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INTRODUÇÃO: A análise da implicação na pesquisa se opõe a uma suposta neutralidade resultante do afastamento do objeto, porque o/a pesquisador/a coloca a sua subjetividade em análise, o contexto histórico-social da pesquisa, assim como, a intersubjetividade de todos os envolvidos nela. A implicação integra o processo de construção do conhecimento na busca de maior compreensão dos fenômenos, sendo um dos conceitos fundamentais da psicossociologia. OBJETIVO: O presente estudo objetiva apresentar um relato de experiência sobre a análise da implicação em uma pesquisa clínico-qualitativa respaldada teórico-metodologicamente pela psicossociologia francesa e psicodinâmica do trabalho. Essa investigação ocorreu entre 2018 e 2022, tendo se dado parcialmente no período da pandemia da COVID-19. METODOLOGIA: Empregaram-se os seguintes dispositivos como método de análise da implicação: os diários de campo, as supervisões, as reuniões de equipe, a participação em um grupo de convivência e a psicoterapia individual. Assim, a pesquisadora procurou abordar os seus afetos e sentimentos envolvidos ao longo das etapas da pesquisa. RESULTADOS E DISCUSSÃO: Foi possível, pois, evidenciar a implicação como fonte, paradoxalmente, de processos criativos e, em alguns casos, também de alienação. CONCLUSÃO: Apesar da identificação de alguns destes aspectos negativos da implicação da pesquisadora, se pode ampliar o conhecimento sobre o objeto da pesquisa.

INTRODUCTION: The implication analysis is opposed to a supposed neutrality because the researcher analyzes his own subjectivity, his historical and social context, as well as the intersubjectivity of the actors involved in a research. Implication analysis is one of the fundamental concepts of psychosociology. It enables one to understand phenomena and builds knowledge. OBJECTIVE: The present study aims to present an experience report about an implication analysis of a clinical-qualitative research that was based on French psychosociology and psychodynamics of work theory and methodology. This investigation happened from 2018 to 2022, partially carried out during the COVID-19 pandemic. METHOD: There were used the following resources to access the implication analysis: dailies, supervisions, team meetings, participation in a reflection group, and individual psychotherapy. Thus, the researcher related feelings and affections involved in each one of the research stages. RESULTS AND DISCUSSION: This study highlighted the implication as a source that paradoxically allows creative processes but also, in some cases, alienation. CONCLUSION: Despite some negative aspects of the implication researcher, it was possible to expand the knowledge about the research object.

INTRODUCCIÓN: El análisis de la implicación en la investigación se opone a una supuesta neutralidad resultante de la distancia del objeto porque el investigador analiza su propia subjetividad, el contexto histórico-social de la investigación, así como la intersubjetividad de todos los involucrados en la investigación. La implicación forma parte del proceso de construcción del conocimiento en la búsqueda de una mejor comprensión de los fenómenos, siendo uno de los conceptos fundamentales de la psicosociología. OBJETIVO: Este estudio tiene como objetivo presentar un relato de experiencia sobre el análisis de la implicación en una investigación clínico-cualitativa sustentada teórica y metodológicamente por la psicossociologia francesa y la psicodinámica del trabajo. Esta investigación se llevó a cabo entre 2018 y 2022, habiéndose realizado parcialmente durante el período de la pandemia de COVID-19. MÉTODO: Se utilizaron como método de análisis de la implicación los siguientes dispositivos: diarios de campo, supervisiones, reuniones de equipo, participación en un grupo de convivencia y psicoterapia individual. Así, la investigadora buscó abordar sus afectos y sentimientos involucrados a lo largo de las etapas de la investigación. RESULTADOS Y DISCUSIÓN: Este estudio destacó la implicación como fuente, paradójicamente, de procesos creativos y, en algunos casos, alienación. CONCLUSIÓN: A pesar de la identificación de algunos de estos aspectos negativos de la implicación de la investigadora, se logró ampliar el conocimiento sobre el objeto de investigación.

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BACKGROUND: Cutaneous leishmaniasis (CL) is characterized by potentially disfiguring skin ulcers carrying significant social stigma. To mitigate systemic drug exposure and reduce the toxicity from available treatments, studies addressing new local therapeutic strategies using available medications are coming up. This review systematically compiles preclinical and clinical data on the efficacy of amphotericin B (AmB) administered locally for cutaneous leishmaniasis. METHODOLOGY: Structured searches were conducted in major databases. Clinical studies reporting cure rates and preclinical studies presenting any efficacy outcome were included. Exclusion criteria comprised nonoriginal studies, in vitro investigations, studies with fewer than 10 treated patients, and those evaluating AmB in combination with other antileishmanial drug components. PRINCIPAL FINDINGS: A total of 21 studies were identified, encompassing 16 preclinical and five clinical studies. Preclinical assessments generally involved the topical use of commercial AmB formulations, often in conjunction with carriers or controlled release systems. However, the variation in the treatment schedules hindered direct comparisons. In clinical studies, topical AmB achieved a pooled cure rate of 45.6% [CI: 27.5-64.8%; I2 = 79.7; p = 0.002), while intralesional (IL) administration resulted in a 69.8% cure rate [CI: 52.3-82.9%; I2 = 63.9; p = 0.06). In the direct comparison available, no significant difference was noted between AmB-IL and meglumine antimoniate-IL administration (OR:1.7; CI:0.34-9.15, I2 = 79.1; p = 0.00), however a very low certainty of evidence was verified. CONCLUSIONS: Different AmB formulations and administration routes have been explored in preclinical and clinical studies. Developing therapeutic technologies is evident. Current findings might be interpreted as a favorable proof of concept for the local AmB administration which makes this intervention eligible to be explored in future well-designed studies towards less toxic treatments for leishmaniasis.

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Cutaneous leishmaniasis (CL) is a neglected tropical disease. The treatment is restricted to drugs, such as meglumine antimoniate and amphotericin B, that exhibit toxic effects, high cost, long-term treatment, and limited efficacy. The development of new alternative therapies, including the identification of effective drugs for the topical and oral treatment of CL, is of great interest. In this sense, a combination of topical photodynamic therapy (PDT) with chloroaluminum phthalocyanine liposomes (Lip-ClAlPc) and the oral administration of a self-emulsifying drug delivery system containing fexinidazole (SEDDS-FEX) emerges as a new strategy. The aim of the present study was to prepare, characterize, and evaluate the efficacy of combined therapy with Lip-ClAlPc and SEDDS-FEX in the experimental treatment of Leishmania (Leishmania) major. Lip-ClAlPc and SEDDS-FEX were prepared, and the antileishmanial efficacy study was conducted with the following groups: 1. Lip-ClAlPc (0.05 mL); 2. SEDDS-FEX (50 mg/kg/day); 3. Lip-ClAlPc (0.05 mL)+SEDDS-FEX (50 mg/kg/day) combination; 4. FEX suspension (50 mg/kg/day); and 5. control (untreated). BALB/c mice received 10 sessions of topical Lip-ClAlPc on alternate days and 20 consecutive days of SEDDS-FEX or FEX oral suspension. Therapeutical efficacy was evaluated via the parasite burden (limiting-dilution assay), lesion size (mm), healing of the lesion, and histological analyses. Lip-ClAlPc and SEDDS-FEX presented physicochemical characteristics that are compatible with the administration routes used in the treatments. Lip-ClAlPc+SEDDS-FEX led to a significant reduction in the parasitic burden in the lesion and spleen when compared to the control group (p < 0.05) and the complete healing of the lesion in 43% of animals. The Lip-ClAlPc+SEDDS-FEX combination may be promising for the treatment of CL caused by L. major.

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The main challenges associated with leishmaniasis chemotherapy are drug toxicity, the possible emergence of resistant parasites, and a limited choice of therapeutic agents. Therefore, new drugs and assays to screen and detect novel active compounds against leishmaniasis are urgently needed. We thus validated Leishmania braziliensis (Lb) and Leishmania infantum (Li) that constitutively express the tandem tomato red fluorescent protein (tdTomato) as a model for large-scale screens of anti-Leishmania compounds. Confocal microscopy of Lb and Li::tdTomato revealed red fluorescence distributed throughout the entire parasite, including the flagellum, and flow cytometry confirmed that the parasites emitted intense fluorescence. We evaluated the infectivity of cloned promastigotes and amastigotes constitutively expressing tdTomato, their growth profiles in THP-1 macrophages, and susceptibility to trivalent antimony, amphotericin, and miltefosine in vitro. The phenotypes of mutant and wild-type parasites were similar, indicating that the constitutive expression of tdTomato did not interfere with the evaluated parameters. We applied our validated model to a repositioning strategy and assessed the susceptibility of the parasites to eight commercially available drugs. We also screened 32 natural plant and fungal extracts and 10 pure substances to reveal new active compounds. The infectivity and Glucantime treatment efficacy of BALB/c mice and golden hamsters infected with Lb and Li::tdTomato mutant lines, respectively, were very similar compared to animals infected with wild-type parasites. Standardizing our methodology would offer more rapid, less expensive, and easier assays to screen of compounds against L. braziliensis and L. infantum in vitro and in vivo. Our method could also enhance the discovery of active compounds for treating leishmaniasis.

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Emetic tartar (ET), was used in the treatment of leishmaniasis but its use was discontinued due to its low therapeutic index. Liposomes have been shown to be a promising strategy for delivery of bioactive substances in the region of interest, in order to reduce and/or eliminate undesirable effects. In the present study, liposomes containing ET were prepared and characterized to evaluate acute toxicity as well as their leishmanicidal action using BALB/c mice with an inoculum of Leishmania (Leishmania) infantum. Liposomes were composed of egg phosphatidylcholine and 3ß-[N-(N',N'-dimethylaminoethane)-carbamoyl]cholesterol, with an average diameter of 200 nm, zeta potential of +18 mV, and ET encapsulated into liposomes at a concentration near 2 g/L. Healthy mice were treated with ET or liposome containing ET (Lip-ET) in a single dose of 16 mg/kg of Sb3+ intravenously and observed for 14 days. The death of two animals in the ET-treated group and no deaths in the Lip-ET-treated group was observed. Higher hepatic and cardiac toxicity were observed in animals treated with ET when compared to animals treated with Lip-ET, blank liposomes (Blank-Lip) and PBS. The study of antileishmanial efficacy was conducted by intraperitoneal administration of Lip-ET, for ten consecutive days. It was observed by limiting dilution that treatments with liposomal formulations containing ET, as well as Glucantime®, led to a significant reduction in parasitic load in spleen and liver (p < 0.05) when compared to the untreated control group.

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RESUMO A pandemia de Covid-19 tem levado os países periféricos, como o Brasil, a se confrontarem não apenas com novos desafios, mas com a exacerbação de tantos outros que sequer foram solucionados. Os inúmeros problemas decorrentes da pandemia atingem de maneira desigual a população tanto no que diz respeito ao acesso ao tratamento assistencial quanto às medidas para mitigar a contaminação. O presente artigo parte da hipótese de as profundas desigualdades sociais em saúde, associadas a fatores políticos e econômicos que perpassam a sociedade brasileira, integrarem condicionantes que poderão levar a Covid-19 ser incluída no grupo de Doenças Negligenciadas. Por meio de revisão de literatura não sistematizada, levanta as principais características referentes aos aspectos clínicos e às demandas ao sistema de proteção social brasileiro, analisando os pontos de contato entre ambas, tendo como base a matriz comum das desigualdades sociais. Acredita-se que os caminhos possíveis para que essa hipótese não se confirme será apostar na elaboração de políticas públicas com ênfase na solidariedade, nos direitos humanos, no fortalecimento da governança global e no agir ético de cada pessoa rumo ao desenvolvimento sustentável para todo o planeta.

ABSTRACT The COVID-19 pandemic has led underdeveloped countries, such as Brazil, to face not only new challenges, but the exacerbation of so many others that have not even been solved. The countless problems resulting from the pandemic affect the population in an unequal way, both with regard to access to care treatment and measures to mitigate contamination. This article starts from the hypothesis that the deep social inequalities in health, associated with political and economic factors that permeate Brazilian society, integrate conditions that could lead to COVID-19 becoming part of the group of Neglected Diseases. Through a non-systematic literature review, it raises the main characteristics related to the clinical aspects and the demands of the Brazilian social protection system, analyzing the points of contact between them, based on the common matrix of social inequalities. It is believed that the possible ways for this hypothesis not to be confirmed will be to invest in the elaboration of public policies with an emphasis on solidarity, human rights, the strengthening of global governance and the ethical action of each person towards sustainable development for the entire planet.

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OBJECTIVES: To evaluate the in vitro activity and in vivo efficacy of fexinidazole against the main species that cause visceral and cutaneous New World leishmaniasis. METHODS: The inhibitory concentrations of fexinidazole against Leishmania (Leishmania) infantum chagasi, Leishmania (Leishmania) amazonensis and Leishmania (Viannia) braziliensis in amastigotes were determined by in vitro activity assays. For the in vivo evaluation, animals were infected with L. (L.) infantum chagasi, L. (L.) amazonensis, L. (V.) braziliensis or Leishmania (Viannia) guyanensis and divided into groups: (i) control; and (ii) treated with oral fexinidazole, from 50 to 300 mg/kg/day. For cutaneous leishmaniasis, the size of the lesion was determined weekly after the beginning of the treatment. Upon completion, parasites were recovered from the spleen and liver, or skin lesion and spleen, and evaluated by a limiting dilution assay. RESULTS: All Leishmania isolates were susceptible to fexinidazole in the in vitro assays. The viable parasites in the liver and spleen were reduced with 100 and 300 mg/kg/day, respectively, for L. (L.) infantum chagasi. For the species causing cutaneous leishmaniasis, the viable parasites in lesions and the size of the lesions were reduced, starting from 200 mg/kg/day. The viable parasites in the spleen were also reduced with 200 and 300 mg/kg/day for L. (V.) braziliensis and L. (L.) amazonensis. CONCLUSIONS: Considering the defined parameters, fexinidazole showed in vitro and in vivo activity against all tested species. This drug may represent an alternative treatment for the New World species.

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Progress toward the improvement of meglumine antimoniate (MA), commercially known as Glucantime, a highly effective but also toxic antileishmanial drug, has been hindered by the lack of knowledge and control of its chemical composition. Here, MA was manipulated chemically with the aim of achieving an orally effective drug. MA compounds were synthesized from either antimony pentachloride (MA-SbCl5) or potassium hexahydroxyantimonate [MA-KSb(OH)6] and prepared under a low polymerization state. These compounds were compared to Glucantime regarding chemical composition, permeation properties across a cellulose membrane and Caco-2 cell monolayer, and uptake by peritoneal macrophages. MA-SbCl5 and MA-KSb(OH)6 were characterized as less polymerized and more permeative 2:2 Sb-meglumine complexes than Glucantime, which consisted of a mixture of 2:3 and 3:3 Sb-meglumine complexes. The antileishmanial activities and hepatic uptake of all compounds were evaluated after oral administration in BALB/c mice infected with Leishmania infantum chagasi, as a model of visceral leishmaniasis (VL). The synthetic MA compounds given at 300 mg Sb/kg of body weight/12 h for 30 days significantly reduced spleen and liver parasite burdens, in contrast to those for Glucantime at the same dose. The greater activity of synthetic compounds could be attributed to their higher intestinal absorption and accumulation efficiency in the liver. MA-SbCl5 given orally was as efficacious as Glucantime by the parenteral route (80 mg Sb/kg/24 h intraperitoneally). These data taken together suggest that treatment with a less-polymerized form of MA by the oral route may be effective for the treatment of VL.

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This work aimed to optimise a new nanoemulsion (NE) formulation loaded with Amphotericin B (AmB) and to evaluate its in vivo antileishmanial activity and in vitro haemolytic toxicity. The influence of gradual increases in pressure, using a high-pressure homogeniser, was evaluated. The NE was characterised for droplet size, polydispersity index, zeta potential and encapsulation efficiency (EE). For antileishmanial activity studies, AmB-NE was administered intravenously in mice infected by Leishmania infantum chagasi, which causes Visceral Leishmaniasis (VL). When the NE was submitted to gradual increases in pressure, the PI values and droplet size decreased. The droplet size (∼145 nm) was lower than that obtained in previous studies. The zeta potential was negative and the EE was almost 100%. The haemolytic toxicity, evaluated on human red blood cells, for AmB-loaded NE was lower than that observed for the conventional AmB (C-AmB). C-AmB at 2 mg/kg was very toxic. In contrast, administration of the AmB-loaded NE, at same dose, did not result in any sign of acute toxicity, promoting a significant reduction in parasite burden as compared to the C-AmB. These findings suggest that this new AmB-loaded NE constitutes an attractive alternative for the treatment of VL due to improved efficacy and lower toxicity.

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INTRODUCTION:: The drugs available for visceral leishmaniasis (VL) treatment in Brazil have specific characteristics in terms of operability, effectiveness, toxicity, and cost. The aim of this study was to estimate the direct costs of therapies recommended by the Ministry of Health (MH) for VL treatment in Brazil. METHODS:: The analytical perspective used was that adopted by the Brazilian Public Health System. Three drugs and four regimens were included: 1) N-methyl glucamine antimoniate intramuscularly at 20mg per kg per day for 30 days; 2) N-methyl glucamine antimoniate intravenously at 20mg per kg per day for 30 days; 3) amphotericin B deoxycholate at 1mg per kg per day for 21 days; and 4) liposomal amphotericin B at 3mg per kg per day for a 7 days treatment. RESULTS:: The estimated direct costs of treatment for an adult patient using N-methylglucamine antimoniate administered via the intramuscular and intravenous routes were USD 418.52 and USD 669.40, respectively. The estimated cost of treatment with amphotericin B deoxycholate was USD 1,522.70. Finally, the estimated costs of treatment with liposomal amphotericin B were USD 659.79, and USD 11,559.15 using the price adopted by the WHO and the Drug Regulation Board, respectively. CONCLUSIONS:: This analysis indicates the economic feasibility of replacing N-methyl glucamine antimoniate with liposomal amphotericin B, which allows a shorter treatment period with less toxicity compared with other treatments, provided that the purchase value used by the WHO and transferred to the MH is maintained.

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