RESUMO
Immunogenicity induced by recombinant plasmids based on the BAB1_0267 and BAB1_0270 open reading frames (ORFs) of Brucella abortus 2308 was evaluated. Bioinformatics analyses indicate that the BAB1_0267 and BAB1_0270 ORFs encode a protein with a SH3 domain and a Zn-dependent metalloproteinase, respectively. Both ORFs have important effects on intracellular survival and replication of B. abortus 2308, mediated via professional and non-professional phagocytic cells. Our results show that immunization with the recombinant plasmid based on the BAB1_0267 ORF significantly increases the production of IgG1, levels of IFN-γ and the lymphoproliferative response of splenocytes. However, BAB1_0267 did not provide significant levels of protection. The plasmid based on the BAB1_0270 significantly increased IgG2a production, levels of IFN-γ and TNF-α, and the lymphoproliferative response of splenocytes. These results demonstrate that immunization with the BAB1_0270 derived recombinant plasmid induce a Th1-type immune response, correlated with a heightened resistance to B. abortus 2308 infection in mice. It is concluded that the Th1-type immune response against bacterial Zn-dependent metalloproteinase induces a protective response in mice, and that pV270 recombinant plasmid is an effective candidate microbicide against brucellosis.
Assuntos
Brucella abortus/genética , Brucella abortus/imunologia , Brucelose/imunologia , Brucelose/prevenção & controle , DNA Recombinante , Fases de Leitura Aberta/genética , Plasmídeos/genética , Vacinas de DNA , Animais , Proteínas de Bactérias/genética , Proteínas de Bactérias/imunologia , Contagem de Colônia Microbiana , Citocinas/análise , DNA Bacteriano , Modelos Animais de Doenças , Feminino , Genes Bacterianos/genética , Imunoglobulina G/biossíntese , Interferon gama/análise , Metaloendopeptidases , Camundongos , Camundongos Endogâmicos BALB C , Fagócitos/imunologia , Sobrevida , VacinaçãoRESUMO
BACKGROUND: Atrioventricular nodal reentrant tachycardia (AVNRT) and atrioventricular reentrant tachycardia (AVRT) often terminate spontaneously, presumably due to changes in the electrophysiological properties of the reentrant circuit. However, the mechanism of spontaneous termination of these arrhythmias is incompletely understood. METHODS: We included 70 consecutive patients with reentrant supraventricular tachycardias (35 AVNRT, 35 AVRT) in whom the arrhythmia ended spontaneously during the electrophysiologic study. We determined in each patient the duration of the induced arrhythmia, site of block, beat-to-beat oscillations in tachycardia cycle-length (CL), A-H, H-V, H-A and V-A intervals. RESULTS: In 21/34 (62%) patients with AVNRT and 19/30 (63%) with orthodromic AVRT, tachycardia termination was preceded by progressive increase in tachycardia CL due to prolongation of the A-H interval (Mobitz type-I pattern). In 13/34 patients with AVNRT (38%) and 11/30 with orthodromic AVRT (37%), termination occurred suddenly without a preceding change in CL, with block ensuing retrogradely either in the fast AV nodal pathway or the accessory pathway (Mobitz type-II pattern). In 4/5 patients with antidromic AVRT the tachycardia ended at the retrograde limb with previous prolongation of the VA interval. CONCLUSION: Spontaneous termination of AVNRT and AVRT is a time-related phenomenon. Despite different pathways being involved in these two reentrant tachycardias, termination can follow antegrade or retrograde block in similar ratio (60% antegradely and 40% retrogradely). Antegrade block is preceded by prolongation of the AH interval (Mobitz type-I), whereas retrograde block occurs unexpectedly in the retrograde limb (Mobitz type-II). Fatigue of conduction appears to be involved in this phenomenon.
Assuntos
Nó Atrioventricular/fisiopatologia , Fascículo Atrioventricular/fisiopatologia , Eletrocardiografia , Taquicardia por Reentrada no Nó Atrioventricular/fisiopatologia , Taquicardia Paroxística/fisiopatologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Frequência Cardíaca/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Remissão Espontânea , Estudos Retrospectivos , Adulto JovemRESUMO
Lidocaine-sensitive, repetitive atrial tachycardia is an uncommon arrhythmia. The electrophysiologic substrate is still unknown, and the pharmacologic responses have not been fully explored. The aim of this study was to investigate the effects of intravenous adenosine and verapamil in patients with lidocaine-sensitive atrial tachycardia. In 9 patients with repetitive uniform atrial tachycardia, the response to intravenous adenosine (12 mg), lidocaine (1 mg/kg body weight), and verapamil (10 mg) were sequentially investigated. Simultaneous 12-lead electrocardiogram (ECG) was recorded at baseline and continuously monitored thereafter. Tracings were obtained at regularly timed intervals right after the administration of each drug to evaluate changes in the arrhythmia characteristics. Repetitive atrial tachycardia was abolished by intravenous lidocaine in the 9 patients within the first 2 minutes after the end of injection. Adenosine suppressed the arrhythmia in 2 patients and shortened the runs of atrial ectopic activity in 1 patient, while verapamil was effective in 2 patients, 1 of them insensitive to adenosine and the other 1 sensitive to this agent. In 5 patients, the arrhythmia was abolished by radiofrequency ablation at different sites of the right atrium. Lidocaine-sensitive atrial tachycardia may eventually be also suppressed by adenosine and/or verapamil. This suggests that this enigmatic arrhythmia may be caused by different underlying electrophysiologic substrates and that at least in some cases, delayed afterdepolarizations seem to play a determining role.