RESUMEN
The data on the effects of aerobic training on plasma antioxidant vitamins are conflicting. Additionally, most studies focus on the oxidative profiles of professional athletes, but limited information is available for amateur athlete populations. The aim of this study was to evaluate the effects of high-intensity exercise on antioxidant vitamins in non-professional runners with varying levels of aerobic power. Eighty-one male runners underwent an incremental test to exhaustion. The study population was then divided into the following tertiles according to VO2max: Group L (LowVO2max, less than 44.2 mLkg-1min-1), Group M (MediumVO2max, 44.2-49.7 mLkg-1min-1) and Group H (HighVO2max, >49.7). Comparative analyses were performed between Groups L and H. The total antioxidant capacity (TAC), Vitamin (Vit) E, Vitamin A, ß-carotene, lycopene and thiobarbituric acid-reactive substances (TBARS) were determined before and 60 min after exercise testing. After the stress test, Vit A decreased and TBARS increased in Group L, whereas no changes in the vitamin concentrations, TAC induction and TBARS reduction were observed in group H. In individuals with low VO2max, an incremental test determined lipid-peroxidation and Vitamin A consumption, whereas H Group increases TAC that buffer TBARS production.
Asunto(s)
Antioxidantes/metabolismo , Ejercicio Físico/fisiología , Aptitud Física/fisiología , Carrera/fisiología , Vitamina A/sangre , Adulto , Antioxidantes/análisis , Prueba de Esfuerzo , Humanos , MasculinoRESUMEN
Acute abdominal aortic thrombosis is a rare and potential fatal event, which occurs in adult subjects. We present the case of a 72-year-old-man, who referred to the emergency Department of our hospital because of persistent severe abdominal and perineal pain. Doppler ultrasounds and computerized tomography angiography revealed the acute thrombosis of the abdominal aorta. Immediate revascularization through aortic thrombo-endoarterectomy resolved the disease.
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Aorta Abdominal , Enfermedades de la Aorta/etiología , Fibrilación Atrial/complicaciones , Trombosis/etiología , Enfermedad Aguda , Anciano , Humanos , MasculinoRESUMEN
Published data regarding asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA), L-arginine (L-ARG) and nitric oxide fraction in exhaled air (FeNO) in pediatric bronchial asthma are limited. Many question remain open about plasma concentration of these substances. The aim of this study is to evaluate ADMA, SDMA, L-ARG and FeNO concentration in allergic pediatric mild asthmatic patients in respect to healthy subjects. In this case-control study 60 children (50 asthmatics and 10 healthy) underwent a complete clinical visit, baseline respiratory function, allergy tests and biochemical analyses. The statistical significance of the different concentrations between the two groups were studied using one-way analysis of variance (ANOVA). A p value less than 0.05 was considered statistically significant. The mean plasma ADMA (0.58 vs 0.68 micromol/L), SDMA (0.40 vs 0.45 micromol/L) and L-ARG (52.2 vs 74.13 micromol/L) concentration were significantly lower (p less than 0.001) in the asthmatic patients in respect to healthy subjects (control group). The concentration of FeNO was significantly higher in the asthmatic subjects in respect to the control group (9.18 vs 4.2 micromol/L; p less than 0.001). Low plasma concentrations of ADMA, SDMA, L-ARG and high concentration of FeNO are associated with bronchial asthma and indicate an important role in airway disease through NO metabolism.
Asunto(s)
Arginina/análogos & derivados , Arginina/sangre , Asma/sangre , Óxido Nítrico/sangre , Adolescente , Biomarcadores/sangre , Niño , Femenino , Humanos , MasculinoRESUMEN
Evidence from epidemiological and clinical studies suggests a possible correlation between serum antioxidant levels and cardiovascular disease risk. High plasma concentrations of lycopene have been associated with reduced prevalence of cardiovascular disease. The aim of this study is to compare plasma concentrations of lycopene in subjects with or without ultrasonic evidence of asymptomatic carotid atherosclerosis. One hundred and twenty subjects underwent physical examination, ultrasonic measurement of common carotid artery intima-media thickness and serum profile analysis. Logistic regression methods and analysis of variance were used to determine whether differences existed between participants with or without evidence of carotid atherosclerosis. Of the 120 participants, 58 exhibited evidence of carotid atherosclerosis. Participants with ultrasonic evidence of carotid atherosclerosis exhibited significantly higher serum concentrations of total cholesterol, LDL-cholesterol and triglycerides. In contrast, participants with ultrasonic evidence of carotid atherosclerosis exhibited significantly lower plasma concentrations of lycopene. These data suggest that higher serum levels of lycopene may play a protective role versus cardiovascular diseases, in particular carotid atherosclerosis.
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Carotenoides/sangre , Enfermedades de las Arterias Carótidas/sangre , LDL-Colesterol/sangre , Triglicéridos/sangre , Adulto , Anciano , Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Femenino , Humanos , Licopeno , Masculino , Persona de Mediana Edad , UltrasonografíaRESUMEN
We present a clinical case report regarding recurrent atrial fibrillation in a patient with ulcerative colitis treated with azathioprine. Atrial fibrillation represents the most common sustained cardiac arrhythmia, occurring in 1-2% of the general population and characterized by seemingly disorganized atrial depolarizations without effective atrial contraction. Several mechanisms determine this arrhythmia; in particular remodelling (structural, mechanical and electrical alteration related to atrial fibrillation). The pro-arrhythmic effect of azathioprine may be evaluated during immunosuppressive therapy to be aware of this serious but reversible adverse effect.
Asunto(s)
Fibrilación Atrial/inducido químicamente , Azatioprina/efectos adversos , Colitis Ulcerosa/tratamiento farmacológico , Inmunosupresores/efectos adversos , Femenino , Humanos , Persona de Mediana Edad , RecurrenciaRESUMEN
Isolated left ventricular noncompaction (ILVNC) is a congenital abnormality in the structure of ventricular tissue due to amorphogenetic defect during embryogenesis. This rare entity can be easily diagnosed by the characteristic appearance of prominent trabeculations and deep inter-trabecular spaces. Clinical manifestations of this disease include benign and malignant ventricular arrhythmia, congestive heart failure signs, cardio-embolic events (stroke), mitral and pulmonary valve incompetence, and reduced global ventricular systolic function. We present the case report of a 58-year-old man with ILVNC.
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Cardiomiopatías/complicaciones , Ventrículos Cardíacos/anomalías , Humanos , Masculino , Persona de Mediana EdadRESUMEN
High plasma concentrations of lycopene and beta-carotene have been associated with reduced prevalence of cardiovascular disease. The aim of this study is to compare plasma concentrations of these carotenoids in subjects with or without ultrasonic evidence of asymptomatic carotid atherosclerosis. One hundred and sixty-five subjects underwent physical examination and ultrasonic measurement of common carotid artery intima-media thickness. Analysis of variance and logistic regression methods were used to determine whether differences existed between participants with or without ultrasonic evidence of asymptomatic carotid atherosclerosis. Of the 165 participants, 80 exhibited evidence of carotid atherosclerosis (carotid intima-media thickness>0.8 mm), while 85 did not (carotid intima-media thickness>0.8 mm), while 85 did not (carotid intima-media thickness<0.8 mm). Participants with ultrasonic evidence of carotid atherosclerosis exhibited significantly greater body mass index, significantly higher serum concentrations of total cholesterol, LDL-associated cholesterol and triglycerides, and significantly higher plasma concentrations of uric acid, C-reactive protein and fibrinogen. In contrast, participants with ultrasonic evidence of carotid atherosclerosis exhibited significantly lower plasma concentrations of lycopene and beta-carotene. These results suggest that lycopene and beta-carotene may play important roles in delaying the development of the early asymptomatic stage of carotid atherosclerosis. Encouraging adequate intakes of antioxidant carotenoids may provide an important public health service.
Asunto(s)
Carotenoides/sangre , Enfermedades de las Arterias Carótidas/sangre , Adulto , Anciano , Carotenoides/administración & dosificación , Enfermedades de las Arterias Carótidas/diagnóstico por imagen , Enfermedades de las Arterias Carótidas/prevención & control , Arteria Carótida Común/diagnóstico por imagen , Femenino , Humanos , Lípidos/sangre , Licopeno , Masculino , Persona de Mediana Edad , Factores de Riesgo , Túnica Íntima/diagnóstico por imagen , Túnica Media/diagnóstico por imagen , Ultrasonografía , beta Caroteno/sangreRESUMEN
Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide (NO) associated with an increased risk of cardiovascular disease (CVD). In this study we assessed the relationship between ADMA and asymptomatic carotid intima-media thickness (CIMT). Eighty subjects underwent a complete history and physical examination, determination of serum chemistries and ADMA levels, and carotid ultrasound investigation (CUI). None of the subjects had symptoms of carotid atherosclerosis and nor were they taking any medication. Statistical analyses showed that high plasma levels of ADMA were positively correlated to CIMT (p less than 0.001). Total cholesterol, low density lipoprotein cholesterol, triglycerides and C-reactive protein plasma concentrations were significantly associated with asymptomatic carotid atherosclerosis (p less than 0.001). High serum concentrations of ADMA were associated with early carotid atherosclerotic lesions as measured by CIMT and represent a new marker of asymptomatic carotid atherosclerosis.
Asunto(s)
Arginina/análogos & derivados , Enfermedades de las Arterias Carótidas/sangre , Anciano , Arginina/sangre , LDL-Colesterol/sangre , Femenino , Humanos , Hipercolesterolemia/sangre , Masculino , Persona de Mediana EdadRESUMEN
Few studies have been conducted on the relationship between antioxidant plasma vitamin concentrations, inflammatory markers and carotid atherosclerosis with inconclusive results in endstage renal disease (ESRD) patients. A case-control study was performed to investigate the relationship between plasma antioxidant concentrations, inflammatory markers, and carotid intima-media thickness (CIMT) in healthy subjects and in patients undergoing hemodialysis (HD). We enrolled 40 subjects (20 healthy, 20 with ESRD) asymptomatic for carotid atherosclerosis. After carotid ultrasound investigation (CUI), medical history data, physical examination, venous blood samples were collected. These were analyzed for concentrations of antioxidant vitamins (A, E), carotenoids (lycopene, beta-carotene), inflammatory markers (C-reactive protein, fibrinogen), and lipid profile. Low concentrations of vitamin A, vitamin E, lycopene, and beta-carotene were significantly associated with carotid atherosclerosis in patients with ESRD (p less than 0.001). In addition, high concentration of low density lipoprotein cholesterol and total cholesterol (p less than 0.01), C-reactive protein and fibrinogen (p less than 0.001) were also associated with carotid atherosclerosis, while other laboratory parameters considered (high density lipoprotein cholesterol and triglycerides) were not significantly associated with carotid atherosclerosis. A regular intake of foods rich in antioxidant vitamins with low fat concentrations may slow the progression of atherosclerotic process in this group of patients.
Asunto(s)
Antioxidantes/metabolismo , Proteína C-Reactiva/análisis , Enfermedades de las Arterias Carótidas/etiología , Fallo Renal Crónico/complicaciones , Anciano , Carotenoides/sangre , Enfermedades de las Arterias Carótidas/sangre , Enfermedades de las Arterias Carótidas/patología , Estudios de Casos y Controles , Femenino , Humanos , Licopeno , Masculino , Persona de Mediana Edad , Túnica Íntima/patología , Túnica Media/patología , Vitamina E/sangre , beta Caroteno/sangreRESUMEN
Coronary artery disease (CAD) represents the primary cause of death in Western Countries with an high incidence on human health and community social costs. Oxidative stress induced by reactive oxygen species (ROS) plays an important role in the aetiology of this disease. In particular, the LDL-oxidization has a key role in the pathogenesis of atherosclerosis and cardiovascular heart diseases through the initiation of plaque formation process. Dietary phytochemical products such antioxidant vitamins (A,C,E) and bioactive food components (alpha- and beta-carotene) have shown an antioxidant effect in reducing both oxidative markers stress and LDL-oxidization process. Scientifical evidences support the beneficial roles of phytochemicals in the prevention of some chronic diseases. Lycopene, an oxygenated carotenoid with great antioxidant properties, has shown both in epidemiological studies and supplementation human trials a reduction of cardiovascular risk. However, controlled clinical trials and dietary intervention studies using well-defined subjects population haven't been provided a clear evidence of lycopene in the prevention of cardiovascular diseases. The present short review aims to evaluate the beneficial effect of lycopene in the prevention of cardiovascular disease.
Asunto(s)
Antioxidantes/administración & dosificación , Enfermedades Cardiovasculares/prevención & control , Carotenoides/administración & dosificación , Enfermedades Cardiovasculares/epidemiología , Enfermedades Cardiovasculares/etiología , Carotenoides/química , Carotenoides/farmacología , Suplementos Dietéticos , Humanos , Licopeno , Estrés OxidativoRESUMEN
Bronchial asthma represents the commonest chronic respiratory disease in industrialized countries and its prevalence is increasing throughout the world. This is a chronic inflammatory disease in which the inflammation constitutes an important predisposing condition for airway remodelling and secondary irreversible airflow obstruction. The current approach for the treatment involves many classes of drugs, particularly anti-inflammatory such inhaled and oral corticosteroids and cysteinyl-leukotriene receptor antagonist. The pharmacology of drugs used in asthma represents an important factor that conditioning the effectiveness of therapy. In fact, many studies have demonstrated that some asthmatic patients have particular problems that deserve special treatment. Another important factor of asthma treatment is represented by delivery devices for the inhalation of medications and their correct use because, at the present, it is estimated that compliance to controller anti-asthmatic therapy is no more than 50%. The aim of this review is to focus on the compliance in the treatment of asthma and the use of antiinflammatory therapies with inhaled corticosteroids and leukotriene receptor antagonist drugs.
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Corticoesteroides/administración & dosificación , Antiasmáticos/administración & dosificación , Antiinflamatorios/administración & dosificación , Asma/tratamiento farmacológico , Antagonistas de Leucotrieno/administración & dosificación , Cooperación del Paciente , Administración por Inhalación , Humanos , Nebulizadores y VaporizadoresRESUMEN
Cysteinyl leukotrienes (Cys-LTs) are potent proinflammatory mediators derived from arachidonic acid through the 5-lypoxigenase (5-LO) pathway. They exert important pharmacological effects by interaction with at least two different receptors: Cys-LT(1) and Cys-LT(2). By competitive binding to the Cys-LT(1) receptor, leukotriene receptor antagonist drugs such as montelukast, zafirlukast, and pranlukast, block the effects of Cys-LTs and alleviate the symptoms of many chronic diseases, especially bronchial asthma and allergic rhinitis. Evidence obtained by randomized clinical trials as also by direct experience derived from patients suffering from asthma and allergic rhinitis justifies a broader role for leukotrienes receptor antagonists (LTRAs). Recently published studies and case reports have demonstrated beneficial effects of LTRAs on other diseases commonly associated with asthma (exercise induced asthma, rhinitis, chronic obstructive pulmonary disease, interstitial lung disease, chronic urticaria, atopic dermatitis, allergic fungal disease, nasal polyposis, and paranasal sinus disease) as well as other diseases not connected to asthma (migraine, respiratory syncytial virus postbronchiolitis, systemic mastocytosis, cystic fibrosis, pancreatitis, vulvovaginal candidiasis, cancer, atherosclerosis, eosinophils cystitis, otitis media, capsular contracture, and eosinophilic gastrointestinal disorders). The aim of this review is to show the most recent applications and effectiveness in clinical practice of the LTRAs.
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Antiasmáticos/uso terapéutico , Asma/tratamiento farmacológico , Antagonistas de Leucotrieno/uso terapéutico , Leucotrienos/metabolismo , Rinitis/tratamiento farmacológico , Antiasmáticos/efectos adversos , Antiasmáticos/farmacología , Araquidonato 5-Lipooxigenasa/metabolismo , Ácido Araquidónico/metabolismo , Enfermedad Crónica/clasificación , Enfermedad Crónica/tratamiento farmacológico , Cisteína/metabolismo , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Humanos , Antagonistas de Leucotrieno/efectos adversos , Antagonistas de Leucotrieno/farmacología , Resultado del TratamientoRESUMEN
OBJECTIVE: Scientific evidence suggests that lycopene and antioxidant vitamins have significant antioxidant and protective effects. METHODS: This case-control study included 96 subjects (40 asthmatics, 56 healthy control subjects). Baseline blood samples, pulmonary function tests, and clinical and alimentary histories were collected. All subjects were grouped by age, sex, cigarette smoking habit, body mass index, alimentary intake, and atopic status. RESULTS: Serum lycopene concentration was significantly lower in asthmatic subjects than in healthy control subjects (0.10+/-0.7 micromoL/L vs. 0.16+/-0.8 micromoL/L--p<0.001). Serum vitamin A concentration was significantly lower in asthmatics (2.38+/-0.37 micromoL/L) in respect to control subjects (3.06+/-0.56 micromoL/L) (p<0.01). Plasma serum concentration of vitamin E and beta-carotene were not found to be different in the two groups. CONCLUSIONS: Dietary supplementation or adequate intake of lycopene and vitamin A rich foods may be beneficial in asthmatic subjects.
Asunto(s)
Antioxidantes/análisis , Asma/sangre , Carotenoides/sangre , Vitaminas/sangre , Adulto , Análisis de Varianza , Asma/fisiopatología , Índice de Masa Corporal , Estudios de Casos y Controles , Ingestión de Energía , Femenino , Volumen Espiratorio Forzado , Humanos , Licopeno , Masculino , Persona de Mediana Edad , Ápice del Flujo Espiratorio , Fumar , Capacidad Vital , Vitamina A/sangre , Vitamina E/sangre , beta Caroteno/sangreRESUMEN
INTRODUCTION: The aim of this study was to evaluate the effects of high-dose vitamin E supplementation (1200 mg/day) on reducing both microalbuminuria (MA) and oxidative stress in patients with type 1 diabetes mellitus (T1DM) and persistent MA. METHODS: We performed a 12-month, randomized, placebo-controlled, double-blind cross-over trial in ten Caucasian young adults (7m/3f; mean age 18.87 +/- 2.91 years) with T1DM and persistent MA. At baseline and at end of the treatment period, determination of albumin excretion rate (AER) and HbA(1c) and evaluation of the oxidant/antioxidant status were performed. RESULTS: At the beginning of the study, AER and HbA(1c) were not significantly different between the vitamin E and placebo group. No differences in terms of oxidant and antioxidant status were found between the two groups. This was associated with no significantly different urinary VEGF and TGF-beta levels. After 6 months, no significant differences in AER were observed between the two groups (p = 0.59). However, plasma and LDL-vitamin E content were significantly higher in the vitamin E group compared to the placebo group (p = 0.0001 and p = 0.004, respectively). This was associated with a significantly longer lag phase (p = 0.002) and lower MDA (p = 0.049). However, no statistically significant differences were detected in terms of VEGF and TGF-beta urinary levels. CONCLUSION: These data demonstrate that high-dose vitamin E supplementation reduces markers of oxidative stress and improves antioxidant defence in young patients with T1DM. However, although it positively affects the oxidant/antioxidant status, vitamin E supplementation does not reduce AER in patients with T1DM and persistent MA.
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Diabetes Mellitus Tipo 1/fisiopatología , Suplementos Dietéticos , Estrés Oxidativo/efectos de los fármacos , Vitamina E/uso terapéutico , Adolescente , Adulto , Edad de Inicio , Albuminuria/tratamiento farmacológico , Albuminuria/prevención & control , Índice de Masa Corporal , Niño , Creatinina/orina , Estudios Cruzados , Método Doble Ciego , Femenino , Humanos , Lipoproteínas LDL/sangre , Lipoproteínas LDL/efectos de los fármacos , Masculino , Selección de Paciente , Placebos , Vitamina E/administración & dosificaciónAsunto(s)
Asma/diagnóstico , Carotenoides/sangre , Adulto , Estudios de Casos y Controles , Femenino , Humanos , Licopeno , MasculinoRESUMEN
Increasing evidence suggests that fat soluble vitamins and micronutrients have the potential for local modulation of follicular development. Cigarette smoking has been associated with accelerated follicular depletion and derangement of reproductive functions. The present study was initiated to investigate the impact of cigarette smoking on follicular and plasma concentrations of vitamin A, vitamin E, lycopene and beta-carotene. Samples were collected from 17 smokers and 43 non-smoking women undergoing assisted reproduction techniques. Assays were carried out by a reverse-phase high-pressure liquid chromatography (HPLC) method. Smokers had significantly (P < 0.05) lower levels of follicular fluid beta-carotene in comparison to non-smokers (0.02 +/- 0.02 vs. 0.09 +/- 0.02, respectively). No other significant influences on follicular and plasma concentrations were noted. Smokers showed a significantly (P < 0.05) lower fertilization rate in comparison to non-smokers, (55.9 % vs. 71.5 % , respectively). It is postulated that follicular depletion of the antioxidant beta-carotene occurs in response to oxidative stress imposed by cigarette smoke.
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Líquido Folicular/metabolismo , Fase Folicular/metabolismo , Fumar/metabolismo , Vitaminas/metabolismo , Adulto , Envejecimiento/metabolismo , Carotenoides/metabolismo , Cromatografía Líquida de Alta Presión , Femenino , Humanos , Infertilidad Femenina/metabolismo , Licopeno , Persona de Mediana Edad , Vitamina A/metabolismo , Vitamina E/metabolismo , beta Caroteno/metabolismoRESUMEN
OBJECTIVE: To investigate whether enhanced oxidant stress in patients undergoing percutaneous transluminal coronary angioplasty (PTCA) is associated with a higher concentration of non-high density lipoprotein (HDL) cholesterol at baseline, and whether this contributes to the inflammatory reaction and luminal renarrowing after PTCA. DESIGN: An ex vivo and in vitro study of 46 patients who underwent PTCA and who had repeat angiograms after six months. Blood samples were collected immediately before PTCA, and at 24 hours, 48 hours, and 15 days after. SETTING: Tertiary referral centre. SUBJECTS: 46 patients (30 male, 16 female; mean (SD) age, 62 (5) years) with stable or unstable angina who underwent elective PTCA. MAIN OUTCOME MEASURES: Continuous variable luminal loss as defined by change in minimum lumen diameter during follow up, normalised for vessel size; lag phase of low density lipoprotein to in vitro oxidation; plasma fluorescent products of lipid peroxidation (FPLP); plasma vitamin C and E; interleukin (IL) 1beta secretion from unstimulated monocytes; plasma C reactive protein (CRP). RESULTS: Restenosis occurred in 12 patients (26%). Oxidant stress after PTCA was greater (p < 0.0001 at 15 days) in the patients with restenosis and showed a significant correlation with the preprocedural concentration of non-HDL cholesterol (p < 0.001). Inflammatory reaction (as reflected by IL-1beta production and CRP) and late lumen loss were linearly correlated (p < 0.001) with lag phase and FPLP throughout the study, and inversely (p < 0.05) with vitamin C and E measured at two and 15 days after PTCA. CONCLUSIONS: This study provides evidence for the critical role of cholesterol dependent oxidant stress in the pathophysiology of restenosis after PTCA. The findings raise the possibility that drugs capable of modulating oxidant status might provide a novel form of adjuvant treatment in patients with hypercholesterolaemia undergoing PTCA.
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Angioplastia Coronaria con Balón , LDL-Colesterol/sangre , Reestenosis Coronaria/etiología , Monocitos/fisiología , Estrés Oxidativo , Proteína C-Reactiva/análisis , Reestenosis Coronaria/sangre , Femenino , Humanos , Interleucina-1/análisis , Activación de Linfocitos , Masculino , Persona de Mediana EdadAsunto(s)
Arginina/farmacología , Hipercolesterolemia/tratamiento farmacológico , Selectina-P/efectos de los fármacos , Adulto , Anciano , Arginina/administración & dosificación , Femenino , Humanos , Hipercolesterolemia/sangre , Masculino , Persona de Mediana Edad , Óxido Nítrico/sangre , Selectina-P/sangre , SolubilidadRESUMEN
BACKGROUND: Unstable angina is associated with enhanced lipid peroxidation and reduced antioxidant defenses. We have previously reported aspirin failure in the suppression of enhanced thromboxane (TX) biosynthesis in a subset of episodes of platelet activation in this setting. We tested the hypothesis that the in vivo formation of the F(2)-isoprostane 8-iso-prostaglandin (PG)F(2alpha), a bioactive product of arachidonic acid peroxidation, is enhanced in unstable angina and contributes to aspirin-insensitive TX biosynthesis. METHODS AND RESULTS: Urine samples were obtained from patients with unstable angina (n=32), stable angina (n=32), or variant angina (n=4) and from 40 healthy subjects for the measurement of immunoreactive 8-iso-PGF(2alpha) and 11-dehydro-TXB(2). 8-Iso-PGF(2alpha) excretion was significantly higher in patients with unstable angina (339+/-122 pg/mg creatinine) than in matched patients with stable angina (236+/-83 pg/mg creatinine, P:=0.001) and control subjects (192+/-71 pg/mg creatinine, P:<0.0001). In patients with unstable angina, 8-iso-PGF(2alpha) was linearly correlated with 11-dehydro-TXB(2) excretion (rho=0.721, P:<0.0001) and inversely correlated with plasma vitamin E (rho=-0.710, P:=0. 004). Spontaneous myocardial ischemia in patients with variant angina or ischemia elicited by a stress test in patients with stable angina was not accompanied by any change in 8-iso-PGF(2alpha) excretion, thus excluding a role of ischemia per se in the induction of increased F(2)-isoprostane production. CONCLUSIONS: These findings establish a putative biochemical link between increased oxidant stress and aspirin-insensitive TX biosynthesis in patients with unstable angina and provide a rationale for dose-finding studies of antioxidants in this setting.
Asunto(s)
Angina Inestable/tratamiento farmacológico , Antioxidantes/uso terapéutico , Aspirina/uso terapéutico , Dinoprost/análogos & derivados , Inhibidores de Agregación Plaquetaria/uso terapéutico , Tromboxano A2/biosíntesis , Angina Inestable/metabolismo , Ciclooxigenasa 1 , Ciclooxigenasa 2 , Dinoprost/biosíntesis , Dinoprost/orina , Relación Dosis-Respuesta a Droga , Resistencia a Medicamentos , F2-Isoprostanos , Humanos , Isoenzimas/antagonistas & inhibidores , Masculino , Proteínas de la Membrana , Persona de Mediana Edad , Estrés Oxidativo , Prostaglandina-Endoperóxido Sintasas , Tromboxano A2/sangre , Factores de TiempoRESUMEN
BACKGROUND: Increased formation of 8-iso-prostaglandin (PG) F(2alpha) and thromboxane (TX) A(2), potent agonists of platelet and vascular thromboxane (TH)/PGH(2) receptors, has been detected in cigarette smokers. We performed a randomized, double-blind, placebo-controlled study of the effects of vitamin E (300, 600, and 1200 mg/d, each dose for 3 consecutive weeks) on 8-iso-PGF(2alpha) and TXA(2) biosynthesis in 46 moderate cigarette smokers. METHODS AND RESULTS: Urinary immunoreactive 8-iso-PGF(2alpha) and 11-dehydro-TXB(2), plasma vitamin E, and serum TXB(2) were measured by previously validated techniques. Baseline urinary 8-iso-PGF(2alpha) and 11-dehydro-TXB(2) excretion averaged 241+/-78 and 430+/-293 pg/mg creatinine, respectively. Urinary 8-iso-PGF(2alpha) was significantly correlated with 11-dehydro-TXB(2) (r=0.360, n=138, P<0.0001). Baseline plasma vitamin E levels averaged 20.6+/-4.9 micromol/L and were inversely correlated with urinary 11-dehydro-TXB(2) (r=-0.304, P=0.039) but not with 8-iso-PGF(2alpha) (r=-0.227, P=0.129). Vitamin E supplementation caused a dose-dependent increase in its plasma levels that reached a plateau at 600 mg (42.3+/-11.2 micromol/L, P<0. 001). This was not associated with any statistically significant change in urinary 8-iso-PGF(2alpha) or 11-dehydro-TXB(2) excretion. CONCLUSIONS: Supplementation with pharmacological doses of vitamin E has no detectable effects on lipid peroxidation and thromboxane biosynthesis in vivo in healthy subjects with a mild degree of oxidant stress. These findings are consistent with the hypothesis that the basal rate of lipid peroxidation is a major determinant of the response to vitamin E supplementation and have implications for the use of vitamin E in healthy subjects as well as for the design and interpretation of clinical trials of antioxidant intervention.