RESUMO
BACKGROUND: Previous studies have established that mycobacterial infections ameliorate allergic inflammation. However, a non-infectious approach that controls allergic responses might represent a safer and more promising strategy. The 60-65 kDa heat shock protein (Hsp) family is endowed with anti-inflammatory properties, but it is still unclear whether and how single mycobacterial Hsp control allergic disorders. OBJECTIVE: Therefore, in this study we determined whether the administration of Mycobacterial leprae Hsp65 expressed by recombinant a DNA plasmid could attenuate a previously established allergic response. METHODS: We used an experimental model of airway allergic inflammation to test the effects of immunotherapy with DNA encoding Hsp65. Allergic mice, previously sensitized and challenged with ovalbumin, were treated with tree intramuscular doses of recombinant DNA encoding Hsp65. After treatment, mice received a second allergen challenge and the allergic response was measured. RESULTS: We found that immunotherapy attenuated eosinophilia, pulmonary inflammation, Th2 cytokine and mucus production. Moreover, we showed that the inhibition of allergic response is dependent on IL-10 production. Both Hsp65 and allergen-specific IL-10-producing cells contributed to this effect. Cells transferred from DNA-immunized mice to allergic mice migrated to allergic sites and down-modulated the Th2 response. CONCLUSIONS AND CLINICAL RELEVANCE: Our findings clearly show that immunotherapy with DNA encoding Hsp65 can attenuate an established Th2 allergic inflammation through an IL-10-dependent mechanism; moreover, the migration of allergen- and Hsp65-specific cells to the allergic sites exerts a fundamental role. This work represents a novel contribution to the understanding of immune regulation by Hsp65 in allergic diseases.
Assuntos
Proteínas de Bactérias , Chaperonina 60 , DNA Recombinante/administração & dosagem , Imunoterapia/métodos , Interleucina-10/metabolismo , Hipersensibilidade Respiratória/terapia , Animais , Proteínas de Bactérias/genética , Proteínas de Bactérias/imunologia , Chaperonina 60/genética , Chaperonina 60/imunologia , DNA Recombinante/imunologia , Modelos Animais de Doenças , Feminino , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Humanos , Interleucina-10/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mycobacterium leprae/imunologia , Hipersensibilidade Respiratória/imunologia , Resultado do TratamentoRESUMO
AIM: The aim of the present study was to clinically evaluate the oral mucosa lesions of leprosy patients during and after multi-drug therapy. METHODS: Clinical examination, medical and dental history examination was performed in 100 leprosy patients. RESULTS: The results revealed that 71 patients, 50 men and 21 women, exibited oral lesions. The most frequent lesions were: fissured tongue (18 cases), inflammatory papillary hyperplasia (16 cases), chronic atrophic candidiasis (10 cases), fibroma (10 cases), erythematous candidiasis (eight cases), and traumatic ulceration (seven cases). CONCLUSION: We conclude that leprosy-related lesions are not present in patients undergoing treatment for leprosy, probably due to response to multidrug therapy.
Assuntos
Hanseníase/complicações , Doenças da Boca/etiologia , Idoso , Brasil , Estudos Transversais , Dermatoses Faciais/etiologia , Feminino , Humanos , Hansenostáticos/uso terapêutico , Hanseníase/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/patologiaRESUMO
We describe long-term therapy for paracoccidioidomycosis occurring in a 61-year-old house-painter from Venezuela. The diagnostic examinations made in South America had shown pulmonary granulomatous lesions and an osteolytic pattern of the left knee that had been considered suspect of malignant disease with an indication for limb amputation. With the aid of fine needle aspiration biopsy (FNAB) and culture examination we diagnosed an osteomyelitis by Paracoccidioides brasiliensis and initiated therapy with itraconazole, 400 mg per day, reduced to 200 mg per day after 2 months. At the end of 2 years of drug therapy, we observed complete regression of the pulmonary lesions and of the osteolytic area of the left knee. Moreover, we have periodically observed our patient to verify his clinical development and he is still in good health. We suggest that this pathology be considered in differential diagnosis of leprosy, tuberculosis, leishmaniasis, and systemic mycoses, even in non-endemic areas.
Assuntos
Antifúngicos/administração & dosagem , Itraconazol/administração & dosagem , Osteomielite/tratamento farmacológico , Paracoccidioides/isolamento & purificação , Paracoccidioidomicose/tratamento farmacológico , Biópsia por Agulha , Esquema de Medicação , Humanos , Articulação do Joelho , Masculino , Pessoa de Meia-IdadeRESUMO
Sulfon bloord levels obstained injecting intramuscularly into rabbits, rats, guinea pig and dogs, oily suspension of sulfon are lower than those obtained with watery suspensions in the first 48 hours, but last longer. The sulfon blood levels obtained injecting sulfon watery suspension in gelatine does not pratically differ from those obtained injecting sulfon watery suspension in carboxymethylcellulose, those obtained by chaulmoogra oil suspension of sulfon are longer than those obtained by arachis oil suspension. However from the 192nd-240th hour, according to the animal species, the sulfon blood levels obtained with watery or oil suspensions minimal: for instance at 192nd hour rat´s sulfonemia after sulfon injection (0,125g/Kg) is 1,5 y/ml when the sulfon is suspensed in chaulmoogra oil, 1,2 y/ml in gelatin or in carboxymethylcellulose watery solutions. Successively sulfon blood levels are so reduced that it is doubtful their antibacteric efficacity