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1.
Sci Rep ; 13(1): 18606, 2023 10 30.
Artigo em Inglês | MEDLINE | ID: mdl-37903875

RESUMO

The COVID-19 pandemic has caused a severe global health and economic crisis, with significant consequences for human mortality and morbidity. Therefore, there is an urgent need for more studies on the immune response to SARS-CoV-2 infection, both to enhance its effectiveness and prevent its deleterious effects. This study presents the chronology of antibodies during six months after infection in hospitalized patients and the kinetics of serum soluble mediators of the cellular response triggered by SARS-CoV-2. Samples and clinical data from 330 patients hospitalized at the Hospital da Baleia in Belo Horizonte, Brazil, who were suspected of having COVID-19, were collected at the time of hospitalization and during 6 months after infection. The immune response was analyzed by enzyme-linked immunosorbent assay (ELISA) and flow cytometry. There was a significant difference in IgM specific antibody titers from the 7th to 60th days after infection between COVID-19 negative and positive patients. Soon after 60 days after infection, antibody levels started to reduce, becoming similar to the antibody levels of the COVID-19 negative patients. IgG specific antibodies started to be detectable after 9 days of infection and antibody levels were comparatively higher in positive patients as soon as after 7 days. Furthermore, IgG levels remained higher in these patients during the complete period of 180 days after infection. The study observed similar antibody profiles between different patient groups. The soluble systemic biomarkers evaluated showed a decrease during the six months after hospitalization, except for CCL11, CXCL8, CCL3, CCL4, CCL5, IL-6, IFN-g, IL-17, IL-5, FGF-basic, PDGF, VEGF, G-CSF, and GM-CSF. The results indicate that IgM antibodies are more prominent in the early stages of infection, while IgG antibodies persist for a longer period. Additionally, the study identified that patients with COVID-19 have elevated levels of biomarkers after symptom onset, which decrease over time.


Assuntos
COVID-19 , Humanos , SARS-CoV-2 , Formação de Anticorpos , Pandemias , Anticorpos Antivirais , Biomarcadores , Imunoglobulina G , Imunoglobulina M
2.
Setúbal; s.n; 20190000.
Tese em Português | BDENF - enfermagem (Brasil) | ID: biblio-1392498

RESUMO

A Ventilação Mecânica Invasiva é reconhecida como processo terapêutico adjuvante à pessoa acometida de insuficiência respiratória. Em correlação com os seus benefícios, existe a probabilidade de ocorrência de complicações a nível respiratório e motor. Neste contexto, é realçada a importância de realizar um desmame ventilatório precoce. A eficácia e eficiência do desmame ventilatório, requerem do Enfermeiro Especialista em Enfermagem de Reabilitação as competências para elaborar, desenvolver e implementar um plano de intervenção individual, baseado numa avaliação criteriosa do doente. Este relatório surge no decurso da análise ao processo de aquisição e sedimentação de competências comuns do Enfermeiro Especialista, específicas em Enfermagem de Reabilitação, bem como a obtenção de competências de mestre. Este processo foi realizado através das várias fases do plano de intervenção aplicado ao doente submetido a Ventilação Mecânica Invasiva, com o objetivo de desenvolver competências científicas, técnicas e humanas especializadas, ao longo do processo de desmame ventilatório.


Mechanical Invasive Ventilation is recognized as an adjuvant therapeutic process for the person suffering from respiratory failure. In correlation with its benefits, there is a probability of respiratory and motor complications. In this context, the importance of early weaning is emphasized. The efficacy and efficiency of ventilatory weaning require the Nurse Specialist in Rehabilitation Nursing the skills to design, develop and implement an individual intervention plan, based on a careful evaluation of the patient. This report arises during the analysis of the process of acquisition and solidification of common competences of the Specialist Nurse, specific in Rehabilitation Nursing, as well as the acquisition of master's competences. This process was carried out through the various phases of the intervention plan applied to the patient submitted to Mechanical Invasive Ventilation, with the objective of developing specialized scientific, technical and human skills throughout the ventilatory weaning process.


Assuntos
Respiração Artificial , Ventilação , Enfermagem em Reabilitação , Desmame
3.
RNA ; 25(6): 727-736, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30902835

RESUMO

The human immunodeficiency virus type 1 (HIV-1) genomic RNA (vRNA) has two major fates during viral replication: to serve as the template for the major structural and enzymatic proteins, or to be encapsidated and packaged into assembling virions to serve as the genomic vRNA in budding viruses. The dynamic balance between vRNA translation and encapsidation is mediated by numerous host proteins, including Staufen1. During HIV-1 infection, HIV-1 recruits Staufen1 to assemble a distinct ribonucleoprotein complex promoting vRNA encapsidation and viral assembly. Staufen1 also rescues vRNA translation and gene expression during conditions of cellular stress. In this work, we utilized novel Staufen1-/- gene-edited cells to further characterize the contribution of Staufen1 in HIV-1 replication. We observed a marked deficiency in the ability of HIV-1 to dissociate stress granules (SGs) in Staufen1-deficient cells and remarkably, the vRNA repositioned to SGs. These phenotypes were rescued by Staufen1 expression in trans or in cis, but not by a dsRBD-binding mutant, Staufen1F135A. The mistrafficking of the vRNA in these Staufen1-/- cells was also accompanied by a dramatic decrease in viral production and infectivity. This work provides novel insight into the mechanisms by which HIV-1 uses Staufen1 to ensure optimal vRNA translation and trafficking, supporting an integral role for Staufen1 in the HIV-1 life cycle, positioning it as an attractive target for next-generation antiretroviral agents.


Assuntos
Grânulos Citoplasmáticos/virologia , Proteínas do Citoesqueleto/genética , HIV-1/fisiologia , Interações Hospedeiro-Patógeno , RNA Viral/genética , Proteínas de Ligação a RNA/genética , Vírion/genética , Transporte Biológico , Grânulos Citoplasmáticos/metabolismo , Proteínas do Citoesqueleto/deficiência , Regulação da Expressão Gênica , Células HCT116 , Humanos , Plasmídeos/química , Plasmídeos/metabolismo , Ligação Proteica , Biossíntese de Proteínas , RNA Viral/metabolismo , Transdução de Sinais , Transfecção , Vírion/metabolismo , Montagem de Vírus/genética , Replicação Viral/genética
4.
Retrovirology ; 16(1): 3, 2019 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-30732620

RESUMO

BACKGROUND: Mammalian cells harbour RNA quality control and degradative machineries such as nonsense-mediated mRNA decay that target cellular mRNAs for clearance from the cell to avoid aberrant gene expression. The role of the host mRNA decay pathways in macrophages in the context of human immunodeficiency virus type 1 (HIV-1) infection is yet to be elucidated. Macrophages are directly infected by HIV-1, mediate the dissemination of the virus and contribute to the chronic activation of the inflammatory response observed in infected individuals. Therefore, we characterized the effects of four host mRNA decay proteins, i.e., UPF1, UPF2, SMG6 and Staufen1, on viral replication in HIV-1-infected primary monocyte-derived macrophages (MDMs). RESULTS: Steady-state expression levels of these host mRNA decay proteins were significantly downregulated in HIV-1-infected MDMs. Moreover, UPF2 and SMG6 inhibited HIV-1 gene expression in macrophages to a similar level achieved by SAMHD1, by directly influencing viral genomic RNA levels. Staufen1, a host protein also involved in UPF1-dependent mRNA decay and that acts at several HIV-1 replication steps, enhanced HIV-1 gene expression in MDMs. CONCLUSIONS: These results provide new evidence for roles of host mRNA decay proteins in regulating HIV-1 replication in infected macrophages and can serve as potential targets for broad-spectrum antiviral therapeutics.


Assuntos
HIV-1/fisiologia , Interações Hospedeiro-Patógeno , Macrófagos/virologia , Estabilidade de RNA , Proteínas de Ligação a RNA/metabolismo , Replicação Viral , Células Cultivadas , Regulação da Expressão Gênica , Humanos
5.
Retrovirology ; 15(1): 42, 2018 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-29954456

RESUMO

BACKGROUND: The ability of human immunodeficiency virus type 1 (HIV-1) to form a stable viral reservoir is the major obstacle to an HIV-1 cure and post-transcriptional events contribute to the maintenance of viral latency. RNA surveillance proteins such as UPF1, UPF2 and SMG6 affect RNA stability and metabolism. In our previous work, we demonstrated that UPF1 stabilises HIV-1 genomic RNA (vRNA) and enhances its translatability in the cytoplasm. Thus, in this work we evaluated the influence of RNA surveillance proteins on vRNA expression and, as a consequence, viral reactivation in cells of the lymphoid lineage. METHODS: Quantitative fluorescence in situ hybridisation-flow cytometry (FISH-flow), si/shRNA-mediated depletions and Western blotting were used to characterise the roles of RNA surveillance proteins on HIV-1 reactivation in a latently infected model T cell line and primary CD4+ T cells. RESULTS: UPF1 was found to be a positive regulator of viral reactivation, with a depletion of UPF1 resulting in impaired vRNA expression and viral reactivation. UPF1 overexpression also modestly enhanced vRNA expression and its ATPase activity and N-terminal domain were necessary for this effect. UPF2 and SMG6 were found to negatively influence viral reactivation, both via an interaction with UPF1. UPF1 knockdown also resulted in reduced vRNA levels and viral gene expression in HIV-1-infected primary CD4+ T cells. CONCLUSION: Overall, these data suggest that RNA surveillance proteins affect HIV-1 gene expression at a post-transcriptional level. An elucidation of the role of vRNA metabolism on the maintenance of HIV-1 persistence can lead to the development of novel curative strategies.


Assuntos
Regulação Viral da Expressão Gênica , Infecções por HIV/metabolismo , Infecções por HIV/virologia , HIV-1/fisiologia , RNA Helicases/metabolismo , Telomerase/metabolismo , Transativadores/metabolismo , Fatores de Transcrição/metabolismo , Ativação Viral , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD4-Positivos/virologia , Linhagem Celular , Citometria de Fluxo , Expressão Gênica , Técnicas de Silenciamento de Genes , Genoma Viral , Interações Hospedeiro-Patógeno , Humanos , Ligação Proteica , Provírus/genética , RNA Helicases/genética , Processamento Pós-Transcricional do RNA , Estabilidade de RNA , RNA Viral , Proteínas de Ligação a RNA , Telomerase/genética , Transativadores/genética , Fatores de Transcrição/genética , Latência Viral
6.
RNA ; 24(2): 219-236, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29127210

RESUMO

The nucleocapsid (NC) is an N-terminal protein derived from the HIV-1 Gag precursor polyprotein, pr55Gag NC possesses key functions at several pivotal stages of viral replication. For example, an interaction between NC and the host double-stranded RNA-binding protein Staufen1 was shown to regulate several steps in the viral replication cycle, such as Gag multimerization and genomic RNA encapsidation. In this work, we observed that the overexpression of NC leads to the induction of stress granule (SG) assembly. NC-mediated SG assembly was unique as it was resistant to the SG blockade imposed by the HIV-1 capsid (CA), as shown in earlier work. NC also reduced host cell mRNA translation, as judged by a puromycylation assay of de novo synthesized proteins, and this was recapitulated in polysome profile analyses. Virus production was also found to be significantly reduced. Finally, Staufen1 expression completely rescued the blockade to NC-mediated SG assembly, global mRNA translation as well as virus production. NC expression also resulted in the phosphorylation of protein kinase R (PKR) and eIF2α, and this was inhibited with Staufen1 coexpression. This work sheds light on an unexpected function of NC in host cell translation. A comprehensive understanding of the molecular mechanisms by which a fine balance of the HIV-1 structural proteins NC and CA act in concert with host proteins such as Staufen1 to modulate the host stress response will aid in the development of new antiviral therapeutics.


Assuntos
Biossíntese de Proteínas , Proteínas de Ligação a RNA/metabolismo , Produtos do Gene gag do Vírus da Imunodeficiência Humana/metabolismo , Linhagem Celular , Grânulos Citoplasmáticos/metabolismo , DNA Helicases/metabolismo , Fator de Iniciação 2 em Eucariotos/metabolismo , Fator de Iniciação 3 em Eucariotos/metabolismo , HIV-1/fisiologia , Células HeLa , Humanos , Proteínas de Ligação a Poli-ADP-Ribose/metabolismo , RNA Helicases/metabolismo , Proteínas com Motivo de Reconhecimento de RNA/metabolismo , RNA Mensageiro/metabolismo , eIF-2 Quinase/metabolismo , Produtos do Gene gag do Vírus da Imunodeficiência Humana/antagonistas & inibidores
7.
ACS Med Chem Lett ; 8(9): 958-962, 2017 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-28947944

RESUMO

This work describes the synthesis and biological evaluation of an anchimerically activated proTide of 2'-C-ß-methylguanosine as an inhibitor of dengue virus 2 (DENV-2). The proTide incorporates a chemically cleavable 2-(methylthio)ethyl moiety and a HINT1 hydrolyzable tryptamine phosphoramidate. Inhibition of DENV-2 replication by proTide 6 was 5-fold greater than the parent nucleoside while displaying no apparent cytotoxicity. Furthermore, we demonstrate with a HINT1 inhibitor that the anti DENV-2 activity of the proTide correlates with the activity of HINT1. Taken together, these results demonstrate that a phosphoramidate based pronucleotide that undergoes an initial nonenzymatic activation step based on anchimeric assistance followed by P-N bond cleavage by HINT1 can be prepared.

8.
PLoS Negl Trop Dis ; 11(7): e0005775, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28715409

RESUMO

Zika virus (ZIKV), a member of the Flaviviridae family, is the most recent emerging arbovirus with pandemic potential. During infection, viruses trigger the host cell stress response, leading to changes in RNA translation and the assembly of large aggregates of stalled translation preinitiation complexes, termed stress granules (SGs). Several reports demonstrate that flaviviruses modulate the assembly of stress granules (SG). As an emerging pathogen, little is known however about how ZIKV modulates the host cell stress response. In this work, we investigate how ZIKV modulates SG assembly. We demonstrate that ZIKV negatively impacts SG assembly under oxidative stress conditions induced by sodium arsenite (Ars), a treatment that leads to the phosphorylation of eIF2α. By contrast, no measurable difference in SG assembly was observed between mock and ZIKV-infected cells treated with sodium selenite (Se) or Pateamine A (PatA), compounds that trigger eIF2α-independent SG assembly. Interestingly, ZIKV infection markedly impaired the phosphorylation of eIF2α triggered in Ars-treated infected cells, and the abrogation of SG assembly in ZIKV-infected cells is, at least in part, dependent on eIF2α dephosphorylation. These data demonstrate that ZIKV elicits mechanisms to counteract host anti-viral stress responses to promote a cellular environment propitious for viral replication.


Assuntos
Grânulos Citoplasmáticos/metabolismo , Fator de Iniciação 2 em Eucariotos/metabolismo , Interações Hospedeiro-Patógeno , Replicação Viral , Zika virus/imunologia , Zika virus/fisiologia , Animais , Linhagem Celular , Humanos , Biossíntese de Proteínas
9.
Arch Virol ; 162(6): 1577-1587, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28213871

RESUMO

Mayaro virus (MAYV) is an arthropod-borne virus and a member of the family Togaviridae, genus Alphavirus. Its infection leads to an acute illness accompanied by long-lasting arthralgia. To date, there are no antiviral drugs or vaccines against infection with MAYV and resources for the prevention or treatment of other alphaviruses are very limited. MAYV has served as a model to study the antiviral potential of several substances on alphavirus replication. In this work we evaluated the antiviral effect of seven new derivatives of thieno[2,3-b]pyridine against MAYV replication in a mammalian cell line. All derivatives were able to reduce viral production effectively at concentrations that were non-toxic for Vero cells. Molecular modeling assays predicted low toxicity risk and good oral bioavailability of the substances in humans. One of the molecules, selected for further study, demonstrated a strong anti-MAYV effect at early stages of replication, as it protected pre-treated cells and also during the late stages, affecting virus morphogenesis. This study is the first to demonstrate the antiviral effect of thienopyridine derivatives on MAYV replication in vitro, suggesting the potential application of these substances as antiviral molecules against alphaviruses. Additional in vivo research will be needed to expand the putative therapeutic applications.


Assuntos
Alphavirus/efeitos dos fármacos , Antivirais/química , Antivirais/farmacologia , Piridinas/farmacologia , Tiofenos/farmacologia , Animais , Chlorocebus aethiops , Humanos , Piridinas/síntese química , Piridinas/química , Piridinas/toxicidade , Tiofenos/síntese química , Tiofenos/química , Tiofenos/toxicidade , Células Vero , Replicação Viral/efeitos dos fármacos
10.
Virology ; 502: 73-83, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-28013103

RESUMO

Stress granules (SGs) are dynamic cytoplasmic aggregates of translationally silenced mRNAs that assemble in response to environmental stress. SGs appear to play an important role in antiviral innate immunity and many viruses have evolved to block or subvert SGs components for their own benefit. Here, we demonstrate that intracellular Ebola virus (EBOV) replication and transcription-competent virus like particles (trVLP) infection does not lead to SG assembly but leads to a blockade to Arsenite-induced SG assembly. Moreover we show that EBOV VP35 represses the assembly of canonical and non-canonical SGs induced by a variety of pharmacological stresses. This SG blockade requires, at least in part, the C-terminal domain of VP35. Furthermore, results from our co-immunoprecipitation studies indicate that VP35 interacts with multiple SG components, including G3BP1, eIF3 and eEF2 through a stress- and RNA-independent mechanism. These data suggest a novel function for EBOV VP35 in the repression of SG assembly.


Assuntos
Grânulos Citoplasmáticos/virologia , Ebolavirus/metabolismo , Doença pelo Vírus Ebola/virologia , Proteínas Virais Reguladoras e Acessórias/metabolismo , Proteínas de Transporte/metabolismo , Grânulos Citoplasmáticos/metabolismo , DNA Helicases , Ebolavirus/química , Ebolavirus/genética , Fator de Iniciação 2 em Eucariotos/metabolismo , Fator de Iniciação 3 em Eucariotos/metabolismo , Doença pelo Vírus Ebola/metabolismo , Interações Hospedeiro-Patógeno , Humanos , Proteínas de Ligação a Poli-ADP-Ribose , Ligação Proteica , Domínios Proteicos , RNA Helicases , Proteínas com Motivo de Reconhecimento de RNA , Proteínas Virais Reguladoras e Acessórias/química , Proteínas Virais Reguladoras e Acessórias/genética
11.
Viruses ; 8(6)2016 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-27231932

RESUMO

The mammalian target of rapamycin (mTOR) is a central regulator of gene expression, translation and various metabolic processes. Multiple extracellular (growth factors) and intracellular (energy status) molecular signals as well as a variety of stressors are integrated into the mTOR pathway. Viral infection is a significant stress that can activate, reduce or even suppress the mTOR signaling pathway. Consequently, viruses have evolved a plethora of different mechanisms to attack and co-opt the mTOR pathway in order to make the host cell a hospitable environment for replication. A more comprehensive knowledge of different viral interactions may provide fruitful targets for new antiviral drugs.


Assuntos
Vírus de DNA/fisiologia , Interações Hospedeiro-Patógeno , Vírus de RNA/fisiologia , Transdução de Sinais , Estresse Fisiológico , Serina-Treonina Quinases TOR/metabolismo , Replicação Viral , Animais , Vírus de DNA/patogenicidade , Humanos , Vírus de RNA/patogenicidade
12.
PLoS One ; 9(2): e88619, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24520405

RESUMO

The 30 different species of mRNAs synthesized during the HIV-1 replication cycle are all capped and polyadenilated. Internal ribosome entry sites have been recognized in the 5' untranslated region of some mRNA species of HIV-1, which would contribute to an alternative mechanism of initiation of mRNA translation. However, the Cap-dependent translation is assumed to be the main mechanism driving the initiation of HIV-1 protein synthesis. In this work, we describe a cell system in which lower to higher levels of transient expression of the poliovirus 2A protease strongly inhibited cellular Cap-dependent translation with no toxic effect to the cells during a 72-hour time frame. In this system, the synthesis of HIV-1 proteins was inhibited in a temporal dose-dependent way. Higher levels of 2A protease expression severely inhibited HIV-1 protein synthesis during the first 24 hours of infection consequently inhibiting viral production and infectivity. Intermediate to lower levels of 2A Protease expression caused the inhibition of viral protein synthesis only during the first 48 hours of viral replication. After this period both protein synthesis and viral release were recovered to the control levels. However, the infectivity of viral progeny was still partially inhibited. These results indicate that two mechanisms of mRNA translation initiation contribute to the synthesis of HIV-1 proteins; during the first 24-48 hours of viral replication HIV-1 protein synthesis is strongly dependent on Cap-initiation, while at later time points IRES-driven translation initiation is sufficient to produce high amounts of viral particles.


Assuntos
Cisteína Endopeptidases/metabolismo , DNA Intergênico/genética , HIV-1/genética , Biossíntese de Proteínas/efeitos dos fármacos , Capuzes de RNA/metabolismo , Proteínas Virais/metabolismo , Sobrevivência Celular , Fator de Iniciação Eucariótico 4G/metabolismo , HIV-1/fisiologia , Células HeLa , Humanos , Linfócitos/metabolismo , Plasmídeos/metabolismo , Polirribossomos/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Replicação Viral/efeitos dos fármacos
13.
PLoS One ; 8(12): e82504, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24376541

RESUMO

Dengue virus infection is a serious public health problem in endemic areas of the world where 2.5 billion people live. Clinical manifestations of the Dengue infection range from a mild fever to fatal cases of hemorrhagic fever. Although being the most rapidly spreading mosquito-borne viral infection in the world, until now no strategies are available for effective prevention or control of Dengue infection. In this scenario, the development of compounds that specifically inhibit viral replication with minimal effects to the human hosts will have a substantial effect in minimizing the symptoms of the disease and help to prevent viral transmission in the affected population. The aim of this study was to screen compounds with potential activity against dengue virus from a library of synthetic naphthoquinones. Several 1,2- and 1,4-pyran naphthoquinones were synthesized by a three-component reaction of lawsone, aldehyde (formaldehyde or arylaldehydes) and different dienophiles adequately substituted. These compounds were tested for the ability to inhibit the ATPase activity of the viral NS3 enzyme in in vitro assays and the replication of dengue virus in cultured cells. We have identified two 1,4-pyran naphthoquinones, which inhibited dengue virus replication in mammal cells by 99.0% and three others that reduced the dengue virus ATPase activity of NS3 by two-fold in in vitro assays.


Assuntos
Antivirais/farmacologia , Vírus da Dengue/fisiologia , Naftoquinonas/farmacologia , Piranos/farmacologia , Replicação Viral/efeitos dos fármacos , Adenosina Trifosfatases/antagonistas & inibidores , Adenosina Trifosfatases/metabolismo , Animais , Morte Celular/efeitos dos fármacos , Chlorocebus aethiops , Relação Dose-Resposta a Droga , Avaliação Pré-Clínica de Medicamentos , Células Hep G2 , Humanos , Naftoquinonas/síntese química , Naftoquinonas/química , Piranos/síntese química , Piranos/química , Células Vero , Proteínas não Estruturais Virais/antagonistas & inibidores , Proteínas não Estruturais Virais/isolamento & purificação
14.
J Med Virol ; 85(4): 563-74, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23417613

RESUMO

Progression towards AIDS can vary from 5 to 10 years from the establishment of the primary infection by HIV-1 to more than 10 years in the complete absence of antiretroviral therapy. Several factors can contribute to the outcome of HIV infection, including host genetic and viral replicating characteristics. Historically, nef-deleted viral genomes have been associated with disease progression. Therefore, the lentiviral Nef protein is regarded as a progression factor. The objective of this work was to characterize the nef gene from a group of treatment naive patients infected with HIV-1 for more than 10 years. These patients were classified as long-term non-progressors, elite controller, and slow-progressors according to clinical and laboratorial data. A premature stop codon within the nef gene leading to the expression of a truncated peptide was observed on samples from the elite controller patient. For the slow-progressor patients, several degrees of deletions at the C-terminal of Nef were observed predicting a loss of function of this protein. The vif gene was characterized for these patients and a rare mutation that predicts a miss localization of the Vif protein to the nucleus of infected cells that could prevent its function as an APOBEC neutralization factor was also observed. These data indicate the importance of the HIV accessory proteins as factors that contribute to the outcome of AIDS.


Assuntos
Síndrome da Imunodeficiência Adquirida/virologia , Sobreviventes de Longo Prazo ao HIV , HIV-1/genética , HIV-1/patogenicidade , Mutação , Produtos do Gene nef do Vírus da Imunodeficiência Humana/genética , Produtos do Gene vif do Vírus da Imunodeficiência Humana/genética , Progressão da Doença , Humanos
15.
Int J Pediatr Otorhinolaryngol ; 76(9): 1332-8, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22796193

RESUMO

OBJECTIVE: To characterize the P(1) component of long latency auditory evoked potentials (LLAEPs) in cochlear implant users with auditory neuropathy spectrum disorder (ANSD) and determine firstly whether they correlate with speech perception performance and secondly whether they correlate with other variables related to cochlear implant use. METHODS: This study was conducted at the Center for Audiological Research at the University of São Paulo. The sample included 14 pediatric (4-11 years of age) cochlear implant users with ANSD, of both sexes, with profound prelingual hearing loss. Patients with hypoplasia or agenesis of the auditory nerve were excluded from the study. LLAEPs produced in response to speech stimuli were recorded using a Smart EP USB Jr. system. The subjects' speech perception was evaluated using tests 5 and 6 of the Glendonald Auditory Screening Procedure (GASP). RESULTS: The P(1) component was detected in 12/14 (85.7%) children with ANSD. Latency of the P(1) component correlated with duration of sensorial hearing deprivation (*p=0.007, r=0.7278), but not with duration of cochlear implant use. An analysis of groups assigned according to GASP performance (k-means clustering) revealed that aspects of prior central auditory system development reflected in the P(1) component are related to behavioral auditory skills. CONCLUSIONS: In children with ANSD using cochlear implants, the P(1) component can serve as a marker of central auditory cortical development and a predictor of the implanted child's speech perception performance.


Assuntos
Córtex Auditivo/fisiologia , Implante Coclear , Implantes Cocleares , Potenciais Evocados Auditivos/fisiologia , Perda Auditiva Neurossensorial/fisiopatologia , Percepção da Fala/fisiologia , Criança , Pré-Escolar , Feminino , Perda Auditiva Central , Perda Auditiva Neurossensorial/terapia , Humanos , Masculino
16.
Rev. bras. educ. espec ; 16(3): 359-373, set.-dez. 2010. tab
Artigo em Português | LILACS | ID: lil-574765

RESUMO

INTRODUÇÃO: A inclusão do deficiente auditivo na escola é assegurada pelo poder público no Brasil por documentos oficiais e o sistema FM é um instrumento da tecnologia assistiva que o professor deve ter acesso. OBJETIVO: traduzir e adaptar para a Língua Portuguesa o questionário FM Listening Evaluation for children. MÉTODOS: A tradução e adaptação do questionário FM Listening Evaluation incluíram a tradução para o idioma português, adaptação lingüística e revisão das equivalências gramatical e idiomática e adaptação; também foi avaliada a reprodutibilidade intra-pesquisadores. O questionário foi aplicado nos professores e na fonoaudióloga de 12 crianças de sete a treze anos deficientes auditivas, usuárias de Aparelho de Amplificação Sonora Individual e adaptadas com sistema FM. RESULTADOS: A tradução e adaptação do questionário resultaram no novo inventário:AVALIAÇÃO DO SISTEMA FM, apresentando diferença significativa entre os resultados de ruído e: via auditiva e silêncio; - distância e: via auditiva e silêncio; - via auditiva e: ruído, distância e silêncio; - silêncio e: ruído, distância e via auditiva. Houve diferença significativa sem e com o Sistema FM, sendo que neste a pontuação foi sempre maior. Na comparação intrapesquisadores evidenciou-se diferença significativa entre: pontuação total com FM; via auditiva sem FM e ruído com FM. CONCLUSÃO: O questionário Avaliação do Sistema FM foi considerado um instrumento confiável para verificação e acompanhamento dos benefícios do Sistema FM podendo favorecer assim o processo de inclusão escolar do aluno deficiente auditivo.


INTRODUCTION: The inclusion of children with hearing impairments in schools is guaranteed by the Brazilian government by means of official legislation. The FM system is an assistive technology instrument to which regular teachers should have access. OBJECTIVE: To translate and adapt to Portuguese the FM Listening Evaluation questionnaire for children and assess its reliability. METHODS: The translation and adaptation to the FM Listening Evaluation included translation into Portuguese, linguistic adaptation and revision of the grammatical and idiomatic equivalences and adaptation; inter-researcher reproducibility was also evaluated. The questionnaire was administered to the teachers and speech-language pathologists of 12 children aged seven to thirteen years with hearing impairment; the children used hearing aids and had been adapted to the FM system. RESULTS: The translation and adaptation of the questionnaire resulted in new inventory: FM EVALUATION SYSTEM, presenting a significant difference between the results of noise and: hearing pathways and silence; - distance and: hearing pathways and silence; - hearing pathways and: noise, distance and silence; - silence and: noise, distance and hearing pathways. There was significant difference with and without the FM system, in which the score was always higher. Intra-examiner comparison revealed a significant difference between the total score with FM, via FM and hearing no noise with FM. CONCLUSION: The questionnaire Rating System FM was considered a reliable instrument for verifying and monitoring the benefits of FM system, in order to promote the process of educational inclusion for students with hearing impairments.

17.
Rev. Soc. Bras. Fonoaudiol ; 15(2): 191-196, 2010. ilus, tab
Artigo em Português | LILACS | ID: lil-553427

RESUMO

OBJETIVO: Traduzir e adaptar culturalmente para a língua portuguesa o questionário Early Listening Function (ELF), e avaliar a confiabilidade do mesmo. MÉTODOS: Foi realizada a tradução do questionário para o idioma Português, revisão das equivalências gramatical e idiomática (traduções reversas) e adaptações linguística e cultural. Além disso, foi avaliada a reprodutibilidade intra-pesquisadores. Após a tradução, o ELF foi aplicado, em ambiente silencioso e ruidoso, em 30 crianças entre zero e três anos de idade, sem histórico de risco para deficiência auditiva, ausência de queixa familiar quanto ao desenvolvimento global da criança e sem indicadores de perda auditiva incapacitante, em diferentes distâncias, em 12 situações de detecção auditiva. RESULTADOS: Os resultados foram analisados com estudo estatístico descritivo a partir da pontuação obtida no ELF. CONCLUSÃO: O instrumento ELF foi traduzido e adaptado culturalmente para a população estudada. No Português, sua denominação manteve a sigla ELF. O estudo permitiu verificar sua confiabilidade para observação e acompanhamento das etapas iniciais do comportamento auditivo.


PURPOSE: To translate and adapt the Early Listening Function (ELF) questionnaire into the Brazilian Portuguese language, and to evaluate the reliability of the test. METHODS: It was carried out the translation of the ELF questionnaire into Brazilian Portuguese, the review of grammatical and idiomatic equivalents (reversed translations), and linguistic and cultural adaptation. Moreover, the intra-researcher reproducibility was evaluated. After the translation, the ELF was carried out with 30 children between zero and three years old, with no history of hearing loss risk, lack of family complaint regarding the overall development of the child, and no indicators of hearing loss disability. The questionnaire was applied in 12 cases of hearing detection at different distances, in quiet and noisy environments. RESULTS: Results were analyzed using a descriptive statistical study based on the results obtained on the ELF score sheet. CONCLUSION: The ELF questionnaire was translated and culturally adapted for the studied population. In Brazilian Portuguese, its designation maintained the acronym ELF. The study verified the instrument's reliability for observing and monitoring the initial stages of hearing behavior.


Assuntos
Humanos , Recém-Nascido , Lactente , Pré-Escolar , Diagnóstico Precoce , Desenvolvimento da Linguagem , Perda Auditiva/diagnóstico , Inquéritos e Questionários , Tradução , Transtornos da Audição/diagnóstico
18.
Arq. int. otorrinolaringol. (Impr.) ; 13(1): 16-23, jan.-mar. 2009. tab, graf
Artigo em Inglês, Português | LILACS | ID: lil-529410

RESUMO

Introdução: A queixa mais frequente dos usuários de implante coclear tem sido reconhecer e compreender o sinal da fala na presença do ruído. Pesquisas investigam a percepção da fala dos usuários de implante coclear, enfocando aspectos como os efeitos da diminuição da relação sinal/ruído na percepção da fala, o reconhecimento da fala no ruído, com diferentes tipos de implante coclear e estratégias de codificação da fala e os efeitos da estimulação biaural na percepção da fala no ruído. Objetivo: 1 - Avaliar a percepção de fala em adultos usuários de implante coclear, em diferentes posições quanto à apresentação do estimulo; 2 - comparar os índices de reconhecimento de fala nas posições frontal, ipsilateral e contralateral e 3 - analisar o efeito da adaptação monoaural na percepção da fala com ruído. Método: Avaliados 22 adultos usuários de implante coclear quanto à percepção da fala. Os indivíduos foram submetidos à avaliação de reconhecimento das sentenças, com ruído competitivo na relação sinal/ruído +10 decibeis em três posições: frontal, ipsilateral e contralateral ao lado implantado. Resultados: Os resultados demonstraram maior índice de reconhecimento da fala na posição ipsilateral (100%) e o menor índice de reconhecimento da fala com sentenças na posição contralateral (5%). Conclusão: O desempenho da percepção da fala em indivíduos implantados é prejudicado quando é introduzido o ruído competitivo, o índice de reconhecimento da fala é melhor quando a fala é apresentada ipsilateralmente, e consequentemente é pior quando é apresentada contralateralmente ao implante coclear, e há maior prejuízo na inteligibilidade da fala quando existe apenas entrada monoaural.


Introduction: The most frequent complaint of the cochlear implant users has been to recognize and understand the speech signal in the presence of noise. Researches have been developed on the speech perception of users of cochlear implant with focus on aspects such as the effect of the reduction to the signal/noise ratio in the speech perception, the speech recognition in the noise, with different types of cochlear implant and strategies of speech codification and the effects of the binaural stimulation in the speech perception in noise. Objective: 1-To assess the speech perception in cochlear implant adult users in different positions regarding the presentation of the stimulus, 2-to compare the index of speech recognition in the frontal, ipsilateral and contralateral positions and 3-to analyze the effect of monoaural adaptation in the speech perception with noise. Method: 22 cochlear implant adult users were evaluated regarding the speech perception. The individuals were submitted to sentences recognition evaluation, with competitive noise in the signal/noise ratio +10 decibels in three positions: frontal, ipsilateral and contralateral to the cochlear implant side. Results: The results demonstrated the largest index of speech recognition in the ipsilateral position (100%) and the lowest index of speech recognition with sentences in the contralateral position (5%). Conclusion: The performance of speech perception in cochlear implant users is damaged when the competitive noise is introduced, the index of speech recognition is better when the speech is presented ipsilaterally, and it's consequently worse when presented contralaterally to the cochlear implant, and there are more damages in the speech intelligibility when there is only monoaural input.


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Adulto , Implante Coclear , Ruído , Perda Auditiva/reabilitação , Percepção da Fala
19.
Arq. int. otorrinolaringol. (Impr.) ; 13(1): 49-54, jan.-mar. 2009. tab, graf
Artigo em Inglês, Português | LILACS | ID: lil-529416

RESUMO

Introdução: Fisiologicamente, indivíduos expostos ao ruído, podem desenvolver uma patologia muito comum, a perda auditiva induzida por níveis de pressão sonora elevada. Objetivo: Investigar por meio de um estudo transversal, a prevalência de perda auditiva ocupacional em trabalhadores expostos a níveis de pressão sonora acima de 85 dB NPS. Método: Participaram deste estudo 400 prontuários de trabalhadores expostos a níveis de pressão sonora acima de 85 dB NPS, locados em empresas de diferentes segmentos. Resultados: Nesta amostra, foram observadas diferenças estatisticamente significante entre os limiares de baixas e altas frequências e que o tempo de trabalho influenciou na piora dos limiares nas altas frequências bilateralmente. Quanto à lateralidade não foram constatadas diferenças significativas entre as orelhas, assim como a ausência da correlação entre zumbido e perda auditiva. Conclusões: Um trabalho intensivo de promoção da saúde auditiva e/ou prevenção de perdas auditivas, deve ser enfatizado, principalmente para trabalhadores expostos a níveis elevados de ruído ocupacional, além da utilização, de forma adequada, de equipamento de proteção auditiva individual.


Introduction: Physiologically, the individuals exposed to the noise may develop a very common pathology; the occupational noise induced hearing loss. Objective: Research the by means of a cross-sectional study, prevalence of occupational hearing loss in workers exposed to noise pressure levels over 85 dB NPL. Method: 400 records of workers exposed to noise pressure levels above 85 db NPS, working in companies of different segments. Results: In this sample, statistically significant differences were observed between the low and high frequencies thresholds and that the work duration influenced in the worsening of high frequencies thresholds bilaterally. As for the laterality no significant differences were confirmed between the ears, as well as the absence of correlation between tinnitus and hearing loss. Conclusion: An intensive work of auditory health promotion and/or auditory loss prevention must be emphasized, especially for workers exposed to high level occupational noises, as well as the appropriate features of individual auditory protection equipment.


Assuntos
Humanos , Masculino , Feminino , Audiometria , Exposição Ambiental , Perda Auditiva , Ruído Ocupacional , Saúde Ocupacional
20.
J Appl Oral Sci ; 17 Suppl: 57-62, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-21499656

RESUMO

UNLABELLED: The study of brainstem auditory evoked potentials (BAEP) allows obtaining the electrophysiological activity generated in the cochlear nerve to the inferior colliculus. In the first months of life, a period of greater neuronal plasticity, important changes are observed in the absolute latency and inter-peak intervals of BAEP, which occur up to the completion of the maturational process, around 18 months of life in full-term newborns, when the response is similar to that of adults. OBJECTIVE: The goal of this study was to establish normal values of absolute latencies for waves I, III and V and inter-peak intervals I-III, III-V and I-V of the BAEP performed in full-term infants attending the Infant Hearing Health Program of the Speech-Language Pathology and Audiology Course at Bauru School of Dentistry, Brazil, with no risk history for hearing impairment. MATERIAL AND METHODS: The stimulation parameters were: rarefaction click stimulus presented by the 3ª insertion phone, intensity of 80 dBnHL and a rate of 21.1 c/s, band-pass filter of 30 and 3,000 Hz and average of 2,000 stimuli. A sample of 86 infants was first divided according to their gestational age in preterm (n=12) and full-term (n=74), and then according to their chronological age in three periods: P1: 0 to 29 days (n=46), P2: 30 days to 5 months 29 days (n=28) and P3: above 6 months (n= 12). RESULTS: The absolute latency of wave I was similar to that of adults, generally in the 1st month of life, demonstrating a complete process maturity of the auditory nerve. For waves III and V, there was a gradual decrease of absolute latencies with age, characterizing the maturation of axons and synaptic mechanisms in the brainstem level. CONCLUSION: Age proved to be a determining factor in the absolute latency of the BAEP components, especially those generated in the brainstem, in the first year of life.


Assuntos
Percepção Auditiva/fisiologia , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Fatores Etários , Análise de Variância , Nervo Coclear/crescimento & desenvolvimento , Estudos de Coortes , Estudos Transversais , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Tempo de Reação , Fatores de Tempo
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