Biomedical subjects

Y C Zeng

Publications and source records attributed to Y C Zeng.

At least 19 recordsLinked to original sources

PubMed2000

HIV-1 infected mononuclear phagocyte secretory products affect neuronal physiology leading to cellular demise: relevance for HIV-1-associated dementia.

Viral and cellular products from HIV-1-infected and/or immune competent mononuclear phagocytes (MP) (brain macrophages and microglia) affect neuronal function during HIV-1-associated dementia (HAD). Neurotoxic MP factors include, but are not limited to, pro-inflammatory cytokines, chemokines, platelet activating factor, arachidonic acid and its metabolites, nitric oxide, progeny virions and viral structural and regulatory proteins. The mechanisms for immune-mediated neural injury in HAD, only now, are being unraveled. In this regard, we reviewed the current knowledge of how postmitotic neurons, which can neither divide nor be replaced, are damaged by MP secretory activities. Linking neuronal function with brain MP activation was made possible by placing viral and/or immune products onto neurons and measuring cell signaling events or through ex vivo electrophysiological tests on MP-treated brain slices. Such linkages are shown, in this report, by select demonstrations of MP factors which cause neuronal dysfunction in HAD.

AIDS Dementia Complex↗

PubMed1999

Intracellular CXCR4 signaling, neuronal apoptosis and neuropathogenic mechanisms of HIV-1-associated dementia.

The mechanism(s) by which HIV-1 affects neural injury in HIV-1-associated dementia (HAD) remains unknown. To ascertain the role that cellular and viral macrophage products play in HAD neurotoxicity, we explored one potential route for neuronal demise, CXCR4. CXCR4, expressed on lymphocytes and neurons, is both a part of neural development and a co-receptor for HIV-1. Its ligand, stromal cell-derived factor-1alpha (SDF-1alpha), affects neuronal viability. GTP binding protein (G-protein) linked signaling after neuronal exposure to SDF-1alpha, virus-infected monocyte-derived macrophage (MDM) secretory products, and virus was determined. In both human and rat neurons, CXCR4 was expressed at high levels. SDF-1alpha/beta was detected predominantly in astrocytes and at low levels in MDM. SDF-1beta/beta was expressed in HAD brain tissue and upregulated in astrocytes exposed to virus infected and/or immune activated MDM conditioned media (fluids). HIV-1-infected MDM secretions, virus and SDF-1beta induced a G inhibitory (Gi) protein-linked decrease in cyclic AMP (cAMP) and increase inositol 1,4, 5-trisphosphate (IP3) and intracellular calcium. Such effects were partially blocked by antibodies to CXCR4 or removal of virus from MDM fluids. Changes in G-protein-coupled signaling correlated, but were not directly linked, to increased neuronal synaptic transmission, Caspase 3 activation and apoptosis. These data, taken together, suggest that CXCR4-mediated signal transduction may be a potential mechanism for neuronal dysfunction during HAD.

AIDS Dementia Complex↗

PubMed1999

Neuroprotective effects of riluzole: an electrophysiological and histological analysis in an in vitro model of ischemia.

The protective effects of riluzole against the neuronal damage caused by O2 and glucose deprivation (ischemia) was investigated in rat cortical slices by recording electrophysiologically the cortico-cortical field potential and by evaluating histologically the severity of neuronal death. Five minutes of ischemia determined an irreversible depression of the amplitude of the field potential. In addition, this insult caused a clear enhancement of the number of death cells that were specifically colored with trypan blue (a vital colorant which stains altered cells). We found that riluzole, which by itself depressed the synaptic transmission, neuroprotected when perfused 15-20 min before and during ischemia. In fact, due to the treatment with riluzole, the ischemia-induced irreversible depression of the field potential recovered and less cells were stained with trypan blue. These findings demonstrate that riluzole prevents neuronal death in an in vitro model of ischemia and suggest a therapeutic use of this drug in order to reduce the pathophysiological outcomes of stroke.

Animals↗

PubMed1999

Soluble HIV-1 infected macrophage secretory products mediate blockade of long-term potentiation: a mechanism for cognitive dysfunction in HIV-1-associated dementia.

It is generally accepted that viral and cellular products from immune competent mononuclear phagocytes (MP) (brain macrophages and microglia) underlie the neuropathogenesis of HIV-1-associated dementia (HAD). What remains unanswered, however, is the composition of and mechanisms for such MP-induced neurological dysfunctions. In attempts to address these issues culture fluids from HIV-1ADA-infected monocyte-derived macrophages (MDMs) (depleted or enriched with progeny virus) were placed onto the CA1 area of rat hippocampal brain slices (the site of mammalian learning and memory) and neuronal long-term potentiation (LTP) assayed. LTP was induced by high frequency stimulation (HFS). Lipopolysaccharide (LPS) served as a surrogate macrophage activator. Synaptic strength was assayed by the initial slope of evoked field excitatory postsynaptic potentials (EPSPs). Synaptic potentiation following HFS was observed in slices incubated with uninfected (control) MDM culture fluids. The magnitude of the LTP response was 150.2 +/- 21.10% compared to basal levels (n=6). Synaptic strength was enhanced in virus-infected (135.7+/-28.9%, n=8) and LPS-activated MDM (123.3+/-5.1%, n=7) but at lower levels than controls. The lowest levels of LTP were in brain slices incubated with virus-infected and LPS-activated MDM fluids at (109.5+/-9.9% n=12). Interestingly, bath application of progeny HIV-1 virions showed minimal LTP effects. Virus-infected, LPS-activated MDM fluids, with progenyvirus, reduced synaptic strength but were not statistically different than replicate culture fluids depleted of virus. In contrast, IL-1beta and quinolinic acid, significantly diminished synaptic strength. These results, taken together, suggest that soluble HIV-1-infected MDM secretory products, but not virus per se, significantly affect LTP. This electrophysiological system, which monitors neuronal function following cell exposure to HIV-1 infected materials could provide a novel testing ground for therapeutics designed to protect brain function in HAD.

AIDS Dementia Complex↗

PubMed1998

Purification to homogeneity and properties of plant glucosidase I.

Glucosidase I was purified about 3600-fold to apparent homogeneity from the microsomal fraction of mung bean seedlings. The purified enzyme removed the terminal alpha1,2-linked glucose from Glc3Man9GlcNAc2-peptide or the endoglucosaminidase H (Endo H)-released oligosaccharide. Glucosidase I activity was inhibited by kojibiose [Glc(alpha1-2)Glc], but not by other glucose disaccharides. Removal of up to four mannose residues from the N-linked oligosaccharide had little effect on its utilization as a substrate for glucosidase I. The enzyme had a subunit molecular weight of 97 kDa on SDS gels and this was shifted to 94 kDa after treatment with Endo H or Endo F, suggesting that glucosidase I is an N-glycoprotein having one oligomannose-type oligosaccharide. Amino acid sequences of this enzyme showed considerable identity to the enzyme cloned from a human hippocampus cDNA library. The enzyme was inhibited by castanospermine, deoxynojirimycin, MDL, and trehazolin, but not by australine or kifunensine. On the other hand, the other processing glucosidase, glucosidase II, is sensitive to inhibition by australine, but not by trehazolin. Thus, these two inhibitors are useful to distinguish glucosidase I from glucosidase II. The mung bean glucosidase I is quite sensitive to the histidine modifying reagent diethyl pyrocarbonate, whereas the pig liver glucosidase I is not. On the other hand, pig liver and pig brain glucosidase I preparations are sensitive to the sulfhydryl reagent NEM (N-ethylmaleimide), whereas the plant enzyme is not. These sensitivities to amino acid modifiers suggest significant differences between the plant and animal glucosidase I, in terms of catalytic site or protein conformation.

Amino Acid Sequence↗

PubMed1995

Opposite modulation of 4-aminopyridine and hypoxic hyperexcitability by A1 and A2 adenosine receptor ligands in rat hippocampal slices.

The effects of the adenosine receptor antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX), and of the adenosine agonists N6-cyclopentyladenosine (CPA), N6-(2-phenylisopropyl)adenosine (R-PIA), and 2-[p-(carboxyethyl)phenylethylamino]-5'-N-ethylcarboxamidoadenosin e (CGS 21680) were investigated on the hyperexcitability induced in the CA1 area of rat hippocampal slices by hypoxia or the epileptogenic agent 4-aminopiridine. Slice perfusion with the mixed adenosine receptor agonist R-PIA (0.2 microM) significantly (P < 0.05) decreased: (i) the number of slices showing a transient CA1 epileptiform bursting during the hypoxic period; (ii) the duration of the hypoxia-induced epileptiform bursting. Conversely, slice perfusion with the selective A1 adenosine receptor antagonists DPCPX (0.2 microM) or with the selective A2 adenosine receptor agonist CGS 21680 significantly (P < 0.05) increased the number of slices showing a transient CA1 epileptiform bursting during the hypoxic period but did not affect the duration of the hypoxia-induced epileptiform bursting. Neither drug significantly affected the number of slices showing functional recovery after hypoxia. Slice perfusion with DPCPX (0.2 microM) also significantly increased (P < 0.05) the number of slices showing a persistent CA1 epileptiform bursting during the reoxygenation period, while the other drugs failed to affect it. Slice perfusion with the selective A1 adenosine receptor agonist CPA (2 microM) or R-PIA (5 microM) significantly (P < 0.05) decreased the duration of the CA1 epileptiform bursting induced by 100 microM 4-aminopyridine. CGS 21680 (5 microM) perfused together with CPA (2 microM) significantly (P < 0.05) counteracted the inhibitory effects of the A1 adenosine receptor agonist on 4-aminopyridine epileptiform bursting, while it failed by itself to directly affect the 4-aminopyridine epileptiform bursting duration. The results produce evidence for a selective opposite modulation by A1 and A2 adenosine agonists in the control of hippocampal hyperexcitability induced by hypoxia or 4-aminopyridine but not in the post-hypoxic functional recovery.

4-Aminopyridine↗

PubMed1995

Microanatomical and electrophysiological changes of the rat dentate gyrus caused by lesions of the nucleus basalis magnocellularis.

The effect of unilateral or bilateral lesions of the nucleus basalis magnocellularis (NBM) on the dentate gyrus of the hippocampus were assessed using microanatomical and electrophysiological techniques. NBM is the main cholinergic basal forebrain nucleus that supplies the fronto-parietal cortex. Lesions were induced using the neurotoxin ibotenic acid or a radio-frequency system and did not affect glutamic acid decarboxylase activity both in the frontal cortex and in the hippocampus. At 4 weeks after lesioning, a loss of choline acetyltransferase (ChAT) activity and of ChAT-immunoreactive fibres was observed in the frontal cortex but not in the hippocampus and no changes in the density of granule neurons of the dentate gyrus or in the hippocampal long-term potentiation (LTP) were noticeable. At 8 weeks after lesioning the loss of both ChAT activity and of ChAT-immunoreactive fibres persisted in the frontal cortex of NBM-lesioned rats. Moreover, at this time a significant decrease in the density of granule neurons in the dentate gyrus accompanied by a reduced probability of dentate LTP induction were observed in both ibotenic acid- and radio-frequency-lesioned rats. These findings have shown that although NBM does not send direct cholinergic projections to the hippocampus, lesions of this cholinergic nucleus are accompanied by delayed neurodegenerative changes involving the dentate gyrus. This suggests the occurrence of indirect connections between NBM and the hippocampus, the functional relevance of which should be explored.

Animals↗

PubMed1995

Effect of long-term treatment with L-deprenyl on the age-dependent microanatomical changes in the rat hippocampus.

Chronic treatment with L-deprenyl increases both mean and maximum life span and improves cognitive functions in the aged rat. The present study was designed to evaluate whether long-term treatment with L-deprenyl at a dosage not inhibiting the monoamine oxidase-B (MAO-B) (1.25 mg/kg/day) or inhibiting the enzyme activity (5 mg/kg/day) had any effect on the age-dependent microanatomical changes in the rat hippocampus. The hippocampus was chosen in view of its key role in learning and memory functions. Treatment with L-deprenyl started at 19 months and lasted until the 24th month of age. Age-matched untreated rats were used as a control, whereas 11-month-old rats were used as an adult reference group. The number of nerve cell and glial fibrillary acidic protein-immunoreactive astrocyte profiles in the CA1 and CA3 fields of the hippocampus and in the dentate gyrus was decreased and increased, respectively in aged compared with adult rats. Treatment with 5 mg/kg/day, but not with 1.25 mg/kg/day L-deprenyl increased the number of neuronal profiles and decreased the number of astrocytes in the hippocampus of aged rats. The density of zinc stores in the associative intrahippocampal pathway of mossy fibres, which was decreased in aged animals, was increased after treatment with the two doses of L-deprenyl. Lipofuscin accumulation within the cytoplasm of pyramidal neurons of the hippocampus was reduced dose dependently by L-deprenyl treatment. These results suggest that long-term treatment with L-deprenyl is able to counter the expression of age-dependent microanatomical changes in the rat hippocampus. These effects seem only partially correlated with the MAO-B inhibitory activity of L-deprenyl.

Aging↗

PubMed1995

Age-related changes in brain microanatomy: sensitivity to treatment with the dihydropyridine calcium channel blocker darodipine (PY 108-068).

The influence of aging and of treatment with the dihydropyridine Ca2+ antagonist darodipine (PY 108-068) on the age-related microanatomical changes of rat brain were studied in male Wistar rats treated from the 18th to the 24th month of age with an oral dose of 5 mg/kg/day of darodipine. Twelve-month-old untreated rats were used as an adult reference group. A decreased number of nerve cells and of alkaline phosphatase-positive capillaries and an increased lipofuscin deposition were observed in the frontal and occipital cortex, in the hippocampus, and in the cerebellar cortex of rats of 24 months in comparison with 12-month-old animals. The number of nerve cells was higher in the occipital cortex and in the hippocampus, but not in the frontal cortex and in the cerebellar cortex, of darodipine-treated rats in comparison with age-matched untreated animals. Lipofuscin deposition is reduced in all the brain areas investigated. The density of alkaline phosphatase-reactive capillaries is also increased in the frontal and occipital cortex and in the hippocampus of aged rats treated with darodipine. The above results suggest that treatment with darodipine is able to counter some microanatomical changes occurring in the brain of aged rats and involving not only microvascular parameters. The occipital (visual) cortex and the hippocampus were the cerebral areas more sensitive to treatment with darodipine. The possible relevance of these findings is discussed.

Aging↗

PubMed1994

Muscarinic cholinergic receptors in the hippocampus of aged rats: influence of choline alphoscerate treatment.

The present study was designed to investigate age-dependent changes of muscarcinic M1 and M2 cholinergic receptors in the rat hippocampus using radioreceptor assay and autoradiographic techniques with [3H]pirenzepine and [3H]AF-DX 116 as ligands. The analysis was performed on 2-, 12- and 27-month-old male Wistar rats, considered young, adult and old, respectively. Moreover, the influence of a 6-month treatment with choline alphoscerate on the density and pattern of M1 and M2 cholinergic receptors was assessed. Choline alphoscerate (L-alpha-glyceryl phosphorylcholine) is a precursor in the biosynthesis of several brain phospholipids which increases the availability of acetylcholine in various tissues. Muscarinic M1 cholinergic receptors were significantly decreased with increasing age whereas M2 cholinergic receptors did not show changes. Choline alphoscerate treatment countered, in part, the loss of muscarinic M1 receptor sites in old rats. Light microscope autoradiography revealed a loss of silver grains developed after exposure of sections of hippocampus to [3H]pirenzepine in the stratum oriens of CA1 and CA3 fields in rats of 12 and 27 months in comparison with young animals. Choline alphoscerate restored, in part, the decrease of silver grains noted in old rats. Quantitative analysis of the density of silver grains developed in the cell body of pyramidal neurons of CA1 and CA3 fields processed for the demonstration of muscarinic M1 receptor sites revealed a decrease of these grains in rats of 27 months in comparison with younger cohorts. These findings suggest that the reduction in muscarinic M1 sites noticeable between 2- and 12-month rats is probably dependent on the loss of nerve cells and/or terminals in these hippocampal fields rather than to a reduction of their density per neuron. Treatment with choline alphoscerate increased the expression of muscarinic M1 cholinergic receptors within the cell body of pyramidal neurons of CA1 and CA3 fields compared to age-matched control old rats. Consistent with radioreceptor assay data, no changes in the density of muscarinic M2 cholinergic receptors in the animal groups examined were demonstrated by light microscope autoradiography. The possible pharmacological relevance of the increased expression of muscarinic M1 cholinergic receptors elicited by choline alphoscerate in the hippocampus of aged rats is discussed.

Aging↗

PubMed1994

Neuroanatomy of aging brain. Influence of treatment with L-deprenyl.

The present study was designed to assess the influence of long term L-deprenyl treatment on some microanatomical parameters of aging rat frontal cortex and hippocampus. Male Sprague-Dawley rats of 19 months of age were divided into three groups. Rats of the first group received an oral daily dose of 1.25 mg/kg L-deprenyl; animals of the second group were treated with an oral daily dose of 5 mg/kg L-deprenyl, whereas rats of the third group were left untreated and used as control. Treatment lasted for 5 months, and rats were sacrificed at 24 months. At this age they were considered to be old. Another group of 11-month-old rats was used as an adult reference group. The density of nerve cell profiles and of glial fibrillary acidic protein (GFAP) immunoreactive astrocytes was decreased and increased respectively in the frontal cortex and in the different portions of the hippocampus in old in comparison with adult rats. A decrease in the intensity of sulfide silver staining in the mossy fibers of the hippocampus was also observed in old rats. Moreover, a cytoplasmatic accumulation of lipofuscin was noticeable in old rats as well as a significant increase of the monoamine-oxidase (MAO) B reactivity both in the frontal cortex and in the hippocampus. A higher density of nerve cell profiles, of sulfide silver staining, and fewer astrocyte profiles were noticeable in the frontal cortex and in the hippocampus of old rats treated with 5 mg/kg/day of L-deprenyl. This dose of the compound also significantly reduced lipofuscin accumulation and MAO-B reactivity in old rats. However, the lower dose of the compound did not cause any statistically significant effect on the microanatomical parameters investigated with the exception of sulfide silver staining and lipofuscin accumulation, which were increased and decreased respectively after 1.25 mg/kg per day of L-deprenyl. The above results suggest that long-term treatment with L-deprenyl is able to counter some microanatomical changes typical of the aging frontal cortex and hippocampus in the rat. These changes seem to be in part related to the MAO-B inhibitory activity of L-deprenyl.

Aging↗

PubMed1994

Influence of long-term treatment with L-deprenyl on the age-dependent changes in rat brain microanatomy.

The present study was designed to assess whether treatment with the monoamine oxidase-B (MAO-B) inhibitor L-deprenyl, which has been documented to increase both mean and maximum survival in aged rats as well as sexual performance and cognitive function, has any effect on the age-related microanatomical changes occurring in the rat brain. Male Sprague-Dawley rats received a subcutaneous injection of 0.25 mg/kg L-deprenyl every other day from the 19th to the 24th month of age. Age-matched control rats were injected with saline, whereas 11-month-old untreated rats were used as an adult reference group. Both body and brain weight were increased as a function of age, and they were unaffected by treatment with L-deprenyl. The density of nerve cell profiles in the frontal cortex, in the CA-1 and CA-3 subfields of the hippocampus, in the dentate gyrus and in the cerebellar cortex were decreased in aged rats in comparison with adult rats. The density of nerve cell profiles in the above brain areas of L-deprenyl-treated rats was not significantly higher in comparison with age-matched control animals with the exception of Purkinje neuron profiles. The intensity of Nissl's staining, which may be related to the protein synthetic capabilities of nerve cells, is reduced within pyramidal neurons of the hippocampus and Purkinje neurons of the cerebellar cortex of aged rats. The intensity of Nissl's staining in L-deprenyl-treated rats was not different from adult rats. Lipofuscin deposition was significantly increased within the cytoplasm of pyramidal neurons of the frontal cortex, of the CA-3 subfield of the hippocampus and of Purkinje neurons of the cerebellar cortex. L-Deprenyl administration decreased lipofuscin accumulation within the cytoplasm of the above mentioned nerve cell types. The density of sulphide-silver staining in the intrahippocampal pathway of mossy fibres, which participate in the elaboration of passive avoidance responses, is decreased in aged rats. Treatment with L-deprenyl counters this age-related reduction. The above results suggest that long-term treatment with L-deprenyl is able to counter the expression of some microanatomical changes typical of aging brain.

Aging↗

PubMed1994

Influence of treatment with L-deprenyl on the structure of the cerebellar cortex of aged rats.

Treatment with L-deprenyl increases mean and maximum life span in the rat and reverses memory and learning deficits associated with old age. Since only sparse information is available concerning the influence of L-deprenyl administration on the aging brain microanatomy, we have investigated the effect of long-term treatment with L-deprenyl on the structure of the cerebellar cortex in the aged rat. The cerebellar cortex was used since it represents a useful model for assessing age-related changes in nervous system anatomy and function. Male Sprague-Dawley rats were treated from the 19th to the 24th month of age with a daily oral dose of 1.25 mg/kg or 5 mg/kg L-deprenyl. Age-matched rats were left untreated and used as a control group. Eleven-month-old untreated rats were used as an adult reference group. The density of Purkinje and granule neuron profiles as well as the intensity of Nissl's staining within the cytoplasm of Purkinje neurons were reduced in 24-month in comparison with 11-month rats. Moreover, an increased accumulation of lipofuscin was noticeable in the cytoplasm of Purkinje neurons of old rats as well as an increase in MAO-B activity in the molecular layer of the cerebellar cortex. The two doses of L-deprenyl increased the density of both Purkinje and granule neuron profiles and the intensity of Nissl's staining in the cytoplasm of Purkinje neurons and reduced lipofuscin deposition within Purkinje neurons. The lower dose of L-deprenyl caused only a slight decrease in MAO-B activity, whereas the 5-mg/kg/day dose remarkably reduced it. These results suggest that long-term treatment with L-deprenyl counters the expression of some age-related microanatomical changes in the rat cerebellar cortex. The possible independence of the effects of the compound on age-related microanatomical changes of the cerebellar cortex and on MAO-B inhibitory activity is discussed.

Aging↗

PubMed1993

Effects of calcium and paired-pulse stimulation on hypoxia-induced hippocampal electrical changes.

The influence of calcium concentration changes (2 and 4 mM) and of the paired-pulse stimulation (PPS) paradigm on the effects of hypoxia has been investigated in rat hippocampal slices. Because a high calcium concentration (4 mM) facilitates paired-pulse inhibition (PPI) at a 15-ms interpulse interval, the influence of hypoxia-induced effects were tested against calcium-induced PPI. In the PPS, unconditioned response at calcium concentrations of 2 and 4 mM, and 15- or 30-ms interpulse intervals of stimulation, no significant differences were found in the latency to induce a 50% amplitude decrease of the CA1 population spikes during hypoxia. On the contrary, in the conditioned response the latency to induce a 50% amplitude decrease of CA1 population spikes was significantly increased (p < 0.01) at 4 mM calcium, 15-ms interpulse interval with respect to experiments with 2 mM calcium, at 15- or 30-ms interpulse intervals. The data indicate that PPI is strongly affected during the early phases of hypoxia and also suggest that drugs increasing PPI could be successfully used for the treatment of brief anoxic or ischemic functional alterations.

Animals↗

PubMed1992

Purification and characterization of a strictly specific beta-D-fucosidase from Aspergillus phoenicis.

Although beta-D-fucosidase (beta-D-fucohydrolase, EC 3.2.1.38) has been isolated from various sources, all those enzymes were associated with a high activity of beta-D-galactosidase and/or beta-D-glucosidase. We have purified a specific beta-D-fucosidase in electrophoretically homogeneous form from crude extracts of Aspergillus phoenicis by polyethyleneglycol 8000-phosphate buffer aqueous two-phase separation, and successive chromatography on DEAE-Sephadex A-50, hydroxyapatite, and Sephadex G-100 columns. The molecular weight of the enzyme was estimated to be 57,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and 50,000 to 60,000 by gel filtration on Sephadex G-100. The enzyme showed optimum activity at pH 6.0 and 40 degrees C; it was stable in the pH range 5.5-6.5 and below 35 degrees C. The Km and the Vmax values for pNP-beta -D-fucoside were 2.4 mM, and 12.8 mumol.min-1.mg-1, respectively. The enzyme was strongly inhibited by sulfhydryl group reagents, p-chloromercuribenzoate, n-ethylmaleimide, and iodoacetate. It was also inhibited by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide, diethyl pyrocarbonate, and N-bromosuccinimide. Thus, -SH and -COOH groups and histidyl and tryptophyl residues were essential for enzyme activity. The purified beta-D-fucosidase showed high specificity toward p-nitrophenyl-beta-D-fucoside. The enzyme was inhibited by D-fucose and D-fucono-gamma-lactone, but not by D-galactose, D-galactono-gamma-lactone, D-glucose, or D-glucono-gamma-lactone; the latter compounds are specific inhibitors of beta-D-galactosidase and beta-D-glucosidase, respectively. Thus, this enzyme is the most strictly specific beta-D-fucosidase when compared with those previously reported.

Aspergillus↗

PubMed1992

Effects of adenosinergic drugs on hypoxia-induced electrophysiological changes in rat hippocampal slices.

The effects of adenosinergic antagonists caffeine and DPCPX, and of the adenosinergic agonists L-PIA, CPA and CGS 21680 were investigated on fully and partially reversible hypoxia-induced electrophysiological changes in rat hippocampal slices. The influence of a high potassium solution and of the N-methyl-D-aspartate antagonist dizocilpine (MK 801) was also tested. The latency to obtain a 50% decrease in the amplitude of the CA1 population spike (CA1 PS) during a short- (5-10 min) lasting hypoxic period was significantly increased (P less than 0.01) by slice perfusion with caffeine (50 microM), DPCPX (0.2 microM), and by increasing (from 3 to 4 mM) the potassium concentration in the medium bathing the hippocampal slices. The latency was significantly decreased (P less than 0.01) by slice perfusion with L-PIA (0.2 microM) and CPA (0.05 microM). It was not significantly modified by CGS 21680 (5 microM). The incidence of reappearance of the CA1 PS during reoxygenation after long- (45 min) lasting hypoxia was significantly increased (P less than 0.05) by slice perfusion with MK 801 (50 microM), while it was not significantly affected by slice perfusion with caffeine (50 microM) or DPCPX (0.2 microM) or L-PIA (0.2 microM) or CPA (0.05 microM) or CGS 21680 (5 microM). The results indicate a prevalent involvement of the A1 adenosine receptors in the early mechanisms underlying hypoxia-induced reversible changes. Adenosine seems to have a limited role in the late mechanisms occurring after a long-lasting hypoxic period.

Adenosine↗

PubMed1992

Inhibitory influence of morphinans on ictal and interictal EEG changes induced by cortical application of penicillin in rabbits: a comparative study with NMDA antagonists and pentobarbitone.

The effects of dextrorphan (DX) and dextromethorphan (DM) were tested using the electroencephalogram (EEG) and behavioral effects induced by topical cortical application of penicillin in rabbits. For comparison, the influence of the NMDA antagonists, dizocilpine (MK 801) and 3-((+-(-)2-carboxypiperazine-4-yl)propyl-1-phosphonic acid (CPP), and of pentobarbitone was investigated. Intracortical injection of 500 IU of penicillin produced an EEG spiking followed by a repeated generalization of the electrical and behavioral symptoms. Within a few minutes, DX (5-15 mg/kg, IV) or pentobarbitone (5-10 mg/kg, IV) reduced dose dependently and significantly (p less than 0.01) the interictal and ictal EEG and behavioral effects elicited by cortical injection of 500 IU of penicillin. Higher doses of pentobarbitone (20 mg/kg, IV) but not of DX (20 mg/kg, IV) completely blocked the ictal behavioral and EEG effects elicited by cortical injection of 500 IU of penicillin. Within a few minutes, MK 801 (0.1-0.2 mg/kg, IV) or CPP (10-20 mg/kg, IV) reduced dose dependently and significantly (p less than 0.01) the ictal EEG and behavioral effects elicited by cortical injection of 500 IU of penicillin, while they did not affect the penicillin-induced interictal EEG changes. Higher doses of MK 801 (0.3 mg/kg, IV) completely blocked the ictal behavioral and EEG effects elicited by cortical injection of 500 IU of penicillin. Within a few minutes, DM (10-20 mg/kg, IV) blocked the behavioral effects, but failed to affect either the interictal or the ictal EEG effects induced by cortical injection of 500 IU of penicillin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Highly ouabain-sensitive alpha 3 isoform of Na+,K(+)-ATPase in human brain.

The Na+,K(+)-ATPase alpha 3 isoform has recently been demonstrated immunochemically in human brain. Conclusive biochemical evidence, however, is still lacking. In this study, a unique 50-kDa polypeptide, which is known to be specific to the rat alpha 3 isoform, has been found in human brainstem Na+,K(+)-ATPase following formic acid treatment of the purified alpha isoform proteins. Human alpha 3 Na+,K(+)-ATPase is also highly sensitive to ouabain inhibition, with a 50% ouabain inhibition value of 1.0 x 10(-7) M. These results provide clear and direct evidence for the existence of the alpha 3 isoform in human brain.

Animals↗