Antibody Complementarity-Determining Regions (CDRs) Can Display Differential Antimicrobial, Antiviral and Antitumor Activities

Background: Complementarity-determining regions (CDRs) are immunoglobulin (Ig) hypervariable domains that determine specific antibody (Ab) binding. We have shown that synthetic CDR-related peptides and many decapeptides spanning the variable region of a recombinant yeast killer toxin-like antiidiotypic Ab are candidacidal in vitro. An alanine-substituted decapeptide from the variable region of this Ab displayed increased cytotoxicity in vitro and/or therapeutic effects in vivo against various bacteria, fungi, protozoa and viruses. the possibility that isolated CDRs, represented by short synthetic peptides, may display antimicrobial, antiviral and antitumor activities irrespective of Ab specificity for a given antigen is addressed here.Methodology/Principal Findings: CDR-based synthetic peptides of murine and human monoclonal Abs directed to: a) a protein epitope of Candida albicans cell wall stress mannoprotein; b) a synthetic peptide containing well-characterized B-cell and T-cell epitopes; c) a carbohydrate blood group A substance, showed differential inhibitory activities in vitro, ex vivo and/or in vivo against C. albicans, HIV-1 and B16F10-Nex2 melanoma cells, conceivably involving different mechanisms of action. Antitumor activities involved peptide-induced caspase-dependent apoptosis. Engineered peptides, obtained by alanine substitution of Ig CDR sequences, and used as surrogates of natural point mutations, showed further differential increased/unaltered/decreased antimicrobial, antiviral and/or antitumor activities. the inhibitory effects observed were largely independent of the specificity of the native Ab and involved chiefly germline encoded CDR1 and CDR2 of light and heavy chains.Conclusions/Significance: the high frequency of bioactive peptides based on CDRs suggests that Ig molecules are sources of an unlimited number of sequences potentially active against infectious agents and tumor cells. the easy production and low cost of small sized synthetic peptides representing Ig CDRs and the possibility of peptide engineering and chemical optimization associated to new delivery mechanisms are expected to give rise to a new generation of therapeutic agents.Department of Education, Universities and Research, Basque GovermentFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Istituto Superiore di Sanita, National Research Project on A.I.D.S.Cariparma Banking FoundationBrazilian National Research CouncilUniv Parma, Sez Microbiol, Dipartimento Patol, I-43100 Parma, ItalyUniv Basque Country, Fac Med Odontol, Dept Inmunol, Microbiol Parasitol, Bilbao, SpainUniv Basque Country, Dept Enfermeria I, Bilbao, SpainUniv Milan, Dipartimento Sci Cliniche L Sacco, Sez Malattie Infettive Immunopatol, Milan, ItalyUniv Studi Parma, Dipartimento Clin Med, Nefrol Sci Prev, Parma, ItalyUniversidade Federal de São Paulo, Departamento Microbiol, Imunol Parasitol, Unidade Oncol Expt, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biofis, São Paulo, BrazilUniversidade Federal de São Paulo, Departamento Microbiol, Imunol Parasitol, Unidade Oncol Expt, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biofis, São Paulo, BrazilDepartment of Education, Universities and Research, Basque Goverment: IT-264-07FAPESP: 06/50634-2Istituto Superiore di Sanita, National Research Project on A.I.D.S.: 50G.30Istituto Superiore di Sanita, National Research Project on A.I.D.S.: 40D.14Cariparma Banking Foundation: 2004.0190Brazilian National Research Council: research fellowshipWeb of Scienc

Autoadjusting-CPAP effect on serum Leptin concentrations in Obstructive Sleep Apnoea patients

© 2008 Drummond et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution Licens

Il progetto del nuovo Palazzetto dello Sport di Gallicano (Lucca)

Il progetto di un palazzetto dello sport rappresenta una significativa opportunità per pensare ad una struttura polivalente con caratteristiche di grande flessibilità, in modo da consentire la pratica del maggior numero di discipline sportive indoor, ma anche lo svolgimento di manifestazioni a carattere culturale o ricreativo. Nel presente lavoro viene illustrato il progetto preliminare del nuovo Palazzetto dello Sport di Gallicano che ha alla base un Documento preliminare all’avvio della progettazione (DPP) redatto con verifiche di valore, prendendo cioè a riferimento le utilità delle funzioni in rapporto ai costi globali necessari per produrre e gestire l’opera nella vita utile ipotizzata. Il metodo seguito è l’Analisi del Valore come da norme europee UNI EN 1325-1:1998 e UNI EN 12973:2003. Successivamente viene sviluppata una analisi illuminotecnica che ha riguardato in particolare l’illuminazione artificiale dell’area di gioco. Sulla base dei requisiti illuminotecnici previsti dalla norma europea UNI EN 12193:2001 per le varie discipline sportive, anche nel caso di riprese televisive a colori, sono stati individuati diversi livelli di accensione, ognuno caratterizzato da requisiti minimi di illuminamento orizzontale, illuminamento verticale e grado di uniformità

Association between high sensitivity C-reactive protein, heart rate variability and corrected QT interval in patients with chronic inflammatory arthritis.

Background The risk of sudden cardiac death is increased in chronic inflammatory arthritis, particularly rheumatoid arthritis (RA). To evaluate the putative effect of systemic inflammation on heart rate variability (HRV) and ventricular repolarization in chronic inflammatory arthritis, we analyzed in these patients the possible relationship among HRV parameters, QT interval, and high sensitivity C-reactive protein (hsCRP). Methods One hundred-one patients with chronic inflammatory arthritis underwent a 15-minute ambulatory twelve-channel electrocardiogram-recording, to evaluate HRV and QT interval, as well as a venous withdrawal for hsCRP as an estimation of ongoing systemic inflammation. Results In patients with chronic inflammatory arthritis, hsCRP is inversely correlated with HRV and directly with QTc duration, but while hsCRP is associated with HRV independently from any other investigated factor, the association between hsCRP and QTc seems to be an indirect consequence of the autonomic dysfunction itself. Within the whole cohort of patients, those subjects having elevated hsCRP levels displayed both a significant reduction in HRV and a prolongation of QTc with respect to patients with a normal hsCRP value. A similar, although less marked, degree of HRV depression and QTc prolongation was found in RA patients when compared to subjects with spondyloarthritis (SpA) and healthy controls. Conclusions These data provide evidence of a link between systemic inflammation and the arrhythmic risk in patients with chronic inflammatory arthritis, also putatively explaining, at least in part, how the different inflammatory load characterizing RA and SpA parallels the different risks of cardiovascular death in these two conditions

Derivação com veias de membro superior após trombólise de aneurisma de artéria poplítea: alternativa para salvamento de membro Arm vein bypass after popliteal artery aneurysm thrombolysis: an alternative for limb salvage

Os autores relatam um caso de aneurisma de artéria poplítea trombosado em que se realizou fibrinólise com sucesso na fase aguda. Foram utilizadas veias de braço para realização do enxerto e exclusão do aneurisma, pois o paciente havia sido previamente submetido à safenectomia bilateral e revascularização do miocárdio com as veias do outro braço. Apesar das dificuldades, o salvamento do membro foi alcançado.<br>The authors report a case of a thrombosed popliteal artery aneurysm successfully treated by fibrinolysis in its acute stage. Arm veins were used to perform a bypass and aneurysm exclusion, since the patient had previously been submitted to bilateral saphenous vein stripping and myocardial revascularization using the veins of the other arm. Despite the difficulties, limb salvage was achieved