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Importance: Transcranial direct current stimulation (tDCS) is moderately effective for depression when applied by trained staff. It is not known whether self-applied tDCS, combined or not with a digital psychological intervention, is also effective. Objective: To determine whether fully unsupervised home-use tDCS, combined with a digital psychological intervention or digital placebo, is effective for a major depressive episode. Design, Setting, and Participants: This was a double-blinded, sham-controlled, randomized clinical trial with 3 arms: (1) home-use tDCS plus a digital psychological intervention (double active); (2) home-use tDCS plus digital placebo (tDCS only), and (3) sham home-use tDCS plus digital placebo (double sham). The study was conducted between April 2021 and October 2022 at participants' homes and at Instituto de Psiquiatria do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, Brazil. Included participants were aged 18 to 59 years with major depression and a Hamilton Depression Rating Scale, 17-item version (HDRS-17), score above 16, a minimum of 8 years of education, and access to a smartphone and internet at home. Exclusion criteria were other psychiatric disorders, except for anxiety; neurologic or clinical disorders; and tDCS contraindications. Interventions: tDCS was administered in 2-mA, 30-minute prefrontal sessions for 15 consecutive weekdays (1-mA, 90-second duration for sham) and twice-weekly sessions for 3 weeks. The digital intervention consisted of 46 sessions based on behavioral therapy. Digital placebo was internet browsing. Main Outcomes and Measures: Change in HDRS-17 score at week 6. Results: Of 837 volunteers screened, 210 participants were enrolled (180 [86%] female; mean [SD] age, 38.9 [9.3] years) and allocated to double active (n = 64), tDCS only (n = 73), or double sham (n = 73). Of the 210 participants enrolled, 199 finished the trial. Linear mixed-effects models did not reveal statistically significant group differences in treatment by time interactions for HDRS-17 scores, and the estimated effect sizes between groups were as follows: double active vs tDCS only (Cohen d, 0.05; 95% CI, -0.48 to 0.58; P = .86), double active vs double sham (Cohen d, -0.20; 95% CI, -0.73 to 0.34; P = .47), and tDCS only vs double sham (Cohen d, -0.25; 95% CI, -0.76 to 0.27; P = .35). Skin redness and heat or burning sensations were more frequent in the double active and tDCS only groups. One nonfatal suicide attempt occurred in the tDCS only group. Conclusions and Relevance: Unsupervised home-use tDCS combined with a digital psychological intervention or digital placebo was not found to be superior to sham for treatment of a major depressive episode in this trial. Trial Registration: ClinicalTrials.gov Identifier: NCT04889976.

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Fungi are becoming increasingly resistant, especially the new strains. Therefore, this work developed nanoemulsions (NE) containing micafungin (MICA), in order to improve its action against infections caused by Candida auris. The NEs were composed of the surfactants polyoxyethylene (20) cetyl ether (Brij 58®)/soy phosphatidylcholine at 10%, sunflower oil/cholesterol at 10%, and 80% PBS. The NEs were characterized by Dynamic Light Scattering (DLS). For the microbiological in vitro evaluation the determination of the minimum inhibitory concentration (MIC), ergosterol/sorbitol, time kill and biofilms tests were performed. Additionally, the antifungal activity was also evaluated in a Galleria mellonella model. The same model was used in order to evaluate acute toxicity. The NE showed a size of ∼ 42.12 nm, a polydispersion index (PDI) of 0.289, and a zeta potential (ZP) of -3.86 mV. NEM had an average size of 41.29 nm, a PDI of 0.259, and a ZP of -4.71 mV. Finally, both nanoemulsions showed good stability in a storage period of 3 months. Although NEM did not show activity in planktonic cells, it exhibited action against biofilm and in the in vivo infection model. In the alternative in vivo model assay, it was possible to observe that both, NEM and free MICA at 0.2 mg/l, was effective against the infection, being that NEM presented a better action. Finally, NEM and free MICA showed no acute toxicity up to 4 mg/l. NEM showed the best activities in in vitro in mature antibiofilm and in alternative in vivo models in G. mellonella. Although, NEs showed to be attractive for MICA transport in the treatment of infections caused by C. auris in vitro and in vivo studies with G. mellonella, further studies should be carried out, in mice, for example.

Candida auris is a fungus that can cause infections in the human body. As it is a microorganism with a high potential for resistance, it is extremely important to develop new therapeutic alternatives. Thus, nanotechnology, the science that studies materials with extremely small sizes, can be considered a promising method in the treatment of these infections.

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ABSTRACT Objective: to analyze the prevalence of practices in childbirth care, obstetric and neonatal adverse events and their association with care models in three public health services. Method: this is a prospective cohort study carried out with 548 dyads, postpartum women and their newborns, whose pregnancy was of usual risk and vaginal birth, admitted to hospital in three public services, one with an exclusive care model by nurse-midwives (service A), one with a collaborative model involving obstetric doctors and nurses (service B) and one with an exclusive medical care model (service C). Initially, an interview was carried out with participants, and a second contact was carried out 42 days after birth to complement the collection of the adverse event outcome. Results: in service A, no woman underwent the Kristeller maneuver, episiotomy, directed pushing or more than one vaginal examination per hour. Meanwhile, in service C, 19.3%, 39.9%, 77.1% and 26.3% of women underwent these interventions, respectively. Adverse events occurred in 19.2% of the dyads. Occurrence of adverse events was associated with not using partograph (p=0.001; OR: 11.03; CI: 2.64-45.99) and episiotomy (p=0.042; OR: 1.72; CI: 1. 02-2.91). The mean probability of experiencing an adverse event was 5% in service A, 21% in service B and 24% in service C. Conclusion: adverse events had a lower mean probability of occurrence in the service exclusively operated by nurse-midwives, in which greater application of recommendations for labor and birth care was identified.

RESUMEN Objetivo: analizar la prevalencia de prácticas en la atención del childbirth, eventos adversos obstétricos y neonatales y su asociación con los modelos de atención en tres servicios públicos de salud. Método: estudio de cohorte prospectivo realizado con 548 binomios, puérperas y sus recién nacidos, cuyo embarazo fue de riesgo habitual y childbirth vaginal, hospitalizados en tres servicios públicos, uno con modelo de atención exclusiva por enfermeras obstétricas (servicio A), otro con modelo colaborativo. modelo con la labor de médicos y enfermeras obstetras (servicio B) y otro con un modelo de asistencia médica exclusiva (servicio C). Inicialmente se realizó una entrevista a los participantes y se realizó un segundo contacto a los 42 días del nacimiento para complementar la recopilación del resultado del evento adverso. Resultados: en el servicio A ninguna mujer fue sometida a maniobra de Kristeller, episiotomía, pujo dirigido o más de un examen vaginal por hora. Mientras tanto, en el servicio C, el 19,3%, 39,9%, 77,1% y 26,3% de las mujeres se sometieron a estas intervenciones, respectivamente. Los eventos adversos ocurrieron en el 19,2% de los binomios. La aparición de eventos adversos se asoció con la no utilización del partographa (p=0,001; OR: 11,03; IC: 2,64-45,99) y episiotomía (p=0,042; OR: 1,72; IC: 1,02-2,91). La probabilidad promedio de experimentar un evento adverso fue del 5% en el servicio A, del 21% en el servicio B y del 24% en el servicio C. Conclusión: los eventos adversos tuvieron menor probabilidad promedio de ocurrencia en el servicio operado exclusivamente por enfermeras obstétricas, en el que se identificó mayor aplicación de las recomendaciones de asistencia al childbirth y nacimiento.

RESUMO Objetivo: analisar a prevalência de práticas na atenção ao parto, eventos adversos obstétricos e neonatais e sua associação com modelos assistenciais em três serviços de saúde públicos. Método: estudo coorte prospectivo realizado com 548 binômios, puérperas e seus recém-nascidos, cuja gestação foi de risco habitual e o parto vaginal, internados em três serviços públicos, sendo um com modelo de assistência exclusivo por enfermeiras obstetras (serviço A), um com modelo colaborativo com atuação de médicos e enfermeiras obstetras (serviço B) e um com modelo de assistência exclusiva médica (serviço C). Inicialmente, foi realizada uma entrevista com as participantes e um segundo contato foi realizado após 42 dias do parto para complementar a coleta do desfecho evento adverso. Resultados: no serviço A, nenhuma mulher foi submetida à manobra de Kristeller, episiotomia, incentivos a puxos dirigidos ou mais de um toque vaginal por hora. Enquanto, no serviço C, 19,3%, 39,9%, 77,1% e 26,3% das mulheres foram submetidas a essas intervenções, respectivamente. Os eventos adversos ocorreram em 19,2% dos binômios. A ocorrência dos eventos adversos foi associada ao não uso do partograma (p=0,001; OR: 11,03; IC: 2,64-45,99) e episiotomia (p=0,042; OR: 1,72; IC: 1,02-2,91). A probabilidade média de apresentar algum evento adverso foi de 5% no serviço A, 21% no serviço B e 24% no serviço C. Conclusão: os eventos adversos apresentaram menor probabilidade média de ocorrência no serviço com atuação exclusiva de enfermeiras obstetras, no qual se identificou maior aplicação das recomendações para assistência ao parto e nascimento.

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ETHNOPHARMACOLOGICAL RELEVANCE: Piper methysticum G. Forst, popularly known as kava, is a traditional medicinal plant native from South Pacific islands and widely used to treat anxiety, depression and stress. The psychoactive properties are related to the kavalactones, mainly kavain. AIM OF THE STUDY: To evaluate the biopharmaceutical properties of synthetic kavain and when present in kava dried extracts by means of equilibrium solubility and intestinal permeability studies in the Caco-2 cell model. MATERIALS AND METHODS: The equilibrium solubility of kavain was performed using a shake flask incubator at 37 °C in different media at physiological pH range (1.2-6.8). The intestinal permeability of kavain evaluated in Caco-2 cells in the presence and absence of the P-glycoprotein inhibitor verapamil. Kavain concentrations were determined by reversed phase high performance liquid chromatography (HPLC). RESULTS: HPLC methods were developed and fully validated for kavain quantitation. Kavain demonstrated low solubility and the pH of the aqueous media did not affect its solubility. Kavain was found to be highly permeable and efflux of kavain mediated by P-glycoprotein was not significant during intestinal permeation. CONCLUSION: The results of biopharmaceutical studies provided useful information for predicting availability of kavain from the gastrointestinal tract and this compound was ranked as BCS Class II, exhibiting dissolution rate-limited absorption.

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Fungal infections are one of the main public health problems, especially in immunocompromised patients, nosocomial environments, patients with chronic diseases, and transplant recipients. These diseases are increasingly frequent and lethal because the microorganism has a high capacity to acquire resistance to available therapy. The main resistance factors are the emergence of new strains and the uncontrolled use of antifungals. It is, therefore, important to develop new methods that contribute to combating fungal diseases in the clinical area. Natural products have considerable potential for the development of new drugs with antifungal activity, mainly due to their biocompatibility and low toxic effect. This promising antimicrobial activity of natural products is mainly due to the presence of flavonoids, terpenes, and quinones, which explains their antifungal potential. Pharmaceutical nanotechnology has been explored to enhance the delivery, selectivity, and clinical efficacy of these products. Nanotechnological systems provide a safe and selective environment for various substances, such as natural products, improving antifungal activity. However, further safety experiments (in vivo or clinical trials) need to be carried out to prove the therapeutic action of natural products, since they may have undesirable, toxic, and mutagenic effects. Therefore, this review article addresses the main nanotechnological methods using natural products for effective future treatment against the main fungal diseases.

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Galleria mellonella is a model that uses adult larvae to assess the prophylactic, therapeutic, and acute toxic potential of substances. Given their benefits, G. mellonella models are being employed in investigations of systemic infections caused by highly resistant microorganisms. Among the multiresistant microorganisms, we highlight Candida auris, a yeast with high mortality potential and resistance. Among the potential drugs, amphotericin B (AmB) stands out; however, microbial resistance episodes and side effects caused by low selectivity have been observed. The incorporation of AmB into a nanoemulsion (NE) can contribute to the control of C. auris infections and resistance as well as decrease the side effects of this drug. This study aimed to develop AmB-loaded NE (NEA) and evaluate its antifungal action against C. auris in G. mellonella. NEs were obtained by using sunflower oil and cholesterol as the oily phase, polyoxyethylene 20 cetyl ether (Brij® 58) and soy phosphatidylcholine as the surfactant system, and PBS buffer as the aqueous phase. An alternative in vivo assay with G. mellonella for acute toxicity and infection was performed using adult stage larvae (200 mg to 400 mg). According to the obtained results, NE and NEA exhibited sizes of 43 and 48 nm, respectively. The PDI was 0.285 and 0.389 for NE and NEA, respectively. The ZP showed electronegativity for both systems, with -3.77 mV and -3.80 mV for NE and NEA, respectively. Acute toxicity showed that free AmB had greater acute toxicity potential than NEA. The survival assay showed high larval viability. NEA had a better antifungal profile against systemic infection in G. mellonella. It is concluded that the alternative model proved to be an efficient in vivo assay to determine the toxicity and evaluate the therapeutic property of free AmB and NEA in systemic infections caused by C. auris.

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Myrcia bella is a medicinal plant used for the treatment of diabetes, hemorrhages, and hypertension in Brazilian folk medicine. Considering that plant extracts are attractive sources of new drugs, the aim of the present study was to verify the influence of incorporating 70% hydroalcoholic of M. bella leaves in nanostructured lipid systems on the mutagenic and antifungal activities of the extract. In this work, we evaluated the antifungal potential of M. bella loaded on the microemulsion against Candida sp for minimum inhibitory concentration, using the microdilution technique. The system was composed of polyoxyethylene 20 cetyl ether and soybean phosphatidylcholine (10%), grape seed oil, cholesterol (10%: proportion 5/1), and purified water (80%). To investigate the mutagenic activity, the Ames test was used with the Salmonella Typhimurium tester strains. M. bella, either incorporated or free, showed an important antifungal effect against all tested strains. Moreover, the incorporation surprisingly inhibited the mutagenicity presented by the extract. The present study attests the antimicrobial properties of M. bella extract, contributing to the search for new natural products with biological activities and suggesting caution in its use for medicinal purposes. In addition, the results emphasize the importance of the use of nanotechnology associated with natural products as a strategy for the control of infections caused mainly by the genus Candida sp.

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Amphotericin B (AmB) is an important antifungal agent available in the clinical practice with the action mechanism related to the inhibition of ergosterol molecule present in the fungal cell wall. Given this, in order to expand AmB knowledge, this review article gathers important information of the AmB physical, chemical, and biological properties. In addition, the main analytical methods for quantifying and determining the AmB were also reported in this review, such as high-performance liquid chromatography (HPLC), liquid chromatography, tandem mass spectrophotometry (LC-MS/MS), immunoenzymatic assay (ELISA), capillary zone electrophoresis (CE) stands out and among others. Based in this review article, the scientific community will have important information to choose the best method for analysis in their scientific or clinical research, providing greater security and reliability in the obtained results.

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Peptic ulcer disease (PUD) is a common condition that is induced by acid and pepsin causing lesions in the mucosa of the duodenum and stomach. The pathogenesis of PUD is a many-sided scenario, which involves an imbalance between protective factors, such as prostaglandins, blood flow, and cell renewal, and aggressive ones, like alcohol abuse, smoking, Helicobacter pylori colonisation, and the use of non-steroidal anti-inflammatory drugs. The standard oral treatment is well established; however, several problems can decrease the success of this therapy, such as drug degradation in the gastric environment, low oral bioavailability, and lack of vectorisation to the target site. In this way, the use of strategies to improve the effectiveness of these conventional drugs becomes interesting. Currently, the use of drug delivery systems is being explored as an option to improve the drug therapy limitations, such as antimicrobial resistance, low bioavailability, molecule degradation in an acid environment, and low concentration of the drug at the site of action. This article provides a review of oral drug delivery systems looking for improving the treatment of PUD.

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BACKGROUND: Cardiomegaly on chest X-ray is an independent predictor of death in individuals with chronic Chagas cardiomyopathy (CCC). However, the correlation between increased cardiothoracic ratio (CTR) on chest X-ray and left ventricular end-diastolic diameter (LVEDD) on echocardiography is not well established in this population. OBJECTIVES: To assess the relationship between chest X-ray and LVEDD on echocardiography in patients with Chagas disease and its applicability to the Rassi score. METHODS: Retrospective study on 63 Chagas disease outpatients who underwent chest X-ray and echocardiography. Cardiomegaly on chest X-ray was defined as a CTR>0.5. LVEDD was analyzed as a continuous variable. ROC curve was used to evaluate the ability of LVEDD in detecting cardiomegaly by chest X-ray, with a cut-off point defined by the highest sum of sensitivity and specificity. RESULTS: Median age 61 years [interquartile range 48-68], 56% were women. CCC was detected in 58 patients, five patients had the indeterminate form of Chagas disease. Cardiomegaly was detected in 28 patients. The area under the ROC curve for LVEDD was 0.806 (95%CI: 0.692-0.919). The optimal cut-off for LVEDD was 60 mm (sensitivity = 64%, specificity = 89%). The use of LVEDD on echocardiography as a surrogate for CTR on chest X-ray changed the Rassi score values of 14 patients, with a reduction in the presumed risk in 10 of them. CONCLUSION: LVEDD on echocardiography is an appropriate, highly specific parameter to distinguish between the presence and absence of cardiomegaly on chest X-ray in Chagas disease. (Arq Bras Cardiol. 2021; 116(1):68-74).

FUNDAMENTO: Cardiomegalia pela radiografia de tórax (RXT) é preditor independente de morte em indivíduos com cardiomiopatia crônica da doença de Chagas (CCDC). Contudo, a correlação entre o aumento do índice cardiotorácico (ICT) na RXT e do diâmetro telediastólico do ventrículo esquerdo (DDVE) pela ecocardiografia (ECO) nessa população não está bem definida. OBJETIVOS: Analisar a relação entre cardiomegalia pela RXT e DDVE pela ECO em pacientes com doença de Chagas (DC) e sua aplicabilidade ao escore de Rassi. MÉTODOS: Estudo retrospectivo incluiu 63 pacientes ambulatoriais com DC avaliados por RXT e ECO. Cardiomegalia na RXT foi definida como ICT > 0,5. DDVE foi avaliado como variável contínua. Curva ROC foi utilizada para avaliar o potencial do DDVE para identificação de cardiomegalia pela RXT, com ponto de corte definido pela maior somatória de sensibilidade e especificidade. RESULTADOS: Idade mediana = 61 anos [intervalo interquartil: 48-68], 56% mulheres. CCDC foi identificada em 58 pacientes; 5 tinham a forma indeterminada da DC. Cardiomegalia foi detectada em 28 indivíduos. A área sob a curva ROC do DDVE para identificação de cardiomegalia foi de 0,806 (IC 95%: 0,692-0,919). O ponto de corte ótimo para DDVE foi de 60 mm (sensibilidade = 64%, especificidade = 89%). O uso do DDVE pela ECO em substituição ao ICT pela RXT alterou o escore de Rassi em 14 pacientes, e em 10 deles houve redução do risco presumido. CONCLUSÃO: DDVE pela ECO é parâmetro adequado e com alta especificidade para distinguir entre presença e ausência de cardiomegalia na RXT na DC. (Arq Bras Cardiol. 2021; 116(1):68-74).

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Resumo Fundamento Cardiomegalia pela radiografia de tórax (RXT) é preditor independente de morte em indivíduos com cardiomiopatia crônica da doença de Chagas (CCDC). Contudo, a correlação entre o aumento do índice cardiotorácico (ICT) na RXT e do diâmetro telediastólico do ventrículo esquerdo (DDVE) pela ecocardiografia (ECO) nessa população não está bem definida. Objetivos Analisar a relação entre cardiomegalia pela RXT e DDVE pela ECO em pacientes com doença de Chagas (DC) e sua aplicabilidade ao escore de Rassi. Métodos Estudo retrospectivo incluiu 63 pacientes ambulatoriais com DC avaliados por RXT e ECO. Cardiomegalia na RXT foi definida como ICT > 0,5. DDVE foi avaliado como variável contínua. Curva ROC foi utilizada para avaliar o potencial do DDVE para identificação de cardiomegalia pela RXT, com ponto de corte definido pela maior somatória de sensibilidade e especificidade. Resultados Idade mediana = 61 anos [intervalo interquartil: 48-68], 56% mulheres. CCDC foi identificada em 58 pacientes; 5 tinham a forma indeterminada da DC. Cardiomegalia foi detectada em 28 indivíduos. A área sob a curva ROC do DDVE para identificação de cardiomegalia foi de 0,806 (IC 95%: 0,692-0,919). O ponto de corte ótimo para DDVE foi de 60 mm (sensibilidade = 64%, especificidade = 89%). O uso do DDVE pela ECO em substituição ao ICT pela RXT alterou o escore de Rassi em 14 pacientes, e em 10 deles houve redução do risco presumido. Conclusão DDVE pela ECO é parâmetro adequado e com alta especificidade para distinguir entre presença e ausência de cardiomegalia na RXT na DC. (Arq Bras Cardiol. 2021; 116(1):68-74)

Abstract Background Cardiomegaly on chest X-ray is an independent predictor of death in individuals with chronic Chagas cardiomyopathy (CCC). However, the correlation between increased cardiothoracic ratio (CTR) on chest X-ray and left ventricular end-diastolic diameter (LVEDD) on echocardiography is not well established in this population. Objectives To assess the relationship between chest X-ray and LVEDD on echocardiography in patients with Chagas disease and its applicability to the Rassi score. Methods Retrospective study on 63 Chagas disease outpatients who underwent chest X-ray and echocardiography. Cardiomegaly on chest X-ray was defined as a CTR>0.5. LVEDD was analyzed as a continuous variable. ROC curve was used to evaluate the ability of LVEDD in detecting cardiomegaly by chest X-ray, with a cut-off point defined by the highest sum of sensitivity and specificity. Results Median age 61 years [interquartile range 48-68], 56% were women. CCC was detected in 58 patients, five patients had the indeterminate form of Chagas disease. Cardiomegaly was detected in 28 patients. The area under the ROC curve for LVEDD was 0.806 (95%CI: 0.692-0.919). The optimal cut-off for LVEDD was 60 mm (sensitivity = 64%, specificity = 89%). The use of LVEDD on echocardiography as a surrogate for CTR on chest X-ray changed the Rassi score values of 14 patients, with a reduction in the presumed risk in 10 of them. Conclusion LVEDD on echocardiography is an appropriate, highly specific parameter to distinguish between the presence and absence of cardiomegaly on chest X-ray in Chagas disease. (Arq Bras Cardiol. 2021; 116(1):68-74)

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The objectives of this study were to extract and purify Bixin from the seeds of Bixa orellana and to evaluate its hypoglycemic activity in vivo, as well as, to conduct an in silico study of selectivity on peroxisome proliferator-activated receptors via molecular docking and molecular dynamics simulations. Oral administration of Bixin (10 mg/kg) significantly reduced their glucose level that was alloxan-induced diabetic rats. Bixin showed in silico selectivity on peroxisome proliferator-activated receptors (PPARs), particularly by the peroxisome proliferator-activated receptor gamma (PPARγ), which supports the hypoglycemic activity of Bixin. From the results obtained, it can be inferred that Bixin presents hypoglycemic characteristics, which was confirmed by the results obtained from the in vivo and in silico tests. Bixin may act by other pathways to control blood glucose and thus it is possible that it presents a different toxicity profile than troglitazone, rosiglitazone and pioglitazone. However, more studies on the activity and toxicity of Bixin are needed to evaluate for further clinical use. Communicated by Ramaswamy H. Sarma.

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Micafungin is characterized as one of the most active available drugs for candidemia treatment; however, their use is also associated in prophylaxis protocols in cases of invasive fungal infections. The use of this drug is widely appreciated in the medical field due to be the most active echinocandin available for invasive fungal infections. In order to provide important parameters related to the chemical, physical, biological and therapeutic characteristics, this review article gathers important research results that demonstrate the biological potential of this drug, as well as to present analytical methods that can be used to determine the antifungal potential and a monitoring of administered dosages. Important studies about the methods most commonly used in biological activity evaluation and determination/quantification by analytical methods are provided in this review article. With the data provided, the scientific community will have the possibility to choose the analytical methods and biological that can be employed in clinical and scientific research to provide greater safety and reliability of the results to be found.

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Metronidazole (MT) is an important drug available for Helicobacter pylori infection treatment. However, in the past few years, this drug has presented effective reduction for infection control, one of the most important reasons is attributed to the reduction of retention time in the stomach environment. Mucoadhesive nanostructured polyelectrolyte complexes (nano PECs) based on chitosan (CS) and hypromellose phthalate (HP) were rationally developed using a full factorial design (21 × 21 × 31), for the incorporation of MT based on the enhancement of the antimicrobial potential against active Helicobacter pylori, in the stomach. Different mass ratios of CS:HP (w/w) were tested, reaching the most promising ratios of 1:0.1, 1:0.5, and 1:1, and two methods of polymers addition (pouring-I and drip-II) were also evaluated. From method I, the obtained particles presented a diameter in the range of 811-1293 nm (Z-average) and a polydispersity index (PDI) between 0.47 and 0.88. By method II, there was a significant reduction in diameter and PDI to 553-739 nm and 0.23 at 0.34, respectively. The drug incorporation also resulted in a reduction in the diameter and PDI of the nano PECs. All samples showed positive zeta potential, about 20 mV, and a high percentage of MT incorporation (±95%). The method factor presented a greater influence on the nano PECs characteristics. Interactions in the system constituents were indicated by the FTIR data. Nano PECs mucoadhesiveness was observed and the composition and charge density were responsible for this phenomenon. MT dissolution evaluation showed the similarity of the dissolution profiles of free and loaded MT, in which almost 100% of the drug was in the simulated gastric medium in 120 min of testing. The in vitro antimicrobial potential against H. pylori of loaded nano PECs were measured and the minimum inhibitory concentration observed for free MT was >2000 µg/mL, while for the incorporated MT lower values were observed, showing an increase in the encapsulated MT activity.

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The crescent number of cases of candidiasis and the increase in the number of infections developed by non-albicans species and by multi-resistant strains has taken the attention of the scientific community, which has been searching for new therapeutic alternatives. Among the alternatives found the use of nanosystems for delivery of drugs already commercialized and new biomolecules have grown, in order to increase stability, solubility, optimize efficiency and reduce adverse effects. In view of the growing number of studies involving technological alternatives for the treatment of candidiasis, the present review came with the intention of gathering studies from the last two decades that used nanotechnology for the treatment of candidiasis, as well as analysing them critically and pointing out the future perspectives for their application with this purpose. Different studies were considered for the development of this review, addressing nanosystems such as metallic nanoparticles, mesoporous silica nanoparticles, polymeric nanoparticles, liposomes, nanoemulsion, microemulsion, solid lipid nanoparticle, nanostructured lipid carrier, lipidic nanocapsules and liquid crystals; and different clinical presentations of candidiasis. As a general overview, nanotechnology has proven to be an important ally for the treatment against the diversity of candidiasis found in the clinic, whether in increasing the effectiveness of commercialized drugs and reducing their adverse effects, as well as allowing exploring more effectively properties therapeutics of new biomolecules.

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BACKGROUND: Vaginal infections caused by non-albicans species have become common in women of all age groups. The resistance of species such as Candida parapsilosis to the various antifungal agents is a risk factor attributed to these types of infections, which instigates the search for new sources of active compounds in vulvovaginal candidiasis (VCC) therapy. OBJECTIVE: This study evaluated the antifungal activity of Syngonanthus nitens Bong. (Ruhland) derivatives and employed a lipid nanoemulsion as a delivery system.' METHODS: In this study, a lipid nanoemulsion was employed as a delivery system composed of Cholesterol (10%), soybean phosphatidylcholine: Brij 58 (1: 2) and PBS (pH 7.4) with the addition of 0.5% of a chitosan dispersion (80%), and evaluated the antifungal activity of S. nitens Bong. (Ruhland) derivatives against planktonic cells and biofilms of Candida parapsilosis. By a biomonitoring fractionation, the crude extract (EXT) and one fraction (F2) were selected and incorporated into a lipid nanoemulsion (NL) composed of cholesterol (10%), a 1:2 mixture of soybean phosphatidylcholine:polyoxyethylene -20- cetyl ether (10%), and phosphate buffer solution (pH 7.4) with a 0.5% chitosan dispersion (80%). The NL presented a diameter size between 50-200 nm, pseudoplastic behavior, and positive charge. The EXT and five fractions were active against planktonic cells. RESULTS AND DISCUSSION: The incorporation of EXT and F2 into the NL increased antifungal activity and enhanced the anti-biofilm potential. This study classified the use of an NL as an important tool for the administration of S. nitens derivatives in cases of infections caused by this C. parapsisilosis. CONCLUSION: This work concluded that S. nitens derivatives were important sources of active molecules against C. parapsilosis and the use of a lipid nanoemulsion was an important tool to promote more effective F2 release and to improve the antifungal activity aiming the control of C. parapsilosis infections.

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Metal nanoparticles are a promising approach for the development of new antimicrobial systems. Silver nanoparticles (AgNP) have a significant antibacterial activity through bacterial surface adsorption and oxidative stress induction, as indicated by recent observations. This research aimed to use endophytic fungi from the genus Trichoderma spp. isolated from the Bertholletia excelsa (Brazil-nut) seeds and the soil to biosynthesize AgNPs and also test their antibacterial activity. The use of these fungi for this purpose not only valorizes the Amazon biodiversity but it also uses cleaner and cheaper processes, being part of the Green Chemistry concept. The particles were analyzed through Ultraviolet-Visible Spectroscopy and ZetaSizer and the band of absorption at 420 nm was analyzed through Localized Surface Plasmon Resonance. After characterization, the AgNP were tested for antibacterial activity against several bacterial strains, when it was observed that their antibacterial activity was superior in Gram-negative bacteria.

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PURPOSE: Vulvovaginal candidiasis (VVC) is an opportunistic fungal infection that adversely affects a woman's health, due to unpleasant symptoms, therapeutic challenges, and the emergence of resistant strains. The association of natural products and nanotechnology is important to improve the antifungal potential of medicinal plants. We aimed to evaluate the in vitro and in vivo anti-Candida albicans activity of unloaded (EO) and loaded (ME+EO) essential oil of Cymbopogon nardus in the microemulsion (ME). METHODS: The chemical analysis of the EO was performed by gas chromatography-mass spectrometry. The ME and ME+EO were characterized by scattering, zeta potential, polarized light microscopy, rheological assays, mucoadhesiveness and transmission electronic microscopy. The in vitro antifungal activity of the EO and ME+EO were evaluated by microdilution technique. The toxicity of EO and ME+EO was analyzed on human cell line HaCat and using alternative model assay with Artemia salina. The experimental in vivo VVC was performed in female mice (C57BL/6). RESULTS: The main compounds of the EO were found to be citronellal, geranial, geraniol, citronellol, and neral. The formulations exhibited suitable size, homogeneity, negative charge, isotropic behavior, highly organized structure, and pseudoplastic behavior, for vaginal application. TEM photomicrographs showed possible EO droplets inside the spherical structures. The EO, when loaded into the ME, exhibited an improvement in its antifungal action against C. albicans. The EO was not toxic against brine shrimp nauplii. An in vivo VVC assay showed that the use of the ME significantly improved the action of the EO, since only the ME+EO promoted the eradication of the fungal vaginal infection on the third day of treatment. CONCLUSION: The EO and ME+EO are promising alternatives for the control of fungal infections caused by C. albicans, once the use of nanotechnology significantly improved the antifungal action of the EO, especially in an in vivo model of VVC.

Assuntos

RESUMO

We have previously reported on the activity of different extracts from Astronium sp. against Candida albicans, with the hydroethanolic extract prepared from leaves of A. urundeuva, an arboreal species widely distributed in arid environments of South America and often used in folk medicine, displaying the highest in vitro activity. Here we have further evaluated the antifungal activity of this extract against strains of C. albicans and C. glabrata, the two most common etiological agents of candidiasis. The extract was tested alone and loaded into a nanostructured lipid system (10% oil phase, 10% surfactant and 80% aqueous phase, 0.5% Poloxamer 407®). In vitro susceptibility assays demonstrated the antifungal activity of the free extract and the microemulsion against both Candida species, with increased activity against C. glabrata, including collection strains and clinical isolates displaying different levels of resistance against the most common clinically used antifungal drugs. Checkerboard results showed synergism when the free extract was combined with amphotericin B against C. albicans. Serial passage experiments confirmed development of resistance to fluconazole but not to the free extract upon prolonged exposure. Although preformed biofilms were intrinsically resistant to treatment with the extract, it was able to inhibit biofilm formation by C. albicans at concentrations comparable to those inhibiting planktonic growth. Cytotoxicity assays in different cell lines as well as an alternative model using Artemia salina L. confirmed a good safety profile of the both free and loaded extracts, and an in vivo assay demonstrated the efficacy of the free and loaded extracts when used topically in a rat model of vaginal candidiasis. Overall, these results reveal the promise of the A. urundeuva leaves extract to be further investigated and developed as an antifungal.

RESUMO

OBJECTIVE: Migraine is a common condition in the pediatric population and causes a significant impact on the quality of life. Atopic disorders are some of the migraine comorbidities. We hypothesized that allergic rhinitis could aggravate migraine in the pediatric population. METHODS: This cross-sectional study consecutively evaluated 90 pediatric outpatients (46 children 6-12 years of age; 44 adolescents up to 18 years of age) who sought medical assistance because of migraine at a general neurology clinic in Passo Fundo, RS, Brazil. They, and their parents, were given three questionnaires, to evaluate the diagnosis of current allergic rhinitis, allergic rhinoconjunctivitis and seasonal allergic rhinitis, as well as the disability caused by headache (ISAAC - International Study of Asthma and Allergies in Childhood; CARATkids - Control of Allergic Rhinitis and Asthma Test for Children; PedMIDAS - Pediatric Migraine Disability Assessment). The study was approved by the local ethics committee. RESULTS: According to the ISAAC questionnaire, children with current allergic rhinoconjunctivitis in the last year showed higher scores on the PedMIDAS than those patients without atopy (median and interquartile range 26 [10-58] vs. 5 [1-13], p = 0.008). A significant positive correlation of CARATkids scores with PedMIDAS scores was found (p = 0.007, rho = 0.39). After including other putative predictors of migraine disability (age, body mass index, time since onset of migraine) in a multiple regression analysis, only the scores on the CARATkids remained a significant independent variable correlated with PedMIDAS scores (p = 0.001; R = 0.55; R2 = 0.30). CONCLUSIONS: Current allergic rhinoconjunctivitis is related to enhanced disability caused by headache in childhood migraine.

Assuntos