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.

Treatment with Lycopodium clavatum 200dH Intensifies Kidney and Liver Injury in Mice Infected with Toxoplasma gondii.

The effects of infection with Toxoplasma gondii vary from asymptomatic to the development of alterations in various organs (including the liver and kidneys) which may be irreversible, and lead to the death of the host. Whereas homeopathy is an alternative and effective method for treating various diseases, including those caused by protozoa, we questioned the effect of using Lycopodium clavatum in mice infected with T. gondii. One hundred male Swiss mice, 60 days old, were divided into four groups (n = 25/group): NIC (uninfected and untreated control), IC (infected and treated with un-dynamized 7% alcohol solution [vehicle]), G48 (infected and treated 48 h before infection and treated three more times; at 2, 4, and 6 days post-infection (dpi) with L. clavatum 200dH), and G72 (infected and treated for 3 consecutive days before infection with L. clavatum 200dH). In this study, physiological, histopathological, and immunological parameters were evaluated. The L. clavatum 200dH intensified renal damage in mice infected with T. gondii from 7 dpi, causing severe and progressive alterations during this period, such as various degrees of inflammation, edema, atrophy, and tubular cystic dilation, degenerated tubules with intra-cytoplasmic vacuoles and coalescing spots, severe vascular lesions, glomerulonephritis, and peri-glomerular congestion. In the G72 animals, which received L. clavatum 200dH, more severe cortex damage was observed (91.66-96.66%) as compared to the IC group (55-80%) and more renal corpuscle, and renal tubule injury was observed (80 ± 5 to 96.7% ± 2.89 of the total area) during all periods, as compared to the IC group (p < 0.05). Both groups presented high liver enzyme levels, and the highest values for AST were observable at 60 dpi. We observed significant increases of type I and III collagen, as well as high levels of TGF-ß1 in both organs of the treated animals, the main factor involved in fibrosis in areas damaged by the process. L. clavatum 200dH intensifies kidney and liver alterations in mice infected with T. gondii. Our results reinforce caution when indicating administration schemes and dosages for ultra-diluted drugs.

Judicialização do acesso a medicamentos no município de Ivinhema, Mato Grosso do Sul / Judicialization of access to medicines in the municipality of Ivinhema, Mato Grosso do Sul, Brazil / Judicialización del acceso a medicamentos en la ciudad de Ivinhema, Mato Grosso do Sul, Brasil

Objetivo: conhecer o perfil das requisições de medicamentos na esfera administrativa, recebidas pela Secretaria de Saúde do Município de Ivinhema, Mato Grosso do Sul, no ano de 2017. Métodos: estudo descritivo, retrospectivo, com foco em base documental. Definiuse como universo da pesquisa os ofícios recebidos pelo departamento jurídico da Secretaria de Saúde no Município de Ivinhema/MS, no período de primeiro de janeiro a 31 de dezembro de 2017. As variáveis concatenadas foram: quantificação das requisições de medicamentos no período supracitado; classificação da autoria dos ofícios recebidos; características dos medicamentos requeridos: pertinência à rede de assistência farmacêutica do SUS e classificação pela Anatomical Therapeutic Chemical Classification (ATC), de acordo com a recomendação da Organização Mundial de Saúde. Resultados: foram recebidos 59 ofícios, requisitando um total de 169 medicamentos. Desse total, 118 (69,8%) não faziam parte da rede de assistência farmacêutica do SUS. Dos 51 (30,2%) medicamentos listados na rede pública de saúde, 38 (74,5%) estavam elencados na Relação Estadual de Medicamentos Essenciais (Resme) e 13 (25,5%), na lista do componente especializado. Os fármacos solicitados com maior frequência foram: ácido acetilsalicílico (3,5%), metoprolol e cilostazol (2,4%). A maioria das requisições recebidas veio da Defensoria Pública (93,2%). Além disso, segundo a classificação terapêutica dos medicamentos solicitados, verificou-se que os grupos anatômicos mais frequentes foram: sistema nervoso central (31,9%), sistema cardiovascular (26,0%) e sangue e órgãos hematopoiéticos (10,6%). Conclusão: a maioria dos ofícios era de autoria da Defensoria Pública e requisitavam medicamentos que não faziam parte da rede de assistência farmacêutica do SUS

Objective: to know the profile of medicines requests in the administrative level, received by the Secretary of Health of Ivinhema, Mato Grosso do Sul, Brazil, in 2017. Methodology: descriptive, retrospective study, focusing on documentary basis. The universe of research was defined as the documents received by the law department of Secretary of Health of Ivinhema, Mato Grosso do Sul, from January 1 to December 31, 2017. The variables studied were: quantification of medicines requests; authorship classification of the received documents; characteristics of the required medicines: relevance to the SUS pharmaceutical assistance network and classification by the Anatomical Therapeutic Chemical Classification (ATC), according to the recommendation of the World Health Organization. Results: 59 documents were received, requesting a total of 169 medicines. Of this total, 118 (69.8%) were not part of SUS's pharmaceutical assistance network. Of the 51 (30.2%) medicines listed in the public health network, 38 (74.5%) were listed in the State List of Essential Medicines (Resme), and 13 (25.5%) in the specialized component list. The most frequently requested medicines were acetylsalicylic acid (3.5%), metoprolol and cilostazol (2.4%).Most of the documents received came from the Public Defender's Office (93.2%). In addition, according to the therapeutic classification of the medicine requested, it was found that the most frequent anatomical groups were: central nervous system (31.9%), cardiovascular system (26.0%) and blood and hematopoietic organs (10.6%). Conclusion: Most of the documents were from the Public Defender's and requested medicines that were not part of SUS's pharmaceutical assistance network.

Objetivo: conocer el perfil de las requisiciones de medicamentos en la esfera administrativa, recibidas por la Secretaría de Salud del Municipio de Ivinhema, Mato Grosso do Sul, en el año 2017. Metodología: estudio descriptivo, retrospectivo con foco en base documental. Se definió como universo de la investigación los oficios recibidos por el departamento jurídico de la Secretaría de Salud en el Municipio de Ivinhema/MS, en el período del primero de enero al 31 de diciembre de 2017. Las variables concatenadas fueron: cuantificación de las solicitudes de drogas en el período mencionado; clasificación de autoría de los oficios recibidas; características de los medicamentos requeridos: relevancia para la red de atención farmacéutica del SUS y clasificación según la Clasificación Química Terapéutica Anatómica (ATC), según la recomendación de la Organización Mundial de la Salud. Resultados: recibieron 59 oficios, solicitando un total de 169 medicamentos. De este total, 118 (69,8%) no formaban parte de La red de Asistencia Farmacéutica del SUS. De los 51 (30,2%) medicamentos listados en la red pública de salud, 38 (74,5%) estaban enumerados en la Lista Estatal de Medicamentos Esenciales (Resme) y 13 (25,5%) en la lista del componente especializado. Los fármacos solicitados com mayor frecuencia fueron: ácido acetilsalicílico (3,5%), metoprolol y cilostazol (2,4%). La mayoría de las acciones recibidas vinieron de La Defensoría Pública (93,2%). Además, según La clasificación terapéutica de los medicamentos solicitados, se verificó que los grupos anatómicos más frecuentes fueron: sistema nervioso central (31,9%), sistema cardiovascular (26,0%) y sangre y órganos hematopoyéticos (10,6%). Conclusion: La mayoría de los documentos provenían de la Oficina del Defensor Público y solicitaban medicamentos que no formaban parte de la red de asistencia farmacéutica del SUS.

Effects of associations of tannins from Anacardium occidentale and Anadenanthera colubrina with cephalosporin against bovine Staphylococcus aureus isolates / Efeitos da associação de taninos de Anacardium occidentale e Anadenanthera colubrina à cefalosporina sobre Staphylococcus aureus isolados de bovinos

The association of natural compounds isolated from medicinal plants with conventional antibiotics, both with similar mechanisms of action, have become a viable alternative strategy to overcome the problem of drug resistance. This study aimed to evaluate the in vitro antimicrobial activity of tannic substances present in the bark of Anacardium occidentale and Anadenanthera colubrina against samples of Staphylococcus aureus when in combination with cephalexin. These combinations were evaluated by determining the minimum inhibitory concentration (MIC). For this purpose, tannins and cephalexin were serially dissolved in distilled water at concentrations ranging from 0.976 mg/mL to 500 mg/mL and 2 mg/mL to 512 mg/mL, respectively. When combined, the compounds inhibited S. aureus growth forming halos ranging from 0.9 to 46 mm with an MIC of 7.8 mg/mL (tannins) and 4 µg/mL (cephalexin). The resulting effect of the combination of natural and synthetic substances with similar mechanisms of action presented better results than when tested alone. Thus, the conclusion is that both the tannins and cephalexin had their antimicrobial action enhanced when used in combination, enabling the use of lower concentrations while maintaining their antibacterial effect against strains of S. aureus.(AU)

A associação de compostos naturais, isolados de plantas medicinais, com antibióticos convencionais, com mecanismos de ação semelhantes, torna-se uma estratégia alternativa e viável para superar o problema da resistência. Assim, nosso objetivo foi avaliar a atividade antimicrobiana in vitro de substâncias tânicas presentes na casca de Anacardium occidentale e Anadenanthera colubrina associadas à cefalexina, sobre amostras de Staphylococcus aureus. Avaliamos essa associação por meio da determinação da concentração mínima inibitória. Dessa forma, taninos e a cefalexina foram dissolvidos de forma seriada em água destilada em concentrações variando de 0,976 mg/mL a 500 mg/mL e 2 µg/mL a 512 µg/mL, respectivamente. Quando associados, inibiram o crescimento de S. aureus formando halos que variaram de 0,9 a 46 mm com concentração mínima inibitória de 7,8 mg/mL (taninos)/ 4 µg/mL (cefalexina). O efeito resultante da associação de substâncias, natural e sintética, com mecanismos de ação semelhantes, apresentou resultados superiores aos observados quando testados isoladamente. Podemos concluir que os taninos e a cefalexina tiveram sua ação antimicrobiana potencializada quando utilizados em associação, permitindo o uso de uma menor concentração, mantendo seu efeito antibacteriano sobre cepas de S. aureus.(AU)

Beneficial immunomodulatory and neuro digestive effect in Trypanosoma cruzi infection after Lycopodium clavatum 13c treatment.

Studies show that highly diluted medications demonstrate benefits in treating infections, constituting an alternative for their treatment. The present study evaluated the effects of Lycopodium clavatum, dynamization 13c, in Wistar rats infected with T. cruzi. In this study 42 male rats were intraperitoneally inoculated with T. cruzi - Y strain and allocated into groups: IC (infected control group) and Ly (treated with L. clavatum 13c). The cytokines dosage (IFN-γ, IL-12, IL-10, IL-4), quantification and morphometry of myenteric neurons were evaluated. The treatment with L. clavatum modifies the immune response, with increase of IFN-γ on day 10 a.i. and IL-12 on day 24 a.i., decrease of IL-10 concentration on day 10 a.i. and subsequent increase of this cytokine and IL-4 on day 24 a.i., affording a bigger number of myenteric neurons compared to IC group. Thus, L. clavatum 13c promoted on rats infected with T. cruzi a beneficial immunomodulatory action reducing the pathogenic progression of digestive 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.

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)

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: Evaluation of PCR as a Laboratory Tool to Follow up the Evolution of Parasite Load.

BACKGROUND: The study evaluated qualitative PCR, primers 121-122 as a tool to follow up evolution parasite load of Trypanosoma cruzi. METHODS: The study was conducted at the State University of Maringa, in 2015. Step 1, dilutions 1/10 were performed from T. cruzi-Y strain to obtain preparations of 50,000-0.05 parasites/mL from which DNA were extracted, quantified, and amplified. Step 2, the extracted DNA in the dilutions 5-0.05 parasites/mL was re-diluted 1/10, 1/100, 1/1000, quantified, and amplified. Polyacrylamide gels were photographed and thicknesses of the 330 bp kDNA fragments were measured. RESULTS: Step 1, in the dilutions 50,000-50 parasites/mL kDNA fragments had same thickness and, dilutions 5-0.05 parasites/mL showed progressive decrease in thicknesses and staining intensity of the 330 bp fragments. Step 2, demonstrated that dilutions of five (re-dilutions 1/10 and 1/100) and 0.5 (1/10) parasites/mL produced similar thicknesses of the 330 bp fragments obtained in Step 1. However, very dilute DNA samples make difficult to reproduce the fragments thicknesses. CONCLUSION: PCR, despite its limitations, was able to detect progressive decrease in thicknesses/staining intensity of kDNA fragments in the dilutions 5-0.05 parasites/mL. Hence, has the potential to be used to follow-up evolution of parasite load, not by quantifying the number of parasites, but by dynamic evolution of the fragments thicknesses during etiological treatment.

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)...

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

Homeopathy in parasitic diseases

Background: The use of homeopathic medicines has increased, partly because conventional drugs do not always elicit the desired effects, and partly because their side effects might compromise the patient’s’ adherence to treatment. Several studies showed benefits in the use of highly diluted medicines for the treatment of infectious diseases. Aim: The aim of the present review was to perform a critical discussion about aspects of homeopathy and the current status of veterinary experimentation, as well as of the use of highly diluted drugs in infectious and parasitic diseases. The main aspects of effects, therapeutic regimens and / or dynamizations used in various models are discussed. Methods: Articles published since 2000 in journals included in databases PubMed and SciELO and specialized journals sought for and reviewed using keywords “parasitic diseases/homeopathy” and “parasitic diseases/ ultra-dilutions”. Results: Several recent experimental studies demonstrated the biological effect of highly diluted medications on parasitic infections, with reduction of the number of parasites and improvement of the clinical condition of the affected animals. Several articles exhibit problems in the description of methods, which threaten the reproducibility of experiments. Conclusion: The acknowledgment of homeopathy depends on the credibility of investigators. Although research on homeopathy has clearly increased in recent years, relative to both implementation of more consistent methods and description of data and methods, improvement is still required. Precise and detailed descriptions will contribute to advance the use of homeopathy, so that society at large might benefit in actual practice. (AU)

Introdução: O uso de homeopáticos tem crescido devido o fato de que medicamentos convencionais algumas vezes não produzem o efeito esperado e também devido os seus efeitos indesejados que comprometem a adesão ao tratamento. Alguns trabalhos mostram os benefícios da utilização de medicamentos ultradiluídos no tratamento de doenças infecciosas. Objetivo: Esta revisão é uma discussão crítica sobre os aspectos da homeopatia, o estado atual da experimentação veterinária e o uso de medicamentos ultradiluídos nas infecções e doenças parasitárias. Os principais aspectos dos efeitos, esquemas de tratamento e/ou dinamizações utilizadas nos diferentes modelos são discutidos. Metodologia: Uma revisão de artigos publicados desde 2000 em revistas indexadas nos bancos de dados PubMed e Scielo e revistas especializadas foi utilizada para pesquisa das palavras-chave: parasitoses/ homeopatia e parasitoses/ ultradiluídos. Resultados: Experimentos recentes demonstraram o efeito biológico dos medicamentos ultradiluídos nas infecções parasitárias, com redução no número de parasitos e melhora da condição clínica nos animais tratados. Alguns artigos apresentaram problemas na descrição da metodologia o que pode comprometer a reprodutibilidade dos experimentos. Conclusão: O conhecimento da homeopatia depende da credibilidade dos grupos de pesquisa. Embora nos últimos anos a pesquisa em homeopatia tenha apresentado um claro desenvolvimento, tanto na implantação de metodologias mais consistentes quanto na descrição dos dados e métodos publicados, muito ainda deve ser melhorado neste campo. Descrições precisas e detalhadas poderiam contribuir para o avanço do uso da homeopatia, o que poderia beneficiar a comunidade em geral , na prática, a partir destes resultados. (AU)

Homeopathy in parasitic diseases

Background: The use of homeopathic medicines has increased, partly because conventional drugs do not always elicit the desired effects, and partly because their side effects might compromise the patient’s’ adherence to treatment. Several studies showed benefits in the use of highly diluted medicines for the treatment of infectious diseases. Aim: The aim of the present review was to perform a critical discussion about aspects of homeopathy and the current status of veterinary experimentation, as well as of the use of highly diluted drugs in infectious and parasitic diseases. The main aspects of effects, therapeutic regimens and / or dynamizations used in various models are discussed. Methods: Articles published since 2000 in journals included in databases PubMed and SciELO and specialized journals sought for and reviewed using keywords “parasitic diseases/homeopathy” and “parasitic diseases/ ultra-dilutions”. Results: Several recent experimental studies demonstrated the biological effect of highly diluted medications on parasitic infections, with reduction of the number of parasites and improvement of the clinical condition of the affected animals. Several articles exhibit problems in the description of methods, which threaten the reproducibility of experiments. Conclusion: The acknowledgment of homeopathy depends on the credibility of investigators. Although research on homeopathy has clearly increased in recent years, relative to both implementation of more consistent methods and description of data and methods, improvement is still required. Precise and detailed descriptions will contribute to advance the use of homeopathy, so that society at large might benefit in actual practice.

Introdução: O uso de homeopáticos tem crescido devido o fato de que medicamentos convencionais algumas vezes não produzem o efeito esperado e também devido os seus efeitos indesejados que comprometem a adesão ao tratamento. Alguns trabalhos mostram os benefícios da utilização de medicamentos ultradiluídos no tratamento de doenças infecciosas. Objetivo: Esta revisão é uma discussão crítica sobre os aspectos da homeopatia, o estado atual da experimentação veterinária e o uso de medicamentos ultradiluídos nas infecções e doenças parasitárias. Os principais aspectos dos efeitos, esquemas de tratamento e/ou dinamizações utilizadas nos diferentes modelos são discutidos. Metodologia: Uma revisão de artigos publicados desde 2000 em revistas indexadas nos bancos de dados PubMed e Scielo e revistas especializadas foi utilizada para pesquisa das palavras-chave: parasitoses/ homeopatia e parasitoses/ ultradiluídos. Resultados: Experimentos recentes demonstraram o efeito biológico dos medicamentos ultradiluídos nas infecções parasitárias, com redução no número de parasitos e melhora da condição clínica nos animais tratados. Alguns artigos apresentaram problemas na descrição da metodologia o que pode comprometer a reprodutibilidade dos experimentos. Conclusão: O conhecimento da homeopatia depende da credibilidade dos grupos de pesquisa. Embora nos últimos anos a pesquisa em homeopatia tenha apresentado um claro desenvolvimento, tanto na implantação de metodologias mais consistentes quanto na descrição dos dados e métodos publicados, muito ainda deve ser melhorado neste campo. Descrições precisas e detalhadas poderiam contribuir para o avanço do uso da homeopatia, o que poderia beneficiar a comunidade em geral , na prática, a partir destes resultados.

Highly diluted medication reduces parasitemia and improves experimental infection evolution by Trypanosoma cruzi.

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.

Uma abordagem sobre o uso da hidroxiureia e do transplante de células-tronco hematopoéticas no tratamento da anemia falciforme / An approach about the use of hydrxyurea and of hematopoietic stem cells in the treatment of sickle cell disease

As opções terapêuticas mais estudadas atualmente e disponíveis para tratamento da anemia falciforme (AF) são o transplante de células-tronco hematopoéticas (TCTH) e a hidroxiureia (HU). Este trabalho teve como objetivo revisar artigos nas bases científicas (Scielo, Pubmed, Biblioteca Cochrane) e livros especializados que abordassem: segurança, benefícios, riscos e lacunas no uso destas terapias em crianças, jovens e adultos portadores desta hemoglobinopatia. O TCTH apesar de ser a única medida curativa é considerado de risco, sendo realizado apenas em indivíduos selecionados (principalmente crianças e jovens). A presença de estudos observacionais demonstra elevados índices de sobrevivência livre de eventos e baixa taxa de mortalidade, porém muitos pesquisadores ainda discutem a importância da realização de estudos multicêntricos, randomizados e controlados que melhor avaliem os benefícios e riscos deste tratamento. As mesmas discussões são observadas em estudos associados a utilização da HU no alívio de sintomas relacionados à AF, estudos apontam a HU como efetiva principalmente na diminuição das crises dolorosas e hospitalizações. Porém, muitas perguntas sobre seus efeitos permanecem sem respostas, muitos pesquisadores ainda questionam sua potencialidade carcinogênica e toxicidades quando utilizada por longo período em indivíduos adultos e principalmente em crianças e adolescentes. A baixa quantidade ou ausência de trabalhos prospectivos, randomizados e controlados das principais ou novas formas de tratamento da AF, são lacunas e empecilhos que dificultam a melhora da qualidade de vida ou cura dos pacientes portadores de AF.

The most currently studied and available therapeutic options for the treatment of sickle cell disease (SCD) are hematopoietic cell transplantation (HCT) and hydroxyurea (HU). This study had as object to review articles on scientific bases (Scielo, Pubmed, Cochrane Library) and specialized books that approached: safety, benefits, risks and gaps on the use of these therapies on children, youngster and adults with this hemoglobinopathy. HCT, despite of being the only curative measure, is considered of high risk, performed only in selected individuals (children and youngster, principally). The presence of observational studies shows high rates of events-free survival and low rate of mortality, but many authors still discuss the importance of the execution of multicenter, randomized and controlled studies, which evaluate the benefits and risks of this treatment. The same discussions are observed in studies associated with the use of HU on the relief of symptoms related to SCD, several studies point to HU as effective mainly on the decrease of painful crises and hospitalizations. However, many questions about its use and effects remain unanswered, many researchers question about its carcinogenic potentiality and toxicity when it is used for extended periods on adults and principally on children and youngsters. The lack or absence of prospective, randomized and controlled works for the main or new forms of SCD treatment, made gaps and trammels that difficult the improvement of life quality or cure for the SCD patients.

Different forms of administration of biotherapy 7dH in mice experimentally infected by Trypanosoma cruzi produce different effects.

OBJECTIVE: To evaluate the effects of different forms of administration of the blood trypomastigotes biotherapy 7dH in mice experimentally infected with Trypanosoma cruzi. MATERIAL AND METHODS: Male swiss mice were inoculated with 1400 blood trypomastigotes of the Y strain of T. cruzi and allocated into 5 treatment groups: IC (distilled water); TCBZ (benznidazole); TBA(7dH) (biotherapy 7dH 20 days after infection); TBB(7dH)7 (biotherapy 7dH seven days before infection); TBB(7dH)30 (biotherapy 7dH 30 days before infection). Parasitological parameters assessed included pre-patent and patent periods, parasitemia peak, total parasitemia, mortality and survival rates. Cure index was obtained by fresh blood examination, hemoculture and polymerase chain reaction (PCR). RESULTS: The TBB(7dH)7 group showed a reduction in parasitemia peak, parasitemia area under the curve and total parasitemia. TBB(7dH)30 showed a tendency to increased pre-patent and survival periods, peak parasitemia was increased without increased total parasitemia. TBA(7dH) did not present significant alterations in the parasitological parameters analyzed. CONCLUSIONS: Biotherapy 7dH given before infection (7 or 30 days) produces different effects suggesting modulation of the host's immune system. The effects range from reduced parasitemia to its effective increase. The use of biotherapy to treat T. cruzi infection including dose, potency and schedule deserves further investigation.

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)

Prevalência de anemias em gestantes do município de Campo Mourão – PR entre os períodos de 2005 a 2008 / Prevalence of anemia among pregnant women in the city of Campo Mourão – PR between the periods 2005 to 2008

As gestantes constituem um dos grupos mais vulneráveis a adquirir anemias (carenciais). Este trabalho teve como objetivo verificar a prevalência de anemias em gestantes atendidas em Unidades Básicas de Saúde em Campo Mourão, de 2005 a 2008. Como instrumento de coleta de dados, foram utilizados os prontuários das gestantes e as seguintes variáveis: idade, situação conjugal, escolaridade, dosagem dehemoglobina e medicamentos prescritos para anemia. A prevalência de anemias nas gestantes foi de 6,18% e a maioria (70,07%) apresentava valores de hemoglobina entre 9,6 a 10,8 g/dL. A faixa etária mais acometida encontrava-se entre 18 a 26 anos (55,12%) e, com relação ao grau de escolaridade, amaioria (62,20%) possuía ensino fundamental e médio completo e cerca da metade das gestantes eramcasadas. O medicamento antianêmico mais prescrito foram os sais de ferro (88,18%). A suplementação oral de ferro é a intervenção padrão para prevenção e tratamento da anemia durante a gestação. Neste estudo a prevalência de gestantes anêmicas foi considerada segundo a OMS um leve problema de saúde pública, sendo a grande maioria classificada como anemia moderada. Os resultados obtidos em nosso estudo possuem grande relevância, principalmente como fonte de futuras comparações e monitoramento da saúde na população de gestantes de Campo Mourão.

Pregnant women are one of the most vulnerable groups to acquire anemia (deficiency). Based on it, this study aimed verifying the prevalence of anemia among pregnant women, who were taken cared in Basic Health Units in Campo Mourão, from 2005 to 2008. As a tool for data collection were used the medical registrations of pregnant women and the following variables: age, marital status, hemoglobin dosage,and prescribed drugs for anemia. The prevalence of anemia among pregnant women was 6.18%, the majority (70.07%) had hemoglobin values between 9.6 to 10.8 g/dL, the most affected age group was between 18 and 26 (55.12%), in relation to the level of education, the majority (62.20%) had primary and secondary school complete and about half of the women were married, the most prescribed medicationfor anemia were the salts of iron (88.18%). Oral supplementation of iron is the standard intervention forprevention and treatment of anemia during pregnancy. In this study, the prevalence of pregnant womenwith anemia was considered, according to the WHO, a mild public health problem, which most cases being classified as moderate anemia. The results obtained in our study are very important, especially as a source for future comparisons and monitoring the health of pregnant women in Campo Mourão.