A new l-amino acid oxidase from Bothrops jararacussu snake venom: Isolation, partial characterization, and assessment of pro-apoptotic and antiprotozoal activities.

A new l-amino acid oxidase (LAAO) from Bothrops jararacussu venom (BjussuLAAO-II) was isolated by using a three-step chromatographic procedure based on molecular exclusion, hydrophobicity, and affinity. BjussuLAAO-II is an acidic enzyme with pI=3.9 and molecular mass=60.36kDa that represents 0.3% of the venom proteins and exhibits high enzymatic activity (4884.53U/mg/mim). We determined part of the primary sequence of BjussuLAAO-II by identifying 96 amino acids, from which 34 compose the N-terminal of the enzyme (ADDRNPLEECFRETDYEEFLEIARNGLSDTDNPK). Multiple alignment of the partial BjussuLAAO-II sequence with LAAOs deposited in the NCBI database revealed high similarity (95-97%) with other LAAOs isolated from Bothrops snake venoms. BjussuLAAO-II exerted a strong antiprotozoal effect against Leishmania amazonensis (IC50=4.56µg/mL) and Trypanosoma cruzi (IC50=4.85µg/mL). This toxin also induced cytotoxicity (IC50=1.80µg/mL) and apoptosis in MCF7 cells (a human breast adenocarcinoma cell line) by activating the intrinsic and extrinsic apoptosis pathways, but were not cytotoxic towards MCF10A cells (a non-tumorigenic human breast epithelial cell line). The results reported herein add important knowledge to the field of Toxinology, especially for the development of new therapeutic agents.

New carbohydrazide derivatives of 1H-pyrazolo[3,4-b]pyridine and trypanocidal activity.

This paper reports the in vitro trypanocidal activity evaluation of new carbohydrazide derivatives from 3-methyl-1-phenyl-1H-pyrazolo[3,4-b]pyridine, substituted at C-6 position by phenyl, methyl or trifluoromethyl group. These compounds were evaluated in order to identify the antiparasitic profile against trypomastigote and amastigote forms of Trypanosoma cruzi. The 4-carbohydrazide derivatives presented different profiles of activity. In the investigation of the chemical structure influence in the trypanocidal activity, the results indicated there are large lipophilicity and volume differences among these derivatives. The complementarities of their stereoelectronic and physical-chemical aspects seem to be relevant for the biological activity against T. cruzi.

Efeito de bioterápico na eosinofilia durante a SLMV experimental / Biotherapic effect in eosinophilia during experimental VLMS

O Toxocara canis (Tc) é um parasito pertencente ao filo Nematódeo que possui como hospedeiro definitivo os cães, O homem é hospedeiro paratênico e contamina-se acidentalmente ao ingerir ovos contendo larvas infectantes (L3) do parasito, as quais são liberadas e atravessam a mucosa intestinal, atingem a circulação, Durante este processo migratório, antígenos de excreção e secreção (TES) são liberados provocando intensa reação inflamatória, do tipo Th2, caracterizando a síndrome, denominada Larva Migrans Visceral (SLMV), As principais características desta doença crônica são as eosinofilias sanguínea e tecidual persistentes, Desse modo, torna-se importante a busca por terapias que contribuam com a redução dos quadros inflamatórios com intensa eosinofilia, Assim, o uso deste bioterápico, produzido a partir do extrato antigênico de ovos e larvas de (Tc), e seu efeito no recrutamento de leucócitos totais, células mononucleares e eosinófilos no sangue, para o espaço broncoalveolar e para a cavidade peritoneal de camundongos infectados pelo (Tc) foi investigado, Foram utilizados camundongos fêmeas (Swiss), divididos nos grupos: Controle (C), Infectado (Tc), Imunizado (Im+Tc) e Tratado (Tc+Bio), Os animais Tc, Im+Tc e Tc+Bio receberam 500 ovos/animal por gavagem, Posteriormente, os animais foram eutanasiados no 18º dia da infecção e o número das células nos compartimentos foi determinado, Os resultados obtidos demonstraram que, Im+Tc, assim como nos Tc+Bio tiveram redução significativa dessas células nos compartimentos analisados quando comparados grupo Tc, Assim, sugeriu-se que a bioterapia modulou negativamente o recrutamento de células inflamatórias, principalmente eosinófilos no sangue, pulmão e intestino demonstrando um potencial anti-inflamatório desse bioterápico na SLMV experimental...

The Toxocara canis (Tc) is a parasite that belongs to the nematode phylum and has dogs as definitive host. The men can be accidentally contaminated by ingesting eggs containing infective larvae of the parasite. These larvae, when ingested, pass through the intestinal mucosa, reach the portal circulation and migrate through different tissues of the host. During this process, excretory-secretory antigens (TES) are released causing an intense inflammatory reaction, the Th2 type, characterizing the syndrome, called Visceral Larva migrans (VLMS). The main features of this chronic disease are blood and tissue eosinophilias. Thus, it is important to search for therapies that may contribute to the reduction of inflammatory conditions with intense eosinophilia. In this study, we investigated the use of a biotherapic produced from the antigenic extract from eggs and larvae (Tc) and its effect on the recruitment of total leukocyte, mononuclear cells and eosinophils in blood, bronchoalveolar space and peritoneal cavity of mice infected with (Tc). Female mice (Swiss) were used divided in three groups: control (C), Infected (Tc) Immunized (Im + Tc) and Treaty (Tc + Bio). The animals Tc, Im + Tc and Tc + Bio received 500 eggs / animal by gavage. Subsequently, the animals were euthanized on day 18 after infection and the number of cells in the compartments was determined. Our results showed that, Im + Tc, as in Tc + Bio had reduced these cells in compartments analyzed compared to Tc group. Thus, it was suggested that the biotherapy negatively modulated the recruitment of inflammatory cells, particularly eosinophils in blood, lung and intestine demonstrating an anti-inflammatory potential of the biotherapic in the experimental VLMS...

Preparation, characterization and evaluation of the in vivo trypanocidal activity of ursolic acid-loaded solid dispersion with poloxamer 407 and sodium caprate

Ursolic acid is a promising candidate for treatment of Chagas disease; however it has low aqueous solubility and intestinal absorption, which are both limiting factors for bioavailability. Among the strategies to enhance the solubility and dissolution of lipophilic drugs, solid dispersions are growing in popularity. In this study, we employed a mixture of the surfactants poloxamer 407 with sodium caprate to produce a solid dispersion containing ursolic acid aimed at enhancing both drug dissolution and in vivo trypanocidal activity. Compared to the physical mixture, the solid dispersion presented higher bulk density and smaller particle size. Fourier Transform Infrared Spectroscopy results showed hydrogen bonding intermolecular interactions between drug and poloxamer 407. X-ray diffractometry experiments revealed the conversion of the drug from its crystalline form to a more soluble amorphous structure. Consequently, the solubility of ursolic acid in the solid dispersion was increased and the drug dissolved in a fast and complete manner. Taken together with the oral absorption-enhancing property of sodium caprate, these results explained the increase of the in vivo trypanocidal activity of ursolic acid in solid dispersion, which also proved to be safe by cytotoxicity evaluation using the LLC-MK2 cell line.

O ácido ursólico é um candidato promissor para o tratamento da doença de Chagas, contudo este fármaco possui baixa solubilidade aquosa e limitada absorção intestinal, ambos os fatores limitantes da biodisponibilidade. Entre as estratégias para potencializar a solubilidade e a dissolução de fármacos lipofílicos, as dispersões sólidas estão crescendo em popularidade. Neste estudo, empregamos mistura dos tensoativos, poloxamer 407 e caprato de sódio, para produzir dispersão sólida contendo ácido ursólico, com o objetivo de aumentar tanto a dissolução do fármaco quanto a atividade tripanocida in vivo. Comparada à mistura física, a dispersão sólida apresentou maior densidade e menor tamanho de partícula. Os resultados da análise de espectroscopia no infravermelho com transformada de Fourier mostraram interações intermoleculares do tipo ligações de hidrogênio entre o fármaco e o poloxamer 407. Os experimentos de difratometria de raio-X revelaram a conversão do fármaco de sua forma cristalina para a forma amorfa, mais solúvel. Consequentemente, a solubilidade do ácido ursólico em dispersão sólida foi aumentada e o fármaco dissolveu-se de maneira mais rápida e completa. Em conjunto com as propriedades promotoras de absorção oral do caprato de sódio, estes resultados explicaram o aumento da atividade tripanocida in vivo do ácido ursólico em dispersão sólida, que também se provou segura após avaliação de citotoxicidade empregando a linhagem celular LLC-MK2.

Trypanocidal activity of Brazilian plants against epimastigote forms from Y and Bolivia strains of Trypanosoma cruzi

Chagas disease is one of the main public health problems in Latin America. Since the available treatments for this disease are not effective in providing cure, the screening of potential antiprotozoal agents is essential, mainly of those obtained from natural sources. This study aimed to provide an evaluation of the trypanocidal activity of 92 ethanol extracts from species belonging to the families Annonaceae, Apiaceae, Cucurbitaceae, Lamiaceae, Lauraceae, Moraceae, Nyctaginaceae, and Verbenaceae against the Y and Bolivia strains of Trypanosoma cruzi. Additionally, cytotoxic activity on LLCMK2 fibroblasts was evaluated. Both the trypanocidal activity and cytotoxicity were evaluated using the MTT method, in the following concentrations: 500, 350, 250, and 100 µg/mL. Benznidazole was used for positive control. The best results among the 92 samples evaluated were obtained with ethanol extracts of Ocotea paranapiacabensis (Am93) and Aegiphila lhotzkiana (Am160). Am93 showed trypanocidal activity against epimastigote forms of the Bolivia strain and was moderately toxic to LLCMK2 cells, its Selectivity Index (SI) being 14.56, while Am160 showed moderate trypanocidal activity against the Bolivia strain and moderate toxicicity, its SI being equal to 1.15. The screening of Brazilian plants has indicated the potential effect of ethanol extracts obtained from Ocotea paranapiacabensis and Aegiphila lhotzkiana against Chagas disease.

Estudio cariométrico de placentas de ratones con infección aguda por diferentes cepas de Trypanosoma cruzi / Karyometric study of placentas from mice with acute infection by different strains of Trypanosoma cruzi

El objetivo de este trabajo fue evaluar cariometricamente las alteraciones causadas por diferentes cepas de T. cruzi en la placenta del ratón. Ratones hembras de 60 días, grávidas, fueron inoculadas, intraperitonealmente, con 2 x 10(5) tripomastigotes sanguíneos de las cepas colombiana, Y, Solivia o RC del T. cruzi. Fueron observadas claras diferencias en las alteraciones cariométricas de las células trofoblásticas gigantes y de las células trofoblásticas de la zona esponjosa. Los resultados demostraron que las cepas colombiana y RC causan alteraciones tanto en las células trofoblásticas gigantes como en las células del trofoblasto esponjoso, mientras que las cepas Y y Bolivia provocan alteraciones solamente en las células trofoblásticas gigantes. Es posible concluir que cada cepa posee características propias y que, a pesar del tipo similar de transmisión, presenta matices diferenciales en el proceso de la patogénesis placentaria.

The objective of this work was to evaluate karyometrically the alterations caused by different strains of Trypanosoma cruzi in the mouse placenta. Pregnant mice, 60-day old, were intraperitoneally inoculated with 2 x 10(5) bloodstream trypomastigotes of the Colombian, Y, Bolivia or RC strain of T cruzi. There were observed clear differences in the karyometric alterations of the trophoblast giant cells and in the spongiotrophoblast cells. The results demonstrate that the Colombian and RC strains cause alterations both in the trophoblast giant cells and in the spongiotrophoblast cells, whereas the Y and Bolivia strains provoke alterations only in the trophoblast giant cells. It is possible concluding that each strain has its own characteristics and that, in spite of the similar type of transmission, it show differential nuances in the placental pathogenic process.

Intraoperative topical administration of mitomycin C, in different concentrations, on the cicatrization of mioplasties of the dorsal rectus of rabbits / Administração tópica per-operatória da mitomicina C, em diferentes concentrações, sobre a cicatrização de mioplastias do reto dorsal de coelhos

Myoplasties of the extraocular muscle may cause adhesions between the operated muscle and the adjacent tissues, commonly generating cicatricial strabismus. With the purpose of reducing to a minimum the occurrence of adhesion, the effects of mitomycin C, an antifibrotic agent, were studied in concentrations of 0.008 percent, 0.02 percent, and 0.04 percent applied during intraoperative of myoplasties of the superior rectus muscle of rabbits. Fifty six animals were divided in five groups. During the postoperative, the operated areas were washed with physiological solution. Eye drop instillation to prevent inflammation and bacterial infection were used. The method to analyze the results consisted of clinical and histological evaluation and statistical analyzes. We also evaluated at the same time the amount of basic fibroblast growth factor (FGF-2) by immunohistochemical study. Clinically, more adhesions were found in the eyes of the control group than in the groups of treated eyes. However there was no significant statistics difference between the two groups (P>0.05). Histologically, mitomycin C caused a delayed cicatrization in the mioplastic areas, specially in the group who received the 0.02 percent concentration. The immunohistochemical showed FGF-2 marking in fibroblasts and macrophages, but between the groups there wasn't no difference. Based on those results, mitomycin C in the utilized concentrations was capable of delaying the cicatrization and consequently avoid the secondary strabismus without undesirable side effects.

Mioplastias da musculatura extra-ocular podem ensejar aderências entre o músculo operado e os tecidos adjacentes, produzindo, não raro, estrabismos cicatriciais. Com intuito de se minimizar a ocorrência de aderências, investigaram-se os efeitos da mitomicina C, como agente antifibrótico, em concentrações ascendentes de 0,008, 0,02 e 0,04 por cento, aplicada no per-operatório de mioplastias do reto superior do bulbo do olho de coelhos. Operaram-se 56 animais, que compuseram cinco grupos. No pós-operatório, instituíram-se limpeza com solução fisiológica das áreas operadas e profilaxia antimicrobiana e antiinflamatória, na forma de colírio. Avaliações clínica, histológica e imunoistoquímica, em que se estudou o fator de crescimento fibroblástico-básico (FGF-2), e estatística compuseram os métodos de análise dos resultados. Encontraram-se, clinicamente, mais aderências nos olhos-controle, comparativamente aos tratados, embora sem diferença estatística (P>0,05). À histologia, verificou-se que a mitomicina C ensejou retardo da cicatrização junto às áreas das mioplastias, notadamente no grupo que a recebeu, à concentração de 0,02 por cento. A imunoistoquímica revelou marcação do FGF-2 em fibroblastos e macrófagos indistintamente entre os grupos. Com base nos resultados, permite-se admitir que a mitomicina C, nas concentrações em que foi empregada, retardou a cicatrização e, por conseguinte, o estrabismo secundário, sem ensejar efeitos colaterais.

Morfometría de la parótida de ratón infectado por la cepa RAL de Trypanosoma cruzi en función del sexo / Morphometry of the parotid Gland in mice infected by the RAL strain of Trypanosoma cruzi in function of the sex

Fueron estudiadas las alteraciones y el nivel de deterioro de las parótidas de animales infectados con la cepa RAL de Trypanosoma cruzi. Se utilizaron ratones albinos (Mus musculus) de ambos sexos, debido al dimorfismo sexual de las glándulas salivares, inoculados con 2 x 104 tripomastigotes sanguíneos de la cepa RAL del T. cruzi. Los animales fueron sacrificados al 12° día de infección, coincidiendo con el pico parasitémico. La parótida fue procesada histológicamente y, posteriormente, evaluada histopatológica y morfométricamente. Los resultados permitieron verificar intenso parasitismo en la glándula, la que presentó desorganización estructural y atrofia generalizada de acinos y conductos, más intensos en las hembras. Concluyendo, la cepa RAL del T. cruzi mostró un comportamiento atípico en relación a otras cepas, causando modificaciones más evidentes en las hembras, debido, posiblemente, a alteraciones hormonales desencadenadas por el T. cruzi.

They were studied the alterations and the level of deterioration of the parotid gland in mice infected with the RAL strain oí Trypanosoma cruzi. They were used albino mice (Mus musculus) of both sexes, due to the existence of sexual dimorphism of the salivary glands, inoculated with 2 x 104 blood trypomastigotes of the RAL strain of T cruzi. The animals were sacrificed at the 12th day of infection, coinciding with the parasitemic peak, and the parotid gland was histologically processed and histopathologically and histometrically studied. The results allow verifying intense parasitism in the parotid gland with structural disorganization and widespread atrophy of acini and ducts, more marked in the females. Concluding, the RAL strain of T cruzi shows an atypical behavior in relation to other strains, provoking more clear modifications in the females, probably due to the hormonal alterations motivated by the T cruzi.

Synthesis, in vitro evaluation, and SAR studies of a potential antichagasic 1H-pyrazolo[3,4-b]pyridine series.

The development of new drugs against Trypanosoma cruzi is still required since the only two drugs currently used cause severe side effects. In this work we described the synthesis, the in vitro biological evaluation, and the SAR results of 1H-pyrazolo[3,4-b]pyridine derivatives, a new antichagasic agent series. The presence of fluorine, hydroxyl or nitro group at Y position resulted in at least one or two promising compounds in each set of derivatives (6f, 6g, 6i, 6l, and 6m). The SAR study showed that trypanocidal activity observed depends on both geometric and stereoelectronic parameters (MEP and frontier molecular orbitals HOMO and LUMO). We also used the Osiris program for calculating and comparing the fragment based druglikeness of the most active derivative (6g) (IC(50)=1.9microg/mL), the inactive compound (6o), and the current toxic antichagasic drugs (nifurtimox and benznidazole). Interestingly 6g presented a potential druglikeness higher than nifurtimox and benznidazole while 6o presented the lowest value among them.

Estudio morfométrico del hígado de ratón en la enfermedad de Chagas experimental / Morphometrical study of the mouse liver in the experimental Chagas' disease

El objetivo de este trabajo fue caracterizar histopatológicamente y morfométricamente las alteraciones del tejido hepático de ratón, durante la fase aguda de la infección por la cepa MORC-2 de Trypanosoma cruzi. Esta cepa mostró acentuado tropismo por el hígado, con numerosos nidos de amastigotes en los cortes examinados. El hígado de los animales infectados estaba constituido por células menores, con citoplasma granuloso. En algunas áreas, los sinusoides estaban congestionados y las células de Kupffer hipertróficas e hiperplásicas. El tejido hepático mostró focos circunscritos de células inflamatorias en áreas de necrosis, sinusoides, en torno de las venas centrolobulillares y de los espacios porta. La vena centrolobulillar estaba dilatada y congestionada, con necrosis focales y ruptura de la pared en algunos campos. Los espacios porta estaban desorganizados, a veces, con intenso infiltrado inflamatorio. En algunas áreas fue posible observar degeneración cística (spongis hepatis). Por todo el tejido hepático se observaron nidos de amastigotes, de tamaño variable, algunos rodeados por infiltrado inflamatorio crónico. En el espacio porta, el volumen relativo de los conductos biliares y vasos sanguíneos, así como la densidad de superficie de las arterias fueron mayores en el grupo infectado.

The objective of this work was to characterize histopatologically and morphometrically the alterations of the mouse liver during the acute infection by the MORC-2 strain of Trypanosoma cruzi. This strain showed marked tropism by the liver, with numerous nests of amastigotes in the examined sections. The liver of the infected animals was constituted by smaller cells, with granular cytoplasm. In some areas, the sinusoids were congested and the Kuppfer cells were hipertrofied and hiperplasic. The hepatic tissue showed circumscribed foci of inflammatory cells into necrotic areas, sinusoids, around the contrilobular veins and the portal spaces. The centrilobular vein was dilated and congested, with focal necrosis and rupture of the wall in some regions. The portal spaces were disorganized, sometimes with intense inflammatory infiltrate. In some areas it was possible to observe cystic degeneration (spongis hepatis). In the hepatic tissue, nests of amastigotes, of variable sizes, were observed, some surrounded by chronic inflammatory infiltrate. In the portal space, the relative volume of the biliary ducts and blood vessels, as well as the surface density of the arteries was greater in the infected group.

Biological activities and chemical composition of crude extracts from Chresta exsucca

As atividades tripanocida, leishmanicida, antibacteriana e antifungica dos extratos brutos de Chresta exsucca foram investigadas. Formas tripomastigotas do Trypanosoma cruzi, formas amastigotas de Leishmania amazonensis e vinte cepas de microrganismos, incluindo bactérias Gram-positivas, Gram-negativas e leveduras, foram utilizadas nos ensaios biológicos. Os melhores resultados foram obtidos para a atividade leishmanicida. A composição química dos extratos hexânicos e etanólicos dessa espécie foi determinada empregando-se técnicas cromatográficas como HRGC e HPLC-ESI-MS, respectivamente. Esteróides, triterpenos e flavonóides foram identificados.

Trypanocidal activity of Meliaceae and Rutaceae plant extracts

The in vitro trypanocidal activity of 22 extracts and 43 fractions of plants belonging to the families Meliaceae and Rutaceae was evaluated. The extracts from leaves of Conchocarphus heterophyllus and branches of Trichilia ramalhoi were the most active. The trypanocidal activity seems to be increased by fractionation of the extracts. Fractions from C. heterophyllus and Galipea carinata were the most active and a 100 percent lysis of the parasites was observed for five fractions. From one of them were isolated two flavonoids: flavone and 7-methoxyflavone, which showed weak trypanocidal activity. The results obtained from the extracts and fractions revealed that the order Rutales is a promising source for the search of new drugs for Chagas disease. Phytochemical studies with the other active fractions are underway in order to isolate compounds, which could be associated with observed activities.

Avaliação da atividade biológica do bioterápico in vivo sob as formas amastigotas na infecção experimental determinada por Leishmania (Viannia) braziliensis / Evaluation of the biological activity

As infecções por agentes do gênero Leishmania constituem um importante problema de saúde pública na Américas, sendo o Brasil o país que apresenta a mais alta incidência. Transmitida por fêmeas do inseto do gênero Lutzomyia, a Leishmania (Viannia) braziliensis, agente etiológico da Leishmaniose tegumentar americana (LTA), é uma zoonose, que impõe como principal característica patogênica uma infecção que varia de casos benignos, apresentando-se como lesão localizada, a casos que chegam a atingir tecidos mais profundos. O tratamento para essa doença é altamente tóxico, provocando diversos efeitos colaterais. Com base nesse fato, o objetivo deste trabalho foi avaliar o bioterápico (realizado com formas infectantes da Leishmania) como um tratamento alternativo para a Leishmaniose. Camundongos machos Mus musculus foram previamente infectados com a Leishmania (Viannia) braziliensis e depois tratados por três meses. Nos primeiros 30 dias de tratamento houve uma redução no diâmetro das lesões; no final, observou-se uma agravação dessas lesões, mas quando se comparou o grupo tratado com o controle negativo, as lesões estavam significantemente menores, mostrando um efeito terapêutico do bioterápico.

Estudo comparativo dos índices de cura de camundongos tratados com quimioterápicos e Trypanosominum (TC D30) / Comparative study of the healing level of mice treated with chemotherapics and trypanosominum TC D30

Carlos Chagas, em 1909, ao descobrir a infecçäo humana determinada pelo Trypanossoma cruzi descortinou uma doença em nosso continente que perdura até os nossos dias. Após sua descoberta, a doença humana tem se revelado sob várias formas de manifestaçäo e apresenta lesöes que refletem a extrema complexidade de sua patogenia

Tropismo tissular de diferentes cepas do Trypanosoma cruzi. V. Estudo histopatológico das alterações da glândula parótida de camundongos infectados com a cepa RC / Histopathological study of the alterations on mouse parotid gland infected by RC strain of the Trypanosoma cruzi

Os autores examinaram morfológica e morfometricamente a glândula parótida de camundongos inoculados com a cepa RC do Trypanosoma cruzi, na fase aguda da infecção. As células acinares mostraram-se com eosinofilia reduzida, cromatina condensada, núcleos menores e deslocados para o polo basal, além de luz reduzida. Os ductos estão dilatados e com células mais baixas. Os septos conjuntivos estão aumentados e com intenso infiltrado linfoplasmocitário. Formas amastigotas estão presentes nas células acinares e ductulares, no tecido conjuntivo inter e intralobular, no músculo dos vasos sangüíneos e dentro da luz dos ductos estriados

Estudo comparativo dos indices de cura de camundongos tratados com quimioterapicos e trypanosominum (TC D 30) / Comparative analysis of the cure rate in mices treated with chemoterapics and trypanosominum (TC D 30)

Trypanosoma cruzi strain isolated from wild mamals or from man and studied in the laboratory show different characteristics that permit their individualization. Blood trypamastigotes exhibit different morphological patterns according to the strain studied. Tropism for different tissues has also been reported. Morphologically, there are wide, thin and intermediate forms wose proportions vary. The results obtained by different investigations in the treatment of Chagas disease are discrepant in different geographic areas, probably because of a relationship with different populations of T.cruzi. In the presentestudy, we investigated experimentally the susceptibility of two polar species, i.e. two species with predominance of thin and wide forms, respectively (Y e Bolivia strains) to the action of Nifurtimax, Benzonidazol and Trypanosaminum (TC D30). Groups of 30 mice aged 60 days were inoculated with 10.4 bloodstream forms of the Y and Bolivia strains of T.cruzi. On the third day of infection, the animals were treated with 100 mg/Kg of both chemotherapeutic agents and with 5 dropsof Trypanosaminum (TC D 30) orally for 20 days. Each animal was evaluated for parasitemia and behavior. Xenodiagnosis and blood cultures were carried out after 40 days. The results showed: a) a sharp resistance of the Bolivia strain to the chemotherapeutic agents, while the Y strain was more susceptible; b) identical susceptibility of the Y and Bolivia strains to treatment with Trypanosominum. We infer from these data that the chemotherapeutic agents act on the parasitic formsby destroying them or not, with sharp differences when different populations areinvolved. In contrast, Trypanosaminum (TC D 30) may act on the stimulating the imunologic response, wich may destroy the etiologic agents through a specific response mechanism, regardless of the characteristics of the strain studied

Eletroforese de vasodilatadores coronarianos / Electrophoresis of coronary vasodilators

Os vasodilatadores coronarianos dinitrato de isossorbida e 1, 1, 1-tris (nitratometil) propano foram completamente separados por eletroforese unidimensional em papel (qualitativo Klabin), nos tempos de 15, 30, 60, 90 e 120 minutos, empregando-se eletrólitos de diversas concentraçöes, sob um gradiente de potencial de 12,6 v/cm

Comportamento de formas sangüícolas do Trypanosoma cruzi obtidas de camundongos utilizados como filtros biológicos em cultura e em triatomíneo / Behavior of the T. cruzi blood forms obtained from mice used as biological filters in culture of triatomine

Camundongos normais, utilizados como filtros biológicos, foram inoculados endovenosamente, com tripomastigotas sangüícolas da derivada RCL da cepa RC do T. cruzi. Decorridas 48 horas, os animais foram submetidos ao xenodiagnóstico e à punçäo cardíaca para semeadura do sangue em meio de Warren. No estômago dos triatomíneos e em cultura a 28-C, os tripomastigotas diferenciaram-se em formas arredondadas (esferomastigotas e/ou amastigotas). Esse comportamento das formas sangüícolas largas tem sido observado com freqüência e nos leva a inferir que a biologia do T. cruzi näo estaria apenas relacionada com a cepa, mas, eventualmente, com populaçöes do parasita