Raquel Fonseca Rodrigues

Synthesis and activity of novel tetrazole compounds and their pyrazole-4-carbonitrile precursors against Leishmania spp

A new series of 5-(1-aryl-3-methyl-1H-pyrazol-4-yl)-1H-tetrazole derivatives (4a-m) and their precursor 1-aryl-3-methyl-1H-pyrazole-4-carbonitriles (3a-m) were synthesized and evaluated as antileishmanials against Leishmania braziliensis and Leishmania amazonensis promastigotes in vitro. In parallel, the cytotoxicity of these compounds was evaluated on the RAW 264.7 cell line. The results showed that among the assayed compounds the substituted 3-chlorophenyl (4a) (IC50/24h=15±0.14 μM) and 3,4-dichlorophenyl tetrazoles (4d) (IC50/24h=26±0.09 μM) were the most potent against L. braziliensis promastigotes, as compared the reference drug pentamidine, which presented IC50=13±0.04 μM. In addition, 4a and 4d derivatives were less cytotoxic than pentamidine. However, these tetrazole derivatives (4) and pyrazole-4-carbonitriles precursors (3) differ against each of the tested species and were more effective against L.braziliensis than on L. amazonensis.

The in vivo activity of 1,3,4-thiadiazolium-2-aminide compounds in the treatment of cutaneous and visceral leishmaniasis

OBJECTIVES Researchers have recently investigated the biological activities of mesoionic (MI) compounds, which have shown in vitro activity against many species of Leishmania, as well as Trypanosoma cruzi. The main goal of this study was to evaluate and compare the activity of three MI compounds against Leishmania amazonensis and Leishmania infantum infection in vivo. METHODS The experiments were carried out using BALB/c mice infected with L. amazonensis or L. infantum as a highly sensitive murine model. The infected mice were treated with MI-HH, MI-4-OCH(3), MI-4-NO(2) or meglumine antimoniate by different routes (intralesional, topical or intraperitoneal). RESULTS Treatment with MI-4-OCH(3) and MI-4-NO(2) efficiently contained the progression of cutaneous and visceral leishmaniasis in comparison with the control group or mice treated with meglumine antimoniate. Interestingly, these MI compounds did not produce toxicological effects after treatment. Furthermore, treatment with these compounds led to a modulation of the immune response that was correlated with disease control. In this study, MI compounds, and MI-4-NO(2) in particular, exhibited high activity in the L. infantum murine model. In the L. amazonensis model, intralesional treatment with MI-4-OCH(3) or MI-4-NO(2) showed greater therapeutic efficacy than treatment with meglumine antimoniate, and the new topical formulations of these compounds also displayed great activity in the cutaneous leishmaniasis model. CONCLUSIONS Upon comparison of each MI compound, MI-4-NO(2) was clearly the compound with the greatest activity in these two in vivo infection models by each administration route tested.

The histopathological and immunological pattern of CBA mice infected with Leishmania amazonensis after treatment with pyrazole carbohydrazide derivatives.

Because there is no vaccine in clinical use, control of Leishmaniasis relies almost exclusively on chemotherapy and the conventional treatments exhibit high toxicity for patients and emerging drug resistance. Recently, we showed that oral treatment with synthetic pyrazole carbohydrazide compounds induced lower parasite load in draining lymph nodes and reduced skin lesion size without causing any toxic effects in an experimental murine infection model with Leishmania amazonensis. In this study, CBA mice were infected in the footpad with L. amazonensis and then orally treated with pyrazole carbohydrazides derivatives, such as BrNO(2), NO(2)Cl and NO(2)Br and their histopathological and immunological effects were then investigated. Epidermis and dermis had lower levels of inflammatory infiltration compared to the infected untreated control mice. In the dermis of treated animals, the numbers of vacuolated macrophages containing intracellular parasites were far lower than in infected untreated animals. In addition to dermal macrophages, we also observed a mixed inflammatory infiltrate containing lymphocytes and granulocyte cells. Lower numbers of B cells (B220+) and T lymphocytes (CD3+) were identified in the lesions of treated mice compared with the untreated, infected mice. In draining lymph node cells, the number of T lymphocytes (CD3+) was decreased, and the numbers of B cells (CD19+) and CD8+ T cells were increased in infected mice, when compared with the non-infected control group. In additional, we have shown that infected treated and untreated lymph node cells had similar levels of TGF-β and IFN-γ mRNA expression, whereas IL-4 was expressed at a lower level in the treated group. Increased levels of the specific anti-Leishmania IgG2a or IgG3 antibody subclass were observed in NO(2)Cl or BrNO(2)-treated group, respectively. Overall, our experimental findings suggest that pyrazole carbohydrazides exert modulation of IL-4 expression and B cell levels; however, further evaluation is required to determine the optimal treatment regime.

Antileishmanial Activity of 1,3,4-Thiadiazolium-2-Aminide in Mice Infected with Leishmania amazonensis

ABSTRACT The efficacy of two mesoionic derivatives (MI-H-H and MI-4-OCH3) was evaluated in CBA/J mice infected with Leishmania amazonensis. Treatment with these compounds demonstrated that the MI-4-OCH3 derivative and the reference drug meglumine antimoniate (Glucantime) presented significant activity relative to an untreated control. No apparent hepatic or renal toxicity due to these mesoionic compounds was found.

CONSULTA COLETIVA DE PRÉ-NATAL: UMA NOVA PROPOSTA PARA UMA ASSISTÊNCIA INTEGRAL

This article describes the Collective Prenatal Consultation as a new healthcare methodology, which is performed according to government standards, but collectively. Relaxation and sensitization techniques are used, as well as group dynamics, including a collective exam of the pregnant women. The Collective Consultation is carried out in a welcoming environment, which provides clarification and socialization of experiences and information, centered on those women. The healthcare professional records every obstetric parameter and behavior in the patient’s prenatal card and history file. Priority is given to the principle of integrality and citizenship, with the aim to break the biomedical care paradigm, thus favoring humanized and comprehensive care to the women.This article describes the Collective Prenatal Consultation as a new healthcare methodology, which is performed according to government standards, but collectively. Relaxation and sensitization techniques are used, as well as group dynamics, including a collective exam of the pregnant women. The Collective Consultation is carried out in a welcoming environment, which provides clarification and socialization of experiences and information, centered on those women. The healthcare professional records every obstetric parameter and behavior in the patients prenatal card and history file. Priority is given to the principle of integrality and citizenship, with the aim to break the biomedical care paradigm, thus favoring humanized and comprehensive care to the women.

Care of adolescents sheltered in maternity hospitals from the perspective of health professionals

Resumen pt: Objetivo: Discutir aspectos determinantes de uma assistencia de qualidade a adolescentes gravidas, abrigadas em uma maternidade, conforme a otica de prof...OBJETIVO: Discutir aspectos determinantes de una asistencia de calidad a adolescentes embarazadas, albergadas en una maternidad, conforme la optica de profesionales de salud. METODOS: Estudio de abordaje cualitativo, exploratorio, realizado en una maternidad del Municipio de Rio de Janeiro - RJ, referencia para jovenes albergadas. Los sujetos del estudio fueron 14 profesionales del equipo de salud. Los datos fueron tratados, conforme a la tecnica del analisis de contenido. RESULTADOS: Emergieron del analisis dos categorias: Caracteristicas de la atencion de los profesionales de salud de la maternidad direccionadas a la madre adolescente albergada y su hijo; Caracteristicas de la organizacion/estructura de la maternidad que afectan la atencion a las adolescentes albergadas embarazadas. CONCLUSION: Se hace necesario incorporar las practicas norteadoras de la integralidad/interdisciplinaridad del servicio. La estigmatizacion de estas jovenes significa uno de los mayores desafios a la asistencia y al cuidado integral. El espacio de la maternidad configura un rico ambiente para el proceso dialogico enfermero-adolescente.

Collective prenatal consultation: a new proposal for comprehensive health care

This article describes the Collective Prenatal Consultation as a new healthcare methodology, which is performed according to government standards, but collectively. Relaxation and sensitization techniques are used, as well as group dynamics, including a collective exam of the pregnant women. The Collective Consultation is carried out in a welcoming environment, which provides clarification and socialization of experiences and information, centered on those women. The healthcare professional records every obstetric parameter and behavior in the patient’s prenatal card and history file. Priority is given to the principle of integrality and citizenship, with the aim to break the biomedical care paradigm, thus favoring humanized and comprehensive care to the women.This article describes the Collective Prenatal Consultation as a new healthcare methodology, which is performed according to government standards, but collectively. Relaxation and sensitization techniques are used, as well as group dynamics, including a collective exam of the pregnant women. The Collective Consultation is carried out in a welcoming environment, which provides clarification and socialization of experiences and information, centered on those women. The healthcare professional records every obstetric parameter and behavior in the patients prenatal card and history file. Priority is given to the principle of integrality and citizenship, with the aim to break the biomedical care paradigm, thus favoring humanized and comprehensive care to the women.

Synthesis of New Conjugates 1H-Pyrazolo[3,4-b]pyridine-phosphoramidate and Evaluation against Leishmania amazonensis

In this research three series of substituted 1H-pyrazolo[3,4-b]pyridine phosphoramidates were synthesized and characterized by infrared, H, C, and P nuclear magnetic resonance (NMR) spectroscopy and high-resolution mass spectrometry. The products were obtained in good yields (67-83%) under mild conditions by nucleophilic aromatic substitution reaction of aminoalkylphosphoramidates over 4-chloro-1H-pyrazolo[3,4-b]pyridines. These compounds were evaluated as antileishmanials against Leishmania amazonensis promastigotes in vitro. Among all, compounds of a series showed expressive antileishmanial activity. Two of them emerged as the most active, with IC50 values of 6.44 ± 1.49 and 12.25 ± 0.68 μM. The cytotoxicity of this series was assessed on murine cells and presented values similar to the reference drug pentamidine.

Assistência às adolescentes abrigadas em maternidade sob a ótica de profissionais de saúde

Resumen pt: Objetivo: Discutir aspectos determinantes de uma assistencia de qualidade a adolescentes gravidas, abrigadas em uma maternidade, conforme a otica de prof...OBJETIVO: Discutir aspectos determinantes de una asistencia de calidad a adolescentes embarazadas, albergadas en una maternidad, conforme la optica de profesionales de salud. METODOS: Estudio de abordaje cualitativo, exploratorio, realizado en una maternidad del Municipio de Rio de Janeiro - RJ, referencia para jovenes albergadas. Los sujetos del estudio fueron 14 profesionales del equipo de salud. Los datos fueron tratados, conforme a la tecnica del analisis de contenido. RESULTADOS: Emergieron del analisis dos categorias: Caracteristicas de la atencion de los profesionales de salud de la maternidad direccionadas a la madre adolescente albergada y su hijo; Caracteristicas de la organizacion/estructura de la maternidad que afectan la atencion a las adolescentes albergadas embarazadas. CONCLUSION: Se hace necesario incorporar las practicas norteadoras de la integralidad/interdisciplinaridad del servicio. La estigmatizacion de estas jovenes significa uno de los mayores desafios a la asistencia y al cuidado integral. El espacio de la maternidad configura un rico ambiente para el proceso dialogico enfermero-adolescente.

Asistencia a las adolescentes albergadas en una maternidad bajo la óptica de profesionales de salud

Resumen pt: Objetivo: Discutir aspectos determinantes de uma assistencia de qualidade a adolescentes gravidas, abrigadas em uma maternidade, conforme a otica de prof...OBJETIVO: Discutir aspectos determinantes de una asistencia de calidad a adolescentes embarazadas, albergadas en una maternidad, conforme la optica de profesionales de salud. METODOS: Estudio de abordaje cualitativo, exploratorio, realizado en una maternidad del Municipio de Rio de Janeiro - RJ, referencia para jovenes albergadas. Los sujetos del estudio fueron 14 profesionales del equipo de salud. Los datos fueron tratados, conforme a la tecnica del analisis de contenido. RESULTADOS: Emergieron del analisis dos categorias: Caracteristicas de la atencion de los profesionales de salud de la maternidad direccionadas a la madre adolescente albergada y su hijo; Caracteristicas de la organizacion/estructura de la maternidad que afectan la atencion a las adolescentes albergadas embarazadas. CONCLUSION: Se hace necesario incorporar las practicas norteadoras de la integralidad/interdisciplinaridad del servicio. La estigmatizacion de estas jovenes significa uno de los mayores desafios a la asistencia y al cuidado integral. El espacio de la maternidad configura un rico ambiente para el proceso dialogico enfermero-adolescente.