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J A Rodríguez

Publications and source records attributed to J A Rodríguez.

At least 19 recordsLinked to original sources
PubMed2006

A density functional theory study of the dissociation of H2 on gold clusters: importance of fluxionality and ensemble effects.

Density functional theory was employed to calculate the adsorption/dissociation of H2 on gold surfaces, Au(111) and Au(100), and on gold particles from 0.7 (Au14) to 1.2 nm (Au29). Flat surfaces of the bulk metal were not active towards H2, but a different effect was observed in gold nanoclusters, where the hydrogen was adsorbed through a dissociative pathway. Several parameters such as the coordination of the Au atoms, ensemble effects and fluxionality of the particle were analyzed to explain the observed activity. The effect of the employed functional was also studied. The flexibility of the structure, i.e., its adaptability towards the adsorbate, plays a key role in the bonding and dissociation of H2. The interaction with hydrogen leads to drastic changes in the structure of the Au nanoparticles. Furthermore, it appears that not only low coordinated Au atoms are needed because H2 adsorption/dissociation was only observed when a cooperation between several (4) active Au atoms was allowed.

Journal Article↗
PubMed2006

Independent association of matrix metalloproteinase-10, cardiovascular risk factors and subclinical atherosclerosis.

OBJECTIVES: Circulating levels of matrix metalloproteinase (MMP)-10 are related to inflammation in asymptomatic subjects with cardiovascular risk factors. Whether MMP-10 is associated with the severity of atherosclerosis remains to be determined. This study examines the relationship of systemic MMP-10 levels with atherosclerotic risk factors and subclinical atherosclerosis. METHODS AND RESULTS: Circulating levels of MMP-1, -9 and -10, and markers of inflammation [fibrinogen, interleukin-6, von Willebrand factor, and high-sensitivity C-reactive protein (hs-CRP)] were measured in 400 subjects (mean age 54.3 years, 77.7% men) with cardiovascular risk factors but free from clinical cardiovascular disease. Subclinical atherosclerosis was evaluated by both the mean carotid intima-media thickness (IMT) and the presence of atherosclerotic plaques with the use of B-mode ultrasound in all subjects. MMP-10 levels were positively correlated with fibrinogen (r = 0.24, P < 0.001), hs-CRP (r = 0.14, P < 0.01) and carotid IMT (r = 0.17, P < 0.01). The association between MMP-10 and IMT remained significant in multiple regression analysis (P < 0.02) when controlling for traditional atherosclerotic risk factors and inflammatory markers. Such an association was not observed for MMP-1 and -9. Subjects in the highest MMP-10 tertile had significantly higher carotid IMT (adjusted odds ratio 6.3, 95% confidence interval 1.3-31.4, P = 0.024). In addition, MMP-10 levels were significantly higher in patients with carotid plaques (n = 78) than in those with no plaques after adjusting for age and sex (P < 0.01). CONCLUSION: Higher serum MMP-10 levels were associated with inflammatory markers, increased carotid IMT and atherosclerotic plaques in asymptomatic subjects. Circulating MMP-10 may be useful to identify subclinical atherosclerosis in subjects free from cardiovascular disease.

C-Reactive Protein↗
PubMed2006

High-performance liquid magneto-chromatography.

High-performance liquid magneto-chromatography (HPLMC) is a new chromatography technique with two distinctive features: (a) a high surface area stationary phase with paramagnetic properties composed of magnetite embedded in a silica gel, and (b) a magnetic field (variable intensity 0-5.5 mT) that selectively retains paramagnetic substances in the stationary phase depending on their magnetic susceptibility. The system can also be used to separate diamagnetic compounds such as biologically active organic molecules, but these first need to be complexed with Fe and Cu compounds to render them paramagnetic. Herein, we describe the experimental setup and the relationship between the retention factor and the magnetic field intensity, i.e., the force interaction of the complexes in relation to the magnetized magnetite. The expression derived also provides the effective magnetic susceptibility (Deltachi) of the components separated.

Amino Acids↗
PubMed2006

Renewable stationary phase liquid magnetochromatography: determining aspartame and its hydrolysis products in diet soft drinks.

A new chromatographic modality that does not require high pressures and also allows renewal of the stationary phase as desired is reported. The technique is based on a thin layer paramagnetic stationary phase (Fe3O4-SiO2) retained on the inner wall of a minicolumn through the action of an external magnetic field, which also plays an important role in separating the analytes. Accordingly, the name "renewable stationary phase liquid magnetochromatography", or RSP-LMC, has been proposed for it. The technique was used to separate and quantify the sugar substitute alpha-aspartame and its constituent amino acids (hydrolysis products), L-aspartic acid and L-phenylalanine, in diet fizzy soft drinks. When the results obtained for alpha-aspartame were compared with those obtained using HPLC as a reference method, no significant differences were observed. The system proposed is fully automated, making it an economic, competitive alternative to conventional methods of determining alpha-aspartame and its amino acid components.

Journal Article↗
PubMed2006

The 4G/5G PAI-1 polymorphism influences the endothelial response to IL-1 and the modulatory effect of pravastatin.

BACKGROUND: Increased plasminogen activator inhibitor (PAI-1) levels lead to impaired fibrinolytic function associated with higher cardiovascular risk. PAI-1 expression may be regulated by different inflammatory cytokines such as interleukin-1alpha (IL-1). Several polymorphisms have been described in the PAI-1 gene. AIM: We examined the influence of the 4G/5G polymorphism in the promoter region on IL-1alpha-induced PAI-1 expression by human umbilical vein endothelial cells (HUVEC) in presence or absence of pravastatin. METHODS AND RESULTS: Genotyped HUVEC were incubated with IL-1alpha (500 U mL(-1)) in presence or absence of pravastatin (1-10 microm). PAI-1 expression was analyzed by real time polymerase chain reaction (PCR), and PAI-1 antigen measured in supernatants by ELISA. IL-1alpha increased PAI-1 secretion in a genotype-dependent manner, and higher values were observed for 4G/4G compared with both 4G/5G and 5G/5G cultures (P < 0.05). Preincubation of HUVEC with 10 microm pravastatin significantly reduced IL-1-induced PAI-1 expression in 4G/4G HUVEC compared with untreated cultures (177.5% +/- 24.5% vs. 257.9% +/- 39.0%, P < 0.05). Pravastatin also attenuated the amount of secreted PAI-1 by 4G/4G HUVEC after IL-1 stimulation (5020.6 +/- 165.7 ng mL(-1) vs. 4261.1 +/- 309.8 ng mL(-1), P < 0.05). This effect was prevented by coincubation with mevalonate, indicating a dependence on HMG-CoA reductase inhibition. CONCLUSIONS: The endothelial 4G/5G PAI-1 genotype influences the PAI-1 response to IL-1alpha and the modulatory effect of pravastatin. As increased PAI-1 levels have been linked to cardiovascular disease the observed endothelial modulation by pravastatin may have potential clinical implications.

Analysis of Variance↗
PubMed2005

Inhaled nitric oxide through a noninvasive ventilation device to assess reversibility of pulmonary hypertension in selecting recipients for heart transplant.

INTRODUCTION: Pulmonary hypertension (PHT) is an independent risk factor for right ventricular failure and death after heart transplant. Nitric oxide (NO) is a powerful and selective vasodilator, indicated in this scenario, but its response is unpredictable. Thus, it should be assessed prior to the intervention. However, preoperative assessment has not been widespread due to its difficulties and risks. OBJECTIVE: We describe herein a pulmonary vasodilatory test with NO administered through a noninvasive ventilation (NIMV) device. We also assessed the effect of NO in patients with severe PHT owing to cardiac disease. Assessment of the utility of the test to select patients for heart transplant. METHODS: We enrolled 19 patients with severe PHT for a preoperative assessment for heart transplant. Thresholds used were as follows: systolic pulmonary arterial pressure (SPAP) > or =65 mm Hg, transpulmonary gradient (TPG) > or =15 mm Hg, and pulmonary vascular resistance (PVR) > or =4.5 Wood units (WU). NO was administered through a modified noninvasive ventilation device. Cardiac output and pulmonary pressures were measured simultaneously by right heart catheterization. RESULTS: All patients agreed to be enrolled in the test. No difficulties, interruptions, or severe complications happened in any case. Basal and NO average measured values were SPAP (74.16 and 57.95 mm Hg), PVR (7.5 and 3.7 WU), and TPG (23.25 and 12.58 mm Hg). The differences were significant (P < .05) for all three tests. We consider acceptable for heart transplant a response that reduces PHT to a moderate grade. Using these criteria 14 patients were accepted and 11 underwent heart transplant. Two deaths in the postoperative period were both secondary to mediastinal bleeding and not related to right ventricular failure. CONCLUSIONS: A pulmonary vasodilatory test with NO administered through a NIMV device was feasible and useful to select suitable heart transplant recipients with severe pulmonary hypertension.

Administration, Inhalation↗
PubMed2005

Long-term results of heart transplant in recipients older and younger than 65 years: a comparative study of mortality, rejections, and neoplasia in a cohort of 445 patients.

BACKGROUND: Whether being older than 65 years should be considered an absolute counterindication to heart transplant (HT), as it is in some centers, is controversial. In our centre, patients older than 65 years are accepted for HT if they satisfy stringent conditions. The aim of this study was to examine whether heart recipients older than 65 years have a greater risk of rejection, neoplasia, or mortality than younger ones. METHODS: We studied 445 patients who underwent HT between April 1991 and December 2003, 42 of whom were older than 65 years and 403 who were 65 years or younger. The parameters evaluated were the cumulative incidences of neoplasias and rejections (ISHLT grade > or = 3A), and the survival rates 1 month, 1 year, and 5 years post-HT. RESULTS: The two groups had similar percentages of patients with at least one rejection episode (< or =65 years 56.9%, >65 years 51.3%; P > .05), and although there were proportionally almost twice as many tumors in the older group (14.2%) as in the younger (7.9%), this difference was not statistically significant either. Nor were there any significant differences in survival, the 1-month, 1-year, and 5-year rates being 87.8%, 82.1%, and 68.8%, respectively, in the younger group and 85.7%, 78.6%, and 73.4%, respectively, in the older. CONCLUSIONS: Among carefully selected patients aged more than 65 years, HT can be performed without incurring greater risk of rejection, malignancy, or death than is found among recipients younger than 65 years.

Age Factors↗
PubMed2005

Monocyte cyclooxygenase-2 activity: a new therapeutic target for atherosclerosis?

It is now widely accepted that atherosclerosis is a complex chronic inflammatory disorder of the arterial tree associated with several risk factors. From the initial phases of leukocyte recruitment to eventual rupture of vulnerable atherosclerotic plaques, a low-grade inflammation, also termed microinflammation, appears to play a key pathogenetic role. Experimental and clinical evidence suggests that cyclooxygenase-2 (COX-2), an enzyme which catalyzes the generation of prostaglandins from arachidonic acid, also contributes to lesion formation. COX-2 has been detected in macrophages, smooth muscle cells and endothelial cells in human atherosclerotic lesions. Several studies have also reported the presence of COX-2 in the shoulder region of atherosclerotic plaques, mainly colocalizing with macrophages and MMPs, enzymes that are involved in the destabilization of atherosclerotic plaques, leading to rupture and atherothrombotic syndromes (i.e. acute myocardial infarction). We have recently assessed monocyte COX-2 activity and the production of PGE(2) in a population of apparently healthy subjects free from clinically overt atherosclerosis. We found an association between increased PGE(2) and increasing number of cardiovascular risk factors and carotid intima-media thickness, a noninvasive surrogate marker of atherosclerosis, independently of traditional and non traditional cardiovascular risk factors. Our findings support the notion that the COX-2/PGE(2)axis may have a role in atherosclerosis, and this might be an attractive therapeutic target. COX-2 inhibitors, collectively called coxibs (celecoxib, rofecoxib, valdecoxib, lumiracoxib, etc), held a promise of improved treatment of arthritis without the gastrointestinal side effects associated with aspirin and other nonsteroidal anti-inflammatory drugs. However, clinical studies raise several clinically relevant questions as to their beneficial role in atherosclerosis prevention, because of increased thrombogenicity and cardiovascular risk. Only well designed large scale clinical trials can provide the answer as to the net effect of selective COX-2 inhibition on cardiovascular events before this new class of anti-inflammatory drugs can be incorporated into the armamentarium of atherosclerosis.

Arteriosclerosis↗
PubMed2004

Production and evaluation of alloantibodies against sheep MHC Class I antigens.

In this work more than 600 sera obtained from three different sources (parous ewes and directed immunizations with whole blood or leucocytes) were tested for cytotoxic antilymphocyte antibodies. A high incidence of cytotoxic antibodies in pregnancy-stimulated animals was confirmed. For the sake of comparison, a comprehensive review of other studies in sheep and other species was performed. There are several different reasons that could explain the differences found between these studies, among them the time of sampling and the cytotoxic assay procedures. Moreover, antibodies were also found in non-pregnant females which may imply that pregnancy is not the only stimulus for antibody production and environmental factors, such as molecular mimicry between infectious agents and lymphocyte antigens, could be the reason for their appearance. In the case of alloimmunizations with leucocytes or whole blood the results were very close to those obtained in goats. Taking into account the Strength Index, the immunization sera were of higher quality. Our results support the methodology of Nesse and Larsen since one injection of whole blood of the lamb is an easy procedure that produces alloantisera with a high value for major histocompatibility complex Class I antigens typing.

Animals↗
PubMed2004

The oral combination of thalidomide, cyclophosphamide and dexamethasone (ThaCyDex) is effective in relapsed/refractory multiple myeloma.

We evaluate the efficacy of the oral combination of thalidomide, cyclophosphamide and dexamethasone (ThaCyDex) in 71 refractory/relapsed multiple myeloma patients, including a prognostic analysis to predict both response and survival. Patients received thalidomide at escalating doses (200-800 mg/day), daily cyclophosphamide (50 mg/day) and pulsed dexamethasone (40 mg/day, 4 days every 3 weeks). On an intention-to-treat basis and using the EBMT response criteria, 2% patients reached complete response (CR), 55% partial response (PR) and 26% minor response (MR) yielding a total response (CR+PR+MR) rate of 83% after 3 months of therapy. After 6 months of therapy, responses were maintained including a 10% CR. The 2-year progression free and overall survival were 57 and 66%, respectively. A favorable response was associated with beta2 microglobulin < or =4 mg/dl, platelets >80 x 10(9)/l and nonrefractory disease. Regarding survival, low beta2 microglobulin (< or =4 mg/dl), age (< or =65 years) and absence of extramedullary myelomatous lesion were associated with a longer survival. Major adverse effects included constipation (24%), somnolence (18%), fatigue (17%) and infection (13%). Only 7% of patients developed a thrombo-embolic event. ThaCyDex is an oral regimen that induces a high response rate and long remissions, particularly in relapsing patients with beta2 microglobulin < or =4 mg/dl and < or =65 years.

Administration, Oral↗
PubMed2004

Neutrophil responses to CRP are not dependent on polymorphism of human FcgammaRIIA (R131H).

IgG2a mediated in vitro phagocytosis is less effective for individuals homozygous for Fcgamma RIIaR131 allele and such individuals are also more susceptible to certain infections. It has been reported that CRP binds to Fcgamma RIIaR131 but not Fcgamma RIIaH131 and since Fcgamma RIIa is also a major Fc receptor on neutrophils it would be expected that normal healthy donors who did not have at least one copy of Fcgamma RIIaR131 would not respond to CRP. We examined responses reported to be dependent on FcgammaRIIa but no difference between groups was observed in CRP mediated phagocytosis of S. pneumoniae, reactive oxygen production, or IL-8 synthesis. This suggests that either neutrophil receptors other than Fcgamma RIIa are responsible for CRP mediated responses or differences in CRP binding to the forms of Fcgamma RIIa are comparatively minor.

C-Reactive Protein↗
PubMed2003

Antioxidant vitamins increase the collagen content and reduce MMP-1 in a porcine model of atherosclerosis: implications for plaque stabilization.

Degradation of extracellular matrix, particularly interstitial collagen, promotes plaque instability and contributes to restenosis after vascular injury. We have explored the effects of vitamins C and E on the collagen content and metalloproteinase-1 (MMP-1) expression after angioplasty in hypercholesterolemic pigs. Iliac angioplasty was performed on 18 minipigs divided into three diet groups: a normal-cholesterol (NC), a high-cholesterol (HC) and a high-cholesterol plus vitamins C+E (HCV). Four weeks later, after sacrifice, the vascular collagen content and MMP-1 protein expression, along with the plasma caseinolytic activity and lipid peroxidation, were measured. MMP-1 was also determined in arterial rings stimulated with native low-density lipoproteins (LDL) isolated from experimental groups. Cholesterol-rich diet augmented plasma lipid peroxidation (P<0.05), reduced the collagen content and increased vascular MMP-1 expression after injury (P<0.05). Enhanced caseinolytic activity (identified as MMP-1) was also observed in HC plasma samples and in supernatants from arterial rings incubated with HC-LDL. Vitamins C and E markedly increased neointimal collagen content (P<0.01), reduced the hypercholesterolemia-induced changes in vascular MMP-1 (P<0.05) and diminished plasma and ex vivo caseinolytic activity. Vitamins C and E may help stabilize atherosclerotic plaque after angioplasty and favor vascular remodeling by increasing collagen content and reducing vascular MMP-1 expression in porcine hypercholesterolemia.

Analysis of Variance↗
PubMed2003

Different expression of MMPs/TIMP-1 in human atherosclerotic lesions. Relation to plaque features and vascular bed.

BACKGROUND: Proteolytic imbalance might determine arterial remodeling and plaque destabilization in atherosclerotic vessels. The aim of this study was to examine differences in the patterns of metalloproteinases (MMPs) and MMP inhibitor (TIMP-1) expression in advanced human atheromas, both in relation to the plaque features and the vascular bed involved. METHODS AND RESULTS: Immunohistochemistry for MMP-1, -3, -9 and TIMP-1 as well as the collagen content were measured in vascular sections from patients undergoing peripheral revascularization (carotid n=11, femoral n=23) and aorto-coronary bypass surgery (mammary arteries n=20, as controls). Increased expression of all MMPs was detected in atherosclerotic as compared with control sections (P<0.01). Aneurysmal plaques showed a significant increase of MMP-1 and-3 and a reduction in total collagen (P<0.05) in relation to occlusive lesions. Calcification areas in atherosclerotic plaques were consistently associated with increased TIMP-1 expression (P<0.01). Finally, MMP-9 expression was higher in occlusive lesions from carotid than femoral arteries (P<0.01). CONCLUSIONS: Aneurysm lesions expressed higher MMP-1 and-3 expression than occlusive plaques, and MMP-9 was mainly detected in carotid as compared with femoral arteries. TIMP-1 was associated with arterial calcification. These differences in the MMPs/TIMP-1 expression might determine the evolution of advanced atherosclerotic plaques and contribute to its vulnerability.

Aged↗
PubMed2003

Renal dysfunction after orthotopic heart transplantation: incidence, natural history, and risk factors.

BACKGROUND: Renal dysfunction is a common complication after orthotopic heart transplantation (HT). The importance of factors other than exposure to immunosuppressive drugs is unclear. The purpose of this study was to determine the incidence and natural history of renal dysfunction following heart transplantation, and to evaluate a number of variables as risk factors for this condition. METHODS: We examined the creatinine levels at 1, 6, 12, 24, and 60 months in 262 consecutive heart transplant patients who survived at least 1 year. The potential risk factors included pre- and posttransplantation diabetes mellitus, arterial hypertension, and drugs used to control arterial hypertension. RESULTS: 17.2% of patients showed mild renal dysfunction (creatinine 1.5-2.5 mg/dL) and 1.9% moderate dysfunction (creatinine >2.5 mg/dL) at 1 month; 29.8% showed mild and 1.1% moderate dysfunction at 6 months; 33.2% showed mild and 1.9% moderate dysfunction at 1 year; 40% showed mild, 0.9% moderate and 0.4% severe dysfunction (requiring dialysis or renal transplantation) at 2 years; and 43.6% showed mild, 1.7% moderate and 0.9% severe dysfunction at 5 years. None of the conditions analyzed as possible risk factors showed a significant association with renal dysfunction except the use of diuretics. CONCLUSION: The incidence of renal dysfunction after orthotopic heart transplantation was 33.6% within the first year after transplant and 44% within the first five years, although more than 95% of cases were mild. The incidence increased with time after transplantation. Renal dysfunction seems likely to be multifactorial in origin, but no individual risk factors were identified.

Creatinine↗
PubMed2002

[Non-invasive continuous positive airways pressure for post-extubation laryngitis in pediatric patients].

UNLABELLED: Post-extubation laryngeal edema (PLE) is a common complication (10-15%) in pediatric intensive care units, and some authors have reported high failure rates for conventional treatment. HYPOTHESIS: Non-invasive continuous positive airways pressure (CPAP) in children with PLE may have a lower failure rate than conventional management. PATIENTS AND METHOD: Twenty-five patients were needed to detect a difference between the two treatment groups. The patients were assigned to receive the conventional treatment (nebulized epinephrin and humidified oxygen) or the experimental treatment (non-invasive CPAP treatment for 18 hours), using a randomized block design (10-patient blocks). After 9 months, the study was halted when a significant difference emerged between the two groups. RESULTS: Of 270 children extubated during the study, 28 (10.3%) developed PLE and 25 met the enrollment requirements. Thirteen were assigned to conventional therapy and 12 to CPAP. General characteristics, time of intubation, FiO2 upon admission, use of corticoids before extubation and scores for respiratory difficulty upon admission were similar in the two groups (p > 0.05). With conventional therapy, 5 (38.5%) children improved and 8 patients worsened or remained the same. Eleven (91.7%) of the patients receiving CPAP improved (p = 0.01). Those who failed on conventional treatment were prescribed CPAP and all then improved, although one had to be re-intubated. CONCLUSION: The hypothesis was confirmed. CPAP treatment reduced the failure rate by 53.2% in comparison with conventional therapy.

Age Factors↗
PubMed2001

[A case of Carney syndrome].

The Carney complex is an autosomal dominant syndrome characterised by multiple neoplasies, including myxomas at various sites (cardiac, cutaneous, mammary), spotty pigmentation, endocrine overactivity (Cushing's syndrome, acromegalia), testicular tumours and schwannomas. This report describes the case of a 43-year-old woman with an acute inferior myocardial infarction, probably due to coronary embolization from a large left atrial myxoma and who presented this association. A brief review of the Carney complex is provided after discussion of this rare case that required an screening of family members.

Adult↗
PubMed2001

Hyperhomocysteinemia in liver cirrhosis: mechanisms and role in vascular and hepatic fibrosis.

Numerous clinical and epidemiological studies have identified elevated homocysteine levels in plasma as a risk factor for atherosclerotic vascular disease and thromboembolism. Hyperhomocysteinemia may develop as a consequence of defects in homocysteine-metabolizing genes; nutritional conditions leading to vitamin B(6), B(12), or folate deficiencies; or chronic alcohol consumption. Homocysteine is an intermediate in methionine metabolism, which takes place mainly in the liver. Impaired liver function leads to altered methionine and homocysteine metabolism; however, the molecular basis for such alterations is not completely understood. In addition, the mechanisms behind homocysteine-induced cellular toxicity are not fully defined. In the present work, we have examined the expression of the main enzymes involved in methionine and homocysteine metabolism, along with the plasma levels of methionine and homocysteine, in the liver of 26 cirrhotic patients and 10 control subjects. To gain more insight into the cellular effects of elevated homocysteine levels, we have searched for changes in gene expression induced by this amino acid in cultured human vascular smooth muscle cells. We have observed a marked reduction in the expression of the main genes involved in homocysteine metabolism in liver cirrhosis. In addition, we have identified the tissue inhibitor of metalloproteinases-1 and alpha1(I)procollagen to be upregulated in vascular smooth muscle cells and liver stellate cells exposed to pathological concentrations of homocysteine. Taken together, our observations suggest (1) impaired liver function could be a novel determinant in the development of hyperhomocysteinemia and (2) a role for elevated homocysteine levels in the development of liver fibrosis.

Arteriosclerosis↗