RESUMO
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.
Assuntos
Cardiotônicos/farmacologia , Doença de Chagas/tratamento farmacológico , Doença de Chagas/imunologia , Coração/efeitos dos fármacos , Miocárdio/imunologia , Fósforo/farmacologia , Animais , Doença de Chagas/patologia , Modelos Animais de Doenças , Coração/parasitologia , Homeopatia , Interferon gama/sangue , Masculino , Miocárdio/patologia , Ratos , Ratos Wistar , Trypanosoma cruzi/imunologia , Fator de Necrose Tumoral alfa/sangueRESUMO
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.
Assuntos
Antiprotozoários/uso terapêutico , Doença de Chagas/tratamento farmacológico , Homeopatia , Inflamação/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Estreptófitas , Animais , Antiprotozoários/administração & dosagem , Antiprotozoários/farmacologia , Doença de Chagas/parasitologia , Conium , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Inflamação/patologia , Lycopodium , Masculino , Camundongos , Extratos Vegetais/administração & dosagem , Extratos Vegetais/farmacologia , Distribuição Aleatória , Trypanosoma cruzi/efeitos dos fármacosRESUMO
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.
Assuntos
Antiparasitários/farmacologia , Produtos Biológicos/farmacologia , Doença de Chagas/tratamento farmacológico , Homeopatia/métodos , Tripanossomicidas/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Animais , Antiparasitários/uso terapêutico , Produtos Biológicos/uso terapêutico , Terapia Biológica , Relação Dose-Resposta a Droga , Humanos , Tripanossomicidas/uso terapêuticoRESUMO
BACKGROUND: There is no published information about the use of different protocols to administer a highly diluted medication.Evaluate the effect of different protocols for treatment with biotherapic T. cruzi 17 dH (BIOT(Tc17dH)) on clinical/parasitological evolution of mice infected with T. cruzi-Y strain. METHODS: A blind, randomized controlled trial was performed twice, using 60 28-day-old male Swiss mice infected with T. cruzi-Y strain, in five treatment groups: CI - treated with a 7% ethanol-water solution, diluted in water (10 µL/mL) ad libitum; BIOT(PI) - treated with BIOT(Tc17dH) in water (10 µL/mL) ad libitum during a period that started on the day of infection; BIOT(4DI) - treated with BIOT(Tc17dH) in water (10 µL/mL) ad libitum beginning on the 4th day of infection; BIOT(4-5-6) - treated with BIOT(Tc17dH) by gavage (0.2 mL/ animal/day) on the 4th, 5th and 6th days after infection; BIOT(7-8-9) - treated with BIOT(Tc17dH) by gavage (0.2 mL/ animal/day) on the 7th, 8th and 9th days after infection. We evaluated: parasitemia; total parasitemia (P(total)); maximum peak of parasites; prepatent period (PPP) - time from infection to detection of the parasite in blood; patent period (PP) - period when the parasitemia can be detected in blood; clinical aspects; and mortality. RESULTS: Parasitological parameters in the BIOT(PI) and mainly in the BIOT(4PI) group showed better evolution of the infection compared to the control group (CI), with lower P(total), lower maximum peak of parasites, higher PPP, lower PP and longer survival times. These animals showed stable body temperature and higher weight gain and water consumption, with more animals having normal-appearing fur for longer periods. In contrast, groups BIOT(4-5-6) and BIOT(7-8-9) showed worse evolution of the infection compared to the control group, considering both parasitological and clinical parameters. The correlation analysis combined with the other data from this study indicated that the prepatent period is the best parameter to evaluate the effect of a medication in this model. CONCLUSIONS: The BIOT(4DI) group showed the best clinical and parasitological evolution, with lower parasitemia and a trend toward lower mortality and a longer survival period. The prepatent period was the best parameter to evaluate the effect of a medication in this model.
Assuntos
Antiparasitários/farmacologia , Produtos Biológicos/farmacologia , Terapia Biológica , Doença de Chagas/tratamento farmacológico , Homeopatia , Trypanosoma cruzi/efeitos dos fármacos , Animais , Doença de Chagas/sangue , Doença de Chagas/parasitologia , Doença de Chagas/fisiopatologia , Modelos Animais de Doenças , Masculino , Camundongos , Parasitemia/tratamento farmacológico , Fatores de Tempo , Trypanosoma cruzi/crescimento & desenvolvimentoRESUMO
The study of the effect of different ways of treatment using highly diluted substances is rare in the literature. Some authors consider the dose irrelevant, justifying that the action of the medication highly diluted is qualitative [1-3]. Others emphasize the importance of quantity and frequency of administration of the highly diluted substance for a successful treatment [4,5]. The model of murine infection by T. cruzi is widely studied and it is an excellent tool to study the effect of highly diluted substances.There is a difference in the effect of the medication highly diluted depending on the way of treatment used. For mice, the use of drug diluted in water offered frequently, results in better benefits. The clinical use of these results in humans, should consider the allometric system medication dosage which takes into account the metabolic rate of each organism.(AU)
Assuntos
Animais , Camundongos , Toxoplasmose , BioterápicosRESUMO
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)
Assuntos
Trypanosoma cruzi , BioterápicosRESUMO
Introduction: Toxoplasmosis is a zoonosis that represents a serious public health problem, caused by Toxoplasma gondii, which affects 20-90% of the world human population [1,2]. It is a serious problem especially when considering the congenital transmission due to congenital sequels. Treatment with highly diluted substances is one of the alternative/complementary medicines most employed in the world [3,4]. The current ethical rules regarding the number of animals used in animal experimental protocols with the use of more conservative statistical methods [5] can not enhance the biological effects of highly diluted substances observed by the experience of the researcher.}Conclusion: Bootstrap seems to be an interesting methodology for the analysis of data obtained from experiments with highly diluted substances. Experiments involving highly diluted substances and infection of mice with T. gondii should be better work with experimental groups using 17 animals at least.(AU)
Introdução: A toxoplasmose é uma zoonose causada pelo Toxoplasma gondii, que atinge de 20-90% da população humana mundial [1,2] sendo um sério problema de saúde pública, sobretudo ao se considerar a transmissão congênita com suas conseqüências e seqüelas. O tratamento com substâncias ultradiluídas é uma das práticas alternativas / complementares mais empregadas no mundo [3,4]. As regras éticas atuais quanto ao número de animais utilizados nos protocolos de experimentação animal juntamente com o uso de métodos estatísticos mais conservadores [5] não conseguem valorizar efeitos biológicos de substâncias ultra-diluídas percebidos pela experiência do pesquisador.Conclusão: O Bootstrap mostrou ser uma metodologia interessante para a análise de dados derivados de experimentos com substâncias ultra-diluídas. Experimentos envolvendo substâncias ultra-diluídas e a infecção de camundongos pelo T. gondii deveriam trabalhar com grupos experimentais utilizando, no mínimo, 17 animais.(AU)