The effects of food on the pharmacokinetics of mycophenolate mofetil in healthy horses.

Additional immunomodulatory treatment is needed for the management of immune-mediated disease in horses. Mycophenolate mofetil (MMF) is an immunomodulatory agent used in human and veterinary medicine for the prevention of graft rejection and the management of autoimmune diseases. Few studies exist investigating the pharmacokinetics of MMF in horses.

Pharmacokinetics and tolerability of multiple-day oral dosing of mycophenolate mofetil in healthy horses.

Background: Additional efficacious immunomodulatory treatment is needed for the management of immune-mediated disease in horses. Mycophenolate mofetil (MMF) is an immunosuppressive drug that warrants assessment as a viable therapeutic agent for horses.

Hypothesis/objectives: To evaluate the pharmacokinetics (PK) of multiple-day oral dosing of MMF in healthy horses and to determine the tolerability of this dosing regimen.

Noncompartmental pharmacokinetics of three intravenous mycophenolate mofetil concentrations in healthy Standardbred mares.

Background: Mycophenolate mofetil (MMF) is the prodrug of mycophenolic acid (MPA) which acts as an immunosuppressive agent. During the biotransformation of MMF to MPA, additional metabolites including MPA phenol glucuronide (MPAG), MPA acyl glucuronide (AcMPAG) and MPA phenol glucoside (MPG) are formed.

Objective: To define the noncompartmental pharmacokinetic (PK) parameters of three single doses of intravenous (i.

Is low-level laser therapy useful as an adjunctive treatment for canine acral lick dermatitis? A randomized, double-blinded, sham-controlled study.

Background: Conventional therapy for canine acral lick dermatitis (ALD) consists of systemic antibiotics and anti-anxiety medications. Low-level laser therapy (LLLT) is a noninvasive therapy used to treat inflammatory and painful conditions.

Hypothesis/objectives: The primary objective was to determine whether LLLT with conventional therapy would be beneficial as an adjunct treatment for ALD.

Identification of Recurrent Activating Mutations in Primary Canine Pulmonary Adenocarcinoma.

Purpose: Naturally occurring primary canine lung cancers share clinicopathologic features with human lung cancers in never-smokers, but the genetic underpinnings of canine lung cancer are unknown. We have charted the genomic landscape of canine lung cancer and performed functional characterization of novel, recurrent mutations occurring in canine pulmonary adenocarcinoma (cPAC).

Experimental Design: We performed multiplatform genomic sequencing of 88 primary canine lung tumors or cell lines.

Canine osteosarcoma genome sequencing identifies recurrent mutations in and the histone methyltransferase gene .

Osteosarcoma (OS) is a rare, metastatic, human adolescent cancer that also occurs in pet dogs. To define the genomic underpinnings of canine OS, we performed multi-platform analysis of OS tumors from 59 dogs, including whole genome sequencing ( = 24) and whole exome sequencing (WES;  = 13) of primary tumors and matched normal tissue, WES ( = 10) of matched primary/metastatic/normal samples and RNA sequencing ( = 54) of primary tumors. We found that canine OS recapitulates features of human OS including low point mutation burden (median 1.

Bacteriology and cytology of otic exudates in 41 cavalier King Charles spaniels with primary secretory otitis media.

Background: Primary secretory otitis media (PSOM) in the cavalier King Charles spaniel (CKCS) is similar to otitis media with effusion (OME) in humans. A proposed aetiology of OME is inflammation of the middle ear mucosa, usually due to bacterial infection, leading to auditory tube dysfunction.

Hypothesis/objectives: Our objective was to characterize the microbiological and cytological findings of otic exudates from the external ear canal (EEC) (n = 68) and middle ear (ME) (n = 69) from 41 CKCSs with PSOM.

An evaluation of veterinary allergen extract content and resultant canine intradermal threshold concentrations.

Background: Limited information is available for dogs on threshold concentrations (TCs), and the protein composition of common allergenic extracts produced by different manufacturers.

Hypothesis/objectives: To characterize the protein heterogeneity of tree, grass, weed and mite allergens from different lots of allergenic extracts, and to determine intradermal TCs for healthy dogs using extracts from two manufacturers.

Animals: Twenty five privately owned, clinically healthy dogs and ten purpose-bred beagle dogs.

Conductive hearing loss in four dogs associated with the use of ointment-based otic medications.

Background: Hearing loss (HL) is classified as conductive when sound transmission is compromised in the ear canal or middle ear, or sensorineural when there is an abnormality of the receptor cells of the cochlea or auditory pathway. Hearing in dogs is evaluated using the brainstem auditory evoked response (BAER) test.

Hypothesis/objectives: Our objective was to characterize BAER findings pre- and post-ear flushing in four dogs with acute HL following application of an ointment-based otic medication containing betamethasone, clotrimazole and gentamicin in a mineral oil-based system containing a plasticized hydrocarbon gel.

In vitro bactericidal activity of blue light (465 nm) phototherapy on meticillin-susceptible and meticillin-resistant Staphylococcus pseudintermedius.

Background: Staphylococcus pseudintermedius is the most common cause of bacterial skin infections in dogs. Meticillin-resistant infections have become more common and are challenging to treat. Blue light phototherapy may be an option for treating these infections.

Human Genetic Relevance and Potent Antitumor Activity of Heat Shock Protein 90 Inhibition in Canine Lung Adenocarcinoma Cell Lines.

Background: It has been an open question how similar human and canine lung cancers are. This has major implications in availability of human treatments for dogs and in establishing translational models to test new therapies in pet dogs. The prognosis for canine advanced lung cancer is poor and new treatments are needed.

Effect of feeding on the pharmacokinetics of oral minocycline in healthy research dogs.

Background: The effect of food on minocycline oral absorption in dogs is unknown.

Objective: The objective was to determine the pharmacokinetics of minocycline after administration of a single oral dose in fed and fasted dogs.

Methods: Ten research hounds were administered oral minocycline (approximately 5 mg/kg) with and without food, in a crossover study, with a one-week wash-out between treatments.

Evaluation of canine-specific minocycline and doxycycline susceptibility breakpoints for meticillin-resistant Staphylococcus pseudintermedius isolates from dogs.

Background: Using the US Clinical and Laboratory Standards Institute (CLSI) human tetracycline breakpoints to predict minocycline and doxycycline susceptibility of Staphylococcus pseudintermedius (SP) isolates from dogs is not appropriate because they are too high to meet pharmacokinetic/pharmacodynamic data using a standard dose. New breakpoints have been approved for doxycycline and proposed for minocycline. Revised breakpoints are four dilutions lower than tetracycline breakpoints, providing a more conservative standard for classification of isolates.

Equine intradermal test threshold concentrations for house dust mite and storage mite allergens and identification of stable acari fauna.

Background: House dust mite (HDM) and storage mite (SM) stable fauna and their associated equine intradermal test (IDT) threshold concentrations (TCs) for the midwestern region of the USA are unknown.

Hypothesis/objectives: To determine IDT TCs and serum IgE concentrations for two HDM and three SM species in clinically normal horses over two seasons, and to identify the mite taxa and habitats in a stable.

Animals: Thirty-eight clinically normal horses.

Canine pulmonary adenocarcinoma tyrosine kinase receptor expression and phosphorylation.

Background: This study evaluated tyrosine kinase receptor (TKR) expression and activation in canine pulmonary adenocarcinoma (cpAC) biospecimens. As histological similarities exist between human and cpAC, we hypothesized that cpACs will have increased TKR mRNA and protein expression as well as TKR phosphorylation. The molecular profile of cpAC has not been well characterized making the selection of therapeutic targets that would potentially have relevant biological activity impossible.

At the crossroads: EGFR and PTHrP signaling in cancer-mediated diseases of bone.

The epidermal growth factor receptor is a well-established cancer therapeutic target due to its stimulation of proliferation, motility, and resistance to apoptosis. Recently, additional roles for the receptor have been identified in growth of metastases. Similar to development, metastatic spread requires signaling interactions between epithelial-derived tumor cells and mesenchymal derivatives of the microenvironment.

The calcium-sensing receptor is necessary for the rapid development of hypercalcemia in human lung squamous cell carcinoma.

The calcium-sensing receptor (CaR) is responsible for the regulation of extracellular calcium (Ca(2+) (o)) homeostasis. CaR activation has been shown to increase proliferation in several cancer cell lines; however, its presence or function has never been documented in lung cancer. We report that Ca(2+) (o)-activated CaR results in MAPK-mediated stimulation of parathyroid hormone-related protein (PTHrP) production in human lung squamous cell carcinoma (SCC) lines and humoral hypercalcemia of malignancy (HHM) in vivo.

The midregion, nuclear localization sequence, and C terminus of PTHrP regulate skeletal development, hematopoiesis, and survival in mice.

The functions of parathyroid hormone-related protein (PTHrP) on morphogenesis, cell proliferation, apoptosis, and calcium homeostasis have been attributed to its N terminus. Evidence suggests that many of these effects are not mediated by the N terminus but by the midregion, a nuclear localization sequence (NLS), and C terminus of the protein. A knock-in mouse lacking the midregion, NLS, and C terminus of PTHrP (Pthrp(Delta/Delta)) was developed.

Reconstitution of amphiregulin-epidermal growth factor receptor signaling in lung squamous cell carcinomas activates PTHrP gene expression and contributes to cancer-mediated diseases of the bone.

Parathyroid hormone-related protein (PTHrP) is the causative factor of the paraneoplastic syndrome humoral hypercalcemia of malignancy (HHM) and it also contributes to osteolytic metastases, both of which are common complications of squamous carcinomas of the lung. Inhibition of autocrine epidermal growth factor receptor (EGFR) signaling has been shown to reduce plasma calcium and PTHrP concentrations in two lung squamous cell carcinoma xenograft models of HHM. The purpose of this study was to investigate the mechanism by which EGFR is activated and stimulates PTHrP gene expression in lung squamous carcinoma cell lines.