165 research outputs found
In memoriam Madga Olivero, alla signora della lirica
No full textRicordo del soprano Magda Olivero, deceduta più che centenaria, conosciuta dall'autore ed inserita in monografia dedicata a 108 stelle della lirica.Ricollection of soprano Magda Olivero, who died over 100, known personally to the author and entering his book on 108 stars of Opera
Immune response to vaccines in children with celiac disease
No full textCeliac disease (CD) is an immune-mediated systemic condition evoked by ingestion of gluten and related prolamines in genetically susceptible subjects. The disease is featured by a variable combination of clinical signs, specific antibodies, HLA-DQ2 and HLA-DQ8 haplotypes, and enteropathy. Vaccination is the most potent intervention for infectious disease prevention. Several factors including age, gender, ethnicity, quality and quantity of vaccine antigen, doses, and route of administration can influence immune response to vaccination, although the main cause of variation in the responsiveness among vaccine recipients is host genetic variability. The HLA system has a fundamental role in identifying the antigens introduced into the host with the vaccines and in the development of specific antibodies, and some HLA phenotypes have been associated with a less effective immunological response. The available literature indicates that the immunological response to vaccines in CD children does not differ markedly from that of general population and antibody titres are high enough to provide long-term protection, except for hepatitis B virus vaccine. In this article, we review and discuss the scarce literature in this field in order to provide clinical practice guidelines to achieve the most efficient monitoring of the response to vaccines in pediatric CD patients
On the semantics of artifactual and social kind terms
No full textHilary Putnam’s proposal of extending the scope of his famous externalist semantic theory to artifactual (e.g. ‘pencil’, ‘chair’, ‘television’, etc.) and social kind terms (e.g. ‘pediatrician’, ‘university’, ‘money’, etc.) has opened an ongoing debate, which is the main focus and basis of the present work. By contrast, the same semantic account limited to words for natural substances and species (e.g. ‘water’, ‘gold’, ‘tiger’, etc.) has become very popular and quite widely adopted, since it seems to give a convincing explanation of how the semantics of these terms works. The first part of the present work is dedicated to a twofold purpose: on the one hand, I aim to argue that Putnam’s argument about the semantics of artifactual (and social) kind terms fails in its goal; on the other hand, – on the strength of the considerations drawn out from this analysis – I point out that the main positions which characterize the aforementioned debate do not succeed in their intent either. In the second part, I focus on remarking that the criticisms of Externalism arise already even when accounting for some of usually believed steady cases. I aim to argue, in this respect, that all problems of Putnam’s Semantic Externalism – as applied not only to artifactual and social kind words, but across the board – are a consequence of the fact that Putnam implicitly relies on a hyperrealist view on modality. Such a modal approach notoriously encounters several problems. In order to bypass those problems, Amie Thomasson proposes an alternative approach to modality: Modal Normativism. I aim to highlight that adopting a normativist approach commits us to abandon Putnam’s Externalism and to embrace a hybrid theory of reference. Such view on reference combined with Modal Normativism – I intend to show – not only overcomes the semantic weaknesses of Putnam’s Externalism, but it also accounts for those controversial cases emerged within the debate, as much as by the opponents of Putnam’s semantic view in general. Such alternative approaches combined constitute – I therefore argue – a more tenable and attractive account of the semantics of our kind terms. Within the perspective I here advocate for the debates about artifactual and social kind terms, as much as in general about the controversial cases Externalism has difficulties to explain, can be seen – I suggest – as metalinguistic negotiations. With such a notion – advanced by Tim Sundell and David Plunkett and taken up by Thomasson – we gain the further advantage of accounting for the importance of the debate while still preserving the advantages of a deflationary approach
Immuno-pharmacological characterization of the NMDA autoreceptors regulating glutamate release in the hippocampus: relevance to anti-NMDA receptor autoimmune diseases.
No full textSpecial Issue — From Foundations of Quantum Mechanics to Quantum Information and Quantum Metrology & Sensing, “Quantum 2017”; Author Index Volume 15 (2017)
No full textImmuno-Pharmacological Characterization of Presynaptic GluN3A-Containing NMDA Autoreceptors: Relevance to Anti-NMDA Receptor Autoimmune Diseases
No full textMouse hippocampal glutamatergic nerve endings express presynaptic release-regulating NMDA autoreceptors (NMDARs). The presence of GluN1, GluN2A, GluN2B, and GluN3A subunits in hippocampal vesicular glutamate transporter type 1-positive synaptosomes was confirmed with confocal microscopy. GluN2C, GluN2D, and GluN3B immunopositivity was scarcely present. Incubation of synaptosomes with the anti-GluN1, the anti-GluN2A, the anti-GluN2B, or the anti-GluN3A antibody prevented the 30 μM NMDA/1 μM glycine-evoked [ 3 H]d-aspartate ([ 3 H]d-ASP) release. The NMDA/glycine-evoked [ 3 H]d-ASP release was reduced by increasing the external protons, consistent with the participation of GluN1 subunits lacking the N1 cassette to the receptor assembly. The result also excludes the involvement of GluN1/GluN3A dimers into the NMDA-evoked overflow. Complement (1:300) released [ 3 H]d-ASP in a dizocilpine-sensitive manner, suggesting the participation of a NMDAR-mediated component in the releasing activity. Accordingly, the complement-evoked glutamate overflow was reduced in anti-GluN-treated synaptosomes when compared to the control. We speculated that incubation with antibodies had favored the internalization of NMDA receptors. Indeed, a significant reduction of the GluN1 and GluN2B proteins in the plasma membranes of anti-GluN1 or anti-GluN2B antibody-treated synaptosomes emerged in biotinylation studies. Altogether, our findings confirm the existence of presynaptic GluN3A-containing release-regulating NMDARs in mouse hippocampal glutamatergic nerve endings. Furthermore, they unveil presynaptic alteration of the GluN subunit insertion in synaptosomal plasma membranes elicited by anti-GluN antibodies that might be relevant to the central alterations occurring in patients suffering from autoimmune anti-NMDA diseases
Prolonged activation of CXCR4 hampers the release-regulating activity of presynaptic NMDA receptors in rat hippocampal synaptosomes
No full textWe investigated the impact of the prolonged exposure of rat hippocampal synaptosomes to CXCL12 (3 nM) on the NMDA-mediated release of [ 3 H]D-aspartate ([ 3 H]D-Asp) or [ 3 H]noradrenaline ([ 3 H]NA). Synaptosomes were stimulated twice with NMDA/CXCL12 and the amount of the NMDA-evoked tritium release (S1 and S2) quantified to calculate the S2/S1 ratio. The S2/S1 ratio for both transmitters was drastically decreased by 3 nM CXCL12 between the two stimuli (CXCL12-treated synaptosomes) in a AMD3100-sensitive manner. The phosphorylation of the GluN1 subunit in Ser 896 was reduced in CXCL12-treated synaptosomes, while the overall amount of GluN1 and GluN2B proteins as well as the GluN2B insertion in synaptosomal plasmamembranes were unchanged. We conclude that the CXCR4/NMDA cross-talk is dynamically regulated by the time of activation of the CXCR4s. Our results unveil a functional cross-talk that might account for the severe impairments of central transmission that develop in pathological conditions characterized by CXCL12 overproduction
Immunopharmacological characterization of presynaptic release-regulating AMPA autoreceptors in the cortex of mice
No full textIntroduction In recent year we demonstrated that antibodies recognizing the outer sequence of receptor subunit proteins permit the pharmacological characterization of the presyanptic release-regulating receptors in isolated nerve endings (Olivero et al., 2019). This study was recently extended to AMPA receptors and aims at characterizing the subunit composition of these receptors in the cortex of adult mice. Methods Cortical synaptosomes were incubated with one of the following antibodies: rabbit anti-GluA1 (1:500) or rabbit anti-GluA2 (1:500) or mouse anti-GluA3 (1:500) or rabbit anti-GluA4 (1:500) and then labelled with a radioactive tracer, i.e. [3H]D-aspartate, which allows to monitor the exocytotic-like release of glutamate from nerve endings. Synaptosomes were up-down superfused and tritium exocytosis elicited by exposing them to a mild depolarizing stimulus (50 uM AMPA /1 uM cyclothiazide, for 90 seconds). Four superfusate fractions were collected and measured for radioactivity to quantify the AMPA-evoked release of glutamate. Confocal microsopy and western blot analysis was performed to support by a biochemical point of view the functional observations. Results Bichemical results Confocal microscopy demonstrated a diffuse colocalization of AMPA receptor subunits (namely GluA1, GluA2, GluA3 and GluA4 receptor proteins) with syntaxin-1A, consistent with the presynaptic expression of the AMPA receptors. To verify the presence of the AMPA subunits on glutamatergic nerve endings, we also performed confocal microscopy using VGLUT-1 (vesicular glutamate transporter-1) as a marker for glutamatergic terminals. Again, a diffuse GluA1, GluA2, GluA3 and GluA4- immunoreactivity was observed in VGLUT-1 immunopositive cortical synaptosomes. In a whole these results indicate the presence of AMPA receptor subunits in presyanptic glutamatergic particles isolated from the cortex of adult mice. Functional results Synaptosomes were incubated in the absence or in the presence of anti‐GluA1, anti‐GluA2, anti‐GluA3 and anti‐GluA4 antibodies (one antibody for each preparation) and the release of preloaded [3H]‐D‐Asp elicited by AMPA (50μM) in the presence of ciclotiazide (10μM) quantified. The results showed a significant increase of the AMPA-evoked [3H]‐D‐Asp in cortical synaptosomes incubated with anti-GluA3 when compared to antibody untreated control. Differently, the AMPA-evoked [3H]‐D‐Asp release from synaptosome incubated with anti‐GluA1, and anti‐GluA4 antibodies was unchanged when compared to control. Further studies are required to define the impact of anti-GluA2 antibodies on the same functional paradigm. Discussion and conclusion We have demonstrated that AMPA receptors exist in cortical glutamatergic synaptosomes and control glutamate release. A significant increase in glutamate release was observed when cortical synaptosomes were incubated with anti-GluA3. The mechanism at the basis of this functional modification remains so far unexplored. Rasmussen’s encephalitis is a rare chronic neurological disorder characterized by unilateral inflammation of the cerebral cortex, drug-resistant epilepsy, and progressive neurological and cognitive deterioration. The disease is typified by high levels of antibody directed against the GluA3 subunit of AMPA receptors. Given that one of the hallmarks of Rasmussen’s encephalitis is abnormally high synaptic glutamate release, resulting in excitotoxicity, we propose that the auto-antibody anti-GluA3, by increasing the release of AMPA-evoked glutamate release, can have a role in this detrimental event
Type 1 diabetes mellitus and hyperadrenocorticism in a ferret
No full textDiabetes mellitus (DM) was diagnosed in a 6-year-old neutered male ferret with polyuria/polydipsia, symmetrical alopecia, and weight loss. Laboratory tests revealed severe hyperglycemia, glucosuria, and increased steroid hormone profile. Abdominal ultrasound revealed a bilateral enlargement of the adrenal glands. Significant clinical improvement was achieved with insulin-and leuprolide acetate-based therapy. After 2 months of therapy, the ferret showed a severe ketoacidosis, and the owner decided to euthanize the animal. Histological findings revealed carcinoma of the left adrenal cortex and cortical hyperplasia of the right adrenal gland. Moderate, chronic, and active pancreatitis with a marked decrease in the number of beta-cells was also present. This is the first reported case of type 1 DM associated with hyperadrenocorticism and chronic pancreatitis in a ferret.[...
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