Resumen Objetivos: Identificar las alteraciones histopatológicas en órganos de ratas Wistar para evaluar los efectos tóxicos del uso del Extracto de Hoja Cruda de Annona muricata (AMRLE) solo o en asociación con DMBA. Configuración y diseño: Se utilizaron sesenta ratas hembras Wistar, se separaron en grupos y se trataron con una dosis única de 65 mg/kg de DMBA y/o con 50, 100 y 200 mg/kg de AMRLE. Se utilizaron tinciones de hematoxilina-eosina (HE) y azul de metileno al 1% en el análisis histopatológico y la cuantificación de criptas aberrantes (CA) y focus de criptas aberrantes (FCA). En el análisis estadístico se utilizaron las pruebas de Fischer y Kruskal Wallis. Resultados: La administración de 65 mg/kg de DMBA y/o 50, 100 y 200 mg/kg de AMRLE no influyó en el desarrollo del peso. Se observaron algunas alteraciones histopatológicas (esteatosis hepática; focus inflamatórios en el hígado, riñón y pulmón; hiperplasia, ectasia en epitelio de la glándula mamaria e hiperplasia linfoide pulmonar) y el desarrollo de CA y FCA en el colon intestinal en todos los grupos, excepto en el grupo control negativo, sin diferencias estadísticas entre los grupos analizados. Conclusiones: Las alteraciones histopatológicas y la formación de CA y FCA no mostraron diferencias estadísticamente significativas entre los grupos analizados. Sin embargo, aunque AMRLE tiene efectos antioxidantes debido a la presencia de componentes fenólicos, aún existe la formación de algunos procesos patológicos que pueden estar relacionados con la acción tóxica aislada del DMBA y/o asociados con otros componentes de AMRLE, ya que estos cambios no fueron observados en el grupo control negativo.

Abstract Aims: To identify the histopathological alterations in organs of Wistar rats to evaluate toxic effects of use of Annonamuricata Raw Leaf Extract (AMRLE) alone or in association with DMBA. Settings and Design: Sixty female Wistar rats were used, separated into groups and treated with a single dose of 65 mg/kg of DMBA and/or with 50; 100 and 200 mg/kg of AMRLE. Hematoxylin-Eosin (HE) and 1% methylene blue stains were used in the histopathological analysis and quantification of Aberrant Crypts (ACs) and Aberrant Crypt Focus (ACF). Fischer and Kruskal Wallis tests were used in the statistical analysis. Results: The administration of 65 mg/kg of DMBA and/or 50, 100 and 200 mg/kg of AMRLE did not influence weight development. Some histopathological alterations (hepatic steatosis; inflammatory foci in the liver, kidney and lung; pulmonary lymphoid hyperplasia, ectasia and hyperplasia in mammary gland epithelium) and the development of ACs and ACF in the intestinal colon were observed in all groups, except in the group negative control, with no statistical difference between analysed groups. Conclusions: Histopathological alterations and the formation of ACs and ACF did not show a statistically significant difference between the groups analysed. However, although AMRLE has antioxidant effects due to the presence of phenolic components, there was still the formation of some pathological processes that may be related to the isolated toxic action of DMBA and/or associated with other components of AMRLE, since these changes were not seen in the negative control group.

RESUMO Objetivos: analisar as tendências da mortalidade por câncer colorretal em mulheres no Brasil, Estados e Regiões. Métodos: estudo ecológico, de séries temporais, com análise de tendência dos óbitos por câncer colorretal de mulheres, no período de 2008 a 2019. Para análise de tendência, foi utilizado o modelo de regressão polinomial. Resultados: analisaram-se 48.225 óbitos de mulheres por câncer colorretal. Houve tendência crescente da mortalidade em mulheres brasileiras, com diferenças regionais, em razão das desigualdades nos padrões socioeconômicos, políticos e culturais. Destacando um aumento na Região Sul, com as maiores taxas, de 7,32 em 2008 para 8,65 em 2019, seguida pela Região Sudeste, com taxas de mortalidade por câncer colorretal de 6,72 e 9,05 em 2008 e 2019, respectivamente. Conclusões: observa-se um aumento das taxas de mortalidade por câncer colorretal, demonstrando a necessidade do incremento das políticas públicas direcionadas às estratégias de rastreamento e diagnóstico precoce do câncer colorretal em mulheres.

ABSTRACT Objectives: to analyze colorectal cancer mortality trends in women in Brazil and its regions and states. Methods: ecological, time-series study with trend analysis of deaths caused by colorectal cancer in women in Brazil and its regions and states between 2008 and 2019. Polynomial regression was used to treat the data. Results: 48,225 deaths of women caused by colorectal cancer were examined. There was an increasing mortality trend in Brazilian women, with regional differences that resulted from socioeconomic, political, and cultural inequalities. The South Region stood out with the highest rate (7.32) in 2008, which increased to 8.65 in 2019, followed by the Southeast Region, whose rates were 6.72 and 9.05 in 2008 and 2019, respectively. Conclusions: colorectal cancer mortality increased, which indicates the need to expand public policies oriented toward screening and early diagnosis of colorectal cancer in women.

RESUMEN Objetivos: analizar las tendencias de mortalidad por cáncer colorrectal de mujeres en Brasil, Estados y Regiones. Métodos: estudio ecológico, de series temporales, con análisis de tendencia de decesos por cáncer colorrectal en mujeres, entre 2008 y 2019. Para análisis de tendencia se utilizó el modelo de regresión polinomial. Resultados: se analizaron 48.225 decesos de mujeres por cáncer colorrectal. Se observó tendencia creciente de mortalidad en las mujeres brasileñas, con diferencias regionales debidas a desigualdades de estándares socioeconómicos, políticos y culturales. Se manifiesta un aumento en la Región Sur, con tasa de 7,32 en 2008 incrementando a 8,65 en 2019, siguiéndole la Región Sudeste, con tasas de mortalidad de cáncer colorrectal de 6,72 y 9,05 en 2008 y 2019. Conclusiones: se observa aumento de tasas de mortalidad por cáncer colorrectal, demostrándose necesidad de incrementar las políticas públicas orientadas a estrategias de rastreo y diagnóstico precoz del cáncer colorrectal en mujeres.

The clinical manifestations and prognosis of cutaneous leishmaniasis (CL) can be influenced by the immune response of the patient and the species of the parasite. A case of atypical clinical presentation of CL, with development of non-characteristic lesions, poor response to therapy, and a long time to resolution is reported. Confirmatory laboratory tests included parasite detection, indirect immunofluorescence, Montenegro skin test, polymerase chain reaction, and parasite identification by multilocus enzyme electrophoresis. The parasite was identified as Leishmaniabraziliensis. The lesion was unresponsive to three complete courses of N-methylglucamine antimoniate intramuscular, and to treatment with pentamidine. The patient did not tolerate amphotericin B. The lesion finally receded after treatment with intravenous N-methylglucamine antimoniate. It is essential to ensure the accuracy of diagnosis and the appropriate treatment, which can include the use a second choice drug or a different route of administration.

The herbaceous shrub Tetradenia riparia has been traditionally used to treat inflammatory and infectious diseases. Recently, a study showed that T. riparia essential oil (TrEO) obtained in summer has antileishmanial effects, although these results could be influenced by seasonal variation. This study evaluated the activity of the TrEO obtained in different seasons against Leishmania (Leishmania) amazonensis, in vitro and in vivo. The compounds in the TrEO were analysed by gas chromatography-mass spectrometry; terpenoids were present and oxygenated sesquiterpenes were the majority compounds (55.28%). The cytotoxicity and nitric oxide (NO) production were also tested after TrEO treatment. The TrEO from all seasons showed a 50% growth inhibitory concentration for promastigotes of about 15 ng/mL; at 30 ng/mL and 3 ng/mL, the TrEO reduced intracellular amastigote infection, independently of season. The TrEO from plants harvested in summer had the highest 50% cytotoxic concentration, 1,476 ng/mL for J774.A1 macrophages, and in spring (90.94 ng/mL) for murine macrophages. NO production did not change in samples of the TrEO from different seasons. The antileishmanial effect in vivo consisted of a reduction of the parasite load in the spleen. These results suggest that the TrEO has potential effects on L. (L.) amazonensis, consonant with its traditional use to treat parasitic diseases.

Abstract:INTRODUCTION:The Montenegro skin test (MST) has good clinical applicability and low cost for the diagnosis of American tegumentary leishmaniasis (ATL). However, no studies have validated the reference value (5mm) typically used to discriminate positive and negative results. We investigated MST results and evaluated its performance using different cut-off points.METHODS:The results of laboratory tests for 4,256 patients with suspected ATL were analyzed, and 1,182 individuals were found to fulfill the established criteria. Two groups were formed. The positive cutaneous leishmaniasis (PCL) group included patients with skin lesions and positive direct search for parasites (DS) results. The negative cutaneous leishmaniasis (NCL) group included patients with skin lesions with evolution up to 2 months, negative DS results, and negative indirect immunofluorescence assay results who were residents of urban areas that were reported to be probable sites of infection at domiciles and peridomiciles.RESULTS:The PCL and NCL groups included 769 and 413 individuals, respectively. The mean ± standard deviation MST in the PCL group was 12.62 ± 5.91mm [95% confidence interval (CI): 12.20-13.04], and that in the NCL group was 1.43 ± 2.17mm (95% CI: 1.23-1.63). Receiver-operating characteristic curve analysis indicated 97.4% sensitivity and 93.9% specificity for a cut-off of 5mm and 95.8% sensitivity and 97.1% specificity for a cut-off of 6mm.CONCLUSIONS:Either 5mm or 6mm could be used as the cut-off value for diagnosing ATL, as both values had high sensitivity and specificity.