Diagnosis and Long-term Treatment of Suspected Congenital Hypothyroidism in a Pigeon (Columba livia domestica).

An approximately 6-month-old domestic pigeon (Columba livia domestica) was presented for lethargy and an inability to perform its first molt. The pigeon was obese, had anatomical characteristics of a chick, including cere and plumage, and had a ventral coelomic soft tissue mass. Initial blood work was unremarkable. A computed tomographic scan confirmed excessive fat deposition in the coelom and a mass adherent to the liver. A fine-needle aspirate of the mass indicated fat accumulation. A thyroid-stimulating hormone (TSH) test was planned for this pigeon and 3 presumed euthyroid pigeons. Each pigeon was administered 80 µg (∼230 µg/kg) of recombinant human TSH. Blood was drawn at time 0 and 3 and 6 hours after administration of recombinant human TSH. Plasma total thyroxine (TT4) was measured in duplicate with an in-house analyzer and a reference laboratory. After recombinant human TSH administration, healthy pigeons showed a 4- to 21-fold increase in TT4, whereas the hypothyroid pigeon had all values <0.12 µg/dL. The pigeon was prescribed 20 µg of compounded levothyroxine twice daily. In the following months, the pigeon molted and developed adult features. The ventral coelomic soft tissue mass disappeared and repeated computed tomography scans showed a decreased amount of body fat and a reduction in the size of the coelomic mass. Levothyroxine was further adjusted multiple times according to additional TT4 testing to a dose of 2.5 µg once daily. The pigeon has been under treatment with levothyroxine for more than 2 years. Here we present the first reported case of confirmed hypothyroidism in a pigeon. Diagnosis with a TSH stimulation test was unequivocal, even when only considering the results of the in-house analyzer. Levothyroxine treatment resolved clinical signs and could be titrated to an appropriate dose.

A porcine model of phenylketonuria generated by CRISPR/Cas9 genome editing.

Phenylalanine hydroxylase-deficient (PAH-deficient) phenylketonuria (PKU) results in systemic hyperphenylalaninemia, leading to neurotoxicity with severe developmental disabilities. Dietary phenylalanine (Phe) restriction prevents the most deleterious effects of hyperphenylalaninemia, but adherence to diet is poor in adult and adolescent patients, resulting in characteristic neurobehavioral phenotypes. Thus, an urgent need exists for new treatments. Additionally, rodent models of PKU do not adequately reflect neurocognitive phenotypes, and thus there is a need for improved animal models. To this end, we have developed PAH-null pigs. After selection of optimal CRISPR/Cas9 genome-editing reagents by using an in vitro cell model, zygote injection of 2 sgRNAs and Cas9 mRNA demonstrated deletions in preimplantation embryos, with embryo transfer to a surrogate leading to 2 founder animals. One pig was heterozygous for a PAH exon 6 deletion allele, while the other was compound heterozygous for deletions of exon 6 and of exons 6-7. The affected pig exhibited hyperphenylalaninemia (2000-5000 µM) that was treatable by dietary Phe restriction, consistent with classical PKU, along with juvenile growth retardation, hypopigmentation, ventriculomegaly, and decreased brain gray matter volume. In conclusion, we have established a large-animal preclinical model of PKU to investigate pathophysiology and to assess new therapeutic interventions.

Resurrecting FUS: Adrenal Androgens as an Ultimate Cause of Hematuria, Periuria, Pollakuria, Stranguria, Urolithiasis and Obstruction in Neutered Cats.

Although many authors have doubted that "feline urological syndrome" (FUS) describes a real pathogenetic entity, because it subsumes such a large variety of signs, Sumner's recent finding that urethral obstruction occurs most frequently in springtime adds to a large body of evidence that lower urinary tract problems occur most commonly in late winter and spring. This suggests that FUS may be a unitary disorder, with a hormonal basis, driven by increasing day length. We argue that rising adrenal androgens (AA) in neutered cats induce stress, and other more concrete manifestations of FUS through androgen-driven mechanisms.

Use of a GnRH vaccine, GonaCon, for prevention and treatment of adrenocortical disease (ACD) in domestic ferrets.

Adrenocortical disease (ACD) is a common problem in surgically sterilized, middle-aged to old ferrets (Mustela putorius furo). The adrenal tissues of these ferrets develop hyperplasia, adenomas, or adenocarcinomas, which produce steroid hormones including estradiol, 17-hydroxyprogesterone, and androstenedione. Major clinical signs attributable to overproduction of these hormones are alopecia (hair loss) in both sexes and a swollen vulva in females. Pruritus, muscle atrophy, hind limb weakness, and sexual activity or aggression are also observed in both sexes. Males can develop prostatic cysts, prostatitis, and urethral obstruction. ACD is thought to be linked to continuous and increased LH secretion, due to lack of gonadal hormone feedback in neutered ferrets. This continuous elevated LH acts on adrenal cortex LH receptors, resulting in adrenal hyperplasia or adrenal tumor. This study investigated whether the immunocontraceptive vaccine GonaCon, a GnRH vaccine developed to reduce the fertility of wildlife species and the spread of disease, could prevent or delay onset of ACD and treat alopecia in ferrets with existing ACD. Results showed that GonaCon provided relief from ACD by causing production of antibodies to GnRH, probably suppressing production and/or release of LH. Treatment caused many ACD symptoms to disappear, allowing the ferrets to return to a normal life. The study also found that the probability of developing ACD was significantly reduced in ferrets treated with GonaCon when young (1-3 years old) compared to untreated control animals. GonaCon caused injection site reaction in some animals when administered as an intramuscular injection but caused few side effects when administered subcutaneously. Both intramuscular and subcutaneous vaccination resulted in similar levels of GnRH antibody titers. Subcutaneous vaccination with GonaCon is thus recommended to prevent the onset of ACD and as a possible treatment for ACD-signs in domestic ferrets.

Assessment of route of administration and dose escalation for an adenovirus-based influenza A Virus (H5N1) vaccine in chickens.

Highly pathogenic avian influenza (HPAI) virus causes one of the most economically devastating poultry diseases. An HPAI vaccine to prevent the disease in commercial and backyard birds must be effective, safe, and inexpensive. Recently, we demonstrated the efficacy of an adenovirus-based H5N1 HPAI vaccine (Ad5.HA) in chickens. To further evaluate the potential of the Ad5.HA vaccine and its cost-effectiveness, studies to determine the minimal effective dose and optimal route of administration in chickens were performed. A dose as low as 10(7) viral particles (vp) of adenovirus-based H5N1 vaccine per chicken was sufficient to generate a robust humoral immune response, which correlated with the previously reported level of protection. Several routes of administration, including intratracheal, conjunctival, subcutaneous, and in ovo routes, were evaluated for optimal vaccine administration. However, only the subcutaneous route of immunization induced a satisfactory level of influenza virus-specific antibodies. Importantly, these studies established that the vaccine-induced immunity was cross-reactive against an H5N1 strain from a different clade, emphasizing the potential of cross-protection. Our results suggest that the Ad5.HA HPAI vaccine is safe and effective, with the potential of cross-clade protection. The ease of manufacturing and cost-effectiveness make Ad5.HA an excellent avian influenza vaccine candidate with the ability to protect poultry from HPAI virus infection. Considering the limitations of the influenza vaccine technology currently used for poultry applications, any effort aimed at overcoming those limitations is highly significant.

Ferret cardiology.

Cardiac disease in pet ferrets is common and includes dilated cardiomyopathy, arrhythmias, and acquired valvular disease. Clinical presentation of cardiac disease in ferrets may be similar to dog or cats, although hind limb weakness may be a prominent feature. Radiography, ECG, and ultrasound are all useful tools in the diagnosis of cardiac disease in ferrets. Therapeutics for cardiac disease in ferrets is based on recommendations for dogs and cats. The prognosis for cardiac disease in ferrets varies from fair to guarded, depending on underlying disease.

Clinical and endocrine responses to treatment with deslorelin acetate implants in ferrets with adrenocortical disease.

OBJECTIVE: To evaluate the clinical and endocrine responses of ferrets with adrenocortical disease (ACD) to treatment with a slow-release implant of deslorelin acetate. ANIMALS: 15 ferrets with ACD. PROCEDURE: Ferrets were treated SC with a single slow-release, 3-mg implant of deslorelin acetate. Plasma estradiol, androstenedione, and 17-hydroxyprogesterone concentrations were measured before and after treatment and at relapse of clinical signs; at that time, the adrenal glands were grossly or ultrasonographically measured and affected glands that were surgically removed were examined histologically. RESULTS: Compared with findings before deslorelin treatment, vulvar swelling, pruritus, sexual behaviors, and aggression were significantly decreased or eliminated within 14 days of implantation; hair regrowth was evident 4 to 6 weeks after treatment. Within 1 month of treatment, plasma hormone concentrations significantly decreased and remained decreased until clinical relapse. Mean time to recurrence of clinical signs was 13.7 +/- 3.5 months (range, 8.5 to 20.5 months). In 5 ferrets, large palpable tumors developed within 2 months of clinical relapse; 3 of these ferrets were euthanatized because of adrenal gland tumor metastasis to the liver or tumor necrosis. CONCLUSIONS AND CLINICAL RELEVANCE: In ferrets with ACD, a slow-release deslorelin implant appears promising as a treatment to temporarily eliminate clinical signs and decrease plasma steroid hormone concentrations. Deslorelin may not decrease adrenal tumor growth in some treated ferrets. Deslorelin implants may be useful in the long-term management of hormone-induced sequelae in ferrets with ACD and in treatment of animals that are considered at surgical or anesthetic risk.

Characterization of a ribonuclease gene and encoded protein from the reptile, Iguana iguana.

In this work we identify an intronless open reading frame encoding an RNase A ribonuclease from genomic DNA from the Iguana iguana IgH2 cell line. The iguana RNase is expressed primarily in pancreas, and represents the majority of the specific enzymatic activity in this tissue. The encoded sequence shares many features with its better-known mammalian counterparts including the crucial His12, Lys40 and His114 catalytic residues and efficient hydrolytic activity against yeast tRNA substrate (k(cat)/K(m)=6 x 10(4) M(-1) s(-1)), albeit at a reduced pH optimum (pH 6.0). Although the catalytic activity of the iguana RNase is not diminished by human placental RI, iguana RNase is not bactericidal nor is it cytotoxic even at micromolar concentrations. Phylogenetic analysis indicates moderate (46%) amino acid sequence similarity to a pancreatic RNase isolated from Chelydra serpentina (snapping turtle) although no specific relationship could be determined between these RNases and the pancreatic ribonucleases characterized among mammalian species. Further analysis of ribonucleases from non-mammalian vertebrate species is needed in order to define relationships and lineages within the larger RNase A gene superfamily.

A third report of "golf ball disease" in an Amazon River dolphin (Inia geoffrensis) associated with Streptococcus iniae.

An Amazon River dolphin (Inia geoffrensis) developed a dermatologic syndrome characterized by the occurrence of slow-growing, nodular, s.c. abscesses. Initial biopsies, cultures, and cytologic analysis of needle aspirates from the abscesses indicated steatitis with probable secondary, gram-negative bacterial infection. Treatment with dietary vitamin E supplement and broad-spectrum antibiotics yielded minimal improvement. Subsequent cultures revealed Streptococcus iniae in addition to several gram-negative bacteria. Vigorous surgical management of the abscesses, including lancing, debridement, and irrigation, combined with antimicrobial therapy specific for Streptococcus and gram-negative organisms, and improvement of the animal's diet and environmental water quality led to gradual recovery. When the animal was ill, it demonstrated an inflammatory leukogram and transient uremia. Streptococcus iniae is a serious pathogen of aquacultured fishes and humans and should be included in the differential diagnosis of chronic dermatopathy in river dolphins. Specific antimicrobial therapy, excellent water quality, surgical management of abscesses, and adherence to sanitary protocols should be observed in cases of suspected S. iniae infection in dolphins.

D-galactosamine based canine acute liver failure model.

BACKGROUND: Appropriate preclinical evaluation of a bioartificial liver assist device (BAL) demands a large animal model, as presented here, that demonstrates many of the clinical features of acute liver failure and that is suitable for clinical qualitative and quantitative evaluation of the BAL. A lethal canine liver failure model of acute hepatic failure that removes many of the artifacts evidenced in prior canine models is presented. METHODS: Six male hounds, 24-30 kg, under isoflurane anesthesia, were administered 1.5 g/kg D-galactosamine intravenously. Canine supportive care followed a well-defined management protocol that was guided by electrolyte and invasive monitoring consisting of arterial pressure, central venous pressure, extradural intracranial pressure (ICP), pulmonary artery pressure, and end-tidal CO2. The animals were treated until death-equivalent, defined as inability to sustain systolic blood pressure >80 mmHg for 20 minutes despite maximal fluids and 20 microg/kg/min dopamine infusion. RESULTS: The mean survival time was 43.7+/-4.6 hours (mean+/-SE). All animals showed evidence of progressive liver failure characterized by increasing liver enzymes (aspartate transaminase from 26 to 5977 IU/L; alanine transaminase from 32 to 9740 IU/L), bilirubin (0.25 to 1.30 mg/dl), ammonia (19.8 to 85.3 micromol/L), and coagulopathy (prothrombin time from 8.7 to 46 s). Increased lability and elevations in intracranial pressures were observed. All animals were refractory to maintenance of cerebral perfusion pressure even with only moderately elevated intracranial pressure. Severe neurologic obtundation, seen in 2 of 6 animals, was associated with elevations of ICP above 50 mmHg. Post-mortem liver histology showed evidence of massive hepatic necrosis. Postmortem blood and ascites microbial growth was consistent with possible translocation of intestinal microbes. CONCLUSIONS: The improved lethal canine liver failure model presented here reproduces many of the clinical features of acute liver failure. The model may prove useful for qualitative and quantitative evaluation of BALs.