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Biomedical subjects

K E Light

Publications and source records attributed to K E Light.

At least 19 recordsLinked to original sources

Intragastric intubation of alcohol during postnatal development of rats results in selective cell loss in the cerebellum.

Postnatal alcohol exposure produces reductions in the number of Purkinje cells in the rat cerebellum. The goal of this study was to determine if the method of postnatal alcohol exposure would influence the degree of vulnerability of the Purkinje cells. Previously reported studies from other laboratories have demonstrated cerebellar Purkinje cell count reductions following postnatal alcohol exposure via artificial rearing and vapor inhalation techniques. This study used gastric intubation to administer alcohol (3.6 g ethanol/kg body weight, bid) to male rat pups from postnatal days 4-10. Peak blood alcohol levels were 203 +/- 12.7 mg/dl on postnatal day 6. On postnatal day 10, the animals were perfused, and brain weights were obtained. Body weight was not significantly altered by the postnatal alcohol exposure, yet the wet weights of the cerebral cortex and whole brain were significantly reduced. Although the cerebellar weight was not significantly reduced, the overall number of Purkinje cells measured in the cerebellar vermis was significantly reduced by 24% compared with the isocaloric and normal control groups. The pattern of vulnerability for the individual cerebellar lobules was similar to the previously reported studies, indicating that alcohol's teratogenicity transcends experimental paradigm and is remarkably consistent, when relatively similar blood alcohol profiles are established.

Animals

Effects of adult aging on the movement complexity factor of response programming.

The interaction effects between adult aging and incremental levels of movement complexity were studied in young, middle-aged, and older healthy females. Utilizing a two-choice reaction time (RT) paradigm, movement complexity as a factor of response programming was varied in a microswitch pressing task by altering the number of sides of the body and the number of fingers controlled. The speed of response programming was found to be age dependent and to interact with movement complexity across age groups. The results confirmed that as movement complexity increases, the effects of adult aging on RT increase. This study further emphasizes the robustness of the movement complexity x age effect, in that older individuals were found to be much more sensitive to small changes in movement complexity than younger subjects. The comparison results of three adult age groups suggested this sensitivity to movement complexity is progressive over the adult life span.

Adult

Information processing for motor performance in aging adults.

Movement control systems are altered by the aging process. A growing body of research exists that explains the known changes that occur with aging, and many of those changes are related to central nervous system (CNS) effects. This article reviews motor control and learning issues related to CNS information-processing effects of aging and the effects of practice and physical conditioning on reactive capacity. The extensive variability in motor-performance abilities of older people is addressed, and the significance of individual differences is emphasized.

Adult

Exposure of rats to ethanol from postnatal days 4 to 8: alterations of cholinergic neurochemistry in the cerebral cortex and corpus striatum at day 20.

Male and female rat pups were administered ethanol (3 g/kg/dose) twice daily by intragastric intubation between postnatal Day (PN) 4 and 8. Pups were maternally reared throughout the exposure period and until sacrifice on PN20. The consequences of this growth spurt exposure to ethanol were measured by an impact upon body growth, as well as upon specific growth parameters and cholinergic neurochemical factors within the cerebral cortex and corpus striatum. Specific endpoints included muscarinic receptor binding dynamics, acetylcholinesterase (AChE) and choline acetyltransferase (CAT) activities, regional wet weights, and subcellular protein content. In male pups, ethanol resulted in a significant enhancement of body weight gain and an increase in striatal but not cortical mass. Additionally, ethanol exposure resulted in a significant increase in striatal muscarinic receptor affinity, regardless of gender. This was accompanied by evidence of a significantly greater density of striatal muscarinic receptors in males versus females, regardless of treatment. Overall, the ethanol-associated effects are suggestive of a drug-induced developmental delay. Gender-specific, treatment-independent differences were also detected in the developing brain regions. Thus, regardless of treatment, cerebral cortical S1-level protein content was found to be significantly greater in males than in females. Furthermore, there were gender-based, significant differences in AChE activity within the striatum of control pups (males greater than females). Ethanol exposure resulted in a loss of this gender-based difference. We conclude that the cholinergic neurochemical development occurring in the striatum of the female rat brain between PN4 and 8 is exquisitely sensitive to ethanol-induced developmental delays which are not remediable by 12 subsequent days of maternal rearing in the absence of ethanol exposure.

Acetylcholinesterase

Exposure of rats to ethanol from postnatal days 4 to 8: alterations of cholinergic neurochemistry in the hippocampus and cerebellum at day 20.

Brief neonatal ethanol exposure (3.0 g/kg/dose, twice daily; postnatal day (PN) 4 to PN8) resulted in cholinergic neurochemical alterations in the cerebellum, but not the hippocampus of rats assayed on PN20. Analysis revealed that the binding affinity of cerebellar muscarinic receptors for [3H]quinuclidinyl benzilate was decreased by ethanol, but only in female pups. Other gender-specific but treatment-independent cerebellar differences were identified as well, including lower levels of choline acetyltransferase activity and S1-level (1,000 x g) crude protein in males and females, respectively. No evidence of ethanol-induced cholinergic change was noted in the hippocampus of the same pups on PN20. However, collapsed across treatment, male hippocampi were found to contain less S1-level protein than their female counterparts. Neither muscarinic receptor density nor acetyl cholinesterase activity were found to differ between treatments or genders, in either brain region. Consistent with the developmental timetables for regional cholinergic synaptogenesis in the rat, observations on PN20 confirm a hypothesis of cerebellar cholinergic vulnerability and hippocampal cholinergic resilience to neonatal ethanol insult.

Acetylcholinesterase

Antagonistic activity of tiotidine and ranitidine on guinea-pig and rabbit atria.

Isolated, spontaneously beating atrial pairs from rabbits and guinea-pigs were used to determine and to compare the activity of ranitidine and tiotidine as antagonists of histamine stimulated chronotropic activity. Ranitidine produced a classical competitive, reversible antagonism of histamine effects with a pA2 in rabbit atria of 8.2. In contrast, tiotidine produced both a dextral shift of the log dose-response curve, as well as a previously unreported suppression in the maximal response produced by histamine. In accordance with receptor theory, this type of activity represents a dualistic antagonism of histamine chronotropic responses.

Animals

Alteration of dopamine metabolism in different brain regions of the rabbit by estradiol and tamoxifen.

Tamoxifen citrate, a mixed estrogen agonist-antagonist, and estradiol 17-beta administered separately for 14 days significantly reduced dopamine and dihydroxyphenylacetic acid in the cortex and hypothalamus regions of the brain in immature female rabbits. In addition to these areas, estradiol also reduced dopamine and dihydroxyphenylacetic acid in the striatum but tamoxifen treatment significantly reduced only dihydroxyphenylacetic acid concentration in the striatum. When estradiol and tamoxifen were injected together, dopamine and dihydroxyphenylacetic acid concentrations were reduced only in the cortex. Specific binding of [3H]spiperone to dopamine receptors was significantly increased by both estradiol and tamoxifen in the hypothalamus but only tamoxifen increased dopamine binding in the striatum. A low dose of tamoxifen, either alone or in combination with estradiol, increased uterine weight, but a higher dose of tamoxifen was neither an estrogen agonist nor antagonist. These studies indicate that estradiol and tamoxifen alter dopamine metabolism in the various regions of brain differentially. The estrogen agonist activity of tamoxifen does not correspond to antidopaminergic action of estradiol in the striatum.

3,4-Dihydroxyphenylacetic Acid

Characterization of (3H)-spiperone binding to alpha 1-adrenergic receptors in a smooth muscle cell line.

Although (3H)-spiperone has been demonstrated to interact at both dopamine (D2) and serotonin (S2) receptors, it remains a popular choice for characterization of the D2-receptor using both in vitro and in vivo and in vivo assay techniques. Using a clonal smooth muscle cell culture line (DDT1 MF-2), which has previously viously been characterized as possessing alpha 1- and beta 2-adrenergic receptors, we have found that (3H)-spiperone also has a significant affinity for alpha 1-adrenergic receptors. Our results are consistent with other literature reports which have suggested that spiperone may interact at alpha 1-receptors and we have characterized this interaction. We have also found an additional, high affinity binding site for spiperone on these cells which may represent a D2 - receptor. Characterization of this high-affinity site has been difficult since it is present in very low density. We conclude that (3H)-spiperone binds with high affinity to at least three known neurotransmitter receptor sites: D2-dopamine, S2-serotoninn and alpha 1-adrenergic. The binding to the alpha 1-adrenergic receptor exhibits stereospecificity and a considerable degree of similarity in pharmacological profile to the D2-dopamine receptor.

Animals

Altered calcium concentration and rabbit atrial H1-receptors.

Rabbit atria were incubated in various concentrations of calcium (0.9, 1.8 and 3.6 mM) and then homogenized and histamine H1-receptors analysed by radioligand binding using (3H)-pyrilamine. Only atria incubated in 3.6 mM calcium showed an alteration in (3H)-pyrilamine binding. In these tissues the Kd of H1-receptors for (3H)-pyrilamine was increased suggesting a decrease in the affinity of the H1-receptor. That this decreased affinity is due to altered calcium concentrations was demonstrated by showing that no change in histamines' chronotropic effects were produced by decreasing the sodium concentration to produce the same calcium/sodium ratio compared to high calcium alone. We conclude that calcium has effects directly on H1-receptor affinity and appears to produce a decrease in the ability of histamine to bind.

Animals

Central and peripheral receptors in guinea-pigs exposed to simulated high altitude.

Guinea-pigs, chronically exposed to simulated high altitude of 6000 m, showed alterations in some, but not all, neurotransmitter-receptor systems. Thus, peripheral (cardiac) beta-adrenergic receptors were decreased in numbers (Bmax) with an increased affinity although no alterations in endogenous cardiac norepinephrine content were found. In contrast, H1-histamine receptors in the guinea-pig ventricle and brain showed no changes in Bmax or affinity. Dopamine receptors of the caudate nucleus showed no differences between control and altitude-exposed guinea-pigs, although previous reports demonstrated a significant increase (19%) in the content of endogenous dopamine of the caudate. Thus, chronic exposure to simulated high altitude altered beta-adrenergic receptors so that they were more sensitive to small ligand concentrations and less sensitive to large ligand concentrations.

Altitude

Low-load prolonged stretch vs. high-load brief stretch in treating knee contractures.

This study was designed to compare the results of a traditional method of stretching knee flexion contractures by high-load brief stretch (HLBS) with the results of an experimental method of prolonged knee extension by skin traction, low-load prolonged stretch (LLPS). End range of passive knee extension was measured by standard goniometry. Subjects were 11 nonambulatory residents of a nursing home who had demonstrated gradually progressive bilateral knee contractures. Each subject served as his or her own control with one lower limb receiving LLPS and the other limb receiving HLBS and passive range of motion (PROM). Sequential medical trials were used as the clinical research design. Whether comparing the LLPS limb PROM measurements pretreatment and posttreatment (p less than or equal to .05) or the HLBS to the LLPS limb PROM recordings posttreatment (p less than or equal to .05), the results demonstrated a preference for LLPS in the treatment of knee contractures in the immobile nursing home resident.

Aged

Alterations in CNS amine levels by acclimatization to hypobaric hypoxia.

Rabbits were acclimatized to simulated high altitude (SHA) (hypobaric hypoxia) at 6000 M (350 torr) on alternate days for 70 days. The norepinephrine levels of the midbrain were lower in the acclimatized animal compared to the controls (p less than 0.06) and 3,4 dihydroxyphenylacetic acid (DOPAC) was significantly higher (p less than 0.04) in the striatum of control than in the test animals. The mean dopamine (DA) levels in the striatum of the test animals were higher than the controls. The ratio of DOPAC/DA was 2.0 for the controls and 0.4 for the SHA brains which suggests reduced dopamine turnover in the striatum of the SHA rabbits. Rats acclimatized in the same manner did not show any difference in the NE or DA levels between the control and SHA animals, possibly the result of species differences.

3,4-Dihydroxyphenylacetic Acid

Differential activity of enantiomers of amphetamine in rats.

Administration of single doses of d-amphetamine (0.5-4.0 mg/kg i.p.) to adult, male rats produced the expected dose-related increases in spontaneous motor activity. This effect was reduced by pretreatment with alpha-methylparatyrosine (alpha MT) and virtually unaffected by pretreatment with pargyline or parachlorophenylalanine (PCPA). Single doses of l-amphetamine (0.25-8.0 mg/kg) evoked an initial decrease in activity followed by increased activity of smaller magnitude than that caused by the d-isomer. The depressant effects of the l-isomer were prolonged by pretreatment with alpha MT, and abolished by pretreatment with pargyline or PCPA.

Amphetamine

Alterations in norepinephrine and dopamine content in selected brain areas of guinea pigs adapted to simulated high altitude.

The alterations in brain content of norepinephrine (NE) and dopamine (DA) were studied in guinea pigs adapted to simulated high altitude (hypobaric hypoxia) equivalent to 5500 meters. The animals were adapted for 46 days over a period of 82 days to a pressure of 375 mm Hg. The animals were then killed and the following brain parts dissected: cerebellum, neocortex, caudate head/basal forebrain, diencephalon/rhinencephalon, and brain stem. NE and DA content were analyzed by high pressure liquid chromatography with electrochemical detection by a technique described. Results showed a significant increase of NE and DA in neocortex; a significant increase of DA but not NE in caudate/basal forebrain, and a significant decrease of NE and not DA in diencephalon/rhinencephalon.

Acclimatization

Elevation of serum and ventricular norepinephrine content in the diabetic rat.

Experimental diabetes was induced in rats by IV administration of 65 mg/kg streptozotocin. After 12 days, the rats were anesthetized with ether; the hearts were excise and perfusion washed. The atria and basilar portion of ventricle were freeze clamped, weighed and assayed for content of norepinephrine (NE), epinephrine (E) and dopamine (DA) using high pressure liquid chromatography with electrochemical detection. The serum concentration and adrenal content of NE, E and DA were also assayed. Results showed a significant increase in NE and DA in diabetic rat ventricles compared to control. The serum concentration of NE was significantly increased in diabetics while E showed no change.

Adrenal Glands