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1.
Int J Mol Sci ; 25(10)2024 May 15.
Artículo en Inglés | MEDLINE | ID: mdl-38791419

RESUMEN

Human malignancies are one of the major health-related issues throughout the world and are anticipated to rise in the future. Despite huge investments made in anticancer drug development, limited success has been obtained and the average number of FDA approvals per year is declining. So, an increasing interest in drug repurposing exists. Metformin (MET) and aspirin (ASP) possess anticancer properties. This work aims to test the effect of these two drugs in combination on colorectal cancer (CRC) cells in vitro. The effects of MET and/or ASP on cell proliferation, viability, migratory ability, anchorage-independent growth ability (colony formation), and nutrient uptake were determined in two (HT-29 and Caco-2) human CRC cell lines. Individually, MET and ASP possessed antiproliferative, cytotoxic, and antimigratory effects and reduced colony formation in HT-29 cells (BRAF- and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α (PI3KCA)-mutant), although MET did not affect either 3H-deoxy-D-glucose or 14C-butyrate uptake and lactate production, and ASP caused only a small decrease in 14C-butyrate uptake. Moreover, in these cells, the combination of MET and ASP resulted in a tendency to an increase in the cytotoxic effect and in a potentiation of the inhibitory effect on colony formation, although no additive antiproliferative and antimigratory effects, and no effect on nutrient uptake and lactate production were observed. In contrast, MET and ASP, both individually and in combination, were almost devoid of effects on Caco-2 cells (BRAF- and PI3KCA-wild type). We suggest that inhibition of PI3K is the common mechanism involved in the anti-CRC effect of both MET, ASP and their combination and, therefore, that the combination of MET + ASP may especially benefit PI3KCA-mutant CRC cases, which currently have a poor prognostic.


Asunto(s)
Aspirina , Movimiento Celular , Proliferación Celular , Neoplasias Colorrectales , Metformina , Humanos , Metformina/farmacología , Aspirina/farmacología , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Proliferación Celular/efectos de los fármacos , Células CACO-2 , Movimiento Celular/efectos de los fármacos , Células HT29 , Mutación , Sinergismo Farmacológico , Supervivencia Celular/efectos de los fármacos , Antineoplásicos/farmacología , Fosfatidilinositol 3-Quinasa Clase I/genética , Fosfatidilinositol 3-Quinasa Clase I/metabolismo , Fosfatidilinositol 3-Quinasa Clase I/antagonistas & inhibidores , Línea Celular Tumoral
2.
Cytokine ; 169: 156307, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37487380

RESUMEN

Inflammatory bowel disease (IBD) is a group of chronic and life-threating inflammatory diseases of the gastrointestinal tract. The active intestinal absorption of bile salts is reduced in IBD, resulting in higher luminal concentrations of these agents that contribute to the pathophysiology of IBD-associated diarrhea. Butyrate (BT) is a short-chain fatty acid produced by colonic bacterial fermentation of dietary fibers. BT utilization is impaired in the intestinal inflamed mucosa of IBD patients. Our aim was to investigate the link between IBD and bile acid absorption, by testing the effect of the pro-inflammatory cytokines TNF-α and IFN-γ and of BT upon 3H-TC uptake by Caco-2 cells. The proinflammatory cytokines TNF-α and IFN-γ inhibit Na+-independent, non-ASBT (sodium-dependent bile acid transporter)-mediated 3H-TC uptake by Caco-2 cells. The inhibitory effect of these cytokines on Na+-independent 3H-TC uptake is PI3K- and JAK/STAT1-mediated. These two compounds upregulate ASBT expression levels, but no corresponding increase in Na+-dependent component of 3H-TC is observed. Moreover, BT was also found to inhibit 3H-TC uptake and showed an additive effect with IFN-γ in reducing 3H-TC uptake. We conclude that an interaction between BT and bile acids appears to exist in IBD, which may participate in the link between diet, microbiota and IBD.


Asunto(s)
Citocinas , Enfermedades Inflamatorias del Intestino , Humanos , Células CACO-2 , Citocinas/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Butiratos/farmacología , Ácido Taurocólico/farmacología , Ácido Taurocólico/metabolismo , Enfermedades Inflamatorias del Intestino/metabolismo , Mucosa Intestinal/metabolismo , Ácidos y Sales Biliares
3.
Exp Cell Res ; 429(2): 113670, 2023 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-37290498

RESUMEN

Butyrate (BT) is important in the prevention and inhibition of colorectal cancer (CRC). Inflammatory bowel disease, a risk factor for CRC, is associated with higher levels of proinflammatory cytokines and bile acids. The aim of this work was to investigate the interaction of these compounds in inhibiting BT uptake by Caco-2 cells, as a mechanism contributing to the link between IBD and CRC. TNF-α, IFN-γ, chenodeoxycholic acid (CDCA) and deoxycholic acid (DCA) markedly reduce 14C-BT uptake. All these compounds appear to inhibit MCT1-mediated BT cellular uptake at a posttranscriptional level, and, because their effect is not additive, they are most probably inhibiting MCT1 by a similar mechanism. Correspondingly, the antiproliferative effect of BT (MCT1-dependent) and of the proinflammatory cytokines and CDCA were not additive. In contrast, the cytotoxic effect of BT (MCT1-independent) and of the proinflammatory cytokines and CDCA were additive. In conclusion, proinflammatory cytokines (TNF-α and IFN-γ) and bile acids (DCA and CDCA) inhibit MCT1-mediated BT cellular uptake. These proinflammatory cytokines and CDCA were found to interfere with the antiproliferative effect of BT, mediated by an inhibitory effect upon MCT1-mediated cellular uptake of BT.


Asunto(s)
Ácidos y Sales Biliares , Citocinas , Humanos , Ácidos y Sales Biliares/farmacología , Butiratos/farmacología , Células CACO-2 , Factor de Necrosis Tumoral alfa/farmacología , Ácido Quenodesoxicólico/farmacología
4.
Can J Physiol Pharmacol ; 101(2): 90-105, 2023 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-36688470

RESUMEN

Phenolic acids are recognized as chemopreventive and chemotherapeutic agents. Altered glucose and glutamine metabolism are recognized hallmarks of cancer cells. We aimed to test the influence of phenolic acids on glucose and glutamine cellular uptake by a breast (MCF-7) and a pancreatic (AsPC-1) cancer cell line. Several phenolic acids (caffeic, ferrulic, proctocatechuic, coumaric and gallic acid) affected 3H-glutamine and/or 3H-deoxy-d-glucose (3H-DG) uptake. Gallic acid (100 µM) caused a 3-fold increase in 3H-DG uptake by AsPC-1 cells, associated with a 3.7-fold increase in lactic acid production. Gallic acid stimulated GLUT1-mediated 3H-DG uptake and increased the affinity of this transporter for 3H-DG. We further verified that gallic acid does not change GLUT1 transcription rates and cellular redox state and that its effect does not involve PI3K, mTOR and MAP kinases and is not associated with a proproliferative effect. Gallic acid also increased 3H-DG uptake by MCF-7 cells, although less potently. Further investigation is necessary to elucidate the cellular pathways involved in this effect of gallic acid.


Asunto(s)
Ácido Gálico , Neoplasias Pancreáticas , Humanos , Ácido Gálico/farmacología , Transportador de Glucosa de Tipo 1 , Glutamina , Glucosa/metabolismo , Células MCF-7 , Neoplasias Pancreáticas/tratamiento farmacológico
5.
Cell Biochem Funct ; 40(2): 127-137, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35014047

RESUMEN

Type 2 diabetes mellitus (T2DM) is linked to an increased risk of breast cancer. We aimed to investigate how T2DM-associated characteristics (high levels of glucose, insulin, leptin, inflammatory mediators and oxidative stress) influence breast cancer carcinogenesis, in DMBA-treated (MCF-12ADMBA ) and non-treated breast epithelial (MCF-12A) cell lines. Insulin (50 nM) promotes cell proliferation, 3 H-DG uptake and lactic acid production in both cell lines. The stimulatory effects of insulin upon cell proliferation and 3 H-DG uptake were hampered by rapamycin, LY294001 and BAY-876, in both cell lines. In conclusion, hyperinsulinemia, one important characteristic of T2DM, contributes to the initiation of breast cancer by a PI3K- and mTOR-dependent mechanism involving increased GLUT1-mediated glucose uptake. SIGNIFICANCE: The pro-proliferative effect of insulin in human breast epithelial DMBA-transformed and non-transformed cell lines is PI3K-, mTOR- and GLUT1-dependent.


Asunto(s)
Neoplasias de la Mama , Diabetes Mellitus Tipo 2 , Neoplasias de la Mama/inducido químicamente , Neoplasias de la Mama/metabolismo , Línea Celular Tumoral , Femenino , Transportador de Glucosa de Tipo 1/metabolismo , Humanos , Insulina/metabolismo , Insulina/farmacología , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismo
6.
Life Sci ; 286: 120054, 2021 Dec 01.
Artículo en Inglés | MEDLINE | ID: mdl-34662550

RESUMEN

AIMS: Type 2 diabetes mellitus (T2DM) is a risk factor for breast cancer initiation and progression. Glutamine (GLN) is a critical nutrient for cancer cells. The aim of this study was to investigate the effect of T2DM-associated compounds upon GLN uptake by breast cancer cells. MAIN METHODS: The in vitro uptake of 3H-GLN by breast cancer (MCF-7 and MDA-MB-231) and non-tumorigenic (MCF-12A) cell lines was measured. KEY FINDINGS: 3H-GLN uptake in the three cell lines is mainly Na+-dependent and sensitive to the ASCT2 inhibitor GPNA. IFN-γ increased total and Na+-dependent 3H-GLN uptake in the two breast cancer cell lines, and insulin increased total and Na+-dependent 3H-GLN uptake in the non-tumorigenic cell line. GPNA abolished the increase in 3H-GLN uptake promoted by these T2DM-associated compounds. ASCT2 knockdown confirmed that the increase in 3H-GLN uptake caused by IFN-γ (in breast cancer cells) and by insulin (in non-tumorigenic cells) is ASCT2-dependent. IFN-γ (in MDA-MB-231 cells) and insulin (in MCF-12A cells) increased ASCT2 transcript and protein levels. Importantly, the pro-proliferative effect of IFN-γ in breast cancer cell lines was associated with an increase in 3H-GLN uptake which was GPNA-sensitive, blocked by ASCT2 knockdown and mediated by activation of the PI3K-, STAT3- and STAT1 intracellular signalling pathways. SIGNIFICANCE: IFN-γ and insulin possess pro-proliferative effects in breast cancer and non-cancer cell lines, respectively, which are dependent on an increase in ASCT2-mediated glutamine transport. Thus, an effective inhibition of ASCT2-mediated glutamine uptake may be a therapeutic strategy against human breast cancer in T2DM patients.


Asunto(s)
Sistema de Transporte de Aminoácidos ASC/metabolismo , Neoplasias de la Mama/metabolismo , Interferón gamma/metabolismo , Antígenos de Histocompatibilidad Menor/metabolismo , Sistema de Transporte de Aminoácidos ASC/fisiología , Apoptosis/efectos de los fármacos , Transporte Biológico , Neoplasias de la Mama/inmunología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Proliferación Celular/fisiología , Complicaciones de la Diabetes/fisiopatología , Diabetes Mellitus/fisiopatología , Femenino , Glutamina/metabolismo , Humanos , Interferón gamma/inmunología , Interferón gamma/fisiología , Antígenos de Histocompatibilidad Menor/fisiología , Factores de Riesgo , Transducción de Señal/efectos de los fármacos , Sodio
7.
Molecules ; 26(19)2021 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-34641482

RESUMEN

Gunnera tinctoria, an underexplored invasive plant found in Azores, Portugal, was studied regarding its nutritional, antioxidant, and antitumoral properties. Higher antioxidant activity was found in baby leaves, followed by adult leaves and inflorescences. A phenolic fraction of the plant was enriched using adsorbent resin column chromatography (DiaionTM HP20LX, and Relite EXA90). Antitumoral effects were observed with the enriched fractions in breast (MCF-7) and pancreatic (AsPC-1) cancer cell lines, being more pronounced in the latter. To improve protection and membrane absorption rates of phenolic compounds, nano-phytosomes and cholesterol-conjugated phytosomes coated with natural polymers were loaded with the enriched fraction. The particles were characterized, and their physiochemical properties were evaluated and compared. All samples presented anionic charge and nanometer size in relation to the inner layer and micrometer size regarding the external layers. In addition, the molecular arrangement of phenolics within both types of phytosomes were studied for the first time by molecular docking. Polarity and molecular size were key factors on the molecular arrangement of the lipid bilayer. In conclusion, G. tinctoria showed to be an interesting source of nutrients and phenolic compounds with anti-tumoral potential. Moreover, phytosome loading with these compounds can increase their stability and bioavailability having in view future applications.


Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Antioxidantes/farmacología , Magnoliopsida/química , Neoplasias/tratamiento farmacológico , Extractos Vegetales/farmacología , Humanos , Simulación del Acoplamiento Molecular , Neoplasias/patología , Valor Nutritivo , Células Tumorales Cultivadas
8.
Eur J Pharmacol ; 898: 173980, 2021 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-33647254

RESUMEN

Obesity and type 2 diabetes mellitus (T2DM) associate with increased incidence and mortality from many cancers, including breast cancer. The mechanisms involved in this relation remain poorly understood. Our study aimed to investigate the in vitro effect of high levels of glucose, insulin, leptin, TNF-α, INF-γ and oxidative stress (induced with tert-butylhydroperoxide (TBH)), which are associated with T2DM, upon glucose uptake by breast cancer (MCF-7 and MDA-MB-231) and non-cancer (MCF-12A) cells and to correlate this effect with their effects upon cellular characteristics associated with cancer progression (cell proliferation, viability, migration, angiogenesis and apoptosis). 3H-DG uptake was markedly inhibited by a selective GLUT1 inhibitor (BAY-876) in all cell lines, proving that 3H-DG uptake is mainly GLUT1-mediated. TBH (2.5 µM), insulin (50 nM), leptin (500 ng/ml) and INF-y (100 ng/ml) stimulate GLUT1-mediated 3H-DG (1 mM) uptake by both ER-positive and triple-negative breast cancer cell lines. TBH and leptin, but not insulin and INF-γ, increase GLUT1 mRNA levels. Insulin and leptin (in both ER-positive and triple-negative breast cancer cell lines) and TBH (in the triple-negative cell line) have a proproliferative effect and leptin possesses a cytoprotective effect in both breast cancer cell lines that can contribute to cancer progression. The effects of TBH, insulin, leptin and INF-γ upon breast cancer cell proliferation and viability are GLUT1-dependent. In conclusion, T2DM-associated characteristics induce changes in GLUT1-mediated glucose uptake that can contribute to cancer progression. Moreover, we conclude that BAY-876 can be a strong candidate for development of a new effective anticancer agent against breast cancer.


Asunto(s)
Neoplasias de la Mama/metabolismo , Transportador de Glucosa de Tipo 1/metabolismo , Glucosa/metabolismo , Insulina/farmacología , Interferón gamma/farmacología , Leptina/farmacología , Estrés Oxidativo/efectos de los fármacos , Factor de Necrosis Tumoral alfa/farmacología , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Diabetes Mellitus Tipo 2/metabolismo , Femenino , Transportador de Glucosa de Tipo 1/antagonistas & inhibidores , Humanos , Células MCF-7 , Invasividad Neoplásica , Neovascularización Patológica , Pirazoles/farmacología , Quinolinas/farmacología , Transducción de Señal , terc-Butilhidroperóxido
9.
Food Funct ; 11(4): 3471-3482, 2020 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-32242198

RESUMEN

The antioxidant potential and phenolic profile of infusions prepared with cherry stems from different commercial brands were studied. The phenolic profile of each infusion was characterized by UHPLC-ESI-QTOF-MS and 44 phenolic compounds belonging to eight distinct classes (hydroxybenzoic acids, hydroxycinnamic acids, phenylpropanoic acids, flavan-3-ols, flavonols, flavanones, flavones and isoflavones) were tentatively identified. For the first time, salicylic acid was identified in cherry stem infusions. In cell-based assays, all the infusions tended to inhibit lipid peroxidation and presented no cytotoxicity. Significant differences (p < 0.05) were found between a sample sold in bulk (lower antioxidant activity by DPPH˙ inhibition, ferric reducing antioxidant power, and oxygen radical absorbance capacity assays; lower amounts of total phenolics and flavonoids and a different quantitative phenolic profile) and samples sold in packages. These, in turn, were very similar to each other and revealed a high antioxidant potential and a very rich phenolic profile. These results reflect not only the antioxidant potential of cherry stem infusions but also the need to globally harmonize the control and regulation of herbal products in order to ensure in the market products with high quality, safety and efficacy.


Asunto(s)
Antioxidantes/química , Fenoles/química , Extractos Vegetales/química , Prunus avium , Cromatografía Líquida de Alta Presión , Humanos , Peroxidación de Lípido/efectos de los fármacos , Extractos Vegetales/farmacología , Tallos de la Planta , Espectrometría de Masa por Ionización de Electrospray
10.
Eur J Nutr ; 59(1): 151-165, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-30631887

RESUMEN

PURPOSE: Metabolic syndrome (MS) is a major public health issue worldwide and fructose consumption has been associated with MS development. Recently, we showed that the dietary polyphenol chrysin is an effective inhibitor of fructose uptake by human intestinal epithelial cells. Therefore, our aim was to investigate if chrysin interferes with the development of MS induced by fructose in an animal model. METHODS: Adult male Sprague-Dawley rats (220-310 g) were randomly divided into four groups: (A) tap water (control), (B) tap water and a daily dose of chrysin (100 mg/kg) by oral administration (chrysin) (C) 10% fructose in tap water (fructose), and (D) 10% fructose in tap water and a daily dose of chrysin (100 mg/kg) by oral administration (fructose + chrysin). All groups were fed ad libitum with standard laboratory chow diet and dietary manipulation lasted 18 weeks. RESULTS: Fructose-feeding for 18 weeks induced an increase in serum triacylglycerols, insulin and angiotensin II levels and in hepatic fibrosis and these changes did not occur in fructose + chrysin rats. Moreover, the increase in both systolic and diastolic blood pressure which was found in fructose-fed animals from week 14th onwards was not observed in fructose + chrysin animals. In contrast, the increase in energy consumption, liver/body, heart/body and right kidney/body weight ratios, serum proteins, serum leptin and liver triacylglycerols observed in fructose-fed rats was not affected by chrysin. CONCLUSIONS: Chrysin was able to protect against some of the MS features induced by fructose-feeding.


Asunto(s)
Dieta/métodos , Flavonoides/farmacología , Fructosa/administración & dosificación , Síndrome Metabólico/metabolismo , Síndrome Metabólico/prevención & control , Animales , Modelos Animales de Enfermedad , Flavonoides/metabolismo , Masculino , Polifenoles/metabolismo , Polifenoles/farmacología , Ratas , Ratas Sprague-Dawley
11.
Eur J Pharmacol ; 859: 172533, 2019 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-31301308

RESUMEN

Cancer is a major cause of death in both developed and developing countries. Polyphenols, abundantly found in plants, possess many anticarcinogenic properties, including inhibition of cancer cell proliferation, tumor growth, angiogenesis, metastasis and inflammation, as well as pro-apoptotic effects. Our study aimed to investigate the effects of a complex of (+)-catechin with 2 lysines (Cat:Lys) on cancer and non-cancer cells. For this, the in vitro effects of Cat:Lys on the viability, growth, proliferation, apoptosis, nutrient uptake and migration of breast, pancreatic and colorectal cancer and non-cancer cell lines was evaluated. We found that Cat:Lys exerted antiproliferative and cytotoxic effects in all breast, pancreatic and colorectal cell lines tested, but with a much less marked amplitude in non-cancer cell lines. It nevertheless interfered with nutrient (3H-deoxy-D-glucose and 3H-lactate) uptake and with lactate production in both cancer and non-cancer cell lines. Cat:Lys was found to possess selective antimigratory effects in breast, pancreatic and colorectal cancer cell lines compared to non-cancer cell lines. Cat:Lys also exerted pro-apoptotic effects in all the cancer cell lines that we tested, but not in non-cancer breast and pancreatic cell lines. The antimigratory, but not the pro-apoptotic, effects of Cat:Lys were found to be mediated by JAK2/STAT3 and Wnt pathway inhibition. In conclusion, Cat:Lys is a strong candidate for the development of new, effective anticancer agents against cancer.


Asunto(s)
Apoptosis/efectos de los fármacos , Catequina/química , Movimiento Celular/efectos de los fármacos , Lisina/química , Polifenoles/química , Polifenoles/farmacología , Antineoplásicos/química , Antineoplásicos/farmacología , Transporte Biológico/efectos de los fármacos , Neoplasias de la Mama/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Neoplasias Colorrectales/patología , Glucosa/metabolismo , Humanos , Ácido Láctico/metabolismo , Neoplasias Pancreáticas/patología
12.
Food Funct ; 10(8): 4566-4576, 2019 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-31314039

RESUMEN

Intake of fructose-containing sugars is epidemiological and experimentally linked to metabolic syndrome (MS). We recently verified that the dietary polyphenol chrysin was able to abolish some of the metabolic changes induced by fructose-feeding in the rat. Because the role of the intestine upon fructose-induced MS is poorly understood, we decided to investigate the influence of fructose, in vivo, on the intestinal environment and the ability of chrysin to interfere with the putative observed changes. For this, adult male Sprague-Dawley rats were treated for 18 weeks as follows: (A) tap water (CONT), (B) tap water and chrysin (100 mg kg-1 day-1) (CHRY), (C) 10% fructose in tap water (FRUCT), and (D) 10% fructose in tap water and chrysin (100 mg kg-1 day-1) (FRUCT + CHRY). Our findings show that the relative expression of SGLT1 and GLUT2 mRNA were not affected by fructose-feeding and/or chrysin. In contrast, GLUT5 mRNA expression was markedly increased in fructose-fed animals, and this effect was reduced by chrysin. However, the apparent permeability to 14C-FRUCT was markedly and similarly decreased in FRUCT, CHRY and FRUCT + CHRY rats. Jejunal villus width and crypt depth were significantly higher in FRUCT and FRUCT + CHRYS rats, respectively. Finally, chrysin did not alter gut microbiota composition, but fructose significantly increased Lactobacillus and E. coli. Moreover, FRUCT + CHRY rats had an increase on the Firmicutes to Bacteroidetes ratio. This is the first report showing that chrysin is able to interfere with the effects of fructose at the intestinal level, which may contribute to the fructose-induced MS features.


Asunto(s)
Flavonoides/administración & dosificación , Microbioma Gastrointestinal/efectos de los fármacos , Intestinos/microbiología , Síndrome Metabólico/tratamiento farmacológico , Animales , Bacterias/clasificación , Bacterias/genética , Bacterias/aislamiento & purificación , Fructosa/efectos adversos , Fructosa/metabolismo , Transportador de Glucosa de Tipo 2/genética , Transportador de Glucosa de Tipo 2/metabolismo , Humanos , Masculino , Síndrome Metabólico/etiología , Síndrome Metabólico/metabolismo , Síndrome Metabólico/microbiología , Ratas , Ratas Sprague-Dawley , Transportador 1 de Sodio-Glucosa/genética , Transportador 1 de Sodio-Glucosa/metabolismo
13.
Toxicol Res (Camb) ; 7(6): 1236-1246, 2018 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-30542607

RESUMEN

The pathogenesis of various gastrointestinal diseases, including gastrointestinal cancers and inflammatory bowel disease, is associated with increased oxidative stress levels. We aimed to investigate the effect of oxidative stress induced by tert-butylhydroperoxide (TBH) on the uptake of 3H-deoxy-d-glucose (3H-DG) and 14C-fructose by the human intestinal Caco-2 cell line. TBH (500 µM; 24 h) increased lipid peroxidation (TBARS) levels and was not cytotoxic. TBH (500 µM; 24 h) increased uptake of both low (SGLT1-mediated) and high concentrations (SGLT1- and GLUT2-mediated) of 3H-DG, but did not affect absorption of 14C-fructose (GLUT2- and GLUT5-mediated). The polyphenol chrysin abolished the increase in TBARS levels and the increase in uptake of both low and high concentrations of 3H-DG induced by TBH. On the other hand, TBH blocked the inhibitory effect of chrysin on 14C-fructose uptake. 3H-DG uptake, but not 14C-fructose uptake, was sensitive to sweet taste receptor (STRs) inhibition (with lactisole). The inhibitory effect of lactisole in relation to uptake of 3H-DG (10 nM) (SGLT1-mediated), but not in relation to uptake of 3H-DG (50 mM) (SGLT1- and GLUT2-mediated), was abolished in the presence of TBH. So, these results show that the stimulatory effect of STRs on SGLT1-mediated transport is dependent on oxidative stress levels. In conclusion, this work shows that uptake of both 3H-DG and 14C-fructose is sensitive to oxidative stress levels. Moreover, it suggests that the three distinct transporters involved in the intestinal absorption of glucose and fructose (SGLT1, GLUT2 and GLUT5) have different sensitivities to oxidative stress levels, SGLT1 being the most sensitive and GLUT5 the least.

14.
Obes Facts ; 11(4): 287-293, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-29991056

RESUMEN

OBJECTIVE: To analyze the associations between height and BMI categories in a Portuguese representative sample. METHODS: This is a cross-sectional study with a representative sample of 32,644 Portuguese adults (52.4% females). Sociodemographic and lifestyle characteristics were obtained along with self-reported height and weight. We performed generalized linear models to assess the differences in attained height across BMI categories; analyses were adjusted for age, gender, education, family income per month, proxy reporting information, dietary patterns, and smoking. RESULTS: BMI categories included underweight and normal weight (46.4%), overweight (37.6%), obese class I and II (15.2%), and obese class III (0.8%). Adults with normal weight had a significantly higher height (females +7 cm and males +5 cm) when compared to obese class III. As BMI categories increased, height decreased. In females and males, after adjusting for confounders, estimates of attained height decreased when compared to the unadjusted model (ß = -0.049, 95% CI = -0.050; -0.049 and ß = -0.030, 95% CI = -0.031; -0.029, respectively), although they remained still significant. CONCLUSION: Our results suggest a significant difference in attained height between BMI categories. Future intervention programs aiming at preventing overweight and obesity should monitor sociodemographic, health and environmental conditions that affect attained height potential.


Asunto(s)
Estatura , Índice de Masa Corporal , Adulto , Anciano , Anciano de 80 o más Años , Peso Corporal , Estudios Transversales , Conducta Alimentaria , Femenino , Humanos , Estilo de Vida , Masculino , Persona de Mediana Edad , Obesidad/epidemiología , Sobrepeso/epidemiología , Portugal/epidemiología , Encuestas y Cuestionarios , Delgadez/epidemiología , Adulto Joven
15.
Rev Port Cardiol (Engl Ed) ; 37(8): 669-677, 2018 Aug.
Artículo en Inglés, Portugués | MEDLINE | ID: mdl-30055948

RESUMEN

OBJECTIVES: To characterize specific knowledge on cardiovascular disease, particularly stroke and myocardial infarction (MI), and its relationship with sociodemographic factors, health literacy and clinical history, among the Portuguese population. METHODS: In a cross-sectional study conducted in 2012, a total of 1624 Portuguese-speaking residents of mainland Portugal, aged between 16 and 79 years, were assessed through face-to-face interviews using a structured questionnaire. RESULTS: Around 30% of participants were unable to estimate the risk of MI or stroke. On average, those who responded estimated that 34.2% and 35.6% of Portuguese will suffer a stroke or MI, respectively, during their lifetime. "Not smoking" (36.8%) and a "healthy diet" (32.8%) were identified as the most important behaviors for prevention of cardiovascular disease, and less than half of the participants responded that the most appropriate option in the presence of acute cardiovascular signs or symptoms was to call the emergency number. "Dependence on daily activities" (90.7%) and "impaired speech" (89.8%) were frequently recognized as consequences of stroke, while "heart failure" (86.4%) and "dependence on daily activities" (85.3%) were the most frequently identified consequences of MI. Overall, participants with adequate health literacy revealed more appropriate cardiovascular health-related knowledge. CONCLUSIONS: There are important gaps in cardiovascular health-related knowledge in the Portuguese population. Health education strategies and practices should be sensitive to the differences in health literacy described herein, in order to improve cardiovascular health knowledge among the Portuguese population.


Asunto(s)
Enfermedades Cardiovasculares , Conocimientos, Actitudes y Práctica en Salud , Adolescente , Adulto , Anciano , Enfermedades Cardiovasculares/diagnóstico , Enfermedades Cardiovasculares/epidemiología , Estudios Transversales , Femenino , Alfabetización en Salud , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/epidemiología , Portugal , Autoinforme , Factores Socioeconómicos , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiología , Adulto Joven
16.
Reprod Toxicol ; 77: 33-42, 2018 04.
Artículo en Inglés | MEDLINE | ID: mdl-29425713

RESUMEN

Preeclampsia is a pregnancy disorder characterized by high maternal blood pressure, fetal growth restriction and intrauterine hypoxia. Folic acid is a vitamin required during pregnancy. In this work, we investigated the relationship between preeclampsia and the intake of distinct doses of folic acid during pregnancy. Considering that preeclampsia is associated with increased placental oxidative stress levels, we investigated the effect of oxidative stress induced by tert-butylhydroperoxide (TBH) in human trophoblast-derived cells cultured upon deficient/low, physiological and supra-physiological folic acid levels. The negative effect of TBH upon thiobarbituric acid reactive substances (TBARS), total, reduced and oxidized glutathione, cell viability, cell proliferation, culture growth and cell migration was more marked under folic acid excess. This study suggests more attention on the dose administered, and ultimately, on the overall folic acid levels during pregnancy, in the context of preeclampsia risk.


Asunto(s)
Ácido Fólico/farmacología , Estrés Oxidativo/efectos de los fármacos , Trofoblastos/citología , terc-Butilhidroperóxido/toxicidad , Apoptosis/efectos de los fármacos , Línea Celular , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Glutatión/metabolismo , Glutatión Peroxidasa/metabolismo , Humanos , L-Lactato Deshidrogenasa/metabolismo , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo
17.
Ortodontia ; 42(4): 293-296, set.-out. 2009. ilus
Artículo en Portugués | LILACS, BBO - Odontología | ID: lil-708294

RESUMEN

O corpo humano possui milhares de triângulos e este artigo visa a apresenta mais um, que se baseia no eixo X- y. O trabalho introduz a análise cefalornétrica do par cartesiano. Trata-se de uma análise triangular, em que são apresentados dois triânguloshistóricos, o de Bonwill (1887) e o de Tweed (1954).


The human body has thousands of triangle and this manuscript aimed at presenting one more, which is based on the X- Y axis. This article introduces the Cephalometric Analysis of the Cartesian Pair. A Triangular Analysis is described and two historic triangles are presented, namely the Bonwill (1887) and lhe Tweed (1954) triangles.


Asunto(s)
Cefalometría , Articuladores Dentales , Cara/anatomía & histología
18.
Ortodontia ; 40(4): 313-315, out.-dez. 2007. ilus
Artículo en Portugués | LILACS, BBO - Odontología | ID: lil-542781

RESUMEN

A análise cefalométrica triangular basal tem origem na análise cefalométrica triangular e o apoio da análise de Volta Redonda. Consiste em um triângulo baseado nos pontos: basio, násio e ínfero. Por ser matéria muito nova, não é de admirar a análise triangular basal não ter caso clínico; entretanto, fizemos algumas considerações que podem ser Caso Clínico ou Resumo.


Asunto(s)
Humanos , Cefalometría , Raíz del Diente , Anodoncia , Diente
19.
Nursing (Ed. bras., Impr.) ; 9(102): 1106-1110, nov. 2006. ilus
Artículo en Portugués | LILACS, BDENF - Enfermería | ID: lil-516586

RESUMEN

Este trabalho tem como objetivo descrever as técnicas de avaliação de lesões tissulares agudas e crônicas apresentando suas vantagens e desvantagens. Os dados foram descritos a partir da experiência de professores, enfermeiros e alunos no Ambulatório de Cirurgia do Hospital Universitário Antonio Pedro, com clientes portadores de úlceras. Destacam-se as facilidades e dificuldades encontradas no desenvolvimento de cada técnica. A observação sistematizada, minuciosa das úlceras através do decalque, da medida simples, da fotografia e dos registros de enfermagem possibilitam avaliar o processo cicatricial de feridas de várias etiologias.


Asunto(s)
Humanos , Cicatrización de Heridas , Registros de Enfermería
20.
Arq Neuropsiquiatr ; 63(3A): 618-24, 2005 Sep.
Artículo en Portugués | MEDLINE | ID: mdl-16172711

RESUMEN

Forty-three patients with epilepsy resistant to drug therapy were submitted to temporal lobe epilepsy surgery at the Instituto de Neurologia de Curitiba, from 1998 to 2003. Thirty-nine patients (90.6%) had mesial temporal sclerosis, and four had brain tumors. According to Engel's rating, 83.7% from 37 patients with complete postoperative evaluation were classified as Class I (free of disabling seizure). Postoperative complications (18.6%) were evaluated, with one case of surgical wound infection, one case of hydrocephalus, one case of cerebrospinal fluid fistula, two cases of transient palsy of the trochlear nerve and one case of transient hemiparesis. No death related to epilepsy surgery was found in our study.


Asunto(s)
Neoplasias Encefálicas/complicaciones , Craneotomía/métodos , Epilepsia del Lóbulo Temporal/cirugía , Lóbulo Temporal/cirugía , Adulto , Neoplasias Encefálicas/cirugía , Electroencefalografía , Epilepsia del Lóbulo Temporal/etiología , Femenino , Estudios de Seguimiento , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Pruebas Neuropsicológicas , Estudios Retrospectivos , Esclerosis/complicaciones , Esclerosis/cirugía , Lóbulo Temporal/patología , Resultado del Tratamiento
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