Treatment of Ezetimibe lowers total and low-density lipoprotein cholesterol in hypercholesterolemic dogs with hyperadorenocorticism.

Ezetimibe is a cholesterol absorption inhibitor that blocks the intestinal absorption of both biliary and dietary cholesterol, thereby lowering primarily low density lipoprotein-cholesterol (LDL-chol) in human studies. This study aimed to investigate the effects of ezetimibe on dyslipidemia control in nine dogs with hypercholesterolemia. Changes in total cholesterol (T-chol) and each lipoprotein fractions were evaluated at 0, 2, and 4 months following initiation of ezetimibe treatment. A significant decrease in T-chol was observed, and a mean T-chol concentration below 400 mg/dL was achieved at 2 and 4 months. Furthermore, a significant decrease in LDL-chol was observed (-53.3% and -64.3% at 2 and 4 months, respectively). Taken together, treatment of ezetimibe could lower LDL-chol levels in dogs with hypercholesterolemia.

Successful treatment of feline hyperadrenocorticism with pituitary macroadenoma using radiation therapy: a case study.

A 10-year-old castrated male cat showing behavioral (irritation, prowling, and tumbling) and cutaneous abnormalities such as dermal fragility was diagnosed as hyperadrenocorticism with pituitary macroadenoma, concurrent with insulin dependent diabetes mellitus. Pituitary enlargement (18.0 mm) was observed during magnetic resonance imaging. High endogenous adrenocorticotropic hormone levels (>2,500 pg/ml) were also observed. Although trilostane treatment (5-10 mg/head, daily) was commenced, the clinical signs did not disappear. Insulin and trilostane treatment were discontinued on day 86 after first day of radiation therapy (4 Gy/12 fractions). After radiation therapy, a decreased pituitary tumor size (10.7 mm) was observed on day 301; neurological and dermatological signs exhibited remission. Radiation therapy is the treatment of choice for feline hyperadrenocorticism with pituitary macroadenoma with neurological signs.

Utility of a corticotropin-releasing hormone test to differentiate pituitary-dependent hyperadrenocorticism from cortisol-producing adrenal tumors in dogs.

BACKGROUND: Hyperadrenocorticism (HAC) is a common endocrine disorder in dogs; however, there are no reports on the use of the corticotropin-releasing hormone test (CRHT) to differentiate between pituitary-dependent hyperadrenocorticism (PDH) and cortisol-producing adrenal tumors (CPATs), both causative of HAC. OBJECTIVES: To evaluate the usefulness of CRHT as a tool to differentiate between PDH and CPAT in dogs and to determine the reference intervals for CRHT in healthy, PDH, and CPAT dogs. ANIMALS: Dogs diagnosed with PDH (n = 21), CPAT (n = 6), and healthy beagle dogs (n = 33). METHODS: This prospective study included dogs with a definitive diagnosis of PDH and CPAT and healthy beagle dogs, in which CRHT was performed, were prospectively evaluated. We investigated the correlations of CRHT (endogenous adrenocorticotropic hormone [ACTH] concentration, endogenous ACTH concentration [EAC], and poststimulation ACTH concentration [PAC]) with pituitary-to-brain ratio (PBR) (in PDH) and with indices of adrenal ultrasonography (smaller and larger adrenal gland dorsoventral thickness in PDH and CPAT). RESULTS: For EAC, the area under the curve (AUC) was 0.95, with a cutoff value of 26.3 pg/mL (sensitivity: 90.62%, specificity: 87.50%). The AUC for PAC was 0.96 with a cutoff value of 54.5 pg/mL (sensitivity: 100.00%, specificity: 66.67%). The 95% reference interval for CRHT in healthy (control) dogs ranged 5.00 to 79.8 pg/mL (1.10-17.57 pmol/L) for EAC, and 1.92 to 153.42 pg/mL (0.42-33.78 pmol/L) for PAC. There was no significant correlation between PBR and CRHT, nor adrenal size and CRHT. CONCLUSIONS AND CLINICAL IMPORTANCE: CRHT appears to be a rapid and reliable test for differentiating PDH from CPAT in dogs.

Relationship between anti-insulin antibody production and severe insulin resistance in a diabetic cat.

A 5-year-old castrated male domestic shorthair cat was diagnosed with diabetic ketoacidosis and severe insulin resistance. Although the conventional treatment for diabetic ketoacidosis was provided, the cat required frequent hospitalization because of severe dehydration and repeated diabetic ketoacidosis. We detected anti-insulin antibodies for human in this cat. Serum insulin-binding IgG levels were markedly elevated compared with those in healthy cats and other diabetic cats. We initiated prednisolone to suppress the effects of anti-insulin antibodies. After initiation of prednisolone, the cat was gradually recovered with increasing activity and appetite. Furthermore, satisfactory glycemic control was achieved with combined subcutaneous injection of insulin detemir and insulin degludec.

Relationship between anti-insulin antibody production and severe insulin resistance in a diabetic cat.

A 5-year-old castrated male domestic shorthair cat was diagnosed with diabetic ketoacidosis and severe insulin resistance. Although the conventional treatment for diabetic ketoacidosis was provided, the cat required frequent hospitalization because of severe dehydration and repeated diabetic ketoacidosis. We detected anti-insulin antibodies for human in this cat. Serum insulin-binding IgG levels were markedly elevated compared with those in healthy cats and other diabetic cats. We initiated prednisolone to suppress the effects of anti-insulin antibodies. After initiation of prednisolone, the cat was gradually recovered with increasing activity and appetite. Furthermore, satisfactory glycemic control was achieved with combined subcutaneous injection of insulin detemir and insulin degludec.

Comparison of cholesterol levels among lipoprotein fractions separated by anion-exchange high-performance liquid chromatography in periparturient Holstein-Friesian dairy cows.

Changes in lipoprotein profiles occur in dairy cows during the periparturient period and in cows with transition cow disease. Here, the lipoprotein profiles of Holstein-Friesian dairy cows during the periparturient period were obtained by anion-exchange, high-performance liquid chromatography to evaluate the usefulness of lipoprotein profile evaluation during the periparturient period and in cows with fatty liver and milk fever. Lipoprotein levels (including total and high- (HDL-C) and low-density lipoprotein (LDL-C) cholesterol) in 10 healthy cows were low 4 weeks prepartum, with the lowest values at calving or within 1 week of calving; the values increased at 8 weeks postpartum. The lipoprotein levels were measured in 16 cows diagnosed with fatty liver (n=10) or milk fever (n=6) and compared to 10 healthy dairy cows. A significant difference was observed in HDL-C between healthy cows (at calving and 1 week postpartum), and the fatty liver and milk fever cows. Cows with fatty liver and milk fever had a lower mean HDL-C than the 10 healthy dairy cows at calving and 1 week postpartum. HDL-C might be a good indicator of energy balance for differentiating healthy cows from those with transition cow disease.

The effect of Insulin Degludec on glycemic control in diabetic cats over a 12-month period.

Insulin degludec (IDeg) is a long-acting basal insulin recently developed for use in humans. This study aimed to investigate the effects of IDeg on glycemic control in diabetic cats. Changes in body weight, IDeg dosage, and glycated albumin (GA) were evaluated at 0, 1, 3, 6, 9, and 12 months following initiation of IDeg. A significant decrease in GA was observed and a mean GA level below 25% was achieved between 3 and 12 months. Furthermore, a significant increase in body weight was observed between 3 and 12 months. The mean IDeg dose was 0.75 ± 0.68 IU/kg/day at 12 months. Taken together, long-term glycemic control was successfully achieved in diabetic cats using IDeg.

Comparison of the effects of four commercially available prescription diet regimens on the fecal microbiome in healthy dogs.

The effects of prescription diets on canine intestinal microbiota are unknown. In this study, we used next generation sequencing to investigate the impact of four commercially available prescription diet regimens on the fecal microbiome in six healthy dogs. The diet regimens used were as follows: weight-loss diet, low-fat diet, renal diet, and anallergenic diet. We found a significantly decreased proportion of phylum Actinobacteria with the weight-loss diet compared to the anallergenic diet. There were no significant differences in the proportion of phylum Bacteroidetes between the four diets. The proportion of phylum Firmicutes was significantly decreased with the weight-loss diet compared to the anallergenic diet. The proportion of phylum Fusobacteria was significantly increased with the weight-loss diet compared to the anallergenic diet. There were no significant differences in the proportion of phylum Proteobacteria after consumption of the four diets. We therefore demonstrated that commercial prescription diet influences the fecal microbiome in healthy dogs. These results might be useful when choosing a prescription diet for targeting a disease.

Long-term management and postmortem examination in a diabetic cat with acromegaly treated with two courses of radiation therapy.

A 12-year-old, castrated male cat with diabetes mellitus was diagnosed with acromegaly and examined with magnetic resonance imaging (enlarged pituitary gland, 8 mm); serum hormone concentrations were measured. After the first course of radiation therapy (4 Gy, 12 fractions), insulin administration was not required from day 420 after diagnosis. Enlarged pituitary tumor (8 mm) recurred, and insulin dosage amount of the cat was increased on day 1,065. The second course of radiation therapy (6 Gy, 4 fractions) was performed on day 1,201 and insulin administration was again discontinued. However, the cat died from lymphoma on day 1,397. Postmortem examination revealed pituitary adenoma. Most tumor cells were positive for chromogranin A, synaptophysin, and growth hormone immunohistochemistry. The pancreatic islet cells revealed diffuse hyperplasia. We achieved long-term successful management of an acromegalic cat with two courses of RT. However, a protocol for a second course of RT for feline recurrent pituitary tumor should be further discussed.

Time-action profiles of insulin degludec in healthy dogs and its effects on glycemic control in diabetic dogs.

Insulin degludec (IDeg) is a new insulin formulation that facilitates long-term control of glucose level in humans. In this study, we investigated the effects of IDeg on glycemic control in dogs. Its time-action profiles were monitored in healthy dogs using an artificial pancreas apparatus under euglycemic conditions. At 9.0-13.5 hr post-IDeg injection, an indistinct peak of glucose level was detected. Moreover, the action of IDeg was persistent for >20 hr. Both IDeg and neutral protamine Hagedorn insulin (NPH) lowered blood glucose concentrations in diabetic dogs, but IDeg caused postprandial hyperglycemia and a somewhat lower preprandial glucose level than that caused by NPH. IDeg might be ineffective in concurrently preventing postprandial hyperglycemia and preprandial hypoglycemia in a single-agent administration.

Successful treatment of refractory demodicosis and transient papules with a single dose of fluralaner in a dog with uncontrolled severe endocrine disease.

A 12-year-old female Shih-Tzu with hyperadrenocorticism and hypothyroidism developed concurrent refractory generalized demodicosis that did not respond to doramectin treatment. Although amitraz treatment was effective, the dog developed severe diabetes, which resulted in the cessation of amitraz and trilostane. Attempts to control the diabetes were unsuccessful, and its hyperadrenocorticism was left untreated, leading to the recurrence of demodicosis. However, demodicosis went into complete remission with a single dose of fluralaner. Transient erythematous papules appeared on the trunk three days after the administration of fluralaner, but no other adverse reactions were noted. We demonstrated that fluralaner is a potent treatment for demodicosis, and skin eruptions are possible after the first dose of the drug.

Pituitary size alteration and adverse effects of radiation therapy performed in 9 dogs with pituitary-dependent hypercortisolism.

The purpose of this study was to determine the therapeutic and/or adverse effects of radiation therapy (RT) against pituitary tumors in dogs with pituitary-dependent hypercortisolism, as monitored by frequent post-RT detailed MRI examinations, clinical signs, and changes in hormone concentrations. Nine dogs with an adrenocorticotropic hormone (ACTH)-secreting pituitary mass diagnosed by magnetic resonance imaging (MRI) underwent RT for 4weeks (total of 48Gy in 4-Gy fractions). Pituitary height/brain area (P/B) value, clinical signs, basal plasma ACTH concentrations, serum cortisol concentrations (pre- and post-ACTH stimulation test) and adverse effects of RT were evaluated before and post-RT. The P/B value was significantly lower in all nine dogs post-RT. One dog lacking any neurological signs demonstrated no change in clinical signs pre and post-RT. Out of 8 dogs which exhibited neurological signs pre-RT, half of them demonstrated complete resolution of their signs, whereas the other half showed transient resolution. In all animals with recurrence of neurological signs, pituitary tumor regrowth was not observed; however, MRI revealed moderate to severe pituitary hemorrhage. Late adverse effect (bilateral otitis media) was observed in three of nine dogs post-RT. RT did not induce any significant changes in the dogs' basal plasma ACTH concentration and pre- and post-ACTH serum cortisol concentrations. In conclusion, RT is effective to reduce pituitary size and the mass effect, but does not appear to affect blood hormone concentrations, necessitating additional medical treatment against hypercortisolism. Periodic MRI imaging post-RT enables early detection of adverse effects of RT.

Application of three hygrometers under different skin conditions in dogs: dry, moist and haired skin.

BACKGROUND: Hydration is one parameter of skin barrier function. The Skicon-200EX® and Corneometer CM825® are hygrometers used to measure skin hydration in humans based on different measurement methods. The ASA-MX3® is a hygrometer used to obtain measurements at haired skin sites in humans. HYPOTHESIS/OBJECTIVES: To validate three hygrometers to measure skin dryness in dogs. ANIMALS: Six clinically normal research dogs. METHODS: In vivo evaluation of three hygrometers for three different skin types was performed. Measurement of hydration was performed at five different regional sites. Dry and moist skin were induced by treatment with a sorbent and petrolatum, respectively, and measurements were collected for 120 min. Skin sites with three different hair lengths were evaluated to determine whether hair would interfere with hydration measurements. RESULTS: All three hygrometers obtained measurements at the nonhaired skin sites, except the ASA-MX3® hygrometer at the ear site. At the dry skin sites the Skicon-200EX® hygrometer detected a significant decrease of water content for longer than the other devices. At the moist skin sites the Corneometer CM825® and ASA-MX3® hygrometers showed a significant increase in water content. The ASA-MX3® hygrometer was the only device that could obtain measurements at sites with hair. CONCLUSIONS AND CLINICAL IMPORTANCE: The Skicon-200EX® hygrometer was the most sensitive for detecting skin dryness, whereas the Corneometer CM825® and ASA-MX3® hygrometers detected an emollient effect. Only the ASA-MX3® could provide measurements at the haired sites. This study may assist in the selection of a hygrometer based on the purpose of use.

Evaluation of newly developed veterinary portable blood glucose meter with hematocrit correction in dogs and cats.

This study evaluated the accuracy of a newly developed veterinary portable blood glucose meter (PBGM) with hematocrit correction in dogs and cats. Sixty-one dogs and 31 cats were used for the current study. Blood samples were obtained from each dog and cat one to six times. Acceptable results were obtained in error grid analysis between PBGM and reference method values (glucose oxidation methods) in both dogs and cats. Bland-Altman plot analysis revealed a mean difference between the PBGM value and reference method value of -1.975 mg/dl (bias) in dogs and 1.339 mg/dl (bias) in cats. Hematocrit values did not affect the results of the veterinary PBGM. Therefore, this veterinary PBGM is clinically useful in dogs and cats.

Contribution of oral triamcinolone to treating proliferative and necrotising otitis externa in a 14-year-old Persian cat.

CASE SUMMARY: A 14-year-old female spayed cat was referred for recurrent otitis externa and unusual proliferative lesions in both ear canals. The affected pinnae and external ear canals were covered with large reddish-to-dark-brown verrucous and necrotic tissue. Friable material and exudates occluded both ear canals. Proliferative lesions developed in both ears 2-3 weeks before referral. The histopathological diagnosis from two biopsies obtained from the friable materials with endoscopic biopsy forceps was proliferative and necrotising otitis externa (PNOE). Treatment was initiated with once-daily application of a potent topical glucocorticoid (mometasone furoate) to both ears. Although the auricle and vertical ear canals responded well, no improvement was seen in the horizontal part of the ear canal after 9 weeks. Therefore, oral triamcinolone (0.9 mg/kg q24h) was added for 1 week, and was then tapered (q48h) for 3 weeks. Most lesions resolved, and after a further 2 weeks of prednisolone (2 mg/kg q48h) there was complete resolution. No recurrence was observed during a 2 year follow-up period. RELEVANCE AND NOVEL INFORMATION: PNOE commonly occurs in kittens, but it can develop in older cats. To our knowledge, the PNOE in this case is the oldest age of onset reported. This condition is rare and was only described recently, and therapeutic options appear limited. According to previously published reports, steroid therapy is ineffective, and tacrolimus is the only treatment known to achieve resolution. However, oral and topical glucocorticoids were beneficial in this case.

Cholesterol concentrations in lipoprotein fractions separated by anion-exchange-high-performance liquid chromatography in healthy dogs and dogs with hypercholesterolemia.

Anion-exchange (AEX)-high-performance liquid chromatography (HPLC) for measurement of cholesterol can be used to separate serum lipoproteins (high-density lipoprotein (HDL); low-density lipoprotein (LDL); intermediate-density lipoprotein (IDL); very-low-density lipoprotein (VLDL)) in humans. However, AEX-HPLC has not been applied in veterinary practice. We had three objectives: (i) the validation of AEX-HPLC methods including the correlation of serum cholesterol concentration in lipoprotein fraction measured by AEX-HPLC and gel permeation-HPLC (GP-HPLC) in healthy dogs and those with hypercholesterolemia was investigated; (ii) the reference intervals of lipoprotein fractions measured by AEX-HPLC from healthy dogs (n=40) was established; (iii) lipoprotein fractions from the serum of healthy dogs (n=12) and dogs with hypercholesterolemia (n=23) were compared. Analytic reproducibility and precision of AEX-HPLC were acceptable. Positive correlation between serum concentrations of total cholesterol (Total-Chol), HDL cholesterol (HDL-Chol), LDL cholesterol (LDL-Chol)+IDL cholesterol (IDL-Chol), and VLDL cholesterol (VLDL-Chol) was noted for AEX-HPLC and GP-HPLC in healthy dogs and dogs with hypercholesterolemia. Reference intervals measured by AEX-HPLC for serum concentrations of Total-Chol, HDL-Chol, and LDL-Chol were determined to be 2.97-9.32, 2.79-6.57, 0.16-3.28mmol/L (2.5-97.5% interval), respectively. Furthermore, there was significant difference in lipoprotein profiles between healthy and dogs with hypercholesterolemia. These results suggest that AEX-HPLC can be used to evaluate lipoprotein profiles in dogs and could be a new useful indicator of hyperlipidemia in dogs.

The effect of a herbal paste and oil extract on the lipid content of canine hair fibres.

BACKGROUND: Application of herbal paste and oil to a dog's coat and body before rinsing (often combining with shampooing) is a cosmetic therapy available in Japan. It is highly appreciated by users, who claim that the treatment makes the coat shinier, improves volume and eliminates tangles. However, there has been no scientific evaluation of such treatments. HYPOTHESIS/OBJECTIVES: Improvement of hair condition is derived from oils such as sebum and conditioning oils because chemicals are not used. Therefore, we examined nonpolar lipids (the primary lipids in dog hair) and the botanical oils used in this therapy. ANIMALS: Hair samples were obtained from six beagle dogs. METHODS: Groups were based on different combinations of the following processes: rinsing, shampooing, herbal therapy and herbal therapy with oil extract. Analysis of lipids was performed by high performance thin layer chromatography. RESULTS: The processes of shampooing and herbal therapy were associated with an equivalent reduction in cholesterol ester and triglyceride (TG). However, hair treated by herbal therapy combined with oil extract had an almost three-fold higher TG content, even after shampooing. CONCLUSIONS AND CLINICAL IMPORTANCE: This study demonstrated that the herbal therapy was able to coat hair samples with TG that was not removed with rinsing. Further investigation is required to evaluate the possible benefits of the application of botanical products containing lipids, such as TG, on hair coat quality in dogs.

Proliferative and necrotizing otitis externa in a kitten: successful treatment with intralesional and topical corticosteroid therapy.

Proliferative and necrotising otitis externa (PNOE) is a very rare disease affecting the ear canals and concave pinnae of kittens. This report describes a 5-month-old cat with PNOE. Histopathological examination confirmed the diagnosis. Treatment was initiated with local injection of methylprednisolone acetate into the lesions. The cat was subsequently treated with clobetasol propionate cream, a potent topical glucocorticoid ointment. The cat showed marked improvement. While topical treatment with tacrolimus, an immunosuppressive agent, is reported to be an effective therapy, to the best of our knowledge, this is the first report to treat PNOE with local corticosteroid therapy.

Molecular Characterization of the Cytidine Monophosphate-N-Acetylneuraminic Acid Hydroxylase (CMAH) Gene Associated with the Feline AB Blood Group System.

Cat's AB blood group system (blood types A, B, and AB) is of major importance in feline transfusion medicine. Type A and type B antigens are Neu5Gc and Neu5Ac, respectively, and the enzyme CMAH participating in the synthesis of Neu5Gc from Neu5Ac is associated with this cat blood group system. Rare type AB erythrocytes express both Neu5Gc and Neu5Ac. Cat serum contains naturally occurring antibodies against antigens occurring in the other blood types. To understand the molecular genetic basis of this blood group system, we investigated the distribution of AB blood group antigens, CMAH gene structure, mutation, diplotypes, and haplotypes of the cat CMAH genes. Blood-typing revealed that 734 of the cats analyzed type A (95.1%), 38 cats were type B (4.9%), and none were type AB. A family of three Ragdoll cats including two type AB cats and one type A was also used in this study. CMAH sequence analyses showed that the CMAH protein was generated from two mRNA isoforms differing in exon 1. Analyses of the nucleotide sequences of the 16 exons including the coding region of CMAH examined in the 34 type B cats and in the family of type AB cats carried the CMAH variants, and revealed multiple novel diplotypes comprising several polymorphisms. Haplotype inference, which was focused on non-synonymous SNPs revealed that eight haplotypes carried one to four mutations in CMAH, and all cats with type B (n = 34) and AB (n = 2) blood carried two alleles derived from the mutated CMAH gene. These results suggested that double haploids selected from multiple recessive alleles in the cat CMAH loci were highly associated with the expression of the Neu5Ac on erythrocyte membrane in types B and AB of the feline AB blood group system.

Measurement of transepidermal water loss (TEWL) in cats with experimental skin barrier dysfunction using a closed chamber system.

BACKGROUND: A closed chamber evaporimeter is suitable for measuring transepidermal water loss (TEWL) in cats because of the compact device size, tolerance to sudden movement and short measuring time. TEWL is a representative parameter for skin barrier dysfunction, which is one of the clinical signs of atopic dermatitis in humans and dogs. Measurement of feline TEWL has been reported, but applicability of this parameter has not been validated. HYPOTHESIS/OBJECTIVES: The aims of this study were to determine if tape stripping is a valid experimental model in cats for studying TEWL and to determine if a closed chambered system is a suitable measurement tool for cats. ANIMALS: Ten clinically normal cats. METHODS: In order to evaluate variation of the measured values, TEWL was measured at the right and left side of the three clipped regions (axillae, lateral thigh and groin). Subsequently, TEWL was measured using sequential tape stripping of the stratum corneum as a model of acute barrier disruption. RESULTS: The variations between both sides of the three regions showed no significant difference. Sequential tape stripping was associated with increasing values for TEWL. CONCLUSIONS AND CLINICAL IMPORTANCE: Feline TEWL was shown to reflect changes in the skin barrier in an experimental model using a closed chamber system and has the potential for evaluating skin barrier function in cats with skin diseases.