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1.
Int J Emerg Med ; 17(1): 19, 2024 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-38331724

RESUMO

BACKGROUND: Monkshood, a toxic plant containing a potent cardio- and neurotoxin called aconitine, can lead to a range of symptoms, including nausea, vomiting, dizziness, seizures, and cardiac arrhythmias. Mortality associated with this intoxication are due to ventricular tachyarrhythmias which are difficult to treat and often refractory in nature. CASE PRESENTATION: We present a case of a 17-year-old female patient who presented to the emergency department after intentionally ingesting a monkshood plant and developed atrioventricular dissociation and frequent ventricular ectopy. The patient was successfully treated with activated charcoal, supportive care, and cardiac monitoring. CONCLUSION: This case highlights the importance of early recognition of aconitine poisoning and the need for prompt supportive care, cardiac rhythm monitoring, and preemptive antiarrhythmic treatment planning.

2.
J Colloid Interface Sci ; 571: 267-274, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32203763

RESUMO

HYPOTHESIS: The shape of colloidal particles affects the structure of colloidal dispersions. The effect of the cube shape on the thermodynamics of colloidal cube dispersions has not yet been studied experimentally. Static light scattering measurements on colloidal cubic silica shells at finite concentrations allows us to measure the structure factor of colloidal cube fluids and to test theoretical predictions for the equation of state of hard convex superballs. EXPERIMENTS: Hollow silica nanocubes of varying concentrations in N,N,-dimethylformamide were studied with static light scattering. The structure factor was extracted from the scattering curves using experimental form factors. From this experimental structure factor, the specific density of the particles, and the osmotic compressibility were obtained. This osmotic compressibility was then compared to a theoretical equation of state of hard superballs. FINDINGS: The first experimental structure factors of a stable cube fluid are presented. The osmotic compressibility of the cube fluid can be described by the equation of state of a hard superball fluid, showing that silica cubes in N,N,-dimethylformamide with LiCl effectively interact as hard particles.

3.
J Colloid Interface Sci ; 571: 419-428, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31813577

RESUMO

HYPOTHESIS: Colloidal cubic silica shells, prepared from cuprous oxide cubes, with a typical size of 100 nm are promising model particles for scattering studies on dilute, as well as concentrated fluids, of non-spherical colloids. EXPERIMENTS: Small angle X-ray scattering, and static light scattering are employed to determine form factors of cubic silica shells and silica covered cuprous oxide cubes. Contrast variation experiments are performed to assess the refractive index and optical homogeneity of the cubic silica shells, which is important for the extension of the scattering study to concentrated dispersions of cubic shells in Part II (Dekker, submitted for publication). RESULTS: The experimental form factors, which compare well to theoretical form factors, manifest cubic silica shells that are dispersed as single stable colloids with a shape intermediate between a sphere and a perfect cube. Contrast variation demonstrates that the silica shells are optically homogeneous, with a refractive index that is independent of the shell thickness. The results presented here open up the possibility to extract structure factors from light scattering measurements on concentrated cube dispersions in Part II.

4.
Clin Exp Immunol ; 198(3): 381-389, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31487400

RESUMO

Vaccination against meningococcal serogroup B is recommended for patients with a complement deficiency; however, although immunogenicity in this patient group has been shown, efficacy has not yet been established. In this study, we collected serum from children with a complement deficiency in the alternative pathway or in late terminal pathway before and after vaccination with multi-component meningococcal serogroup B (MenB)-4C. MenB-4C is a multi-component, protein-based vaccine against MenB consisting of factor H-binding protein, Neisserial heparin-binding protein, Neisserial adhesion A and outer membrane vesicles containing Porin A. We assessed the vaccine immunogenicity and vaccine-mediated protection by a whole cell enzyme-linked immunosorbent assay with Neisseria meningitidis serogroup B strains H44/76, 5/99 and NZ98/254, which shows that vaccination induced antibody titers against meningococcus. We show that the classical serum bactericidal activity assay with exogenous serum indicates the presence of vaccine-induced antibodies and capacity to activate complement-mediated pathogen lysis. However, in children with a late terminal pathway deficiency, no complement-mediated pathogen lysis was observed when autologous serum was applied in the serum bactericidal activity assay, demonstrating a lack of serum bactericidal activity in children with complement deficiencies. However, MenB-4C vaccination still induced effective complement-dependent opsonophagocytic killing against N. meningitidis serogroup B in reconstituted whole blood with autologous serum from children with an alternative pathway or late terminal pathway deficiency. These findings support the recommendation to vaccinate all complement-deficient children against MenB.


Assuntos
Doenças da Deficiência Hereditária de Complemento/imunologia , Meningite Meningocócica/imunologia , Vacinas Meningocócicas/imunologia , Neisseria meningitidis Sorogrupo B/imunologia , Proteínas Opsonizantes/imunologia , Fagocitose/imunologia , Adolescente , Adulto , Anticorpos Antibacterianos/imunologia , Criança , Fator H do Complemento/imunologia , Fator H do Complemento/metabolismo , Feminino , Doenças da Deficiência Hereditária de Complemento/microbiologia , Doenças da Deficiência Hereditária de Complemento/terapia , Humanos , Masculino , Meningite Meningocócica/microbiologia , Meningite Meningocócica/terapia , Vacinas Meningocócicas/administração & dosagem , Neisseria meningitidis Sorogrupo B/fisiologia , Proteínas Opsonizantes/metabolismo , Vacinação
5.
Ned Tijdschr Geneeskd ; 160: D74, 2016.
Artigo em Holandês | MEDLINE | ID: mdl-27353162

RESUMO

BACKGROUND: Underwater birth is becoming increasingly popular because of the advantages for the mother. Women who deliver in this way feel less pain and therefore pain relief is less frequently needed during the delivery. But what seems to be forgotten is the fact that aspiration of water by the neonate could take place during an underwater birth, resulting in respiratory distress. CASE DESCRIPTION: A one-day-old neonate was admitted because of tachypnoea following underwater delivery at home. The respiratory rate of the neonate was one hundred breaths per minute without evident signs of dyspnoea. Chest radiography showed bilateral patches on the lungs consistent with aspiration of bathwater. After seven days of intravenous antibiotic treatment, the neonate recovered and could be discharged home. CONCLUSION: An underwater birth may cause respiratory problems in the neonate. If a pregnant woman wants to deliver under water, she should also be advised of the potential detrimental consequences for the neonate.


Assuntos
Banhos , Parto , Aspiração Respiratória/diagnóstico , Aspiração Respiratória/etiologia , Água , Feminino , Humanos , Recém-Nascido , Gravidez , Aspiração Respiratória/terapia
6.
Clin Microbiol Infect ; 20(12): 1316-22, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24975428

RESUMO

The aim of this study was to quantify the value of clinical predictors available in the emergency department (ED) in predicting Streptococcus pneumoniae as the cause of community-acquired pneumonia (CAP). A prospective, observational, cohort study of patients with CAP presenting in the ED was performed. Pneumococcal aetiology of CAP was based on either bacteraemia, or S. pneumoniae being cultured from sputum, or urinary immunochromatographic assay positivity, or positivity of a novel serotype-specific urinary antigen detection test. Multivariate logistic regression was used to identify independent predictors and various cut-off values of probability scores were used to evaluate the usefulness of the model. Three hundred and twenty-eight (31.0%) of 1057 patients with CAP had pneumococcal CAP. Nine independent predictors for pneumococcal pneumonia were identified, but the clinical utility of this prediction model was disappointing, because of low positive predictive values or a small yield. Clinical criteria have insufficient diagnostic capacity to predict pneumococcal CAP. Rapid antigen detection tests are needed to diagnose S. pneumoniae at the time of hospital admission.


Assuntos
Infecções Comunitárias Adquiridas/diagnóstico , Técnicas de Apoio para a Decisão , Serviços Médicos de Emergência/métodos , Pneumonia Pneumocócica/diagnóstico , Streptococcus pneumoniae/isolamento & purificação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Infecções Comunitárias Adquiridas/microbiologia , Serviço Hospitalar de Emergência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia Pneumocócica/microbiologia , Estudos Prospectivos , Adulto Jovem
7.
Rev Sci Instrum ; 85(3): 033903, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24689596

RESUMO

A sensitive dielectric spectroscopy setup is built to measure the response of nanoparticles dispersed in a liquid to an alternating electric field over a frequency range from 10(-2) to 10(7) Hz. The measured complex permittivity spectrum records both the rotational dynamics due to a permanent electric dipole moment and the translational dynamics due to net charges. The setup consists of a half-transparent capacitor connected in a bridge circuit, which is balanced on pure solvent only, using a software-controlled compensating voltage. In this way, the measured signal is dominated by the contributions of the nanoparticles rather than by the solvent. We demonstrate the performance of the setup with measurements on a dispersion of colloidal CdSe quantum dots in the apolar liquid decalin.

8.
Rev Sci Instrum ; 84(3): 036109, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23556861

RESUMO

The sensitivity of an imperfectly balanced impedance bridge is limited by the remaining offset voltage. Here, we present a procedure for offset reduction in impedance measurements using a lock-in amplifier, by applying a complex compensating voltage external to the bridge. This procedure takes into account instrumental damping and phase shifting, which generally occur at the high end of the operational frequency range. Measurements demonstrate that the output of the circuit rapidly converges to the instrumentally limited noise at any frequency.

9.
Neth J Med ; 71(10): 502-7, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24394734

RESUMO

INTRODUCTION: According to the Dutch guidelines, severity of community acquired pneumonia (CAP) (mild, moderate-severe, severe) should be based on either PSI, CURB65 or a 'pragmatic' classification. In the last mentioned, the type of ward of admission, as decided by the treating physician, is used as classifier: no hospital admission is mild, admission to a general ward is moderate-severe and admission to an intensive care unit (ICU) is severe CAP. Empiric antibiotic recommendations for each severity class are uniform. We investigated, in 23 hospitals, which of the three classification systems empirical treatment of CAP best adhered to, and whether a too narrow spectrum coverage (according to each of the systems) was associated with a poor patient outcome (in-hospital mortality or need for ICU admission). PATIENTS AND METHODS: Prospective observational study in 23 hospitals. RESULTS: 271 (26%) of 1047 patients with CAP confirmed by X-ray were categorised in the same severity class with all three classification methods. Proportions of patients receiving guideline-adherent antibiotics were 62.9% (95% CI 60.0-65.8%) for the pragmatic, 43.1% (95% CI 40.1-46.1%) for PSI and 30.5% (95% CI 27.8-33.3%) for CURB65 classification. 'Under-treatment' based on the pragmatic classification was associated with a trend towards poor clinical outcome, but no such trend was apparent for the other two scoring systems. CONCLUSIONS: Concordance between three CAP severity classification systems was low, implying large heterogeneity in antibiotic treatment for CAP patients. Empirical treatment appeared most adherent to the pragmatic classification. Non-adherence to treatment recommendations based on the PSI and CURB65 was not associated with a poor clinical outcome.


Assuntos
Antibacterianos/uso terapêutico , Infecções Comunitárias Adquiridas/tratamento farmacológico , Fidelidade a Diretrizes/normas , Pneumonia/tratamento farmacológico , Índice de Gravidade de Doença , Idoso , Infecções Comunitárias Adquiridas/diagnóstico , Infecções Comunitárias Adquiridas/diagnóstico por imagem , Quimioterapia Combinada , Feminino , Mortalidade Hospitalar , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Países Baixos , Pneumonia/diagnóstico , Pneumonia/diagnóstico por imagem , Quinolonas/uso terapêutico , Radiografia Torácica , Resultado do Tratamento , beta-Lactamases/uso terapêutico
11.
J Phys Condens Matter ; 24(24): 245101, 2012 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-22569199

RESUMO

This paper describes an integrated setup for fluorescence recovery after photobleaching (FRAP) for determining translational and rotational Brownian diffusion simultaneously, ensuring that these two quantities are measured under exactly the same conditions and at the same time in dynamic experiments. The setup is based on translational-FRAP with a fringe pattern of light for both the bleaching and monitoring of fluorescently labeled particles, and rotational-FRAP, which uses the polarization of a short bleach light pulse to create a polarization anisotropy. The fringe pattern of the probe beam is modulated in conjunction with a synchronized lock-in amplifier giving a fast, sensitive, ensemble-averaged measurement compared to microscope-image based techniques. The experimental polarization geometry we used ensures that the fluorescence emission is collected without polarization bias. Therefore, only the orientation of the absorption dipole moment of the fixed dye in the particles is measured, which simplifies interpretation of the data. The polarization is modulated rapidly between two orthogonal polarization states, giving the polarization anisotropy in one, single measurement. The rotational and translational Brownian diffusion of anisotropic colloids is measured for ellipsoids of revolution. This experiment shows that in this case the rotational correlation function matches a three-exponential decay in accordance with theoretical predictions.


Assuntos
Coloides/química , Recuperação de Fluorescência Após Fotodegradação/métodos , Rotação , Anisotropia , Difusão , Fatores de Tempo
12.
J Phys Condens Matter ; 23(19): 194108, 2011 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-21525548

RESUMO

We demonstrate the suitability of polarization microscopy to study the recently discovered (parallel) nematic-(perpendicular) nematic phase separation. This novel type of phase transition is induced by applying an external magnetic field to a nematic liquid crystal of boardlike colloidal goethite and is due to an interplay between the intrinsic magnetic properties of goethite and the collective effect of liquid crystal formation. It is shown that the intense ochre colour of goethite does not preclude the use of polarization microscopy and interference colours, and that dichroism can give valuable qualitative information on the nature of the phases, their anchoring and their sedimentation and order parameter profiles. We also apply these techniques to study 'nematic-nematic tactoids': nematic droplets sedimenting within a nematic medium with mutually perpendicular orientations.


Assuntos
Compostos de Ferro/química , Compostos de Ferro/síntese química , Cristais Líquidos/química , Magnetismo/instrumentação , Microscopia de Polarização/métodos , Minerais/química , Minerais/síntese química , Transição de Fase , Birrefringência , Cristalização , Microesferas , Propriedades de Superfície
13.
Chem Phys Lipids ; 164(1): 9-15, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20932964

RESUMO

Temperature-controlled Atomic Force Microscopy (TC-AFM) in Contact Mode is used here to directly image the mechanisms by which melting and crystallization of supported, hydrated DPPC bilayers proceed in the presence and absence of the model peptide WALP23. Melting from the gel L(ß)' to the liquid-crystalline L(α) phase starts at pre-existing line-type packing defects (grain boundaries) in absence of the peptide. The exact transition temperature is shown to be influenced by the magnitude of the force exerted by the AFM probe on the bilayer, but is higher than the main transition temperature of non-supported DPPC vesicles in all cases due to bilayer-substrate interactions. Cooling of the fluid L(α) bilayer shows the formation of the line-type defects at the borders between different gel-phase regions that originate from different nuclei. The number of these defects depends directly on the rate of cooling through the transition, as predicted by classical nucleation theory. The presence of the transmembrane, synthetic model peptide WALP23 is known to give rise to heterogeneity in the bilayer as microdomains with a striped appearance are formed in the DPPC bilayer. This striated phase consists of alternating lines of lipids and peptide. It is shown here that melting starts with the peptide-associated lipids in the domains, whose melting temperature is lowered by 0.8-2.0°C compared to the remaining, peptide-free parts of the bilayer. The stabilization of the fluid phase is ascribed to adaptations of the lipids to the shorter peptide. The lipids not associated with the peptide melt at the same temperature as those in the pure DPPC supported bilayer.


Assuntos
1,2-Dipalmitoilfosfatidilcolina/química , Bicamadas Lipídicas/química , Microscopia de Força Atômica , Peptídeos/química , Cristalização , Transição de Fase , Temperatura
14.
Rev Sci Instrum ; 79(1): 013901, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18248044

RESUMO

A sensitive balanced differential transformer was built to measure complex initial parallel magnetic susceptibility spectra in the 0.01-1000 Hz range. The alternating magnetic field can be chosen sufficiently weak that the magnetic structure of the samples is only slightly perturbed and the low frequencies make it possible to study the rotational dynamics of large magnetic colloidal particles or aggregates dispersed in a liquid. The distinguishing features of the setup are the novel multilayered cylindrical coils with a large sample volume and a large number of secondary turns (55 000) to measure induced voltages with a good signal-to-noise ratio, the use of a dual channel function generator to provide an ac current to the primary coils and an amplitude- and phase-adjusted compensation voltage to the dual phase differential lock-in amplifier, and the measurement of several vector quantities at each frequency. We present the electrical impedance characteristics of the coils, and we demonstrate the performance of the setup by measurement on magnetic colloidal dispersions covering a wide range of characteristic relaxation frequencies and magnetic susceptibilities, from chi approximately -10(-5) for pure water to chi>1 for concentrated ferrofluids.

15.
Langmuir ; 22(4): 1822-7, 2006 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-16460113

RESUMO

We report on the preparation of monodisperse, fluorescent hematite-silica core-shell ellipsoids, with adjustable shapes ranging from spindles to nearly spheres, that are suitable for optical rotational diffusion studies. Hematite cores are grafted with poly(vinylpyrrolidone) which ensures colloidal stability during the silica coating provided by the base-catalyzed hydrolysis and polymerization of tetraethoxysilane. Using tetramethylammonium hydroxide as base instead of the volatile ammonia facilitates continuous seeded growth of silica to colloids with a desired aspect ratio. A convenient feature of the hematite-silica particles is the rapid dissolution of the iron oxide core by acid, producing hollow silica ellipsoids that can be optically matched to near transparency. The control of shape and size of the silica ellipsoids, their optical properties, and the fairly high yield in comparison to other preparation methods for nonspherical model colloids make the ellipsoids very suitable for quantitative studies. As a case in point, we have measured the rotational diffusion coefficient of fluorescent ellipsoids with rotational fluorescence recovery after photobleaching. Dye-labeled ellipsoids can be imaged with confocal microscopy.

16.
J Chem Phys ; 120(9): 4517-29, 2004 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-15268620

RESUMO

We report a polarized fluorescence recovery after photobleaching (pFRAP) method to measure the rotational dynamics of fluorescent colloids over a wide dynamic range. The method is based on the polarization anisotropy in the fluorescence intensity, generated by bleaching of fluorescently labeled particles with an intense pulse of linearly polarized laser light. The rotational mobilities of the fluorescent particles can be extracted from the relaxation kinetics of the postbleach fluorescence polarization anisotropy. Our pFRAP setup has access to correlation times over a range of time scales from tens of microseconds to tens of seconds, and is highly sensitive, so very low concentrations of labeled particles can be probed. We present a detailed description of the theoretical background of pFRAP. The performance of the equipment is demonstrated for fluorescent colloidal silica spheres, dispersed in pure solvents as well as in fd-virus suspensions.


Assuntos
Coloides/análise , Coloides/química , Recuperação de Fluorescência Após Fotodegradação/métodos , Modelos Químicos , Modelos Moleculares , Fenômenos Biomecânicos , Simulação por Computador , Difusão , Microesferas , Conformação Molecular , Rotação , Estresse Mecânico
17.
FEMS Immunol Med Microbiol ; 34(4): 267-75, 2002 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-12443826

RESUMO

Neisseria meningitidis expresses a range of lipooligosaccharide (LOS) structures, comprising of at least 13 immunotypes (ITs). Meningococcal LOS is subject to phase variation of its terminal structures allowing switching between ITs, which is proposed to have functional significance in disease. The objectives of this study were to investigate the repertoire of structures that can be expressed in clinical isolates, and to examine the role of phase-variable expression of LOS genes during invasive disease. Southern blotting was used to detect the presence of LOS biosynthetic genes in two collections of meningococci, a global set of strains previously assigned to lineages of greater or lesser virulence, and a collection of local clinical isolates which included paired throat and blood isolates from individual patients. Where the phase-variable genes lgtA, lgtC or lgtG were identified, they were amplified by PCR and the homopolymeric tracts, responsible for their phase-variable expression, were sequenced. The results revealed great potential for variation between alternate LOS structures in the isolates studied, with most strains capable of expressing several alternative terminal structures. The structures predicted to be currently expressed by the genotype of the strains agreed well with conventional immunotyping. No correlation was observed between the structural repertoire and virulence of the isolate. Based on the potential for LOS phase variation in the clinical collection and observations with the paired patient isolates, our data suggest that phase variation of LOS structures is not required for translocation between distinct compartments in the host.


Assuntos
Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Regulação Bacteriana da Expressão Gênica , Variação Genética , Lipopolissacarídeos/biossíntese , Neisseria meningitidis/patogenicidade , Proteínas de Bactérias/química , Genótipo , Humanos , Lipopolissacarídeos/química , Infecções Meningocócicas/microbiologia , Neisseria meningitidis/genética , Neisseria meningitidis/crescimento & desenvolvimento , Fenótipo , Reação em Cadeia da Polimerase , Análise de Sequência de DNA
18.
J Colloid Interface Sci ; 250(2): 303-15, 2002 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-16290668

RESUMO

Atomic force microscopy (AFM) is used to study the size, shape, and polydispersity of a variety of magnetic and nonmagnetic model colloids, previously imaged by transmission electron microscopy (TEM) only. Both height and phase images are analyzed and special attention is given to 3D morphology and softness of particles, as well as structures and presence of secondary components in the colloid, difficult to investigate with TEM. Several methods of tip characterization followed by deconvolution were applied in order to improve the accuracy of lateral diameter determination. In the case of magnetite particles dispersed in conventional ferrofluids, we explore both experimentally and theoretically the possibility of using magnetic force microscopy (MFM). We propose and discuss several models which allow to estimate the magnetic moment of a single domain superparamagnetic sphere using MFM, which cannot be done with other techniques; alternatively the tip magnetization can be determined.

19.
Vaccine ; 20(3-4): 352-8, 2001 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-11672897

RESUMO

A clinical phase II trial with the RIVM hexavalent OMV vaccine containing six different PorAs was carried out in toddlers (2-3 years) and schoolchildren (7-8 years) in The Netherlands. Children were vaccinated three times (0, 2, 8 months). Sera after two and three vaccinations were analysed for serum bactericidal activity (SBA) and isotype distribution in whole cell enzyme linked immunosorbent assay (ELISA). The SBA after vaccination against the six PorAs was significantly different. We investigated whether the age specific and PorA specific differences in SBA titers correlated with differences in PorA specific IgG isotype distribution. The SBA titers were higher in toddlers compared with schoolchildren. After vaccination, IgG1 antibodies dominated the response followed by IgG3 antibodies. IgG2 levels were low, whereas IgG4 was not detected. Irrespective of PorA, IgG total and isotype specific titers after two and three vaccinations were significantly higher in toddlers than in schoolchildren. A weak correlation was found between IgG total or IgG1 and SBA. Although the immunogenicity of the six PorAs is very different, the isotype distribution was similar for all six tested PorAs. We conclude that the RIVM hexavalent PorA vesicle vaccine induces bactericidal antibodies mainly of the IgG1 and IgG3 isotypes that are considered to be most important for protection against disease. The isotype distribution of the response is not age-dependent.


Assuntos
Anticorpos Antibacterianos/sangue , Atividade Bactericida do Sangue , Isotipos de Imunoglobulinas/sangue , Vacinas Meningocócicas/imunologia , Porinas/imunologia , Criança , Pré-Escolar , Ensaio de Imunoadsorção Enzimática , Humanos , Vacinação
20.
Microb Pathog ; 30(3): 139-48, 2001 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-11273739

RESUMO

The major outer membrane protein PorA of Neisseria meningitidis is the target for bactericidal serosubtyping antibodies and is currently considered as a potential vaccine candidate against group B meningococcal disease. Although the minor antigenic variability of the PorA has been increasingly recognized and described, its implication for vaccine design remains unclear. In this study, the protective activity of murine monoclonal PorA specific antibodies against four isogenic meningococcal P1.7,16 target strains, the prototype P1.7,16a and three loop 4 point mutation variants (designated P1.7,16b to d) constructed from reference strain H44/76 (B:15:P1.7,16a), was evaluated in the infant rat infection model. All monoclonal antibodies had been obtained by immunization of mice with outer membrane protein preparations from meningococcal serosubtype P1.7,16 reference strain H44/76. A challenge dose of 10(5)cfu/pup was given i.p. 1-2 h after the i.p. injection of 1:100 diluted antibodies, and the development of bacteremia was assessed by culturing blood samples taken 6 h after challenge. MN14C11.6, a reference monoclonal antibody for serosubtype P1.7 epitope located in predicted loop 1 (VR1) identical in all the variants, was equally protective against all loop 4 variants. The three P1.16 specific monoclonal antibodies tested (MN5C11G, MN12H2 and 62D12-8) all completely protected animals against the prototype P1.7,16a, variably against the P1.7,16b and P1.7,16c, but not against the P1.7,16d variant. Our findings therefore suggest that certain subtype variants may escape protection in vivo conferred by PorA specific antibodies.


Assuntos
Anticorpos Antibacterianos/imunologia , Anticorpos Monoclonais/imunologia , Imunização Passiva , Infecções Meningocócicas/imunologia , Neisseria meningitidis/imunologia , Porinas/imunologia , Animais , Modelos Animais de Doenças , Humanos , Técnicas Imunoenzimáticas , Infecções Meningocócicas/microbiologia , Infecções Meningocócicas/prevenção & controle , Neisseria meningitidis/crescimento & desenvolvimento , Ratos , Ratos Wistar
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