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1.
Nat Immunol ; 13(7): 691-700, 2012 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-22683743

RESUMO

The human leukocyte antigens HLA-B27 and HLA-B57 are associated with protection against progression of disease that results from infection with human immunodeficiency virus type 1 (HIV-1), yet most people with alleles encoding HLA-B27 and HLA-B57 are unable to control HIV-1. Here we found that HLA-B27-restricted CD8(+) T cells in people able to control infection with HIV-1 (controllers) and those who progress to disease after infection with HIV-1 (progressors) differed in their ability to inhibit viral replication through targeting of the immunodominant epitope of group-associated antigen (Gag) of HIV-1. This was associated with distinct T cell antigen receptor (TCR) clonotypes, characterized by superior control of HIV-1 replication in vitro, greater cross-reactivity to epitope variants and enhanced loading and delivery of perforin. We also observed clonotype-specific differences in antiviral efficacy for an immunodominant HLA-B57-restricted response in controllers and progressors. Thus, the efficacy of such so-called 'protective alleles' is modulated by specific TCR clonotypes selected during natural infection, which provides a functional explanation for divergent HIV-1 outcomes.


Assuntos
Infecções por HIV/imunologia , HIV-1/imunologia , Antígenos HLA-B/imunologia , Antígeno HLA-B27/imunologia , Receptores de Antígenos de Linfócitos T/imunologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/virologia , Células Cultivadas , Epitopos de Linfócito T/imunologia , Infecções por HIV/sangue , Infecções por HIV/virologia , Sobreviventes de Longo Prazo ao HIV , Humanos , Perforina/imunologia , Replicação Viral/imunologia , Produtos do Gene gag do Vírus da Imunodeficiência Humana/imunologia
2.
Int J Mol Sci ; 24(16)2023 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-37629114

RESUMO

SARS-CoV-2 infection might cause a critical disease, and patients' follow-up is based on multiple parameters. Oxidative stress is one of the key factors in the pathogenesis of COVID-19 suggesting that its level could be a prognostic marker. Therefore, we elucidated the predictive value of the serum non-enzymatic total antioxidant capacity (TAC) and that of the newly introduced TAC/lymphocyte ratio in COVID-19. We included 61 COVID-19 (n = 27 ward, n = 34 intensive care unit, ICU) patients and 29 controls in our study. Serum TAC on admission was measured by an enhanced chemiluminescence (ECL) microplate assay previously validated by our research group. TAC levels were higher (p < 0.01) in ICU (median: 407.88 µmol/L) than in ward patients (315.44 µmol/L) and controls (296.60 µmol/L). Besides the classical parameters, both the TAC/lymphocyte ratio and TAC had significant predictive values regarding the severity (AUC-ROC for the TAC/lymphocyte ratio: 0.811; for TAC: 0.728) and acute kidney injury (AUC-ROC for the TAC/lymphocyte ratio: 0.747; for TAC: 0.733) in COVID-19. Moreover, the TAC/lymphocyte ratio had significant predictive value regarding mortality (AUC-ROC: 0.752). Serum TAC and the TAC/lymphocyte ratio might offer valuable information regarding the severity of COVID-19. TAC measured by our ECL microplate assay serves as a promising marker for the prediction of systemic inflammatory diseases.


Assuntos
Antioxidantes , COVID-19 , Humanos , COVID-19/diagnóstico , SARS-CoV-2 , Estresse Oxidativo , Linfócitos
3.
J Pers Assess ; 104(6): 747-758, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35061565

RESUMO

The Experiences in Close Relationships - Revised (ECR-R) is a widely used self-report instrument to assess adult romantic attachment. The present study aimed at examining the factor structure, reliability, construct validity, and temporal stability of the Hungarian version of the ECR-R (ECR-R-HU) in a nationally representative community sample (N = 958). The original avoidance and anxiety dimensions of the ECR-R could only be identified, when reversed-item method factors and residual correlations were included in the confirmatory factor analysis (CFA). The Avoidance and Anxiety subscales of the ECR-R-HU showed high reliabilities and adequate temporal stability over 4 months. The subscales were not significantly associated with respondents' age, gender, and residence type, while being engaged in a romantic relationship was related to significantly lower scores on both subscales. Correlations with measures of family functioning problems, perceived stress, depressed mood, and well-being were significant and in the expected directions. These results confirm the ECR-R-HU as a reliable and valid assessment tool.


Assuntos
Relações Interpessoais , Apego ao Objeto , Adulto , Humanos , Psicometria/métodos , Reprodutibilidade dos Testes , Hungria , Inquéritos e Questionários
4.
Int J Mol Sci ; 20(17)2019 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-31443385

RESUMO

Biopolymer coated magnetite nanoparticles (MNPs) are suitable to fabricate biocompatible magnetic fluid (MF). Their comprehensive characterization, however, is a necessary step to assess whether bioapplications are feasible before expensive in vitro and in vivo tests. The MNPs were prepared by co-precipitation, and after careful purification, they were coated by chondroitin-sulfate-A (CSA). CSA exhibits high affinity adsorption to MNPs (H-type isotherm). We could only make stable MF of CSA coated MNPs (CSA@MNPs) under accurate conditions. The CSA@MNP was characterized by TEM (size ~10 nm) and VSM (saturation magnetization ~57 emu/g). Inner-sphere metal-carboxylate complex formation between CSA and MNP was proved by FTIR-ATR and XPS. Electrophoresis and DLS measurements show that the CSA@MNPs at CSA-loading > 0.2 mmol/g were stable at pH > 4. The salt tolerance of the product improved up to ~0.5 M NaCl at pH~6.3. Under favorable redox conditions, no iron leaching from the magnetic core was detected by ICP measurements. Thus, the characterization predicts both chemical and colloidal stability of CSA@MNPs in biological milieu regarding its pH and salt concentration. MTT assays showed no significant impact of CSA@MNP on the proliferation of A431 cells. According to these facts, the CSA@MNPs have a great potential in biocompatible MF preparation for medical applications.


Assuntos
Sulfatos de Condroitina/química , Materiais Revestidos Biocompatíveis/química , Nanopartículas de Magnetita/química , Adsorção , Técnicas de Química Sintética , Coloides/química , Concentração de Íons de Hidrogênio , Cinética , Nanopartículas de Magnetita/ultraestrutura , Análise Espectral
5.
J Virol ; 88(15): 8349-54, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24829350

RESUMO

UNLABELLED: Increasing data suggest that NK cells can mediate antiviral activity in HIV-1-infected humans, and as such, novel approaches harnessing the anti-HIV-1 function of both T cells and NK cells represent attractive options to improve future HIV-1 immunotherapies. Chronic progressive HIV-1 infection has been associated with a loss of CD4(+) T helper cell function and with the accumulation of anergic NK cells. As several studies have suggested that cytokines produced by CD4(+) T cells are required to enhance NK cell function in various infection models, we hypothesized that reconstitution of HIV-1-specific CD4(+) T-cell responses by therapeutic immunization would restore NK cell activity in infected individuals. Using flow cytometry, we examined the function of CD4(+) T cells and NK cells in response to HIV-1 in subjects with treated chronic HIV-1 infection before and after immunization with an adjuvanted HIV-1 Gp120/NefTat subunit protein vaccine candidate provided by GlaxoSmithKline. Vaccination induced an increased expression of interleukin-2 (IL-2) by Gp120-specific CD4(+) T cells in response to HIV-1 peptides ex vivo, which was associated with enhanced production of gamma interferon (IFN-γ) by NK cells. Our data show that reconstitution of HIV-1-specific CD4(+) T-cell function by therapeutic immunization can enhance NK cell activity in HIV-1-infected individuals. IMPORTANCE: NK cells are effector cells of the innate immune system and are important in the control of viral infection. Recent studies have demonstrated the crucial role played by NK cells in controlling and/or limiting acquisition of HIV-1 infection. However, NK cell function is impaired during progressive HIV-1 infection. We recently showed that therapeutic immunization of treated HIV-1-infected individuals reconstituted strong T-cell responses, measured notably by their production of IL-2, a cytokine that can activate NK cells. The current study suggests that reconstitution of T-cell function by therapeutic vaccination can enhance NK cell activity in individuals with chronic HIV-1 infection. Our findings provide new insights into the interplay between adaptive and innate immune mechanisms involved in HIV-1 immunity and unveil opportunities to harness NK cell function in future therapeutic vaccine strategies to target HIV-1.


Assuntos
Vacinas contra a AIDS/imunologia , Vacinas contra a AIDS/uso terapêutico , Linfócitos T CD4-Positivos/imunologia , Infecções por HIV/imunologia , Infecções por HIV/terapia , HIV-1/imunologia , Células Matadoras Naturais/imunologia , Adulto , Feminino , Citometria de Fluxo , Produtos do Gene tat/imunologia , Proteína gp120 do Envelope de HIV/imunologia , Humanos , Imunofenotipagem , Interferon gama/metabolismo , Interleucina-2/metabolismo , Masculino , Pessoa de Meia-Idade , Vacinação/métodos , Vacinas de Subunidades Antigênicas/imunologia , Vacinas de Subunidades Antigênicas/uso terapêutico , Vacinas Sintéticas/imunologia , Vacinas Sintéticas/uso terapêutico , Produtos do Gene nef do Vírus da Imunodeficiência Humana/imunologia
6.
Langmuir ; 30(51): 15451-61, 2014 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-25517214

RESUMO

Magnetite nanoparticles (MNPs) with biocompatible coatings are good candidates for MRI (magnetic resonance imaging) contrasting, magnetic hyperthermia treatments, and drug delivery systems. The spontaneous surface induced polymerization of dissolved organic matter on environmental mineral particles inspired us to prepare carboxylated core-shell MNPs by using a ubiquitous polyphenolic precursor. Through the adsorption and in situ surface polymerization of gallic acid (GA), a polygallate (PGA) coating is formed on the nanoparticles (PGA@MNP) with possible antioxidant capacity. The present work explores the mechanism of polymerization with the help of potentiometric acid-base titration, dynamic light scattering (for particle size and zeta potential determination), UV-vis (UV-visible light spectroscopy), FTIR-ATR (Fourier-transformed infrared spectroscopy by attenuated total reflection), and XPS (X-ray photoelectron spectroscopy) techniques. We observed the formation of ester and ether linkages between gallate monomers both in solution and in the adsorbed state. Higher polymers were formed in the course of several weeks both on the surface of nanoparticles and in the dispersion medium. The ratio of the absorbances of PGA supernatants at 400 and 600 nm (i.e., the E4/E6 ratio commonly used to characterize the degree of polymerization of humic materials) was determined to be 4.3, similar to that of humic acids. Combined XPS, dynamic light scattering, and FTIR-ATR results revealed that, prior to polymerization, the GA monomers became oxidized to poly(carboxylic acid)s due to ring opening while Fe(3+) ions reduced to Fe(2+). Our published results on the colloidal and chemical stability of PGA@MNPs are referenced thoroughly in the present work. Detailed studies on biocompatibility, antioxidant property, and biomedical applicability of the particles will be published.


Assuntos
Biomimética/métodos , Ácidos Carboxílicos/química , Meio Ambiente , Ácido Gálico/química , Nanopartículas de Magnetita/química , Polimerização , Adsorção , Minerais/química , Tamanho da Partícula , Propriedades de Superfície , Água/química
7.
ScientificWorldJournal ; 2014: 152972, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25685831

RESUMO

Bile salt aggregates are promising candidates for drug delivery vehicles due to their unique fat-solubilizing ability. However, the toxicity of bile salts increases with improving fat-solubilizing capability and so an optimal combination of efficient solubilization and low toxicity is necessary. To improve hydrophilicity (and decrease toxicity), we substituted hydroxyl groups of several natural bile acid (BA) molecules for oxogroups and studied their intrinsic molecular association behavior. Here we present the comparative Langmuir trough study of the two-dimensional (2D) association behavior of eight natural BAs and four oxoderivatives (traditionally called keto-derivatives) floated on an aqueous subphase. The series of BAs and derivatives showed systematic changes in the shape of the compression isotherms. Two types of association could be distinguished: the first transition was assigned to the formation of dimers through H-bonding and the second to the hydrophobic aggregation of BA dimers. Hydrophobic association of BA molecules in the films is linked to the ability of forming H-bonded dimers. Both H-bond formation and hydrophobic association weakened with increasing number of hydroxyl groups, decreasing distance between hydroxyl groups, and increasing oxosubstitution. The results also show that the Langmuir trough method is extremely useful in selecting appropriate BA molecules to design drug delivery systems.


Assuntos
Ácidos e Sais Biliares/química , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Oxirredução
8.
Int J Mol Sci ; 15(7): 11387-402, 2014 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-24968275

RESUMO

Total antioxidant capacity assays are recognized as instrumental to establish antioxidant status of biological samples, however the varying experimental conditions result in conclusions that may not be transposable to other settings. After selection of the complexing agent, reagent addition order, buffer type and concentration, copper reducing assays were adapted to a high-throughput scheme and validated using model biological antioxidant compounds of ascorbic acid, Trolox (a soluble analogue of vitamin E), uric acid and glutathione. A critical comparison was made based on real samples including NIST-909c human serum certified sample, and five study samples. The validated method provided linear range up to 100 µM Trolox, (limit of detection 2.3 µM; limit of quantification 7.7 µM) with recovery results above 85% and precision <5%. The validated developed method with an increased sensitivity is a sound choice for assessment of TAC in serum samples.


Assuntos
Antioxidantes/análise , Análise Química do Sangue/métodos , Cobre/química , Ácido Ascórbico/sangue , Cromanos/sangue , Glutationa/sangue , Ensaios de Triagem em Larga Escala/métodos , Humanos , Oxirredução , Ácido Úrico/sangue
9.
Retrovirology ; 10: 74, 2013 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-23866914

RESUMO

BACKGROUND: Natural killer (NK) cells constitutively express high levels of Tim-3, an immunoregulatory molecule recently proposed to be a marker for mature and functional NK cells. Whether HIV-1 infection modulates the expression of Tim-3 on NK cells, or the levels of its ligand Galectin-9 (Gal-9), and how signaling through these molecules affects the NK cell response to HIV-1 remains inadequately understood. RESULTS: We analyzed Tim-3 and Gal-9 expression in a cohort of 85 individuals with early and chronic HIV-1 infection, and in 13 HIV-1 seronegative control subjects. HIV-1 infection was associated with reduced expression of Tim-3 on NK cells, which was normalized by HAART. Plasma concentrations of Gal-9 were higher in HIV-1-infected individuals than in healthy individuals. Interestingly, Gal-9 expression in immune cells was significantly elevated in early infection, with monocytes and dendritic cells displaying the highest expression levels, which correlated with HIV-1 viral loads. In vitro, Gal-9 triggered Tim-3 downregulation on NK cells as well as NK cell activation. CONCLUSIONS: Our data suggest that high expression levels of Gal-9 during early HIV-1 infection can lead to enhanced NK cell activity, possibly allowing for improved early control of HIV-1. In contrast, persistent Gal-9 production might impair Tim-3 activity and contribute to NK cell dysfunction in chronic HIV-1 infection.


Assuntos
Galectinas/sangue , Regulação da Expressão Gênica , HIV-1/imunologia , HIV-1/fisiologia , Interações Hospedeiro-Patógeno , Células Matadoras Naturais/imunologia , Proteínas de Membrana/genética , Antirretrovirais/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Células Dendríticas/imunologia , Galectinas/genética , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Infecções por HIV/virologia , Receptor Celular 2 do Vírus da Hepatite A , Humanos , Monócitos/imunologia
10.
J Virol ; 86(12): 6986-93, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22496218

RESUMO

Natural killer (NK) cells play a critical role in the control of HIV-1 infection, and NK cells that respond to HIV-1 peptides have been recently described. However, the mechanisms by which NK cells recognize HIV-1 antigens are not fully understood. We investigated NK cell activation in response to HIV-1 peptides during early and chronic HIV-1 clade B infection using a whole-blood assay and multiparameter flow cytometry. Antibody-mediated NK cell activation in response to HIV-1 peptides was not detected in HIV-1-uninfected individuals. In contrast, 79% of individuals with chronic infection and 22% of individuals with early infection had detectable gamma interferon (IFN-γ) NK cell responses to HIV-1 antigens (P < 0.00001). IFN-γ- and tumor necrosis factor alpha (TNF-α)-producing NK cells most frequently targeted Env gp120 (median of 4% and range of 0 to 31% of all NK cells). NK cells rarely targeted other HIV-1 proteins such as Gag, Pol, and Nef. Antibody-mediated NK cell responses to peptides mapped predominantly to Env protein, required the presence of plasma or plasma IgG, and resulted in lower CD16 expression on NK cells, suggesting an antibody-mediated activation of NK cells. Further studies are needed to assess the consequences of these antibody-mediated NK cell responses for HIV-1 disease progression and vaccine-induced protection from infection.


Assuntos
Anticorpos Antivirais/imunologia , Proteína gp120 do Envelope de HIV/imunologia , Infecções por HIV/imunologia , HIV-1/imunologia , Células Matadoras Naturais/imunologia , Doença Crônica , Feminino , Infecções por HIV/virologia , HIV-1/classificação , HIV-1/genética , HIV-1/isolamento & purificação , Humanos , Imunoglobulina G/imunologia , Interferon gama/imunologia , Ativação Linfocitária , Masculino
11.
Blood ; 117(19): 5112-22, 2011 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-21403126

RESUMO

Under persistent antigenic stimulation, virus-specific CD8⁺ T cells become increasingly dysfunctional and up-regulate several inhibitory molecules such as killer lectin-like receptor G1 (KLRG1). Here, we demonstrate that HIV-1 antigen-specific T cells from subjects with chronic-progressive HIV-1 infection have significantly elevated KLRG1 expression (P < .001); show abnormal distribution of E-cadherin, the natural ligand of KLRG1, in the intestinal mucosa; and have elevated levels of systemic soluble E-cadherin (sE-cadherin) that significantly correlate with HIV-1 viral load (R = 0.7, P = .004). We furthermore demonstrate that in the presence of sE-cadherin, KLRG1(hi) HIV-1-specific CD8⁺ T cells are impaired in their ability to respond by cytokine secretion on antigenic stimulation (P = .002) and to inhibit viral replication (P = .03) in vitro. Thus, these data suggest a critical mechanism by which the disruption of the intestinal epithelium associated with HIV-1 leads to increased systemic levels of sE-cadherin, which inhibits the effector functions of KLRG1(hi)-expressing HIV-1-specific CD8⁺ T cells systemically.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Caderinas/metabolismo , Infecções por HIV/imunologia , Lectinas Tipo C/biossíntese , Transativadores/biossíntese , Linfócitos T CD8-Positivos/metabolismo , Caderinas/imunologia , Moléculas de Adesão Celular/imunologia , Moléculas de Adesão Celular/metabolismo , Separação Celular , Colo/imunologia , Colo/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Citometria de Fluxo , Imunofluorescência , Infecções por HIV/metabolismo , HIV-1/imunologia , Humanos , Imuno-Histoquímica , Lectinas Tipo C/imunologia , Ativação Linfocitária/imunologia , Masculino , Receptores Imunológicos , Transativadores/imunologia , Replicação Viral/imunologia
12.
Int J Mol Sci ; 14(7): 14550-74, 2013 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-23857054

RESUMO

Despite the large efforts to prepare super paramagnetic iron oxide nanoparticles (MNPs) for biomedical applications, the number of FDA or EMA approved formulations is few. It is not known commonly that the approved formulations in many instances have already been withdrawn or discontinued by the producers; at present, hardly any approved formulations are produced and marketed. Literature survey reveals that there is a lack for a commonly accepted physicochemical practice in designing and qualifying formulations before they enter in vitro and in vivo biological testing. Such a standard procedure would exclude inadequate formulations from clinical trials thus improving their outcome. Here we present a straightforward route to assess eligibility of carboxylated MNPs for biomedical tests applied for a series of our core-shell products, i.e., citric acid, gallic acid, poly(acrylic acid) and poly(acrylic acid-co-maleic acid) coated MNPs. The discussion is based on physicochemical studies (carboxylate adsorption/desorption, FTIR-ATR, iron dissolution, zeta potential, particle size, coagulation kinetics and magnetization measurements) and involves in vitro and in vivo tests. Our procedure can serve as an example to construct adequate physico-chemical selection strategies for preparation of other types of core-shell nanoparticles as well.


Assuntos
Coloides/química , Nanopartículas de Magnetita/química , Resinas Acrílicas/química , Adsorção , Animais , Ácidos Carboxílicos/química , Compostos Férricos/química , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Tamanho da Partícula , Ratos , Cauda/patologia
13.
J Anesth ; 27(4): 618-22, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23314695

RESUMO

Mortality due to septic-shock-induced respiratory failure remains high. A recent meta-analysis suggested that IgM-enriched immunoglobulin treatment may be beneficial in these patients. In this prospective randomised controlled pilot study we investigated the effects of IgM-enriched immunoglobulin treatment in patients with early septic shock accompanied by severe respiratory failure. 33 patients were randomly allocated to receive 5 ml/kg (predicted body weight) IgM-enriched immunoglobulin (16 patients) or placebo (17 patients), respectively, via 8 h IV-infusion for three consecutive days. Daily Multiple Organ Dysfunction Scores (MODS) were calculated. Serum C-reactive protein (CRP) and procalcitonin (PCT) levels were monitored daily. For statistical analysis two-way ANOVA was used. Daily MODS showed ongoing multiple system organ failure without significant resolution during the 8 days. Median length of ICU stay, mechanical ventilation, vasopressor support during the ICU stay and 28-day mortality were nearly identical in the two groups. Serum PCT levels showed no significant difference between the two groups, however, CRP levels were significantly lower in the IgM-enriched immunoglobulin group on days 4, 5 and 6, respectively. In this study the use of IgM-enriched immunoglobulin preparation failed to produce any improvement in the organ dysfunction as compared to standard sepsis therapy.


Assuntos
Imunoglobulina M/uso terapêutico , Insuficiência de Múltiplos Órgãos/tratamento farmacológico , Insuficiência de Múltiplos Órgãos/etiologia , Choque Séptico/complicações , Choque Séptico/tratamento farmacológico , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Estudos Prospectivos
14.
J Infect Dis ; 205(10): 1495-500, 2012 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-22427677

RESUMO

Regulatory T cells (Tregs) are potent immune modulators, but their role in human immunodeficiency virus type 1 (HIV-1) pathogenesis remains poorly understood. We performed a detailed analysis of the frequency and function of Tregs in a large cohort of HIV-1-infected individuals and HIV-1 negative controls. While HIV "elite controllers" and uninfected individuals had similar Treg numbers and frequencies, the absolute numbers of Tregs declined in blood and gut-associated lymphoid tissue in patients with chronic progressive HIV-1 infection. Despite quantitative changes in Tregs, HIV-1 infection was not associated with an impairment of ex vivo suppressive function of flow-sorted Tregs in both HIV controllers and untreated chronic progressors.


Assuntos
Infecções por HIV/imunologia , HIV-1/imunologia , Linfócitos T Reguladores/fisiologia , Estudos de Casos e Controles , Doença Crônica , Estudos de Coortes , Progressão da Doença , Citometria de Fluxo , Infecções por HIV/virologia , Humanos , Contagem de Linfócitos , Tecido Linfoide/imunologia , RNA Viral/sangue , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/virologia , Carga Viral
15.
Langmuir ; 28(48): 16638-46, 2012 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-23140279

RESUMO

Magnetite nanoparticles (MNPs) coated with poly(acrylic acid-co-maleic acid) polyelectrolyte (PAM) have been prepared with the aim of improving colloidal stability of core-shell nanoparticles for biomedical applications and enhancing the durability of the coating shells. FTIR-ATR measurements reveal two types of interaction of PAM with MNPs: hydrogen bonding and inner-sphere metal-carboxylate complex formation. The mechanism of the latter is ligand exchange between uncharged -OH groups of the surface and -COO(-) anionic moieties of the polyelectrolyte as revealed by adsorption and electrokinetic experiments. The aqueous dispersion of PAM@MNP particles (magnetic fluids - MFs) tolerates physiological salt concentration at composition corresponding to the plateau of the high-affinity adsorption isotherm. The plateau is reached at small amount of added PAM and at low concentration of nonadsorbed PAM, making PAM highly efficient for coating MNPs. The adsorbed PAM layer is not desorbed during dilution. The performance of the PAM shell is superior to that of poly(acrylic acid) (PAA), often used in biocompatible MFs. This is explained by the different adsorption mechanisms; metal-carboxylate cannot form in the case of PAA. Molecular-level understanding of the protective shell formation on MNPs presented here improves fundamentally the colloidal techniques used in core-shell nanoparticle production for nanotechnology applications.


Assuntos
Resinas Acrílicas/química , Materiais Biocompatíveis/química , Desenho de Fármacos , Nanopartículas de Magnetita/química , Imãs/química , Maleatos/química , Adsorção , Materiais Biocompatíveis/toxicidade , Proliferação de Células/efeitos dos fármacos , Coloides , Células HeLa , Humanos , Concentração de Íons de Hidrogênio , Teste de Materiais , Sais/química , Propriedades de Superfície
16.
J Virol ; 84(20): 10784-91, 2010 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-20702625

RESUMO

Dendritic cells represent a specialized class of professional antigen-presenting cells that are responsible for priming and maintaining antigen-specific effector cell responses and regulating immune activation by cytokine secretion. In HIV-1 infection, myeloid dendritic cells are highly dysfunctional, but mechanisms contributing to their functional alterations are not well defined. Here, we show that soluble molecules of the nonclassical major histocompatibility complex class Ib (MHC-Ib) antigen HLA-G are highly upregulated in the plasma during progressive HIV-1 infection, while levels of membrane-bound HLA-G surface expression on dendritic cells, monocytes, and T cells only slightly differ among HIV-1 progressors, HIV-1 elite controllers, and HIV-1-negative persons. These elevated levels of soluble HLA-G in progressive HIV-1 infection likely result from increased secretion of intracellularly stored HLA-G molecules in monocytes and dendritic cells and contribute to a functional disarray of dendritic cells by inhibiting their antigen-presenting properties, while simultaneously enhancing their secretion of proinflammatory cytokines. Interestingly, we observed that these immunoregulatory effects of soluble HLA-G were mainly mediated by interactions with the myelomonocytic HLA class I receptor leukocyte immunoglobulin-like receptor B2 (LILRB2; ILT4), while binding of soluble HLA-G to its alternative high-affinity receptor, LILRB1 (ILT2), appeared to be less relevant for its immunomodulatory functions on dendritic cells. Overall, these results demonstrate a critical role for soluble HLA-G in modulating the functional characteristics of professional antigen-presenting cells in progressive HIV-1 infection and suggest that soluble HLA-G might represent a possible target for immunotherapeutic interventions in HIV-1-infected persons.


Assuntos
Células Dendríticas/imunologia , Infecções por HIV/imunologia , HIV-1 , Antígenos HLA/metabolismo , Antígenos de Histocompatibilidade Classe I/metabolismo , Glicoproteínas de Membrana/metabolismo , Receptores Imunológicos/metabolismo , Adulto , Apresentação de Antígeno , Antígenos CD/genética , Antígenos CD/metabolismo , Estudos de Casos e Controles , Progressão da Doença , Feminino , Sobreviventes de Longo Prazo ao HIV , Antígenos HLA-G , Humanos , Técnicas In Vitro , Receptor B1 de Leucócitos Semelhante a Imunoglobulina , Masculino , Glicoproteínas de Membrana/antagonistas & inibidores , Glicoproteínas de Membrana/genética , Pessoa de Meia-Idade , RNA Interferente Pequeno/genética , Receptores Imunológicos/antagonistas & inibidores , Receptores Imunológicos/genética , Solubilidade , Regulação para Cima , Adulto Jovem
17.
J Virol ; 84(18): 9463-71, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20631139

RESUMO

Elite controllers maintain undetectable levels of HIV-1 replication in the absence of antiretroviral therapy, but the correlates of immune protection in this patient population are ill defined. Here, we demonstrate that in comparison to patients with progressive HIV-1 infection or healthy persons not infected with HIV-1, elite controllers have circulating myeloid dendritic cells with significantly increased antigen-presenting properties, while their ability to secrete proinflammatory cytokines is substantially diminished. This unique functional profile is associated with a distinct surface expression pattern of immunomodulatory leukocyte-immunoglobulin-like receptors (LILR) and a strong and selective upregulation of LILRB1 and LILRB3. Blockade of these two receptors by monoclonal antibodies or short interfering RNA (siRNA) abrogated the specific antigen-presenting properties of dendritic cells, implying an important regulatory role of these molecules. These data reveal previously unrecognized innate components of immune protection against HIV-1 in elite controllers and offer novel perspectives for the manipulation of host immunity for the prevention and treatment of HIV-1 infection.


Assuntos
Apresentação de Antígeno , Antígenos CD/metabolismo , Células Dendríticas/imunologia , Infecções por HIV/imunologia , Sobreviventes de Longo Prazo ao HIV , HIV-1/imunologia , Receptores Imunológicos/metabolismo , Adulto , Anticorpos Monoclonais/imunologia , Antígenos CD/imunologia , Citocinas/metabolismo , Feminino , Inativação Gênica , Humanos , Receptor B1 de Leucócitos Semelhante a Imunoglobulina , Masculino , Pessoa de Meia-Idade , Receptores Imunológicos/antagonistas & inibidores , Receptores Imunológicos/imunologia , Adulto Jovem
18.
Orv Hetil ; 152(12): 469-74, 2011 Mar 20.
Artigo em Húngaro | MEDLINE | ID: mdl-21388944

RESUMO

UNLABELLED: Medical years are very important in shaping the attitudes of future doctors. It is proven that doctors who smoke do not advise their patient to stop smoking. We have to know the students' smoking habits and attitudes about smoking cessation to make them interested in the fight against tobacco. AIMS: To investigate medical students' smoking habits and attitudes about cessation. METHODS: We applied the Hungarian translation of the Global Health Professionals Student Survey. Medical students from the first and fifth year filled in the survey anonymously during the seminars. Statistical analysis was performed with SPSS. RESULTS: In both years 245 students filled in the questionnaire. In the first year 30.8%, in the fifth year 38.9% of the students were defined as smokers. During the academic study the number of daily smokers and the number of smoked cigarettes increases. Students require training about smoking cessation, however they would entrust it to a specialist. CONCLUSIONS: Based on our data we need a teaching block in the curricula about smoking and smoking cessation.


Assuntos
Abandono do Hábito de Fumar , Fumar/epidemiologia , Estudantes de Medicina/estatística & dados numéricos , Adolescente , Adulto , Idade de Início , Atitude , Criança , Feminino , Humanos , Hungria/epidemiologia , Masculino , Papel do Médico , Distribuição por Sexo , Fumar/efeitos adversos , Abandono do Hábito de Fumar/métodos , Abandono do Hábito de Fumar/estatística & dados numéricos , Prevenção do Hábito de Fumar , Inquéritos e Questionários , Adulto Jovem
19.
Orv Hetil ; 152(38): 1535-43, 2011 Sep 18.
Artigo em Húngaro | MEDLINE | ID: mdl-21896445

RESUMO

UNLABELLED: In their institute authors teach medical communication skills in three languages (Hungarian, English and German) for medical students in the first year of their studies. In order to improve teaching methods, authors wanted to explore the attitudes of students towards the communication skills learning. For this purpose authors applied the Communication Skills Attitudes Scale created by Rees et al., which is an internationally accepted and well adaptable instrument. AIMS: In this survey authors wanted to validate the Hungarian and German version of the Communication Skills Attitudes Scale. In addition, their aim was to analyze possible differences between the attitudes of each of the three medical teaching programs. METHODS: Questionnaires were filled anonymously at the beginning of the practices. Principal component analysis with varimax rotation was performed to evaluate the attitudes using the SPSS 10.5 version for analysis. RESULTS: Authors created a model consisting of 7 factors. Factors were the following: 1: respect and interpersonal skills; 2: learning; 3: importance of communication within medical profession; 4: excuse; 5: counter; 6: exam; 7: overconfidence. It was found that students had mainly positive attitudes. Except the learning factor, all other factors showed significant differences between the three medical teaching programs. CONCLUSIONS: although students had mainly positive attitudes toward learning communication skills, there were negative attitudes which can be partly modified by improving the teaching methods. However, results may create a proper base for further research to help improving communication skills teaching methods of the authors.


Assuntos
Atitude do Pessoal de Saúde , Comunicação , Educação de Graduação em Medicina , Relações Interpessoais , Idioma , Estudantes de Medicina/estatística & dados numéricos , Inquéritos e Questionários/normas , Adolescente , Análise Fatorial , Feminino , Humanos , Aprendizagem , Masculino , Estudantes de Medicina/psicologia , Traduções , Adulto Jovem
20.
Orv Hetil ; 152(21): 828-33, 2011 May 22.
Artigo em Húngaro | MEDLINE | ID: mdl-21546341

RESUMO

UNLABELLED: In some countries strict tobacco control measures successfully reduced the number of smokers. Although these measures do not have immediate effects, they may serve as investments in the future healthcare. Health care experts should take part actively in the decision making. AIMS: To investigate medical students' relation to smoking and their attitudes about tobacco control measures. METHODS: Authors applied the Hungarian translation of the Global Health Professionals Student Survey. Medical students from the first and fifth year answered its questions anonymously. Statistical analysis was performed with SPSS. RESULTS: Altogether 245 students completed the questionnaire. It was found that the knowledge of students about health damages caused by tobacco smoking was very good. However, a large number of students are exposed to tobacco smoke (68% of them at home and 85% at public places). Their opinion about tobacco control measures reflects recent law, as only 43% of the students would support a smoking ban in bars and discotheques. CONCLUSIONS: Hungarian health care experts have to take part with more effort in the prevention of tobacco smoking. Medical students have to be trained in this field.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Fumar , Estudantes de Medicina/estatística & dados numéricos , Adulto , Feminino , Humanos , Hungria/epidemiologia , Masculino , Fumar/legislação & jurisprudência , Prevenção do Hábito de Fumar , Marketing Social , Estudantes de Medicina/psicologia , Inquéritos e Questionários , Poluição por Fumaça de Tabaco , Adulto Jovem
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