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1.
Rev. baiana saúde pública ; 47(1): 210-226, 20230619.
Artigo em Português | LILACS | ID: biblio-1438358

RESUMO

A vacina constitui um dos principais métodos de prevenção contra doenças. Em 1973, o Brasil criou o Programa Nacional de Imunizações a fim de promover a imunização gratuita para a população, o que mais tarde tornou o país em referência mundial em vacinação. No entanto, a recusa vacinal ainda é um grande problema de saúde pública, sendo o movimento antivacina um dos destaques dessa realidade. Dessa forma, o objetivo deste artigo é avaliar como o movimento antivacina impacta na saúde pública no Brasil através da diminuição da cobertura vacinal. Trata-se de uma pesquisa de metodologia mista, com uma primeira etapa qualitativa, composta de uma revisão integrativa nas plataformas PubMed, LILACS e SciELO, no período de 2010 a 2020, e uma pesquisa documental em portais de movimentos antivacina; e uma segunda etapa quantitativa, em que foi realizado um estudo epidemiológico do tipo ecológico, com consulta nas bases eletrônicas do Datasus e no Sistema de Informações do Programa Nacional de Imunizações (SI-PNI), no período de 2010 a 2022. No período investigado, apenas em 2015 o Brasil alcançou a meta preconizada de cobertura vacinal, diferentemente dos anos seguintes, que apresentaram oscilações preocupantes. As publicações apresentam argumentos utilizados pelos grupos antivacina, evidenciados entre 2015 e 2019, período em que os dados de cobertura vacinal oscilaram. Assim, conclui-se que a ascensão do movimento antivacina é um dos fatores que influenciaram na queda da vacinação no Brasil, a exemplo do sarampo e da febre amarela.


The vaccine is one of the main methods of preventing diseases. Since 1973, Brazil created the National Immunization Program to ensure free immunization to the population, which later made the country a world reference in vaccination. However, vaccine refusal is still a great public health issue, and the anti-vaccine movement stand out in this reality. Thus, the purpose of this article is to evaluate how the anti-vaccine movement affects public health in Brazil with vaccination coverage reduction. This is a mixed methodology study, with first a qualitative step, composed of an integrative review in the platforms PubMed, LILACS, and SciELO, in the period from 2010 to 2020,and a documental research in portals of anti-vaccination movements; and a second quantitative step, where an epidemiological study of the ecological type was carried out, with consultation in the electronic databases of DATASUS and in the Information System of the National Immunization Program (SI-PNI) in the period of 2010 to 2022. In the investigative period, only in 2015 Brazil managed to reach the recommended vaccination coverage goal, unlike in the following years, which showed worrying fluctuations. The publications summarize arguments used by the anti-vaccination groups, evidenced between 2015 and 2019, a period in which the vaccination coverage data fluctuated. Therefore, it is clear that the rise of the anti-vaccination movement is a factor that influenced the drop in vaccination numbers in Brazil, with yellow fever and measles as examples.


La vacuna es uno de los principales métodos de prevención de enfermedades. En 1973, Brasil creó el Programa Nacional de Inmunización con el fin de promover la inmunización gratuita para la población, lo que luego convirtió al país en un referente mundial en vacunación. Sin embargo, la negativa de la vacuna sigue siendo un problema importante en la salud pública, y el movimiento antivacunas es uno de los aspectos más destacados de esta realidad. Así, el objetivo de este artículo es evaluar cómo el movimiento antivacunas impacta en la salud pública en Brasil mediante la disminución de la cobertura de vacunación. Se trata de un estudio epidemiológico mixto, con una primera etapa cualitativa, consistente en una revisión integradora en las plataformas PubMed, Lilacs y SciELO, en el período de 2010 a 2020, y una investigación documental en portales de movimientos antivacunas; y una segunda etapa cuantitativa, en la que se realizó un estudio epidemiológico de tipo ecológico, con consulta en las bases de datos electrónicas de DATASUS y en el Sistema de Información del Programa Nacional de Inmunización (SI-PNI), en el período de 2010 a 2022. Entre eses años, solo el año 2015 logró alcanzar la meta recomendada, a diferencia de los años siguientes, que mostraron fluctuaciones preocupantes en la cobertura de vacunación. Las publicaciones mostraron los argumentos utilizados por los grupos antivacina, evidenciados entre 2015 y 2019, período en que los datos de cobertura de la vacuna fluctuaron. Así, se concluye que la asunción del movimiento antivacunación es uno de los factores que influye en la caída de la vacunación en Brasil, como en el sarampión y la fiebre amarilla.


Assuntos
Humanos , Cobertura Vacinal/estatística & dados numéricos
2.
J Gen Virol ; 104(4)2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-37010894

RESUMO

Drug repurposing is a valuable source of new antivirals because many compounds used to treat a variety of pathologies can also inhibit viral infections. In this work, we have tested the antiviral capacity of four repurposed drugs to treat Bunyamwera virus (BUNV) infection in cell cultures. BUNV is the prototype of the Bunyavirales order, a large group of RNA viruses that includes important pathogens for humans, animals and plants. Mock- and BUNV-infected Vero and HEK293T cells were treated with non-toxic concentrations of digoxin, cyclosporin A, sunitinib and chloroquine. The four drugs inhibited BUNV infection with varying potency in Vero cells, and all except sunitinib also in HEK293T cells, with digoxin rendering the lowest half maximal inhibitory concentration (IC50). Since digoxin rendered the best results, we selected this drug for a more detailed study. Digoxin is an inhibitor of the Na+/K+ ATPase, a plasma membrane enzyme responsible for the energy-dependent exchange of cytoplasmic Na+ for extracellular K+ in mammalian cells and involved in many signalling pathways. Digoxin was shown to act at an early time point after viral entry reducing the expression of the viral proteins Gc and N. Effects on the cell cycle caused by BUNV and digoxin were also analysed. In Vero cells, digoxin favoured the transition from G1 phase of the cell cycle to S phase, an effect that might contribute to the anti-BUNV effect of digoxin in this cell type. Transmission electron microscopy showed that digoxin impedes the assembly of the characteristic spherules that harbour the BUNV replication complexes and the morphogenesis of new viral particles. Both BUNV and digoxin induce similar changes in the morphology of mitochondria that become more electron-dense and have swollen cristae. The alterations of this essential organelle might be one of the factors responsible for digoxin-induced inhibition of viral infection. Digoxin did not inhibit BUNV infection in BHK-21 cells that have a digoxin-resistant Na+/K+ ATPase, which suggests that the effects of the blockade of this enzyme is a key factor of the antiviral activity of digoxin in BUNV-infected Vero cells.


Assuntos
Vírus Bunyamwera , Humanos , Animais , Chlorocebus aethiops , Vírus Bunyamwera/genética , Células Vero , Digoxina/farmacologia , Sunitinibe , Células HEK293 , Antivirais/farmacologia , Técnicas de Cultura de Células , Adenosina Trifosfatases , Mamíferos
3.
Medicine (Baltimore) ; 102(1): e32233, 2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36607852

RESUMO

BACKGROUND: The use of electronic cigarettes is one of the current public health problems on increasing alert, has been growing at an accelerating rate, and has become a public health emergency. Its importance is explained by the continuous growth and acceleration of oncological rates among all ages versus the absence of high-quality evidence, correlated to the use of nicotine derived products, being at their regular versions or the new ones. Available preclinical data indicate that activation of the sympathetic nervous system by nicotine inhaled from e-cigarettes may stimulate cancer development and growth by several mechanisms, which results can significantly reduce life's quality. This systematic review and meta-analysis protocol aims to clarify the connection between the use of electronic cigarettes by adults over the age of 18 and the development of malignant neoplastic diseases. METHOD: The proposed systematic review and meta-analysis will be reported conforming to the preferred reporting items for systematic reviews and meta-analyses guidelines. Will include the following studies: case-control or cohort studies showing adults (18 years old age) using e-cigarettes. There will be no language or publication period restrictions. Articles published, but not peer-reviewed, will not be included in the review. Data will be entered in the Review Manager software (RevMan5.2.3). For dichotomous outcomes, we extracted or calculated the OR and 95% CI for each study. In case of heterogeneity (I²>50%), the random-effects model will be used to combine the studies to calculate the OR and 95% CI.


Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Neoplasias , Adulto , Humanos , Pessoa de Meia-Idade , Adolescente , Nicotina/efeitos adversos , Revisões Sistemáticas como Assunto , Metanálise como Assunto , Saúde Pública , Neoplasias/epidemiologia , Neoplasias/etiologia
4.
Rev. crim ; 65(1): 27-40, 2023.
Artigo em Espanhol | LILACS | ID: biblio-1427730

RESUMO

La presente investigación jurídico-propositiva se ocupó de analizar el desarrollo de la finalidad educativa de las sanciones en el Sistema de Responsabilidad Penal para Adolescentes (SRPA), mediante la realización de entrevistas semiestructuradas a las autoridades administrativas y judiciales que imponen y vigilan las sanciones; en complemento con el análisis de los datos suministrados por los operadores del sistema sobre los adolescentes infractores de la Ley Penal, en particular de los autores del delito de hurto en la ciudad de Barranquilla (Colombia) durante el 2017 y 2018. Se encontró que 275 adolescentes ingresaron al SRPA por este delito punible; 211 cumplieron su medida no privativa de la libertad en el Centro Luz de Esperanza, donde desarrollan un proceso integrado por terapias individuales, grupales y familiares, simultáneo a los ciclos educativos, que al parecer son insuficientes para el logro de la finalidad educativa de la sanción, atendiendo los índices de reincidencia que se presentan. Se propuso un proceso educativo que desarrolle enfoques diferenciales, inclusivos y permanentes, que más allá de escolarizarlos los involucre en un proyecto de vida.


The present legal-propositional research was concerned with analyzing the development of the educational purpose of sanctions in the System of Criminal Responsibility for Adolescents (SRPA), by conducting semistructured interviews with administrative and judicial authorities who impose and monitor sanctions; in complement with the analysis of data provided by operators of the system on adolescent offenders of the Criminal Law, particularly perpetrators of the crime of theft in the city of Barranquilla (Colombia) during 2017 and 2018. It was found that 275 adolescents entered the SRPA for this punishable offense; 211 served their non-custodial measure in the Luz de Esperanza Center, where they develop a process integrated by individual, group and family therapies, simultaneous to the educational cycles, which apparently are insufficient for the achievement of the educational purpose of the sanction, attending to the recidivism rates that occur. It was proposed an educational process that develops differential, inclusive and permanent approaches, which, beyond schooling, involves them in a life project.


Esta pesquisa jurídico-propositiva preocupou-se em analisar o desenvolvimento do propósito educacional das sanções no Sistema de Responsabilidade Criminal para Adolescentes (SRPA), realizando entrevistas semi-estruturadas com autoridades administrativas e judiciais que impõem e monitoram sanções; além da análise dos dados fornecidos pelos operadores do sistema sobre adolescentes infratores do direito penal, em particular os autores do crime de furto na cidade de Barranquilla (Colômbia) durante 2017 e 2018. Foi constatado que 275 adolescentes entraram na SRPA por este delito punível; 211 serviram sua medida não-custodial no Centro Luz de Esperanza, onde desenvolvem um processo integrado por terapias individuais, grupais e familiares, simulta-neamente com os ciclos educativos, que aparentemente são insuficientes para o cumprimento do objetivo educativo da sanção, considerando as taxas de reincidência que ocorrem. Foi proposto um processo educacional que desenvolve abordagens diferenciadas, inclusivas e permanentes que vão além da escolaridade e as envolvem em um projeto de vida.


Assuntos
Humanos , Adolescente , Roubo , Crime , Responsabilidade Penal , Direito Penal , Criminosos , Reincidência , Jurisprudência
5.
J Virol ; 92(12)2018 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-29618643

RESUMO

The mature envelope glycoprotein (Env) spike on the surfaces of human immunodeficiency virus type 1 (HIV-1)-infected cells and virions is derived from proteolytic cleavage of a trimeric gp160 glycoprotein precursor. In these studies, we compared the conformations of cleaved and uncleaved membrane Envs with truncated cytoplasmic tails to those of stabilized soluble gp140 SOSIP.664 Env trimers. Deletion of the gp41 cytoplasmic tail did not significantly affect the sensitivity of viruses with the HIV-1AD8 Env to inhibition by antibodies or a CD4-mimetic compound. After glutaraldehyde fixation and purification from membranes, a cleaved Env exhibited a hydrodynamic radius of ∼10 nm and an antibody-binding profile largely consistent with that expected based on virus neutralization sensitivity. The purified cleaved Env trimers exhibited a hollow architecture with a central void near the trimer axis. Uncleaved Env, cross-linked and purified in parallel, exhibited a hydrodynamic radius similar to that of the cleaved Env. However, the uncleaved Env was recognized by poorly neutralizing antibodies and appeared by negative-stain electron microscopy to sample multiple conformations. Compared with membrane Envs, stabilized soluble gp140 SOSIP.664 Env trimers appear to be more compact, as reflected in their smaller hydrodynamic radii and negative-stain electron microscopy structures. The antigenic features of the soluble gp140 SOSIP.664 Env trimers differed from those of the cleaved membrane Env, particularly in gp120 V3 and some CD4-binding-site epitopes. Thus, proteolytic maturation allows the membrane-anchored Env to achieve a conformation that retains functional metastability but masks epitopes for poorly neutralizing antibodies.IMPORTANCE The entry of human immunodeficiency virus type 1 (HIV-1) into host cells is mediated by the envelope glycoprotein (Env) spike on the surface of the virus. Host antibodies elicited during natural HIV-1 infection or by vaccination can potentially recognize the Env spike and block HIV-1 infection. However, the changing shape of the HIV-1 Env spike protects the virus from antibody binding. Understanding the shapes of natural and man-made preparations of HIV-1 Envs will assist the development of effective vaccines against the virus. Here, we evaluate the effects of several Env modifications commonly used to produce Env preparations for vaccine studies and the determination of structure. We found that the cleavage of the HIV-1 Env precursor helps Env to assume its natural shape, which resists the binding of many commonly elicited antibodies. Stabilized soluble Envs exhibit more compact shapes but expose some Env elements differently than the natural Env.


Assuntos
Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Anticorpos Anti-HIV/imunologia , HIV-1/imunologia , Produtos do Gene env do Vírus da Imunodeficiência Humana/imunologia , Animais , Linhagem Celular Tumoral , Cães , Glutaral/química , Células HEK293 , Proteína gp120 do Envelope de HIV/imunologia , Proteína gp120 do Envelope de HIV/metabolismo , Proteína gp41 do Envelope de HIV/genética , Humanos , Conformação Proteica , Multimerização Proteica , Produtos do Gene env do Vírus da Imunodeficiência Humana/metabolismo
6.
Córdoba; s.n; 2015. 40 p. ilus.
Tese em Espanhol | LILACS | ID: biblio-971321

RESUMO

En el presente estudio se busca determinar el nivel de satisfacción de los profesionales y pacientes en centros de atención primaria de la salud. Se realizó el estudio entre 60 personas entre profesionales y pacientes, y lo relevante es que la mayoría de los pacientes están conformes con los servicios brindados en cuanto a la atención médica, la infraestructura, la solicitud de turnos, etc., desconociendo algunas cuestiones puntuales como la falta de insumos. En cambio desde el punto de vista de los profesionales se valoró negativamente la posibilidad de ascender en el puesto de trabajo, las condiciones de infraestructura y la falta de insumos.


In the following investigation it is searched to determine the level of satisfaction of professional and patients in the basic attention of health. This study was done among 60 people. They were professional and patients and it is very important to emphasize that the majority of the patients are satisfied with the service given. Not only with the medical attention, the place but also with the request of appointments, etc; and not paying attention to the lack of elements. On the other hand from the point of view of professionals the possibility of being promoted in their jobs, the conditions of the place and the lack of elements were not taken in count.


Assuntos
Masculino , Feminino , Humanos , Satisfação do Paciente , Satisfação no Emprego , Atenção Primária à Saúde/organização & administração , Serviços Básicos de Saúde , Centros Comunitários de Saúde/organização & administração , Mão de Obra em Saúde/organização & administração , Argentina
7.
Curr Opin Virol ; 8: 1-9, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24814823

RESUMO

Hepatitis B virus (HBV) polymerase and human immunodeficiency virus (HIV) reverse transcriptase are structurally related. However, the HBV enzyme has a protein priming activity absent in the HIV enzyme. Approved nucleoside/nucleotide inhibitors of the HBV polymerase include lamivudine, adefovir, telbivudine, entecavir and tenofovir. Although most of them target DNA elongation, guanosine and adenosine analogs (e.g. entecavir and tenofovir, respectively) also impair protein priming. Major mutational patterns conferring nucleoside/nucleotide analog resistance include the combinations rtL180M/rtM204(I/V) (for lamivudine, entecavir, telbivudine and clevudine) and rtA181V/rtN236T (for adefovir and tenofovir). However, development of drug resistance is very slow for entecavir and tenofovir. Novel nucleoside/nucleotide analogs in advanced clinical trials include phosphonates similar to adefovir or tenofovir, and new tenofovir derivatives with improved pharmacological properties.


Assuntos
Antivirais/farmacologia , DNA Polimerase Dirigida por DNA/genética , DNA Polimerase Dirigida por DNA/metabolismo , Farmacorresistência Viral , Vírus da Hepatite B/efeitos dos fármacos , Nucleosídeos/farmacologia , Nucleotídeos/farmacologia , Vírus da Hepatite B/enzimologia , Humanos , Mutação de Sentido Incorreto
8.
J Virol ; 87(13): 7234-45, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23637418

RESUMO

The tripartite motif protein TRIM5α restricts particular retrovirus infections by binding to the incoming capsid and inhibiting the early stage of virus infection. The TRIM5α RING domain exhibits E3 ubiquitin ligase activity and assists the higher-order association of TRIM5α dimers, which promotes capsid binding. We characterized a panel of RING domain mutants of the rhesus monkey TRIM5α (TRIM5α(rh)) protein. The RING domain function that significantly contributed to retroviral restriction depended upon the restricted virus. The E3 ubiquitin ligase activity of the RING domain contributes to the potency of HIV-1 restriction. Nonetheless, TRIM5α(rh) mutants without detectable E3 ubiquitin ligase activity still blocked reverse transcription and inhibited HIV-1 infection at a moderate level. When TRIM5α(rh) capsid binding was weakened by substitution with a less efficient B30.2/SPRY domain, the promotion of higher-order association by the RING domain was more important to HIV-1 restriction than its E3 ubiquitin ligase activity. For the restriction of N-tropic murine leukemia virus (N-MLV) and equine infectious anemia virus (EIAV) infection, promotion of higher-order association represented the major contribution of the RING domain. Thus, both identity of the target virus and the B30.2/SPRY domain-mediated affinity for the viral capsid determine the relative contribution of the two known RING domain functions to TRIM5α restriction of retrovirus infection.


Assuntos
Capsídeo/metabolismo , HIV-1 , Vírus da Anemia Infecciosa Equina , Vírus da Leucemia Murina , Proteínas/metabolismo , Infecções por Retroviridae/metabolismo , Animais , Western Blotting , Linhagem Celular , Cães , Proteínas de Fluorescência Verde/metabolismo , Humanos , Macaca mulatta , Microscopia de Fluorescência , Proteínas/genética , Infecções por Retroviridae/genética , Especificidade da Espécie , Ubiquitina-Proteína Ligases/metabolismo
9.
J Virol ; 86(17): 8974-86, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22696649

RESUMO

Metastable conformations of the gp120 and gp41 envelope glycoproteins of human immunodeficiency virus type 1 (HIV-1) and simian immunodeficiency virus (SIV) must be maintained in the unliganded state of the envelope glycoprotein trimer. Binding of gp120 to the primary receptor, CD4, triggers the transition to an open conformation of the trimer, promoting interaction with the CCR5 chemokine receptor and ultimately leading to gp41-mediated virus-cell membrane fusion and entry. Topological layers in the gp120 inner domain contribute to gp120-trimer association in the unliganded state and to CD4 binding. Here we describe similarities and differences between HIV-1 and SIVmac gp120. In both viruses, the gp120 N/C termini and the inner domain ß-sandwich and layer 2 support the noncovalent association of gp120 with the envelope glycoprotein trimer. Layer 1 of the SIVmac gp120 inner domain contributes more to trimer association than the corresponding region of HIV-1 gp120. On the other hand, layer 1 plays an important role in stabilizing the CD4-bound conformation of HIV-1 but not SIVmac gp120 and thus contributes to HIV-1 binding to CD4. In SIVmac, CD4 binding is instead enhanced by tryptophan 375, which fills the Phe 43 cavity of gp120. Activation of SIVmac by soluble CD4 is dependent on tryptophan 375 and on layer 1 residues that determine a tight association of gp120 with the trimer. Distinct biological requirements for CD4 usage have resulted in lineage-specific differences in the HIV-1 and SIV gp120 structures that modulate trimer association and CD4 binding.


Assuntos
Antígenos CD4/metabolismo , Proteína gp120 do Envelope de HIV/metabolismo , Infecções por HIV/metabolismo , HIV-1/metabolismo , Glicoproteínas de Membrana/metabolismo , Síndrome de Imunodeficiência Adquirida dos Símios/metabolismo , Vírus da Imunodeficiência Símia/metabolismo , Proteínas do Envelope Viral/metabolismo , Sequência de Aminoácidos , Animais , Antígenos CD4/química , Antígenos CD4/genética , Células COS , Linhagem Celular , Linhagem da Célula , Chlorocebus aethiops , Regulação Viral da Expressão Gênica , Proteína gp120 do Envelope de HIV/química , Proteína gp120 do Envelope de HIV/genética , Infecções por HIV/virologia , HIV-1/química , HIV-1/classificação , HIV-1/genética , Humanos , Glicoproteínas de Membrana/química , Glicoproteínas de Membrana/genética , Dados de Sequência Molecular , Filogenia , Ligação Proteica , Multimerização Proteica , Estrutura Terciária de Proteína , Alinhamento de Sequência , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Vírus da Imunodeficiência Símia/química , Vírus da Imunodeficiência Símia/classificação , Vírus da Imunodeficiência Símia/genética , Especificidade da Espécie , Proteínas do Envelope Viral/química , Proteínas do Envelope Viral/genética
10.
Protein Expr Purif ; 71(2): 123-31, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20176110

RESUMO

Hepatitis C virus encodes two enveloped glycoproteins, E1 and E2, which are involved in viral attachment and entry into target cells. We have obtained in insect cells infected by recombinant baculovirus a chimeric secreted recombinant protein, E1(341)E2(661,) containing the ectodomains of E1 and E2. The described procedure allows the purification of approximately 2mg of protein from 1L of culture media. Sedimentation velocity experiments and SDS-PAGE in the absence of reducing agents indicate that the protein has a high tendency to self-associate, the dimer being the main species observed. All the oligomeric forms observed maintain a conformation which is recognized by the conformation-dependent monoclonal antibody H53 directed against the E2 ectodomain. The spectroscopic properties of E1(341)E2(661) are those of a three-dimensionally structured protein. Moreover, the chimeric protein is able to bind to human antibodies present in HCV-positive human sera. Accordingly, this chimeric soluble polypeptide chain may be a valuable tool to study the structure-function relationship of HCV envelope proteins.


Assuntos
Anticorpos Monoclonais/metabolismo , Hepacivirus/imunologia , Hepacivirus/metabolismo , Proteínas do Envelope Viral/imunologia , Proteínas do Envelope Viral/metabolismo , Animais , Anticorpos Monoclonais/genética , Anticorpos Monoclonais/imunologia , Baculoviridae/genética , Eletroforese em Gel de Poliacrilamida , Hepacivirus/genética , Humanos , Proteínas Recombinantes de Fusão/imunologia , Proteínas Recombinantes de Fusão/metabolismo , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/metabolismo , Proteínas do Envelope Viral/genética
11.
Virus Res ; 139(1): 91-9, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19027804

RESUMO

We describe the structural and antigenic properties of a soluble form of hepatitis C virus E2 envelope protein ectodomain ending at residue 661 (E2(661)) which is obtained in large quantities in a baculovirus/insect cell system. The protein is secreted to the cellular medium by virus-infected cells. E2(661) is glycosylated and possesses a high tendency to self-associate. In fact, analytical ultracentrifugation and size exclusion chromatography studies show that the purified protein is mainly composed of dimers, trimers and tetramers being the dimer the smallest species present in solution. The secondary structure was determined by deconvolution of the far-UV circular dichroism spectrum yielding 8% alpha-helix structure, 47% extended structure and 45% non-ordered structure. The near-UV CD spectrum is indicative of a folded structure. The fluorescence emission spectrum indicates that Trp residues occupy a relatively low hydrophobic environment. Finally, E2(661) binds to a monoclonal conformation specific antibody and to antibodies present in human sera from HCV-positive patients. All these features suggest that the secreted protein possesses a native-like conformation. The use of this independent folding domain may contribute to shed light on the biology of HCV and could also be used as a vaccine in the prevention of HCV infection.


Assuntos
Hepacivirus/química , Proteínas do Envelope Viral/química , Sequência de Aminoácidos , Animais , Antígenos Virais/imunologia , Epitopos/imunologia , Regulação Viral da Expressão Gênica , Glicosilação , Hepacivirus/genética , Hepacivirus/metabolismo , Humanos , Dados de Sequência Molecular , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/genética , Proteínas Recombinantes de Fusão/metabolismo , Análise Espectral
12.
J Immunol ; 181(8): 5510-21, 2008 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-18832708

RESUMO

Gp120 is a critical component of the envelope of HIV-1. Its role in viral entry is well described. In view of its position on the viral envelope, gp120 is a part of the retrovirus that immune cells encounter first and has the potential to influence antiretroviral immune responses. We propose that high levels of gp120 are present in tissues and may contribute to the failure of the immune system to fully control and ultimately clear the virus. Herein, we show for the first time that lymphoid tissues from acutely HIV-1/SIV (SHIV)-KB9-infected macaques contain deposits of gp120 at concentrations that are high enough to induce suppressive effects on T cells, thus negatively regulating the antiviral CTL response and contributing to virus survival and persistence. We also demonstrate that SHIV-KB9 gp120 influences functional T cell responses during SHIV infection in a manner that suppresses degranulation and cytokine secretion by CTLs. Finally, we show that regulatory T cells accumulate in lymphoid tissues during acute infection and that they respond to gp120 by producing TGFbeta, a known suppressant of cytotoxic T cell activity. These findings have significant implications for our understanding of the contribution of non-entry-related functions of HIV-1 gp120 to the pathogenesis of HIV/AIDS.


Assuntos
Síndrome da Imunodeficiência Adquirida/imunologia , Linfócitos T CD8-Positivos/imunologia , Proteína gp120 do Envelope de HIV/imunologia , HIV-1/patogenicidade , Glicoproteínas de Membrana/imunologia , Síndrome de Imunodeficiência Adquirida dos Símios/imunologia , Vírus da Imunodeficiência Símia/patogenicidade , Linfócitos T Reguladores/imunologia , Proteínas do Envelope Viral/imunologia , Síndrome da Imunodeficiência Adquirida/genética , Animais , Células CHO , Cricetinae , Cricetulus , Proteína gp120 do Envelope de HIV/genética , HIV-1/genética , HIV-1/imunologia , Humanos , Imunidade Celular , Tecido Linfoide/imunologia , Tecido Linfoide/virologia , Macaca mulatta , Glicoproteínas de Membrana/genética , Síndrome de Imunodeficiência Adquirida dos Símios/genética , Vírus da Imunodeficiência Símia/genética , Vírus da Imunodeficiência Símia/imunologia , Linfócitos T Reguladores/virologia , Fator de Crescimento Transformador beta/imunologia , Proteínas do Envelope Viral/genética
13.
Virology ; 353(1): 52-67, 2006 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-16808956

RESUMO

We investigated possible interactions between HIV-1 receptor (CD4) and the main coreceptors CXCR4 and CCR5. We found that CD4 and CXCR4 coexpressed in 293T cells form a complex that can be immunoprecipitated with antibodies directed against the extracellular domain of either protein. Mutagenesis revealed that the CD4/CXCR4 interaction maps to two previously uncharacterized basic motifs in the cytoplasmic domain of CD4. HIV-1 envelope glycoprotein-mediated membrane fusion was found to be independent of the ability of CD4 and CXCR4 to interact, whether fusion was studied in a virus-cell or a cell-cell model. However, this interaction might explain the adaptation of HIV-1 to CXCR4 as an alternative to CCR5. We found that CXCR4 also interacts with the cytoplasmic domain of CD8alpha in a way that is similar to the CD4/CXCR4 interaction. The CD4/CXCR4 and CD8alpha/CXCR4 interactions may thus be involved in cellular signaling pathways shared by the CD4 and CD8alpha molecules.


Assuntos
Antígenos CD4/metabolismo , Antígenos CD8/metabolismo , HIV-1/metabolismo , Fusão de Membrana/fisiologia , Receptores CXCR4/fisiologia , Proteínas do Envelope Viral/metabolismo , Antígenos CD4/química , Antígenos CD4/genética , Antígenos CD8/química , Antígenos CD8/genética , Linhagem Celular , Humanos , Mutagênese Sítio-Dirigida , Estrutura Terciária de Proteína , Receptores CCR5/metabolismo , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/metabolismo
14.
Biochim Biophys Acta ; 1758(6): 755-63, 2006 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-16777058

RESUMO

Based on the predicted capacity to interact with membranes at the interface, we have found three regions in the ectodomain of the hepatitis C virus envelope glycoprotein E2 (430-449, 543-560 and 603-624) with the ability to destabilize membranes. Three peptides corresponding to the sequence of these regions have been synthesized and their interaction with liposomes have been characterized. The three peptides were able to insert deeply into the hydrophobic core of negatively charged phospholipids as stated by fluorescence depolarization of the probe 1,6-diphenyl-1,3,5-hexatriene. Peptides E2(430-449) and E2(603-624) were able to induce aggregation of phosphatidylglycerol vesicles in a concentration-dependent manner both at neutral and acidic pH while peptide E2(543-560) did not induce any increase of optical density at 360 nm in the concentration range studied. The three peptides induced lipid mixing and the release of the internal contents in a dose-dependent manner when acidic phospholipids were used. Fourier transformed infrared spectroscopy indicated that the peptides adopted mainly a beta-sheet conformation which is not modified by the presence of acidic phospholipids. Taken together, our results point out to the involvement of these three regions in the fusion mechanism of HCV at the plasma membrane level.


Assuntos
Proteínas do Envelope Viral/fisiologia , Membrana Celular/fisiologia , Polarização de Fluorescência , Proteínas do Envelope Viral/química
15.
Arch. venez. farmacol. ter ; 23(2): 150-158, 2004. tab, graf
Artigo em Espanhol | LILACS | ID: lil-419067

RESUMO

Con el objetivo de evaluar el efecto de la combinación losartan más hidroclorotiazida (HCTZ) sobre la presión arterial y en la producción de óxido nítrico (ON) en pacientes hipertensos "non dippers", se realizó un estudio prospectivo donde se evaluaron 12 pacientes (6 de cada sexo) con edad promedio de 52.42 ± 2.52 años e hipertensión severa de reciente diagnóstico (PAS/PAD) en la consulta-posición sentada: 188 ± 5.22/116.17 ± 1.22 mmHg). Los pacientes inicialmente fueron evaluados en placebo en forma ciego-simple, por un máximo de 3 semanas, durante ese período fueron examinados semanalmente; luego recibieron la combinación de losartan (100 mg) + HCTZ (25 mg), en una toma diaria durante 12 semanas. Un monitorio de presión arterial durante 24 horas y los niveles séricos y urinarios (24 horas) de ON fueron practicado al final de la etapa placebo y de medicación activa. En la etapa placebo el promedio de la PAS/PAD 24 horas fue de 158.6 ± 4.67/102.2 ± 2.57 mmHg; la presión de pulso (PP) de 56.5 ± 2.70 mmHg y la frecuencia cardiaca (FC) fue de 74.8 ± 1.81/min. El promedio diurno fue 159.3 ± 4.35/103.0 ± 2.50 mmHg; y el promedio nocturno de 154.9 ± 5.33/98.9 ± 3.12 mmHg. La PP diurna era de 56.05 ± 3.05 mmHg y la nocturna de 55.89 ± 3.41 mmHg. Luego de 12 semanas de terapia combinada, el promedio de la PAS/PAD se redujo a 140.3 ± 4.83 (p menor igual 0.001) /90.9 ±3.27 mmHg (p menor igual 0.002); la PP presentó descenso a 49.8 ± 2.46 mmHg (p menor igual 0.006) y la FC pasó a 77.9 ± 2.17 ppm (p menor igual 0.08). La PAS/PAD diurna fue de 135,01 ± 4.37) /88.15 ± 3.10 mmHg (p menor igual 0.002) respectivamente. La PAS/PAD nocturna fue de 140.9 ± 4.62 (p menor igual 0.035)/91.5 ± 3.24 mmHg. (p menor igual 0.05). La PP diurna y nocturna sufrieron reducciones a 49.9 ± 2.36 (p menor igual 0.007) y 50.33 ± 3.06 mmHg (p menor igual 0.05) respectivamente. El ON sérico pasó de 40.89 ± 5.69 uM/L en la etapa placebo a 67.35 ± 6.96 µM/L (p menor igual 0.007) al final de la medicación activa; mientras que la concentración urinaria pasó de 69.71 ± 3.68 uM/L a 79.64 ± 4.25 uM/L (p menor igual 0.16); el clearence urinario de ON no fue modificado significativamente durante la terapia antihipertensiva y pasó de 1.14 ± 0.32 ml/min 1.15 ± 0.14 ml/min (p menor igual 0.9). La combinación losartan (100 mg) más hidroclorotiazida (25 mg) en una toma diaria disminuyó la presión arterial nocturna sin modificar el patrón "non dippers" de pacientes con hipertensión arterial severa


Assuntos
Humanos , Masculino , Adulto , Feminino , Pessoa de Meia-Idade , Hipertensão/terapia , Hidroclorotiazida , Losartan , Pressão Sanguínea , Farmacologia , Terapêutica , Venezuela
19.
An. salud ment ; 8(1/2): 186-220, 1992. tab
Artigo em Espanhol | LILACS, LIPECS | ID: lil-666494

RESUMO

Se ha estudiado una población urbana de la ciudad de Lima asentada en un área de tipo ôslumõ. Sus pobladores estaban integrados, en su mayoría, por personas procedentes de provincias, en particular de la Sierra, principalmente obreros no calificados, distribuidos en diferentes grupos domésticos. Se les aplicó el Indice Médico de Cornell en una fase preliminar de una investigación de morbilidad psiquiátrica. Los resultados obtenidos han revelado incidencia elevadísima de ansiedad, síntomas depresivos, tendencias hipocondriacas, inadecuación y agresividad en la muestra explorada. Se analizan los resultados apreciándose diferencias en función del sexo, edad, composición familiar y fenómenos migratorios. Se señalan posibles factores sociales y culturales en el condicionamiento de la patología emocional encontrada. Este estudio ha comprobado, una vez más, la valides del I. M. C. como instrumento de exploración preliminar o screening para la identificación de los casos con desórdenes emocionales significativos.


Assuntos
Morbidade , Psiquiatria , Área Urbana , Índice Médico de Cornell , Peru
20.
Obstet. ginecol. latinoam ; 45(5/6): 180-9, mayo-jun. 1987. ilus
Artigo em Espanhol | LILACS | ID: lil-47846

RESUMO

El embarazo no deseado en adolescentes es un problema de creciente actualidad con implicancias médicas y sicosociales. Se entrevistaron 295 adolescentes embarazadas del consultorio de ginecología infantojuvenil de la 1§ Catédra de Ginecología de la U.B.A. Se analizaron las características médicas de estas gestaciones, las motivaciones psicológicas que las originaron y sus consecuencias sociales. En base a estos resultados se diferencian los grupos de alto riesgo y se dan pautas metodológicas para el médico que enfrenta esta situación


Assuntos
Gravidez , Adolescente , Humanos , Feminino , Gravidez na Adolescência , Gravidez não Desejada
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