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2.
J Biol Inorg Chem ; 29(1): 159-168, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38182820

RESUMO

Melanoma is the most aggressive and lethal type of skin cancer due to its characteristics such as high metastatic potential and low response rate to existing treatment modalities. In this way, new drug prototypes are being studied to solve the problem of treating patients with melanoma. Among these, ruthenium-based metallopharmaceuticals may be promising alternatives due to their antitumor characteristics and low systemic toxicity. In this context, the present study evaluated the antineoplastic effect of the ruthenium complex [Ru(mtz)(dppe)2]PF6-2-mercaptothiazoline-di-1,2-bis(diphenylphosphine) ethaneruthenium(II), namely RuMTZ, on human melanoma (A-375) and murine (B16-F10) cells, considering different approaches. Through XTT colorimetric and clonogenic efficiency assays, the complex revealed the selective cytotoxic activity, with the lowest IC50 (0.4 µM) observed for A375 cells. RuMTZ also induced changes in cell morphology, increased cell population in the sub-G0 phase and inhibiting cell migration. The levels of γH2AX and cleaved caspase 3 proteins were increased in both cell lines treated with RuMTZ. These findings indicated that the cytotoxic activity of RuMTZ on melanoma cells is related, at least in part, to the induction of DNA damage and apoptosis. Therefore, RuMTZ exhibited promising antineoplastic activity against melanoma cells.


Assuntos
Antineoplásicos , Complexos de Coordenação , Melanoma , Rutênio , Tiazolidinas , Humanos , Animais , Camundongos , Rutênio/farmacologia , Complexos de Coordenação/farmacologia , Melanoma/tratamento farmacológico , Ligantes , Antineoplásicos/farmacologia , Apoptose , Dano ao DNA , Linhagem Celular Tumoral
3.
Artigo em Inglês | MEDLINE | ID: mdl-38270618

RESUMO

Melanoma, an aggressive and potentially fatal skin cancer, is constrained by immunosuppression, resistance, and high toxicity in its treatment. Consequently, there is an urgent need for innovative antineoplastic agents. Therefore, this study investigated the antimelanoma potential of guttiferone E (GE). In an allogeneic murine B16 melanoma model, GE was administered subcutaneously and intraperitoneally. Antitumor evaluation included tumor volume/weight measurements and histopathological and immunohistochemical analysis. Furthermore, the toxicity of the treatments was evaluated through body/organ weights, biochemical parameters, and genotoxicity. Subcutaneous administration of 20 mg/kg of GE resulted in a significant reduction in both tumor volume and weight, effectively suppressing melanoma cell proliferation as evidenced by a decrease in mitotic figures. The tumor growth inhibition rate was equivalent to 54%. This treatment upregulated cleaved caspase-3, indicating apoptosis induction. On the other hand, intraperitoneal administration of GE showed no antimelanoma effect. Remarkably, GE treatments exhibited no toxicity, evidenced by non-significant differences in body weight gain, as well as organ weight, biochemical parameters of nephrotoxicity and hepatotoxicity, and genotoxic damage. This study revealed, for the first time, the efficacy of subcutaneous administration of GE in reducing melanoma, in the absence of toxicity. Furthermore, it was observed that the apoptotic signaling pathway is involved in the antimelanoma property of GE. These findings offer valuable insights for further exploring GE's therapeutic applications in melanoma treatment.

4.
Trop Med Int Health ; 28(6): 476-485, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37060253

RESUMO

OBJECTIVE: To analyse the spatial, temporal and spatial-temporal patterns of infant mortality associated with congenital toxoplasmosis in Brazil between the years 2000 and 2020. METHODS: Ecological study of time series, with spatial analysis and spatiotemporal scan of infant mortality associated with congenital toxoplasmosis from the records of deaths of the Mortality Information System of the Brazilian Ministry of Health. The rates were smoothed by the Local Empirical Bayesian model. The Global Moran Index, Global Geary's Contiguity and Getis-Ord General statistics were calculated for spatial autocorrelation assessment. The trends were evaluated by the Joinpoint method. RESULTS: We identified 1183 infant deaths associated with congenital toxoplasmosis in Brazil between 2000 and 2020. The predominant characteristics were male sex (52.1%), post-neonatal age group (51.9%), white race/colour (45.7%), and Southeast region of residence (40.0%). The infant mortality rate associated with congenital toxoplasmosis showed an increasing trend in the country in the years analysed. The spatial analysis showed heterogeneous distribution of mortality in the Brazilian territory and found no evidence of spatial autocorrelation; but spatial-temporal analysis identified three risk clusters involving 703 municipalities. CONCLUSION: Infant mortality associated with congenital toxoplasmosis is a persistent public health problem in Brazil. The risk factors male sex, indigenous race/colour, early neonatal age, North and Northeast regions and risk clusters mapped in this study should be observed for future analysis and planning of health care policies in the control of infant deaths associated with congenital toxoplasmosis. Health surveillance strategies and public health policies need to be strengthened.


Assuntos
Toxoplasmose Congênita , Lactente , Recém-Nascido , Humanos , Masculino , Feminino , Brasil/epidemiologia , Fatores de Tempo , Teorema de Bayes , Toxoplasmose Congênita/epidemiologia , Análise Espacial , Mortalidade Infantil , Análise Espaço-Temporal , Morte do Lactente
5.
World Neurosurg ; 174: 62, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36906086

RESUMO

Fluorescein (FS) was first used to visualize malignant brain tumors in 1948. FS accumulates in malignant gliomas where the blood-brain barrier is disrupted and provides intraoperative visualization that is similar to preoperative contrast-enhanced T1 images in which gadolinium accumulation is seen.1 FS can be viewed under white light, but the use of an operating microscope fitted with a dedicated filter (YELLOW 560 nm Filter, Carl Zeiss Meditec, Oberkochen, Germany) allows us to significantly reduce the dose needed to highlight tumoral tissue.1,2 FS is excited at 460-500 nm and emits a green, fluorescent emission wavelength at 540-690 nm.2 It is virtually free of side effects and has low costs3 (approximately 6.9 USD each vial: Brazil). Video 1 presents a case of a 63-year-old man who underwent a left temporal craniotomy to remove a temporal polar tumor. The FS is administered at the time of anesthesia before a craniotomy. The tumor was then removed with standard microneurosurgical technique by the alternating use of white light and YELLOW 560 nm filter illumination. The use of FS was found "helpful" to discriminate the brain tissue and tumor tissue (bright yellow). Fluorescein-guided technique with a dedicated filter on the surgical microscope is safe and allows complete resection of high-grade gliomas.


Assuntos
Neoplasias Encefálicas , Glioma , Masculino , Humanos , Pessoa de Meia-Idade , Fluoresceína , Corantes Fluorescentes , Glioma/diagnóstico por imagem , Glioma/cirurgia , Glioma/patologia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/patologia , Encéfalo/patologia , Procedimentos Neurocirúrgicos/métodos
6.
J Biochem Mol Toxicol ; 37(3): e23282, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36541366

RESUMO

Melanoma is the most aggressive and lethal type of skin cancer, characterized by therapeutic resistance. In this context, the present study aimed to investigate the cytotoxic potential of manool, a diterpene from Salvia officinalis L., in human (A375) and murine (B16F10) melanoma cell lines. The analysis of cytotoxicity using the XTT assay showed the lowest IC50 after 48 h of treatment with the manool, being 17.6 and 18.2 µg/ml for A375 and B16F10, respectively. A selective antiproliferative effect of manool was observed on the A375 cells based on the colony formation assay, showing an IC50 equivalent to 5.6 µg/ml. The manool treatments led to 43.5% inhibition of the A375 cell migration at a concentration of 5.0 µg/ml. However, it did not affect cell migration in the B16F10 cells. Cell cycle analysis revealed that the manool interfered in the cell cycle of the A375 cells, blocking the G2/M phase. No changes in the cell cycle were observed in the B16F10 cells. Interestingly, manool did not induce apoptosis in the A375 cells, but apoptosis was observed after treatment of the B16F10 cells. Additionally, manool showed an antimelanoma effect in a reconstructed human skin model. Furthermore, in silico studies, showed that manool is stabilized in the active sites of the tubulin dimer with comparable energy concerning taxol, indicating that both structures can inhibit the proliferation of cancer cells. Altogether, it is concluded that manool, through the modulation of the cell cycle, presents a selective antiproliferative activity and a potential antimelanoma effect.


Assuntos
Diterpenos , Melanoma , Neoplasias Cutâneas , Humanos , Animais , Camundongos , Linhagem Celular Tumoral , Melanoma/metabolismo , Diterpenos/farmacologia , Apoptose , Técnicas de Cultura de Células , Proliferação de Células
7.
Arq. ciências saúde UNIPAR ; 27(6): 3063-3078, 2023.
Artigo em Português | LILACS-Express | LILACS | ID: biblio-1437413

RESUMO

Este estudo teve como objetivo identificar os principais desafios enfrentados por pessoas com Transtorno do Espectro Autista (TEA) na vida adulta. Trata-se de uma revisão integrativa abrangendo artigos publicados entre os anos de 2017 e 2022, disponíveis nas bases de dados: Scopus, PubMed e a Biblioteca Virtual em Saúde. Após a seleção e a organização dos estudos, o corpus foi constituído por oito artigos que abordavam esses desafios de pessoas adultas com TEA e suas experiências no âmbito da saúde, polifarmácia, socialização e a correlação com outros transtornos psiquiátricos. Os estudos contribuíram para um entendimento sobre as problemáticas enfrentadas pelo grupo, somado às suas necessidades e percepções, apontando a carência de apoio na transição para a vida adulta, a escassez de qualificação profissional na assistência a pessoas com TEA e a ausência de adaptações do ambiente para com os indivíduos, coadjuvando com o aumento de transtornos mentais e isolamento social.


This study aimed to identify the main challenges faced by people with Autistic Spectrum Disorder (ASD) in adulthood. This is an integrative review covering articles published between the years 2017 and 2022, available in the databases: Scopus, PubMed and the Virtual Health Library. After the selection and organization of the studies, the corpus consisted of eight articles that addressed these challenges of adult people with ASD and their experiences in the realm of health, polypharmacy, socialization, and the correlation with other psychiatric disorders. The studies contributed to an understanding of the problems faced by the group, in addition to their needs and perceptions, pointing out the lack of support in the transition to adulthood, the lack of professional qualification in assisting people with ASD, and the lack of adaptations of the environment for individuals, contributing to the increase of mental disorders and social isolation.


Este estudio tuvo como objetivo identificar los principales desafíos que enfrentan las personas con trastorno del espectro autista (TEA) en la edad adulta. Se trata de una revisión integradora que abarca artículos publicados entre los años 2017 y 2022, disponibles en las bases de datos: Scopus, PubMed y Biblioteca Virtual de Salud. Tras la selección y organización de los estudios, el corpus quedó compuesto por ocho artículos que abordaron estos retos de las personas adultas con TEA y sus experiencias en el contexto de la salud, la polifarmacia, la socialización y la correlación con otros trastornos psiquiátricos. Los estudios contribuyeron para la comprensión de los problemas enfrentados por el grupo, sumados a sus necesidades y percepciones, señalando la falta de apoyo en la transición para la edad adulta, la falta de cualificación profesional en la asistencia a las personas con TEA y la falta de adaptaciones del ambiente para los individuos, contribuyendo para el aumento de los trastornos mentales y del aislamiento social.

8.
Fish Physiol Biochem ; 48(6): 1449-1462, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36480096

RESUMO

The objective of this work was to develop a food additive for the sex reversal of Nile tilapia (Oreochromis niloticus) based on a simple oil in water (O/W) nanoemulsion with testosterone propionate for incorporation into commercial feed. Oil screening and evaluation of the organoleptic and physicochemical characteristics were carried out to determine the best formulation. A palatability test was also performed. Sex reversal test was assayed using 5 experimental groups: negative control - macerated feed without hormone; free testosterone - macerated feed with 60 mg/kg of testosterone propionate diluted in ethanol; and macerated feed with testosterone propionate nanoemulsion at a concentration of 30, 60, and 90 mg/kg. Stable nanoemulsions (size 76-210 nm) with testosterone propionate were produced. All nanoemulsion-added feed was palatable to tilapia. We obtained sex reversal values of ≈65, 75, and 72% in the groups of 30, 60, and 90 mg/kg, respectively. We can conclude that the nanoemulsion showed promising results; it is capable of inducing sex reversal in tilapia, is suitable as a commercial product, and has the potential to promote safety for rural staff and reduce the environmental impact of hormones.


Assuntos
Ciclídeos , Propionato de Testosterona , Tilápia , Animais , Testosterona , Ração Animal
9.
Toxicol Res (Camb) ; 11(5): 750-757, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36337250

RESUMO

INTRODUCTION: Red propolis is synthetized from exudates of Dalbergia ecastophyllum (L) Taub. and Symphonia globulifera L.f., presents isoflavones, guttiferone E, xanthochymol, and oblongifolin B and has anti-inflammatory, antioxidant, and antiproliferative activities. OBJECTIVES: This study aimed to evaluate the antigenotoxic and anticarcinogenic potential of red propolis hydroalcoholic extract (RPHE) in rodents. METHODS: The influence of RPHE in doxorubicin (DXR)-induced genotoxicity was investigated through the micronucleus test in Swiss mice. Blood samples were also collected to investigate oxidative stress, hepatotoxicity, and nephrotoxicity. Was investigated the influence of RPHE in 1,2-dimethylhydrazine (DMH)-induced aberrant crypt foci, as well as its influence in proliferating cell nuclear antigen (PCNA) and the cyclooxygenase-2 (COX-2) expression in colon of rats, by immunohistochemistry. RESULTS: The results showed that RPHE (48 mg/kg) reduced DXR-induced genotoxicity. Animals treated with DXR showed significantly lower GSH serum levels in comparison to the negative control. RPHE treatments did not attenuated significantly the DXR-induced GSH depletion. No difference was observed in cytotoxicity parameters of mice hematopoietic tissues between the treatment groups, as well as the biochemical parameters of hepatotoxicity and nephrotoxicity. RPHE (12 mg/kg) reduced the DMH-induced carcinogenicity and toxicity, as well as DMH-induced PCNA and COX-2 expression in colon tissue. CONCLUSION: Therefore, was observed that the RPHE has chemopreventive effect, associated to antiproliferative and anti-inflammatory activities.

10.
World Neurosurg ; 166: 168, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35953036

RESUMO

Sylvian arteriovenous malformations (sAVMs) are rare and account for approximately 8%-11% of all intracranial arteriovenous malformations (AVMs).1 Because of their proximity to eloquent structures such as the motor speech center, insular cortex, and internal capsule, microsurgical resection of sAVMs remains a challenge. Several classifications have already been suggested for sAVMs, such as Sugita and Yasargil.1,2 It is well established that for low-grade AVMs, results of the microsurgical resection are excellent and tend to favor surgery,1-3 but in high-grade AVM, a multimodal assessment is necessary for formulating treatment strategies.1 In Video 1, we demonstrate the surgical resection of a ruptured sylvian temporal AVM. This AVM was localized in the superior surface of the temporal lobe, and its nidus was just beneath the cortical surface of this lobe. Because it was 5.1 cm at its largest diameter, had a deep drainage vein, and was localized adjacent to the Wernicke area, we classified it as a Spetzler-Martin grade IV AVM.4 Despite the high-grade AVM, microsurgical treatment was the choice in this ruptured AVM and there was no increase in morbidity.


Assuntos
Embolização Terapêutica , Malformações Arteriovenosas Intracranianas , Humanos , Malformações Arteriovenosas Intracranianas/diagnóstico por imagem , Malformações Arteriovenosas Intracranianas/cirurgia , Microcirurgia/métodos , Lobo Temporal/cirurgia , Resultado do Tratamento
11.
Cogit. Enferm. (Online) ; 27: e80433, Curitiba: UFPR, 2022. tab
Artigo em Português | LILACS, BDENF - Enfermagem | ID: biblio-1394313

RESUMO

RESUMO Objetivo: construir e validar um cenário de simulação clínica sobre a testagem rápida e aconselhamento para o HIV em gestantes. Método: estudo metodológico, de validação de aparência e conteúdo, desenvolvido no período de junho a outubro de 2020 por meio da técnica Delphi. Para a validação, foram incluídos os juízes que obtiveram cinco ou mais pontos segundo os critérios de Fehring adaptados. Os dados foram analisados mediante o cálculo do Índice de Validade de Conteúdo (IVC). Resultados: depois da primeira rodada Delphi, dois itens (5,7%) não atingiram o I-CVI necessário para validação em todos os critérios avaliados, que foram: comportamental, objetividade, simplicidade, clareza, relevância, precisão, variedade, modalidade, tipicidade e credibilidade. Ao final da segunda rodada Delphi, todos os itens (100%) atingiram o I-CVI necessário para validação. Conclusão: o roteiro se mostrou válido, contribuindo para subsidiar o ensino da testagem e do aconselhamento de gestante sobre o HIV.


ABSTRACT Objective: to construct and validate a clinical simulation scenario on rapid HIV testing and counseling in pregnant women. Method: methodological study, of appearance and content validation, developed between June and October 2020 through the Delphi technique. For validation, the judges who obtained five or more points according to the adapted Fehring criteria were included. The data were analyzed by calculating the Content Validity Index (CVI). Results: After the first Delphi round, two items (5.7%) did not reach the I-CVI required for validation in all the criteria evaluated, which were: behavioral, objectivity, simplicity, clarity, relevance, accuracy, variety, modality, typicality, and credibility. At the end of the second Delphi round, all items (100%) reached the I-CVI required for validation. Conclusion: the script proved to be valid, contributing to subsidize the teaching of HIV testing and counseling of pregnant women.


RESUMEN Objetivo: construir y validar un escenario de simulación clínica sobre pruebas rápidas y asesoramiento para el VIH en mujeres embarazadas. Método: estudio metodológico, de valoración de la apariencia y el contenido, desarrollado en el período de junio a octubre de 2020 mediante la técnica Delphi. Para la validación, se incluyeron los jueces que obtuvieron cinco o más puntos según los criterios adaptados de Fehring. Los datos se analizaron calculando el Índice de Validez del Contenido (IVC). Resultados: Tras la primera ronda Delphi, dos ítems (5,7%) no alcanzaron el I-CVI requerido para la validación en todos los criterios evaluados, que fueron: comportamiento, objetividad, simplicidad, claridad, relevancia, precisión, variedad, modalidad, tipicidad y credibilidad. Al final de la segunda ronda Delphi, todos los ítems (100%) alcanzaron el I-CVI requerido para la validación. Conclusión: el rodillo se mostró válido, contribuyendo a subvencionar la enseñanza de la prueba y el asesoramiento de gestores sobre el VIH.


Assuntos
Humanos , Feminino , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Infecções por HIV/diagnóstico , Aconselhamento Diretivo/métodos , Treinamento por Simulação/métodos , Teste de HIV/métodos , Reprodutibilidade dos Testes , Técnica Delfos , Simulação de Paciente
12.
Eur J Pharm Sci ; 173: 106173, 2022 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-35331860

RESUMO

Amphotericin B (AmB) has been the gold standard to treat systemic fungal infections. The use of AmB is restricted to hospitals because it poses several risks, mainly risks related to its high nephrotoxicity. Given the importance of this drug in medicine, new therapeutics and AmB formulations with nanotechnological improvements are required and could bring many benefits to patients. A new drug formulation with gastro-resistant coated granules has been proposed. The lipid-based system containing AmB was produced and used as raw material in the granulation/coated process. The new developed formulation (AmB-NP-GR) was characterized by optical microscopy, granulometry, and atomic force microscopy (AFM) after disintegration test. AmB-NP-GR showed granular shape, with most granules measured between 250 and 500 µm (37 ± 7% w/w). The AFM images indicated that the granule formulation should disintegrate in the intestine, to release the lipid-based carriers, making them available for absorption and allowing them to reach the blood circulation. The developed formulation was administered to rats in a single dose of 4.0 or 8.0 mg kg-1 and the pharmacokinetics was studied. The samples were analyzed by liquid chromatography coupled to mass spectrometry. Before the pharmacokinetic studies were conducted, the bioanalytical method was validated according to the EMA guideline and all evaluated parameters agreed with this guideline. The pharmacokinetic results showed that Cmax was similar for both doses and that tmax was reached at 4-12 h for dose of 4.0 mg kg-1 and 4 h for dose of 8.0 mg kg-1. The half-life related to the dose of 8.0 mg kg-1 increased significantly compared to the dose of 4.0 mg kg-1 (an increase of more than 3 times). In addition, the mean residence time related to the dose of 8.0 mg kg-1 was 4 times higher than for the lower dose. The clearance value showed to be higher for the lower dose. Together, these results provide important conclusions for experimental design of other in vivo safety and efficacy studies of AmB-NP-GR.


Assuntos
Leishmaniose , Micoses , Anfotericina B/química , Animais , Antifúngicos/química , Humanos , Leishmaniose/tratamento farmacológico , Lipídeos/química , Micoses/tratamento farmacológico , Ratos
13.
J Pharm Pharmacol ; 74(5): 740-749, 2022 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-35299250

RESUMO

OBJECTIVES: Dalbergia ecastaphyllum (L.) Taub. is a semi-prostrate species associated with estuaries, mangroves and dunes. This plant species has great ecological and economic importance, especially concerning apiculture pasture and Brazilian red propolis production. In this study, non-clinical toxicological evaluations of the hydroalcoholic extract of D. ecastaphyllum stems (DEHE), the resin production source, were conducted. In addition, the action of DEHE on genomic instability and colon carcinogenesis was investigated. METHODS AND RESULTS: The extract's chemical profile was analysed by HPLC, and medicarpin, vestitol and neovestitol were found as major compounds. DEHE showed an IC50 equivalent to 373.2 µg/ml and LC50 equal 24.4 mg/L, when evaluated using the XTT colorimetric test and the zebrafish acute toxicity assay, respectively. DEHE was neither genotoxic nor cytotoxic at the highest dose, 2000 mg/kg, by peripheral blood micronucleus test. The treatments DEHE (6 and 24 mg/kg) led to the reduction of micronuclei induced by doxorubicin (DXR) in mice. Furthermore, significantly higher serum levels of reduced glutathione were observed in animals treated with DEHE plus DXR, revealing an antioxidant effect. Treatments with DEHE (48 mg/kg) led to a significant reduction in pre-neoplastic lesions induced by the 1,2-dimethylhydrazine (DMH) carcinogen in the rat colon. Immunohistochemical analysis revealed significantly lower levels of expression of COX-2 (86%) and PCNA (83%) in the colon of rats treated with DEHE plus DMH, concerning those treated with the carcinogen. CONCLUSIONS: These results indicate the involvement of anti-inflammatory and antiproliferative pathways in the protective effect of DEHE.


Assuntos
Dalbergia , Própole , Animais , Camundongos , Ratos , Brasil , Carcinógenos , Quimioprevenção , Dalbergia/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Própole/química , Própole/farmacologia , Peixe-Zebra
14.
J Nat Prod ; 85(2): 426-432, 2022 02 25.
Artigo em Inglês | MEDLINE | ID: mdl-35157797

RESUMO

The manool diterpene, found in abundance in Salvia officinalis L., showed a selective cytotoxic effect against murine melanoma cells. Therefore, the present study aimed to evaluate the antitumor potential of manool in a murine melanoma model, administered by three routes: oral, subcutaneous, and intraperitoneal. In addition, the antimelanoma effect of manool (orally) combined with cisplatin (subcutaneous) was evaluated. The results obtained revealed that manool, administered by the three routes, was able to significantly decrease the mass and frequency of mitosis of the tumor tissue. The data obtained revealed that manool, at a dose of 20 mg/kg, was able to significantly decrease the tumor mass when administered by the three routes, with the percentages of reduction being equivalent to 62.4% (oral), 48.5% (intraperitoneal), and 38.8% (subcutaneous), without toxic effects. The treatment of manool plus cisplatin led to 86.7% reduction in tumor mass, higher than that observed in treatment with manool or cisplatin alone (50.7%), although signs of toxicity have been observed. The results also showed that treatments with manool (20 mg/kg orally) and/or cisplatin did not alter the activity of caspase 3 cleaved in tumor tissue. Therefore, manool revealed a promising antimelanoma effect, but without involvement of the caspase 3 cleaved pathway.


Assuntos
Diterpenos , Melanoma , Animais , Caspase 3 , Cisplatino/farmacologia , Diterpenos/farmacologia , Diterpenos/uso terapêutico , Melanoma/tratamento farmacológico , Camundongos
15.
J Biochem Mol Toxicol ; 35(12): e22917, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34541749

RESUMO

Phytochemicals have been suggested as an effective strategy for cancer prevention. Within this context, triterpene betulinic acid (BA) exhibits several biological properties but its chemopreventive effect has not been fully demonstrated. The present study investigated the antigenotoxic potential of BA against doxorubicin (DXR)-induced genotoxicity using the mouse peripheral blood micronucleus assay, as well as its anticarcinogenic activity against 1,2dimethylhydrazine (DMH)-induced colorectal lesions in rats. Micronuclei (MN) assay and aberrant crypt foci assay were used to assess the antigenotoxic and the anticarcinogenic potential, respectively. The molecular mechanisms underlying the anticarcinogenic activity of BA were evaluated by assessing anti-inflammatory (COX-2) and antiproliferative (PCNA) pathways. The results demonstrated that BA at the dose of 0.5 mg/kg bodyweight exerted antigenotoxic effects against DXR, with a reduction of 70.2% in the frequencies of chromosomal damage. Animals treated with BA showed a 64% reduction in the number of preneoplastic lesions when compared to those treated with the carcinogen alone. The levels of COX-2 and PCNA expression in the colon were significantly lower in animals treated with BA and DMH compared to those treated with the carcinogen alone. The chemopreventive effect of BA is related, at least in part, to its antiproliferative and anti-inflammatory activity, indicating a promising potential of this triterpene in anticancer therapies, especially for colorectal cancer.


Assuntos
Anticarcinógenos/farmacologia , Antimutagênicos/farmacologia , Inibidores de Ciclo-Oxigenase 2/farmacologia , Ciclo-Oxigenase 2/efeitos dos fármacos , Triterpenos Pentacíclicos/farmacologia , Antígeno Nuclear de Célula em Proliferação/efeitos dos fármacos , Animais , Proliferação de Células/efeitos dos fármacos , Neoplasias Colorretais/induzido quimicamente , Neoplasias Colorretais/prevenção & controle , Ciclo-Oxigenase 2/metabolismo , Doxorrubicina/toxicidade , Inflamação/prevenção & controle , Masculino , Camundongos , Lesões Pré-Cancerosas/induzido quimicamente , Lesões Pré-Cancerosas/prevenção & controle , Transdução de Sinais/efeitos dos fármacos , Ácido Betulínico
16.
BMC Infect Dis ; 21(1): 827, 2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34404348

RESUMO

BACKGROUND: According to the literature, 25% to 50% of antimicrobials prescribed in hospitals are unnecessary or inappropriate, directly impacting antimicrobial resistance. Thus, the present study aimed to evaluate the use of antimicrobials in a university hospital in Northeast Brazil, using days of therapy (DOT) and length of therapy (LOT) indicators in accordance with the latest national and international recommendations for monitoring the use of antimicrobials. METHODS: This is an observational, prospective analytical study conducted in a teaching hospital, with 94 active beds, distributed between the intensive care unit (ICU), the surgical clinic (SUR), the medical clinic (MED), the pneumology/infectology department (PNE/INF) and pediatrics (PED). The duration of the study was from the beginning of January to the end of December 2018. RESULTS: During the study period, a total of 11,634 patient-days were followed up and 50.4% of the patients were found to have received some antimicrobial, with a significant reduction in use of 1% per month throughout the year. Patients were receiving antimicrobial therapy for 376 days in every 1000 days of hospitalization (LOT = 376/1000pd). Overall, the 1st-generation cephalosporins and fluoroquinolones were the most used in respect of the number of prescriptions and the duration of therapy. The calculated global DOT/LOT ratio showed that each patient received an average of 1.5 antimicrobials during the hospital stay. The incidence of antimicrobial resistance, globally, for both methicillin-resistant Staphylococcus aureus (methicillin R), Carbapenem-resistant Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii (Carbapenem R), was 1 per 1000 patient-days. CONCLUSIONS: The results obtained from the analyses revealed that half of the patients admitted to the hospital who took part in the study were exposed to the use of antimicrobials at some point during their stay. Although moderate, it is noteworthy that there was a decline in the use of antimicrobials throughout the year. The indicators used in this study were found to be very effective for gathering data on the use of antimicrobials, and assessing the results of the initiatives taken as part of the Stewardship program.


Assuntos
Anti-Infecciosos , Staphylococcus aureus Resistente à Meticilina , Antibacterianos/uso terapêutico , Carbapenêmicos , Criança , Hospitais , Humanos , Estudos Prospectivos
17.
Rev. enferm. UFPE on line ; 15(1): [1-14], jan. 2021. ilus, tab
Artigo em Português | BDENF - Enfermagem | ID: biblio-1145809

RESUMO

Objetivo: verificar, na literatura, as características das consultas de pré-natal às gestantes para oferecimento do teste rápido para o Vírus da Imunodeficiência Humana. Método: trata-se de um estudo bibliográfico, descritivo, tipo revisão integrativa da literatura, sem limite temporal, realizado por meio das bases de dados BDENF, LILACS, MEDLINE, CINAHL, Scopus e Web of Science. Incluíram-se artigos originais em português, inglês ou espanhol. Analisaram-se os dados de forma descritiva. Resultados: identificaram-se 1726 publicações, das quais dez compuseram a amostra. Verificaram-se, em geral, as características do estudo e as estratégias para a melhoria das consultas, do aconselhamento e do oferecimento de testes efetivos. Conclusão: conclui-se que a análise dos estudos permitiu a síntese de características, conteúdos, recursos e técnicas de abordagem, além de lacunas e dificuldades tanto dos profissionais quanto das gestantes para a efetivação do aconselhamento para a execução dos testes rápidos para o Vírus da Imunodeficiência Humana em gestantes.(AU)


Objective: to verify, in the literature, the characteristics of prenatal consultations to pregnant women to offer the rapid test for the Human Immunodeficiency Virus. Method: It is a bibliographic, descriptive, integrative literature review type study, without time limit, carried out through the BDENF, LILACS, MEDLINE, CINAHL, Scopus and Web of Science databases. Original articles in Portuguese, English or Spanish are included. The data were analyzed in a descriptive manner. Results: 1726 publications were identified, of which ten composed the sample. In general, the characteristics of the study and the strategies for the improvement of consultations, counseling and offer of effective tests were verified. Conclusion: it is concluded that the analysis of the studies allowed the synthesis of characteristics, contents, resources and techniques of approach, besides gaps and difficulties of both professionals and pregnant women for the realization of counseling for the execution of rapid tests for the Human Immunodeficiency Virus in pregnant women.


Objetivo: verificar, en la literatura, las características de las consultas prenatales a gestantes para ofrecer la prueba rápida del Virus de Inmunodeficiencia Humana. Método: se trata de una revisión bibliográfica, descriptiva, integradora de la literatura, sin límite de tiempo, realizada utilizando las bases de datos BDENF, LILACS, MEDLINE, CINAHL, Scopus y Web of Science. Se incluyeron artículos originales en portugués, inglés o español. Los datos se analizaron de forma descriptiva. Resultados: se identificaron 1726 publicaciones, de las cuales diez componen la muestra. En general, se verificaron las características del estudio y las estrategias para mejorar las consultas, el asesoramiento y la oferta de pruebas efectivas. Conclusión: se concluye que el análisis de los estudios permitió la síntesis de características, contenidos, recursos y técnicas de abordaje, además de vacíos y dificultades tanto de los profesionales como de las gestantes para la efectividad del asesoramiento para la ejecución de las pruebas rápidas para el Virus de la Inmunodeficiencia Humana en mujeres embarazadas.(AU)


Assuntos
Humanos , Feminino , Gravidez , Cuidado Pré-Natal , Atenção Primária à Saúde , Infecções por HIV , Infecções por HIV/diagnóstico , Síndrome de Imunodeficiência Adquirida , HIV , Gestantes , Saúde Materna , MEDLINE , LILACS
18.
Trans R Soc Trop Med Hyg ; 115(8): 854-862, 2021 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-33205148

RESUMO

BACKGROUND: Leptospirosis is an endemic disease in Brazil of social and economic relevance related to behavioural and socioenvironmental factors. This study aimed to analyse the spatiotemporal distribution of the incidence of leptospirosis and its association with social determinants in health in a state of northeastern Brazil. METHODS: An ecological study of temporal series with techniques of spatial analysis using secondary data of the cases of leptospirosis notified in the Information System of Notifiable Diseases of the state of Sergipe (2008-2017) was conducted. The analysis of temporal trends was performed using Poisson regression. Spatial analyses were performed using the Moran index, the local empirical Bayesian model, scan statistics and spatial regression. RESULTS: The incidence rate decreased from 3.66 to 1.44 cases per 100 000 inhabitants in 2008 and 2017, respectively. Leptospirosis was associated with social inequities, mostly affecting males aged 20-49 y living in urban areas. The space-time scan indicated the formation of a risk cluster in municipalities in the metropolitan region of the state. CONCLUSIONS: The data indicated the persistence of leptospirosis transmission, maintaining a pattern of high endemicity in some municipalities associated with social inequities. The study showed the temporal and spatial dynamics of the disease to better target specific actions for prevention and control.


Assuntos
Leptospirose , Teorema de Bayes , Brasil/epidemiologia , Cidades , Análise por Conglomerados , Humanos , Incidência , Leptospirose/epidemiologia , Masculino , Estudos Retrospectivos , Fatores de Risco , Análise Espacial , Análise Espaço-Temporal
19.
Arch. Health Sci. (Online) ; 27(1): 70-75, jan-mar.2020.
Artigo em Português | LILACS-Express | LILACS | ID: biblio-1369546

RESUMO

Introdução: O ensino da ciência da enfermagem passa por um momento de transmutação para empreender componentes curriculares que superem o conceito médio de qualidade. Sendo assim, a simulação clínica adquire importância crescente, pois se utiliza de tecnologias para reproduzir cenários que simulam a prática, em ambiente controlado e realista, permitindo o alinhamento da prática à teoria, a atualização das técnicas do cuidado, reflexão sobre o saber fazer e como está fazendo, ganho de confiança, desenvolvimento da agilidade, além de enriquecer a vivência clínica a partir da experimentação de situações diversas. Objetivo: Identificar as características e repercussões do uso da simulação como estratégia para o ensino-aprendizagem em enfermagem. Métodos: Revisão integrativa da literatura realizada no período de novembro a dezembro de 2019, nas bases de dados BDENF, LILACS e PUBMED, por meio dos descritores enfermagem, simulação, ensino, aprendizagem e educação. Foram encontradas 362 publicações, das quais 14 fizeram parte da amostra final. Para análise dos estudos foi construído um quadro contendo as principais características dos trabalhos. Resultados: Identificaram-se estudos que abordaram os modelos de simuladores, as temáticas de aplicação dos cenários e as consequências de sua aplicação. Foi unânime a identificação dos benefícios nas habilidades cognitivas e não cognitivas gerados pela implementação da estratégia de ensino simulado. Verificou-se que a maior parte dos estudos realizou a simulação de alta fidelidade (42,9%), seguida pela de baixa fidelidade (35,7%) e o paciente simulado (7,1%). Constatou-se que os estudos abordaram as seguintes temáticas: dor, imunização e atendimento ao hipertenso, ressuscitação cardiopulmonar, problemas respiratórios, diabetes, avaliação cardiotorácica, feridas, e saúde mental. Quanto às repercussões, pode-se destacar estímulo ao estímulo ao pensamento crítico-reflexivo, crescimento pessoal e profissional, melhoria da destreza na realização de procedimentos, favorece ensino clínico de maneira humana e holística, favorece relação interpessoal e a comunicação. Conclusão: O estudo possibilitou identificar as características e repercussões do uso da simulação como estratégia de ensinoaprendizagem em enfermagem.

20.
J Toxicol Environ Health A ; 83(21-22): 673-686, 2020 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-32886024

RESUMO

Licochalcone A (LicoA) is a flavonoid derived from Glycyrrhiza spp. plants. The present study aimed to investigate the antioxidant, cytotoxic, genotoxic, and chemopreventive effects of LicoA in in vitro and in vivo systems. The results showed that LicoA (197.1 µM) scavenged 77.92% of free radicals. Concentrations of 147.75 µM or higher LicoA produced cytotoxicity in Chinese hamster ovary (CHO) fibroblasts. LicoA treatments of 4.43 to 10.34 µM did not exert genotoxic activity, but at 11.8 µM significantly lowered nuclear division indexes, compared to negative control, revealing cytotoxicity. Lower concentrations (1.85 to 7.39 µM) exhibited protective activity against chromosomal damage induced by doxorubicin (DXR) or methyl methanesulfonate (MMS) in CHO cells. LicoA exerted no marked influence on DXR-induced genotoxicity in mouse erythrocytes, but reduced pre-neoplastic lesions induced by 1,2-dimethylhydrazine (DMH) in rat colon at 3.12 to 50 mg/kg b.w. Biochemical markers and body weight indicated no apparent toxicity. These findings contribute to better understanding the mechanisms underlying LicoA-initiated activity as a promising chemopreventive compound. ABBREVIATIONS: AC, aberrant crypts; ACF, aberrant crypt foci; ALT, alanine aminotransferase; AST, aspartate aminotransferase; BOD, biochemical oxygen demand; CHO, Chinese hamster ovary fibroblast; DMH, 1,2-dimethylhydrazine; DMSO, dimethyl sulfoxide; DPPH, 2,2-diphenyl-1-picrylhydrazyl; DXR, doxorubicin hydrochloride; EDTA, ethylenediaminetetraacetic acid; GA, gallic acid; LicoA, licochalcone A; MMS, methyl methanesulfonate; MNBC, micronucleated binucleated cells; MNPCE, micronucleated polychromatic erythrocyte; NCE, normochromatic erythrocyte; NDI, nuclear division index; PBS, phosphate-buffered saline; PCE, polychromatic erythrocyte; XTT, 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide.


Assuntos
Antioxidantes/farmacologia , Chalconas/farmacologia , Citotoxinas/farmacologia , Mutagênicos/farmacologia , Substâncias Protetoras/farmacologia , Animais , Masculino , Camundongos
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