RESUMO
Extracts from different plant sources have been shown to modify starch digestion from carbohydrate-rich foods and lower resulting glycemia. It was hypothesized that extracts rich in polyphenols, added to white bread, would improve the glycemic response and insulin response and increase satiety in healthy participants. An in vitro dose-response analysis was performed to determine the optimal dose of a variety of extracts (baobab fruit extract, green tea extract, grape seed extract, and resveratrol) for reducing rapidly digestible starch in white bread. The 2 extracts with the greatest sugar reducing potential were then used for the human study in which 13 volunteers (9 female and 4 male) were recruited for a crossover trial of 3 different meals. On separate days, participants consumed a control white bread, white bread with green tea extract (0.4%), and white bread with baobab fruit extract (1.88%). Glycemic response, insulin response, and satiety were measured 3 hours postprandially. Although enriched breads did not reduce glycemic response or hunger, white bread with added baobab fruit extract significantly (P < .05) reduced the total (0-180 minutes) and segmental insulin area under the curve at 0 to 90, 0 to 120, and 0 to 150 minutes, and therefore reduced the amount of insulin needed for a given blood glucose response. This preliminary research suggests that there is potential for baobab fruit extract added into white bread to improve insulin economy in healthy adults.
Assuntos
Antioxidantes/administração & dosagem , Pão/análise , Alimentos Fortificados/análise , Índice Glicêmico , Insulina/metabolismo , Extratos Vegetais/administração & dosagem , Resposta de Saciedade , Adansonia/química , Adulto , Antioxidantes/efeitos adversos , Pão/efeitos adversos , Estudos Cross-Over , Feminino , Manipulação de Alimentos , Alimentos Fortificados/efeitos adversos , Frutas/química , Extrato de Sementes de Uva/administração & dosagem , Extrato de Sementes de Uva/efeitos adversos , Humanos , Insulina/sangue , Secreção de Insulina , Masculino , Pessoa de Meia-Idade , Extratos Vegetais/efeitos adversos , Período Pós-Prandial , Resveratrol , Método Simples-Cego , Estilbenos/administração & dosagem , Estilbenos/efeitos adversos , Chá/química , Adulto JovemRESUMO
BACKGROUND: Consumers increasingly choose food supplements in addition to their diet. Research on supplement users finds they are likely to be female, older and well-educated; Furthermore, supplement users are often characterised as being especially health-oriented, an observation which is termed the 'inverse supplement hypothesis'. However, results are dependent on the substance in question. Little is known so far about botanicals in general, and more specifically, little is known about resveratrol. The psychographic variables of food supplement users are yet relatively underexplored. By comparing US and Danish respondents, we aimed to identify whether sociodemographic variables, health status, health beliefs and behaviour and interest in food aspects specifically relevant to resveratrol (e.g., naturalness, indulgence, and Mediterranean food) explain favourable attitudes and adoption intentions toward resveratrol supplements. METHODS: A survey sent to a representative online panel in the United States and Denmark was analysed using linear regression. RESULTS: We find that sociodemographic variables contribute little to explaining favourable attitudes toward and adoption intentions of resveratrol supplements, except for the negative association with higher education in the United States. The inverse supplement hypothesis was not confirmed. Belief in the favourable health effects of resveratrol and usage of complementary and alternative medicine positively affect attitudes and adoption intention. An interest in the indulgence dimension of food explains positive attitudes in the United States and adoption intentions in both countries. CONCLUSIONS: The results indicate that potential consumers of resveratrol supplements are identified by their usage of complementary and alternative medicine, rather than by sociodemographic variables. They are not characterised by especially healthy behaviours, which contradicts the inverse supplement hypothesis. Instead, potential consumers of resveratrol supplements may be characterised by their focus on the indulgence dimension of food.
Assuntos
Terapias Complementares/estatística & dados numéricos , Suplementos Nutricionais/estatística & dados numéricos , Conhecimentos, Atitudes e Prática em Saúde , Intenção , Estilbenos/administração & dosagem , Adulto , Atitude , Dinamarca , Dieta , Comportamento Alimentar , Feminino , Comportamentos Relacionados com a Saúde , Nível de Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Resveratrol , Fatores Socioeconômicos , Estados UnidosRESUMO
The wound healing stands as very complex and dynamic process, aiming the re-establishment of the damaged tissue's integrity and functionality. Thus, there is an emerging need for developing biopolymer-based composites capable of actively promoting cellular proliferation and reconstituting the extracellular matrix. The aims of the present work were to prepare and characterize biopolymer-functionalized porous silicon (PSi) microparticles, resulting in the development of drug delivery microsystems for future applications in wound healing. Thermally hydrocarbonized PSi (THCPSi) microparticles were coated with both chitosan and a mixture of chondroitin sulfate/hyaluronic acid, and subsequently loaded with two antibacterial model drugs, vancomycin and resveratrol. The biopolymer coating, drug loading degree and drug release behavior of the modified PSi microparticles were evaluated in vitro. The results showed that both the biopolymer coating and drug loading of the THCPSi microparticles were successfully achieved. In addition, a sustained release was observed for both the drugs tested. The viability and proliferation profiles of a fibroblast cell line exposed to the modified THCPSi microparticles and the subsequent reactive oxygen species (ROS) production were also evaluated. The cytotoxicity and proliferation results demonstrated less toxicity for the biopolymer-coated THCPSi microparticles at different concentrations and time points comparatively to the uncoated counterparts. The ROS production by the fibroblasts exposed to both uncoated and biopolymer-coated PSi microparticles showed that the modified PSi microparticles did not induce significant ROS production at the concentrations tested. Overall, the biopolymer-based PSi microparticles developed in this study are promising platforms for wound healing applications.
Assuntos
Biopolímeros/química , Portadores de Fármacos/química , Silício/química , Cicatrização/efeitos dos fármacos , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Liberação Controlada de Fármacos , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Humanos , Microscopia Eletrônica de Varredura , Tamanho da Partícula , Porosidade , Espécies Reativas de Oxigênio/metabolismo , Resveratrol , Espectroscopia de Infravermelho com Transformada de Fourier , Estilbenos/administração & dosagem , Estilbenos/uso terapêutico , Vancomicina/administração & dosagem , Vancomicina/uso terapêuticoAssuntos
Antioxidantes/administração & dosagem , Longevidade/fisiologia , Estilbenos/administração & dosagem , Vinho , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Doenças Cardiovasculares/prevenção & controle , Suplementos Nutricionais , Humanos , Resveratrol , Estilbenos/farmacologia , Estilbenos/uso terapêuticoRESUMO
The present study aimed to prospectively monitor the vascular disrupting effect of M410 by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in rabbits with VX2 liver tumors. Twenty-eight rabbits bearing VX2 tumors in the left lobe of the liver were established and randomly divided into treatment and control groups, intravenously injected with 25 mg/kg M410 or sterile saline, respectively. Conventional and DCE-MRI data were acquired on a 3.0-T MR unit at pretreatment, 4 h, 1, 4, 7 and 14 days post-treatment. Histopathological examinations [hematoxylin and eosin (H&E) and CD34 immunohistochemisty staining] were performed at each time point. The dynamic changes in tumor volume, kinetic DCE-MRI parameter [volume transfer constant (Ktrans)] and histological data were evaluated. Tumors grew slower in the M410 group 4-14 days following treatment, compared with rapidly growing tumors in the control group (P<0.05). At 4 h, 1 and 4 days, Ktrans significantly decreased in the M410 group compared with that in the control group (P<0.05). However, Ktrans values were similar in the two groups for the other time points studied. The changes in DCE-MRI parameters were consistent with the results obtained from H&E and CD34 staining of the tumor tissues. DCE-MRI parameter Ktrans may be used as a non-invasive imaging biomarker to monitor the dynamic histological changes in tumors following treatment with the vascular targeting agent M410.
Assuntos
Inibidores da Angiogênese/administração & dosagem , Bibenzilas/administração & dosagem , Neoplasias Hepáticas Experimentais/patologia , Imageamento por Ressonância Magnética/métodos , Organofosfatos/administração & dosagem , Estilbenos/administração & dosagem , Inibidores da Angiogênese/síntese química , Inibidores da Angiogênese/farmacocinética , Animais , Bibenzilas/síntese química , Bibenzilas/farmacocinética , Biomarcadores Tumorais/metabolismo , Linhagem Celular Tumoral , Neoplasias Hepáticas Experimentais/tratamento farmacológico , Masculino , Organofosfatos/síntese química , Organofosfatos/farmacocinética , Coelhos , Estilbenos/síntese química , Estilbenos/farmacocinéticaRESUMO
Resveratrol, a natural product, has been reported to have antioxidant activities such as the scavenging of free radicals. This compound could be used in the dermocosmetic field to protect the skin from oxidative stress. In this work, the percutaneous profile of resveratrol in ethanol solutions through pig skin was determinated by an in vitro methodology. The percutaneous absorption of resveratrol was measured and compared with trolox, an analogous of Vitamin E. Both antioxidants were found in all skin sections (stratum corneum, epidermis, and dermis). Besides, the free radical scavenging activity of resveratrol and trolox has been evaluated using DPPH method. The effective dose (ED50) of compounds and DPPH radical inhibition in each skin layer were evaluated. Under the conditions used for these experiments, it can be deduced that resveratrol is more efficient than trolox as an antioxidant, also in the inner skin layers. The cosmeto-textiles with an active substance incorporated into their structure are increasingly used in the cosmetics and pharmaceutical industries. The action of several cosmeto-textiles on the skin was assessed by in vitro and in vivo methodologies. Samples of these cosmeto-textiles were prepared with resveratrol incorporated into cotton and polyamide fabrics. An in vitro percutaneous absorption was used to demonstrate the delivery of the resveratrol from the textile to the different skin layers (stratum corneum, epidermis, and dermis). Additionally, these cosmeto-textiles containing the antioxidant were applied onto the forearms of volunteers to evaluate the textiles' efficacy in skin penetration. The antioxidant's antiradical capacity was evaluated using the DPPH method. Results showed that resveratrol could be detected in the dermis, epidermis, and stratum corneum (SC) by an in vitro percutaneous absorption method and was also detected in the outermost layers of the SC by an in vivo method (stripping). A smaller amount of resveratrol was penetrated through the skin layers when cosmeto-textiles were used compared to direct topical application of the antioxidant solution. The cosmeto-textiles investigated can act as a reservoir system capable of progressively deliver the active substance to the skin layers. From the skin penetration profiles and the antioxidant efficacy assessment of resveratrol, it is possible to ameliorate the inherent antioxidant capacity of skin.
Assuntos
Antioxidantes/administração & dosagem , Cosméticos/administração & dosagem , Absorção Cutânea/fisiologia , Estilbenos/administração & dosagem , Têxteis , Adulto , Animais , Antioxidantes/farmacocinética , Cromanos/administração & dosagem , Cromanos/farmacocinética , Cosméticos/farmacocinética , Feminino , Humanos , Técnicas de Cultura de Órgãos , Resveratrol , Pele/efeitos dos fármacos , Pele/metabolismo , Absorção Cutânea/efeitos dos fármacos , Estilbenos/farmacocinética , SuínosRESUMO
STUDY QUESTION: Can resveratrol and epigallocatechin-3-gallate (EGCG) inhibit the growth and survival of endometriotic-like lesions in vivo in a BALB/c model of endometriosis, and in vitro in primary cultures of human endometrial epithelial cells (EECs)? SUMMARY ANSWER: Resveratrol and EGCG exerted a potent inhibitory effect on the development of endometriosis in a BALB/c murine model and on the survival of EECs. WHAT IS KNOWN ALREADY: Endometriosis is a common condition associated with infertility and pelvic pain in women of reproductive age. Resveratrol and EGCG are two polyphenols with anticarcinogenic and antioxidant properties that have been proposed as natural therapies to treat endometriosis. STUDY DESIGN, SIZE, DURATION: Fifty-six 2-month-old female BALB/c mice underwent surgical induction of endometriosis. Treatments with resveratrol or EGCG started 15 days post-surgery and continued for 4 weeks. Human biopsies were taken with a metal Novak curette from the posterior uterine wall from 16 patients with untreated endometriosis and 15 controls who underwent diagnostic laparoscopy for infertility. MATERIALS, SETTING, METHODS: After the treatments, animals were sacrificed and lesions were counted, measured, excised and fixed. Immunohistochemistry for proliferating cell nuclear antigen and CD34 was performed for cell proliferation and vascularization assessment in the lesions. The terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) technique was performed for apoptosis evaluation. Peritoneal fluid was collected to analyze vascular endothelial growth factor levels. Human EECs were purified from proliferative-phase endometrial biopsies and cultured. The effect of both polyphenols on cell proliferation was determined by a colorimetric assay using the CellTiter 96®AQueous One Solution Cell Proliferation Assay kit and on apoptosis by the TUNEL technique, using an In Situ Cell Death Detection Kit with Fluorescein. MAIN RESULTS: In the mouse model, both treatments significantly reduced the mean number (P < 0.05 versus control) and the volume of established lesions (P < 0.05 versus control). Treatments consistently statistically significantly diminished cell proliferation (resveratrol P < 0.01 and EGCG P < 0.05, versus control), reduced vascular density (resveratrol P < 0.01 and EGCG P < 0.001, versus control) and increased apoptosis within the lesions (resveratrol P < 0.01 and EGCG P < 0.05, versus control). Both compounds induced reduction in human EEC proliferation (P < 0.05 versus basal) and increased apoptosis (P < 0.05 versus basal) in primary cultures. LIMITATIONS: In vitro studies were only carried out in epithelial cells from human eutopic endometrium. WIDER IMPLICATIONS OF THE FINDINGS: The present findings are promising and will assist the development of novel natural treatments for endometriosis. STUDY FUNDING: This study was supported by ANPCYT (PICT 6384 BID 1201 OC-AR) and CONICET (PIP 5471), Argentina. None of the authors has any conflict of interest to declare.
Assuntos
Antioxidantes/uso terapêutico , Catequina/análogos & derivados , Modelos Animais de Doenças , Endometriose/tratamento farmacológico , Endométrio/efeitos dos fármacos , Enteropatias/tratamento farmacológico , Estilbenos/uso terapêutico , Inibidores da Angiogênese/administração & dosagem , Inibidores da Angiogênese/efeitos adversos , Inibidores da Angiogênese/farmacologia , Inibidores da Angiogênese/uso terapêutico , Animais , Antioxidantes/administração & dosagem , Antioxidantes/efeitos adversos , Antioxidantes/farmacologia , Apoptose/efeitos dos fármacos , Catequina/administração & dosagem , Catequina/efeitos adversos , Catequina/farmacologia , Catequina/uso terapêutico , Proliferação de Células , Células Cultivadas , Relação Dose-Resposta a Droga , Endometriose/patologia , Endometriose/fisiopatologia , Endometriose/prevenção & controle , Endométrio/irrigação sanguínea , Endométrio/metabolismo , Endométrio/patologia , Feminino , Humanos , Injeções Intraperitoneais , Enteropatias/patologia , Enteropatias/fisiopatologia , Enteropatias/prevenção & controle , Camundongos , Camundongos Endogâmicos BALB C , Neovascularização Patológica/etiologia , Neovascularização Patológica/prevenção & controle , Distribuição Aleatória , Resveratrol , Estilbenos/administração & dosagem , Estilbenos/efeitos adversos , Estilbenos/farmacologiaRESUMO
Benvitimod is a newly synthesized non-steroid small molecule being developed as a candidate drug for the treatment of inflammatory skin diseases. Here a rapid, sensitive and specific high performance liquid chromatography-tandem mass spectrometry (LC/ESI/MS/MS) method was developed for the determination of benvitimod in human plasma. The samples were alkalified with disodium tetraborate firstly, and then extracted by methyl tert-butyl ether. Fluorophenyl-benvitimod was used as internal standard (I.S.). Chromatographic separation was performed on an Ultra C(18) column (150mm×2.1mm, 5.0µm). The mixed mobile phase delivered at 300µl/min was CH3CN/H2O, 76.65:23.35 (v/v), containing 0.2mmol/L NH(4)COOH. Detection and quantitation was performed by electrospray ionization (ESI) and multiple reaction monitoring (MRM) in the negative ion mode. The most intense [M-H](-) MRM transition of benvitimod at m/z 253.1â211.0 was used for benvitimod quantitation and the transition at m/z 270.9â229.2 was used to monitor I.S. The calibration curve was linear within the concentration range of 0.1-10.0ng/mL (r>0.99). The lower limit of quantification (LLOQ) was 0.1ng/mL. The extraction recovery was above 80%. The accuracy expressed as relative error (RE) was less than 1.03%. The intra- and inter-day precisions were less than 11.81%. The freeze-thaw stability was also investigated and it was found that both benvitimod and the I.S. were quite stable. This method is especially useful for the pharmacokinetic study of benvitimod.
Assuntos
Anti-Inflamatórios não Esteroides/sangue , Cromatografia Líquida de Alta Pressão/métodos , Resorcinóis/sangue , Estilbenos/sangue , Espectrometria de Massas em Tandem/métodos , Administração Tópica , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/farmacocinética , Estabilidade de Medicamentos , Humanos , Psoríase/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Reprodutibilidade dos Testes , Resorcinóis/administração & dosagem , Resorcinóis/farmacocinética , Sensibilidade e Especificidade , Estilbenos/administração & dosagem , Estilbenos/farmacocinéticaRESUMO
Unmodified or as a poly[lactide-co-glycolide] nanoparticle, tetraiodothyroacetic acid (tetrac) acts at the integrin αvß3 receptor on human cancer cells to inhibit tumor cell proliferation and xenograft growth. To study in vitro the pharmacodynamics of tetrac formulations in the absence of and in conjunction with other chemotherapeutic agents, we developed a perfusion bellows cell culture system. Cells were grown on polymer flakes and exposed to various concentrations of tetrac, nano-tetrac, resveratrol, cetuximab, or a combination for up to 18 days. Cells were harvested and counted every one or two days. Both NONMEM VI and the exact Monte Carlo parametric expectation maximization algorithm in S-ADAPT were utilized for mathematical modeling. Unmodified tetrac inhibited the proliferation of cancer cells and did so with differing potency in different cell lines. The developed mechanism-based model included two effects of tetrac on different parts of the cell cycle which could be distinguished. For human breast cancer cells, modeling suggested a higher sensitivity (lower IC50) to the effect on success rate of replication than the effect on rate of growth, whereas the capacity (Imax) was larger for the effect on growth rate. Nanoparticulate tetrac (nano-tetrac), which does not enter into cells, had a higher potency and a larger anti-proliferative effect than unmodified tetrac. Fluorescence-activated cell sorting analysis of harvested cells revealed tetrac and nano-tetrac induced concentration-dependent apoptosis that was correlated with expression of pro-apoptotic proteins, such as p53, p21, PIG3 and BAD for nano-tetrac, while unmodified tetrac showed a different profile. Approximately additive anti-proliferative effects were found for the combinations of tetrac and resveratrol, tetrac and cetuximab (Erbitux), and nano-tetrac and cetuximab. Our in vitro perfusion cancer cell system together with mathematical modeling successfully described the anti-proliferative effects over time of tetrac and nano-tetrac and may be useful for dose-finding and studying the pharmacodynamics of other chemotherapeutic agents or their combinations.
Assuntos
Antineoplásicos/farmacologia , Modelos Biológicos , Tiroxina/análogos & derivados , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados , Antineoplásicos/administração & dosagem , Apoptose/efeitos dos fármacos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Técnicas de Cultura de Células/instrumentação , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cetuximab , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/patologia , Biologia Computacional , Quimioterapia Combinada , Feminino , Humanos , Método de Monte Carlo , Nanopartículas/administração & dosagem , Resveratrol , Estilbenos/administração & dosagem , Tiroxina/administração & dosagem , Tiroxina/farmacologiaRESUMO
Despite potential therapeutic efficacy of resveratrol on colitis and colorectal cancer, rapid absorption and metabolism at the upper gastro-intestinal (GI) tract prevent its clinical application. To overcome this, we attempted to develop colon-specific multi-particulate calcium-pectinate (Ca-pectinate) formulations of resveratrol. However, they were unable to prevent premature drug release at the upper GI tract. Thus, glutaraldehyde (Glu) was used for further cross-linking of the pectin chains. The formulation conditions and procedure were optimized from the in vitro drug release study. The optimized formulation was subjected to in vivo pharmacokinetic study in rats and compared with the unmodified Ca-pectinate and suspension formulation of resveratrol. Spherical particles (â¼1 mm diameter) with high drug encapsulation were produced. Low cross-linking solution pH (1.5), minimum Glu concentration (2.5%) and cross-linking time (2 h) were crucial to exhibit colon-specific drug release. As Glu was added in the cross-linking solution, cross-linking between pectin chains and Glu occurred simultaneously during Ca-pectinate network formation, which appeared as a cost-effective formulation technique. Most importantly, the pharmacokinetic study demonstrated in vivo colon-specific drug release from the optimized formulation, while faster drug release was observed from the unmodified and suspension formulations. Hence, the developed formulation has potential to be used as colon-specific delivery system of resveratrol.
Assuntos
Colo/metabolismo , Glutaral/metabolismo , Pectinas/metabolismo , Estilbenos/metabolismo , Absorção , Animais , Cloreto de Cálcio/química , Química Farmacêutica/economia , Reagentes de Ligações Cruzadas/metabolismo , Portadores de Fármacos/química , Composição de Medicamentos , Concentração de Íons de Hidrogênio , Masculino , Microesferas , Tamanho da Partícula , Pectinas/química , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Resveratrol , Estilbenos/administração & dosagem , Estilbenos/química , Estilbenos/farmacocinética , Tecnologia Farmacêutica/métodos , Fatores de TempoRESUMO
The aim of this study was to use magnetic resonance (MR) techniques to non-invasively compare the effects of the three leading vascular disrupting agents, namely combretastatin A-4 disodium phosphate (CA4DP), 5,6-dimethylxanthenone-4-acetic acid (DMXAA) and ZD6126. A C3H mouse mammary carcinoma grown in the right rear foot of female CDF1 mice was used and treatments performed when tumours had reached 200 mm3 in volume. Drugs were prepared fresh before each experiment and intraperitoneally injected into restrained non-anaesthetised mice. Tumour response was evaluated using 31P-MR spectroscopy and T1- and T2- weighted imaging with a 7-Tesla, horizontal bore magnet, before and up to 24 hours after treatment. All three drugs significantly decreased bioenergetic status and pH, and did so in a time and dose dependent fashion, but there were differences; the decrease by CA4DP occurred more rapidly than for DMXAA or ZD6126, while DMXAA had a narrow window of activity compared to CA4DP and ZD6126. Changes in T1 weighted images for all three agents suggested a dose dependent increase in tumour oedema within three hours after treatment, consistent with an increase in vessel permeability. Using T2 weighted images there was some evidence of haemorrhagic necrosis by DMXAA, but such necrosis was limited following treatment with CA4DP or ZD6126.
Assuntos
Imageamento por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética/métodos , Neoplasias Mamárias Animais/diagnóstico , Neoplasias Mamárias Animais/tratamento farmacológico , Compostos Organofosforados/uso terapêutico , Estilbenos/uso terapêutico , Xantonas/uso terapêutico , Inibidores da Angiogênese/uso terapêutico , Animais , Antineoplásicos/uso terapêutico , Feminino , Concentração de Íons de Hidrogênio , Camundongos , Camundongos Endogâmicos C3H , Nucleosídeos , Fosfatos , Estilbenos/administração & dosagem , Fatores de Tempo , Resultado do TratamentoRESUMO
Cardiovascular diseases are the leading cause of death in developed countries where the common pathological substrate underlying this process is atherosclerosis. Several new concepts have emerged in relation to mechanisms that contribute to the regulation of the vascular diseases and associated inflammatory effects. Recently, potential antioxidants (vitamin E, polyphenols) have received much attention as potential anti-atherosclerotic agents. Among the polyphenols with health benefic properties, resveratrol, a phytoalexin of grape, seem to be a good candidate protecting the vascular walls from oxidation, inflammation, platelet aggregation, and thrombus formation. In this review, we focus on the mechanism of resveratrol cardiovascular benefic effects. We analyze, in relation with the different steps of atherosclerotic process, the resveratrol properties at multiple levels, such as cellular signaling, enzymatic pathways, apoptosis, and gene expression. We show and discuss the relationship with reactive oxygen species, regulation of pro-inflammatory genes including cycloxygenases and cytokines in molecular inflammatory and aging processes, and how the regulation of these activites by resveratrol can lead to a prevention of vascular diseases.
Assuntos
Envelhecimento , Doenças Cardiovasculares/prevenção & controle , Promoção da Saúde , Estilbenos/administração & dosagem , Arteriosclerose , Células Espumosas , Humanos , Lipoproteínas/sangue , Macrófagos , Músculo Liso Vascular , Neovascularização Patológica , Estresse Oxidativo , Agregação Plaquetária , Resveratrol , VasodilataçãoRESUMO
PURPOSE: Clinical evaluation of novel agents that target tumor blood vessels requires pharmacodynamic end points that measure vascular damage. Positron emission tomography (PET) was used to measure the effects of the vascular targeting agent combretastatin A4 phosphate (CA4P) on tumor and normal tissue perfusion and blood volume. PATIENTS AND METHODS: Patients with advanced solid tumors were enrolled onto part of a phase I, accelerated-titration, dose-escalation study. The effects of 5 to 114 mg/m2 CA4P on tumor, spleen, and kidney were investigated. Tissue perfusion was measured using oxygen-15 (15O)-labeled water and blood volume was measured using 15O-labeled carbon monoxide (C15O). Scans were performed immediately before, and 30 minutes and 24 hours after the first infusion of each dose level of CA4P. All statistical tests were two sided. RESULTS: PET data were obtained for 13 patients with intrapatient dose escalation. Significant dose-dependent reductions were seen in tumor perfusion 30 minutes after CA4P administration (mean change, -49% at >or= 52 mg/m2; P =.0010). Significant reductions were also seen in tumor blood volume (mean change, -15% at >or= 52 mg/m2; P =.0070). Although by 24 hours there was tumor vascular recovery, for doses >or= 52 mg/m2 the reduction in perfusion remained significant (P =.013). Thirty minutes after CA4P administration borderline significant changes were seen in spleen perfusion (mean change, -35%; P =.018), spleen blood volume (mean change, -18%; P =.022), kidney perfusion (mean change, -6%; P =.026), and kidney blood volume (mean change, -6%; P =.014). No significant changes were seen at 24 hours in spleen or kidney. CONCLUSION: CA4P produces rapid changes in the vasculature of human tumors that can be assessed using PET measurements of tumor perfusion.