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Biomedical subjects

E Fadda

Publications and source records attributed to E Fadda.

32 records · Page 2Linked to original sources
PubMed1990

[3H]D-serine labels strychnine-insensitive glycine recognition sites of rat central nervous system.

In the central nervous system, glycine binds to two recognition sites; one of them (G2), associated with the glutamate receptor, is insensitive to strychnine. Strychnine-insensitive sites were predominant in the forebrain areas and bound D-serine and D-alanine better than the respective L stereoisomers. [3H]D-serine was a more selective radioligand than [3H]glycine for the strychnine-insensitive sites. In the forebrain, the binding of both ligands was inhibited by the putative G2 receptor antagonists, 7-chlorokynurenate and 3-amino-1-hydroxy-2-pyrrolidone, while in pons and in spinal cord only the latter drug was effective. This may indicate the heterogeneity of strychnine-insensitive glycine recognition sites.

Animals↗
PubMed1989

Kynurenate and 2-amino-5-phosphonovalerate interact with multiple binding sites of the N-methyl-D-aspartate-sensitive glutamate receptor domain.

By studying the binding of [3H]glycine and [3H]glutamate to rat synaptic membranes in the presence of 2-amino-5-phosphonovalerate (APV) and kynurenate (KYN) we have demonstrated that KYN is more potent than APV in displacing [3H]glycine, while an opposite order of potency was seen in displacing [3H]glutamate. Moreover, 2-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) inhibited only [3H]glutamate binding. The [3H]MK-801 specific binding was inhibited by all of the above antagonists; this action was abolished by glutamate, while glycine partially reversed only the action of KYN. Hence, KYN inhibits glutamate receptors by preferentially interfering with glycine recognition sites, while APV preferentially interacts with N-methyl-D-aspartate (NMDA) recognition sites.

2-Amino-5-phosphonovalerate↗
PubMed1989

Glycine and D-serine act as positive modulators of signal transduction at N-methyl-D-aspartate sensitive glutamate receptors in cultured cerebellar granule cells.

In cultures of rat neonatal cerebellar granule cells the signal transduction at ionotropic NMDA-sensitive glutamate receptors (GC1) was measured as an increase of influx of 45Ca2+. This transmitter-mediated influx of Ca2+ was enhanced by glycine and D-serine in a dose-dependent manner. D-Alanine was less active than glycine and D-serine, while L-alanine and L-serine were inactive. These amino acids failed to activate basal influx of Ca2+. Activation of calcium influx at GC2 receptors by kainate was unchanged by the amino acids mentioned above. Glycine and D-serine increased the potency but failed to change the efficacy of GC1 agonists. This action was not changed by strychnine. The enhancement of aspartate signal transduction by glycine and D-serine was inhibited by the noncompetitive GC1 receptor antagonist, phencyclidine, but was even more evident in presence of Mg2+ ions. Hence, glycine and D-serine may function as positive allosteric modulators of signal transduction at NMDA-sensitive (GC1) glutamate receptors.

Animals↗
PubMed1989

Endocrine, hematological and immunological changes in surgical patients undergoing general anesthesia.

Some hematological endocrine, and immunological reactions in surgical patients under general anesthesia were studied. While serum cortisol, fT4, T4, rT3 levels increased, TBG, TSH, fT3 and T3 decreased. Cortisol increase and T3 and fT3 decrease were still significant three days after surgery. TSH and T3 decrease was significantly related to cortisol increase. CD4 (helper-inducer) cells dropped, rosettes, CD 5, CD 8, CD 16 (NK) and T HLA-DR (activated) number of cells did not change significantly. The decrease in CD 4 subset was significantly related to cortisol increase. Thus surgery was followed by a reduced thyroid function and decreased CD 4 subset. However this was observed also in the few patients in whom the serum cortisol level did not change. These reactions may represent immunosuppression occurring in the postoperative period.

Adult↗
PubMed1989

Different modes of action of 3-amino-1-hydroxy-2-pyrrolidone (HA-966) and 7-chlorokynurenic acid in the modulation of N-methyl-D-aspartate-sensitive glutamate receptors.

The N-methyl-D-aspartate (NMDA)-sensitive glutamate receptors are known to be inhibited by 3-amino-1-hydroxy-2-pyrrolidone (HA-966) and 7-chlorokynurenic acid (Cl-KYN), which act at the glycine-regulated allosteric modulatory center. In this work we show that, in synaptic membranes prepared from rat brain, Cl-KYN and HA-966 inhibit the binding of [3H]glycine. Moreover, Cl-KYN can also completely inhibit the binding of [3H]glutamate to the primary transmitter recognition site for the NMDA receptor, whereas HA-966 only partially reduces this binding. Cl-KYN also abolishes the binding of the NMDA receptor antagonist [3H]3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP). In contrast, HA-966 increases [3H]CPP binding, affecting the affinity but not the maximal number of binding sites. This increase is inhibited by glycine and Cl-KYN. The binding of [3H] (+)-5-methyl-10,11-dihydro-5H-dibenzocyclohepten-5,10-imine maleate (MK-801), used as an index of NMDA receptor activation, is completely inhibited by Cl-KYN but only partially by HA-966. In addition, HA-966, but not Cl-KYN, increases the potency of CPP in inhibiting [3H]MK-801 binding. Our results demonstrate that Cl-KYN and HA-966 differ in their ability to modulate the NMDA receptor, perhaps acting at distinct but overlapping recognition sites. Furthermore, our results suggest that agonist and antagonist recognition sites of the NMDA receptor may be independently regulated by glycine and HA-966, which would result, respectively, in a positive and negative allosteric modulation of the NMDA receptor complex.

Animals↗
PubMed1988

Glycine and D-serine increase the affinity of N-methyl-D-aspartate sensitive glutamate binding sites in rat brain synaptic membranes.

In previously frozen and extensively washed brain membranes [3H]glutamate binds to a single population of sites characteristic of the NMDA-sensitive glutamate receptor subtype. This binding cannot be displaced by glycine and D-serine, but actually is enhanced by these amino acids in a dose-dependent manner. Glycine and D-serine increase the affinity of glutamate binding without changing the density of binding sites. These results delineate glycine as an allosteric modulator of the recognition site for the NMDA-sensitive glutamate receptor.

Animals↗
PubMed1988

Pertussis toxin inhibits signal transduction at a specific metabolotropic glutamate receptor in primary cultures of cerebellar granule cells.

In primary cultures of cerebellar granule cells, glutamate receptors have been classified into metabolotropic (GP1 and GP2) and ionotropic (GC1 and GC2). The GP1 and GC1 receptors are negatively modulated by magnesium and noncompetitively inhibited by phencyclidine; GP2 and GC2 receptors are insensitive to inhibition by magnesium and phencyclidine (Costa, Fadda, Kozikowski, Nicoletti and Wroblewski, 1988). Exposure of cultured cerebellar granule cells to pertussis toxin (PTX, 1 microgram/ml for 14-16 hr) reduced the stimulation of the hydrolysis of inositol phospholipids (PI) by the GP2 receptor agonists, glutamate and quisqualate in the presence of magnesium, but did not inhibit the stimulation of the hydrolysis of PI by GP1 receptor agonists. The stimulation of the hydrolysis of PI by the muscarinic cholinergic receptor agonist, carbamylcholine, remained unchanged after pretreatment with pertussis toxin. In membranes prepared from cerebellar granule cells in primary culture, the addition of guanosine 5'-0-(3-thiotriphosphate) (GTP-gamma-s), a nonhydrolyzable analogue of GTP, enhanced the hydrolysis of PI and reduced the Bmax of quisqualate-displaceable binding of [3H]glutamate. These results indicate that, in primary cultures of cerebellar granule cells, a specific class of metabolotropic glutamate receptors (the GP2 receptor) is coupled with the hydrolysis of PI through a pertussis toxin-sensitive GTP-binding protein.

Animals↗
PubMed1987

Lesions of putative glutamatergic pathways potentiate the increase of inositol phospholipid hydrolysis elicited by excitatory amino acids.

The stimulation of inositol phospholipid (PI) hydrolysis by excitatory amino acids was measured in the rat hippocampus or striatum after 3 different chemical or surgical lesions of putative glutamatergic pathways. Intrahippocampal infusions of kainate preferentially destroyed neurons in the CA3-4 areas, denervating the CA1 area of the ipsilateral and contralateral hippocampus. Infusions of colchicine selectively destroyed granule cells of fascia dentata, denervating the CA3 area of the ipsilateral hippocampus. Ablation of the frontal cortex selectively reduced the glutamatergic afferents to the striatum. These 3 lesions potentiated the ibotenate, glutamate and quisqualate stimulation of PI hydrolysis, while N-methyl-D-aspartate remained ineffective. This stimulation was inhibited by 2-amino-4-phosphonobutyric acid but not by phencyclidine. These lesions also increased the stimulation of PI hydrolysis elicited by norepinephrine, but failed to enhance the stimulation by carbamylcholine. These results support the hypothesis that signal transduction in a subclass of excitatory amino acid receptors present in rat brain may undergo plastic modifications following denervation.

Amino Acids↗
PubMed1987

Phencyclidine is a negative allosteric modulator of signal transduction at two subclasses of excitatory amino acid receptors.

Phencyclidine (PCP) and some of its pharmacological congeners inhibit the signal transduction at specific excitatory amino acid receptors of cerebellar granule cells in primary cultures. These drugs do not bind to the transmitter recognition sites, and affinity of this specific binding site is increased by the presence of the transmitter bound to its recognition sites. PCP inhibits phosphatidylinositol phosphate hydrolysis mediated by Mg2+-sensitive glutamate receptors (GP1) but not that mediated by Mg2+-insensitive glutamate receptors (GP2). In addition, PCP inhibits Ca2+ influx and cGMP formation mediated by the activation of Mg2+-sensitive glutamate receptors (GC1) but not that mediated by Mg2+-insensitive glutamate receptors (GC2). In this cell culture the activation of phosphatidylinositol phosphate hydrolysis by muscarinic receptor agonists is not affected by PCP. Since PCP inhibits noncompetitively GP1 and GC1 signal transduction it may act as a negative allosteric modulator of signal transduction at both receptors. The pharmacological profile of PCP and its congeners delimits a class of drugs modulating allosterically the action of the primary transmitter at GP1 and GC1 receptors. These drugs need the presence of the transmitter to act and they cannot be termed inverse agonists because they are devoid of activity in the absence of the transmitter; moreover, they do not bind to the transmitter recognition site nor do they prevent the transmitter binding to its recognition sites.

Allosteric Regulation↗
PubMed1986

Immunological features of endemic goiter.

Some immune aspects of simple endemic goiter have been studied through a comparison of IgG, IgA, IgM, kappa and lambda chains, and C3 and C4 in the peripheral blood of 59 patients operated on for goiter and the peripheral blood of 49 normal controls. The median IgM was lower in the goiter blood. The incidence of thyroglobulin (Tg) and microsomal (Mi) antibodies (Abs) was 20.3% in goiter blood and that of nonthyroid autoAbs was 37%. Active and total rosetted blood lymphocytes were counted and OKT3, OKT4, OKT8, Leu 1, Leu3a, Leu2b, T DR+, and NK cell populations were classified. Helper T cells were occasionally decreased when goiter was associated with lymphocytic thyroiditis. The NK percentage was sometimes higher in goiter blood, whereas the T DR+ percentage was not significantly different in the two groups. Lymphocyte infiltration (LI) was noted in 32% of goiters (about 5% with a diffuse and nodular pattern). A prevalence of helper/inducer cells was observed among the infiltrating T cells. HLA-DR antigen (Ag) positive epithelial cells were seen, not only in LI areas. Granular deposits of IgG, IgA, IgM, and C3 on the follicular basal membrane were stained in 6.7% of goiters Patterns histologically and immunologically similar to those in Hashimoto's thyroiditis may therefore be observed in long-standing simple endemic goiter, suggesting that an autoimmune mechanism may be involved in its pathogenesis.

Autoantibodies↗
PubMedDate not supplied

Polyaromatic hydrocarbons administered in humans by dermal route increase total IgE.

Inhalation of polyaromatic hydrocarbons (PAHs) extracted from diesel exhaust particles (DEP) enhances local (nasal) production of IgE in humans. The aim of the present research is to investigate whether in humans dermal exposure to PAHs which are not extracted from DEPs increases serum IgE, and whether host factors modify the immunologic effect. In thirty-two patients with acute psoriatic lesions, a cream containing 3% of coal tar (which holds a variety of PAHs) was applied to the skin for 24 hours. Serum IgE were measured before (IgE0) and four (IgE4) and eight (IgE8) days after application. Replicated means were compared by analysis of variance for repeated measures and by the Newman-Keuls' test. IgE0, IgE4 and IgE8 were 151.19, 159.69 (a 6% excess) and 170.90 kU/L (a 13% excess) respectively; pairwise comparison showed IgE8 was significantly higher than IgE0 (p<0.05). At multiple linear regression analysis, the percentage increase in serum IgE across observation days was the dependent variable against age, sex, cigarettes/day, urinary 1-pyrenol, atopy, skin area treated, and grams of cream. Of the independent variables, only age had a significant (p<0.028) influence: the younger the age, the higher the IgE response to PAHs. We conclude that whatever the source and the route of entry (skin or respiratory tract), PAHs increase total serum IgE, mainly in younger age groups.

Administration, Cutaneous↗
PubMedDate not supplied

[Ventilatory functions in subjects exposed to hydrogen peroxide at levels below the TLV: longitudinal study].

In the bottling departments of a beverage processing plant, exposure to hydrogen peroxide was below TLV from 1995 to 2001. Forced vital capacity (FVC), forced expiratory volume 1st second (FEV1), and FEV1/FVC were compared between exposed and unexposed workers. Using sparse data collected from 1993 to 2002, changes over time (slope) were calculated for each functional index in each subject. The slope was the dependent variable at multiple regression analysis with exposure and smoking as predictive variables. Using complete data collected from 2000 to 2002 in fewer subjects, the longitudinal changes were assessed by repeated measures analysis of variance. Both methods provide same results: with respect to unexposed, in exposed workers FVC increased, FEV1/was unchanged and FEV1/FVC decreased; the latter difference was no more significant when FVC slope was added as covariate to the model. In conclusion, the findings seem to support the current TLV for hydrogen peroxide. There were no similar studies in the literature.

Forced Expiratory Volume↗
PubMedDate not supplied

[Changes in risk factors for spontaneous abortion in an area with high concentrations of shoe manufacture after a preventive intervention].

Risk factors of spontaneous abortion were investigated in two matched case-control studies in 1987-88 and 1997-99. An history of previous abortions significantly increased the risk in both studies. Lifestyle (coffee) and occupational (exposure to organic solvents) factors were associated with a significantly increased risk in the first but not in the second calendar period, following a community intervention with advice given to workers, employers, and physicians; the latter also counseled a greater use of medicines against spontaneous abortion.

Abortion, Spontaneous↗