Ricardo José Di Masso

Protected Trypanosoma cruzi infection in rats born to mothers receiving interferon-gamma during gestation is associated with a decreased intramacrophage parasite growth and preferential synthesis of specific IgG2b antibodies

We demonstrated that administration of interferon gamma (IFN-gamma) to pregnant rats conferred partial resistance in their offspring to further challenge with Trypanosoma cruzi. Because of the effects of IFN-gamma on macrophage activation and immunoglobulin isotype selection, offspring were now studied to ascertain whether this intervention modifies the in vitro replication of T. cruzi and nitric oxide (NO) production by peritoneal macrophages (PE), together with the anti-T. cruzi IgG isotypes. To evaluate the possibility of a detrimental effect of IFN-gamma, serum levels of anti-sulphatide autoantibodies were also investigated. Offspring were born to mothers undergoing one of the following procedures during gestation: treatment with recombinant rat IFN-gamma, 50,000 IU/rat, five times/week for 3 weeks, which was started on the day of mating; infection with 10(6) trypomastigotes of T. cruzi at 7, 14, and 21 days after mating plus IFN-gamma treatment as given to the former group; the same protocol except that physiological saline was injected instead of IFN-gamma; injection of physiological saline only. Offspring were challenged at weaning with a similar dose of T. cruzi, to constitute four groups of infected young, plus an additional group of age-matched uninfected rats born to control mothers. PE were harvested at day 7 postinfection (pi), exposed to parasites and further investigated for the replication of T. cruzi and NO production, whereas ELISA studies for measuring serum anti-T. cruzi IgG subclasses and anti-sulphatide autoantibodies were performed at day 30 pi. The number of intracellular parasites in PE was markedly decreased in young born to IFN-gamma-treated mothers, this not being accompanied by higher nitrite levels in culture supernatants. Offspring delivered by IFN-gamma-treated mothers showed no higher serum concentrations of anti-sulphatide autoantibodies, but exhibited a preferential synthesis of anti-T. cruzi IgG2b antibodies. This rat isotype is known to fix complement and constitutes the rat counterpart of IgG2a mouse immunoglobulins whose synthesis is favoured by IFN-gamma.

Novel albendazole formulations given during the intestinal phase of Trichinella spiralis infection reduce effectively parasitic muscle burden in mice

Trichinellosis is a zoonotic disease affecting people all over the world, for which there is no speedy and reliable treatment. Albendazole (ABZ), an inexpensive benzimidazole used in oral chemotherapy against helminthic diseases, has a broad spectrum activity and is well tolerated. However, the low absorption and variable bioavailability of the drug due to its low aqueous solubility are serious disadvantages for a successful therapy. In this study, we evaluated the in vivo antiparasitic activity of three novel solid microencapsulated formulations, designed to improve ABZ dissolution rate, in a murine model of trichinellosis. Both ABZ and the microparticulate formulations were administered during the intestinal phase of the parasite cycle, on days 5 and 6 post-infection. This protocol significantly decreased muscle larval burden measured in the parenteral phase, on day 30 post-infection, when compared with the untreated control. Moreover, two of the three microencapsulated formulations both strongly and consistently reduced worm burden.

Efficacy of albendazole:β-cyclodextrin citrate in the parenteral stage of Trichinella spiralis infection

Albendazole-β-cyclodextrin citrate (ABZ:C-β-CD) inclusion complex in vivo antiparasitic activity was evaluated in the parenteral phase of Trichinella spiralis infection in mice. An equimolar complex of ABZ:C-β-CD was prepared by spray-drying and tested in CBi-IGE male mice orally infected with L1 infective larvae. Infected animals were treated with 50 or 30mg/kg albendazole, (ABZ) equivalent amounts of the ABZ:C-β-CD complex and non treated (controls). Mice received a daily dose on days 28, 29 and 30 post-infection. A week later, larval burden and percentage of encysted dead larvae were assessed in the host by counting viable and non-viable larvae in the tongue. Complexation of ABZ with C-β-CD increased the drug dissolution efficiency nearly eightfold. At 37 days p-i, the reduction percentage in muscle larval load was 35% in mice treated with 50mg/kg/day ABZ and 68% in those given the complex. Treatment with the lower dose showed a similar decrease in parasite burden. Treated animals showed a high percentage of nonviable larvae, the proportion being significantly higher in mice receiving the complex than in control animals (72-88% vs. 11%, P=0.0032). These data indicate that ABZ:C-β-CD increases bioavailability and effectiveness of ABZ against encapsulated Trichinella larvae, thus allowing the use of small doses.

Asymptotic weight and maturing rate in mice selected for body conformation

Padroes de crescimento de 4 linhagens de camundongos selecionados para a conformacao do corpo foram analisadas com a funcao logistica, de modo a se obterem informacoes basais a respeito da relacao entre o peso assintotico e a taxa de maturacao do peso corporal. Duas linhagens foram selecionadas divergentemente, favorecendo a correlacao fenotipica entre o peso corporal e o comprimento da cauda (selecao agonistica: CBi+, peso corporal elevado e cauda longa; CBi-, peso corporal reduzido e cauda curta), enquanto que as outras duas linhagens foram geradas por uma selecao disruptiva feita contra a correlacao entre os caracteres acima citados (selecao antagonistica: CBi/C, peso corporal elevado e cauda curta; CBi/L, peso corporal reduzido e cauda longa). Os parâmetros logisticos A (peso assintotico) e k (taxa de maturacao) comportaram-se em camundongos CBi/C e CBi- e em femeas CBi+ conforme esperado, em termos da relacao genetica negativa entre o tamanho maduro e a precocidade de maturacao. Um padrao alterado de crescimento foi encontrado em camundongos CBi/L e em machos CBi+, porque no primeiro genotipo, selecionado para reduzido peso corporal, o tempo decorrido para a maturacao aumentou, enquanto que no ultimo, selecionado para elevado peso corporal, houve um aumento nao significante no mesmo carater. De acordo com o criterio de selecao, fontes diferentes de variacao genetica para o peso corporal puderam ser exploradas: uma inversamente associada com precocidade de maturacao (selecao agonistica) e a outra independente da taxa de maturacao (selecao antagonistica), mostrando que a variacao genetica de A e parcialmente independente de k.

A mammary adenocarcinoma murine model suitable for the study of cancer immunoediting

BackgroundCancer immunoediting is a dynamic process composed of three phases: elimination (EL), equilibrium (EQ) and escape (ES) that encompasses the potential host-protective and tumor-sculpting functions of the immune system throughout tumor development. Animal models are useful tools for studying diseases such as cancer. The present study was designed to characterize the interaction between mammary adenocarcinoma M-406 and CBi, CBi− and CBi/L inbred mice lines.ResultsThe mammary adenocarcinoma M-406 developed spontaneously in a CBi mouse. CBi/L and CBi− mice were artificially selected for body conformation from CBi. When CBi mice are s.c. challenged with M-406, tumor growths exponentially in 100% of animals, while in CBi− the tumor growths briefly and then begins a rejection process in 100% of the animals. In CBi/L the growth of the tumor shows the three phases: 51.6% in ES, 18.5% in EQ and 29.8% in EL.ConclusionsThe results obtained support the conclusion that the system M-406 plus the inbred mouse lines CBi, CBi− and CBi/L, is a good murine model to study the process of tumor immunoediting.