Phosphorus protects cardiac tissue by modifying the immune response in rats infected by Trypanosoma cruzi.

AIM: This study evaluates and correlates the number of myocarditis focuses and production of cytokines in Rattus norvegicus (Wistar lineage), experimentally infected with T. Cruzi and treated with Phosphorus. METHODS: In two blind, controlled and randomized trials, 53 45-day-old, male animals were allocated into groups Control (n=24): Control group infected and treated with 7% hydroalcoholic solution, the preparation vehicle of the test medication; and Phosphorus (n=24 on days 0, 5, 10 and 24 after infection): group infected and treated with Phosphorus 13cH, diluted 10-26 and dynamized (test medication). The animals were inoculated intraperitoneally with 5×106 blood trypomastigotes of T. cruzi-Y strain. The medication was administered overnight (16 consecutive hours), diluted in water (1mL/100mL) in amber water bottles. The animals were treated 2days before and 2, 4, and 6days after infection. Enumeration of inflammatory foci in cardiac tissue (Hematoxylin-Eosin) and dosage of cytokines TNF-α and IFN-γ in the serum were performed on days 0, 5, 10 and 24 after infection, using three animals/group. Mann-Whitney, Friedman ANOVA, Spearman correlation (p<0.05), and Statistica Single User Software version 13.2 were used for data analysis. RESULTS: The animals treated with Phosphorus 13cH had high concentration of INF-É£ on the 5th day of infection with significant decrease on the 10th and 24th days (p<0.05), and high concentration of TNF-α on the 5th and 10th days of infection with decrease on the 24th day (p<0.05). The treatment with Phosphorus caused a significant increase of INF-É£ and TNF-α on the 5th day of infection compared with the Control (p<0.05), with reestablishment on the 24th day, as well as in the Control group. The group treated with Phosphorus had 52.5% less number of myocarditis focuses in heart than Control group (p<0.05) on the 10th day of infection. The significant increase in cytokines on the5th day of infection in the Phosphorus group is related to a significant decrease in the number of inflammatory foci in cardiac tissue on the 10th day of infection in this group. DISCUSSION AND CONCLUSION: Treatment with Phosphorus 13cH promotes beneficial effects in T. cruzi infection in Wistar rats by modulating the secretion of IFN-γ and TNF-α with decreased inflammation in cardiac tissue. These results reinforce the importance of considering the use of homeopathy for establishing new therapeutic approaches in the management of patients with Chagas disease.

Increased of the hepatocytes and splenocytes apoptosis accompanies clinical improvement and higher survival in mice infected with Trypanosoma cruzi and treated with highly diluted Lycopodium clavatum.

Recent evidence includes apoptosis as a defense against Trypanosoma cruzi infection, which promotes an immune response in the host induced by T cells, type 1, 2 and 17. Currently, there is no medicine completely preventing the progression of this disease. We investigated the immunological and apoptotic effects, morbidity and survival of mice infected with T. cruzi and treated with dynamized homeopathic compounds 13c: Kalium causticum (GCaus), Conium maculatum, (GCon), Lycopodium clavatum (GLy) and 7% alcohol solution (control, vehicle compounds, GCI). There was significant difference in the increase of apoptosis in the treated groups, compared with GCI, which might indicate action of the compounds in these cells. Infected animals treated with Lycopodium clavatum presented better performance compared with other groups. GLy showed a higher amount of hepatocytes and splenocytes undergoing apoptosis, higher number of apoptotic bodies in the liver, predominance of Th1 response, increased TNF-α and decreased IL-6, higher survival, lower morbidity, higher water consumption, body temperature, tendency to higher feed intake and weight gain compared with GCI. Conium maculatum had worse results with increased Th2 response with increased IL-4, worsening of the infection with early mortality of the animals. Together, these data suggest that highly diluted medicines modulate the immune response and apoptosis, affecting the morbidity of animals infected with a highly virulent strain of T. cruzi, being able to minimize the course of infection, providing more alternative approaches in the treatment of Chagas disease.

Highly diluted medication reduces tissue parasitism and inflammation in mice infected by Trypanosoma cruzi.

AIM: To evaluate the effects of Kalium causticum, Conium maculatum, and Lycopodium clavatum 13cH in mice infected by Trypanosoma cruzi. MATERIALS AND METHODS: In a blind, controlled, randomized study, 102 male Swiss mice, 8 weeks old, were inoculated with 1400 trypomastigotes of the Y strain of T. cruzi and distributed into the following groups: CI (treated with 7% hydroalcoholic solution), Ca (treated with Kalium causticum 13cH), Co (treated with Conium maculatum 13cH), and Ly (treated with Lycopodium clavatum 13cH). The treatments were performed 48 h before and 48, 96, and 144 h after infection. The medication was repertorized and prepared in 13cH, according to Brazilian Homeopathic Pharmacopoeia. The following parameters were evaluated: infectivity, prepatent period, parasitemia peak, total parasitemia, tissue tropism, inflammatory infiltrate, and survival. Statistical analysis was conduced considering 5% of significance. RESULTS: The prepatent period was greater in the Ly group than in the CI group (p = 0.02). The number of trypomastigotes on the 8th day after infection was lower in the Ca group than in the CI group (p < 0.05). Total parasitemia was significantly lower in the Ca, Co, and Ly groups than in the CI group. On the 12th day after infection, the Ca, Co, and Ly groups had fewer nests and amastigotes/nest in the heart than the CI group (p < 0.05). Decreases in the number of nests and amastigotes in the intestine were observed in the Ly group compared with the CI group (p < 0.05). In the liver (day 12), Ly significantly prevented the formation of inflammatory foci compared with the other groups. In skeletal muscle, Co and Ly decreased the formation of inflammatory foci compared with CI (p < 0.05). Ly afforded greater animal survival compared with CI, Ca, and Co (p < 0.05). The animals in the Co group died prematurely compared with the CI group (p = 0.03). CONCLUSIONS: Ly with 13cH potency had significantly more benefits in the treatment of mice infected with T. cruzi, reducing the number of blood parasites, amastigote nests in tissue, and the number of amastigotes per nest and increasing animal survival.

Different treatment schemes and dynamizations of Trypanosoma cruzi biotherapies: what information do they transfer to the organism in infected mice?

BACKGROUND: The use of biotherapies in Trypanosoma cruzi infection can provide an understanding about effects of these highly diluted medications. OBJECTIVES: To evaluate different treatment schemes and dynamizations of biotherapies prepared from blood trypomastigotes (buffy coat) in mice infected with T. cruzi. METHODS: Swiss mice infected with Y strain of T. cruzi were divided into two experiments. Experiment 1, all treated groups received biotherapy 7dH (10 µL/mL ad libitum) in different treatment schemes: TB7dH - treated 3 days before infection; TBA7dH - treated 3 days before and after infection; TBAe.d.7dH - treated 3 days before infection and every day after infection and IC - infection control. Experiment 2, all treated groups received medication in different dynamizations 3 days before and after infection (10 µL/mL ad libitum): TBA15dH - treated with biotherapy 15dH; TBA16dH - treated with biotherapy 16dH; TBA17dH - treated with biotherapy 17dH; TBAp.chords - treated with biotherapy 'potency chords' and IC - infection control. We evaluated parasitological and clinical parameters. RESULTS: Experiment 1 showed that different treatment schemes with biotherapy 7dH produced different effects on infection evolution. TBA7dH group had the best outcome, with lower parasitemia, higher survival, and better clinical evolution compared to IC. Experiment 2 showed that biotherapy 'potency chords' had effects different from the individual dynamizations that it contained (15dH, 16dH, and 17dH). Animals that had patent parasitemia had delayed emergence of parasites in blood and subsequent increase in parasitemia, but had better clinical evolution compared to IC. CONCLUSIONS: The effects of T. cruzi biotherapies depend on frequency at which they are administered, dynamization, and host-parasite relationship/individual susceptibility of treated organism. Biotherapy appeared to transfer to infected organism 'antigenic information' related to parasite and 'disease information' related to molecules produced by host's immune response and contained in the buffy coat used to prepare the medication.

Trypanosoma cruzi: biotherapy made from trypomastigote modulates the inflammatory response.

UNLABELLED: This study evaluates the effect of Trypanosoma cruzi biotherapy 17dH (BIOT) on mice of different ages, infected with the protozoa concerned. METHOD: Performing a blind, controlled, randomized by drawing experiment, 110 animals four or eight-week-old, Swiss, male mice were divided into infected control treated hydroalcoholic 7% (CI-4 = 34 or CI-8 = 21 animals) and infected control treated with biotherapy 17dH-0.2 mL/animal/20 consecutive days/oral regimen (BIOT-4 = 33 or BIOT-8 = 21 animals). Animals were inoculated intraperitoneally with 1400 trypomastigote, T. cruzi Y-strain. Parasitological, immunological and histopathologic parameters were evaluated statistically, using Statistica-8.0 and R 3.0.2 program to analysis of survival. The study was approved by the Ethics Committee for Animal Experimentation/UEM. RESULTS: Four-week-old mice showed no statistical difference in parasitemia (P = 0.5718) between the treated and control group. Eight-week-old mice from the treated group had a higher parasite peak (P = 0.0424) and higher parasitemia (P < 0.005) than the control. To both groups of 4 and 8 weeks of age, treated or untreated, survival of mice was higher in the treated group than in the control, although it was not statistically significant (p-value = 0.32, 0.55 respectively). Four-week-old mice displayed a spleen section with a number of amastigote nests significantly higher in BIOT-4 than CI-4 (P = 0.01). In eight-week-old mice the number of amastigote nests (P < 0.001) and inflammatory foci (P < 0.06-10% significance) in the liver section were smaller in BIOT-8 than CI-8. Spleen giant cells were significantly higher in CI-8 than in BIOT-8 (P < 0.01). Eight-week-old animals treated with biotherapy showed higher parasitemia and lower tissue parasitism. Opposite pattern was observed in four-week-old animals. CONCLUSION: There is a difference of high diluted medication effect in four and eight-week-old mice. In the group of animals 8 weeks the immunomodulatory effect seems to have been higher. Hence, treatment with the medicine produced from T. cruzi modulates the inflammatory response with increased apoptosis and decreased serum levels of TGF-ß.

Effects of Highly Diluted Drugs on Experimental Infection with Trypanosoma cruzi In Vivo: Systematic Review.

Objective: To investigate, through a systematic review, the effects of the use of highly diluted drugs in the treatment of experimental infection with Trypanosoma cruzi. Design: The authors searched for scientific publications in the databases PubMed, Web of Science, SCOPUS, LILACS, and the Google Scholar search system, from 2000 to 2018, following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement. According to the criteria established, a total of 22 studies were included. Settings/Location: The study took place at the State University of Maringá, Maringá, PR, Brazil. Subjects: Male mice (Mus musculus) or rats (Rattus norvegicus). Interventions: Highly diluted drugs. Outcome measures: The parameters evaluated in the studies were parasitological, clinical, immunological, histopathological and hematological. Results: The studies demonstrated that the effects of highly diluted drugs are related to their dynamizations, treatment regimen, and host susceptibility to T. cruzi infection, and depend on the initial information transmitted to the treated organism, making this information the "model" of how the treated organism will react. Regardless of the mechanism of action, these drugs provide a decrease in inflammation, which is one of the central phenomena of the pathogenesis of T. cruzi infection. Conclusions: This systematic review brings out the importance of the T. cruzi infection model as a reliable and valid model for studying different effects produced by highly diluted drugs. Considering the findings and in a broader perspective, this study contributes to considering these drugs as a possible way of dealing with "treatment" in general, presents the need to reexamine the biochemical model and develop a model for the effect of high dilutions in general, as well as for the treatment of parasitic infections.

Análise histopatológica dos efeitos do bioterápico 200dh em camundongos infectados por Trypanosoma Cruzi / Histopathological analysis of the effects of 200dh biotherapeutic in mice infected with Trypanosoma Cruzi

O Trypanosoma cruzi é um protozoário que instaura uma infecção grave em seu hospedeiro vertebrado, podendo causar danos irreversíveis, principalmente em suas células musculares, conhecida como a doença tripanossomíase ou Doença de Chagas. dicação disponível no mercado, que combate esse parasito, não é completamente eficiente e produz danos indesejáveis e irreversíveis, fazendo-se necessário a busca por outros campos da medicina, em termos de medicação, para combater essa doença. Nesse sentido, pesquisas com medicamentos homeopáticos têm se revelado promissoras no combate ao parasito, sobretudo as formas amastigotas, que são mais difíceis de serem exterminadas. Os bioterápicos são os homeopáticos que obtiveram maior sucesso em relação à infecção por T. cruzi, uma vez que esses medicamentos possuem seu princípio ativo retirado do próprio parasito, suas toxinas, parte de membros, realizando uma terapia conhecida como isoterapia ­ cura pelo igual. Resultados encontrados indicam que o bioterápico 200dH atua coagindo o sistema imune a combater o T. cruzi em cobaias contaminadas, fomentando uma resposta imune celular e humoral mais eficiente do que a fisiológica. Acredita-se que esse medicamento atue estimulando as células de defesa, que passarão a responder de forma antígeno- -específico, favorecendo o combate de amastigotas. Esse processo, provavelmente, é iniciado pela estimulação do macrófago, que por sua vez, de acordo com os resultados encontrados, inicia uma cascata inflamatória, com predominância da via Th1, fomentando a produção de IL4, IL-10 e interferon, auxiliando no combate as amastigotas.

The trypanosoma cruzi is a protozoan that causes a serious infeccion in the vertebrate host, being capable of causing irreversible damages mainly in the muscle cells, also known as trypanosomiasis disease or Chagas Disease. The commercially available drug medication which fights this parasite is not completely efficient and causes undesirable and irreversible damages making it necessary to search for other fields of medicine in terms of medication to combat this disease. Therefore research with homeopathic medicines has being promising in the fight against the parasite, especially the amastigote forms, which are more difficult to be exterminated. Biotherapics are the homeopathic ones that have been more successful in relation to T. cruzi infection, since these drugs have their active principle removed from the parasite itself, its toxins, part of its members, performing a therapy known as isotherapy - cure by the same. The results indicates that the 200dH biotherapic acts by coercing the immune system to fight T. cruzi in contaminated guinea pigs, promoting a cellular and humoral imune response more efficient than the physiological one. It is believed that this medicine works by stimulating the defense cells which will respond in an antigen-specific manner favoring the fight against amastigotes. This process is probably initiated by the stimulation of the macrophage which in turn, according to the remains found, initiates an inflammatory cascade with predominance of the Th1 pathway, promoting the production of IL-4e IL-5 and interferon helping to combat amastigotes

Current drug therapy and pharmaceutical challenges for Chagas disease.

One of the most significant health problems in the American continent in terms of human health, and socioeconomic impact is Chagas disease, caused by the protozoan parasite Trypanosoma cruzi. Infection was originally transmitted by reduviid insects, congenitally from mother to fetus, and by oral ingestion in sylvatic/rural environments, but blood transfusions, organ transplants, laboratory accidents, and sharing of contaminated syringes also contribute to modern day transmission. Likewise, Chagas disease used to be endemic from Northern Mexico to Argentina, but migrations have earned it global. The parasite has a complex life cycle, infecting different species, and invading a variety of cells - including muscle and nerve cells of the heart and gastrointestinal tract - in the mammalian host. Human infection outcome is a potentially fatal cardiomyopathy, and gastrointestinal tract lesions. In absence of a vaccine, vector control and treatment of patients are the only tools to control the disease. Unfortunately, the only drugs now available for Chagas' disease, Nifurtimox and Benznidazole, are relatively toxic for adult patients, and require prolonged administration. Benznidazole is the first choice for Chagas disease treatment due to its lower side effects than Nifurtimox. However, different strategies are being sought to overcome Benznidazole's toxicity including shorter or intermittent administration schedules-either alone or in combination with other drugs. In addition, a long list of compounds has shown trypanocidal activity, ranging from natural products to specially designed molecules, re-purposing drugs commercialized to treat other maladies, and homeopathy. In the present review, we will briefly summarize the upturns of current treatment of Chagas disease, discuss the increment on research and scientific publications about this topic, and give an overview of the state-of-the-art research aiming to produce an alternative medication to treat T. cruzi infection.

Biotherapic 200dH is harmful to acute murine infection with Trypanosoma cruzi

Biotherapics employed to treat mice infected by Trypanosoma cruzi were carried out with encouraging results. The aim of this study was evaluated the effect of biotherapic of Trypanosoma cruzi 200dH, using two different schedules of treatment. Swiss male mice, aged 56 days-old were infected intraperitonealy with 1,400 blood trypomastigotes of Trypanosoma cruzi Y strain and were divided into groups: C.I.- infected animals, E.D. â€" Infected animals treated from the day 1 until the end of the experiment; 200dH S.D. â€" Infected animals treated on the day 1. Parasitological, clinical and immunological parameters were evaluated. The group of animals that received the medicine in a single dose presented higher value to total parasitaemia and lower value of pre patent period compared to control untreated group (p<0.05), as well as the number of amastigotes which was also higher for this group (S.D.) (p<0.05). Clinically, the S.D.group presented more stable temperature (p<0.05) but not presented another clinical difference among treatments. IL-6 and TNF-α presented similar dosage among treated groups as well as IL-4 and IL-10. IL-17A and INF-γ, presented highest values to S.D. group (p<0.05). All animals died until the 20th day of infection. The lack of improvement in clinical and parasitological parameters, the untimely death and the immunological imbalance display the harmful evolution of the experimental infection by T. cruzi using biotherapic 200dH. The results could be useful for homeopathic physicians. In human clinical use, the choice of dynamizations and treatment schedule should consider acute and chronic diseases to achieve the expected results. (AU)

The Association of Ponderal Benznidazole with its Ultra-high Diluted Formula Reduces the Toxic Effects and Allows Increasing of Dose in Dose-dependent Protocol in Mice Infected with Trypanosoma cruzi

Although several diseases are treated by toxic drugs, their side effects may hamper adherence to the therapy. The aim of this study is to evaluate the effect of the association of ponderal benznidazole (BZ) with its ultra-high diluted (UHD) formula on clinical and parasitological parameters of mice infected by Trypanosoma cruzi (T. cruzi). 24 non-isogenic Swiss mice were divided into groups: CI – infected animals treated with 7% alcohol; BZp – infected animals treated with BZ (500 mg/ kg) from the beginning of infection; BZp+d – infected animals treated with ponderal BZ and with UHD BZ, which started to be administered four days after the beginning of treatment with ponderal BZ; CNI - group of non-treated and non-infected animals. The UHD medicine was prepared according to Phamacopoeia until 30x. The different treatment schedules were statistically compared through parasitological and clinical parameters. The group BZp+d displayed more favorable clinical evolution than the group BZp, with improvement of mass gain, feed conversion and water intake, presenting data approximated to CNI group. The significant increase of the body temperature of BZp+d group indicates an activation of the immune system which was not observed in the other groups. Moreover, the anti-parasitic effect of the ponderal drug was maintained in all parasitological parameters of this group. By reducing the side effects and maintaining the action of the ponderal drug, the combination of toxic drugs with their UHD formula could be considered a way of improving efficacy of the treatment. (AU)

A infecção por Trypanossoma cruzi é um problema de saúde pública e o único medicamento disponível no Brasil é o benznidazol (BZ), com efeitos limitados e tóxicos. Estudos anteriores com BZ na dose de 200 mg/kg indicaram que a administração de BZ diluído (30d) controla os efeitos tóxicos da droga em dose ponderal, sem alterar a sua ação terapêutica. Sob essa perspectiva e considerando a ação do BZ dose dependente, aumentar a quantidade de droga administrada significaria uma melhora na eficácia do tratamento. Portanto, este trabalho teve como objetivo avaliar o efeito do BZ ponderal (BZP), na dose de 500 mg/kg associado com BZ diluído (BZD) nos parâmetros clínicos de camundongos infectados por T. cruzi. Em estudo cego, controlado e randomizado, foram utilizados 23 camundongos suíços, machos, com 8 semanas divididos em grupos: CNI - Não infectados e não tratados; CI - Infectados e tratados com álcool 7 %; BZP - Infectados tratados com BZ (500 mg/kg de peso/ animal) a partir do início da infecção; BZP + BZD - Infectados e tratados com a associação de BZP e BZD. Os medicamentos foram administrados por gavagem (0,2 mL/ dia/ animal). O BZP foi administrado a partir da constatação da infecção. O BZ diluído foi preparado de acordo com a Farmacopeia Homeopática Brasileira e administrado 4 dias após o início do tratamento com BZP. Os parâmetros clínicos, avaliados diariamente, incluíram: peso, consumo de ração e água, temperatura e quantidade de excretas. A análise clínica apontou melhores resultados nos grupos BZP e BZP + BZD, mostrando melhor evolução de peso, consumo de ração, água e excretas quando comparado aos grupos não tratados (p< 0.05). A associação BZP + BZDobteve melhor evolução de peso, consumo de água e produção de excretas (p< 0.05) quando comparada com o grupo tratado BZP, revelando-se uma alternativa para diminuir os efeitos indesejados do medicamento convencional, permitindo o aumento da dose administrada e maior eficácia do tratamento. A associação destes medicamentos deve ser explorada em outras condições clínicas onde existem poucos medicamentos disponíveis e efeitos colaterais que comprometem a terapêutica

The Association of Ponderal Benznidazole with its Ultra-high Diluted Formula Reduces the Toxic Effects and Allows Increasing of Dose in Dose-dependent Protocol in Mice Infected with Trypanosoma cruzi

Although several diseases are treated by toxic drugs, their side effects may hamper adherence to the therapy. The aim of this study is to evaluate the effect of the association of ponderal benznidazole (BZ) with its ultra-high diluted (UHD) formula on clinical and parasitological parameters of mice infected by Trypanosoma cruzi (T. cruzi). 24 non-isogenic Swiss mice were divided into groups: CI – infected animals treated with 7% alcohol; BZp – infected animals treated with BZ (500 mg/ kg) from the beginning of infection; BZp+d – infected animals treated with ponderal BZ and with UHD BZ, which started to be administered four days after the beginning of treatment with ponderal BZ; CNI - group of non-treated and non-infected animals. The UHD medicine was prepared according to Phamacopoeia until 30x. The different treatment schedules were statistically compared through parasitological and clinical parameters. The group BZp+d displayed more favorable clinical evolution than the group BZp, with improvement of mass gain, feed conversion and water intake, presenting data approximated to CNI group. The significant increase of the body temperature of BZp+d group indicates an activation of the immune system which was not observed in the other groups. Moreover, the anti-parasitic effect of the ponderal drug was maintained in all parasitological parameters of this group. By reducing the side effects and maintaining the action of the ponderal drug, the combination of toxic drugs with their UHD formula could be considered a way of improving efficacy of the treatment...

A infecção por Trypanossoma cruzi é um problema de saúde pública e o único medicamento disponível no Brasil é o benznidazol (BZ), com efeitos limitados e tóxicos. Estudos anteriores com BZ na dose de 200 mg/kg indicaram que a administração de BZ diluído (30d) controla os efeitos tóxicos da droga em dose ponderal, sem alterar a sua ação terapêutica. Sob essa perspectiva e considerando a ação do BZ dose dependente, aumentar a quantidade de droga administrada significaria uma melhora na eficácia do tratamento. Portanto, este trabalho teve como objetivo avaliar o efeito do BZ ponderal (BZP), na dose de 500 mg/kg associado com BZ diluído (BZD) nos parâmetros clínicos de camundongos infectados por T. cruzi. Em estudo cego, controlado e randomizado, foram utilizados 23 camundongos suíços, machos, com 8 semanas divididos em grupos: CNI - Não infectados e não tratados; CI - Infectados e tratados com álcool 7 %; BZP - Infectados tratados com BZ (500 mg/kg de peso/ animal) a partir do início da infecção; BZP + BZD - Infectados e tratados com a associação de BZP e BZD. Os medicamentos foram administrados por gavagem (0,2 mL/ dia/ animal). O BZP foi administrado a partir da constatação da infecção. O BZ diluído foi preparado de acordo com a Farmacopeia Homeopática Brasileira e administrado 4 dias após o início do tratamento com BZP. Os parâmetros clínicos, avaliados diariamente, incluíram: peso, consumo de ração e água, temperatura e quantidade de excretas. A análise clínica apontou melhores resultados nos grupos BZP e BZP + BZD, mostrando melhor evolução de peso, consumo de ração, água e excretas quando comparado aos grupos não tratados (p< 0.05)...

Biology of Trypanosoma cruzi: An update / Biología del Trypanosoma cruzi: Actualización

Chagas disease, an illness caused by the protozoan Trypanosoma cruzi, is clinically and epidemiologically important in Latin America, and particularly in Brazil. This article presents the main biological characteristics of Trypanosoma cruzi, emphasizing ultrastructural, morphological, evolutionary, transcriptomic, and proteomic aspects. With this purpose a literature review was conducted, which allowed for the construction of different sections of the text. The efforts to expand the knowledge of this protist biology may bring positive implications for the understanding of the pathogenesis, control, and above all, treatment of patients affected by this disease.

A moléstia de Chagas, enfermidade causada pelo protozoário Trypanosoma cruzi, apresenta grande relevância clínica e epidemiológica na America Latina, com destaque para o Brasil. Neste artigo serão apresentadas as principais características biológicas do Trypanosoma cruzi, enfatizando-se os aspectos ultra-estruturais, morfológicos, evolutivos, transcriptômicos e proteômicos. Para tanto, foi realizada revisão da literatura, a qual subsidiou a construção de diferentes seções do texto. As investidas para ampliar o conhecimento acerca da biologia do protista poderão trazer implicações positivas para a compreensão da patogênese, do controle e, sobretudo, do tratamento dos pacientes portadores da moléstia.

Influência da idade e esquema de tratamento na parasitemia de camundongos infectados pelo Trypanosoma cruzi tratados com bioterápico de alta potência / Influence of age and ways of treatment in the parasitemia in mice infected with Trypanosoma cruzi treated with high potency biotherapy

ABSTRACTIntroduction: The infection of mice by Trypanosoma cruzi is well known, making this a good model for understanding the effect of highly diluted medications. Mice of different ages show different responses to biotherapic T. cruzi [1]. Other data from our laboratory using biotherapic treatment at low potencies show that long lasting treatment has a better effect in mice infected with T. cruzi. However, the use of high potency biotherapics in mice of different ages infected with T. cruzi has not been analysed yet.Conclusion: The age and the ways of treatment used are important factors to be considered when using a highly diluted medication. The clinical use of these results in humans, should take into consideration the allometric system of medication dosage which takes into account the metabolic rate of each organism.(AU)

Introdução: A infecção murina pelo Trypanosoma cruzi é bem conhecida, fazendo deste um bom modelo para o entendimento do efeito de medicamentos ultradiluídos. Camundongos de diferentes idades mostram diferentes respostas a bioterápico de T. cruzi [1]. Outros dados do nosso laboratório utilizando tratamento com bioterápico em baixas potências mostram que o tratamento prolongado exerce melhor efeito em camundongos infectados pelo T. cruzi. No entanto, a utilização de bioterápicos em alta potência em camundongos de diferentes idades infectados pelo T. cruzi ainda não foi explorada.Conclusão: A idade e o esquema de tratamento utilizado são fatores importantes a serem considerados na utilização de medicamento ultradiluído. A utilização clínica destes resultados em humanos, deve considerar o sistema alométrico de dosagem de medicamentos que leva em conta a taxa metabólica de cada organismo.(AU)

Avaliação do efeito de bioterápicos 15x,16x, 17x e acorde de potências de T. cruzi sobre a infeção experimental pelo Trypanosoma cruzi / Evaluation of biotherapies T. cruzi 15x, 16x, 17x and ?potency chords? in experimental infection by Trypanosoma cruzi

Background: The biotherapies are drugs widely utilized against infectious diseases. Biotherapies? profylatic and therapeutic action against Chagas Disease is currently being investigated, but it is needed to develop further controlled experiments ?in vivo?, which could define more clearly: dilution, dose, time of use and, if possible, the action mechanisms of these ultradiluted medicaments [1,2].Conclusions: Superior effect was obtained with biotherapies 17x and ?Potency Chords?, both for clinical and parasitological parameters. ?Potency chords? has proper effect which distinguishes it from the individual effects of the dilutions that compound it.(AU)

Introdução: Os bioterápicos são medicamentos amplamente utilizados contra doenças infecciosas. A ação profilática e terapêutica dos bioterápicos contra a doença de Chagas está atualmente sendo investigada, havendo ainda a necessidade do desenvolvimento de novos experimentos controlados ?in vivo?, que definam mais claramente: diluição, dose, tempo de utilização e se possível mecanismos de ação destes ultradiluídos [1,2].Conclusão: O melhor efeito foi obtido com bioterápico 17x e Acorde de potências, para parâmetros clínicos e parasitológicos. O Acorde de potências apresenta efeito próprio que o diferencia dos efeitos individuais das diluições que o compõem.(AU)

Efeito de bioterápico T. cruzi 7x em diferentes esquemas terapêuticos sobre a infeção experimental pelo Trypanosoma cruzi. / Effect of biotherapy T. cruzi 7x in several therapeutic schemes on experimental infection by Trypanosoma cruzi.

Background: Biotherapy is used against infectious diseases treatment and prophylaxis and has been investigated by many researchers [1,2]. Aim: Assess the effect of biotherapy 7x T. cruzi on several treatment schemes, upon experimental infection by T. cruzi.Conclusions: Best effect was obtained TBBA7x3days, both for clinical and parasitological parameters. It?s possible to speculate that in this regimen, biotherapy was able to modulate, more effectively, the host?s immune system, decreasing the number of parasites.(AU)

Introdução: A utilização de bioterápicos para o tratamento e profilaxia de doenças infecciosas, como doença de Chagas, tem sido investigado por diversos pesquisadores [1,2]. Objetivo: Avaliar o efeito do bioterápico 7x de T. cruzi em diferentes esquemas de tratamento, na infecção experimental pelo T. cruzi.Conclusões: O melhor efeito foi obtido com o grupo TBAD7x3dias, para parâmetros clínicos e parasitológicos, sendo possível especular que neste esquema o bioterápico foi capaz de modular, de forma mais eficaz, o sistema imunológico do hospedeiro, diminuindo o número de parasitos.(AU)

Bioterápico 17DH T. cruzi em uso prolongado melhora clinicamente camundongos infectados pelo Trypanosoma cruzi / Biotherapic T. cruzi 17DH when continuously used clinically improves mice infected with Trypanosoma cruzi.

Introduction: In Trypanosoma cruzi infection, the pathogenesis is the result of a rupture in the host - parasite relationship [1]. This rupture is related to the imbalance of the vital force of the host, expressed through signs and symptoms, defined by Hahnemann (1995)[2] as being the source of the disease. There is no research in the literature about the clinical evolution of mice experimentally infected with T. cruzi and treated in different ways using biotherapic. Therefore, this is an area to be studied in the future.Conclusion: The use of biotherapic T. cruzi 17DH for a long period causes clinical improvement of the infected mice with Trypanosoma cruzi. The clinical use of these results in human beings should consider the allometric medicine dosage which takes into account the metabolic rate of each organism(AU)

Introdução: Na infecção pelo Trypanosoma cruzi, a patogenia é resultado do rompimento do equilíbrio da relação parasito - hospedeiro (Tafuri, 1987), que está relacionada com o desequilíbrio da força vital do hospedeiro, expressando-se através de sinais e sintomas, definido por Hahnemann (2007), como sendo a origem da doença. Não existe na literatura trabalhos que abordem a evolução clínica de camundongos experimentalmente infectados pelo T. cruzi e tratados com diferentes esquemas de tratamento utilizando bioterápico. Sendo assim, é necessária a realização de estudos com este objetivo.Conclusão: O uso prolongado do bioterápico 17DH T. cruzi melhora clinicamente camundongos infectados pelo T. cruzi. A utilização clínica destes resultados em humanos, deve considerar o sistema alométrico de dosagem de medicamentos que leva em conta a taxa metabólica de cada organismo.(AU)

Perspectiva del manejo homeopático de las enfermedades tropicales / Perspective of homeopathic management of tropical diseases

Se calcula que cerca de 2700 millones de personas en el mundo viven en condiciones de pobreza y más de 1000 millones de personas se encuentran afectadas por una o varias enfermedades tropicales desatendidas. Las poblaciones más vulnerables son aquellas que viven en condiciones socioeconómicas de pobreza, las comunidades indígenas y los afrodescendientes. La OMS ha encaminado estrategias de integración en salud, que abarquen la problemática global de estas comunidades y en un marco de inclusión resalta los aportes que las Medicinas Tradicionales y Complementarias pueden proporcionar en la atención primaria de las enfermedades. La homeopatía, ha contribuido a través de la historia al control y tratamiento de las enfermedades epidémicas e incursiona en la investigación científica dando a conocer su utilidad en los distintos ámbitos de manejo de las Enfermedades Tropicales. Objetivo: Identificar las perspectivas del uso de la homeopatía como sistema médico complejo en el manejo de las enfermedades tropicales. Metodología: abordaje de tipo descriptivo, se realizó la búsqueda de la literatura disponible en diferentes bases de datos indexadas usando términos MeSH y palabras clave de interés. Resultados: Se encontró un total de 734 artículos en las bases de datos seleccionadas, estos artículos fueron distribuidos así: 558 para Malaria, 46 para Enfermedad de Chagas, 61 para Leishmaniasis, 64 para Dengue y 8 para Chikungunya. Del total de artículos se seleccionaron 24 que cumplieron con el criterio de selección y fueron clasificados como sigue: 6 en Malaria, 8 en Enfermedad de Chagas, 3 en Leishmaniasis, 5 en Dengue y 2 en Chikungunya. Conclusiones: La homeopatía ha presentado avances en términos de investigación y plantea tratamientos encaminados al uso de medicamentos constitucionales, del Genio epidémico y Nosodes para el manejo de las Enfermedades Tropicales con fines preventivos y de forma coadyuvante con la Medicina Convencional

Action of Canova® medicine onto peritoneal resident macrophages infected with Trypanosoma cruzi / Ação do medicamento Canova® em macrófagos peritoniais residentes infectados por Trypanosoma cruzi

Approximately 20 million of people are chronically infected with Trypanosoma cruzi in Latin America. The present work investigated the action of the homeopathic medicine Canova® in in vitro experimental infections with T.cruzi, type Y, using Swiss mice peritoneal resident macrophages. Our results demonstrated that Canova® induced a decrease in the production of H2O2 and TNF-alpha at 20% and 40% concentrations when compared to the control RPMI. However, when compared with this medicine excipient, there was a significant decrease of these nediators at 40% concentration only. The production of NO and the phagocytic activity were not affected. TNF-alpha inhibits the T.cruzi replication in peritoneal macrophages in vitro, becoming an important agent of infection control by this parasite. Within this context, Canova®, unlike what has been reported to other infections, would function as a stimulator of the infection, since it inhibited the production of TNF-alpha by peritoneal resident macrophages in vitro. Further studies should be carried out with elicited macrophages, in order to confirm the Canova® inhibitory activity on the production of TNF-alpha and other mediators in macrophages infected by T.cruzi.

Aproximadamente 20 milhões de pessoas são cronicamente infectadas pelo Trypanosoma cruzi na América Latina. O presente trabalho investigou a ação do medicamento homeopático Canova® em infecções experimentais in vitro com Trypanosoma cruzi, cepa Y, usando macrófagos residentes peritoniais de ratos Swiss. Os resultados mostraram que Canova® induz uma diminuição significativa da produção de H2O2 e TNF-alfa em concentrações de 20% e 40%, quando comparado com o controle RPMI. Quando comparado com o excipiente do medicamento, observou-se uma diminuição na concentração destes mediadores apenas na concentração de 40%. A produção de NO e a atividade fagocítica não foram afetadas. TNF-alfa inibe a replicação do protozoário em macrófagos peritoniais in vitro, mostrando-se um importante agente para o controle da infecção pelo parasita. Portanto, o medicamento Canova® poderia estimular o processo de infecção, pois promoveu inibição da produção de TNF-alfa por macrófagos peritoniais residentes in vitro. Estudos adicionais devem ser realizados com macrófagos elicitados, a fim de confirmar a atividade inibitória da Canova® sobre a produção de TNF-alfa e outros mediadores em macrófagos infectados por T. cruzi.