Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 29
Filtrar
1.
Int J Mol Sci ; 25(10)2024 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-38791472

RESUMO

Yellow pitahaya is a tropical fruit that has gained popularity in recent years. Natural elicitors are compounds that can stimulate the resistance and quality of fruits. The objective of this study was to evaluate the effects of natural elicitors, methyl salicylate (MeSa), methyl jasmonate (JaMe), salicylic acid (SA) and oxalic acid (OA) at concentrations of 0.1 mM (MeSa and JaMe) and 5 mM (SA and OA), applied to the yellow pitahaya fruits under greenhouse conditions. After full blossom, four applications were made with a frequency of 15 days. At the time of harvest and after storage, the following variables were evaluated: firmness (whole fruit), total soluble solids (TSS), total acidity (TA), phenolics and carotenoids (in the pulp), while phenolics, carotenoids, macronutrients and micronutrients were determined in the peel. The results showed MeSa advanced the fruit maturation, according to higher TSS, lower TA and firmness than MeJa-treated fruits, for which a delayed ripening process was shown. All treatments induced a higher polyphenolic concentration during storage. Regarding the alternative use of the peel as a by-product, the application of natural elicitors significantly increased the content of polyphenols, carotenoids, macronutrients and micronutrients in the peel, especially MeSa, which can be used as a bioactive compound in the food industry. In conclusion, the results indicate that natural elicitors can be an alternative to improve the quality and shelf life of yellow pitahaya fruits.


Assuntos
Acetatos , Cactaceae , Carotenoides , Ciclopentanos , Armazenamento de Alimentos , Frutas , Oxilipinas , Ácido Salicílico , Frutas/química , Frutas/efeitos dos fármacos , Frutas/metabolismo , Frutas/crescimento & desenvolvimento , Oxilipinas/farmacologia , Ciclopentanos/farmacologia , Ciclopentanos/metabolismo , Acetatos/farmacologia , Carotenoides/metabolismo , Armazenamento de Alimentos/métodos , Cactaceae/química , Cactaceae/crescimento & desenvolvimento , Cactaceae/metabolismo , Ácido Salicílico/farmacologia , Salicilatos/farmacologia , Salicilatos/metabolismo , Fenóis/análise , Ácido Oxálico/metabolismo
2.
Food Chem Toxicol ; 177: 113852, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37244598

RESUMO

The ostrich oil (OO) has been topically used for decades to treat skin diseases. Its oral use has been encouraged through e-commerce advertising several health benefits to OO without scientific evidence on its safety or effectiveness. This study presents the chromatographic profile of a commercially available OO and its acute and 28-day repeated dose in vivo toxicological profiles. OO anti-inflammatory and antinociceptive effects were also investigated. Omega-9 (ω-9; oleic acid; 34.6%) and -6 (linoleic acid; 14.9%) were detected as OO main constituents. A high single dose of the OO (2 g/kg of ω-9) demonstrated no or low acute toxicity. However, when orally treated with OO (30-300 mg/kg of ω-9) for 28 consecutive days, mice exhibited altered locomotor and exploratory activities, hepatic damage, and increased hindpaw sensitivity accompanied by increased levels of cytokine and brain-derived neurotrophic factor in their spinal cords and brains. Lack of anti-inflammatory or antinociceptive activities was also evidenced in 15-day-OO treated mice. These results indicate that chronic consumption of OO induces hepatic injury, in addition to neuroinflammation and subsequent hypersensitivity and behavioural changes. Thus, there is no evidence to support OO use to treating illness in humans.


Assuntos
Struthioniformes , Humanos , Animais , Camundongos , Azeite de Oliva/química , Doenças Neuroinflamatórias , Testes de Toxicidade , Analgésicos/toxicidade
3.
Inflammopharmacology ; 30(6): 2489-2504, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35867292

RESUMO

The effects of Piper malacophyllum (C. Pesl) C. DC extracts and its isolated compounds were analysed in a mouse model of primary dysmenorrhoea (PD). Female Swiss mice (6-8 weeks old) on proestrus were intraperitoneally treated with estradiol benzoate for 3 days, to induce PD. Twenty-four hours later, animals were treated 24 h later with vehicle, plant extract, gibbilimbol B, 4,6-dimethoxy-5-E-phenylbutenolide, mixture of 4,6-dimethoxy-5-E-phenylbutenolide and 4,6-dimethoxy-5-Z-phenylbutenolide, or ibuprofen. One hour later, oxytocin was injected and the numbers of abdominal writhing were counted. Then, mice were euthanized and uteri were collected for morphometrical and histological analyses. The effects of P. malacophyllum in inflammation were investigated in mouse peritoneal neutrophils culture stimulated with LPS or fMLP (chemotaxis and mediator release). Finally, uterus contractile and relaxing responses were assessed. Similar to ibuprofen, P. malacophyllum extract and isolated compounds reduced abdominal writhing in mice with PD. Histology indicated a marked neutrophil and mast cell infiltrate in the uterus of PD animals which was attenuated by the extract. The compounds and the extract reduced neutrophil chemotaxis and inflammatory mediator release by these cells. Reduced TNF levels were also observed in uteri of PD mice treated with P. malacophyllum. The extract did not affect spontaneous uterine contractions nor those induced by carbachol or KCl. However, it caused relaxation of oxytocin-induced uterine contraction, an effect blunted by H1 receptor antagonist. Overall the results indicate that P. malacophyllum may represent interesting natural tools for reliving PD symptoms, reducing the triad of pain, inflammation and spasmodic uterus behaviour.


Assuntos
Dismenorreia , Piper , Extratos Vegetais , Animais , Feminino , Camundongos , Modelos Animais de Doenças , Dismenorreia/tratamento farmacológico , Ibuprofeno , Inflamação , Mastócitos , Neutrófilos , Ocitocina/farmacologia , Piper/química , Extratos Vegetais/farmacologia
4.
Rev. Fac. Nac. Salud Pública ; 40(1): e5, ene.-abr. 2022. tab, graf
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1394643

RESUMO

Resumen Objetivo: Presentar el estudio mediante el cual se construyó una ruta integral de atención en salud (RIAS) para la atención del paciente amputado de miembro inferior por causas traumática, vascular o diabetes mellitus, cuyo fin es implementar las recomendaciones de la Guía de práctica clínica del paciente amputado y garantizar la atención integral en salud de esta población en Colombia. Con la ruta se pretende orientar a los actores involucrados en la ejecución de intervenciones individuales para el diagnóstico, el tratamiento y la rehabilitación, e impactar en los desenlaces en salud y equidad de esta población. Metodología: Este estudio responde a una estrategia de mejoramiento de la atención en salud. Para esto, se revisó el Manual metodológico para la elaboración e implementación de las RIAS; se creó el grupo desarrollador de la ruta; se priorizaron y describieron las intervenciones en función del proceso continuo de atención en salud; se evaluó la práctica asistencial actual con grupos focales de pacientes y profesionales; se formularon los resultados esperados en el proceso de gestión y atención en salud (hitos), y se elaboró el diagrama de la ruta. Resultados: A partir de la Guía de práctica clínica se elaboraron 25 intervenciones individuales priorizadas y caracterizadas según el actor responsable, la población objetivo y el entorno. Para cada una de las intervenciones se presentan resultados esperados en salud, calidad de prestación de servicios, aspectos relacionados con la equidad, y la perspectiva de pacientes y actores involucrados con la atención. Se construyeron los indicadores para el seguimiento e implementación de la ruta. Conclusión: Se construyó la primera ruta integral de atención en salud del paciente con amputación de miembro inferior, de acuerdo con los lineamientos del manual del Ministerio de Salud y de la Protección Social.


Abstract Objective: Build an Integral Health Care Pathway for the care of patients with lower limb amputation due to traumatic, vascular or diabetes mellitus causes, in order to implement the recommendations of the cpg for amputee patients and guarantee comprehensive health care for this population in Colombia. Methodology: This study is a strategy to improve health care. Carried out by a review of the Methodological Manual for the Development and Implementation of Comprehensive Health Care Pathway, then the development group was created. A process of prioritization and description of required individual interventions was developed based on health care. Evaluation of current care practice with focus groups, formulation of milestones and development of the intervention diagram. Results: 25 individual interventions were prioritized and characterized according to the responsible actor, target population and environment. Expected results in health, quality of service delivery, issues related to equity, as well as the perspective of patients and actors involved with care are shown. Indicators were built for monitoring and implementation of the pathway. Conclusion: With the previous results, the first Integral Health Care Pathway for the Lower Limb Amputee Patient was developed. It intends to guide the actors involved, when executing individual interventions for the diagnosis, treatment and rehabilitation, to impact outcomes in health and equity of this group .


Resumo Objetivo: Construir uma Rota de Atenção Integral à Saúde do Paciente Amputado do Membro Inferior por causas traumáticas, vasculares ou diabetes mellitus, com a finalização de implementar as recomendações do gpc do paciente amputado e garantir a atenção integral na saúde desta población em Colômbia. Metodologia: Este estudo responde a uma estratégia para melhorar os cuidados de saúde. Foi realizada uma revisão do Manual Metodológico para o Desenvolvimento e Implementação de Rotas Integrais de Atenção à Saúde, criação do grupo de desenvolvimento da rota. Um processo de priorização e descrição das intervenções individuais necessárias foi desenvolvido com base na continuidade dos cuidados de saúde. Avaliação da prática assistencial atual com grupos focais, formulação de marcos e desenvolvimento do diagrama de intervenção. Resultados: 25 intervenções individuais foram priorizadas e caracterizadas de acordo com o ator responsável, população-alvo e ambiente. Determinação dos resultados esperados em saúde, qualidade da prestação de serviços, questões relacionadas a equidade, bem como a perspectiva de pacientes e atores envolvidos no atendimento. Foram construídos indicadores para o monitoramento e implementação da rota. Conclusão: Com os resultados anteriores, foi construída a primeira Rota de Atenção Integral à Saúde do paciente com amputação de membros inferiores por causas traumáticas e neurovasculares, com sua implementação, visando orientar os atores envolvidos na execução de intervenções individuais para a diagnóstico, tratamento e reabilitação, impactar os resultados em saúde e eqüidade dessa população.

5.
J Ethnopharmacol ; 283: 114736, 2022 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-34648899

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Sambucus nigra L. is a plant of European origin and popularly known as elder, elderberry, black elder, European elder, European elderberry, and European black elderberry, being described in pharmacopoeia of several countries. Its flowers and berries have been used in folk medicine to treat feverish conditions, coughing, nasal congestion, and influenza besides its popular use as anti-inflammatory, analgesic, and diuretic agent. AIM OF THE STUDY: The aim of this investigation was to elucidate the anti-inflammatory and the relaxant effect of the lyophilized aqueous extract obtained from S. nigra's flowers on in vivo and in vitro inflammation assays and on the isolated rat vascular and airway smooth muscle tissue. MATERIAL AND METHODS: The anti-inflammatory activity of the extract was investigated using carrageenan-induced inflammation model in the subcutaneous tissue of male Swiss mice orally treated with S. nigra extract (30, 100, 300 or 600 mg/kg). Leukocyte influx and the secretion of chemical mediators were quantified in the inflamed exudate. Additionally, histological analysis of the pouches was performed. N-Formyl-methionine-leucine-phenylalanine-induced chemotaxis, lipopolysaccharide-induced TNF, IL-6, IL-1ß, IL-10 and NO production, and adhesion molecule expression (CD62L, CD49d and CD18, flow cytometry) were analyzed in vitro using oyster glycogen-recruited peritoneal neutrophils or macrophages (RAW 264.7) stimulated with LPS and treated with the extract (1, 10 or 100 µg/mL). The resolution of inflammation was accessed by efferocytosis assay, and the antinociceptive activity was investigated using carrageenan-induced mechanical hypersensitivity. Finally, the effect of the extract was evaluated in isolated rat aorta and trachea rings. RESULTS: The oral treatment with S. nigra promoted reduction in the neutrophil migration as well as the decrease of TNF, IL-1ß and IL-6 levels in the inflamed exudate. In vitro treatment with S. nigra decreased NO2-, TNF, IL-1ß and IL-6 and promoted increase of IL-10 in LPS-stimulated neutrophils. Similarly, the extract reduced the NO2-, TNF and IL-6 in LPS-stimulated macrophages. Rutin, the major constituent of S. nigra extract reduced NO2-, TNF, IL-1ß, and IL-6 and promoted the increase of IL-10 in LPS-stimulated neutrophils supernatant. The extract also shed CD62L and CD18 expressions. The extract was able to increase the efferocytosis of apoptotic neutrophils by increasing the IL-10 and decreasing the TNF levels. Additionally, the extract reduced the hypersensitivity induced by carrageenan and promoted a relaxant effect in isolated vascular and non-vascular rat tissue. CONCLUSIONS: S. nigra flowers extract presents anti-inflammatory effect by modulating macrophage and neutrophil functions including the production of inflammatory mediators and cell migration, by promoting efferocytosis and consequently the resolution of acute inflammation, besides exerting antinociceptive effects, scientifically proving its popular use as medicinal plant. Allied to the relaxant effect in both vascular and non-vascular smooth muscle tissue, S. nigra extract represents an important tool for the management of acute inflammation.


Assuntos
Anti-Inflamatórios/farmacologia , Inflamação/tratamento farmacológico , Extratos Vegetais/farmacologia , Sambucus nigra/química , Administração Oral , Animais , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/isolamento & purificação , Movimento Celular/efeitos dos fármacos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Flores , Macrófagos/efeitos dos fármacos , Macrófagos/patologia , Masculino , Camundongos , Neutrófilos/efeitos dos fármacos , Neutrófilos/metabolismo , Extratos Vegetais/administração & dosagem , Células RAW 264.7 , Ratos , Ratos Wistar
6.
J Immunol Res ; 2021: 9957451, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34337087

RESUMO

BACKGROUND: Solanum diploconos (Mart.) Bohs is a native Brazilian plant belonging to the Solanaceae family, popularly known as "tomatinho do mato" and poorly investigated. Herein, we presented for the first time evidence for the anti-inflammatory and wound healing activities of S. diploconos fruit hydroalcoholic extract. Material and Methods. In vitro fMLP-induced chemotaxis, LPS-induced inflammatory mediator levels (cytokines by ELISA and NO release by Griess reaction), and adhesion molecule expression (CD62L, CD49d, and CD18, by flow-cytometry) were assessed in neutrophils treated with different concentrations of the extract. Inflammation resolution was measured by the efferocytosis assay and the healing activity by in vivo and in vitro assays. The air pouch model of carrageenan-induced inflammation in Swiss mice was used to investigate the in vivo anti-inflammatory effects of the extract. Leukocyte influx (by optical microscopy) and cytokine release were quantified in the pouch exudates. Additionally, the acute and subacute toxic and genotoxic effects of the extract were evaluated. RESULTS: In vitro, the extract impaired neutrophil chemotaxis and its ability to produce and/or release cytokines (TNFα, IL-1ß, and IL-6) and NO upon LPS stimuli (p < 0.01). LPS-treated neutrophils incubated with the extract presented increased CD62L expression (p < 0.01), indicating a reduced activation. An enhanced efferocytosis of apoptotic neutrophils by macrophages was observed and accompanied by higher IL-10 and decreased TNFα secretion (p < 0.01). In vivo, similar results were noted, including reduction of neutrophil migration, protein exudation, and cytokine release (p < 0.01). Also, the extract increased fibroblast proliferation and promoted skin wound healing (p < 0.01). No signs of toxicity or genotoxicity were observed for the extract. CONCLUSION: S. diploconos fruit extract is anti-inflammatory by modulating neutrophil migration/activation as well macrophage-dependent efferocytosis and inflammatory mediator release. It also indicates its potential use as a healing agent. Finally, the absence of acute toxic and genotoxic effects reinforces its possible use as medicinal product.


Assuntos
Anti-Inflamatórios/farmacologia , Inflamação/tratamento farmacológico , Extratos Vegetais/farmacologia , Solanum/química , Cicatrização/efeitos dos fármacos , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/uso terapêutico , Carragenina/administração & dosagem , Carragenina/imunologia , Quimiotaxia de Leucócito/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Frutas/química , Humanos , Inflamação/imunologia , Masculino , Camundongos , Neutrófilos/efeitos dos fármacos , Neutrófilos/imunologia , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/uso terapêutico , Ratos , Testes de Toxicidade Aguda , Testes de Toxicidade Subaguda , Cicatrização/imunologia
7.
J Ethnopharmacol ; 267: 113487, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33091500

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Synadenium grantii Hook. f., popularly known as "janaúba" or "leiterinha", is used in the folk medicine to treat gastric disorders, some types of neoplasias and inflammatory diseases. AIM OF THE STUDY: The aim of this study was to show the anti-inflammatory activity of the methanol extract obtained from S. grantii stems and also certify the safety of the extract performing toxicological analysis. MATERIAL AND METHODS: The anti-inflammatory activity was investigated using carrageenan-induced inflammation in the subcutaneous tissue of male Swiss mice orally pre-treated with the S. grantii extract (1, 3 or 10 mg/kg). The leukocyte influx (optical microscopy) and secretion of chemical mediators (TNF, IL-6 and IL-1ß, by enzyme-linked immunosorbent assay) were quantified in the inflamed exudate. The toxicity was investigated using the dose-fixed procedure (acute toxicity) and repeated dose 28-day (subacute toxicity) in mice orally treated with S. grantii extract. The open field and rota-rod test were used to evaluate possible interference of adverse effect of S. grantii on motor coordination, locomotor and exploratory activity. RESULTS: The analysis of the inflammatory exudate of S. grantii-treated mice demonstrated reduction in the polymorphonuclear cells (PMN) migration to the inflamed tissue, as well as the reduction of the pro-inflammatory cytokines TNF and IL-1ß. Furthermore, the acute and sub-acute toxicity studies did not show significant changes in body weight, general behaviour, biochemical parameters, organ weight and liver and kidney histopathological analysis. However, animals acutely treated with S. grantii presented reduction in the number of crosses in relation to the vehicle group, without significant difference in the number of elevations and latency time between the groups in rota-rod test. The obtained results allow to set the NOAEL (Non-observed-adverse-effect level) in 100 mg/kg for this specie of rodent. CONCLUSIONS: Together, the results herein obtained show that S. grantii extract presented anti-inflammatory activity by decreasing the influx of PMN to the inflamed tissue, as well as the cytokines TNF and IL-1ß levels. In addition, S. grantii extract seemed not to present significant acute or subacute toxicity when administered to mice, demonstrating for the first time the safety of this extract, when orally administered.


Assuntos
Anti-Inflamatórios/farmacologia , Citocinas/metabolismo , Euphorbiaceae , Mediadores da Inflamação/metabolismo , Inflamação/prevenção & controle , Leucócitos/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Anti-Inflamatórios/isolamento & purificação , Anti-Inflamatórios/toxicidade , Carragenina , Quimiotaxia de Leucócito/efeitos dos fármacos , Modelos Animais de Doenças , Euphorbiaceae/química , Euphorbiaceae/toxicidade , Feminino , Inflamação/induzido quimicamente , Inflamação/metabolismo , Leucócitos/metabolismo , Masculino , Camundongos , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/toxicidade , Fatores de Tempo , Testes de Toxicidade Aguda , Testes de Toxicidade Subaguda
8.
Arch. pediatr. Urug ; 90(6): 321-327, dic. 2019. tab, graf
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1055032

RESUMO

Resumen: Los nevos melanocíticos congénitos son una proliferación melanocítica benigna presente al nacimiento o que surgen en los primeros 2 o 3 años de vida. Habitualmente se clasifican, según su tamaño, en pequeños, medianos y grandes. Su importancia radica en el potencial riesgo de desarrollar melanoma, en la repercusión que tienen en la calidad de vida de quien los padece y en la asociación con disrafismo y tumores del sistema nervioso central. A mayor tamaño, mayor riesgo de desarrollar melanoma en el nevo o fuera de él. Describiremos las características epidemiológicas, clínicas dermatoscópicas y revisaremos el manejo y seguimiento de los nevos congénitos.


Summary: Congenital melanocytic nevi are a benign melanocytic proliferation present either from birth or during the first 2 or 3 years of life. They are usually classified according to size as: small, medium and large. Their importance lies on the potential risk of developing melanoma, on the impact they have on the patient's quality of life and on its association with dysraphism and tumors of the central nervous system. The larger the size of the nevi, the higher the risk of developing melanoma inside or outside the nevus. We will describe the epidemiological and dermatoscopic clinical characteristics and review the management and follow-up of congenital nevi.


Resumo: Os nevos melanocíticos congênitos são uma proliferação melanocítica benigna presente desde o nascimento ou durante os primeiros 2 ou 3 anos de vida. Eles são geralmente classificados de acordo com o seu tamanho como: pequenos, médios ou grandes. Sua importância está no risco potencial de desenvolver melanoma, no impacto que eles têm na qualidade de vida do paciente e na sua associação com disrafismo e tumores do sistema nervoso central. Quanto maior o tamanho dos nevos, maior o risco de desenvolver melanoma dentro ou fora do nevo. Descreveremos as características clínicas epidemiológicas e dermatoscópicas dos nevos congênitos e revisaremos o seu gerenciamento e acompanhamento.

9.
Front Pharmacol ; 10: 1008, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31572186

RESUMO

Neurodegenerative diseases share the fact that they derive from altered proteins that undergo an unfolding process followed by formation of ß-structures and a pathological tendency to self-aggregate in neuronal cells. This is a characteristic of tau protein in Alzheimer's disease and several tauopathies associated with tau unfolding, α-synuclein in Parkinson's disease, and huntingtin in Huntington disease. Usually, the self-aggregation products are toxic to these cells, and toxicity spreads all over different brain areas. We have postulated that these protein unfolding events are the molecular alterations that trigger several neurodegenerative disorders. Most interestingly, these events occur as a result of neuroinflammatory cascades involving alterations in the cross-talks between glial cells and neurons as a consequence of the activation of microglia and astrocytes. The model we have hypothesized for Alzheimer's disease involves damage signals that promote glial activation, followed by nuclear factor NF-kß activation, synthesis, and release of proinflammatory cytokines such as tumor necrosis factor (TNF)-α, interleukin (IL)-1, IL-6, and IL-12 that affect neuronal receptors with an overactivation of protein kinases. These patterns of pathological events can be applied to several neurodegenerative disorders. In this context, the involvement of innate immunity seems to be a major paradigm in the pathogenesis of these diseases. This is an important element for the search for potential therapeutic approaches for all these brain disorders.

10.
J Ethnopharmacol ; 244: 112133, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31377260

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The leaves of Eugenia species are widely used in popular medicine to treat several diseases, such as arthritis, rheumatism and diabetes. Eugenia umbelliflora O. Berg is popularly known in Brazil as "baguaçu", name also conferred to Eugenia jambolana probably due to their apparent similarity. Although the popular use scientifically proved of E. jambolana as anti-diabetes and also as anti-inflammatory, there are only two scientific studies demonstrating anti-ulcer and bactericide activities of E. umbelliflora leaves extract, without reference to its possible anti-inflammatory activity. AIM OF THE STUDY: The aim of this study was to show the anti-oxidant and anti-inflammatory activity of the methanol extract obtained from E. umbelliflora leaves (EuL) using in vitro and in vivo protocols. MATERIALS AND METHODS: The total phenolic content was evaluated using the folin-Ciocalteu colorimetric method and phloroglucinols content by HPLC. The anti-oxidant activity was evaluated by ORAC, ABTS•+, DPPH, and metal chelation methods. The anti-inflammatory activity was investigated using carrageenan-induced inflammation in the subcutaneous tissue of male Swiss mice orally pre-treated with the EuL (0.3, 1 or 3 mg/kg). The leukocyte influx (optical microscopy) and secretion of chemical mediators (TNF, IL-6, IL-1ß and CXCL1, by enzyme-linked immunosorbent assay) were quantified in the inflamed exudate. Histological analysis of the pouches was also performed. The anti-hypersensitive activity was investigated using carrageenan-induced mechanical hypersensitivity and mice were then evaluated using the von Frey filaments. The Open Field test was used to evaluate possible interference of adverse effect of EuL on locomotor activity that could lead to misinterpretation of the hypersensitivity evaluation. RESULTS: The EuL demonstrated important and moderate reducing capacity on ABTS•+ and DPPH assays, respectively, but with slight activity in ORAC test. It reflects low protection against cell damage. The EuL also presented 30% of phenolic compounds. The phloroglucinols content of EuL was 25.9 mg/g, 18.4 mg/g and 16.6 mg/g of eugenial C, eugenial D and eugenial E, respectively. The in vivo analysis of the inflammatory exudate of EuL-treated mice demonstrated reduction in the polymorphonuclear cells (PMN) migration to the inflamed tissue, as well as the reduction of the pro-inflammatory cytokine IL-1ß. Histologically, it was observed evident decrease in the oedema, formed essentially by non-haemorrhagic fibrin exudate, as well as PMN infiltrate, when compared with control mice injected with carrageenan. Furthermore, the extract also presented effective reduction of the mechanical hypersensitivity induced by carrageenan without any interference in animal's locomotor and exploratory activity. CONCLUSIONS: Together, the results herein obtained show that EuL presented anti-inflammatory activity by decreasing the influx of PMN to the inflamed tissue, as well as the cytokine IL-1ß level. This anti-inflammatory activity was also accompanied by significant anti-hypersensitive effect. The effects presented by EuL seem not to be correlated with an antioxidant activity. However other extract chemical compounds could be responsible for its important anti-inflammatory effects.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antioxidantes/uso terapêutico , Edema/tratamento farmacológico , Eugenia , Extratos Vegetais/uso terapêutico , Animais , Anti-Inflamatórios/química , Antioxidantes/química , Carragenina , Citocinas/imunologia , Edema/induzido quimicamente , Edema/imunologia , Hipersensibilidade/tratamento farmacológico , Hipersensibilidade/imunologia , Locomoção/efeitos dos fármacos , Masculino , Camundongos , Compostos Fitoquímicos/análise , Compostos Fitoquímicos/uso terapêutico , Extratos Vegetais/química , Folhas de Planta
11.
Anticancer Agents Med Chem ; 19(5): 667-676, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30734686

RESUMO

BACKGROUND: It was recently demonstrated that the phthalimide N-(4-methyl-phenyl)-4- methylphthalimide (MPMPH-1) has important effects against acute and chronic pain in mice, with a mechanism of action correlated to adenylyl cyclase inhibition. Furthermore, it was also demonstrated that phthalimide derivatives presented antiproliferative and anti-tumor effects. Considering the literature data, the present study evaluated the effects of MPMPH-1 on breast cancer bone metastasis and correlated painful symptom, and provided additional toxicological information about the compound and its possible metabolites. METHODS: In silico toxicological analysis was supported by in vitro and in vivo experiments to demonstrate the anti-tumor and anti-hypersensitivity effects of the compound. RESULTS: The data obtained with the in silico toxicological analysis demonstrated that MPMPH-1 has mutagenic potential, with a low to moderate level of confidence. The mutagenicity potential was in vivo confirmed by micronucleus assay. MPMPH-1 treatments in the breast cancer bone metastasis model were able to prevent the osteoclastic resorption of bone matrix. Regarding cartilage, degradation was considerably reduced within the zoledronic acid group, while in MPMPH-1, chondrocyte multiplication was observed in random areas, suggesting bone regeneration. Additionally, the repeated treatment of mice with MPMPH-1 (10 mg/kg, i.p.), once a day for up to 36 days, significantly reduces the hypersensitivity in animals with breast cancer bone metastasis. CONCLUSION: Together, the data herein obtained show that MPMPH-1 is relatively safe, and significantly control the cancer growth, allied to the reduction in bone reabsorption and stimulation of bone and cartilage regeneration. MPMPH-1 effects may be linked, at least in part, to the ability of the compound to interfere with adenylylcyclase pathway activation.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Ósseas/tratamento farmacológico , Neoplasias da Mama/patologia , Ftalimidas/uso terapêutico , Animais , Antineoplásicos/toxicidade , Neoplasias Ósseas/secundário , Modelos Animais de Doenças , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ftalimidas/toxicidade
12.
Inflammopharmacology ; 27(3): 613-620, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29948493

RESUMO

OBJECTIVE: This study aimed to evaluate the effects of the methanol extract of Synadenium grantii Hook f. stems and its main isolated compound Query3,4,12,13-tetraacetylforbol-20-phenylacetate (1) on experimental dysmenorrhea in mice. METHODS: Female Swiss mice (n = 6-15) of 6-8 weeks old were used, selected according to the period of the estrous cycle. Animals in proestrus were treated intraperitoneally (i.p.) for 3 days with estradiol. They orally received, on the 4th day, S. grantii extract, the compound 1, ibuprofen or hyoscine butylbromide (Buscopan compound®). Then they were injected (i.p.) with oxytocin 1 h later and individually observed regarding the abdominal writhing for 45 min. The uterus was weighed, photographed and fixed in paraffin for histological analysis. KEY FINDINGS: The extract inhibited the abdominal writhing and similar results were obtained with compound 1 and the positive control drugs Ibuprofen and hyoscine butylbromide. Reduction of uterus volume and histological inflammatory parameters, such as oedema and leukocyte infiltrate, were observed in animals treated with the extract and compound 1. CONCLUSIONS: Our data show promising activity of the extract against dysmenorrhea, indicating important anti-inflammatory activity. Compound 1 appears to be, at least in part, the main responsible for this promising biological effect.


Assuntos
Dismenorreia/tratamento farmacológico , Euphorbia/química , Extratos Vegetais/farmacologia , Animais , Brometo de Butilescopolamônio/farmacologia , Modelos Animais de Doenças , Edema/tratamento farmacológico , Feminino , Ibuprofeno/farmacologia , Camundongos , Fitoterapia/métodos
13.
Salud UNINORTE ; 34(3): 696-704, sep.-dic. 2018. graf
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1004623

RESUMO

Resumen Objetivo: Describir, interpretar y analizar los sentimientos de las personas con diabetes en el transcurrir de su enfermedad. Método: Estudio cualitativo, fenomenológico; se realizó en el Hospital Chepén (La Libertad, Perú) a 10 personas entre 50 y 70 años, determinado por la saturación del discurso y que cumplieron los criterios de inclusión. Los datos fueron recolectados con entrevista a profundidad. Se consideran tres momentos: descripción, reducción y comprensión, que incluye el análisis ideográfico y nomotético hasta llegar a generalidades. Resultados: Se generaron cuatro unidades de significado principales de acuerdo al mayor número de convergencias: sufrimiento, miedo, resignación y fe en Dios, que se agruparon en dos grandes unidades: "viviendo con sufrimiento y miedo para aceptar mi enfermedad" y" teniendo resignación y fe en Dios para aprender a vivir con mi enfermedad". También expresaron cólera, soledad, autoconfianza, desesperanza, culpabilidad, negación, sensibilidad, envidia y alegría, que indican la develación y comprensión del fenómeno vivenciado por las personas con diabetes. Conclusiones: En la convivencia con una enfermedad crónica todos enfrentan el duelo como proceso natural necesario, que causa principalmente sufrimiento, miedo que culmina con la aceptación, pero cuando dicho proceso no es satisfactorio se opta por la resignación; de ahí la importancia para enfermería de tomar en cuenta el universo emocional del paciente para comprenderlo, poniéndose en su lugar y ayudarlo a que aprenda a vivir con su enfermedad y mejorar su calidad de vida.


Abstract Objective: To describe, interpret and analyze the feelings of people with diabetes in the course of their illness. Method: A qualitative, phenomenological study was conducted at the Chepén Hospital (La Libertad, Peru), on 10 people between 50 and 70 years old, determined by speech saturation and who met the inclusion criteria. The data collected was with an in-depth interview. Three moments are considered: description, reduction and comprehension that includes the ideographic and nomothetic analysis reaching generalities. Results: four main units of meanings were generated according to the greatest number of convergences: suffering, fear, resignation and faith in God, which were grouped into two main units of meanings: "living with suffering and fear to accept my illness" and "having resignation and faith in God to learn to live with my disease". They also expressed anger, loneliness, self-confidence, hopelessness, guilt, denial, sensitivity, envy and joy, indicating the unveiling and understanding of the phenomenon experienced by people with diabetes. Conclusions: In cohabitation with a chronic illness, all face bereavement as a necessary natural process, which causes mainly suffering, fear that culminates with acceptance, but when this process is not satisfactory the person chooses resignation, hence the importance for nursing take into account the emotional universe of the patient to understand it, putting themselves in his place and helping him to learn to live with his illness and improve his quality of life.

14.
Int J Mol Sci ; 19(7)2018 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-29937518

RESUMO

The LrtA protein of Synechocystis sp. PCC 6803 intervenes in cyanobacterial post-stress survival and in stabilizing 70S ribosomal particles. It belongs to the hibernating promoting factor (HPF) family of proteins, involved in protein synthesis. In this work, we studied the conformational preferences and stability of isolated LrtA in solution. At physiological conditions, as shown by hydrodynamic techniques, LrtA was involved in a self-association equilibrium. As indicated by Nuclear Magnetic Resonance (NMR), circular dichroism (CD) and fluorescence, the protein acquired a folded, native-like conformation between pH 6.0 and 9.0. However, that conformation was not very stable, as suggested by thermal and chemical denaturations followed by CD and fluorescence. Theoretical studies of its highly-charged sequence suggest that LrtA had a Janus sequence, with a context-dependent fold. Our modelling and molecular dynamics (MD) simulations indicate that the protein adopted the same fold observed in other members of the HPF family (ß-α-ß-ß-ß-α) at its N-terminal region (residues 1­100), whereas the C terminus (residues 100­197) appeared disordered and collapsed, supporting the overall percentage of overall secondary structure obtained by CD deconvolution. Then, LrtA has a chameleonic sequence and it is the first member of the HPF family involved in a self-association equilibrium, when isolated in solution.


Assuntos
Proteínas de Bactérias/química , Proteínas Ribossômicas/química , Ribossomos/química , Synechocystis/química , Motivos de Aminoácidos , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Clonagem Molecular , Escherichia coli/genética , Escherichia coli/metabolismo , Expressão Gênica , Vetores Genéticos/química , Vetores Genéticos/metabolismo , Simulação de Dinâmica Molecular , Conformação Proteica em alfa-Hélice , Conformação Proteica em Folha beta , Dobramento de Proteína , Domínios e Motivos de Interação entre Proteínas , Multimerização Proteica , Estabilidade Proteica , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Proteínas Ribossômicas/genética , Proteínas Ribossômicas/metabolismo , Ribossomos/metabolismo , Soluções , Synechocystis/metabolismo , Termodinâmica
15.
Ter. psicol ; 33(3): 181-193, Dec. 2015. ilus, tab
Artigo em Espanhol | LILACS | ID: lil-772370

RESUMO

La sociedad española de Reumatología (SER) (rivera et al., 2006) recomienda la escala de ansiedad y Depresión Hospitalaria (Hospital anxiety and Depression Scale - HADS, Zigmond y Snaith, 1983) para la evaluación clínica de ansiedad y depresión en Fibromialgia (FM). sin embargo, no constan índices de sensibilidad/especificidad ni puntos de corte en FM. Con el objetivo de comprobar aplicabilidad, propiedades psicométricas y sensibilidad/especificidad del HAD en FM, se evaluó a 131 pacientes ambulatorios del Hospital de san Vicente (alicante, España), utilizando como criterios externos BDI y STAI-E. se analizaron ítems, consistencia interna y estructura factorial mediante análisis confirmatorio y puntos de corte con curvas ROC. Se replicó la estructura de dos factores. La fiabilidad es adecuada (HADA=.80, HADD=.85). Se muestran diferentes puntos de corte con sensibilidad/especificidad superior al 70 por ciento para cada subescala. El Had presenta propiedades psicométricas óptimas en población FM, mostrándose útil como instrumento de "screening" de sintomatología ansioso-depresiva en esta población.


Spanish Society of Rheumatology (SER) (Rivera et al., 2006) suggests the Hospital Anxiety and Depression Scale (HADS, Zigmond y Snaith, 1983) for clinical assessment of anxiety and depression in fibromyalgia (FM). However, there is no HAD-FM cut-off yet. Aiming to assess applicability, psychometric properties and sensitivity/specificity of HADS in FM, 131 outpatients were assessed at San Vicente Hospital (Fibromyalgia service, Alicante, Spain), using like external criteria BDI and STAI-E. Item analysis was performed, calculating the internal consistency and factor structure study by confirmatory factor analysis (CFA). The cut-off points were found by ROC curves. Two-factor structure was replicated. Reliability is adequate (HADA=.80, HADD=.85). Several cut-off points are showed with sensitivity and specificity levels >70 percent for both subscales. HADS has optimal psychometric properties in FM and its useful as a screening tool to assess anxious-depressive symptoms in FM patients.


Assuntos
Humanos , Feminino , Ansiedade/diagnóstico , Depressão/diagnóstico , Escalas de Graduação Psiquiátrica , Fibromialgia/psicologia , Análise Fatorial , Assistência Ambulatorial , Curva ROC , Inquéritos e Questionários , Estudos Transversais , Psicometria , Sensibilidade e Especificidade
16.
Cad Saude Publica ; 28(9): 1699-712, 2012 Sep.
Artigo em Espanhol | MEDLINE | ID: mdl-23033185

RESUMO

In Medellín, Colombia, homicides have been the leading cause of death since 1986. Their proportion among total deaths increased from 3.5% in 1976 to 42% in 1991 and subsequently decreased to 7% in 2006. From 1979 to 2008, there were 81,166 homicides (annual mean, 2,706). The homicide rates per 100,000 inhabitants were 44 in 1979 and 47 in 2008, with a peak of 388 in 1991. The current article analyzes homicides in 30 years (1979-2008) using a random sample of 3,414 forensic autopsy reports. The vast majority of victims were males, 92.8% (95%CI: 91.8%; 93.6%), mostly low-income young people from 27 to 33 years of age. Most homicides involved revenge, fights, or armed robberies. The study showed different periods in the homicide epidemic: the first 15 years, with a rapid increase, the second, with a steady decline until 1998, and the third, with a fluctuating but overall steep decline in the last 10 years. This long-term study on violence in Medellin opens possibilities for analyzing and identifying more consistent policies for intervention.


Assuntos
Homicídio/estatística & dados numéricos , Violência/estatística & dados numéricos , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Causas de Morte , Criança , Pré-Escolar , Cidades/estatística & dados numéricos , Colômbia/epidemiologia , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Política Pública , Estudos Retrospectivos , Distribuição por Sexo , Condições Sociais , Fatores Socioeconômicos , Adulto Jovem
17.
Cad. saúde pública ; Cad. Saúde Pública (Online);28(9): 1699-1712, set. 2012. ilus, tab
Artigo em Espanhol | LILACS | ID: lil-650790

RESUMO

El homicidio en Medellín, Colombia, se convirtió en la primera causa de muerte desde 1986 y su participación del total de muertes pasó de 3,5% en 1976 a 42% en 1991 y 7% en 2006. Entre 1979 y 2008 hubo 81.166 homicidios (2.706 promedio/año). La tasa de homicidios por 100.000 habitantes fue 44 en 1979 y 47 en 2008, con un máximo de 388 en 1991. Se describen características de los homicidios en 30 años, entre 1979 y 2008, por quinquenios, mediante una muestra aleatoria de 3.414 necropsias médico-legales. Los muertos fueron hombres 92.8% (IC95%: 91,8; 93,6), jóvenes con promedios de edad entre 27 y 33 años, residentes en estratos socio-económicos bajos, con predominó de los móviles ajustes de cuentas, riñas y atracos. Se evidenciaron tres periodos diferentes de la epidemia de homicidios: el primero de incremento acelerado 15 años, el segundo de descenso sostenido hasta 1998 y el tercero ondulante y descenso abrupto en los 10 últimos años. Estos resultados de larga duración de la violencia en la ciudad abren posibilidades analíticas para encontrar políticas más consistentes de intervención.


In Medellín, Colombia, homicides have been the leading cause of death since 1986. Their proportion among total deaths increased from 3.5% in 1976 to 42% in 1991 and subsequently decreased to 7% in 2006. From 1979 to 2008, there were 81,166 homicides (annual mean, 2,706). The homicide rates per 100,000 inhabitants were 44 in 1979 and 47 in 2008, with a peak of 388 in 1991. The current article analyzes homicides in 30 years (1979-2008) using a random sample of 3,414 forensic autopsy reports. The vast majority of victims were males, 92.8% (95%CI: 91.8%; 93.6%), mostly low-income young people from 27 to 33 years of age. Most homicides involved revenge, fights, or armed robberies. The study showed different periods in the homicide epidemic: the first 15 years, with a rapid increase, the second, with a steady decline until 1998, and the third, with a fluctuating but overall steep decline in the last 10 years. This long-term study on violence in Medellin opens possibilities for analyzing and identifying more consistent policies for intervention.


Assuntos
Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Homicídio/estatística & dados numéricos , Violência/estatística & dados numéricos , Distribuição por Idade , Causas de Morte , Cidades/estatística & dados numéricos , Colômbia/epidemiologia , Política Pública , Estudos Retrospectivos , Distribuição por Sexo , Condições Sociais , Fatores Socioeconômicos
18.
Fungal Genet Biol ; 49(9): 731-43, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22760060

RESUMO

UaY is the specific ZnII(2)Cys(6) transcriptional activator of the purine utilisation pathway in Aspergillus nidulans. Previous work has determined the consensus binding sequence by EMSA and foot-printing. We determine here that it binds as a dimer to its cognate CGG-N(6)-CCG sites. We identify the uaY109 mutation, which has been shown to affect differentially the expression of a number of UaY-regulated genes, as a F112I substitution in the DNA-binding motif dimerisation domain. We isolated back mutants, revertants carrying different residues at the same position (I112N and I112M) and intragenic suppressors mapping in the first loop of the Zn cluster (N75T and N75K). We have analysed the original mutant and its revertants by growth tests and by their effects on the mRNA steady states of five UaY-regulated genes. We have determined the effect of the different mutations on UaY dimerisation, on the apparent Kdiss of the UaY DNA-binding domain to appropriate DNA sequences and on the methylation interference pattern. We have attempted to rationalise these phenotypes by modelling the UaY DNA binding domain on the structure of the highly similar Ppr1p. However, modelling of the wild-type and mutant proteins provides only a partial explanation for the observed phenotypes. This suggests that the mutated residues may have other roles besides the obvious ones inferred from their position in the sequence and by the similarity of UaY and Ppr1p.


Assuntos
Aspergillus nidulans/genética , Proteínas Fúngicas/química , Proteínas Fúngicas/genética , Mutação , Transativadores/química , Transativadores/genética , Motivos de Aminoácidos , Sequência de Aminoácidos , Aspergillus nidulans/química , Aspergillus nidulans/metabolismo , Dimerização , Regulação para Baixo , Proteínas Fúngicas/metabolismo , Dados de Sequência Molecular , Ligação Proteica , Conformação Proteica , Estrutura Terciária de Proteína , Alinhamento de Sequência , Transativadores/metabolismo
19.
Rev. cuba. hig. epidemiol ; 49(3): 399-409, sep.-dic. 2011.
Artigo em Espanhol | LILACS | ID: lil-615320

RESUMO

INTRODUCCIÓN: La gestión y el desarrollo acelerado de la salud de los trabajadores en el país demandan la introducción de tecnología de punta para optimizar sus acciones. OBJETIVOS. Elaborar una herramienta que permita de forma interactiva conocer rápidamente la distribución geográfica de nuestras ocupaciones, el tipo de riesgo y los recursos humanos capacitados con que cuenta el subsistema de salud ocupacional. MÉTODOS. Fue elaborado un sistema automatizado computacional Macromedia (multimedia) Flash MX en una plataforma operativa Windows XP. Se confeccionó una encuesta que inventariaba los datos del municipio en relación con las principales industrias y centros laborales, los riesgos más importantes, los recursos humanos y materiales y la capacitación con que cuentan los recursos humanos dedicados a la salud ocupacional de ese municipio. RESULTADOS. El instrumento permitió el análisis rápido y fácil por áreas geográficas relacionadas con los riesgos del trabajo y demás información solicitada. Los resultados del municipio Arroyo Naranjo son mostrados como ejemplo de aplicabilidad del sistema, así como de sus interacciones.


INTRODUCTION: The management and the accelerated development of the workers' health in our country to demand the introduction of point technology to optimize its actions. OBJECTIVES: To design a tool allows in a interactive way to know quickly the geographical distribution of our jobs, the type of risk and the trained human resources available in the occupational health subsystem. METHODS: A Macromedia (multimedia) automated computed system was designed in a Windows XP functional platform as well as a survey to make an inventory of municipal data in relation to the main industries and working centers, the more important risks, the human and material resources and the training available for human resources involved in the occupational health of this municipality. RESULTS: The tool allows us a fast and easy analysis by geographical areas related to the work risks and other requested information. The results of Arroyo Naranjo municipality are showed as an example of applicability of system, as well as its interactions.

20.
BMC Immunol ; 11: 32, 2010 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-20576124

RESUMO

BACKGROUND: Mast cells have recently gained new importance as immunoregulatory cells that are involved in numerous pathological processes. One result of these processes is an increase in mast cell numbers at peripheral sites. This study was undertaken to determine the mast cell response in the peritoneal cavity and bone marrow during repopulation of the peritoneal cavity in rats. RESULTS: Two mast cell specific antibodies, mAb AA4 and mAb BGD6, were used to distinguish the committed mast cell precursor from more mature mast cells. The peritoneal cavity was depleted of mast cells using distilled water. Twelve hours after distilled water injection, very immature mast cells could be isolated from the blood and by 48 hours were present in the peritoneal cavity. At this same time the percentage of mast cells in mitosis increased fourfold. Mast cell depletion of the peritoneal cavity also reduced the total number of mast cells in the bone marrow, but increased the number of mast cell committed precursors. CONCLUSIONS: In response to mast cell depletion of the peritoneal cavity, a mast cell progenitor is released into the circulation and participates in repopulation of the peritoneal cavity, while the committed mast cell precursor is retained in the bone marrow.


Assuntos
Células da Medula Óssea/citologia , Linhagem da Célula , Mastócitos/citologia , Cavidade Peritoneal/citologia , Células-Tronco/citologia , Animais , Células da Medula Óssea/efeitos dos fármacos , Contagem de Células , Linhagem da Célula/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Separação Celular , Feminino , Separação Imunomagnética , Injeções Intraperitoneais , Masculino , Mastócitos/efeitos dos fármacos , Mastócitos/ultraestrutura , Mitose/efeitos dos fármacos , Ratos , Ratos Wistar , Células-Tronco/efeitos dos fármacos , Fatores de Tempo , Água/administração & dosagem , Água/farmacologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA