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For the treatment of diabetes mellitus (DM) in dogs, novel insulins with decreased injection frequency while maintaining safety and efficacy are desirable. Insulin fused with immunoglobulin-fragment-crystallizable (Fc) has an ultra-long plasma half-life because it recycles through cells, protected from proteolysis.Glycemic control can be achieved in diabetic dogs with a recombinant fusion protein of a synthetic insulin and canine Fc (AKS-218d) administered subcutaneously once-weekly.Five client-owned dogs with naturally occurring DM.Prospective clinical trial in dogs with DM that were recruited from the UC Davis Veterinary Teaching Hospital and local veterinary clinics. Dogs previously controlled using intermediate-acting insulin q12h were transitioned to once-weekly injections of a preliminary construct identified as AKS-218d. The dose of AKS-218d was titrated weekly for 8 weeks based on clinical response and continuous interstitial glucose monitoring. Clinical signs, body weight, serum fructosamine concentrations, and mean interstitial glucose concentrations (IG) over the preceding week were compared between baseline (before AKS-218d) and during the last week of treatment. Data were compared using nonparametric paired tests.Once-weekly AKS-218d, compared to baseline twice-daily insulin therapy, resulted in no significant changes in clinical signs, median (range) body weight (+0.4 kg [-0.5-1.1]; P = .6), fructosamine concentration (-75 mmol/L [-215 to +126]; P = .4), or mean IG (+81 mg/dL [-282 to +144]; P = .8). No adverse reactions were reported.Control of clinical signs, body weight, and maintenance of glycemia was achieved with this once-weekly novel insulin construct in 4 of 5 dogs.

Objectives The aim of this study was to determine the safety and efficacy of the nucleoside analog GS-441524 for cats suffering from various forms of naturally acquired feline infectious peritonitis (FIP). Methods Cats ranged from 3.4–73 months of age (mean 13.6 months); 26 had effusive or dry-to-effusive FIP and five had non-effusive disease. Cats with severe neurological and ocular FIP were not recruited. The group was started on GS-441524 at a dosage of 2.0 mg/kg SC q24h for at least 12 weeks and increased when indicated to 4.0 mg/kg SC q24h. Results Four of the 31 cats that presented with severe disease died or were euthanized within 2–5 days and a fifth cat after 26 days. The 26 remaining cats completed the planned 12 weeks or more of treatment. Eighteen of these 26 cats remain healthy at the time of publication (OnlineFirst, February 2019) after one round of treatment, while eight others suffered disease relapses within 3–84 days. Six of the relapses were non-neurological and two neurological. Three of the eight relapsing cats were treated again at the same dosage, while five cats had the dosage increased from 2.0 to 4.0 mg/kg q24h. The five cats treated a second time at the higher dosage, including one with neurological disease, responded well and also remain healthy at the time of publication. However, one of the three cats re-treated at the original lower dosage relapsed with neurological disease and was euthanized, while the two remaining cats responded favorably but relapsed a second time. These two cats were successfully treated a third time at the higher dosage, producing 25 long-time survivors. One of the 25 successfully treated cats was subsequently euthanized due to presumably unrelated heart disease, while 24 remain healthy. Conclusions and relevance GS-441524 was shown to be a safe and effective treatment for FIP. The optimum dosage was found to be 4.0 mg/kg SC q24h for at least 12 weeks.

Feline infectious peritonitis (FIP) is caused by a mutant biotype of the feline enteric coronavirus. The resulting FIP virus (FIPV) commonly causes central nervous system (CNS) and ocular pathology in cases of noneffusive disease. Over 95% of cats with FIP will succumb to disease in days to months after diagnosis despite a variety of historically used treatments. Recently developed antiviral drugs have shown promise in treatment of nonneurological FIP, but data from neurological FIP cases are limited. Four cases of naturally occurring FIP with CNS involvement were treated with the antiviral nucleoside analogue GS‐441524 (5‐10 mg/kg) for at least 12 weeks. Cats were monitored serially with physical, neurologic, and ophthalmic examinations. One cat had serial magnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis (including feline coronavirus [FCoV]) titers and FCoV reverse transcriptase [RT]‐PCR) and serial ocular imaging using Fourier‐domain optical coherence tomography (FD‐OCT) and in vivo confocal microscopy (IVCM). All cats had a positive response to treatment. Three cats are alive off treatment (528, 516, and 354 days after treatment initiation) with normal physical and neurologic examinations. One cat was euthanized 216 days after treatment initiation following relapses after primary and secondary treatment. In 1 case, resolution of disease was defined based on normalization of MRI and CSF findings and resolution of cranial and caudal segment disease with ocular imaging. Treatment with GS‐441524 shows clinical efficacy and may result in clearance and long‐term resolution of neurological FIP. Dosages required for CNS disease may be higher than those used for nonneurological FIP.

Objectives The safety and efficacy of the 3C-like protease inhibitor GC376 was tested on a cohort of client-owned cats with various forms of feline infectious peritonitis (FIP). Methods Twenty cats from 3.3–82 months of age (mean 10.4 months) with various forms of FIP were accepted into a field trial. Fourteen cats presented with wet or dry-to-wet FIP and six cats presented with dry FIP. GC376 was administered subcutaneously every 12 h at a dose of 15 mg/kg. Cats with neurologic signs were excluded from the study. Results Nineteen of 20 cats treated with GC376 regained outward health within 2 weeks of initial treatment. However, disease signs recurred 1–7 weeks after primary treatment and relapses and new cases were ultimately treated for a minimum of 12 weeks. Relapses no longer responsive to treatment occurred in 13 of these 19 cats within 1–7 weeks of initial or repeat treatment(s). Severe neurologic disease occurred in 8/13 cats that failed treatment and five cats had recurrences of abdominal lesions. At the time of writing, seven cats were in disease remission. Five kittens aged 3.3–4.4 months with wet FIP were treated for 12 weeks and have been in disease remission after stopping treatment and at the time of writing for 5–14 months (mean 11.2 months). A sixth kitten was in remission for 10 weeks after 12 weeks of treatment, relapsed and is responding to a second round of GC376. The seventh was a 6.8-year-old cat with only mesenteric lymph node involvement that went into remission after three relapses that required progressively longer repeat treatments over a 10 month period. Side effects of treatment included transient stinging upon injection and occasional foci of subcutaneous fibrosis and hair loss. There was retarded development and abnormal eruption of permanent teeth in cats treated before 16–18 weeks of age. Conclusions and relevance GC376 showed promise in treating cats with certain presentations of FIP and has opened the door to targeted antiviral drug therapy.

Background Struvite urolithiasis with bacterial urinary tract infection (UTI) is commonly reported in dogs; few data exist to describe successful dissolution protocols in dogs with naturally occurring disease. We hypothesized that a dry therapeutic urinary diet combined with targeted antimicrobial therapy can effectively dissolve presumptive struvite cystolithiasis in dogs with naturally occurring urease-producing bacterial UTI. Results Ten dogs with presumed infection-induced struvite cystolithiasis based on lower urinary tract signs (LUTS), radiodense cystoliths, and urease-producing bacterial UTI were enrolled. At enrollment, antimicrobials and dry therapeutic urinary diet were dispensed. In addition to lack of radiographic resolution of urolithiasis, dogs with persistent clinical signs were considered non-responders. There was no significant difference in pH between responders and non-responders; USG was significantly higher in the responder group. Recheck visits continued until radiographic dissolution or failure was documented. Five of the 10 dogs achieved radiographic dissolution of cystolithiasis within a median of 31 days (range 19–103). In the other 5 dogs, surgical urolith removal was necessary due to persistent LUTS (3 dogs within 2 weeks) or lack of continued dissolution noted radiographically (1 dog with numerous cystoliths failed at day 91; 1 dog failed by day 57 with questionable owner compliance). Conclusions Dissolution of urinary tract infection induced struvite cystoliths can be accomplished in some dogs fed this dry therapeutic urinary diet in conjunction with antimicrobial therapy. Case selection could increase the likelihood of successful dissolution; however, if calcium phosphate is present, this could also prevent stone dissolution. If clinical signs persist despite diet and antimicrobials, stone removal is advised. Electronic supplementary material The online version of this article (10.1186/s12917-019-1992-8) contains supplementary material, which is available to authorized users.

Metaphyseal osteopathy (MO) (hypertrophic osteodystrophy) is a developmental disorder of unexplained etiology affecting dogs during rapid growth. Affected dogs experience relapsing episodes of lytic/sclerotic metaphyseal lesions and systemic inflammation. MO is rare in the general dog population; however, some breeds (Weimaraner, Great Dane and Irish Setter) have a much higher incidence, supporting a hereditary etiology. Autoinflammatory childhood disorders of parallel presentation such as chronic recurrent multi-focal osteomyelitis (CRMO), and deficiency of interleukin-1 receptor antagonist (DIRA), involve impaired innate immunity pathways and aberrant cytokine production. Given the similarities between these diseases, we hypothesize that MO is an autoinflammatory disease mediated by cytokines involved in innate immunity. To characterize immune dysregulation in MO dogs we measured serum levels of inflammatory markers in 26 MO and 102 control dogs. MO dogs had significantly higher levels (pg/ml) of serum Interleukin-1beta (IL-1β), IL-18, IL-6, Granulocyte-macrophage colony stimulating factor (GM-CSF), C-X-C motif chemokine 10 (CXCL10), tumor necrosis factor (TNF), and IL-10. Notably, recovered MO dogs were not different from dogs during active MO disease, providing a suggestive mechanism for disease predisposition. This is the first documentation of elevated immune markers in MO dogs, uncovering an immune profile similar to comparable autoinflammatory disorders in children.

In order to evaluate the genetic structure of purebred dogs, six Y chromosome microsatellite markers were used to analyze DNA samples from 824 unrelated dogs from 50 recognized breeds. A relatively small number of haplotypes (67) were identified in this large sample set due to extensive sharing of haplotypes between breeds and low haplotype diversity within breeds. Fifteen breeds were characterized by a single Y chromosome haplotype. Breed-specific haplotypes were identified for 26 of the 50 breeds, and haplotype sharing between some breeds indicated a common history. A molecular variance analysis (AMOVA) demonstrated significant genetic variation across breeds (63.7%) and with geographic origin of the breeds (11.5%). A network analysis of the haplotypes revealed further relationships between the breeds as well as deep rooting of many of the breed-specific haplotypes, particularly among breeds of African origin.

Upper respiratory tract infection (URI) propagates readily within cats in shelters and often results in euthanasia of affected cats. In a case-control evaluation of 573 cats in eight shelters in California in 2001 and 2002, the prevalence of feline calicivirus (FCV) was from 13 to 36%, feline herpesvirus (FHV) was from 3 to 38%, and prevalence of Bordetella bronchiseptica, Chlamydophila felis, and Mycoplasma species was from 2 to 14%. Cats with URI tended to be housed in isolation, dehydrated, and younger than cats without URI, and infected with FHV, Mycoplasma species, FCV, or C felis. Shelters differed in the prevalence of pathogens and many cats appeared positive for infection after about 1 week of sheltering. It is helpful for shelters to understand the risk factors associated with URI in order to evaluate the costs and benefits of treatment and improve their procedures to decrease the incidence of URI within their facilities. Antiherpetics and antimycoplasmal drugs may be beneficial for individual animal care. Results document the utility of comprehensive URI surveillance and herd management for specific pathogens typical in that shelter.

Objective—To investigate the correlation of cumulative rhinoscopic findings of hyperemia, mucus accumulation, and turbinate destruction with the type and severity of inflammatory infiltrates in nasal biopsy specimens of cats with or without upper respiratory tract disease. Design—Prospective study. Animals—Cats with (n = 11) and without (6) upper respiratory tract disease and cats with unknown medical histories (27). Procedures—Lesions of hyperemia, mucus accumulation, and turbinate destruction detected rhinoscopically were each scored (scale, 0 [absent] to 3 [severe]), and a cumulative rhinoscopic score for each nasal cavity was calculated. Fifty biopsy specimens were examined histologically, and inflammatory infiltrates (lymphoplasmacytic or neutrophilic) were graded as absent, mild, moderate, or severe. Cumulative rhinoscopic scores and inflammation grades were compared for each specimen-cavity combination. Results—In cats of known disease status, there was a positive but weak correlation between cumulative rhinoscopic scores and inflammation grades in biopsy specimens. In cats of unknown disease status, there was no similar correlation. Biopsy specimens with minimal inflammation were commonly obtained from nasal cavities with low rhinoscopic scores; specimens with moderate or severe inflammatory changes were frequently obtained from cavities that appeared normal rhinoscopically. Type of inflammatory infiltrates was not correlated with rhinoscopic signs of inflammation. Conclusions and Clinical Relevance—The correlation of rhinoscopic findings with inflammation severity in nasal biopsy specimens (determined histologically) was weak or lacking in cats of known and unknown disease status, respectively. Results indicated that rhinoscopy with biopsy provides more complete evaluation of nasal disease than rhinoscopy alone in cats. ( J Am Vet Med Assoc 2004;225: 395–400)