Characterisation of feline renal cortical fibroblast cultures and their transcriptional response to transforming growth factor beta 1

Chronic kidney disease (CKD) is common in geriatric cats, and the most prevalent pathology is chronic tubulointerstitial inflammation and fibrosis. The cell type predominantly responsible for the production of extra-cellular matrix in renal fibrosis is the myofibroblast, and fibroblast to myofibroblast differentiation is probably a crucial event. The cytokine TGF-β1 is reportedly the most important regulator of myofibroblastic differentiation in other species. The aim of this study was to isolate and characterise renal fibroblasts from cadaverous kidney tissue of cats with and without CKD, and to investigate the transcriptional response to TGF-β1

A Novel Unstable Duplication Upstream of HAS2 Predisposes to a Breed-Defining Skin Phenotype and a Periodic Fever Syndrome in Chinese Shar-Pei Dogs

Hereditary periodic fever syndromes are characterized by recurrent episodes of fever and inflammation with no known pathogenic or autoimmune cause. In humans, several genes have been implicated in this group of diseases, but the majority of cases remain unexplained. A similar periodic fever syndrome is relatively frequent in the Chinese Shar-Pei breed of dogs. In the western world, Shar-Pei have been strongly selected for a distinctive thick and heavily folded skin. In this study, a mutation affecting both these traits was identified. Using genome-wide SNP analysis of Shar-Pei and other breeds, the strongest signal of a breed-specific selective sweep was located on chromosome 13. The same region also harbored the strongest genome-wide association (GWA) signal for susceptibility to the periodic fever syndrome (praw = 2.3×10−6, pgenome = 0.01). Dense targeted resequencing revealed two partially overlapping duplications, 14.3 Kb and 16.1 Kb in size, unique to Shar-Pei and upstream of the Hyaluronic Acid Synthase 2 (HAS2) gene. HAS2 encodes the rate-limiting enzyme synthesizing hyaluronan (HA), a major component of the skin. HA is up-regulated and accumulates in the thickened skin of Shar-Pei. A high copy number of the 16.1 Kb duplication was associated with an increased expression of HAS2 as well as the periodic fever syndrome (p<0.0001). When fragmented, HA can act as a trigger of the innate immune system and stimulate sterile fever and inflammation. The strong selection for the skin phenotype therefore appears to enrich for a pleiotropic mutation predisposing these dogs to a periodic fever syndrome. The identification of HA as a major risk factor for this canine disease raises the potential of this glycosaminoglycan as a risk factor for human periodic fevers and as an important driver of chronic inflammation

Novel Allelic Variants in the Canine Cyclooxgenase-2 (Cox-2) Promoter Are Associated with Renal Dysplasia in Dogs

Renal dysplasia (RD) in dogs is a complex disease with a highly variable phenotype and mode of inheritance that does not follow a simple Mendelian pattern. Cox-2 (Cyclooxgenase-2) deficient mice have renal abnormalities and a pathology that has striking similarities to RD in dogs suggesting to us that mutations in the Cox-2 gene could be the cause of RD in dogs. Our data supports this hypothesis. Sequencing of the canine Cox-2 gene was done from clinically affected and normal dogs. Although no changes were detected in the Cox-2 coding region, small insertions and deletions of GC boxes just upstream of the ATG translation start site were found. These sequences are putative SP1 transcription factor binding sites that may represent important cis-acting DNA regulatory elements that govern the expression of Cox-2. A pedigree study of a family of Lhasa apsos revealed an important statistical correlation of these mutant alleles with the disease. We examined an additional 22 clinical cases from various breeds. Regardless of the breed or severity of disease, all of these had one or two copies of the Cox-2 allelic variants. We suggest that the unusual inheritance pattern of RD is due to these alleles, either by changing the pattern of expression of Cox-2 or making Cox-2 levels susceptible to influences of other genes or environmental factors that play an unknown but important role in the development of RD in dogs

Intermittent hemodialysis in dogs with chronic kidney disease stage III

ABSTRACT: Intermittent hemodialysis (IHD) is a form of renal replacement that is used in veterinary medicine for cases involving drug removal, electrolyte imbalance, acute kidney injury, and chronic kidney disease (CKD). The aim of the present study was to verify the efficacy of IHD in dogs with CKD staged at grade III and to evaluate the effect of IHD on quality of life. Twelve dogs with CKD at stage III met the inclusion criteria and were divided equally into two groups. The control group (n=6) received only clinical treatment and intravenous fluid therapy, and the hemodialysis group (n=6) received clinical and IHD treatments. Blood samples were collected before and after treatments in both groups. We evaluated complications and clinical parameters of IHD every 30 minutes. Hemodialysis decreased serum urea, creatinine, and phosphorus. Despite the evident removal of nitrogen compounds, dialysis treatment did not increase survival time in these patients. The results of this study do not support the early use of dialysis in dogs with chronic kidney disease stage III

AVALIAÇÃO DO VOLUME CORRENTE DE AR EM CÃES SUBMETIDOS A TORACOTOMIA EM BLOCO

A freqüência respiratória e o volume corrente de ar foram medidos em cães submetidos a técnica de toracotomia em bloco. Os animais foram tranqüilizados com acetilpromazina e anestesiados com tiopental sódico, acompanhado de entubação endotraqueal e utilização de mini-respirador automático à pressão positiva intermitente. Os valores do volume-minuto, freqüência respiratória e volume corrente foram registrados nos seguintes tempos: antes da indução de anestesia (T0), no final da cirurgia (T1), 24 horas (T2) e 7 dias depois do término da cirurgia (T3), respectivamente. Nos animais do grupo II, no final da cirurgia (Tempo 1) e 24 horas após (Tempo 2), foi feita anestesia local infiltrativa dos nervos intercostais junto das costelas seccionadas para comparação das prováveis alterações da mecânica respiratória e do volume corrente de ar no período pós-operatório. A técnica da toracotomia em bloco não provocou alterações da mecânica respiratória durante o período pós-operatório