RESUMO
OBJECTIVE: To compare autonomic heart rate variability (HRV) parameters at rest and during active stand in a population of SSc patients, taking into account SSc subsets age-matched to healthy control subjects. METHODS: Sixty-nine consecutive SSc patients were enrolled in study; these included 12 subjects with early SSc, 39 with limited cutaneous (lcSSc) and 18 with diffuse cutaneous SSc (dcSSc) along with 36 age- and sex-matched healthy controls (HC). ECG and respiration were recorded in supine position and in orthostatism (ORT). HRV analysis was performed on samples of 300 beats. Spectral analysis identified two oscillatory components, low frequency (LFnu, sympathetic) and high frequency (HFnu, vagal). Symbolic analysis identified three patterns, 0â¯V%, (sympathetic) and 2UV% and 2LV%, (vagal). The %∆ORT was calculated from the differences between HRV in ORT and SUP, normalized (%) by the HRV values at rest. RESULTS: SSc as a whole had higher markers of sympathetic (LF, 0â¯V%) and lower markers of vagal modulation (HR, 2UV%, 2LV%) compared to HCs. In addition, %∆LFnu, %∆HFnu, %∆0â¯V, %∆2UV and %∆2LV were lower in SSc than HC. dcSSc and lcSSc were dissimilar to HC as far as rest indexes were concerned (↑LF/HF, ↑LFnu, ↓HFnu, ↑0â¯V% and ↓2UV%) while no differences could be detected between HC and EaSSc. CONCLUSION: SSc showed a reduced vagal and increased sympathetic modulation at rest and a blunted autonomic response to ORT in comparison to HC. These alterations were mostly detectable in the advanced and fibrotic forms of SSc (dcSSc and lcSSc), while EaSSc were similar to HC.
Assuntos
Sistema Nervoso Autônomo/fisiologia , Frequência Cardíaca , Postura , Escleroderma Sistêmico/fisiopatologia , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Cardiovasculares , Escleroderma Sistêmico/classificação , Decúbito DorsalRESUMO
RNA interference (RNAi) is a process that is induced by double stranded RNA and involves the degradation of specific sequences of mRNA in the cytoplasm of the eukaryotic cells. It has been used as an antiviral tool against many viruses, including flaviviruses. The genus Flavivirus contains the most important arboviruses in the world, i.e., dengue (DENV) and yellow fever (YFV). In our study, we investigated the in vitro and in vivo effect of RNAi against YFV. Using stable cell lines that expressed RNAi against YFV, the cell lines were able to inhibit as much as 97% of the viral replication. Two constructions (one against NS1 and the other against E region of YFV genome) were able to protect the adult Balb/c mice against YFV challenge. The histopathologic analysis demonstrated an important protection of the central nervous system by RNAi after 10 days of viral challenge. Our data suggests that RNAi is a potential viable therapeutic weapon against yellow fever.