ABSTRACT The arachidonate pathway of human, feline, canine, equine, mink, porcine, and bovine platelets was evaluated by determining the formation of arachidonate-induced malondialdehyde (MDA), thrombin-induced MDA and thrombin-induced... more
ABSTRACT The arachidonate pathway of human, feline, canine, equine, mink, porcine, and bovine platelets was evaluated by determining the formation of arachidonate-induced malondialdehyde (MDA), thrombin-induced MDA and thrombin-induced thromboxane (Tx) B2. In addition, arachidonate-induced platelet aggregation responses were monitored. Arachidonate activated platelets from every animal species evaluated and induced formation of TxB2 and MDA. There were, however, considerable species differences in the importance of the pathway in mediating the basic platelet reaction. Platelets from mink, pigs, and cows did not aggregate to arachidonate (0.5 mM) and in response to thrombin produced less than 0.5 nmoles of MDA/3 × 108 platelets and less than 10 nmoles of TxB2/1011 platelets. Human platelets had a well-developed arachidonate pathway, as they formed more than 1.0 nmoles of MDA/3 × 108 platelets and more than 50 nmoles of TxB2/1011 platelets in response to thrombin and irreversibly aggregated in response to arachidonate. Feline platelets exhibited considerable intraspecies variation in the arachidonate pathway. Canine platelets generally formed more than 1.0 nmole of MDA/3 × 108 platelets in response to thrombin; yet, platelets from some dogs did not irreversibly aggregate in response to arachidonate. Equine platelets aggregated in response to arachidonate but the aggregation was reversible and they formed between 1.0 and 0.5 nmoles of MDA/3 × 108 platelets when incubated with thrombin.
Research Interests: Chemistry, Medicine, Cats, Platelet, Dogs, and 12 moreThrombin, Humans, Platelet aggregation, Animals, Horses, Clinical Sciences, Cattle, Swine, Thrombosis, Mink, Malondialdehyde, and Blood platelets
Bone marrow stromal cells (BMSCs) isolated from humans and rodents have been shown to generate neural cells under specific culture conditions and after transplantation in the central nervous system. The apparent plasticity of BMSCs has... more
Bone marrow stromal cells (BMSCs) isolated from humans and rodents have been shown to generate neural cells under specific culture conditions and after transplantation in the central nervous system. The apparent plasticity of BMSCs has therefore been a target of intensive research in attempt to develop a novel therapy for neurological diseases. Canines sustain neurological disorders (e.g., traumatic spinal cord injury) that closely mirror pathology of those in humans. Therefore, we evaluated neural differentiation properties of canine BMSCs to provide insights into basic characterization of these cells for future neurotransplantation trials in canine patients with neurological disorders. We demonstrate that canine BMSCs form spherical cellular aggregates on anti-adhesive culture substrate in serum-free culture media, which morphologically and phenotypically resemble spherical aggregates of neural progenitor cells, so-called neurospheres. Upon dissociation and subculture on adhesive substrate, canine BMSCs express neuronal (ss capital SHA, Cyrillic-tubulin) and glial (GFAP, A2B5, and CNPase) markers. Formation of spherical aggregates appears to be a critical preceding process for some of the glial marker expression (CNPase and A2B5). However, expression of more mature neuronal (MAP2) and glial (MBP) markers could not be induced with the protocol used in this study. We suggest that induction of canine BMSCs into cells with neural progenitor cell characteristics is possible and that these cells may have the potential for future cellular therapy for neurological disorders.
Research Interests: Genetics, Pathology, Zoology, Biology, Spinal Cord Injury, and 14 moreMedicine, Dogs, Animals, Central Nervous System, Bone marrow, Neurons, Phenotype, Stromal Cells, Biological markers, Culture Media, Bone Marrow Cells, Neurosphere, Bone marrow stromal cells, and Paediatrics and reproductive medicine
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Bone marrow stromal cells (BMSCs) have gained considerable attention as a potential source for cell transplantation therapies for a variety of diseases due to their accessibility, proliferative capacity, and multilineage differentiation... more
Bone marrow stromal cells (BMSCs) have gained considerable attention as a potential source for cell transplantation therapies for a variety of diseases due to their accessibility, proliferative capacity, and multilineage differentiation properties. Canine BMSCs have been shown to contribute to regeneration of osseous tissues, but knowledge about their biology is currently limited. In the present study, we investigated the frequency of adult canine BMSCs in bone marrow, morphological features, growth kinetics, and osteogenic as well as adipogenic differentiation properties in vitro. Our data suggest that adult canine bone marrow contains approximately one BMSC in every 2.38 x 10(4) bone marrow mononucleated cells (0.0042 +/- 0.0019%, n = 5). Primary BMSC cultures consisted of morphologically heterogeneous adherent cell populations from which spindle-shaped cells grew and became the predominant cell type. Growth kinetics patterns were dependent on the initial cell seeding densities, resulting in the highest fold increase at lower cell density. In the presence of osteogenic and adipogenic inducers, primary BMSCs underwent morphological and phenotypic changes characteristic of osteogenic and adipogenic differentiation, respectively. This study provides insights into basic characterization of adult canine BMSCs.
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Regional concentrations of tryptophan, serotonin (5HT), 5-hydroxyindoleacetic acid (5HIAA), norepinephrine, and dopamine were determined in the ovine brain. Tryptophan concentrations varied between 18.6 nmoles/g of tissue (hypothalamus,... more
Regional concentrations of tryptophan, serotonin (5HT), 5-hydroxyindoleacetic acid (5HIAA), norepinephrine, and dopamine were determined in the ovine brain. Tryptophan concentrations varied between 18.6 nmoles/g of tissue (hypothalamus, midbrain) and 26.9 nmoles/g (cerebellum). The 5HT concentrations varied 0.34 nmoles/g (cerebellum) and 3.75 nmoles/g (midbrain). The concentration of 5HIAA varied between 1.78 nmoles/g (cerebellum) and 5.02 nmoles/g (hypothalamus). Large concentrations of norepinephrine were found in the hypothalamus (4.37 nmoles/g) and midbrain (2.08 nmoles/g), while the frontal cortex, thalamaus, hippocampus, and cerebellum were all relatively low in norepinephrine (0.65 to 0.95 nmoles/g). The concentration of dopamine was between 0.32 nmoles/g (hippocampus) and 39.8 nmoles/g (caudate nucleus). Generally, the distribution of these compounds in the ovine brain is similar to their regional distribution in other mammalian species. It was observed, however, that the ratio of 5HT/5HIAA appears to be relatively lower in sheep than in other species, suggesting that interspecies differences in the metabolism of 5HT or elimination of 5HIAA (or both) may exist.
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Superoxide dismutase (SOD), a free radical scavenger with anti-inflammatory activity, was administered IM to horses. Ex vivo platelet aggregation in response to arachidonic acid was monitored to determine whether exogenous SOD altered... more
Superoxide dismutase (SOD), a free radical scavenger with anti-inflammatory activity, was administered IM to horses. Ex vivo platelet aggregation in response to arachidonic acid was monitored to determine whether exogenous SOD altered equine platelet prostaglandin metabolism. Preparations of platelet-rich plasma obtained before SOD administration were incubated with different concentrations of SOD and were aggregated with arachidonic acid. Superoxide dismutase did not exert a demonstrable effect, either ex vivo or in vitro. Aspirin abolished arachidonic acid-induced platelet aggregation in vitro. This indicates that SOD (in the resting state) does not exert an effect on platelet-derived free radicals that could alter the arachidonic acid pathway of equine platelets, that equine platelets do not release free radicals, or that equine platelets are insensitive to the products formed from free radicals by SOD.
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ABSTRACT The arachidonate pathway of canine platelets was assessed in dogs of varying ages by examination of platelet aggregation to arachidonic acid and by measurement of arachidonic acid-induced platelet malondialdehyde production. As... more
ABSTRACT The arachidonate pathway of canine platelets was assessed in dogs of varying ages by examination of platelet aggregation to arachidonic acid and by measurement of arachidonic acid-induced platelet malondialdehyde production. As age increased, arachidonic acid-induced platelet aggregation showed a progressive prolongation in the lag phase before aggregation. The production of malondialdehyde by canine platelets significantly decreased with increasing age. Dogs affected with ceroid lipofuscinosis showed similar declines in platelet aggregation and malondialdehyde production, but at an earlier age. This suggests that changes occur in canine platelet reactivity during natural aging and in a disease of “premature” aging. The lack of change in platelet numbers and volume suggests that the alterations reported were related to the aging process rather than to advancing vascular disease. The findings support the free radical theory of aging.
Research Interests: Endocrinology, Chemistry, Medicine, Free Radical, Biological Sciences, and 11 morePlatelet, Internal Medicine, Platelet aggregation, Age, Peripheral Vascular Disease, Malondialdehyde, Arachidonic Acid, Mean platelet volume, Vascular Disease, Psychology and Cognitive Sciences, and Medical and Health Sciences
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SummaryWhole blood platelet counts, coagulation profiles and in vitro platelet function tests were monitored in newborn foals during the first week of life. Platelet counts, mean platelet volumes and thrombin‐induced malondialdehyde... more
SummaryWhole blood platelet counts, coagulation profiles and in vitro platelet function tests were monitored in newborn foals during the first week of life. Platelet counts, mean platelet volumes and thrombin‐induced malondialdehyde production were not different from adult mares. Prothrombin and partial thromboplastin times were slightly, but not significantly, longer for neonatal blood samples than for mare samples. Platelet aggregation responses to serotonin, arachidonic acid or adrenaline did not change during the study. On the other hand, adenosine diphosphate‐induced aggregation and collagen‐induced aggregation increased progressively over the first week of life. Adrenaline exposure diminished adenosine diphosphate‐induced aggregation only during the first 12 h of life. The results of this study indicate that the haemostatic mechanisms of equine neonates are immature at birth and that, during the maturation period, the equine neonate may be at risk of platelet‐associated haemorrhagic disorders.
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SummaryThe effects of a single intramuscular administration of polysulfated glycosaminoglycan (PSGAG, Adequan®a) on activated partial thromboplastin time (APTT), prothrombin time (PT), complete blood count (CBC), biochemical profile and... more
SummaryThe effects of a single intramuscular administration of polysulfated glycosaminoglycan (PSGAG, Adequan®a) on activated partial thromboplastin time (APTT), prothrombin time (PT), complete blood count (CBC), biochemical profile and urinalysis were determined in six adult cats. An injection of 5 mg/kg of PSGAG was given to three of the cats, and an injection of 25 mg/kg was given to the other three cats. Following a seven-day crossover interval, the doses were reversed. Serial blood and urine samples were collected over a 48-hour period after each injection. Administration of PSGAG resulted in a transient, dose-dependent increase of APTT and PT. Prolonged bleeding from the venipuncture sites in the 25 mg/kg group was observed. Some of the CBC, biochemical profile, and urinalysis values changed following treatment, but clinically significant adverse reactions were not noticed.Polysulfated glycosaminoglycan (Adequan®) is a heparin analogue with chondroprotective and anticoagulant ...
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BackgroundLevetiracetam is used to manage status epilepticus (SE) and cluster seizures (CS) in humans. The drug might be absorbed after rectal administration and could offer a practical adjunct to rectal administration of diazepam in... more
BackgroundLevetiracetam is used to manage status epilepticus (SE) and cluster seizures (CS) in humans. The drug might be absorbed after rectal administration and could offer a practical adjunct to rectal administration of diazepam in managing SE and CS.HypothesisLevetiracetam is rapidly absorbed after rectal administration in dogs and maintains target serum concentrations for at least 9 hours.AnimalsSix healthy privately owned dogs between 2 and 6 years of age and weighing 10–20 kg.MethodsLevetiracetam (40 mg/kg) was administered rectally and blood samples were obtained immediately before (time zero) and at 10, 20, 40, 60, 90, 180, 360, and 540 minutes after drug administration. Dogs were observed for signs of adverse effects over a 24‐hour period after drug administration.ResultsCLEV at 10 minutes was 15.3 ± 5.5 μg/mL (mean, SD) with concentrations in the target range (5–40 μg/mL) for all dogs throughout the sampling period. Cmax (36.0 ± 10.7 μg/mL) and Tmax (103 ± 31 minutes) valu...
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ObjectiveThe objective of this pilot study was to describe the application and first preliminary data of a novel MRI and CT compatible patient‐specific facemask for stereotactic brain biopsy of intracranial lesions in dogs.MethodsFive... more
ObjectiveThe objective of this pilot study was to describe the application and first preliminary data of a novel MRI and CT compatible patient‐specific facemask for stereotactic brain biopsy of intracranial lesions in dogs.MethodsFive client‐owned dogs presenting for neurological deficits consistent with forebrain disease were included in the study. All dogs had MRI findings consistent with an intracranial lesion. Using images obtained from either MRI or CT, a virtual three‐dimensional model of each dog's face was generated. The contact surface of each dog's face was selected for facemask design and a target point for biopsy was chosen using specialised software and toolkits. A patient‐specific facemask with an attached biopsy port with premeasured and preselected trajectory was then fabricated by a 3D printer. The facemasks were sterilised and used intraoperatively to obtain biopsy samples. Biopsy samples were submitted for both cytological and histopathological evaluation....
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Following previous studies in rats, the ability of two chemical delivery systems (CDSs) to deliver benzyl penicillin (1) to the central nervous system of rabbits and dogs was investigated. One of the systems (3) was a diester of methylene... more
Following previous studies in rats, the ability of two chemical delivery systems (CDSs) to deliver benzyl penicillin (1) to the central nervous system of rabbits and dogs was investigated. One of the systems (3) was a diester of methylene diol, and the other (5) a diester of ethylene 1,2-diol; in both, one hydroxyl group of the diol was esterified by the 3-carboxylic acid group of benzylpenicillin, and the other by the carboxy group of an N-methyldihydropyridine (dihydrotrigonelline). The basis of the system is the ability of the dihydropyridine components to undergo oxidation to quaternary pyridinium salts (2 from 3, and 4 from 5). In vitro relative stability studies were first performed in 10% rabbit brain homogenate, rabbit CSF and dog CSF. The results showed that the CDSs (3 and 5) were more stable than the corresponding quaternary salts (2 and 4). Hydrolysis of 2 and 3 resulted in the release of 1, whereas hydrolysis of 4 and 5 released both 1 and the hydroxyethyl ester (6) of 1. In vivo distribution studies were performed in rabbits and dogs. After i.v. administration of equimolar doses of 1 or the CDSs, levels of 1 in brain and CSF were substantially higher and more prolonged in the cases of the CDSs than in the case of 1 itself. Brain levels of 1 were lower following administration of 5, as compared with 3, due to the release of the intermediate compound, the hydroxyethyl ester (6) of 1, which was not hydrolyzed efficiently to 1 in rabbit or dog brain. The substantially increased and prolonged penicillin levels following administration of the CDSs arise as the result of improved penetration of the lipophilic CDSs across the blood-brain barrier, and a "lock-in" effect of the corresponding quaternary salts generated in situ.
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An anorectic, adult West African dwarf crocodile was examined because of bilateral hind limb paresis. Clinical findings included multiple skin wounds, osteomyelitis of the distal portions of the right radius and ulna, severe anemia, and... more
An anorectic, adult West African dwarf crocodile was examined because of bilateral hind limb paresis. Clinical findings included multiple skin wounds, osteomyelitis of the distal portions of the right radius and ulna, severe anemia, and Serratia marcescens bacteremia. The crocodile died after a blood transfusion. At necropsy, hemorrhage in the subarachnoid space, suppurative polyarthritis, and gastric ulceration were found. Serratia marcescens and Morganella morganii were isolated from multiple tissues and body fluids. It was concluded that the bilateral paresis was caused by severe septic arthritis secondary to bacteremia, and that the crocodile died from spinal injury caused by the blood transfusion into the supravertebral vein.
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ABSTRACT DM in the German Shepherd is an immune-related disorder whose clinical signs are explained by a widespread degeneration of the white matter pathways in the thoracolumbar spinal cord. Therapy includes exercise, vitamin... more
ABSTRACT DM in the German Shepherd is an immune-related disorder whose clinical signs are explained by a widespread degeneration of the white matter pathways in the thoracolumbar spinal cord. Therapy includes exercise, vitamin supplementation, and EACA medication. Avoiding unnecessary surgical procedures is also important to preclude permanent deterioration that can result following surgery in DM patients. In dogs other than German Shepherds, other identifiable causes should be treated. Additional confirmation of the diagnosis of DM may be assisted by performing cell-mediated immune studies or other serodiagnostic tests as they become available.
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Whole blood platelet counts, coagulation profiles and in vitro platelet function tests were monitored in newborn foals during the first week of life. Platelet counts, mean platelet volumes and thrombin-induced malondialdehyde production... more
Whole blood platelet counts, coagulation profiles and in vitro platelet function tests were monitored in newborn foals during the first week of life. Platelet counts, mean platelet volumes and thrombin-induced malondialdehyde production were not different from adult mares. Prothrombin and partial thromboplastin times were slightly, but not significantly, longer for neonatal blood samples than for mare samples. Platelet aggregation responses to serotonin, arachidonic acid or adrenaline did not change during the study. On the other hand, adenosine diphosphate-induced aggregation and collagen-induced aggregation increased progressively over the first week of life. Adrenaline exposure diminished adenosine diphosphate-induced aggregation only during the first 12 h of life. The results of this study indicate that the haemostatic mechanisms of equine neonates are immature at birth and that, during the maturation period, the equine neonate may be at risk of platelet-associated haemorrhagic disorders.
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ABSTRACT: From December, 1997, through November, 2000, 306 deaths were documented among adult and subadult American alligators (Alligator mississippiensis) of Lake Griffin, Florida (USA). Some live alligators were lethargic and... more
ABSTRACT: From December, 1997, through November, 2000, 306 deaths were documented among adult and subadult American alligators (Alligator mississippiensis) of Lake Griffin, Florida (USA). Some live alligators were lethargic and unresponsive to approach. To deter-mine ...
Research Interests: Electron Microscopy, International organizations, Mortality, Female, Animals, and 15 moreFlorida, Male, Electromyography, Autopsy, Fresh water, Peripheral Nerve, Sciatic Nerve, Conduction Velocity, International Organizations, Nervous System, Seasons, National wildlife refuge, Light microscopy, Clinical Signs, and Neurologic Examination
Monitoring phenobarbital levels in dogs has not traditionally taken free-to-bound serum phenobarbital levels into consideration. This study was designed to evaluate free-to-bound phenobarbital in healthy research dogs during the... more
Monitoring phenobarbital levels in dogs has not traditionally taken free-to-bound serum phenobarbital levels into consideration. This study was designed to evaluate free-to-bound phenobarbital in healthy research dogs during the initiation of therapy with phenobarbital. These findings were compared with the levels obtained during routine therapeutic monitoring of phenobarbital in epileptic dogs. This appears to be the first descriptive study which has looked at free-to-bound phenobarbital in clinical canine patients. During the first week of therapy in healthy canine subjects, the free-to-bound ratio was 0.7 due to the high degree of protein-binding of serum phenobarbital. This was in contrast to the level of protein-binding in epileptic patients receiving phenobarbital chronically, with a free-to-bound ratio of 3.0 ± 2.7. Moreover, during the initiation of therapy with phenobarbital, some of the bound fraction could be displaced with sulfadimethoxine indicating that free-to-bound p...
A 2-year-old Boston Terrier was referred because of depression and hindlimb and tail paresis. Clinical examination and serum biochemical analysis resulted in a diagnosis of encephalomyelitis and myositis. Results of testing for... more
A 2-year-old Boston Terrier was referred because of depression and hindlimb and tail paresis. Clinical examination and serum biochemical analysis resulted in a diagnosis of encephalomyelitis and myositis. Results of testing for Dirofilaria immitis were positive. Gross and histologic examination revealed an aberrant adult heartworm infection resulting in thrombosis of the femoral artery and multiple muscular branches, with subsequent muscle necrosis and inflammation in one hindlimb. Additionally, an unusual larval-tissue interaction to microfilariae yielded a multifocal encephalomyelitis in the brain and spinal cord.
Research Interests: Dogs, Brain, Animals, Spinal Cord, Male, and 4 moreMuscles, Myositis, Veterinary Sciences, and Encephalomyelitis
An interaction between blood platelets and adult heartworms was examined in vitro. Surfaces of glutaraldehyde-fixed heartworms, which were taken from infected dogs washed, and incubated in platelet-rich plasma (PRP), were evaluated by... more
An interaction between blood platelets and adult heartworms was examined in vitro. Surfaces of glutaraldehyde-fixed heartworms, which were taken from infected dogs washed, and incubated in platelet-rich plasma (PRP), were evaluated by scanning electron microscopy. Adherence of platelets to heartworms occurred only with PRP from infected dogs. Aggregation to epinephrine and adenosine diphosphate of PRP incubated with heartworms was monitored. Seemingly, platelet activation to heartworm membranes occurs in dogs with heartworm disease. The increased platelet reactivity was also observed in dogs with occult heartworm disease, indicating that the presence of circulating microfilaria was not important for this process. The ability to transfer the reactivity to heartworm-negative platelets by suspending them in heartworm-positive plasma indicated that this reactivity resided in the plasma. The processes leading to platelet activation may be responsible for the platelet-associated vascular ...
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Progressive myelopathy in the German shepherd dog is a degenerative neurologic disease of unknown etiology. Results presented in a previous study indicated a depression in the response to thymus-dependent mitogens by peripheral blood... more
Progressive myelopathy in the German shepherd dog is a degenerative neurologic disease of unknown etiology. Results presented in a previous study indicated a depression in the response to thymus-dependent mitogens by peripheral blood leukocytes obtained from dogs with progressive myelopathy. Data presented here indicate that this depressed response to mitogens was associated with the presence of peripheral blood suppressor cells. Suppressor cell activity was detected in dogs that were severely affected with PM, but was not apparent in dogs that were mildly affected. Peripheral blood leukocytes obtained from dogs with progressive myelopathy suppressed the mitogenic response to autologous lymph node cells as well as allogeneic normal canine peripheral blood cells. The suppressor cells had the capacity to suppress mixed leukocyte reactions. Suppressor cell activity was radioresistant. Both nylon wool-adherent and -nonadherent peripheral blood leukocyte populations contained suppressor ...
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The pharmacokinetics of a dihydropyridine-pyridinium salt-type chemical delivery system (CDS) for brain-targeted delivery of estradiol (E2) were examined in dogs. Parameters evaluated in vitro included stability in buffers and biological... more
The pharmacokinetics of a dihydropyridine-pyridinium salt-type chemical delivery system (CDS) for brain-targeted delivery of estradiol (E2) were examined in dogs. Parameters evaluated in vitro included stability in buffers and biological fluids and plasma protein binding. In vivo studies examined drug and metabolite concentrations in plasma, urine, and cerebrospinal fluid as well as in selected brain regions. The administered lipophilic E2-CDS disappeared very quickly from plasma and was not detected in urine. The oxidized drug form, E2-Q+, was excreted unchanged or as a conjugate in the urine for as long as 2 weeks. Plasma levels were below assay detection limits at later times. Pharmacokinetic analysis of urine E2-Q+ levels allowed estimation of a half-life of 2.2 days. Amounts of E2-Q+ excreted into the urine were proportional to the dose but averaged only 13.9% of the dose, indicating that other routes of excretion must be considered. CSF levels were below the limit of detection...