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Effetti post-infusionali dell’Infliximab e dell’Abatacept sul metabolismo del calcio in pazienti affetti da artrite reumatoide
No full textL’infiammazione cronica e la perdita di densità ossea sono due fenomeni strettamente legati.
Tale associazione è particolarmente evidente nell’Artrite Reumatoide (AR), malattia infiammatoria cronica caratterizzata da poliartrite simmetrica con infiammazione sinoviale, danno cartilagineo ed erosioni ossee.
Diversi fattori sono responsabili della perdita ossea nei pazienti affetti da artrite, quali la ridotta mobilità delle articolazioni colpite, l’aumento della vascolarizzazione, l’uso di farmaci steroidei, e non ultimo la liberazione di mediatori locali generati dalla flogosi articolare, in particolare il tumor necrosis factor alpha (TNF-α).
Il TNF-alfa è una molecola infiammatoria chiave nell’AR e la sua inibizione terapeutica determina un significativo miglioramento nei segni e sintomi delle patologie artritiche.
D’altra parte, il TNF-α ha un notevole effetto sull’osso: l’overespressione di TNF-α non solo è coinvolta nelle erosioni locali, ma induce anche perdita di massa ossa in maniera sistemica; possiamo pertanto considerarlo come un importante link tra infiammazione cronica e perdita di massa ossea.
Il TNF-α partecipa attivamente al processo patogenetico del danno articolare, rappresentando un mediatore fondamentale nell’azione del catabolismo del tessuto osseo attraverso la stimolazione dei processi di riassorbimento e l’inibizione dei processi di neoformazione ossea.
L’avvento dei farmaci in grado di bloccare il TNF-α ha migliorato la qualità di vita dei pazienti affetti da artrite, riducendo in modo significativo l’infiammazione articolare, la progressione radiologica della malattia e, di conseguenza, la disabilità.
Lo scopo della presente ricerca è stato quello di valutare se la terapia con farmaci biologici, in particolare Infliximab e Abatacept, possa influenzare il metabolismo osseo e prevenire il danno strutturale.
In particolare col presente studio si e’focalizzata l’attenzione sul momento acuto dell’infusione dei due farmaci biologici sopracitati in pazienti affetti da A.R. e si sono analizzati i cambiamenti postinfusionali dal punto di vista biochimico-clinico nel metabolismo del calcio nei due differenti gruppi di pazienti.
Lo studio, in aperto, è stato condotto su un gruppo di 11 pazienti con diagnosi di AR seguiti presso l’U.O. Semplice Clinica Reumatologica del Dipartimento di Medicina dell’Ospedale S.Pietro, che assumevano terapia stabile da almeno sei mesi, nel periodo compreso tra ottobre 2008 e febbraio 2009.
I risultati della nostra ricerca dimostrano che gli effetti positivi sull’andamento dell’ A.R. determinati dalla terapia con farmaci ad azione anti TNF-α sono associati ad un evidente miglioramento di differenti parametri del metabolismo osseo, indicando un generale effetto protettivo sul tessuto osseo.
Nasce in questo contesto il termine “Osteoimmunologia”, che identifica una nuova e moderna area di ricerca interdisciplinare che studia le interazioni e le connessioni molecolari e cellulari tra osso e sistema immunitario, i risvolti clinici di tale complessa architettura ed apre la prospettiva a nuove strategie terapeutiche.
E’ interessante notare come farmaci con un meccanismo farmacologico molto diverso, l’uno anti-TNFα e l’altro immunosoppressore selettivo, abbiano un effetto diverso nella riduzione della calcemia e nel metabolismo del calcio in generale: una spiegazione parziale consiste nel fatto che il secondo farmaco ha effetti anti- TNF-α solo indiretti essendo l’Abatacept un immunomodulatore selettivo per il segnale chiave di costimolazione mentre i farmaci anti TNF-α, come ad esempio l’Infliximab, hanno un legame stretto e immediatamente forte con il TNF-α tale da poter spiegare la drastica riduzione della calcemia.
La concentrazione sierica del calcio è risultata infatti diminuita in modo statisticamente significativa dal tempo pre-infusionale (media 9.34± 0,54 DS) al tempo post-infusionale (media 8.67±0.74 DS) nei pazienti in trattamento con Infliximab (P=0.0002) e non ha subito modificazioni significative dal tempo preinfusionale (media 9.92±1.12 DS) al tempo postinfusionale (media 9.35±0.67 DS) in quelli trattati con Abatacept (P=0.1212, ns).
La concentrazione della fosfatasi alcalina (ALP), marcatore del turnover osseo di neoformazione, è risultata diminuita in modo statisticamente significativa dal tempo preinfusionale (media 78.11±27.95 DS) al tempo postinfusionale (media 70.22±26.80 DS) nei pazienti in trattamento con Infliximab (P=0.001) ed è risultata diminuita dal tempo preinfusionale (media 80.87±30.32 DS) al tempo postinfusionale (media 75.37±28.24 DS) anche nei pazienti in trattamento con Orencia (P=0.01).
Non abbiamo osservato modificazioni significative dei livelli sierici del fosforo e del PTH, in accordo con la necessità di un maggiore numero di ore per attivare i meccanismi coinvolti nella loro sintesi. L'esiguo numero di pazienti non permette di chiarire completamente il ruolo che l'Abatacept svolge sul magnesio e se, il riscontro di diminuiti livelli dopo l'infusione di tale farmaco, possa essere dovuto all'azione della molecola.
I nostri dati, seppur preliminari, supportano il ruolo che i nuovi farmaci biologici per la cura dell'AR, Infliximab e Abatacept, svolgono nel metabolismo osseo: sarà necessario un numero maggiore di pazienti per confermare tali risultati.Chronic inflammation and bone density reduction are two closely related phenomena.
This is particularly evident in rheumatoid arthritis (RA), a chronic inflammatory disease characterized by symmetric polyarthritis, synovial inflammation, cartilage damage and bone erosion.
Pathogenetic factors involved in bone loss in arthritis are: joints immobility, increased vascularization, use of corticosteroids and, not least, the release of inflammation mediators released locally, as Tumor Necrosis Factor Alpha (TNF-alpha).
TNF-alpha is a key inflammatory citochine in RA and its therapeutic inhibition results in a significant improvement of the clinical manifestations of the disease. TNF-alpha has a striking action on bone metabolism: TNF overespression is involved in local erosion but it also leads to bone mass loss through a systemic way. It can therefore be considered as an important link between chronic inflammation and bone mass reduction. TNF-alpha has an active role in joint’s damage pathogenesis as it is a key mediator in catabolism of bone through the stimulation of bone re-absorption and inhibition of newly-formed bone.
On a clinical point of view, the introduction of drugs inhibiting TNF-alpha improved patient’s quality of life, significantly reducing joints inflammation, radiological progression of disease and, therefore, clinical manifestations and disability. By now many evidences suggest that the inhibition of TNF-alpha is able to prevent not only iuxta-articular osteoporosis but also the loss of bone mass in a systemic manner. The aim of this study was to assess the effect of biological drugs, in particular Infliximab and Abatacept, on bone metabolism and on prevention of structural damage. We studied the acute effects of Infliximab and Abatacept infusion in AR patients and we analyze the postinfusional effects as clinical biochemical changes in calcium metabolism in the two groups of patients.
We observed that the positive effects on AR patients treated with anti TNF-α drugs are associated with an improvement of markers of bone metabolism, indicating a general protective effect on bone.
In this context, we can suggest the term "Osteoimmunologia" as a new and modern field of research focused on molecular and cellular interactions between immune system and bone.
The clinical implications of this complex architecture opens a view on new therapeutic strategies. It is interesting to observe that drugs acting on different signal pathways, one is an anti-TNFα drug and the other is a selective immunomodulator, show a different effect in calcium metabolism.
A possible and partial explanation to that could be found in the fact that Abatacept inhibit TNF only in an indirect way as it is selective for RANK pathway.
On the contrary anti TNF-α drug, such as Infliximab, have a close and strong link to TNF-α that could explain the drastic reduction of calcium. The observation of no significant variation of serum phosphorus and PTH after the infusion could possibly been explained considering that the time of drug infusion could be too short to let the kidney act as a counter-regulator.
On the other hand, the significant reduction of magnesiemia in the group of patients on Orencia versus the group treated with Infliximab is still unclear.
We have to consider that possibly the too small number of patients studied could have partially compromised the results.
Further investigation on this interesting field and on a larger group of subjects is necessary to confirm our preliminary data and eventually find out new considerations.
Chronic inflammation and bone density reduction are two closely related phenomena.
This is particularly evident in rheumatoid arthritis (RA), a chronic inflammatory disease characterized by symmetric polyarthritis, synovial inflammation, cartilage damage and bone erosion.
Pathogenetic factors involved in bone loss in arthritis are: joints immobility, increased vascularization, use of corticosteroids and, not least, the release of inflammation mediators released locally, as Tumor Necrosis Factor Alpha (TNF-alpha).
TNF-alpha is a key inflammatory citochine in RA and its therapeutic inhibition results in a significant improvement of the clinical manifestations of the disease. TNF-alpha has a striking action on bone metabolism: TNF overespression is involved in local erosion but it also leads to bone mass loss through a systemic way. It can therefore be considered as an important link between chronic inflammation and bone mass reduction. TNF-alpha has an active role in joint’s damage pathogenesis as it is a key mediator in catabolism of bone through the stimulation of bone re-absorption and inhibition of newly-formed bone.
On a clinical point of view, the introduction of drugs inhibiting TNF-alpha improved patient’s quality of life, significantly reducing joints inflammation, radiological progression of disease and, therefore, clinical manifestations and disability. By now many evidences suggest that the inhibition of TNF-alpha is able to prevent not only iuxta-articular osteoporosis but also the loss of bone mass in a systemic manner. The aim of this study was to assess the effect of biological drugs, in particular Infliximab and Abatacept, on bone metabolism and on prevention of structural damage. We studied the acute effects of Infliximab and Abatacept infusion in AR patients and we analyze the postinfusional effects as clinical biochemical changes in calcium metabolism in the two groups of patients.
We observed that the positive effects on AR patients treated with anti TNF-α drugs are associated with an improvement of markers of bone metabolism, indicating a general protective effect on bone.
In this context, we can suggest the term "Osteoimmunologia" as a new and modern field of research focused on molecular and cellular interactions between immune system and bone.
The clinical implications of this complex architecture opens a view on new therapeutic strategies. It is interesting to observe that drugs acting on different signal pathways, one is an anti-TNFα drug and the other is a selective immunomodulator, show a different effect in calcium metabolism.
A possible and partial explanation to that could be found in the fact that Abatacept inhibit TNF only in an indirect way as it is selective for RANK pathway.
On the contrary anti TNF-α drug, such as Infliximab, have a close and strong link to TNF-α that could explain the drastic reduction of calcium. The observation of no significant variation of serum phosphorus and PTH after the infusion could possibly been explained considering that the time of drug infusion could be too short to let the kidney act as a counter-regulator.
On the other hand, the significant reduction of magnesiemia in the group of patients on Orencia versus the group treated with Infliximab is still unclear.
We have to consider that possibly the too small number of patients studied could have partially compromised the results.
Further investigation on this interesting field and on a larger group of subjects is necessary to confirm our preliminary data and eventually find out new considerations
Le voci dell'ironia: analisi dei profili acustici della comunicazione ironica
No full textSecondo il modello neicoico, qui proposto, l’ironia, in quanto citazione (o
menzione), consiste in uno script interattivo nel quale, sulla spinta di un evento focale,
il commento dialogico esprime l’intenzione dell’ironista attraverso il processo antifrastico
e la sincodifica per «colpire» l’ironizzato (blame by praise o praise by blame). Facendo
ricorso all’analisi acustica dei profili soprasegmentali di frasi standard inserite in appositi
brani induttori letti da 50 soggetti non-attori, si sono accertate la presenza e la
natura di rilevanti differenze vocali non-verbali fra l’ironia sarcastica e l’ironia bonaria,
in enunciati sia a bassa sia ad alta contestualizzazione (effetto di contestualizzazione;
esperimenti 1 e 2). Si è inoltre verificato che, pure nella condizione in cui si attribuisce
un «peso specifico» maggiore alla stringa linguistica (ipotesi dell’ironia «correttiva»), si
assiste a una maggiore marcatura dei tratti soprasegmentali (effetto di correttività; esperimento
3). Infine, dal confronto tra l’ironia sarcastica e il disprezzo esplicito, nonché
tra l’ironia bonaria e l’elogio esplicito, emerge una precisa modalità di sincodifica contrastiva,
in funzione della quale le voci dell’ironia non coincidono né con quella del disprezzo
né con quella dell’elogio, ma assumono un profilo caricaturale ed enfatico specifico
(effetto di contrastività; esperimento 4). Il commento ironico, in sintesi, pur essendo
chiaro senza essere esplicito, fruisce congiuntamente dell’efficacia della parola e dei
benefici del silenzio nella gestione delle relazioni interpersonali.According to the "neicoic model", proposed here, irony, as "quotation" (or "mention"), consists of an interactive script, grounded on the focal event "trigger", in which the dialogic comment shows the ironist's intention through the antiphrastic process and syncoding to "hit" the victim of the irony (blame by praise or praise by blame). Through the acoustic analysis of the suprasegmental profiles of standard phrases inserted into inductors expressly composed and read by 50 naive subjects, the presence and the nature of significant differences between sarcastic and kind irony in low- and high-context utterances ("contextualization effect"; experiments 1 and 2) have been verified. It has also been observed that, where more "specific weight" is given to the linguistic stream ("corrective irony" hypothesis), a markedness of suprasegmental features emerges ("correctivity effect"; experiment 3). Lastly, from the comparison between sarcastic irony and blame, and between kind irony and praise, there exists a precise manner of "contrastive syncoding", whereby the voices of irony do not coincide with those of direct blame or praise, but assume a specific caricature and emphatic profile ("contrastivity effect"; experiment 4). The ironic comment, although clear without being explicit, can at the same time enjoy the effectiveness of the word and the benefits of the silence in the management of social relationships
Stili della comunicazione ironica in funzione della variabilità indessica
No full textL'articolo descrive gli stili della comunicazione ironica in funzione della variabilità indessicale. Analizza indici verbali quali il riferimento personale e indici vocali non verbali quali lo speech rat
How Not to Say It Explicitly: The Communicative Function of Irony [Come non dirlo esplicitamente: le funzioni comunicative dell'ironia]
No full textl'ironia è una figura retorica in cui vi è una incongruità, discordanza oppure una involontaria connessione con il vero, che va al di là del semplice ed evidente significato della parola.
L'ironia verbale e situazionale viene spesso usata intenzionalmente per enfatizzare l'affermazione di una verità. La forma ironica della similitudine, del sarcasmo o della litote può includere l'enfasi di un significato mediante l'uso deliberato di una locuzione che afferma l'esatto opposto della verità, o che drasticamente e ovviamente sminuisce una connessione di fatto. In questo contributo si esaminano le funzioni psicologiche e comunicative dell'ironia e la funzione pragmatica del "non dire esplicitamente
Le miopatie infiammatorie idiopatiche
No full textIdiopathic inflammatory myopathies (IIMs) are a group of acquired diseases, characterized by immuneinflammatory processes primarily involving skeletal muscle. According to recent classification criteria, five major diseases have been identified: polymyositis (PM), dermatomyositis (DM), immune-mediated necrotizing myopathy (IMNM), juvenile idiopathic myositis (JIM) and sporadic inclusion body myositis (sIBM). Although the etiology of IIMs is still incompletely understood, there is much evidence supporting the involvement of genetic, immunological, and environmental factors. In recent years, many new biomarkers have been identified as useful indicators for diagnosis, disease subtypes, prognosis, or response to treatment of IIM
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
From blame by praise to praise by blame: analysis of vocal patterns in ironic communication
No full textIrony, as "quotation" and "fencing game," consists of an interactive script,
grounded on a focal event "trigger," in which the dialogic comment shows the
ironist's intention through an antiphrastic process and syncoding to "hit" the
victim of the irony (blame by praise or praise by blame). Through acoustic
analysis of the suprasegmental profiles of standard phrases inserted into
inductors expressly composed and read by 50 naive subjects, the presence and
nature of significant differences between sarcastic and kind irony in low- and
high-context utterances (contextualization effect--Experiments 1 and 2) have been
verified. It has also been observed that, where more "specific weight" is given
to the linguistic stream (corrective irony hypothesis), a markedness of
suprasegmental features emerges (correctivity effect--Experiment 3). Finally,
comparison between sarcastic irony and blame and between kind irony and praise
shows that there exists a precise manner of contrastive syncoding, whereby the
voices of irony do not coincide with those of direct blame or praise, but assume
a specific caricature and emphatic profile (contrastivity effect--Experiment 4)
You' re a Real Genius!: Irony as miscommunication design
No full textIn a standard (rhetoric) perspective ironic communication is
considered a semantic inversion between the literal (primary) meaning and the
nonliteral (implicated) one. Nevertheless, in common use irony is not
necessarily bound to the rhetoric concept of semantic inversion. Rather, it can be
defined as an alteration of a reference aiming at stressing the reality of a fact by
means of the apparent dissimulation of its true nature.
In a communicative perspective, irony aims to get an effective protection of
interpersonal relationships, so as to leave wide ranges of freedom for managing
both meanings and interaction.
The point of view herein followed concerns irony as a paradigmatic expression
of miscommunication, since it is a chance in widening the psychological space
available to the communicators. Irony as miscommunication fits rather well the
MaCHT framework proposed by Anolli. In fact, by means of an ironic remark,
the speaker can lay the responsibility of the ironic value of the utterance on the
intention ascription of the interlocutor.
In particular, the present chapter intends to sketch out a new theoretical
perspective of ironic communication as miscommunication, by proposing the
fencing game (or irony situation) model. Here irony is not considered only as a
comment or remark at a linguistic level but also as a complex communicative
interaction between interlocutors, depending on contextual constraints and
opportunities
Verbal and vocal non verbal strategies of communication within cross-gender relationships in conflicting and cooperative contexts
No full text- …
