RESUMEN
PURPOSE: The pathogenesis of persistent allergic rhinitis with chronic and refractory nasal obstruction is still unknown. Inflammation and tissue remodeling are known to play a role, but this has not been studied thoroughly. The purpose of this study is to identify the profile of gene expression of inflammatory and remodeling markers in nasal mucosa of patients with PAR and chronic obstruction. METHODS: After informed consent, we obtained nasal mucosa tissue from five aeroallergen-sensitized PAR patients undergoing anterior turbinectomy, and control non-sensitized individuals undergoing cerebrospinal fluid fistula repair or rhinoplasty. We assessed the expression of 34 genes related to inflammation and tissue remodeling using the real-time polymerase chain reaction (qPCR) to quantify each mRNA. RESULTS: IL-4 mRNA was upregulated in nasal mucosa of all five patients; CCR3, CCR8 and Eotaxin-2 were upregulated in four out of five patient samples; while IL-5 and IL-13 were upregulated in two of them. TGF-ß1 was not upregulated in PAR samples. mRNA from metalloproteinases MMP-7, MMP13 and MMP15 were upregulated in three out of five samples. Our results indicate a typical mRNA expression profile of the infiltrating inflammatory Th2 cells and eosinophils, combined with altered gene expression of remodeling-related proteins in stromal cells from the mucosa. CONCLUSION: Prolonged allergen challenge can lead to persistent upregulation of genes for inflammatory mediators such as IL-4 Th2/eosinophil cytokines, chemokines and receptors, which may play an important role in maintaining PAR with chronic nasal obstruction. Our findings may have therapeutic implications, including the use of anti-IL4, -CCR3 or -MMP therapy to ameliorate the condition.
Asunto(s)
Mediadores de Inflamación , Interleucina-4/análisis , Metaloproteasas/análisis , Mucosa Nasal/inmunología , Obstrucción Nasal , Receptores CCR3/análisis , Rinitis Alérgica/inmunología , Adulto , Biomarcadores/análisis , Femenino , Perfilación de la Expresión Génica , Humanos , Mediadores de Inflamación/análisis , Mediadores de Inflamación/clasificación , Masculino , Persona de Mediana Edad , Obstrucción Nasal/etiología , Obstrucción Nasal/inmunología , Rinitis Alérgica/complicaciones , Rinitis Alérgica/patología , Tiempo , Regulación hacia ArribaRESUMEN
Antigen-5 is one of the major allergens identified in wasp venoms, and despite the fact that its biological function is still unknown, many studies have demonstrated its allergenicity. In this study, the biochemical and structural characterization of antigen-5 from the venom of the social wasp Polybia paulista are reported. A gel-based mass spectrometry strategy with CID fragmentation methods and classical protocols of protein chemistry, which included N- and C-terminal sequencing, were used to assign the complete sequence and determine the presence/location of the post-translational modifications (PTMs) of this protein. Six different isoforms of antigen-5 were identified in the crude venom of P. paulista ; the most abundant, which corresponds to the intact form of this protein, was recognized by the pool of human specific-IgE. This protein was extensively sequenced through CID mass spectrometry, and a series of PTMs were observed such as hydroxylation, phosphorylation, and glycosylation. Sequence data revealed that this protein has 59.3-93.7% identity with antigen-5 proteins from other known vespid venoms. The molecular model of P. paulista antigen-5 shows that this protein has three α-helices, one 310 helix, and four ß-sheets covering 28 and 17.9% of the sequence, respectively. The identification and characterization of allergenic compounds is essential for the development of advanced component-resolved allergy diagnostics and treatment.
Asunto(s)
Alérgenos/inmunología , Procesamiento Proteico-Postraduccional , Proteómica , Venenos de Avispas/inmunología , Alérgenos/química , Secuencia de Aminoácidos , Animales , Electroforesis en Gel Bidimensional , Datos de Secuencia Molecular , Homología de Secuencia de Aminoácido , AvispasRESUMEN
The phospholipases A(1) (PLA(1) s) from the venom of the social wasp Polybia paulista occur as a mixture of different molecular forms. To characterize the molecular origin of these structural differences, an experimental strategy was planned combining the isolation of the pool of PLAs from the wasp venom with proteomic approaches by using 2-D, MALDI-TOF-TOF MS and classical protocols of protein chemistry, which included N- and C-terminal sequencing. The existence of an intact form of PLA(1) and seven truncated forms was identified, apparently originating from controlled proteolysis of the intact protein; in addition to this, four of these truncated forms also presented carbohydrates attached to their molecules. Some of these forms are immunoreactive to specific-IgE, while others are not. These observations permit to raise the hypothesis that naturally occurring proteolysis of PLA(1) , combined with protein glycosylation may create a series of different molecular forms of these proteins, with different levels of allergenicity. Two forms of PLA(2) s, apparently related to each other, were also identified; however, it was not possible to determine the molecular origin of the differences between both forms, except that one of them was glycosylated. None of these forms were immunoreactive to human specific IgE.
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Fosfolipasas A1/análisis , Venenos de Avispas/análisis , Avispas/química , Animales , Glicosilación , Inmunoglobulina E/inmunología , Isoenzimas/análisis , Isoenzimas/química , Isoenzimas/inmunología , Espectrometría de Masas , Fosfolipasas A1/química , Fosfolipasas A1/inmunología , Proteómica , Análisis de Secuencia de Proteína , Venenos de Avispas/inmunologíaAsunto(s)
Alérgenos/química , Epítopos de Linfocito B/química , Venenos de Avispas/inmunología , Adulto , Alérgenos/inmunología , Secuencia de Aminoácidos , Animales , Epítopos de Linfocito B/inmunología , Femenino , Humanos , Inmunoglobulina E/inmunología , Inmunoglobulina G/inmunología , Masculino , Persona de Mediana Edad , Péptidos/inmunología , Avispas/inmunología , Adulto JovenRESUMEN
Since the first description of the syndrome of sideroblastic anemia with immunodeficiency, fevers and development delay (SIFD), clinical pictures lacking both neurological and hematological manifestations have been reported. Moreover, prominent skin involvement, such as with relapsing erythema nodosum, is not a common finding. Up to this moment, no genotype and phenotype correlation could be done, but mild phenotypes seem to be located in the N or C part. B-cell deficiency is a hallmark of SIFD syndrome, and multiple others immunological defects have been reported, but not high levels of double negative T cells. Here we report a Brazilian patient with a novel phenotype of SFID syndrome, carrying multiple immune defects and harboring a novel mutation on TRNT1 gene.
Asunto(s)
Anemia Sideroblástica/diagnóstico , Anemia Sideroblástica/etiología , Discapacidades del Desarrollo/diagnóstico , Susceptibilidad a Enfermedades , Fiebre , Síndromes de Inmunodeficiencia/diagnóstico , Fenotipo , Alelos , Biopsia , Análisis Mutacional de ADN , Femenino , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Genotipo , Humanos , Linfocitos/inmunología , Linfocitos/metabolismo , MutaciónRESUMEN
The study reported here is a classical bottom-up proteomic approach where proteins from wasp venom were extracted and separated by 2-DE; the individual protein spots were proteolytically digested and subsequently identified by using tandem mass spectrometry and database query with the protein search engine MASCOT. Eighty-four venom proteins belonging to 12 different molecular functions were identified. These proteins were classified into three groups; the first is constituted of typical venom proteins: antigens-5, hyaluronidases, phospholipases, heat shock proteins, metalloproteinases, metalloproteinase-desintegrin like proteins, serine proteinases, proteinase inhibitors, vascular endothelial growth factor-related protein, arginine kinases, Sol i-II and -II like proteins, alpha-glucosidase, and superoxide dismutases. The second contained proteins structurally related to the muscles that involves the venom reservoir. The third group, associated with the housekeeping of cells from venom glands, was composed of enzymes, membrane proteins of different types, and transcriptional factors. The composition of P. paulista venom permits us to hypothesize about a general envenoming mechanism based on five actions: (i) diffusion of venom through the tissues and to the blood, (ii) tissue, (iii) hemolysis, (iv) inflammation, and (v) allergy-played by antigen-5, PLA1, hyaluronidase, HSP 60, HSP 90, and arginine kinases.
Asunto(s)
Mordeduras y Picaduras de Insectos/fisiopatología , Proteínas de Insectos/aislamiento & purificación , Proteómica/métodos , Venenos de Avispas/química , Avispas/química , Animales , Brasil , Biología Computacional , Electroforesis en Gel Bidimensional , Glicosilación , Procesamiento de Imagen Asistido por Computador , Immunoblotting , Mordeduras y Picaduras de Insectos/genética , Mordeduras y Picaduras de Insectos/metabolismo , Proteínas de Insectos/metabolismo , Espectrometría de Masas en Tándem , Venenos de Avispas/metabolismo , Avispas/metabolismoRESUMEN
BACKGROUND: Food allergy and eosinophilic esophagitis are a substantial and evolving public health issue. Clinicians should know the relationship between these diseases and how one may predispose to the other. This can help minimize misdiagnosis. OBJECTIVE: The objective of this study was to assess esophageal eosinophilia and eosinophilic esophagitis frequency in patients with persistent cow's milk allergy and anaphylaxis manifestations. METHODS: Patients with persistent cow's milk allergy with anaphylaxis manifestations were enrolled from 2012 through 2016 at the São Paulo University Hospital, Brazil. All of them were submitted to endoscopy despite the presence or absence of gastrointestinal symptoms. Demographics data, atopic comorbidities, medication use, endoscopic findings, and esophageal eosinophilia frequency were evaluated. RESULTS: Eighty-nine patients were selected. The median age was 8 years. It was observed that 34 of 89 patients (38.2%; 95% confidence interval [CI]: 28.14%-49.16%) presented with esophageal eosinophilia. Five patients (7.1%) presented proton pump inhibitor-responsive esophageal eosinophilia, and 10 patients (14.2%) presented eosinophilic esophagitis. We found that 29.4% were asymptomatic patients, 23.5% had nonspecific symptoms, 23.5% had persistent typical symptoms, and 23.5% had intermittent typical symptoms. There was an association with inflammatory endoscopy findings in 21 patients (61.7%). CONCLUSIONS: This description demands scientific attention because it is the highest frequency of esophageal eosinophilia yet described in a group of patients with cow's milk allergy presenting with anaphylaxis. Eosinophilic esophagitis is a condition that can coexist "silently" with an IgE-mediated food allergy and is most often underestimated and underdiagnosed.
Asunto(s)
Anafilaxia , Esofagitis Eosinofílica/diagnóstico , Hipersensibilidad a la Leche , Adolescente , Adulto , Biopsia , Niño , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
The biochemical and functional characterization of wasp venom toxins is an important prerequisite for the development of new tools both for the therapy of the toxic reactions due to envenomation caused by multiple stinging accidents and also for the diagnosis and therapy of allergic reactions caused by this type of venom. PLA(1) was purified from the venom of the neotropical social wasp Polybia paulista by using molecular exclusion and cation exchange chromatographies; its amino acid sequence was determined by using automated Edman degradation and compared to the sequences of other vespid venom PLA(1)'s. The enzyme exists as a 33,961.40 Da protein, which was identified as a lipase of the GX class, liprotein lipase superfamily, pancreatic lipases (ab20.3) homologous family and RP2 sub-group of phospholipase. P. paulista PLA(1) is 53-82% identical to the phospholipases from wasp species from Northern Hemisphere. The use restrained-based modeling permitted to describe the 3-D structure of the enzyme, revealing that its molecule presents 23% alpha-helix, 28% beta-sheet and 49% coil. The protein structure has the alpha/beta fold common to many lipases; the core consists of a tightly packed beta-sheet constituted of six-stranded parallel and one anti-parallel beta-strand, surrounded by four alpha-helices. P. paulista PLA(1) exhibits direct hemolytic action against washed red blood cells with activity similar to the Cobra cardiotoxin from Naja naja atra. In addition to this, PLA(1) was immunoreactive to specific IgE from the sera of P. paulista-sensitive patients.
Asunto(s)
Fosfolipasas A1/química , Venenos de Avispas/enzimología , Avispas/enzimología , Secuencia de Aminoácidos , Animales , Humanos , Immunoblotting , Inmunoglobulina E , Modelos Moleculares , Datos de Secuencia Molecular , Fosfolipasas A1/metabolismo , Conformación ProteicaRESUMEN
INTRODUCTION: Allergic rhinitis is considered the most prevalent respiratory disease in Brazil and worldwide, with great impact on quality of life, affecting social life, sleep, and also performance at school and at work. OBJECTIVE: To compare the efficacy and safety of two formulations containing mometasone furoate in the treatment of mild, moderate, or severe persistent allergic rhinitis after four weeks of treatment. METHODS: Phase III, randomized, non-inferiority, national, open study comparing mometasone furoate in two presentations (control drug and investigational drug). The primary endpoint was the percentage of patients with reduction of at least 0.55 in nasal index score (NIS) after four weeks of treatment. Secondary outcomes included total nasal index score score after four and 12 weeks of treatment; individual scores for symptoms of nasal obstruction, rhinorrhea, sneezing, and nasal pruritus; as well as score for pruritus, lacrimation, and ocular redness after four and 12 weeks of treatment. The study was registered at clinicaltrials.gov with the reference number NCT01372865. RESULTS: The efficacy primary analysis demonstrated non-inferiority of the investigational drug in relation to the control drug, since the upper limit of the confidence interval (CI) of 95% for the difference between the success rates after four weeks of treatment (12.6%) was below the non-inferiority margin provided during the determination of the sample size (13.7%). Adverse events were infrequent and with mild intensity in most cases. CONCLUSION: The efficacy and safety of investigational drug in the treatment of persistent allergic rhinitis were similar to the reference product, demonstrating its non-inferiority.
Asunto(s)
Antialérgicos/uso terapéutico , Furoato de Mometasona/uso terapéutico , Rinitis Alérgica/tratamiento farmacológico , Adolescente , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
Introdução: A dermatite atópica (DA) é uma doença inflamatória da pele, multifatorial, crônica e recorrente, caracterizada por lesões eczematosas e prurido intenso. Nos casos graves refratários aos tratamentos tópicos, tem se utilizado imunossupressão sistêmica para o controle da doença, sendo a ciclosporina considerada por muitos como terapia de escolha. Este estudo visa avaliar a incidência e gravidade dos eventos adversos relacionados ao uso de ciclosporina em pacientes com DA grave. Métodos: Estudo retrospectivo observacional com análise de prontuários de pacientes com dermatite atópica grave em uso de ciclosporina atendidos em hospital terciário no período de 3 anos. Resultados: Avaliados 80 pacientes com dermatite atópica grave usando ciclosporina, com média de idade de 25,5 anos e 41 do sexo feminino (51,3%). Foram relatados eventos adversos em 25 pacientes. O tempo médio de uso de ciclosporina no grupo com eventos adversos foi de 29,3 meses. Os eventos de maior gravidade foram alteração da função renal e hipertensão, sendo mais observados nos casos de doença mais refratária, quando o uso de ciclosporina foi muito prolongado, superior a 60 meses. As reações evidenciadas foram: hipertensão arterial 40%, alteração renal 20%, náuseas/vômitos 16%, cefaleia 12%, herpes de repetição 12% e outros 4%. Os eventos adversos normalizaram após suspensão da ciclosporina. Conclusão: Pacientes com dermatite atópica grave que usaram ciclosporina por tempo prolongado tiveram maior frequência de eventos adversos potencialmente graves. Todos os efeitos adversos normalizaram após a suspensão de medicação.
Rationale: Atopic dermatitis (AD) is an inflammatory, multifactorial, chronic, recurrent skin disease characterized by eczematous lesions and intense itching. In severe cases refractory to topical treatments, systemic immunosuppression has been used to control the disease, and cyclosporine is largely considered firstline therapy. This study aims to assess the incidence and severity of adverse events related to the use of cyclosporine in patients with severe AD. Methods: This retrospective observational study analyzed medical records of patients with severe atopic dermatitis using cyclosporine treated at a tertiary hospital over a 3-year period. Results: Eighty patients with severe atopic dermatitis using cyclosporine were evaluated. Their mean age was 25.5 years, and 41 (51.3%) were female. Adverse events were reported in 25 patients. The mean duration of cyclosporine treatment in the group with adverse events was 29.3 months. The most serious events were changes in renal function and hypertension, which were most often observed in cases of more refractory disease, when the use of cyclosporine was very prolonged (over 60 months). The adverse reactions were hypertension (40%), renal changes (20%), nausea/vomiting (16%), headache (12%), recurrent herpes (12%) and others (4%). Adverse events were under control after cyclosporine was discontinued. Conclusion: Patients with severe atopic dermatitis who used cyclosporine for a long time had a higher frequency of potentially serious adverse events. All adverse effects were under control after discontinuation of medication.
Asunto(s)
Humanos , Ciclosporina , Ciclosporinas/efectos adversos , Dermatitis Atópica , Cefalea , Hipertensión , Náusea , Pacientes , Terapéutica , Estudios Retrospectivos , Terapia de Inmunosupresión , Efectos Colaterales y Reacciones Adversas Relacionados con MedicamentosRESUMEN
As doenças autoinflamatórias são doenças inflamatórias raras cujo cerne imunológico baseia-se na imunidade inata. A maioria das doenças autoinflamatórias tem início na idade pediátrica, mas pouco se sabe sobre as doenças que se iniciam na vida adulta. O diagnóstico é feito por exclusão, e, quando possível, com auxílio de técnicas moleculares. Este artigo tem como objetivo relatar um caso de doença autoinflamatória de início na vida adulta e a partir dele estabelecer fluxograma de auxílio ao diagnóstico.
Autoinflammatory diseases are rare inflammatory conditions whose immunopathology relies essentially on innate immunity. The majority of autoinflammatory diseases have their onset in childhood, but little is known about diseases that initiate in adulthood. Diagnosis is made by exclusion and with the aid of molecular techniques whenever possible. This article describes a case of autoinflammatory disease that started in adulthood, and aims to propose a flowchart to aid in the diagnosis of these conditions.
Asunto(s)
Humanos , Femenino , Adulto , Fiebre Mediterránea Familiar , Colchicina , Enfermedades Autoinflamatorias Hereditarias , Inmunidad Innata , Terapéutica , Tomografía de Emisión de Positrones , DiagnósticoRESUMEN
A doença sistêmica relacionada à IgG4 é uma doença emergente, recentemente descrita, caracterizada clinicamente por aumento parcial ou total de um órgão, e, por isso, com amplo espectro de manifestações clínicas. Esta é uma doença sistêmica fibroinflamatória, patologicamente provocada pela infiltração de plasmoblastos IgG4 positivos que levam à inflamação eosinofílica do tecido e, consequentemente, fibrose estoriforme. Quando o diagnóstico é precoce, a melhora clínica e resposta sustentada com corticosteroides sistêmicos é impressionante. O diagnóstico é baseado em critérios patológicos, mas, recentemente, alguns trabalhos têm descrito que plasmoblastos no soro podem servir como um fator independente para auxiliar no diagnóstico da doença. Este artigo descreve uma apresentação atípica da doença relacionada à IgG4, em um paciente linfopênico com medição inconclusiva de plasmoblastos no soro.
IgG4-related systemic disease is a recently described, emerging condition, clinically characterized by partial or total enlargement of an organ, with a broad spectrum of clinical manifestations. It is a systemic fibroinflammatory condition caused by the infiltration of IgG4-positive plasmablasts that lead to eosinophilic inflammation of tissues and consequently storiform fibrosis. When diagnosis is early, clinical improvement and maintained response achieved with systemic corticosteroids is impressive. Diagnosis is based on pathological criteria, but recent papers have described that serum plasmablasts may serve as an independent factor to aid in diagnosis. This paper describes an atypical presentation of IgG4-related disease in a lymphopenic patient with inconclusive serum plasmablast measurement.
Asunto(s)
Humanos , Femenino , Persona de Mediana Edad , Enfermedad Relacionada con Inmunoglobulina G4 , Enfermedad Relacionada con Inmunoglobulina G4/diagnóstico , Linfopenia , Serositis , Eosinófilos , HipergammaglobulinemiaRESUMEN
As doenças autoinflamatórias sistêmicas são um grupo de doenças raras recentemente descritas, mas que vêm ganhando espaço no cenário clínico. Caracterizam-se por alterações da imunidade inata, portanto sem a presença de linfócito T autorreator ou autoanticorpo, e que respondem ao bloqueio de uma única citocina. Esta revisão tem como objetivo analisar a base imunofisiológica destas doenças e descrever brevemente cada uma delas com suas características clínicas mais importantes.
Systemic autoinflammatory diseases are a group of rare diseases only recently described but rapidly growing in importance in the clinical setting. They are characterized by innate immunity impairment, i.e., absence of autoreactive T lymphocytes or autoantibodies, and respond to individual cytokine blockade. The objective of this review was to analyze the immunophysiological basis of these diseases and to briefly describe each of them along with their most relevant clinical characteristics.
Asunto(s)
Humanos , Autoanticuerpos , Linfocitos T , Citocinas , Enfermedades Raras , Inmunidad Innata , Fiebre Mediterránea Familiar , Piodermia Gangrenosa , Acné Vulgar , Síndrome de Schnitzler , Deficiencia de Mevalonato Quinasa , Síndromes Periódicos Asociados a Criopirina , LipodistrofiaRESUMEN
ABSTRACT INTRODUCTION: Allergic rhinitis is considered the most prevalent respiratory disease in Brazil and worldwide, with great impact on quality of life, affecting social life, sleep, and also performance at school and at work. OBJECTIVE: To compare the efficacy and safety of two formulations containing mometasone furoate in the treatment of mild, moderate, or severe persistent allergic rhinitis after four weeks of treatment. METHODS: Phase III, randomized, non-inferiority, national, open study comparing mometasone furoate in two presentations (control drug and investigational drug). The primary endpoint was the percentage of patients with reduction of at least 0.55 in nasal index score (NIS) after four weeks of treatment. Secondary outcomes included total nasal index score score after four and 12 weeks of treatment; individual scores for symptoms of nasal obstruction, rhinorrhea, sneezing, and nasal pruritus; as well as score for pruritus, lacrimation, and ocular redness after four and 12 weeks of treatment. The study was registered at clinicaltrials.gov with the reference number NCT01372865. RESULTS: The efficacy primary analysis demonstrated non-inferiority of the investigational drug in relation to the control drug, since the upper limit of the confidence interval (CI) of 95% for the difference between the success rates after four weeks of treatment (12.6%) was below the non-inferiority margin provided during the determination of the sample size (13.7%). Adverse events were infrequent and with mild intensity in most cases. CONCLUSION: The efficacy and safety of investigational drug in the treatment of persistent allergic rhinitis were similar to the reference product, demonstrating its non-inferiority.
Resumo Introdução: A rinite alérgica é considerada a doença respiratória mais prevalente no Brasil e em todo o mundo, com grande impacto na qualidade de vida; além de, afetar a vida social, o sono e também o desempenho na escola e no trabalho. Objetivo: Comparar a eficácia e segurança de duas formulações contendo furoato de mometasona no tratamento da rinite alérgica persistente leve, moderada ou grave por um período de quatro semanas. Método: Trata-se de um estudo nacional aberto de fase III, randomizado, de não inferioridade de comparação do furoato de mometasona em duas apresentações (medicação de controle e fármaco sob investigação). O ponto final primário foi o percentual de pacientes com redução mínima de 0,55 no escore de índice nasal (EIN) após quatro semanas de tratamento. Os desfechos secundários foram: escore NIS total após 4 e 12 semanas de tratamento; escores individuais para sintomas de obstrução nasal, rinorréia, espirros e prurido nasal, bem como escores para prurido, lacrimejamento e hiperemia conjuntival após 4 e 12 semanas de tratamento. O estudo foi registrado em clinicaltrials.gov com o número de referência NCT01372865. Resultados: A análise de eficácia primária demonstrou não inferioridade do fármaco sob investigação em relação à medicação de controle, visto que o limite superior do intervalo de confiança (IC) de 95% para a diferença entre os percentuais de sucesso após quatro semanas de tratamento (12,6%) situava-se abaixo da margem de não inferioridade proporcionada durante a determinação do tamanho da amostra (13,7%). Eventos adversos foram pouco frequentes e de leve intensidade na maioria dos casos. Conclusão: A eficácia e a segurança de um fármaco experimental no tratamento da rinite alérgica persistente foram similares às do produto de referência, o que demonstrou sua não inferioridade.
Asunto(s)
Humanos , Masculino , Femenino , Adolescente , Adulto , Persona de Mediana Edad , Anciano , Antialérgicos/uso terapéutico , Rinitis Alérgica/tratamiento farmacológico , Furoato de Mometasona/uso terapéutico , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
AIM OF THE STUDY: This study assessed the involvement of endogenous glucocorticoids (GCs) in the anti-arthritic properties of bee venom (BV) on antigen-induced arthritis (AIA) in rabbits. MATERIALS AND METHODS: BV (1.5-6 microg/kg/day) was injected for 7 days before AIA induction, whereas the control group received sterile saline. The total and differential leukocyte count, PGE(2) levels in synovial fluid and synovial membrane cell infiltrate were evaluated. The contribution of GCs to BV action was assessed in rabbits treated with BV plus metyrapone, an inhibitor of GC synthesis, or RU-38 486, a steroid antagonist. RESULTS: Treatment with BV (1.5 microg/kg/day) reduced the leukocyte count and PGE(2) level (18571+/-1909 cells/mm(3) and 0.49+/-0.05 ng/mL, respectively) as well as the cellular infiltrate compared with the control group (40968+/-5248 cells/mm(3) and 2.92+/-0.68 ng/mL, p<0.05). The addition of metyrapone to BV treatment completely reversed the inhibition of AIA, whereas RU-38 486 was ineffective. CONCLUSION: Our data show that bee venom treatment prevents the development of antigen-induced arthritis in rabbits through the action of GCs.
Asunto(s)
Antiinflamatorios/farmacología , Antígenos/administración & dosificación , Artritis Experimental/tratamiento farmacológico , Venenos de Abeja/farmacología , Glucocorticoides/fisiología , Animales , Antiinflamatorios/uso terapéutico , Venenos de Abeja/uso terapéutico , Dinoprostona/metabolismo , Recuento de Leucocitos , Metirapona/administración & dosificación , Mifepristona/administración & dosificación , ConejosRESUMEN
UNLABELLED: Allergic rhinitis affects 10-30% of the population, negatively impacting one's quality of life and productivity. It has been associated with sinusitis, otitis media, sleep disorders, and asthma. Rupatadine is a second generation antihistamine with increased affinity to histamine receptor H1; it is also a potent PAF (platelet-activating factor) antagonist. It starts acting quite quickly, offers long lasting effect, and reduces the chronic effects of rhinitis. AIM: this study aims to assess the efficacy and safety of rupatadine in the treatment of persistent allergic rhinitis. MATERIALS AND METHOD: this is a multi-centric open prospective study. This study included 241 patients from 13 centers in Brazil and was held between October of 2004 and August of 2005. Signs and symptoms of rhinitis and tolerance to medication were analyzed after one and two weeks of treatment. RESULTS: reduction on general scores from 8.65 to 3.21 on week 2 (p<0.001). All signs and symptoms improved significantly in the first day of treatment (p<0.001), except for nasal congestion and secretion, which improved from the second day of treatment (p<0.001). Adverse events occurred in 19.9% of the cases, 27.7% on week 1. CONCLUSION: rupatadine effectively controls persistent allergic rhinitis; it is safe and presents low incidence of side effects.
Asunto(s)
Ciproheptadina/análogos & derivados , Antagonistas de los Receptores Histamínicos H1 no Sedantes/uso terapéutico , Rinitis Alérgica Perenne/tratamiento farmacológico , Adulto , Ciproheptadina/efectos adversos , Ciproheptadina/uso terapéutico , Femenino , Antagonistas de los Receptores Histamínicos H1 no Sedantes/efectos adversos , Humanos , Masculino , Estudios Prospectivos , Índice de Severidad de la EnfermedadRESUMEN
Allergic rhinitis affects 10-30 percent of the population, negatively impacting one's quality of life and productivity. It has been associated with sinusitis, otitis media, sleep disorders, and asthma. Rupatadine is a second generation antihistamine with increased affinity to histamine receptor H1; it is also a potent PAF (platelet-activating factor) antagonist. It starts acting quite quickly, offers long lasting effect, and reduces the chronic effects of rhinitis. AIM: this study aims to assess the efficacy and safety of rupatadine in the treatment of persistent allergic rhinitis. MATERIALS AND METHOD: this is a multi-centric open prospective study. This study included 241 patients from 13 centers in Brazil and was held between October of 2004 and August of 2005. Signs and symptoms of rhinitis and tolerance to medication were analyzed after one and two weeks of treatment. RESULTS: reduction on general scores from 8.65 to 3.21 on week 2 (p<0.001). All signs and symptoms improved significantly in the first day of treatment (p<0.001), except for nasal congestion and secretion, which improved from the second day of treatment (p<0.001). Adverse events occurred in 19.9 percent of the cases, 27.7 percent on week 1. CONCLUSION: rupatadine effectively controls persistent allergic rhinitis; it is safe and presents low incidence of side effects.
A rinite alérgica acomete 10 a 30 por cento da população, interferindo na qualidade de vida e na capacidade produtiva. Está associada à sinusite, otite, roncopatias e asma. A Rupatadina é um anti-histamínico de segunda geração, com elevada afinidade ao receptor histamínico H1 e potente inibição do fator ativador plaquetário (PAF). Tem rápido início de ação, longa duração e reduz os efeitos crônicos da rinite. OBJETIVO: Avaliar a eficácia e segurança da rupatadina no tratamento da rinite alérgica persistente. MATERIAL E MÉTODO: Estudo multicêntrico, aberto, prospectivo. Foram selecionados 241 pacientes em 13 centros no Brasil durante o período de outubro de 2004 a agosto de 2005. Foram analisados os sinais e sintomas da rinite e a tolerabilidade após 1 e 2 semanas. RESULTADOS: Redução do escore geral de 8,65 para 3,21 na semana 2 (p<0,001). Todos os sinais e sintomas melhoraram significativamente, e no primeiro dia de tratamento (p<0,001), com exceção da obstrução e secreção nasal, a partir do segundo dia (P<0,001). A frequência de eventos adversos foi 19,9 por cento, sendo 27,7 por cento na 1ª semana. CONCLUSÕES: A rupatadina é eficaz no controle da rinite alérgica persistente, é segura e apresenta baixos índices de efeitos colaterais.