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Introduction: Crohn's disease (CD) involves activation of mast cells (MC) and NF-кB in parallel with the PPAR-α/NLRP3 inflammasome/IL-1ß pathway in the inflamed colon. Whether polyphenols from maqui (Aristotelia chilensis) represent a natural alternative treatment for CD is unclear. Therefore, we used an animal model of 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced CD-like colitis to investigate protective effects of maqui extract through monitoring NLRP3 inflammasome and MC activation in colon tissue. Methods: Maqui extract was administered via orogastric route to mice after (post-Treatment group) or prior (pre-Treatment group) to TNBS-induction. Colon pathology was characterized by histoarchitectural imaging, disease activity index (DAI), and assessing NF-кB, p-NF-кB, PPAR-α/NLRP3 expression and IL-1ß levels. Results: Compared to mice treated with TNBS alone administration of anthocyanin-rich maqui extract improved the DAI, colon histoarchitecture and reduced both colon wet-weight and transmural inflammation. Induction with TNBS significantly increased colonic NLPR3 inflammasome activation, while co-treatment with maqui extract (either post- or pre-Treatment) significantly downregulated NLRP3, ASC and caspase-1 levels, which manifested as reduced colonic IL-1ß levels. Supplemented maqui extract marginally diminished NF-кB activity in epithelial cells but reached statistical significance in immune cells (as judged by decreased NF-кB phosphorylation). PPAR-α signaling was largely unaffected by Maqui whereas MC infiltration into the colon mucosa and submucosa decreased and their level of degranulation was suppressed. Conclusion: These outcomes show the post- and pre- Treatment effect of a polyphenolic extract rich in anthocyanins from maqui the acute phase of TNBS- induced CD-like colitis is linked to suppression of the NLRP3 inflammasome and reduced MC responses. These data indicate that maqui extract represents a potential nutraceutical for the treatment of inflammatory bowel disease (IBD).
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Antocianinas , Colite , Doença de Crohn , Animais , Camundongos , Antocianinas/uso terapêutico , Colite/induzido quimicamente , Colite/tratamento farmacológico , Doença de Crohn/induzido quimicamente , Doença de Crohn/tratamento farmacológico , Inflamassomos/metabolismo , Mastócitos/metabolismo , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Receptores Ativados por Proliferador de PeroxissomoRESUMO
The best conservation method for native Chilean berries has been investigated in combination with an implemented large-scale extract of maqui berry, rich in total polyphenols and anthocyanin to be tested in intestinal epithelial and immune cells. The methanolic extract was obtained from lyophilized and analyzed maqui berries using Folin-Ciocalteu to quantify the total polyphenol content, as well as 2,2-diphenyl-1-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP), and oxygen radical absorbance capacity (ORAC) to measure the antioxidant capacity. Determination of maqui's anthocyanins profile was performed by ultra-high-performance liquid chromatography (UHPLC-MS/MS). Viability, cytotoxicity, and percent oxidation in epithelial colon cells (HT-29) and macrophages cells (RAW 264.7) were evaluated. In conclusion, preservation studies confirmed that the maqui properties and composition in fresh or frozen conditions are preserved and a more efficient and convenient extraction methodology was achieved. In vitro studies of epithelial cells have shown that this extract has a powerful antioxidant strength exhibiting a dose-dependent behavior. When lipopolysaccharide (LPS)-macrophages were activated, noncytotoxic effects were observed, and a relationship between oxidative stress and inflammation response was demonstrated. The maqui extract along with 5-aminosalicylic acid (5-ASA) have a synergistic effect. All of the compiled data pointed out to the use of this extract as a potential nutraceutical agent with physiological benefits for the treatment of inflammatory bowel disease (IBD).
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OBJECTIVES: The aim of this study was to evaluate the effect of the dietary supplementation of an alpha- and gamma-tocopherol mixture (1:5 ratio) in the adipose tissue expansion, hepatic steatosis, and expression of inflammatory markers induced by consumption of a high-fat diet (HFD) in mice. METHODS: Male C57BL/6 J mice were fed for 12 wk and divided into the following: 1) control diet (CD; 10% fat, 20% protein, 70% carbohydrates); 2) CD + TF (CD plus alpha-tocopherol: 0.7 mg/kg/d, gamma-tocopherol: 3.5 mg/kg/d); 3) HFD (60% fat, 20% protein, 20% carbohydrates); and 4) HFD + TF (HFD plus alpha-tocopherol: 0.7 mg/kg/d, gamma-tocopherol: 3.5 mg/kg/d). General parameters, adipocyte size, liver steatosis, adipose and hepatic tumor necrosis factor-α (TNF-α) and interleukin-1 ß (IL-1ß) expression, hepatic nuclear factor kappa B (NF-κB), and peroxisome proliferator-activated receptor α (PPAR-α) levels were evaluated. RESULTS: Tocopherol supplementation in HFD-fed mice showed a significant decrease in the body weight (19%) and adipose tissue weight (52%), adipose tissue/body weight ratio (36%), and serum triacylglycerols (56%); a 42% decrease (P < 0.05) of adipocyte size compared to HFD; attenuation of liver steatosis by decreasing (P < 0.05) lipid vesicles presence (90%) and total lipid content (75%); and downregulation of inflammatory markers (TNF-α and IL-1ß), along with an upregulation of hepatic PPAR-α expression and its downstream-regulated genes (ACOX and CAT-1), and an inhibition of hepatic NF-κB activation. CONCLUSION: The present study suggests that alpha- and gamma-tocopherol (1:5 ratio) supplementation attenuates the adipocyte enlargement, hepatic steatosis, and metabolic inflammation induced by HFD in association with PPAR-α/NF-κB modulation.
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Dieta Hiperlipídica , Fígado Gorduroso , Tecido Adiposo , Animais , Dieta Hiperlipídica/efeitos adversos , Suplementos Nutricionais , Modelos Animais de Doenças , Fígado Gorduroso/etiologia , Fígado Gorduroso/prevenção & controle , Fígado , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Expansão de Tecido , gama-Tocoferol/farmacologiaRESUMO
OBJECTIVE: The aim of this study was to evaluate the contribution of tocopherols present in Rosa mosqueta oil (RM) in the prevention of high-fat diet (HFD)-induced alterations. METHODS: Male C57 BL/6 J mice (n = 9/group) were fed for 12 wk and divided into four groups: control (CD; 10% kcal fat, 20% kcal protein, 70% kcal carbohydrates); HFD (60% as fat, 20% kcal protein, 20% kcal carbohydrates); HFD + RM (0.01 mL/g body weight/d); and HFD + RM- without tocopherols (0.01 mL/g body weight/d). Parameters of obesity, liver steatosis (histology, triacylglycerols content), inflammation (adipose NLRP3 inflammasome, tumor necrosis factor-α and interleukin-1 ß expression, hepatic nuclear factor-κB) and oxidative stress (hepatic Nrf2 activation, carbonylated proteins) were evaluated. RESULTS: Liver steatosis, inflammatory, and oxidative stress parameters were significantly (P < 0.05) increased in the HFD + RM- compared with the HFD + RM, with no differences between HFD and HFD + RM-. CONCLUSION: The present study suggests that α- and γ-tocopherols from RM may have an important role in the prevention of alterations induced by HFD.
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Dieta Hiperlipídica/efeitos adversos , Inflamação/prevenção & controle , Estresse Oxidativo/efeitos dos fármacos , Óleos de Plantas/farmacologia , Rosa , alfa-Tocoferol/farmacologia , gama-Tocoferol/farmacologia , Animais , Modelos Animais de Doenças , Fígado Gorduroso/prevenção & controle , Masculino , Camundongos , Camundongos Endogâmicos C57BLRESUMO
Amitriptyline, a tricyclic antidepressant, has been proposed as an antitumoral drug in oxidative therapy. Its pro-apoptotic effects, mediated by high reactive oxygen species generation, have been already described. In this study we analysed the effect of amitriptyline on the biosynthesis of coenzyme Q10 (CoQ), an essential component for electron transport and a potent membrane antioxidant involved in redox signaling. We treated H460 cells, a non-small-cell lung cancer cell line, with amitriptyline and we analysed CoQ levels by HPLC and CoQ biosynthesis rate, as well as the enzymes involved in CoQ biosynthesis by real-time PCR and Western blot. Amitriptyline treatment induced a dose-dependent decrease in CoQ levels in tumor cells. CoQ decreased levels were associated with down-regulation of the expression of COQ4 gene, as well as decreased Coq4 and Coq6 protein levels. Our findings suggest that the effect of amitriptyline on CoQ biosynthesis highlights the potential of this drug for antitumoral oxidative therapy.
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Amitriptilina/farmacologia , Neoplasias Pulmonares/patologia , Ubiquinona/análogos & derivados , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Humanos , Cinética , Espécies Reativas de Oxigênio/metabolismo , Ubiquinona/biossíntese , Ubiquinona/metabolismoRESUMO
El artículo presenta una aproximación psicosocial al conflicto del País Vasco desde el modelo dinámico/sistémico del conflicto (Coleman, 2006). La investigación se llevó a cabo a partir de 60 entrevistas en profundidad realizadas a personas de distintos sectores de la sociedad vasca, analizadas a partir de un análisis de contenido por categorización, y de un análisis interpretativo fenomenológico. Los resultados apuntan a cinco elementos centrales del conflicto: las manifestaciones de violencia y sus formas de legitimación, la vulneración de necesidades humanas básicas, la interdependencia negativa de las identidades colectivas, cuestiones políticas e ideológicas. Igualmente, se mencionan tres factores adicionales -polarización social, emociones y aspectos cognitivos-. Finalmente, se interpreta el conjunto de datos sobre el conflicto vasco a partir del modelo dinámico/sistémico.
The paper presents a psychosocial approach to Basque Country conflict from the dynamical system model of conflict (Coleman, 2006). Research was make throughout 60 interviews fulfilled with people of different sectors of basque society, and were analyzed by categorization content analysis and by interpretative fhenomenologycal analysis. Results point to five central elements of conflict: violence manifestations and there legitimation forms, violation of Basic Human Needs, negative interdependence of collective identities, political and ideological issues. Three additional factors are also mentionated -social polarization, emotional and cognitive issues-. Finally, we explain the whole dates about basque conflict throughout dynamic/ systemic model.
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Violência , Conflito Psicológico , Pesquisa QualitativaRESUMO
INTRODUCTION: The essential issue in conservative treatment is the quality in breast preservation. When risk factors for local relapse exist, a tumour bed boost is required, but the boost choice remains controversial. Prospectively, we studied long-term toxicity, cosmetic outcome and prognostic factors. MATERIALS AND METHODS: After conservative treatment, 115 patients received a single dose of 7 Gy HDR-brachytherapy (HDR-BT) boost between June 1996 and December 2005. Late toxicity was assessed using the LENT-SOMA scale. For esthetic assessment, a subjective scale was used for patients and a modified Fehlauer scale for physicians. Mean age was 56.6 years. Invasive ductal carcinoma (78 %) and lumpectomy (60 %) were predominantly reported. 48 % received chemotherapy (CT). RESULTS: Regarding toxicity, 39 % of patients reported breast pain, 75 % fibrosis, 56 % telangiectasias, 19 % lymphoedema, and 51 % retraction/atrophy. Concerning management, 22 % of patients with pain and 45 % with lymphoedema were treated. The esthetic result was found satisfactory by 96 % of the patients and 85 % of the physicians. Fibrosis was influenced by CT and a larger irradiated volume and telangiectasias by a greater implant volume. CONCLUSIONS: HDR-BT boost shows good cosmetic effects with acceptable toxicity. Patients overestimate the esthetic outcome. LENT/SOMA is useful to assess chronic toxicity.
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Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Mama/efeitos da radiação , Mama/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Braquiterapia/efeitos adversos , Mama/patologia , Neoplasias da Mama/patologia , Fracionamento da Dose de Radiação , Feminino , Humanos , Mastectomia Segmentar , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do TratamentoRESUMO
BACKGROUND AND PURPOSE: Conservative treatment represents the current therapy for early-stage breast cancer. When risk factors for local relapse exist, a tumour bed boost is required. Retrospectively, we evaluated the prognostic factors influencing local recurrence (LR), overall survival (OS) and disease-free survival (DFS). MATERIAL AND METHODS: After conservative treatment, 210 patients received a single-dose HDR brachytherapy (HDRBT) boost between June 1996 and December 2005. Mean age was 57 years; 75% had invasive ductal carcinoma. The most frequent surgery was lumpectomy (55.7%); 39.4% were G3, 18.6% intraductal component >25% and only 22% had negative margins. RESULTS: With a mean follow-up of 85 months, at 5 and 10 years the OS was 93% and 88%, DFS 92% and 89%, and LR 3.6% and 5.3%, respectively. For LR, the risk factors were carcinoma in situ, N+ and involved margins, whereas for metastasis, the risk factors were T2 tumours, stage III, N+ and the presence of local recurrence. CONCLUSIONS: HDR-BT boost in one fraction is an effective, simple and safe method for reducing LR. The outpatient setting and shorter treatment duration represent undeniable advantages.
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Braquiterapia , Neoplasias da Mama/radioterapia , Carcinoma Ductal de Mama/radioterapia , Carcinoma Lobular/radioterapia , Recidiva Local de Neoplasia/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/patologia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Prognóstico , Estudos RetrospectivosRESUMO
OBJECTIVE: To determine whether the intravesical use of hyaluronic acid (HA) reduces acute and late vesical toxicity induced by radiotherapy. METHODS: Single-centre retrospective study of patients diagnosed with cervical and endometrial cancer treated with brachytherapy (BT) with or without intravesical instillation of HA. Patients were assigned consecutively to the two treatment groups. Forty milligrams of HA was instilled intravesically for approximately 30 min prior to each BT session. Rates of acute and late vesical toxicity were recorded using the RTOG criteria. RESULTS: Ninety-five clinical histories were reviewed (48 with HA instillation and 47 without). Surgery had been performed in 85.3% of cases, external radiotherapy in 76.8% and chemotherapy in 25.3%. There were no significant differences between groups with regard to the total number of BT sessions, dose per session, total dose or biological equivalent dose. In all the sessions the percentage of patients presenting acute vesical toxicity was lower in the HA group, the differences being statistically significant (p<0.05) after the 2nd (20.8% vs. 40.4%) and 4th sessions (10.9% vs. 31.9%). No patients in the HA group presented vesical toxicity after six months of follow-up. Over the whole study period, the percentage of patients presenting vesical toxicity of degree 2 or more was significantly lower in the HA group (2.08% vs. 12.8%; p<0.05). CONCLUSION: Vesical instillations of HA decrease the incidence and the degree of acute vesical toxicity induced by high-dose BT, and reduce the percentage of patients that develop toxicity of degree 2 or more.