Factors associated with the expansion of leishmaniasis in urban areas: a systematic and bibliometric review (1959-2021).

This work describes a systematic and bibliometric review of the factors that contribute to the expansion of leishmaniasis in urban areas. Three scientific databases were used: Scientific Electronic Library (SciELO), Scopus and Web of Science, encompassing all original and review articles between 1959 and 2021. Three descriptors were used: "leishmaniasis" AND "urban" AND "rural." Planning, execution, summarization, and selection processes were performed using StArt (State of the Art through Systematic Review) software. We obtained a total of 304 articles, 60 of which concerned canine leishmaniasis. The factors associated with the expansion of leishmaniasis in urban areas are interrelated, including socioenvironmental and economic complexity, the type of leishmaniasis, the reservoirs, vectors, deforestation, disorderly occupation of space, poor sanitary conditions, and human migration trends. A lack of diagnosis and underreporting of cases in some regions may reflect the increase of cases seen in urban areas. A majority (n = 121) of studies were conducted in Brazil, followed by Iran (n = 43). In relation to publications; in general, output has increased over the years, particularly in 2021. The majority of published studies were in the area of epidemiology (n = 158).

Chemical fingerprinting of the Brazilian medicinal plant Calea pinnatifida (R. Br.) Less. (Asteraceae) collected at different altitudes.

Calea pinnatifida (R. Br.) Less. is a plant of Brazilian folk medicine. We evaluated the influence of environmental factors on the chemical profile of C. pinnatifida collected during the winter season. C. pinnatifida leaves, alongside soil samples, were collected from two sites of different altitude. Plant samples were sequentially extracted, while soil samples were subject to compositional analysis. Plant extracts were compared using HPTLC-UV, using chemometric analyses to compare samplings harvested at both altitudes. Two marker metabolites, calein A (1) and acetylportentol (2), were isolated from samples collected at the respective altitudes. The differing metabolic profiles observed may be a result of the influence of environmental factors.

Preclinical studies of hydroalcoholic extract of Calea uniflora Less / Estudios preclínicos de extracto hidroalcohólico de Calea uniflora Less

Calea uniflora Less known popularly as Arnica in Brazil, is a native plant from Brazil, popular used by coastal populations from south of Santa Catarina. The purpose of this study was to verify the safety profile in of hydroalcoholic extract of C. uniflora in florescences.The hydroalcoholic extract of C. uniflora in florescences was evaluated for its acute and sub-acute toxicity. Acute topical toxicity was performed using the methodology of guideline 402 from OECD. Acute oral toxicity was performed using the methodology of guideline 423 from OECD and sub-acute toxicity was performed using the methodology adapted of guideline 407 from OECD. The single dose for oral or topical administration of C. uniflora showed DL50> 5000 mg/kg b.w. The sub-acute treatment induced animal death in groups, which was administered extract in the doses 100, 250, 500 and 1000 mg/kg. The main signs of toxicity observed were respiratory difficulty, increase in lung weigh, lung damage and muscular relation. The topical or oral administration of C. uniflora extract in short period did not caused toxicological effects in animals, however, when administered for a longer period and in concentrations of 250, 500 and 1000 mg/kg (oral.) caused lung damage and even the death of the animal.

Calea uniflora Less conocida popularmente como Arnica en Brasil, es una planta nativa de Brasil, popularmente utilizada por poblaciones costeras del sur de Santa Catarina. El objetivo de este estudio fue verificar el perfil de seguridad del extracto hidroalcoólico de inflorescencias de C. uniflora. El extracto hidroalcoólico de inflorescencias de C. uniflora fue evaluado en cuanto a su toxicidad aguda y subaguda. La toxicidad tópica aguda se realizó utilizando la metodología de la directriz 402 de la OECD. La toxicidad oral aguda fue realizada usando la metodología de la directriz 423 de la OECD y la toxicidad subaguda fue realizada usando la metodología adaptada de la directriz 407 de la OECD. La dosis única para administración oral o tópica de C. uniflora mostro DL50> 5000 mg/kg. El tratamiento subagudo indujo la muerte de animales en grupos a los que se administró extracto en las dosis de 100, 250, 500 y 1000 mg/kg. Los principales signos de toxicidad observados fueron dificultad respiratoria, aumento del peso del pulmón, daño pulmonar y relación muscular. La administración tópica oral del extracto de C. uniflora a corto plazo no causó efectos toxicológicos en los animales, mientras que, cuando se administró por un período mayor y en las concentraciones de 250, 500 y 1000 mg/kg (oral) causaron danos en los pulmones y hasta la muerte del animal.

Isolation of erythrinan alkaloids from the leaves and flowers of Erythrina speciosa

Abstract In this paper, we describe the extraction of three alkaloids from the leaves and flowers of Erythrina speciosa, a plant documented in the literature to possess a range of potential medicinal applications. Two alkaloids were isolated from both leaves and flowers, with erythrartine being isolated from both plant parts. In agreement with the literature, we also isolated erysotrine from the flowers. The second alkaloid isolated from the leaves, and reported in this species for the first time, was (+)-11β-hydroxyerysotramidine.

Evaluation of genotoxicity and coumarin production in conventional and organic cultivation systems of Mikania glomerata Spreng.

Mikania glomerata Sprengel, popularly known as "guaco," is used in Brazilian folk medicine for several inflammatory and allergic conditions. Besides, the popular use "guaco" is indicated by the Brazilian Ministry of Health as a safe and effective herbal medicine. The biological activity of M. glomerata extracts is due to the presence of the coumarins, a large family of phenolic substances found in plants and is made of fused benzene and α-pyrone rings. Considering that there are few data on the biological effects of the extracts of M. glomerata, mainly in genetic level, this work aims to evaluate, in vitro, the genotoxicity and coumarin production in M. glomerata in conventional and organic growing. The data showed that the organic culture system showed double the concentration of coumarin being significantly more productive than the conventional system. Besides, the results of comet assay suggest that extracts of M. glomerata cultivated in a conventional system was genotoxic, increased DNA damage levels while the organic extracts seem to have antigenotoxic effect possibly due to the concentration of coumarins. Additional biochemical investigations are necessary to elucidate the mechanisms of action of M. glomerata extracts, which were found to have a role in protection against DNA damage.

Designed mono- and di-covalent inhibitors trap modeled functional motions for Trypanosoma cruzi proline racemase in crystallography.

Chagas disease, caused by Trypanosoma cruzi, affects millions of people in South America and no satisfactory therapy exists, especially for its life threatening chronic phase. We targeted the Proline Racemase of T. cruzi, which is present in all stages of the parasite life cycle, to discover new inhibitors against this disease. The first published crystal structures of the enzyme revealed that the catalytic site is too small to allow any relevant drug design. In previous work, to break through the chemical space afforded to virtual screening and drug design, we generated intermediate models between the open (ligand free) and closed (ligand bound) forms of the enzyme. In the present work, we co-crystallized the enzyme with the selected inhibitors and found that they were covalently bound to the catalytic cysteine residues in the active site, thus explaining why these compounds act as irreversible inhibitors. These results led us to the design of a novel, more potent specific inhibitor, NG-P27. Co-crystallization of this new inhibitor with the enzyme allowed us to confirm the predicted protein functional motions and further characterize the chemical mechanism. Hence, the catalytic Cys300 sulfur atom of the enzyme attacks the C2 carbon of the inhibitor in a coupled, regiospecific-stereospecific Michael reaction with trans-addition of a proton on the C3 carbon. Strikingly, the six different conformations of the catalytic site in the crystal structures reported in this work had key similarities to our intermediate models previously generated by inference of the protein functional motions. These crystal structures span a conformational interval covering roughly the first quarter of the opening mechanism, demonstrating the relevance of modeling approaches to break through chemical space in drug design.

Potencial antibacteriano e perfil farmacognóstico das folhas de Hibiscus acetosella Welw Ex Hiern / Antibacterial potential and pharmacognostic profile of Hibiscus acetosella Welw Ex Hiern

Introdução: as Hisbiscus pertencentes à família Malvaceae são amplamente utilizadas na área ornamental e vem ganhando espaço na área alimentícia com suas flores comestíveis e corantes naturais. Alguns estudos demonstraram atividade antibacteriana de algumas espécies deste gênero frente a diversos microorganismos. Hibiscus acetosella, também conhecida popularmente como vinagreira, possui em literatura científica pouca informação sobre sua composição química e ação antibacteriana. Objetivo: caracterizar o perfil farmacognóstico relacionando com a ação microbiológica das folhas de H. acetosella. Metodologia: o perfil farmacognóstico foi realizado através de testes de precipitação, teste colorimétrico, quantificação de compostos fenólicos e análise cromatográfica do extrato hidroalcoólico e das frações das folhas de H. acetocella. A ação antibacteriana do extrato hidroalcoólico (60 mg) e frações (25 mg) foi analisada frente aos microorganismos Staphylococcus aureus, Escherichia coli e Pseudomonas aeruginosa por meio do método de difusão em ágar. Resultados: a análise farmacognóstica apresentou resultados positivos para as classes de substâncias: taninos, flavonoides, cumarinas, heterosídeos cardiotônicos e alcaloides. O extrato hidroalcoólico possui aproximadamente 352,85 mg/L de polifenóis totais. As frações com caráter mais polar (n-butanol e acetato de etila) apresentaram efeito relevante contra os microorganismos S. aureus e P. aeruginosa. Conclusão: os resultados demonstraram que ação antibacteriana pode estar relacionada com a classe de com compostos fenólicos, uma vez que as frações que apresentaram melhor resultado possuem maior concentração destes metabólitos.

Introduction: the Hisbiscus belonging to the family Malvaceae are widely used in the ornamental area and have been gaining space in the food area with its edible flowers and natural dyes. Some studies have demonstrated antibacterial activity of some species of this genus against different microorganisms. Hibiscus acetosella, also popularly known as vinegar, has little scientific information about chemical composition and antibacterial action. Objective: caracterizar o perfil farmacognóstico relacionando com a ação microbiológica das folhas de H. acetosella. Method: the pharmacognostic profile was performed through precipitation tests, colorimetric test, quantification of phenolic compounds and chromatographic analysis of the hydroalcoholic extract and the fractions of the leaves of H. acetocella. The antibacterial action of the hydroalcoholic extract (60 mg) and fractions (25 mg) were analyzed against the microorganisms Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa through the agar diffusion method. Results: the pharmacognostic analysis presented positive results for the classes of substances: tannins, flavonoids, coumarins, cardiotonic heterosides and alkaloids. The hydroalcoholic extract has approximately 352.85 mg / L of total polyphenols. The most polar fractions (n-butanol and ethyl acetate) had a significant effect against the S. aureus and P. aeruginosa microorganisms. Conclusions: the results showed that the antibacterial action may be related to the class of phenolic compounds, since the fractions presented the best antibacterial result have a higher concentration of these metabolites.

Levantamento dos cursos de farmácia do sul do Brasil que oferecem disciplina de radiofármacos (ou similar) / Colleges of pharmacy in southern Brazil providing disciplines of radiopharmaceuticals

A radiofarmácia é a área da ciência responsável pelas substâncias radioativas utilizadas na terapia ou diagnóstico médico. Entre os profissionais que atuam nesta área, destaca-se o farmacêutico, que possui a responsabilidade técnica das empresas produtoras deste tipo de fármaco. Devido à importância deste profissional, este estudo teve por objetivo analisar a grade curricular dos cursos de farmácia de instituições de ensino superior - IES do sul do Brasil (Paraná, Santa Catarina e Rio Grande do Sul), somente aquelas certificadas pelo Ministério da Educação - e-MEC, com vistas a identificar quais instituições oferecem disciplina especifica e/ou similar de radiofármacos. As grades curriculares foram obtidas via internet através do site de cada instituição. Das cinquenta e seis IES consultadas, apenas cinco oferecem uma disciplina específica na sua grade curricular que aborda a aplicação da radioatividade na área farmacêutica, sendo elas o Centro Universitário Metodista, Universidade Federal de Pelotas, Universidade Federal do Rio Grande do Sul, Pontifícia Universidade Católica do Paraná e Universidade Federal do Paraná. Não foram avaliadas as ementas, pois não estavam disponíveis online. Dentre estas apenas três IES apresentaram carga horária mínima de 40 horas, que possibilita o registro do profissional pela Comissão Nacional de Energia Nuclear (CNEN) sem a necessidade de prestar o exame obrigatório realizado pela CNEN.

Radiopharmacy is an essential and integral part of nuclear medicine. Preparation of reactive substances has to be carried out by competent professionals, who must be able to demonstrate knowledge of all areas of the specialty. Given the responsibilities of the pharmacist, this study aimed at analyzing the curriculum of the college of pharmacy at Universities of the Southern Brazil offering the discipline of radiopharmacy (or similar). The curriculum of pharmacy institutions in Paraná, Santa Catarina and Rio Grande do Sul states, certified by the Ministry of Education site (e-MEC) was obtained from the website of each institution and evaluated. From the 56 universities found, only five have a specific discipline of radioactivity in the pharmaceutical area in their curriculum. They are Methodist University, Federal University of Pelotas, Federal University of Rio Grande do Sul, PUC-Paraná and Federal University of Paraná. Only three institutions presented 40 hours of lessons, the minimum required to the registration of the professional by the National Commission of Nuclear Energy.

Kavain analogues as potential analgesic agents.

BACKGROUND: Kavalactones are pharmacologically active compounds present in preparations of the root trunk of Piper methysticum Forst, known as kava. This work describes the analgesic activity of some synthesized analogues of synthetic kavain, which is the main component of kava. METHODS: The essays were initially performed against the writhing test in mice, and the most promising compound was analyzed using other classical models of nociception, including formalin-, capsaicin-, glutamate-induced nociception, the hot plate test, and measurement of motor performance. RESULTS: The results indicated that compound 6-(4-fluorophenyl)-4-methoxy-5,6-dihydropyran-2-one (2d) exerts potent and dose-dependent analgesic activity, inhibiting abdominal constrictions caused by acetic acid in mice, and being more active than some reference drugs. It also presented activity in the other models of pain, with the exception of the hot plate test and the measurement of motor performance. CONCLUSIONS: Although compound 2d exerts antinociceptive activity, the mechanism of action remains uncertain, but it does not involve the opioid system and does not appear to be associated with non-specific effects such as changes in locomotor activity or motor coordination.

Evaluation of the genotoxic and antigenotoxic potential of Melissa officinalis in mice

Melissa officinalis (L.) (Lamiaceae), a plant known as the lemon balm, is native to the east Mediterranean region and west Asia. Also found in tropical countries, such as Brazil, where it is popularly known as "erva-cidreira" or "melissa", it is widely used in aqueous- or alcoholic-extract form in the treatment of various disorders. The aim was to investigate in vivo its antigenotoxicity and antimutagenicity, as well as its genotoxic/mutagenic potential through comet and micronucleus assaying. CF-1 male mice were treated with ethanolic (Mo-EE) (250 or 500 mg/kg) or aqueous (Mo-AE) (100 mg/kg) solutions of an M. officinalis extract for 2 weeks, prior to treatment with saline or Methyl methanesulfonate (MMS) doses by intraperitoneal injection. Irrespective of the doses, no genotoxic or mutagenic effects were observed in blood and bone-marrow samples. Although Mo-EE exerted an antigenotoxic effect on the blood cells of mice treated with the alkylating agent (MMS) in all the doses, this was not so with Mo-AE. Micronucleus testing revealed the protector effect of Mo-EE, but only when administered at the highest dose. The implication that an ethanolic extract of M. officinalis has antigenotoxic/antimutagenic properties is an indication of its medicinal relevance.

Antinociceptive effects of some synthetic delta-valerolactones.

PURPOSE: A series of delta-valerolactones has been synthesized in good yields, by reaction of ethyl acetoacetate with several aldehydes in presence of LDA. METHODS AND RESULTS: The in vivo analgesic activity of these compounds has been evaluated. The results indicate that the lactones synthesized showed an important antinociceptive effect at 10 mg/kg, administered intraperitoneally in mice, which significantly inhibited the abdominal constrictions induced by acetic acid when compared to acetylsalicylic acid and acetaminophen in the same dose, and increased significantly the thermal sensibility at the hot-plate method, although they were less effective than morphine in the same assay. CONCLUSIONS: The antinociceptive models employed here reveal a potential analgesic effect of the delta-valerolactones synthesized. Further investigations are needed to discern which mechanism of action is concern.

Química combinatória: moderna ferramenta para a obtenção de candidatos a protótipos de novos fármacos / Combinatorial chemistry: advanced tool for drug leads discovery

A Química combinatória (QC) é atualmente uma das mais promissoras ferramentas para a descoberta e o desenvolvimento de novas moléculas com potencialidades terapêuticas. Nesta metodologia de síntese os produtos são formados simultaneamente e podem ser testados biologicamente em uma só vez, seja em forma de misturas ou separadamente. A principal meta desta nova metodologia é reduzir o tempo necessário para a obtenção de um novo fármaco. A síntese de quimiotecas pode ser realizada através da utilização de polímeros insolúveis, solúveis ou pela tradicional síntese em solução, sendo que cada uma delas apresenta características que podem ser vantajosas ou não, dependendo da metodologia utilizada...