RESUMEN
Herpesviruses have two distinct life cycle stages, latency and lytic replication. Epstein-Barr virus (EBV), a gamma-herpesvirus, establishes latency in vivo and in cultured cells. Cell lines harboring latent EBV can be induced into the lytic cycle by treatment with chemical inducing agents. In the Burkitt lymphoma cell line HH514-16 the viral lytic cycle is triggered by butyrate, a histone deacetylase (HDAC) inhibitor. Butyrate also alters expression of thousands of cellular genes. However, valproic acid (VPA), another HDAC inhibitor with global effects on cellular gene expression blocks EBV lytic gene expression in Burkitt lymphoma cell lines. Valpromide (VPM), an amide derivative of VPA, is not an HDAC inhibitor, but like VPA blocks induction of the EBV lytic cycle. VPA and VPM are the first examples of inhibitors of initial stages of lytic reactivation. We compared the effects of VPA and VPM, alone and in combination with butyrate, on host cellular gene expression using whole transcriptome analysis (RNA-seq). Gene expression was analyzed 6 h after addition of the compounds, a time before the first EBV lytic transcripts are detected. The results address two alternative, yet possibly complementary, mechanisms for regulation of EBV lytic reactivation. First, cellular genes that were up- or down-regulated by butyrate, but no longer altered in the presence of VPA or VPM, represent genes that correlated with EBV lytic reactivation. Second, genes regulated similarly by VPA and VPM in the absence and presence of butyrate are candidates for suppressors of EBV reactivation. Two genes upregulated by the lytic cycle inhibitors, CHAC1 and SLC7A11, are related to redox status and the iron-dependent cell death pathway ferroptosis. This study generates new hypotheses for control of the latency to lytic cycle switch of EBV and provides the first description of effects of the anti-convulsant drug VPM on global human cellular gene expression.
Asunto(s)
Linfoma de Burkitt , Infecciones por Virus de Epstein-Barr , Ácido Valproico/análogos & derivados , Humanos , Linfoma de Burkitt/tratamiento farmacológico , Linfoma de Burkitt/genética , Herpesvirus Humano 4/fisiología , Inhibidores de Histona Desacetilasas/farmacología , Inhibidores de Histona Desacetilasas/metabolismo , Infecciones por Virus de Epstein-Barr/tratamiento farmacológico , Activación Viral , Perfilación de la Expresión Génica , Butiratos/farmacologíaRESUMEN
Melinjo (Gnetum gnemon L.) seed extract (MSE) and its active ingredient gnetin C (GC), a resveratrol dimer, have been shown to possess a broad spectrum of pharmacological activities. In this study, we investigated the antitumor activity of MSE and GC using human and murine tumor cell culture models in vitro. The antitumor activity of GC was compared with trans-resveratrol (tRV), a stilbenoid polyphenol. Our results show that MSE and GC at clinically achievable concentrations significantly inhibited the proliferation of pancreatic, prostate, breast, and colon cancer cell types (P < 0.05), without affecting normal cells. Interestingly, GC exerts enhanced antitumor activity than that of tRV (P < 0.05). MSE and GC significantly induced apoptosis in all the cancer cells, indicating MSE and GC inhibit tumor cell growth by inducing apoptosis (P < 0.001). Our findings provide evidence that MSE might induce apoptosis in cancer cells via caspase-3/7-dependent and -independent mechanisms. However, GC might trigger both early and late stage apoptosis in cancer cells, at least in part by activating caspase 3/7-dependent mechanisms. Furthermore, the antitumor efficacy of MSE observed in vitro was also validated in a widely used colon-26 tumor-bearing mouse model. Oral administration of MSE at 50 and 100 mg/kg per day significantly inhibited tumor growth, intratumoral angiogenesis, and liver metastases in BALB/c mice bearing colon-26 tumors (P < 0.05). In conclusion, our findings provide evidence that MSE and GC have potent antitumor activity. Most importantly, we provide the first evidence that MSE inhibits tumor growth, intratumoral angiogenesis, and liver metastasis in a colon-26 tumor-bearing mice.
Asunto(s)
Antineoplásicos Fitogénicos/farmacología , Neoplasias del Colon/patología , Gnetum/química , Extractos Vegetales/farmacología , Semillas/química , Animales , Antineoplásicos Fitogénicos/química , Apoptosis/efectos de los fármacos , Caspasas/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Neoplasias del Colon/tratamiento farmacológico , Neoplasias del Colon/metabolismo , Modelos Animales de Enfermedad , Femenino , Humanos , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/secundario , Ratones , Extractos Vegetales/química , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
It is widely believed that the US health care system needs to transition from a culture of reactive treatment of disease to one of proactive prevention. As a tool for understanding the appropriate allocation of spending to prevention versus treatment (including research into improved prevention and treatment), a simple Markov model is used to represent the flow of individuals among states of health, where the transition rates are governed by the magnitude of appropriately-lagged expenditures in each of these categories. The model estimates the discounted cost and discounted effectiveness (measured in quality adjusted life years or QALYs) associated with a given spending mix, and it allows computing the marginal cost-effectiveness associated with additional spending in a category. We apply the model to explore interactions of alternative investments in cardiovascular disease (CVD) and to identify an optimal spending mix. Under the assumptions of our model structure, we find that the marginal cost-effectiveness of prevention of CVD varies with changes in spending on treatment (and vice versa), and that the optimal mix of CVD spending (i.e., the spending mix that maximizes the overall QALYs achieved) would, indeed, shift spending from treatment to prevention.
Asunto(s)
Enfermedades Cardiovasculares/terapia , Gastos en Salud/estadística & datos numéricos , Investigación sobre Servicios de Salud/métodos , Servicios Preventivos de Salud/economía , Enfermedades Cardiovasculares/prevención & control , Análisis Costo-Beneficio , Investigación sobre Servicios de Salud/estadística & datos numéricos , Humanos , Cadenas de Markov , Modelos Econométricos , Años de Vida Ajustados por Calidad de Vida , Estados UnidosRESUMEN
BACKGROUND: The process of randomization is used commercially to harden fats as an alternative to partial hydrogenation, but its effects on cardiovascular disease risk factors are uncertain. OBJECTIVE: The objective was to compare the chronic and acute effects of randomization of a fat rich in 1,3-distearyl, 2-oleyl glycerol on fasting and postprandial lipids, glucose, insulin, and activated clotting factor VII (FVIIa) concentrations. DESIGN: A crossover design study in 16 men compared fasting and postprandial lipid, glucose, insulin, and FVIIa concentrations at baseline and after a 3-wk diet providing 30 g unrandomized or randomized shea butter and sunflower oil blends (SSOBs), both of which contained approximately 50% stearic acid. Fecal fat excretion was measured during each dietary period. Postprandial changes were assessed after the consumption of meals providing 50 g test fat. A subsequent study compared postprandial changes after the consumption of an oleic acid-rich sunflower oil meal and an unrandomized SSOB meal. RESULTS: Both SSOBs were well digested and absorbed. Randomization did not affect fasting or postprandial lipid, glucose, insulin, or FVIIa concentrations. Compared with the oleic acid-rich meal, the unrandomized SSOB resulted in 53% lower postprandial lipemia, 23% higher hepatic lipase activity, and a 25% lower postprandial increase in FVIIa concentration. The solid fat contents at 37 degrees C were 22%, 41%, and 0% with the unrandomized SSOB, randomized SSOB, and oleic acid-rich meals, respectively. CONCLUSIONS: Stearic acid-rich triacylglycerol in both unrandomized and randomized forms does not adversely affect lipid risk factors for cardiovascular disease. The high proportion of solid fat at 37 degrees C may explain the decreased postprandial lipemic response.
Asunto(s)
Factor VIIa/análisis , Lípidos/sangre , Ácidos Oléicos/química , Ácidos Oléicos/farmacología , Aceites de Plantas/química , Aceites de Plantas/farmacología , Adulto , Glucemia/análisis , Glucemia/efectos de los fármacos , Colesterol/sangre , Estudios Cruzados , Factor VIIa/efectos de los fármacos , Humanos , Insulina/sangre , Lipasa/sangre , Lípidos/fisiología , Masculino , Ácido Oléico/análisis , Periodo Posprandial , Ácidos Esteáricos/análisis , Aceite de Girasol , Triglicéridos/análisisRESUMEN
The process of interesterification results in changes in triacylglycerol (TAG) structure and is used to increase the melting point of dietary fats. The acute health effects of this process on palmitic acid-rich fats are uncertain with regard to postprandial lipemia, insulin and factor VII activated (FVIIa) concentrations. Two randomized crossover trials in healthy male subjects compared the effects of meals containing 50 g fat [interesterified palm oil (IPO) versus native palm oil (NPO); n=20, and IPO versus high-oleic sunflower oil (HOS); n=18], on postprandial changes in lipids, glucose, insulin, chylomicron composition and FVIIa. Compared with NPO, IPO decreased postprandial TAG and insulin concentrations. Both NPO and IPO increased FVIIa concentrations postprandially; mean increases at 6 h were 21 and 19%, respectively. Compared with HOS, IPO decreased postprandial TAG (47% lower incremental area under the curve) and reduced the postprandial increase in FVIIa concentration by 64% at 6 h; no significant differences in hepatic and total lipase activities or insulin concentrations were noted. All three test meals increased postprandial leukocyte counts (average 26% at 6 h). The fatty acid composition of the chylomicron TAG was similar to the test fats following all test meals. It is concluded that interesterification of palm oil does not result in adverse changes in postprandial lipids, insulin or FVIIa compared to high oleate and native palm oils.
Asunto(s)
Factor VII/metabolismo , Lípidos/química , Ácido Palmítico/química , Periodo Posprandial , Triglicéridos/farmacología , Adolescente , Adulto , Glucemia/metabolismo , Quilomicrones/metabolismo , Estudios Cruzados , Grasas de la Dieta/administración & dosificación , Grasas de la Dieta/farmacología , Ésteres , Humanos , Insulina/sangre , Insulina/metabolismo , Leucocitos/citología , Leucocitos/efectos de los fármacos , Leucocitos/metabolismo , Metabolismo de los Lípidos/efectos de los fármacos , Masculino , Persona de Mediana Edad , Aceite de Palma , Aceites de Plantas/administración & dosificación , Aceites de Plantas/farmacología , Aceite de Girasol , Triglicéridos/administración & dosificación , Triglicéridos/químicaRESUMEN
BACKGROUND: Insulin resistance is associated with elevated plasma triacylglycerol, low HDL concentrations, elevated postprandial lipemia, and a predominance of small, dense LDLs (sdLDLs). It has been hypothesized that the dietary ratio of n-6 to n-3 (n-6:n-3) polyunsaturated fatty acids (PUFAs) may have favorable effects on these risk factors by increasing insulin sensitivity. OBJECTIVE: The objective was to measure changes in insulin sensitivity, lipoprotein size, and postprandial lipemia after a 6-mo alteration in n-6:n-3. DESIGN: In a randomized, parallel design in 258 subjects aged 45-70 y, we compared 4 diets providing 6% of energy as PUFAs with an n-6:n-3 between 5:1 and 3:1 with a control diet that had an n-6:n-3 of 10:1. The diets were enriched in alpha-linolenic acid, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), or both. Insulin sensitivity was assessed with the homeostatic model assessment of insulin resistance and the revised quantitative insulin sensitivity test. RESULTS: Dietary intervention did not influence insulin sensitivity or postprandial lipase activities. Fasting and postprandial triacylglycerol concentrations were lower, and the proportion of sdLDLs decreased (by 12.7%; 95% CI: -22.9%, 2.4%), with an n-6:n-3 of approximately 3:1, which was achieved by the addition of long-chain n-3 PUFAs (EPA and DHA). CONCLUSIONS: Decreasing the n-6:n-3 does not influence insulin sensitivity or lipase activities in older subjects. The reduction in plasma triacylglycerol after an increased intake of n-3 long-chain PUFAs results in favorable changes in LDL size.
Asunto(s)
Grasas Insaturadas en la Dieta/administración & dosificación , Ácidos Grasos Omega-3/administración & dosificación , Ácidos Grasos Omega-6/administración & dosificación , Resistencia a la Insulina , Insulina/metabolismo , Lipoproteínas LDL/sangre , Triglicéridos/sangre , Anciano , Grasas Insaturadas en la Dieta/sangre , Ácidos Docosahexaenoicos/administración & dosificación , Ácidos Docosahexaenoicos/sangre , Ácido Eicosapentaenoico/administración & dosificación , Ácido Eicosapentaenoico/sangre , Ácidos Grasos Omega-3/sangre , Ácidos Grasos Omega-6/sangre , Femenino , Humanos , Hiperlipidemias/metabolismo , Lipasa/metabolismo , Lipoproteínas HDL/sangre , Lipoproteínas HDL/química , Lipoproteínas LDL/química , Masculino , Persona de Mediana Edad , Tamaño de la Partícula , Posmenopausia , Periodo Posprandial , Ácido alfa-Linolénico/administración & dosificación , Ácido alfa-Linolénico/sangreRESUMEN
OBJECTIVE: Previous studies have demonstrated benefits of high-dose long-chain omega-3 polyunsaturated fatty acid (LC omega-3 PUFA) supplements on metabolic risk. Effects of increased dietary omega-3 PUFA, via oily fish and/or plant-derived omega-3 PUFAs, are less clear and may be modulated by the omega-6:omega-3 PUFA of the habitual diet. This study examined the effect on cardiovascular disease risk markers of reducing dietary omega-6:omega-3 PUFA by changes in linoleic acid:alpha-linolenic acid (LA:LNA) and/or increasing LC omega-3 PUFA. It tested whether decreases in LA:LNA modulate effects of LC omega-3 PUFA. METHODS: One hundred forty-two subjects, recruited to a 24-wk randomized study, were assigned to a control group or one of four interventions. Intervention groups received two portions of oily fish (4.5 g eicosapentaenoic acid + docosahexanoic acid) or white fish (0.7 g eicosapentaenoic acid + docosahexanoic acid) per week, and replaced habitual household fats with ones high in sunflower (high LA:LNA) or rapeseed (low LA:LNA) oil. RESULTS: Modest dietary manipulations of omega-6 and omega-3 PUFAs resulted in significant group x time interactions for serum triacylglycerols (TAGs; P = 0.05); at 24 wk the control and two oily fish groups showed lower TAG than did the white fish/sunflower group (P = 0.05). Reductions in TAG, associated with increased oily fish intakes, were maximized when combined with lower dietary LA:LNA. There were no significant changes in several other cardiovascular disease risk markers. CONCLUSIONS: Two portions of oily fish per week led to significant reductions in TAG relative to consumption of two portions of white fish per week. Changes in TAG were maximized when combined with lower LA:LNA.
Asunto(s)
Enfermedades Cardiovasculares/prevención & control , Grasas Insaturadas en la Dieta/administración & dosificación , Aceites de Pescado , Obesidad/sangre , Triglicéridos/sangre , Biomarcadores/sangre , Enfermedades Cardiovasculares/sangre , Ácidos Grasos Monoinsaturados , Ácidos Grasos Omega-3/administración & dosificación , Ácidos Grasos Omega-6/administración & dosificación , Femenino , Aceites de Pescado/administración & dosificación , Aceites de Pescado/química , Humanos , Ácido Linoleico/administración & dosificación , Masculino , Persona de Mediana Edad , Aceites de Plantas , Aceite de Brassica napus , Factores de Riesgo , Aceite de Girasol , Ácido alfa-Linolénico/administración & dosificaciónRESUMEN
BACKGROUND: Elevated fibrinogen, activated factor XII (FXIIa), and factor VII coagulant activity (FVIIc) are associated with higher risk of fatal ischemic heart disease. This study tested the hypothesis that lowering the dietary ratio of n-6 to n-3 polyunsaturated fatty acids (n-6:n-3) would modify these risk factors in older men and women. OBJECTIVE: The objective of the study was to measure fasting hemostatic risk factors and postprandial changes in activated FVII (FVIIa) concentrations after a 6-mo alteration in dietary n-6:n-3. DESIGN: In a randomized, parallel design in 258 subjects aged 45-70 y, we compared 4 diets providing 6% of energy as polyunsaturated fatty acids at an n-6:n-3 between 5:1 and 3:1 with a control diet that had an n-6:n-3 of 10:1. The diets were enriched in alpha-linolenic acid, eicosapentaenoic (EPA) and docosahexaenoic (DHA) acid, or both. RESULTS: Fasting and 3-h plasma triacylglycerol concentrations were 11.1% and 7.2% lower with the diet that had an n-6:n-3 of approximately 3:1 and that was enriched with EPA and DHA than with the other diets. Fasting fibrinogen, FXIIa, FVIIc, FVIIa, and FVII antigen and postprandial FVIIa were not influenced by the diets. Avoiding foods high in fat the day before measurement decreased FVIIc and FVIIa by 8% and 19.2%, respectively. A test meal containing 50 g fat resulted in a mean 47% (95% CI: 42%, 52%) increase in FVIIa 6 h later, but the response did not differ by n-6:n-3. CONCLUSION: Decreasing the n-6:n-3 to approximately 3:1 by increasing the intake of EPA and DHA lowers fasting and postprandial plasma triacylglycerol concentrations in older persons but does not influence hemostatic risk factors.
Asunto(s)
Factor VII/análisis , Factor XIIa/análisis , Ácidos Grasos Omega-3/administración & dosificación , Ácidos Grasos Omega-6/administración & dosificación , Fibrinógeno/análisis , Triglicéridos/sangre , Anciano , Área Bajo la Curva , Grasas Insaturadas en la Dieta/administración & dosificación , Grasas Insaturadas en la Dieta/sangre , Ácidos Docosahexaenoicos/administración & dosificación , Ácidos Docosahexaenoicos/sangre , Ácido Eicosapentaenoico/administración & dosificación , Ácido Eicosapentaenoico/sangre , Ayuno/sangre , Ácidos Grasos Omega-3/sangre , Ácidos Grasos Omega-6/sangre , Femenino , Hemostasis/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Isquemia Miocárdica/sangre , Isquemia Miocárdica/epidemiología , Periodo Posprandial , Factores de Riesgo , Ácido alfa-Linolénico/administración & dosificación , Ácido alfa-Linolénico/sangreRESUMEN
The intake of long-chain n-3 PUFA, including DHA (22 : 6n-3), is associated with a reduced risk of CVD. Schizochytrium sp. are an important primary source of DHA in the marine food chain but they also provide substantial quantities of the n-6 PUFA docosapentaenoic acid (22 : 5n-6; DPA). The effect of this oil on cardiovascular risk factors was evaluated using a double-blind randomised placebo-controlled parallel-design trial in thirty-nine men and forty women. Subjects received 4 g oil/d for 4 weeks; the active treatment provided 1.5 g DHA and 0.6 g DPA. Active treatment increased plasma concentrations of arachidonic acid, adrenic acid, DPA and DHA by 21, 11, 11 and 88 mg/l respectively and the proportions of DPA and DHA in erythrocyte phospholipids by 78 and 27 % respectively. Serum total, LDL- and HDL-cholesterol increased by 0.33 mmol/l (7.3 %), 0.26 mmol/l (10.4 %) and 0.14 mmol/l (9.0 %) compared with placebo (all P < or =0.001). Factor VII (FVII) coagulant activity increased by 12 % following active treatment (P = 0.006). There were no significant differences between treatments in LDL size, blood pressure, plasma glucose, serum C-reactive protein, plasma FVII antigen, FVII activated, fibrinogen, von Willebrand factor, tocopherol or carotenoid concentrations, plasminogen activator inhibitor-1, creatine kinase or troponin-I activities, haematology or liver function tests or self-reported adverse effects. Overall, the oil was well tolerated and did not adversely affect cardiovascular risk.
Asunto(s)
Suplementos Dietéticos , Ácidos Docosahexaenoicos/administración & dosificación , Eucariontes/química , Ácidos Grasos Insaturados/administración & dosificación , Triglicéridos/administración & dosificación , Adulto , Presión Sanguínea/fisiología , Proteína C-Reactiva/análisis , Enfermedades Cardiovasculares/etiología , Colesterol/sangre , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Ácidos Docosahexaenoicos/sangre , Método Doble Ciego , Eritrocitos/química , Factor VII/análisis , Ácidos Grasos/sangre , Ácidos Grasos Insaturados/sangre , Femenino , Humanos , Masculino , Fosfolípidos/química , Factores de Riesgo , Triglicéridos/químicaRESUMEN
We tested the hypothesis that dietary alpha-linolenic acid (ALA) can exert effects on markers of cardiovascular risk similar to that produced by its longer chain counterparts in fish-oil. A dietary intervention study was undertaken to examine the effects of an ALA-enriched diet in 57 men expressing an atherogenic lipoprotein phenotype (ALP). Subjects were randomly assigned to one of three diets enriched either with flaxseed oil (FXO: high ALA, n = 21), sunflower oil (SO: high linoleic acid, n = 17), or SO with fish-oil (SOF n = 19) for 12 weeks, resulting in dietary intake ratios of n-6:n-3 PUFA of 0.5, 27.9 and 5.2, respectively. The relative abundance of ALA and EPA in erythrocyte membranes increased on the FXO diet (p < 0.001), whereas both EPA and DHA increased after fish-oil (p < 0.001). There were significant decreases in total plasma cholesterol within (FXO -12.3%, p = 0.001; SOF -7.6%, p = 0.014; SO -7.3%, p = 0.033) and between diets (p = 0.019), and decreases within diets after 12 weeks for HDL cholesterol on flaxseed oil (FXO -10%, p=0.009), plasma TG (-23%, p < 0.001) and small, dense LDL (-22% p = 0.003) in fish-oil. Membrane DHA levels were inversely associated with the changes in plasma TG ( p= 0.001) and small, dense LDL (p<0.05) after fish-oil. In conclusion, fish-oil produced predictable changes in plasma lipids and small, dense LDL (sdLDL) that were not reproduced by the ALA-enriched diet. Membrane DHA levels appeared to be an important determinant of these fish-oil-induced effects.
Asunto(s)
Arteriosclerosis/etiología , Enfermedades Cardiovasculares/etiología , Dieta , Aceites de Pescado/farmacología , Lipoproteínas/sangre , Ácido alfa-Linolénico/farmacología , Adulto , Biomarcadores/sangre , Ácidos Docosahexaenoicos/sangre , Ácido Eicosapentaenoico , Membrana Eritrocítica/metabolismo , Ácidos Grasos/sangre , Ácidos Grasos Insaturados/sangre , Aceites de Pescado/administración & dosificación , Humanos , Aceite de Linaza/administración & dosificación , Aceite de Linaza/farmacología , Lípidos/sangre , Lipoproteínas HDL/sangre , Lipoproteínas LDL/sangre , Masculino , Persona de Mediana Edad , Fenotipo , Fosfolípidos/sangre , Aceites de Plantas/administración & dosificación , Aceites de Plantas/farmacología , Factores de Riesgo , Aceite de Girasol , Ácido alfa-Linolénico/administración & dosificaciónRESUMEN
Studies of the effects of dietary fatty acids on the haemostatic system, and their potential relevance for the thrombotic component of coronary heart disease (CHD), have a pedigree as long as those linking dietary fat, plasma lipoprotein metabolism and atheroma. Achievements have not been as impressive, however, partly owing to the relatively slow evolution of our understanding of the complicated physiology, biochemistry and pathology of haemostasis and fibrinolysis, which remains incomplete. Progress was also retarded up to 1980 by a general reluctance to acknowledge the pathogenic importance of thrombosis for myocardial infarction. Interest in dietary fat and the haemostatic mechanism re-emerged with reports of associations of haemostatic variables with plasma triacylglycerol levels and risk of CHD. This review summarises the history, focuses on evidence for dietary C18-unsaturated fatty acids as important determinants of factor VII (FVII) activation and plasminogen activator inhibitor type 1 (PAI-1) levels, and discusses possible underlying mechanisms involving ATP binding cassette (ABC) transporters and peroxisome proliferator-activated receptors. The potential relevance of these effects for CHD is discussed. In the presence of unstable atheromatous plaques, increased levels of activated FVII and PAI-1 induced by diets rich in mixtures of saturated and unsaturated fats may raise the risk of occlusive thrombosis in the event of plaque rupture.
Asunto(s)
Coagulación Sanguínea/fisiología , Enfermedad Coronaria/fisiopatología , Grasas de la Dieta/metabolismo , Ácidos Grasos/metabolismo , Hemostasis/fisiología , Colesterol/metabolismo , Grasas de la Dieta/farmacología , Factor VII/farmacología , Ácidos Grasos/farmacología , Fibrinólisis/fisiología , Humanos , Infarto del Miocardio/fisiopatología , Fosfolípidos/metabolismo , Inhibidor 1 de Activador Plasminogénico/farmacología , Periodo Posprandial , Trombosis , Triglicéridos/metabolismoRESUMEN
Inductively coupled plasma cavity ringdown spectroscopy (ICP-CRDS) is applied to isotopic measurements of uranium. We have successfully obtained the isotopic-resolved spectra of uranium at three different atomic/ionic transition lines, 286.57, 358.49, and 409.01 nm. Of the three lines, the largest isotope shift of approximately 9 pm was measured at the 286.57 ionic line. Isotopic-resolved spectra were recorded in ratio of 1:1 (235U/238U, 2.5 micrograms/mL) and at the natural abundance ratio of 0.714% (235U/238U, 1.25 micrograms/mL 235U). The smallest measurable isotope shift of approximately 3 pm was determined for the 409.01 nm ion spectral line. Detection limits (DL) were obtained under optimized ICP operating conditions to be in the range of 70-150 ng/mL, except for the 238U component of the 286.57 nm line (300 ng/mL). This latter result was determined to be due to a strong, previously unreported, absorption interference from the argon plasma. The 235U isotope component (DL 70 ng/mL) was found to be unaffected. This work demonstrates the applicability of ICP-CRDS for uranium isotopic measurements. The potential of development of a field-deployable, on-line uranium isotope monitor using plasma-CRDS is discussed.
Asunto(s)
Gases/análisis , Calor , Isótopos/análisis , Isótopos/clasificación , Análisis Espectral/métodos , Uranio/análisis , Uranio/clasificación , Isótopos/química , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Uranio/químicaRESUMEN
The aim of the present study was to compare the response of a range of atherogenic and thrombogenic risk markers to two dietary levels of saturated fatty acid (SFA) substitution with monounsaturated fatty acids (MUFA) in students living in a university hall of residence. Although the benefits of such diets have been reported for plasma lipoproteins in high-risk groups, more needs to be known about effects of more modest SFA-MUFA substitutions over the long term and in young healthy adults. In a parallel design over 16 weeks, fifty-one healthy young subjects were randomised to one of two diets: (1) a moderate-MUFA diet in which 16 g dietary SFA/100 g total fatty acids were substituted with MUFA (n 25); (2) a high-MUFA diet in which 33 g dietary SFA/100 g total fatty acids were substituted with MUFA (n 26). All subjects followed an 8-week run-in diet (reference diet), with a fatty acid composition close to the UK average values. There were no differences in plasma lipid responses between the two diets over 16 weeks of the study with similar reductions in total cholesterol (P<0.001) and LDL-cholesterol (P<0.01) in both groups; a small but significant reduction in HDL-cholesterol was also observed in both groups (P<0.01). Platelet responses to ADP (P<0.01) and arachidonic acid (P<0.05) differed with time on the two diets; at 16 weeks, platelet aggregatory response to ADP was significantly lower on the high-MUFA than the moderate-MUFA (P<0.01) diet; ADP responses were also significantly lower within this group at 8 (P<0.05) and 16 (P<0.01) weeks compared with baseline. There were no differences in fasting factor VII activity (factors VIIc and VIIag), fibrinogen concentration or tissue-type plasminogen activator activity between the diets. There were no differences in postprandial factor VIIc responses to a standard meal (area under the curve) between the diets after 16 weeks, but postprandial factor VIIc response was lower than on the high-MUFA diet compared with baseline (P<0.01). In conclusion, a high-MUFA diet sustains potentially beneficial effects on platelet aggregation and postprandial activation of factor VII. Moderate or high substitution of MUFA for SFA achieves similar reductions in fasting blood lipids in young healthy subjects.
Asunto(s)
Grasas Insaturadas en la Dieta/administración & dosificación , Ácidos Grasos Monoinsaturados/administración & dosificación , Agregación Plaquetaria , Adulto , Análisis de Varianza , Área Bajo la Curva , Arteriosclerosis/sangre , Arteriosclerosis/prevención & control , Colesterol/sangre , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Factor VII/metabolismo , Femenino , Humanos , Masculino , Periodo Posprandial , Factores de Riesgo , Método Simple Ciego , Trombosis/sangre , Trombosis/prevención & controlRESUMEN
Dietary alpha-linolenic acid (ALA) can be converted to long-chain (n-3) PUFA in humans and may potentially reproduce the beneficial effects of eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids on risk factors for coronary heart disease (CHD). This study compared the effects of increased intakes of ALA with those of dietary EPA and DHA on blood coagulation and fibrinolytic factors in fasting subjects. A placebo-controlled, parallel study was conducted in 150 moderately hyperlipidemic subjects, age 25-72 y. Subjects were randomly assigned to one of five interventions and consumed a total intake of 0.8 or 1.7g/d EPA+DHA, 4.5 or 9.5g/d ALA or control (linoleic acid; LA) for 6 mo. Fatty acids were incorporated into 25 g of fat spread, which replaced the subject's normal spread and three capsules. Long-term supplementation with either dietary EPA+DHA or estimated biologically equivalent amounts of ALA did not affect factors VIIa, VIIc, VIIag, XIIa, XIIag, fibrinogen concentrations, plasminogen activator inhibitor-1 or tissue plasminogen activator activity compared with the control. (n-3) PUFA of plant or marine origin do not differ from one another or from LA in their effect on a range of blood coagulation and fibrinolytic factors.
Asunto(s)
Coagulación Sanguínea/efectos de los fármacos , Fibrinólisis/efectos de los fármacos , Hiperlipidemias/sangre , Biología Marina , Adulto , Anciano , Método Doble Ciego , Ácidos Grasos Omega-3 , Femenino , Humanos , Masculino , Persona de Mediana Edad , PlacebosRESUMEN
This study evaluated the effects of substituting dietary saturated fatty acids (SFAs) with monounsaturated fatty acids (MUFAs) on postprandial chylomicron (triacylglycerol (TAG), apolipoprotein B-48 (apo B-48) and retinyl ester (RE)), chylomicron particle size and factor VII (FVII) response when subjects were given a standard meal. In a controlled sequential design, 51 healthy young subjects followed an SFA-rich diet (Reference diet) for 8 weeks after which half of the subjects followed a moderate MUFA diet (n=25) and half followed a high MUFA diet (n=26) for 16 weeks. Fasting lipoprotein and lipid measurements were evaluated at baseline and at 8-week intervals during the Reference and MUFA diets. In 25 of the subjects (n=12 moderate MUFA, n=13 high MUFA), postprandial responses to a standard test meal containing RE and 13C-tripalmitin were investigated at the end of the Reference and the MUFA diet periods. Although there were no differences in the postprandial lipid markers (TAG, RE, 13C-TAG) on the two diets, the postprandial apo B-48 response (incremental area under the curve (IAUC)) was reduced by 21% on the moderate MUFA diet (NS) and by 54% on the high MUFA diet (P<0.01). The postprandial peak concentrations of apo B-48 were reduced by 33% on the moderate MUFA diet (P<0.01) and 48% on the high MUFA diet (P<0.001). Fasting values for factor VII activity (FVIIc), activated factor VII (FVIIa) or factor VII antigen (FVIIag) did not differ significantly when subjects were transferred from Reference to MUFA diets. However, the postprandial increases in coagulation FVII activity (FVIIc) were 18% lower and of activated FVII (FVIIa) were 17% lower on the moderate MUFA diet (NS). Postprandial increases in FVIIc and FVIIa were 50% (P<0.05) and 29% (P<0.07) lower on the high MUFA diet and the area under the postprandial FVIIc response curve (AUC) was also lower on the high MUFA diet (P<0.05). Significantly higher ratios of RE:apo B-48 (P<0.001) and 13C-palmitic acid:apo B-48 (P<0.01) during both MUFA diets suggest that the CMs formed carry larger amounts of dietary lipids per particle, reflecting an adaptation to form larger lipid droplets in the enterocyte when increased amounts of dietary MUFAs are fed. Smaller numbers of larger chylomicrons may explain attenuated activation of factor VII during the postprandial state when the background diet is rich in MUFA.
Asunto(s)
Quilomicrones/química , Grasas Insaturadas en la Dieta/administración & dosificación , Factor VII/metabolismo , Ácido Palmítico/metabolismo , Adulto , Apolipoproteína B-48 , Apolipoproteínas B/análisis , Apolipoproteínas B/metabolismo , Quilomicrones/metabolismo , Dieta , Grasas de la Dieta/administración & dosificación , Ácidos Grasos/administración & dosificación , Femenino , Humanos , Masculino , Tamaño de la Partícula , Periodo Posprandial , Triglicéridos/metabolismoRESUMEN
BACKGROUND: Soybeans contain estrogenic isoflavones that may influence plasma concentrations of transforming growth factor beta(1) (TGF-beta(1)) and plasma lipid and hemostatic risk factors for coronary heart disease. OBJECTIVE: We compared the effects of moderate intakes of soy protein containing intact phytoestrogens (high-isoflavone diet) and soy protein from which most of the phytoestrogens had been extracted (low-isoflavone diet) on active TGF-beta(1) concentrations and plasma lipid and hemostatic risk factors for coronary heart disease. DESIGN: A randomized crossover trial was conducted in 22 young, healthy, normolipidemic subjects (5 men and 17 women) who consumed diets providing 56 or 2 mg isoflavones/d for 17 d each with a 25-d washout period between treatments. Fasting blood samples were obtained on days 13 and 14 of each treatment to measure plasma isoflavone, lipid, fibrinogen, and active TGF-beta(1) concentrations and factor VII coagulant and plasminogen activator inhibitor type 1 activities. RESULTS: Plasma isoflavone concentrations were 100-999 times greater after the high-isoflavone diet than after the low-isoflavone diet (P < 0.05). Plasma HDL-cholesterol and apolipoprotein A-I concentrations were 4% (95% CI: 1%, 8%) and 6% (95% CI: 3%, 10%) higher, respectively, after the high-isoflavone diet than after the low-isoflavone diet (P < 0.01 for both). CONCLUSION: Compared with soy protein from which most of the phytoestrogens have been extracted, soy protein with intact phytoestrogens increases HDL-cholesterol and apolipoprotein A-I concentrations but does not influence LDL-cholesterol, TGF-beta(1), or fibrinogen concentrations; factor VII coagulant activity; or plasminogen activator inhibitor type 1 activity in normolipidemic, healthy subjects.