Re-evaluating the placebo response in recent canine dietary epilepsy trials.

The placebo response is a common phenomenon. Limited evidence is available about its magnitude in canine epilepsy trials, even though it can significantly influence the efficacy evaluation of new treatments. It was hypothesised that the placebo response is diminished when epilepsy trials are conducted in a prospective crossover design. Seizure data spanning six months from three previous multicenter epilepsy studies were analysed. The monthly seizure frequency of 60 dogs diagnosed with idiopathic epilepsy was calculated, comparing baseline data with placebo treatment. Furthermore, differentiation was made between dogs randomised to the placebo group early (Phase 1: first 3 months) or later during the study (Phase 2: second 3 months).The analysis did not reveal any placebo response in terms of monthly seizure frequency. Instead, an increase was noted during the placebo treatment period, with a mean of 2.95 seizures per month compared to 2.30 seizures per month before study entry (p = 0.0378). Additionally, a notable phase effect was observed. Dogs receiving the placebo in the second study phase exhibited a significant increase in monthly seizure frequency compared to baseline (p = 0.0036). Conversely, no significant difference from baseline was observed for dogs receiving the placebo in the first study phase. These findings underscore the considerable variability in placebo responses observed in trials for canine epilepsy, contrasting with previous limited data. The identified phase effect should be carefully considered in the design and evaluation of canine epilepsy trials to ensure a more accurate assessment of efficacy for new treatments.

Efficacy evaluation of a commercially available MCT enriched therapeutic diet on dogs with idiopathic epilepsy treated with zonisamide: a prospective, randomized, double-blinded, placebo-controlled, crossover dietary preliminary study.

BACKGROUND: Idiopathic epilepsy (IE) is a common, chronic brain dysfunction in dogs. Recently, the effect of feeding a diet enriched with medium-chain triglycerides (MCTs) on seizure frequency has been evaluated in several studies in dogs with IE. However, most dogs with IE in previous studies were treated with phenobarbital as the main antiseizure medication (ASM). In Japan, zonisamide (ZNS) is the most prescribed ASM for dogs with IE. The interaction between ZNS and various nutrients including MCTs and the potential effects on treatment efficacy resulting from combining these therapies have not been previously studied. A prospective, randomized, double-blinded, placebo-controlled, crossover dietary study was conducted. Dogs (n = 7) treated with ZNS were fed either a placebo diet (PL) or Purina ProPlan Veterinary Diet NeuroCare (NC) for 3 months, after which treatments were crossed over and continued for another 3 months. Seizure frequency (seizures/month; sz/m), blood tests including concentrations of ZNS and ß-hydroxybutyric acid, and owner's visual analogue scale score were collected from all dogs for both treatment periods. RESULTS: There was no significant difference in the seizure frequency between PL (2.95 ± 0.80 sz/m) and NC (1.90 ± 0.57 sz/m) during the 6 months of trial. Three of 7 dogs showed ≥ 50% seizure reduction, and 1 of those 3 dogs achieved seizure freedom in NC period. However, 2 of 7 dogs had no changes in epileptic seizure frequency, 2 of 7 dogs had a deterioration in seizure frequency in the NC period. Feeding the MCT diet concurrent with ZNS showed no apparent adverse effects and did not affect ZNS concentration. CONCLUSIONS: This study indicated that the commercially available MCT-enriched diet (NC) can be safely used concurrently with ZNS for dogs with IE.

A six-month prospective, randomised, double-blinded, placebo-controlled, crossover, dietary trial design to investigate the potential of psychobiotics on seizure semiology and comorbidities in canine epilepsy: study protocol.

BACKGROUND: Epilepsy is the most common chronic neurological disease in dogs. More than two-thirds of these patients suffer from associated behavioural comorbidities. The latter could have their origin in partially overlapping pathomechanisms, with the intestinal microbiome as a potential key link between them. The current arsenal of drugs for epilepsy management remains limited. Most canine patients continue to have seizures despite treatment and the occurrence of comorbidities is not sufficiently addressed, limiting quality of life of affected dogs and owners. Therefore, novel additional epilepsy management options are urgently needed. The microbiome-gut-brain axis may serve as a new target for the development of innovative multimodal therapeutic approaches to overcome current shortcomings in epilepsy management. METHODS: A six-month prospective, randomised, double-blinded, placebo-controlled, crossover, dietary trial was designed to investigate the potential of the psychobiotic Bifidobacterium longum on behavioural comorbidities in canine epilepsy. Seizure semiology will be evaluated as a secondary outcome measure. Thirty-four privately owned dogs are planned to be included in the ongoing study meeting the following inclusion criteria: Dogs displaying increased anxiety/fear behaviour since the start of the idiopathic epilepsy. Tier II confidence level of the International Veterinary Epilepsy Task Force for the diagnosis of idiopathic epilepsy, with a maximum seizure interval of 3 month and a minimum of three generalised seizures within that period and chronically treated with at least one antiseizure drug without improvement in seizure frequency Each dog will receive the allocated supplement (probiotic vs. placebo) alongside its normal diet for a 3-month period. After a three-week wash out period, the second phase starts by administering the respective other supplement for another 3 months. DISCUSSION: The current study considers modern high-quality standards for epilepsy medication trials. Common biasing effects should be limited to a possible minimum (regression-to-the mean effect, placebo effect, observer effect), ensuring a high validity and accuracy of the acquired results, thus enabling a representative nature of the efficacy of Bifidobacterium longum as add-on supplement for dogs suffering from epilepsy and its comorbidities. This publication should provide a description of the study procedure and data acquisition methods, including prognosed statistical analysis.

Dietary medium chain triglycerides for management of epilepsy: New data from human, dog, and rodent studies.

Many studies show that glucose metabolism in epileptic brain areas can be impaired. Energy is crucial to maintain normal brain function, including ion and neurotransmitter balances. Energy deficits can lead to disruption of ion gradients, which can trigger neuronal depolarization and generation of seizures. Thus, perturbed metabolic processing of glucose in epileptogenic brain areas indicates a specific nutritional need for people and animals with epilepsy, as they are likely to benefit from auxiliary brain fuels other than glucose. Ketogenic diets provide the ketone bodies acetoacetate and ß-hydroxybutyrate, which can be used as auxiliary fuel by the brain. In approximately 50% children and adults with certain types of epilepsy, who can tolerate and maintain these dietary regimens, seizure frequency can be effectively reduced. More recent data demonstrate that addition of medium chain triglycerides (MCTs), which provide the medium chain fatty acids octanoic and decanoic acid, as well as ketone bodies as auxiliary brain energy, can be beneficial in rodent seizure models, and dogs and humans with epilepsy. Here, this evidence is reviewed, including tolerance in 65% of humans, efficacy studies in dogs, possible anticonvulsant mechanisms of actions of MCTs, and specifically decanoic acid as well as metabolic and antioxidant mechanisms. In conclusion, MCTs are a promising adjunct to standard pharmacological treatment for both humans and dogs with epilepsy, as they lack central nervous system side effects found with current antiepileptic drugs. There is now a need for larger clinical trials in children, adults, and dogs to find the ideal composition and doses of MCTs and the types of epilepsy that respond best.

An Assessment of the Stability of the Canine Oral Microbiota After Probiotic Administration in Healthy Dogs Over Time.

The administration of an oral probiotic has been demonstrated to impact oral microbial diversity in humans but has not been examined in canines. The objective of this study was to test the hypothesis that oral probiotic administration would impact the oral microbiota of canines compared to control. Working canines in training (n = 13) were assigned to Test or Control groups and acclimated to one of three commercially available study diets utilizing common protein sources (Purina Pro Plan Savor lamb, Purina Pro Plan Sport chicken, Purina Pro Plan Focus salmon) for a minimum of 30 days prior to initiation of the study. Following acclimation, dogs in the Test group began a daily regimen of oral probiotic (Fortiflora® Purina, St. Louis, MO) top-dressed on their midday feeding. Control dogs received their midday feeding with no probiotic. All dogs were sampled once weekly via oral pediatric swabs across the 7-week study. Next generation sequencing (Illumina, MiSeq) was utilized to develop microbial profiles specific to treatment, diet, and time. Bacterial composition was dominated by eight phyla (Proteobacteria 43.8%, Bacteroidetes 22.5%, Firmicutes 18.9%, Actinobacteria 6.1%, Fusobacteria 3.6%, Gracilibacteria 2.1%, SR1 Absconditabacteria 1.5%, and Saccharibacteria 1.3%) representing more than 99% of the relative abundance of the microbial composition. Probiotic administration failed to impact relative abundance at any taxonomic level (P > 0.05). Similarly, no effect on the oral microbiota was measured for diet (P > 0.05). Comparison using a Jaccard Index demonstrate a consistent microbial profile over the 7-week study with no impact evidenced by study week (P = 0.19). The data also revealed a profile of ubiquitous taxa that were present across all dogs and all samples regardless of breed, sex, diet, treatment or other factors. These genera include Actinomyces, Corynebacterium, Capnocytophaga, Flavobacterium, Gemella, Abiotrophia, Streptococcus, and Frederiksenia. These data demonstrate the stability of canine oral microbiota over time.

Efficacy of medium chain triglyceride oil dietary supplementation in reducing seizure frequency in dogs with idiopathic epilepsy without cluster seizures: a non-blinded, prospective clinical trial.

BACKGROUND: Despite appropriate antiseizure drug (ASD) treatment, around two-thirds of dogs with idiopathic epilepsy (IE) have seizures long-term and 20-30per cent of affected dogs remain poorly controlled. METHODS: The current study aim is to test in a field trial the efficacy and tolerability of a commercially available diet enriched with 6.5per cent medium chain triglyceride (MCT) oil in dogs (n=21) with at least a tier 1 idiopathic epilepsy diagnosis, without cluster seizures, in 10 veterinary practices across Europe. Each dog's quality of life (QoL), ataxia, sedation and frequency and severity of seizures were recorded by owners throughout the study. RESULTS: The mean seizure frequency per month, averaged over the entire 84-day study, significantly (P=0.04) decreased 32per cent compared with the baseline monthly seizure frequency recorded during the month immediately before feeding the diet. Similarly, the seizure days rate (days/month) also declined (P<0.001) by 42per cent. QoL was reported as very good to excellent (>8.5/10) in 20 of the 21 dogs before starting the diet and this remained unchanged during the trial. CONCLUSIONS: This study demonstrates the use of a diet enriched with MCTs as an adjunct to ASD treatment may have some antiseizure properties for dogs diagnosed with IE, as demonstrated in previous studies.

Usefulness of muscle condition score and ultrasonographic measurements for assessment of muscle mass in cats with cachexia and sarcopenia.

OBJECTIVE: To compare muscle condition scores (MCSs) and muscle ultrasonographic measurements in cats with and without muscle loss and to evaluate repeatability and reproducibility of MCS assessment. ANIMALS: 40 cats of various ages, body condition scores (BCSs), and MCSs. PROCEDURES: A prospective cross-sectional study was conducted. Body weight, BCS, MCS, epaxial muscle height (EMH), vertebral epaxial muscle score (VEMS), and forelimb epaxial muscle score (FLEMS) were assessed in each cat. The MCS for each cat was assessed 3 separate times by each of 5 raters. RESULTS: The MCS was significantly correlated with EMH (r = 0.59), VEMS (r = 0.66), and FLEMS (r = 0.41). For MCS, the overall value of the κ coefficient for interrater agreement (reproducibility) was 0.43 and the overall value of the κ coefficient for intrarater agreement (repeatability) ranged from 0.49 to 0.76. CONCLUSIONS AND CLINICAL RELEVANCE: Ultrasonographic measurements of muscle may be useful for assessing muscle loss in individual cats over time. However, for the cats of this study, no advantage was observed for assessment of VEMS or FLEMS over EMH. Substantial repeatability and moderate reproducibility were shown when MCS was used for assessment of muscle mass in cats. Prospective ultrasonographic studies are warranted to evaluate the usefulness of MCS and EMH assessment for evaluation of changes in muscle mass of cats over time.

The Effects of a Ketogenic Medium-Chain Triglyceride Diet on the Feces in Dogs With Idiopathic Epilepsy.

Consumption of diets containing medium chain triglycerides have been shown to confer neuroprotective and behavior modulating effects. We aimed to identify metabolic and microbiome perturbations in feces that are associated with consumption of a medium chain triglyceride ketogenic diet (MCT-KD) in dogs with idiopathic epilepsy. We used 16S rRNA gene sequencing to generate microbiome profiles and ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) to generate lipidomic profiles of canine feces. We made comparisons between the MCT-KD, standardized placebo diet and baseline pre-trial diet phases. Consumption of the MCT-KD resulted in a significant increase in the species richness (α-diversity) of bacterial communities found in the feces when compared to the baseline diet. However, phylogenetical diversity between samples (beta-diversity) was not affected by diet. An unnamed Bacteroidaceae species within genus 5-7N15 was identified by LEfSe as a potential biomarker associated with consumption of the MCT-KD, showing an increased abundance (p = 0.005, q = 0.230) during consumption of MCT-KD. In addition, unclassified members of families Erysipelotrichaceae (p = 0.013, q = 0.335) and Fusobacteriaceae (p = 0.022, q = 0.358) were significantly increased during MCT-KD consumption compared to baseline. Blautia sp. and Megamonas sp. instead were decreased during consumption of either placebo or MCT-KD (p = 0.045, q = 0.449, and p = 0.039, q = 0.449, respectively). Bacteroidaceae, including genus 5-7N15, have previously been associated with non-aggressive behavior in dogs. In addition, 5-7N15 is correlated in humans with Akkermansia, a genus known to be involved in the neuroprotective effect of ketogenic diets in mice models of seizures. Five metabolite features, tentatively identified as long chain triglycerides, were significantly higher after consumption of the placebo diet, but no unique features were identified after consumption of the MCT-KD. The data presented in this study highlight significant changes shown in both the fecal microbiome and lipidome as a result of consumption of the MCT-KD. Elucidating the global canine gut response to MCT consumption will improve our understanding of the potential mechanisms which confer anti-seizure and behavior modulating effects. Further studies should aim to characterize the gut microbiome of both dogs with epilepsy and healthy controls.

Evaluation of the use of muscle condition score and ultrasonographic measurements for assessment of muscle mass in dogs.

OBJECTIVE: To evaluate repeatability and reproducibility of muscle condition score (MCS) in dogs with various degrees of muscle loss; to compare MCS, muscle ultrasonographic measurements, and quantitative magnetic resonance (QMR) measurements; and to identify cutoff values for ultrasonographic measurements of muscle that can be used to identify dogs with cachexia and sarcopenia. ANIMALS: 40 dogs of various age, body condition score (BCS), and MCS. PROCEDURES: A prospective cross-sectional study was conducted. Body weight, BCS, QMR measurements, thoracic radiographic measurements, and muscle ultrasonographic measurements were assessed once in each dog. The MCS for each dog was assessed 3 separate times by 4 separate raters. RESULTS: For the MCS, overall κ for interrater agreement was 0.50 and overall κ for intrarater agreement ranged from 0.59 to 0.77. For both interrater and intrarater agreement, κ coefficients were higher for dogs with normal muscle mass and severe muscle loss and lower for dogs with mild and moderate muscle loss. The MCS was significantly correlated with age (r = -0.62), vertebral epaxial muscle score (VEMS; r = 0.71), forelimb epaxial muscle score (FLEMS; r = 0.58), and BCS (r = 0.73), and VEMS was significantly correlated (r = 0.84) with FLEMS. Cutoff values for identification of mild muscle loss determined by use of VEMS and FLEMS were 1.124 and 1.666, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: MCS had substantial repeatability and moderate reproducibility for assessment of muscle mass in dogs. Prospective studies of MCS, VEMS, and FLEMS for assessment of muscle mass in dogs are warranted.

Diagnostic Ultrasound Detection of Changes in Femoral Muscle Mass Recovery after Tibial Plateau Levelling Osteotomy in Dogs.

OBJECTIVE: The goal of this study was to develop a clinically feasible ultrasound (US) protocol that can detect changes in thigh muscle mass in dogs after stifle surgery. The primary aim of this study was to compare previously described US measurement locations of the canine thigh for detecting changes in muscle mass in dogs recovering from tibial plateau levelling osteotomy (TPLO). STUDY DESIGN: This was a prospective, exploratory pilot study. Adult dogs (n = 7) undergoing pet-owner elected TPLO were enrolled. Twelve different US measurements were performed in triplicate by a single experienced observer. Measurements were performed at 0, 2, 4 and 8 weeks after surgery at a proximal and distal location along the femur. Data from all available time points and locations were analysed for the main effect of time within modalities. RESULTS: A total of 1,008 US measurements were performed. Measurements of the transverse sectional area of the rectus femoris muscle detected significant (p ≤ 0.05) muscle loss between weeks 0 and 2 at the lateral and medial aspects of the distal location (19% and 15% respectively). Measurements of the thigh muscle thickness were significantly (p < 0.01) increased between 2nd- and 8th- week time points at the lateral aspect of the proximal location (26%). CONCLUSION: The proximal femoral location, measured from the lateral aspect, appears to be the most suitable US measurement for detecting increases in femoral muscle mass in dogs recovering from TPLO. The provided pilot data suggest that further research evaluating this outcome measure is indicated.

Evaluation of skin turgor and capillary refill time as predictors of dehydration in exercising dogs.

OBJECTIVE To determine usefulness of skin turgor and capillary refill time (CRT) for predicting changes in hydration status of working dogs after a 15-minute exercise period. ANIMALS 9 exercise-conditioned working dogs between 8 and 108 months of age. PROCEDURES Skin tent time (SkTT; time for tented skin on the forehead to return to an anatomically normal position) and CRT (time for occluded mucous membrane capillary vessels to return to the color visible before occlusion) were measured on dogs in a field setting and by video review. Body weight (BW), SkTT, CRT, and core body temperature were measured before and after a 15-minute exercise period. Exercise challenge was performed on days 1 and 8. RESULTS Time (day 1 vs day 8) did not significantly affect results; therefore, data were pooled for the 2 trial days. Mean ± SE BW decreased (but not significantly) by 0.83 ± 0.27% after exercise. The SkTT increased significantly (both field setting and video review) after exercise. Correlation between SkTT results for the field setting and video review (r = 0.68) was significant. The CRT decreased (but not significantly) after exercise. CONCLUSIONS AND CLINICAL RELEVANCE Dogs became mildly dehydrated (mean BW loss, 0.83%) during a 15-minute exercise period, and the mild dehydration was evident as a visually detectable change in skin turgor. Monitoring the SkTT appeared to be a useful strategy for predicting small shifts in hydration status of dogs during exercise. The CRT decreased and was not a significant predictor of a change in hydration status.

Effects of a nutrient-enriched water with and without poultry flavoring on water intake, urine specific gravity, and urine output in healthy domestic cats fed a dry kibble diet.

OBJECTIVE To investigate water intake and urine measures in healthy cats provided free-choice access to a nutrient-enriched water with (NWP) or without (NW) added poultry flavoring offered at 3 different volumes in addition to tap water (TW). ANIMALS 36 domestic shorthair cats. PROCEDURES Control group cats (n = 4) received dry food with TW ad libitum throughout the study. Cats of the NW and NWP groups (n = 16/group) received the same food with TW only (period 1; 7 days) followed by TW and the assigned treatment ad libitum at 1X, 1.5X, and 2X the volume of TW consumed in period 1 during periods 2 (17 days), 3 (10 days), and 4 (10 days), respectively. Liquid consumption, food intake, and total water intake (from all sources) were measured; urine collected over 48 hours in each period was measured, and urine specific gravity (USG) was determined. Data were analyzed with mixed-effects models. RESULTS TW and food calorie intake were similar among groups in period 1; TW consumption by control cats did not differ during the study. Liquid consumed by drinking increased 18%, 57%, and 96% for the NWP group in periods 2, 3, and 4, respectively, with increases of 25% and 44% for the NW group in periods 3 and 4, respectively, compared with period 1 values for the same groups. Increased urine output and decreased USG were significantly associated with period and treatment. CONCLUSIONS AND CLINICAL RELEVANCE Increasing the volumes of NW or NWP offered to healthy cats led to increased free liquid consumption and was associated with greater urine output and dilution as measured by USG. Studies are warranted to determine whether these treatments provide health benefits for cats in need of greater water consumption.

Working Dogs Drinking a Nutrient-Enriched Water Maintain Cooler Body Temperature and Improved Pulse Rate Recovery After Exercise.

Exercise-related physiological changes were evaluated in hydrated, exercise-conditioned working dogs with free access to tap water (TW) with or without a nutrient-enriched water supplement (NW). Physiological samples and measures were collected before and after work-related field tasks in a warm and moderately humid ambient environment. In a cross-over design study, 12 dogs (age range 8-23 months) were evaluated on 3 separate occasions within each period with exercise bouts up to 30 min, on days -4, 3, and 11. Dogs were offered either ad libitum TW or portion-controlled NW daily plus ad libitum TW. Prior to and serially after exercise, pulse rate (PR), core (BTcore) and ear (BTear) temperature were recorded. Urine was collected first thing in the morning, whereas blood samples collected and body weight (BW) recorded pre- and immediately post exercise. Ambient temperature was above 21.7°C (71°F) and relative humidity ranged from 36 to 76%. Activity parameters, AM urine measures, post-exercise percent change of BW, resting PR and resting BTcore did not differ between treatment groups on any exercise day. At the completion of exercise, mean BTcore for all dogs ranged from 104.8 to 105.6°F. Immediate post-exercise BTear was always lower compared to BTcore and means ranged from 103.3 to 104.0°F. The effect of time was highly significant (P < 0.001) for both BT measures with both BTcore and BTear recovering to resting levels by 60 min post exercise. PR and several blood values showed a significant main effect of time. Over the recovery period, dogs in the NW group had lower mean BTear and PR by 0.6°F and 3.4 bpm, respectively. Daily ingestion of a NW in combination with free access to TW can reduce the post-exercise-related BTcore and BTear hyperthermia, and improve pulse rate recovery following exercise in this population of working dogs undergoing 30 min bout of exercise.

Metabolic perturbations associated with the consumption of a ketogenic medium-chain TAG diet in dogs with idiopathic epilepsy.

Consumption of diets containing medium-chain TAG (MCT) has been shown to confer neuroprotective effects. We aim to identify the global metabolic perturbations associated with consumption of a ketogenic diet (medium-chain TAG diet (MCTD)) in dogs with idiopathic epilepsy. We used ultra-performance liquid chromatography-MS (UPLC-MS) to generate metabolic and lipidomic profiles of fasted canine serum and made comparisons between the MCTD and standardised placebo diet phases. We identified metabolites that differed significantly between diet phases using metabolite fragmentation profiles generated by tandem MS (UPLC-MS/MS). Consumption of the MCTD resulted in significant differences in serum metabolic profiles when compared with the placebo diet, where sixteen altered lipid metabolites were identified. Consumption of the MCTD resulted in reduced abundances of palmitoylcarnitine, octadecenoylcarnitine, stearoylcarnitine and significant changes, both reduced and increased abundances, of phosphatidylcholine (PC) metabolites. There was a significant increase in abundance of the saturated C17 : 0 fatty acyl moieties during the MCTD phase. Lysophosphatidylcholine (17 : 0) (P=0·01) and PC (17:0/20:4) (P=0·03) were both significantly higher in abundance during the MCTD. The data presented in this study highlight global changes in lipid metabolism, and, of particular interest, in the C17 : 0 moieties, as a result of MCT consumption. Elucidating the global metabolic response of MCT consumption will not only improve the administration of current ketogenic diets for neurological disease models but also provides new avenues for research to develop better diet therapies with improved neuroprotective efficacies. Future studies should clarify the involvement and importance of C17 : 0 moieties in endogenous MCT metabolic pathways.

Effects of a nutrient-enriched water on water intake and indices of hydration in healthy domestic cats fed a dry kibble diet.

OBJECTIVE To evaluate the effects of drinking nutrient-enriched water (NW) on water intake and indices of hydration in healthy domestic cats fed a dry kibble diet ad libitum. ANIMALS 18 domestic shorthair cats. PROCEDURES Group-housed cats were assigned to tap water (TW; n = 9) or NW (9) groups. All cats received TW at baseline (days -7 to -1). No changes were made to the food-water regimen for the TW group. The NW group received NW instead of TW from days 0 through 10, then received TW and NW in separate bowls (days 11 through 56). Food intake was measured through day 10; liquid consumed by drinking was measured throughout the study. Blood and urine samples were collected at predetermined times for analyses; 48-hour urine collection (days 28 through 30 or 31 through 33) was performed to assess output volume and aid endogenous creatinine-based glomerular filtration rate (GFR) determination. Data were analyzed with linear mixed-effects models. RESULTS Baseline TW and calorie intake were similar between groups. The NW treatment was significantly associated with increased liquid consumption during the treatment phase. Mean urine output was significantly higher in the NW group (15.2 mL/kg/d) than in the TW group (10.3 mL/kg/d). Mean GFR (1.75 vs 1.87 mL/min/kg, respectively) did not differ between groups. Effects of treatment and time were each significant for urine specific gravity and osmolality and urine creatinine, phosphate, and urea nitrogen concentrations, with lower values for the NW group. CONCLUSIONS AND CLINICAL RELEVANCE Results suggested that consumption of the NW can increase liquid intake and improve measures of hydration in healthy cats. These effects may offer health benefits to some cats in need of greater water consumption.

Total Water Intake and Urine Measures of Hydration in Adult Dogs Drinking Tap Water or a Nutrient-Enriched Water.

Water intake and urine measures were evaluated in dogs offered tap water (TW) or a nutrient-enriched water (NW) supplement while fed dry food with ad libitum TW in a bucket. Baseline (day-7) urine specific gravity (USG) was analyzed from healthy, adult small breed dogs (n = 21; 2-11 years). Dogs (N = 16) were selected with ≥1.015 USG, then equally divided into 2 groups balanced for USG. Groups received either TW or NW in a bowl for 56 days. Dose for each dog was 0.5:1 water-to-calorie ratio (mL:kcal ME/d) from days 1-49 to evaluate sustained intake of a moderate volume, or 2:1 water-to-calorie ratio from days 50-56 to evaluate short-term intake of a large volume, based on baseline food calorie intake. Daily food calorie and total liquid intake (TLI; g/d; sum of NW or TW in a bowl and bucket water) was used to calculate weekly intake. USG was measured on days -7, 14, 42, 56. Calorie intake was not different (P > 0.49). A significant (P < 0.001) time-by-treatment interaction resulted for TLI with baseline similar between groups and no difference between weeks for the TW group. Following baseline, NW group had increased (P < 0.05) TLI every week, except for week 2 (P = 0.07). A significant (P < 0.002) time-by-treatment interaction resulted for USG, with baseline similar between groups and no difference between sampling days for the TW group (varied by ≤ 0.006 g/mL), whereas NW group was lower (P < 0.01) on days 42 (1.018 g/mL) and 56 (1.014 g/mL) vs. baseline (1.026 g/mL). This study indicates that all dogs offered the NW supplement increased their TLI and produced a more dilute urine, which suggests an improvement in indices associated with chronic hydration.

Environmental and Physiological Factors Associated With Stamina in Dogs Exercising in High Ambient Temperatures.

This IACUC approved study was performed to evaluate the environmental, physiological, and hematological components that contribute to stamina following successive bouts of exercise that included searching (5-min), agility (5-min), and ball retrieve (<10-min). Regularly exercised dogs (N = 12) were evaluated on five separate occasions. The population consisted of eight males and four females ranging in age from 8 to 23 months, which included six Labrador retrievers, three German shepherds, and one each English springer spaniel, German wirehaired pointer, and Dutch shepherd. The exercise period was up to 30 min with 5 min of intermittent rest between the exercise bouts or until a designated trainer determined that the dog appeared fatigued (e.g., curled tongue while panting, seeking shade, or voluntary reluctance to retrieve). At the end of the exercise period, pulse rate (PR), core temperature, blood lactate, and venous blood gas were collected. The median outdoor temperature was 28.9°C (84°F) (IQR; 27.2-30°C/81-86°F) and median humidity was 47% (IQR; 40-57%). Median duration of exercise was 27 min (IQR; 25-29). No dog showed signs of heat stress that required medical intervention. The components used to measure stamina in this study were total activity, post-exercise core body temperature (CBT), and increase in CBT. When controlling for breed, total activity, as measured by omnidirectional accelerometer device, could be predicted from a linear combination of the independent variables: pre-exercise activity (p = 0.008), post-exercise activity (p < 0.001), outdoor temperature (p = 0.005), reduction in base excess in extracellular fluid compartment (BEecf) (p = 0.044), and decrease in TCO2 (p = 0.005). When controlling for breed and sex, increase in CBT could be predicted from a linear combination of the independent variables: study day (p = 0.005), increase in PR (p < 0.001), increase in lactate (p = 0.001), reduction in BEecf (p = 0.031), increase in glucose (p = 0.044), increase in hematocrit (p = 0.032), and increase in hemoglobin (p = 0.038). This study suggests that the influence of outdoor temperature, pre- and post-exercise activity, and the metabolic parameters are important components of stamina associated with exertion.

The effects of a post-exercise carbohydrate and protein supplement on repeat performance, serum chemistry, insulin and glucagon in competitive weight-pulling dogs.

The physiological demands of weight-pulling dogs have yet to be investigated. Two groups of competitive weight-pulling dogs both underwent two identical pull series 3 h apart. The control group (n 8) was compared with a group fed a rapidly digestible carbohydrate and protein supplement after the first pull series (n 9). Blood was drawn before and after each pull series as well as at 15 and 30 min after the first pull series finished. Biochemistry values remained unremarkable throughout the study in both groups regardless of supplementation or exercise over time. Lactic acid showed mild significant increases post-exercise (2·1 (sd 1·2) mmol/l) compared with baseline (1·4 (sd 0·3) mmol/l; P = 0·03) after the initial pull series. When examining the effects of time there was a significant increase in insulin from baseline (median of 10·8 (range 6·8-17·4) µIU/ml) compared with 30 min after supplementation (17·0 (range 8·1-33·0) µIU/ml) and at 3 h after supplementation (19·2 (range 9·7-53·4) µIU/ml). In the treatment group there was also a time effect, with glucagon being elevated from baseline (median of 100 (range 79-115) pg/ml) compared with 30 min after supplementation (114 (range 90-183) pg/ml) and after the second pull series (131 (range 107-152) pg/ml). Evaluation of each dog's ability to pull the same or greater amount of weight on the second pull series revealed no significant differences. In conclusion, weight-pulling dogs have mild elevations in lactate reflecting little anaerobic metabolism compared with other canine sprinting athletes; hormonal changes associated with carbohydrate absorption are reflected within the treatment group, and supplementation had no effect on performance.

Effects of a ketogenic diet on ADHD-like behavior in dogs with idiopathic epilepsy.

OBJECTIVES: Epilepsy in humans and rodent models of epilepsy can be associated with behavioral comorbidities including an increased prevalence of attention-deficit/hyperactivity disorder (ADHD). Attention-deficit/hyperactivity disorder symptoms and seizure frequency have been successfully reduced in humans and rodents using a ketogenic diet (KD). The aims of this study were (i) to describe the behavioral profile of dogs with idiopathic epilepsy (IE) while on a standardized nonketogenic placebo diet, to determine whether ADHD-like behaviors are present, and (ii) to examine the effect of a ketogenic medium chain triglyceride diet (MCTD) on the behavioral profile of dogs with idiopathic epilepsy (IE) compared with the standardized placebo control diet, including ADHD-like behaviors. METHODS: A 6-month prospective, randomized, double-blinded, placebo-controlled, crossover dietary trial comparing the effects of the MCTD with a standardized placebo diet on canine behavior was carried out. Dogs diagnosed with IE, with a seizure frequency of at least 3 seizures in the past 3months (n=21), were fed the MCTD or placebo diet for 3months and were then switched to the alternative diet for 3months. Owners completed a validated behavioral questionnaire to measure 11 defined behavioral factors at the end of each diet period to report their dogs' behavior, with three specific behaviors hypothesized to be related to ADHD: excitability, chasing, and trainability. RESULTS: The highest scoring behavioral factors in the placebo and MCTD periods were excitability (mean±SE: 1.910±0.127) and chasing (mean±SE: 1.824±0.210). A markedly lower trainability score (mean±SE: 0.437±0.125) than that of previously studied canine populations was observed. The MCTD resulted in a significant improvement in the ADHD-related behavioral factor chasing and a reduction in stranger-directed fear (p<0.05) compared with the placebo diet. The latter effect may be attributed to previously described anxiolytic effects of a KD. CONCLUSIONS: These data support the supposition that dogs with IE may exhibit behaviors that resemble ADHD symptoms seen in humans and rodent models of epilepsy and that a MCTD may be able to improve some of these behaviors, along with potentially anxiolytic effects.