Estudio de la formación de las células espumosas en el actinomicetoma experimental

El presente artículo está basado en la investigación “Estudio de la formación de las células espumosas en el actinomicetoma experimental inducido por Nocardia brasiliensis”, galardonada con el Premio de Investigación UANL 2013, en la categoría de Ciencias de la Salud, otorgado en sesión solemne del Consejo Universitario, en septiembre de 201

Los extractos de Mycobacterium tuberculosis inducen la producción selectiva de citocinas inflamatorias y receptores de membrana

Antecedentes: en la etapa inicial de la tuberculosis aumenta la concentración de citocinas inflamatorias, mientras que las Th1 y Th2 se producen después de activarse las células T. Los receptores CD14, CD64, CD206 y TLR4 participan en la respuesta contra patógenos intracelulares. Objetivo: analizar las fracciones de Mycobacterium tuberculosis que estimulan la expresión de CD14, CD64, CD206 y TLR4, y su influencia en la producción de IL-1β, IL-2, IL-4, IL-10, TNF-α e IFN-γ. Pacientes y métodos: se estimularon células mononucleares de sangre venosa periférica de voluntarios sanos PPD-positivos a M. tuberculosis con: a) bacterias completas, b) proteínas secretoras-excretoras de la bacteria, c) extracto proteínico, d) extracto lipídico y e) extracto de polisacáridos. Las citocinas del sobrenadante se cuantificaron mediante ELISA y las moléculas de superficie se analizaron por citometría de flujo. Resultados: las bacterias completas estimularon la expresión de CD14 y CD206 y la producción de IFN-γ, IL-1β e IL-2. El extracto proteínico estimuló la expresión de CD14, CD206 y TLR4 y la producción de IFN-g, TNF-α, IL-1β e IL-2. El extracto lipídico influyó en la expresión de CD14, CD206 y en la producción de IFN-γ. El extracto polisacárido estimuló la producción de IL-10 e IFN-γ. Las proteínas secretoras-excretoras estimularon la producción de IFN-γ e IL-2. Conclusiones: los extractos proteínicos y de polisacáridos de M. tuberculosis estimulan la producción de importantes citocinas inflamatorias y la expresión de receptores en la membrana de fagocitos mononucleares para modular el sistema inmunitario del hospedero

Proteína C reactiva, marcador inflamatorio asociado con ANCA en tuberculosis pulmonar

Antecedentes: la proteína C reactiva es uno de los marcadores inflamatorios denominados “reactantes de fase aguda” que se produce en el hígado en respuesta a procesos infecciosos o inflamatorios. En los pacientes con tuberculosis se ha descrito la formación de anticuerpos anticitoplasma de neutrófi los (ANCA). Objetivo: determinar la concentración de proteína C reactiva, evaluar su comportamiento como marcador de la respuesta inflamatoria y analizar su correlación con los ANCA en los pacientes con tuberculosis pulmonar, antes y después de iniciar el tratamiento antifímico. Pacientes: se eligieron pacientes con sospecha de tuberculosis pulmonar. Una vez confirmado el diagnóstico, se obtuvieron las muestras de suero para analizar los datos clínicos y de laboratorios. La determinación de ANCA se realizó con estuches comerciales de inmunofluorescencia y la de proteína C reactiva con ELISA, antes y después de iniciar el tratamiento antifímico. Resultados: se obtuvieron 50 muestras de suero de pacientes con tuberculosis pulmonar. En la primera (94%) y segunda obtención (90%) de los sueros se registró un valor de proteína C reactiva menor de 5 mg/L. El valor promedio de proteína C reactiva fue de 3.05 ± 8.27 mg/L en la primera muestra y de 4.49 ± 11.2 mg/L en la segunda (p = 0.46). Los pacientes positivos a ANCA tuvieron valores más altos de proteína C reactiva en su segunda muestra (p = 0.001). Discusión: existe una asociación entre la proteína C reactiva y la producción de anticuerpos anticitoplasma de neutrófilos en un subgrupo de pacientes con tuberculosis pulmonar. Su significación es incierta, pero quizá desempeñan alguna función patogénica en la respuesta inflamatoria pulmonar

MASTer cell: chief immune modulator and inductor of antimicrobial immune response

Mast cells have long been recognized for their involvement in allergic pathology through the immunoglobulin E (IgE)-mediated degranulation mechanism. However, there is growing evidence of other “non-canonical” degranulation mechanisms activated by certain pathogen recognition receptors. Mast cells release several mediators, including histamine, cytokines, chemokines, prostaglandins, and leukotrienes, to initiate and enhance inflammation. The chemical nature of activating stimuli influences receptors, triggering mechanisms for the secretion of formed and new synthesized mediators. Mast cells have more than 30 known surface receptors that activate different pathways for direct and indirect activation by microbes. Different bacterial strains stimulate mast cells through various ligands, initiating the innate immune response, which aids in clearing the bacterial burden. Mast cell interactions with adaptative immune cells also play a crucial role in infections. Recent publications revealed another “non-canonical” degranulation mechanism present in tryptase and chymase mast cells in humans and connective tissue mast cells in mice, occurring through the activation of the Mas-related G protein–coupled receptor (MRGPRX2/b2). This receptor represents a new therapeutic target alongside antibiotic therapy. There is an urgent need to reconsider and redefine the biological role of these MASTer cells of innate immunity, extending beyond their involvement in allergic pathology

Nocardia brasiliensis Induces Formation of Foamy Macrophages and Dendritic Cells In Vitro and In Vivo

Foamy cells have been described in various infectious diseases, for example in actinomycetoma induced by Nocardia brasiliensis. These cells are generally considered to be macrophages, although they present dendritic cell (DC)-specific surface markers. In this study, we determined and confirmed the lineage of possible precursors of foamy cells in vitro and in vivo using an experimental actinomycetoma model in BALB/c mice. Bone marrow-derived macrophages (BMDM) or DC (BMDC) were infected in vitro with N. brasiliensis or labeled with carboxyfluorescein diacetate succinimidyl ester (CFSE). Both, macrophages and DC, differentiated into foamy cells after in vitro infection. CFSE-labeled BMDM or BMDC were tested for phagocytosis and CD11c/CD11b receptors markers expression before being transferred into the actinomycetoma lesion site of infected mice. In vivo studies showed that BMDM and BMDC were traced at the site where foamy cells are present in the experimental actinomycetoma. Interestingly, many of the transferred BMDM and BMDC were stained with the lipiddroplet fluorophore Nile Red. In conclusion, macrophages and DC cells can be differentiated into foamy cells in vitro and in vivo during N. brasiliensis infection

A negative pressure device for the treatment of diabetic foot.

Background: We studied the use of a negative pressure device designed by one of the authors (JATB) to determine if it shortens healing time and lowers the amputation level in patients with diabetic foot. Methods: Twenty-two patients in two randomized groups were studied. The characteristics of the ulcer according to the Wagner classification, superficial and deep sensitivity, and the status of the pulses were documented. In group 1, the control group, conventional treatment was used. Group 2, the experimental group, was also treated conventionally but a negative pressure device was added. The wounds were treated until healed or for one year. A statistical analysis was carried out with parametric tests that compared the evolution of the ulcer and the amputation level in both groups. Results: The ulcer closed by one year of follow-up in ten patients from each group, representing 90.9% of the patients. A statistically significant difference was not observed between the groups. Conclusions: After one year of evolution, a statistically significant difference in ulcer healing was not found in either group

Mycetoma Medical Therapy

Medical treatment of mycetoma depends on its fungal or bacterial etiology. Clinically, these entities share similar features that can confuse diagnosis, causing a lack of therapeutic response due to inappropriate treatment. This review evaluates the response to available antimicrobial agents in actinomycetoma and the current status of antifungal drugs for treatment of eumycetoma

Low dose of sublingual immunotherapy in patients with allergic rhinitis in a randomized double-blind placebocontrolled study

Background: Few placebo controlled studies for sublingual immunotherapy (SLIT) have been performed so far in Latin America, and some issues like treatment scheme and doses remain uncertain Objective: to asses improvement in nasal, pharyngeal and ocular symptoms with low doses of SLIT to Dermatophagoides pteronyssinus comparing it with a placebo, in a Mexican population with allergic rhinitis (AR). Methods: a prospective, double-blind placebo-controlled, randomized study, with 32, patients with chronic, moderate to severe AR; 16 patients were treated with SLIT and 16 with placebo for 6 months with a total dose of D. pteronyssinus (Der p1) of 50.4 mcg. Nasal, pharyngeal and ocular symptoms were monitored using a symptoms diary to evaluate the degree of improvement and reduction in the use of medication. Results: Significant lower symptom and drug scores were found in SLIT group where 85% of patients showed clinical improvement. On the placebo group, 24% of patients improved and 76% had no response or worsened; 94% of patients on SLIT required less symptomatic medication compared with the placebo group. There was a reduction in positivity to cutaneous test to D. pteronyssinus in 50% of the patients on SLIT, whereas placebo patients remained all positiv

Do immunoglobulin G and immunoglobulin E anti- l -asparaginase antibodies have distinct implications in children with acute lymphoblastic leukemia? A cross-sectional study

Background: l-Asparaginase is essential in the treatment of childhood acute lymphoblastic leukemia. If immunoglobulin G anti-l-asparaginase antibodies develop, they can lead to faster plasma clearance and reduced efficiency as well as to hypersensitivity reactions, in which immunoglobulin E can also participate. This study investigated the presence of immunoglobulin G and immunoglobulin E anti-l-asparaginase antibodies and their clinical associations. Methods: Under 16-year-old patients at diagnosis of B-cell acute lymphoblastic leukemia confirmed by flow cytometry and treated with a uniform l-asparaginase and chemotherapy protocol were studied. Immunoglobulin G anti-l-asparaginase antibodies were measured using an enzyme-linked immunosorbent assay. Intradermal and prick skin testing was performed to establish the presence of specific immunoglobulin E anti-l-asparaginase antibodies in vivo. Statistical analysis was used to investigate associations of these antibodies with relevant clinical events and outcomes. Results: Fifty-one children were studied with 42 (82.35%) having anti-l-asparaginase antibodies. In this group immunoglobulin G antibodies alone were documented in 10 (23.8%) compared to immunoglobulin E alone in 18 (42.8%) patients. Immunoglobulin G together with immunoglobulin E were simultaneously present in 14 patients. Children who produced exclusively immunoglobulin G or no antibodies had a lower event-free survival (p-value = 0.024). Eighteen children (35.3%) relapsed with five of nine of this group who had negative skin tests suffering additional relapses (range: 2–4), compared to none of the nine children who relapsed who had positive skin tests (p-value < 0.001). Conclusion: Children with acute lymphoblastic leukemia and isolated immunoglobulin G anti-l-asparaginase antibodies had a higher relapse rate, whereas no additional relapses developed in children with immunoglobulin E anti-l-asparaginase antibodies after the first relapse