Anti-pseudo-allergic components in licorice extract inhibit mast cell degranulation and calcium influx / 中国天然药物

Pseudo-allergic reactions (PARs) widely occur upon application of drugs or functional foods. Anti-pseudo-allergic ingredients from natural products have attracted much attention. This study aimed to investigate anti-pseudo-allergic compounds in licorice. The anti-pseudo-allergic effect of licorice extract was evaluated in rat basophilic leukemia 2H3 (RBL-2H3) cells. Anti-pseudo-allergic compounds were screened by using RBL-2H3 cell extraction and the effects of target components were verified further in RBL-2H3 cells, mouse peritoneal mast cells (MPMCs) and mice. Molecular docking and human MRGPRX2-expressing HEK293T cells (MRGPRX2-HEK293T cells) extraction were performed to determine the potential ligands of MAS-related G protein-coupled receptor-X2 (MRGPRX2), a pivotal target for PARs. Glycyrrhizic acid (GA) and licorice chalcone A (LA) were screened and shown to inhibit Compound48/80-induced degranulation and calcium influx in RBL-2H3 cells. GA and LA also inhibited degranulation in MPMCs and increase of histamine and TNF-α in mice. LA could bind to MRGPRX2, as determined by molecular docking and MRGPRX2-HEK293T cell extraction. Our study provides a strong rationale for using GA and LA as novel treatment options for PARs. LA is a potential ligand of MRGPRX2.

Caracterización de pacientes alérgicos a picadura de abeja que reciben inmunoterapia / Characterization of allergic patients to bee sting that receive immunotherapy

La alergia al veneno de abejas provoca reacciones de leves a severas con compromiso para la vida. La inmunoterapia con veneno de himenópteros es un tratamiento eficaz y protege a los pacientes alérgicos de sufrir reacciones sistémicas ante nuevas picaduras. Nos propusimos caracterizar los pacientes alérgicos a picaduras de abeja que reciben inmunoterapia. Se realizó un estudio observacional descriptivo de corte longitudinal en pacientes alérgicos a las picaduras de abeja tratados con inmunoterapia de extracto de abeja en el Hospital Universitario General Calixto García de La Habana, Cuba. La muestra fue de 17 pacientes que cumplieron los criterios de inclusión. Usamos técnicas de estadística descriptiva: promedio, probabilidad y puntaje estandarizado, así como técnicas de estadística inferencial tales como Chi cuadrado, verificando asociación significativa entre las variables; el nivel de significación empleado fue del 5 por ciento (p˂0,05). La tercera década de la vida fue la edad promedio de los pacientes. Se observó predominio del sexo masculino y residencia en zona urbana. Alrededor de la mitad de los pacientes tenían rinitis y antecedentes familiares de asma. Todos los pacientes tuvieron reacciones locales, la mayoría se re-expusieron a la picadura; de ellos, solo el 20 por ciento presentaron reacciones alérgicas sistémicas después de la inmunoterapia. Se concluye que la reactividad cutánea al extracto de abeja se redujo con el tratamiento de inmunoterapia(AU)

Allergy to bee venom may cause from mild to severe reactions threatening the patient´s life. Immunotherapy with hymenopter venom is an effective treatment that can protect allergic patients from suffering systemic reactions to new stings. The aim of this study was to characterize allergic patients to bee sting that receive immunotherapy. A descriptive longitudinal observational study was carried out in allergic patients to bee sting receiving immunotherapy with bee extracts in the University Hospital General Calixto García, Havana, Cuba. A sample of 17 patients with inclusion criteria was analyzed. Descriptive statistical techniques were used: mean, probability, standardized score, as well as, inferential statistic techniques such as the Chi square; verifying significant association between variables. The level of signification was 5 percent (p˂0.05). The third decade of life was the average age of the patients in this study; male sex and, urban residents were predominant. Around half of the patients had rhinitis and family history of asthma. All patients had local reactions; most of the patients were re-exposed to stings. Only 20 percent of patients reported systemic allergic reaction after immunotherapy. Skin reactivity to bee extract was reduced with the immunotherapy(AU)

A case of levocetirizine-induced liver injury

Levocetirizine is a second-generation nonsedative antihistaminic agent that has been demonstrated to be safe and effective for treating allergic disease. There was only one case report of levocetirizine-induced liver toxicity, but a liver biopsy was not performed. In this article, we present the first case of levocetirizine-induced liver injury with histologic findings. A 48-year-old man was hospitalized with jaundice and generalized pruritus that had developed after 2 months of therapy with levocetirizine for prurigo nodularis. Laboratory findings revealed acute hepatitis with cholestasis. A liver biopsy demonstrated portal inflammation and hepatitis with apoptotic hepatocytes. The patient fully recovered 3 weeks after withdrawing levocetirizine. Although levocetirizine is safe and effective, physicians should be aware of its potential hepatotoxicity.

Clinical characteristics of children and adolescents with severe therapy-resistant asthma in Brazil / Características clínicas de crianças e adolescentes brasileiros com asma grave resistente a terapia

AbstractObjective: To describe the clinical characteristics, lung function, radiological findings, and the inflammatory cell profile in induced sputum in children and adolescents with severe therapy-resistant asthma (STRA) treated at a referral center in southern Brazil.Methods: We retrospectively analyzed children and adolescents (3-18 years of age) with uncontrolled STRA treated with high-dose inhaled corticosteroids and long-acting β2 agonists. We prospectively collected data on disease control, lung function, skin test reactivity to allergens, the inflammatory cell profile in induced sputum, chest CT findings, and esophageal pH monitoring results.Results: We analyzed 21 patients (mean age, 9.2 ± 2.98 years). Of those, 18 (86%) were atopic. Most had uncontrolled asthma and near-normal baseline lung function. In 4 and 7, induced sputum was found to be eosinophilic and neutrophilic, respectively; the inflammatory cell profile in induced sputum having changed in 67% of those in whom induced sputum analysis was repeated. Of the 8 patients receiving treatment with omalizumab (an anti-IgE antibody), 7 (87.5%) showed significant improvement in quality of life, as well as significant reductions in the numbers of exacerbations and hospitalizations.Conclusions: Children with STRA present with near-normal lung function and a variable airway inflammatory pattern during clinical follow-up, showing a significant clinical response to omalizumab. In children, STRA differs from that seen in adults, further studies being required in order to gain a better understanding of the disease mechanisms.

ResumoObjetivo: Descrever as principais características clínicas, a função pulmonar, as características radiológicas e o perfil inflamatório do escarro induzido de crianças e adolescentes com asma grave resistente a terapia (AGRT) tratados em um centro de referência do sul do Brasil.Métodos: Foram analisadas retrospectivamente crianças e adolescentes de 3-18 anos com diagnóstico de AGRT não controlada acompanhados durante pelo menos 6 meses e tratados com doses elevadas de corticoide inalatório associado a um β2-agonista de longa duração. Foram coletados prospectivamente dados relativos ao controle da doença, função pulmonar, teste cutâneo para alérgenos, perfil inflamatório do escarro induzido, TC de tórax e pHmetria esofágica.Resultados: Foram analisados 21 pacientes (média de idade: 9,2 ± 2,98 anos). Dos 21, 18 (86%) eram atópicos. A maioria apresentava asma não controlada e função pulmonar basal próxima do normal. Em 4 e 7 pacientes, o escarro induzido revelou-se eosinofílico e neutrofílico, respectivamente, e 67% dos pacientes que repetiram o exame apresentaram mudança no perfil inflamatório. Dos 8 pacientes que receberam omalizumabe (um anticorpo anti-IgE), 7 (87,5%) apresentaram melhora importante da qualidade de vida, com redução importante das exacerbações e hospitalizações.Conclusões: Crianças com AGRT apresentam função pulmonar próxima do normal e padrão inflamatório das vias aéreas variável durante o seguimento clínico, com importante resposta clínica ao omalizumabe. A AGRT em crianças difere da AGRT em adultos, e são necessários mais estudos para esclarecer os mecanismos da doença.

effect of olopatadine 0.1% ophthalmic solution on ocular and nasal symptoms in patients with seasonal allergic rhino- conjunctivitis

To evaluate the effect of olopatadine 0.1% ophthalmic solution twice daily on ocular and nasal symptoms in patients with seasonal allergic rhino-conjunctivitis. This study was conducted at the Ophthalmology and ear, nose and throat [ENT] clinics on patients with seasonal allergic rhino-conjunctivitis during spring and early summer seasons [March to end of June] in 2010 at Princess Haya Al Hussein hospital in the south of Jordan and in 2011 at Prince Rashid Bin Al Hassan hospital in the north of Jordan. The patients were divided randomly into 2 groups; group A [50 patients] received Olopatadine 0.1% ophthalmic solution [Patanol] twice daily, group B [51 patients] received placebo in the form of balanced salt solution. All patients attended ENT and Ophthalmology clinics weekly for 2 visits; they were reviewed regarding the improvement of ocular symptoms [itching, redness and lacrimation] and nasal symptoms [sneezing, itchy nose and runny nose]. In those patients who received Olopatadine 0.1% ophthalmic solution, after two weeks 98%, 98% and 90% of them showed satisfactory improvement according to a scale of 1 to 5 marked by the patients for itching, lacrimation and redness respectively compared to 14%, 12% and 6% in group B respectively [P-value <0.05]. Regarding nasal symptoms 90%, 84% and 78% of patients in group A showed satisfactory improvement regarding sneezing, running nose and nasal itching respectively compared to 8%, 16% and 10% in group B [P-value <0.05]. The treatment of ocular allergy positively impacts nasal symptoms. The use of ocular solution of Olopatadine 0.1% ophthalmic solution twice daily has an excellent effect on ocular symptoms and good effect on nasal symptoms, this effect was more significant at two weeks of treatment. Olopatadine 0.1% ophthalmic solution is a well-tolerated drug and may be considered as a primary treatment for patients with seasonal allergic rhino-conjunctivitis

Antihistamínicos Parte 1 - Historia y características de los receptores histaminérgicos / Antihistamines. Part 1 - History and characteristics of histaminergic receptors

Los antihistamínicos han sido usados durante los últimos 50 años y se han convertido en los medicamentos de mayor prescripción en el mundo. En este artículo se revisa el desarrollo de nuestro conocimiento referente a la histamina en el transcurso del siglo, como mediador biológico almacenado y liberado mayormente por los basófilos y mastocitos; mediador biológico situado en diferentes tejidos corporales, y otras células, con un papel fisiológico fundamental en el control de la secreción de ácido gástrico y un papel fisiopatológico en una gama de trastornos alérgicos. La síntesis y estudios farmacológicos de agonistas y antagonistas selectivos han establecido la existencia de cuatro tipos de receptores de histamina y antagonistas de ellos, que han encontrado muy importantes aplicaciones terapéuticas. Debido al aumento de la prevalencia de las enfermedades alérgicas según el Libro Blanco de Alergia (WAO), se deben crear normas que promuevan el uso de los antihistamínicos de manera adecuada y racional. De esta manera, la correcta elección debe ser realizada de acuerdo a su eficacia, tolerabilidad, seguridad, grupo etario, situaciones y precauciones particulares en pacientes con algún riesgo incrementado. El crear normas que promuevan una práctica terapéutica óptima o uso racional de dichos medicamentos. Elegirlos de acuerdo a su eficacia, tolerabilidad, seguridad, grupo etario, situaciones y precauciones especiales en pacientes portadores de ciertas enfermedades de riesgo a utilizarlos.(AU)

Antihistamines have been used for the last 50 years and have become the most prescribed medications in the world. In this article we review the development of our knowledge regarding histamine in the course of the century, as a biological mediator stored and released mostly by basophils and mast cells; biological mediator located in different body tissues, and other cells, with a fundamental physiological role in the control of gastric acid secretion and a physiopathological role in a range of disorders allergic The synthesis and pharmacological studies of selective agonists and antagonists have established the existence of four types of histamine receptors and antagonists of them, who have found very important therapeutic applications. Due to the increased prevalence of allergic diseases according to the White Paper on Allergy (WAO), standards should be created that promote the use of antihistamines in an adequate and rational way. In this way, the correct choice must be made in accordance to its efficacy, tolerability, safety, age group, situations and special precautions in patients with an increased risk. The creation of norms that promote an optimal therapeutic practice or rational use of said medications. Choose them according to their effectiveness, tolerability, safety, age group, situations and special precautions in patients with certain risk diseases to use them.

Glucocorticoid hypersensitivity syndrome: a case report / Síndrome de la hipersensibilidad glucocorticoidea reporte de caso

Glucocorticoid hypersensitivity syndrome has been reported to date only in several patients. This article describes a unique case of this syndrome in a 24-year old female admitted to hospital because of arterial hypertension and obesity. Although her clinical picture suggested Cushing's syndrome, she had low adrenocorticotropic hormone (ACTH) and cortisol levels with a poor response to corticotrophin-releasing hormone and Synacthen. In turn, an overnight dexamethasone suppression test with 0.25 mg of dexamethasone led to a dramatic decrease in morning cortisol. A diagnosis of glucocorticoid hypersensitivity was made and the patient started treatment with ketoconazole and cabergoline, which resulted in some clinical improvement. This case illustrates the need for clinical awareness of glucocorticoid hypersensitivity in patients suspected of Cushing's syndrome.

El síndrome de la hipersensibilidad glucocorticoidea ha sido reportado hasta la fecha en varios pacientes. Este artículo describe un caso único de este síndrome en una mujer de 24 años, ingresada en el hospital debido a hipertensión arterial y obesidad. Aunque su cuadro clínico hizo pensar en el síndrome de Cushing, presentaba un bajo nivel tanto de hormona adrenocorticotropa (ACTH) como de cortisol, acompañado de una respuesta pobre a la hormona liberadora de corticotropina y al synacthen. A su vez, una prueba de supresión de la dexametasona realizada durante la noche con 0.25 mg de dexametasona, condujo a una disminución dramática del cortisol en la mañana. Se hizo un diagnóstico de hipersensibilidad glucocorticoide, y la paciente empezó el tratamiento con ketoconazol y cabergolina, lo cual trajo como consecuencia cierta mejoría clínica. Este caso ilustra la necesidad de una mayor conciencia clínica en torno a la hipersensibilidad glucocorticoidea en pacientes sospechosos de padecer el síndrome de Cushing.

Effect of the 5-HT4 receptor and serotonin transporter on visceral hypersensitivity in rats

Visceral hypersensitivity plays an important role in motor and sensory abnormalities associated with irritable bowel syndrome, but the underlying mechanisms are not fully understood. The present study was designed to evaluate the expression of the 5-HT4 receptor and the serotonin transporter (SERT) as well as their roles in chronic visceral hypersensitivity using a rat model. Neonatal male Sprague-Dawley rats received intracolonic injections of 0.5% acetic acid (0.3-0.5 mL at different times) between postnatal days 8 and 21 to establish an animal model of visceral hypersensitivity. On day 43, the threshold intensity for a visually identifiable contraction of the abdominal wall and body arching were recorded during rectal distention. Histological evaluation and the myeloperoxidase activity assay were performed to determine the severity of inflammation. The 5-HT4 receptor and SERT expression of the ascending colon were monitored using immunohistochemistry and Western blot analyses; the plasma 5-HT levels were measured using an ELISA method. As expected, transient colonic irritation at the neonatal stage led to visceral hypersensitivity, but no mucosal inflammation was later detected during adulthood. Using this model, we found reduced SERT expression (0.298 ± 0.038 vs 0.634 ± 0.200, P < 0.05) and increased 5-HT4 receptor expression (0.308 ± 0.017 vs 0.298 ± 0.021, P < 0.05). Treatment with fluoxetine (10 mg·kg-1·day-1, days 36-42), tegaserod (1 mg·kg-1·day-1, day 43), or the combination of both, reduced visceral hypersensitivity and plasma 5-HT levels. Fluoxetine treatment increased 5-HT4 receptor expression (0.322 ± 0.020 vs 0.308 ± 0.017, P < 0.01) but not SERT expression (0.219 ± 0.039 vs 0.298 ± 0.038, P = 0.654). These results indicate that both the 5-HT4 receptor and SERT play a role in the pathogenesis of visceral hypersensitivity, and its mechanism may be involved in the local 5-HT level.

Alergia ocular / Ocular allergy

En el presente artículo revisaremos los aspectos más relevantes de la alergia ocular: su epidemiología, fisiopatología, cuadros clínicos y su terapéutica. Se encontrará una descripción más detallada de la fisiopatología ya que es, sin duda, la base del éxito terapéutico

In the present article we will review the most important aspectsof ocular allergy: its epidemiology, physiopathology, clinicalcharacteristics and treatment. A more detailed description ofthe physiopathology is addressed because is the basis for asuccessful treatment.

Evaluation of anti-allergic activity of gossypin and suramin in mast cell-mediated allergy model.

The mast cell-mediated allergic reactions are involved in many allergic diseases, such as asthma, allergic rhinitis and sinusitis. Stimulation of mast cells initiates the process of degranulation, resulting in the release of mediators such as histamine and an array of inflammatory cytokines. In this report, we investigated the effect of gossypin (a biflavonoid) and suramin (a synthetic polysulphonated naphtylurea) on the mast cell-mediated allergy model, and studied the possible mechanism of their action. Both gossypin and suramin inhibited (P<0.001) compound 48/80-induced systemic anaphylaxis reactions, antiprurities (P<0.001) and reduced the histamine release in rats. Further, both showed significant (P<0.001) protection against rat peritoneal mast cells activated by compound 48/80. Thus, our findings provide evidence that gossypin and suramin inhibit mast cell-derived allergic reactions.

Algunos aspectos de la prevención primaria y secundaria en alergia y asma / Strategies for primary and secondary prevention of asthma and allergy

Existe un aumento en la prevalencia de las enfermedades alérgicas y el asma. Dicho incremento es más notable en la población urbana de los países occidentales más industrializados. Enfermedades como el eczema atópico, la alergia a alimentos, la rinoconjuntivitis alérgica y el asma bronquial, entre otras, además de generar costos millonarios a los distintos estados, afectan notablemente la calidad de vida de la población que las padece, reflejándose en un gran ausentismo escolar y laboral entre otros aspectos. Las enfermedades alérgicas y el asma surgen de la interacción de factores genéticos y factores ambientales. Dicha interacción que provocará la sensibilización atópica y posteriormente el desarrollo de las distintas enfermedades, comienza en la vida fetal intrauterina, siendo clave el primer, y tal vez el segundo año de vida. Se describen diversas estrategias de prevención primaria para evitar la sensibilización, entre las que se destacan, el control ambiental para evitar o disminuir el contacto a diversos aeroalérgenos interiores, la manipulación en la dieta fomentando lactancia materna exclusiva hasta los 4 a 6 meses, utilizando en niños de riesgo fórmulas hidrolizadas como suplemento, evitar el tabaquismo en la embarazada y el pasivo en los niños pequeños. Entre las estrategias en la prevención secundaria, es decir, el evitar el desarrollo de una enfermedad alérgica después de la sensibilización, se destaca nuevamente el control ambiental (se mencionan distintos consejos de la OMS), la inmunoterapia con alérgenos y la farmacoterapia (antihistamínicos). Por último, se mencionan la influencia de la polución ambiental y el potencial papel de la terapia génica.

There has been an increase in the prevalence of asthma and allergic diseases, more notably in urban population of western developed countries diseases such as atopic eczema, food allergy, allergic rhinoconjunctivitis and bronchial asthma, among other, not only generate millionaire costs to the different states, but also considerably affect the quality of life of the population suffering them, which is reflected in a great work and school absence, among other aspects. Allergic diseases and asthma develop from the interaction between genes and environment. Such an interaction will cause allergic sensitization and lately the development of different diseases. It starts in fetal life and becomes more important in the first, and perhaps second, year of life. Different strategies for primary prevention are described to avoid atopic sensitization, such as allergen avoidance of indoor allergens, diet manipulation to avoid cow's milk protein with exclusive breast feeding until four to six months of life; use of hydrolyzed milk formulae as a replacement for or supplement to breast-feeding, late introduction of solid food, avoidance of active smoking among pregnant women and passive smoking in children. Among other strategies for secondary prevention, this is to avoid the development of an allergic disease after sensitization has occurred, again allergen avoidance is mentioned (with advice measures by WHO), allergen immunotherapy and medication (antihistamines). At last, the influence of air pollution and the potential use of gene therapy are also considered.

Alergia al venono de himenópteros / Hymenoptera venom allergy

La alergia al veneno de himenópteros es un hecho epidemiológicamente significativo. Alrededor del 0.15% al 3% de la población general tiene historia de reacciones sistémicas causada por picaduras de insectos. Entre los himenópteros más comunes que provocan este tipo de reacciones se encuentran: abejas, abejorros, avispas y hormigas. Las manifestaciones clínicas varian desde reacciones locales (eritema, edema, prurito o dolor) hasta reacciones sitémicas, e incluso shock anafilçactico con riesgo vital. El manejo inmediato depende de la intensidad de la reacción y abarca desde la aplicaión de frío local y el uso de antihistamínicos orales y corticoides tópicos y orales hasta, en los casos más severos, la administración de adrenaina inyectable. En relación con el tratamiento a largo plazo, la inmunoterapia específica ha demostrado ser muy efectiva en la reducción del riesgo de reacción severa frente a la posterior picadura de insecto.

Effect of single application of sodium fluoride gel to the hypersensitivity of teeth

Dental hypersensitivity is a worldwide problem that involves almost every body at some stage of life. Periodontal problems, attritions, abrasions, erosions of dental necks and dental treatment procedures etc. are the major causes of the dental hypersensitivity. Different modalities have been and are being used to reduce the discomfort of the patients. Nowadays a number of toothpastes are available for reduction of the problem with variable results. The problem if reduced is reduced at a slow speed with this toothpaste. A prompt relief is a genuine demand of the patient. Anything, which is simple to use, and effective immediately, is the need of day. Present study was designed to calculate the efficacy of Sodium Fluoride [NaF] gel in relieving dental hypersensitivity of different origins. 184 patients coming with a complaint of general dental hypersensitivity due to [1] Gingivitis/ Calculus [2] Periodontal Therapies [3] Abrasions and Erosions etc. were included. In this study NaF gel was applied all around, all of the teeth with the help of disposable syringe. Patients were recalled the next day, after one week, two week, and 4 week time. The relief of symptoms was assessed by the patient's verbal response. There was a prompt relief of symptoms in all of patients. 75% of the patients felt good relief [75 -100% reduction] of discomfort after 4 weeks time. 17% of patients had moderate relief [50-75% reduction] after 4 weeks while only 7% had poor relief [less than 50%]. The results were analyzed by t-test and Carl Pearson coefficient of correlation tests. Application of NaF gel might be a good single application agent for relief of dental hypersensitivity. Toothpastes may be used in conjunction with NaF gel application

Prevalencia de alergia al veneno de abeja entre los apicultores del sudoeste de la provincia de Buenos Aires / Prevalence of venom bee allergy in beekeepers of the Southwest of the Provincia de Buenos Aires

Objetivos. Relevar la prevalencia de racciones alérgicas (RA) por picaduras de abejas (Apis mellifera), así como el grado de conocimiento entre los apicultores y salas médicas en cuanto a los tratamientos y medidas de prevención. Materiales y métodos. Preguntas ak hoc en una encuesta realizada a apicultores, en 18 partidos del sudoeste bonaerense (proyecto financiado por el Consejo Federal de Inversiones). Resultados. De los 1.335 encuestados, el 97% alguna vez fue picado por una abeja, el 23% manifestó RA de diferente grado, el resto tuvo reacciones normales. Las RA son más frecuentes entre los 5 a 30 minutos posteriores a la picadura. En 8% de los que tuvieron RA necesitó ser medicado. El 94% de éstos fue medicado con algún tipo de corticoide. El 98% conoce el peligro de la picadura de abeja, y sólo el 71% respondió qué tratamiento aplicar en ese caso. Entre ellos, el 90% usaría algún tipo de corticoide (7% adrenalina y 2% antihistamínicos). Sólo el 6,6% sabe que tienen que usar adrenalina en caso de shock anafiláctico. El 1,6% de los apicultores sabe qué tratamiento se les aplicó. También representa un 1,1% del total de apicultores que debieron ser medicados en un hospital o sala. Conclusión. La actividad supone un riesgo alto de picaduras y la mayoría de los apicultores no cuentan con información suficiente para afrontar esta tarea con los conocimientos sobre prevención o tratamiento adecuados. Hay poco conocimiento en las salas asistenciales sobre el tratamiento de urgencia en un shock anafiláctico y su prevención.

Anti-IgE monoclonal antibody for treatment of asthma and other manifestations related to allergic diseases

OBJETIVO: Descrever as características farmacológicas, a eficácia e a segurança do omalizumabe, o primeiro anticorpo monoclonal anti-IgE aprovado para uso clínico, uma nova opção de tratamento da asma e das doenças alérgicas. FONTES DE DADOS: Pesquisa não sistemática na MEDLINE. Os principais artigos de revisão ou ensaios clínicos foram escolhidos com base em sua relevância segundo a opinião dos autores. SíNTESE DOS DADOS: O artigo destaca o importante papel da IgE na patogênese da doença alérgica, a lógica biológica para o uso da anti-IgE, as evidências que definiram a sua indicação atual na asma não controlada e possíveis indicações futuras, bem como as recomendações para uso clínico com doses ajustadas pelo peso e níveis séricos de IgE. O omalizumabe foi aprovado para uso em pacientes com asma grave não controlada que apresentem teste cutâneo positivo a pelo menos um aeroalérgeno relevante ou que apresentem IgE sérica alérgeno-específica para alérgenos relevantes, e cujo nível de IgE total esteja entre 30 e 700 UI/mL. Por enquanto, o uso deve ser restrito a pacientes maiores de 12 anos, mas é possível que a droga seja aprovada para uso a partir dos 6 anos de idade. CONCLUSÕES: Em alguns pacientes, a asma grave não é controlada com as opções de tratamento disponíveis para prevenção de sintomas e exacerbações, exigindo o uso freqüente ou prolongado de corticosteróides sistêmicos. Esses pacientes poderiam se beneficiar de tratamento com anti-IgE depois de reavaliação meticulosa das possíveis razões para a falta de controle da sua asma.

OBJECTIVES: To report on the pharmacology, efficacy and safety of omalizumab , a new option for the treatment of asthma and allergic diseases and the first monoclonal anti-IgE antibody approved for clinical use. SOURCES: MEDLINE, a non-systematic search including reviews and original papers, chosen according to their relevance in the authors' opinion. SUMMARY OF THE FINDINGS: The paper emphasizes the central role IgE plays in allergic diseases and the biological rationale for its use, the evidence upon which the current recommendations for the use of anti-IgE in uncontrolled asthma are based and its possible future applications, in addition to the recommendation that in clinical practice doses must be adjusted for weight and serum IgE levels. Omalizumab was approved in Brazil for patients with severe uncontrolled asthma presenting with a positive skin prick test for one or more relevant aeroallergen, or IgE specific to a relevant allergen detected in serum, having a total IgE level of between 30 and 700 UI/mL. For the time being its use should be restricted to patients aged 12 years or more, but there are prospects that it will be licensed for use with children over 6 years old. CONCLUSIONS: Some severe asthma cases cannot be controlled with the regular treatment options aimed at preventing symptoms and exacerbations, and so require frequent or prolonged use of systemic corticosteroids. These patients may benefit from treatment with anti-IgE, after a meticulous reevaluation of possible reasons for the failure to control asthma.

New antihistamines: a critical view

OBJETIVO: Avaliar criticamente os mais novos anti-histamínicos anti-H1 e os diferentes termos utilizados para denominá-los, com base na revisão de evidências sobre o papel dos anti-H1 no tratamento das doenças alérgicas. FONTES DOS DADOS: Artigos originais, revisões e consensos indexados nos bancos de dados MEDLINE e PUBMED de 1998 a 2006. Palavra chave: anti-histamínicos. SíNTESE DOS DADOS: Os anti-histamínicos de segunda geração diferenciam-se dos de primeira geração por sua elevada especificidade e afinidade pelos receptores H1 periféricos e pela menor penetração no sistema nervoso central (SNC), com conseqüente redução dos efeitos sedativos. Embora os anti-histamínicos de segunda geração sejam, geralmente, melhor tolerados do que seus predecessores, alguns efeitos adversos, principalmente cardiotoxicidade, surgiram com alguns deles. Nos últimos 20 anos, novos compostos, com diferentes farmacocinéticas, foram sintetizados. A maioria deles manifesta propriedades antiinflamatórias que independem de sua atividade no receptor H1. Aprimoramentos mais recentes, geralmente na forma de metabólitos ativos, levaram ao uso do termo anti-histamínico de terceira geração. Esse termo surgiu espontaneamente, sem uma descrição clara de seu significado e implicações clínicas, criando grande confusão entre os profissionais da saúde. CONCLUSÕES: Com base nas evidências sobre anti-histamínicos anti-H1, nenhum deles pode ser considerado como "anti-histamínico de terceira geração". Para tanto, seria preciso comprovar que a nova classe de anti-histamínicos possui vantagens clínicas distintas sobre os compostos existentes e preenche pelo menos três pré-requisitos: ausência de cardiotoxicidade, de interações medicamentosas e de efeitos sobre o SNC.

OBJECTIVE: To perform a critical evaluation of the more recent H1 antihistamines and the various terms used to describe them, based on a review of evidence on their role in the treatment of allergic disorders. SOURCES: Original articles, reviews and consensus documents published from 1998 to 2006 and indexed in the MEDLINE and PubMed databases. Keyword: antihistamines. SUMMARY OF THE FINDINGS: Second-generation antihistamines differ from first-generation ones because of their elevated specificity and affinity for peripheral H1 receptors and because of their lower penetration of the central nervous system (CNS), having fewer sedative effects as a result. Whilst second-generation antihistamines are in general better tolerated than their predecessors, some adverse effects, principally cardiotoxicity, have been observed with some of them. Over the last 20 years, new compounds with different pharmacokinetic properties have been synthesized. The majority of these exhibit anti-inflammatory properties that are independent of their action on the H1 receptor. More recent improvements, generally in the form of active metabolites, led to the use of the term third-generation antihistamines. This term emerged spontaneously, with no clear definition of its meaning or clinical implications, creating great confusion among healthcare professionals. CONCLUSIONS: On the basis of the evidence on H1 antihistamines, none of them deserve the title"third-generation antihistamine." As the Consensus Group on New Generation Antihistamines concluded, to merit this definition, a new class of antihistamines would have to demonstrate distinct clinical advantages over existing compounds and fulfill at least three prerequisites: they should be free from cardiotoxicity, drug interactions and effects on the CNS.

Acute myocardial ischemia following accidental intravenous administration of epinephrine in high concentration.

Inadvertent and accidental epinephrine overdose might result in potentially lethal complications. We present a case of acute epinephrine toxicity resulting in acute myocardial ischemia in a young boy with combined variable immunodeficiency syndrome who developed severe allergic reaction to intravenous immunoglobulin, and was subsequently given epinephrine by mistake intravenously rather than subcutaneously. He developed significant ischemic changes in standard 12-lead electrocardiogram, transiently raised cardiac enzymes, reduced left ventricular systolic function, pulmonary edema and pulmonary hemorrhage. It is suggested that special precautionary measures should be taken regarding the dose and the route while administering epinephrine to avoid mishaps.