PubMed Health⌕ Search

Biomedical subjects

E Head

Publications and source records attributed to E Head.

50 records · Page 3Linked to original sources
PubMed1993

The effect of L-deprenyl on behavior, cognitive function, and biogenic amines in the dog.

Behavioral and pharmacological effects of oral administration of L-deprenyl in the dog are described. Spontaneous behavior is unaffected at doses below 3 mg/kg while at higher doses there was stereotypical responding. There was evidence of improved cognitive function in animals chronically treated with a 1 mg/kg dose but the effectiveness varied considerably between subjects. Chronic administration produced a dose dependent inhibition in brain, kidney and liver monoamine oxidase B, and had no effect on monoamine oxidase A. There were also dose dependent increases in brain phenylethylamine and in plasma levels of amphetamine. Dog platelets did not have significant levels of MAO-B. Brain dopamine and serotonin metabolism were unaffected by L-deprenyl at doses up to 1 mg/kg. It appears that for the dog, deamination of catecholamines is controlled by MAO-A. Nevertheless, it is suggested that L-deprenyl serves as a dopaminergic agonist, and there is also evidence that it affects adrenergic transmission. These catecholaminergic actions may account for the effects of L-deprenyl on behavior and cognitive function.

Administration, Oral↗
PubMed1992

Changes in spontaneous behavior in the dog following oral administration of L-deprenyl.

An open-field activity test was developed for studying the effect of a single oral dose (range of 0.1-5 mg/kg) of L-deprenyl on spontaneous behavior in the dog. A computer program was used to quantify observations of locomotor activity, directed sniffing, urination, grooming, inactivity, jumping, rearing, and vocalization during a 10-min baseline and posttreatment session. Three dose-dependent behavioral changes were observed: an overall decrease in directed sniffing, an increase in total locomotor activity in females, and a decrease in frequency of urination in males. These effects were only seen at the dose levels of 2 mg/kg or higher. Computer-assisted tracings of behavioral patterns showed increased stereotypical behavior and decreased exploratory behavior at the high-dose levels. These behavioral effects are most likely due to either increased levels of phenylethylamine resulting from inhibition of monoamine oxidase B and/or the production of amphetamines as a result of the metabolism of L-deprenyl.

Aging↗
PubMed1985

Exophiala jeanselmei infection in a postrenal transplant patient.

We report a case of Exophiala jeanselmei infection in a postrenal transplant patient. He had verrucous lesions on the thigh and abdomen in which clinical and histologic changes resembled those characteristic of chromoblastomycosis. However, the morphologic features of the fungus seen in the tissue sections made it necessary to diagnose this case as phaeohyphomycosis. The patient was treated successfully by complete excision of the lesion on the abdomen and with oral ketoconazole.

Adult↗
PubMed1985

Actinomycetoma caused by Nocardiopsis dassonvillei.

We report a case of mycetoma caused by Nocardiopsis dassonvillei in a 39-year-old man. He had multiple nodules and draining sinuses on the anterior aspect of his right leg just below the knee. Few cream-colored granules were seen in the exudate. The biopsy specimen showed gram-positive, non-acid-fast granules with distinct borders. An aerobic actinomycete isolated from the lesion was identified as N dassonvillei. We think that this is the first reported case of mycetoma caused by N dassonvillei.

Actinomycetales↗
PubMedDate not supplied

Effects of chronic oral administration of L-deprenyl in the dog.

Dogs were administered capsules containing L-deprenyl daily over 3 weeks at dose levels of 0, 0.1, 0.5, and 1.0 mg/kg. Spontaneous behavior was measured using a canine open field test, and was not significantly affected by L-deprenyl. Plasma levels of amphetamine showed a clear dose-dependent elevation 2 h and was not significantly affected by L-deprenyl. Plasma levels of amphetamine showed a clear dose-dependent elevation 2 h following treatment, but were markedly lower after 24 h, and were undetectable 5 days following the last treatment. Plasma levels of phenylethylamine were increased, but were highly variable. Animals sacrificed 1 day following the last treatment showed a dose-dependent inhibition of monoamine oxidase B in the brain, liver, and kidney, whereas monoamine oxidase A was unaffected in these tissues. L-Deprenyl also caused an increase in phenylethylamine in the striatum and hypothalamus, but not in the neocortex. Brain levels of DA, DOPAC, 3-MT, HVA, 5-HT, and 5-HIAA were unaffected. The pharmacological profile for the dog is distinct from that of other species in that long-term treatment did not produce any significant inhibition of MAO-A activity. The absence of an effect on biogenic amines or metabolites suggests that the metabolism of dopamine is mediated at least in part through pathways other than MAO-B in the normal adult dog.

Amphetamine↗
PubMedDate not supplied

The canine as an animal model of human aging and dementia.

The aged canine displays many features that make it an excellent model for studying the progression of pathology in brain aging and linking these findings to learning, memory and other cognitive functions. Canines develop extensive beta-amyloid deposition within neurons and their synaptic fields, which appears to give rise to senile plaques. These plaques are primarily of the early diffuse subtype. Aged canines also exhibit accumulations of lipofuscin, cerebral vascular changes, dilation of the ventricles, and cytoskeletal changes. Neurofibrillary tangles (NFTs) are not present in the aged canine. Thus, the aged canine brain provides a suitable model for studying early degeneration normally considered to be pre-Alzheimer's. This supposition is also supported by behavioral data. We have found that the extent of beta-amyloid deposition correlates with a decline in select measures of cognitive function. These data provide the first evidence of a correlation between beta-amyloid accumulation and cognitive decline in the absence of NFTs. We summarize four lines of evidence that support using the aged canine as a model of human aging: (a) Aged canines develop aspects of neuropathology similar to that observed in aged humans; (b) Veterinarians have observed that many canines exhibit a clinical syndrome of age-related cognitive dysfunction; (c) Aged canines are deficient on a variety of neuropsychological tests of cognitive function; (d) The level of beta-amyloid accumulation correlates with cognitive dysfunction in the canine. These data indicate that the aged canine is a particularly useful model for studying age-related cognitive dysfunction (ARCD), early neuronal changes associated with aging, and the initial stages of senile plaque formation.

Aging↗
PubMedDate not supplied

Diffuse plaques contain C-terminal A beta 42 and not A beta 40: evidence from cats and dogs.

Recent reports have suggested that beta-amyloid (A beta) species of variable length C-termini are differentially deposited within early and late-stage plaques and the cerebrovasculature. Specifically, longer C-terminal length A beta 42/3 fragments (i.e., A beta forms extending to residues 42 and/or 43) are thought to be predominant within diffuse plaques while both A beta 42/3 and A beta 40 (A beta forms terminating at residue 40) are present within a subset of neuritic plaques and cerebrovascular deposits. We sought to clarify the issue of differential A beta deposition using aged canines, a partial animal model of Alzheimer's disease that exhibits extensive diffuse plaques and frequent vascular amyloid, but does not contain neuritic plaques or neurofibrillary tangles. We examined the brains of 20 aged canines, 3 aged felines, and 17 humans for the presence of A beta immunoreactive plaques, using antibodies to A beta 1(-17), A beta 17(-24), A beta 1(-28), A beta 40, and A beta 42. We report that plaques within the canine and feline brain are immunopositive for A beta 42 but not A beta 40. This is the first observation of nascent AD pathology in the aged feline brain. Canine plaques also contained epitopes within A beta 1(-17), A beta 17(-24), and A beta 1(-28). In all species examined, vascular deposits were immunopositive for both A beta 40 and A beta 42. In the human brain, diffuse plaques were preferentially A beta 42 immunopositive, while neuritic plaques and vascular deposits were both A beta 40 and A beta 42 immunopositive. However, not all neuritic plaques contain A beta 40 epitopes.

Aging↗
PubMedDate not supplied

Region-specific age at onset of beta-amyloid in dogs.

Cortical patterns of beta-amyloid (Abeta) deposition were evaluated in 40 beagle dogs ranging in age from 2 to 18 years. Abeta deposition in the prefrontal, occipital, parietal and entorhinal cortices was visualized by using an antibody against Abeta1-42. A logistic regression was used to estimate differences in age-at-onset and rate of deposition of Abeta as a function of brain region. The earliest and most consistent site of Abeta deposition with age was in the prefrontal cortex. Entorhinal Abeta deposition was not consistently observed until the age of 14 years, but was present in a subset of dogs under the age of 14 years. These regional vulnerabilities to Abeta accumulation are similar to those seen in the aging human. By using parameters derived from regression analyses, it may be possible to predict the presence of Abeta within specific brain regions in individual dogs. We propose that these models will be a useful tool to evaluate interventions that delay the age of onset or slow the rate of accumulation of Abeta in the dog.

Aging↗
PubMedDate not supplied

Dietary enrichment counteracts age-associated cognitive dysfunction in canines.

Advanced age is accompanied by cognitive decline indicative of central nervous system dysfunction. One possibly critical causal factor is oxidative stress. Accordingly, we studied the effects of dietary antioxidants and age in a canine model of aging that parallels the key features of cognitive decline and neuropathology in humans. Old and young animals were placed on either a standard control food, or a food enriched with a broad spectrum of antioxidants and mitochondrial enzymatic cofactors. After 6 months of treatment, the animals were tested on four increasingly difficult oddity discrimination learning problems. The old animals learned more slowly than the young, making significantly more errors. However, this age-associated decline was reduced in the animals fed the enriched food, particularly on the more difficult tasks. These results indicate that maintenance on foods fortified with complex mixtures of antioxidants can partially counteract the deleterious effects of aging on cognition.

Aging↗
PubMedDate not supplied

Magnetic resonance imaging of anatomic and vascular characteristics in a canine model of human aging.

Dogs exhibit both neuroanatomical and cognitive changes as a function of age that parallel those seen in aging humans. This study describes in vivo changes in neuroanatomical and cerebrovascular characteristics of the canine brain as a function of age in a group of dogs ranging from 4 to 15 years old. Dynamic contrast-enhanced magnetic resonance imaging (MRI) was used to measure the kinetics of contrast agents in the brain. Measures of vascular volume and blood-brain barrier (BBB) permeability were derived from a pharmacokinetic analysis. Cortical atrophy and ventricular enlargement were characteristic features of the aged canine brain. Vascular volume did not vary as a function of age and BBB permeability exhibited a nonsignificant increasing trend with age. However, BBB dysfunction was detected in one middle-aged dog that in addition to having unusually large ventricles, demonstrated an early onset of diffuse senile plaques at postmortem. These findings indicate that BBB dysfunction detected by magnetic resonance imaging may be useful for predicting and potentially diagnosing early pathological conditions.

Aging↗
PubMedDate not supplied

Visual-discrimination learning ability and beta-amyloid accumulation in the dog.

Young, middle-aged, and old beagle dogs were tested on several visual-discrimination tasks: reward- and object-approach learning, object discrimination and reversal, long-term retention of a reversal problem, and a size-discrimination task. Beta-amyloid accumulation in the entorhinal, prefrontal, parietal, and occipital cortices was quantified using immunohistochemical and imaging techniques at the conclusion of cognitive testing. Middle-aged and old dogs were impaired in size-discrimination learning. In each task, a subset of aged dogs was impaired relative to age-matched peers. Beta-amyloid accumulation was age-dependent. However, not all middle-aged and old dogs showed beta-amyloid accumulation in the entorhinal cortex. The error scores from dogs tested with a nonpreferred object during visual discrimination learning and from reversal learning were correlated with beta-amyloid in the prefrontal but not entorhinal cortex. Size-discrimination and reward and object-approach learning error scores were correlated with beta-amyloid accumulation in the entorhinal but not prefrontal cortex. The results of these studies support an association between cognitive test and the location and extent of beta-amyloid pathology.

Amyloid beta-Peptides↗
PubMedDate not supplied

Landmark discrimination learning in the dog.

Allocentric spatial memory was studied in dogs of varying ages and sources using a landmark discrimination task. The primary goal of this study was to develop a protocol to test landmark discrimination learning in the dog. Using a modified version of a landmark test developed for use in monkeys, we successfully trained dogs to make a spatial discrimination on the basis of the position of a visual landmark relative to two identical discriminanda. Task performance decreased, however, as the distance between the landmark and the "discriminandum" was increased. A subgroup of these dogs was also tested on a delayed nonmatching to position spatial memory task (DNMP), which relies on egocentric spatial cues. These findings suggest that dogs can acquire both allocentric and egocentric spatial tasks. These data provide a useful tool for evaluating the ability of canines to use allocentric cues in spatial learning.

Animals↗