The clinical and histopathological effects of prednisone on acute radiation-induced dermatitis in dogs: a placebo-controlled, randomized, double-blind, prospective clinical trial

This study evaluated and compared the clinical and histopathological effects of prednisone on acute radiation-induced dermatitis (ARID) in dogs treated with 48 Gray of fractionated irradiation targeted to the skin surface. The study was designed as a double-blind, randomized, placebo-controlled prospective clinical trial. Twenty-two otherwise healthy companion dogs completed the clinical study. Three dogs were excluded from complete histopathological analysis because the owner declined one (one dog) or both (two dogs) biopsies. The study duration for each dog was 36 days from the start of radiation therapy (RT) to the first re-examination post RT. Dogs were treated with either oral prednisone at 0.5 mg kg(-1) or sugar pill, daily. All dogs received 48 Gray of fractionated, standardized RT, beginning 2 weeks after tumour excision. Acute Radiation Morbidity Scores, Cutaneous Toxicity Extent and Severity scores, digital images, and impression cytology were carried out on days 1, 8, 15, 22 and 36. Four-millimetre skin specimens from days 15 (RT-11) and 36 (2 weeks after the last RT dose) were scored by a pathologist and a dermatologist, blind to specimen identity. A one-way analysis of variance for longitudinal data was used to compare scores between groups. Spearman's rho correlation coefficient was used to measure strength of association between clinical and histopathology scores (HPS). There was no significant difference in CUTES, AMS or HPS scores between groups. There was a strong correlation between clinical and HPS scores. Prednisone did not decrease ARID severity clinically or histopathologically.     

Evaluation of a novel animal milk oligosaccharide biosimilar: macronutrient digestibility and gastrointestinal tolerance,fecal metabolites,and fecal microbiota of healthy adult dogs and in vitro genotoxicity assays

Milk oligosaccharides (MO) are bioactive compounds in mammalian milk that provide health benefits to neonates beyond essential nutrients. GNU100, a novel animal MO biosimilar, was recently tested in vitro, with results showing beneficial shifts in microbiota and increased short-chain fatty acid (SCFA) production, but other effects of GNU100 were unknown. Three studies were conducted to evaluate the safety, palatability, and gastrointestinal (GI) tolerance of GNU100. In study 1, the mutagenic potential of GNU100 was tested using a bacterial reverse mutation assay and a mammalian cell micronucleus test. In study 2, palatability was assessed by comparing diets containing 0% vs. 1% GNU100 in 20 adult dogs. In study 3, 32 adult dogs were used in a completely randomized design to assess the safety and GI tolerance of GNU100 and explore utility. Following a 2-wk baseline, dogs were assigned to one of four treatments and fed for 26 wk: 0%, 0.5%, 1%, and 1.5% GNU100. On weeks 2, 4, and 26, fresh fecal samples were collected to measure stool quality, immunoglobulin A, and calprotectin, and blood samples were collected to measure serum chemistry, inflammatory markers, and hematology. On weeks 2 and 4, fresh fecal samples were collected to measure metabolites and microbiota. On week 4, total feces were collected to assess apparent total tract macronutrient digestibility. Although revertant numbers were greater compared with the solvent control in tester strain WP2uvrA(pKM101) in the presence of metabolic activation (S9) in the initial experiment, they remained below the threshold for a positive mutagenic response in follow-up confirmatory tests, supporting that GNU100 is not mutagenic. Similarly, no cytotoxicity or chromosome damage was observed in the cell micronucleus test. The palatability test showed that 1% GNU100 was strongly preferred (P < 0.05; 3.6:1 consumption ratio) over the control. In study 3, all dogs were healthy and had no signs of GI intolerance or illness. All diets were well accepted, and food intake, fecal characteristics, metabolite concentrations, and macronutrient digestibilities were not altered. GNU100 modulated fecal microbiota, increasing evenness and Catenibacterium, Megamonas, and Prevotella (SCFA producers) and reducing Collinsella. Overall, the results suggest that GNU100 is palatable and well-tolerated, causes no genotoxicity or adverse effects on health, and beneficially shifts the fecal microbiota, supporting the safety of GNU100 for the inclusion in canine diets.     

A double-blind,randomized, placebo-controlled study of pimobendan in dogs with dilated cardiomyopathy

A double-blind, randomized, placebo-controlled study was conducted to examine the effect on heart failure class and survival of pimobendan, an oral calcium-sensitizing inodilator, in dogs with dilated cardiomyopathy (DCM). Pimobendan (0.3-0.6 mg/kg body weight/d) or placebo was administered to English Cocker Spaniels (CSs; n = 10) and Doberman Pinschers (DPs: n = 10) that had DCM in addition to background therapy of furosemide, enalapril, and digoxin. Addition of pimobendan to standard triple therapy was associated with a significant improvement in heart failure class, regardless of breed (P < .02, Mann-Whitney rank sum test). Overall, 8 of 10 animals in the pimobendan-treated group, and 1 of 10 animals in the placebo group improved their heart failure status by at least I modified New York Heart Association functional class after initial stabilization (P = .005, Fisher's exact test). Pimobendan had no significant effect on survival in the CSs (P = 0.77, log-rank test), but DPs treated with pimobendan had significantly longer survival times compared with placebo (P < .02, log-rank test), with a median survival time of 329 days in the pimobendan group compared with 50 days in the placebo group, and a hazard ratio of 3.4 (95% confidence interval 1.4-39.8). Pimobendan resulted in significant improvement in heart failure class when added to standard therapy in this group of dogs with DCM, and may have contributed to improved survival in DPs.     

The effect of thyroid replacement in dogs with suboptimal thyroid function on owner-directed aggression: A randomized,double-blind,placebo-controlled clinical trial

The efficacy of thyroid hormone replacement therapy (THRT) as treatment for owner-directed aggression in client-owned dogs with borderline low thyroid hormone levels was evaluated by means of a 6-week-long, parallel design, double-blind placebo-controlled study. The designation of “borderline hypothyroid” was made if the dog's free normal thyroxine (T4) value was frankly low or in the bottom 20th percentile of the normal range and either total T4, total triiodothyronine (T3), or free T3 was frankly low or in the bottom 30th percentile of the normal range. The presence of thyroid autoantibodies also qualified a dog for enrollment. Owners recorded the number of aggressive episodes directed toward family members on a daily basis for 8 weeks (2-week baseline phase and 6-week study phase). Twenty-nine dogs completed the study; 14 in a treatment group and 15 in a placebo group. The median number of aggressive episodes per day decreased significantly from baseline in both treated and placebo group dogs in weeks 1-2, 3-4, 5-6, and week 6 (treatment, χ² = 24.8, P < 0.001; placebo, χ² = 20.2, P < 0.001), however the median frequency of aggression was significantly lower in the treatment group (1.21 episodes/day) than in the placebo group (1.71 episodes/day) during week 6 of the study (χ² = 4.047, P = 0.044). Three thyroxine-treated dogs had borderline-low thyroid levels on the final day of the study (day 42). When aggression frequency was compared between the treatment and placebo groups after the removal of 3 thyroxine-treated dogs, the treatment group did not have a significantly lower aggression frequency than the placebo group during week 6 (Kruskal–Wallis statistic: χ² = 3.035, n = 26, P = 0.08). The authors discuss the role of thyroid hormones in the regulation of aggression and other cognitive issues and provide rationale for using THRT in dogs exhibiting owner-directed aggression that also have low normal or baseline thyroid hormone levels.     

Gastric mucosal lesions in dogs with acute intervertebral disc disease: characterization and effects of omeprazole or misoprostol

We characterized gastric mucosal lesions in dogs with acute degenerative disc disease treated by surgery and corticosteroid administration. The effect of omeprazole and misoprostol on gastric lesions in these dogs was also evaluated. Dogs were randomly assigned to 1 of 2 treatment groups or to the control group. Treatment consisted of omeprazole at 0.7 mg/kg orally once daily, or misoprostol at 2 microg/kg orally 3 times daily. All 3 groups received dexamethasone at 2 mg/kg on day 0, prednisolone at 2 mg/kg on day 1. prednisolone at 1 mg/kg on day 2, and prednisolone at 0.5 mg/kg on all further days (range, 5-6 days). Endoscopic examination was performed on day 0 and 5-6 days later. Four regions of the stomach were qualitatively scored from 1 to 12 based on the presence of submucosal hemorrhage, erosion, or ulceration, with ulceration receiving the highest numerical score. Nineteen of 25 dogs had gastric mucosal lesions at the beginning of the study. No significant difference was found in the gastric lesion score among the 3 groups at the end of the study. Gastric mucosal lesions were concluded to be common in dogs with acute degenerative disc disease treated with corticosteroids. Neither omeprazole nor misoprostol at the doses used was effective in healing or preventing the further development of gastric mucosal lesions.     

Effects of a 1% hydrocortisone conditioner on haematological and biochemical parameters, adrenal function testing and cutaneous reactivity to histamine in normal and pruritic dogs

The purpose of this double-blinded study was to examine the effects of a 1% hydrocortisone, leave-on conditioner on haematological and biochemical parameters, adrenal function tests, and cutaneous reaction to serial dilutions of histamine phosphate in normal dogs and those with pruritic dermatitis. Groups 1 and 2 each consisted of eight normal dogs. Seven pruritic dogs comprised Group 3. All dogs were bathed twice weekly for 6 weeks. Groups 1 and 3 had 1% hydrocortisone conditioner applied after each bath. Group 2 had vehicle from the conditioner applied after each bath. The amount of 1% hydrocortisone applied to the treated dogs ranged from 278 to 416 mg/m². Haematological and biochemical analysis and adrenocorticotrophic hormone (ACTH) stimulation tests were performed on all dogs on days 0, 14, 28, and 42. Mean values for all blood and serum parameters remained within normal limits during the study. Post-ACTH cortisol levels were significantly lower in Group 3 compared to Groups 1 and 2 on day 42 (P < 0.05) and when averaged over all days of the study (P < 0.05 and P < 0.01, respectively). Serum alkaline phosphatase levels were significantly lower in Group 3 on day 0, compared to days 14 (P < 0.05), 28 (P < 0.01), and 42 (P = 0.05). All dogs received intradermal injections of buffered saline and five serial dilutions of histamine phosphate on days 0, 14, 28, and 42. No significant differences were apparent among the groups in subjective and objective evaluation of intradermally injected dilutions of histamine. In this study, the use of a 1% hydrocortisone leave-on conditioner did not result in clinically evident adverse effects, and only minor changes in blood parameters were detected. Although mean values in all groups remained within reference ranges throughout the study, the finding of statistically significant lower post-ACTH cortisol concentrations in the pruritic dogs (Group 3) suggests that absorption of hydrocortisone may have occurred. The results of this study also show that this product does not significantly suppress cutaneous reactivity to histamine in normal and pruritic dogs.     

Effect of a novel animal milk oligosaccharide biosimilar on macronutrient digestibility and gastrointestinal tolerance,fecal metabolites,and fecal microbiota of healthy adult cats

GNU100 is a novel animal milk oligosaccharide (AMO) biosimilar. In a recent in vitro fermentation study, GNU100 was shown to be fermentable by feline gastrointestinal microbiota and lead to increased short-chain fatty acid production. Our objectives herein were to evaluate the palatability, safety, and gastrointestinal tolerance of GNU100 in healthy adult cats. Exploratory end-points were measured to assess utility. In study 1, 20 adult cats were used to test the palatability of diets containing 0% or 1% GNU100. In study 2, 32 (mean age = 1.9 yr; mean body weight = 4.6 kg) male (n = 12) and female (n = 20) adult cats were used in a completely randomized design. After a 2-wk baseline, cats were assigned to one of the following treatment groups and fed for 26 wk: control (CT, no GNU100), low dose (LD, 0.5% GNU100), medium dose (MD, 1.0% GNU100), and high dose (HD, 1.5% GNU100). On weeks 2, 4, and 26, fresh fecal samples were collected for the measurement of stool quality and immune and inflammatory markers and on weeks 2 and 4 for microbiota and metabolites. On week 4, total feces were collected to measure apparent total tract macronutrient digestibility. On weeks 2, 4, and 26, blood samples were collected for serum chemistry, hematology, and inflammatory marker measurement. The palatability test showed that 1% GNU100 was strongly preferred (P < 0.05), with GNU100 having a 17.6:1 consumption ratio compared with control. In the long-term study, all cats remained healthy, without any signs of gastrointestinal intolerance or illness. All diets were well accepted, resulting in similar (P > 0.05) food intake, fecal characteristics, immunoglobulin A, and calprotectin, and dry matter, organic matter, fat, and crude protein digestibilities. Fecal butyrate was greater (P = 0.02) in cats fed HD than cats fed LD or MD. Fecal indole was lower (P = 0.02) in cats fed HD than cats fed LD. Cats fed CT had a higher (P = 0.003) relative abundance of Actinobacteria than cats fed LD. The relative abundance of Peptococcus was impacted by diet and time. At 4 wk, Campylobacter was lower in fecal samples of cats fed HD. Overall, the data suggest that dietary GNU100 supplementation was highly palatable, well tolerated, did not cause detrimental effects on fecal quality or nutrient digestibility, increased fecal butyrate concentrations, and reduced fecal indole concentrations, supporting the safety of GNU100 for inclusion in feline diets and suggesting potential benefits on gastrointestinal health of cats.     

The effects of capsaicin topical therapy in dogs with atopic dermatitis: a randomized,double-blinded,placebo-controlled,cross-over clinical trial

Abstract The efficacy of twice daily topical application of capsaicin (0.025%) for the management of pruritus in dogs with atopic dermatitis (AD) was evaluated in double-blinded, placebo-controlled study. Twelve dogs with AD were randomly assigned to either 0.025% capsaicin or vehicle lotion applied twice daily for 6 weeks. After a 4-week wash-out period, treatments were switched. Significant improvement was reported by owners ( P  = 0.0006), but not by investigators. Owners noted temporary worsening of pruritus after the first week of capsaicin therapy. Overall capsaicin was well tolerated. Substance P (SP) concentrations in the skin did not correlate with the severity of the pruritus and did not change significantly over time and between treatments. Lesional skin had less SP than nonlesional skin ( P  = 0.03). These observations suggest that topical capsaicin should be further evaluated as an adjunctive antipruritic agent in dogs with AD.     

Comparison of the sedative effects of intranasal or intramuscular dexmedetomidine at low doses in healthy dogs: a randomized clinical trial

ObjectiveTo compare the sedative effects of dexmedetomidine administered either intranasally or intramuscularly to healthy dogs.Study designProspective, randomized, blinded, clinical trial.AnimalsA group of 16 client-owned healthy dogs.MethodsDogs were randomly allocated to one of two groups that were administered dexmedetomidine 5 μg kg^–1 via either the intranasal route (IN_Dex), through a mucosal atomization device in one nostril, or the intramuscular route (IM_Dex), into the epaxial muscles. Ease of intranasal administration, sedation score, onset of sedation, cardiopulmonary variables, mechanical nociceptive thresholds (MNTs) and response to venous catheterization were recorded at 0 (baseline), 5, 10, 15, 20, 25, 30, 35, 40 and 45 minutes, following drug administration. Data were compared with the one-way anova, Mann-Whitney U test, and chi-square test, where appropriate.ResultsGroups were not different for age, sex, weight, body condition score or temperament. Sedation scores, MNTs and response to intravenous catheter placement were not different when dexmedetomidine was administered by either route (p = 0.691; p = 0.630 and p = 0.435, respectively). Onset of sedation was not different between groups IN_Dex and IM_Dex reaching a score of 4.2 ± 0.9 and 5.5 ± 1.2 at 9 ± 5 and 8 ± 4 minutes, respectively (p = 0.467). The highest sedation score was achieved at 30 and 35 minutes and sedation scores were 9.7 ± 2.0 and 9.5 ± 2.3 in groups IN_Dex and IM_Dex, respectively (p = 0.799). Respiratory rate was higher in group IN_Dex (p = 0.014), while there were no differences between routes in heart rate (p = 0.275), systolic (p = 0.957), diastolic (p = 0.837) or mean arterial pressure (p = 0.921).Conclusions and clinical relevanceIntranasal administration of dexmedetomidine at 5 μg kg^–1 provides effective sedation in healthy dogs.     

The echocardiographic effects of romifidine in dogs with and without prior or concurrent administration of glycopyrrolate

Objective To determine the cardiopulmonary response to romifidine (RO) in the dog with or without prior or concurrent administration of glycopyrrolate. Study Design Randomized, cross‐over experimental study. Animals Six (three male, three female) cross‐bred dogs weighing 23 ± 2.4 kg. Methods Two‐dimensional guided M‐mode echocardiography was performed in conscious dogs simultaneously with measurement of systolic arterial blood pressure (SBP) and heart rate (HR). Dimensions of the left ventricle (LVID), interventricular septum (IVS), and left ventricular free wall (LVFW) were obtained in systole (S) and diastole (D). Amplitude of motion (Amp) of the IVS and LVFW were also measured. From these, measures of wall stress (WS) and fractional shortening (FS) of the left ventricle were derived. Baseline echocardiographic measurements were recorded, following which one of the five treatments was administered. Glycopyrrolate (G) 0.01 mg kg^?1, or saline (S) 0.5 mL, was administered IM as pre‐medication (Gp or Sp), or G was administered concurrently (Gc) with romifidine (RO). Treatments were: T₁, Sp + RO (40 μg kg^?1); T₂, Gp + RO (40 μg kg^?1); T₃, Sp + RO (120 μg kg^?1); T₄, Gp + RO (120 μg kg^?1); and T₅, Sp + Gc +RO (120 μg kg^?1). Romifidine or RO + Gc was administered SC 20 minutes after pre‐medication (time 0), and further measurements were taken 10, 20, 30, 60, and 90 minutes after RO. Results Echocardiographic indices of cardiac systolic function (LVID‐S, FS, Amp‐LVFW) and HR were decreased in RO‐sedated dogs (p < 0.0001) . The magnitude of change in cardiac indices was least with low‐dose RO. At most sampling times, high‐dose RO produced significantly more alteration in cardiac indices. Systolic blood pressure increased in all treatment groups, with the greatest increases in those groups receiving G. Glycopyrrolate significantly increased HR; however, cardiac indices were further reduced. Wall stress significantly increased, with a more dramatic increase in groups receiving G. Conclusions Indices of LV systolic function were reduced in RO‐sedated dogs in a dose‐related manner. Glycopyrrolate further reduced these indices and dramatically increased measurements of wall stress in dogs sedated with RO. Clinical relevance Use of low‐dose RO minimizes cardiac dysfunction; however, it should still be used cautiously in dogs with cardiomyopathy or heart failure. The routine use of G is not recommended to alleviate the bradycardia associated with RO in conscious dogs.