterogeneous uptake pattern in the majority of euthyroid dogs, and hormone status and tumor circumscription (P = .003), with well-circumscribed margins in the majority of hypothyroid and hyperthyroid dogs. Thoracic SPECT imaging was available in 39 dogs and identified metastatic lesions in 15 dogs. Thoracic radiographs were performed in 14 of these dogs, and detected metastases in 3 dogs. CONCLUSIONS AND CLINICAL IMPORTANCE: SPECT imaging is a viable imaging technique to screen for thoracic metastasis and wider use of SPECT imaging is recommended in dogs with thyroid neoplasia.

Pharmacokinetics, absolute bioavailability and tolerability of ketamine after intranasal administration to dexmedetomidine sedated dogs.

Intranasal ketamine has recently gained interest in human medicine, not only for its sedative, anaesthetic or analgesic properties, but also in the management of treatment resistant depression, where it has been shown to be an effective, fast acting alternative treatment. Since several similarities are reported between human psychiatric disorders and canine anxiety disorders, intranasal ketamine could serve as an alternative treatment for anxiety disordered dogs. However, to the authors knowledge, intranasal administration of ketamine and its pharmacokinetics have never been described in dogs. Therefore, this study aimed to examine the pharmacokinetics, absolute bioavailability and tolerability of intranasal ketamine administration compared with intravenous administration. Seven healthy, adult laboratory Beagle dogs were included in this randomized crossover study. The dogs received 2 mg/kg body weight ketamine intravenously (IV) or intranasally (IN), with a two-week wash-out period. Prior to ketamine administration, dogs were sedated intramuscularly with dexmedetomidine. Venous blood samples were collected at fixed times until 480 min post-administration and ketamine plasma concentrations were determined by liquid chromatography-tandem mass spectrometry. Cardiovascular parameters and sedation scores were recorded at the same time points. Non-compartmental pharmacokinetic analysis revealed a rapid (Tmax = 0.25 ± 0.14 h) and complete IN bioavailability (F = 147.65 ± 49.97%). Elimination half-life was similar between both administration routes (T1/2el IV = 1.47 ± 0.24 h, T1/2el IN = 1.50 ± 0.97 h). Heart rate and sedation scores were significantly higher at 5 and 10 min following IV administration compared to IN administration, but not at the later time-points.

Kinetic analysis of [18F] altanserin bolus injection in the canine brain using PET imaging.

BACKGROUND: Currently, [18F] altanserin is the most frequently used PET-radioligand for serotonin2A (5-HT2A) receptor imaging in the human brain but has never been validated in dogs. In vivo imaging of this receptor in the canine brain could improve diagnosis and therapy of several behavioural disorders in dogs. Furthermore, since dogs are considered as a valuable animal model for human psychiatric disorders, the ability to image this receptor in dogs could help to increase our understanding of the pathophysiology of these diseases. Therefore, five healthy laboratory beagles underwent a 90-min dynamic PET scan with arterial blood sampling after [18F] altanserin bolus injection. Compartmental modelling using metabolite corrected arterial input functions was compared with reference tissue modelling with the cerebellum as reference region. RESULTS: The distribution of [18F] altanserin in the canine brain corresponded well to the distribution of 5-HT2A receptors in human and rodent studies. The kinetics could be best described by a 2-Tissue compartment (2-TC) model. All reference tissue models were highly correlated with the 2-TC model, indicating compartmental modelling can be replaced by reference tissue models to avoid arterial blood sampling. CONCLUSIONS: This study demonstrates that [18F] altanserin PET is a reliable tool to visualize and quantify the 5-HT2A receptor in the canine brain.

PET quantification of [18F]MPPF in the canine brain using blood input and reference tissue modelling.

Numerous studies have shown that the serotonin1A (5-HT1A) receptor is implicated in the pathophysiology and treatment of several psychiatric and neurological disorders. Furthermore, functional imaging studies in a variety of species have demonstrated that 4-(2´-Methoxyphenyl)-1-[2´-(N-2´´-pyridinyl)-p- [18F]fluorobenzamidoethylpiperazine ([18F]MPPF) is a valid and useful PET tracer to visualize the 5HT1A receptor. However, to our knowledge, [18F]MPPF has never been demonstrated in the canine brain. The ability to image the 5HT1A receptor with PET in dogs could improve diagnosis and therapy in both canine and human behavioural and neuropsychiatric disorders. To examine the potential use of [18F]MPPF in dogs, five healthy adult laboratory beagles underwent a 60-minutes dynamic PET scan with [18F]MPPF while arterial blood samples were taken. For each region of interest, total distribution volume (VT) and corresponding binding potential (BPND) were calculated using the 1-tissue compartment model (1-TC), 2-Tissue compartment model (2-TC) and Logan plot. The preferred model was chosen based on the goodness-of-fit, calculated with the Akaike information criterium (AIC). Subsequently, the BPND values of the preferred compartment model were compared with the estimated BPND values using three reference tissue models (RTMs): the 2-step simplified reference tissue model (SRTM2), the 2-parameter multilinear reference tissue model (MRTM2) and the Logan reference tissue model. According to the lower AIC values of the 2-TC model compared to the 1-TC in all ROIs, the 2-TC model showed a better fit. Calculating BPND using reference tissue modelling demonstrated high correlation with the BPND obtained by metabolite corrected plasma input 2-TC. This first-in-dog study indicates the results of a bolus injection with [18F]MPPF in dogs are consistent with the observations presented in the literature for other animal species and humans. Furthermore, for future experiments, compartmental modelling using invasive blood sampling could be replaced by RTMs, using the cerebellum as reference region.

The long-term effects of single and repeated subanaesthetic ketamine administration on regional cerebral blood flow in healthy dogs measured with 99mTc-HMPAO SPECT.

Subanaesthetic ketamine has recently been established as an effective and rapid treatment for major depressive disorder showing antidepressant effects for up to 1 week on average. The use of repeated ketamine infusions has been put forward to augment and to prolong the antidepressant response and increase the remission rates. The underlying neurobiological mechanisms responsible for ketamine's antidepressant effects remain unclear. Nevertheless, it has been shown, both in dogs and humans, that ketamine can alter neuronal perfusion and therefore neuronal function in brain regions involved in psychiatric and behavioural disorders. Consequently, the aim of the current placebo controlled study was to assess the long-term effects on cerebral perfusion of single and repeated subanaesthetic ketamine infusions in dogs. Twelve healthy, laboratory dogs were scanned at six different time points following single and repeated ketamine administration, using Single Photon Emission Computed Tomography with the radiotracer 99mTc-hexamethylpropylene amine oxime. We hypothesised that repeated infusions could lead to more prolonged perfusion alterations in brain regions critical for behaviour regulation. We found that repeated subanaesthetic ketamine administration did not result in more prolonged cerebral perfusion alterations compared to a single ketamine administration.

Behavior in dogs with spontaneous hypothyroidism during treatment with levothyroxine.

BACKGROUND: Thyroid hormone supplementation anecdotally has been described as a valid treatment option for dogs with aggression-related problems. However, prospective, controlled, and blinded trials evaluating behavior and neurohormonal status in hypothyroid dogs during treatment with levothyroxine are lacking. OBJECTIVE: Levothyroxine supplementation will have a significant influence on the behavior and neurohormonal status of dogs with spontaneous hypothyroidism. ANIMALS: Twenty client-owned dogs diagnosed with spontaneous hypothyroidism. METHODS: This prospective study was to evaluate the behavior of dogs, which was screened at initial presentation, and after 6 weeks, and 6 months of treatment with levothyroxine (starting dosage 10 µg/kg PO q12h) using the standardized Canine Behavioral Assessment and Research Questionnaire (C-BARQ). At each time period, circulating serotonin and prolactin (PRL) concentrations were evaluated using a commercially validated ELISA kit and heterologous radioimmunoassay, respectively. RESULTS: After 6 weeks of thyroid hormone supplementation, C-BARQ scores demonstrated a significant increase in activity of hypothyroid dogs (P < .01). No significant change in any of the behavioral signs was observed after 6 months of treatment. No significant difference in circulating concentrations of serotonin (P > .99 and P = .46) and PRL (P = .99 and P = .37) were noted between the 6-week and 6-month periods compared with baseline. CONCLUSIONS AND CLINICAL IMPORTANCE: The results of this study indicate increased activity of hypothyroid dogs after 6 weeks of thyroid hormone supplementation. None of the hypothyroid dogs in this cohort showed a significant change in any of the evaluated behavioral signs and neurohormonal status after 6 months of thyroid hormone supplementation.

The influence of subanaesthetic ketamine on regional cerebral blood flow in healthy dogs measured with 99mTc-HMPAO SPECT.

Subanaesthetic ketamine has recently been proven to be a highly effective and fast acting alternative treatment for several psychiatric disorders. The mechanisms responsible for ketamine's antidepressant effects remain unclear, but a possible explanation could be that ketamine interacts with regional cerebral blood flow (rCBF). Therefore, the effects of two subanaesthetic ketamine doses on rCBF were evaluated. Twelve dogs were randomly assigned to one of the three treatment conditions (condition saline, condition 0.5 mg/kg ketamine or condition 2 mg/kg ketamine) and received in total five saline or ketamine infusions, with one week interval. Single Photon Emission Computed Tomography (SPECT) scans with the radiotracer 99mTc-hexamethylpropylene amine oxime were performed before the start of the infusions (baseline) and 24 hours after the first (single) and last (multiple) infusion. After a wash out period of 3 months, the animals were again assigned to one of the three treatment conditions described above and the infusion/scan protocol was repeated. During the infusions, cardiovascular parameters were evaluated every ten minutes. A one-way repeated measure ANOVA was set up to assess perfusion index for each ketamine dose for the left frontal cortex (alpha = 0.05). The remaining 11 brain regions were post hoc assessed. Perfusion index was significantly increased in the left frontal cortex and in the thalamus 24 hours after single and multiple ketamine infusions compared to baseline in the 2 mg/kg condition. No clinically relevant cardiovascular effects were observed during the ketamine infusions. This study shows that subanaesthetic ketamine can increase neuronal perfusion and therefore alter neuronal function in brain regions involved in depression and anxiety disorders. These perfusion increases may possibly contribute to ketamine's beneficial effects in these psychiatric disorders.

Regional alterations of cerebral [18F]FDG metabolism in the chronic unpredictable mild stress- and the repeated corticosterone depression model in rats.

Preclinical research has been indispensable in the exploration of the neurological basis of major depressive disorder (MDD). The present study aimed to examine effects on regional brain activity of two frequently used depression models, the chronic unpredictable mild stress (CUMS)- and the chronic corticosterone (CORT) depression model. The CUMS and CORT depression model were induced by exposing male Long-Evans rats to a 4-week procedure of unpredictable mild stressors or a 3-week procedure of chronic corticosterone, respectively. Positron emission tomography with [18F]FDG was performed to determine alterations in regional brain activity. In addition, depressive- and anxiety-like behaviour was assessed via the forced swim test and the open field test, respectively. The chronic CORT administration, but not the CUMS model, significantly induced depressive-like behaviour and elevated plasma corticosterone levels. Compared to control, induction of the CORT depression model resulted in a significantly reduced glucose consumption in the insular cortex and the striatum, and a significantly elevated consumption in the cerebellum and the midbrain. Induction of the CUMS model replicated the findings with respect to the activity in the striatum region, and cerebellum, but missed significance in the insular cortex and the midbrain. Based on the alterations in behaviour and regional [18F]FDG uptake, a superior face validity and construct validity can be observed after induction of depression via chronic CORT injections, compared to the used CUMS paradigm.

Analysis of iodinated quorum sensing peptides by LC-UV/ESI ion trap mass spectrometry.

Five different quorum sensing peptides (QSP) were iodinated using different iodination techniques. These iodinated peptides were analyzed using a C18 reversed phase HPLC system, applying a linear gradient of water and acetonitrile containing 0.1% (m/v) formic acid as mobile phase. Electrospray ionization (ESI) ion trap mass spectrometry was used for the identification of the modified peptides, while semi-quantification was performed using total ion current (TIC) spectra. Non-iodinated peptides and mono- and di-iodinated peptides (NIP, MIP and DIP respectively) were well separated and eluted in that order. Depending on the used iodination method, iodination yields varied from low (2%) to high (57%).