Evaluation of nephrotoxicity and ototoxicity of aminosidine (paromomycin)-allopurinol combination in dogs with leishmaniosis due to Leishmania infantum: A randomized, blinded, controlled study.

Canine leishmaniosis due to Leishmania infantum is a widespread zoonotic disease. Although aminosidine can be an effective treatment, current therapeutic recommendations do not advocate its use, mainly due to concerns regarding the potential nephrotoxicity and ototoxicity of this drug. The aim of this randomized, blinded, controlled study was to evaluate the nephrotoxicity and ototoxicity of aminosidine-allopurinol combination and compare it with that of meglumine antimonate-allopurinol combination in non-azotemic dogs with leishmaniosis. Forty dogs with leishmaniosis were randomly assigned to be treated with either aminosidine at 15 mg/kg, subcutaneously, once daily for 28 days (group A) or with meglumine antimonate at 100 mg/kg, subcutaneously, once daily for 28 days (group B). In addition to either drug, dogs in both groups were administered allopurinol at 10 mg/kg per os twice daily for 2 months. Kidney function was evaluated through measurement of serum creatinine, urea nitrogen, inorganic phosphorus, and cystatin-c concentrations and complete urinalysis, including protein-to-creatinine ratio, at baseline and after 14, 28, and 60 days from the beginning of the treatment. At the same time points, vestibular and auditory functions were evaluated through neurological examination and brainstem auditory evoked response (BAER) recordings of wave I, wave V, inter-wave I-V latencies, and minimum hearing thresholds. None of the dogs developed clinicopathological evidence of kidney disease during the study. Serum creatinine concentration increased >0.3 mg/dl over baseline in 2 dogs in group A and in 5 dogs in group B. Parameters of kidney function were not significantly different or were improved compared to baseline and the only difference between the two groups was the lower concentration of serum creatinine in group A. None of the dogs developed peripheral vestibular syndrome or hearing impairment. At the end of the study, parameters of auditory function were not significantly different or were improved compared to baseline and there were no differences between the two groups. The results of this study show that the nephrotoxicity and ototoxicity of aminosidine, when administered to non-azotemic dogs with leishmaniosis at 15 mg/kg subcutaneously once daily for 28 days along with allopurinol, is minimal and does not differ from that of meglumine antimonate.

Deafness and vestibular dysfunction in a Doberman Pinscher puppy associated with a mutation in the PTPRQ gene.

BACKGROUND: A congenital syndrome of hearing loss and vestibular dysfunction affects Doberman Pinschers. Its inheritance pattern is suspected to be autosomal recessive and it potentially represents a spontaneous animal model of an autosomal recessive syndromic hearing loss. HYPOTHESIS/OBJECTIVES: The objectives of this study were to use whole genome sequencing (WGS) to identify deleterious genetic variants in candidate genes associated with the syndrome and to study the prevalence of candidate variants among a population of unaffected Doberman Pinschers. ANIMALS: One affected Doberman Pinscher and 202 unaffected Doberman Pinschers. METHODS: WGS of the affected dog with filtering of variants against a database of 154 unaffected dogs of diverse breeds was performed. Confirmation of candidate variants was achieved by Sanger sequencing followed by genotyping of the control population of unaffected Doberman Pinschers. RESULTS: WGS and variant filtering identified an alteration in a gene associated with both deafness and vestibular disease in humans: protein tyrosine phosphatase, receptor type Q (PTPRQ). There was a homozygous A insertion at CFA15: 22 989 894, causing a frameshift mutation in exon 39 of the gene. This insertion is predicted to cause a protein truncation with a premature stop codon occurring after position 2054 of the protein sequence that causes 279 C-terminal amino acids to be eliminated. Prevalence of the variant was 1.5% in a cohort of 202 unaffected Doberman Pinschers; all unaffected Doberman Pinschers were heterozygous or heterozygous for the reference allele. CONCLUSION AND CLINICAL IMPORTANCE: We report the identification of a genetic alteration on the PTPRQ gene that is associated with congenital hearing and vestibular disorder in a young Doberman Pinscher dog.

Endogenous retrovirus insertion in the KIT oncogene determines white and white spotting in domestic cats.

The Dominant White locus (W) in the domestic cat demonstrates pleiotropic effects exhibiting complete penetrance for absence of coat pigmentation and incomplete penetrance for deafness and iris hypopigmentation. We performed linkage analysis using a pedigree segregating White to identify KIT (Chr. B1) as the feline W locus. Segregation and sequence analysis of the KIT gene in two pedigrees (P1 and P2) revealed the remarkable retrotransposition and evolution of a feline endogenous retrovirus (FERV1) as responsible for two distinct phenotypes of the W locus, Dominant White, and white spotting. A full-length (7125 bp) FERV1 element is associated with white spotting, whereas a FERV1 long terminal repeat (LTR) is associated with all Dominant White individuals. For purposes of statistical analysis, the alternatives of wild-type sequence, FERV1 element, and LTR-only define a triallelic marker. Taking into account pedigree relationships, deafness is genetically linked and associated with this marker; estimated P values for association are in the range of 0.007 to 0.10. The retrotransposition interrupts a DNAase I hypersensitive site in KIT intron 1 that is highly conserved across mammals and was previously demonstrated to regulate temporal and tissue-specific expression of KIT in murine hematopoietic and melanocytic cells. A large-population genetic survey of cats (n = 270), representing 30 cat breeds, supports our findings and demonstrates statistical significance of the FERV1 LTR and full-length element with Dominant White/blue iris (P < 0.0001) and white spotting (P < 0.0001), respectively.

Brainstem auditory evoked potential testing in Dalmatian dogs in Brazil / Potencial evocado auditivo de tronco encefálico em cães da raça Dálmata no Brasil

The brain stem auditory-evoked potential (BAEP) is an electrophysiologic test that detects and records the electrical activity in the auditory system from cochlea to midbrain, generated after an acoustic stimulus applied to the external ear. The aim of this study is to obtain normative data for BAEP in Dalmatian dogs in order to apply this to the evaluation of deafness and other neurologic disorders. BAEP were recorded from 30 Dalmatian dogs for a normative Brazilian study. Mean latencies for waves I, III, and V were 1.14 (±0.09), 2.62 (±0.10), and 3.46 (±0.14) ms, respectively. Mean inter-peak latencies for I-III, III-V, and I-V intervals were 1.48 (±0.17), 0.84 (±0.12), and 2.31 (±0.18) ms, respectively. Unilateral abnormalities were found in 16.7% of animals and bilateral deafness was seen in one dog. The normative data obtained in this paper is compatible with other published data. As far as we know this is the first report of deafness occurrence in Dalmatian dogs in Brazil...

O potencial evocado auditivo de tronco encefálico (BAEP) é um teste eletrodiagnóstico que detecta e registra a atividade elétrica do sistema auditivo desde a cóclea até o tronco encefálico, gerada após a emissão de um estímulo acústico na orelha externa. O objetivo deste estudo é obter dados normativos para o BAEP em cães da raça Dálmata para usá-lo para detecção de surdez e de outras alterações neurológicas. BAEP foi obtido de 30 cães da raça Dálmata para um estudo normativo no Brasil. As latências médias para as ondas I, III e V foram 1,14ms (±0,09); 2,62ms (±0,10) e 3,46ms (±0,14), respectivamente. A média das latências dos intervalos I-III, III-V e I-V foi 1,48ms (±0,17); 0,84ms (±0,12) e 2,31ms (±0,18), respectivamente. Alteração unilateral foi observada em 16,7% dos animais, e surdez bilateral foi observada em um cão. Os dados normativos obtidos neste trabalho são compatíveis com outros dados já publicados. Segundo a revisão realizada, este é o primeiro relato da ocorrência de surdez em cães da raça Dálmata no Brasil...

Evaluation of otoacoustic emissions in clinically normal alert puppies.

OBJECTIVE: To evaluate distortion product otoacoustic emission (DPOAE) measurements in puppies with normal hearing. ANIMALS: 23 clinically normal 7.5-to 10.5-week-old puppies. PROCEDURES: A cross-sectional study was performed. The DPOAE measurements were obtained with a commercially available distortion product otoacoustic measurement system and were performed in a quiet, non-sound-attenuated room. All measurements were obtained from alert puppies and were repeated 1 or 2 times to ensure that the measurements were replicable. Results that were a minimum of 8 dB higher than the noise floor were accepted. Values from the first trial in which emissions were obtained at all test frequencies were used for analysis. RESULTS: Otoacoustic emission measurements were easily obtained, robust, reliable, and consistent with auditory brainstem response and behavioral results. CONCLUSIONS AND CLINICAL RELEVANCE: Hearing screening in alert puppies can be accomplished reliably and rapidly with otoacoustic emissions testing. Results supported the possibility of the use of DPOAE measurement in hearing screening of dogs.