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Biomedical subjects

A Leon

Publications and source records attributed to A Leon.

At least 145 records · Page 8Linked to original sources
PubMed1990

[Diagnosis and prevention of candidiasis in intensive care patients].

Invasive candidiasis infections remain a major complication in I.C.U. patients. Numerous attempts have been made to evaluate potential prophylactic methods. Various agents have been tested. Gastrointestinal tract constitutes one of the major reservoirs for Candida species. One major problem is the difficulty in establishing an accurate, early, diagnosis of invasive fungal infection. A prospective randomized, controlled blind study was performed to assess the ability of oral Amphotericin B to prevent candidiasis in selected I.C.U. patients. Fifty one patients with serious infection and antibiotherapy were randomized to receive either oral Amphotericin B (2 g/day) or placebo, and observed until discharge. All patients were screened weekly for sites culture positive, sero-conversion and oesophagitis. Invasive candidiasis developed in 45% of patients receiving Amphotericin B compared with 41% receiving placebo. C. Albicans persists in the surveillance cultures. However a significant reduction of the colonization by the yeasts and a significant reduction of oesophagitis was demonstrated among the Amphotericin B group. No benefit was found in the total number of hospital days. Digestive decontamination can be successfully managed by Amphotericin B in I.C.U. patients but failed to prevent invasive candidiasis.

Adult↗
PubMed1990

Nerve growth factor induces a dose-dependent and long-lasting increase of choline acetyltransferase activity in the septal area and hippocampus of uninjured rats.

The effect of nerve growth factor (NGF) on the intact septohippocampal cholinergic system of adult rats was studied. Nerve growth factor was continuously infused at different doses (5-100 micrograms) for two weeks into the lateral ventricle of adult rats. Controls received intracerebroventricular infusion of equal amounts of cytochrome c. Nerve growth factor treatment was capable of inducing a dose-dependent increase of choline acetyltransferase activity (ChAT) in septal area and ventral hippocampus. In both areas, the NGF-induced rise of ChAT activity was sustained for at least one week after infusion, then it progressively declined towards control values. By three and five weeks, using NGF at 25 and 100 micrograms respectively, ChAT increase was still significant in both septum and ventral hippocampus. The present findings corroborate a role for NGF in adult septohippocampal cholinergic system and indicate that the "pharmacological" modulation of these neurons by NGF may last several weeks following withdrawal of this trophic factor.

Animals↗
PubMed1990

Monosialoganglioside effects following cerebral ischemia: relationship with anti-neuronotoxic and pro-neuronotrophic effects.

Increasing evidence is available indicating that systemically administered GM1 is able to provide for functional recovery in different experimental models of CNS injury, including cerebral ischemia. Current evidence indicates that the GM1 effects are associated, in the acute phase, with attenuation of secondary neuronal damage due to its capability to antagonize excitatory amino acid-related neurotoxicity in vivo as in vitro. Furthermore, the ganglioside is able to facilitate occurrence of long-term reparative processes, an effect most likely reflecting the potentiation of the action of neuronotrophic factors. This bifaceted action of GM1 makes the ganglioside ideally suited for clinical treatment of patients afflicted by cerebrovascular insufficiencies.

Animals↗
PubMed1990

Hypoxic-ischemic damage and the neuroprotective effects of GM1 ganglioside.

In vitro studies have shown that monosialoganglioside GM1 reduces excitatory amino acid-related neurotoxicity by limiting the downstream consequences of abusive excitatory amino acid receptor stimulation. Systemic administration of GM1 appears to be efficacious in reducing acute neuronal damage and in facilitating medium- and long-term functional recovery after brain injury. We propose that GM1 protective effects in the acute injury phase results from attenuation of excitotoxicity, whereas the functional recovery seen at longer term could reflect GM1 potentiation of neuronotrophic factors. The potential therapeutic efficacy of GM1 administration in humans is suggested by clinical studies demonstrating improved neurologic outcome in stroke patients.

Amino Acids↗
PubMed1989

Phospholipids can influence the interconversion of flat epithelial-like and stellate process-bearing astroglial cells in culture: relationships between molecular structure and biological activity.

Secondary cultures of neonatal rat astroglial cells, maintained in a serum-free, chemically defined medium were treated with several agents known to elevate intracellular cyclic AMP levels in these cells. Earlier studies had shown such drugs to induce a process-bearing (stellate) morphology in the astroglial cells, a response that is antagonized or reversed by the presence of exogenously added gangliosides. As a next step in understanding the basis for such an influence on cell morphologics, we have examined in more detail the molecular specificity of this response. In particular, a variety of phospholipids have been used in substitution of GM1 ganglioside. Natural phosphatidic acid (PA), which physicochemically displays lipophilic and hydrophilic bipolarity as does GM1, was fully active in mimicking the effects of GM1. The ED50 for the morphologic effect of PA was 10 microM, similar to that of GM1. Synthetic PAs (oleic, stearic, palmitic, myristic) had no effect up to 50 microM. Relatively long fatty acid chains were thus required for a PA effect. Other phospholipids including phosphatidylserine could not replace PA. Exposure of the cells to phospholipase D to generate endogenous PA from other phospholipids elicited the morphological response as well. These results indicate that the ability of exogenously supplied lipid molecules to modulate astroglial cell behaviors can be assigned, in functional terms, to a class of molecules having the appropriate balance (which includes PA and GM1) between their hydrophobic and hydrophilic domains.

Animals↗
PubMed1989

Activation of polyphosphoinositide metabolism as a signal-transducing system coupled to excitatory amino acid receptors in astroglial cells.

Excitatory amino acids (EAA) are known to induce an increase in the breakdown of polyphosphoinositides (PI) in brain slices and in dispersed cultures of neurons. We have now used astroglia cultured from newborn rat cerebra to demonstrate that glutamate provokes, in [3H]inositol-labeled cells, an accumulation of inositol phosphates in a time- and concentration-dependent manner. The ED50 value for glutamate was 40 microM. Quisqualate, ibotenate, and kainate were also active, with their relative potencies in the order of quisqualate greater than ibotenate much greater than kainate. No effect was detected with N-methyl-D-aspartate and quinolinic acid in the absence of Mg2+. The nonselective glutamate receptor antagonist gamma-D-glutamylglycine fully inhibited glutamate agonist-induced PI breakdown. A brief pretreatment of the astroglial cells with phorbol esters negated these effects of EAA receptor agonists, suggesting a feedback role for protein kinase C in phospholipase C action. Glutamate also elevated cytosolic free Ca2+ in Fura-2-loaded astroglial cells, as assessed by digital fluorescence imaging microscopy. Since a close metabolic partnership is known to exist between neurons and glia, these findings may have important functional consequences for neural cells in vivo.

Animals↗
PubMed1989

Incorporation of exogenous ganglioside GM1 into neuroblastoma membranes: inhibition by calcium ion and dependence upon membrane protein.

Since exogenous gangliosides are known to promote neuritogenesis, the incorporation of exogenous GM1 into neuroblastoma membranes was examined. Neuro-2A cells, synchronized in the G1/G0 phase, were suspended in HEPES buffered saline containing 10(-4) M [3H]GM1, and membrane incorporation was measured as radioactivity remaining with the cell pellet following incubation with serum-containing medium and trypsin. Calcium ion (0.01 to 10 mM) reduced incorporation of exogenous GM1, due to its interaction with GM1 micelles in solution. When cells were treated with proteases prior to incubation with GM1, the inhibitory effect of Ca2+ was lost and total incorporation into membranes was lowered by approximately one order of magnitude. Pretreatment of cells with 0.05% trypsin resulted in an inhibition of GM1 incorporation within 5 minutes. When trypsinized cells were resuspended in complete growth medium, the cells recovered the ability to incorporate GM1 with time, and this paralleled labeling of cellular protein with [3H]leucine. The role of membrane protein in the incorporation of exogenous GM1 could not be explained by the lytic release of cytosolic transfer proteins nor the artifactual coating of the cell surface by serum proteins. These results suggest that the incorporation of exogenous gangliosides into cellular membrane lipid bilayers cannot be fully explained by considerations of lipophilicity alone, and leads us to propose that initial recognition by membrane protein(s) is necessary.

Animals↗
PubMed1989

Ganglioside function in the development and repair of the nervous system. From basic science to clinical application.

Gangliosides play important roles in the normal physiological operations of the nervous system, in particular that of the brain. Changes in ganglioside composition occur in the mammalian brain not only during development, but also in aging and in several neuropathological situations. Gangliosides may modulate the ability of the brain to modify its response to cues or signals from the microenvironment. For example, cultured neurons are known to respond to exogenous ganglioside with changes characteristic of cell differentiation. Gangliosides can amplify the responses of neurons to extrinsic protein factors (neuronotrophic factors) that are normal constituents of the neuron's environment. The systemic administration of monosialoganglioside also potentiates trophic actions in vivo and improves neural responses following various types of injury to the adult mammalian central nervous system. The possible molecular mechanism(s) underlying the ganglioside effects may reflect an action in modulating ligand-receptor linked transfer of information across the plasma membrane of the cell.

Animals↗
PubMed1989

Basic fibroblast growth factor promotes the survival and development of mesencephalic neurons in culture.

Neuronotrophic effects of basic fibroblast growth factor (bFGF) have been reported for some central nervous system neurons. Here we report that also rat mesencephalic neurons are responsive to bFGF. bFGF produces a significant increase in the number of neurite-bearing cells, as well as in the degree of their fiber network. The present findings also provide the first evidence that bFGF can affect, in a concentration-dependent manner, at least two defined CNS neuronal populations, i.e., dopaminergic and gabaergic neurons. This effect was quantified by assessing the specific [3H]dopamine and [gamma-14C]aminobutyric acid uptakes with time in culture. Stimulation of uptake was more pronounced for dopaminergic neurons, suggesting a relative specificity in the actions of bFGF. These effects of bFGF were completely blocked by affinity-purified polyclonal antibodies. The possibility that bFGF plays a key role in normal nervous system development or function is discussed.

Animals↗
PubMed1989

Monosialoganglioside GM1 protects against anoxia-induced neuronal death in vitro.

Excitatory dicarboxylic amino acid neurotransmitters, particularly glutamate, have been implicated in mediating neuronal cell injury in brain ischemia-anoxia, epilepsy, and stroke. Glutamate neurotoxicity has been demonstrated in several in vitro models, as well as its prevention by a variety of agents, including several sialic acid-containing glycosphingolipid species, gangliosides. We have now examined ganglioside effects in anoxic exposed cultures of granule cells from Postnatal Day 8 rat cerebellum. Cells between 10 and 12 days in vitro were placed into an anoxic atmosphere or subjected to a chemical model of anoxia by a pulse exposure to rotenone. Widespread neuronal degeneration of neuronal cell bodies and their associated neurite network was seen the following day. These effects on cell vitality at the morphological level were quantitatively confirmed by measuring the photometric reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide to a blue formazan product. This neuronal injury was abolished by the specific N-methyl-D-aspartate receptor noncompetitive antagonists Mg2+, phencyclidine and MK-801, suggesting that this subtype of glutamate receptor is involved in the pathogenesis of anoxic granule cell injury. Pretreatment for 30 to 60 min or more or concurrent treatment with ganglioside GM1 largely prevented the ensuing neuronal death (ED50 = 25 microM), even 4 days later. Degeneration induced by exogenous glutamate was equally reduced. Asialo GM1 (lacking sialic acid) was ineffective. These results are consistent with the observed beneficial effects of the gangliosides in ischemic brain injury models in vivo.

Animals↗
PubMed1989

Thermoregulatory response to thermal challenge in seasonal affective disorder: a preliminary report.

It has recently been proposed that alterations in central dopamine (DA) functional activity may, in part, account for certain behavioral changes observed in seasonal affective disorder (SAD) during the winter. To explore this possibility, a preliminary study of thermoregulatory heat loss to an endogenous heat challenge--a strongly DA-dependent process--was undertaken in groups of four SAD woman and four nonpsychiatric control women across three conditions (winter, after successful phototherapy, and summer). Homeostatic heat loss during recovery from heat challenge in SAD, but not in control, subjects was found to be a significant function of light condition and of clinical state. Thermoregulatory heat loss in SAD subjects was significantly blunted in winter during depression, was similar in efficiency to control subjects after a successful antidepressant response to phototherapy, and tended to be more efficient than controls in summer during a euthymic state. Results raise the possibility that a common effect of phototherapy and summer light conditions is a facilitation of central DA activity in SAD.

Adult↗
PubMed1989

Simultaneous recording of local electrical activity, partial oxygen tension and temperature in the rat hippocampus with a chamber-type microelectrode. Effects of anaesthesia, ischemia and epilepsy.

A miniature multiple thin-film recording sensor was used to measure simultaneously the electrical activity, oxygen content and temperature of brain tissue. The chamber-type potential sensor was an Ag/AgCl electrode covered by an Si3N4 (silicon nitride) chamber. The chamber-type oxygen sensor consisted of an Au-Ag/AgCl two-electrode electrochemical cell embedded in an electrolyte-filled Si3N4 chamber. The temperature sensor was a thin-film germanium resistor. The different sensors were spaced 300 microns apart. Anaesthetics (pentobarbital, chloral hydrate, chlornembutal, halothane) were shown to depress electrical activity and to increase local oxygen tension in the hippocampus. Halothane, but not the other anaesthetics, also increased the current output of the oxygen sensor when tested in saline bath, indicating that the apparent increase in measured oxygen levels during halothane anaesthesia was partly due to an electrochemical effect of halothane on the oxygen sensors. The decrease of tissue oxygen consumption produced by the other anaesthetics is likely to be the result of metabolic depression. Cerebral ischemia, evoked by cauterization of the vertebral arteries and occlusion of the carotid arteries for 30 min, resulted in the disappearance of both spontaneous and evoked electrical activity in the hippocampus and a decrease of both local temperature and oxygen tension. There was a marked overshoot of the oxygen tension to above preocclusion level following the release of the carotid arteries. As soon as electrical activity returned, the oxygen tension fell again, often below the lowest level seen during the ischemic period. This secondary decrease of oxygen level could be reversed by administration of supplementary small doses of anaesthetic. The anaesthetic-induced increase in oxygen tension was accompanied by a marked decrease in electroencephalogram amplitude and frequency. During electrically induced seizures a decrease in hippocampal oxygen content occurred and was accompanied by an increase of local temperature. Since the rectal temperature was kept constant, the changes in temperature are likely to reflect changes in blood perfusion of the recorded area. These findings are in agreement with previous observations made with conventional electrodes. In addition, the miniature size of the chamber-type microelectrode assembly allows a correlated monitoring of parallel physiological changes with high spatial and temporal resolution during anaesthesia, ischemia and epilepsy.

Action Potentials↗
PubMed1989

Nerve growth factor affects uninjured, adult rat septohippocampal cholinergic neurons.

The effect of nerve growth factor on the intact versus injured septohippocampal cholinergic system of adult rats was studied. Nerve growth factor was continuously infused into the lateral ventricle of adult uninjured rats or rats that had received unilateral partial transection of the fimbria. Controls (operated and unoperated) received intraventricular infusion of cytochrome c. After 2 weeks of nerve growth factor or cytochrome c treatments, choline acetyltransferase and acetylcholinesterase activities were measured in the septal area and in the hippocampus (divided into dorsal, medial and ventral parts). The continuous infusion of nerve growth factor resulted in a marked dose-dependent increase of choline acetyltransferase activity in both septum and hippocampus of adult unlesioned rats. In lesioned rats the nerve growth factor treatment was capable of inducing choline acetyltransferase activity in the hippocampus of not only the lesioned but also the unlesioned side, as well as in the septal area. In addition, nerve growth factor affected choline acetyltransferase activity differently in the hippocampus of the operated side with respect to the contralateral side or in unoperated animals. The chronic infusion of nerve growth factor did not affect acetylcholinesterase activity in the septum or in the hippocampus of either lesioned or unlesioned rats. The present findings indicate that nerve growth factor is capable of modulating the function of not only damaged but also normal adult forebrain cholinergic neurons. This suggests that nerve growth factor may modulate the function of these neurons in adulthood.

Acetylcholinesterase↗
PubMed1989

Evidence for a physiological role of nerve growth factor in the central nervous system of neonatal rats.

Forebrain cholinergic neurons have been shown to respond in vivo to administration of nerve growth factor (NGF) with a prominent and selective increase of choline acetyltransferase (ChAT) activity. This has suggested that NGF can act as a trophic factor for these neurons. To test this hypothesis directly, anti-NGF antibodies (and their Fab fragments) were intracerebroventricularly injected into neonatal rats to neutralize endogenously occurring NGF. The anti-NGF antibody administration produced a decrease of ChAT activity in the hippocampus, septal area, cortex, and striatum of rat pups. This finding was substantiated by a concomitant decrease of immunopositive staining for ChAT in the septal area. These effects indicate that the occurrence of endogenous NGF in the CNS is physiologically relevant for regulating the function of forebrain cholinergic neurons.

Animals↗
PubMed1989

Stimulation of inositol phospholipid hydrolysis by excitatory amino acids is enhanced in brain slices from vulnerable regions after transient global ischemia.

Stimulation of inositol phospholipid hydrolysis by transmitter receptor agonists was measured in slices from hippocampus, cerebral cortex, and corpus striatum at various intervals after transient global ischemia in rats. Ischemia was induced through the four-vessel occlusion model. Stimulation of [3H]inositol monophosphate formation by excitatory amino acids was greatly enhanced in hippocampal slices prepared from ischemic rats at 24 h or 7 days after reperfusion. This potentiation was more evident using ibotenic acid and was also observed in cerebral cortex, but not in corpus striatum. This regional profile correlated with the pattern of ischemia-induced neuronal damage observed under our experimental conditions. The enhanced responsiveness to excitatory amino acids was always accompanied by an increase in both basal and norepinephrine-stimulated [3H]inositol monophosphate formation. In contrast, stimulation of [3H]inositol monophosphate formation by carbamylcholine was not modified in hippocampal or cortical slices from ischemic animals.

Animals↗