Publications by authors named "Jonathan P Mochel"

73 Publications

Computed tomography evaluation of proposed implant corridors in canine thoracic vertebrae.

Vet Surg 2021 Jul 12. Epub 2021 Jul 12.

Department of Veterinary Clinical Sciences, Iowa State University College of Veterinary Medicine, Ames, Iowa, USA.

Objective: Identify acceptable implant corridors in the normal canine thoracic vertebrae (T) from T1 to T9.

Study Design: Retrospective study.

Sample Population: Computed tomographic (CT) studies of normal canine thoracic spines (n = 39).

Methods: CT imaging studies of normal T1-T9 canine spines were evaluated by five independent observers. Each identified a proposed corridor, measured the width, length, and angle off mid-sagittal that the corridor occupied.

Results: CT studies were from 39 dogs weighing 3.19-60 kg (mean 10.72, SD 9.9 kg). Vertebral corridors ranged in average width from 3.8 to 5.2 mm, the widest being located at T1. They ranged in average length from 13.3 to 17.5 mm, shortest being T1 and longest being T6. The angle of corridors varied the most between individual vertebrae at T1-T3. The average corridor angles were: T1 = 38°, T2 = 32°, T3 = 27°, T4 = 26°. T5-T9 angle ranged from 23° to 24°.

Conclusion: The average dimensions of corridors measured in dogs weighing 3.1-60 kg were consistent with those of commercially available cortical screws and pins.

Clinical Significance: Corridor trajectories identified in this population can be achieved from a dorsal approach between T5 and T9. A dorsal approach for implant placement would be challenging for T1-T4 due to the variability found in these vertebrae as well as regional anatomical constraints.
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http://dx.doi.org/10.1111/vsu.13680DOI Listing
July 2021

Corrigendum: Comparative Pharmacokinetics of Meloxicam Between Healthy Post-partum vs. Mid-lactation Dairy Cattle.

Front Vet Sci 2021 26;8:665021. Epub 2021 May 26.

Department of Veterinary Diagnostic and Production Animal Medicine, Iowa State University College of Veterinary Medicine, Ames, IA, United States.

[This corrects the article DOI: 10.3389/fvets.2020.00548.].
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http://dx.doi.org/10.3389/fvets.2021.665021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8188475PMC
May 2021

Focused ultrasound of the caudal vena cava in dogs with cavitary effusions or congestive heart failure: A prospective, observational study.

PLoS One 2021 28;16(5):e0252544. Epub 2021 May 28.

Department of Clinical Sciences, College of Veterinary Medicine, North Carolina State University, Raleigh, North Carolina, United States of America.

Introduction: Ultrasonographic indices of the inferior vena cava are useful for predicting right heart filling pressures in people.

Objectives: To determine whether ultrasonographic indices of caudal vena cava (CVC) differ between dogs with right-sided CHF (R-CHF), left-sided CHF (L-CHF), and noncardiac causes of cavitary effusion (NC).

Materials And Methods: 113 dogs diagnosed with R-CHF (n = 51), L-CHF (30), or NC effusion (32) were enrolled. Seventeen of the R-CHF dogs had pericardial effusion and tamponade. Focused ultrasound was performed prospectively to obtain 2-dimensional and M-mode subxiphoid measures of CVC maximal and minimal size (CVCmax and CVCmin), CVCmax indexed to aortic dimension (CVC:Ao), and CVC collapsibility index (CVC-CI). Variables were compared between study groups using Kruskal-Wallis and Dunn's-Bonferroni testing, and receiver operating characteristics curves were used to assess sensitivity and specificity.

Results: All sonographic CVC indices were significantly different between R-CHF and NC dogs (P < 0.001). Variables demonstrating the highest diagnostic accuracy for discriminating R-CHF versus NC were CVC-CI <33% in 2D (91% sensitive and 96% specific) and presence of hepatic venous distension (84% sensitive and 90% specific). L-CHF dogs had higher CVC:Ao and lower CVC-CI compared to NC dogs (P = 0.016 and P = 0.043 in 2D, respectively) but increased CVC-CI compared to the R-CHF group (P < 0.001).

Conclusions: Ultrasonographic indices of CVC size and collapsibility differed between dogs with R-CHF compared to NC causes of cavitary effusions. Dogs with L-CHF have CVC measurements intermediate between R-CHF and NC dogs.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0252544PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8162640PMC
May 2021

Radiation exposure associated with percutaneous fluoroscopically guided lag screw fixation for sacroiliac luxation in dogs.

Vet Surg 2021 Jul 6;50(5):1065-1075. Epub 2021 May 6.

Iowa State University College of Veterinary Medicine, Ames, Iowa, United States.

Objective: To determine radiation exposure to surgical personnel and to evaluate the accuracy of a modified percutaneous lag screw fixation technique for sacroiliac luxation (SIL) under fluoroscopic guidance in dogs.

Study Design: Cadaveric experimental study.

Sample Population: Seventeen beagle cadavers with iatrogenic SIL.

Methods: Seventeen beagles with iatrogenic SIL underwent reduction and stabilization with 3.5-mm screws. Hypodermic needles (14 gauge) and fluoroscopy were used to orient two Kirschner wires for temporary stabilization and to guide drilling of glide and pilot holes using cannulated drill bits. Duration of surgery and radiation exposure were recorded. Postoperative computed tomographic evaluation of screw position and angulation was performed.

Results: Average time for fixation was 15.85 minutes (range, 6.37-33.5). Cumulative radiation doses of 0.4 mrem for the dominant arm of the assistant and 0 mrem for the primary surgeon were recorded. The mean dorsoventral and craniocaudal screw angles were 0.68° ± 3.4° (range - 5.4° to 9.5°) and 1.9° ± 3.2° (range - 4.3° to 9.1°), respectively. Sixteen of the 17 dogs had 100% sacral screw purchase, with the remaining case achieving 93.4% purchase.

Conclusion: Fluoroscopy-assisted percutaneous placement of 3.5-mm cortical screws in lag fashion performed with 14-gauge needles in conjunction with Kirschner wires and cannulated drill bits yielded repeatable accurate screw placement with low levels of ionizing radiation exposure to the surgical team.

Clinical Significance: The described technique may be a viable method for minimally invasive osteosynthesis fixation of SIL with low levels of radiation exposure to the surgical team. These results provide evidence to support further evaluation of radiation exposure in clinical cases and can aid in study design and sample size determination.
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http://dx.doi.org/10.1111/vsu.13613DOI Listing
July 2021

Short-term outcomes of 59 dogs treated for ilial body fractures with locking or non-locking plates.

Vet Surg 2021 Jul 6;50(5):1076-1086. Epub 2021 May 6.

Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, Iowa, USA.

Objective: To determine the influence of plating systems on the clinical outcomes in dogs treated for ilial fractures.

Design: Retrospective study.

Animals: Fifty-nine dogs (63 hemipelves).

Methods: Radiographs and medical records of dogs with ilial fractures presented to Iowa State University between 2003 and 2019 were reviewed. After fracture reduction, fractures were fixed with a locking plate system (LPS) or non-locking plate system (NLS). Perioperative, long-term complications, and follow-up data were recorded. The frequency of implant failure and pelvic collapse were compared using a logistic and linear regression analysis, respectively. Where the univariate test was statistically significant, a multivariate analysis across categories was performed to identify statistically different categories.

Results: LPS and NLS implants were used in 25/63 and 38/63 hemipelves, respectively. Median follow-up time was 8 weeks (3-624 weeks). Implant failure occurred in 18/63 (29%) of fracture repairs, consisting of 17 with NLS and 1 with LPS. Revision surgery was recommended in five cases of implant failure, all with NLS. The probability of implant failure was higher when fractures were fixed with NLS (p = .0056). All other variables evaluated did not seem to influence outcome measures.

Conclusion: The variable with the most influence on the outcomes of dogs treated for ilial fractures consisted of the fixation method (NLS vs. LPS). Fractures repaired with NLS were nearly 20 times more likely to fail than those repaired with LPS.

Clinical Relevance: Surgeons should consider repairing ilial body fractures in dogs with LPS to reduce the risk of short-term implant failure.
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http://dx.doi.org/10.1111/vsu.13656DOI Listing
July 2021

Comparison of Canine and Human Physiological Factors: Understanding Interspecies Differences that Impact Drug Pharmacokinetics.

AAPS J 2021 04 27;23(3):59. Epub 2021 Apr 27.

Certara UK Limited, Simcyp Division, 1 Concourse Way, Sheffield, S1 2BJ, UK.

This review is a summary of factors affecting the drug pharmacokinetics (PK) of dogs versus humans. Identifying these interspecies differences can facilitate canine-human PK extrapolations while providing mechanistic insights into species-specific drug in vivo behavior. Such a cross-cutting perspective can be particularly useful when developing therapeutics targeting diseases shared between the two species such as cancer, diabetes, cognitive dysfunction, and inflammatory bowel disease. Furthermore, recognizing these differences also supports a reverse PK extrapolations from humans to dogs. To appreciate the canine-human differences that can affect drug absorption, distribution, metabolism, and elimination, this review provides a comparison of the physiology, drug transporter/enzyme location, abundance, activity, and specificity between dogs and humans. Supplemental material provides an in-depth discussion of certain topics, offering additional critical points to consider. Based upon an assessment of available state-of-the-art information, data gaps were identified. The hope is that this manuscript will encourage the research needed to support an understanding of similarities and differences in human versus canine drug PK.
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http://dx.doi.org/10.1208/s12248-021-00590-0DOI Listing
April 2021

Inflammation, negative affect, and amyloid burden in Alzheimer's disease: Insights from the kynurenine pathway.

Brain Behav Immun 2021 07 26;95:216-225. Epub 2021 Mar 26.

Department of Symptom Research, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Background: Depressive symptoms in Alzheimer's disease (AD) predict worse cognitive and functional outcomes. Both AD and major depression inflammatory processes are characterized by shunted tryptophan metabolism away from serotonin (5-HT) and toward the neuroinflammatory kynurenine (Kyn) pathway. The present study assessed associations between Kyn and behavioral, neuroanatomical, neuropathological, and physiological outcomes common to both AD and negative affect across the AD continuum.

Methods: In 58 cognitively normal, 396 mild cognitive impairment, and 112 AD participants from the Alzheimer's Disease Neuroimaging Initiative-1 (ADNI1) cohort, serum markers of 5-HT, tryptophan, and Kyn were measured and their relationships investigated with immunologic markers, affect and functional outcomes, CSF markers of beta-amyloid (Aβ) and tau, and regional gray matter.

Results: A higher Kyn/Tryptophan ratio was linked to many inflammatory markers, as well as lower functional independence and memory scores. A higher Kyn/5-HT ratio showed similar associations, but also strong relationships with negative affect and neuropsychiatric disturbance, executive dysfunction, and global cognitive decline. Further, gray matter atrophy was seen in hippocampus, anterior cingulate, and prefrontal cortices, as well as greater amyloid and total tau deposition. Finally, using moderated-mediation, several pro-inflammatory factors partially mediated Kyn/5-HT and negative affect scores in participants with subclinical Aβ (i.e., Aβ-), whereas such associations were fully mediated by Complement 3 in Aβ+ participants.

Conclusion: These findings suggest that inflammatory signaling cascades may occur during AD, which is associated with increased Kyn metabolism that influences the pathogenesis of negative affect. Aβ and the complement system may be critical contributing factors in this process.
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http://dx.doi.org/10.1016/j.bbi.2021.03.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8187283PMC
July 2021

Effect of prazosin on feline recurrent urethral obstruction.

J Feline Med Surg 2021 Mar 22:1098612X211001283. Epub 2021 Mar 22.

Lakeshore Veterinary Specialists, Glendale, WI, USA.

Objectives: The aim of this study was to determine if male cats treated with 7 days of prazosin following relief of urethral obstruction (UO) experienced decreased rates of recurrent urethral obstruction (rUO) within 30 days vs those treated with 7 days of placebo.

Methods: All castrated male cats presenting for the first time with UO from May 2014 to August 2017 were eligible for enrollment. Exclusion criteria included the administration of medications or passage of a urinary catheter prior to referral, the presence of heart disease or hypertension requiring medication, prior treatment with glucocorticoids, non-steroidal anti-inflammatory medications, prazosin or phenoxybenzamine, or radiographic identification of cystoliths. Cats were treated with standardized anesthetic and analgesic protocols, standardized indwelling urinary catheter management, and were hospitalized for care. A random numbers table was generated prior to study initiation and cats were randomized to receive either prazosin (0.5 mg PO q12h for 7 days) or placebo in a blinded fashion. A 30-day follow-up with owners via telephone was performed to identify the rate of rUO. Cats that did not receive the full course of study medication were removed from the analysis. The study was unblinded at the end of data collection.

Results: Eighty cats were enrolled and 65 cats completed the study; 12 were excluded because they did not receive the study medication. Sixteen of 65 cats experienced rUO (25%). Of the 16 cats experiencing rUO, five received placebo (n = 5/28 [18%]) and 11 received prazosin (n = 11/37 [30%]). Ten of the cats that experienced rUO reblocked while still hospitalized. There was no significant difference in frequency of rUO in cats treated with prazosin vs placebo ( = 0.27).

Conclusions And Relevance: Prazosin administered at 0.5 mg PO q12h did not decrease the rate of rUO in this population of obstructed male cats vs placebo. These results further support evidence suggesting that prazosin may not be beneficial in prevention of feline rUO.
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http://dx.doi.org/10.1177/1098612X211001283DOI Listing
March 2021

Influence of Schirmer strip wetness on volume absorbed, volume recovered, and total protein content in canine tears.

Vet Ophthalmol 2021 Mar 15. Epub 2021 Mar 15.

Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, USA.

Objective: Determine the protein content and volume of tears sampled by Schirmer strips wetness ranging from 20 to 35 mm.

Animals Studied: Ten healthy beagle dogs.

Procedures: Each dog underwent 20 tear collections per day (10 sessions in each eye, spaced by ≥1 h) for 4 separate days, providing 200 tear samples for each length of wetness evaluated: 20, 25, 30, and 35 mm. A Schirmer strip was placed in each eye until the selected mm-mark was reached, calculating the volume absorbed (VA) as the difference between the post- and pre-collection weight (assuming 1 mg~1 µL for tear fluid), and the volume recovered (VR) as the amount pipetted from the tube following centrifugation. Total protein content (TPC) was measured with infrared spectroscopy. Outcome measures were compared with the Kruskal-Wallis test.

Results: Median values for VA (µL), VR (µL) and TPC (mg/mL) were as follows: 20 mm (18, 10, 5.94), 25 mm (22, 12.5, 5.97), 30 mm (25.5, 16, 5.89), and 35 mm (31, 22.5, 7.13). Both VA and VR were significantly greater (p < .001) for Schirmer strips wetness of 35»30»25»20 mm. TPC was significantly greater (p < .001) for 35 > 20-30 mm, but not among other groups (p = 1.000).

Conclusions: The study established normative data to consider when canine studies use Schirmer strips to collect tears for bioanalytical purposes (eg, proteomics, pharmacokinetics). Although 35 mm yielded higher VA and VR, the higher TPC could be explained by greater disruption of ocular surface homeostasis. Absorption to 20-30 mm is the suggested length of strip wetness for bioanalytical tear collection in dogs.
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http://dx.doi.org/10.1111/vop.12876DOI Listing
March 2021

A Multi-Institutional Retrospective Analysis of Toceranib Phosphate for Presumed or Confirmed Canine Aortic Body Chemodectomas.

Front Vet Sci 2021 5;8:635057. Epub 2021 Feb 5.

Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, United States.

Aortic body tumors, specifically chemodectomas, are the second most common type of canine cardiac tumor; however, information about treatment is currently lacking. This study included dogs with a presumptive or definitive diagnosis of an aortic body chemodectoma that underwent treatment with toceranib phosphate. Cases were solicited via the American College of Veterinary Internal Medicine Cardiology, Internal Medicine, and Oncology listservs using an electronic survey. Cox multivariate analysis of factors potentially impacting survival time was completed. Twenty-seven (27) cases were included in analysis. The clinical benefit rate (complete remission, partial remission, or stable disease >10 weeks) was 89%. A median survival time of 478 days was found for those receiving toceranib alone ( = 14), which was not statistically different from those treated with additional modalities (521 days). No factors evaluated statistically impacted outcome. Further, prospective studies are warranted to evaluate the use of toceranib for the treatment of canine aortic body chemodectomas.
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http://dx.doi.org/10.3389/fvets.2021.635057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892462PMC
February 2021

Emerging Roles of Urine-Derived Components for the Management of Bladder Cancer: One Man's Trash Is Another Man's Treasure.

Cancers (Basel) 2021 Jan 23;13(3). Epub 2021 Jan 23.

SMART Translational Medicine, Department of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA 50011-1250, USA.

Urinary bladder cancer (UBC) is the most common malignancy of the urinary tract in humans, with an estimated global prevalence of 1.1 million cases over 5 years. Because of its high rates of recurrence and resistance to chemotherapy, UBC is one of the most expensive cancers to treat, resulting in significant health care costs. The development of innovative molecular and cellular tools is necessary to refine patient stratification and help predict response to treatment. Urine is an underused resource of biological components shed from bladder tumors, such as exfoliated cells and extracellular vesicles, that could serve as molecular fingerprints and provide valuable biological insights into tumor phenotype and mechanisms of resistance to chemotherapy. Additionally, characterization of urine-derived extracellular vesicles and cells could be used as reliable biomarkers for prediction of response to neoadjuvant therapy.
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http://dx.doi.org/10.3390/cancers13030422DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7865365PMC
January 2021

Pharmacokinetics and Tissue Levels of Pantoprazole in Neonatal Calves After Intravenous Administration.

Front Vet Sci 2020 27;7:580735. Epub 2020 Nov 27.

Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA, United States.

Neonatal calves are at risk of developing abomasal ulceration, but there is a lack of pharmacokinetic data for potential anti-ulcerative therapies, such as pantoprazole, in ruminant species. The study objectives were to estimate plasma pharmacokinetic parameters for pantoprazole in neonatal dairy calves after intravenous (IV) administration. A secondary objective was to quantify the concentrations of pantoprazole in edible tissues after IV dosing. Pantoprazole was administered to 9 neonatal Holstein calves at a dose of 1 mg/kg IV. Plasma samples were collected over 24 h and analyzed via HPLC-MS for determining pantoprazole concentrations. Pharmacokinetic parameters were derived via non-compartmental analysis. Tissue samples were collected at 1, 3, and 5 days after administration and analyzed via HPLC-MS. Following IV administration, plasma clearance, elimination half-life, and volume of distribution of pantoprazole were estimated at 4.46 mL/kg/min, 2.81 h, and 0.301 L/kg, respectively. The global extraction ratio was estimated at 0.053 ± 0.015. No pantoprazole was detected in the edible tissues 1, 3, or 5 days after administration. A metabolite, pantoprazole sulfone was detected in all the edible tissues 1 and 3 days after administration. The reported plasma clearance for pantoprazole is less than that reported for alpacas but higher than reported in foals. The elimination half-life in calves appears to be longer than observed in foals and alpacas. While pantoprazole sulfone was detected in the tissues after IV administration, further research is needed as to the metabolism and potential tissue accumulation of other pantoprazole metabolites in calves. Future pharmacodynamic studies are necessary to determine the efficacy of pantoprazole on abomasal acid suppression in calves.
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http://dx.doi.org/10.3389/fvets.2020.580735DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7728716PMC
November 2020

Genetic Factors of Alzheimer's Disease Modulate How Diet is Associated with Long-Term Cognitive Trajectories: A UK Biobank Study.

J Alzheimers Dis 2020 ;78(3):1245-1257

Department of Food Science and Human Nutrition, Iowa State University, Ames, IA, USA.

Background: Fluid intelligence (FI) involves abstract problem-solving without prior knowledge. Greater age-related FI decline increases Alzheimer's disease (AD) risk, and recent studies suggest that certain dietary regimens may influence rates of decline. However, it is uncertain how long-term food consumption affects FI among adults with or without familial history of AD (FH) or APOE4 (ɛ4).

Objective: Observe how the total diet is associated with long-term cognition among mid- to late-life populations at-risk and not-at-risk for AD.

Methods: Among 1,787 mid-to-late-aged adult UK Biobank participants, 10-year FI trajectories were modeled and regressed onto the total diet based on self-reported intake of 49 whole foods from a Food Frequency Questionnaire (FFQ).

Results: Daily cheese intake strongly predicted better FIT scores over time (FH-: β= 0.207, p < 0.001; ɛ4-: β= 0.073, p = 0.008; ɛ4+: β= 0.162, p = 0.001). Alcohol of any type daily also appeared beneficial (ɛ4+: β= 0.101, p = 0.022) and red wine was sometimes additionally protective (FH+: β= 0.100, p = 0.014; ɛ4-: β= 0.59, p = 0.039). Consuming lamb weekly was associated with improved outcomes (FH-: β= 0.066, p = 0.008; ɛ4+: β= 0.097, p = 0.044). Among at risk groups, added salt correlated with decreased performance (FH+: β= -0.114, p = 0.004; ɛ4+: β= -0.121, p = 0.009).

Conclusion: Modifying meal plans may help minimize cognitive decline. We observed that added salt may put at-risk individuals at greater risk, but did not observe similar interactions among FH- and AD- individuals. Observations further suggest in risk status-dependent manners that adding cheese and red wine to the diet daily, and lamb on a weekly basis, may also improve long-term cognitive outcomes.
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http://dx.doi.org/10.3233/JAD-201058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7895545PMC
January 2020

Pharmacokinetics of Oral Prednisone at Various Doses in Dogs: Preliminary Findings Using a Naïve Pooled-Data Approach.

Front Vet Sci 2020 19;7:571457. Epub 2020 Oct 19.

Department of Biomedical Sciences, SMART Pharmacology, College of Veterinary Medicine, Iowa State University, Ames, IA, United States.

This pilot study aimed to determine the plasma pharmacokinetics of prednisone and its active metabolite prednisolone following oral prednisone administration in dogs-using dosing regimens that cover anti-inflammatory to immuno-suppressive biological effects. Six healthy Beagle dogs were given 0.5, 1, 2, and 4 mg/kg prednisone orally once daily for 5 days, each successive course separated by a washout period of 9 days. At steady-state (Day 4), a sparse sampling design allowed for collection of blood from 2/6 individuals for each of the following time points: 0, 15, 30, 60, 90, 120, 240, 480, and 720 min. Prednisone and prednisolone were quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Oral prednisone was rapidly converted to prednisolone in dogs (≤ 30 min), with plasma prednisolone reaching ~6-fold greater levels (0-656.1 ng/mL) than prednisone (0-98.8 ng/mL) overall. The ratio of plasma prednisolone/prednisone was constant across the dosing regimens, indicating a non-saturation of the hepatic 11-β-hydroxysteroid dehydrogenase that converts the prodrug to the active metabolite in dogs. The level of both corticosteroids increased with increasing dosing regimens, albeit in a non-linear manner. Non-compartmental pharmacokinetic parameters are described, including peak concentration (C), time of peak concentration (T), area under the concentration-time curve (AUC), and the elimination half-life (t ) for both corticosteroids, as well as clearance and volume of distribution during the terminal phase (V) for the administered drug (prednisone). In sum, the present study utilizes a sparse sampling and naïve pooled-data approach to estimate pharmacokinetic parameters for prednisone and prednisolone, providing supporting preliminary knowledge that can be used to optimize corticosteroid efficacy and minimize toxicity in canine patients.
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http://dx.doi.org/10.3389/fvets.2020.571457DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7604266PMC
October 2020

Tear Film Pharmacokinetics and Systemic Absorption Following Topical Administration of 1% Prednisolone Acetate Ophthalmic Suspension in Dogs.

Front Vet Sci 2020 27;7:571350. Epub 2020 Oct 27.

Department of Biomedical Sciences, SMART Pharmacology, College of Veterinary Medicine, Iowa State University, Ames, IA, United States.

The study aimed to determine the tear film pharmacokinetics following topical administration of 1% prednisolone acetate-assessing whether two drops would provide a superior kinetic profile compared to one drop-and to determine the fraction of an eye drop that reaches the systemic circulation in dogs. Two separate experiments were conducted in eight healthy Beagle dogs: (i) Instillation of 1 drop (35 μL) or 2 drops (70 μL) of 1% prednisolone acetate ophthalmic suspension in each eye, followed by tear collections with Schirmer strips from 0 to 720 min; (ii) Instillation of 1 or 2 drops of 1% prednisolone acetate in both eyes 4 times daily for 3 days, followed by blood collection 10-15 min after each topical administration on Day 3. Tear and blood samples were analyzed with high performance liquid chromatography to determine the levels of prodrug (prednisolone acetate), active metabolite (prednisolone) and total prednisolone (prednisolone = prodrug + active metabolite). Prednisolone levels represented 10 and 72% of prednisolone concentrations in tears and plasma, respectively, indicating a greater hydrolysis of prodrug in the blood vs. tear compartment. For eyes receiving one or two drops, tear film prednisolone concentrations were high (~3.1 mg/mL) immediately following topical administration but rapidly decreased by ~45% at 1 min and ~95% at 15 min. No differences were noted between 1 vs. 2 drops in tear film prednisolone concentrations (including maximal concentration, C) or residual drug levels in tears at any time point ( ≥ 0.097); however, instillation of 2 drops provided a higher average tear concentration (C) and overall drug exposure to the ocular surface (AUC) over the 12-h sampling period ( = 0.009). Average plasma prednisolone concentration represented ≤ 2% of the dose applied to the ocular surface, and did not differ significantly for dogs receiving 1 drop (17 ng/mL) or 2 drops (20 ng/mL) 4 times daily for 3 days ( = 0.438). In sum, topical corticotherapy is beneficial for inflammatory conditions of the canine anterior segment given the relatively high concentrations achieved in tears, although caution is warranted to prevent unwanted local or systemic adverse effects.
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http://dx.doi.org/10.3389/fvets.2020.571350DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7652929PMC
October 2020

Impact of diurnal variation, sex, tear collection method, and disease state on tear protein levels in dogs.

Vet Ophthalmol 2020 Nov 28;23(6):994-1000. Epub 2020 Oct 28.

Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, USA.

Objective: To investigate the effects of various biological factors on total protein concentration (TPC) and serum albumin levels in canine tears.

Animals Studied: 10 healthy beagles (5 female, 5 male) were used.

Procedures: Experiments were conducted on separate days, collecting tears with either capillary tubes or Schirmer strips, as follows: (i) Tear collection at 3 hours intervals (from 6 am to 12 am); and (ii) Tear collection before and 20 minutes following topical histamine application (1, 10, 375 mg/mL) to induce mild, moderate, and severe conjunctivitis, respectively. TPC and serum albumin were measured with infrared spectroscopy and ELISA, respectively.

Results: Tear film TPC and serum albumin ranged from 9.7-26.1 mg/mL and 6.4-1662.6 µg/mL, respectively. Protein levels did not differ significantly among time points (P ≥ .080). Median coefficient of variation (CV%) was lower with Schirmer strips compared to capillary tubes for both TPC (12% vs 15%, P = .020) and serum albumin (57% vs 78%, P = .232). TPC (P < .001), but not serum albumin was greater in male vs. female dogs. Serum albumin, but not TPC (P ≥ .099), increased significantly with each grade of conjunctivitis severity (P < .001), with no differences between collection devices (P ≥ .322); median increase was 106%, 1389%, and 2871% in eyes with mild, moderate, and severe conjunctivitis, respectively.

Conclusions: There is no apparent diurnal variation in canine tear protein levels. Blood-tear barrier breakdown with conjunctivitis allows serum albumin to leak into the tear film at high concentrations. Schirmer strips compare well with capillary tubes for bioanalytical purposes in healthy and diseased eyes, and this collection method may offer improved reproducibility for protein quantification.
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http://dx.doi.org/10.1111/vop.12840DOI Listing
November 2020

Non-Linear Mixed-Effects Pharmacokinetic Modeling of the Novel COX-2 Selective Inhibitor Vitacoxib in Cats.

Front Vet Sci 2020 24;7:554033. Epub 2020 Sep 24.

Department of Veterinary Pharmacology and Toxicology, College of Veterinary Medicine, China Agricultural University, Beijing, China.

The objective of this study was to develop a non-linear mixed-effects (NLME) model to describe the disposition kinetics of vitacoxib in cats following intravenous (I.V) and oral (P.O) (single and multiple) dosing. Data from six consecutive studies with 16 healthy neutered domestic short hair cats were pooled together to build a pharmacokinetic (PK) model using NLME. Population PK parameters were estimated using the stochastic approximation expectation maximization (SAEM) algorithm implemented in Monolix 2019R2. A two-compartment mammillary disposition model with simultaneous zero- and first-order absorption best described the PK of vitacoxib in plasma after oral dosing. The systemic CL of vitacoxib was found to be low (110 ml/h), with a steady-state volume of distribution (VSS) of 3.42 L in cats. Results from the automated covariate search in Monolix 2019R2 showed that bodyweight had a significant effect on the central volume of distribution of vitacoxib. Lastly, using Monte Carlo simulations, we investigated the time course of several dosages of vitacoxib from 0.01 to 8 mg/kg. Using this simulation set, we found a range of reasonable dosages that produce therapeutic plasma concentrations of vitacoxib for 24 h or more in cats.
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http://dx.doi.org/10.3389/fvets.2020.554033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7546276PMC
September 2020

Comparative Pharmacokinetics of Meloxicam Between Healthy Post-partum vs. Mid-lactation Dairy Cattle.

Front Vet Sci 2020 8;7:548. Epub 2020 Sep 8.

Department of Veterinary Diagnostic and Production Animal Medicine, Iowa State University College of Veterinary Medicine, Ames, IA, United States.

Lactating dairy cattle are at risk for various painful conditions throughout their life, such as lameness, parturition, mastitis, and metabolic disorders. These conditions necessitate adequate methods of analgesia to address welfare concerns through efficacious pain mitigation. As no method of analgesia has been approved for lactating dairy cattle, to date, research is necessary to determine effective pain management strategies for dairy cattle. In both the European Union and Canada, meloxicam has been approved for use in lactating dairy cattle as a methodology for pain control. The objective of this study was to characterize the pharmacokinetics of meloxicam administered orally and intravenously to lactating dairy cattle in the post-partum vs. mid-lactation period. In this parallel study design, 12 healthy, lactating Holsteins were enrolled within 24 h of freshening and randomly allocated to intravenous (0.2 mg/kg) or oral (1.0 mg/kg) meloxicam administration treatment groups. They were matched based on parity to 12, healthy cows that were considered mid-lactation [>150 days-in-milk (DIM)] to receive the same treatment. Based on meloxicam formulation, sampling times varied and plasma was collection via jugular venipuncture for 6 days. Plasma drug concentrations were evaluated using liquid chromatography coupled with mass spectroscopy and pharmacokinetic properties were evaluated using non-compartmental (i.e., statistical moments) analysis. Results indicated a decreased systemic clearance of meloxicam in post-partum relative to mid-lactation cows, which resulted in a longer half-life and increased total exposure independent of mode of administration. These results suggest a need for dose adjustments based on stage in lactation and further assessment of the impact of days-in-milk on milk withholding period.
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http://dx.doi.org/10.3389/fvets.2020.00548DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7506135PMC
September 2020

Pharmacokinetics of Intravenous, Intramuscular, Oral, and Transdermal Administration of Flunixin Meglumine in Pre-wean Piglets.

Front Vet Sci 2020 28;7:586. Epub 2020 Aug 28.

Swine Medicine Education Center, College of Veterinary Medicine, Iowa State University, Ames, IA, United States.

Castration and tail-docking of pre-wean piglets are common procedures that are known to induce pain and would benefit from pain mitigation. Flunixin meglumine (FM) is a non-steroidal anti-inflammatory drug currently approved in the United States for pyrexia in swine and lameness pain in cattle. The objective of this study was to establish the pharmacokinetic (PK) parameters resulting from intravenous (IV), intramuscular (IM), oral (PO) and transdermal (TD) administration of FM in pre-wean piglets. FM was administered to thirty-nine pre-wean piglets at a target dose of 2.2 mg/kg for IV and IM and 3.3 mg/kg for PO and TD route. Plasma was collected at twenty-seven time points from 0 to 9 days after FM administration and concentrations were determined using ultra-high performance liquid chromatography coupled with mass spectrometry (UPLC-MS). Pharmacokinetic data were analyzed using noncompartmental analysis (NCA) methods and nonlinear mixed-effects (NLME). Initial plasma concentration for IV (C) 11,653 μg/L and mean peak plasma concentrations (C) 6,543 μg/L (IM), 4,883 μg/L (PO), and 31.5 μg/L (TD) were measured. The time points of peak FM concentrations (t) were estimated 30 min, 1 h, and 24 h for IM, PO, and TD, respectively. The bioavailability () of PO and IM FM was estimated at >99%, while the bioavailability of TD FM was estimated to be 7.8%. The reported C of FM after IM and PO administration is consistent with therapeutic concentration ranges that mitigate pain in other species and adult pigs. However, the low estimated concentration of FM after TD dosing is not expected to mitigate pain in pre-wean piglets. The low of TD FM suggests that expanding the surface area of application is unlikely to be sufficient to establish an effective TD dose for pain, while the high bioavailability for PO FM should allow for an effective dose regimen to be established.
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http://dx.doi.org/10.3389/fvets.2020.00586DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7485418PMC
August 2020

Serum albumin and total protein concentration in the tear film of horses with healthy or diseased eyes.

Vet Ophthalmol 2021 Jan 12;24(1):20-27. Epub 2020 Sep 12.

Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, USA.

Objective: To determine total protein content (TPC) and serum albumin levels in the tears of horses with healthy or diseased eyes.

Animals Studied: Forty-two horses with healthy eyes and 11 horses with unilateral (n = 10) or bilateral (n = 1) ocular disease.

Procedure: Each eye underwent an ophthalmic examination including detailed conjunctivitis scoring and tear collection with Schirmer strips. TPC and serum albumin levels were quantified in tear samples and compared among healthy eyes, affected eyes, and contralateral unaffected eyes. The impact of the following variables on lacrimal protein levels were assessed: age, breed, and sex (healthy eyes), as well as conjunctivitis score (diseased eyes).

Results: Lacrimal TPC ranged from 7.0 to 19.5 mg/mL in healthy eyes, while serum albumin ranged from 71.1 to 711.3 µg/mL (~1.6% of TPC) and was higher in tears of aged and female horses (P ≤ .033). Eyes with ocular disease had significantly greater (P ≤ .001) serum albumin in tears (median 679.6 µg/mL) compared to contralateral unaffected eyes (130.0 µg/mL) and eyes of the reference population (200.7 µg/mL). However, lacrimal TPC did not differ significantly among the 3 groups. Scoring of palpebral conjunctival hyperemia trended toward a positive association with serum albumin in tears (r = 0.49, P = .062).

Conclusions: The protein profile in equine tears differs in health and disease. Serum albumin in tears increases with ocular disease and, similar to other species, might serve as a biomarker for ocular insult in horses. Future studies could investigate the protein levels in horses with specific ocular conditions and help determine the biological importance of albumin on the equine ocular surface.
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http://dx.doi.org/10.1111/vop.12822DOI Listing
January 2021

Evaluation of a Respiratory Disease Induction Model for Goats ().

Comp Med 2020 10 9;70(5):323-328. Epub 2020 Sep 9.

Veterinary Microbiology and Preventive Medicine, Iowa State University, Ames, Iowa.

Infectious respiratory diseases are a serious health concern worldwide. However, few models describe the experimental induction of lung infection, or the effect of experimental infection on clinical pathologic parameters in goats. Goats offer benefits compared to cattle because of size and tractability and compared to sheep with regard to specific features of their anatomy. In previous experimental models of infection in goats, coadministration of an immunosuppressive dose of a corticosteroid is common; however, protocols that use corticosteroid often note mortality as an adverse effect. We therefore investigated an infection protocol that did not use immunosuppression but instead relied on 2 intratracheal inoculations of in healthy meat goats to induce clinical and hematologic changes associated with respiratory infection. Healthy Boer or Boer-Kiko cross goats ( = 6; age, 10 mo) were inoculated with and were monitored over a 312-h period for clinical and hematologic parameters of infection. After induction of pneumonia, the goats had a significant 1.2 °C rise in rectal temperature and auscultatable rales for up to 96 h. Lymphocyte counts, serum amyloid A values, and respiratory scores were significantly different before and after induction of disease and were consistent with respiratory infection. No mortality was associated with this experimental infection, and minimal gross pathologic changes were noted at study termination. The clinical and pathologic findings of this study suggest a potentially reproducible method of establishing clinical respiratory infection in goats. The repeated intratracheal inoculation method of inducing caprine respiratory disease can be used to produce experimental respiratory disease in goats when the use of corticosteroid is not desirable. With the feasibility of this method established, additional research evaluating the optimal dose and frequency of administration is needed.
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http://dx.doi.org/10.30802/AALAS-CM-20-000002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7574216PMC
October 2020

CSF glucose tracks regional tau progression based on Alzheimer's disease risk factors.

Alzheimers Dement (N Y) 2020 24;6(1):e12080. Epub 2020 Aug 24.

Department of Food Science and Human Nutrition Iowa State University Ames Iowa USA.

Introduction: Glucose hypometabolism and tau formation are key features of Alzheimer's disease (AD). Less is known about the relationship between fasting glucose and regional tau accumulation.

Methods: Cerebrospinal fluid (CSF) glucose was linearly regressed on regional tau (flortaucipir) among 169 Alzheimer's Disease Neuroimaging Initiative (ADNI3) participants. Flortaucipir uptake was examined by Braak stages and regions of interest (ROIs). Interactions were explored between CSF glucose and AD risk factors including regional amyloid beta (Aβ), sex, Apolipoprotein E ε4 (ε4) status, AD parental family history (AD FH), and cognitive impairment (CI).

Results: Interactions found higher CSF glucose tracked less tau in ROIs or Braak stages I/II (women, ε4+, regional Aβ), III/IV (AD FH+, regional Aβ), and V/VI (AD FH+). CI drove Braak III-VI associations.

Discussion: Among women and ε4 carriers, higher CSF glucose tracked less early-stage tau. Higher CSF glucose may reflect compensation against tau spreading in CI, Aβ+, or AD FH+.
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http://dx.doi.org/10.1002/trc2.12080DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7443745PMC
August 2020

Treatment With Hydrolyzed Diet Supplemented With Prebiotics and Glycosaminoglycans Alters Lipid Metabolism in Canine Inflammatory Bowel Disease.

Front Vet Sci 2020 30;7:451. Epub 2020 Jul 30.

Department of Veterinary Clinical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, United States.

Canine inflammatory bowel disease (IBD) is a chronic, immunologically mediated intestinal disorder, resulting from the complex interaction of genetic, environmental and immune factors. Hydrolyzed diets are used in dogs with food-responsive diarrhea (FRD) to reduce adverse responses to immunostimulatory proteins. Prebiotics (PRBs) and glycosaminoglycans (GAGs) have previously been demonstrated to show anti-inflammatory activity in the intestinal mucosa. Notably, hydrolyzed diets combined with the administration of PRBs and GAGs offer a promising approach for the treatment of canine IBD. Our aim was to investigate the effects of hydrolyzed diet and GAG+PRB co-treatment on the serum metabolomic profile of IBD dogs. Dogs with IBD randomly received either hydrolyzed diet supplemented with GAGs and PRBs (treatment 1) or hydrolyzed diet alone (treatment 2) for 10 weeks. A targeted metabolomics approach using mass spectrometry was performed to quantify changes in the serum metabolome before and after treatment and between treatment 1 and 2. Principal component analysis (PCA), partial least squares-discriminant analysis (PLS-DA), hierarchical cluster analysis (HCA) and univariate statistics were used to identify differences between the treatment groups. PCA, PLS-DA, and HCA showed a clear clustering of IBD dogs before and after hydrolyzed diet, indicating that the treatment impacted the serum metabolome. Univariate analysis revealed that most of the altered metabolites were involved in lipid metabolism. The most impacted lipid classes were components of cell membranes, including glycerophospholipids, sphingolipids, and di- and triglycerides. In addition, changes in serum metabolites after GAG+PRB co-treatment suggested a possible additional beneficial effect on the lipid metabolism in IBD dogs. In conclusion, the present study showed a significant increase in metabolites that protect gut cell membrane integrity in response to hydrolyzed diet alone or in combination with GAG+PRB co-treatment. Administration of such treatment over 70 days improved selected serum biomarkers of canine IBD, possibly indicating improved intestinal membrane integrity.
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http://dx.doi.org/10.3389/fvets.2020.00451DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7406657PMC
July 2020

An eye on the dog as the scientist's best friend for translational research in ophthalmology: Focus on the ocular surface.

Med Res Rev 2020 11 31;40(6):2566-2604. Epub 2020 Jul 31.

Department of Biomedical Sciences, SMART Pharmacology, College of Veterinary Medicine, Iowa State University, Ames, Iowa, USA.

Preclinical animal studies provide valuable opportunities to better understand human diseases and contribute to major advances in medicine. This review provides a comprehensive overview of ocular parameters in humans and selected animals, with a focus on the ocular surface, detailing species differences in ocular surface anatomy, physiology, tear film dynamics and tear film composition. We describe major pitfalls that tremendously limit the translational potential of traditional laboratory animals (i.e., rabbits, mice, and rats) in ophthalmic research, and highlight the benefits of integrating companion dogs with clinical analogues to human diseases into preclinical pharmacology studies. This One Health approach can help accelerate and improve the framework in which ophthalmic research is translated to the human clinic. Studies can be conducted in canine subjects with naturally occurring or noninvasively induced ocular surface disorders (e.g., dry eye disease, conjunctivitis), reviewed herein, and tear fluid can be easily retrieved from canine eyes for various bioanalytical purposes. In this review, we discuss common tear collection methods, including capillary tubes and Schirmer tear strips, and provide guidelines for tear sampling and extraction to improve the reliability of analyte quantification (drugs, proteins, others).
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http://dx.doi.org/10.1002/med.21716DOI Listing
November 2020

Impact of acute conjunctivitis on ocular surface homeostasis in dogs.

Vet Ophthalmol 2020 Sep 15;23(5):828-833. Epub 2020 Jul 15.

SMART Pharmacology, Department of Biomedical Sciences, College of Veterinary Medicine, Iowa State University, Ames, IA, USA.

Objective: To investigate the effects of acute conjunctivitis on tear film characteristics and corneal sensitivity in dogs.

Animals Studied: Eight female spayed Beagle dogs (1.5-2 years old, 7.5-10 kg).

Procedures: On two consecutive days, one randomly selected eye in each dog received 1 or 375 mg/mL histamine solution to induce mild or severe conjunctivitis, while the contralateral eye served as control. Diagnostic tests were performed in the following order: fluorescein instillation and repeated tear collection over 20 minutes (to determine tear volume [TV] and turnover rate [TTR] by fluorophotometry), Schirmer tear test-1 (STT-1), tear ferning, corneal esthesiometry, and tear film breakup time (TFBUT).

Results: Results are presented as median values for severe conjunctivitis, mild conjunctivitis, and control eyes. Eyes with severe conjunctivitis had significantly higher STT-1 (24, 19.5, 17.5 mm/min; P = .002) and significantly lower TFBUT (10.5, 13.5, 15.5 s; P = .002), but no changes were noted in corneal tactile sensation (2, 2.5, 2.5 cm) or tear ferning (grades 2, 2, 2.5). Severe conjunctivitis significantly increased TV by nearly 10-fold (631, 97, 65 µL) initially (reflex tearing), although basal TV returned rapidly (<5 minutes) in all eyes (46, 58, 48 µL). Finally, there was a nonsignificant trend for higher reflex TTR in the conjunctivitis vs control eyes (68, 58, 43%/min).

Conclusions: Experimentally induced conjunctivitis increases tear quantity and decreases tear quality in dogs, but has no impact on corneal sensitivity. Changes in tear film dynamics could affect ocular pharmacology (eg, precorneal retention time), although homeostasis of lacrimal volume and drainage is rapidly restored.
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http://dx.doi.org/10.1111/vop.12804DOI Listing
September 2020

Walking in the Light: How History of Physical Activity, Sunlight, and Vitamin D Account for Body Fat-A UK Biobank Study.

Obesity (Silver Spring) 2020 08 22;28(8):1428-1437. Epub 2020 Jun 22.

Department of Food Science and Human Nutrition, Iowa State University, Ames, Iowa, USA.

Objective: The high prevalence of vitamin D deficiency and obesity drives the need for successful strategies that elevate vitamin D levels, prevent adipogenesis, and stimulate lipolysis. This study provides a theoretical model to evaluate how physical activity (PA) and sunlight exposure influence serum vitamin D levels and regional adiposity. This study hypothesized a posteriori that sunlight is associated with undifferentiated visceral adiposity by increasing the ratio of brown to white adipose tissue.

Methods: Using 10-year longitudinal data, accelerometry, a sun-exposure questionnaire, and regional adiposity quantified by dual-energy x-ray absorptiometry imaging, a structural-equation mediation model of growth curves was constructed with a data-driven methodology.

Results: Sunlight and PA conjointly increased serum vitamin D. Changes in vitamin D levels partially mediated how sunlight and PA impacted adiposity in visceral and subcutaneous regions within a subjective PA model. In an objective PA model, vitamin D was a mediator for subcutaneous regions only. Interestingly, sunlight was associated with less adiposity in subcutaneous regions but greater adiposity in visceral regions.

Conclusions: Sunlight and PA may increase vitamin D levels. For the first time, this study characterizes a positive association between sunlight and visceral adiposity. Further investigation and experimentation are necessary to clarify the physiological role of sunlight exposure on adipose tissue.
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http://dx.doi.org/10.1002/oby.22852DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7501143PMC
August 2020

Recapitulation of the accessible interface of biopsy-derived canine intestinal organoids to study epithelial-luminal interactions.

PLoS One 2020 17;15(4):e0231423. Epub 2020 Apr 17.

Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX, United States of America.

Recent advances in canine intestinal organoids have expanded the option for building a better in vitro model to investigate translational science of intestinal physiology and pathology between humans and animals. However, the three-dimensional geometry and the enclosed lumen of canine intestinal organoids considerably hinder the access to the apical side of epithelium for investigating the nutrient and drug absorption, host-microbiome crosstalk, and pharmaceutical toxicity testing. Thus, the creation of a polarized epithelial interface accessible from apical or basolateral side is critical. Here, we demonstrated the generation of an intestinal epithelial monolayer using canine biopsy-derived colonic organoids (colonoids). We optimized the culture condition to form an intact monolayer of the canine colonic epithelium on a nanoporous membrane insert using the canine colonoids over 14 days. Transmission and scanning electron microscopy revealed a physiological brush border interface covered by the microvilli with glycocalyx, as well as the presence of mucin granules, tight junctions, and desmosomes. The population of stem cells as well as differentiated lineage-dependent epithelial cells were verified by immunofluorescence staining and RNA in situ hybridization. The polarized expression of P-glycoprotein efflux pump was confirmed at the apical membrane. Also, the epithelial monolayer formed tight- and adherence-junctional barrier within 4 days, where the transepithelial electrical resistance and apparent permeability were inversely correlated. Hence, we verified the stable creation, maintenance, differentiation, and physiological function of a canine intestinal epithelial barrier, which can be useful for pharmaceutical and biomedical researches.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0231423PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7164685PMC
July 2020

A Retrospective Clinical Investigation of the Safety and Adverse Effects of Pantoprazole in Hospitalized Ruminants.

Front Vet Sci 2020 17;7:97. Epub 2020 Mar 17.

Veterinary Diagnostic and Production Animal Medicine, College of Veterinary Medicine, Iowa State University, Ames, IA, United States.

Clinical safety data for the use of gastroprotectants in hospitalized ruminants is lacking. In human patients, multiple adverse effects are possible from the use of pantoprazole including hematologic and electrolyte abnormalities as well as anaphylaxis and edema. The medical records of all hospitalized cattle, goats, and sheep administered pantoprazole over an ~5-year period were retrospectively analyzed for adverse effects. Seventy-nine eligible patients were observed. Hypomagnesemia was observed after pantoprazole administration in 10 cattle; however, no significant changes were noted when compared to baseline before pantoprazole administration. Significant changes were noted in serum indicators of hepatic and renal function; however, these represented downward trends that were most likely clinically insignificant. Anaphylaxis after pantoprazole administration was not observed; however, seven cattle displayed edema after pantoprazole administration. Veterinary clinicians should be aware of the potential for hypomagnesemia in hospitalized ruminants being administered pantoprazole and monitor patients accordingly. While these preliminary retrospective results indicate that pantoprazole may be a safe adjunctive therapy in hospitalized ruminants, additional studies are necessary to further determine the safety and toxicity of pantoprazole in ruminants.
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http://dx.doi.org/10.3389/fvets.2020.00097DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7089877PMC
March 2020

Evaluation of dose-response effects of short-term oral prednisone administration on clinicopathologic and hemodynamic variables in healthy dogs.

Am J Vet Res 2020 Apr;81(4):317-325

Objective: To determine whether a dose-response relationship exists between short-term oral prednisone administration and common clinicopathologic variables, cardiovascular biomarkers, and systolic arterial blood pressure (SAP) in healthy dogs.

Animals: 8 healthy Beagles.

Procedures: Dogs underwent five 5-day experiments (no prednisone treatment [control condition] and prednisone administration at 0.5, 1, 2, and 4 mg/kg, PO, q 24 h), with a 9-day washout period between protocols. Analyses performed before and after treatments included a CBC, serum biochemical analysis, and determination of SAP, fractional excretion of electrolytes, urine protein-to-creatinine ratio, glomerular filtration rate (GFR), serum N-terminal pro B-type natriuretic peptide (NT-proBNP) and plasma cortisol concentrations, and plasma renin activity. Linear mixed-effects modeling was used to compare changes in variables from baseline (day 1 for the same experiment) among treatment conditions.

Results: Changes in serum glucose concentration and GFR were significantly greater after administration of prednisone at 4 mg/kg than for the control condition. Fractional excretion of sodium was decreased from baseline when dogs received 0.5, 1, or 4 mg of prednisone/kg, compared with results for the control condition. Several expected changes in clinicopathologic values were observed after prednisone administration at any dose. Changes in serum NT-proBNP concentration, plasma renin activity, and SAP did not differ from changes for the control condition at any prednisone dose.

Conclusions And Clinical Relevance: Oral prednisone administration did not affect SAP, NT-proBNP concentration, or measures of renin-angiotensin-aldosterone system activation in healthy laboratory-housed dogs but was associated with relative increases in GFR and serum glucose concentration.
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http://dx.doi.org/10.2460/ajvr.81.4.317DOI Listing
April 2020
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