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Author(s):  
Margaret M. Ewald ◽  
Amy J. Rankin ◽  
Jessica M. Meekins ◽  
Geraldine Magnin ◽  
Butch KuKanich

Abstract OBJECTIVE To quantify plasma concentrations of prednisolone and dexamethasone (peripheral and jugular) and cortisol following topical ophthalmic application of 1% prednisolone acetate and 0.1% dexamethasone to healthy adult dogs. ANIMALS 12 purpose-bred Beagles. PROCEDURES Dogs received 1 drop of 1% prednisolone acetate (n = 6) or neomycin polymyxin B dexamethasone (ie, 0.1% dexamethasone; 6) ophthalmic suspension in both eyes every 6 hours for 14 days. Blood samples (peripheral and jugular) were collected on days 0, 1, 7, and 14 and analyzed for plasma prednisolone and dexamethasone concentrations. Plasma cortisol concentrations were measured at the beginning of the study and following topical drug administration. RESULTS Both drugs demonstrated systemic absorption. Prednisolone was detected on days 1, 7, and 14 (median plasma concentration, 24.80 ng/mL; range, 6.20 to 74.00 ng/mL), and dexamethasone was detected on days 1, 7, and 14 (2.30 ng/mL; 0 to 17.70 ng/mL). Neither prednisolone nor dexamethasone were detected in plasma samples on day 0 (baseline). Sampling from the jugular vein resulted in higher plasma drug concentrations than from a peripheral vein when samples from each day were combined. Plasma cortisol concentrations were significantly lower than baseline following 14 days of treatment with topical prednisolone acetate and dexamethasone. CLINICAL RELEVANCE Prednisolone and dexamethasone are detected in the plasma of healthy dogs following topical ophthalmic administration 4 times/d with prednisolone concentrations being close to a physiologic dose of orally administered prednisolone. Additional research is needed to evaluate the systemic absorption of these medications in dogs with ocular inflammation.


PLoS ONE ◽  
2022 ◽  
Vol 17 (1) ◽  
pp. e0262336
Author(s):  
Jennifer M. Reinhart ◽  
Gabriela A. R. de Oliveira ◽  
Lauren Forsythe ◽  
Zhong Li

Theophylline is an important drug for treatment of canine chronic bronchitis and bradyarrhythmias, but new products require validation since pharmacokinetics in dogs can vary by formulation. A new, 503B outsourcing facility-produced theophylline product (OFT) is available for veterinary use. Outsourcing facilities have many advantages over traditional compounding sources including current good manufacturing practice compliance. The purpose of this study was to establish the pharmacokinetics of OFT in dogs. Eight healthy dogs received 11 mg/kg intravenous aminophylline and 10 mg/kg oral OFT followed by serial blood sampling in a two-way, randomized, crossover design with 7-day washout. Plasma theophylline concentrations were quantified by liquid chromatography-mass spectrometry. Bioavailability, maximum concentration, time to maximum concentration, half-life and area under the curve were: 97 ± 10%, 7.13 ± 0.71 μg/mL, 10.50 ± 2.07 h, 9.20 ± 2.87 h, and 141 ± 37.6 μg*h/mL, respectively. Steady-state predictions supported twice daily dosing of the OFT, but specific dosage recommendations are hindered by lack of a canine-specific therapeutic range for plasma theophylline concentration. These findings suggest that the OFT is well absorbed and can likely be dosed twice daily in dogs, but future pharmacodynamic and clinical studies are needed to establish a definitive therapeutic range for theophylline in this species.


Author(s):  
Claudia Giannetto ◽  
Seyed Mehdi Rajaei ◽  
Arman Abdous ◽  
Hesam Ostadhasan ◽  
Hannah Emami Alagha ◽  
...  

Abstract OBJECTIVE To evaluate the effects of long-term (30-day) oral administration of melatonin on tear production, intraocular pressure (IOP), and concentration of melatonin in the tears and serum of healthy dogs. ANIMALS 20 healthy sexually intact adult male dogs. PROCEDURES 10 dogs were given melatonin (0.3 mg/kg, PO, q 24 h, administered in food at 9 am), and 10 dogs were given a placebo. Tear and serum melatonin concentrations, IOP, and tear production (determined with a Schirmer tear test) were recorded before (baseline) and 30 minutes, 3 hours, and 5 hours after administration of melatonin or the placebo on day 1 and 30 minutes after administration of melatonin or the placebo on days 8, 15, and 30. RESULTS Data collection time had significant effects on tear production, IOP, and tear melatonin concentration but not on serum melatonin concentration. Treatment (melatonin vs placebo) had a significant effect on tear melatonin concentration, but not on tear production, IOP, or serum melatonin concentration; however, tear melatonin concentration was significantly different between groups only 30 minutes after administration on day 1 and not at other times. CLINICAL RELEVANCE In healthy dogs, long-term administration of melatonin at a dosage of 0.3 mg/kg, PO, every 24 hours did not have any clinically important effects on tear production, IOP, or serum or tear melatonin concentrations.


Author(s):  
Brook A. Niemiec ◽  
Jerzy Gawor ◽  
Shuiquan Tang ◽  
Aishani Prem ◽  
Janina A. Krumbeck

Abstract OBJECTIVE To compare the bacteriome of the oral cavity in healthy dogs and dogs with various stages of periodontal disease. ANIMALS Dogs without periodontal disease (n = 12) or with mild (10), moderate (19), or severe (10) periodontal disease. PROCEDURES The maxillary arcade of each dog was sampled with a sterile swab, and swabs were submitted for next-generation DNA sequencing targeting the V1–V3 region of the 16S rRNA gene. RESULTS 714 bacterial species from 177 families were identified. The 3 most frequently found bacterial species were Actinomyces sp (48/51 samples), Porphyromonas cangingivalis (47/51 samples), and a Campylobacter sp (48/51 samples). The most abundant species were P cangingivalis, Porphyromonas gulae, and an undefined Porphyromonas sp. Porphyromonas cangingivalis and Campylobacter sp were part of the core microbiome shared among the 4 groups, and P gulae, which was significantly enriched in dogs with severe periodontal disease, was part of the core microbiome shared between all groups except dogs without periodontal disease. Christensenellaceae sp, Bacteroidales sp, Family XIII sp, Methanobrevibacter oralis, Peptostreptococcus canis, and Tannerella sp formed a unique core microbiome in dogs with severe periodontal disease. CONCLUSIONS AND CLINICAL RELEVANCE Results highlighted that in dogs, potential pathogens can be common members of the oral cavity bacteriome in the absence of disease, and changes in the relative abundance of certain members of the bacteriome can be associated with severity of periodontal disease. Future studies may aim to determine whether these changes are the cause or result of periodontal disease or the host immune response.


Author(s):  
Brook A. Niemiec ◽  
Jerzy Gawor ◽  
Shuiquan Tang ◽  
Aishani Prem ◽  
Janina A. Krumbeck

Abstract OBJECTIVE To investigate the mycobiome of the oral cavity in healthy dogs and dogs with various stages of periodontal disease. ANIMALS 51 dogs without periodontal disease (n = 12) or with mild (10), moderate (19), or severe (10) periodontal disease. PROCEDURES The whole maxillary arcade of each dog was sampled with a sterile swab, and swabs were submitted for next-generation DNA sequencing targeting the internal transcribed spacer 2 region with a commercial sequencing platform. RESULTS Fungi were detected in all samples, with a total of 320 fungal species from 135 families detected in the data set. No single fungal species was found in all samples. The 3 most frequently found fungal species were Cladosporium sp (46/51 samples), Malassezia restricta (44/51 samples), and Malassezia arunalokei (36/51 samples). Certain fungi, specifically those of the family Didymellaceae, the family Irpicaceae, and the order Pleosporales, were significantly associated with different stages of periodontitis. Mycobial analysis indicated that Cladosporium sp could be considered part of the core oral cavity mycobiome. CONCLUSIONS AND CLINICAL RELEVANCE Results highlighted that fungi are present in the oral cavity of dogs and are characterized by substantial species diversity, with different fungal communities associated with various stages of periodontal disease. The next-generation DNA sequencing used in the present study revealed substantially more species of fungi than previous culture-based studies.


2022 ◽  
Vol 50 ◽  
Author(s):  
Luciene Maria Martinello Romão ◽  
Amanda Sarita Cruz Aleixo ◽  
Felipe Gazza Romão ◽  
Mayra De Castro Ferreira Lima ◽  
Miriam Tsunemi ◽  
...  

Background: The modulation of heart rate by autonomic nervous system may be evaluated by the heart rate variability (HRV), which illustrates the fluctuations between RR intervals. To evaluate this analysis, the intervals between 2 QRS complexes are measured. In general, high HRV values are expected in healthy individuals; otherwise, low values are indicative of organism dysfunction. Studies conducted in healthy humans show that HRV suffers reduction with ageing and that there is autonomic immaturity in neonates. The aim of this study was to describe the characteristic pattern of cardiac autonomic behavior in healthy dogs in different age groups through short-term HRV analysis.Materials, Methods & Results: A total of 87 healthy dogs were studied. HRV was analyzed in time and frequency domain, using Holter and heart rate monitor. It was observed that puppies (below one year old) presented a lower parasympathetic predominance and, consequently, lower HRV values on time domain (SDNN, PNN50% e RMSSD) compared to the other 2 groups and on frequency domain (LF, HF and LF/HF) compared to the adult animals group (between 1 and 7-year-old), which presented higher HRV values when compared to the other groups. Elderly dogs (over 8-year-old) exhibited a natural tendency to decrease cardiac parasympathetic HRV indexes.Discussion: The use of the HRV method as a prognostic index and as an arrhythmogenic marker for various canine heart diseases presents interesting perspectives. However, before it may be employed for these purposes, a better understanding should be established regarding the physiological behavior of autonomic cardiac modulation in different age groups to serve as a basis for future analyses. This study observed that puppies presented higher values for HR and, therefore, shorter RR intervals than the other groups (adult and elderly dogs), what was observed on Holter and heart rate monitor methods (HRM). There were significant differences between puppies and the other 2 groups (adults and elderly) for all time-domain variables using both methods (Holter and HRM methods). SDNN was significantly lower in puppies compared to adults and elderly dogs. In addition, both RMSSD and PNN50%, which were more reliable over shorter periods of time, also presented means and medians that were significantly lower in puppies. Regarding frequency-domain HRV parameters observed on Holter method, these indexes were decreased on the elderly group compared to adult dogs, which is a possible effect of aging. Also, puppies revealed lower frequency-domain HRV parameters on both methods when compared to adult dogs. The influence of age on HRV is possibly related to the stage of development of an individual, starting at conception up to the maturity in relation to the mechanisms that cause variations in HR. There are studies in humans that suggest a gradual increase in parasympathetic activity during childhood, followed by a steady decrease as aging occur. The present study observed the same pattern in dogs. The balance between sympathetic and parasympathetic systems is influenced by age in dogs, which alters HRV values in the short-term. The HRV method´s analysis is relatively simple and non-invasive for assessing cardiac autonomic function; also, it is widely used in human medicine as a risk measure for sudden cardiac death. The 24-hour HRV analysis is highly challenging, as it is time-consuming, expensive, delays diagnosis, and has a large number of artifacts; in this way, standards for its short-term analysis were developed. Keywords: cardiology, autonomic nervous system, heart rate monitor, Holter.


Author(s):  
Caitlin E. Doran ◽  
Stephanie McGrath ◽  
Lisa R. Bartner ◽  
Breonna Thomas ◽  
Alastair E. Cribb ◽  
...  

Abstract OBJECTIVE To assess drug-drug interactions between cannabidiol (CBD) and phenobarbital (PB) when simultaneously administered to healthy dogs. ANIMALS 9 healthy, purpose bred Beagles. PROCEDURES A 3-phase prospective, randomized pharmacokinetic (PK) interaction study of CBD and PB was performed as follows: phase 1, CBD PK determination and evaluation of CBD tolerability by 3 single-dose CBD (5 mg/kg, 10 mg/kg, and 20 mg/kg) protocols followed by 2-week CBD dosing; phase 2, a single-dose, 3-way, crossover PK study of CBD (10 mg/kg), PB (4 mg/kg), or CBD (10 mg/kg) administration plus PB (4 mg/kg); and phase 3, evaluation of chronic PB (4 mg/kg, q 30 d) administration followed by single-dose CBD (10 mg/kg) PK study. RESULTS Although there were variations in CBD PK variables in dogs receiving CBD alone or in conjunction with PB, significance differences in CBD PK variables were not found. No significant difference was observed in PB PK variables of dogs receiving PB alone or with CBD. During chronic CBD administration, mild gastrointestinal signs were observed in 5 dogs. At daily CBD doses of 10 to 20 mg/kg/d, hypoxia was observed in 5 dogs and increased serum alkaline phosphatase (ALP) activities (range, 301 to 978 U/L) was observed in 4 dogs. A significant increase in ALP activity was observed with chronic administration of CBD during phase 1 between day 0 and day 14. CONCLUSIONS AND CLINICAL RELEVANCE No significant PK interactions were found between CBD and PB. Dose escalation of CBD or adjustment of PB in dogs is not recommended on the basis of findings of this study.


2022 ◽  
Vol 23 (1) ◽  
pp. 475
Author(s):  
Yong-ho Choe ◽  
Tai-Young Hur ◽  
Sung-Lim Lee ◽  
Seunghoon Lee ◽  
Dajeong Lim ◽  
...  

Abnormalities in animals cloned via somatic cell nuclear transfer (SCNT) have been reported. In this study, to produce bomb-sniffing dogs, we successfully cloned four healthy dogs through SCNT using the same donor genome from the skin of a male German shepherd old dog. Veterinary diagnosis (X-ray/3D-CT imaging) revealed that two cloned dogs showed normal phenotypes, whereas the others showed abnormal shortening of the mandible (brachygnathia inferior) at 1 month after birth, even though they were cloned under the same conditions except for the oocyte source. Therefore, we aimed to determine the genetic cause of brachygnathia inferior in these cloned dogs. To determine the genetic defects related to brachygnathia inferior, we performed karyotyping and whole-genome sequencing (WGS) for identifying small genetic alterations in the genome, such as single-nucleotide variations or frameshifts. There were no chromosomal numerical abnormalities in all cloned dogs. However, WGS analysis revealed variants of Wnt signaling pathway initiators (WNT5B, DVL2, DACT1, ARRB2, FZD 4/8) and cadherin (CDH11, CDH1like) in cloned dogs with brachygnathia inferior. In conclusion, this study proposes that brachygnathia inferior in cloned dogs may be associated with variants in initiators and/or regulators of the Wnt/cadherin signaling pathway.


2021 ◽  
Author(s):  
Heather Wilson-Robles ◽  
Thomas Bygott ◽  
Theresa Kathleen Kelly ◽  
Tasha Miller ◽  
Pamela Miller ◽  
...  

Abstract Background: Cell free DNA, in the form of nucleosomes, is released into circulation during apoptosis and necrosis in a variety of diseases. They are small fragments of chromosomes that are composed of DNA wrapped around a histone core made of four duplicate histone proteins forming an octamer. The nucleosome compartment is a relatively uninvestigated area of circulating tumor biomarkers in dogs. The objectives of this study were to quantify and better characterize nucleosomes in 528 dogs with various common malignancies and 134 healthy dogs. Results: The sensitivity of elevated circulating nucleosome concentrations for the detection of cancer in all dogs was 49.8% with a specificity of 97% with an area under the curve of 68.74%. The top 4 malignancies detected by the test included lymphoma, hemangiosarcoma, histiocytic sarcoma and malignant melanoma. The malignancies least likely to be detected were soft tissue sarcomas and mast cell tumors. Conclusions: A variety of tumor types may cause elevated nucleosome concentations in dogs. Tumors of hematopoietic origin are most likely to cause elevations and local tumors such as soft tissue sarcomas are least likely to cause elevations in plasma nucleosome concentrations.


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