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Journal of veterinary internal medicine [journal]
- Effect of Dietary Nonstructural Carbohydrate Content on Activation of 5'-Adenosine Monophosphate-Activated Protein Kinase in Liver, Skeletal Muscle, and Digital Laminae of Lean and Obese Ponies. [JOURNAL ARTICLE]
- J Vet Intern Med 2014 Apr 20.
In EMS-associated laminitis, laminar failure may occur in response to energy failure related to insulin resistance (IR) or to the effect of hyperinsulinemia on laminar tissue. 5'-Adenosine-monophosphate-activated protein kinase (AMPK) is a marker of tissue energy deprivation, which may occur in IR.To characterize tissue AMPK regulation in ponies subjected to a dietary carbohydrate (CHO) challenge.Twenty-two mixed-breed ponies.Immunohistochemistry and immunoblotting for total AMPK and phospho(P)-AMPK and RT-qPCR for AMPK-responsive genes were performed on laminar, liver, and skeletal muscle samples collected after a 7-day feeding protocol in which ponies stratified on body condition score (BCS; obese or lean) were fed either a low-CHO diet (ESC + starch, approximately 7% DM; n = 5 obese, 5 lean) or a high-CHO diet (ESC + starch, approximately 42% DM; n = 6 obese, 6 lean).5'-Adenosine-monophosphate-activated protein kinase was immunolocalized to laminar keratinocytes, dermal constituents, and hepatocytes. A high-CHO diet resulted in significantly decreased laminar [P-AMPK] in lean ponies (P = .03), but no changes in skeletal muscle (lean, P = .33; obese, P = .43) or liver (lean, P = .84; obese, P = .13) [P-AMPK]. An inverse correlation existed between [blood glucose] and laminar [P-AMPK] in obese ponies on a high-CHO diet.Laminar tissue exhibited a normal response to a high-CHO diet (decreased [P-AMPK]), whereas this response was not observed in liver and skeletal muscle in both lean (skeletal muscle, P = .33; liver, P = .84) and obese (skeletal muscle, P = .43; liver, P = .13) ponies.
- A Homozygous KCNJ10 Mutation in Jack Russell Terriers and Related Breeds with Spinocerebellar Ataxia with Myokymia, Seizures, or Both. [JOURNAL ARTICLE]
- J Vet Intern Med 2014 Apr 7.
Juvenile-onset spinocerebellar ataxia has been recognized in Jack Russell Terriers and related Russell group terriers (RGTs) for over 40 years. Ataxia occurs with varying combinations of myokymia, seizures, and other signs of neurologic disease. More than 1 form of the disease has been suspected.The objective was to identify the mutation causing the spinocerebellar ataxia associated with myokymia, seizures, or both and distinguish the phenotype from other ataxias in the RGTs.DNA samples from 16 RGTs with spinocerebellar ataxia beginning from 2 to 12 months of age, 640 control RGTs, and 383 dogs from 144 other breeds along with the medical records of affected dogs were studied.This case-control study compared the frequencies of a KCNJ10 allele in RGTs with spinocerebellar ataxia versus control RGTs. This allele was identified in a whole-genome sequence of a single RGT with spinocerebellar ataxia and myokymia by comparison to whole-genome sequences from 81 other canids that were normal or had other diseases.A missense mutation in the gene coding for the inwardly rectifying potassium channel Kir4.1 (KCNJ10:c.627C>G) was significantly (P < .001) associated with the disease. Dogs homozygous for the mutant allele all had spinocerebellar ataxia with varying combinations of myokymia and seizures.Identification of the KCNJ10 mutation in dogs with spinocerebellar ataxia with myokymia, seizures, or both clarifies the multiple forms of ataxia seen in these breeds and provides a DNA test to identify carriers.
- Serum Biomarkers of Clinical and Cytologic Response in Dogs with Idiopathic Immune-Mediated Polyarthropathy. [JOURNAL ARTICLE]
- J Vet Intern Med 2014 Apr 3.
Immune-mediated polyarthopathy (IMPA) is common in dogs, and is monitored by serial arthrocenteses.Plasma C-reactive protein (CRP), interleukin-6 (IL-6), and CXCL8 (interleukin-8) would serve as noninvasive markers of joint inflammation in IMPA.Nine client-owned dogs with idiopathic IMPA; 6 healthy controls.Prospective study. Plasma CRP, IL-6, and CXCL8 were measured by ELISA at baseline, 2, and 4 weeks during treatment with prednisone at 50 mg/m(2) /day. Arthrocenteses, the canine brief pain inventory (CBPI), and accelerometry collars were used to assess joint inflammation, lameness, and mobility at all 3 time points.C-reactive protein concentrations were higher in IMPA dogs (median 91.1 μg/mL, range 76.7-195.0) compared with controls (median <6.3 μg/mL, <6.3-13.7; P = .0035), and were significantly lower at week 2 (10.6 μg/mL, <6.3-48.8) and week 4 (<6.3 μg/mL, <6.3-24.4; P < .001). C-reactive protein was correlated with median CBPI scores (r = 0.68; P = .0004), joint cellularity (r = 0.49, P = .011), and mobility by accelerometry (r = -0.42, P = .048). Plasma IL-6 concentrations were also higher in IMPA dogs (median 45.9 pg/mL), compared with controls (median <15.7 pg/mL; P = .0008). IL-6 was lower in IMPA dogs by week 4 (<15.7 pg/mL; P = .0099), and was modestly correlated with CBPI scores (r = 0.47, P = .023). CXCL8 did not differ significantly between IMPA and healthy dogs.Plasma CRP and IL-6 might be useful surrogate markers of synovial inflammation and disease activity in dogs with IMPA.
- A Randomized Study Assessing the Effect of Diet in Cats with Hypertrophic Cardiomyopathy. [JOURNAL ARTICLE]
- J Vet Intern Med 2014 Apr 3.
Diet might influence progression of hypertrophic cardiomyopathy (HCM).To investigate whether diet composition could alter clinical, biochemical, or echocardiographic variables in cats with HCM.Twenty-nine cats with HCM (International Small Animal Cardiac Health Council stage 1b) examined at a university teaching hospital.Randomized, placebo-controlled trial. After physical examination, echocardiogram, and blood collection, cats were randomized to 1 of 3 diets, which varied in carbohydrate and fat content and ingredients. Measurements were repeated after 6 months.There were no significant differences among the 3 groups at baseline. After 6 months, there were no significant changes in the primary endpoints, left ventricular free wall (Group A, P = .760; Group B, P = .475; Group C, P = .066) or interventricular septal thickness in diastole (Group A, P = .528; Group B, P = .221; Group C, P = .097). Group A had significant increases in BUN (P = .008) and cholesterol (P = .021), while Group B had significant increases in BUN (P = .008), cholesterol (P = .007), and triglycerides (P = .005), and significant decreases in NT-proBNP (P = .013) and hs-troponin I (P = .043). Group C had significant decreases in body weight (P = .021), left atrial dimension (P = .035), interventricular septal thickness in systole (P = .038), and liver enzymes (P = .034-.038).These data suggest that diet might influence some clinical, biochemical, and echocardiographic variables in cats with HCM.
- Pulmonary Disease Potentially Associated with Nicoletella semolina in 3 Young Horses. [JOURNAL ARTICLE]
- J Vet Intern Med 2014 Apr 1.
- Intra-abdominal Mycobacterium tuberculosis Infection in a Dog. [JOURNAL ARTICLE]
- J Vet Intern Med 2014 Apr 1.
- Pro-tumorigenic Effects of Transforming Growth Factor Beta 1 in Canine Osteosarcoma. [JOURNAL ARTICLE]
- J Vet Intern Med 2014 Mar 31.
Transforming growth factor beta 1 (TGFβ1) is a pleiotropic cytokine that contributes to reparative skeletal remodeling by inducing osteoblast proliferation, migration, and angiogenesis. Organic bone matrix is the largest bodily reservoir for latent TGFβ1, and active osteoblasts express cognate receptors for TGFβ1 (TGFβRI and TGFβRII). During malignant osteolysis, TGFβ1 is liberated from eroded bone matrix and promotes local progression of osteotropic solid tumors by its mitogenic and prosurvival activities.Canine osteosarcoma (OS) cells will possess TGFβ1 signaling machinery. Blockade of TGFβ1 signaling will attenuate pro-tumorigenic activities in OS cells. Naturally occurring primary OS samples will express cognate TGFβ1 receptors; and in dogs with OS, focal malignant osteolysis will contribute to circulating TGFβ1 concentrations.Thirty-three dogs with appendicular OS.Expression of TGFβ1 and its cognate receptors, as well as the biologic effects of TGFβ1 blockade, was characterized in OS cells. Ten spontaneous OS samples were characterized for TGFβRI/II expressions by immunohistochemistry. In 33 dogs with OS, plasma TGFβ1 concentrations were quantified and correlated with bone resorption.Canine OS cells secrete TGFβ1, express cognate receptors, and TGFβ1 signaling blockade decreases proliferation, migration, and vascular endothelial growth factor secretion. Naturally occurring OS samples abundantly and uniformly express TGFβRI/II, and in OS-bearing dogs, circulating TGFβ1 concentrations correlate with urine N-telopeptide excretion.Canine OS cells possess TGFβ1 signaling machinery, potentially allowing for the establishment of an autocrine and paracrine pro-tumorigenic signaling loop. As such, TGFβ1 inhibitors might impede localized OS progression in dogs.
- The Effect of Tramadol and Indomethacin Coadministration on Gastric Barrier Function in Dogs. [JOURNAL ARTICLE]
- J Vet Intern Med 2014 Mar 31.
Tramadol is a centrally acting analgesic that is often used in conjunction with nonsteroidal anti-inflammatory drugs (NSAIDs). The effect of coadministration of tramadol and indomethacin on gastric barrier function in dogs is unknown.That coadministration of a nonselective NSAID (indomethacin) and tramadol would decrease recovery of barrier function as compared with acid-injured, indomethacin-treated, and tramadol-treated mucosa.Gastric mucosa of 10 humanely euthanized shelter dogs.Ex vivo study. Mounted gastric mucosa was treated with indomethacin, tramadol, or both. Gastric barrier function, prostanoid production, and cyclooxygenase expression were quantified.Indomethacin decreased recovery of transepithelial electrical resistance after injury, although neither tramadol nor the coadministration of the two had an additional effect. Indomethacin inhibited production of gastroprotective prostanoids prostaglandin E2 (acid-injured PGE2 : 509.3 ± 158.3 pg/mL, indomethacin + acid injury PGE2 : 182.9 ± 93.8 pg/mL, P < .001) and thromboxane B2 (acid-injured TXB2 : 233.2 ± 90.7 pg/mL, indomethacin + acid injury TXB2 : 37.9 ± 16.8 pg/mL, P < .001), whereas tramadol had no significant effect (PGE2 P = .713, TXB2 P = .194). Neither drug had an effect on cyclooxygenase expression (COX-1 P = .743, COX-2 P = .705). Acid injury induced moderate to marked epithelial cell sloughing, which was unchanged by drug administration.There was no apparent interaction of tramadol and a nonselective cyclooxygenase in this ex vivo model. These results suggest that if there is an adverse interaction of the 2 drugs in vivo, it is unlikely to be via prostanoid inhibition.
- The Clinical Efficacy of Dietary Fat Restriction in Treatment of Dogs with Intestinal Lymphangiectasia. [JOURNAL ARTICLE]
- J Vet Intern Med 2014 Mar 27.
Intestinal lymphangiectasia (IL), a type of protein-losing enteropathy (PLE), is a dilatation of lymphatic vessels within the gastrointestinal tract. Dietary fat restriction previously has been proposed as an effective treatment for dogs with PLE, but limited objective clinical data are available on the efficacy of this treatment.To investigate the clinical efficacy of dietary fat restriction in dogs with IL that were unresponsive to prednisolone treatment or showed relapse of clinical signs and hypoalbuminemia when the prednisolone dosage was decreased.Twenty-four dogs with IL.Retrospective study. Body weight, clinical activity score, and hematologic and biochemical variables were compared before and 1 and 2 months after treatment. Furthermore, the data were compared between the group fed only an ultra low-fat (ULF) diet and the group fed ULF and a low-fat (LF) diet.Nineteen of 24 (79%) dogs responded satisfactorily to dietary fat restriction, and the prednisolone dosage could be decreased. Clinical activity score was significantly decreased after dietary treatment compared with before treatment. In addition, albumin (ALB), total protein (TP), and blood urea nitrogen (BUN) concentration were significantly increased after dietary fat restriction. At 2 months posttreatment, the ALB concentrations in the ULF group were significantly higher than that of the ULF + LF group.Dietary fat restriction appears to be an effective treatment in dogs with IL that are unresponsive to prednisolone treatment or that have recurrent clinical signs and hypoalbuminemia when the dosage of prednisolone is decreased.
- Short- and Long-Term Cure Rates of Short-Duration Trimethoprim-Sulfamethoxazole Treatment in Female Dogs with Uncomplicated Bacterial Cystitis. [JOURNAL ARTICLE]
- J Vet Intern Med 2014 Mar 27.
Long-duration beta-lactam antibiotics are used for empirical treatment in female dogs with uncomplicated bacterial cystitis. However, women with bacterial cystitis are treated with short-duration potentiated sulfonamides because longer courses of beta-lactams result in lower cure and higher recurrence rates.Short-duration potentiated sulfonamide treatment is more efficacious than long-duration beta-lactam treatment in achieving clinical and microbiological cures in female dogs with uncomplicated bacterial cystitis.Thirty-eight client-owned female dogs.Randomized, double-blinded, placebo-controlled clinical trial. Dogs were treated with TMP-SMX (15 mg/kg PO q12h for 3 days followed by a placebo capsule PO q12h for 7 days; Group SDS; n = 20) or cephalexin (20 mg/kg PO q12h for 10 days; Group LDBL; n = 18). Dogs were monitored for clinical and microbiological cure during treatment and at short- and long-term follow-up.No statistically significant differences were found between treatment groups in clinical cure rates after 3 days of treatment (89% SDS, 94% LDBL; P = 1.00) and 4 days (85% SDS, 72% LDBL; P = .44) or >30 days (50% SDS, 65% LDBL; P = .50) after conclusion of treatment or in microbiological cure rates 4 days (59% SDS, 36% LDBL; P = .44) or >30 days (44% SDS, 20% LDBL; P = .40) after conclusion of treatment.We did not identify a difference in cure rates between short-duration sulfonamide and long-duration beta-lactam treatments in female dogs with uncomplicated cystitis. Long-term cure rates in both treatment groups were low. In some female dogs, "uncomplicated" bacterial cystitis may be more complicated than previously recognized.