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Biomedical subjects

E Melamed

Publications and source records attributed to E Melamed.

At least 199 records · Page 11Linked to original sources

The assessment of changes in brain volume using combined linear measurements. A CT-scan study.

All linear measurements employed for evaluation of brain atrophy, were performed on 148 computed tomograms of patients aged 28 to 84 without evidence of any nervous system disorder. These included size of lateral, third and fourth ventricles, width of the Sylvian and frontal interhemispheric fissures and cortical sulci and size of the pre-pontine cistern. Various parameters indicated decrease in brain mass with age. Since the atrophic process is a diffuse phenomenon, integration of several measurements evaluating separate brain regions was made. The bicaudate ratio and the Sylvian fissure ratio (representing both central and cortical atrophy) were combined arithmetically, resulting in a correlation of 0.6390 with age (P less than 0.0005). With a computed canonical correlation analysis; a formula was obtained which combined measurements of the lateral and third ventricles, the Sylvian fissure and the pre-pontine cistern. This formula yielded a correlation of 0.67795 (P less than 0.0005). These linear measurements will allow simple and reliable assessement of reduction in brain volume during the normal aging process and in disorders accompanied by brain atrophy.

Adult↗

The dopaminergic amacrine system and its response to light stimulation in rats with inherited retinal dystrophy.

In both the RCS mutant strain of rats with hereditary progressive retinal dystrophy and in controls, concentrations of dopamine (DA) and its metabolic DOPAC increased steeply in retina from 14 to 60 days postnatally with no further elevations in older animals indicating normal dopaminergic system evolution in the RCS rats. In 60-, 90-, and 135-day-old but not in younger (14- and 30-day-old) RCS rats killed in the light phase of the light-dark cycle, retinal DA, and more markedly DOPAC levels, were lower than those in age-matched controls. In normal rats aged 24, 35 and 70 days that were dark-adapted for 24 hr, 2-hr light exposure increased DA and mainly DOPAC levels in retina. LIght stimulation after dark adaptation elevated retinal DA and DOPAC only in 24- but not in 35- or 70-day-old RCS rats. In RCS rats with advanced retinal dystrophy, decreases in retinal DA and DOPAC levels and lack of response of DA amacrine cells to light exposure are probably secondary to degeneration or impairment of photoreceptors which are no longer capable of transmitting light stimuli onto DA neurons in retina.

3,4-Dihydroxyphenylacetic Acid↗

Effect of central serotonin depletion on adrenocortical responses to neural stimuli.

In view of the possible role of serotonin in adrenocortical regulation, basal plasma corticosterone concentrations and the response to ether stress, photic, acoustic, or sciatic nerve stimulation, were studied in rats with 5,7-dihydroxytryptamine or vehicle injected into the raphe nuclei. The neurotoxin inhibited the response to photic stimulation without affecting the other modalities. This may suggest that the depletion of brain serotonin has a differential effect on the transmission of neural impulses which activate the adrenal cortex.

Acoustic Stimulation↗

Adrenocortical responses to ether stress and neural stimuli in rats following the injection of 6-hydroxydopamine into the medial forebrain bundle.

Adrenocortical responses, as expressed by changes in plasma corticosterone concentrations, after ether stress, or photic, acoustic, or sciatic nerve stimulation were studied in rats, with 6-hydroxydopamine or vehicle injected into the medial forebrain bundle (MFB). The neurotoxin partially inhibited the response to photic stimulation only, indicating the involvement of MFB catecholaminergic fibers in the transmission of this response which stimulates adrenocortical secretion.

Acoustic Stimulation↗

Suppression of L-dopa-induced circling in rats with nigral lesions by blockade of central dopa-decarboxylase: implications for mechanism of action of L-dopa in parkinsonism.

Dopamine (DA) elevations in rat striatum produced by combined administration of L-dopa and carbidopa were abolished when L-dopa was injected with NSD-1015, an inhibitor of central dopa-decarboxylase. In all rats with unilateral 6-OH-DA nigral lesions, L-dopa-induced contraversive circling occurred after carbidopa, but was totally abolished (in 60%) or markedly suppressed after pretreatment with NSD-1015. Administration of the DA metabolites DOPAC and HVA systemically and of 3-methoxytyramine intrastriatally evoked no circling in animals with 6-OH-DA lesions. In rats with unilateral nigrotomies, the direction of L-dopa-induced circling was reversed and became ipsiversive after DA receptors were reduced by the addition of kainic acid lesions in ipsilateral striata. Findings provide evidence that circling in rats--and by analogy, efficacy in parkinsonians--requires the decarboxylation of exogenous L-dopa and interaction of the formed DA with DA receptors in striatum.

Animals↗

Coexistence of severe parkinsonism and tardive dyskinesia as side effects of neuroleptic therapy.

Neuroleptic-induced parkinsonism and tardive dyskinesia are caused, respectively, by blockade and supersensitivity of dopaminergic receptors in striatum, and represent contrasting syndromes with regard to clinical presentation and management. Two patients are described in whom parkinsonism and tardive dyskinesia developed and coexisted, with marked severity, during chronic neuroleptic administration. Pharmacologic manipulations accelerating nigrostriatal transmission improved akinesia but intensified the dyskinesias, whereas suppression had opposite effects. It is hypothesized that the coexistence of these two opposing side effects is due to simultaneous blockade and supersensitivity of two different subclasses of striatal dopaminergic receptors.

Aged↗

Differential effect of acute and chronic haloperidol administration on dopamine turnover in rat nigrostriatal and retinal dopaminergic neurons.

Haloperidol-induced increases in DOPAC and HVA declined in the striatum but remained unchanged in the retina after chronic pretreatment with haloperidol (1-4 weeks). DA concentrations were unaffected in the striatum but decreased in the retina after acute or chronic haloperidol administration. Light stimulation increased both retinal DA and DOPAC. The findings indicate that acute and chronic haloperidol affect nigrostriatal and retinal DA neurons differentially. In addition, DA neurons in retina respond differently to activations by haloperidol and light.

3,4-Dihydroxyphenylacetic Acid↗

Role of medial forebrain bundle catecholaminergic fibers in the modulation of glucocorticoid negative feedback effects.

The possible role of medial forebrain bundle (MFB) catecholaminergic fibers in the previously observed MFB-mediated modulation of hypothalamic sensitivity to glucocorticoid negative feedback effects has been investigated. MFB catecholaminergic fibers were destroyed by bilateral MFB injections of 6-hydroxydopamine (6-OHDA) to adult male rats. The inhibitory effect of dexamethasone (10 micrograms, i.p., 4 h) upon the adrenocortical secretory response to ether stress, as estimated by serum corticosterone levels, was enhanced in the 6-OHDA-treated animals, as compared to vehicle-injected controls. This study suggests that MFB noradrenergic neurons are at least partially responsible for the MFB-mediated modulation of hypothalamic sensitivity to glucocorticoid hormones.

Animals↗

Treatment of status epilepticus with thiopentone sodium anaesthesia in a child.

A 4-month-old infant was admitted to the Pediatric Intensive Care Unit with Pneumococcal meningitis. A few hours after admission he developed intractable convulsions that could not be stopped with phenytoin, phenobarbitone and a continuous drip of diazepam. Thiopentone sodium anaesthesia was induced for 24 h terminating the status epilepticus. The clinical course, correlary EEG findings, treatment protocol and blood levels of the drugs given are described in detail.

Anesthesia, General↗

Combined administration of direct dopamine receptor agonists and L-dopa does not interfere with utilization of exogenous L-dopa in rat corpus striatum.

The effect of combined administration of L-dopa with apomorphine or with bromocriptine on rat striatal concentrations of dopamine (DA), dihydroxyphenylacetic (DOPAC) and dopa was investigated. Injections of apomorphine or bromocriptine alone decreased striatal DOPAC levels indicating suppression of DA turnover in nigrostriatal terminals. The dopa-induced elevations in striatal concentrations of DA, DOPAC and dopa were similar among animals injected with L-dopa alone or in combination with apomorphine or bromocriptine. These findings suggest that although direct DA receptor agonists decrease striatal DA turnover, they do not interfere with utilization of exogenous L-dopa in striatum.

3,4-Dihydroxyphenylacetic Acid↗

Hippocampal cell nuclear binding of corticosterone following 5,7-dihydroxytryptamine.

Adult male rats were injected into the lateral brain ventricle with 5,7-dihydroxytryptamine (5,7-DHT). They were adrenalectomized 5-7 days later and, following an additional 24 h, the specific in vitro [3H]corticosterone binding capacity of dorsal hippocampal slices was determined by estimation of uptake of radioactivity by the nuclear fraction. Specific corticosterone (CS) binding was reduced by 50-70% in the neurotoxin-treated as compared to vehicle-injected animals. Brain serotonin and 5-hydroxyindoleacetic acid concentrations were depleted by 50-70% in the 5,7-DHT-injected rats. These results suggest that the maintenance of normal dorsal hippocampal CS binding capacity is dependent upon the integrity of endogenous brain serotoninergic neuronal systems.

3,4-Dihydroxyphenylacetic Acid↗

Effect of exercise on cerebral circulation.

The effect of supine physical exercise on cerebral blood flow (CBF) was measured in 30 normal subjects with the 133Xe inhalation technique. The CBF measurements were correlated to changes in PCO2, heart rate, and blood pressure, and to cardiac output and right atrial pressure in 10 of the subjects who underwent Swan-Ganz catheterization. No significant change was found in CBF during physical exercise, although a marked increase in cardiac output, blood pressure, and right atrial pressure and a mild decrease in PCO2 were found. Cerebrovascular resistance increased by 38%, in contrast to a decrease of 33% in the peripheral vascular resistance. The factors that affect the mechanism of cerebrovascular autoregulation during exercise are discussed.

Adult↗

Effect of decortication on striatal dopamine turnover.

In rat striatum, frontal decortication did not affect the basal and the haloperidol-induced increases in dopamine (DA) turnover and the elevation in DA and dihydroxyphenylacetic acid concentrations produced by systemic administration of L-Dopa. These findings fail to support a role for the corticostriatal afferents in modulation of dopamine synthesis and release by nigrostriatal neurons. They suggest that DA receptors presumably localized on presynaptic corticostriatal terminals do not mediate the acceleration of DA turnover induced by neuroleptics. Data also indicate that corticostriatal terminals do not represent a locus for decarboxylation of exogenous L-Dopa to DA in the striatum.

3,4-Dihydroxyphenylacetic Acid↗