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Objetivos: Describir las afecciones dermatológicas más frecuentes en los pacientes con la COVID-19 y precisar si su presencia puede ser utilizada para establecer un diagnóstico temprano o para predecir la evolución de la infección. Métodos: Se realizó una revisión en PubMed/MEDLINE y EMBASE de todos los artículos publicados entre enero 1 y noviembre 1 de 2020, con los términos de la búsqueda centrados en “SARS-CoV-2”, “COVID-19” y “Enfermedades cutáneas”. Resultados: Cumplieron los criterios de inclusión 83 estudios. Lesiones de la piel han sido reportadas en 0.2 % de los pacientes. Las erupciones maculopapulares/morbiliformes, la urticaria y el angioedema, el patrón acral parecido a sabañones y las lesiones vesiculares fueron las dermatosis más frecuentemente informadas. Existen diferencias de opinión entre los investigadores, acerca de un posible valor diagnóstico o pronóstico de las afecciones cutáneas asociadas con la infección. Conclusiones: Es recomendable considerar el diagnóstico de la infección por SARS-CoV-2 en pacientes que consultan por presentar lesiones cutáneas, urticaria o angioedema con o sin otros síntomas de la infección y en especial si existe algún antecedente de exposición reciente a otros sujetos infectados.

Introduction Pollens are an important source of allergens that trigger rhinitis or asthma. The allergenic extracts of pollens used to diagnose and treat allergies contain different allergenic antigens. Isolated allergenic proteins are employed in in vitro assays, skin tests and allergenic-specific immunotherapy. Calcium-binding allergens are clinically relevant antigens, and their allergenicity can be affected by Ca2+ binding. In this work, a calmodulin was identified as an allergen from Amaranthus palmeri pollen, an important source of pollinosis in Europe, Asia and North America. Materials and methods Allergenic calmodulin from A. palmeri pollen was isolated by size-exclusion chromatography and reverse-phase chromatography and identified by mass spectrometry. Sensitization to isolated calmodulin was evaluated by skin prick tests in patients with allergy to A. palmeri pollen. Results Size-exclusion chromatography yielded two fractions that were recognized by the IgE of patients allergic to A. palmeri pollen. Mass spectrometry analysis of the fractions from reverse-phase chromatography showed peptide sequences that identified a calmodulin. Skin prick tests showed that the isolated calmodulin was recognized by 56% of patients allergic to A. palmeri pollen. Conclusion A. palmeri pollen calmodulin could be a clinically relevant allergen in patients sensitized to this source.

"Antecedentes : la urticaria crónica espontánea es una enfermedad común en los adultos, sobre todo entre las mujeres; esta entidad con frecuencia está relacionada con padecimientos autoinmunitarios. Objetivo : evaluar, mediante estudios de laboratorio, si los pacientes con urticaria crónica espontánea tuvieron signos de autoinmunidad. Material y método : estudio transversal de 35 pacientes del área de Alergia e Inmunología del Hospital Juárez de México, diagnosticados con urticaria crónica espontánea. Se les realizó biometría hemática completa, anticuerpos antitiroideos (antiperoxidasa y tiroglobulina), anticuerpos antinucleares, factor reumatoide, anticoagulante lúpico, células LE, prueba cutánea de suero autólogo ( Autologus Serum Skin Test , ASST), complemento (C3 y C4); como estudios adicionales se les realizó prueba de Helicobacter pylori , perfil tiroideo (T3,T4, TSH) y dímero D. Resultados : evaluamos 35 pacientes adultos, 27 eran mujeres. La prueba ASST fue positiva en cuatro pacientes, los anticuerpos antinucleares fueron negativos en todos los casos, pero los anticuerpos antitiroideos resultaron positivos en cuatro pacientes. Las células LE, anticoagulante lúpico, complemento, dímero D, perfil tiroideo y Helicobacter pylori fueron normales o negativos y el factor reumatoide fue positivo en un paciente. Todos los pacientes antitiroideos positivos eran mujeres y de ellas, 26 tuvieron ASST negativa. La correlación entre ASST y AAT no fue significativa. Conclusiones : en nuestro estudio, la mayoría de los pacientes con urticaria crónica espontánea eran mujeres y sólo cuatro tuvieron la prueba ASST positiva, pero esto no se correlaciona con existencia de anticuerpos antitiroideos. La mayor parte de los estudios realizados resultaron normales, por lo que sugerimos no hacer estudios de labo - ratorio innecesarios en esta afección."

Existen cuatro tipos de receptores histaminérgicos. Los síntomas de alergia, especialmente rinoconjuntivitis alérgica y urticaria, son principalmente causados por activación del receptor H1; por ende, los antihistamínicos H1 orales (anti-H1) forman parte integral del tratamiento de estas enfermedades. Los antihistamínicos son agonistas inversos, porque estabilizan la forma inactiva del receptor. Los antihistamínicos H1 de primera generación producen efectos adversos por varios mecanismos: sedación (fijación a receptores H1 cerebrales), boca seca, retención urinaria, aumento de peso (baja selectividad: estimulación de los receptores de serotonina, muscarina y alfa-adrenérgicos) e interacciones medicamentosas (con sustrato de citocromo P450-3A4). Los antihistamínicos H1 de segunda generación son generalmente más seguros. Las nuevas guías de tratamiento de la rinitis alérgica y urticaria recomiendan como manejo de primera intención a los antihistamínicos H1 de segunda generación. En urticaria se recomienda hasta cuadruplicar su dosis en caso necesario. El aumento de la eficacia en el control de la urticaria con cuádruple dosis, sin que se afecte la seguridad, se ha documentado para bilastina, desloratadina y levocetirizina (rupatadina). Respecto de ebastina y fexofenadina, hasta ahora, sólo se comprobó la seguridad de cuádruple dosis. Una rigurosa excepción son astemizol y terfenadina, que a concentraciones séricas elevadas pueden causar taquicardia ventricular. No se recomiendan los antihistamínicos H1 de primera generación y aumentar su dosis no es seguro.

This article reviews biologic treatments that are currently applied for the treatment of severe chronic urticaria. Monoclonal anti-immunoglobulin E (omalizumab) is effective and safe in many patients, but accessibility and cost constitute barriers to its wider use. Questions on the optimal duration of the treatment and possible symptom recurrences after discontinuing the drug are still raised. A discussion is presented about several other biologics currently under investigation with potential to be incorporated in the near future in patients with severe chronic urticaria.

This update and revision of the international guideline for urticaria was developed following the methods recommended by Cochrane and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) working group. It is a joint initiative of the Dermatology Section of the European Academy of Allergology and Clinical Immunology (EAACI), the Global Allergy and Asthma European Network (GALEN) and its Urticaria and Angioedema Centers of Reference and Excellence (UCAREs and ACAREs), the European Dermatology Forum (EDF; EuroGuiDerm), and the Asia Pacific Association of Allergy, Asthma and Clinical Immunology with the participation of 64 delegates of 50 national and international societies and from 31 countries. The consensus conference was held on 3 December 2020. This guideline was acknowledged and accepted by the European Union of Medical Specialists (UEMS). Urticaria is a frequent, mast-cell-driven disease that presents with wheals, angioedema, or both. The lifetime prevalence for acute urticaria is approximately 20%. Chronic urticaria, i.e. chronic spontaneous urticaria and chronic inducible urticaria, is disabling, impairs quality of life, and affects performance at work and school. This updated version of the international guideline for urticaria covers the definition and classification of urticaria and outlines expert-guided and evidence-based diagnostic and therapeutic approaches for the different subtypes of urticaria. This article is protected by copyright. All rights reserved.

Background Mechanical ventilators are essential biomedical devices for the respiratory support of patients with SARS-CoV-2 infection. These devices can be transmitters of bacterial pathogens. Therefore, it is necessary to implement effective disinfection procedures. The aim of this work was to show the impact of the modification of a cleaning and disinfection method of mechanical ventilators of patients with SARS-CoV-2 and ventilator-associated pneumonia. Methods A total of 338 mechanical ventilators of patients infected with SARS-CoV-2 and ESKAPE bacteria were divided in two groups. Group A and B were subjected to cleaning and disinfection with superoxidation solution-Cl/enzymatic detergent and isopropyl alcohol, respectively. Both groups were cultured for the detection of ESKAPE bacteria. The isolates were subjected to tests for identification, resistance, adherence, and genomic typing. Results Contamination rates of 21.6% (n = 36) were identified in group A. The inspiratory limb was the circuit involved in most cases of postdisinfection contamination. Acinetobacter baumanni, Pseudomonas aeruginosa, and multi-resistant Klebsiella pneumoniae were the pathogens involved in the contamination cases. The pathogens were highly adherent and in the case of A. baumanni, clonal dispersion was detected in 14 ventilators. Disinfection with enzymatic detergents allows a 100% reduction in contamination rates. Conclusions The implementation of cleaning and disinfection with enzymatic detergents/isopropyl alcohol of mechanical ventilators of patients with SARS-CoV-2 and ESKAPE bacteria had a positive impact on postdisinfection microbial contamination rates.

La pandemia actual de COVID-19 ha representado un reto mayúsculo para la sociedad y la comunidad médica, no solo por su alta contagiosidad sino por la variabilidad de las manifestaciones clínicas y su comportamiento impredecible bajo diferentes contextos sanitarios. Ante ello, las medidas preventivas específicas son relevantes para evitar o disminuir contagios entre pacientes y personal de las unidades de salud, considerando que el periodo presintomático durante el cual el individuo contagiado ya puede transmitir el virus varía entre cinco y seis o hasta 14 días, según datos de la Organización Mundial de la Salud. Además, un paciente infectado puede estar asintomático, incluso, algunas personas después de haber padecido COVID-19 pueden continuar expulsando virus por algunos días más después de recuperarse.

Antecedentes: En México, la inmunoterapia con alérgenos (ITA) y con veneno de himenópteros (VIT) se practica tradicionalmente combinando criterios de las escuelas europea y estadounidense; los dos tipos de extractos están comercialmente disponibles en México. Para una ITA adecuada es crucial un diagnóstico oportuno.Objetivo: Presentar GUIMIT 2019, Guía Mexicana de Inmunoterapia 2019, de base amplia, actualizada, que abarca temas de diagnóstico, indicaciones, dosificación, mecanismos, efectos adversos de la ITA y expectativas con esta modalidad de tratamiento.Método: Con la participación de múltiples grupos mexicanos de alergólogos, que incluían los centros formadores universitarios en alergia e inmunología, se desarrolló el documento de la guía según la metodología ADAPTE. Las guías de inmunoterapia de la European Academy of Allergy and Clinical Immunology, The American Academy of Allergy, Asthma and Immunology, German Society for Allergology and Clinical Immunology y del American College of Allergy, Asthma, and Immunology se seleccionaron como guías fuente, ya que recibieron la puntuación AGREE-II más alta entre las guías internacionales disponibles; su evidencia conforma la base científica de GUIMIT 2019.Resultados: En GUIMIT 2019 se emiten recomendaciones fuertes o débiles (sugerencias) acerca de temas directamente relacionados con el diagnóstico in vivo o in vitro de las enfermedades alérgicas mediadas por IgE, la preparación y aplicación de ITA o VIT y sus efectos adversos; se incluye la revisión de las modalidades de ITA para el futuro. Todos los argumentos que se exponen fueron discutidos y votados con > 80 % de aprobación.Conclusión: Un grupo amplio y diverso de expertos en ITA y VIT emitió recomendaciones transculturizadas basadas en evidencia, que alcanzaron consenso; con ellas se pretende mejorar y homologar la práctica de la inmunoterapia en México.

Background:Both, allergen immunotherapy (AIT) and SARS-COV-2 infection cause a set of immunologic changes that respectively vary during the course of the treatment or the disease.Objective:To review immune changes brought along by each of these entities and how they might interrelate.Methods:We start presenting a brief review of the structure of the new coronavirus and how it alters the functioning of the human immune system. Subsequently, we describe the immune changes induced by AIT and how these changes could be favorable or unfavorable in the allergic patient infected with SARS-CoV-2 at a particular point of time during the evolving infection.Results:We describe how a healthy immune response against SARS-CoV-2 develops, versus an immune response that is initially suppressed by the virus, but ultimately overactivated, leading to an excessive production of cytokines (cytokine-storm-like). These changes are then linked to the clinical manifestations and outcomes of the patient. Reviewing the immune changes secondary to AIT, it becomes clear how AIT is capable of restoring a healthy innate immunity. Investigators have previously shown that the frequency of respiratory infections is reduced in allergic patients treated with AIT. On the other hand it also increases immunoregulation.Conclusion:As there are many variables involved, it is hard to predict how AIT could influence the allergic patient's reaction to a SARS-CoV-2 infection. In any case, AIT is likely to be beneficial for the patient with allergic rhinitis and/or allergic asthma in the context of the SARS-CoV-2 pandemic as controlling allergic diseases leads to a reduced need for contact with healthcare professionals. The authors remind the reader that everything in this article is still theoretical, since at the moment, there are no published clinical trials on the outcome of COVID-19 in allergic patients under AIT.

Introduction In light of the current COVID-19 pandemic, during which the world is confronted with a new, highly contagious virus that suppresses innate immunity as one of its initial virulence mechanisms, thus escaping from first-line human defense mechanisms, enhancing innate immunity seems a good preventive strategy. Methods Without the intention to write an official systematic review, but more to give an overview of possible strategies, in this review article we discuss several interventions that might stimulate innate immunity and thus our defense against (viral) respiratory tract infections. Some of these interventions can also stimulate the adaptive T- and B-cell responses, but our main focus is on the innate part of immunity. We divide the reviewed interventions into: 1) lifestyle related (exercise, >7 h sleep, forest walking, meditation/mindfulness, vitamin supplementation); 2) Non-specific immune stimulants (letting fever advance, bacterial vaccines, probiotics, dialyzable leukocyte extract, pidotimod), and 3) specific vaccines with heterologous effect (BCG vaccine, mumps-measles-rubeola vaccine, etc). Results For each of these interventions we briefly comment on their definition, possible mechanisms and evidence of clinical efficacy or lack of it, especially focusing on respiratory tract infections, viral infections, and eventually a reduced mortality in severe respiratory infections in the intensive care unit. At the end, a summary table demonstrates the best trials supporting (or not) clinical evidence. Conclusion Several interventions have some degree of evidence for enhancing the innate immune response and thus conveying possible benefit, but specific trials in COVID-19 should be conducted to support solid recommendations.

Antecedentes: Existe incremento de reacciones adversas a medicamentos y pocos estudios para el diagnóstico.Objetivo: Determinar la utilidad de pruebas modificadas de degranulación de basófilos (DB) y del factor inhibidor de la migración de leucocitos (LIF, leukocyte migration inhibition factor) para comprobar la hipersensibilidad a medicamentos.Métodos: Se estudiaron 177 pacientes, de uno y otro sexo, con diagnóstico de hipersensibilidad a medicamentos, en quienes se determinó pruebas modificadas de DB, LIF, o ambas entre 2009 y 2014. Se parearon con controles positivos, negativos y población no alérgica. Las solicitudes se emitieron de acuerdo con el tipo de hipersensibilidad, considerando tipo I a DB y tipo IV a LIFResultados: 170 pacientes (96.04%) fueron positivos al menos a un medicamento (RR, 4.71). Se realizaron 561 pruebas modificadas de DB (73.62%) y 201 de LIF (26.37%). El sexo femenino fue más frecuente (64.41%); la edad promedio fue de 38.5 años. La prueba modificada de DB resultó positiva en 70.23% y la de LIF en 67.16%. La sensibilidad de las pruebas se incrementó en forma complementaria y a dos diluciones. La correlación de las pruebas fue altamente significativa.Conclusiones: Las mujeres presentan más reacciones a fármacos. La prueba modificada de DB es útil en cualquier edad. Como los medicamentos pueden activar uno u otro mecanismo de hipersensibilidad es importante solicitar las pruebas simultáneamente.

Introducción: El factor de transferencia (FT) es el extracto dializable de leucocitos con propiedades de transferencia de inmunidad celular. Su uso se ha extendido en el tratamiento de una amplia gama de padecimientos inmunológicos, infecciosos y como coadyuvante de padecimientos oncológicos. A pesar de ello, no se conocen completamente aspectos importantes de su perfil proteico, concentraciones de componentes y mecanismos de acción.Objetivos: Analizar los perfiles proteicos de diferentes factores de transferencia comercializados en México.Métodos: Se obtuvieron y analizaron 6 FT comercializados en México. Se realizó la cuantificación de proteínas por el método de Bradford, cromatografía líquida de alta resolución (HPLC) y electroforesis en geles de poliacrilamida (SDS-PAGE). Todas las muestras fueron analizadas por duplicado.Resultados: Las concentraciones de proteínas totales de todos los FT analizados fueron menores de 0.2 mg/mL. Los perfiles cromatográficos mostraron diferencias en algunos FT. La concentración de proteínas resultó de 6 hasta casi mil veces más baja en comparación con lo informado por algunos fabricantes.Conclusión: Casi la totalidad de los factores de transferencia comercializados en México carecen de un etiquetado y registro sanitario que cumpla con las normas oficiales vigentes.

Background: Urticaria is a disease that a fth of the population shall suffer once in a lifetime. Recent clinical guidelines have proposed some fundamental changes in the diagnosis and treatment of urticaria, making the development of a national, multidisciplinary guideline, with wide acceptability among different professional groups –both specialists and primary health care workers–, necessary in Mexico. Material and method: Internationally recognized tools for guideline- development were used. An interdisciplinary group of clinical experts (some of them knowledgeable in methodology of guideline develop - ment) determined the objectives and scope of the Evidence Based Clinical Practice Guideline with SCOPE. It was decided to adapt and transculturize international guidelines on the diagnosis and treatment of urticaria. With AGREE-II three high-quality guidelines (Zuberbier 2014, Sanchez-Borges 2012, Powell 2007) were selected to function as basic guidelines (BG). A set of Clinical Questions was formulated that lead to recommendations/suggestions, based on these BG, taking into account the cultural and economic background of Mexico, according to GRADE recommendation development. Results: By a formal process of discussion and voting during several working-sessions, experts and rst level healthcare physicians deter - mined the wording of the nal guideline, taking particularly care of developing a document, adjusted to the reality, values and preferences of the Mexican patients. The use of oral second generation, non-sedating antihistamines as rst line treatment is emphasized. Conclusion: This document is an Evidence Based Clinical Practice Guideline for the diagnosis and treatment of acute and chronic urticaria, based on three, high quality, international guidelines. It was developed by a multidisciplinary group. Tables and algorithms make the guideline user-friendly for both, rst line health care physicians and specialists

Background Laboratory testing of various diagnostic extracts has shown lower potencies for several European and Mexican extracts relative to the US Food and Drug Administration (FDA) reference (10,000 BAU/mL). Quantitative skin prick testing (QSPT) with Dermatophagoides pteronyssinus extracts have previously shown a similar picture. Objective To compare European and Mexican Bermuda grass (BG) and cat diagnostic extracts against an FDA-validated extract using QSPT. Methods Six diagnostic BG and cat extracts (1 reference FDA extract, 3 European extracts, 1 imported nonstandardized extract from the United States, and 1 Mexican extract) were tested with quadruplicate QSPT, as a concentrate and as 2 serial 2-fold dilutions, in cat and BG allergic individuals. Results BG showed good dose response in wheal size for the concentrate (1:2–1:4 dilutions; steep part of the curve). Cat showed poorer dose response. The Wilcoxon test for linked random samples was used to investigate whether the distribution of the reference differed from each of the test extracts to a statistically significant degree (2-sided asymptotic significance, α = .05). All BG and 2 cat extracts were statistically less potent than the 10,000 BAU/mL US reference. European BG extracts were 7,700, 4,100, and 1,600 BAU/mL, and cat extracts were 12,500, 4,400, and 5,100 BAU/mL. Conclusions The potency of some diagnostic extracts of BG and cat used in Europe, Mexico, and the United States differs, with the US extracts being generally more potent. On the basis of provocation tests, optimal diagnostic concentrations should be determined. Similar comparisons using other manufacturers and therapeutic extracts might be interesting.

Despite the use of newer immunosuppressors such as sirolimus (SRL) and tacrolimus (TRL) in heart transplantation, the rate of humoral rejection has remained unchanged. The aim of this study was to analyze the immunologic and histologic effects of cyclosporine (CsA), SRL, and TRL in a porcine model of arterial transplantation.Each transplant recipient animal (n = 49) received an autograft and an allograft and was then allocated to one of four treatment groups and a 7- or 30-day follow-up period, as follows: a WOT group (without immunosuppressor treatment), 7 days (n = 6) and 30 days (n = 5); a CsA group, 7 days (n = 5) and 30 days (n = 6); an SRL group, 7 days (n = 7) and 30 days (n = 8); and a TRL group, 7 days (n = 6) and 30 days (n = 6). The presence of donor-specific antibodies (DSA) was tested at the end of the follow-up period. Morphometric parameters and inflammatory infiltration were analyzed in the explanted grafts.At 30-day follow-up, SRL was the only treatment capable of suppressing DSA formation (0 of 7 vs 4 of 5 in the WOT group; p0.05). SRL completely prevented aneurismal dilation and reduced the number of macrophages in the allografts. TRL treatment achieved a greater reduction of T lymphocytes. CsA did not prevent the reduction in total vascular area at 7 days that was achieved with the SRL and TRL groups. Animals treated with CsA had the largest number of T lymphocytes and macrophages in both follow-up periods.SRL prevented DSA formation and reduced the number of macrophages as compared with TRL and CsA.

Background In liver transplantation, mycophenolate mofetil (MMF) is habitually administered using fixed doses. We assessed whether mycophenolic acid (MPA) monitoring could be advisable in liver transplant patients. Methods In 15 liver transplant patients receiving tacrolimus, daclizumab and MMF (1 g bid, orally), we determined the 12-hour plasma MPA pharmacokinetic profile after one dose of MMF at days 6, 10, and 16, and months 3 and 6. The inhibitory capacity of serum MPA on proliferation of CEM cells, a cell line insensitive to other immunosuppressants, was also determined. Results A large interindividual variability in MPA profiles was observed at any time. Regardless of a gradual increase in individual MPA AUC and C(0) over time following transplantation, a substantial proportion of patients had these parameters below the ranges recommended in other organ transplantations throughout the study. When MPA AUC and C(0) were within the recommended ranges, CEM proliferation was inhibited by almost all serum samples, but when these pharmacokinetic parameters were below the recommended ranges, CEM proliferation was very variable and, therefore, unpredictable. No relationship between MPA pharmacokinetics and the efficacy of MMF could be established (only one patient developed rejection), probably due to the concomitant administration of tacrolimus and daclizumab. Gastrointestinal symptoms were the only adverse events with a significant relationship with MPA levels. Conclusions During the first postoperative months, exposure to MPA is low in a considerable proportion of liver transplant patients receiving MMF at a fixed dose of 1 g bid. MPA monitoring appears necessary in these patients.

Herein we describe a series of potent and selective PPARgamma agonists with moderate PPARalpha affinity and little to no affinity for other nuclear receptors. In vivo studies in a NIDDM animal model (ZDF rat) showed that these compounds are efficacious at low doses in glucose normalization and plasma triglyceride reduction. Compound 1b (LY519818) was selected from our SAR studies to be advanced to clinical evaluation for the treatment of type II diabetes.

We investigated the relationship between the pharmacokinetics and pharmacodynamics of cyclosporine in 15 stable renal transplant patients in order to define an effective and safe therapeutic range. The area under the curve of the first 4 h (AUC(0-4)), trough (C(0)) and 2 h (C(2)) levels showed median values of 1655 ng x h/ml, 114 ng/ml and 384 ng/ml, respectively. C(2) showed a strong correlation with AUC(0-4) (r=0.942, p=0.0005). C(0) correlated poorly with C(2) and AUC(0-4) (r=0.596, p=0.019 and r=0.538, p=0.031, respectively). Calcineurine activity (CNa) was 6.74% at 0 h and 3.90% at 2 h, representing significant reductions (82% and 89.6%, respectively; p0.0005) compared with normal healthy controls (median basal value 37.4%). IL-2 production was 349 pg/ml at 0 h and 276.35 pg/ml at 2 h; both results were significantly lower (reductions of 44.5% and 56.1%, respectively; p=0.04 and 0.005) than the controls of 629.1 pg/ml. IFN-gamma at 2 h post-dose (8.16 UI/ml) was significantly lower (72.1% reduction, p=0.005) than in controls (29.2 UI/ml). There was a good correlation between CNa and IFN-gamma production, particularly at 2 h post-dose (r=0.537, p=0.007), and a fair correlation between CNa and IL-2 concentration (p=0.030, r=0.426). C(2) showed an inverse significant correlation with CNa (Spearman's p=0.000, r=-0.753), IL-2 (p=0.000, r=-0.725) and IFN-gamma (p=0.000, r=-0.701) production. In treated patients, the Emax inhibitory sigmoidal model showed that a C(2) of 279 ng/ml was needed to achieve a 50% inhibition (EC50) of IL-2 and INF-gamma production. The results demonstrated a significant inhibition of calcineurin activity and IL-2 and IFN-gamma production in patients receiving cyclosporine monotherapy compared to healthy controls. A median C(2) value of 384 ng/ml was associated with a good degree of inhibition of CNa and IL-2 and IFN-gamma synthesis, and the lack of rejection episodes and relevant toxicity.

Suboptimal doses of mycophenolate mofetil (MMF) are frequently employed in renal transplant (Tx) patients, with drug-related side effects or low weight. The aim of this study was to compare the mycophenolic acid (MPA) pharmacokinetic profile and its pharmacodynamic effect on patients receiving either standard (2 g) or low (1.5 g or 1 g) MMF doses, in order to evaluate the therapeutic efficacy of such low doses in inhibiting IMPDH activity. Twenty-seven stable renal Tx recipients aged 18-65 years, with a post-Tx follow-up of 38.5 +/- 44.8 months (6-166 months), receiving 1 g (n = 10), 0.75 g (n = 7) and 0.5 g (n = 10) MMF twice a day in association with cyclosporine and prednisone, were included. The control group was made up of untreated healthy volunteers (n = 5). Plasma concentrations of MPA were analyzed by reverse-phase HPLC. IMPDH activity was determined in lymphocytes by the measurement of 3H release from [2,8-(3)H] hypoxantine. The mean value of areas under the concentration-time curves (AUC(0-12)) of MPA throughout the 12-h dosing interval in patients treated with 2 g was higher than the corresponding data in patients receiving 1.5 g or 1 g bid, but no statistical differences were observed between the three groups. There was no correlation between MPA-AUC(0-12) values and MMF dose (expressed in g/day or g/kg per day). Predose MPA concentrations correlated only weakly with the respective MPA-AUC(0-12) values (r2 from 0.385 to 0.655), whereas an acceptable correlation was observed between MPA Cmax and MPA-AUC(0-12) (r2 from 0.626 to 0.759) in 2 g, 1.5 g, and 1 g MMF groups. An inverse relationship between MPA concentrations and IMPDH activity was observed. In general, the maximum MPA concentration was achieved from 1 h to 2 h after dosing, and the maximum inhibition of IMPDH was also from 1 h to 2 h after dosing. The evaluation of IMPDH activity demonstrated that there was a significant statistical difference between samples from 0 to 1 h (P = 0.008) and 0 to 2 h (P = 0.04). In conclusion, concentration-time profiles of renal transplant recipients administered 0.75 g and 0.5 g twice a day are slightly lower than those from the 2 g group, but nor significantly. On the other hand, inhibition of IMPDH activity was comparable in the three groups, indicating considerable interindividual pharmacodynamic variability. Pharmacodynamic monitoring of the degree of immunosuppression and its correlation with MPA plasma concentrations will be assessed further in future studies.

Background. The hyperacute rejection induced by natural antibodies is the first barrier to the success of pig to human organ xenotransplantation. When this barrier is overcome, an infiltrate of mainly monocytes and natural killer cells can be observed. Nitric oxide (NO) has been described to be involved in allo- and xenorejection, and to participate in the regulation of monocyte infiltration in other models. Methods. We have studied the capacity of human monocytes and natural antibodies to induce the production of NO by pig endothelial cells, by measuring NO2, a stable end product of NO. Results. Human monocytes can induce HuProVim (HUP), a pig endothelial line, and “in situ, ex vivo” pig endothelial cells to produce NO2. This NO2 production was inhibited by N G -nitro-L-arginine-methylester and N G -monomethyl-L-arginine, inhibitors of NO production. This induction can be observed even if cells are separated by a semipermeable membrane, which indicates that it is a result of soluble factors. Activated cells continue producing NO after triggering for 1 hr. No NO2 production was observed after activation of HUP cells with recombinant human interleukin (IL)1a, IL-1b, IL-6, IL-10, transforming growth factor-b1, IL-2, IL-4, interferon-g, or recombinant human tumor necrosis factor-a (rhTNF-a) alone. Only the combination of rhTNF-a1rIL-1a or rIL-1b, and rhTNF-a1rIL1a1IFN-g induces some NO production. Human natural anti-pig antibodies, which had been described to induce cytoskeleton changes on endothelial cells, do not induce NO production. Conclusions. Our data show that human monocytes induce the production of NO by pig endothelial cells. The inducing signal is soluble and cannot be provided by human anti-pig natural antibodies. The possible use of pigs as an organ source for transplantation into humans is now widely considered. For this reason, the interaction of the cells of the human immune system with pig cells is raising increasing interest. The first barrier to the success of transplantation of pig organs to humans is the hyperacute rejection (1). In some cases in which the barrier of the naturally occurring antibodies was overcome in pig to primates model, an important percentage of cells infiltrating the pig organs were monocytes and natural killer (NK*) cells (2). Similar results have been found in a human-rat ex vivo

The use of mycophenolate mofetil in combination with highly active antiretroviral therapy (HAART) has been proposed in order to inhibit HIV replication. Due to the low doses involved, pharmacokinetic-pharmacodynamic monitoring is recommended.The aim of this study was to characterise the pharmacokinetic and pharmacodynamic monitoring of low doses of mycophenolate mofetil (0.25 g twice daily) in HIV-infected patients treated with HAART and after programmed discontinuation of HAART, in order to assess whether low doses of this immunosuppressive agent provide a biological effect.Mycophenolic acid (MPA) plasma levels (assessed by high-performance liquid chromatography) and the capacity of patients' sera to inhibit CEM cell line proliferation (assessed by (3)H-thymidine uptake) were measured post-dose at 0, 20, 40 minutes and 1, 2, 4, 6, 8, 10 and 12 hours in nine HIV-infected patients treated with a combination of abacavir, nelfinavir and efavirenz (HAART) and mycophenolate mofetil 0.25 g twice daily at days 7, 28, 120 and 150 (30 days without HAART) after the treatment initiation. A control group of eight patients was treated with HAART alone.In the 35 post-dose curves analysed, no differences were found in MPA levels between days 7, 28, 120 and 150: area under the plasma concentration-time curve - mean value 15.3 mg . h/L, range 10.4-24.4 mg . h/L; minimum plasma concentration - mean value 0.60 mg/L, range 0.20-4.67 mg/L; maximum plasma concentration mean value 2.60 mg/L, range 0.94-7.98 mg/L. Pretreatment patients' sera did not inhibit CEM proliferation. Post-treatment patients' sera inhibited CEM proliferation to40% in 25 of 35 curves at 0 hours (six of nine patients), in 34 of 35 curves at 1 hour, in 32 of 35 curves at 2 hours, in 22 of 35 curves at 4 hours, and in 8 of 35 curves at 12 hours. The MPA level versus CEM proliferation inhibition had a concentration that produces 50% of the maximum drug effect (EC(50)) of 0.33 mg/L. Viral load at day 150 was200 copies/mL in all control patients and in three of nine patients receiving mycophenolate mofetil. These three patients were the only ones repeatedly unable to inhibit pre-dose CEM proliferation to40%.Mycophenolate mofetil pharmacokinetic profiles in HIV patients under HAART are not significantly different from those found in transplant patients. Sera from the majority of patients receiving low doses of mycophenolate mofetil inhibited lymphocyte proliferation during most of the inter-dose interval, despite low MPA plasma levels. For some patients, higher doses may be necessary: the capacity of sera to inhibit CEM proliferation may help to identify these patients.

Background: There is a correlation between cyclosporine (CsA) pharmacokinetics (PK) and pharmacodynamics (PD), especially 2 hours after drug administration. Aim: To evaluate the relationship between CsA PK and PD profiles in two groups of stable renal transplant patients treated with CsA alone or CsA plus mycophenolate mofetil (CsA+MMF), so as to define the best target for C 2 and clarify the impact of concomitant immunosuppression. Methods: Thirty-eight stable renal transplant recipients were treated with CsA (n = 20) or CsA+MMF (n = 18). Twelve nontreated normal healthy controls (NHC) were also included. Calcineurin activity (CNa), IL-2 production, and CsA levels were measured at 0 and 2 hours postdose. Results: There were no significant differences in median CsA C 2 values and CNa between the CsA alone and the CsA+MMF groups (388 μg/L and 497.5 μg/L and CNa 2h; 3.92% alkaline phosphatase [AP]; 3.94% AP, respectively). In vitro production of IL-2 was significantly lower in the CsA+MMF group than in the CsA group (median IL-2 2h: 280.52 ng/L, 169.48 ng/L, P

Background: Graft survival depends on adequate immunosuppression. To evaluate the effect on the immune system of immunosuppressive therapies using calcineurin inhibitors (CNIs), several pharmacodynamic indices have been proposed to complement pharmacokinetic data. In this preliminary study we compared some of these parameters during combined immunosuppressant therapies. Methods: We treated 65 stable renal transplant recipients with cyclosporin A (CsA; n = 16), tacrolimus (TRL; n = 10); CsA + mycophenolate mofetil (MMF; n = 14); TRL + MMF (n = 13), and MMF (n = 12). Twelve nontreated healthy controls were also included. Calcineurin activity (CNA) in peripheral blood mononuclear cells was measured using 32P-labeled peptide. Interleukin-2 (IL-2) and interferon-γ production in phytohemagglutinin-activated whole blood were measured at 0 and 2 h postdose. The areas under the curves, cmin, cmax, and concentration at 2 h (c2 h) were also measured. Results: We found no differences in CNA between groups receiving CNIs alone or combined with MMF [median (25th–75th percentiles)]: CsA2 h, 3.87 (3.00–6.85)% alkaline phosphatase (AP); CsA+MMF2 h, 3.90 (1.78–5.19)% AP; TRL2 h, 5.68 (3.02–16.00)% AP; TRL+MMF2 h, 11.80 (4.05–14.63)% AP. In vitro IL-2 production was significantly lower in the groups receiving combined therapy than in groups receiving CNIs alone [median (25th–75th percentiles)]: CsA2 h, 276.52 (190.41–385.25) ng/L; CsA+MMF2 h, 166.48 (81.06–377.01) ng/L (P Conclusions: The measurement of CNA may be of help in following the effect on the immune system of CNI treatments, even in combined therapies, but does not reflect the additional effect of MMF. In contrast, IL-2 in vitro production reflects the effect of both MMF and CNIs.

Background Allergic diseases affect 20% of world population and allergic rhinitis (AR) is the most common, alone or associated with asthma. Antigen-specific immunotherapy has been world-desensitizing type studied showing that it is capable of modifying the natural history of the disease through changes in the immune response increasing the role of clones of lymphocytes T helper type I (LTh1) and inhibiting the activity of type 2 (LTh2). Dialyzable leukocyte extract or transfer factor (TF) has shown the same stimulatory effect. Objective Evaluate the synergistic effect of TF associated with SLIT in patients with RA. Material and Methods We studied 94 patients with RA. We included randomized into 2 groups (47 each one) both received antigen-specific sublingual immunotherapy (SLITAE) and also in group 1 was given oral TF Unit at one 200 mg monthly for 3 months, and group 2 placebo. We used a control group only to compared the normal results. All patients underwent complete blood count (BHC), immunoglobulins, quantification of cell-type lymphocyte CD3, CD4, CD8, interleukin (IL2, IL4, IL5, IL10, TNF and IFN). The nasal symptoms were evaluated monthly for 3 months, with test score symptoms questionary 4 (TSSQ4) and auto-evaluation by scale Linker. Results We studied 94 AR patients (50% women and 50% men, range age between 5 and 40 years). Indoor antigens (mites, house dust and cockroach) were the main cause of allergy. Allergic patients had more eosinophiles and IgE than the healthy controls (P < 0.05). The number of CD8+ lymphocytes was slightly reduced in group 2 after treatment (P < 0.05), whereas the amount of IL-4 and IFN ƒnwere increased in both groups (P < 0.005) and the amount of IL-10 was significantly increased in group 1 (P < 0.01) after treatment. Clinical evaluation was with initial TSSQ4 of 11.6 before handling and 5.1 (44%) after, with significant improvement (P < 0.0001) and Likert score was reduced 69% than the star the treatment. Conclusions The TF along with SLITAE in the treatment of patients with RA did not alter the clinical improvement induced by SLITAE alone for 3 months of treatment, but the combination increased production of IL 10 and production of IFNg.

Background Allergic diseases such as asthma, atopic dermatitis and allergic rhinitis are common disorders that have increased its prevalence over the past thirty years. Atopic diseases have a genetic basis, with expression of different phenotypes associated with chromosome 5 (5q23-25, IL-4, IL-5, IL-9, IL-13 and GM-CSF), 6 (molecules of class I and II human leukocyte antigen) 11 (11q13: β subunit of high affinity receptor for IgE) and 12 (12q: IFN-gamma, nitric acid synthase). Asthma is defined as a chronic inflammatory disease of airway and is the most common chronic disease in children characterized by wheezing. Wheezing may occur even once it is up to 50% of all infants and children under 3 years old and topic dermatitis affecting over 10% of children. Objective To define incidence and prevalence of asthma and others allergic diseases in population of less than 5 years of age in Juarez Hospital Mexico. Results We evaluated 11,346 allergic patients on 4 years period (January 2007 to December 2010). Two thousand three hundred ninety six were ≤5 years (21.11%); 10.2% a year old or younger, 16.7% 2 years old, 18.5% had 3 years, 24.7% of 4 years and 30% 5 years old. Nine hundred ninety two patients (41.4%) were females and 1.404 (58.6%) male. One thousand two hundred thirty eight patients (51.7%) had only one diagnostic finding as most frequent cause of consultation allergic rhinitis (59.6%), followed by asthma (23%), atopic dermatitis (5.1%), prurigo by insect (4.3), immunodeficiency (1.2%) the rest had various pathologies such as contact dermatitis, gastro esophageal reflux, oral allergy syndrome, and others. The remaining patients 48.3% (1158) had more than one diagnostic. The most common associations were asthma and rhinitis 716 (30%), 72 patients (3%) with asthma and atopic dermatitis, 48 patients (2%) with some immune deficiency and asthma and/or rhinitis, 12 (0.5%) with prurigo and atopic dermatitis, 8 (0.3%) with urticaria and 11 patients (4.5%) with other diagnoses such as reflux or infections. Conclusions Allergic diseases are common on pediatric population and children under 5 years old asthma and rhinitis is theprincipal cause of consultation.

Mexico 2009 faced the H1N1VI influenza pandemic, a complex immunologic and clinical host response, whose defense mechanisms have yet to be identified. Lack of information on clinical an immunological features in pediatric population with H1N1VI, delay detection of patients at risk of contracting it. This study aims to identify specific immunologic and/or clinical features of pediatric patients with H1N1VI in a federal Hospital in Mexico City. Methods Single-center, observational, non-experimental, prospective trail from September to October 2009, for pediatric patients arriving to Emergency room of Juarez Hospital, with suspicion of H1N1VI, needing to be younger than 17 years, and agree and sign the consent form by tutor. Samples obtained were peripheral blood, and pharyngeal exudate. From blood LS, Cytokine levels, and routine measurements (CBC, BCH) were investigated; the pharyngeal sample underwent PCR study to viral genetic material. Complementary studies such as arterial blood gases or Torax radiography were realized as needed. Results 32 patients participated. PCR results confirmed 18 cases (56%), 1 patient resulted positive for SII. The average age was 9 years old; 12 (67%) were female, and 6 (33%) were male. The mean amount of days from symptom onset to receiving medical attention was 2.5 days. Main symptoms and signs were fever, malaise, cough, rhinorrhea, and headache. Associated risk factors included malnutrition and tobacco exposure. It was demonstrated an elevation of IL-8, followed by IL-6, IL-12 and IL-10. Blood analysis proved no significant findings, though cases of neutrophilia and leukopenia were detected. Conclusions Limited resources, restricted participation from all the possible H1N1VI patients, thus biasing results due to small sample size; however, the obtained data is consistent with existing reports, nevertheless the information is not enough to establish standardized recommendations. Further collaboration among centers, is needed to identify features that can prompt H1N1VI early identification and prevention in pediatric population.

Background Urticaria is a skin disease characterized by rapid emergence of hives, accompanied or not with angioedema. Usually lasts less than 24 hours. Approximately 12 to 24 per cent of the population will have hives or angioedema at least once in their life. Some patients with chronic urticaria has been classified as autoimmune. The autologous serum skin test (ASST) has been used to show pro-inflammatory circulating endogenous factors and it is regarded as a test for autorreactividad. The autorreactividad does not define an autoimmune urticaria, but may be an indicator of the presence of auto- reactive antibodies with the capacity of to activate the mast cells however functional antibodies need to be confirmed through of release of basophils histamine test from basophils (BHRA) and its specificity immunoassay (Western Blot or ELISA)-confirmed. Objective: to evaluate the auto-reactivity by autologous serum skin test in patients with chronic urticaria idiopathic in a study of 8 years. Material and methods: we made 216 ASST and autologous plasma skin test (APST) in patients with chronic urticaria without specific cause identified, of any age, during the period of 2003 to 2011. Results Thirty five thousand patients were evaluated only 261 patients not identified the cause (0.6%) and we realized ASST, of these 190 (88%) were negative, and 26 (12%) were positive, 20 (76.9 %) were female and 6 (23.1%) male, the median of age for women was 30 years ago with medium of 28 and men average 29 years and median 20. Of the 26 patients one was positive for anti-thyroglobulin senior titles (1: 170) .dos with positive anti unclears and one with pANCA and cANCA positive of a total of 216 patients, 156 (72.2) had APST and 60 (27.8%) were positive, 46 (76.6%) women and 14 (23.3 %) men. Mc Neman concordance between tests P < 0.0001 and Kappa index gives us a highly significant concordance P < 0.0001. The correlation between ASST and APST by Sperman was high significance value of P < 0.001. The correlation of both tests was moderately high (76.8%).

We have generated seven monoclonal antibodies (mAb) that recognize the T200 molecule. These mAb have been classified by competitive binding assay in flow cytometry into three groups each reacting with a different epitope of the T200 molecule: (a) 136-4B5, that shows a sialic acid nature, (b) 135-4H9, 135-4C5, 144-2, 155-2 and (c) 72-5D3, 124-2H12b. A heterogeneous effect was observed when they were tested on an anti-immunogiobulin-induced B cell proliferation. Whereas 72-5D3 and 135-4H9 mAb inhibited the proliferative response of B cells, 136-4B5 mAb greatly enhanced it, both effects being dose dependent. We can conclude that anti-CD45 mAb have a different and contrary functional behavior on anti-Ig-induced B cell proliferation, depending on the epitope recognized. The basis for such a difference could reside in the glucidic nature of the epitope recognized by the 136-4B5 mAb.

Background: Mycophenolic acid (MPA), a metabolite of mycophenolate mofetil (MMF), is an immunosuppressive agent that inhibits inosine monophosphate dehydrogenase (IMPDH), a key enzyme in the ex novo synthesis of GTP. We measured IMPDH activity in peripheral blood mononuclear cells (PBMCs) from MMF-treated patients to evaluate the efficacy of MMF in individual patients. Methods: IMPDH activity was measured by 3H released from [2,8-3H]IMP that had been formed in the cells from added [2,8-3H]hypoxanthine in PBMCs of 35 renal transplant recipients treated with cyclosporin A and corticoids plus MMF: 2 g (n = 10), 1.5 g (n = 7), 1 g (n = 10), or 0 g (n = 8) per day. An alternative method, based on the capacity of the patients’ sera to inhibit spontaneous proliferation of the CEM cell line, was also analyzed. Results: The IMPDH activity of PBMCs in transplanted patients was highly variable. For the method based on CEM cell line proliferation: (a) cell proliferation was inhibited only in MMF-treated patients; (b) there was a clear postdose increase in inhibition; (c) inhibition was not affected by other immunosuppressants in vitro or in vivo; (d) inhibition from predose to predose sample was correlated; and (e) when the MMF dosage was Conclusions: Measurement of the inhibition of CEM cell line proliferation by sera from MMF-treated patients may be useful for evaluating the relative efficacy of MMF treatment in individual patients, especially those receiving low doses of MMF.

Urticaria and angioedema lasting more than 6 weeks have been designated as chronic urticaria (CU). It encompasses two major subtypes: chronic spontaneous urticaria (CSU) (previously known as chronic idiopathic urticaria) (CIU) and chronic inducible urticaria. CSU has been defined as wheals and/or angioedema that are endogenous and independent of any external physical stimulus. It affects 0.5 to 1% of the population [1]. In 40 to 45% of patients with CSU autoantibodies to the high affinity IgE receptor (FcϵRI) or to IgE itself are thought to play a psathogenic role, whereas 55 to 60% of cases are considered idiopathic [2]. Inducible urticarias include all forms of physical urticarias (cold-induced, heat-induced, solar, and pressure urticaria). According to the International Guidelines for the management of urticaria and angioedema non-sedating, second generation antihistamines (NSAHs) are recommended for the treatment of CU [3]. Nevertheless, a considerable proportion of patients do not respond sufficiently to NSAHs. According to Humphreys and Hunter up to 40% of patients with CU may not achieve good control with antihistaminic therapy [4]. They reported that out of 390 CU patients who were treated with antihistamines 44% responded well, 29% became asymptomatic, and 15% showed partial improvement. In a recent paper from Japan it was observed that the improvement rates (defined as a urticaria symptom score UAS ≤ 3) in 117 CU patients who received standard doses of AHs were 36.6% at 12 months, 51.2% at 24 months, and 66.1% at 60 months, while the remission rates were 11.5%, 13.9%, and 27.7%, respectively [5]. In patients that do not respond to standard doses, the next step in guideline-based therapy is to increase AH doses up to 4 times [3]. Investigations assessing the response to various NSAHs have demonstrated that up-dosing is significantly more effective in reducing symptoms of CU than standard-dose treatment [6]. According to Kaplan, high-dose antihistamines are effective in 45-60% of patients with CSU [7], while about one third are antihistamine resistant regardless of which dose is used [8, 9]. The present article is a review of the literature on the treatment of CU with increased doses of NSAHs in order to investigate if there are differences in efficacy between the various second generation AHs that have been studied in controlled protocols. It must be noticed, however, that it is difficult to find clinical investigations that strictly follow the criteria recommended by the guidelines on the management of urticaria, and therefore studies included in this review were those in which higher doses of NSAHs were used regardless of the clinical response to conventional doses. AHs included in this review are desloratadine, levocetirizine, fexofenadine, and the recently introduced NSAHs rupatadine and bilastine. Bilastine belongs to the piperidine class of antihistamines as do loratadine, desloratadine, and fexofenadine. Like other antihistamines bilastine is an H1 receptor inverse agonist. In vitro studies have shown that bilastine has a high specific affinity for the H1-receptor but it has no or very low affinity for 30 other tested receptors. The affinity for the H1 receptor is 3 and 6 times higher than for cetirizine and fexofenadine, respectively [10, 11]. Rupatadine fumarate is a new potent, long acting, orally active dual antagonist of both histamine H1 and Platelet-Activating Factor (PAF) receptors. In in vivo and in vitro studies rupatadine was as potent or even more potent than other second generation antihistamines (loratadine, terfenadine and cetirizine) or selective PAF antagonists [12].