FC-41 A prospective pilot study on the use of cyclosporin on feline allergic diseases

This study evaluated the efficacy of Phytopica^TM, a proprietary blend of standardised plant extracts, in canine atopic dermatitis (AD). One hundred twenty dogs with perennial AD were recruited on the basis of history and clinical signs, and a positive intradermal allergen test or rFcεRIα serology to perennial allergens. Other pruritic dermatoses were eliminated by antimicrobial treatment, skin scrapings, Sarcoptes serology, flea control and a 6-week food trial. Exclusion criteria included antimicrobial therapy within 7 days, antihistamines within 14 days, oral/topical glucocorticoids or cyclosporin within 28 days, and parenteral glucocorticoids, essential fatty acids or immunotherapy within 56 days of entry into the study. Dogs [minimum Canine Atopic Dermatitis Extent and Severity Index (CADESI) = 25] were randomly allocated to receive placebo, 100, 200 or 400 mg/kg Phytopica^TM daily for 12 weeks. Their CADESI was assessed every 4 weeks. A modified intention-to-treat population was analysed. The mean reductions in CADESI scores at the end of treatment compared to baseline were 4.4% (100 mg/kg; n  = 30), 23.4% (200 mg/kg; n  = 29, P  < 0.01), 8.5% (400 mg/kg; n  = 29) and 3.9% (placebo; n  = 29). For more severely affected dogs (minimum CADESI ≥ 50 at baseline), there was significant reduction in mean CADESI score (29.3%, P  = 0.038) only in the 200 mg/kg treatment group ( n  = 14). In conclusion, this study demonstrates that Phytopica^TM is an effective nonsteroidal treatment for canine AD.
Funding: Phytopharm plc.     

Management of canine atopic dermatitis using the plant extract PYM00217: a randomized, double-blind, placebo-controlled clinical study

This study evaluated PYM00217, a proprietary blend of plant extracts, in the management of canine atopic dermatitis (AD). One hundred and twenty dogs were diagnosed with perennial AD on the basis of history, clinical signs, a positive test for perennial allergens and elimination of other dermatoses. Exclusion criteria included antimicrobials within 7 days, antihistamines within 14 days, oral/topical glucocorticoids or ciclosporin within 28 days, and parenteral glucocorticoids, essential fatty acids or immunotherapy within 56 days. Flea control, shampoos and ear cleaners were permitted. Dogs with a minimum canine atopic dermatitis extent and severity index (CADESI) of 25 were randomly allocated to receive PYM00217 (100, 200 or 400 mg kg-1 day-1) or placebo for 12 weeks. The mean reductions in CADESI (intention-to-treat population) were 3.9% (placebo; n=29), 4.4% (100 mg kg-1 day-1; n=30), 23.4% (200 mg kg-1 day-1; n=29) and 8.5% (400 mg kg-1 day-1; n=29). The reduction in the 200 mg kg-1 day-1 group was significant (P<0.01). For dogs with a baseline CADESI>or=50, the mean changes were +10.6% (placebo; n=12), +0.6% (100 mg kg-1 day-1; n=14), -29.3% (200 mg kg-1 day-1; n=14) and -3.4% (400 mg kg-1 day-1; n=15). The 200 mg kg-1 day-1 dose was significantly more effective than placebo (P=0.038). No serious adverse effects were reported. Minor adverse effects seen in 10% (placebo and 100 mg kg-1 day-1), 24% (200 mg kg-1 day-1) and 42% (400 mg kg-1 day-1) of cases were mainly minor gastrointestinal disorders and only five cases required cessation of dosing. Two dogs (one in each of the 100 mg kg-1 day-1 and 200 mg kg-1 day-1 groups) refused to eat the medicated food. In conclusion, PYM00217 at 200 mg kg-1 appears to be an effective, palatable and well-tolerated treatment for canine AD.     

Are transepidermal water loss and clinical signs correlated in canine atopic dermatitis? A compilation of studies

Background – Cutaneous impairment plays a crucial role in atopic dermatitis (AD). Transepidermal water loss (TEWL) measurement is an indirect assessment of skin barrier function and correlates with disease severity in humans. Skin impairment also exists in canine AD; however, concerns exist regarding variability and reliability of TEWL measurements in dogs. Hypothesis/Objectives – The purposes of this retrospective study were twofold: first, to investigate the correlation between severity of dermatitis [measured by Canine Atopic Dermatitis Extent and Severity Index (CADESI)] and TEWL; and second, to evaluate whether increased TEWL at a young age correlates with disease severity later in life. Methods – Data from atopic beagles and dogs with natural AD were analysed. Transepidermal water loss was measured in atopic beagles (n = 24) with an open chamber and in dogs with naturally occurring AD with a closed chamber device (two studies, with n = 14 and n = 18). Pearson product–moment correlation was used for analyses. Transepidermal water loss of the inguinal region, axilla, antebrachial flexure and pinna was analysed. Correlations were investigated for each study, separately first and then jointly. They included CADESI and TEWL of individual regions, total CADESI and total TEWL of all measured regions, and total CADESI and TEWL of key regions. Results – In atopic beagles, TEWL measured at 1 year of age pre‐ and post‐allergen challenge was correlated with CADESI at 1, 3 and 6 years of age. Overall, low correlation coefficients were found; therefore, a biologically relevant connection could not be demonstrated. The main significant positive correlation was found between TEWL in the pinna and total CADESI. Conclusions and clinical importance – It is concluded that TEWL does not correlate with disease severity.     

The efficacy of cyclosporine A in cats with presumed atopic dermatitis: a double blind, randomised prednisolone-controlled study

The objective of this study was to compare the efficacy of cyclosporine A (CsA) and prednisolone in feline atopic dermatitis (AD) in a randomised, controlled double blind study. Twenty-nine cats with feline AD were randomly allocated to two groups. Eleven cats were treated orally with prednisolone (1mg/kg SID) and 18 were treated with CsA (5mg/kg/day) for 4 weeks. At day 0 (D0) and D28, skin lesions were graded by means of the canine atopic dermatitis extent and severity index (CADESI). Skin biopsies and intradermal allergy tests were performed at D0 and blood samples for haematology and serum biochemistry were collected at D0 and D28. During the trial the cat owners were asked to evaluate the intensity of the pruritus once weekly on a linear analog scale and to record side effects. Based on the CADESI there was no significant difference between the two groups in the amount of remission (P=0.0562) or in the number of cats that improved by >25% (P=0.0571). The effect of CsA and prednisolone on pruritus as evaluated by the owners was not significantly different (P=0.41) between the two groups. No serious side effects were observed. The conclusion was that CsA is an effective alternative to prednisolone therapy in cats with presumed atopic dermatitis.     

Pharmacokinetics of a controlled‐release liposome‐encapsulated hydromorphone administered to healthy dogs

The purpose of the study was to assess the pharmacokinetics of liposome‐encapsulated (DPPC‐C) hydromorphone administered intravenously (IV) or subcutaneously (SC) to dogs. A total of eight healthy Beagles aged 12.13 ± 1.2 months and weighing 11.72 ± 1.10 kg were used. Dogs randomly received liposome encapsulated hydromorphone, 0.5 mg/kg IV (n = 6), 1.0 mg/kg (n = 6), 2.0 mg/kg (n = 6), or 3.0 mg/kg (n = 7) SC with a 14–28 day washout between trials. Blood was sampled at serial intervals after drug administration. Serum hydromorphone concentrations were measured using liquid chromatography with mass spectrometry. Serum concentrations of hydromorphone decreased rapidly after IV administration of the DPPC‐C formulation (half‐life = 0.52 h, volume of distribution = 12.47 L/kg, serum clearance = 128.97 mL/min/kg). The half‐life of hydromorphone after SC administration of DPPC‐C formulation at 1.0, 2.0, and 3.0 mg/kg was 5.22, 31.48, and 24.05 h, respectively. The maximum serum concentration normalized for dose (C_MAX/D) ranged between 19.41–24.96 ng/mL occurring at 0.18–0.27 h. Serum hydromorphone concentrations fluctuated around 4.0 ng/mL from 6–72 h after 2.0 mg/kg and mean concentrations remained above 4 ng/mL for 96 h after 3.0 mg/kg DPPC‐C hydromorphone. Liposome‐encapsulated hydromorphone (DPPC‐C) administered SC to healthy dogs provided a sustained duration of serum hydromorphone concentrations.     

Effect of ammonium‐iron‐hexa‐cyanoferrate and of the covariates age,gender, weight,season and calendar time on radiocaesium contamination of wild boars living in the wild in Bavaria

Feed with Ammonium‐iron‐hexa‐cyanoferrate (AFCF; 1250 mg AFCF/kg) was fed between March 2009 and March 2011 to wild boars in a territory of 4.5 km² (experimental group, EXP). One hundred and forty similar territories in the same county (500 km², spruce forest, agriculture) served as control (CON). Data for comparison from all territories were available from March 2005 to March 2011. Wild boars could move between, into and from the territories. Lean skeletal muscle meat (500 g) of all wild boars that were killed by humans (hunting and traffic accidents) was investigated for gamma‐radiation from ¹³⁷Cs with a becquerel monitor with a sodium iodide scintillator crystal (range of detection 20–9999 Bq/kg). The wild boars were weighed, and gender and age were determined. For the analyses of effects, multivariable regression models were fitted with the ¹³⁷Cs concentration as response variable. There was a significant difference between the ¹³⁷Cs contamination of wild boars from CON (563 ± 932 Bq/kg meat, n = 1253) and EXP (236 ± 276 Bq/kg meat; n = 45). ¹³⁷Cs contamination decreased with increasing body weight by ?5 Bq/kg meat/kg body weight increase (p < 0.05). Females had higher Bq measurements than males (by +80 Bq/kg meat, p < 0.05). Piglets were lower than adults, but turn‐coats higher. From November to May, contamination was higher (by +500 to +600 Bq/kg meat, p < 0.05) than during the rest of the year. In 2010, contamination was higher (by +200 to + 300 Bq/kg meat, p < 0.05) in comparison with the other years under observation. When all covariates were controlled for, the effect of AFCF was highly significant. Interaction analyses showed that the intervention decreased ¹³⁷Cs contamination by ?500 Bq/kg meat during November to May and by ?200 Bq/kg meat during the rest of the year. In summary, AFCF feeding reduces ¹³⁷Cs contamination of wild boars living in the wild significantly, particularly during the season from November to May.     

Efficacy of an essential fatty acid-enriched diet in managing canine atopic dermatitis: a randomized, single-blinded, cross-over study

Evidence suggests that high-quality diets enriched with essential fatty acids (EFA) and other nutrients can ameliorate canine atopic dermatitis (AD). This study compared such a diet (Eukanuba Veterinary Diets Dermatosis FP) with a home-cooked equivalent (fish and potato) in a randomised, single-blinded, cross-over trial. Twenty dogs with perennial AD were randomly assigned to receive either the test (group A) or the control diet (group B) for 1 month, followed by the contrasting diet for a further month. Canine Atopic Dermatitis Extent and Severity Index (CADESI version 2) and pruritus (visual analogue scale) scores were recorded at days 0, 30 and 60. Eight dogs in each group completed the study. CADESI scores significantly declined when dogs were fed the test diet (group A P < 0.01; group B P < 0.001), and increased (group A P < 0.05) or remained steady (group B) on the control diet. CADESI scores decreased in 15 of 16 dogs fed the test diet, but this was less than 50% in all cases. Pruritus scores also declined when dogs were fed the test diet compared to the control diet, but this was only significant for group A (P = 0.027). Pruritus was reduced in 11 of 16 dogs fed the test diet, but this was 50% or more in only two dogs. This trial provides evidence for the efficacy of Eukanuba Veterinary Diets Dermatosis FP in canine AD, although it is likely that most cases will require adjunct therapy. The mechanism is unclear, but may involve increased and balanced EFA levels.     

Short‐term intake of β‐carotene‐supplemented diets enhances ovarian function and progesterone synthesis in goats

The effect of β‐carotene supplementation upon luteal activity, measured as number (CLT) and volume (VLT) of corpus luteum, and P4 synthesis in goats, was evaluated. Goats (n = 22, 34 months) were randomly assigned to one of two experimental groups: (i) β‐carotene [Beta, n = 10; body weight (BW = 44.8 ± 1.45 kg), body condition score (BCS = 3.25 ± 0.07)], and (ii) Control (Control, n = 12; BW = 45.30 ± 1.32 kg, BCS = 3.33 ± 0.06). Upon oestrus synchronization, the Beta group received 50 mg of β‐carotene per day during 35 days pre‐ and 17 days post‐ovulation. The day 4, 8, 12 and 16 post‐ovulation, blood samples were collected for quantification of serum P4 concentrations by radioimmmunoassay, and transrectal ultrasonographic scanning was performed at day 18 for evaluating CLT and VLT. Overall, CLT and VLT mean were 3.10 and 2211.1 mm³ respectively. The Beta‐goats depicted both the largest values for CLT (p = 0.07) and serum P4 levels (p = 0.05), with no differences (p = 0.53) for VLT between treatments. Results suggest a higher efficiency within the cellular‐enzymatic groups defining the steroidogenic pathways in the β‐carotene‐supplemented goats, generating a larger P4 synthesis. The last is essential for ovulation of healthy oocytes, maintenance of uterine quiescence, nourishment and survival of the embryo around implantation; all of them of paramount significance during the maternal recognition of pregnancy process.     

Olive leaves (Olea europea L.) and α‐tocopheryl acetate as feed antioxidants for improving the oxidative stability of α‐linolenic acid‐enriched eggs

Ninety‐six brown Lohmann laying hens were equally assigned into four groups with six replicates. Hens within the control group were fed a corn–soybean‐based diet supplemented with 4% linseed oil. Two other groups were given the same diet further supplemented with 5 or 10 g ground olive leaves/kg feed, while the diet of the fourth group was further supplemented with 200 mg α‐tocopheryl acetate/kg. Supplementing diets with olive leaves had no effect on egg production, feed intake and egg traits. Eggs collected 28 days after feeding the experimental diets were analysed for lipid hydroperoxides and malondialdehyde (MDA) content, fatty acid profile, α‐tocopherol concentrations and susceptibility to iron‐induced lipid oxidation. Olive leaves were also analysed for total and individual phenolics, and total flavonoids, whereas their antioxidant capacity was determined using both the DPPH (1,1‐diphenyl‐2‐picrylhydrazyl) and ABTS (2,2‐azinobis3‐ethylbenzothiazoline‐6‐sulphonic acid) radical scavenging activity assays. Results showed that neither α‐tocopheryl acetate nor olive leaves supplementation exerted (p > 0.05) any effect on the fatty acid composition of n‐3 eggs. Supplementing the diet with 5 g olive leaves/kg had no (p > 0.05) effect on the hydroperoxide levels of n‐3 eggs, while supplementing with 10 g olive leaves/kg or 200 mg α‐tocopheryl acetate/kg, the lipid hydroperoxide levels were reduced (p ≤ 0.05) compared to control. However, although hydroperoxides were reduced, MDA, a secondary lipid oxidation product, was not affected (p > 0.05). Iron‐induced lipid oxidation increased MDA values in eggs from all groups, the increase being higher (p ≤ 0.05) in the control group and the group supplemented with 5 g olive leaves/kg. The group supplemented with 10 g olive leaves/kg presented MDA values lower (p ≤ 0.05) than the control but higher (p ≤ 0.05) than the α‐tocopheryl acetate group, which presented MDA concentrations lower (p ≤ 0.05) than all other experimental diets at all incubation time points.     

Comparative activity of pradofloxacin and marbofloxacin against coagulase‐positive staphylococci in a pharmacokinetic–pharmacodynamic model based on canine pharmacokinetics

Körber‐Irrgang, B., Wetzstein, H.‐G., Bagel‐Trah, S., Hafner, D., Kresken, M. Comparative activity of pradofloxacin and marbofloxacin against coagulase‐positive staphylococci in a pharmacokinetic–pharmacodynamic model based on canine pharmacokinetics. J. vet. Pharmacol. Therap.  35 , 571–579. Pradofloxacin (PRA), a novel veterinary 8‐cyano‐fluoroquinolone (FQ), is active against Staphylococcus pseudintermedius, the primary cause of canine pyoderma. An in vitro pharmacokinetic–pharmacodynamic model was used to compare the activities of PRA and marbofloxacin (MAR) against three clinical isolates of S. pseudintermedius and reference strain Staphylococcus aureus ATCC 6538. Experiments were performed involving populations of 10¹⁰ CFU corresponding to an inoculum density of approximately 5 × 10⁷ CFU/mL. The time course of free drug concentrations in canine serum was modelled, resulting from once daily standard oral dosing of 3 mg of PRA/kg and 2 mg of MAR/kg. In addition, experimentally high doses of 6 mg of PRA/kg and 16 mg of MAR/kg were tested against the least susceptible strain. Viable counts were monitored over 24 h. At concentrations associated with standard doses, PRA caused a faster and more sustained killing than MAR of all strains. The ratios of free drug under the concentration–time curve for 24 h over MIC and the maximum concentration of free drug over MIC were at least 90 and 26, and 8.5 and 2.1 for PRA and MAR, respectively. At experimentally high doses, PRA was superior to MAR in terms of immediate killing. Subpopulations with reduced susceptibility to either FQ did not emerge. We conclude that PRA is likely to be an efficacious therapy of canine staphylococcal infections.     

Efficacy of Ivermectin Delivered via a Controlled‐Release Capsule against Small Lungworms (Protostrongylidae) in Sheep

To evaluate the efficacy of an ivermectin controlled‐release capsule (CRC), which delivers 1.6 mg ivermectin per day intraruminally for 100 days to sheep weighing 40–80 kg (IVOMEC^® Maximizer^TMCR Capsule for adult sheep, Merial), against small lungworms two studies with 48 naturally infected adult female Merino Landrace sheep were conducted. The sheep were allocated by restricted randomization based on bodyweight to untreated controls or received an ivermectin CRC. Eight sheep per group were necropsied 35, 70 or 105 days post‐treatment. Lungworms were recovered by dissection or peptic digestion of the lungs. Baermann/Wetzel technique was used for faecal lungworm larval counts at weekly intervals. The efficacy of treatment was 100% against Dictyocaulus filaria and Protostrongylus rufescens (P < 0.05) at each necropsy day. The efficacy against Protostrongylus brevispiculum, Cystocaulus ocreatus and Neostrongylus linearis increased from 35 to 105 days after administration of the CRC and was found to be 100% (P < 0.01), 96.6% (P < 0.01) or 99% (P < 0.01), respectively, at 105 days post‐treatment. The reductions of Muellerius capillaris counts varied and were 96.2% (P < 0.05) at 70 days post‐treatment and 44.6% (P > 0.1) at 105 days post‐treatment. Faecal lungworm larvae disappeared nearly completely from at least 3 weeks after the ivermectin CRC administration for all protostrongylid species including M. capillaris so that pasture infectivity will be subsequently significantly reduced.     

Investigation on the effects of ciclosporin (Atopica) on intradermal test reactivity and allergen‐specific immunoglobulin (IgE) serology in atopic dogs

The ability to use ciclosporin (Atopica^®: Novartis Animal Health, Greensboro, NC, USA) prior to intradermal testing (IDT) would help avoid exacerbation of clinical disease that can be associated with drug withdrawal. This study evaluated the effects of 30 days of administration of ciclosporin at a dose of 5 mg/kg once daily on IDT reactivity (immediate phase reactions) in a group of dogs with atopic dermatitis (AD) with initial positive IDT reactions. 16 dogs diagnosed with AD were included in the study. Eight dogs (group A) were treated with ciclosporin orally at 5 mg/kg once daily for 30 days. Eight dogs (group P) were treated with a placebo orally once daily for 30 days. IDT was performed at day 0 and day 30 on all dogs enrolled using a standardized panel of 45 aqueous allergens (Greer Laboratories, Lenoir, NC, USA) appropriate to our geographical region. IDT reactivity was assessed by both subjective and objective methods at 15 min post‐intradermal injection. Serum for allergen‐specific immunoglobulin (IgE) serology was obtained at day 0 and day 30. The study was designed as a double‐blinded, placebo‐controlled, cross‐over study. Data were analysed using a split‐plot analysis of variance with the grouping factor of treatment and the repeat factor of time (SAS System for Windows). At week 4, ciclosporin did not have a statistically significant effect on IDT reactivity or serology results. It therefore appears that, no withdrawal is recommended to evaluate immediate phase reactions.     

Prognostic impact of neoadjuvant aglepristone treatment in clinicopathological parameters of progesterone receptor‐positive canine mammary carcinomas

Neoadjuvant treatment of canine mammary carcinomas with the progesterone receptor (PR) antagonist aglepristone has a PR expression‐related inhibiting effect on proliferation index (PI). The aim of this study was to evaluate the effect of the treatment in the disease‐free period (DFP) and overall survival (OS) of canine mammary carcinomas. Fifty female dogs with mammary carcinomas were treated with aglepristone (n = 34) or oil vehicle (n = 16) before surgery (day 15). PR expression and PI were analysed by immunohistochemistry in samples taken at days 1 and 15. Epidemiological and clinicopathological data were assessed. DFP and OS data were retrieved every 4–6 months for at least 24 months after surgery. Aglepristone treatment increased DFP of animals bearing PR+ tumours with size smaller than 3 cm, complex and mixed tumours, with histologic grades I and II, and with PI ≤ 10%. Although further studies are necessary, current evidence points to treatment with aglepristone as useful for the management of canine mammary tumours.     

The glucocorticoid sparing efficacy of PhytopicaTM in the management of canine atopic dermatitis

This double-blind randomized placebo-controlled trial indicates that Phytopica™ can be an effective glucocorticoid sparing agent in canine atopic dermatitis (AD). Twenty-two dogs with perennial AD [Canine Atopic Dermatitis with Severity Index (CADESI-03) ≥ 60] were given 200 mg/kg Phytopica™ or an identical placebo in food once daily for 56 days. All dogs were initially given 0.4 mg/kg methyl-prednisolone once daily, which was then adjusted according to the daily pruritus score (0–100 mm visual analogue scale). The cumulative dose and pruritus score were lower in the Phytopica™ than the placebo group. There were statistically significant time and treatment effects for the methyl-prednisolone dose and pruritus score, but there were no significant differences between the Phytopica™ and placebo groups in the proportion of dogs that achieved a > 50% reduction in dose or pruritus scores at day 56; the mean CADESI-03 scores at days 0, 28 and 56; the numbers achieving >50% reduction in CADESI-03 at days 28 and 56; or in the owners' global efficacy score at days 28 and 56. Adverse events included diarrhoea (three Phytopica™ and one placebo treated dog), polyuria/polydipsia (three dogs in each group), and polyphagia, intermittent anorexia and panting (one dog each in the placebo group). None of these by themselves required withdrawal of treatment.     

Zinc–carnosine and vitamin E supplementation does not ameliorate gastrointestinal side effects associated with ciclosporin therapy of canine atopic dermatitis

Chelated zinc–carnosine and vitamin E [GastriCalm^® (GCM); Teva Animal Health] is marketed as an anti‐emetic supplement for dogs to assist the repair of damaged stomach and intestinal mucosa. The purpose of this prospective, double‐blinded, placebo‐controlled trial was to determine whether GCM reduced the frequency of vomiting, diarrhoea and appetite changes during initiation of ciclosporin (Atopica^®; Novartis Animal Health) therapy for the treatment of canine atopic dermatitis. Sixty privately owned dogs diagnosed with atopic dermatitis were randomly assigned to GCM (n = 30) or placebo (n = 30) groups. All dogs received ～5 mg/kg ciclosporin (range, 3.5–5.8 mg/kg) once daily. Dogs <13.6 kg received half a tablet of GCM or placebo; dogs ≥13.6 kg received one tablet once daily. GastriCalm^® or placebo was administered 30 min prior to eating, and the ciclosporin was administered 2 h after feeding. Owners recorded episodes of vomiting, diarrhoea and appetite changes. Dogs were examined on days 0 and 14. Forty‐one of 60 dogs (68.3%) had at least one episode of vomiting, diarrhoea or appetite change, leaving nine placebo dogs (30%) and ten GCM dogs (33.3%) free of adverse events (AE). Twenty‐seven of 60 dogs (45%) vomited, and 15 of 60 (25%) had diarrhoea. There was no significant difference in episodes of individual AEs, but the placebo group had a significantly lower total AE score (summation of episodes of appetite change, vomiting and diarrhoea; P = 0.022). Small dogs (<6.82 kg) had significantly fewer total AEs in both treatment groups and tolerated ciclosporin better than larger dogs (P < 0.05).     

Positive association between a glutathione‐S‐transferase polymorphism and lymphoma in dogs

Glutathione‐S‐transferase enzymes (GSTs) play an important role in the detoxification of environmental carcinogens. Defective GST genotypes are over‐represented in human cancers; in particular, low activity GSTT1 genotypes are risk factors for non‐Hodgkin lymphoma. We hypothesized that defective GSTT1 genotypes would be associated with lymphoma risk in dogs. To address this, we resequenced the exons, splice junctions, and 3′‐UTR of canine GSTT1 in dogs with lymphoma (n = 93) and age‐matched unaffected dogs (n = 86). Of 27 canine GSTT1 variants identified, the I2+28 G>A was significantly associated with lymphoma [odds ratio (OR) 6.26, 95% confidence interval (CI), 1.77–22.2], with the AA genotype found in 18.3% of affected dogs but only 3.5% of controls (P = 0.002). This intronic variant was predicted to perturb GSTT1 mRNA splicing, and may increase lymphoma risk by impairing detoxification of environmental chemicals. Confirmation of this finding in a larger population of dogs may support the inclusion of GSTT1 genotyping in epidemiologic studies of canine lymphoma risk.     

Alterations in lycopene concentration and Z‐isomer content in egg yolk of hens fed all‐E‐isomer‐rich and Z‐isomer‐rich lycopene

Effects of feeding lycopene isomers to laying hens on egg qualities such as lycopene concentration and color of the yolk were investigated. Firstly, to evaluate the dietary transfer of lycopene to egg yolk, (all‐E)‐lycopene–rich diets (lycopene content, 100, 200, or 300 mg/kg diet) were fed to hens for 21 days. Lycopene in egg yolk could be detected after 4 days or more from the start of feeding, and the lycopene concentration increased according to the feed amount and period. Even though most of the dietary lycopene was the all‐E‐isomer, more than 65% of lycopene in egg yolk was present as Z‐isomers. Thus, the effect of lycopene Z‐isomer content in the diet (lycopene content, 200 mg/kg diet; lycopene Z‐isomer content, 35.1% or 61.3%) on egg qualities was investigated. As the Z‐isomer content increased, the lycopene concentration in the egg yolk increased, for example, when fed a diet rich in Z‐isomers (61.3%), the lycopene concentration in the egg yolk was approximately three times higher than when fed the (all‐E)‐lycopene–rich diet for 21 days. The results indicated that Z‐isomers of lycopene had higher bioavailability and/or higher transfer efficiency to the egg yolk than the all‐E‐isomer.     

Comparison of once-daily versus twice-weekly terbinafine administration for the treatment of canine Malassezia dermatitis - a pilot study

Background – Terbinafine, an allylamine antifungal, is used in pulsatile dose regimens for superficial mycoses in human medicine. Objectives – To compare the clinical efficacy of twice‐weekly versus once‐daily terbinafine administration to determine whether preliminary proof‐of‐concept evidence exists for pulsatile administration of terbinafine in the treatment of canine Malassezia dermatitis and to determine whether twice‐weekly treatment results in fewer clinical and owner‐perceived adverse events. Animals – Twenty client‐owned dogs with Malassezia dermatitis. Methods – In this randomized, single‐blinded clinical trial, dogs were randomly assigned to receive terbinafine (30 mg/kg) either once daily for 21 days (n = 10) or once daily on two consecutive days per week for six doses (n = 10). On day 0 and day 21, a mean yeast count was calculated from eight anatomical locations via adhesive tape‐strip cytology, clinical lesion scores were assigned to the same locations, and owners assessed pruritus using a visual analog scale. Results – There was no significant difference between treatment groups with respect to the reduction in mean yeast count (P = 0.343) and clinical lesion scores (P = 0.887). Pruritus measured by visual analog scale was significantly decreased in the twice‐weekly treatment group compared with the daily treatment group (P = 0.047). Seven of 20 dogs had a clinically measurable or owner‐reported adverse event during treatment that included gastrointestinal disturbances, excessive panting and elevated hepatic enzymes, with no significant difference noted between treatment groups. Conclusions and clinical importance – This pilot study indicates that twice‐weekly terbinafine administration may be an effective alternative treatment for canine Malassezia dermatitis and merits further investigation.     

COX‐2, mPGES‐1 and EP2 receptor immunohistochemical expression in canine and feline malignant mammary tumours

Prostaglandin (PG) signalling is involved in human and animal cancer development. PG E₂ (PGE₂) tumour‐promoting activity has been confirmed and its production is controlled by Cyclooxygenase‐2 (COX‐2) and microsomal PGE synthase‐1 (mPGES‐1). Evidence suggests that mPGES‐1 and COX‐2 contribute to carcinogenesis through the EP2 receptor. The aim of our study was to detect by immunohistochemistry COX‐2, mPGES‐1 and EP2 receptor expression in canine (n = 46) and feline (n = 50) mammary tumours and in mammary non‐neoplastic tissues. COX‐2 positivity was observed in 83% canine and 81% feline mammary carcinomas, mPGES‐1 in 75% canine and 66% feline mammary carcinomas and the EP2 receptor expression was observed in 89% canine and 54% feline carcinomas. The frequency of COX‐2, EP2 receptor and mPGES‐1 expression was significantly higher in carcinomas than in non‐neoplastic tissues and adenomas. COX‐2, mPGES‐1 and EP2 receptor expression was strongly associated. These findings support a role of the COX‐2/PGE2 pathway in the pathogenesis of these tumours.