Differences in allergen-specific basophil activation and T cell proliferation in atopic dermatitis patients with comorbid allergic rhinoconjunctivitis treated with a monoclonal anti-IL-4Rα antibody or allergen-specific immunotherapy.

BACKGROUND: Atopic dermatitis (AD), a chronic inflammatory disorder, is often accompanied by allergic rhinoconjunctivitis (ARC) as a co-morbidity. The use of a monoclonal anti-IL-4Rα antibody has been effective in controlling moderate to severe AD symptoms. Allergen-specific immunotherapy (AIT) is widely used for the treatment of ARC and asthma. The effects of AIT on basophil reactivity/effector functions have already been examined and used as indicators of the treatment efficacy. However, it is unclear, how an anti-IL-4Rα antibody can influence allergen-specific immune responses of basophils and T cells of AD patients with comorbid ARC. OBJECTIVE: To investigate the effect of a monoclonal anti-IL-4Rα antibody on the in vitro allergic responses of basophils and T cells deriving from AD patients with comorbid ARC. METHODS: Blood samples of 32 AD patients were obtained before, after 4 and 16 weeks of an anti-IL-4Rα antibody therapy (300 mg subcutaneously/2 weeks; n = 21) or AIT (daily sublingual application; n = 11). Patients treated with an anti-IL-4Rα antibody were grouped according to their serum specific immunoglobulin E levels and ARC symptoms, while patients receiving an AIT were additionally grouped according to the allergen specificity of their AIT. Basophil activation test and T cell proliferation assays were undertaken after an in vitro allergen stimulation. RESULTS: A significant reduction of the immunoglobulin E levels and the allergen-specific T cell proliferation was observed in AD patients treated with an anti-IL-4Rα -antibody, while the allergen-specific basophil activation/sensitivity were found to be significantly increased. In patients receiving an AIT, the in vitro allergen-specific basophil activation and the T cell proliferation were found to be significantly decreased in response to seasonal allergens. CONCLUSIONS: An IL-4Rα blockade induced by a monoclonal anti-IL-4Rα antibody leads to an increased activity/sensitivity of early effector cells (such as basophils), in contrast to a decreasing reactivity observed under an AIT. The late-phase T cell reaction to allergens did not differ between the herein assessed treatments.

In vitro Conversion into CD4+CD25+Foxp3+ Induced Regulatory T Cells Is Reduced in Atopic Dermatitis Patients.

BACKGROUND: Atopic dermatitis (AD) is one of the most common inflammatory skin diseases, with an increasing incidence in clinical practice. AD models have demonstrated that TGF-ß signaling is compromised in regulatory T cells (Tregs). OBJECTIVES: This study aimed to investigate the TGF-ß-dependent in vitro conversion of CD4+CD25- T cells derived from AD-patients into CD4+CD25+Foxp3+ induced Tregs (iTregs) in comparison to healthy controls. METHODS: To analyze in vitro iTreg conversion, human CD4+CD25- T cells were cultured on anti-CD3-coated plates in the presence of TGF-ß and IL-2 for up to 3 days. Consequently, the underlying mechanism of impaired CD4+CD25+Foxp3+ iTreg generation was explored by focusing on TGF-ß signaling. Finally, the functionality of iTregs was investigated. RESULTS: Conversion of CD4+CD25-Foxp3- into CD4+CD25+Foxp3+ iTregs was diminished in AD individuals. Impaired iTreg generation was accompanied by a reduced surface expression of GARP (glycoprotein A repetitions predominant), a marker for activated Tregs. A reduced expression of Smad3 mRNA was revealed in CD4+CD25- T cells. Interestingly, the suppressive quality of iTregs was found to be equal in cells derived from AD and healthy donors. CONCLUSION: The signaling effect of TGF-ß receptors on the suppressor quality of iTreg conversion is conserved. Impaired iTreg generation might be a reason for the lack of immune suppression in AD patients and contributes to the chronicity of the disease.

The ocular surface: from physiology to the ocular allergic diseases.

Allergic conjunctivitis (AC) is an inflammation of the conjunctiva secondary to an immune response to exogenous antigens, usually called allergens. In fact, AC is a syndrome that involves the entire ocular surface, including conjunctiva, lids, cornea, and tear film. The signs and symptoms of AC have a meaningful effect on comfort and patient health, and could be influenced by environment, genetics and immune regulation mechanisms, all of which work together in a complex immunological homeostasis. Dysregulation in such immune responses could turn into a variety of ocular allergic diseases (OAD). This review describes some of the current understanding of cellular and molecular pathways involved in different OAD.

La conjuntivitis alérgica es la inflamación de la conjuntiva secundaria a una respuesta inmunitaria contra antígenos exógenos, usualmente llamados alergenos. De hecho, la conjuntivitis alérgica es un síndrome que involucra la totalidad de la superficie ocular, incluyendo la conjuntiva, los párpados, la córnea y la película lagrimal. Los signos y síntomas de la conjuntivitis alérgica tienen un efecto significativo en el bienestar y salud del paciente y pueden ser influidos por el ambiente, la genética y mecanismos de regulación inmunológicos, todos los cuales trabajan en conjunto en una compleja homeostasia inmunológica. La disregulación de estos mecanismos puede desembocar en una gran variedad de enfermedades alérgicas oculares. Esta revisión describe algunos de los conocimientos celulares y moleculares actuales, involucrados en las diferentes enfermedades alérgicas oculares.

Pharmacological evidence that spinal α(2C)- and, to a lesser extent, α(2A)-adrenoceptors inhibit capsaicin-induced vasodilatation in the canine external carotid circulation.

During a migraine attack capsaicin-sensitive trigeminal sensory nerves release calcitonin gene-related peptide (CGRP), producing cranial vasodilatation and central nociception; hence, trigeminal inhibition may prevent this vasodilatation and abort migraine headache. This study investigated the role of spinal α2-adrenoceptors and their subtypes (i.e. α(2A), α(2B) and/or α(2C)-adrenoceptors) in the inhibition of the canine external carotid vasodilator responses to capsaicin. Anaesthetized vagosympathectomized dogs were prepared to measure arterial blood pressure, heart rate and external carotid conductance. The thyroid artery was cannulated for one-min intracarotid infusions of capsaicin, α-CGRP and acetylcholine. A cannula was inserted intrathecally for spinal (C1-C3) administration of 2-amino-6-ethyl-4,5,7,8-tetrahydro-6H-oxazolo-[5,4-d]-azepin-dihydrochloride (B-HT 933; a selective α2-adrenoceptor agonist) and/or the α2-adrenoceptor antagonists rauwolscine (α(2A/2B/2C)), 2-[(4,5-dihydro-1H-imidazol-2-yl)methyl]-2,3-dihydro-1-methyl-1H-isoindole maleate (BRL44408; α(2A)), imiloxan (α(2B)) or acridin-9-yl-[4-(4-methylpiperazin-1-yl)-phenyl]amine (JP-1302; α(2C)). Infusions of capsaicin, α-CGRP and acetylcholine dose-dependently increased the external carotid conductance. Intrathecal B-HT 933 (1000 and 3100 µg) inhibited the vasodilator responses to capsaicin, but not those to α-CGRP or acetylcholine. This inhibition, abolished by rauwolscine (310 µg), was: (i) unaffected by 3,100 µg imiloxan; (ii) partially blocked by 310 µg of BRL44408 or 100 µg of JP-1302; and (iii) abolished by 1,000 µg of BRL44408 or 310 µg of JP-1302. Thus, intrathecal B-HT 933 inhibited the external carotid vasodilator responses to capsaicin. This response, mediated by spinal α2-adrenoceptors unrelated to the α(2B)-adrenoceptor subtype, resembles the pharmacological profile of α(2C)-adrenoceptors and, to a lesser extent, α(2A)-adrenoceptors.

Financiamiento de la atención a la salud de la población de la tercera edad / Health care financing for the elderly

Determinar el financiamento directo de la atención a la salud de los adultos mayores en México y hacer una estimación de los gastos que este servicio implica. Material y métodos. Se estimaron las necesidadesde atención a la salud de los ancianos con base en estadísticas censales y en la Encuesta Nacional de Salud II. Enseguida se estimaron las tendencias en el uso de servicios entre los adulto mayores, de acuerdo con la información emitida por distintas instituciones del sector salud. Finalmente, después de haber analizado la aplicación de distintos modelos de atención a la salud en los ancianos en otros países y de haber proyectado las futuras demandas al respecto en México, se estimó el gasto mediante dos métodos: a) con base en una fórmula que incluye egresos, costo día/cama y días de estancia, y b) calculando el gasto de hospitalización y consulta a partir del número de egresos. Resultados. La necesidad actual de atención del adulto mayor supera la capacidad del sistema de salud para proveer los servicios adecuados. De acuerdo con el segundo método de estimación, en 1994 se gastó 4.9 por ciento del presupuesto del sector público en la atención hospitalaria para la población de más de 60 años. Conclusiones. En México, los adultos mayores se han convertido en una prioridad por la naturaleza de sus necesidades y demandas; su atención es una de las fuentes de costos más importantes en los servicios hospitalarios. Es necesario, por tanto, desarrollar una agenda de investigación que permita programar, planear y presupuestar el gasto en asistencia médica para el anciano

Objetive. To determine the direct financial requirements for providing health care to the elderly in Mexico along with an estimation of the current expenditures from services provided to this same population. Material and methods. Health care needs for the elderly were estimated from the censuses and the database of the National Health Survey II. In addition, service use trends for the aged were obtained from health sector statistical yearbooks. Finally, the amounts of expenditures were estimated by two methods: a) using a formula that considers hospital discharges, daily bed costs and length of stay; and b) inferring hospital expenditures and ambulatory visits from the numbers of hospital discharges. Results. Currently health care needs of the aged outnumber the amount of resources and the capacity of the health care sector to meet these needs. Our estimates for the year 1994 show that 4.9% of the total budget available to public health care institutions was dedicated to hospital services provided to the elderly. Conclusions. In Mexico, the aged population health needs are already a priority, due to the particular nature of their needs and demand. Taking care of this population demands an important fraction of the resources spent in hospital services. To correctly plan and allocate resources for providing health care to this population developing a research agenda is an important requirement.

Fibrotecoma (Fibroma)de ovario / Fecofibrona (fibrona) of ovary

Se describe un caso de fibrotecoma de ovàrio en una mujer de 48 años, con la presencia de tumoraciòn pèlvica dolorosa y ascitis. Microscopicamente muestra la presencia de cèlulas fusiformes con disposiciòn entrecruzada sin mitosis anormales entremezcladas con nidos de cèlulas tecales. Tumor que se origina en el estroma ovàrico raras veces en un fibroma de, consistencia dura, al corte con aspecto arremolinado blanquesino, con tonos amarillentos, benigno

Balística: implicaciones quirúrgicas en lesiones pleuropulmonares / Balistics: surgical implications in pleuropulmonary lesions

El incremento de la frecuencia y complejidad de las lesiones por proyectil de arma de fuego obliga al conocimiento de los principios que rigen los efectos de los proyectiles en los tejidos. En el presente artículo se revisan los conceptos de balística aplicables al tratamiento de las lesiones pleuropulmonares y se presentan los lineamientos generales de la conducta quirúrgica.

Consideraciones sobre las funciones no respiratorias del pulmón / Non respiratory function of lung

La función principal del aparato respiratorio es el intercambio de gases. Sin embargo, el aparato respiratorio desarrolla otras funciones: I. La corriente de aire sirve para una gran variedad de fenómenos sin los cuales nos sería difícil vivir; II. Las del metabolismo propio del pulmón; III. Las de absorción y eliminación de diversas substancias; IV. Las del mecanismo de defensa, y V. en las que participa en el sistema general del organismo. Actualmente se conocen con más profundidad estas funciones y se hace hincapié en algunas de ellas que nos explican mejor el comportamiento del pulmón en las diversas circunstancias a las que está expuesto.