Evaluation of antifungal activity, mechanisms of action and toxicological profile of the synthetic amide 2-chloro-N-phenylacetamide.

Aspergillus niger causes infections such as otitis and pulmonary aspergillosis in immunocompromised individuals. Treatment involves voriconazole or amphotericin B, and due to the increase in fungal resistance, the search for new compounds with antifungal activity has intensified. In the development of new drugs, cytotoxicity and genotoxicity assays are important, as they allow predicting possible damage that a molecule can cause, and in silico studies predict the pharmacokinetic properties. The aim of this study was to verify the antifungal activity and the mechanism of action of the synthetic amide 2-chloro-N-phenylacetamide against Aspergillus niger strains and toxicity. 2-Chloro-N-phenylacetamide showed antifungal activity against different strains of Aspergillus niger with minimum inhibitory concentrations between 32 and 256 µg/mL and minimum fungicides between 64 and 1024 µg/mL. The minimum inhibitory concentration of 2-chloro-N-phenylacetamide also inhibited conidia germination. When associated with amphotericin B or voriconazole, 2-chloro-N-phenylacetamide had antagonistic effects. Interaction with ergosterol in the plasma membrane is the probable mechanism of action.2-Chloro-N-phenylacetamide has favorable physicochemical parameters, good oral bioavailability and absorption in the gastrointestinal tract, crosses the blood-brain barrier and inhibits CYP1A2. At concentrations of 50 to 500 µg/mL, it has little hemolytic effect and a protective effect for type A and O red blood cells, and in the cells of the oral mucosa it promotes little genotoxic change. It is concluded that 2-chloro-N-phenylacetamide has promising antifungal potential, favorable pharmacokinetic profile for oral administration and low cytotoxic and genotoxic potential, being a promising candidate for in vivo toxicity studies.

Tephrosia toxicaria (Sw.) Pers. extracts: Screening by examining aedicidal action under laboratory and field conditions along with its antioxidant, antileishmanial, and antimicrobial activities.

An increase in the incidence of arboviral, microbial and parasitic infections, and to disorders related to oxidative stress has encouraged the development of adjuvant therapies based on natural formulations, such as those involving plant extracts. Thus, to expand the repertoire of the available therapeutic options, this study aimed to describe the versatility of Tephrosia toxicaria (Sw.) (Pers., 1807) extracts for the control of arbovirus vectors, as well as their antioxidant, antileishmanial, and antimicrobial potential. Among the aqueous and hydroethanolic extracts obtained, the hydroethanolic extract from roots (RHA) was identified as the most active larvicide extract demonstrating, respectively, the lowest lethal concentration (mg/mL) for 50%, 90% and 99% of Aedes aegypti (L., 1762) and Aedes albopictus (S., 1894) larvae, observed at 24 h (0.33, 0.84 and 1.80; 0.32, 0.70 and 1.32) and 48 h (0.17, 0.51 and 1.22; 0.26, 0.47 and 0.78) post-exposure. Field assays revealed that RHA (0.84 mg/mL) is a potential oviposition deterrent, reducing egg-laying by approximately 90%. RHA (0.1 mg/mL) also exhibited antioxidant activity for the following tests: total antioxidant capacity (286.86 mg AAE/g), iron (87.16%) and copper (25.64%) chelation, and superoxide scavenging (10%). In the cell culture assays, RHA (0.1 mg/mL) promoted regeneration of metabolic activity (92% cell viability) in cells exposed to oxidative stress. Furthermore, RHA displayed weak antileishmanial activity (IC50 = 3.53 mg/mL) against Leishmania amazonensis and not exhibit antimicrobial activity. The extraction favored the concentration of carbohydrates in RHA, in addition to lectins and protease inhibitors, with molecular masses estimated between 10 and 24 kDa. Cytotoxicity and phytotoxicity analyses of RHA suggested its biosecurity. Thus, RHA is a multivalent extract with insecticide and antioxidant properties at low and safe concentrations. However, others studies on its indirect toxic effects are ongoing to ensure the complete safety of RHA.

Four diterpenes identified in silico were isolated from Hyptidinae and demonstrated in vitro activity against Mycobacterium tuberculosis.

Plants of Hyptidinae subtribe (Lamiaceae - family), as Mesosphaerum sidifolium, are a source of bioactive molecules. In the search for new drug candidates, we perform chemical characterization of diterpenes isolated from the aerial parts of M. sidifolium was carried out with uni- and bidimensional NMR spectral data, and evaluate in silico through the construction of a predictive model followed by in vitro testing Mycobacterium tuberculosis and Mycobacterium smegmatis. Resulted in the isolation of four components: Pomiferin D (1), Salviol (2), Pomiferin E (3) and 2α-hydroxysugiol (4), as well as two phenolic compounds, rosmarinic and caffeic acids. In silico model identified 48 diterpenes likely to have biological activity against M. tuberculosis. The diterpenes isolated were tested in vitro against M. tuberculosis demonstrating MIC = 125 µM for 4 and 1, while 2 and 3 -MIC = 250 µM. These compounds did not show biological activity at these concentrations for M. smegmatis.

Epidemiological aspects of visceral leishmaniasis in Rio Grande do Norte, Brazil

Visceral Leishmaniasis (VL) is a parasitic disease caused by Leishmania protozoa and transmitted by the bite of sand fly insects. This study aimed to describe the epidemiological aspects of VL in Rio Grande do Norte (RN), using variables inserted in the Information System for Notifiable Diseases, for the period from 2013 to 2019. The chi-square test of independence was used with p<0.05 considered statistically significant. 635 cases of VL were reported in RN, with stability of new cases in the analyzed period. 60% of cases were autochthonous, 84 (50.2%) municipalities in RN had autochthonous cases, with 70 (18.2%) cases in Natal and 58 (15.1%) in Mossoró. The most affected age group was 20-59 year old (57.3%) followed by 0-9 year old (23.8%), 10-19 year old (10.4%) and 60 year old or older (8.5%). There was a positive association between the 0-9 and 10-19 ranges with females and 20-59 with males (p=0.0001). Among the 532 individuals, 54.5% had a low level of education, and these, as well as the illiterate, associated with males (p=0.001). 85.3% of 612 cases were in black/brown group and 77.1% of 632 in urban/periurban residents. 27.6% of 500 were co-infected with HIV, 77.5% in males and 89.8% in adults. 70.7% progressed to cure and 6.8% died from VL. The study shows that the control measures adopted within the scope of the National Program for the Control of Leishmaniasis should be reassessed since there has been no decrease in cases, even though it has had stability over the years in Natal and a tendency to growth in Mossoró, the most affected areas.

Avaliação da citotoxicidade in vitro e genotoxicidade ex-vivo em compostos da Pavonia glazioviana Gürke (Malvaceae / Evaluation of in vitro cytotoxicity and ex-vivo genotoxicity in compounds from Pavonia glazioviana Gürke(Malvaceae)

Introdução: as terapias alternativas que utilizam plantas medicinais e fitoterápicos são bastante comuns no Brasil. Dentre várias espécies vegetais brasileiras utilizadas em terapias destacam-se as espécies da família Malvaceae. Objetivos: o presente estudo teve como objetivo avaliar a citotoxicidade in vitro e a genotoxicidade ex-vivo em compostos da Pavonia glazioviana Gürke espécie brasileira pertencente à família Malvaceae. Metodologia: métodos in vitro foram utilizados para verificar o potencial citotóxico por meio de ensaios hemolíticos e anti-hemolíticos e da análise genotóxica ex-vivo. O Extrato Etanólico Bruto (EEB) e Fração Clorofórmico (FC) foram obtidos na amostra vegetal utilizada neste estudo. Resultados: os produtos EEB-Pg e FC-Pg apresentaram baixo efeito citotóxico apenas nas concentrações de 50 e 100 µg / mL. As amostras expostas às concentrações de 500 e 1000 µg / mL apresentaram índice hemolítico alto a moderado com lise superior a 60%. Foi descrito efeito anti-hemolítico moderado em todas as amostras tratadas com 500 e 1000 µg / mL, com hemólise < 60%. Além disso, os compostos mostraram baixo efeito genotóxico ex-vivo, com um índice geral de células normais superior a 84% em todas as concentrações. Conclusões: os resultados sugerem um baixo perfil tóxico dos compostos obtidos da espécie Pavonia glazioviana, indicando limites seguros para o uso desses produtos naturais.

Introduction: alternative therapies using medicinal plants and herbal medicines are quite common in Brazil. Among several Brazilian plant species used in therapies, the species of the Malvaceae family stand out. Objetctives: the present study aimed to evaluate the in vitro cytotoxicity and ex-vivo genotoxicity in compounds of the Brazilian Pavonia glazioviana Gürke belonging to the Malvaceae family. Methodology: in vitro methods were used to verify the cytotoxic potential through hemolytic and antihemolytic assays and the ex-vivo genotoxic analysis. The Crude Etanolic Extract (CEE) and Cloroformic Fraction (CF) was obtained in vegetal sample used on this study. Results: the CEE-Pg and CF-Pg products only showed a low cytotoxic effect at the concentrations of 50 and 100 µg/mL. The exposure to the concentrations of 500 and 1000 µg/mL showed a high to moderate hemolytic index with lysis higher than 60%. A moderate anti-hemolytic effect was described in all samples treated with 500 and 1000 µg/mL, with hemolysis <60%. In addition, the compounds showed low ex-vivo genotoxic effect with a general index of normal cells greater than 84% at all concentrations. Conclusion: the results suggest a low toxic profile of the compounds obtained from the Pavonia glazioviana Gürke species belonging to the Malvaceae family, indicating safe limits for the use of these natural products.

The antifungal and antibiofilm activity of Cymbopogon nardus essential oil and citronellal on clinical strains of Candida albicans.

OBJECTIVE: This study investigated the antifungal and antibiofilm activity of Cymbopogon nardus essential oil (EO) and its major compound, citronellal, in association with miconazole and chlorhexidine on clinical strains of Candida albicans. The likely mechanism(s) of action of C. nardus EO and citronellal was further determined. MATERIALS AND METHODS: The EO was chemically characterized by gas chromatography coupled with mass spectrometry (GC-MS). The antifungal activity (MIC/MFC) and antibiofilm effects of C. nardus EO and citronellal were determined by the microdilution method, and their likely mechanism(s) of action was determined by the sorbitol and ergosterol assays. Then, the samples were tested for a potential association with standard drugs through the checkerboard technique. Miconazole and chlorhexidine were used as positive controls and the assays were performed in triplicate. RESULTS: The GC-MS analysis tentatively identified citronellal as the major compound in C. nardus EO. Both samples showed antifungal activity, with MIC of 256 µg/mL, as compared to 128 µg/mL and 8 µg/mL of miconazole and chlorhexidine, respectively. C. nardus EO and citronellal effectively inhibited biofilm formation (p < 0.05) and disrupted preformed biofilms (p < 0.0001). They most likely interact with the cell membrane, but not the cell wall, and did not present any synergistic activity when associated with standard drugs. CONCLUSION: C. nardus EO and citronellal showed strong in vitro antifungal and antibiofilm activity on C. albicans. CLINICAL RELEVANCE: Natural products have been historically bioprospected for novel solutions to control fungal biofilms. Our data provide relevant insights into the potential of C. nardus EO and citronellal for further clinical testing. However, additional bioavailability and toxicity studies must be carried out before these products can be used for the chemical control of oral biofilms.

Antifungal activity of 2-chloro-N-phenylacetamide, docking and molecular dynamics studies against clinical isolates of Candida tropicalis and Candida parapsilosis.

AIMS: This study evaluated the antifungal, antibiofilm and molecular docking of 2-chloro-N-phenylacetamide against clinical isolates of Candida tropicalis and Candida parapsilosis. METHODS AND RESULTS: Minimum inhibitory concentration (MIC) of the test drugs was determined by microdilution. A1Cl obtained MIC values ranging from 16 and 256 µg/ml. Fluconazole MIC ranging from 16 and 512 µg/ml. MIC of A1Cl showed fungicide activity, emphasizing the solid antifungal potential of this drug. An association study was performed with A1Cl and fluconazole (checkerboard), revealing indifference by decreasing. Thus, we conducted this study using A1Cl isolated. In the micromorphological assay, the test drugs reduced the production of virulence structures compared to the control (concentration-dependent effect). A1Cl inhibited in vitro biofilm formation at all concentrations tested (1/4MIC to 8 × MIC) (p < 0.05) and reduced mature biofilm biomass (p < 0.05) against C. tropicalis and C. parapsilosis. In the ex vivo biofilm susceptibility testing (human nails fragments), A1Cl inhibited biofilm formation and reduced mature biofilm biomass (p < 0.05) more than 50% at MIC. Fluconazole had a similar effect at 4 × MIC. In silico studies suggest that the mechanism of antifungal activity of A1Cl involves the inhibition of the enzyme dihydrofolate reductase (DHFR) rather than geranylgeranyltransferase-I. CONCLUSIONS: The results suggest that A1Cl is a promising antifungal agent. Furthermore, this activity is related to attenuation of expression of virulence factors and antibiofilm effects against C. tropicalis and C. parapsilosis. SIGNIFICANCE AND IMPACT OF THE STUDY: Our study provides the first evidence that A1Cl, a novel synthetic drug, has fungicidal effects against C. tropicalis and C. parapsilosis. Furthermore, in vitro and ex vivo biofilms assays have demonstrated the potential antibiofilm of A1Cl. The mechanism of action involves inhibiting the enzyme DHFR, which was supported by in silico analyses. Therefore, this potential can be explored as a therapeutic alternative for onychomycosis and, at the same time, contribute to decreasing the resistance of clinical isolates of C. tropicalis and C. parapsilosis.

Antibacterial effect of isoeugenol against Pseudomonas aeruginosa

Abatsract Pseudomonas aeruginosa is an important nosocomial pathogen and its clinical importance is mainly related to nosocomial infections. Increased rates of bacterial resistance in recent years has led WHO to publish a global priority list to guide research and discovery of new antibiotics, where P. aeruginosa is among the group of bacteria for which there is a critical level of priority for new drugs to be discovered. In this context, isoeugenol appears as an interesting alternative and the objective of this study was to investigate its action against P. aeruginosa. Isoeugenol presented significant antibacterial activity, with minimum inhibitory concentration (MIC) of 64µg/mL and minimum bactericidal concentration (MBC) of 128µg/mL, and was considered bactericidal against this species. Molecular docking revealed interactions that suggest that isoeugenol may bind to the enzyme Penicillin-Binding Protein 3 and interfere with the bacterial cell wall synthesis process. This study reinforces the antibacterial potential of this compound and emphasizes that more studies are needed in order to better investigate its mechanism of antibacterial action.

Epidemiological profile of people affected by tuberculosis in Campina Grande ­ PB, between 2014 and 2018 / Perfil epidemiológico de acometidos por tuberculose em Campina Grande ­ PB, entre os anos de 2014 a 2018

Introduction: tuberculosis is a bacteriosis caused by the etiological agent Mycobacterium tuberculosis, which initially affects the lungs, however it can become extrapulmonary. Although this infection is an important public health problem in Brazil, epidemiological studies on this disease are scarce. Objective: thus, the present study aimed to elucidate the epidemiological profile of people affected by tuberculosis in Campina Grande ­ PB, between the years 2014 to 2018. Methodology: this is an epidemiological, retrospective, analytical and documentary study, in which data were collected from the Department of Informatics of the "Sistema Único de Saúde". Results: Between 2014 and 2018, 795 cases of tuberculosis were reported in Campina Grande-PB, with 2018 having the highest number of cases (24.6%). The epidemiological profile of those affected was predominantly male, aged 20 to 39 years, with low schooling, mixed race and residents of the urban area. When associating sex with immunosuppressive factors, a statistically significant association was observed between, HIV, the state of acquired immunodeficiency syndrome (AIDS) and alcoholism (p <0.05). Conclusion: in this way, the data of this research can guide the development of indicators and public policies for the most susceptible population.

Introdução: a tuberculose é uma bacteriose causada pelo agente etiológico Mycobacterium tuberculosis, que inicialmente acomete os pulmões, entretanto pode tornar-se extrapulmonar. Mesmo esta infecção tratando-se de um importante problema de saúde pública no Brasil, há grande escassez de estudos epidemiológicos referentes a essa doença. Objetivo: o presente estudo teve como objetivo elucidar o perfil epidemiológico de acometidos por tuberculose em Campina Grande, PB, entre os anos de 2014 a 2018. Metodologia: trata-se de um estudo epidemiológico, retrospectivo, analítico e documental, em que os dados foram coletados a partir do Departamento de Informática do Sistema Único de Saúde. Resultados: entre 2014 a 2018, foram notificados 795 casos de tuberculose em Campina Grande, PB, sendo que o ano de 2018 foi aquele com o maior número de casos ­ 24,6%. O perfil epidemiológico de acometidos foi, predominantemente, de indivíduos do gênero masculino, com 20 a 39 anos de idade, baixa escolaridade, etnia parda e residentes da zona urbana. Ao associar o gênero com os fatores imunossupressores, observouse associação estatisticamente significativa entre VIH, estado de SIDA e alcoolismo (p<0,05). Conclusão: assim, os dados desta pesquisa podem nortear o desenvolvimento de indicadores e políticas públicas para a população mais susceptível.

Dermatophytoses in patients attended from a private clinical analysis laboratory in João Pessoa-PB, between 2015 to 2019 / Dermatofitoses em pacientes atendidos em um laboratório privado de João Pessoa-PB, entre 2015 a 2019

Introduction: dermatophytoses or "tineas" are characterized by being mycoses caused by fungi of the genera Epidermophyton, Trichophyton and Microsporum. These mycotic infections can present themselves as a form of lesions that affect the skin, hair and nails of individuals of both genders and all ages. Objective: to elucidate the epidemiological profile of dermatophytoses in patients examined by a private clinical analysis laboratory in João Pessoa-PB, between 2015 and 2019. Methodology: this is an epidemiological, analytical, retrospective and documentary study, in which data collection took place at the Clinical Pathology Laboratory ­ "HEMATO", located in João Pessoa ­ PB. Results: the profile of those affected was predominantly female (58.5%), 18 to 59 years old (38.4%), white (53.6%) and with lesions, mainly in skin glabrous (38.5%), feet (33.3%) and nails (12.8%). When relating the age group to the injury site, it was noticed that injuries on glabrous skin, feet and nails, were more frequent in individuals aged 18 to 59 years, while injuries to the scalp were mostly found in individuals younger than 18 years old. The most prevalent species were M. canis (31.9%) and T.rubrum (31.9%). When correlating the fungal species with the lesion site, it was noted that M. canis was the main agent responsible for lesions in glabrous skin, scalp and hands, while T. rubrum was predominantly observed in nails and T. mentagrophytes in feet. Conclusion: it is concluded that the data present in this research can promote the development of indicators and public policies for the population most susceptible to dermatophytosis.

Introdução: dermatofitoses ou tineas se caracterizam por serem micoses causadas por fungos dos gêneros Epidermophyton, Trichophyton e Microsporum. Essas infecções micóticas podem se apresentar na forma de lesões que acometem pele, pelo e unhas de indivíduos de ambos os gêneros e todas as idades. Objetivo: elucidar o perfil epidemiológico de dermatofitoses de pacientes atendidos por um laboratório privado de análises clínicas em João Pessoa-PB, entre 2015 a 2019. Metodologia: trata-se de um estudo epidemiológico, analítico, retrospectivo e documental, em que a coleta de dados ocorreu no Laboratório de Patologia Clínica ­ HEMATO, localizado em João Pessoa ­ PB. Resultados: o perfil de acometidos foi predominantemente de indivíduos do sexo feminino (58,5%), com 18 a 59 anos de idade (38,4%), brancos (53,6%) e com lesões, principalmente, em pele glabra (38,5%), pés (33,3%) e unhas (12,8%). Ao relacionar a faixa etária com o local da lesão, percebeu-se que lesões em pele glabra, pés e unhas, foram mais frequentes em indivíduos de 18 a 59 anos, enquanto que lesões no couro cabeludo foram majoritariamente encontradas em indivíduos menos de 18 anos. As espécies mais prevalentes foram M. canis (31,9%) e T. rubrum (31,9%). Ao correlacionar a espécie fúngica com o local da lesão, notou-se que M. canis foi o principal agente responsável por lesões em pele glabra, couro cabeludo e mãos, enquanto T. rubrum foi predominantemente observado em unhas e T. mentagrophytes em pés. Conclusão: os dados obtidos nesta pesquisa podem fomentar o desenvolvimento de indicadores e políticas públicas para a população mais susceptível às dermatofitoses.

Main laboratory methods used for the isolation and identification of Staphylococcus spp / Principales métodos de laboratorio utilizados para el aislamiento e identificación de Staphylococcus spp / Principais métodos laboratorais utilizados para o isolamento e identificação de Staphylococcus spp

SUMMARY Introduction: Laboratory diagnosis related to clinical microbiology is highly complex, due to subjectivity when interpreting the results. Among bacterial pathogens, those linked to the Staphylococcus genus are relevant from a clinical and epidemiological point of view. Aim: To review the literature relative to the main laboratory methods used for the isolation and identification of microorganisms of the genus Staphylococcus. Methodology: The study was based on a literature search between 2000 and 2020, in the BVS, PubMed, Scielo, ScienceDirect and CAPES Periodical databases. Regarding its laboratory diagnosis, microscopy is used by the Gram method to verify the bacterium's morphology; novobiocin test, aiming to trace coagulase negative strains; use of biochemical tests, such as coagulase and cata-lase tests; identification through the use of selective and nonspecific culture media, such as blood agar (in which the hemolytic patterns of pathogens are observed), salty mannitol agar (specific to the species of Staphylococcus aureus) and DNAse agar (selective to S. aureus strains , S. intermedius and S. hyicus). Results: The Staphylococcus genus is of great clinical importance in the field of public health. Thus, the quality and speed of diagnosis are essential to promote measures to combat these pathogens, contributing to the well-being and survival of those affected.

RESUMEN Introducción: El diagnóstico de laboratorio relacionado con la microbiología clínica es muy complejo, debido a la subjetividad al interpretar los resultados. Entre los patógenos bacterianos, los relacionados con el género Staphylococcus son relevantes desde un punto de vista clínico y epidemiológico. Objetivo: Revisar la literatura relacionada con los principales métodos de laboratorio utilizados para el aislamiento e identificación de microorganismos del género Staphylococcus. Metolodogía: El estudio se basó en una búsqueda bibliográfica entre 2000 y 2020, en las bases de datos BVS, PubMed, Scielo, ScienceDirect y Periódicos CAPES. En cuanto a su diagnóstico de laboratorio, se utilizan la microscopía y el método de Gram para verificar la morfología de la bacteria; prueba de novobiocina, con el objetivo de rastrear cepas negativas de coagulasa; uso de pruebas bioquímicas, como las pruebas de coagulasa y catalasa; identificación mediante el uso de medios de cultivo selectivos e inespecíficos, como agar sangre (en el que se observan los patrones hemolíticos de los patógenos), agar manitol salado (específico para la especie de Staphylococcus aureus) y agar ADNse (selectivo para cepas de Staphylococcus aureus), Staphylococcus intermedius y Staphylococcus hyicus). Resultados: El género Staphylococcus es de gran importancia clínica en el campo de la salud pública. Por lo tanto, la calidad y la velocidad del diagnóstico son esenciales para promover medidas para combatir estos patógenos, contribuyendo al bienestar y la supervivencia de los afectados.

RESUMO Introdução: O diagnóstico laboratorial relacionado à microbiologia clínica é de elevada complexidade, em virtude da subjetividade perante na interpretação dos resultados. Dentre os patógenos bacterianos, os vinculados ao gênero Staphylococcus são relevantes desde o ponto de vista clínico e epidemiológico. Objetivo: Fazer uma revisão narrativa sobre os principais métodos laboratoriais utilizados para o isolamento e identificação de microrganismos do gênero Staphylococcus. Metodologia: O estudo baseou-se em uma pesquisa na literatura entre o período de 2000 a 2020, nas bases de dados BVS, PubMed, Scielo, ScienceDirect e Periódico CAPES. Quanto ao seu diagnóstico laboratorial utiliza-se a microscopia, através do método de Gram, para verificação da morfologia da bactéria; teste da novobiocina, objetivando o rastrearmento de cepas coagulase negativa; uso de provas bioquímicas, como os testes de coagulase e catalase; identificação por meio da utilização de meios de cultura seletivos e inespecíficos, como o agar sangue (em que se observa os padrões hemolíticos dos patógenos), agar manitol salgado (específico a espécie de Staphylococcus aureus) e agar ADNse (seletivo as estirpes de Staphylococcus aureus, Staphylococcus intermedius e Staphylococcus hyicus). Resultados: O gênero Staphylococcus é de grande importância clínica no âmbito da saúde pública. Assim, a qualidade e rapidez do diagnóstico são imprescindíveis para promover medidas de combate a esses patógenos, contribuindo para o bem-estar e sobrevida dos acometidos.

Food nitrates and nitrites as possible causes of cancer: A review / Nitratos y nitratos alimentarios como posibles causas de cáncer: una revisión / Nitratos e nitratos dietéticos como possíveis causas de câncer: uma revisão

SUMMARY Introduction: Nitrates and nitrites can be found in meat and dairy products, vegetables, and fruits. The consumption of these preservatives has been associated with the emergence of gastric, colorectal cancer and non-Hodgkin's lymphoma, although studies are still inconclusive. Methodology: It is a review of literature of the narrative type, in which there was a recovery of articles published in English and Portuguese, in the databases SciELO, Lilacs, Science Direct and Capes journals. Articles related to nitrates and nitrites in foods were included, as well as articles that correlated the consumption of these preservatives with the appearance of cancers, regardless of the year of publication, although articles published between the years 2009 to 2019 were prioritized. Results: Nitrates and nitrites are generally associated with industrialized food products; therefore, it is possible to observe the presence of these salts in a wide variety of foods. The excessive consumption of nitrates and nitrites, whether through water or food, has been associated with a great diversity of diseases, stimulating the development of several studies investigating, including, the correlation between the consumption of these preservatives and the appearance of cancers. Conclusion: It is observed that nitrates and nitrites form compounds with a carcinogenic potential, making them interesting to avoid excessive consumption of these preservatives.

RESUMEN Introducción: Los nitratos y nitritos pueden ser encontrados en carnes y productos lácteos, verduras y frutas. El consumo de estos conservantes ha sido asociado con la aparición de cáncer gástrico, colorrectal y linfoma no Hodgkin, aunque los estudios aún no son concluyentes. Metodología: Se hizo una revisión de tipo narrativo de la literatura, en la que se recuperaron artículos publicados en inglés y portugués, en las bases de datos SciELO, Lilacs, Science Direct y revistas Capes. Se incluyeron artículos relacionados con nitratos y nitritos en alimentos, así como artículos que correlacionaban el consumo de estos conservantes con la aparición de cánceres, independientemente del año de publicación, aunque se priorizaron artículos publicados entre los años 2009 a 2019. Resultados: Los nitratos y nitritos se asocian generalmente con productos alimenticios industrializados; por tanto, es posible observar la presencia de estas sales en una amplia variedad de alimentos. El consumo excesivo de nitratos y nitritos, ya sea a través del agua o de los alimentos, se ha asociado a una gran diversidad de enfermedades, estimulando el desarrollo de varios estudios que investigan, entre ellos, la correlación entre el consumo de estos conservantes y la aparición de cánceres. Conclusión: Así, se observa que los nitratos y nitritos, forman compuestos con potencial carcinogénico, por lo que resulta interesante evitar el consumo excesivo de estos conservantes.

RESUMO Introdução: Nitratos e nitritos podem ser encontrados em carnes e laticínios, vegetais e frutas. O consumo desses conservantes tem sido associado ao desenvolvimento de câncer gástrico e colorretal e linfoma não Hodgkin, embora os estudos ainda não sejam conclusivos. Metodologia: Trata-se de uma revisão de literatura do tipo narrativa, na qual houve a recuperação de artigos publicados em inglês e português, nas bases de dados SciELO, Lilacs, Science Direct e Periódicos Capes. Foram incluídos artigos relacionados a nitratos e nitritos em alimentos, bem como artigos que correlacionassem o consumo desses conservantes com o aparecimento de cânceres, independentemente do ano de publicação, embora tenham sido priorizados os artigos publicados entre os anos de 2009 a 2019. Resultados: Nitratos e nitritos são geralmente associados a produtos alimentícios industrializados; portanto, é possível observar a presença desses sais em uma grande variedade de alimentos. O consumo excessivo de nitratos e nitritos, seja pela água ou pelos alimentos, tem sido associado a uma grande diversidade de doenças, estimulando o desenvolvimento de diversos estudos que investiguem, inclusive, a correlação entre o consumo desses conservantes e o aparecimento de cânceres. Conclusão: Assim, observa-se que nitratos e nitritos formam compostos com potencial carcinogê-nico, por isso é interessante evitar o consumo excessivo desses conservantes.

In silico, in vitro and ex-vivo Toxicological Profiling of 5,7,4'-Trihydroxyflavone-8-C-ß-Glucopyranoside - Vitexin

This study aimed to evaluate the in silico, in vitro, and ex-vivo toxicity of vitexin, the flavonoid 5,7,4'- trihydroxyflavone-8-C-ß-glucopyranoside from Waltheria viscosissima. The chemical structure and predicted bioactive properties were also in silico analyzed. The in vitro and ex-vivo assays were performed according to the Ethics Code of the World Medical Association and were approved by the Ethics Committee of University Center of Patos (protocol number: 3.621.284). In silico analysis suggested that the molecule presents good oral bioavailability and good absorption; penetrating biological membranes. The toxicity tests revealed the potential effectiveness of the molecule in cellular protection against free radicals, in addition to possible antimutagenic, anticarcinogenic, antioxidant, antineoplastic, anti-inflammatory, anti-hemorrhagic and apoptosis agonist activity. Hemolytic and genotoxic assessment detected low hemolysis rates in human red blood cells and no cellular toxicity against oral mucosa cells. The data suggest that vitexin is a safe molecule for possible therapeutic application and its toxicity profile indicates viability for future studies.

Antifungal action of α-pinene against Candida spp. isolated from patients with otomycosis and effects of its association with boric acid.

The genus Candida is one of the main causes of otomycosis. The growing index of fungal strains resistant to antifungals makes necessary the search for new agents and α-pinene is a phytoconstituent present in plants with remarkable antimicrobial activity, which becomes an interesting object of study. Thus, the objective of this research was to evaluate the antifungal activity of α-pinene against Candida species isolated from otomycosis, determining the Minimum Inhibitory and Fungicide Concentrations, micromorphological analysis and verifying the effects of the association with boric acid. α-pinene showed significant antifungal activity, with greater inhibitory activity against C. parapsilosis, fungicidal action and proved to be effective in inhibiting fungal structures, such as pseudo-hyphae and promoting a marked decrease in blastoconidia. The combination of α-pinene with boric acid produced additive effects that may be interesting for use in clinical practice.

The impact that ß-citronellol isomers have on the biofilm formation of Candida yeasts.

Infections associated with biofilms developed by Candida spp. are becoming a great problem due to its resistance against the immune response of the host and the action of antifungal agents. Hence, finding substances that can inhibit the development of biofilms increases the likelihood that these compounds one day can become good antifungals applied in the clinic. The aim of this study was to evaluate the effect of ß-citronellol enantiomers on the biofilm formation by Candida albicans and Candida tropicalis isolated from bloodstream infections. Inhibition was evaluated by reading microplates treated with different concentrations of R-(+)-ß-citronellol, S-(-)-ß-citronellol and amphotericin B, compared to negative control, in spectrophotometer at 590 nm. All tested concentrations of ß-citronellol enantiomers inhibited the biofilm formation of Candida. However, it is still necessary to evaluate the behavior of these isomers on mature biofilms, so that they can become more viable as antifungal therapeutical agents.

Investigation of ethnomedicinal use of Commiphora leptophloeos (Mart.) J. B. Gillett (Burseraceae) in treatment of diarrhea.

ETHNOPHARMACOLOGICAL RELEVANCE: Commiphora leptophloeos (Mart.) J.B. Gillett, popularly known as "imburana", "imburana-de-cheiro" or "imburana-de-espinho", has been used in folk medicine for the treatment of gastrointestinal diseases, such as diarrhea. The indian tribes "Kairir-Shokó and shokó use the bark to treat diarrhea. However, there is no scientific evidence to justify the therapeutic use of this species. AIM OF THE STUDY: To investigate the ethnomedicinal use of Commiphora leptophloeos, with respect to the antimicrobial, antisecretory, antimotility and antispasmodic activities of the crude ethanolic extract obtained from its leaves (CL-EtOHL) and the mechanism underlying this action in rodents. MATERIAL AND METHODS: In the evaluation of antibacterial and antifungal activities was determined the minimum inhibitory concentration (MIC) of the extract, against different strains of bacteria and fungi. All experimental protocols were approved by the Animal Ethics Committee of the Federal University of Paraíba (045/2016). In addition, behavioral screening and acute toxicity assessment of CL-EtOHL were performed in female mice (n = 6). In the investigation of antidiarrheal activity (n = 6), frequency of defecation and number of liquid stools, were classified during 4 h, and intestinal fluid and transit were measured. In addition, the antispasmodic effect on rat ileum (n = 5) was also investigated. RESULTS: The ethanolic extract is rich in flavonoids and the main were identified as C-glycosylated flavonoids (isoorientin, orientin, and vitexin). In the evaluation of antimicrobial and antifungal activity, the extract showed moderate efficacy only against the tested strains of Candida krusei ATCC-6258, Candida parapsilosis ATCC-22019 and Candida glabrata ATCC-90030. The extract had no toxic effect until 2000 mg/kg. In castor oil-induced diarrhea, CL-EtOHL inhibited, in a dose-dependent manner, both total defecation frequency (ED50 = 380.4 ± 145.4 mg/kg) and the number of watery stools (ED50 = 151.2 ± 76.3 mg/kg). The extract showed no effect on fluid accumulation or normal intestinal transit. On the other hand, when the animals were pretreated with castor oil, the extract decreased the distance traveled by the activated charcoal (ED50 = 177.0 ± 50.3 mg/kg). In the investigation of antispasmodic effect, CL-EtOHL antagonized the contractions induced by KCl 30 mM (IC50 = 208.2 ± 25.9 µg/mL) and CCh 10-6 M (IC50 = 95. ± 22.0 µg/mL). To verify the participation of muscarinic receptors in this effect, cumulative carbachol curves were performed in the absence and presence of the extract, and a non-competitive pseudo-irreversible antagonism of these receptors was observed. CONCLUSION: The data indicate that ethanol extract obtained from the leaves of Commiphora leptophloeos has an antidiarrheal effect due to inhibition of the intestinal motility and antispasmodic effect, through the antagonism of muscarinic receptors. In addition, we suggest that flavonoids isolated from CL-EtOHL may be responsible for antidiarrheal activity of this extract. This explains its ethnomedicinal use in the treatment of diarrhea.

Study of the antifungal activity of ibuprofen and its association with amphotericin B or ketoconazole against Candida spp / Estudio de la actividad antifúngica del ibuprofeno y su asociación con anfotericina B o ketoconazol contra Candida spp / Estudo da atividade antifúngica do ibuprofeno e sua associação com anfotericina B ou cetoconazol contra Candida spp

SUMMARY The objective was evaluating the antifungal activity of ibuprofen alone and when associated with amphotericin B or ketoconazole against Candida species. Strains of C. albicans, C. tropicalis, C. guilliermondii, C. krusei and C. parapsilosis were used. The minimum inhibitory concentration (MIC) was determined by the microdilution method and the association study performed through the checkerboard assay. The concentration of 512 μg/mL inhibited approximately 65% of the tested strains, while against 35% of the strains presented MIC values above 2048 μg/mL. Associations of ibuprofen with amphotericin B against C. tropicalis and ibuprofen with ketoconazole against C. krusei showed synergistic effect. Antagonistic effects were evidenced in the combination of ibuprofen with amphotericin B against C. guilliermondii and C. albicans, as well as in the association of ibuprofen with ketoconazole against C. albicans and C. tropicalis. Through the experiments, it was found that ibuprofen showed antifungal activity against most of the Candida species tested. The combinations of ibuprofen and antifungals had synergistic effects. However, antagonistic results were evidenced in the association with ibuprofen, which would make clinical applicability difficult. Therefore, studies of this combined activity should be investigated, considering that this association may be positive for anti-fungal therapy.

RESUMEN El objetivo fue evaluar la actividad antifúngica del ibuprofeno solo y asociado con anfotericina B o ketoconazol contra especies de Candida. Se utilizaron cepas de C. albicans, C. tropicalis, C. guilliermondii, C. krusei y C. parapsilosis. La concentración inhibitoria mínima (MIC) se determinó mediante el método de microdilución y el estudio de asociación fue realizado a través del ensayo de checkboard. La concentración de 512 μg/mL inhibió aproximadamente el 65% de las cepas analizadas, mientras 35% de las cepas presentaron valores de MIC superiores a 2048 μg/mL. Las asociaciones de ibuprofeno con anfotericina B contra C. tropicalis e ibuprofeno con ketoconazol contra C. krusei mostraron un efecto sinérgico. Se evidenciaron efectos antagonistas en la combinación de ibuprofeno con anfotericina B contra C. guilliermondii y C. albicans, así como en la asociación de ibuprofeno con ketoconazol contra C. albicans y C. tropicalis. Se descubrió, a través de los experimentos, que el ibuprofeno mostró actividad antifúngica contra la mayoría de las especies de Candida probadas. Las combinaciones de ibuprofeno y antifúngicos tuvieron efectos sinérgicos. Sin embargo, se evidenciaron resultados antagónicos en la asociación con ibuprofeno, lo que dificultaría la aplicabilidad clínica. Por lo tanto, los estudios de esta actividad combinada deben investigarse, considerando que esta asociación puede ser positiva para la terapia antimicótica.

RESUMO O objetivo do estudo foi avaliar a atividade antifúngica do ibuprofeno sozinho e quando associado com anfotericina B ou cetoconazol contra espécies de Candida. Foram utilizadas cepas fúngicas de C. albicans, C. tropicalis, C. guilliermondii, C. krusei e C. parapsilosis, entre isolados clínicos e cepas padrão. A concentração inibitória mínima (CIM) foi determinada pela técnica de microdiluição e o estudo de associação realizado através do ensaio checkerboard. A concentração de 512 μg/mL foi capaz de inibir, aproximadamente, 65% das cepas ensaiadas, enquanto que 35% das estirpes apresentaram valores da CIM acima de 2048 μg/mL. Associações do ibuprofeno com anfotericina B contra C. tropicalis e ibuprofeno mais cetoconazol contra C. krusei mostraram efeito sinérgico. Efeitos antagônicos foram evidenciados na combinação do ibuprofeno com anfotericina B contra C. guilliermondii e C. albicans, como também na associação do ibuprofeno com cetoconazol contra C. albicans e C. tropicalis. Por meio dos experimentos, pôde-se afirmar que o ibuprofeno exerceu atividade antifúngica contra a maioria das espécies de Candida ensaiadas. Os efeitos das combinações entre o ibuprofeno e os antifúngicos promoveram efeitos sinérgicos. No entanto, resultados antagônicos foram evidenciados na associação com o ibuprofeno, o que dificultaria aplicabilidade clínica. Logo, estudos dessa atividade combinada devem ser investigados, pois esta associação pode traçar pontos positivos na terapia antifúngica.