OBJECTIVE: To explore the use of β-lactoglobulin polymerized using microbial transglutaminase and heating to identify whether protein polymerization could reduce in vivo allergenicity and maintain in vitro and ex vivo immunoreactivity for use in tolerance-induction protocols. METHODS: Based on previous protocols applied in mice and children, we performed in vivo challenges (using a skin prick test) with native and polymerized β-lactoglobulin in adult patients with an IgE-mediated allergy to plactoglobulin. In vitro humoral immunoreactivity was analyzed using immunoblotting. Cell-mediated immunoreactivity was analyzed using ex vivo challenges with native and polymerized β-lactoglobulin and monitored by leukocyte adherence inhibition tests. RESULTS: The skin tests demonstrated that there was a significant reduction in immediate cutaneous reactivity after polymerization. Polymerization did not decrease the immunoblotting detection of s-IgE specific to β-lactoglobulin. Cell-mediated immunoreactivity, as assessed by ex vivo challenges and leukocyte adherence inhibition tests, did not exhibit significant differences between leukocytes challenged with native versus polymerized β-lactoglobulin. CONCLUSIONS: The polymerization of β-lactoglobulin decreased in vivo allergenicity and did not decrease in vitro humoral or ex vivo cell-mediated immunoreactivity. Therefore, we conclude that inducing polymerization using transglutaminase represents a promising technique to produce suitable molecules for the purpose of designing oral/ sublingual tolerance induction protocols for the treatment of allergies.

No presente estudo, realizou-se uma tentativa de indução de resistência a 3 drogas esquistossomicidas em uma cepa brasileira de S. mansoni, segundo o esquema de indução de resistência tipo II preconizado por JANSMA et al. em 1977. Houve insucesso nas 3 tentativas realizadas. A geração parental tratada com a droga durante o estágio imaturo do verme mostrou-se menos suscetível aos quimioterápicos do que as gerações F1 e F2 do verme. Uma hipótese é levantada para a explicação do fato.

In this work, an attempt was made to induceng resistance to 3 schistosomicidal drugs in a Brazilian strain of S. mansoni, according to the Type II resistance induction scheme proposed by JANSMA et al. in 1977. Three attempts were unsuccessful. The parental generation treated with the drug during the immature stage of the worm was less susceptible to the chemotherapeutic agents than generations F1 and F2. A hypothesis is suggested as an explanation.

A suscetibilidade de linhagem brasileira (MAP), nas gerações F1 a F5 de S. mansoni a quatro drogas esquistossomicidas foi descrita em trabalho anterior. Na presente pesquisa os Autores testam a estabilidade da progênie F14 da referida linhagem às quatro drogas e a um novo medicamento, Oltipraz (35,972 RP). Cinco grupos de 12 camundongos infectados com cercárias por meio da imersão da cauda, foram tratados com hycanthone, oxamniquine, niridazole, praziquantel e Oltipraz. Foi utilizado um grupo controle de camundongos infectados e não tratados. A atividade esquistossomicida das drogas foi avaliada pela localização dos vermes no sistema porta, pelas alterações no oograma e percentagem de redução de vermes. A suscetibilidade dos vermes da geração F14 mostrou-se estável em relação àquelas observadas nas progênies F1 a F5; a progênie F14 de vermes foi resistente ao hycanthone e oxamniquine; todavia, for sensível ao niridazole, prazi- quantel e Oltipraz. Os Autores enfatizam a importância do fenômeno de resistência do verme em vista do fato do oxamniquine ser largamente utilizado em áreas do Brasil onde a esquistossomose mansônica é endêmica.

The susceptibility of the MAP Brazilian strain (F1 to F5 progenies) of S. mansoni to four antischistosomal drugs has been reported in a previous study. In the present investigation, progeny F14 of the same strain, was tested for stability to the same 4 drugs. A new medication, Oltipraz (35,972 RP), was added to the study. Five groups of 12 mice infected with cercariae by tail immersion were treated with hycanthone, oxamniquine, niridazole, praziquantel and Oltipraz. An untreated group was used as control. Schistosomal activity was assessed by the localization of worms in the portal vein system, by oogram changes, and percentage of parasite reduction. The stability of the susceptibility of progeny F14 did not change in relation to generations F1 to F5; the progeny was resistant to hycanthone and oxamniquine; but sensitive to niridazole, praziquantel and Oltipraz. We emphasize the importance of the phenomenon of resistance of the worm in view of the fact that oxamniquine has been widely used in Brazilian areas where mansonic schistosomiasis is endemic.