RESUMEN
BACKGROUND AND AIMS: The generation of reactive oxygen species (ROS) plays an important role in the etiology of several pathological conditions. High levels of 8-hydroxy-2-deoxyguanosine (8-OHdG), a biomarker of oxidative damage of DNA, have been found in patients with heart failure (HF). We performed a meta-analysis of the literature to investigate the association between 8-OHdG levels and HF. METHODS AND RESULTS: A systematic search was performed in the PubMed, Web of Science, Scopus, EMBASE databases and studies evaluating 8-OHdG levels in HF patients and controls were included. Differences between cases and controls were expressed as standard mean difference (SMD) or mean difference (MD) with pertinent 95% confidence intervals (95%CI). Impact of clinical and demographic features on effect size was assessed by meta-regression. Six studies (446 HF patients and 140 controls) were included in the analysis. We found that HF patients showed higher 8-OHdG levels than controls (SMD:0.89, 95%CI: 0.68, 1.10). The difference was confirmed both in studies in which 8-OHdG levels were assessed in urine (MD:6.28 ng/mg creatinine, 95%CI: 4.01, 8.56) and in blood samples (MD:0.36 ng/ml, 95%CI: 0.04, 0.69). Interestingly, 8-OHdG levels progressively increased for increasing New York Heart Association (NYHA) class. Meta-regression models showed that none of clinical and demographic variables impacted on the difference in 8-OHdG levels among HF patients and controls. CONCLUSIONS: 8-OHdG levels are higher in HF patients HF than in controls, with a progressive increase for increasing NYHA class. However, larger prospective studies are needed to test 8-OHdG as a biomarker of HF severity and progression.
Asunto(s)
Daño del ADN , Desoxiguanosina/análogos & derivados , Insuficiencia Cardíaca/metabolismo , Miocardio/metabolismo , Estrés Oxidativo , 8-Hidroxi-2'-Desoxicoguanosina , Biomarcadores/metabolismo , Distribución de Chi-Cuadrado , Desoxiguanosina/metabolismo , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/genética , Insuficiencia Cardíaca/fisiopatología , Humanos , Valor Predictivo de las Pruebas , Pronóstico , Factores de Riesgo , Índice de Severidad de la Enfermedad , Volumen Sistólico , Regulación hacia Arriba , Función Ventricular IzquierdaRESUMEN
BACKGROUND: Observational studies suggest that low levels of antioxidants are associated with high risk for coronary artery disease (CAD). We investigated whether the biomarkers of oxidative balance undergo the same modifications in all CAD patient groups, regardless of gender and age. MATERIALS AND METHODS: One hundred sixty-eight CAD patients and 107 healthy controls were assayed for plasma levels of reduced glutathione (GSH), alpha- and gamma-tocopherol (alpha- and gamma-T) as endogenous antioxidants. A damage score (DS), representative of oxidative stress status, was calculated. ANCOVA models were used to test the association between antioxidants, DS and CAD and its modulation by age and gender. RESULTS: The DS was higher in CAD than in controls. GSH levels, were lower in CAD patients (mean +/- SEM: 57.61 +/- 1.87 micromol 10 g(-1) haemoglobin vs. 68.55 +/- 2.23 in controls, P < 0.0006) in males and in older subjects. Levels of other antioxidants exhibited a complex pattern. Overall, no difference was found in alpha- and gamma-T contents between CAD and controls, but lower alpha-T values were observed in CAD females. A significant interaction between CAD status and gender was observed (P = 0.003). CONCLUSIONS: Our study shows that the involvement of antioxidants in CAD is related to patients' characteristics. These findings may be relevant in planning antioxidant therapies.
Asunto(s)
Antioxidantes/análisis , Biomarcadores/análisis , Enfermedad Coronaria/sangre , Glutatión/sangre , Estrés Oxidativo , Vitamina E/sangre , Adulto , Factores de Edad , Anciano , Análisis de Varianza , Estudios de Casos y Controles , Susceptibilidad a Enfermedades , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Factores SexualesRESUMEN
On-pump cardiac surgery may trigger inflammation and accelerate platelet cyclooxygenase-1 renewal, thereby modifying low-dose aspirin pharmacodynamics. Thirty-seven patients on standard aspirin 100 mg once-daily were studied before surgery and randomized within 36 hours postsurgery to 100 mg once-daily, 100 mg twice-daily, or 200 mg once-daily for 90 days. On day 7 postsurgery, immature and mature platelets, platelet mass, thrombopoietin, glycocalicin, leukocytes, C-reactive protein, and interleukin-6 significantly increased. Interleukin-6 significantly correlated with immature platelets. At day 7, patients randomized to 100 mg once-daily showed a significant increase in serum thromboxane (TX)B2 within the 24-hour dosing interval and urinary TXA2 metabolite (TXM) excretion. Aspirin 100 mg twice-daily lowered serum TXB2 and prevented postsurgery TXM increase (P < 0.01), without affecting prostacyclin metabolite excretion. After cardiac surgery, shortening the dosing interval, but not doubling the once-daily dose, rescues the impaired antiplatelet effect of low-dose aspirin and prevents platelet activation associated with acute inflammation and enhanced platelet turnover.
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Aspirina/administración & dosificación , Plaquetas/efectos de los fármacos , Puente de Arteria Coronaria/tendencias , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Enfermedad de la Arteria Coronaria/cirugía , Inhibidores de Agregación Plaquetaria/administración & dosificación , Anciano , Anciano de 80 o más Años , Plaquetas/metabolismo , Puente de Arteria Coronaria/efectos adversos , Enfermedad de la Arteria Coronaria/sangre , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
Hyperhomocysteinemia (HH) has been associated with cardiovascular and autoimmune diseases and oxidative cell damage. Myelodysplastic syndromes (MDS) are associated with autoimmunity (AI) and increased oxidative stress. We tested the association of HH and oxidative stress in 33 MDS patients, by measuring plasma homocysteine and malondialdehyde (MDA). HH was found in 42% of cases, (4/5) cases with associated cardiovascular events (CVE)(80%), and 9/15 cases with associated AI (60%). Thus in MDS, HH was significantly associated with AI/CVE (chi(2) : p=0.0011), and this association seems to be specific, as demonstrated by the comparison of MDS presenting AI/CVE with the ischemic cardiopathy/rheumatoid arthritis control group (13/20, 65% vs 19/69, 27%; chi(2) : p=0.0021). The levels of MDA indicated increased oxidative stress. Our data may suggest that in a subset of MDS, HH may simultaneously contribute to bone marrow myelodysplasia, CVE and AI pathogenesis, possibly through oxidative cell damage.
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Hiperhomocisteinemia/complicaciones , Síndromes Mielodisplásicos/complicaciones , Análisis de Varianza , Autoinmunidad/fisiología , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/etiología , Estudios de Casos y Controles , Ayuno , Homocisteína/sangre , Humanos , Peroxidación de Lípido , Malondialdehído/sangre , Síndromes Mielodisplásicos/sangre , Síndromes Mielodisplásicos/inmunología , Estrés Oxidativo/fisiologíaRESUMEN
A factor reacting with antisera against carcinoembryonic antigen (CEA) was isolated from healthy donors' plasma. Ten different antiCEA sera were absorbed with this plasma factor (P-factor): the antiCEA activity was mostly, or completely, removed in 8 sera. Only 2 of these absorbed sera (here defined as type A) still presented a high CEA binding activity by radioimmunoassay and, on tissue sections, selectively stained most of the colonic adenocarcinomas and areas of severe dysplasia in neoplastic adenomas. Contrary to the behaviour of the antisera against the P-factor, of the unabsorbed antiCEA sera, of a commercially available antiserum and of a monoclonal antibody, the P-absorbed type A antiCEA sera appeared unreactive with normal colonic mucosa and granulocytes. Absorption with the P-factor allows us to obtain antiCEA sera with higher tumor specificity.
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Adenocarcinoma/inmunología , Adenoma/inmunología , Antígeno Carcinoembrionario/inmunología , Neoplasias del Colon/inmunología , Adenocarcinoma/patología , Adenoma/patología , Animales , Especificidad de Anticuerpos , Antígeno Carcinoembrionario/análisis , Neoplasias del Colon/patología , Femenino , Cabras , Histocitoquímica , Humanos , Técnicas para Inmunoenzimas , Técnicas de Inmunoadsorción , Masculino , Ratones , Metástasis de la Neoplasia , Conejos , RadioinmunoensayoRESUMEN
Essential thrombocythaemia (ET) is characterised by enhanced platelet generation and thrombosis. Once daily (od) aspirin incompletely inhibits platelet thromboxane (TX)A2 production in ET. A twice daily (bid) dosing is necessary to fully inhibit TXA2. Whether this dosing regimen affects in vivo prostacyclin (PGI2) biosynthesis is unknown. PGI2 biosynthesis was characterised in 50 ET patients on enteric-coated (EC) aspirin 100 mg od, by measuring its urinary metabolite, 2,3-dinor-6-keto-PGF1α (PGI-M). Moreover, in a crossover study 22 patients poorly responsive to standard aspirin based on serum TXB2 levels (≥4 ng/ml) were randomised to different seven-day aspirin regimens: EC aspirin 100 mg od, 100 mg bid, 200 mg od, or plain aspirin 100 mg od. PGI-M measured 24 hours after the last aspirin intake (EC, 100 mg od) was similar in patients and healthy subjects both on (n=10) and off (n=30) aspirin. PGI-M was unrelated to in vivo TXA2 biosynthesis, and not affected by EC aspirin 100 mg bid or 200 mg od as compared to EC 100 mg od. PGI2 biosynthesis in aspirin-treated ET patients appears unrelated to TXA2 biosynthesis, and not affected by an improved aspirin regimen, demonstrating its vascular safety for future trials.
Asunto(s)
Aspirina/administración & dosificación , Plaquetas/efectos de los fármacos , Epoprostenol/biosíntesis , Trombocitemia Esencial/tratamiento farmacológico , Tromboxano A2/metabolismo , 6-Cetoprostaglandina F1 alfa/análogos & derivados , 6-Cetoprostaglandina F1 alfa/orina , Anciano , Aspirina/efectos adversos , Plaquetas/fisiología , Protocolos Clínicos , Cálculo de Dosificación de Drogas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Agregación Plaquetaria/efectos de los fármacos , Trombocitemia Esencial/diagnósticoRESUMEN
BACKGROUND AND PURPOSE: To compare the effects of regular cigarettes (RCs) and light cigarettes (LCs) on brachial artery flow-mediated dilation (FMD) and sublingual glyceryl trinitrate-induced dilation (GTN), markers of endothelial dependant and independent function, respectively. METHODS: 206 subjects (age 51.5 ± 12.8 yr, 122 men) had their smoking habits recorded and FMD and GTN measured by B-mode ultrasound. Cigarettes were categorized as RCs or LCs according to their content of tar, nicotine and CO. The chronic effect was assessed in current smokers of RCs (n = 85) or LCs (n = 53) and in never smokers (NS; n = 68). The acute effect was assessed in current smokers by measuring FMD before and 10-min after smoking a single regular (n = 29) or light (n = 51) cigarette. RESULTS: FMD was significantly lower in consumers of RCs (6.26%, 95% C.I. 5.58, 6.94) or LCs (5.59%, 95% C.I. 4.74, 6.45) compared to NS (8.68%, 95% C.I. 7.92, 9.44) (both P < 0.0001), but did not differ (P > 0.05) when compared to each other. GTN was similar in the three groups. Analyses adjusted for clinical confounders and for markers involved in oxidative stress, arginine/nitric oxide pathway, and inflammation provided identical results. Smoking a single cigarette, either regular or light, reduced FMD (-0.88% and -1.17%, respectively, both P < 0.05), without significant difference between cigarette type. RCs and LCs produced analogous chronic and acute effects when FMD was calculated with respect to the last 60 s of the low-flow phase (FMD60s). CONCLUSIONS: LCs impair endothelial-dependant vasodilation as much as RCs. Thus, smoking LCs cannot be considered an alternative to the only safe choice of a complete and permanent smoking cessation.
Asunto(s)
Arteria Braquial/fisiología , Fumar/efectos adversos , Fumar/fisiopatología , Productos de Tabaco/efectos adversos , Vasodilatación/fisiología , Adulto , Arteria Braquial/diagnóstico por imagen , Arteria Braquial/metabolismo , Relación Dosis-Respuesta a Droga , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/metabolismo , Endotelio Vascular/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nicotina/efectos adversos , Agonistas Nicotínicos/efectos adversos , Óxido Nítrico/metabolismo , Estrés Oxidativo/fisiología , Fumar/metabolismo , Ultrasonografía , Vasculitis/diagnóstico por imagen , Vasculitis/metabolismo , Vasculitis/fisiopatología , Vasodilatación/efectos de los fármacosRESUMEN
Oxidative stress has been related to various diseases, gender and ageing, and has been measured by various markers. The authors developed a procedure to compute a global oxidative stress index (OXY-SCORE), reflecting both oxidative and antioxidant markers in healthy subjects. Its performance was tested in relation to age and gender and in coronary artery disease (CAD) patients. Eighty-two healthy subjects and 20 CAD patients were enrolled. Plasma free and total malondialdehyde (F- and T-MDA), glutathione disulphide/reduced form ratio (GSSG/GSH) and urine isoprostanes (iPF2alpha-III) levels were combined as oxidative damage markers (damage score). GSH, alpha- and gamma-tocopherol (TH) levels, and individual antioxidant capacity were combined as antioxidant defence indexes (protection score). The OXY-SCORE was computed by subtracting the protection score from the damage score. Among single parameters, T-MDA and iPF2alpha-III significantly correlated with age; only GSH and both tocopherols correlated with male gender in healthy subjects. The OXY-SCORE was positively associated with age (p=0.004) and male gender (p=0.03). As expected, the OXY-SCORE was higher in CAD with a very significant p-value (<0.0001), after adjusting for age, gender and smoking. Combining different markers can potentially provide a powerful index in the evaluation of oxidative stress related to age, gender and CAD status.
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Estrés Oxidativo , Índice de Severidad de la Enfermedad , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Antioxidantes/análisis , Biomarcadores/sangre , Biomarcadores/orina , Enfermedad de la Arteria Coronaria/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Oxidantes/análisis , Factores SexualesRESUMEN
A factor that cross reacts with the carcinoembryonic antigen (CEA), which we call P factor, was isolated from normal human plasma. To demonstrate the difference between this P factor and the nonspecific cross-reacting antigen (NCA), the same anti-CEA serum was absorbed in an identical manner with both the antigens. Absorption was checked by immunohistochemistry by the beta-galactosidase procedure on sections of colonic adenocarcinoma and normal colonic mucosa. The unabsorbed antiserum recognizes both tissues; after absorption with NCA the staining becomes paler on both tissues, but maintains color on the normal colonic mucosa and granulocytes. Only absorption with the P factor will give an unstained field of normal colonic mucosa, thus revealing the tumor structure. Data obtained by us suggest that the NCA (tissue extract) is an antigen that is not suitable to the absorption of anti-CEA serum for immunocytochemistry techniques, whereas the P factor (plasma extract) appears to be utilizable with good results.
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Antígenos de Neoplasias/inmunología , Antígeno Carcinoembrionario/inmunología , Moléculas de Adhesión Celular , Glicoproteínas/análisis , Sueros Inmunes/inmunología , Extractos de Tejidos/inmunología , Absorción , Antígenos de Neoplasias/aislamiento & purificación , Reacciones Cruzadas , Glicoproteínas/inmunología , Glicoproteínas/aislamiento & purificación , Histocitoquímica , HumanosRESUMEN
Various types of extraction were tested to increase the immunological yield of BCA, a CEA-like primary breast cancer associated carcinoma antigen. To allow a comparison, the different extraction techniques were applied to only one breast tumour. The comparison of the various systems was based on two parameters: protein yield and immunological activity, assayed in a RIA 125I CEA-anti CEA system. The following extraction methods were described and compared in this paper: 3M KCl; 1N HClO4; neutral pH extraction (PBS) in the absence and presence of various detergents (anionic, neutral and cationic), basic pH extraction (1N NaOH) and acid pH extraction (1.5M acetic acid) in the presence of urea and various detergents. The more significant systems were applied also to the extraction of CEA, from colonic adenocarcinoma liver metastases. The best results for both the antigens studied were obtained by using neutral detergents (1% NP 40) at neutral pH.
Asunto(s)
Antígenos de Neoplasias/aislamiento & purificación , Neoplasias de la Mama/análisis , Fenómenos Químicos , Química , Femenino , Humanos , Métodos , Octoxinol , PolietilenglicolesRESUMEN
By exploiting the cross-reaction among the antigens associated with a pool of breast carcinomas, preselected according to their antigenic content, a CEA-like BCA, with a specific activity of 1400 U/micrograms has been extracted, by means of 3M KCl, and partially purified by means of ConA Sepharose affinity chromatography and bioabsorption, employing, for the latter, a cross-reacting antiserum (anti CEA). The subsequent labelling, after Sephadex G-200 gel filtration, points out an immunological activity at the apex of the first peak versus anti CBC (or C.BCA) and anti CEA.
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Antígenos de Neoplasias/aislamiento & purificación , Neoplasias de la Mama/análisis , Antígeno Carcinoembrionario/aislamiento & purificación , Absorción , Animales , Fenómenos Químicos , Química , Cromatografía en Gel , Reacciones Cruzadas , Femenino , Cabras/inmunología , Humanos , Cloruro de PotasioRESUMEN
The analytical performance of the Stratus Folate assay for intra-erythrocyte folate determination in normal subjects and in patients affected by folate-related diseases was compared with that of the radioassay (DPC) routinely employed by us. Folate concentrations were measured in freshly obtained EDTA whole blood from 100 subjects. Haemolysis was performed with the appropriate lysis reagent. In addition, to compare two different haemolysis procedures folate determination was carried out in 51 samples haemolysed according to the two procedures in parallel. Data were analyzed using Wilcoxon's test and standardized principal component analysis. Stratus Folate assay and radioassay performances were comparable in terms of analytical characteristics as well as in individual intraerythrocyte folate values across the range of whole blood concentrations examined in the survey. Significant differences were detected between the two different haemolysis procedures only for the radioassay. In conclusion, we observed no significant differences between the two folate determination methods despite their different analytical principles, which indicates the suitability of routine use of the automated non-isotopic Stratus Folate assay for clinical purposes. Moreover, with the latter assay the laboratory staff could choose the more convenient haemolysis procedure.
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Eritrocitos/metabolismo , Ácido Fólico/sangre , Automatización , Ácido Edético , Ayuno/sangre , Fluorometría/métodos , Hemólisis , Humanos , Radioinmunoensayo/métodosRESUMEN
BACKGROUND: Oxidative stress is present in cardiovascular diseases (CVDs), and hyperhomocysteinemia, an independent risk factor for these diseases, may play a role by inducing production of oxygen free radicals. METHODS: To evaluate the possible role of homocysteine (Hcy) in inducing oxidative stress in coronary artery disease (CAD), plasma Hcy was measured in 68 consecutive cardiovascular patients, and plasma malondialdehyde (MDA), both free and total (free + bound), was measured in 40 patients with CAD (18 with chronic stable angina and 22 with unstable angina). As controls, we tested 70 healthy volunteers. Hcy was measured by an immunoenzymatic method and MDA, an index of lipid peroxidation, by gas chromatography-mass spectrometry. RESULTS: Plasma Hcy concentrations were significantly higher in cardiovascular patients than in controls (10.2 vs 8.9 micromol/L; P <0.0002), with no significant difference between values in the stable and unstable angina subgroups. Similarly, total MDA was significantly higher in the CAD group than in the controls (2.6 vs 1.3 micromol/L; P <0.00001), again with no significant difference between stable and unstable angina patients. By contrast, free MDA, which was significantly higher in the CAD patients than the controls (0.4 vs 0.2 micromol/L; P < 0.00001), was also significantly higher in the unstable than in the stable angina group (0.5 vs 0.3 micromol/L; P <0.03). However, no correlation was observed among Hcy and free and total MDA. CONCLUSIONS: Our findings show that a moderate increase of Hcy is associated with CVD but that Hcy at the detected values cannot be considered completely responsible for oxidative damage. That lipid peroxidation is involved in CAD is shown by our observation of significantly increased plasma free and total MDA concentrations compared with controls. Moreover, free MDA values discriminated between unstable and chronic stable angina, and could thus represent a new diagnostic tool.