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Biomedical subjects

E Mezey

Publications and source records attributed to E Mezey.

At least 181 records · Page 10Linked to original sources

Bidirectional neuronal connections between the cerebellar interpositus nucleus and the brainstem (an autoradiographic study).

Ortho- and retrograde axonal labelings were demonstrated in several brainstem nuclei of cat after [3H]-leucine and [3H]-lysine microinjections into the cerebellar interpositus nucleus. Retrogradely labeled perikarya in the lateral reticular and solitary tract nuclei, locus coeruleus, substantia nigra and the raphe nuclei (midbrain raphe, dorsal, pontine and magnus) indicate the existence of possible aminergic afferents to the interpositus nucleus. The anterograde labeling of the neuropil in the above brainstem regions suggests the termination of axons or axon-collaterals originating from the interpositus nucleus.

Animals↗

Beta-adrenergic mechanism of insulin-induced adrenocorticotropin release from the anterior pituitary.

Intraperitoneal administration of insulin to control rats and to rats with pituitary stalk transections or with lesions of the median eminence resulted in increased plasma adrenocorticotropin (ACTH) levels. The insulin-induced stimulation of ACTH release was blocked in both the control and lesioned animals by prior treatment with either the beta-adrenergic antagonist propranolol or the glucocorticoid analog dexamethasone. The direct application of insulin to primary cultures of the anterior pituitary did not evoke ACTH release or affect the maximal ability of corticotropin-releasing factor or epinephrine to stimulate ACTH secretion. The results suggest that insulin stimulates ACTH release by a mechanism in which catecholamines of peripheral origin act directly on the anterior pituitary.

Adrenocorticotropic Hormone↗

Bilateral midbrain transections block the behavioral effects of cholecystokinin on feeding and exploration in rats.

The mechanism by which peripherally administered cholecystokinin (CCK) reduces feeding and exploration involves a sensory feedback pathway from the gastrointestinal regions, via the vagus nerve through the nucleus tractus solitarius (NTS). Bilateral dorsal midbrain transections rostral to the NTS abolish the ability of CCK to reduce food consumption, decrease exploratory approaches, and increase pauses of behavioral inactivity, as compared to these actions of CCK in normal and sham-lesioned control rats, suggesting that ascending NTS fibers are a necessary component in this feedback system.

Afferent Pathways↗

Differential regulation of 'central' and 'peripheral' benzodiazepine binding sites in the rat olfactory bulb.

The density of [3H]flunitrazepam and [3H]Ro 5-4864 binding sites was examined 19-21 and 27-31 days after surgical isolation of the olfactory bulbs. While statistically significant reductions in [3H]flunitrazepam binding were observed in the olfactory bulbs at both intervals, a significant reduction in [3H]Ro 5-4864 binding was observed only at 27-31 days after surgery. No consistent changes in the binding of either radioligand were observed in cerebella. Extirpation of the olfactory bulbs resulted in a significant reduction in the convulsant potency (but not efficacy) of Ro 5-4864, while neither the potency nor efficacy of pentylenetetrazole was affected by this procedure. These results suggest that benzodiazepine receptors and 'peripheral-type' binding sites for benzodiazepines are regulated independently, and that at least a subpopulation of peripheral-type binding sites are associated with neuronal elements in the olfactory bulb. These data also suggest that peripheral-type binding sites for benzodiazepines in the olfactory bulbs may influence the convulsant actions of Ro 5-4864.

Animals↗

On the origin of the serotonergic input to the intermediate lobe of the rat pituitary.

Serotonin-containing nerve fibers have been visualized immunocytochemically in the intermediate lobe of the rat pituitary. A 50% depletion of the serotonin level in the intermediate lobe was obtained in our previous experiment in rats with pituitary stalk transection, which may represent the total neuronally derived serotonin there. In the present studies we have attempted to determine the source of these fibers by examining the effect of hypothalamic and midbrain lesions or fiber transections on serotonin levels and serotonin-containing neuronal elements. Complete hypothalamic deafferentation resulted in a significant reduction of immunostained fibers in the intermediate lobe. A 27% fall in the serotonin content (measured by HPLC and electrochemical detection) and a significant disappearance of immunostained fibers were observed after transecting the ascending fibers from the raphe nuclei towards the hypothalamus. The transection combined with the lesioning of the hypothalamic dorsomedial nuclei resulted in a 50% decrease of serotonin level in the intermediate lobe. The present data therefore suggest that serotonin fibers in the intermediate lobe may originate from cells both in the midbrain raphe and hypothalamic dorsomedial nuclei.

Animals↗

Commentary on the hypermetabolic state and the role of oxygen in alcohol-induced liver injury.

Centrilobular hypoxia has been postulated as a mechanism for the development of hepatocellular necrosis and fibrosis in alcoholic liver disease. Chronic ethanol ingestion in rodents results in increased hepatic oxygen consumption and in a steeper fall in oxygen tension between the periportal and the pericentral area of the lobule, rendering the pericentral area susceptible to hypoxia. Hepatocellular necrosis occurs when ethanol-fed animals are exposed to low atmospheric oxygen. In man, the existence of a hypermetabolic state is more tenuous, but suggested by an increased rate of ethanol elimination after chronic ethanol consumption that has been linked to increased oxygen consumption in animals. Also, decreases in hepatic blood flow and hepatic vein oxygen tension were found in alcoholics with histological evidence of liver-cell necrosis as compared to those without necrosis. It is postulated that in man, reduction in the availability of oxygen to the liver may be caused by miscellaneous conditions such as anemia, respiratory depression or infection, cigarette-smoking, or reduction of hepatic blood flow, but the contribution of one or more of these factors remains to be proven. Trials of the effect of propylthiouracil (PTU) on alcoholic hepatitis are based on the effect of this drug in decreasing the ethanol-induced hypermetabolic state and in preventing hepatocellular necrosis in animals exposed to low atmospheric oxygen. A tentative conclusion of the two small trials that have been completed is that PTU may be beneficial in moderately ill patients with a low mortality, but not useful in severely ill patients with a high mortality.

Alcohol Dehydrogenase↗

Corticotropin-releasing factor-immunoreactive neurons of the paraventricular nucleus become vasopressin positive after adrenalectomy.

The immunoperoxidase technique was used to study the effect of adrenalectomy on vasopressin (VP) immunoreactivity in the hypothalamic paraventricular nucleus of rat. In control animals, relatively few VP-immunostained parvocellular neurons were found in addition to a large population of magnocellular VP neurons. Seven to 14 days after bilateral adrenalectomy, VP immunostaining increased markedly in specific subdivisions of the paraventricular nucleus. In contrast to normal animals, VP immunoreactivity was localized in a large number of parvocellular neurons. Colchicine treatment, on the other hand, did not significantly increase the number of VP-immunostained parvocellular neurons found in control rats. These observations suggest that adrenalectomy increases the number of VP-positive neurons and appears to increase the intensity of VP immunoreactivity specifically in parvocellular neurons. VP parvocellular neurons are confined to those paraventricular nucleus subdivisions that are known to project to the external zone of the median eminence. Moreover, their distribution pattern is very similar, if not identical, to that of the corticotropin-releasing factor (CRF) immunoreactive cells. Parvocellular neurons on adjacent thin sections could be stained for both CRF and VP. Thus, adrenalectomy seems to increase VP staining in CRF immunoreactive parvocellular neurons, which innervate the external zone of the median eminence.

Adrenalectomy↗

Cells of origin of fibres to the retrochiasmatic area: a horseradish peroxidase study.

The afferent connections of the retrochiasmatic area were examined in the rat after microintophoretic application of horseradish peroxidase. Labelled cells were found in amygdaloid nuclei, in the magnocellular preoptic nucleus, in the zona incerta and in all hypothalamic nuclei. In the brainstem reactive neurones were seen in the caudal part of the nucleus of the solitary tract (A2-C2 catecholaminergic cell groups), in and adjacent to the lateral reticular nucleus (A1-C1 catecholaminergic cell groups), in the nuclei reticularis pontis caudalis, pontis oralis, reticularis medullae oblongatae pars dorsalis and nucleus reticularis tegmenti pontis. The parabigeminal nucleus also contained a few labelled cells. A large number of labelled cells were seen around the superior cerebellar peduncle, in the caudal part of the periaqueductal grey and in the peripeduncular nucleus. Scattered cells appeared in the brainstem raphe nuclei, in the locus coeruleus and in the lateral part of the substantia nigra. Although it is not certain that all of these neurones terminate on retrochiasmatic cells, the extensive labelling suggests that this brain area is a critical station of many ascending and descending pathways. These may potentially affect a variety of neuro-endocrine mechanisms via the efferent projections of the retrochiasmatic area.

Animals↗

Relationship between pyridoxal 5'-phosphate deficiency and aminotransferase levels in alcoholic hepatitis.

The relationship between pyridoxal phosphate deficiency and activities of serum and liver aminotransferases was studied in 12 patients with alcoholic hepatitis. Plasma pyridoxal phosphate and the activities of liver aminotransferases were initially decreased in the patients, as compared with mean values in controls with normal hepatic histology. Addition of pyridoxal phosphate to liver homogenates increased liver alanine aminotransferase, but not aspartate aminotransferase, in all patients with initially low plasma pyridoxal phosphate. After 1 mo of abstinence from alcohol, with intake of an adequate diet and pyridoxine supplementation, plasma pyridoxal phosphate increased in all patients with initially low values (p less than 0.02). Serum aspartate aminotransferase decreased, whereas serum alanine aminotransferase increased, resulting in a decrease in their ratio in serum (p less than 0.001). Liver alanine aminotransferase increased (p less than 0.005), whereas liver aspartate aminotransferase remained unchanged. These data suggest that pyridoxal 5'-phosphate depletion is partially responsible for the low serum alanine to aspartate aminotransferase ratio that is typical of patients with alcoholic hepatitis.

Acute Disease↗

Circadian variations in beta-endorphin concentrations in pituitary and in some brain nuclei of the adult male rat.

Using both the 'punch' microdissection and a radioimmunological technique, circadian variations in beta-endorphin concentrations can be observed in the pituitary and in some discrete brain regions of the male rat (Wistar CFY). Animals were synchronized with light from 06.00 to 18.00 h, then darkness. Water and food were available ad libitum. Very well marked circadian rhythms were in evidence in the anterior lobe of the pituitary, the septum, the pons, the medulla oblongata and the cerebellum. There crest time locations were situated between 20.00 and 24.00 h. No significant circadian rhythms but biphasic variations were observed in the intermediate lobe of the pituitary, the POA, the thalamus, the central gray and the caudatus. There crest time locations were synchronized around 08.00 and 20.00 h. The most striking finding was that, regardless of the brain area investigated so far, maximal values were observed a short time after the beginning of the activity period of rats. This fact is identical with the one which has been observed for substance P and LH-RH contents in brain areas where these peptides are mostly present in nerve terminals in high concentrations.

Animals↗

Separation and partial characterization of multiple forms of rat liver alcohol dehydrogenase.

Rat liver alcohol dehydrogenase was purified and four isoenzyme forms, demonstrated by starch gel electrophoresis, were separated by O-(carboxymethyl)-cellulose chromatography. Each of the isoenzymes had a distinct isoelectric point. All isoenzymes were active with both ethanol (or acetaldehyde) and steroid substrates, and had similar Michaelis-Menten constants for each of the substrates and coenzymes studied. The three isoenzymes with the lowest migration toward the cathode exhibited the same pH optimum of 10.7 for ethanol oxidation, a greater activity with 5 beta-androstan-3 beta-ol-17-one than with ethanol as a substrate, and an unchanged electrophoretic mobility following storage in the presence of 100 microM dithiothreitol. By contrast the isoenzyme with the highest mobility toward the cathode exhibited a pH optimum of 9.5 for ethanol oxidation, a low steroid/ethanol ratio of activity, and converted to the migrating pattern of the two isoenzymes with intermediate mobility when stored. The similarities between the isoenzymes of rat liver alcohol dehydrogenase differ considerably from differences in substrate specificity exhibited by isoenzymes of horse liver alcohol dehydrogenase.

Alcohol Dehydrogenase↗

Pituitary stalk section transiently impairs the acquisition of shuttle box avoidance behavior.

Three days after stalk section, rats displayed a marked deficit in acquiring a shuttle box avoidance response. The performance of stalk sectioned rats was similar to that of 3-day hypophysectomized rats. At eighteen days after stalk section acquisition of the avoidance response was, however, not different from that of sham-operated controls. Stalk sectioned rats that showed poor performance at three days and that were tested again at eighteen days displayed similar avoidance behavior at eighteen days as their sham-operated controls. The results suggest that pituitary stalk section impairs performance of an active avoidance response. The transient nature of this effect may be due to disruption and subsequent regeneration of vascular contact between pituitary and brain.

Animals↗

Direct stimulation of beta 2-adrenergic receptors in rat anterior pituitary induces the release of adrenocorticotropin in vivo.

Previous work in our laboratory has shown that stimulation of beta 2-adrenergic receptors on mouse anterior pituitary tumor cells causes the secretion of immunoreactive adrenocorticotropin (ACTH). The present study was designed to test the hypothesis that catecholamines can cause the release of ACTH in vivo by the direct stimulation of beta 2-adrenergic receptors in the rat anterior pituitary. Systemic administration of a beta-adrenergic receptor agonist (-)-isoproterenol resulted in an increase in plasma ACTH levels in intact animals and in rats with transected pituitary stalks. This effect could be blocked by the beta-adrenergic receptor antagonist, propranolol, but not by the specific beta 1-adrenergic receptor antagonist, practolol. Salmefamol, a beta 2-adrenergic receptor agonist also elevated plasma ACTH levels in stalk-sectioned animals. Dexamethasone, a glucocorticoid that inhibits the synthesis and release of ACTH from the anterior pituitary but not the intermediate lobe, prevented the elevation of ACTH secretion by (-)-isoproterenol in stalk-transected rats. These data indicate that beta 2-adrenergic receptors are present on anterior pituitary cells and suggest that catecholamines can directly stimulate ACTH secretion.

Adrenocorticotropic Hormone↗

Serotonergic innervation of the rat pituitary intermediate lobe: decrease after stalk section.

Serotonin (5-HT)-containing nerve fibers and terminals, but not cell bodies, have been demonstrated by light and electron microscopic immunocytochemistry in the intermediate lobe of the rat pituitary. Seven days after pituitary stalk transection, 5-HT immunoreactive fibers disappeared almost entirely from the intermediate lobe. Intermediate lobe 5-HT and 5-hydroxyindoleacetic acid concentrations, measured by high pressure liquid chromatography coupled to electrochemical detection, fell to 56% and 62% of control, respectively. There were no changes in 5-HT concentrations in anterior or posterior lobes of the pituitary or in the median eminence. These findings, and the failure of sympathectomy to cause a drop in pars intermedia 5-HT, indicate that in the intermediate lobe of the pituitary neuronal 5-HT originates in cells situated in the central nervous system.

Animals↗

Meningeal relations of the rat hypothalamo-hypophyseal system. Extravascular fluid spaces in and around the median eminence.

Meningeal relations of the rat pituitary and basal hypothalamus including the pituitary stalk and median eminence, were studied by both light and electron microscopy, and by ink perfusion techniques. The dura mater encapsulates the pituitary gland. The arachnoid covers the basal surface of the hypothalamus except the caudal two-thirds of the median eminence and the pituitary stalk. No arachnoidea, i.e. no subarachnoideal space, was found in the sella. Pia mater covers the entire basal surface of the hypothalamus, including the median eminence and the pituitary stalk, but encapsulates only the posterior lobe of the pituitary. The superficial portal vessels (primary plexus and portal veins) are located in the subdural space, covered by the pia mater. The deep vessels in the median eminence are surrounded by the perivascular space, which is bordered by the vascular and neuropil basement membranes, and separated from the external fluid space around the median eminence only by the pia mater. This special topography suggests that molecules present in the portal vessels or in the cerebrospinal fluid, or in and around the pituitary gland, readily move from one liquid space to another.

Animals↗

Transport of horseradish peroxidase by processes of radial glia from the pial surface into the mouse brain.

The transport of horseradish peroxidase (HRP) applied to exposed pial surfaces of the brain was studied in newborn, 4-, 7- and 12-day-old, and adult mice. In the telencephalon the cell bodies of radial glia were found to accumulate the tracer. Labeled cells occurred in the subventricular zone of the lateral ventricle during the first postnatal week; they became gradually restricted to an area around the stria terminalis (ventrolateral ventricular corner) by day 12. At later stages no HRP transport could be traced from the surface of the telencephalon. In the cerebellum, HRP was transported from the surface to the cell bodies of Bergmann glia in all age groups studied including adult animals. It is concluded that radial glia and their derivatives share the capacity of transporting material between various cerebrospinal fluid compartments.

Animals↗