Morphological variations on vital systems in a conjoined twin.

Conjoined twins (CTs), popularly referred to as Siamese twins, are a rare anomaly due to monochorionic and monoamniotic twin pregnancies. Dicephalus dibrachius dipus, a type of parapagus conjoined twin which is characterized by possessing two arms, two legs, a single trunk and two heads, epidemiologically, is an even rarer occurrence of CTs. In this article, a rare, well-preserved anatomical specimen of a dicephalus dibrachius dipus conjoined twin is presented. This study was conducted in a specimen which is part of the collection of the Embryology Museum of the institution by donation and approved by the Research Ethics Committee (REC). The female conjoined twins were born at full-term by cesarean section in the 1970s and died hours after birth. A thorough anatomical description was made through observational analysis, computed tomography and 3D reconstructed images. Major abnormalities were observed in the cardiovascular, respiratory and digestive systems. The internal anatomy exhibited a heart with three atria, two ventricles, two aortic arches, two pulmonary arteries, one innominate venous trunk and a respiratory system with two tracheas and four lungs. No other report was similar to our three atria heart description. This article provides a thorough anatomical description of all systems, which is valuable information for further studies on CTs.

Efeitos anti-inflamatórios do extrato alcoólico de folhas de garcinia gardneriana na peritonite induzida por lipopolissacarídeo / Anti-inflammatory effects of garcinia gardneriana leaf extract on lipopolysaccharideinduced peritonitis

Introdução: A Garcinia gardneriana é utilizada na medicina tradicional brasileira para o tratamento de tumores, inflamações e alívio de dores, mas as informações científicas são ainda limitadas. Objetivos: Diante do uso popular e o anseio por efeitos colaterais mínimos, o objetivo geral deste estudo foi avaliar as propriedades anti-inflamatórias da G. gardneriana em modelo de peritonite induzido por lipopolissacarideo (LPS). Métodos: Ratos Wistar foram divididos aleatoriamente em 3 grupos (n= 5/ grupo): controle, induzido à peritonite e não tratado e induzido à peritonite e tratado com extrato de folhas alcoólico de G. gardneriana a 4%. A peritonite foi induzida por única injeção intraperitoneal de LPS (1 mg/kg). O tratamento com o extrato foi realizado por gavagem (1 ml), administrado antes e 12h após a injeção do LPS. Os ratos foram eutanasiados após 24h da indução de peritonite. Amostras de sangue foram coletadas para análise plasmática de histamina, o lavado intraperitoneal para quantificação de neutrófilos e o intestino delgado para processamento histológico, quantificação de mastócitos e imuno-histoquímica da expressão da proteína Anexina A1 (AnxA1). Resultados: As análises quantitativas indicaram os efeitos anti-inflamatórios do extrato, pela redução do recrutamento de neutrófilos para a cavidade peritoneal e a diminuição da quantidade de mastócitos na lâmina própria do intestino delgado, comparadas aos animais não tratados. Não houve diferença estatística dos níveis de histamina. A imuno-histoquímica indicou diminuição acentuada da expressão da AnxA1 na mucosa intestinal dos animais tratados. Conclusão: Nossos dados demonstraram que o extrato alcoólico de G. gardneriana tem forte ação anti-inflamatória e potencial terapêutico para o desenvolvimento de fitoterápicos com propriedades anti-inflamatórias

Introduction: Garcinia gardneriana is used in traditional Brazilian medicine for the treatment of tumors, inflammation and relief of pain, but scientific information is still limited. Objective: In the face of popular use and the desire for minimal side effects, the general objective of this study was to evaluate the anti-inflammatory properties of G. gardneriana in a model of lipopolysaccharide-induced peritonitis (LPS). Methods: Wistar rats were randomly divided into 3 groups (n = 5 / group): control, induced to peritonitis and untreated and induced to peritonitis and treated with 4% alcoholic extract of G. gardneriana leaves. Peritonitis was induced by single intraperitoneal injection of LPS (1 mg/kg). Treatment with the extract was performed by gavage (1 ml), given before and 12h after LPS injection. The rats were euthanized 24h after the peritonitis induction. Blood samples were collected for plasma analysis of histamine, intraperitoneal lavage for quantification of neutrophils and the small intestine for histological processing for quantification of mast cells, and immunohistochemical analysis of the expression of Annexin A1 (AnxA1) protein. Results: Quantification analyses indicated the anti-inflammatory effects of the extract by reducing the recruitment of neutrophils into the peritoneal cavity and reducing the amount of mast cells in the lamina propria of the small intestine compared to the untreated animals. There was no statistical difference in the levels of histamine. Immunohistochemical studies indicated a marked decrease of the AnxA1 expression in the intestinal mucosa of the treated animals. Conclusion: Our data demonstrated that the alcoholic extract of G. gardneriana has a strong anti-inflammatory action and therapeutic potential for the development of herbal products with anti-inflammatory properties

Introducción: Garcinia gardneriana se utiliza en la medicina tradicional brasileña para el tratamiento de tumores, inflamaciones y alivio del dolor, pero la información científica aún es limitada. Objetivo: Frente al uso popular y la búsqueda de efectos secundarios mínimos, lo objetivo general de este estudio fue evaluar las propiedades antiinflamatorias de G. gardneriana en un modelo de peritonitis inducido por lipopolisacárido (LPS). Métodos: Se dividieron aleatoriamente ratas Wistar en 3 grupos (n= 5/grupo): control, inducido a peritonitis y no tratado, e inducido a peritonitis y tratado con extracto alcohólico de hojas de G. gardneriana al 4%. La peritonitis fue inducida por una única inyección intraperitoneal de LPS (1 mg/kg). El tratamiento con el extracto se realizó por gavaje (1 ml), administrado antes y 12 horas después de la inyección de LPS. Las ratas fueron sacrificadas después de 24 horas de la inducción de peritonitis. Se recopilaron muestras de sangre para el análisis plasmático de histamina, el lavado intraperitoneal para la cuantificación de neutrófilos y el intestino delgado para el procesamiento histológico, la cuantificación de mastocitos y la inmunohistoquímica de la expresión de la proteína Anexina A1 (AnxA1). Resultados: Los análisis cuantitativos indicaron los efectos antiinflamatorios del extracto, mediante la reducción del reclutamiento de neutrófilos en la cavidad peritoneal y la disminución de la cantidad de mastocitos en la lámina propia del intestino delgado, en comparación con los animales no tratados. No hubo diferencia estadística en los niveles de histamina. La inmunohistoquímica indicó una disminución pronunciada de la expresión de AnxA1 en la mucosa intestinal de los animales tratados. Conclusión: Nuestros datos demostraron que el extracto alcohólico de G. gardneriana tiene una fuerte acción antiinflamatoria y potencial terapéutico para el desarrollo de fitoterapéuticos con propiedades antiinflamatorias.

Cytotoxicity and Genotoxicity Evaluation of Zanthoxylum rhoifolium Lam and In Silico Studies of Its Alkaloids.

The alkaloids isolated from Zanthoxylum rhoifolium have demonstrated great pharmacological potential; however, the toxic profiles of these extracts and fractions are still not well elucidated. This study evaluated the toxicity of the ethanol extract (EEZR) and neutral (FNZR) and alkaloid (FAZR) fractions. Chemical characterization was performed by chromatographic methods: thin-layer chromatography (TLC) and high-performance liquid chromatography coupled with diode array detection (HPLC-DAD). The cytotoxicity of the samples was evaluated in human hepatocellular carcinoma (HepG2) cells using the cell viability method (MTT) and mutagenicity by the Allium cepa assay (ACA). Alkaloids isolated from the species were selected for toxicity prediction using preADMET and PROTOX. The molecular docking of the topoisomerase II protein (TOPOII) was used to investigate the mechanism of cell damage. In the EEZR, FNZR, and FAZR, the presence of alkaloids was detected in TCL and HPLC-DAD analyses. These samples showed a 50% inhibitory concentration (IC50) greater than 400 µg/mL in HepG2 cells. In ACA, time- and concentration-dependent changes were observed, with a significant reduction in the mitotic index and an increase in chromosomal aberrations for all samples. Nuclear sprouts and a micronucleus of the positive control (PC) were observed at 10 µg/mL and in the FAZR at 30 µg/mL; a chromosomal bridge in FNZR was observed at 105 µg/mL, CP at a concentration of 40 µg/mL, and nuclear bud and mitotic abnormalities in the EEZR were observed at 170 µg/mL. The alkaloids with a benzophenanthridine were selected for the in silico study, as structural alterations demonstrated certain toxic effects. Molecular docking with topo II demonstrated that all alkaloids bind to the protein. In summary, the fractionation of Z. rhoifolium did not interfere with toxicity; it seems that alkaloids with a benzophenanthridine nucleus may be involved in this toxicity.

Tendência temporal dos homicídios de mulheres nos estados da região Sudeste do Brasil, de 2007 a 2019 / Timeline trend of homicides of women in the states of the Southeast region of Brazil between 2007 and 2019

Resumo O objetivo deste artigo é analisar a tendência temporal de homicídios de mulheres no período de 2007 a 2019, na região Sudeste do Brasil. Trata-se de um estudo ecológico misto dos homicídios em mulheres, de 2007 a 2019, considerando-se como unidade de análise os anos do estudo e os estados que compõem a região Sudeste. Os dados foram obtidos via Sistema de Informação sobre Mortalidade (SIM) e tabulados pelo TABNET. Empregou-se o modelo de regressão de Prais-Winsten para verificação de tendência de homicídios. Foram registrados 18.415 homicídios de mulheres entre 2007 e 2019 na região Sudeste. Cerca de 9.691 (53,64%) eram mulheres pretas, 5.118 (27,80%) com escolaridade de 4 a 7 anos e 10.841 (58,87%) solteiras. As variações percentuais anuais foram: São Paulo -3,73; IC95% [-6,09; -1,32], Espírito Santo -5,67; IC95% [-7,11; -4,21], Rio de Janeiro -3,86; IC95% [-9,54; 2,17] e Minas Gerais -2,11; IC95% [-4,87; 0,73]. São Paulo e Espírito Santo apresentaram taxas de homicídios de mulheres decrescentes, enquanto Minas Gerais e Rio de Janeiro taxas estacionárias. As maiores taxas de homicídio no período ocorreram em mulheres solteiras, pretas e com escolaridade de quatro a sete anos. Faz-se necessária a construção de redes sociais que viabilizem a proteção integral das mulheres.

Abstract The scope of this article is to analyze the timeline trend of homicides of women between 2007 and 2019, in the Southeast region of Brazil. It is a mixed ecological study of homicides in women, from 2007 to 2019, considering the years of the study and the states that that make up the Southeast region as the unit of analysis. The data were obtained via the Mortality Information System (SIM) and tabulated by TABNET. The Prais-Winten regression model was used to verify the homicide trend. There were 18,415 homicides of women between 2007 and 2019 in the Southeast region. A total of 9,691 (53.64%) were black women, 5,118 (27.8%) had 4 to 7 years of schooling and 10,841 (58.87%) were single. The annual percentage variations were: São Paulo -3.73 ; 95%CI [-6.09; -1.32], Espírito Santo -5.67 ; 95%CI [-7.11;-4.21], Rio de Janeiro -3.86; 95%CI [-9.54; 2.17] and Minas Gerais -2.11 ; 95%CI [-4.87; 0.73]. São Paulo and Espírito Santo presented decreasing homicide rates for women, while Minas Gerais and Rio de Janeiro showed stationary rates. The highest homicide rates in the period were single women, black women and women with 4 to 7 years of schooling. It is necessary to build social networks that ensure the full protection of women.

[Timeline trend of homicides of women in the states of the Southeast region of Brazil between 2007 and 2019]. / Tendência temporal dos homicídios de mulheres nos estados da região Sudeste do Brasil, de 2007 a 2019.

The scope of this article is to analyze the timeline trend of homicides of women between 2007 and 2019, in the Southeast region of Brazil. It is a mixed ecological study of homicides in women, from 2007 to 2019, considering the years of the study and the states that that make up the Southeast region as the unit of analysis. The data were obtained via the Mortality Information System (SIM) and tabulated by TABNET. The Prais-Winten regression model was used to verify the homicide trend. There were 18,415 homicides of women between 2007 and 2019 in the Southeast region. A total of 9,691 (53.64%) were black women, 5,118 (27.8%) had 4 to 7 years of schooling and 10,841 (58.87%) were single. The annual percentage variations were: São Paulo -3.73 ; 95%CI [-6.09; -1.32], Espírito Santo -5.67 ; 95%CI [-7.11;-4.21], Rio de Janeiro -3.86; 95%CI [-9.54; 2.17] and Minas Gerais -2.11 ; 95%CI [-4.87; 0.73]. São Paulo and Espírito Santo presented decreasing homicide rates for women, while Minas Gerais and Rio de Janeiro showed stationary rates. The highest homicide rates in the period were single women, black women and women with 4 to 7 years of schooling. It is necessary to build social networks that ensure the full protection of women.

O objetivo deste artigo é analisar a tendência temporal de homicídios de mulheres no período de 2007 a 2019, na região Sudeste do Brasil. Trata-se de um estudo ecológico misto dos homicídios em mulheres, de 2007 a 2019, considerando-se como unidade de análise os anos do estudo e os estados que compõem a região Sudeste. Os dados foram obtidos via Sistema de Informação sobre Mortalidade (SIM) e tabulados pelo TABNET. Empregou-se o modelo de regressão de Prais-Winsten para verificação de tendência de homicídios. Foram registrados 18.415 homicídios de mulheres entre 2007 e 2019 na região Sudeste. Cerca de 9.691 (53,64%) eram mulheres pretas, 5.118 (27,80%) com escolaridade de 4 a 7 anos e 10.841 (58,87%) solteiras. As variações percentuais anuais foram: São Paulo -3,73; IC95% [-6,09; -1,32], Espírito Santo -5,67; IC95% [-7,11; -4,21], Rio de Janeiro -3,86; IC95% [-9,54; 2,17] e Minas Gerais -2,11; IC95% [-4,87; 0,73]. São Paulo e Espírito Santo apresentaram taxas de homicídios de mulheres decrescentes, enquanto Minas Gerais e Rio de Janeiro taxas estacionárias. As maiores taxas de homicídio no período ocorreram em mulheres solteiras, pretas e com escolaridade de quatro a sete anos. Faz-se necessária a construção de redes sociais que viabilizem a proteção integral das mulheres.

Perfil imuno-histoquímico dos casos de carcinomas mamários da microrregião de catanduva-sp / Immunohistochemical profile of breast carcinoma cases from the microregion of catanduva-sp / Perfil inmunohistoquímico de los casos de carcinomas de mama en la microrregión de catanduva-sp

Introdução: O câncer de mama compreende a principal neoplasia maligna que acomete as mulheres brasileiras, com destaque nos índices de mortalidade. O diagnóstico precoce é preconizado através da mamografia, a qual, quando alterada, sugere realizar biópsia para estudo histopatológico e, caso confirmado um carcinoma mamário, acrescenta-se o estudo imuno-histoquímico para determinação de fatores prognósticos e preditivos para o tumor. Objetivos: Levantar os resultados de análise imuno-histoquímica dos carcinomas mamários diagnosticados pelo Serviço de Patologia do Hospital Emílio Carlos (Catanduva-SP) e estabelecer os principais subtipos moleculares do câncer de mama encontrados nessa população. Material e Método: O estudo foi transversal e retrospectivo, a partir dos relatórios de imunohistoquímica dos carcinomas. Foram relatados idade, sexo, subtipo histológico do tumor e positividade imunohistoquímica para receptor de estrogênio, receptor de progesterona, fator de crescimento epidérmico humano 2, índice de proliferação celular e E-caderina. Os casos foram classificados conforme os critérios estabelecidos pelo Consenso de St. Gallen e os dados apresentados por meio de gráficos e tabelas. Resultados: A amostra foi constituída por n=210 casos de carcinomas mamários, com idade média de 58 anos e predominantemente do sexo feminino. O tipo histológico predominante foi o carcinoma mamário invasivo do tipo não especial. A expressão de receptor de estrogênio ocorreu em 92,86%, progesterona 80,48%, HER2 32,38% e Ki67 alto em 70%. O principal subtipo molecular foi o luminal B. Conclusão: Os casos de carcinomas mamários da microrregião de Catanduva apresentam diferenças quando comparados com estudos nacionais, porém similares a outros de caráter regional

Introduction: Breast cancer is the main malignant neoplasm that affects Brazilian women, especially in mortality rates. Early diagnosis is recommended through mammography, which, when altered, suggests biopsy for histopathological study and, if a breast carcinoma is confirmed, the immunohistochemical study is added for determination of prognostic and predictive factors for the tumor. Objectives: To survey the results of immunohistochemical analysis of breast carcinomas diagnosed by the Pathology Service of Hospital Emílio Carlos (Catanduva-SP) and to establish the main molecular subtypes of breast cancer found in this population. Material and Method: The study was cross-sectional and retrospective, from the reports of immunohistochemistry of carcinomas (CEP/UNIFIPA number 4737142). Age, sex, histological subtype of the tumor and immunohistochemical positivity for estrogen receptor, progesterone receptor, human epidermal growth factor 2, cell proliferation index and E-cadherin were reported. The cases were classified according to the criteria established by the St. Gallen Consensus and the data presented by means of graphs and tables. Results: The sample consisted of n=210 cases of breast carcinomas, with a mean age of 58 years and predominantly female. The predominant histological type was invasive breast carcinoma of the non-special type. Estrogen receptor expression occurred in 92.86%, progesterone 80.48%, HER2 32.38% and high Ki67 in 70%. The main molecular subtype was luminal B. Conclusion: The cases of breast carcinomas in the microregion of Catanduva present differences when compared to national studies, but similar to other regional studies

Introduction: Breast cancer comprises the main malignant neoplasm that affects Brazilian women, especially in mortality rates. Early diagnosis is recommended through mammography, which, when altered, suggests biopsy for histopathological study and, if confirmed a breast carcinoma, the immuno-study is addedto determine prognostic and predictive factors for the tumor. Objectives: To collect the results of immunohistochemical analysis of breast carcinomas diagnosed by the Pathology Service of the Emílio Carlos Hospital (Catanduva-SP) and to establish the main molecular subtypes of breast cancer found in this population. Methods: The study was cross-sectional and retrospective, from the reports of immunohistochemistry of carcinomas. Age, sex, tumor histological subtype and immunohistochemical positivity for estrogen receptor, progesterone receptor, human epidermal growth factor 2, cell proliferation index and E-cadherin were reported. The cases were classified according to the criteria established by the St. Gallen Consensus and the data presented through graphs and tables. Results: The sample consisted of n = 210 cases of breast carcinomas, with a mean age of 58 years and predominantly female. The predominant histological type was nonspecial invasive breast carcinoma. The expression of estrogen receptor occurred in 92.86%, progesterone 80.48%, HER2 32.38% and Ki67 high in 70%. The main molecular subtype was luminal B. Conclusion: The cases of breast carcinomas in the Catanduva microregion show differences when compared to national studies, but similar to others of regional character

Evaluation of the healing properties of Garcinia brasiliensis extracts in a cutaneous wound model.

ETHNOPHARMACOLOGICAL RELEVANCE: Wound healing is a complex process that can leave pathological scars, especially in case of infections from opportunistic microorganisms. In this context, herbal medicines open up great possibilities for investigation. One of the species of interest native to Brazil is Garcinia brasiliensis ("bacupari"). Traditionally known for treating wounds and ulcers, G. brasiliensis presents anti-inflammatory, antioxidant and antimicrobials properties. But, its wound healing profile in experimental models, in order to validate its efficacy, is still litle studied. AIM OF THE STUDY: Thus, the objective of this work was to evaluate, in an infected cutanous wound model, the potential of formulations incorporated with G. brasiliensis leaves extracts. MATERIALS AND METHODS: Crude extract (CE), Ethyl Acetate Fraction (EAF) and Hexanic Fraction (HF) were submitted to phytochemical assays, high performance thin layer chromatography (HTPLC) and cytotoxicity studies. CE and EAF were also tested for microbicidal properties and incorporated in cream and gel formulations at 10% concentration. After stability testing, the gel formulations with CE or EAF at 10% were selected and applied to skin wounds infected or not with Staphylococcus aureus in Wistar rats. The healing potenttial of the extracts was verified by the expression of the protein Annexin A1 (AnxA1), related to the processes of inflammation and antifibrotic function, the cells immunostaining for Gasdermin-D (GSDM-D), a marker of pyroptotic cell death, and the dosage of interleukin-10 (IL-10) and monocyte chemotactic protein (MCP)-1 inflammatory mediators. RESULTS: Phytochemical studies indicated the presence of compounds of pharmacological interest, including Catechin, Quercetin and Berberine in addition to low cytotoxicity of CE and EAF at 10%. After the 6-day topical treatments, CE and EAF gel formulations demonstrated to control the pruritus formation process. The treatments decreased AnxA1 expression and the amount of cells immunostained for GSDM-D, and increased the expression of MCP-1 in infected wounds. CONCLUSIONS: Together, the results show important anti-inflammatory profile and skin healing potential of CE and EAF from G. brasiliensis leaves, even in infected lesions, with therapeutic perspectives.

Caracterização anatomopatológica de leiomiossarcomas uterinos da microrregião de Catanduva-SP / Anatomopathological aspects of uterine leimyosarcomas from the microregion of Catanduva-SP / Caracterización anatomopatológica de los leiomiosarcomas uterinos de la microrregión de Catanduva-SP

Introdução: O leiomiossarcoma é uma neoplasia maligna rara que afeta o corpo uterino. O diagnóstico definitivo ocorre por meio do exame histopatológico, que revela sua histogênese mesenquimal, a qual pode ser validada por marcadores imuno-histoquímicos de musculatura lisa ou do ciclo celular. Objetivos: Levantar a incidência de leiomiossarcomas uterinos diagnosticados pelo Serviço de Patologia do Hospital Emílio Carlos, Catanduva-SP, e descrever as variáveis anatomopatológicas de cada um deles. Material e Método: Foram avaliados os casos de leiomiossarcomas uterinos no período de janeiro de 2018 a agosto de 2021 a partir dos relatórios de exames anatomopatológicos. As variáveis relatadas envolveram idade, tamanho da lesão, grau de diferenciação, invasão linfovascular ou perineural e positividade para marcadores imuno-histoquímicos. Resultados: Encontrou-se 01 caso de leiomiossarcoma, medindo 6,5 cm, grau de diferenciação moderado, 20 mitoses para cada 10 campos de grande aumento e ausência de invasão em vasos e filetes nervosos. A imunomarcação ocorreu para actina de músculo liso, caldesmon, desmina e p16. O índice de proliferação celular medido pelo Ki67 foi alto (>25%). Conclusão: O leiomiossarcoma, embora raro, envolve uma análise criteriosa para sua diferenciação de neoplasias benignas, sendo o exame histopatológico, complementado pela imuno-histoquímica, fundamental nessa etapa. (AU)

Introduction: Leiomyosarcoma is a rare malignant neoplasm that affects the uterine body. The definitive diagnosis occurs through histopathological examination, which reveals its mesenchymal histogenesis, which can be validated by immunohistochemical markers of smooth muscle or cell cycle. Objectives: To raise the incidence of uterine leiomyosarcomas diagnosed by the Pathology Service of the Emílio Carlos Hospital, Catanduva-SP, and describe the anatomopathological variables of each of them. Material and Method: Cases of uterine leiomyosarcomas were evaluated from January 2018 to August 2021 from the reports of anatomopathological examinations. The variables reported involved age, lesion size, degree of differentiation, lymphovascular or perineural invasion and positivity for immunohistochemical markers. Results: One case of leiomyosarcoma was found, measuring 6.5 cm, moderate degree of differentiation, 20 mitoses for every 10 fields of great increase and absence of invasion in vessels and nerve fillets. Immunostaining occurred for smooth muscle actin, caldesmon, desmin and P16. The rate of cell proliferation measured by Ki67 was high (>25%). Conclusion: The leiomyosarcoma, although rare, involves a careful analysis for its differentiation from benign neoplasms, and the histopathological examination, complemented by immunohistochemistry, is fundamental in this stage.(AU)

Introducción: El leiomiosarcoma es una neoplasia maligna rara que afecta al cuerpo uterino. El diagnóstico definitivo se realiza mediante el examen histopatológico, que revela su histogénesis mesenquimal, que puede ser validada por marcadores inmunohistoquímicos de la musculatura lisa o del ciclo celular. Objetivos: Levantar la probabilidad de leiomiosarcomas uterinos diagnosticados por el Servicio de Patología del Hospital Emílio Carlos, Catanduva-SP, y describir las variables anatomopatológicas de cada uno de ellos. Material y Método: Se evaluaron los casos de leiomiosarcomas uterinos en el período comprendido entre enero de 2018 y agosto de 2021 a partir de los info rmes de examen anatomopatológico. Las variables reportadas fueron la edad, el tamaño de la lesión, el grado de diferenciación, la invasión linfovascular o perineural y la positividad de los marcadores inmunohistoquímicos. Resultados: Encontramos 01 caso de leiomiosarcoma, con un tamaño de 6,5 cm, un grado de diferencia moderado, 20 mitosis por cada 10 campos de gran aumento y ausencia de invasión en vasos y filetes nerviosos. La inmunomarcación se dio para la actina del músculo liso, el caldesmón, la desmina y la p16...(AU)

Annexin A1 Mimetic Peptide and Piperlongumine: Anti-Inflammatory Profiles in Endotoxin-Induced Uveitis.

Uveitis is one of the main causes of blindness worldwide, and therapeutic alternatives are worthy of study. We investigated the effects of piperlongumine (PL) and/or annexin A1 (AnxA1) mimetic peptide Ac2-26 on endotoxin-induced uveitis (EIU). Rats were inoculated with lipopolysaccharide (LPS) and intraperitoneally treated with Ac2-26 (200 µg), PL (200 and 400 µg), or Ac2-26 + PL after 15 min. Then, 24 h after LPS inoculation, leukocytes in aqueous humor, mononuclear cells, AnxA1, formyl peptide receptor (fpr)1, fpr2, and cyclooxygenase (COX)-2 were evaluated in the ocular tissues, along with inflammatory mediators in the blood and macerated supernatant. Decreased leukocyte influx, levels of inflammatory mediators, and COX-2 expression confirmed the anti-inflammatory actions of the peptide and pointed to the protective effects of PL at higher dosage. However, when PL and Ac2-26 were administered in combination, the inflammatory potential was lost. AnxA1 expression was elevated among groups treated with PL or Ac2-26 + PL but reduced after treatment with Ac2-26. Fpr2 expression was increased only in untreated EIU and Ac2-26 groups. The interaction between Ac2-26 and PL negatively affected the anti-inflammatory action of Ac2-26 or PL. We emphasize that the anti-inflammatory effects of PL can be used as a therapeutic strategy to protect against uveitis.

Protective effects of piperlongumin in the prevention of inflammatory damage caused by pulmonary exposure to benzopyrene carcinogen.

Benzopyrene is one of the main polycyclic aromatic hydrocarbons with carcinogenic capacity. Research has shown that anti-inflammatory drugs can reduce the incidence of lung cancer. In this scenario, we highlight piperlongumin (PL), an alkaloid from Piper longum with anti-inflammatory properties. Therefore, our aim was to study the effect of PL administration in a model of pulmonary carcinogenesis induced by benzopyrene in Balb/c mice. Animals were divided into 3 groups (n = 10/group): sham (10% DMSO), induced by benzopyrene (100 mg/kg, diluted in DMSO) without treatment (BaP) for 12 weeks and induced by benzopyrene and treated with PL (BaP/PL) (2 mg/kg in 10% DMSO) from the eighth week post-induction. Animals were weighed daily and pletsmography was performed in the 12th week. Genotoxicity and hemoglobin levels were analyzed in blood and quantification of leukocytes in bronchoalveolar lavage (BAL). Lungs were collected for histopathological evaluation, immunohistochemical studies of annexin A1 (AnxA1), cyclooxygenase 2 (COX-2), anti-apoptotic protein Bcl-2 and nuclear transcription factor (NF-kB) and also the measurement of interleukin cytokines (IL)-1ß, IL-17 and tumor necrosis factor (TNF) -α. Treatment with PL reduced the pulmonary parameters (p < 0,001) of frequency, volume and pulmonary ventilation, decreased lymphocytes, monocytes and neutrophils in BAL (p < 0,05) as well as blood hemoglobin levels (p < 0,01). PL administration also reduced DNA damage and preserved the pulmonary architecture compared to the BaP group. Moreover, the anti-inflammatory effect of PL was evidenced by the maintenance of AnxA1 levels, reduction of COX-2 (p < 0,05), Bcl-2 (p < 0,01) and NF-kB (p < 0,001) expressions and decreased IL-1ß, IL-17 (p < 0,01) and TNF-α (p < 0,05) levels. The results show the therapeutic potential of PL in the treatment of pulmonary anti-inflammatory and anti-tumor diseases with promising therapeutic implications.

Historicity of nursing graduate studies in Brazil: an analysis of the Sociology of the Professions.

OBJECTIVES: to analyze the scientific productions about the history of graduate studies in Brazilian nursing in the light of Eliot Freidson's Sociology of the Professions. METHODS: an integrative review, carried out in the databases indexed in Virtual Health Library. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations were followed. Thematic content analysis and Eliot Freidson's concepts were adopted. RESULTS: two categories emerged: "Institutionalization of graduate courses in Brazilian nursing", highlighting the historical process of professionalization in nursing through transition from empirical to professional care, subsidized by the monopoly of the construction of one's own knowledge; "The scientific production of graduate nursing in Brazil", showing the strengthening of a new generation of nurse researchers, given the greater scientificity in teaching due to implementation of graduate studies. FINAL CONSIDERATIONS: the analyzes present the historicity of graduate studies' institutionalization, supporting the understanding of professionalization outlines of Brazilian nursing.

The link between pharmaceuticals and cyanobacteria: a review regarding ecotoxicological, ecological, and sanitary aspects.

Cyanobacteria are important for ecosystem functioning, but eutrophication may affect the surrounding biome by losing ecosystem services and/or through affecting the cyanotoxins production that threatens ecological and human health. Pollution is an environmental issue that affects aquatic ecosystems worldwide, and the knowledge of the role of synthetic chemicals such as pharmaceuticals is still scarce. Therefore, studies coupling these two relevant issues are essential to better understand the ecological risks and the potential threats to public health. Thus, an overview of ecotoxicological tests performed in the literature exposing cyanobacteria to pharmaceuticals and the possible consequences regarding ecological and sanitary aspects was conducted. Moreover, a risk assessment was performed to enable a better understanding of pharmaceuticals affecting cyanobacteria ecology. Most of the studies found in the literature tested isolated pharmaceuticals in laboratory conditions, while others assessed mixture effects on in situ conditions. The endpoints most assessed were growth, photosynthesis, and antioxidant enzyme activity. The studies also point out that cyanobacteria may present resistance or sensitivity depending on the concentrations and the therapeutic class, which may cause a change in the ecosystem dynamics and/or sanitary implications due to cyanotoxin production. The risk assessment highlighted that antibiotics are among the most relevant substances due to the chemical diversity and higher levels found in the environment than other therapeutic classes. This review highlighted gaps regarding cyanotoxin release into aquatic environments due to the occurrence of pharmaceuticals and the need for more realistic experiments to better understand the potential consequences for human and environmental health.

Historicity of nursing graduate studies in Brazil: an analysis of the Sociology of the Professions / Historicidad de los estudios de posgrado en enfermería en Brasil: un análisis de la sociología de las profesiones / Historicidade da pós-graduação em enfermagem no Brasil: uma análise da sociologia das profissões

ABSTRACT Objectives: to analyze the scientific productions about the history of graduate studies in Brazilian nursing in the light of Eliot Freidson's Sociology of the Professions. Methods: an integrative review, carried out in the databases indexed in Virtual Health Library. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations were followed. Thematic content analysis and Eliot Freidson's concepts were adopted. Results: two categories emerged: "Institutionalization of graduate courses in Brazilian nursing", highlighting the historical process of professionalization in nursing through transition from empirical to professional care, subsidized by the monopoly of the construction of one's own knowledge; "The scientific production of graduate nursing in Brazil", showing the strengthening of a new generation of nurse researchers, given the greater scientificity in teaching due to implementation of graduate studies. Final Considerations: the analyzes present the historicity of graduate studies' institutionalization, supporting the understanding of professionalization outlines of Brazilian nursing.

RESUMEN Objetivos: analizar las producciones científicas sobre la historia de los estudios de posgrado en enfermería brasileña a la luz de la Sociología de las Profesiones de Eliot Freidson. Métodos: revisión integradora, realizada en las bases de datos indexadas en la Biblioteca Virtual en Salud, se siguieron las recomendaciones del Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Se adoptaron el análisis de contenido temático y los conceptos de Eliot Freidson. Resultados: se enumeraron dos categorías: "Institucionalización de los posgrados en enfermería brasileña", destacando el proceso histórico de profesionalización de la enfermería a través de la transición del cuidado empírico al profesional, subsidiado por el monopolio de la construcción del conocimiento propio; "La producción científica de la enfermería graduada en Brasil", mostrando el fortalecimiento de la nueva generación de enfermeras investigadoras en el país, dada la mayor cientificidad en la docencia debido a la implementación de estudios de posgrado. Consideraciones Finales: los análisis muestran la historicidad de la institucionalización de los estudios de posgrado, apoyando la comprensión de los trazos de la profesionalización de la enfermería brasileña.

RESUMO Objetivos: analisar as produções científicas acerca da história da pós-graduação em enfermagem brasileira à luz da Sociologia das Profissões de Eliot Freidson. Métodos: revisão integrativa, realizada nas bases indexadas na Biblioteca Virtual da Saúde. Seguiram-se as recomendações da Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Adotaram-se a Análise de Conteúdo Temática e as concepções de Eliot Freidson. Resultados: elencaram-se duas categorias: "Institucionalização da pós-graduação em enfermagem brasileira", ressaltando o processo histórico da profissionalização da enfermagem pela transição de um cuidado empírico para o profissional, subsidiado pelo monopólio da construção de saber próprio; "A produção científica da pós-graduação em enfermagem no Brasil", evidenciando o fortalecimento da nova geração de enfermeiros pesquisadores no país, visto a maior cientificidade no ensino pela implantação da pós-graduação. Considerações Finais: as análises apresentam a historicidade da institucionalização da pós-graduação subsidiando a compreensão dos delineamentos da profissionalização da enfermagem brasileira.

The protected tree Dimorphandra wilsonii (Fabaceae) is a population of inter-specific hybrids: recommendations for conservation in the Brazilian Cerrado/Atlantic Forest ecotone.

BACKGROUNDS AND AIMS: Dimorphandra wilsonii Rizzini, a critically endangered and protected tree, has a restricted distribution in the ecotone between the Cerrado and the Atlantic Forest in south-eastern Brazil. In this area, it co-occurs with D. mollis Benth., a common tree from the Cerrado, and D. exaltata Schott., a rare tree from the Atlantic Forest. Previous studies of D. wilsonii indicated heterozygosity excess at the individual level. Field observation of some intermediate phenotypes between D. wilsonii and both congeners suggests hybridization of D. wilsonii with D. mollis and/or D. exaltata. Here, we tested the hypothesis that D. wilsonii may have originated from hybridization between D. exaltata and D. mollis. We also performed cytogenetic analysis to examine if the heterozygosity excess could be explained by polyploidy in D. wilsonii. METHODS: We evaluated the genetic diversity and population structure of D. wilsonii using 11 nuclear simple sequence repeats (SSRs) genotyped in 152 individuals sampled across the taxon's range. We performed comparative genetic analyses using overlapping SSR markers between D. wilsonii and previously published SSR data in D. mollis and D. exaltata to subsequently perform a series of allelic comparisons, multivariate and Bayesian analysis. KEY RESULTS: Our results suggest that D. wilsonii individuals are most likely to correspond to F1 hybrids between D. exaltata and D. mollis. Cytogenetic analysis indicated that D. wilsonii is diploid with the same chromosome number as D. mollis (2n = 2x = 28). CONCLUSIONS: Our study raises questions about the taxonomic status and the evolutionary future of D. wilsonii. We suggest that the conservation and management strategy for D. wilsonii should be revised and that it should take into account both parental Dimorphandra species in the ecotone, with special emphasis on the threatened D. exaltata. Finally, this study highlights the value of genetic information for the design of conservation strategies.

Effect of piperlongumine during exposure to cigarette smoke reduces inflammation and lung injury.

Chronic obstructive pulmonary disease (COPD) is related to smoking and anti-inflammatory therapy is indicated. Among the mediators with anti-inflammatory properties, we highlight piperlongumine (PL), an alkaloid/amide of Piper longum. Here we evaluated the PL administration on an experimental model of respiratory inflammation resulting from exposure to cigarette smoke. Male Balb/c mice were exposed to burning of 10 commercial cigarettes, 2x/day, for five weeks on specific equipment. PL efficacy was evaluated in control, exposed to smoke without treatment and PL treated (2.0 mg/kg, 3x/week) groups. Animals were weighed and plethysmographic analyses performed at the end of the exposure protocol. Inflammatory cells were evaluated in the bronchoalveolar lavage (BAL) and hemoglobin and glucose in the blood. Lung fragments were processed for histopathological studies and AnxA1, COX-2, NF-kB and neutrophil elastase expressions. Plethysmography revealed that PL maintained pulmonary frequency, volume and ventilation parameters similar to controls, with respiratory volume reduction compared to untreated animals. Final weight was reduced in both exposed groups. PL decreased hemoglobin concentration, attenuated the reduction of glucose levels and reduced influx of lymphocytes, neutrophils and macrophages in BAL. Histopathologically occured infiltration of inflammatory cells, increase of the interalveolar septa and intra-alveolar spaces in untreated animals. But, PL administration recovered lung tissues and, immunohistochemically, promoted increased expression of AnxA1 and reduction of COX-2, NF-kB and neutrophil elastase. Together the results indicate that PL attenuates systemic and pulmonary inflammatory changes, partially by modulating the expression the endogenous AnxA1, and may represent a promising therapy in preventing the inflammation induced by cigarette smoke.

Modulation of the endogenous Annexin A1 in a cigarette smoke cessation model: Potential therapeutic target in reversing the damage caused by smoking?

BACKGROUND: Smoking cessation may help in the reversal of inflammation and damage caused by smoking. The endogenous annexin A1 (AnxA1) protein has anti-inflammatory effects which instigates the understanding of its role in the attenuation of inflammatory processes caused by smoking. MATERIAL AND METHODS: Wistar rats were exposed to cigarette smoke for 8 weeks. After the exposure period, one of the groups remained other 8 weeks in the absence of smoke. Animals not exposed to smoke were used as control. Blood, trachea and lungs were obtained for histopathological, immunohistochemical and biochemical analyses. RESULTS: Loss of cilia of the tracheal lining epithelium was found by smoke exposure, but smoking cessation led to recovery of the tracheal epithelium. Similarly, chronically exposed-to-smoke animals showed increased lymphocytes and macrophages in bronchoalveolar lavage and higher levels of glucose and gamma-GT in their blood. Reduction of lymphocytes, glucose and gamma-GT occurred after smoking cessation. In addition, IL-1ß, IL-6, IL-10, TNF-α and MCP-1 levels were elevated by smoke exposure. Smoking cessation significantly reduced the levels of IL-1ß, IL-6 and MCP-1 but increased the IL-10 concentration. Numerous mast cells and macrophages were observed in the lung of chronically exposed-to-smoke animals with reduction by smoking cigarette abstinence. AnxA1 increased expression and concomitant NF-κB reduction were found in the smoking cessation group. CONCLUSION: Our results showed that cigarette abstinence promoted partial recovery of the inflammatory process. The attenuation of the inflammatory profile may be associated with the overexpression of AnxA1 protein.

Investigation of medicines consumption and disposal in Brazil: A study case in a developing country.

The incorrect disposal of medicines can be harmful to the environment. Here, we aim to understand the consumption and disposal of medicines in Brazil using online forms. 64% of the respondents have the habit to self-medicate. 66% of respondents dispose the disused or expired medicines in the garbage. 71.9% of respondents never receive any information about correct disposal of medicines. 95.2% of respondents believe that residues of medicines can be harmful to the environment. Environmental education can provide information to the population and help to mitigate pharmaceuticals pollution.

Expression of the Annexin A1 and its correlation with matrix metalloproteinases and the receptor for formylated peptide-2 in diffuse astrocytic tumors.

Astrocytomas represent the majority of cerebral gliomas. Studies show that the anti-inflammatory protein Annexin-A1 (ANXA1) is associated with the tumor invasion process and that its actions can be mediated by the receptor for formylated peptides (FPR). Therefore, we evaluated the expression of ANXA1, the receptor FPR2 and matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9) in brain astrocytomas. Detection of proteins was performed in sections of diffuse astrocytomas (grade II), anaplastic astrocytomas (grade III) and glioblastomas (GBM, grade IV) and quantifications were made by densitometry. Our analyses showed increased expression of ANXA1 in astrocytomas of all grades, but especially in GBM. The expression of FPR2 is similar to that found for ANXA1, being higher in GBM. Immunostaining for MMPs is also stronger as the degree of malignancy increases, especially with respect to MMP-9. The positive correlation between ANXA1/FPR2 and ANXA1/MMP-9 was observed in all tumors studied. The data indicate the possible action of ANXA1 and FPR2 on the development and progression of astrocytomas, related to increased expression of MMP-9. Thereby, ANXA1 and FPR2 are involved in the biology and malignancy of diffuse astrocytic tumors.

Mimetic peptide AC2-26 of annexin A1 as a potential therapeutic agent to treat COPD.

Chronic obstructive pulmonary disease (COPD) is related to inflammatory process caused by smoking habit. In this scenario, the anti-inflammatory protein Annexin A1 (AnxA1) may represent a therapeutic alternative. We performed experiments to evaluate the effects of the AnxA1 mimetic peptide Ac2-26 in an initial COPD model by physiological, histopathological, biochemical and immunohistochemical analyses. Weight loss, increased blood pressure, reductions in the pulmonary frequency and ventilation, loss of tracheal cilia, enlargement of the pulmonary intra-alveolar spaces and lymphoid tissue found in untreated smoke-exposed group were attenuated by AnxA1 peptide treatment. The Ac2-26 administration also protected against leukocytes influx in bronchoalveolar lavage (BAL), lung and trachea, and it also led to decreased hemoglobin, glucose, cholesterol, gamma glutamyl transferase and aspartato aminotransferase levels. Similarly, reduction of proinflammatory mediators and higher concentration of anti-inflammatory cytokine were found in macerated lung supernatant, blood plasma and BAL in the treated animals. Besides Ac2-26 group showed reduced tissue expressions of AnxA1, cyclooxygenase-2 and metalloproteinase-9, but formylated peptide receptor 2 (FPR2) overexpression. Our results all together highlighted the protective role of the Ac2-26 mimetic peptide in COPD with promising perspectives.

Anti-inflammatory actions of herbal medicines in a model of chronic obstructive pulmonary disease induced by cigarette smoke.

The effects of four medicinal herbs (Arctium lappa, Plantago major, Mikania glomerata Spreng and Equisetum arvense) with anti-inflammatory properties were evaluated in a chronic obstructive pulmonary disease (COPD) model. Wistar rats were exposed to cigarette smoke during 8 weeks and one of the groups was orally given a solution containing 4% of each alcoholic herbal extracts during the exposure period. Control group was not exposed to smoke or treated. Histopathological, immunohistochemical and biochemical analyzes were performed. Normal blood plasma levels of gamma glutamyl transferase indicated no toxicity of the administered herbal extracts. The treatment reduced leukocytes influx in bronchoalveolar lavage, mast cell and macrophages numbers in lungs, as well as prevented pulmonary congestion and tracheal metaplasia. Herbal mixture also decreased plasma inflammatory mediator levels and pulmonary expression of annexin A1 and nuclear factor-k?. Our data indicate synergistic and protective effects of the used herbal medicines in animals exposed to cigarette smoke as a potential therapeutic strategy.