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- Author or Editor: Daniel R. Rissi x
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Abstract
OBJECTIVE To assess effects of photobiomodulation, silver sulfadiazine, and a topical antimicrobial product for the treatment of experimentally induced full-thickness skin wounds in green iguanas (Iguana iguana).
ANIMALS 16 healthy subadult green iguanas.
PROCEDURES Iguanas were anesthetized, and three 5-mm cutaneous biopsy specimens were obtained from each iguana (day 0). Iguanas were randomly assigned to 2 treatment groups, each of which had a control treatment. Wounds in the topical treatment group received silver sulfadiazine, a topical antimicrobial product, or no treatment. Wounds in the laser treatment group received treatment with a class 4 laser at 5 or 10 J/cm2 or no treatment. Wound measurements were obtained daily for 14 days. Iguanas were euthanized, and treatment sites were evaluated microscopically to detect ulceration, bacterial contamination, reepithelialization, necrosis, inflammation, fibrosis, and collagen maturity.
RESULTS On day 14, wounds treated with a laser at 10 J/cm2 were significantly smaller than those treated with silver sulfadiazine, but there were no other significant differences among treatments. Histologically, there were no significant differences in ulceration, bacterial infection, reepithelialization, necrosis, inflammation, fibrosis, and collagen maturity among treatments.
CONCLUSIONS AND CLINICAL RELEVANCE Photobiomodulation at 10 J/cm2 appeared to be a safe treatment that was tolerated well by green iguanas, but it did not result in substantial improvement in histologic evidence of wound healing, compared with results for other treatments or no treatment.
Abstract
OBJECTIVE
To identify differentially expressed microRNA in the serum and renal tissues of cats with experimentally induced chronic kidney disease (CKD).
SAMPLE
Banked renal tissues and serum from 4 cats.
PROCEDURES
Cats previously underwent 90-minute unilateral ischemia with delayed contralateral nephrectomy 3 months after ischemia. Tissues were collected from the contralateral kidney at the time of nephrectomy and from the ischemic kidney 6 months after nephrectomy (study end). Serum was collected prior to ischemia (baseline serum) and at study end (end point serum). Total RNA was isolated from tissues and serum, and microRNA sequencing was performed with differential expression analysis between the contralateral and ischemic kidney and baseline and end point serum.
RESULTS
20 microRNAs were differentially expressed between ischemic and contralateral kidneys, and 52 microRNAs were differentially expressed between end point and baseline serum. Five microRNAs were mutually differentially expressed between ischemic and contralateral kidneys and baseline and end point serum, with 4 (mir-21, mir-146, mir-199, and mir-235) having increased expression in both the ischemic kidney and end point serum and 1 (mir-382) having increased expression in the ischemic kidney and decreased expression in end point serum. Predicted target search for these microRNA revealed multiple genes previously shown to be involved in the pathogenesis of feline CKD, including hypoxia-inducible factor-1α, transforming growth factor-β, hepatocyte growth factor, fibronectin, and vascular endothelial growth factor A.
CLINICAL RELEVANCE
MicroRNAs were differentially expressed after CKD induction in this preliminary study. Regulation of renal fibrosis in feline CKD may occur through microRNA regulation of mRNAs of pro- and anti-fibrotic genes.
Abstract
OBJECTIVE
To use RNA sequencing (RNAseq) to characterize renal transcriptional activities of genes associated with proinflammatory and profibrotic pathways in ischemia-induced chronic kidney disease (CKD) in cats.
SAMPLES
Banked renal tissues from 6 cats with experimentally induced CKD (renal ischemia [RI] group) and 9 healthy cats (control group).
PROCEDURES
Transcriptome analysis with RNAseq, followed by gene ontology and cluster analyses, were performed on banked tissue samples of the right kidneys (control kidneys) from cats in the control group and of both kidneys from cats in the RI group, in which unilateral (right) RI had been induced 6 months before the cats were euthanized and the ischemic kidneys (IKs) and contralateral nonischemic kidneys (CNIKs) were harvested. Results for the IKs, CNIKs, and control kidneys were compared to identify potential differentially expressed genes and overrepresented proinflammatory and profibrotic pathways.
RESULTS
Genes from the gene ontology pathways of collagen binding (eg, transforming growth factor-β1), metalloendopeptidase activity (eg, metalloproteinase [MMP]-7, MMP-9, MMP-11, MMP-13, MMP-16, MMP-23B, and MMP-28), chemokine activity, and T-cell migration were overrepresented as upregulated in tissue samples of the IKs versus control kidneys. Genes associated with the extracellular matrix (eg, TIMP-1, fibulin-1, secreted phosphoprotein-1, matrix Gla protein, and connective tissue growth factor) were upregulated in tissue samples from both the IKs and CNIKs, compared with tissues from the control kidneys.
CONCLUSIONS AND CLINICAL RELEVANCE
Unilateral ischemic injury differentially altered gene expression in both kidneys, compared with control kidneys. Fibulin-1, secreted phosphoprotein-1, and matrix Gla protein may be candidate biomarkers of active kidney injury in cats.
Abstract
OBJECTIVE
To characterize transcription of profibrotic mediators in renal tissues of cats with ischemia-induced chronic kidney disease (CKD).
SAMPLE
Banked renal tissues from 6 cats with experimentally induced CKD (RI group) and 8 healthy control cats.
PROCEDURES
For cats of the RI group, both kidneys were harvested 6 months after ischemia was induced for 90 minutes in 1 kidney. For control cats, the right kidney was evaluated. All kidney specimens were histologically examined for fibrosis, inflammation, and tubular atrophy. Renal tissue homogenates underwent reverse transcription quantitative PCR assay evaluation to characterize gene transcription of hypoxia-inducible factor-1α (HIF-1α), matrix metalloproteinase (MMP)-2, MMP-7, MMP-9, tissue inhibitor of metalloproteinase-1 (TIMP-1), transforming growth factor-β1, and vascular endothelial growth factor A. Gene transcription and histologic lesions were compared among ischemic and contralateral kidneys of the RI group and control kidneys.
RESULTS
Ischemic kidneys had greater transcript levels of MMP-7, MMP-9, and transforming growth factor-β1 relative to control kidneys and of MMP-2 relative to contralateral kidneys. Transcription of TIMP-1 was upregulated and that of vascular endothelial growth factor A was downregulated in ischemic and contralateral kidneys relative to control kidneys. Transcription of HIF-1α did not differ among kidney groups. For ischemic kidneys, there were strong positive correlations between transcription of HIF-1α, MMP-2, MMP-7, and TIMP-1 and severity of fibrosis.
CONCLUSIONS AND CLINICAL RELEVANCE
Transcription of genes involved in profibrotic pathways remained altered in both kidneys 6 months after transient renal ischemia. This suggested that a single unilateral renal insult can have lasting effects on both kidneys.
Abstract
OBJECTIVE
To report acute and chronic outcomes of cats with chronic kidney disease (CKD) induced by a remnant kidney model.
ANIMALS
32 purpose-bred cats (n = 15 female, n = 17 male).
PROCEDURES
Cats underwent a 2-stage reduction in renal mass through partial arterial ligation of 1 kidney (day 28) and delayed contralateral nephrectomy (day 0), targeting an 11/12th functional nephrectomy. Acute (days −28 – 29) survival and renal function parameters were compared over time, and the latter were evaluated as predictors for acute mortality. Chronic (days 30 to >1,100) survival, renal function, and morphology were described.
RESULTS
Acutely, renal function deteriorated in all cats (mean ± SD baseline and day 28 serum creatinine mean concentration, 1.13 ± 0.23 mg/dL and 3.03 ± 1.20 mg/dL, respectively; P < .001; and GFR, 3.22 mL/min/kg ± 0.12 and 1.21 mL/min/kg ± 0.08, respectively; P < .001). Seven (22%) cats were euthanized after because of clinical signs of uremia after contralateral nephrectomy. Prenephrectomy renal function tests were not significant indicators for survival during this acute phase. Twenty-five cats entered the chronic phase. Ten cats were euthanized at a median of 163 days from nephrectomy because of progressive renal dysfunction. Median survival times were significantly different when stratified by acute kidney injury grade at day 29. Cats in the chronic phase had clinical courses similar to cats with naturally occurring CKD, and most (13/15) were in CKD stage 2.
CLINICAL RELEVANCE
The remnant kidney model is effective at reducing kidney function to an extent that mimics important characteristics of spontaneous CKD in cats.
