Pharmacokinetics of isavuconazole in healthy cats after oral and intravenous administration

BackgroundIsavuconazole is a triazole antifungal drug that has shown good efficacy in human patients. Absorption and pharmacokinetics have not been evaluated in cats.ObjectivesTo determine the pharmacokinetics of isavuconazole in cats given a single IV or PO dose.AnimalsEight healthy, adult research cats.MethodsFour cats received 100 mg capsules of isavuconazole PO. Four cats received 5 mg/kg isavuconazole solution IV. Serum was collected at predetermined intervals for analysis using ultra‐high performance liquid chromatography‐tandem mass spectrometry. Data were analyzed using a 2‐compartment uniform weighting pharmacokinetic analysis with lag time for PO administration and a 2 compartment, 1/y² weighting for IV administration. Predicted 24 and 48‐hour dosing intervals of 100 mg isavuconazole administered PO were modeled and in vitro plasma protein binding was assessed.ResultsBoth PO and IV drug administration resulted in high serum concentrations. Intravenous and PO formulations of isavuconazole appear to be able to be used interchangeably. Peak serum isavuconazole concentrations occurred 5 ± 3.8 hours after PO administration with an elimination rate half‐life of 66.2 ± 55.3 hours. Intersubject variability was apparent in both the PO and IV groups. Two cats vomited 6 to 8 hours after PO administration. No adverse effects were observed in the IV group. Oral bioavailability was estimated to be approximately 88%. Serum protein binding was calculated to be approximately 99.0% ± 0.03%.Conclusions and Clinical ImportanceIsavuconazole might prove to be useful in cats with fungal disease given its favorable pharmacokinetics. Additional studies on safety, efficacy, and tolerability of long‐term isavuconazole use are needed.     

Risk factors and implications associated with renal mineralization in chronic kidney disease in cats

BackgroundNephrocalcinosis is a pathological feature of chronic kidney disease (CKD). Its pathophysiological implications for cats with CKD are unexplored.ObjectivesIdentify nephrocalcinosis risk factors and evaluate its influence on CKD progression and all‐cause mortality.AnimalsFifty‐one euthyroid client‐owned cats with International Renal Interest Society (IRIS) stages 2‐3 azotemic CKD.MethodsRetrospective cohort study. Histopathological kidney sections were assessed for nephrocalcinosis (von Kossa stain). Nephrocalcinosis severity was determined by image analysis (ImageJ). Ordinal logistic regressions were performed to identify nephrocalcinosis risk factors. The influence of nephrocalcinosis on CKD progression and mortality risk were assessed using linear mixed model and Cox regression, respectively. Cats were categorized by their owner‐reported time‐averaged phosphate‐restricted diet (PRD) intake, where PRD comprised ≥50%, 10‐50%, or none of food intake.ResultsNephrocalcinosis was rated as mild‐to‐severe in 78.4% and absent‐to‐minimal in 21.6% of cases. Higher baseline plasma total calcium concentration (tCa; odds ratio [OR] = 3.07 per 1 mg/dL; P = .02) and eating a PRD (10%‐50%: OR = 8.35; P = .01; ≥50%: OR = 5.47; P = .01) were independent nephrocalcinosis risk factors. Cats with absent‐to‐minimal nephrocalcinosis had increasing plasma creatinine (0.250 ± 0.074 mg/dL/month; P = .002), urea (5.06 ± 1.82 mg/dL/month; P = .01), and phosphate (0.233 ± 0.115 mg/dL/month; P = .05) concentrations over a 1‐year period, and had shorter median survival times than cats with mild‐to‐severe nephrocalcinosis.Conclusion and Clinical ImportanceHigher plasma tCa at CKD diagnosis and PRD intake are independently associated with nephrocalcinosis. However, nephrocalcinosis is not associated with rapid CKD progression in cats.     

Diagnostic value of reticulocyte indices for the assessment of the iron status of cats with chronic kidney disease

BackgroundReticulocyte indices have been suggested as alternatives to transferrin saturation (TSAT) for iron status assessment in humans and dogs but they have not been evaluated thoroughly in cats.ObjectivesTo assess the value of the reticulocyte indices for the diagnosis of iron deficiency in cats with chronic kidney disease (CKD) and chronic hematuria associated with subcutaneous ureteral bypasses (SUBs).AnimalsSixty‐four cats: 16 healthy, 14 CKD without SUB, and 34 CKD with SUB.MethodsProspective observational cross‐sectional study of cats presented for routine nephrology visits. Primary outcomes included assessment of the diagnostic values of erythrocyte indices (mean corpuscular volume, hemoglobin, and hemoglobin concentration: MCV, MCH, and MCHC) and reticulocyte indices (mean corpuscular volume, MCVr; corpuscular hemoglobin, CHr), using TSAT as reference.ResultsIron deficiency was diagnosed in 9/64 cats (14%). A receiver‐operating characteristic curve analysis yielded a moderate discriminatory value for CHr in this diagnosis: area under the curve [AUC] = .75 (95% confidence interval, 0.48‐0.89); P = .006; sensitivity 67%, specificity 82% for a cutoff of 15.9 pg. This compared favorably to MCVr (AUC = .63; P = .29), MCV (AUC = .58; P = .45), MCH (AUC = .64; P = .19), and MCHC (AUC = .7; P = .03).Conclusion and Clinical ImportanceCHr added moderate value to the diagnosis of iron deficiency in cats with CKD.     

Outcome of stereotactic body radiation for treatment of nasal and nasopharyngeal lymphoma in 32 cats

BackgroundThe safety and efficacy of stereotactic body radiation therapy (SBRT) in the treatment of localized nasal lymphoma in cats has not been described.HypothesisStereotactic body radiation therapy with or without adjuvant chemotherapy is an effective and well‐tolerated treatment for localized nasal lymphoma in cats.AnimalsThirty‐two client owned cats referred to Colorado State University for the treatment of nasal lymphoma.MethodsRetrospective study of cats treated with SBRT between 2010 and 2020 at Colorado State University. Diagnosis of nasal lymphoma was obtained via cytology or histopathology. Signalment, radiation protocol, concurrent treatments, adverse effects, and survival were recorded.ResultsProgression free survival was 225 days (95% CI 98–514) and median survival time (MST) was 365 days (95% CI 123–531). No significant difference in survival was identified between cats that received 1 versus greater than 1 fraction (MST 427 vs. 123 days, P = 0.88). Negative prognostic factors included cribriform lysis (MST 121 vs. 876 days, P = 0.0009) and intracalvarial involvement (MST 100 vs. 438 days, P = 0.0007). Disease progression was noted in 38% (12/32), locally in 22% (7/32), and systemically in 16% (5/32). No cats developed acute adverse effects. Ten cats developed late adverse effects: keratitis/keratitis sicca (n = 2), alopecia (n = 4), and leukotrichia (n = 4). Twenty‐four cats (75%) had signs consistent with chronic rhinitis.ConclusionsSBRT is effective and well tolerated for treating localized nasal lymphoma in cats. Outcomes for cats with lower stage disease (canine modified Adam''s stage 3 and lower) are comparable to historic data of cats treated with fractionated radiation therapy.     

Association of gastric lymphofollicular hyperplasia with Helicobacter‐like organisms in dogs

BackgroundThe relationships among gastric lymphoid follicular hyperplasia (GLFH), Helicobacter‐like organisms (HLOs), and clinical signs have not been established in dogs.ObjectivesTo evaluate the epidemiologic, clinical, endoscopic, and histopathologic findings associated with GLFH in dogs, and determine the association of GLFH with HLOs and the French Bulldog (FB) breed.AnimalsTwo hundred eighty‐eight dogs that underwent gastroscopy between 2013 and 2016.MethodsRetrospective, cross‐sectional study. Gastric biopsy samples were reviewed and scored for inflammation and HLOs. Dogs were divided into 3 groups: group 1 (63 FBs), group 2 (45 non‐FB brachycephalic dogs), and group 3 (180 nonbrachycephalic dogs). Variables were evaluated for their association with GLFH.ResultsUnivariate analysis determined that intact males, young age, vomiting, gastroscopic findings (discoloration, hemorrhage, and ulcers), and histopathologic findings (gastric lamina propria lymphocytic infiltration and HLO score) were associated with GLFH (P ≤ .03). In the multivariate analysis, GLFH was associated with the HLO score (odds ratio [OR] > 5 for HLO scores 1‐2 and >15 for HLO score of 3; P < .001), with vomiting (OR > 4; P = .01) but not with FB breed (P = .76) and age (P = .1). The HLO score was associated with younger age (P < .001).Conclusion and Clinical ImportanceThe HLO score was associated with a high GLFH score. Vomiting was associated with GLFH. Helicobacter‐like organisms are highly prevalent in young dogs and GLFH is indirectly associated with this factor. Clinical relevance of the identification of GLFH and HLO remains to be determined.     

Expression of adipokines and adipocytokines by epidural adipose tissue in cauda equina syndrome in dogs

BackgroundCompression of epidural adipose tissue (EAT) within the scope of cauda equina syndrome (CES) could lead to an enhanced expression of inflammatory mediators, possibly contributing to pain amplification in dogs.ObjectivesTo analyze expression of inflammatory adipo(‐cyto)kines within the EAT of dogs with CES.AnimalsClient‐owned dogs: 15 dogs with CES and 9 dogs euthanized for unrelated medical reasons (controls).MethodsProspective, experimental study. Epidural adipose tissue and subcutaneous adipose tissue were collected during dorsal laminectomy and used for real‐time quantitative polymerase chain reaction. Tissue explants were cultured for measurements of inflammation‐induced release of cytokines.ResultsResults show a CES‐associated upregulation of the cytokines tumor necrosis factor alpha (TNFα: mean ± SD: 18.88 ± 11.87, 95% CI: 10.90‐26.86 vs 9.66 ± 5.22, 95% CI: 5.29‐14.02, *: P = .04) and interleukin‐ (IL‐) 10 (20.1 ± 9.15, 95% CI: 14.82‐25.39 vs 11.52 ± 6.82, 95% CI: 5.82‐17.22, *: P = .03), whereas the expression of the adipokine leptin was attenuated in EAT of dogs with CES (3.07 ± 2.29, 95% CI: 1.80‐3.34 vs 9.83 ± 8.42, 95% CI: 3.36‐16.30, **: P = .007). Inflammatory stimulation of EAT explant cultures resulted in an enhanced release of IL‐6 (LPS: 5491.55 ± 4438, 95% CI: 833.7‐10 149; HMGB1: 1001.78 ± 522.2, 95% CI: 518.8‐1485; PBS: 310.9 ± 98.57, 95% CI: 228.5‐393.3, ***: P < .001).Conclusion and Clinical ImportanceExpression profile of inflammatory adipo(‐cyto)kines by EAT is influenced from compressive forces acting in dogs with CES and might contribute to amplification of pain.     

Effects of intravenous administration of peripheral blood‐derived mesenchymal stromal cells after infusion of lipopolysaccharide in horses

BackgroundA systemic and dysregulated immune response to infection contributes to morbidity and mortality associated with sepsis. Peripheral blood‐derived mesenchymal stromal cells (PB‐MSC) mitigate inflammation in animal models of sepsis. Allogeneic PB‐MSC administered IV to horses is well‐tolerated but therapeutic benefits are unknown.HypothesisAfter IV lipopolysaccharide (LPS) infusion, horses treated with PB‐MSC would have less severe clinical signs, clinicopathological abnormalities, inflammatory cytokine gene expression, and oxidative stress compared to controls administered a placebo.AnimalsSixteen horses were included in this study.MethodsA randomized placebo‐controlled experimental trial was performed. Sixteen healthy horses were assigned to 1 of 2 treatment groups (1 × 10⁹ PB‐MSC or saline placebo). Treatments were administered 30 minutes after completion of LPS infusion of approximately 30 ng/kg. Clinical signs, clinicopathological variables, inflammatory cytokine gene expression, and oxidative stress markers were assessed at various time points over a 24‐hour period.ResultsA predictable response to IV LPS infusion was observed in all horses. At the dose administered, there was no significant effect of PB‐MSC on clinical signs, clinicopathological variables, or inflammatory cytokine gene expression at any time point. Antioxidant potential was not different between treatment groups, but intracellular ROS increased over time in the placebo group. Other variables that changed over time were likely due to effects of IV LPS infusion.Conclusions and Clinical ImportanceAdministration of allogeneic PB‐MSC did not cause clinically detectable adverse effects in healthy horses. The dose of PB‐MSC used here is unlikely to exert a beneficial effect in endotoxemic horses.     

Ultrasonographic characteristics of the portal venous system of 37 healthy,unsedated, student-owned cats: A prospective study

Objective The aim of this study was to determine portal vein and divisional branch diameters and portal vein velocities in healthy, unsedated cats, using B-mode and Doppler ultrasound.Animal Thirty-seven healthy, adult cats, all owned by students.Procedure Enrollment of cats in the study was done prospectively. Ultrasonographic imaging in both the longitudinal and transverse planes was assessed, with all examinations and measurements done by the same person. The assessment included the following 3 sites: extra-hepatic portion of the portal vein, intra-hepatic branches of the portal vein, and the aorta at the level of the porta hepatis. The Shapiro-Wilk test was used for normality and P < 0.05 was used to define statistical significance.Results Both the extra-hepatic portion of the portal vein and the porta hepatis were identified in all 37 cats (100%), whereas the aorta was recorded in 31 (84%), and the left and right intra-hepatic branches of the portal vein were seen in 29 (78%). Pulsed-wave Doppler ultrasound of the portal vein was obtained in 32 cats (86%). In longitudinal view, average maximal diameter of the extra-hepatic portal vein was 3.6 mm (± 0.7 mm), and the mean portal flow velocity was 14.6 cm/s (± 4.3 cm/s). In transverse view, average maximal diameter was 4.8 mm (± 0.8 mm) for the extra-hepatic portal vein, and 3.1 mm (± 0.8 mm) and 2.6 mm (± 0.7 mm) for the left and right intra-hepatic branches, respectively. The portal-vein-to-aorta ratio averaged 1.2 (± 0.2).Conclusion This study produced sonographic data of the portal venous system in healthy, conscious adult cats, which may be useful during investigation of liver diseases, including congenital and acquired liver diseases.     

Assessment of the effects of erythromycin, neostigmine, and metoclopramide on abomasal motility and emptying rate in calves

OBJECTIVE: To determine and compare the effects of erythromycin, neostigmine, and metoclopramide on abomasal motility and emptying rate in suckling calves. ANIMALS: 6 male Holstein calves (15 to 40 days of age). PROCEDURE: Calves were monitored for 1 hour before being fed milk replacer (60 mL/kg; time, 0 minutes) and then were monitored for another 3 hours. Calves received 6 treatments in randomized order: erythromycin (8.8 mg/kg, IM) at -30 minutes; low-dose erythromycin (0.88 mg/kg, IM) at -30 minutes; erythromycin (8.8 mg/kg, IM) at -30 minutes and neostigmine (0.02 mg/kg, SC) at -30 and 90 minutes; neostigmine (0.02 mg/kg, SC) at -30 and 90 minutes; metoclopramide (0.1 mg/kg, IM) at-30 and 90 minutes; and placebo (2 mL of saline [0.9% NaCl] solution, SC) at -30 minutes. Abomasal volume was calculated from ultrasonographic measurements of abomasal width, length, and height. Abomasal motility and emptying rate were assessed by measuring luminal pressure and change in abomasal volume over time. RESULTS: Administration of erythromycin (8.8 mg/kg) increased the frequency of abomasal luminal pressure waves and the mean abomasal luminal pressure and decreased the half-time of abomasal emptying by 37%. Administration of metoclopramide, neostigmine, and low-dose erythromycin (0.88 mg/kg) did not alter abomasal motility, mean luminal pressure, or emptying rate. CONCLUSIONS AND CLINICAL RELEVANCE: Results indicated that administration of erythromycin at the labeled antimicrobial dose (8.8 mg/kg, IM) exerted an immediate, marked prokinetic effect in healthy suckling calves, whereas administration of metoclopramide or neostigmine did not alter abomasal motility or emptying rate.     

Environmental risk factors for the development of oral squamous cell carcinoma in cats

BackgroundRisk factors for oral squamous cell carcinoma (OSCC) in cats are derived from a single study dated almost 20 years ago. The relationship between inflammation of oral tissues and OSCC is still unclear.ObjectivesTo investigate previously proposed and novel potential risk factors for OSCC development, including oral inflammatory diseases.AnimalsHundred cats with OSCC, 70 cats with chronic gingivostomatitis (CGS), 63 cats with periodontal disease (PD), and 500 controls.MethodsProspective, observational case‐control study. Cats with OSCC were compared with an age‐matched control sample of client‐owned cats and cats with CGS or PD. Owners of cats completed an anonymous questionnaire including demographic, environmental and lifestyle information.ResultsOn multivariable logistic regression, covariates significantly associated with an increased risk of OSCC were rural environment (OR: 1.77; 95% CI: 1.03‐3.04; P = .04), outdoor access (OR: 1.68; 95% CI: 1.07‐2.63; P = .02), environmental tobacco smoke (OR: 1.77; 95% CI: 1.05‐3; P = .03), and petfood containing chemical additives (OR: 1.98; 95% CI: 1.04‐3.76; P = .04). Risk factors shared with CGS and PD were outdoor access and petfood containing chemical additives, respectively. A history of oral inflammation was reported in 35% of cats with OSCC but did not emerge as a risk factor.Conclusions and Clinical ImportanceThe study proposes novel potential risk factors for OSCC in cats. Although a history of inflammatory oral disease was not significantly more frequent compared with random age‐matched controls, OSCC shared several risk factors with CGS and PD.     

Outcomes of esophageal and gastric bone foreign bodies in dogs

BackgroundBone foreign bodies are commonly encountered in small animal practice. Esophageal bone foreign bodies (E‐bFBs) warrant removal, whereas gastric bone foreign bodies might not.ObjectivesDescribe management and outcomes for dogs with esophageal or gastric bone foreign bodies.AnimalsOne hundred twenty‐nine dogs with esophageal (n = 45) or gastric (n = 84) bone foreign bodies.MethodsRetrospective review of medical records.ResultsDogs with E‐bFBs were younger than dogs with gastric bone foreign bodies (median age esophageal, 4 years [IQR 2‐8]; median age gastric, 6 years [IQR 3‐10]; P = .03), and had a higher bone cross‐sectional area relative to body weight (median esophageal, 98.21 mm²/kg [IQR 48.25‐142.6]; median gastric, 28.6 mm²/kg [IQR 17.25‐64.28]; P < .001). Forty‐two of 45 esophageal foreign bodies were resolved non‐surgically and 3 by esophagotomy. Esophageal erosions were more likely with distal entrapment (OR 12.88, [95% CI 31.95‐129.29], P = .01) and longer duration (OR 18.82 [95% CI 2.22‐273.97], P = .01). Sixty‐two of 84 bone gastric foreign bodies were left in situ. Endoscopic removal was successful in 20 of 22 (91%; 95% CI 70‐99) attempts.Conclusions and Clinical ImportanceWhile all E‐bFBs were dislodged either by advancement into the stomach, endoscopic removal, or esophagotomy, the majority of gastric bone foreign bodies were left in situ for dissolution, with no reported complications. Gastric advancement of E‐bFBs should be considered when oral removal is not feasible, and dissolution can be considered even with large bones.     

Evaluation of the Effect of Orally Administered Acid Suppressants On Intragastric pH in Cats

Background

Acid suppressant drugs are a mainstay of treatment for cats with gastrointestinal erosion and ulceration. However, clinical studies have not been performed to compare the efficacy of commonly PO administered acid suppressants in cats.

Hypothesis/Objectives

To compare the effect of PO administered famotidine, fractionated omeprazole tablet (fOT), and omeprazole reformulated paste (ORP) on intragastric pH in cats. We hypothesized that both omeprazole formulations would be superior to famotidine and placebo.

Animals

Six healthy adult DSH colony cats.

Methods

Utilizing a randomized, 4‐way crossover design, cats received 0.88–1.26 mg/kg PO q12h fOT, ORP, famotidine, and placebo (lactose capsules). Intragastric pH monitoring was used to continuously record intragastric pH for 96 hours beginning on day 4 of treatment. Plasma omeprazole concentrations at steady state (day 7) were determined by high performance liquid chromatography (HPLC) with ultraviolet detection. Mean percentage time that intragastric pH was ≥3 and ≥4 were compared among groups using ANOVA with a posthoc Tukey‐Kramer test (α = 0.05).

Results

The mean percentage time ± SD that intragastric pH was ≥3 was 68.4 ± 35.0% for fOT, 73.9 ± 23.2% for ORP, 42.8 ± 18.6% for famotidine, and 16.0 ± 14.2% for placebo. Mean ± SD plasma omeprazole concentrations were similar in cats receiving fOT compared to those receiving ORP and in a range associated with acid suppression reported in other studies.

Conclusions and Clinical Importance

These results suggest that both omeprazole formulations provide superior acid suppression in cats compared to famotidine or placebo. Fractionated enteric‐coated OT is an effective acid suppressant despite disruption of the enteric coating.     

Urinary cortisol‐creatinine ratio in dogs with hypoadrenocorticism

BackgroundBasal serum cortisol (BSC) ≥2 μg/dL (>55 nmol/L) has high sensitivity but low specificity for hypoadrenocorticism (HA).ObjectiveTo determine whether the urinary corticoid:creatinine ratio (UCCR) can be used to differentiate dogs with HA from healthy dogs and those with diseases mimicking HA (DMHA).AnimalsNineteen healthy dogs, 18 dogs with DMHA, and 10 dogs with HA.MethodsRetrospective study. The UCCR was determined on urine samples from healthy dogs, dogs with DMHA, and dogs with HA. The diagnostic performance of the UCCR was assessed based on receiver operating characteristics (ROC) curves, calculating the area under the ROC curve.ResultsThe UCCR was significantly lower in dogs with HA (0.65 × 10⁻⁶; range, 0.33‐1.22 × 10⁻⁶) as compared to healthy dogs (3.38 × 10⁻⁶; range, 1.11‐17.32 × 10⁻⁶) and those with DMHA (10.28 × 10⁻⁶; range, 2.46‐78.65 × 10⁻⁶) (P < .0001). There was no overlap between dogs with HA and dogs with DMHA. In contrast, 1 healthy dog had a UCCR value in the range of dogs with HA. The area under the ROC curve was 0.99. A UCCR cut‐off value of <1.4 yielded 100% sensitivity and 97.3% specificity in diagnosing HA.Conclusions and Clinical ImportanceThe UCCR seems to be a valuable and reliable screening test for HA in dogs. The greatest advantage of this test is the need for only a single urine sample.     

Serum fibroblast growth factor 23 (FGF-23): associations with hyperphosphatemia and clinical staging of feline chronic kidney disease

Fibroblast growth factor 23 (FGF-23) is an independent monitor of the progression of chronic kidney disease (CKD) in human medicine, and FGF-23 may have value as a biomarker in feline CKD. We evaluated the relationship between serum FGF-23 and CKD stages, and the effect of age on FGF-23 in normal cats. We measured FGF-23 and intact parathyroid hormone (iPTH) concentrations by ELISA, with intra- and inter-assay CVs ≤ 15%. The percentage recovery of FGF-23 and iPTH remained stable for up to 7 d in samples stored at −20°C and −80°C. We measured FGF-23 in 304 cats, among which 196 were diagnosed with CKD. The 108 clinically healthy cats were divided into 5 subgroups based on growth stage (0–2 y, 3–6 y, 7–10 y, 11–14 y, ≥ 15 y). No statistical difference was found in FGF-23 among age groups (p = 0.15) or by sex in healthy subjects. Using the International Renal Interest Society guideline, 34 cats were defined as CKD stage 1, 74 stage 2, 51 stage 3, and 37 stage 4. FGF-23 was higher in cats in all CKD stages than in controls. Higher serum phosphorus was observed in stage 3 (p = 0.04) and 4 (p < 0.01) compared to controls. iPTH increased as CKD progressed. Pearson analysis indicated a positive linear relationship between FGF-23 and iPTH (control: r = 0.70, p < 0.01; CKD: r = 0.46, p = 0.02). FGF-23 may be a useful biomarker of feline CKD and may precede hyperphosphatemia in advanced feline CKD.     

Evaluation of a long‐acting injectable formulation of omeprazole in healthy dogs

BackgroundTo evaluate the efficacy of a single intramuscular adminsitration of long‐acting omeprazole (LA‐OMEP) in increasing gastric pH in dogs.HypothesisWe hypothesized that LA‐OMEP would meet in healthy dogs the clinical goals defined for human patients for treatment of gastroduodenal ulceration.AnimalsNine healthy research dogs.MethodsProspective experimental study. Dogs were given a 4 mg/kg intramuscular injection of LA‐OMEP. Intragastric pH was continuously recorded on treatment days 0 to 7. Daily mean pH and mean percentage time (MPT) intragastric pH was ≥3 or ≥4 were determined.ResultsThe mean onset of action for the LA‐OMEP was 98.11 min (SD 46.39). The mean number of days the dogs'' pH met established goals for MPT pH ≥3 was 5.5 days (range, 3‐7) and 5.25 days for MPT pH ≥4 (range, 3‐7). Long‐acting omeprazole met the human clinical goals pH ≥3 for 72 hours in 8/8 of the dogs and MPT pH ≥4 for 96 hours in 7/8 of dogs.Conclusions and Clinical ImportanceThe LA‐OMEP formulation produced gastric acid suppression in healthy dogs for an average of 5 days and up to 7 days, after a single intramuscular injection. No major adverse effects were observed.     

Interstitial lactate,lactate/pyruvate and glucose in rat muscle before,during and in the recovery from global hypoxia

Background

Hypoxia results in an imbalance between oxygen supply and oxygen consumption. This study utilized microdialysis to monitor changes in the energy-related metabolites lactate, pyruvate and glucose in rat muscle before, during and after 30 minutes of transient global hypoxia. Hypoxia was induced in anaesthetised rats by reducing inspired oxygen to 6% O₂ in nitrogen.

Results

Basal values for lactate, the lactate/pyruvate ratio and glucose were 0.72 ± 0.04 mmol/l, 10.03 ± 1.16 and 3.55 ± 0.19 mmol/l (n = 10), respectively. Significant increases in lactate and the lactate/pyruvate ratio were found in the muscle after the induction of hypoxia. Maximum values of 2.26 ± 0.37 mmol/l for lactate were reached during early reperfusion, while the lactate/pyruvate ratio reached maximum values of 35.84 ± 7.81 at the end of hypoxia. Following recovery to ventilation with air, extracellular lactate levels and the lactate/pyruvate ratio returned to control levels within 30–40 minutes. Extracellular glucose levels showed no significant difference between hypoxia and control experiments.

Conclusions

In our study, the complete post-hypoxic recovery of metabolite levels suggests that metabolic enzymes of the skeletal muscle and their related cellular components may be able to tolerate severe hypoxic periods without prolonged damage. The consumption of glucose in the muscle in relation to its delivery seems to be unaffected.     

Determination of solid- and liquid-phase gastric emptying half times in cats by use of nuclear scintigraphy

OBJECTIVE: To use nuclear scintigraphy to establish a range of gastric emptying half times (t1/2) following a liquid or solid meal in nonsedated cats. ANIMALS: 12 clinically normal 3-year-old domestic shorthair cats. PROCEDURE: A test meal of 75 g of scrambled eggs labeled with technetium Tc 99m tin colloid was fed to 10 of the cats, and solid-phase gastric emptying t1/2 were determined by use of nuclear scintigraphy. In a separate experiment, 8 of these cats plus an additional 2 cats were fed 18 ml (n = 5) or 36 ml (n = 5) of a nutrient liquid meal labeled with technetium Tc 99m pentetate. Liquid-phase gastric emptying t1/2 then were determined by use of scintigraphy. RESULTS: Solid-phase gastric emptying t1/2 were between 210 and 769 minutes (median, 330 minutes). Median liquid-phase gastric emptying t1/2 after ingestion of 18 or 36 ml of the test meal were 67 minutes (range, 60 to 96 minutes) and 117 minutes (range, 101 to 170 minutes), respectively. The median t1/2 determined for cats receiving 18 ml of the radiolabeled liquid was significantly less than that determined for cats receiving 36 ml of the test meal. CONCLUSIONS AND CLINICAL RELEVANCE: The protocol was tolerated by nonsedated cats. Solid-phase gastric emptying t1/2 were prolonged, compared with liquid-phase t1/2, and a major factor governing the emptying rate of liquids was the volume consumed. Nuclear scintigraphy may prove useful in assessing gastric motility disorders in cats.     

Analytical performance and method comparison of a quantitative point-of-care immunoassay for measurement of bile acids in cats and dogs

Point-of-care analyzers (POCAs) for quantitative assessment of bile acids (BAs) are scarce in veterinary medicine. We evaluated the Fuji Dri-Chem Immuno AU10V analyzer and v-BA test kit (Fujifilm) for detection of feline and canine total serum BA concentration. Results were compared with a 5th-generation assay as reference method and a 3rd-generation assay, both run on a bench-top analyzer. Analytical performance was assessed at 3 different concentration ranges, and with interferences. For method comparison, samples of 60 healthy and diseased cats and 64 dogs were included. Linearity was demonstrated for a BA concentration up to 130 µmol/L in cats (r = 0.99) and 110 µmol/L in dogs (r = 0.99). The analyzer showed high precision near the lower limit of quantification of 2 µmol/L reported by the manufacturer. Intra- and inter-assay coefficients of variation were < 5% for both species and all concentrations. Interferences were observed for bilirubin (800 mg/L) and lipid (4 g/L). There was excellent correlation with the reference method for feline (r_s = 0.98) and canine samples (r_s = 0.97), with proportional biases of 6.7% and −1.3%, respectively. However, a large bias (44.1%) was noted when the POCA was compared to the 3rd-generation assay. Total observed error was less than total allowable error at the 3 concentrations. The POCA reliably detected feline and canine BA in clinically relevant concentrations.     

Identification and genotyping of feline infectious peritonitis-associated single nucleotide polymorphisms in the feline interferon-γ gene

Feline infectious peritonitis (FIP) is an immune-mediated, highly lethal disease caused by feline coronavirus (FCoV) infection. Currently, no protective vaccine or effective treatment for the disease is available. Studies have found that some cats survive the challenge of virulent FCoV isolates. Since cellular immunity is thought to be critical in preventing FIP and because diseased cats often show a significant decrease in interferon-γ (IFN-γ) production, we investigated whether single nucleotide polymorphisms (SNP) in the feline IFN-γ gene (fIFNG) are associated with the outcome of infection. A total of 82 asymptomatic and 63 FIP cats were analyzed, and 16 SNP were identified in intron 1 of fIFNG. Among these SNP, the fFING + 428 T allele was shown to be a FIP-resistant allele (p = 0.03), and the heterozygous genotypes 01C/T and +408C/T were found to be FIP-susceptible factors (p = 0.004). Furthermore, an fIFNG + 428 resistant allele also showed a clear correlation with the plasma level of IFN-γ in FIP cats. For the identification of these three FIP-related SNP, genotyping methods were established using amplification refractory mutation system PCR (ARMS-PCR) and restriction fragment length polymorphisms (RFLP), and the different genotypes could easily be identified without sequencing. The identification of additional FIP-related SNP will allow the selection of resistant cats and decrease the morbidity of the cat population to FIP.