Atualização dos parâmetros de aquisição do Programa Nacional de Alimentação Escolar com base no Guia Alimentar para a População Brasileira / Actualización de los parámetros de adquisición del Programa Nacional de Alimentación Escolar en base a la Guía Alimentaria para la Población Brasileña / Update of the acquisition parameters of the Brazilian National School Feeding Program based on the Dietary Guidelines for the Brazilian Population

O Guia Alimentar para a População Brasileira é reconhecido como um potente indutor de políticas públicas de alimentação e nutrição. Nessa perspectiva, este artigo apresenta o percurso metodológico e as evidências que subsidiaram a elaboração dos novos parâmetros de aquisição de alimentos do Programa Nacional de Alimentação Escolar (PNAE). Tal elaboração envolveu as análises de: (1) participação dos recursos federais utilizados para compra de alimentos, agrupados segundo a classificação NOVA, empregada no Guia Alimentar para a População Brasileira, pelo conjunto de municípios brasileiros e segundo classificação da execução (positiva ou negativa); (2) cardápios mensais de referência que foram elaborados seguindo recomendações do Guia Alimentar para a População Brasileira; (3) aquisição de alimentos por amostra de 525 municípios, envolvendo a participação relativa dos grupos de alimentos (segundo a NOVA) no total de gastos e de energia e a qualidade nutricional dos alimentos adquiridos; e (4) alimentos ultraprocessados que não devem ser ofertados no ambiente escolar. Foi proposta a adoção dos seguintes parâmetros para participação dos grupos de alimentos em relação ao total de recursos federais empregados na compra de alimentos: ≥ 75% de recursos para alimentos in natura ou minimamente processados; < 20% para alimentos processados ou ultraprocessados e < 5% para ingredientes culinários processados e a ampliação da lista de alimentos cuja aquisição com recursos federais do PNAE é proibida. Esse processo subsidiou a elaboração da Resolução CD/FNDE nº 6, de 8 de maio de 2020, que dispõe sobre o atendimento da alimentação escolar aos alunos da educação básica no âmbito do PNAE.

La Guía Alimentaria para la Población Brasileña está reconocida como un potente inductor de políticas públicas de alimentación y nutrición. Desde esta perspectiva, este artículo presenta la trayectoria metodológica y evidencias que apoyaron la elaboración de los nuevos parámetros de adquisición de alimentos del Programa Nacional de Alimentación Escolar (PNAE). Tal elaboración implicó los análisis de: (1) participación de los recursos federales utilizados para la compra de alimentos, agrupados según la clasificación NOVA, empleada en el Guía Alimentaria para la Población Brasileña, por el conjunto de municipios brasileños, y según la clasificación de la ejecución (positiva o negativa); (2) menús mensuales de referencia que fueron elaborados siguiendo recomendaciones del Guía Alimentaria para la Población Brasileña; (3) adquisición de alimentos mediante una muestra de 525 municipios, implicando la participación relativa de los grupos de alimentos (según NOVA) en el total de gastos y de energía, así como la calidad nutricional de los alimentos adquiridos; y (4) alimentos ultraprocesados que no deben ser ofrecidos en el entorno escolar. Se propuso la adopción de los siguientes parámetros para la participación de los grupos de alimentos, en relación con el total de recursos federales empleados en la compra de alimentos: ≥ 75% de recursos para alimentos in natura o mínimamente procesados; < 20% para alimentos procesados o ultraprocesados, y < 5% para ingredientes culinarios procesados, así como la ampliación de la lista de alimentos, cuya adquisición con recursos federales del PNAE está prohibida. Este proceso apoyó la elaboración de la Resolución CD/FNDE nº 6, del 8 de mayo de 2020, que organiza la atención de la alimentación escolar a alumnos de educación básica en el ámbito del PNAE.

The Dietary Guidelines for the Brazilian Population is acknowledged as a powerful inducer of public food and nutrition policies. In this perspective, this article presents the methodological path and evidence that supported the elaboration of the new parameters of food acquisition of the Brazilian National School Feeding Program (PNAE). This elaboration involved the analyses of: (1) participation of federal resources used to purchase food, grouped according to the NOVA classification, used in Dietary Guidelines for the Brazilian Population, by the set of Brazilian municipalities and according to the classification of the execution (positive or negative); (2) monthly reference menus that were prepared following Dietary Guidelines for the Brazilian Population recommendations; (3) analysis of food acquisition by the sampling of 525 municipalities, involving the relative participation of food groups (according to NOVA) in total expenditures and energy and nutritional quality of purchased foods; and (4) analysis of ultra-processed foods that should not be offered in the school environment. We proposed the adoption of the following parameters for the participation of food groups in relation to the total federal resources used in the purchase of food: ≥ 75% of resources for fresh or minimally processed foods; < 20% for processed or ultra-processed foods and < 5% for processed culinary ingredients, as well as the expansion of the list of foods whose acquisition with federal resources from PNAE is prohibited. This process supported the elaboration of Resolution CD/FNDE n. 6 of May 8, 2020, which provides for the attendance of school feeding to primary education students within the PNAE.

In vitro genotoxicity of nitroimidazoles as a tool in the search of new trypanocidal agents

BACKGROUND Only benznidazole (Bnz) (1) and nifurtimox (Nfx) (2) are licensed for the treatment of Chagas disease although their safety and efficacy profile are far from ideal. Farmanguinhos from Fiocruz has developed seven nitroimidazole compounds (4-10) analogs of megazol (3). OBJECTIVES To evaluate whether the genotoxic effect of 3 was abolished in the seven nitroimidazoles (4-10) analogs using the in vitro alkaline comet assay (CA) and the in vitro cytokinesis-block micronucleus assay (CBMN) in whole human blood cells (WHBC) and correlate this effect with their trypanocidal activity using bloodstream trypomastigote forms of Trypanosoma cruzi. METHODS The toxicity of 3-10 to WHBC in the in vitro CA was determined using the fluorescein diacetate/ethidium bromide assay. DNA damage in the in vitro CA was evaluated according to tail size in four classes (0-3) and methyl methane-sulfonate (MMS) was used as a positive control. The cytotoxicity of 3-10 to WHBC in the CBMN was measured using the cytokinesis-block proliferation index and the replication index. The number of the micronucleate cells in 2,000 binucleate cells by experimental group was determined. Mitomycin C and N-deacetyl-N-methylcolchicine were used as positive controls. FINDINGS Compound 3 showed a significant DNA strand break effect through the in vitro CA and highly significant clastogenic and/or aneugenic effect in the CBMN. Compounds 5, 6, 8, 9 and 10 showed negative results in the CBMN and positive results in the in vitro CA, while the inverse effect was observed for 4 and 7. MAIN CONCLUSIONS Compound 10 was the most promising to proceed with the development as a drug candidate in the treatment of Chagas disease showing absence of chromosomal cytogenetic damage and high activity against T. cruzi, about two times higher than 3 and the clinical drug 1.

Studies of genotoxicity and mutagenicity of nitroimidazoles: demystifying this critical relationship with the nitro group

Nitroimidazoles exhibit high microbicidal activity, but mutagenic, genotoxic and cytotoxic properties have been attributed to the presence of the nitro group. However, we synthesised nitroimidazoles with activity against the trypomastigotes of Trypanosoma cruzi, but that were not genotoxic. Herein, nitroimidazoles (11-19) bearing different substituent groups were investigated for their potential induction of genotoxicity (comet assay) and mutagenicity (Salmonella/Microsome assay) and the correlations of these effects with their trypanocidal effect and with megazol were investigated. The compounds were designed to analyse the role played by the position of the nitro group in the imidazole nucleus (C-4 or C-5) and the presence of oxidisable groups at N-1 as an anion receptor group and the role of a methyl group at C-2. Nitroimidazoles bearing NO2 at C-4 and CH3 at C-2 were not genotoxic compared to those bearing NO 2 at C-5. However, when there was a CH3 at C-2, the position of the NO2 group had no influence on the genotoxic activity. Fluorinated compounds exhibited higher genotoxicity regardless of the presence of CH3 at C-2 or NO2 at C-4 or C-5. However, in compounds 11 (2-CH3; 4-NO2; N-CH2OHCH2Cl) and 12 (2-CH3; 4-NO2; N-CH2OHCH2F), the fluorine atom had no influence on genotoxicity. This study contributes to the future search for new and safer prototypes and provide.

Megazol and its bioisostere 4H-1,2,4-triazole: comparing the trypanocidal, cytotoxic and genotoxic activities and their in vitro and in silico interactions with the Trypanosoma brucei nitroreductase enzyme

Megazol (7) is a 5-nitroimidazole that is highly active against Trypanosoma cruzi and Trypanosoma brucei, as well as drug-resistant forms of trypanosomiasis. Compound 7 is not used clinically due to its mutagenic and genotoxic properties, but has been largely used as a lead compound. Here, we compared the activity of 7 with its 4H-1,2,4-triazole bioisostere (8) in bloodstream forms of T. brucei and T. cruzi and evaluated their activation by T. brucei type I nitroreductase (TbNTR) enzyme. We also analysed the cytotoxic and genotoxic effects of these compounds in whole human blood using Comet and fluorescein diacetate/ethidium bromide assays. Although the only difference between 7 and 8 is the substitution of sulphur (in the thiadiazole in 7) for nitrogen (in the triazole in 8), the results indicated that 8 had poorer antiparasitic activity than 7 and was not genotoxic, whereas 7 presented this effect. The determination of Vmax indicated that although 8 was metabolised more rapidly than 7, it bounds to the TbNTR with better affinity, resulting in equivalent kcat/KM values. Docking assays of 7 and 8 performed within the active site of a homology model of the TbNTR indicating that 8 had greater affinity than 7.

Acute experimental Trypanosoma cruzi infection: establishing a murine model that utilises non-invasive measurements of disease parameters

Trypanosoma cruzi infection has a large public health impact in Latin American countries. Although the transmission rates via blood transfusions and insect vectors have declined sharply in the past 20 years due to policies of the Southern Cone countries, a large number of people are still at risk for infection. Currently, no accepted experimental model or descriptions of the clinical signs that occur during the course of acute murine infection are available. The aim of this work was to use non-invasive methods to evaluate the clinical signs of Balb/c mice infected with the Y strain of T. cruzi. The infected mice displayed evident clinical changes beginning in the third week of infection. The mice were evaluated based on physical characteristics, spontaneous activity, exploratory behaviour and physiological alterations. We hope that the results presented in this report provide parameters that complement the effective monitoring of trypanocidal treatment and other interventions used to treat experimental Chagas disease.

Metabolizable energy of corn hybrids for broiler chickens at different ages / Energia metabolizável de milhos híbridos para frangos de corte em diferentes idades

We determined the values of apparent metabolizable (AME), apparent corrected (AMEn), true (TME) and true corrected (TMEn) energy of six corn hybrids for broiler chickens in phases 1-7, 8-14, 15-21, 22-28, 29-35 and 36-42 day-old birds, using the substitution method (40 percent) of reference diet with the test ingredient. Ross-308 male chicks (1,134) were allotted to metabolism cages and the number of birds per experimental unit was adjusted to suit each bird's density stage in the cage, using six replicates. Simultaneously, birds continue to fast for the determination of metabolic and endogenous losses for each study phase. The birds received water and food ad libitum during the experimental period. The birds were maintained in metabolism cages for seven days, four days for adaptation to the cage and food, and three days for excreta collection. The corn energy values were significantly lower only in the pre-initial phase (1-7 days). Thus, broiler feed formulations of AMEn values for corn of 3563 kcal/kg DM for 1 to 7 days and 3778 kcal/kg DM from 7-day-old birds are recommended.The agronomic characteristics of the corn had no influence on the birds energy levels.

Foram determinados os valores de energia metabolizável aparente (EMA), aparente corrigida (EMAn), verdadeira (EMV) e verdadeira corrigida (EMVn) de seis milhos híbridos para frangos de corte nas fases de 1 a 7, 8 a 14, 15 a 21, 22 a 28, 29 a 35 e 36 a 42 dias de idade das aves, usando o método de substituição (40 por cento) da ração referência pelo ingrediente em teste. Pintos machos Ross-308 (1.134) foram distribuídos em gaiolas de metabolismo, sendo o número de aves por parcela, ajustado em cada fase para adequação da densidade de aves na gaiola, sendo utilizadas 6 repetições por tratamento. Simultaneamente, foram mantidas aves em jejum para a determinação das perdas endógenas e metabólicas para cada fase do estudo. As aves receberam água e ração à vontade durante todo período experimental. As aves foram mantidas nas gaiolas de metabolismo durante sete dias, sendo quatro dias para adaptação à gaiola e à alimentação e três dias para a coleta de excretas. Os valores energéticos dos milhos foram significativamente inferiores somente na fase pré-inicial (1 a 7 dias) em relação às demais. Assim, recomenda-se usar nas formulações os valores de EMAn do milho de 3563/kg MS de 1 a 7 dias e de 3778 kcal/kg MS a partir 7 dias de idade das aves As características agronômicas dos milhos não influíram nos seus teores de energia.

Occurrence of 102 cases of paracoccidioidomycosis in 18 months in the Itaipu Lake region, Western Paraná / Ocorrência de 102 casos de paracoccidioidomicose em 18 meses na região do Lago de Itaipu, Oeste do Paraná

INTRODUCTION: The study investigated the incidence of disease and death events among patients with paracoccidioidomycosis who were residents in the Itaipu Lake region from 2008 to 2009. METHODS: A review of patient records was conducted at the Department of Tuberculosis of the Epidemiology Center of the City of Foz do Iguaçu, Paraná. RESULTS: The results identified 102 new cases of paracoccidioidomycosis in the period described, 72 men and 30 women, and 15 deaths were recorded during the study. CONCLUSIONS: It can be concluded that the Itaipu Lake region is an endemic region.

INTRODUÇÃO: O estudo investigou a incidência da doença e eventos de morte entre os portadores de paracoccidiodomicose residentes na região do Lago de Itaipu, no período de 2008 a 2009. MÉTODOS: Foi realizado levantamento em registros de pacientes do Setor de Tuberculose do Centro de Epidemiologia da Cidade de Foz do Iguaçu, Paraná, entre o período de janeiro de 2008 e julho de 2009. RESULTADOS: Os resultados apontam 102 novos casos de paracoccidiodomicose, 72 homens e 30 mulheres, foram registrados 15 óbitos durante o estudo. CONCLUSÕES: Conclui-se que a região do Lago de Itaipu é uma região endêmica.

In vitro and in vivo experimental models for drug screening and development for Chagas disease

Chagas disease, a neglected illness, affects nearly 12-14 million people in endemic areas of Latin America. Although the occurrence of acute cases sharply has declined due to Southern Cone Initiative efforts to control vector transmission, there still remain serious challenges, including the maintenance of sustainable public policies for Chagas disease control and the urgent need for better drugs to treat chagasic patients. Since the introduction of benznidazole and nifurtimox approximately 40 years ago, many natural and synthetic compounds have been assayed against Trypanosoma cruzi, yet only a few compounds have advanced to clinical trials. This reflects, at least in part, the lack of consensus regarding appropriate in vitro and in vivo screening protocols as well as the lack of biomarkers for treating parasitaemia. The development of more effective drugs requires (i) the identification and validation of parasite targets, (ii) compounds to be screened against the targets or the whole parasite and (iii) a panel of minimum standardised procedures to advance leading compounds to clinical trials. This third aim was the topic of the workshop entitled Experimental Models in Drug Screening and Development for Chagas Disease, held in Rio de Janeiro, Brazil, on the 25th and 26th of November 2008 by the Fiocruz Program for Research and Technological Development on Chagas Disease and Drugs for Neglected Diseases Initiative. During the meeting, the minimum steps, requirements and decision gates for the determination of the efficacy of novel drugs for T. cruzi control were evaluated by interdisciplinary experts and an in vitro and in vivo flowchart was designed to serve as a general and standardised protocol for screening potential drugs for the treatment of Chagas disease.

Experimental chemotherapy for Chagas disease: 15 years of research contributions from in vivo and in vitro studies

Chagas disease, which is caused by the intracellular parasite Trypanosoma cruzi, is a neglected illness with 12-14 million reported cases in endemic geographic regions of Latin America. While the disease still represents an important public health problem in these affected areas, the available therapy, which was introduced more than four decades ago, is far from ideal due to its substantial toxicity, its limited effects on different parasite stocks, and its poor activity during the chronic phase of the disease. For the past 15 years, our group, in collaboration with research groups focused on medicinal chemistry, has been working on experimental chemotherapies for Chagas disease, investigating the biological activity, toxicity, selectivity and cellular targets of different classes of compounds on T. cruzi. In this report, we present an overview of these in vitro and in vivo studies, focusing on the most promising classes of compounds with the aim of contributing to the current knowledge of the treatment of Chagas disease and aiding in the development of a new arsenal of candidates with anti-T. cruzi efficacy.

Contribuição do estudo de Zigman Brener (1961) para a terapia da doença de Chagas / Contribution of the study of Zigman Brener (1961) for the treatment of Chagas disease

Revisões históricas aos avanços científicos para o controle da doença, o Simpósio Internacional Comemorativo do Centenário da Descoberta da Doença de Chagas (1909-2009).

Activity of Brazilian and Bulgarian propolis against different species of Leishmania

Extracts of propolis samples collected in Brazil and Bulgaria were assayed against four Leishmania species - Leishmania amazonensis, L. braziliensis, L. chagasi from the New World, and L. major from the Old World - associated to different clinical forms of leishmaniasis. The composition of the extracts has been previously characterized by high temperature high resolution gas chromatography coupled to mass spectrometry. Considering the chemical differences among the extracts and the behavior of the parasites, it was observed significant differences in the leishmanicidal activities with IC50/1 day values in the range of 2.8 to 229.3 µg/ml . An overall analysis showed that for all the species evaluated, Bulgarian extracts were more active than the ethanol Brazilian extract. As the assayed propolis extracts have their chemical composition determined it merits further investigation the effect of individual components or their combinations on each Leishmania species.

The effect of Bulgarian propolis against Trypanosoma cruzi and during its interaction with host cells

Propolis has shown activity against pathogenic microorganisms that cause diseases in humans and animals. The ethanol (Et-Blg) and acetone (Ket-Blg) extracts from a Bulgarian propolis, with known chemical compositions, presented similar activity against tissue culture-derived amastigotes. The treatment of Trypanosoma cruzi-infected skeletal muscle cells with Et-Blg led to a decrease of infection and of the intracellular proliferation of amastigotes, while damage to the host cell was observed only at concentration 12.5 times higher than those affecting the parasite. Ultrastructural analysis of the effect of both extracts in epimastigotes revealed that the main targets were the mitochondrion and reservosomes. Et-Blg also affected the mitochondrion-kinetoplast complex in trypomastigotes, offering a potential target for chemotherapeutic agents.

Queratosis punctata palmar y plantar: presentación de tres casos / Keratosis puntacta palmaris and plantaris: presentation of three cases

La queratosis punctata palmar y plantar es un desorden cutáneo caracterizado por la presencia de múltiples lesiones hiperqueratósicas, papulares, pequeñas, amarillentas, duras localizadas en palmas y/o plantas. En el estudio histopatológico se observa hiperqueratosis compacta ortoqueratótica que comprime la epidermis produciendo una depresión de la misma en forma de copa o de V, con epidermis acantótica con hipergranulosis, dermis normal o con leve infiltrado linfohistiocitario superficial. Se han descrito asociados con enfermedad de Darier, ictiosis vulgar, atopia, epidermolisis ampollar simple y distrófica dominante, adenocarcinoma de colon y cambios ungueales. Se han planteado la herencia con patrón autosómico dominante o el trabajo manual fuerte como causa de la lesión. Entre los diagnósticos diferenciales se encuentran verruga plana, poroqueratosis palmoplantar, liquen plano palmoplantar, milium coloide, queratosis arsenicales y otras formas de queratodermias palmoplantares punctatas. Se presentan tres casos de pacientes con diagnóstico clínico e histopatológico de queratosis punctata palmar y plantar, del sexo femenino de con edades comprendidas entre 40 y 55 años, quien presentan entre 5 meses y 12 años de evolución. Dos de las pacientes presentan enfermedades asociadas, como son ictiosis vulgar y queratodermia difusa plantar. Se discuten los casos comparándolos con la bibliografía revisada

A critical review on Chagas disease chemotherapy

In this "Critical Review" we made a historical introduction of drugs assayed against Chagas disease beginning in 1912 with the works of Mayer and Rocha Lima up to the experimental use of nitrofurazone. In the beginning of the 70s, nifurtimox and benznidazole were introduced for clinical treatment, but results showed a great variability and there is still a controversy about their use for chronic cases. After the introduction of these nitroheterocycles only a few compounds were assayed in chagasic patients. The great advances in vector control in the South Cone countries, and the demonstration of parasite in chronic patients indicated the urgency to discuss the etiologic treatment during this phase, reinforcing the need to find drugs with more efficacy and less toxicity. We also review potential targets in the parasite and present a survey about new classes of synthetic and natural compounds studied after 1992/1993, with which we intend to give to the reader a general view about experimental studies in the area of the chemotherapy of Chagas disease, complementing the previous papers of Brener (1979) and De Castro (1993)

Cromomicosis: uso del tratamiento combinado de itraconazol y 5- fluorouracilo en fonsecae pedrosoi e itraconazol y criospray en exophiala jeanselmei var lecanii-corni / Chromomycosis: combined treatment; itraconazole and 5-fluorouracil in a case caused by fonsecae pedrosoi and itraconazole plus cryotherapy in another case caused by exophiala jeanselmei var lecanii-corni

Presentamos a dos hombres campesinos agricultores provenientes por separado de El Baúl Estado Cojedes y otro de Araira, Estado Miranda, quienes tras la inoculación traumática en extremidades superiores, presentaron lesión tipo placa verrugosa eritematosa, extensa, con puntillado negro en la superficie, puriginosa, evolución larga (años) aconpañándose de limitación funcional. Los Exámenes de laboratorio de rutina y radiológicos fueron normales. El examen directo micológico con KOH al 10 por ciento demostró la presencia de cuerpos escleróticos. En la histopatología de las lesiones de ambos pacientes se observaron cuerpos redondeados de color marrón cobrizo con granuloma macrofágico bien diferenciado, difuso y focal, invadido por células linfoides y células plasmáticas. Los cultivos micológicos desde el punto de vista macroscópico reportaron colonias oscuras aterciopeladas sugestivas de cromomiceto. Por lo que se procedió a la identificación de los mismos con la técnica del microcultivo en lámina diagnosticando Fonsecae pedrosoi (Estado Cojedes) y Exophiala jeanselmei var. lecanii-corni (Estado Miranda) confirmado por morfología y pruebas fisiológicas. Ambos recibieron tratamiento con Itraconazol en combinación con tratamiento tópico diferente, 5 fluorouracilo ungüento al 5 por ciento y el otro paciente con "criospray" cada 15 días, observando excelente evolución clínica, con recuperación funcional al cabo del 3er mes de tratamiento. Para este momento están aún bajo tratamiento hasta confirmar cura micológica. Ambas especies micológicas son de ubicación inusual en el área geográfica de procedencia de estos pacientes

Doença de Chagas: manual para experimentaçäo animal / Chagas diseases: manual for animal experimentation

Aborda conceitos modernos, focados nos desafios científicos e em toda a complexidade relacionada com a doença: vetores, transmissao, resposta do hospedeiro à infeccçao, normas de segurança para trabalhar com Trypanosoma cruzi, quimioterapia, doença de Chagas humana e modelos experimentais, bem como protocolos e métodos experimentais utilizados nas investigaçoes sobre a moléstia.

Trypanosoma cruzi: effect of phenothiazines on the parasite and its interaction with host cells

Phenothiazines were observed to have a direct effect on Trypanosoma cruzi and on its in vitro interaction with host cells. They caused lysis of trypomastigotes (50 uM/24 h) and,to a lesser extent, epimastigote proliferation. Treatment of infected peritoneal macrophages with 12.5 uM chlorpromazine or triflupromazine inhibited the infection; this effect was found to be partially reversible if the drugs were removed after 24 h of treatment. At 60 uM, the drugs caused damage to amastigotes interiorized in heart muscle cells. However, the narrow margin of toxity between anti-trypanossomal activity and damage to host cells mitigates against in vivo investigation at the present time. Possible hypothesis for the mechanism of action of phenothiazines are discussed

Bacterial chemistry. VI. Biological activities and cytotoxicity of 1, 3-dihydro-2H-indol-2-one derivatives

The biosynthetic pigment from Chromobacterium violaceum BB-78, 1,3-dihydro-2H-indol-2-one and its derivatives exhibit biological activities such as antimicrobial action, low hemolytic effects on red blood cells and in vitro trypanocide activity. A relatively high cytotoxicity on V-79 hamster fibroblast cells of the biosynthetic pigment was found, although with the methylol derivative the toxicity was almost eliminated. The methylol derivative exhibited similar toxicity as Nifurtimox, a known, commercial trypanocide compound

Mechanism of action of a nitroimidazole-thiadiazole derivate upon Trypanosoma cruzi tissue culture amastigotes

Megazol (CL 64,855) a very effective drug in experimental infections by Trypanosoma cruzi, and also in in vitro assays with vertebrate forms of the parasite, had its parasite, had its activity upon macromolecule biosynthesis tested using tissue culture-derived amastigote forms. Megazol presented a drastic inhibition of [3H]-uridine incorporation, suggesting a selective activity upon protein synthesis. Comparing the three drugs, megazol was more potent than nifurtimox and benznidazole in inhibiting protein an DNA synthesis. Megazol showed a 91% of inhibition of [3H]-leucine incorporation whereas nifurtimox and benznidazole, 0% and 2%, respectively. These latter two drugs inhibited the incorporation of all the precursors tested at similar levels, but the concentration of benznidazole was always three times higher, suggesting different mechanisms of action or, more probably, a greater efficiency of the 5-nitrofuran derivate in relation to the 2-nitroimidazole. So, wes conclude that the mode of action of megazol is different from the ones of nifurtimox and benznidazole and that its primary effect is associated with an impairment of protein synthesis

Effect of drugs on Trypanosoma cruzi and on its interaction with heart muscle cell in vitro

As açöes de megazol, nifurtimox, benznidazol e allopurinol sobre o T. cruzi foram investigadas, através de microscopia ótica e eletrônica, pela análise do efeito direto sobre formas amastigotas e tripomastigotas e do efeito sobre a interaçäo de cultura de célula muscular cardíaca com tripomastigotas sangüíneos. A proliferaçäo de amastigotas em meio Warren foi inibida de modo dose-dependente por megazol, nifurtimox e benznidazol. O tratamento de amastigotas (25-50 micronM/24h) e de tripomastigotas (25 micronM/24h) levou a várias alteraçöes ultraestruturais nos parasitas. Estas três drogas tiveram também um efeito potente no tratamento de culturas de células cardíacas infectadas, quando adicionadas desde o início da interaçäo ou após um ou três dias de infecçäo. Os parasitas interiorizados mostraram um padräo de alteraçöes ultraestruturais semelhante ao observado no tratamento direto de formas amastigotas. A cultura primária de célula muscular cardíaca mostrou ser um modelo adequado para o estudo de drogas sobre formas intracelulares de T. cruzi e o ensaio de proliferaçäo de amastigotas em meio axênico, indicado para uma triagem inicial de drogas. Estes parâmetros nos parecem muito confiáveis para uma investigaçäo sistemática do mecanismo de açäo de drogas