RESUMO

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.

Assuntos

Gêmeos Unidos , Humanos , Gravidez , Feminino , Cesárea , Tomografia Computadorizada por Raios X , Imageamento Tridimensional

RESUMO

Inflammation in the established tumor microenvironment (TME) is often associated with a poor prognosis of breast cancer. Bisphenol A (BPA) is an endocrine-disrupting chemical that acts as inflammatory promoter and tumoral facilitator in mammary tissue. Previous studies demonstrated the onset of mammary carcinogenesis at aging when BPA exposure occurred in windows of development/susceptibility. We aim to investigate the inflammatory repercussions of BPA in TME in mammary gland (MG) during neoplastic development in aging. Female Mongolian gerbils were exposed to low (50 µg/kg) or high BPA (5000 µg/kg) doses during pregnancy and lactation. They were euthanized at 18 months of age (aging) and the MG were collected for inflammatory markers and histopathological analysis. Contrarily to control MG, BPA induced carcinogenic development mediated by COX-2 and p-STAT3 expression. BPA was also able to promote macrophage and mast cell (MC) polarization in tumoral phenotype, evidenced by pathways for recruitment and activation of these inflammatory cells and tissue invasiveness triggered by tumor necrosis factor-alpha and transforming growth factor-beta 1 (TGF-ß1). Increase of tumor-associated macrophages, M1 (CD68 + iNOS+) and M2 (CD163+) expressing pro-tumoral mediators and metalloproteases was observed; this aspect greatly contributed to stromal remodeling and invasion of neoplastic cells. In addition, the MC population drastically increased in BPA-exposed MG. Tryptase-positive MCs increased in disrupted MG and expressed TGF-ß1, contributing to EMT process during carcinogenesis mediated by BPA. BPA exposure interfered in inflammatory response by releasing and enhancing the expression of mediators that contribute to tumor growth and recruitment of inflammatory cells that promote a malignant profile.

Assuntos

Fator de Crescimento Transformador beta1 , Microambiente Tumoral , Gravidez , Feminino , Humanos , Compostos Benzidrílicos , Carcinogênese , Fenótipo

RESUMO

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.

Assuntos

Garcinia , Animais , Anti-Inflamatórios/análise , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Compostos Fitoquímicos/análise , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Folhas de Planta/química , Ratos , Ratos Wistar , Cicatrização

RESUMO

Introdução: O benzopireno é um dos principais hidrocarbonetos aromáticos policíclicos presentes no ambiente e com alta capacidade carcinogênica, sendo, portanto, usado em modelos in vivo de carcinogênese pulmonar. Investigações têm mostrado o envolvimento dos mastócitos na modulação do ambiente tumoral e que os fármacos anti-inflamatórios podem reduzir a incidência de câncer de pulmão. Entre as possibilidades terapêuticas estão os fitoterápicos. O extrato de Garcinia brasiliensis, conhecido popularmente como bacupari, mostra propriedades anti-inflamatórias e antitumorais, mas ainda pouco estudado em modelos animais. Objetivos: Avaliar os efeitos da administração do extrato alcoólico de G. brasiliensis em modelo de carcinogênese induzida por benzopireno. Material e Método: O extrato bruto foi obtido por percolação com o uso de 20 g das folhas secas e trituradas de G. brasiliensis e 100 ml de etanol a 70%, por 24h. Ratos Wistar foram divididos em 3 grupos, um controle sem indução ou tratamento, um induzido pelo benzopireno (100 mg/kg, diluído em DMSO e administrado intraperitonealmente, uma única aplicação) e um grupo tratado por gavagem (1 ml) com extrato de bacupari a 4% (3x/semana, por 7 semanas, a partir da 15o semana da indução. Os animais de todos os grupos foram eutanasiados após 21 semanas para coleta dos pulmões que foram processados para análises histopatológicas (HE) e histoquímicas (Azul de Toluidina e Azul de Alcian Safranina) para quantificação dos mastócitos. Resultados: Os resultados das análises histopatológicas mostraram desorganização do parênquima pulmonar, aumento de tecido linfático associado aos brônquios, grande influxo de células inflamatórias e regiões de displasia. Pela coloração de azul de toluidina os mastócitos foram identificados na forma intacta e desgranulada (em processo de ativação). Na coloração conjunta Azul de Alcian e Safranina, os mastócitos corados em azul representam as fases iniciais do processo de maturação, enquanto os corados em vermelho estão maduros. A quantificações evidenciaram maior quantidade de mastócitos desgranulados, azul de Alcian e mistos (corados pelo Azul de Alcian e Safranina) nos grupos tratados com o extrato. Conclusão: Os dados indicam que o ambiente tumoral nos animais tratados mostra maior modulação dos mastócitos, com mais células jovens e ativadas. Mais análises serão realizadas para verificar se a ativação dos mastócitos promovida pelo tratamento com o extrato ocorre para contenção ou promoção do processo tumoral.(AU)

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Introduction: Benzopyrene is one of the main polycyclic aromatic hydrocarbons present in the environment and with a high carcinogenic capacity, being, therefore, used in in vivo models of lung carcinogenesis. Investigations have shown the involvement of mast cells in modulating the tumor environment and that anti-inflammatory drugs can reduce the incidence of lung cancer. Among the therapeutic possibilities are herbal medicines. Garcinia brasiliensis extract, popularly known as bacupari, shows anti-inflammatory and antitumor properties, but still little studied in animal models. Objectives: To evaluate the effects of the administration of the alcoholic extract of G. brasiliensis in a model of carcinogenesis induced by benzopyrene. Material and Methods: The crude extract was obtained by percolation using 20 g of dried and crushed leaves of G. brasiliensis and 100 ml of 70% ethanol for 24 hours. Wistar rats were divided into 3 groups, a control without induction or treatment, one induced by benzopyrene (100 mg/kg, diluted in DMSO and administered intraperitoneally, a single application) and a group treated by gavage (1 ml) with bacupari extract. at 4%...(AU)

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Introducción: El benzopireno es uno de los principales hidrocarburos aromáticos policíclicos presentes en el ambiente y tiene una elevada capacidad carcinogénica, por lo que se utiliza en modelos in vivo de carcinogénesis pulmonar. Las investigaciones han demostrado la implicación de los mastocitos en la modulación del entorno tumoral y que los fármacos antiinflamatorios pueden reducir la incidencia del cáncer de pulmón. Entre las posibilidades terapéuticas están las fitoterapias. El extracto de Garcinia brasiliensis, conocido popularmente como bacupari, muestra propiedades antiinflamatorias y antitumorales, pero todavía está sido poco estudiado en modelos animales. Objetivos: Evaluar los efectos de la administración del extracto alcohólico de G. brasiliensis en el modelo de carcinogénesis inducido por el benzopireno. Material y métodos: El extracto crudo se obtuvo por percolación utilizando 20 g de hojas de G. brasiliensis secas y trituradas y 100 ml de etanol al 70%, durante 24h. Las ratas Wistar fueran divididas en 3 grupos, uno de control sin inducción ni tratamiento, otro inducido por benzopireno (100 mg/kg, diluido en DMSO y administrado por vía intraperitoneal, una sola aplicación) y un grupo tratado por gavage (1ml) con extracto de bacupari 4% (3x/semana, durante 7 semanas, desde la 15ª semana de inducción). Los animales de todos los grupos fueron eutanasiados después de 21 semanas para recoger los pulmones que se procesaron para los análisis histopatológicos (HE) e histoquímicos (azul de toluidina y azul de safranina) para la cuantificación de los mastocitos. Resultados: Los resultados de los análisis histopatológicos mostraron desorganización del parénquima pulmonar, aumento del tejido linfoide asociado a los bronquios, gran afluencia de células inflamatorias y regiones de displasia. Mediante la tinción con azul de toluidina, los mastocitos se identificaron como intactos y degranulados (en proceso de activación). En la tinción conjunta de azul Alcian y Safranina, los mastocitos teñidos de azul representan las fases iniciales del proceso de maduración, mientras que los teñidos de rojo son maduros. La cuantificación mostró una mayor cantidad de mastocitos degranulados, azul Alcian y mixtos (teñidos con azul Alcian-Safranin) en los grupos tratados con el extracto. Conclusión: Los datos indican que el entorno del tumor en los animales tratados muestra una mayor modulación de los mastocitos, con más células jóvenes y activadas. Se llevarán a cabo más análisis para verificar si la activación de los mastocitos promovida por el tratamiento con el extracto se produce para contener o promover el proceso tumoral.(AU)

Assuntos

Animais , Plantas Medicinais , Carcinogênese , Neoplasias Pulmonares , Benzopirenos/administração & dosagem , Ratos Wistar , Anti-Inflamatórios

RESUMO

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.

Assuntos

Anexina A1/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Dioxolanos/uso terapêutico , Peptídeos/uso terapêutico , Uveíte/induzido quimicamente , Uveíte/tratamento farmacológico , Animais , Anexina A1/administração & dosagem , Anexina A1/farmacologia , Anti-Inflamatórios/farmacologia , Cílios/enzimologia , Cílios/patologia , Ciclo-Oxigenase 2/metabolismo , Dioxolanos/administração & dosagem , Dioxolanos/farmacologia , Endotoxinas , Olho/efeitos dos fármacos , Olho/patologia , Mediadores da Inflamação/metabolismo , Masculino , Modelos Biológicos , Monócitos/efeitos dos fármacos , Neutrófilos/efeitos dos fármacos , Peptídeos/administração & dosagem , Peptídeos/farmacologia , Ratos Wistar , Receptores de Lipoxinas/metabolismo , Uveíte/sangue , Uveíte/patologia

RESUMO

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.

Assuntos

Anti-Inflamatórios/farmacologia , Animais , Anexina A1/metabolismo , Benzo(a)pireno/metabolismo , Benzopirenos , Líquido da Lavagem Broncoalveolar , Carcinógenos/metabolismo , Ciclo-Oxigenase 2/metabolismo , Citocinas/metabolismo , Inflamação/metabolismo , Interleucina-1beta , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Neutrófilos/metabolismo , Fator de Necrose Tumoral alfa/metabolismo

RESUMO

Deregulation of VEGFA (Vascular Endothelial Growth Factor A) and NFE2L2 (Nuclear Factor (Erythroid-derived 2)-Like 2), involved in angiogenesis and oxidative stress, can lead to thyroid cancer progression. MiR-17-5p and miR-612 are possible regulators of these genes and may promote thyroid disorders. In order to evaluate the involvement of VEGFA, NFE2L2, hsa-miR-17-5p, and hsa-miR-612 in thyroid pathology, we examined tissue samples from colloid goiter, papillary thyroid cancer (PTC), and a normal thyroid. We found higher levels of VEGFA and NFE2L2 transcripts and the VEGFA protein in goiter and PTC samples than in normal tissue. In the goiter, miR-612 and miR-17-5p levels were lower than those in PTC. Tumors, despite showing lower VEGFA mRNA expression, presented higher VEGFA protein levels compared to goiter tissue. In addition, NRF2 (Nuclear Related Transcription Factor 2) protein levels in tumors were higher than those in goiter and normal tissues. Inhibition of miR-17-5p resulted in reduced NFE2L2 expression. Overall, both transcript and protein levels of NFE2L2 and VEGFA were elevated in PTC and colloid goiter. Hsa-miR-612 showed differential expression in PTC and colloid goiter, while hsa-miR-17-5p showed differential expression only in colloid goiter, suggesting that hsa-miR-17-5p may be a positive regulator of NFE2L2 expression in PTC.

Assuntos

Biomarcadores Tumorais/metabolismo , Bócio Nodular/patologia , MicroRNAs/genética , Fator 2 Relacionado a NF-E2/metabolismo , Câncer Papilífero da Tireoide/patologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Apoptose , Biomarcadores Tumorais/genética , Estudos de Casos e Controles , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Bócio Nodular/genética , Bócio Nodular/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Fator 2 Relacionado a NF-E2/genética , Prognóstico , Câncer Papilífero da Tireoide/genética , Câncer Papilífero da Tireoide/metabolismo , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/metabolismo , Neoplasias da Glândula Tireoide/patologia , Células Tumorais Cultivadas , Fator A de Crescimento do Endotélio Vascular/genética

RESUMO

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.

Assuntos

Anti-Inflamatórios/farmacologia , Dioxolanos/farmacologia , Inflamação/induzido quimicamente , Lesão Pulmonar/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Fumar Tabaco/efeitos adversos , Animais , Anexina A1/metabolismo , Ciclo-Oxigenase 2/metabolismo , Lesão Pulmonar/metabolismo , Lesão Pulmonar/patologia , Lesão Pulmonar/fisiopatologia , Linfócitos/metabolismo , Macrófagos Alveolares/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , NF-kappa B/metabolismo , Neutrófilos , Fumar Tabaco/metabolismo , Fumar Tabaco/patologia , Fumar Tabaco/fisiopatologia

RESUMO

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.

Assuntos

Anexina A1/biossíntese , Astrocitoma/patologia , Biomarcadores Tumorais/biossíntese , Neoplasias Encefálicas/patologia , Receptores de Formil Peptídeo/biossíntese , Receptores de Lipoxinas/biossíntese , Adulto , Idoso , Feminino , Humanos , Masculino , Metaloproteinase 2 da Matriz/biossíntese , Metaloproteinase 9 da Matriz/biossíntese , Pessoa de Meia-Idade

RESUMO

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.

Assuntos

Anexina A1/uso terapêutico , Anti-Inflamatórios/uso terapêutico , Peptídeos/uso terapêutico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Animais , Anexina A1/farmacologia , Anti-Inflamatórios/farmacologia , Líquido da Lavagem Broncoalveolar/citologia , Ciclo-Oxigenase 2/imunologia , Citocinas/imunologia , Feminino , Macrófagos/imunologia , Mastócitos/imunologia , Peptídeos/farmacologia , Doença Pulmonar Obstrutiva Crônica/induzido quimicamente , Doença Pulmonar Obstrutiva Crônica/imunologia , Doença Pulmonar Obstrutiva Crônica/patologia , Ratos Wistar , Fumaça , Produtos do Tabaco

RESUMO

Introdução: A busca por novos agentes terapêuticos tem incentivado as pesquisas com plantas medicinais, pois muitas delas podem apresentar propriedade antimicrobiana e conhecer o potencial citotóxico dos extratos é fundamental para garantir a segurança durante o uso. Objetivo: Avaliar a atividade antimicrobiana e a citotoxicidade hemolítica de Arctium lappa (bardana), Equisetum arvense (cavalinha), Mikania glomerata (guaco), Morus nigra (amora) e Plantago major (tanchagem), amplamente consumidos pela população na forma de chás medicinais. Material e Métodos: Os extratos etanólicos fora preparados a 20% por percolação. Na avaliação antimicrobiana foi utilizada a técnica de difusão em disco, empregando as bactérias Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis, Klebsiella pneumoniae, Acinetobactersp, Enterococcus sp e Salmonella sp. O ensaio de citotoxicidade baseou-se na exposição dos extratos a 5%, 25%, 50%, 75% e 100% em suspensão de hemácias a 37ºC por 30 minutos, seguido de centrifugação e visualização do grau de hemólise. Resultados: Todos os extratos apresentaram inibição de crescimento microbiano, principalmente sobre Acinetobacter sp (amora), Enterococcus sp (amora e cavalinha), K. pneumoniae(amora, bardana e guaco), P. aeruginosa (cavalinha, tanchagem, bardana e guaco) e Salmonellasp (amora e bardana). No ensaio de citotoxicidade, o grau de hemólise foi classificado como baixo para tanchagem e bardana (5%) e médio para cavalinha, guaco e amora (25%) nas concentrações testadas. Conclusão: Os resultados mostram o potencial antimicrobiano dos extratos de amora, bardana, cavalinha, guaco e tanchagem contra bactérias Gram negativas e a baixa citotoxicidade hemolítica confirma a segurança no uso dos mesmos como agentes terapêuticos.

Assuntos

Extratos Vegetais/análise , Antibacterianos , Noxas/análise

RESUMO

Mast cells (MCs) participate in all stages of skin healing and one of their mediators is the Annexin A1 protein (AnxA1), linked to inflammation, proliferation, migration and apoptosis processes, but not studied in thermal burns yet. Therefore, our objectives were to evaluate the behavior of MCs and AnxA1 in a second degree burn model, treated or not with silver sulfadiazine 1% (SDP 1%) and associated to macrophages quantification and cytokines dosages. MCs counts showed few cells in the early stages of repair but increased MCs in the final phases in the untreated group. The normal skin presented numerous tryptase-positive MCs that were reduced after burning in all analyzed periods. Differently, few chymase-positive MCs were observed in the early stages of healing, however, increased chymase-positive MCs were found at the final phase in the untreated group. MCs also showed high immunoreactivity for AnxA1 on day 3 in both groups. In the tissue there was a strong protein expression in the early stages of healing, but in the final phases only in the SDP treated animals. TNF-α, IL-1ß, IL-6, IL-10 and MCP-1 levels and macrophages quantification were increased in inflammation and reepithelialization phases. Reduced IL-1ß, IL-6 and IL-10 levels and numerous macrophages occurred in the treated animals during tissue repair. Our results indicate modulation in the profile of MCs and AnxA1expression during healing by the treatment with SDP 1%, pointing them as targets for therapeutic interventions on skin burns.

Assuntos

Anexina A1/metabolismo , Queimaduras/tratamento farmacológico , Regulação da Expressão Gênica/efeitos dos fármacos , Mastócitos/citologia , Mastócitos/efeitos dos fármacos , Sulfadiazina de Prata/farmacologia , Animais , Queimaduras/imunologia , Queimaduras/metabolismo , Queimaduras/fisiopatologia , Contagem de Células , Proliferação de Células/efeitos dos fármacos , Citocinas/metabolismo , Citoplasma/efeitos dos fármacos , Citoplasma/metabolismo , Derme/efeitos dos fármacos , Derme/patologia , Modelos Animais de Doenças , Epiderme/efeitos dos fármacos , Epiderme/patologia , Histamina/metabolismo , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Ratos , Ratos Wistar , Sulfadiazina de Prata/uso terapêutico , Cicatrização/efeitos dos fármacos

RESUMO

ABSTRACT Objective: To investigate whether swimming could prevent bone loss and could be indicated to assist in treatment of osteoporosis. Methods: Female rats were divided into 4 groups (n=6), two of them were oophorectomized. Animals from two groups, one oophorectomized and another not oophorectomized, underwent aquatic training for eight weeks. After training, the animals were sacrificed and their blood was collected for calcium and alkaline phosphatase serum dosage; the femur was removed and subjected to radiological and histological densitometry analysis to assess bone loss and osteoclast counting on femoral head and neck. Results: Increase in serum calcium was not observed. There was an increasing activity of alkaline phosphatase in the oophorectomized groups. The radiographs suggest that there was a greater bone mass density in the trained groups. Concerning histology, the trained groups had better tissue structural organization than the sedentary groups. In the oophorectomized and sedentary group, higher presence of osteoclasts was observed a. Conclusion: Exercise and oophorectomy did not promote changes in serum calcium levels. The decrease of sex steroids caused by oophorectomy was responsible for severe bone loss, but swimming exercise was able to reduce this loss. Oophorectomy promoted the proliferation of osteoclasts and the exercise proved to be able to diminish it. Level of Evidence I, Experimental Study.

RESUMO

OBJECTIVE: To investigate whether swimming could prevent bone loss and could be indicated to assist in treatment of osteoporosis. METHODS: Female rats were divided into 4 groups (n=6), two of them were oophorectomized. Animals from two groups, one oophorectomized and another not oophorectomized, underwent aquatic training for eight weeks. After training, the animals were sacrificed and their blood was collected for calcium and alkaline phosphatase serum dosage; the femur was removed and subjected to radiological and histological densitometry analysis to assess bone loss and osteoclast counting on femoral head and neck. RESULTS: Increase in serum calcium was not observed. There was an increasing activity of alkaline phosphatase in the oophorectomized groups. The radiographs suggest that there was a greater bone mass density in the trained groups. Concerning histology, the trained groups had better tissue structural organization than the sedentary groups. In the oophorectomized and sedentary group, higher presence of osteoclasts was observed a. CONCLUSION: Exercise and oophorectomy did not promote changes in serum calcium levels. The decrease of sex steroids caused by oophorectomy was responsible for severe bone loss, but swimming exercise was able to reduce this loss. Oophorectomy promoted the proliferation of osteoclasts and the exercise proved to be able to diminish it. Level of Evidence I, Experimental Study.

RESUMO

INTRODUÇÃO: O aumento da sobrevida na fase aguda do paciente grande queimado faz também aumentar a prevalência das sequelas cicatriciais estético-funcionais. Ao pensarmos na relevância clínica da lipoenxertia subcicatricial, necessita-se da compreensão e avaliação microscópica das reais alterações após o procedimento. MÉTODOS: Foram selecionados oito pacientes, vítimas de queimadura por álcool, com tempo médio após queimadura de 12 meses (10-14 meses), sendo submetidos à lipoenxertia subcicatricial associada à Rigottomy. Foram realizadas biópsias cutâneas no pré e pós-operatório tardio com 14 semanas. Avaliados os quesitos: 1 - Melhora estético funcional da cicatriz pela escala de Vancouver; 2 - Análise quantitativa e qualitativa do colágeno cicatricial; 3 -Análise imunohistoquímica da vascularização cicatricial com anti-fator de crescimento derivado do endotélio vascular (antiVEGE). RESULTADOS: Ao compararmos o período pré e pós-lipoenxertia, pôde-se avaliar que houve melhora estético-funcional significativa e, microscopicamente, redefinição entre os limites da derme papilar e reticular; redução quantitativa e reorganização do colágeno, além do decréscimo da vascularização tecidual pela análise imunohistoquímica. CONCLUSÃO: O princípio básico de todo processo cicatricial fisiológico é reestabelecer a homeostasia local, ou seja, as etapas exageradamente intensificadas levam a alterações clínicas catastróficas. Ao realizar a lipoenxertia subcicatricial associada à Rigotomia, foi verificada, neste estudo, a melhora qualitativa e quantitativa do tecido. Sendo assim, torna-se evidente o futuro promissor deste procedimento para a complementação terapêutica das patologias cicatriciais.

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INTRODUCTION: The increase in survival of large burn patients during the acute phase has also increased the prevalence of esthetic-functional scarring sequelae. With regard to the clinical relevance of subcicatricial fat grafting, the actual changes after the procedure need to be understood and microscopically evaluated. METHODS: Eight patients with alcohol burns, with an average time after burn of 12 months (10-14 months), who underwent subcicatricial fat grafting associated with rigotomy were selected. Skin biopsies were performed in before and 14 weeks after operation. The following issues were assessed: 1) esthetic-functional improvement of the scar, by using the Vancouver scar scale; 2) quantitative and qualitative analyses of cicatricial collagen; 3) immunohistochemical analysis of scar vascularization with anti-vascular endothelial growth factor (anti-VEGF) antibody. RESULTS: When comparing the pre- and post-fat grafting period, a significant esthetic-functional improvement and, microscopically, a redefinition of the boundaries of the papillary and reticular dermis were observed, as well as quantitative reduction and reorganization of collagen, in addition to the decrease of the vascularization of the tissue through immunohistochemical analysis. CONCLUSION: The basic principle of the whole physiological healing process is to reestablish local homeostasis, that is, excessively intensified steps that lead to severe clinical changes. When subcicatricial fat grafting associated with rigotomy was performed, qualitative and quantitative improvements of the tissue were verified in this study. Thus, it becomes evident that this procedure can complement the treatment of cicatricial pathologies.

Assuntos

Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , História do Século XXI , Cicatrização , Queimaduras Químicas , Cicatriz , Transplante de Pele , Procedimentos de Cirurgia Plástica , Estudo de Avaliação , Estética , Homeostase , Cicatrização/fisiologia , Queimaduras Químicas/cirurgia , Queimaduras Químicas/complicações , Cicatriz/cirurgia , Cicatriz/complicações , Cicatriz/terapia , Transplante de Pele/efeitos adversos , Transplante de Pele/métodos , Procedimentos de Cirurgia Plástica/efeitos adversos , Procedimentos de Cirurgia Plástica/métodos , Homeostase/fisiologia

RESUMO

PURPOSE: Galectin-1 (Gal-1) is a ß-galactoside-binding protein with diverse biological activities in the pathogenesis of inflammation but has been poorly investigated in terms of ocular inflammation. In the present study, we monitored the anti-inflammatory effects of Gal-1 using the in vivo rodent model of endotoxin-induced uveitis (EIU) and in vitro assays with human RPE (ARPE-19) cells. METHODS: For this purpose, EIU was induced by subcutaneous sterile saline injection of 0.1 ml of lipopolysaccharide (LPS, 1 mg/Kg) in the rat paw, which was maintained under these conditions for 24 h. The therapeutic efficacy of recombinant Gal-1 (rGal-1) was tested in the EIU animals by intraperitoneal inoculation (3 µg/100 µl per animal) 15 min after the LPS injection. In vitro studies were performed using LPS-stimulated ARPE-19 cells (10 µg/ml) for 2, 8, 24 and 48 h, treated or not with rGal-1 (4 µg/ml) or dexamethasone (Dex, 1.0 µM). RESULTS: Gal-1 treatment attenuated the histopathological manifestation of EIU via the inhibition of polymorphonuclear cells (PMN) infiltration in the eye and by causing an imbalance in adhesion molecule expression and suppressing interleukin (IL)-1ß, IL-6, and monocyte chemotactic protein-1 (MCP-1) productions. Immunohistochemical and western blotting analyses revealed significant upregulation of Gal-1 in the eyes induced by EIU after 24 h. In the retina, there was no difference in the Gal-1 expression, which was high in all groups, demonstrating its structural role in this region. To better understand the effects of Gal-1 in the retina, in vitro studies were performed using ARPE-19 cells. Ultrastructural immunocytochemical analyses showed decreased levels of endogenous Gal-1 in LPS-stimulated cells (24 h), while Dex treatment upregulated this protein. The protective effects of rGal-1 on LPS-stimulated cells were associated with the significant reduction of the release of cytokines (IL-8 and IL-6), similar to Dex treatment. Furthermore, rGal-1 and Dex inhibited cyclooxygenase-2 (COX-2) expression in LPS-stimulated cells, as shown by immunofluorescence. CONCLUSIONS: Overall, this study identified potential roles for Gal-1 in ocular inflammation, especially uveitis, and may lead to future therapeutic approaches.

Assuntos

Anti-Inflamatórios não Esteroides/farmacologia , Células Epiteliais/efeitos dos fármacos , Galectina 1/farmacologia , Epitélio Pigmentado da Retina/efeitos dos fármacos , Uveíte/tratamento farmacológico , Uveíte/genética , Animais , Anti-Inflamatórios não Esteroides/imunologia , Anti-Inflamatórios não Esteroides/metabolismo , Linhagem Celular , Quimiocina CCL2/antagonistas & inibidores , Quimiocina CCL2/genética , Quimiocina CCL2/imunologia , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/imunologia , Dexametasona/farmacologia , Modelos Animais de Doenças , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Galectina 1/genética , Galectina 1/imunologia , Regulação da Expressão Gênica , Humanos , Injeções Subcutâneas , Interleucina-1beta/antagonistas & inibidores , Interleucina-1beta/genética , Interleucina-1beta/imunologia , Interleucina-6/antagonistas & inibidores , Interleucina-6/genética , Interleucina-6/imunologia , Lipopolissacarídeos , Infiltração de Neutrófilos/efeitos dos fármacos , Ratos , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/farmacologia , Epitélio Pigmentado da Retina/metabolismo , Epitélio Pigmentado da Retina/patologia , Uveíte/induzido quimicamente , Uveíte/imunologia

RESUMO

The incidence of penile cancer varies between populations but is rare in developed nations. Penile cancer is associated with a number of established risk factors and associated diseases including phimosis with chronic inflammation, human papillomavirus (HPV) infection, poor hygiene and smoking. The objective of this study was to identify genes related to this type of cancer. The detection of HPV was analyzed in 47 penile squamous cell carcinoma samples. HPV DNA was detected in 48.9% of penile squamous cell carcinoma cases. High-risk HPV were present in 42.5% of cases and low-risk HPV were detected in 10.6% of penile squamous cell carcinomas. The RaSH approach identified differential expression of Annexin A1 (ANXA1), p16, RPL6, PBEF1 and KIAA1033 in high-risk HPV positive penile carcinoma; ANXA1 and p16 were overexpressed in penile squamous cells positive for high-risk HPVs compared to normal penile samples by qPCR. ANXA1 and p16 proteins were significantly more expressed in the cells from high-risk HPV-positive penile carcinoma as compared to HPV-negative tumors (p<0.0001) independently of the subtype of the carcinoma. Overexpression of ANXA1 might be mediated by HPV E6 in penile squamous cell carcinoma of patients with high-risk HPVs, suggesting that this gene plays an important role in penile cancer.

Assuntos

Anexina A1/genética , Papillomaviridae/fisiologia , Infecções por Papillomavirus/complicações , Neoplasias Penianas/genética , Neoplasias Penianas/virologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Anexina A1/metabolismo , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Genótipo , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Hibridização de Ácido Nucleico , Papillomaviridae/genética , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/virologia , Neoplasias Penianas/complicações , Neoplasias Penianas/patologia , Reação em Cadeia da Polimerase , Reprodutibilidade dos Testes , Fatores de Risco

RESUMO

PURPOSE: To investigate the role of mast cells and annexin-A1 (Anxa1) in endotoxin-induced uveitis (EIU). METHODS: EIU was induced by injection of lipopolysaccharide (LPS) into the paws of rats, which were then sacrificed after 24 and 48 h. To assess EIU in the absence of mast cells, groups of animals were pretreated with compound 48/80 (c48/80) and sacrificed after 24 h after no treatment or EIU induction. The eyes were used for histological studies and the aqueous humor (AqH) pool was used for the analysis of transmigrated cells and Anxa1 levels. In inflammatory cells, Anxa1 expression was monitored by immunohistochemistry. RESULTS: After 24 h, rats with EIU exhibited degranulated mast cells, associated with elevated numbers of infiltrating leukocytes and the high expression of Anxa1 in the AqH and the neutrophils. After 48 h of EIU, the mast cells were intact, indicating granule re-synthesis, and there was a reduction of neutrophil transmigration and an increase in the number of mononuclear phagocytic cells in ocular tissues. Anxa1 expression was decreased in neutrophils but increased in mononuclear phagocytic cells. In the animals pretreated with c48/80 and subjected to EIU, mast cells responded to this secretagogue by degranulating and few transmigrated neutrophils were observed. CONCLUSTIONS: We report that mast cells are a potential source of pharmacological mediators that are strongly linked to the pathophysiology of EIU, and the endogenous protein Anxa1 is a mediator in the homeostasis of the inflammatory process with anti-migratory effects on leukocytes, which supports further studies of this protein as an innovative therapy for uveitis.

Assuntos

Lipopolissacarídeos , Mastócitos , Uveíte/induzido quimicamente , Uveíte/fisiopatologia , Animais , Anexina A1/metabolismo , Humor Aquoso/citologia , Humor Aquoso/metabolismo , Western Blotting , Contagem de Células , Degranulação Celular , Movimento Celular/efeitos dos fármacos , Olho/patologia , Proteínas do Olho/metabolismo , Homeostase , Imuno-Histoquímica , Leucócitos/patologia , Masculino , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Ratos , Ratos Wistar , Uveíte/patologia , p-Metoxi-N-metilfenetilamina/farmacologia

RESUMO

Mast cells are present in the eye of Gallus domesticus, appearing in the anterior uvea in embryos at stage 39 HH (13th day). In hatching and adult birds, they are present in the sclera, uvea, pectinate ligament, and conjunctiva. Mast cells are absent in the cornea, retina, and pecten oculi. Maturing mast cells in the anterior eye segment appear as round cells having eccentric nuclei and a few cytoplasmic metachromatic granules, whose fluorescence increases during development. Mature cells are more numerous in late development, and their cytoplasm is rich in metachromatic and intensely fluorescent granules. Ultrastructurally, maturing mast cells display progranules and a few electron dense and homogeneous granules on one side of the cell. Mast cells of adult birds possess homogeneous cytoplasmic granules, some of which display protuberances that penetrate hollows of adjoining granules. Heterogeneous granules exhibiting latticed and mottled patterns are also present. The existence of mast cells in the anterior eye segment indicates that these cells might perform a physiological role during development and in aqueous humor outflow. They might modulate exchanges between blood and aqueous humor through chemical mediators present in their granules. © 1996 Wiley-Liss, Inc.