322 research outputs found
Serum microRNAs as biomarkers of human lymphocyte activation in health and disease
No full textInduction of the adaptive immune system is evaluated mostly by assessment of serum antibody titers and T lymphocyte responses in peripheral blood, although T and B cell activation occurs in lymphoid tissues. In recent years, the release of microRNAs (miRNAs) in the extra-cellular environment has been exploited to assess cell functions at distance via measurement of serum miRNAs. Activated lymphocytes release a large amount of nano-sized vesicles (exosomes), containing miRNA, however there are insufficient data to determine whether this phenomenon is reflected in modulation of serum miRNAs. Interestingly, miRNA signatures of CD4+ T cell-derived exosomes are substantially different from intracellular miRNA signatures of the same cells. We have recently identified serum circulating miR-150 as a sensor of general lymphocyte activation and we strongly believe that miRNAs differentially released by specific CD4+ effector T cell subsets (Th1, Th2, Th17, and Treg) may serve as serum biomarkers of their elicitation in lymphoid tissues but also in damaged tissues, potentially providing clinically relevant information about the nature of immune responses in health and disease. © 2014 de Candia, Torri, Pagani and Abrignani
Human T lymphocytes at tumor sites
No full textCD4(+) and CD8(+) T lymphocytes mediate most of the adaptive immune response against tumors. Naïve T lymphocytes specific for tumor antigens are primed in lymph nodes by dendritic cells. Upon activation, antigen-specific T cells proliferate and differentiate into effector cells that migrate out of peripheral blood into tumor sites in an attempt to eliminate cancer cells. After accomplishing their function, most effector T cells die in the tissue, while a small fraction of antigen-specific T cells persist as long-lived memory cells, circulating between peripheral blood and lymphoid tissues, to generate enhanced immune responses when re-encountering the same antigen. A subset of memory T cells, called resident memory T (T(RM)) cells, stably resides in non-lymphoid peripheral tissues and may provide rapid immunity independently of T cells recruited from blood. Being adapted to the tissue microenvironment, T(RM) cells are potentially endowed with the best features to protect against the reemergence of cancer cells. However, when tumors give clinical manifestation, it means that tumor cells have evaded immune surveillance, including that of T(RM) cells. Here, we review the current knowledge as to how T(RM) cells are generated during an immune response and then maintained in non-lymphoid tissues. We then focus on what is known about the role of CD4(+) and CD8(+) T(RM) cells in antitumor immunity and their possible contribution to the efficacy of immunotherapy. Finally, we highlight some open questions in the field and discuss how new technologies may help in addressing them
Why is it so difficult to develop a hepatitis C virus preventive vaccine?
No full textAbstractWith an estimated 3% of the world’s population chronically infected, hepatitis C virus (HCV) represents a major health problem for which an efficient vaccination strategy would be highly desirable. Indeed, chronic hepatitis C is recognized as one of the major causes of cirrhosis, hepatocarcinoma and liver failure worldwide and it is the most common indication for liver transplantation, accounting for 40–50% of liver transplants. Much progress has been made in the prevention of HCV transmission and in therapeutic intervention. However, even if a new wave of directly acting antivirals promise to overcome the problems of low efficacy and adverse effects observed for the current standard of care, which include interferon-a and ribavirin, an effective vaccine would be the only means to definitively eradicate infection and to diminish the burden of HCV-related diseases at affordable costs. Although there is strong evidence that the goal of a prophylactic vaccine could be achieved, there are huge development issues that have impeded reaching this goal and that still have to be addressed. In this article we address the question of whether an HCV vaccine is needed, whether it will eventually be feasible, and why it is so difficult to produce
RICOVERI PER EFFETTI INDESIDERATI DA SOVRADOSAGGIO DI FARMACI PRESSO UN’UNITÀ OPERATIVA CARDIOLOGICA NEL PERIODO 2011-2013
No full textIntroduzione: Le statistiche dei casi di ricovero ospedaliero per effetti indesiderati da sovradosaggio farmacologico sono utili per valutare l’incidenza di tale fenomeno nel mondo reale. Un sovradosaggio farmacologico può avvenire come conseguenza di un’insufficiente o inadeguata comunicazione tra medico e paziente, per autoprescrizione o erronea assunzione di dosaggi superiori a quelli necessari, per erronea assunzione di due farmaci identici come molecola ma con nome commerciale diverso o per effetti collaterali imprevisti.
Materiali e metodi: Sono state esaminate, retrospettivamente, le cartelle cliniche relative a tutti i ricoveri avvenuti presso l’Unità Operativa di Cardiologia del P.O. S. Antonio Abate di Trapani (ASP 9 - Sicilia) nel triennio compreso tra gennaio 2011 e dicembre 2013. Sono state ricercate le ospedalizzazioni avvenute per effetti indesiderati da sovradosaggio di farmaci appartenenti a varie classi quali digitalici, ACE-inibitori, betabloccanti e antiaritmici, in particolare l’amiodarone.
Risultati: Nel triennio in oggetto, su un totale di 7269 ospedalizzazioni, quelli per effetti indesiderati da sovradosaggio farmacologico sono stati 76 (1.05% del totale dei ricoveri). I pazienti ricoverati per tale motivo, 33 di sesso maschile e 43 di sesso femminile, avevano un’età compresa tra 62 e 90 anni. La Figura1 mostra le percentuali relative ai singoli farmaci interessati, secondo cui la principale causa di ricovero ospedaliero per effetti indesiderati da sovradosaggio farmacologico è attribuibile all’amiodarone, antiaritmico di classe III, per i noti effetti collaterali a carico della tiroide e degli occhi. Segue la digitale, che ha causato nei pazienti bradiaritmie e in alcuni casi vere e proprie intossicazioni e, in percentuali minori, gli ACE-inibitori, cause di ipotensione e i betabloccanti, causa di bradicardia e ipotensione. Per tutti i casi l’intervento mirava alla reversione della sintomatologia e alla momentanea sospensione dell’assunzione. Per nessuno dei casi monitorati si è proposto il ricovero in terapia intensiva.
Discussione: I ricoveri ospedalieri per effetti indesiderati da sovradosaggio farmacologico sono ancora un problema abbastanza diffuso nel mondo reale. Gli operatori sanitari, tra cui Medici e Farmacisti, dovrebbero ulteriormente mirare a una corretta informazione dei pazienti e dei loro familiari, in particolare al momento della dimissione, come prezioso e fondamentale strumento di prevenzione di questi danni iatrogenici che, a prescindere dei costi evitabili per il Sistema
Sanitario Nazionale, possono comportare, se non adeguatamente trattati, rischi e gravi conseguenze per la salute
iNKT-cell help to B cells: a cooperative job between innate and adaptive immune responses
No full textT-cell help to B lymphocytes is one of the most important events in adaptive immune responses in health and disease. It is generally delivered by cognate CD4+ T follicular helper (TFH) cells via both cell-to-cell contacts and soluble mediators, and it is essential for both the clonal expansion of antibody (Ab)-secreting B cells and memory B-cell formation. CD1d-restricted invariant natural killer T (iNKT) cells are a subset of innate-like T lymphocytes that rapidly respond to stimulation with specific lipid antigens (Ags) that are derived from infectious pathogens or stressed host cells. Activated iNKT cells produce a wide range of cytokines and upregulate costimulatory molecules that can promote activation of dendritic cells (DCs), natural killer (NK) cells, and T cells. A decade ago, we discovered that iNKT cells can help B cells to proliferate and to produce IgG Abs in vitro and in vivo. This adjuvant-like function of Ag-activated iNKT cells provides a flexible set of helper mechanisms that expand the current paradigm of T-cell-B-cell interaction and highlights the potential of iNKT-cell targeting vaccine formulations
Comptes rendus – Recensioni - Book Reviews
No full textP. BUONGIORNO, A. BALBO, E. MALASPINA (edd.), Rappresentazione e uso dei senatus
consulta nelle fonti letterarie della repubblica e del primo principato /
Darstellung und Gebrauch der senatus consulta in den literarischen Quellen
der Republik und der frühen Kaiserzeit (A. ABRIGNANI).
G.M. MÜLLER, F. MARIANI ZINI (hrsg.), Philosophie in Rom – Römische Philosophie?
Kultur-, literatur- und philosophie-geschichtliche Perspektiven
(F.M. PETRUCCI).
TACITO, Agricola, Saggio introduttivo, nuova traduzione e note di S.
AUDANO (S. MOLLEA)
PANIC DISORDER, ANXIETY, AND CARDIOVASCULAR DISEASES
No full textDifferent data indicate that psychological and/or emotional disorders may play an important role in the natural
history of heart diseases. Although the major evidence is that related to depression, epidemiological data would indicate
that anxiety and panic disorders are highly represented in cardiac patient, thus influencing mortality and morbidity.
The diagnosis of panic disorder in patients with chest pain is crucial to a correct therapeutic approach, as well as to
reduce the risks and costs of inappropriate treatments.
Anxiety and panic may accelerate different direct and indirect processes involved in the pathogenesis of
cardiovascular diseases: lifestyle risk factors, arterial hypertension, myocardial perfusion, autonomic nervous system or
hypothalamus-pituitary-adrenal axis, platelet activation, and inflammation processes. Panic disorder seems to correlate
particularly with sudden death: this suggests that it may be considered one of the main inducers of life-threatening
arrhythmias, rather than to be linked to the development and progression of coronary atherosclerosis.
Beyond hard outcomes, panic disorders produce negative effects on both global adjustment and life quality that
may impair the course of the cardiac diseases. Interestingly, specific antipanic and anxiolytic agents seem to be
particularly effective upon life quality. In any case, adequate controlled clinical trials are necessary in order to confirm
the possibility of cardiovascular risk reduction by means of anxiety and panic disorder treatment
Immunization of Human Volunteers With Hepatitis C Virus Envelope Glycoproteins Elicits Antibodies That Cross-Neutralize Heterologous Virus Strains
No full textHepatitis C vaccines
No full textIt is estimated that 3% of the world's population is chronically
infected by the hepatitis C virus (HCV). Most infections become
chronic and, over time, evolve into chronic hepatitis. The most
unwanted complication of chronic hepatitis is cirrhosis, a massive liver fibrosis, that can lead to liver failure and hepatocellular carcinoma. Indeed, hepatitis C is the leading reason for
liver transplantation worldwide. However, liver transplantation
is not a cure for HCV, as virus recurrence is universal.
Current medical therapy for chronic hepatitis C, consisting
of a combination of pegylated interferon- α (Peg-IFN) and ribavirin, eradicates the virus in fewer than half of treated patients
and is plagued with serious side effects. Although newly developed direct antiviral agents targeting HCV proteins have been
shown to improve virological response, toxicity and resistance
remain major challenges. There is, therefore, a pressing need to
develop vaccination strategies aimed at preventing and possibly eradicating HCV infection. The scientific and clinical challenges that must be addressed and overcome in developing an
efficacious HCV vaccine are substantial but may not be insurmountable. In the last years, considerable progress has been
made in the understanding of HCV virology, pathogenesis, and
immunology. Data indicating the existence of natural immunity against the hepatitis C virus and vaccine efficacy in the
chimpanzee challenge model allow optimism for the development of an effective vaccine against this heterogeneous pathogen that is responsible for much of the chronic liver disease
around the world
HCV can activate B cells via CD81 engagement: a molecular mechanism for B cell autoreactivity and crioglobulinemia in HCV infection
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