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AIM: Urea, the main product of protein catabolism, is a biochemical marker of renal function. Though it is known that serum urea impairs vascular health, the relationship between its concentration and vascular reactivity in vivo has not been explored. Our study was undertaken to investigate possible association between serum urea and endothelial function in subjects without chronic kidney disease (CKD). METHODS: Eighty free-living subjects with serum creatinine ≤1 mg/dL and without CKD were enrolled for the present study. Serum analyses and evaluation of endothelial function were performed in all subjects. Endothelial function was measured using the flow-mediated dilation (FMD) technique. Simple and multiple regression analyses were used to test the association between FMD and considered variables. RESULTS: In correlation analyses FMD was found directly associated with HDL cholesterol (r=0.21; P=0.05) and eGFR (r=0.25; P=0.02) and inversely associated with age (r=-0.26; P=0.02), serum urea (r=-0.37; P<0.01), serum creatinine (r=-0.31; P<0.01) and brachial artery baseline diameter (r=-0.41; P<0.01). In multiple regression analysis only baseline artery diameter and serum urea predicted FMD; age, gender and cardiovascular risk factors did not relate with FMD. CONCLUSION: Our study demonstrates the association between serum urea and FMD, suggesting that the accumulation of waste products of protein metabolism may impair vascular health in subjects without CKD.
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Arteria Braquial/fisiopatología , HDL-Colesterol/sangre , Creatinina/sangre , Urea/sangre , Vasodilatación/fisiología , Adulto , Anciano , Biomarcadores , Estudios Transversales , Endotelio Vascular/fisiopatología , Femenino , Tasa de Filtración Glomerular , Humanos , Fallo Renal Crónico/fisiopatología , Masculino , Persona de Mediana Edad , Análisis de Regresión , Factores de RiesgoRESUMEN
AIM: The aim of this paper was to evaluate the safety and cost-effectiveness of "2-octyl-cyanoacrylate" as skin adhesive in congenital heart surgery. METHODS: From April 2010 to December 2011, we collected data from 300 patients who underwent cardiac surgery for congenital heart disease. We divided our population into 3 groups: group-1 (N.=100):"2-octyl-cyanoacrylate" has been used to replace the intra-dermal suture line; group-2 (N.=100):"2-octyl-cyanoacrylate" has been utilized as a barrier ("add-on measure") in addition to the intra-dermal suture line, group-3 (N.=100) with a standard intra-dermal suture line. RESULTS: Median age of patients was 1.36 years. One-hundred and thirty-nine patients were younger than 12 months and 56 older than 16 years. There were 11 wound dehiscence (3.6%) (2 in group-1 and 9 in group-3, P=0.001) and 1 superficial wound infection (group-1). Six patients (2%) required surgical wound revision (2 in group-1 and 4 in group-3, P=NS). Wound complication was significantly associated to delayed sternal closure (3/12 patients, 25% versus 13/288 patients, 4.5%) (P=0.04). Median cost (intra-/postoperative) for wound treatment was lower in group-1 and 2 (19±5.5 and 23.9±7.4 respectively) when compared to Group-3 (26.7±3.2) (P<0.0001). CONCLUSION: The use of "2-octyl-cyanoacrylate" proved to be safe and effective; the "add-on measure" strategy provided the best cost-effective solution.
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Procedimientos Quirúrgicos Cardíacos/métodos , Cianoacrilatos/administración & dosificación , Cardiopatías Congénitas/cirugía , Adhesivos Tisulares/administración & dosificación , Adolescente , Adulto , Anciano , Niño , Preescolar , Análisis Costo-Beneficio , Cianoacrilatos/efectos adversos , Cianoacrilatos/economía , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Dehiscencia de la Herida Operatoria/epidemiología , Adhesivos Tisulares/efectos adversos , Adhesivos Tisulares/economía , Adulto JovenRESUMEN
AIM: Several investigations report an inverse association between periodontal disease and endothelial function measured by brachial artery Flow-Mediated-Dilatation (FMD) technique. These studies examined endothelial function by using the traditional approach to FMD calculation, that is from diameters assessed at 60 seconds after deflation. Nevertheless, possible relationship between gingival inflammation and endothelial dysfunction observed over this temporal threshold remains still unexplored. The purpose of our study was to explore the relationship between gingival inflammation and endothelial function, by considering the time course of brachial FMD. METHODS: Forty-six free-living white subjects, participating in a cardiovascular disease prevention campaign, were enrolled. FMD was measured at 60s and at 2 and 3 min after forearm ischemia. Maximal FMD was calculated (Peak FMD), for each patient. Gingival Index (GI) was evaluated as measure of gingival inflammation. RESULTS: In univariate analyses, GI was associated with both FMD at 60 sec (r=-0.30, P=0.038) and Peak FMD (r=-0.41, P=0.004). In multiple regression analyses including GI, age, gender, and known risk factors for atherosclerosis, only GI and age were independently and inversely associated with Peak FMD and FMD at 60 s, but this association was stronger with Peak FMD. Moreover, when we divided subjects on the basis of GI value, patients with GI > 1 presented lower Peak FMD and higher prevalence of absent FMD. CONCLUSION: The present study extends previous observations about the negative effects of periodontal disease on endothelial function, highlighting the importance of the evaluation of time course of vascular reactivity.
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Arteria Braquial , Endotelio Vascular/fisiopatología , Gingivitis/fisiopatología , Vasodilatación , Anciano , Arteria Braquial/diagnóstico por imagen , Arteria Braquial/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadística como Asunto , Factores de Tiempo , UltrasonografíaRESUMEN
AIM: The aim of this study was to evaluate the efficacy and cost-effectiveness of fibrinogen/thrombin-coated collagen patch (FTCCP)(TachoSil®) during intraoperative hemostasis in patients with congenital heart disease, who required a reoperation during childhood. METHODS: We reviewed data on the intraoperative blood product requirements and hospital costs of children (age <16 years) who underwent a reoperation for treating their congenital heart disease between January 2009 and December 2011. RESULTS: One-hundred and seventeen patients were included. Median age at surgery was 2.1 years (range 3 days-14.1 years). Main causes of intraoperative bleeding were: 1) reinforcement of suture lines (106 patients, 90.6%); 2) lung lesions (5 patients, 4.2%); 3) epicardial lesions (3 patients, 2.6%); and 4) chest wall lesions (3 patients, 2.6%). At logistic regression the amount of packed red blood cells (PRBC) requirement was significantly higher in patients with preoperative cyanosis (P=0.008, OR=3.85) and in patients who required the use of cardiopulmonary bypass (P=0.005, OR=21.19). The use of FTCCP (N.=90 patients) as first line treatment was significantly associated with a lower PRBC requirement (P=0.0003, OR=0.1) which in addition to the avoidance of other hemostatic/sealant agents, leads to lower hospital cost. CONCLUSION: FTCCP is an effective hemostatic agent which can be safely used during the hemostasis of children requiring reoperations for their congenital heart malformations. When used as first line treatment, with specific indications, FTCCP limited the intraoperative PRBC requirement and the use of other hemostatic/sealant agents thus reducing hospital costs.
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Pérdida de Sangre Quirúrgica/prevención & control , Procedimientos Quirúrgicos Cardíacos , Fibrinógeno/uso terapéutico , Cardiopatías Congénitas/cirugía , Hemostasis Quirúrgica/métodos , Hemostáticos/uso terapéutico , Trombina/uso terapéutico , Adolescente , Factores de Edad , Procedimientos Quirúrgicos Cardíacos/efectos adversos , Procedimientos Quirúrgicos Cardíacos/economía , Niño , Preescolar , Ahorro de Costo , Análisis Costo-Beneficio , Combinación de Medicamentos , Costos de los Medicamentos , Transfusión de Eritrocitos , Femenino , Fibrinógeno/efectos adversos , Fibrinógeno/economía , Cardiopatías Congénitas/economía , Hemostasis Quirúrgica/efectos adversos , Hemostasis Quirúrgica/economía , Hemostáticos/efectos adversos , Hemostáticos/economía , Humanos , Lactante , Recién Nacido , Italia , Modelos Logísticos , Masculino , Oportunidad Relativa , Transfusión de Plaquetas , Reoperación , Estudios Retrospectivos , Factores de Riesgo , Trombina/efectos adversos , Trombina/economía , Factores de Tiempo , Resultado del TratamientoRESUMEN
AIMS: The present investigation was designed to test the association between carotid atherosclerosis and two simple markers of insulin resistance, i.e. HOMA-Index and TyG-Index. MATERIALS AND METHODS: The study was performed in two different cohorts. In the first cohort, 330 individuals were enrolled. Blood pressure, lipids, glucose, waist and cigarette smoking were evaluated. HOMA-IR and TyG-Index were calculated as markers of prevalent hepatic and muscular insulin resistance respectively. Carotid atherosclerosis was assessed by Doppler ultrasonography. The association between cardiovascular risk factors, markers of insulin resistance and carotid atherosclerosis was assessed by multiple logistic regression analyses. In the second cohort, limited to the evaluation of TyG-Index, 1432 subjects were studied. RESULTS: In the first cohort, TyG-Index was significantly associated with carotid atherosclerosis in a model including age, sex, diabetes, cigarette smoking and LDL cholesterol, while HOMA-IR was not. When components of metabolic syndrome were added to the model as dichotomous variables (absent/present), TyG-Index retained its predictive power. The same result was obtained when the metabolic syndrome was added to the model (absence/presence). The association between TyG-Index and carotid atherosclerosis was confirmed in the second cohort. CONCLUSIONS: The present findings suggest that TyG-Index is better associated with carotid atherosclerosis than HOMA-IR.
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Glucemia/metabolismo , Enfermedades de las Arterias Carótidas/diagnóstico , Resistencia a la Insulina/fisiología , Triglicéridos/metabolismo , Biomarcadores/metabolismo , Enfermedades Cardiovasculares/etiología , Enfermedades de las Arterias Carótidas/fisiopatología , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Estudios de Cohortes , Femenino , Homeostasis/fisiología , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Fumar/metabolismoRESUMEN
OBJECTIVE: Alterations of blood and plasma viscosity can promote atherosclerosis. The relationship between viscosity and aging is still controversial. The present study evaluated the influence of aging on blood and plasma viscosity in a group of subjects followed for 11.6 years. METHODS: Forty-five subjects have been evaluated twice 11.6 years apart for hemorheological parameters and coronary heart disease (CHD) risk factors. Plasma viscosity and blood viscosity have been measured with a cone-plate viscometer. Tk has been calculated as index of red blood cell rigidity. CHD risk factors, i.e. obesity, hypertension, hyperlipidemia and diabetes, have been evaluated by routine methods. RESULTS: Hematocrit and plasma viscosity did not change during the study, whereas blood viscosity (shear rate 225/sec: 4.46 ± 0.49 vs. 4.81 ± 0.54 cP, p < 0.0001; shear rate 45/sec: 6.19 ± 0.67 vs. 6.65 ± 0.79 cP, p < 0.0001) and Tk (0.80 ± 0.05 vs. 0.83 ± 0.06, p < 0.005) significantly increased. The percent variation in blood viscosity was not associated with the percent variation in any of the CHD risk factors. Furthermore, the increase in blood viscosity was similar in males and females and in subjects with CHD risk profile worsening or not. CONCLUSION: The present findings demonstrate that blood viscosity increases with age. This increase seems independent of classical CHD risk factors and is disjoined from haematocrit and plasma viscosity, suggesting a possible direct effect of aging on red blood cells.
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Envejecimiento , Viscosidad Sanguínea , Enfermedad Coronaria/etiología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Hematócrito , Humanos , Masculino , Persona de Mediana Edad , Factores de RiesgoRESUMEN
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
The aim of our study was to evaluate the effect of the intravenous contrast media iomeprol on wall shear stress, blood flow and vascular parameters in the common carotid and brachial artery. Thirty outpatients undergoing thoracic or abdominal spiral CT scans were studied. The internal diameter and flow velocity of the common carotid and brachial artery were evaluated by ultrasound, and blood viscosity was measured before and after low osmolality iomeprol (Iomeron 350) injection. The wall shear stress, blood flow and pulsatility index were calculated. To test the differences between groups, the Wilcoxon rank test and Mann Whitney U test were applied. Blood viscosity decreased slightly, but significantly after contrast media (4.6+/-0.7 vs. 4.5+/-0.7 mPa.s, P = 0.02). Contrarily, blood flow and wall shear stress did not change in the common carotid artery, but significantly decreased in the brachial artery (0.9+/-0.4 vs. 0.6+/-0.3 ml/s, P < 0.0001, and 41.5+/-13.9 vs. 35.3+/-11.0 dynes/cm2, P < 0.002, respectively), whereas the pulsatility index significantly increased in the brachial artery (5.0+/-3.3 vs. 7.5+/-5.3, P < 0.001). Iomeprol injection causes blood flow and wall shear stress reduction of the brachial artery; the rise in the pulsatility index suggests an increase in peripheral vascular resistance. Further investigation is needed to evaluate whether these modifications can be clinically relevant.
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Velocidad del Flujo Sanguíneo/efectos de los fármacos , Arteria Braquial/efectos de los fármacos , Arteria Carótida Común/efectos de los fármacos , Medios de Contraste/farmacología , Yopamidol/análogos & derivados , Resistencia Vascular/efectos de los fármacos , Adulto , Viscosidad Sanguínea/efectos de los fármacos , Femenino , Humanos , Yopamidol/farmacología , Masculino , Persona de Mediana Edad , Flujo Pulsátil/efectos de los fármacos , Estadísticas no Paramétricas , Tomografía Computarizada por Rayos XRESUMEN
INTRODUCTION: Hyperhomocysteinemia is one of the causes of the increased incidence of cardiovascular disease in uremia. Since homocysteine (Hcy) metabolism depends on the availability of folate and vitamin B12, we have measured the effects of chronic i.v. supplementation of folinic acid and vitamin B12 in a group of patients on maintenance hemodialysis. METHODS: We compared the blood concentration of total Hcy (tHcy), vitamin B12 and folate and the intraerythrocyte concentration of folate in a group of 27 hemodialysis patients (Treated group), given an i.v supplementation with folinic acid (0.9 mg) and Vitamin B12 (cyanocobalamine 1.5 mg and hydroxycobalamine 1.5 mg) three times per week at the end of each dialysis session with those measured in a similar group of 28 hemodialysis patients without supplementation (No Treatment group). The patients were also characterized for the thermolabile variant (mutation C667-->T) of the enzyme methylene-tetrahydrofolate reductase (tMTHFR). RESULTS: High plasma levels (< 11.7 micromol/L) of tHcy were observed in 54/55 patients. T patients had Hcy values significantly lower than NT ones (31.7+/-3.6 vs. 1.1+/-8.3micromol/L, p < 0.05). Serum vitamin B12 (1200 73.6 vs. 762+/-72.2 pmol/L, p < 0.001) and intraerythrocyte folate levels were also significantly higher in the T group (2176+/-127 vs. 1511+/-156, p < 0.005), while no significant difference was observed for serum folate. The distribution of tMTHFR genotypes was similar in the two groups. Homozygous patients showed higher levels of Hcy in comparison with wild type patients both in the whole population (62.32+/-15.9 vs.30.43+/-3.2, p < 0.05) and in the NT group (87.8+/-25.3 vs.36.8+/-13.1., p < 0.05), while no significant difference was observed among genotypes in the T group. CONCLUSIONS: Uremic patients on hemodialysis, when supplemented with even low i.v. dose of folinic acid and vitamin B12, show significantly lower plasma levels of tHcy than non-supplemented patients.
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Homocisteína/sangre , Leucovorina/administración & dosificación , Diálisis Renal , Vitamina B 12/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Inyecciones Intravenosas , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVES: We have previously demonstrated that vitamin B12 (cobalamin)-deficient central neuropathy in the rat is associated with local overexpression of neurotoxic tumour necrosis factor (TNF)-alpha combined with locally decreased synthesis of neurotrophic epidermal growth factor (EGF). The aims of this study were to investigate whether a similar imbalance also occurs in the serum of adult patients with clinically confirmed cobalamin deficiency and whether it can be corrected by vitamin B12 replacement therapy. PATIENTS AND METHODS: We studied 34 adult patients with severe cobalamin deficiency, 12 patients with pure iron deficiency anaemia and 34 control subjects. Haematological markers of cobalamin deficiency and serum TNF-alpha and EGF levels were measured using commercial kits. Thirteen cobalamin-deficient patients were re-evaluated after 3 and 6 months of parenteral vitamin B12 treatment. RESULTS: TNF-alpha was significantly higher (p < 0.01) and EGF significantly lower (p < 0.01) in the patients with cobalamin deficiency, but both were unchanged in patients with pure iron deficiency anaemia. In cobalamin-deficient patients the serum TNF-alpha levels correlated significantly with plasma total homocysteine levels (r = 0.425; p < 0.02). In the treated patients TNF-alpha and EGF levels normalised concomitantly with clinical and haematological disease remission. CONCLUSIONS: In humans, as in rats, cobalamin concentration appears to be correlated with the synthesis and release of TNF-alpha and EGF in a reciprocal manner, because cobalamin deficiency is accompanied by overproduction of TNF-alpha and underproduction of EGF.
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Factor de Crecimiento Epidérmico/sangre , Factor de Necrosis Tumoral alfa/análisis , Deficiencia de Vitamina B 12/sangre , Adulto , Anciano , Anciano de 80 o más Años , Anemia Hipocrómica/clasificación , Anemia Megaloblástica/sangre , Anemia Megaloblástica/etiología , Animales , Médula Ósea/patología , Factor de Crecimiento Epidérmico/deficiencia , Femenino , Ácido Fólico/sangre , Estudios de Seguimiento , Gastritis Atrófica/sangre , Gastritis Atrófica/etiología , Homocisteína/sangre , Humanos , Hierro/sangre , Deficiencias de Hierro , Masculino , Persona de Mediana Edad , Enfermedades del Sistema Nervioso Periférico/etiología , Ratas , Especificidad de la Especie , Vitamina B 12/uso terapéutico , Deficiencia de Vitamina B 12/complicaciones , Deficiencia de Vitamina B 12/tratamiento farmacológicoRESUMEN
The possible role of folate supplementation in reducing hyperhomocysteinemia in dialysis patients has been reported in several recent papers. However, scant data are available for peritoneal dialysis patients; besides, none of these studies investigated either the role of intraerythrocyte folate concentration or the presence of side effects caused by folate administration. Sixty-six peritoneal dialysis patients with hyperhomocysteinemia (>15 micromol/l) and normal folate status (as assessed by erythrocyte folate level >600 nmol/l) were randomly allocated to receive either oral folate (5 mg/day) or no vitamin supplementation. After 2 months of therapy, patients were requested to answer a questionnaire investigating the occurrence of symptoms possibly related to folate supplementation. Twenty-nine treated patients and 30 untreated controls completed the study. In the treated patients, serum and erythrocyte folate increased significantly (p < 0.0001) (respectively from 10.6 +/- 4.9 to 237 +/- 231 nmol/l and from 1,201 +/- 297 to 2,881 +/- 294 nmol/l) to levels at the uppermost limit of detection by laboratory methods. Serum vitamin B(12) levels did not change. Plasma homocysteine levels decreased from 54 +/- 32 to 23 +/- 14 micromol/l after folate supplementation and remained unchanged in the control group. After 4 months of folate therapy, homocysteine concentration was within the normal range in 5 patients (17%) and below 30 micromol/l in the other 21 (72%). Folate therapy resulted in a decrease in homocysteine of more than 50% in 45% of the patients and decrease of more than 20% in a further 38%. No significant symptoms were reported. Thus, serum and erythrocyte folate increase confirms that normal folate levels are inadequate in dialysis patients, even if serum and erythrocyte levels before folate supplementation cannot predict the effect on homocysteine plasma levels.
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Ácido Fólico/uso terapéutico , Homocisteína/sangre , Enfermedades Renales/terapia , Diálisis Peritoneal/métodos , Anorexia/inducido químicamente , Depresión/inducido químicamente , Regulación hacia Abajo , Eritrocitos/metabolismo , Femenino , Ácido Fólico/efectos adversos , Ácido Fólico/sangre , Humanos , Enfermedades Renales/sangre , Masculino , Persona de Mediana Edad , Trastornos del Inicio y del Mantenimiento del Sueño/inducido químicamente , Vitamina B 12/sangreRESUMEN
BACKGROUND: Hyperhomocysteinaemia is an independent cardiovascular risk factor which can induce vascular lesions, thus contributing to the early development of atherosclerosis. Low-dose folic acid supplementation reduces the pretreatment homocysteine plasma levels by 25-35%. Recent studies report that higher intravenous or oral administration of the active form of folic acid reduces the homocysteine plasma concentration by nearly 70%. The reduction could also be influenced by the thermolabile variant of methylenetetrahydrofolate reductase (tMTHFR) and by the dialysis modality. METHODS: A cross-sectional clinical study was performed to evaluate the effect of a drug containing folinic acid and vitamin B(12) on the plasma homocysteine concentration and whether this variable could also be influenced by the presence of a genetic variant of the methionine pathway and the use of different dialysis modalities. The plasma homocysteine concentration was measured in 55 patients undergoing haemodialysis, 27 of whom have been treated intravenously for megaloblastic anaemia using a drug containing low concentrations of folinic acid and vitamin B(12) at the end of each dialysis session for 6 months. The presence of tMTHFR was sought by molecular analysis, and the role of the dialysis modality was also investigated. RESULTS: The patients given the folic acid treatment had lower homocysteine plasma levels than those not so treated. The plasma homocysteine concentration was significantly higher in the tMRHFR homozygotes than in the patients with a normal genotype, significantly lower in the treated than in the untreated homozygotes, and significantly higher in the untreated homozygotes than in the untreated subgroup with a normal genotype. The homocysteine level was also significantly lower in the patients who underwent convective haemodialysis than in those who received standard bicarbonate dialysis. CONCLUSIONS: A drug containing low concentrations of folinic acid combined with vitamin B(12) using an intermittent intravenous regimen is effective in reducing the homocysteine plasma concentration in uraemic patients. The homocysteine levels seem also to depend on genotype and dialysis modality.
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Homocisteína/sangre , Leucovorina/uso terapéutico , Diálisis Renal , Uremia/terapia , Vitamina B 12/uso terapéutico , Anemia Megaloblástica/tratamiento farmacológico , Estudios Transversales , Femenino , Humanos , Leucovorina/administración & dosificación , Masculino , Metilenotetrahidrofolato Deshidrogenasa (NADP)/metabolismo , Persona de Mediana Edad , Uremia/sangre , Vitamina B 12/administración & dosificaciónRESUMEN
Plasma homocysteine (tHcy) is an important risk factor for atherosclerosis in dialysis patients. Few data were reported on the prevalence and severity of hyperhomocysteinemia in peritoneal dialysis (PD) patients. In addition, little attention was paid to the search of factors possibly involved in the pathogenesis of hyperhomocysteinemia in these patients. A cross-sectional study was performed in 107 stable PD patients. None of them was given folate or vitamin B12 supplementation before or during the study. Plasma tHcy, serum vitamin B12, serum and erythrocyte folate were measured by immunoenzymatic methods. Genetic analysis of the methylentetrahydrofolate-reductase thermolabile mutation (tMTHFR) was performed in 61 patients. 97% of patients had tHcy levels higher than normal. tHcy was not different between men and women, patients with or without malnutrition, with or without clinically evident atherosclerotic vasculopathy, with or without anemia. tHcy levels were significantly higher in homozygotes for the tMTHFR mutation than in patients carrying the wild type form. Significant univariate correlation was found between hyperhomocysteinemia and time since the start of dialysis, serum and erythrocyte folate and vitamin B12. The best fitted model equation was log tHcy = 108.53 + 0.1606 (duration of dialysis) -1.1053 (s-F) -0.7980 (age) 0.0215 (vitamin B12). Our results agree with those reported by other authors in hemodialysis patients. Despite the large number of PD patients with normal serum vitamin B12 and folate status, the relation between tHcy and vitamin B12 or folate suggests that the supplementation of these vitamins could be useful irrespective of their serum levels, especially in younger patients or in those treated for a long period of time with peritoneal dialysis.
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Eritrocitos/química , Ácido Fólico/sangre , Homocisteína/sangre , Diálisis Peritoneal , Vitamina B 12/sangre , Anciano , Estudios Transversales , Femenino , Homocigoto , Humanos , Hiperhomocisteinemia/diagnóstico , Hiperhomocisteinemia/etiología , Hiperhomocisteinemia/genética , Masculino , Metilenotetrahidrofolato Reductasa (NADPH2) , Persona de Mediana Edad , Mutación , Oxidorreductasas actuantes sobre Donantes de Grupo CH-NH/genética , Diálisis Peritoneal/efectos adversosRESUMEN
Wall shear stress contributes to the endothelial production of vasoactive mediators, like nitric oxide (NO). Brachial artery vasodilation that follows increased blood flow is regulated by NO release. Aim of the present study was to investigate whether resting wall shear stress of the brachial artery is related to flow-mediated vasodilation (FMD) induced by forearm ischemia. Wall shear stress was calculated according to the following formula: Wall shear stress=Blood viscosity x Blood velocity/Internal diameter. FMD was calculated as percentage change of brachial artery diameter following forearm ischemia. Twenty-seven healthy male subjects were investigated. Peak wall shear stress and FMD were 37.3+/-12.8 dynes/cm(2) and 110.7+/-5.6%, respectively (mean+/-S.D.). In simple regression analyses, age was inversely associated with wall shear stress (r=48, P<0.01) and, marginally, with FMD (r=0.33, P=0.08). Wall shear stress and FMD were directly related (r=0.60, P<0.001). In multiple regression analysis, including wall shear stress, age, blood pressure, lipids, glucose and Body Mass Index as independent variables, wall shear stress was the only variable independently associated with FMD (standardized beta coefficient=0.690, P=0.005). To avoid the influence of brachial artery size on FMD, the regression analysis was restricted to subjects with similar diameter (n=12). In these subjects wall shear stress continued to be significantly associated with FMD (r=0.69, P=0.01). Our results demonstrate a strong association between resting wall shear stress and FMD in the brachial artery in healthy men in vivo. This association is independent of age and vessel diameter.
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Arteria Braquial/fisiología , Vasodilatación/fisiología , Adulto , Anciano , Viscosidad Sanguínea/fisiología , Arteria Braquial/fisiopatología , Antebrazo/irrigación sanguínea , Humanos , Isquemia/fisiopatología , Masculino , Persona de Mediana Edad , Valores de Referencia , Flujo Sanguíneo Regional/fisiología , Estrés MecánicoRESUMEN
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.
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Angina de Pecho/metabolismo , Homocisteína/sangre , Estrés Oxidativo , Angina de Pecho/sangre , Angina de Pecho/diagnóstico , Angina Inestable/sangre , Angina Inestable/metabolismo , Enfermedad Crónica , Femenino , Cromatografía de Gases y Espectrometría de Masas , Humanos , Hiperhomocisteinemia/sangre , Hiperhomocisteinemia/diagnóstico , Técnicas para Inmunoenzimas , Masculino , Malondialdehído/sangre , Persona de Mediana EdadRESUMEN
BACKGROUND: Plasma homocysteine (Hcy) is an independent risk factor for cardiovascular disease. High levels of plasma Hcy have been observed in end-stage renal disease patients. Few studies have compared peritoneal dialysis (PD) and hemodialysis (HD) patients and few data are available on erythrocyte folate (ery-F) levels in dialysis patients. OBJECTIVES: To evaluate plasma Hcy concentrations, vitamin B12 (B12), and folate status in dialysis patients; to analyze the possible causes of high Hcy levels; to follow up changes in folate and B12 concentrations after 6 months. DESIGN: A cross-sectional observational study. SETTING: Nephrology division and laboratory of hematology in a university and clinical research hospital. PATIENTS: The study included 82 patients treated with PD for 37 + 37 months and 70 patients treated with HD for 136 + 95 months. LABORATORY METHODS: Plasma Hcy was measured by the immunoenzymatic IMx Hcy FPIA method (Abbott Laboratories, Diagnostic Division, Abbott Park, IL, U.S.A.), serum folate (s-F) and ery-F by the Stratus folate fluorometric enzyme-linked assay, and B12 by the Stratus vitamin B12 fluorometric enzyme-linked assay (DADE-Behring, Newark, DE, U.S.A.). RESULTS: Ninety-six percent of PD and 97% of HD patients had Hcy levels above the cutoff (13.5 micromol/L). Homocysteine level was higher in HD than in PD patients, while the prevalence of hyperhomocysteinemia was similar with the two techniques. Erythrocyte folate was significantly higher in PD (1333 +/- 519 pmol/L) than in HD (1049 +/-511 pmol/L, p < 0.01). Statistically significant correlations were observed between Hcy and B12, s-F, ery-F, and dialysis duration. Multivariate analysis showed a strong correlation between s-F and Hcy. After 6 months there were no differences in Hcy, B12, s-F, and ery-F levels. CONCLUSIONS: Plasma Hcy levels were high in more than 95% of our dialysis patients, with no relation to the type of dialysis. Vitamin B12 and folate were normal in the majority of our patients. However, serum folate was the major determinant of Hcy levels. Such a relation between Hcy and folate suggests that levels of folate within the reference interval are inadequate for dialysis patients.
Asunto(s)
Eritrocitos/química , Ácido Fólico/análisis , Homocisteína/sangre , Diálisis Peritoneal/efectos adversos , Diálisis Renal/efectos adversos , Vitamina B 12/sangre , Estudios Transversales , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Factores de TiempoRESUMEN
The localization of atherosclerotic lesions is influenced by hemodynamic factors, namely, shear stress and tensive forces. The present study investigated the relationships between shear stress and circumferential wall tension and between these hemodynamic factors and the intima-media thickness (IMT) of the common carotid artery in healthy men. Fifty-eight subjects were studied. Shear stress was calculated as blood viscosityxblood velocity/internal diameter. Circumferential wall tension was calculated as blood pressurexinternal radius. Blood velocity, internal diameter, and IMT were measured by high-resolution echo-Doppler. Mean shear stress was 12.6+/-3.3 dynes/cm(2) (mean+/-SD; range, 4.8 to 20.4) and was inversely related with age, blood pressure, and body mass index (BMI). Mean circumferential wall tension was 3.4+/-0.6x10(4) dynes/cm (range 2.4 to 5.6) and was directly associated with age and BMI. IMT was inversely associated with shear stress (r=0.55, P<0. 0001) and directly associated with circumferential wall tension (r=0. 43, P<0.0001). Shear stress and circumferential wall tension were inversely correlated (r=0.66, P<0.0001). In multiple regression analysis, shear stress and (marginally) cholesterol were independently associated with IMT, whereas circumferential wall tension, age, and BMI were not. These findings confirm that common carotid shear stress varies among healthy individuals and decreases as age, blood pressure, and BMI increase. Our findings also demonstrate that circumferential wall tension is directly associated with wall thickness, age, and BMI and that shear stress is associated with common carotid IMT independent of other hemodynamic, clinical, or biochemical factors.