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1.
J Antimicrob Chemother ; 79(2): 255-261, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38039097

RESUMO

BACKGROUND: Decreasing medication burden with raltegravir plus lamivudine in virologically suppressed persons with HIV (PWH) maintained efficacy and was well tolerated at 24 weeks, but more comprehensive data over longer follow-up are required. METHODS: Prospective 48 week extension phase of the raltegravir plus lamivudine arm from a previous 24 week pilot randomized clinical trial in which virologically suppressed PWH were randomized 2:1 to switch to fixed-dose combination 150 mg lamivudine/300 mg raltegravir twice daily or to continue therapy. In this 48 week extension phase, raltegravir was dosed at 1200 mg/day and lamivudine 300 mg/day. Primary outcome was the proportion of PWH with treatment failure at Week 48. Secondary outcomes were changes in ultrasensitive plasma HIV RNA, HIV DNA in CD4 cells, serum IL-6, ultrasensitive C-reactive protein and sCD14, body composition, sleep quality, quality of life and adverse effects. RESULTS: Between May 2018 and June 2019, 33 PWH were enrolled. One participant experienced virological failure without resistance mutations and re-achieved sustained virological suppression without therapy discontinuation, and two others discontinued therapy due to adverse effects. Treatment failure was 9% (95% CI 2%-24%) and 3% (95% CI 0%-17%) in the ITT and on-treatment populations. There were significant changes between baseline and Week 48 in serum cytokines but not in other secondary outcomes. CONCLUSIONS: Switching to raltegravir and lamivudine in PWH with virological suppression maintains efficacy and is well tolerated. This maintenance regimen might be a cost-effective option for PWH at risk of drug-drug interactions or needing to avoid specific toxicities of certain antiretroviral drugs or their negative impact on comorbidities.


Assuntos
Fármacos Anti-HIV , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Infecções por HIV , Humanos , Raltegravir Potássico/efeitos adversos , Lamivudina/efeitos adversos , Infecções por HIV/tratamento farmacológico , Fármacos Anti-HIV/efeitos adversos , Estudos Prospectivos , Qualidade de Vida , Quimioterapia Combinada , Carga Viral , Resultado do Tratamento
2.
AIDS Res Hum Retroviruses ; 39(5): 211-221, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36416229

RESUMO

Most of the studies using the colorectal tissue explants challenge model have been conducted after one single dose and before reaching a steady state. We consider that longer exposure as in 28-day postexposure prophylaxis (PEP) course and in an at-risk setting, such as after a sexual risk exposure to HIV could give us valuable information about these drugs. In a substudy we assessed pharmacokinetics, changes on immune system and ex-vivo rectal mucosal susceptibility to HIV-1 infection after taking maraviroc (MVC), raltegravir (RAL), and ritonavir-boosted lopinavir (LPV/r) PEP-based regimens in 30 men who have sex with men. Participants received 28 days of twice-daily MVC (n = 11), RAL (n = 10) or LPV/r (n = 9) all with tenofovir/emtricitabine (TDF/FTC) backbone. Blood, rectal fluid, and rectal tissue samples were collected at days 7, 28, and 90 after starting PEP. The samples obtained at day 90 were considered baseline. All studied antiretrovirals were quantifiable at 7 and 28 days in all tissues. Activation markers were increased in CD4 mucosal mononuclear cells (MMCs) after 28 days of MVC: CD38 + 68.5 versus 85.1, p = .008 and CD38+DR +16.1 versus 26.7, p = .008. Exposure to MVC at both endpoints (7 and 28 days) was associated with significant suppression of HIV-1BAL (p = .005 and p = .028), but we did not observe this effect with RAL or LPV/r. Merging together changes in MMC in all arms, we found a positive correlation in the CD8 T cell lineage between the infectivity at day 7 and activation (CD38+ r = 0.43, p = .025, DR + r = 0.547, p = .003 and 38+DR+ r = 0.526, p = .05), senescence (CD57+CD28- r = 0.479, p = .012), naive cells (RA+CCR7+ r = 0.484, p = .01), and CCR5 expression (r = 0.593, p = .001). We conclude that MVC in combination with TDF/FTC was associated with viral suppression in rectal explants and that overall ex-vivo HIV infectivity correlated with activation and senescence in CD8 MMCs.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Minorias Sexuais e de Gênero , Masculino , Humanos , Maraviroc , Raltegravir Potássico/uso terapêutico , Lopinavir/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/prevenção & controle , Fármacos Anti-HIV/uso terapêutico , Homossexualidade Masculina , Emtricitabina/uso terapêutico , Ritonavir/uso terapêutico , Profilaxia Pós-Exposição
3.
Healthcare (Basel) ; 8(4)2020 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-33227972

RESUMO

Human attention has become an object of study that defines both the design of interfaces and the production of emotions in a digital economy ecosystem. Guided by the control of users' attention, the consumption figures for digital environments, mainly social media, show that addictive use is associated with multiple psychological, social, and physical development problems. The study presented develops a theoretical proposal regarding attention. In the first part, the research analyzes how attention has been studied and how it behaves using three disciplines: neurophysiology, neuropsychology, and economics. In the second part, considering this general framework, the study uses categories of the three disciplines to explain the functioning of social media, with special emphasis on their interactive, attractive, and addictive design. Finally, the article presents, as a practical example of the exposed theory, the main results of two case studies that describe social media consumption among young people. The research shows the relevance of the theoretical study of attention as a key element by which to understand the logics that dominate the interactive design of social media. It also uses a multidisciplinary perspective. The addictive behaviors identified in the two examples support the theoretical proposals and open research lines oriented to the measurement and understanding of the attention given to social media.

4.
Front Immunol ; 11: 823, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32435247

RESUMO

Kick&kill strategies combining drugs aiming to reactivate the viral reservoir with therapeutic vaccines to induce effective cytotoxic immune responses hold potential to achieve a functional cure for HIV-1 infection. Here, we report on an open-label, single-arm, phase I clinical trial, enrolling 15 early-treated HIV-1-infected individuals, testing the combination of the histone deacetylase inhibitor romidepsin as a latency-reversing agent and the MVA.HIVconsv vaccine. Romidepsin treatment resulted in increased histone acetylation, cell-associated HIV-1 RNA, and T-cell activation, which were associated with a marginally significant reduction of the viral reservoir. Vaccinations boosted robust and broad HIVconsv-specific T cells, which were strongly refocused toward conserved regions of the HIV-1 proteome. During a monitored ART interruption phase using plasma viral load over 2,000 copies/ml as a criterium for ART resumption, 23% of individuals showed sustained suppression of viremia up to 32 weeks without evidence for reseeding the viral reservoir. Results from this pilot study show that the combined kick&kill intervention was safe and suggest a role for this strategy in achieving an immune-driven durable viremic control.


Assuntos
Vacinas contra a AIDS/imunologia , Antivirais/uso terapêutico , Depsipeptídeos/uso terapêutico , Infecções por HIV/imunologia , HIV-1/fisiologia , Inibidores de Histona Desacetilases/uso terapêutico , Adulto , Reservatórios de Doenças , Quimioterapia Combinada , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Carga Viral , Viremia , Latência Viral
6.
EClinicalMedicine ; 11: 65-80, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31312806

RESUMO

BACKGROUND: Strong and broad antiviral T-cell responses targeting vulnerable sites of HIV-1 will likely be a critical component for any effective cure strategy. METHODS: BCN01 trial was a phase I, open-label, non-randomized, multicenter study in HIV-1-positive individuals diagnosed and treated during early HIV-1 infection to evaluate two vaccination regimen arms, which differed in the time (8 versus 24 week) between the ChAdV63.HIVconsv prime and MVA.HIVconsv boost vaccinations. The primary outcome was safety. Secondary endpoints included frequencies of vaccine-induced IFN-γ+ CD8+ T cells, in vitro virus-inhibitory capacity, plasma HIV-1 RNA and total CD4+ T-cells associated HIV-1 DNA. (NCT01712425). FINDINGS: No differences in safety, peak magnitude or durability of vaccine-induced responses were observed between long and short interval vaccination arms. Grade 1/2 local and systemic post-vaccination events occurred in 22/24 individuals and resolved within 3 days. Weak responses to conserved HIV-1 regions were detected in 50% of the individuals before cART initiation, representing median of less than 10% of their total HIV-1-specific T cells. All participants significantly elevated these subdominant T-cell responses, which after MVA.HIVconsv peaked at median (range) of 938 (73-6,805) IFN-γ SFU/106 PBMC, representing on average 58% of their total anti-HIV-1 T cells. The decay in the size of the HIV-1 reservoir was consistent with the first year of early cART initiation in both arms. INTERPRETATION: Heterologous prime-boost vaccination with ChAdV63-MVA/HIVconsv was well-tolerated and refocused pre-cART T-cell responses towards more protective epitopes, in which immune escape is frequently associated with reduced HIV-1 replicative fitness and which are common to most global HIV-1 variants. FUNDING: HIVACAT Catalan research program for an HIV vaccine and Fundació Gloria Soler. Vaccine manufacture was jointly funded by the Medical Research Council (MRC) UK and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreements (G0701669. RESEARCH IN CONTEXT: Evidence Before this Study: T cells play an important role in the control of HIV infection and may be particularly useful for HIV-1 cure by killing cells with reactivated HIV-1. Evidence is emerging that not all T-cell responses are protective and mainly only those targeting conserved regions of HIV-1 proteins are effective, but typically immunologically subdominant, while those recognizing hypervariable, easy-to-escape immunodominant 'decoys' do not control viremia and do not protect from a loss of CD4 T cells. We pioneered a vaccine strategy focusing T-cell responses on the most conserved regions of the HIV-1 proteome using an immunogen designated HIVconsv. T cells elicited by the HIVconsv vaccines in HIV-uninfected UK and Kenyan adults inhibited in vitro replication of HIV-1 isolates from 4 major global clades A, B, C and D.Added Value of this Study: The present study demonstrated the concept that epitopes subdominant in natural infection, when taken out of the context of the whole HIV-1 proteome and presented to the immune system by a potent simian adenovirus prime-poxvirus MVA boost regimen, can induce strong responses in patients on antiretroviral treatment and efficiently refocus HIV-1-specific T-cells to the protective epitopes delivered by the vaccine.Implications of all the Available Evidence: Nearly all HIV-1 vaccine strategies currently emphasize induction of broadly neutralizing Abs. The HIVconsv vaccine is one of a very few approaches focussing exclusively on elicitation of T cells and, therefore, can complement antibody induction for better prevention and cure. Given the cross-clade reach on the HIVconsv immunogen design, if efficient, the HIVconsv vaccines could be deployed globally. Effective vaccines will likely be a necessary component in combination with other available preventive measures for halting the HIV-1/AIDS epidemic.

7.
Biochem Pharmacol ; 156: 248-264, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30142322

RESUMO

Current antiretroviral treatment (ART) may control HIV-1 replication but it cannot cure the infection due to the formation of a reservoir of latently infected cells. CD4+ T cell activation during HIV-1 infection eliminates the antiviral function of the restriction factor SAMHD1, allowing proviral integration and the reservoir establishment. The role of tyrosine kinases during T-cell activation is essential for these processes. Therefore, the inhibition of tyrosine kinases could control HIV-1 infection and restrict the formation of the reservoir. A family of tyrosine kinase inhibitors (TKIs) is successfully used in clinic for treating chronic myeloid leukemia (CML). The safety and efficacy against HIV-1 infection of five TKIs was assayed in PBMCs isolated from CML patients on prolonged treatment with these drugs that were infected ex vivo with HIV-1. We determined that the most potent and safe TKI against HIV-1 infection was dasatinib, which preserved SAMHD1 antiviral function and avoid T-cell activation through TCR engagement and homeostatic cytokines. Imatinib and nilotinib showed lower potency and bosutinib was quite toxic in vitro. Ponatinib presented similar profile to dasatinib but as it has been associated with higher incidence of arterial ischemic events, dasatinib would be the better choice of TKI to be used as adjuvant of ART in order to avoid the establishment and replenishment of HIV-1 reservoir and move forward towards an HIV cure.


Assuntos
HIV-1/fisiologia , Leucemia Mielogênica Crônica BCR-ABL Positiva , Leucócitos Mononucleares/efeitos dos fármacos , Leucócitos Mononucleares/virologia , Inibidores de Proteínas Quinases/farmacologia , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células HEK293 , Humanos
8.
J Leukoc Biol ; 99(2): 349-59, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26310829

RESUMO

Regulatory T cells have an important role in immune suppression during HIV-1 infection. As regulatory T cells produce the immunomodulatory molecule adenosine, our aim here was to assess the potential of adenosine removal to revert the suppression of anti-HIV responses exerted by regulatory T cells. The experimental setup consisted of ex vivo cocultures of T and dendritic cells, to which adenosine deaminase, an enzyme that hydrolyzes adenosine, was added. In cells from healthy individuals, adenosine hydrolysis decreased CD4(+)CD25(hi) regulatory T cells. Addition of 5'-N-ethylcarboxamidoadenosine, an adenosine receptor agonist, significantly decreased CD4(+)CD25(lo) cells, confirming a modulatory role of adenosine acting via adenosine receptors. In autologous cocultures of T cells with HIV-1-pulsed dendritic cells, addition of adenosine deaminase led to a significant decrease of HIV-1-induced CD4(+)CD25(hi) forkhead box p3(+) cells and to a significant enhancement of the HIV-1-specific CD4(+) responder T cells. An increase in the effector response was confirmed by the enhanced production of CD4(+) and CD8(+) CD25(-)CD45RO(+) memory cell generation and secretion of Th1 cytokines, including IFN-γ and IL-15 and chemokines MIP-1α/CCL3, MIP-1ß/CCL4, and RANTES/CCL5. These ex vivo results show, in a physiologically relevant model, that adenosine deaminase is able to enhance HIV-1 effector responses markedly. The possibility to revert regulatory T cell-mediated inhibition of immune responses by use of adenosine deaminase, an enzyme that hydrolyzes adenosine, merits attention for restoring T lymphocyte function in HIV-1 infection.


Assuntos
Adenosina Desaminase/farmacologia , Células Dendríticas/efeitos dos fármacos , Infecções por HIV/imunologia , HIV-1 , Subpopulações de Linfócitos T/imunologia , Linfócitos T Reguladores/efeitos dos fármacos , Adenosina/metabolismo , Adenosina-5'-(N-etilcarboxamida)/farmacologia , Antígenos CD/análise , Antígenos de Diferenciação de Linfócitos T/análise , Linfócitos T CD8-Positivos/imunologia , Quimiocinas/metabolismo , Técnicas de Cocultura , Feminino , Fatores de Transcrição Forkhead/análise , Infecções por HIV/patologia , Humanos , Memória Imunológica , Ativação Linfocitária/efeitos dos fármacos , Linfocinas/metabolismo , Masculino , Agonistas do Receptor Purinérgico P1/farmacologia , Subpopulações de Linfócitos T/metabolismo , Linfócitos T Reguladores/química , Linfócitos T Reguladores/metabolismo , Células Th1/metabolismo
10.
Mem. Inst. Invest. Cienc. Salud (Impr.) ; 9(2): 57-63, dic. 2011. tab
Artigo em Espanhol | LILACS, BDNPAR | ID: lil-618662

RESUMO

El virus de la Hepatitis B se transmite por diversas vías incluyendo la sanguínea, vertical y sexual. Pacientes con severas condiciones mentales están sometidos a mayor riesgo de adquirir cualquier infección viral como virus de hepatitis B, C y VIH. La duración de la estadía en las instituciones mentales tiene influencia en el contagio de la enfermedad y largos periodos de permanencia, incrementan la oportunidad para una transmisión viral. El objetivo fue conocer la frecuencia de antígeno de superficie de la hepatitis B y determinar los anticuerpos post vacunales contra la hepatitis en mujeres en edad reproductiva, internadas en un Hospital Psiquiátrico del Ministerio de Salud Pública y Bienestar Social de Asunción- Paraguay. Estudio observacional descriptivo llevado a cabo de mayo 2008 a mayo 2010. Se estudiaron 72 pacientes de sexo femenino, en edad fértil, de 18 a 49 años (promedio de 38 años ± 6). Los sueros fueron analizados para detectar: HBsAg basal y anti-HBs post vacunal por el método de ELISA. En las 72 pacientes estudiadas no se encontró evidencia serológica de la infección por virus de hepatitis B. De las 30 pacientes a quienes se les aplicó 3 dosis de vacuna, 29 presentaron valores protectivos adecuados (mayor a 20 mUI/mL) a los dos meses posteriores a la vacunación, una tuvo un valor inferior a 10 mUI/mL. Con la respuesta obtenida en las pacientes estudiadas en esta institución psiquiátrica, se estaría reduciendo las complicaciones de la hepatitis B e impidiendo la transmisión horizontal a las demás pacientes y al personal de salud de la institución y sobretodo se prevendrá la transmisión de hepatitis B al feto, en casos de embarazo.


Hepatitis virus B is transmitted by various routes including blood, vertical and sexual routes. Patients with severe mental health conditions are at greatest risk of acquiring any viral infection such as hepatitis B, C and HIV. The length of the stay in mental institutions influences the spread of the diseases and long periods of stay increase the opportunity for viral transmission. The objective of this study was to know the frequency of the surface antigen of hepatitis B and determine the post-vaccination antibodies against hepatitis in women of reproductive age, hospitalized in a psychiatric hospital of the Ministry of Public Health and Social Welfare of Asunción, Paraguay. This was an observational descriptive study carried out from May 2008 to May 2010. We studied 72 female patients in childbearing age, from 18 to 49 years (mean 38 years ± 6). Sera were tested for HBsAg and post-vaccination anti-HBs by ELISA. Serological evidence of Hepatitis B virus infection was not found in the 72 patients. Twenty nine out of thirty patients who were administered 3 doses of vaccine had adequate protective values (greater than 20 mIU/mL) at two months after vaccination and one had a value less than 10 mIU/mL. With the response found in the study patients of this mental health institution, the complications of hepatitis B would be reduced and the horizontal transmission to other patients and health personnel of the institution would be prevented and specially the hepatitis B transmission to fetus in case of pregnancy.


Assuntos
Feminino , Anticorpos Anti-Hepatite B , Hepatite B , Saúde Mental , Vírus da Hepatite B
11.
PLoS One ; 6(5): e19644, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21625608

RESUMO

Currently, MVA virus vectors carrying HIV-1 genes are being developed as HIV-1/AIDS prophylactic/therapeutic vaccines. Nevertheless, little is known about the impact of these vectors on human dendritic cells (DC) and their capacity to present HIV-1 antigens to human HIV-specific T cells. This study aimed to characterize the interaction of MVA and MVA expressing the HIV-1 genes Env-Gag-Pol-Nef of clade B (referred to as MVA-B) in human monocyte-derived dendritic cells (MDDC) and the subsequent processes of HIV-1 antigen presentation and activation of memory HIV-1-specific T lymphocytes. For these purposes, we performed ex vivo assays with MDDC and autologous lymphocytes from asymptomatic HIV-infected patients. Infection of MDDC with MVA-B or MVA, at the optimal dose of 0.3 PFU/MDDC, induced by itself a moderate degree of maturation of MDDC, involving secretion of cytokines and chemokines (IL1-ra, IL-7, TNF-α, IL-6, IL-12, IL-15, IL-8, MCP-1, MIP-1α, MIP-1ß, RANTES, IP-10, MIG, and IFN-α). MDDC infected with MVA or MVA-B and following a period of 48 h or 72 h of maturation were able to migrate toward CCL19 or CCL21 chemokine gradients. MVA-B infection induced apoptosis of the infected cells and the resulting apoptotic bodies were engulfed by the uninfected MDDC, which cross-presented HIV-1 antigens to autologous CD8(+) T lymphocytes. MVA-B-infected MDDC co-cultured with autologous T lymphocytes induced a highly functional HIV-specific CD8(+) T cell response including proliferation, secretion of IFN-γ, IL-2, TNF-α, MIP-1ß, MIP-1α, RANTES and IL-6, and strong cytotoxic activity against autologous HIV-1-infected CD4(+) T lymphocytes. These results evidence the adjuvant role of the vector itself (MVA) and support the clinical development of prophylactic and therapeutic anti-HIV vaccines based on MVA-B.


Assuntos
Vacinas contra a AIDS/imunologia , Linfócitos T CD4-Positivos/imunologia , Células Dendríticas/imunologia , Vetores Genéticos/administração & dosagem , Infecções por HIV/imunologia , Poxviridae/genética , Poxviridae/imunologia , Vacinas contra a AIDS/genética , Apoptose/imunologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Quimiocinas/metabolismo , Citocinas/metabolismo , Células Dendríticas/metabolismo , Citometria de Fluxo , Genes env/imunologia , Antígenos HIV/genética , Antígenos HIV/imunologia , Infecções por HIV/genética , Infecções por HIV/metabolismo , HIV-1/genética , HIV-1/imunologia , Humanos , Monócitos/imunologia , Monócitos/metabolismo
12.
Vaccine ; 29(34): 5711-24, 2011 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-21679735

RESUMO

This study provides a detailed description and characterization of the preparation of individualized lots of autologous heat inactivated HIV-1 virions used as immunogen in a clinical trial designed to test an autologous dendritic-cell-based therapeutic HIV-1 vaccine (Clinical Trial DCV-2, NCT00402142). For each participant, ex vivo isolation and expansion of primary virus were performed by co-culturing CD4-enriched PBMCs from the HIV-1-infected patient with PBMC from HIV-seronegative unrelated healthy volunteer donors. The viral supernatants were heat-inactivated and concentrated to obtain 1 mL of autologous immunogen, which was used to load autologous dendritic cells of each patient. High sequence homology was found between the inactivated virus immunogen and the HIV-1 circulating in plasma at the time of HIV-1 isolation. Immunogens contained up to 109 HIV-1 RNA copies/mL showed considerably reduced infectivity after heat inactivation (median of 5.6 log10), and were free of specified adventitious agents. The production of individualized lots of immunogen based on autologous inactivated HIV-1 virus fulfilling clinical-grade good manufacturing practice proved to be feasible, consistent with predetermined specifications, and safe for use in a clinical trial designed to test autologous dendritic cell-based therapeutic HIV-1 vaccine.


Assuntos
Vacinas contra a AIDS/imunologia , Células Dendríticas , HIV-1/imunologia , Vacinas de Produtos Inativados/imunologia , Inativação de Vírus , Vacinas contra a AIDS/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Células Cultivadas , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Células Dendríticas/virologia , Citometria de Fluxo , Infecções por HIV/prevenção & controle , Infecções por HIV/virologia , HIV-1/isolamento & purificação , Humanos , Leucócitos Mononucleares/virologia , Análise de Sequência , Carga Viral
13.
Pediatr. (Asunción) ; 38(1): 12-16, abr. 2011. tab
Artigo em Espanhol | LILACS | ID: lil-598884

RESUMO

El dengue es la virosis transmitida por vectores más frecuente y la que más morbimortalidad ocasiona mundialmente. El dengue es endémico en casi todos los países de la región de las Américas y durante los últimos 25 años se han presentado brotes cíclicos cada 3 a 5 años, con la particularidad que cada año epidémico, ha sido mayor que el que le precedió, siendo considerada como una enfermedad infecciosa emergente y un problema de salud pública global. Este trabajo tuvo por objetivo evaluar las características clínicas y laboratoriales en niños y adolescentes con sospecha de dengue, que concurrieron al Instituto de Investigaciones en Ciencias de la Salud, durante la epidemia en Paraguay del 2007. Se realizó un estudio observacional, descriptivo de corte transverso. Se estudiaron 47 niños y adolescentes con edad promedio de 10 años, de ellos, 12 (30 %) con IgM positiva para el virus dengue. Los síntomas más comunes fueron fiebre, cefalea, dolor retroocular, dolor osteomioarticular y exantema. El dengue sigue siendo un desafío diagnóstico, en particular en niños y como no se cuenta aún con inmunización eficaz o tratamiento específico antiviral, la lucha contra la enfermedad está limitada al control del vector y al tratamiento de los síntomas.


Dengue is the most common vector-borne virus infection and that which causes the highest worldwide morbidity and mortality. Dengue is endemic in almost all countries in the Americas, with cyclical outbreaks occurring every 3 to 5 years over the last 25 years, and with each outbreak year showing higher incidence than the preceding one. Dengue is therefore considered an emerging infectious disease and a global health problem. This study assessed the clinical and laboratory characteristics identified in children and adolescents with suspected dengue examined at the Health Sciences Research Institute of Paraguay during the 2007 epidemic in Paraguay. A cross-sectional observational and descriptive study was conducted of 47 children and adolescents with an average age of 10 years, of whom 12 (30%) were IgM positive for the dengue virus. The most common symptoms were fever, headache, retro-orbital pain, musculoskeletal pain and rash. Dengue remains a diagnostic challenge, particularly in children, and since there is as yet no effective immunization or specific antiviral treatment, combating the disease is limited to vector control and treatment of symptoms.


Assuntos
Criança , Adolescente , Dengue , Dengue/diagnóstico , Dengue/epidemiologia
14.
Immunol Cell Biol ; 87(8): 634-9, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19668260

RESUMO

As host immunological defenses are impaired during HIV infection, it is difficult to elicit good responses when attempting to develop therapeutic vaccines against HIV. To try to solve this situation, adjuvants, particularly cytokines, are currently under evaluation. Owing to the fact that adenosine deaminase (ADA) is a member of the family of growth factor with deaminase activity, we tested whether it could improve immune responses in the development of HIV dendritic-cell-based therapeutic vaccines. A co-culture model approach has been used to test the usefulness of ADA as adjuvant. Monocyte-derived dendritic cells from HIV-infected patients were pulsed with inactivated HIV, matured and co-cultured with autologous T cells. Addition of ADA to the co-cultures resulted in enhanced CD4(+) and CD8(+) T-cell proliferation and robust ADA-induced increase in cytokine production (IFN-gamma, TNF-alpha and IL-6). As IFN-gamma, TNF-alpha and IL-6 promote the Th1 versus Th2 phenotype and improve T helper proliferation responses and antigen-specific CTL responses ADA may be considered a promising candidate for therapeutic vaccine adjuvant.


Assuntos
Adenosina Desaminase/metabolismo , Células Dendríticas/enzimologia , Células Dendríticas/imunologia , HIV-1/imunologia , Linfócitos T/enzimologia , Linfócitos T/imunologia , Adulto , Proliferação de Células , Técnicas de Cocultura , Citocinas/imunologia , Citocinas/metabolismo , Células Dendríticas/metabolismo , Feminino , Infecções por HIV/imunologia , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Linfócitos T/citologia , Linfócitos T/metabolismo , Carga Viral , Inativação de Vírus
15.
Immunology ; 128(3): 393-404, 2009 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20067539

RESUMO

The cell surface association between CD26 and adenosine deaminase (ADA) has a costimulatory function during T-cell activation. Several studies have revealed correlations among CD4(+) CD26(+) T-cell depletion, increased serum levels of ADA, and the evolution of human immunodeficiency virus (HIV) infection, implicating CD26 and ADA in HIV disease progression. In this context, we aimed to determine whether ADA costimulation could be altered during HIV infection. ADA costimulation was investigated in cells from HIV-infected patients (n = 36) in terms of proliferation and cytokine secretion. An effect of ADA on T-cell proliferation was found in HIV-1-infected patients and correlated positively with the CD4(+) percentage and the nadir CD4 count and negatively with viral load, demonstrating that the response depends on the immunological status of the patient. The robust ADA-induced increase in cytokine production [interferon (IFN)-gamma, interleukin (IL)-6 and IL-10] was markedly reduced in T cells from HIV-1-infected subjects. To eliminate some of the variables associated with immunological defects in HIV-1-infected patients, anti-CD3 plus ADA assays with T cells from healthy volunteers were performed in the presence of recombinant glycoprotein 120 (gp120). It was found that gp120 was responsible for the impairment of the ADA-CD26 interaction and consequently of the ADA-induced effect on both costimulation and cytokine production. The gp120-mediated disruption of the CD26-ADA interaction is a novel mechanism that might explain, at least in part, the altered immunological features observed in HIV-1-infected patients and may have significant relevance in AIDS pathogenesis.


Assuntos
Adenosina Desaminase/metabolismo , Linfócitos T CD4-Positivos/metabolismo , Infecções por HIV/imunologia , HIV-1/imunologia , Carga Viral , Adenosina Desaminase/imunologia , Adulto , Idoso , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/patologia , Proliferação de Células , Citocinas/metabolismo , Dipeptidil Peptidase 4/imunologia , Dipeptidil Peptidase 4/metabolismo , Progressão da Doença , Feminino , Proteína gp120 do Envelope de HIV/imunologia , Infecções por HIV/sangue , Infecções por HIV/patologia , Infecções por HIV/fisiopatologia , HIV-1/crescimento & desenvolvimento , HIV-1/patogenicidade , Humanos , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Ligação Proteica
16.
Asunción; EFACIM-EDUNA; ene.2000. 1-6 p. tab.
Monografia em Espanhol | LILACS, BDNPAR | ID: biblio-1018307

RESUMO

Se reconocen varias formas etiológicamente distintas de virus causantes de hepatitis entre las que se encuentran el Virus de la Hepatitis B (VHB) y el Virus de la Hepatitis C (VHC entre otros. Estos virus se transmiten por vía intravenosa, sexual y perinatal y con menor frecuencia por medio de acupuntura, circuncsión, tatuaje y otras perforaciones de la piel. La hepatitis vírica es uno de los principales problemas de salud pública en toda América. Teniendo encuenta la elevada frecuencia mundial de la hepatitis D y C, las altas prevalencia en grupos indigenas sudamericanos considerados las escases de datos nacionales sobre estas enfermedades en tribus indigenas del Paraguay, se ha realizado este estudio efectivo de la corte transverso. La población en estudio incluyo a 178 aborigenes de la parcialidad Ayoreo, provenientes de Kucaani e Islas Alta comunidades ubicadas en el Chaco Paraguayo, en las proximidades Carmelo Peralta e Islas Margarita, a 594 km al noreste de Asunción, frente a la ciudad brasilera de Puerto Murtinho. Se incluyeron individuos de ambos sexos con un rango de edad comprendida entre 15 y 65 años. El presente estudio nos proporciona evidencia de la presencia de VHB y VHC en las poblaciones estudiadas, con una prevalencia de HBsAg de 17.4 por ciento y con el mayor porcentaje (32.3 por ciento) de la posibilidad en mujeres de más de 40 años. La prevalencia del VHC fue del 14,9 por ciento y la distribución fue similar a ambos sexos. Se detecto la presencia coinfecciones en 7 individuos. Son necesarios estudios posteriores que influyan un mayornumero de individuos jóvenes y niños para identificar individuos no infectados. Las personas no infectados obligatoriamente deberian ser vacunados de manera a evitar el contagio, considerando que esta población tiene por costumbre mantener relaciones sexuales libres poco después de la pubertad. De esta manera se estaría previniendo la apariciones de las enfermedades hepatocelulares y la sobre infección por otras hepatitis. Es importante el seguimiento o vigilancia de la infección, así como la educación para la prevención, considerando que estas comunidades viven en condiciones de hacinamiento


Assuntos
Adulto , Hepatite B/prevenção & controle , Hepatite B/transmissão , Hepatite B/virologia , Hepatite C/prevenção & controle , Hepatite C/transmissão , Hepatite C/virologia , Paraguai
17.
Asunción; EFACIM-EDUNA; abr.1999. 65-70 p.
Monografia em Espanhol | LILACS, BDNPAR | ID: biblio-1018276

RESUMO

Este es un estudio descriptivo de muestreo de corte transverso de selección consecutuiva para determinar la prevalencia de los tirioditis autoinmune con pacientes con bocio de nuestro país que concurren a centros de referencia de estudios tiroideos de Asunción y Areas metrpolitanas. Fueron estudiados 159 pacientes de ambos sexo, en quienes se realizaron los desajes de FT4, TSH, anticuerpo anti-microsomales y ecografía tiroidea. Se obtuvo prevalencia de tiroiditis autoinmune de 10.7 por ciento (17/159). El 25.8 por ciento (41/159) de los pacientes presentaron hipertiroidismo clínico y bioquímico; hipotiroidismo el 13.8 por ciento (22/159) y el resto de la población era funcionalmente normal. Además hemos realizado un estudio comparativo entre dos ensayos serológicos, la hemaglutinación indirecta y el inmunorradiométrico para le detección de los anticuerpos anti-microsomales en una muestra seleccionada en forma aleatoria de 54 pacientes, obteniéndose una correlación del 94 por ciento entre métodos. Nuestros resultados demuestran que existe un elevado porcentaje de tiroiditis autoinmune en la población estudiada y que existe una buena concordancia entre ambas técnicas comparadas


Assuntos
Bócio , Tireoidite Autoimune
18.
Asunciòn; EDUNA; sept. 1995. 104-11 p.
Monografia em Espanhol | LILACS, BDNPAR | ID: lil-219962

RESUMO

Habiendo tenido la oportunidad de estudiar a pobladores de una colonia de origen japonès y sus descendientes hemos realizado un estudio descriptivo de corte transversal cuyo objetivo fuè estimar la prevalencia de anticuerpos anti-T.cruzi, anti - T.gondii y Hbs Ag, empleando las tècnicas de inmunofluorescencia indirecta y ELISA, para conocer la respuesta inmune humoral a la enfermedad de chagas, hepatitis B y toxoplasmosis de esta poblaciòn de caracterìsticas muy diferentes al resto de la poblaciòn paraguaya. De la poblaciòn estudiada (63 muestras) se obtuvieron: a. Una prevalencia de HBs Ag de 6.4 por ciento, lo que nos indica que a la zona le corresponde una endemicidad intermedia. b. Una prevalencia de 4.7 por ciento de anticuerpos anti - T-cruzi, lo que serìa de no endèmica y c. Una prevalencia de anticuerpos anti - T.gondii de 79.4 por ciento que es similar a las obtenidas en otras zonas del Paraguay


Assuntos
Toxoplasma , Trypanosoma cruzi/efeitos da radiação , Trypanosoma cruzi/imunologia , Trypanosoma cruzi/parasitologia , Ensaio de Imunoadsorção Enzimática , Antígenos de Superfície da Hepatite B/imunologia , Técnica Indireta de Fluorescência para Anticorpo , Paraguai
20.
Arch. pediatr. Urug ; 64(3): 25-30, oct. 1993. ilus
Artigo em Espanhol | LILACS | ID: lil-157449

RESUMO

En esta publicación, se presenta el análisis de algunos datos relacionados con la marihuana como ser: la distribución de los estudiantes que probaron marihuana, de los que saben donde conseguirla, de los que probaron y saben donde conseguirla, de los que no probaron pero saben donde conseguirla, según sexo y edad. Se plantea la necesidad de implementar reales y efectivos programas preventivos, los cuales son menos costosos que los asistenciales y los de reinserción social. En próximos trabajos, se irán analizando otras variables de interés relacionadas con esta sustancia


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adolescente , Fumar Maconha/epidemiologia , Problemas Sociais , Transtornos Relacionados ao Uso de Substâncias , Uruguai , Educação em Saúde
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