Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 44
Filtrar
1.
Cell Death Dis ; 7: e2168, 2016 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-27031965

RESUMO

Although the mechanisms controlling skeletal muscle homeostasis have been identified, there is a lack of knowledge of the integrated dynamic processes occurring during myogenesis and their regulation. Here, metabolism, autophagy and differentiation were concomitantly analyzed in mouse muscle satellite cell (MSC)-derived myoblasts and their cross-talk addressed by drug and genetic manipulation. We show that increased mitochondrial biogenesis and activation of mammalian target of rapamycin complex 1 inactivation-independent basal autophagy characterize the conversion of myoblasts into myotubes. Notably, inhibition of autophagic flux halts cell fusion in the latest stages of differentiation and, conversely, when the fusion step of myocytes is impaired the biogenesis of autophagosomes is also impaired. By using myoblasts derived from p53 null mice, we show that in the absence of p53 glycolysis prevails and mitochondrial biogenesis is strongly impaired. P53 null myoblasts show defective terminal differentiation and attenuated basal autophagy when switched into differentiating culture conditions. In conclusion, we demonstrate that basal autophagy contributes to a correct execution of myogenesis and that physiological p53 activity is required for muscle homeostasis by regulating metabolism and by affecting autophagy and differentiation.


Assuntos
Autofagia , Diferenciação Celular , Mitocôndrias/metabolismo , Mioblastos/citologia , Células Satélites de Músculo Esquelético/citologia , Cloreto de Amônio/farmacologia , Animais , Autofagia/efeitos dos fármacos , Proteína Beclina-1/antagonistas & inibidores , Proteína Beclina-1/genética , Proteína Beclina-1/metabolismo , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Leupeptinas/farmacologia , Alvo Mecanístico do Complexo 1 de Rapamicina , Camundongos , Camundongos Knockout , Microscopia Confocal , Proteínas Associadas aos Microtúbulos/metabolismo , Complexos Multiproteicos/metabolismo , Fibras Musculares Esqueléticas/citologia , Fibras Musculares Esqueléticas/metabolismo , Mioblastos/metabolismo , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Proteína Supressora de Tumor p53/deficiência , Proteína Supressora de Tumor p53/genética
2.
Food Funct ; 2(7): 395-9, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21894326

RESUMO

Although eggplants are known to be part of a healthy diet, the effects of this fruit on cardioprotection are not known. The present study examined the role of raw and grilled eggplants on cardioprotection using an isolated perfusion heart model. The animals were fed freeze-dried products of either raw or grilled eggplants for 30 days. After 30 days, isolated working hearts were subjected to 30 min ischemia followed by 2 h of reperfusion. Left ventricular function was monitored, and myocardial infarct size and cardiomyocyte apoptosis were assessed. To determine the antioxidant function of eggplants, their DPPH scavenging ability were determined, and polyphenolic components, especially nasunin content, were determined. The chemical composition of raw and grilled eggplants were determined in order to examine whether grilling was associated with major changes in their composition. The results of this study demonstrated eggplants as containing potent cardioprotective compounds judging by their ability to increase left ventricular function, and reduce myocardial infarct size and cardiomyocyte apoptosis. However, there was no difference in cardioprotective ability between the raw and grilled products. The antioxidant vitamins, including vitamin A, vitamin C and ß-carotene, were lower and some of the polyphenolic components, especially nasunin content, were higher in grilled eggplants, but they were unable to demonstrate better cardioprotective properties compared to the raw fruit.


Assuntos
Cardiotônicos/administração & dosagem , Temperatura Alta , Solanum melongena/química , Animais , Antocianinas/análise , Antioxidantes/análise , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Cardiotônicos/análise , Masculino , Malondialdeído/análise , Infarto do Miocárdio/prevenção & controle , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/fisiologia , Polifenóis/análise , Ratos , Ratos Sprague-Dawley , Função Ventricular Esquerda/efeitos dos fármacos , Vitaminas/análise
3.
Oncogene ; 30(41): 4231-42, 2011 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-21532615

RESUMO

The interaction between cancer cells and microenvironment has a critical role in tumor development and progression. Although microRNAs regulate all the major biological mechanisms, their influence on tumor microenvironment is largely unexplored. Here, we investigate the role of microRNAs in the tumor-supportive capacity of stromal cells. We demonstrated that miR-15 and miR-16 are downregulated in fibroblasts surrounding the prostate tumors of the majority of 23 patients analyzed. Such downregulation of miR-15 and miR-16 in cancer-associated fibroblasts (CAFs) promoted tumor growth and progression through the reduced post-transcriptional repression of Fgf-2 and its receptor Fgfr1, which act on both stromal and tumor cells to enhance cancer cell survival, proliferation and migration. Moreover, reconstitution of miR-15 and miR-16 impaired considerably the tumor-supportive capability of stromal cells in vitro and in vivo. Our data suggest a molecular circuitry in which miR-15 and miR-16 and their correlated targets cooperate to promote tumor expansion and invasiveness through the concurrent activity on stromal and cancer cells, thus providing further support to the development of therapies aimed at reconstituting miR-15 and miR-16 in advanced prostate cancer.


Assuntos
Fibroblastos/metabolismo , MicroRNAs/genética , Neoplasias da Próstata/genética , Microambiente Tumoral/genética , Idoso , Idoso de 80 Anos ou mais , Animais , Western Blotting , Linhagem Celular Tumoral , Regulação para Baixo , Fator 2 de Crescimento de Fibroblastos/metabolismo , Fibroblastos/patologia , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Pessoa de Meia-Idade , Neoplasias Experimentais/genética , Neoplasias Experimentais/metabolismo , Neoplasias Experimentais/patologia , Fosforilação , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transplante Heterólogo
4.
Int J Immunopathol Pharmacol ; 22(4): 967-78, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-20074460

RESUMO

This study reports the immunomodulatory activity on human monocyte derived dendritic cells (MDDCs) of a vaccine preparation shown to be effective against an HPV16-related tumour in an animal model. The vaccine is composed of extract from Nicotiana benthamiana leaves containing HPV16 E7 protein expressed by a potato virus X-derived vector (NbPVX-E7). The effect of the extract was evaluated on MDDC differentiation and maturation by monitoring the phenotypic expression of specific markers. The results show that NbPVX-E7 does not induce monocyte differentiation to dendritic cells, but does induce MDDC maturation. Plant extract does not influence MDDC-uptake of E7-FITC while it significantly improves the Ovalbumin-FITC uptake, considered as a model antigen. Importantly, NbPVX-E7-pulsed MDDCs/PBMCs are able to prime human blood-derived lymphocytes from healthy individuals to induce HPV16 E7-specific cytotoxic activity. This is a propaedeutic study for a possible use of E7-containing plant extract in human immunotherapy of HPV-related lesions.


Assuntos
Adjuvantes Imunológicos/farmacologia , Células Dendríticas/imunologia , Linfócitos/imunologia , Nicotiana/metabolismo , Proteínas Oncogênicas Virais/imunologia , Vacinas contra Papillomavirus/imunologia , Extratos Vegetais/imunologia , Plantas Geneticamente Modificadas , Adjuvantes Imunológicos/isolamento & purificação , Apresentação de Antígeno , Diferenciação Celular , Linhagem Celular Tumoral , Sobrevivência Celular , Técnicas de Cocultura , Citotoxicidade Imunológica , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/metabolismo , Relação Dose-Resposta a Droga , Vetores Genéticos , Humanos , Ativação Linfocitária , Linfócitos/efeitos dos fármacos , Masculino , Proteínas Oncogênicas Virais/biossíntese , Proteínas Oncogênicas Virais/genética , Proteínas Oncogênicas Virais/isolamento & purificação , Ovalbumina/imunologia , Ovalbumina/metabolismo , Proteínas E7 de Papillomavirus , Vacinas contra Papillomavirus/biossíntese , Vacinas contra Papillomavirus/genética , Vacinas contra Papillomavirus/isolamento & purificação , Extratos Vegetais/isolamento & purificação , Folhas de Planta , Potexvirus/genética , Proteínas Recombinantes/imunologia , Fatores de Tempo , Nicotiana/genética
5.
Lancet ; 371(9623): 1505-12, 2008 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-18455228

RESUMO

BACKGROUND: Osteoporosis is diagnosed by the measurement of bone mineral density, which is a highly heritable and multifactorial trait. We aimed to identify genetic loci that are associated with bone mineral density. METHODS: In this genome-wide association study, we identified the most promising of 314 075 single nucleotide polymorphisms (SNPs) in 2094 women in a UK study. We then tested these SNPs for replication in 6463 people from three other cohorts in western Europe. We also investigated allelic expression in lymphoblast cell lines. We tested the association between the replicated SNPs and osteoporotic fractures with data from two studies. FINDINGS: We identified genome-wide evidence for an association between bone mineral density and two SNPs (p<5x10(-8)). The SNPs were rs4355801, on chromosome 8, near to the TNFRSF11B (osteoprotegerin) gene, and rs3736228, on chromosome 11 in the LRP5 (lipoprotein-receptor-related protein) gene. A non-synonymous SNP in the LRP5 gene was associated with decreased bone mineral density (rs3736228, p=6.3x10(-12) for lumbar spine and p=1.9x10(-4) for femoral neck) and an increased risk of both osteoporotic fractures (odds ratio [OR] 1.3, 95% CI 1.09-1.52, p=0.002) and osteoporosis (OR 1.3, 1.08-1.63, p=0.008). Three SNPs near the TNFRSF11B gene were associated with decreased bone mineral density (top SNP, rs4355801: p=7.6x10(-10) for lumbar spine and p=3.3x10(-8) for femoral neck) and increased risk of osteoporosis (OR 1.2, 95% CI 1.01-1.42, p=0.038). For carriers of the risk allele at rs4355801, expression of TNFRSF11B in lymphoblast cell lines was halved (p=3.0x10(-6)). 1883 (22%) of 8557 people were at least heterozygous for these risk alleles, and these alleles had a cumulative association with bone mineral density (trend p=2.3x10(-17)). The presence of both risk alleles increased the risk of osteoporotic fractures (OR 1.3, 1.08-1.63, p=0.006) and this effect was independent of bone mineral density. INTERPRETATION: Two gene variants of key biological proteins increase the risk of osteoporosis and osteoporotic fracture. The combined effect of these risk alleles on fractures is similar to that of most well-replicated environmental risk factors, and they are present in more than one in five white people, suggesting a potential role in screening.


Assuntos
Densidade Óssea/genética , Fraturas Ósseas/etiologia , Proteínas Relacionadas a Receptor de LDL/genética , Osteoporose/genética , Osteoprotegerina/genética , Polimorfismo de Nucleotídeo Único/genética , Alelos , Cromossomos Humanos Par 11 , Cromossomos Humanos Par 8 , Feminino , Expressão Gênica , Marcadores Genéticos , Genoma Humano , Genótipo , Humanos , Proteína-5 Relacionada a Receptor de Lipoproteína de Baixa Densidade , Vértebras Lombares , Masculino , Pessoa de Meia-Idade , Osteoporose/complicações
6.
Clin Endocrinol (Oxf) ; 68(4): 652-9, 2008 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17970774

RESUMO

OBJECTIVE: Thyroid hormone action influences many metabolic and synthetic processes, but the degree of regulation attributed to genes and environmental factors affecting normal variation remains controversial. DESIGN: We investigated the magnitude of the genetic and environmental determination of serum concentrations of free (f) T3, fT4, TSH and the fT4 x TSH product and their variation, in a large cohort of twin pairs. Female dizygous and monozygous twins (849 and 213 pairs, respectively) from the TwinsUK registry (mean age 45.5, range 18-80 years) were studied. RESULTS: Comparison of thyroid parameters within various groups showed no differences between smoking categories, and higher serum TSH and lower fT3 in subjects with positive thyroid antibodies. Using structural equation modelling, we estimated the heritable contribution to serum thyroid parameters (with 95% confidence intervals) to be 65% (58%-71%) for TSH, 65% (58%-71%) for the fT4 x TSH product, 39% (20%-55%) for fT4 and 23% (3%-41%) for fT3. CONCLUSIONS: We conclude that genetic regulation is a particularly important determinant of TSH and the fT4 x TSH product, and is a less important determinant of fT4 and fT3 concentrations in Caucasian women. These data from a large well-characterized cohort suggest that while there is a strong heritable contribution to serum TSH, variation in fT4 and fT3 concentrations may be less explained by genetic factors and more driven by environmental effects than previously thought.


Assuntos
Hipófise/fisiologia , Glândula Tireoide/fisiologia , Tireotropina/sangue , Tiroxina/sangue , Tri-Iodotironina/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tireotropina/genética , Tiroxina/genética , Tri-Iodotironina/genética , Gêmeos Dizigóticos/genética , Gêmeos Monozigóticos/genética , Reino Unido
7.
J Agric Food Chem ; 54(18): 6613-22, 2006 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-16939317

RESUMO

Recent studies have documented that grapes and grape juices are equally cardioprotective as red wine. The existing reports implicate that the skin and seeds of the grapes containing polyphenolic antioxidants are instrumental for the cardioprotective properties of grapes. The present study examines if the flesh of grapes also possesses any cardioprotective abilities. Three groups of randomly selected rats were fed, water only (control), flesh of the grapes (2.5 mg/kg b. wt.) or the skins (2.5 mg/kg b. wt.) for 30 days. At the end of the 30 days, isolated perfused hearts were made ischemic for 30 min followed by 2 h of reperfusion in the working mode. The results demonstrated that both flesh and skin of the grapes could protect the hearts from ischemic reperfusion injury as evidenced by improved postischemic ventricular recovery and reduced myocardial infarct size. High performance liquid chromatography (HPLC) revealed that skin and flesh contained comparative amounts of glucose, fructose, tartaric acid, malic acid, shikimic acid, and trans-caftaric acid. In addition, the flesh contained reduced amounts (compared to skin) of cis-coutaric, trans-coutaric, caffeic, p-coumaric, cinnamics, and catechin/epicatechin. Total polyphenolic index was also lower in flesh compared to skin. The anthocyanins were present exclusively in the skin. Electron paramagnetic resonance (EPR) spectrometry of hydroxy radicals indicated that both flesh and skins possessed equal amount of ROS scavenging activities. Total malonaldehyde content in the heart was reduced comparatively with either flesh or skin. The results indicate for the first time that the flesh of grapes are equally cardioprotective as skin, and antioxidant potential of skin and flesh of grapes are comparable with each other despite of the fact that flesh does not possess any anthocyanin activities.


Assuntos
Cardiotônicos/administração & dosagem , Cardiotônicos/análise , Frutas/anatomia & histologia , Frutas/química , Vitis/química , Animais , Antioxidantes/análise , Antioxidantes/farmacologia , Carboidratos/análise , Espectroscopia de Ressonância de Spin Eletrônica , Flavonoides/análise , Masculino , Infarto do Miocárdio/patologia , Infarto do Miocárdio/terapia , Traumatismo por Reperfusão Miocárdica/prevenção & controle , Fenóis/análise , Polifenóis , Ratos , Ratos Sprague-Dawley
8.
Mol Cell Biochem ; 282(1-2): 65-73, 2006 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-16317513

RESUMO

Tomato (Lycopersicon esculentum) is a vegetable rich in antioxidants, such as lycopene, lutein, and zeaxanthin. Their presence is responsible for the characteristic ability of this product to inhibit the formation of reactive oxygen species, including singlet oxygen. The grapes and wines derived from grapes also contain powerful antioxidants. The antioxidant effect is derived from the polyphenols such as resveratrol and proanthocyanidin. Resveratrol is phytoalexin that is synthesized via the activation of the gene, stilbene synthase (STS). We decided to determine if the introduction of this gene into Lycopersicon esculentum Mill could modify its antioxidant activity. Using Electronic Paramagnetic Resonance (EPR) spectroscopy, which permits the detection of antiradical activity, especially *OH (hydroxyl radical), we showed that the antioxidant activity of the products, into which the gene STS had been introduced, was almost double than that of natural products and that their activity was especially pronounced due to ripening. Moreover, resveratrol concentrations in modified tomatoes were much higher than that found in the individual fruit. In the isolated hearts subjected to ischemia/reperfusion, the rats fed with modified tomato exhibited better cardiac performance, reduced myocardial infarct size and decreased number of apoptotic cardiomyocytes, and reduced oxidative stress compared to unmodified tomato or resveratrol alone indicating superior cardioprotective abilities of modified tomatoes.


Assuntos
Aciltransferases/genética , Antioxidantes/metabolismo , Miocárdio/patologia , Traumatismo por Reperfusão/patologia , Solanum lycopersicum , Estilbenos/metabolismo , Animais , Apoptose , Dieta , Espectroscopia de Ressonância de Spin Eletrônica , Radicais Livres/metabolismo , Peroxidação de Lipídeos , Solanum lycopersicum/genética , Solanum lycopersicum/metabolismo , Masculino , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/patologia , Infarto do Miocárdio/fisiopatologia , Miócitos Cardíacos/patologia , Estresse Oxidativo , Plantas Geneticamente Modificadas , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/fisiopatologia , Resveratrol , Estilbenos/uso terapêutico
10.
Drugs Exp Clin Res ; 31(3): 109-14, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16033249

RESUMO

The pool of different carnitine derivatives is formed by carnitine, acetylcarnitine, propionylcarnitine and isovalerylcarnitine. Isovalerylcarnitine is a compound performing activities that differ from those of the other carnitine esters. Its activity on proteolytic enzymes and on the calpain system has been demonstrated in the past. Both the calpain and the caspase systems belong to the protease family and lead to cytochrome activation and apoptosis. The two systems can interact to promote apoptosis. In view of this proapoptotic activity of isovalerylcarnitine, studies were carried out to ascertain whether this carnitine derivative influences cell-reaction processes associated with apoptosis. U937 leukemic cells were selected for these studies because they are a well-established model for the assessment of cellular immune responses. In addition to nuclear morphologic alterations produced by apoptosis that can be detected by specific histochemical and microscopic methods, we also took other cell functions into consideration, such as phagocytosis, cell killing and cell growth, which are indices of immune function related to apoptosis. Unlike reference carnitine forms, isovalerylcarnitine produced an early and marked increase in phagocytosis and also an increase in cell killing. Cell proliferation was reduced. The hypothesis is set forth that isovalerylcarnitine may be a caspase-activating, proapoptotic factor that resembles various anticancer agents, which induce early apoptosis that coincides with early activation of caspase. This hypothesis is supported by the ability of isovalerylcarnitine to induce early phagocytosis and cell killing.


Assuntos
Acetilcarnitina/farmacologia , Apoptose/efeitos dos fármacos , Carnitina/análogos & derivados , Proliferação de Células/efeitos dos fármacos , Fagocitose/efeitos dos fármacos , Carnitina/farmacologia , Linhagem Celular Tumoral , Humanos , Fagocitose/imunologia
11.
Exp Dermatol ; 14(2): 130-7, 2005 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-15679583

RESUMO

The pathogenic mechanism underlying the hyperproliferation of keratinocytes in psoriasis is still not completely clarified. The production of cytokines released by activated T lymphocytes infiltrating the upper dermis probably has a crucial role. Even dermal fibroblasts can participate in the process through the secretion of growth factors, and some studies have reported an increased expression of the insulin-like growth factor 1. Few studies, however, have focused on the possible involvement of the keratinocyte growth factor (KGF/FGF-7) and the fibroblast growth factor 10 (FGF-10/KGF-2), which are secreted by fibroblasts and stimulate keratinocyte proliferation acting through a receptor specifically expressed by epithelial cells. The aim of this study was to investigate the expression of KGF and FGF-10 on the skin of patients with psoriasis by immunohistochemical analysis and to evaluate the correlation with the lymphocyte infiltrate and the epidermal proliferation. Immunostaining for KGF and FGF-10 showed that both the growth factors are upregulated in the upper dermis of psoriatic skin, and that the expression is correlated with the presence of T-cell infiltrate and with keratinocyte proliferation. Our data suggest that in psoriatic lesions activated lymphocytes can stimulate fibroblasts to produce KGF and FGF-10, which in turn contribute to sustain the hyperproliferative status of the keratinocytes.


Assuntos
Fatores de Crescimento de Fibroblastos/biossíntese , Psoríase/metabolismo , Adulto , Biópsia , Western Blotting , Proliferação de Células , Feminino , Fator 10 de Crescimento de Fibroblastos , Fator 7 de Crescimento de Fibroblastos , Humanos , Processamento de Imagem Assistida por Computador , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Pele/patologia , Linfócitos T/metabolismo , Fatores de Tempo
12.
Drugs Exp Clin Res ; 30(3): 111-5, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15366787

RESUMO

The ability of two samples of red wine with different resveratrol concentrations to inhibit hydroxyl radicals (*OH) produced by a Fenton-type reaction was assessed using the method of electronic paramagnetic resonance (EPR). One sample was an autochthonous wine, Uvalino, which has a very high resveratrol concentration; the second was another red wine with a much lower resveratrol concentration. The ability of the sample of Uvalino wine to obstruct hydroxyl radicals was evident, but it wasn't much better than the ability of the sample of wine with a lower resveratrol concentration. The resveratrol concentration of wine is an important factor for the inhibition of the formation of free radicals, especially hydroxyl radicals; however, it is not the only one responsible for this property of wine. Resveratrol concentration can act synergically with other factors, such as polyphenols, which are also contained in wine and have antioxidant properties.


Assuntos
Avaliação Pré-Clínica de Medicamentos/métodos , Espectroscopia de Ressonância de Spin Eletrônica/métodos , Radicais Livres/antagonistas & inibidores , Estilbenos/análise , Vinho/análise , Sinergismo Farmacológico , Flavonoides/análise , Flavonoides/farmacologia , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Radicais Livres/efeitos adversos , Radicais Livres/análise , Itália , Fenóis/análise , Fenóis/farmacologia , Polifenóis , Resveratrol , Estilbenos/farmacologia , Vitis/química , Vitis/classificação , Vinho/classificação
13.
Drugs Exp Clin Res ; 30(5-6): 203-6, 2004.
Artigo em Inglês | MEDLINE | ID: mdl-15700747

RESUMO

A new chemical named parrodienes has been extracted from parrots' plumage. From the chemical point of view, parrodienes are polyunsaturated aldehydes similar to carotenoids. On the basis of this similarity we organized some biological experiments to evaluate the inhibition of lipoperoxidation of cell membranes induced by CCl4, protection against ultraviolet rays, anti-inflammatory activity and protection from an increase of ornithine-decarboxylase as marker of tumoral skin alteration. The results of these experiments showed that unsaturated dienes (parrodienes) play an important role on the inhibition and prevention of many biological processes that are at the basis of different pathological disorders.


Assuntos
Aldeídos/química , Aldeídos/farmacologia , Carotenoides/química , Carotenoides/farmacologia , Papagaios , Aldeídos/uso terapêutico , Animais , Carotenoides/uso terapêutico , Cobaias , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Peroxidação de Lipídeos/fisiologia , Ratos , Pele/efeitos dos fármacos , Pele/metabolismo , Pele/efeitos da radiação
14.
Int J Tissue React ; 24(2): 53-6, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12182233

RESUMO

The objective of this study was to assess whether tyrosol and caffeic acid are able to inhibit lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF)-alpha release. TNF is one of the most important cytokines involved in inflammatory reactions. The results show that both tyrosol and caffeic acid are able to inhibit LPS-induced TNF-alpha release from human monocytes, even at low doses. Their mechanisms of action are discussed and we conclude that high doses of the two compounds are not required to achieve effective inhibition of inflammatory reactions due to TNF-alpha release.


Assuntos
Ácidos Cafeicos/farmacologia , Lipopolissacarídeos/farmacologia , Monócitos/efeitos dos fármacos , Monócitos/metabolismo , Álcool Feniletílico/análogos & derivados , Álcool Feniletílico/farmacologia , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Ácidos Cafeicos/administração & dosagem , Células Cultivadas , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Humanos , Álcool Feniletílico/administração & dosagem , Vinho
15.
Drugs Exp Clin Res ; 28(1): 11-5, 2002.
Artigo em Inglês | MEDLINE | ID: mdl-12073763

RESUMO

Some well-known antioxidant phenols present in extravirgin olive oil have also been found in white wine. Both tyrosol and caffeic acid are phenols that are present not only in extravirgin olive oil, but also in wine, especially white wine. Their antioxidant properties are well known, but their biological effects have not yet been elucidated. In a previous study we found that these substances were able to inhibit tumor necrosis factor alpha release. The present study was carried out to assess whether these compounds are able to inhibit other inflammatory cytokines, such as interleukin-1 beta and interleukin-6. The results show that low concentrations of these phenols, which can be found in the bloodstream after intake of moderate quantities of white wine, exert significant inhibitory activity on the release of several inflammatory cytokines.


Assuntos
Antioxidantes/farmacologia , Ácidos Cafeicos/farmacologia , Interleucina-1/biossíntese , Interleucina-6/biossíntese , Álcool Feniletílico/análogos & derivados , Álcool Feniletílico/farmacologia , Vinho , Células Sanguíneas/efeitos dos fármacos , Células Sanguíneas/metabolismo , Relação Dose-Resposta a Droga , Humanos , Técnicas In Vitro
16.
J Virol ; 75(15): 7161-74, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11435597

RESUMO

Human herpesvirus 8 (HHV-8) is found in immunoblastic B cells of patients with multicentric Castleman's disease (MCD) and, predominantly in a latent form, in primary effusion lymphoma (PEL) cells and Kaposi's sarcoma (KS) spindle cells. Recent studies have shown that upon reactivation, HHV-8 expresses factors that downregulate major histocompatibility class I proteins and coactivation molecules and that may enable productively infected cells to escape cytotoxic T lymphocytes and natural killer cell responses. One of these viral factors is encoded by open reading frame (ORF) K3. Here we show that in PEL cells, ORF K3 is expressed through viral transcripts that are induced very early upon virus reactivation, including bicistronic RNA molecules containing coding sequences from viral ORFs K3 and 70. Specifically, we found that a bicistronic transcript was expressed in the absence of de novo protein synthesis, thereby identifying a novel HHV-8 immediate-early gene product. Several features of the RNA molecules encoding the K3 product, including multiple transcriptional start sites, multiple donor splicing sites, and potential alternative ATG usage, suggest that there exists a finely tuned modulation of ORF K3 expression. By contrast, ORF K3 transcripts are not detected in the majority of cells present in KS lesions that are latently infected by the virus, suggesting that there are other, as-yet-unknown mechanisms of immune evasion for infected KS spindle cells. Nevertheless, because HHV-8 viremia precedes the development of KS lesions and is associated with the recrudescence of MCD symptoms, the prompt expression of ORF K3 in productively infected circulating cells may be important for virus pathogenesis. Thus, molecules targeting host or viral factors that activate ORF K3 expression or inactivate the biological functions of the K3 product should be exploited for the prevention or treatment of HHV-8-associated diseases in at-risk individuals.


Assuntos
Regulação Viral da Expressão Gênica , Herpesvirus Humano 8/genética , Proteínas Imediatamente Precoces/genética , Linfoma/virologia , Fases de Leitura Aberta , Sarcoma de Kaposi/virologia , Proteínas Virais/genética , Sequência de Bases , Linhagem Celular , Mapeamento Cromossômico , DNA Viral , Perfilação da Expressão Gênica , Humanos , Linfoma/patologia , Dados de Sequência Molecular , Hibridização de Ácido Nucleico/métodos , Reação em Cadeia da Polimerase/métodos , RNA Mensageiro , RNA Viral , Sarcoma de Kaposi/patologia , Transcrição Gênica , Células Tumorais Cultivadas
17.
Therapie ; 56(5): 613-6, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11806302

RESUMO

Resveratrol, a phytoalexin found in grapes and wine, has been shown to have anti-inflammatory properties. Since endothelium is activated during inflammation by some cytokines released by macrophages and many other cells, we tested whether resveratrol could modulate endothelial cell activation. We studied the effect of resveratrol treatment in vitro on the expression of vascular cell adhesion molecule-1 by tumour necrosis factor alpha-stimulated human umbilical vein endothelial cells. In addition, we studied the effect of resveratrol treatment in vivo (in a murine experimental model) on the modulation of tumour necrosis factor alpha-induced vascular permeability. Resveratrol, used at the concentrations present in human plasma following moderate wine consumption, was demonstrated to be an inhibitor of the adhesion molecule expression by tumour necrosis factor alpha-stimulated endothelial cells. In addition, resveratrol significantly prevented the cytokine-induced vascular leakage. Our results (both in vitro and in vivo) may explain some aspects of the anti-inflammatory effects of resveratrol.


Assuntos
Inibidores da Angiogênese/farmacologia , Endotélio Vascular/efeitos dos fármacos , Estilbenos/farmacologia , Fator de Necrose Tumoral alfa/farmacologia , Células Cultivadas , Endotélio Vascular/citologia , Endotélio Vascular/fisiologia , Humanos , Resveratrol , Fator de Necrose Tumoral alfa/fisiologia , Veias Umbilicais
18.
Growth Factors ; 19(4): 259-67, 2001.
Artigo em Inglês | MEDLINE | ID: mdl-11811781

RESUMO

C-met immunoreactivity and its co-expression with duct-associated insulin were evaluated in pancreata of non-obese diabetic (NOD) and low-dose streptozotocin (Id-STZ) mice. Diabetic NOD and non-diabetic NOD at the age of 4-8, 15-22 and 30-41 weeks and Balb/c mice at the same age intervals were studied. Ld-STZ mice were studied at day 12 and 24 after STZ administration. A stronger ductal c-met immunoreactivity and a significantly higher number of c-met positive ducts were found in diabetic NOD vs both non-diabetic NOD and Balb/c mice of comparable age. In non-diabetic NOD, the ductal c-met immunoreactivity progressively increased with age and was significantly higher than controls. In 1d-STZ mice a significantly increased ductal c-met immunoreactivity was detected both at day 12 and 24 vs untreated mice. C-met positive ductal cells were also positive for insulin although insulin positive c-met negative ducts were present. This study showed an increased c-met expression and the co-expression of c-met and duct-associated insulin, in both NOD and 1d-STZ mice.


Assuntos
Diabetes Mellitus Experimental/metabolismo , Ilhotas Pancreáticas/metabolismo , Proteínas Proto-Oncogênicas c-met/metabolismo , Animais , Fator de Crescimento de Hepatócito/metabolismo , Imuno-Histoquímica , Insulina/metabolismo , Ilhotas Pancreáticas/citologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos NOD , Microscopia de Fluorescência , Fatores de Tempo
19.
EMBO J ; 19(19): 5123-34, 2000 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-11013215

RESUMO

CD95 (APO-1/Fas) is a member of the tumor necrosis factor receptor family, which can trigger apoptosis in a variety of cell types. However, little is known of the mechanisms underlying cell susceptibility to CD95-mediated apoptosis. Here we show that human T cells that are susceptible to CD95-mediated apoptosis, exhibit a constitutive polarized morphology, and that CD95 colocalizes with ezrin at the site of cellular polarization. In fact, CD95 co-immunoprecipitates with ezrin exclusively in lymphoblastoid CD4(+) T cells and primary long-term activated T lymphocytes, which are prone to CD95-mediated apoptosis, but not in short-term activated T lymphocytes, which are refractory to the same stimuli, even expressing equal levels of CD95 on the cell membrane. Pre-treatment with ezrin antisense oligonucleotides specifically protected from the CD95-mediated apoptosis. Moreover, we show that the actin cytoskeleton integrity is essential for this function. These findings strongly suggest that the CD95 cell membrane polarization, through an ezrin-mediated association with the actin cytoskeleton, is a key intracellular mechanism in rendering human T lymphocytes susceptible to the CD95-mediated apoptosis.


Assuntos
Citoesqueleto de Actina/metabolismo , Apoptose/fisiologia , Fosfoproteínas/metabolismo , Linfócitos T/citologia , Receptor fas/metabolismo , Proteínas Sanguíneas/metabolismo , Western Blotting , Polaridade Celular , Células Cultivadas , Proteínas do Citoesqueleto/metabolismo , Citometria de Fluxo , Imunofluorescência , Humanos , Imuno-Histoquímica , Proteínas de Membrana/metabolismo , Proteínas dos Microfilamentos/metabolismo , Microscopia Eletrônica de Varredura , Microscopia de Vídeo , Oligonucleotídeos Antissenso , Ligação Proteica , Linfócitos T/metabolismo , Receptor fas/fisiologia
20.
Ophthalmology ; 107(6): 1042-6, 2000 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-10857820

RESUMO

PURPOSE: To investigate the adherence of one clinically relevant ocular isolate of Staphylococcus epidermidis to polymethyl methacrylate (PMMA) and Acrysof (Alcon Surgical, Fort Worth, TX) intraocular lenses (IOLs). DESIGN: Experimental study. PARTICIPANTS: The authors examined the in vitro adherence of one clinically relevant ocular isolate of S. epidermidis. Adherence was tested on 12 PMMA IOLs and 12 Acrysof IOLs. METHODS: Six IOLs (three of each type) were placed in different test tubes containing bacterial suspension (10(8) cfu/ml) and incubated at 37 degrees C. At different times (3 minutes, 30 minutes, and 90 minutes), each IOL type was removed from the test tube, rinsed in sterile phosphate-buffered saline, and transferred into sterile brain-heart infusion broth. The broth with the IOL was sonicated on low power for 3 minutes to remove adhered bacteria. Two serial 10-fold dilutions of the broth containing the dislodged bacteria were plated on mannitol agar plates. The plates were incubated overnight at 37 degrees C and then bacterial colonies were counted. All assays were performed in triplicate. Additional lenses (three of each type) were incubated with S. epidermidis for different times (3 minutes, 30 minutes, and 90 minutes) and then examined with scanning electron microscopy. MAIN OUTCOME MEASURES: The number of adhered bacteria per area (mm ) of IOL optic was calculated. Statistical analysis included calculation of arithmetic means and 95% confidence intervals (t test). RESULTS: Direct counting of viable adherent bacteria released by sonication showed that the amount of adhered bacteria per area of IOL optic after 3, 30, and 90 minutes' incubation in S. epidermidis suspension was 0.1 x 10(2)/mm2, 3.6 x 10(2)/mm2, and 11 x 10(2)/mm2 (PMMA IOLs), and 4.4 x 10(2)/mm2, 3.1 x 10(2)/mm2, and 2.3 x 10(2)/mm2 (Acrysof IOLs). Direct counting of adherent bacteria in scanning electron microscopy photographs revealed that the total amount of adhered bacteria per area of IOL optic after 3, 30, and 90 minutes' incubation in S. epidermidis suspension was 1.1 x 10(2)/mm2, 4.4 x 10(2)/mm2, and 5.5 x 10(2)/mm2 (PMMA IOLs) and 13 x 10(2)/mm2, 33.9 x 10(2)/mm2, and 72 x 10(2)/mm2 (Acrysof IOLs). CONCLUSIONS: Results suggest that in vitro adherence of S. epidermidis to IOLs is influenced by IOL materials. After 3 minutes' incubation, Acrysof IOLs appeared to be more permissive to S. epidermidis adherence than PMMA IOLs. The difference was statistically significant (P < 0.05). However, at 90 minutes, Acrysof IOLs had a lower viable bacterial count than did the PMMA IOLs. Bacterial adherence appeared to be greater in areas with surface irregularities. Adherence of S. epidermidis to IOLs may play a role in the pathogenesis of some forms of endophthalmitis after cataract surgery.


Assuntos
Resinas Acrílicas , Aderência Bacteriana , Lentes de Contato Hidrofílicas/microbiologia , Polimetil Metacrilato , Staphylococcus epidermidis/fisiologia , Contagem de Colônia Microbiana , Técnicas In Vitro , Microscopia Eletrônica de Varredura , Staphylococcus epidermidis/isolamento & purificação , Staphylococcus epidermidis/ultraestrutura
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA