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1.
Microorganisms ; 11(11)2023 Nov 08.
Article in English | MEDLINE | ID: mdl-38004740

ABSTRACT

Antimicrobial resistance is a significant concern worldwide; meanwhile, the impact of 3rd generation cephalosporin (3GC) antibiotics on the microbial communities of cattle and resistance within these communities is largely unknown. The objectives of this study were to determine the effects of two-dose ceftiofur crystalline-free acid (2-CCFA) treatment on the fecal microbiota and on the quantities of second-and third-generation cephalosporin, fluoroquinolone, and macrolide resistance genes in Holstein-Friesian dairy cows in the southwestern United States. Across three dairy farms, 124 matched pairs of cows were enrolled in a longitudinal study. Following the product label regimen, CCFA was administered on days 0 and 3 to cows diagnosed with postpartum metritis. Healthy cows were pair-matched based on lactation number and calving date. Fecal samples were collected on days 0, 6, and 16 and pooled in groups of 4 (n = 192) by farm, day, and treatment group for community DNA extraction. The characterization of community DNA included real-time PCR (qPCR) to quantify the following antibiotic resistance genes: blaCMY-2, blaCTX-M, mphA, qnrB19, and the highly conserved 16S rRNA back-calculated to gene copies per gram of feces. Additionally, 16S rRNA amplicon sequencing and metagenomics analyses were used to determine differences in bacterial community composition by treatment, day, and farm. Overall, blaCMY-2 gene copies per gram of feces increased significantly (p ≤ 0.05) in the treated group compared to the untreated group on day 6 and remained elevated on day 16. However, blaCTX-M, mphA, and qnrB19 gene quantities did not differ significantly (p ≥ 0.05) between treatment groups, days, or farms, suggesting a cephamycinase-specific enhancement in cows on these farms. Perhaps unexpectedly, 16S rRNA amplicon metagenomic analyses showed that the fecal bacterial communities from treated animals on day 6 had significantly greater (p ≤ 0.05) alpha and beta diversity than the untreated group. Two-dose ceftiofur treatment in dairy cows with metritis elevates cephamycinase gene quantities among all fecal bacteria while paradoxically increasing microbial diversity.

2.
Nat Commun ; 13(1): 1262, 2022 03 10.
Article in English | MEDLINE | ID: mdl-35273148

ABSTRACT

Drug delivery systems with high content of drug can minimize excipients administration, reduce side effects, improve therapeutic efficacy and/or promote patient compliance. However, engineering such systems is extremely challenging, as their loading capacity is inherently limited by the compatibility between drug molecules and carrier materials. To mitigate the drug-carrier compatibility limitation towards therapeutics encapsulation, we developed a sequential solidification strategy. In this strategy, the precisely controlled diffusion of solvents from droplets ensures the fast in-droplet precipitation of drug molecules prior to the solidification of polymer materials. After polymer solidification, a mass of drug nanoparticles is embedded in the polymer matrix, forming a nano-in-micro structured microsphere. All the obtained microspheres exhibit long-term storage stability, controlled release of drug molecules, and most importantly, high mass fraction of therapeutics (21.8-63.1 wt%). Benefiting from their high drug loading degree, the nano-in-micro structured acetalated dextran microspheres deliver a high dose of methylprednisolone (400 µg) within the limited administration volume (10 µL) by one single intrathecal injection. The amount of acetalated dextran used was 1/433 of that of low drug-loaded microspheres. Moreover, the controlled release of methylprednisolone from high drug-loaded microspheres contributes to improved therapeutic efficacy and reduced side effects than low drug-loaded microspheres and free drug in spinal cord injury therapy.


Subject(s)
Polymers , Spinal Cord Injuries , Drug Carriers , Drug Delivery Systems , Humans , Microspheres , Solvents , Spinal Cord Injuries/drug therapy
3.
Lupus ; : 961203320988586, 2021 Jan 28.
Article in English | MEDLINE | ID: mdl-33509067

ABSTRACT

Introduction: After more than 20 years of sustained work, the Latin American Group for the Study of Lupus (GLADEL) has made a significant number of contributions to the field of lupus, not only in the differential role that race/ethnicity plays in its course and outcome but also in several other studies including the beneficial effects of using antimalarials in lupus patients and the development of consensus guidelines for the treatment of lupus in our region. Methods: A new generation of "Lupus Investigators" in more than 40 centers throughout Latin America has been constituted in order to continue the legacy of the investigators of the original cohort and to launch a novel study of serum and urinary biomarkers in patients with systemic lupus erythematosus. Results: So far, we have recruited 807 patients and 631 controls from 42 Latin-American centers including 339 patients with SLE without renal involvement, 202 patients with SLE with prevalent but inactive renal disease, 176 patients with prevalent and active renal disease and 90 patients with incident lupus nephritis. Conclusions: The different methodological aspects of the GLADEL 2.0 cohort are discussed in this manuscript, including the challenges and difficulties of conducting such an ambitious project.

4.
CES med ; 34(1): 64-73, ene.-abr. 2020. tab, graf
Article in Spanish | LILACS-Express | LILACS | ID: biblio-1149157

ABSTRACT

Resumen La inmunoglobulina A (IgA) es el isotipo de anticuerpo más abundante en los humanos y fundamentalmente participa en la defensa contra las infecciones y el desarrollo de la tolerancia inmune en las mucosas. La deficiencia de IgA es la inmunodeficiencia más frecuente en humanos, pero comúnmente es asintomática y transitoria. Para diagnosticarla, se cuantifica la concentración de IgA en sangre y se evalúa la magnitud de su disminución. De acuerdo con esta evaluación se clasifica en deficiencia parcial (DPIgA) o deficiencia total (DTIgA). Adicionalmente, si solo se afectan los niveles de IgA sin alteraciones de otras inmunoglobulinas séricas como IgM e IgG o subclases de inmunoglobulina G, entonces se denomina como deficiencia selectiva de IgA (DSIgA). La deficiencia selectiva de IgA es de mayor relevancia clínica y considerada un error innato de la inmunidad, aunque su etiología aún es desconocida y clínicamente se asocia a infecciones de los tractos respiratorio y gastrointestinal, alergias y manifestaciones autoinmunes. Se realizó una búsqueda de artículos científicos en PubMed, Scopus, SciELO y Redalyc sobre la deficiencia selectiva de inmunoglobulina A, con el objetivo de realizar una revisión temática sobre las manifestaciones clínicas, el diagnóstico y el adecuado manejo clínico de los pacientes con esta inmunodeficiencia. Se propone un nuevo algoritmo clínico con el objetivo de mejorar el diagnóstico y brindar un adecuado manejo clínico de los pacientes con esta inmunodeficiencia. Un paciente con deficiencia selectiva de IgA se caracteriza por infecciones recurrentes de los tractos gastrointestinal y respiratorio, en asociación con manifestaciones alérgicas y autoinmunes en individuos mayores de cuatro años, con niveles de IgA sérica menores de 7 mg/dL y con niveles normales de IgG e IgM, y en quienes se hayan descartado defectos relacionados con los linfocitos T u otras causas de hipogammaglobulinemia. Con respecto al manejo clínico, se deben ajustar los esquemas de vacunación e implementar profilaxis antibiótica en las infecciones graves y recurrentes. Para mejorar el pronóstico se debe realizar una atención del paciente por un equipo médico interdisciplinario y un seguimiento continuo por un prolongado periodo de tiempo.


Abstract Immunoglobulin A (IgA) is the most abundant antibody isotype in humans and participates in protection against infections and the development of immune tolerance in mucous membranes. IgA deficiency is the most common immunodeficiency in humans, but it is commonly asymptomatic and transient. To diagnose it, the concentration of IgA in blood is quantified and the magnitude of its decrease is evaluated. According to this evaluation, it is classified as partial deficiency (DPIgA) or total deficiency (DTIgA). Additionally, if only IgA levels are affected without alterations in other serum immunoglobulins such as IgM and IgG or subclasses of IgG, then it is referred to as selective IgA deficiency (DSIgA). Selective IgA deficiency is of greater clinical relevance and considered an innate immunity error, although its etiology is still unknown. This immunodeficiency is clinically associated with respiratory and gas- trointestinal tract infections, allergies and autoimmune manifestations. A search of scientific articles was conducted in bibliographic databases PubMed, Scopus, SciELO and Redalyc on selective immunoglobulin A deficiency. Our objective was to perform a review on clinical manifestations, diagnosis, and appropriate clinical management of patients with this immunodeficiency. A new clinical algorithm is proposed in order to improve the diagnosis and provide adequate clinical management of patients with this immunodeficiency. A patient with selective IgA deficiency is characterized by recurrent infections of the gastrointestinal and respiratory tracts, in association with allergic and autoimmune manifestations in individuals older than four years. Serum IgA levels are less than 7 mg/dL, with normal levels of IgG and IgM, and defects related to T lymphocytes or other causes of hypogammaglobulinemia have been ruled out. Regarding clinical management, vaccination schedules should be adjusted and antibiotic prophylaxis should be implemented in severe and recurrent infections. Additionally, to improve prognosis, patient care should be performed by an interdisciplinary medical team and continuous monitoring for a prolonged period of time.

5.
Rheumatol Int ; 39(4): 707-713, 2019 04.
Article in English | MEDLINE | ID: mdl-30539275

ABSTRACT

The aim of this study was to evaluate the reliability of the outcome measures in rheumatology (OMERACT) definitions for ultrasound (US) elementary lesions in gout through an image reading exercise. Images from patients with gout (static images and videos) were collected. As an initial step, we carried out a image reading exercise within the experts of the Pan-American League of Associations for Rheumatology (PANLAR) US Study Group (n = 16). The following step consisted in a web-based exercise with the participation of larger number of sonographers (n = 63) from different centers. Images were rated evaluating the presence/absence of any US elementary lesion. Inter- and intra-reader reliabilities were analyzed using kappa coefficients. Participants were stratified according to their level of experience. In the first exercise, inter-reader kappa values were 0.45 for aggregates, 0.57 for tophus, 0.69 for erosions, and 0.90 for double contour (DC). Intra-reader kappa values were 0.86, 0.76, 0.80, and 0.90, respectively. The web-based exercise showed inter-reader kappa values for aggregates, tophus, erosions, and DC of 0.42, 0.49, 0.69, and 0.79, respectively. The intra-reader kappa values were 0.62, 0.69, 0.77, and 0.85, respectively. Reliability was not influenced by the sonographer's level of experience. The reliability of the new OMERACT US definitions for elementary lesions in gout ranged from moderate to excellent, depending on the type of lesion.


Subject(s)
Gout/diagnostic imaging , Cross-Sectional Studies , Humans , Reproducibility of Results , Ultrasonography
6.
Lupus ; 27(6): 913-919, 2018 May.
Article in English | MEDLINE | ID: mdl-29301472

ABSTRACT

Objective In this paper, we aim to define factors associated with health-related quality of life (HRQoL) in Mestizo patients with systemic lupus erythematosus (SLE). Methods We evaluated patients with SLE from Peru's two largest hospitals between October 2012 and July 2015 to ascertain HRQoL. Using a standard protocol, we incorporated demographic characteristics, clinical manifestations and treatment in our analysis. HRQoL was measured with the LupusQoL, disease activity was ascertained with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), and damage was appraised with the Systemic Lupus International Collaborating Clinics (SLICC)/American College of Rheumatology (ACR) damage index (SDI). The associations between the LupusQoL and these variables were examined using linear regression models. Model selection was based on backward elimination. Results A total of 277 patients fit the inclusion criterion. Of these, 254 (91.7%) were female, the median (interquartile range, IQR) age at diagnosis was 41.5 (33.8-51.8) years, disease duration was 6.5 (2.7-11.3) years. The HRQoL domains most affected were the following: burden to others, fatigue, and intimate relationships. Through multivariate analysis, we determined that older age at diagnosis, higher disease activity, damage, and immunosuppressive drug use were negatively associated with HRQoL. Further, we found that higher socioeconomic status, disease duration, and antimalarial use were positively associated with HRQoL. Conclusion Age at diagnosis, disease activity, damage, and use of immunosuppressive drugs were negatively associated with HRQoL; high socioeconomic status, disease duration, and use of antimalarials were positively associated with HRQoL.


Subject(s)
Indians, South American/psychology , Lupus Erythematosus, Systemic/psychology , Quality of Life , Adult , Age Factors , Antimalarials/therapeutic use , Cross-Sectional Studies , Female , Humans , Immunosuppressive Agents/therapeutic use , Linear Models , Lupus Erythematosus, Systemic/diagnosis , Lupus Erythematosus, Systemic/drug therapy , Lupus Erythematosus, Systemic/ethnology , Male , Middle Aged , Multivariate Analysis , Peru/epidemiology , Severity of Illness Index , Social Class , Surveys and Questionnaires
7.
San Salvador; s.n; 2018. 114 p. graf.
Thesis in Spanish | BISSAL, LILACS | ID: biblio-1148501

ABSTRACT

Propósito: elaborar una propuesta técnica para mejorar el cumplimiento de la cualificación de los profesionales que proveen atención sanitaria a los pacientes de la Unidad de Cuidados Intensivos Neonatales. Material y Métodos: estudio descriptivo y transversal. Resultados: la Cualificación del Personal Médico es Adecuada con un 100% en Cursos NALS y STABLE. En las Competencias Básicas, el personal Médico y de Enfermería obtuvieron 100%. En las Competencias Específicas, Enfermería obtuvo 20% en Curso NALS y ninguno en STABLE. La Cualificación de Terapia Respiratoria es Inadecuada 30%. En las Instalaciones Físicas, no se tiene en el área, Salida de Emergencia, Señalización ni Sistema de alarma. No se cuenta con lavabos en Aislados. El Equipamiento es Adecuado y cuenta con Normas, Reglamentos y Procedimientos. Conclusiones: el Personal Médico y de Enfermería tienen Normas, Reglamentos y Procedimientos establecidos para la atención que proveen. El Personal de Terapia Respiratoria no cuenta con un Manual de Procedimientos. Por lo tanto, los resultados obtenidos se consideran inadecuados ya que la falta de uno afecta el desempeño del otro. Recomendaciones: elaborar un Plan de Educación Continua de Socialización de la aplicación del Manejo del Neonato y Prematuro Crítico dirigido al personal de Enfermería, involucrando al Personal de Terapia Respiratoria


Subject(s)
Quality of Health Care , Hospital Administration
8.
Clin Rheumatol ; 35(12): 2893-2900, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27576331

ABSTRACT

This study aimed to perform an overview of how ultrasound (US) is being used, implemented, and applied in rheumatologic centers in Latin America (LA). A retrospective, multicenter 1-year experience study was undertaken. Eighteen centers from eight countries were involved. The following information were collected: demographic data, indication to perform an US examination, physician that required the examination, and the anatomical region required for the examination. A total of 7167 patients underwent an US examination. The request for US examinations came most frequently from their own institution (5981 (83.45 %)) than from external referral (1186 (16.55 %)). The services that more frequently requested an US examination were rheumatology 5154 (71.91 %), followed by orthopedic 1016 (14.18 %), and rehabilitation 375 (5.23 %). The most frequently scanned area was the shoulder in 1908 cases (26.62 %), followed by hand 1754 (24.47 %), knee 1518 (21.18 %), ankle 574 (8.01 %), and wrist 394 (5.50 %). Osteoarthritis was the most common disease assessed (2279 patients (31.8 %)), followed by rheumatoid arthritis (2125 patients (29.65 %)), psoriatic arthritis (869 patients (12.1 %)), painful shoulder syndrome (545 (7.6 %)), connective tissue disorders (systemic sclerosis 339 (4.7 %), polymyositis/dermatomyositis 107 (1.4 %), Sjögren's syndrome 60 (0.8 %), and systemic lupus erythematosus 57 (0.8 %)). US evaluation was more frequently requested for diagnostic purposes (3981 (55.5 %)) compared to follow-up studies (2649 (36.9 %)), research protocols (339 (4.73 %)), and invasive guided procedures (198 (2.76 %)). US registered increasing applications in rheumatology and highlighted its positive impact in daily clinical practice. US increases the accuracy of the musculoskeletal clinical examination, influence the diagnosis, and the disease management.


Subject(s)
Rheumatic Diseases/diagnostic imaging , Rheumatology/methods , Ultrasonography/statistics & numerical data , Adolescent , Adult , Aged , Aged, 80 and over , Female , Humans , Latin America , Male , Middle Aged , Referral and Consultation , Retrospective Studies , Young Adult
9.
Rev. chil. reumatol ; 28(2): 101-114, 2012. ilus
Article in Spanish | LILACS | ID: lil-691033

ABSTRACT

Las aspiraciones e infiltraciones son procedimientos muy comunes en reumatología. La eficacia de ambos procedimientos depende de la posición correcta de la aguja dentro o alrededor del blanco elegido. Las intervenciones a ciegas con alta frecuencia son fallidas. La ultrasonografía (US) ha demostrado ser más eficaz y más segura como guía de procedimientos porque evita la lesión de estructuras nerviosas, tendinosas, óseas, etc., al facilitar observar la aguja hasta llegar al blanco. Dirigir una aguja por US hace que el procedimiento sea inocuo, de menor costo que la fluoroscopia o tomografía, con la posibilidad de acudir hasta la cama del paciente con los equipos portátiles. La terapia para infiltraciones no se reduce a los esteroides: actualmente se administra proloterapia, plasma rico en plaquetas, entre otros, para lesiones tendinosas con resultados alentadores. Otra de las ventajas del intervencionismo guiado por US es la realización de biopsias para el diagnóstico certero. En este artículo se hace una revisión de la técnica de infiltración de las diferentes regiones articulares y las ventajas que ofrece la US.


The aspirations and injections are common procedures in rheumatology. The efficacy of both procedures depends on the position of the needle within or around the chosen target. Blind interventions with high frequency are unsuccessful. Ultrasonography (U.S.) has proved more effective and safer procedures as a guide because in prevents injury to neural structures, tendon, bone, etc., to facilitate observing the needle to reach the target. U.S. direct needle makes the procedure is safe, lower cost than fluoroscopy or CT, with the possibility of going to the bedside with portable equipment. Therapy for infiltration is not limited to steroids, is currently given prolotherapy, platelet rich plasma for tendon injuries and others with encouraging results. Another advantage of U.S. interventionism is guided biopsies for diagnosis. In this article we review the technique of infiltration from the different regions and joint benefits of the U.S.


Subject(s)
Humans , Rheumatology/methods , Ultrasonography, Interventional/methods , Biopsy, Needle/methods , Injections
10.
Int Immunol ; 16(4): 585-96, 2004 Apr.
Article in English | MEDLINE | ID: mdl-15039389

ABSTRACT

It has been proposed that infections with helminths can protect from the development of allergic diseases. However, epidemiological and experimental studies have yielded conflicting results. Therefore we investigated if an infection with Nippostrongylus brasiliensis influenced the development of allergen-induced Th2 cell responses in mice. We found a decrease in allergen-induced airway eosinophilia and Eotaxin levels in the airways when mice were infected with the helminths 8 weeks, and especially 4 weeks, but not 1 or 2 weeks before ovalbumin (OVA)-airway challenge. While OVA-specific IgG1 and IgE serum levels and cutaneous hypersensitivity reactions were not reduced by the helminth infection, there was a reduction in OVA-specific IgG1 and IgE levels in bronchoalveolar lavage fluid of mice. Suppression of allergen-induced airway eosinophilia and reduction of Eotaxin production was not observed in IL-10 deficient mice. In addition, we found that helminth-induced airway eosinophilia and Eotaxin production was strongly increased in IL-10 deficient mice infected with the helminths in comparison to control mice. Taken together, these results show that infection with N. brasiliensis suppresses the development of allergen-induced airway eosinophilia and that this effect may be mediated by IL-10. Our results support the view that helminth infections can contribute to the suppression of allergies in humans.


Subject(s)
Allergens/immunology , Helminthiasis, Animal/immunology , Respiratory Hypersensitivity/immunology , Anaphylaxis/immunology , Animals , Bronchial Provocation Tests , Bronchoalveolar Lavage Fluid/chemistry , Bronchoalveolar Lavage Fluid/cytology , Bronchoalveolar Lavage Fluid/immunology , CD4-Positive T-Lymphocytes/cytology , CD4-Positive T-Lymphocytes/immunology , CD4-Positive T-Lymphocytes/metabolism , Cell Count , Cells, Cultured , Chemokine CCL11 , Chemokines, CC/metabolism , Eosinophils/cytology , Helminthiasis, Animal/complications , Immunoglobulin E/analysis , Immunoglobulin E/blood , Immunoglobulin E/metabolism , Immunoglobulin G/analysis , Immunoglobulin G/blood , Immunoglobulin G/metabolism , Inflammation/chemically induced , Inflammation/complications , Inflammation/immunology , Interferon-gamma/metabolism , Interleukin-10/genetics , Interleukin-10/immunology , Interleukin-10/metabolism , Interleukins/metabolism , Lymph Nodes/cytology , Macrophages, Alveolar/cytology , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Mice, Knockout , Nippostrongylus/immunology , Ovalbumin/immunology , Respiratory Hypersensitivity/chemically induced , Respiratory Hypersensitivity/complications , Respiratory System/immunology , Skin Tests , Spleen/cytology , Th2 Cells/cytology , Th2 Cells/immunology , Th2 Cells/metabolism , Vaccination
12.
Int J Med Microbiol ; 293(2-3): 123-31, 2003 Jun.
Article in English | MEDLINE | ID: mdl-12868649

ABSTRACT

The incidence, severity, and mortality rate of allergic diseases, such as asthma, atopic dermatitis and rhinitis is increasing in the developed nations of the world, despite the use of steroids and other drugs. The reason for this development is unknown, but has been speculated to be due to a steady decline in infectious diseases. This view is supported by recent epidemiological and experimental findings showing that bacterial infections have the capacity to inhibit the development of allergic disorders. In addition, the exposure to bacterial products such as lipopolysaccharide (LPS) or bacterial DNA is also associated with a decrease in allergen-specific Th2 responses. Although the immunological mechanisms responsible for these protective effects are ill defined, recent publications indicate that they are associated with the induction of Th1 or T regulatory responses. This review focuses on experimental and epidemiological studies addressing the question if bacterial infections or the exposure to bacterial products can inhibit the development of allergic responses.


Subject(s)
Antigens, Bacterial/immunology , Bacterial Infections/immunology , Hypersensitivity/immunology , Animals , DNA, Bacterial/immunology , Humans , Hypersensitivity/etiology , Listeria monocytogenes/immunology , Mycobacterium bovis/immunology , Mycobacterium tuberculosis/immunology , Th2 Cells/immunology
13.
Clin Diagn Lab Immunol ; 9(3): 727-30, 2002 May.
Article in English | MEDLINE | ID: mdl-11986288

ABSTRACT

Infection with Mycobacterium tuberculosis continues to be one of the major global health threats. Strong mycobacterium-specific Th1 immune responses correlate with protection, and decreased Th1 responses correlate with disease progression. In contrast, the impact of Th2 responses on the development of protective immune responses to mycobacteria remains unclear. To analyze whether ongoing Th2 responses present in the lung influence the development of a protective Th1 immune response to mycobacteria, we coinfected mice with the helminth Nippostrongylus brasiliensis and Mycobacterium bovis BCG. We found that the T cells from the lymph nodes of coinfected mice secreted significantly less gamma interferon than did the T cells from mice infected with M. bovis BCG after in vitro stimulation with purified protein from M. tuberculosis when 10(8) CFU of M. bovis BCG were used for the infection. This result indicates that the helminth infection reduced the Th1 immune response to the mycobacteria in the lung. However, mycobacterial clearance was not delayed in the coinfected animals. Importantly, the infection with BCG after the helminth infection did not reduce the helminth-induced Th2 response in the lung, ruling out the possibility that the lack of a reduction in bacterial clearance in the coinfected mice was due to a downmodulation of the helminth-induced Th2 response. Taken together, our results suggest that ongoing Th2 responses in the lung do not necessarily lead to increased susceptibility to mycobacterial infection.


Subject(s)
Lung/microbiology , Nippostrongylus/immunology , Strongylida Infections/immunology , Th2 Cells/immunology , Tuberculosis/microbiology , Animals , Cells, Cultured , Interferon-gamma/biosynthesis , Interferon-gamma/immunology , Interleukin-10/biosynthesis , Interleukin-10/immunology , Interleukin-4/biosynthesis , Interleukin-4/immunology , Interleukin-5/biosynthesis , Interleukin-5/immunology , Lung/immunology , Mice , Mice, Inbred C57BL , Mycobacterium bovis/immunology , T-Lymphocytes/cytology , T-Lymphocytes/immunology , Th1 Cells/immunology , Tuberculosis/immunology
14.
Acta méd. colomb ; 27(2): 125-133, mar.-abr. 2002. tab, graf
Article in Spanish | LILACS | ID: lil-363465

ABSTRACT

Objetivo: describir las principales características moleculares y de expresión celular de las vías coestimuladoras CD28/CD152 - B7 y CD40 - CD40L, destacando sus propiedades inmunomoduladoras en algunas enfermedades como las causadas por microorganismos intracelulares, el cáncer, las alergias y la autoinmunidad. Fuente de los datos: artículos recopilados por los autores durante su trayectoria investigativa en el área de moléculas coestimuladoras. Además, se consultó la base de datos Pubmed (1990-2001) introduciendo las palabras clave "moléculas coestimuladoras, CD28, CD80, CD86, CD152, CD40, CD154". Selección del estudio: se revisaron 100 artículos de los cuales se seleccionaron 42 cuya información estaba relacionada con los tópicos de interés. Extracción de los datos: los artículos se clasificaron por molécula, subdivididos en revisiones o artículos originales y teniendo en cuenta el modelo experimental utilizado. Síntesis de los datos: la información seleccionada describe cómo la activación de linfocitos T CD4+ específicos de antígeno depende de la expresión y función de componentes de la membrana de las células presentadoras de antígeno y los linfocitos T, algunos de los cuales se denominan "moléculas coestimuladoras". Las interacciones entre dichas moléculas coestimuladoras tales como las de la familia B7 (CD80 y CD86) con CD28 y CD152 o entre las moléculas CD40 y CD40L desempeñan un papel importante en la transmisión de señales intracelulares necesarias para lograr una óptima respuesta inmune a diferentes enfermedades. Conclusión: el desarrollo de ensayos de manipulación de las moléculas coestimuladoras en modelos de enfermedades humanas representa una alternativa inmunoterapéutica


Subject(s)
/immunology , /immunology , Autoimmunity
15.
Infectio ; 5(2): 75-85, jun. 2001. graf
Article in Spanish | LILACS | ID: lil-434510

ABSTRACT

Objetivo: el presente trabajo pretende caracterizar la respuesta inmune desarrollada durante la infección con Leishmania (Viannia) panamensis en individuos no expuestos a esta infección. Población del Estudio y Métodos: las células mononucleares de sangre periférica de 16 individuos sanos Montenegro, se infectaron con promastigotes vivos de L. (V) panamensis. Luego de diferentes tiempos post-infección se analizó por citometría de flujo la expresión de membranas de CD69/CD3-CD4-CD8, CD28 y CD152 y la producción intracelular de IFN gamma IL-12, IL-4 e IL-13. Resultados: el mayor porcentaje de células CD69+ se obtuvo después de 48 horas pos-infección utilizando una proporción célula: parásito de 1:10. Se observó una mayor activación en células CD8+ comparadas con las CD4+ aunque los máximos niveles de activación celular se obtuvieron en células CD3 negativas. Se observó un aumento en la expresión de CD 152 hasta las 120 horas pos-infección. La producción de IL4 e IL-13 intracelulares fué detectada en menos del 1 por ciento de la células infectadas. La mayor producción de IFN-gamma e IL-12 se detecto en un 4 por ciento y un 3 por ciento de las células respectivamente, con una mayor respuesta de las 20 horas pos-infección. Conclusiones: en este estudio se observa como las CMSP de individuos sanos, sin contacto previo con L. (V) panamensis proliferan, se activan, modifican la expresión de moléculas coestimuladoras y producen citoquinas luego de la infección con el parásito. Esta respuesta podría ser debida a un fenómeno de reactividad cruzada con otros antígenos o a la presencia de superantígenos en la suspención de promastigotes utilizada


Subject(s)
In Vitro Techniques , Immunity, Cellular , Leishmania guyanensis/immunology , Immune Tolerance , Leishmaniasis
16.
Med. UIS ; 12(1): 19-23, ene.-feb. 1998. graf
Article in Spanish | LILACS | ID: lil-231998

ABSTRACT

El estudio de péptidos antigémicos candidatos al desarrollo de una vacuna contra la malaria por Plasmodium falciparum, ha mostrado la influencia del complejo mayor de histocompatibilidad humano en la respuesta inmune a determinados epítopes parásitarios. El estudio de la asociación entre el Antígeno Leucocitario Humano-B-53 (HLA) y la protección contra malaria severa ha permitido la caracterización de los péptidos presentados por esta molécula definiendo un epítope reconocido por los linfocitos T citotóxicos de los individuos protegidos. A pesar de que existen muchos hallazgos contradictorios, se sugiere la evaluación de este péptido como componente de una vacuna sintética. Otros hallazgos indican que algunas moléculas HLA clase II modifican la respuesta inmune humoral a antígenos parasitarios específicos mostrándose por ejemplo, una asociación positiva entre los portadores del alelo DQw2 y la respuesta de anticuerpos a la secuencia repetitiva (EENV)6 del antígeno Pf155/RESA o una asociación negativa entre los individuos homocigotos al antígeno HLA-DR4 y la respuesta inmune humoral al péptido sintético Spf66. Es importante estudiar los mecanismos por los cuales operan estas asociaciones para definir nuevos péptidos antigénicos potencialmente protectores, verificar el papel de otros genes cuyo locus está ubicado en la región HLA en el desarrollo de susceptibilidad o de resistencia a la infección y aumentar nuestro conocimiento sobre los procesos de selección natural de las moléculas HLA en las poblaciones considerando que el polimorfismo de estas moléculas ha surgido fundamentalmente por el encuentro con diferentes patógenos


Subject(s)
Humans , Major Histocompatibility Complex/drug effects , Major Histocompatibility Complex/immunology , Major Histocompatibility Complex/physiology , Malaria Vaccines/administration & dosage , Malaria Vaccines/antagonists & inhibitors , Malaria Vaccines/genetics , Malaria Vaccines/immunology , Malaria Vaccines/pharmacokinetics , Malaria Vaccines/pharmacology , Malaria Vaccines/standards , Malaria Vaccines/therapeutic use
17.
Biomédica (Bogotá) ; 17(4): 299-305, dic. 1997. tab, graf
Article in Spanish | LILACS | ID: lil-221234

ABSTRACT

El presente estudio fue diseñado para evaluar la eficacia del diagnóstico serológico del absceso hepático amibiano (AHA). Se utilizó una prueba de Elisa para la detección en suero de IgG específica, utilizando una fase sólida con una alta capacidad de adherencia. Se estudiaron 147 personas; 22 pacientes con sospecha clínica y ultrasonográfica de AH, 30 individuos completamente sanos, 9 portadores asintomáticos de E. histolytica, 35 con colitis amibiana pasada, 35 con otras parasitosis intestinales, 9 con otras patologías hepáticas y 6 con colitis amebiana presente. El rendimiento global de la prueba fue analizado por medio de las curvas del receptor-operador y del área bajo la curva. Se determinó que existe una diferencia significativa en la densidad óptica (DO) de los siete grupos estudiados (Kruskal-Wallis entre todos los grupos: p=0,0001); esta diferencia no existe cuando, al comparar, se elimina el grupo 1 del análisis (Kruskal-Wallis exceptuando el grupo 1: p=0,8203). El área bajo la curva ROC fue igual a 0,9941, dato muy cercano al ideal que es 1. Se recomienda la utilización de esta fase sólida teniendo en cuenta la importancia de la fase de bloqueo con albúmina de huevo. Se determinó que, a pesar de estar en una zona donde el diagnóstico de amebiasis es frecuente, las infecciones intestinales por esta ameba no presentan niveles detectables de IgG específica contra E. histolytica por esta prueba. Sin embargo, es importante ampliar la cantidad de personas estudiadas en estos grupos, principalmente, en el grupo de pacientes con otras patologías hepáticas puesto que este grupo incluye las entidades clínicas con las que realmente se debe hacer diagnóstico diferencial de (AHA) (absceso hepático piógeno (AHP), principalmente) para poder realizar la última fase de la evaluación. El estudio de este grupo nos ayudaría a obtener valores reales de sensibilidad, especificidad y valores predictivos y nos darían una estimación real de la capacidad discriminatoria de la prueba para obtener el verdadero valor del área bajo la curva y no el casi ideal que informamos aquí


Subject(s)
Humans , Liver Abscess, Amebic/diagnosis , Serologic Tests
18.
Med. UIS ; 9(3): 116-20, jul.-sept. 1995. tab
Article in Spanish | LILACS | ID: lil-232086

ABSTRACT

INTRODUCCION: El curso de un Absceso Hepático Amebiano (AHA) con tratamiento adecuado presenta una etapa aguda con niveles altos de IgG, IgM, IgA, IgE y respuesta de hipersensibilidad retardada específica negativa, y una etapa de recuperación IgM, IgE e IgA no detectables y respuesta de hipersensibilidad retardada positiva; la IgG continúa positiva por largos períodos de tiempo. Existen muchas evidencias de que la protección en AHA es mediada por la respuesta inmune celular. En la etapa aguda predomina una respuesta humoral probablemente no protectora y en la fase de recuperación una respuesta celular protectora. En este estudio se pruebe la hipótesis de que la severidad del absceso es directamente proporcional al grado de respuesta inmune humoral. MATERIALES Y METODOS: Se estudiaron 10 pacientes con diagnóstico clínico, ecográfico y serológico compatible con AHA, tratados con metronidazol 750 mg/día vía oral por 15 días. Se determinió el tamaño del absceso, velocidad de sedimentación globular, niveles de bilirrubina, transaminasas, fosfatasa alcalina e IgG. Luego se realizaron análisis de regresión lineal relacionando los niveles de IgG con los indicadores clásicos de severidad en AHA (tamaño del absceso, niveles de transaminasas y bilirrubina). RESULTADOS: Los niveles de IgG estuvieron significativamente asociados con: Tamaño del absceso (P=0.0248), ALT (P=0.033) y bilirrubina indirecta (P=0.05); se observó una tendencia de correlación, aunque sin significancia estadística, con la AST (P=0.1529). El tamaño del absceso se correlacionó directamente con el tiempo de evolución (P=0.018); la AST (R=0.595, P=0.210) y ALT (R=0.761, P=0.135) se correlacionaron inversamente. Las diferencias entre los pacientes crónicos y agudos no fueron estadísticamente significativas para la ALT (P=0.0710) y AST (P=0.213). CONCLUSION: La respuesta humoral parece no tener efecto protector en AHA y los niveles de anticuerpos pudieran ser un buen indicador de severidad


Subject(s)
Humans , Liver Abscess, Amebic/diagnosis , Liver Abscess, Amebic/immunology , Liver Abscess, Amebic/microbiology
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