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ABSTRACT

Lipases are water-soluble enzymes that hydrolyze water-insoluble lipid molecules, such as triglycerides, phospholipids, and galactolipids. They are ubiquitous in nature and are present in humans, animals, insects, plants, fungi, and microorganisms. While we commonly consider pancreatic lipase, this review provides an overview of several lipases that are important for the digestion and metabolism of lipids in veterinary species. All of these enzymes have specific functions but share a common α/β-hydrolase fold and a catalytic triad where substrate hydrolysis occurs. The pancreatic lipase gene family is one of the best characterized lipase gene families and consists of 7 mammalian subfamilies: pancreatic lipase, pancreatic lipase related proteins 1 and 2, hepatic lipase, lipoprotein lipase, endothelial lipase, and phosphatidylserine phospholipase A1. Other mammalian lipases that play integral roles in lipid digestion include carboxyl ester lipase and gastric lipase. Although most enzymes have preferred substrate specificity, much overlap occurs across the plethora of lipases because of the similarities in their structures. This has major implications for the development and clinical utilization of diagnostic assays. These implications are further explored in our companion Currents in One Health article by Lim et al in the August 2022 issue of the Journal of American Veterinary Medical Association, which focuses on pancreatic lipase assays for the diagnosis of pancreatitis.

Open access
in American Journal of Veterinary Research

Abstract

OBJECTIVE

To assess the pharmacokinetics, clinical efficacy, and adverse effects of injectable methadone with the pharmacokinetic enhancer fluconazole (methadone-fluconazole), compared with the standard formulation of injectable methadone, in dogs after ovariohysterectomy. We hypothesized that 2 doses of methadone-fluconazole would provide 24 hours of postoperative analgesia.

ANIMALS

3 purpose-bred dogs (pharmacokinetic preliminary study) and 42 female dogs from local shelters (clinical trial) were included.

PROCEDURES

Pharmacokinetics were preliminarily determined. Clinical trial client-owned dogs were blocked by body weight into treatment groups: standard methadone group (methadone standard formulation, 0.5 mg/kg, SC, q 4 h; n = 20) or methadone-fluconazole group (0.5 mg/kg methadone with 2.5 mg/kg fluconazole, SC, repeated once at 6 h; n = 22). All dogs also received acepromazine, propofol, and isoflurane. Surgeries were performed by experienced surgeons, and dogs were monitored perioperatively using the Glasgow Composite Measure Pain Scale–Short Form (CMPS-SF) and sedation scales. Evaluators were masked to treatment.

RESULTS

Findings from pharmacokinetic preliminary studies supported that 2 doses of methadone-fluconazole provide 24 hours of drug exposure. The clinical trial had no significant differences in treatment failures or postoperative CMPS-SF scores between treatments. One dog (methadone-fluconazole group) had CMPS-SF > 6 and received rescue analgesia. All dogs had moderate sedation or less by 1 hour (methadone-fluconazole group) or 4 hours (standard methadone group) postoperatively. Sedation was completely resolved in all dogs the day after surgery.

CLINICAL RELEVANCE

Methadone-fluconazole with twice-daily administration was well tolerated and provided effective postoperative analgesia for dogs undergoing ovariohysterectomy. Clinical compliance and postoperative pain control may improve with an effective twice-daily formulation.

Open access
in American Journal of Veterinary Research

Abstract

OBJECTIVE

To compare the biomechanical properties and gapping characteristics following loop modification of a 3-loop-pulley (3LP) pattern in an ex vivo canine common calcaneal tendon (CCT) avulsion repair model.

SAMPLE

56 skeletally mature hindlimbs from 28 canine cadavers.

PROCEDURES

The CCTs were randomized to 1 of 4 experimental groups (n = 14/group) then sharply transected at the teno-osseous junction. Groups consisted of a 3LP, 4-loop-pulley (4LP), 5-loop-pulley (5LP), or 6-loop-pulley (6LP) pattern with loops placed 60° apart using size-0 polypropylene. Yield, peak, and failure loads, construct stiffness, loads to produce a 3-mm teno-osseous gap, and failure mode were evaluated and compared between groups.

RESULTS

Yield (P = 0.001), peak (P < 0.001), and failure loads (P < 0.001), construct stiffness (P < 0.001), and loads to 3-mm gap formation (P = 0.005) were all significantly greater for 6LP compared to all other groups. Mode of failure did not differ among groups (P = 0.733) with 75% (42/56) of repairs failing by mechanism of core sutures pulling through the tendinous tissue. Pattern modification by increasing the number of loops increased the repair site strength by 1.4, 1.6, and 1.8 times for 4LP, 5LP, and 6LP compared to 3LP, respectively.

CLINICAL RELEVANCE

Increasing the number of suture loops compared to a traditional 3LP repair is a relatively simple technique modification that significantly increases teno-osseous repair site strength and loads required to cause 3-mm gap formation. The results of this study justify further focused investigation of increasing the number of suture loops in vivo for teno-osseous CCT repair in dogs.

Open access
in American Journal of Veterinary Research

Abstract

OBJECTIVE

To examine bicarbonate (HCO3 ) secretion ex vivo in the equine large colon to determine any differences between the right dorsal colon (RDC) and right ventral colon (RVC). The effect of phenylbutazone (PBZ) on HCO3 secretion was examined in the RDC.

ANIMALS

14 healthy horses.

PROCEDURES

In anesthetized horses (n = 10), segments of mucosa from RDC and RVC were harvested to measure HCO3 secretion ex vivo with the pH Stat method. The effect of PBZ on HCO3 secretion in the RDC was studied in 4 additional horses.

RESULTS

Three distinct mechanisms of HCO3 secretion previously described in a murine model were confirmed in the equine colon. The RDC had a greater capacity for electrogenic, Cl-independent HCO3 secretion than the RVC (P = 0.04). In the RDC, all HCO3 secretion was decreased by PBZ (P < 0.02) but was not studied in the RVC because of low baseline secretion.

CLINICAL RELEVANCE

Secretion of HCO3 by the RDC could play a pivotal role in equine colon physiology, because intense microbial fermentation in this site could require HCO3 secretion to buffer short-chain fatty acids. Inhibition of this secretion by PBZ could interfere with mucosal buffering and predispose to changes associated with right dorsal colitis.

Open access
in American Journal of Veterinary Research

Abstract

OBJECTIVES

To determine the pharmacokinetics of butorphanol tartrate incorporated into poloxamer 407 (P407) after subcutaneous administration to orange-winged Amazon parrots (Amazona amazonica).

ANIMALS

Six orange-winged Amazon parrots, ages 28 to 45 years.

PROCEDURES

A sterile formulation of butorphanol in P407 (But-P407) as a 25% gel was created to produce a concentration of 8.3 mg/mL. The formulation was administered SC at a dose of 12.5 mg/kg to all birds. Blood samples were collected at baseline prior to injection (time 0) and then at 0.08, 0.5, 1, 1.5, 4, 8, and 12 hours after drug administration. Butorphanol concentrations were quantitated via liquid chromatography–tandem mass spectrometry. Pharmacokinetic analysis was performed using noncompartmental analysis and a commercially available software program.

RESULTS

Plasma concentrations of butorphanol remained > 100 ng/mL for > 4 hours for some birds (3/5) but were < 100 ng/mL for all birds by the 8-hour mark. Cmax and tmax were 346.9 ± 233.7 ng/mL and 1.3 ± 0.274 hours, respectively. Half-life was 1.56 ± 0.445 hours. No adverse effects were detected.

CLINICAL RELEVANCE

Butorphanol was absorbed from the But-P407 25% by the majority of the orange-winged Amazon parrots in this study (3/5), although to a lesser extent compared to Hispaniolan Amazon parrots. Absorption followed a pharmacokinetic profile compatible with a sustained-release drug. A dose of 12.5 mg/kg, SC, would be expected to provide antinociception for 4 to 8 hours, although pharmacodynamic studies in this species using this formulation have not demonstrated this.

Open access
in American Journal of Veterinary Research

Abstract

OBJECTIVE

To determine (1) if chemokine (C-X-C motif) ligand 1 (CXCL1), matrix metalloproteinase 8 (MMP8), interleukin-10 (IL-10), interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α) can be detected in serum from Asian elephants, and (2) if their concentrations are significantly elevated in Mycobacterium tuberculosis (M.tb) culture–positive elephants compared to –negative elephants. CXCL1, MMP8, IL-10, IFN-γ, and TNF-α were recently identified as potential diagnostic biomarkers for pulmonary tuberculosis in experimental studies in animals and humans. Therefore, we hypothesized that they would be detectable and significantly elevated in M.tb culture–positive elephants compared to M.tb culture–negative elephants.

SAMPLE

101 Asian elephant serum samples, including 91 samples from 6 M.tb-negative elephants and 10 samples from 5 M.tb-positive elephants (none of which exhibited clinical signs of disease). M.tb status was determined by trunk wash culture.

PROCEDURES

Commercially available ELISA kits were used to determine the concentrations of each biomarker in serum samples.

RESULTS

Biomarker concentrations were below the limit of detection for the assay in 100/101 (99%) samples for CXCL1, 98/101 (97%) samples for MMP8, 85/101 (84%) samples for IL-10, 75/101 (74%) samples for IFN-γ, and 45/101 (45%) samples for TNF-α. Multiple M.tb culture–positive elephants did not have detectable levels of any of the 5 biomarkers.

CLINICAL RELEVANCE

CXCL1, MMP8, IL-10, IFN-γ, and TNF-α were not elevated in M.tb culture–positive Asian elephants compared to M.tb culture–negative Asian elephants. This may be related to disease state (ie, clinically asymptomatic). More sensitive assays are needed to better understand the role of these biomarkers in M.tb infection in Asian elephants.

Open access
in American Journal of Veterinary Research

Abstract

OBJECTIVE

To evaluate photobiomodulation therapy in dogs with bilateral hip osteoarthritis.

ANIMALS

20 dogs.

PROCEDURES

Forty joints were assigned to a control group (CG; n = 20) or treatment group (photobiomodulation therapy [PBMT]; 20). CG received a 21-day course of meloxicam, and PBMT received treatment with a Class IV therapeutic laser over 3 weeks. Joint range of motion, thigh girth, the Canine Brief Pain Inventory (divided into pain interference score [PIS] and pain severity score [PSS]), Hudson Visual Analogue Scale, Liverpool Osteoarthritis in Dogs, and Canine Orthopedic Index (COI; divided into function, gait, stiffness, and quality of life) were evaluated before treatment, +8, +15, +30, +60, and +90 days after initial treatment. Results were analyzed with repeated measures ANOVA or Wilcoxon signed ranks test, P < 0.05. Kaplan-Meier estimators were compared with the Breslow test.

RESULTS

Patients had a mean age of 8.3 ± 1.9 years and body weight of 65.7 ± 12.1lb. Osteoarthritis was classified as moderate (n = 26) and severe (14). No differences were found at time 0. Better results were observed in PBMT at +8 days (P = 0.01 for PSS, P = 0.04 for function and COI), +15 days (P = 0.01 for PSS and function, P = 0.02 for PIS and function, P = 0.03 for COI and P = 0.04 for Liverpool Osteoarthritis in Dogs [LOAD]) and +30 days (P = 0.01 for function and gait, P = 0.02 for COI, and P = 0.04 for PIS, PSS, and LOAD). Joint range of motion improved in PBMT from +15 to 90 days. Kaplan-Meier estimators showed that PBMT produced longer periods with better results.

CLINICAL RELEVANCE

PBMT reduced pain levels and improved clinical findings in dogs with hip osteoarthritis.

Open access
in American Journal of Veterinary Research

With over a century of foundational research in animal and human health, the Cornell University College of Veterinary Medicine (CVM) builds on its legacy of addressing current and emerging health issues. Research success has become more dependent than ever on working across disciplines and institutions. CVM values collaborative networks among researchers within Cornell and at other veterinary colleges and with scientists throughout the world. Whether focused on animal health, addressing current human and public health challenges, or prevention of future pandemics, biomedical research meets critical societal needs.

Targeted internal grant programs provide a foundation for animal health and comparative

Open access
in American Journal of Veterinary Research

Abstract

OBJECTIVE

To compare biomechanical strength of 4.75- and 5.5-mm suture anchors when pulled at 45° or 90° angles using 1 versus 2 strands of suture.

SAMPLE

48 synthetic bone block samples.

PROCEDURES

Anchors were inserted into synthetic bone blocks and tested for pullout in 4 configurations (1 suture strand vs 2 strands and 45° vs 90° insertion angle) for a total of 8 groups with 6 samples each. A 3-way ANOVA was used to compare effect of anchor size, strand amount, and angle of pull.

RESULTS

All constructs failed via anchor pullout. Anchor configurations with 2 strands of suture and 4.75-mm anchor (mean, 286 ± 24 N) or 5.5-mm anchor (mean, 300 ± 15 N) had greater pullout strength than configurations with only 1 strand of suture and 4.75-mm anchor (mean, 202 ± 12 N) or 5.5-mm anchor (mean, 286 ± 13.6 N). The 5.5-mm anchors had a higher maximum load to failure under axial pull at 45° (mean, 300 ± 15 N) and 90° (mean, 295 ± 24 N), compared with 4.75-mm anchors at 45° (mean, 202 ± 12 N) and 90° (mean, 208 ± 15 N). There was a higher maximum load to failure for the double-stranded constructs, regardless of anchor size, at both angles of insertion. Anchors inserted at 45° had a higher maximum load to failure than those inserted at 90°. Constructs with 2 strands of suture had a greater pullout strength regardless of the direction of pull.

CLINICAL RELEVANCE

The strength of the anchor construct is likely increased with the use of double-loaded anchors inserted at 45°. Clinicians should consider using 2 strands in clinical cases.

Open access
in American Journal of Veterinary Research

Abstract

OBJECTIVE

To compare sedative, cardiopulmonary, and adverse effects of 3 nalbuphine doses, administered alone or in combination with acepromazine, in dogs.

ANIMALS

6 healthy dogs.

PROCEDURES

Dogs were administered nalbuphine (1.0, 1.5, or 2.0 mg/kg, intravenously [IV]) combined with physiologic saline solution (1 mL, IV; treatments SN1.0, SN1.5, and SN2.0, respectively) or acepromazine (0.05 mg/kg, IV; treatments AN1.0, AN1.5, and AN2.0, respectively) in random order, with a 1-week washout interval between treatments. Sedation scores, heart rate, mean arterial pressure, respiratory rate, and rectal temperature were recorded before and 20 minutes after administration of saline solution or acepromazine (T0), and nalbuphine was administered at T0. Measurements were repeated 15, 30, 60, 90, and 120 minutes after nalbuphine administration.

RESULTS

Treatments SN and AN resulted in at least 120 minutes of mild sedation and 60 minutes of moderate sedation, respectively. Sedation scores were greater for treatments AN1.0, AN1.5, and AN2.0 at various times, compared with scores for treatments SN1.0, SN1.5, and SN2.0, respectively. Administration of nalbuphine alone resulted in salivation and panting in some dogs.

CLINICAL RELEVANCE

All nalbuphine doses promoted mild sedation when administered alone, and moderate sedation when combined with acepromazine. Greater doses of nalbuphine did not increase sedation scores. All treatments resulted in minimal changes in heart rate, respiratory rate, rectal temperature, and mean arterial pressure. Nalbuphine alone resulted in few adverse effects.

Open access
in American Journal of Veterinary Research