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Biomedical subjects

M A Aguirre

Publications and source records attributed to M A Aguirre.

At least 19 recordsLinked to original sources
PubMed2006

Vascular endothelial growth factor expression in monocytes from patients with primary antiphospholipid syndrome.

BACKGROUND: One of the described mechanisms leading to thrombosis in antiphospholipid syndrome (APS) is overexpression of tissue factor (TF) in the monocytes and endothelial cells of patients with antiphospholipid antibodies (aPL). Vascular endothelial growth factor (VEGF) may stimulate monocyte TF expression through its receptor, the tyrosine kinase Flt-1. OBJECTIVES: This study aimed to analyze the following in monocytes of 55 primary APS patients: VEGF and Flt-1 expression levels, their potential regulation by aPL, and the association of VEGF and Flt-1 expression with the increased TF expression found in APS patients. RESULTS: Purified monocytes from APS patients showed higher levels of VEGF and Flt-1 than healthy donors, which further correlated with immunoglobulin G (IgG) anticardiolipin titers and TF expression rank. Moreover, monocyte VEGF and Flt-1 levels were significantly higher in patients with than in patients without previous thrombosis. In vitro, IgG from APS patients increased monocyte VEGF and Flt-1 expression in a dose-dependent manner. VEGF and Flt-1 expression was significantly inhibited by the p38 mitogen-activated protein kinase (MAPK) inhibitor SB203580; this suggests the involvement of this kinase in the aPL-induced VEGF and Flt-1 upregulation. CONCLUSIONS: Our data show, for the first time in vivo, that monocytes from primary APS patients have an increased expression of VEGF and Flt-1. Furthermore, in vitro results indicated that this cytokine is produced by monocytes when treated with aPL, and that the p38 MAPK signaling pathway plays an important role. Thus, VEGF might act as a regulatory factor in aPL-mediated monocyte activation and TF expression, thereby contributing to the proinflammatory-prothrombotic phenotype of APS patients.

Adolescent↗
PubMed2006

Rearrangements in a two-dimensional packing of disks.

Several aspects of the dynamics of a granular two-dimensional (2D) packing of disks slowly tilted until the system loses stability and an avalanche takes place are discussed. The evolution of the system, constructed with monodisperse disks placed on a thin cell, is studied by image analysis. As in the 3D case (packing of spheres), the system undergoes several rearrangements of different magnitude before the avalanche takes place. For thick systems, not only are small rearrangements detected but also displacements of large clusters of disks are observed in the bulk and on the free surface of the packing. In particular, characteristic angles and the avalanche mass were determined for samples of different heights. On thick systems, velocity fields of large rearrangements are presented and changes in the internal structure of the packing produced by these rearrangements are analyzed. It is found that the main effects of rearrangements is to increase the disorder of the system. Also, as the disorder of the system increases its stability threshold decreases.

Journal Article↗
PubMed2006

Antiphospholipid syndrome and tissue factor: a thrombotic couple.

The antiphospholipid syndrome (APS) is characterized by thrombosis and/or pregnancy morbidity in the presence of antiphospholipid antibodies (aPL). Among the thrombogenic mechanisms proposed, it has been suggested that aPL can stimulate tissue factor (TF) expression by endothelial cells (ECs) and monocytes. Moreover, our in vivo studies have shown that APS patients (particularly those with thrombosis) have increased monocyte TF expression. Yet, the molecular mechanism(s) by which aPL induce TF expression has not been completely underscored. In a recent study, we have demonstrated that aPL induces TF expression in monocytes from APS patients by activating, simultaneously and independently, the phosphorylation of MEK-1/ERK proteins, and the p38 MAP kinase-depenent nuclear translocation and activation of NFkappaB/Rel proteins. Understanding the intracellular mechanism(s) of aPL-mediated monocyte activation may help to establish new therapeutic approaches, such as selective inhibition of MAP kinases, to reverse the prothrombotic state in APS. Furthermore, the contribution of TF to a protrombotic state in the APS provides a renewed focus on antithrombotic therapies in current use, including the oral anticoagulation and, more recently, the use of statins, which have been proven to be effective in the inhibition of EC and monocyte TF-expression.

Antibodies, Antiphospholipid↗
PubMed2003

Instabilities in slowly driven granular packing.

In this work, a digital imaging technique is used to study the superficial fluctuations observed when a granular packing is slowly driven to the threshold of instability. The experimental results show the presence of three types of events. Small superficial rearrangements of grains are observed during all the experiments. They present a power-law behavior although the system is not in a critical state as predicted by self-organized criticality models. In thick granular piles, large rearrangements are detected at regular angular intervals. They are related to the threshold of instability of the contact network that relaxes to stable configurations producing internal rearrangements of the grains. Finally, an avalanche is triggered when the superficial beads that are set in motion acquire enough momentum to destabilize grains from layers below.

Journal Article↗
PubMed2002

Simulations in the mathematical modeling of the spread of the Hantavirus.

The range of validity of a recently proposed deterministic (mean field) model of the spread of the Hantavirus infection is studied with the help of Monte Carlo simulations for the evolution of mice populations. The simulation is found to reproduce earlier results on the average but to display additional behavior stemming from discreteness in mice number and from fluctuations of the finite size system. It is shown that mice diffusion affects those additional features of the simulation in a physically understandable manner, higher diffusion constants leading to greater agreement with the mean field results.

Animals↗
PubMed1999

Increased levels of tissue factor mRNA in mononuclear blood cells of patients with primary antiphospholipid syndrome.

Antiphospholipid antibodies (aPL) may stimulate tissue factor (TF) expression in cultured endothelial cells and monocytes, but there are discrepancies as to the expression of TF in the patients with antiphospholipid syndrome (APS). By using reverse transcription and polymerase chain reaction amplification, we have analysed TF mRNA accumulation in freshly isolated mononuclear blood cells (MBC) of 14 patients with primary APS (PAPS) and six normal controls. TF mRNA accumulation was low or absent in uncultured MBC from all normal controls, but was elevated in uncultured MBC from nine of the patients as well as in normal MBC incubated with 100 ng/ml lipopolysaccharide (LPS). Mean levels of TF mRNA, as measured by densitometry, were higher in MBC from patients (N = 14) than in those from controls (N = 6, P = 0.009), and in MBC from patients with a history of thrombosis (N = 9) than in those from patients without thrombosis (N = 5, P = 0.02). Uncultured MBC of patients with thrombosis accumulated TF mRNA at similar levels to LPS-treated normal MBC. Increased levels of TF mRNA were found in eight of ten patients with conventional aPL (ie, anti-cardiolipin antibodies [aCL] and/or lupus anticoagulant [LA]) and little if any accumulation of TF mRNA was observed in three of four patients without aPL at the time of study. These data strongly suggest that circulating monocytes of many patients with PAPS are subjected to an up-regulated TF expression that may well explain their prothrombotic state. Although the presence or absence of TF mRNA in MBC was associated with, respectively, the presence or absence of conventional aPL in 11 of the 14 patients studied, our study cannot exclude the involvement of factors other than aCL or LA in inducing TF expression.

Adult↗
PubMed1998

Prolactin levels in patients with systemic lupus erythematosus: a case controlled study.

Recent accumulated evidence suggests that prolactin (PRL) is an important immunomodulator and might have a role in the pathogenesis of systemic lupus erythematosus (SLE). Our aim was to assess the frequency of hyperprolactinemia in women with SLE and to evaluate its correlation with disease activity. PRL plasma levels were measured in 36 women with SLE and 20 age-matched healthy controls. We excluded patients with renal and/or hepatic failure, pregnant patients and patients taking drugs which could increase PRL levels. Disease activity was assessed using the SLE disease activity index (SLEDAI). Patients with a score > 10 were considered active. In patients and controls, PRL levels were determined by radioimmunoassay (RIA) during the first part of the menstrual cycle (between the 5th and 8th day) (normal value < 20 ng/ml). Ten of 36 (27.7%) SLE patients had high PRL levels (> 20 ng/ml). The mean PRL level was higher in SLE than in the control group (17.1+/-12.9 s.d. vs 9.9+/-3.5, P < 0.01). Patients with active disease had a trend to higher mean PRL levels than inactive patients although this difference was not statistically significant (21.1+/-4.8 vs 14.8+/-6.9, P = 0.09). No correlation was found between PRL levels and SLEDAI score. Furthermore, no significant correlation was found between PRL levels and any clinical or serological finding.

Adolescent↗
PubMed1997

Ethnic differences in insulin resistance and its consequences in older Mexican American and non-Hispanic white women.

BACKGROUND: This study was initiated to test the hypothesis that older, healthy, nondiabetic Mexican American women would be relatively resistant to insulin-mediated glucose disposal, hyperinsulinemic, and dyslipidemic as compared to a matched group of non-Hispanic White (NHW) women. METHODS: The study, cross-sectional in nature, involved 14 Mexican American and 19 NHW healthy, normotensive nondiabetic, postmenopausal women of similar age and body mass index. It took place in the General Clinical Research Center at Stanford Medical Center. Measurements were made of fasting plasma glucose, insulin and lipid concentrations, and plasma glucose and insulin concentrations following a 75 gram oral glucose challenge. Resistance to insulin-mediated glucose disposal was estimated by the steady-state plasma glucose (SSPG) concentration achieved at the end of a 3-hour constant infusion of glucose, insulin, and somatostatin. RESULTS: Mexican American women had significantly greater glucose (p < .001) and insulin (p < .001) responses to the oral glucose challenge than did the NHW women. Resistance to insulin-mediated glucose disposal was increased in Mexican American women (SSPG 195 +/- 25 mg/dl compared to 137 +/- 18 mg/dl in NHW; p < .001). While total cholesterol, low density lipoprotein (LDL)-cholesterol, and triglyceride concentrations were not significantly different in the two ethnic groups, high density lipoprotein (HDL)-cholesterol was significantly lower in the Mexican American women (51 mg/dl vs 61 mg/dl; p = .04). CONCLUSION: Older Mexican American women are more insulin resistant, glucose intolerant, and hyperinsulinemic, and have a lower HDL-cholesterol than a matched group of non-Hispanic White peers. These results were observed despite the exclusion of individuals with non-insulin dependent diabetes mellitus (NIDDM).

Administration, Oral↗
PubMedDate not supplied

[Nutrition surveys in children attending kindergartens in the city of Cordoba].

A nutritional inquest was carried out in 1857 children attending kindergartens in Córdoba, Argentina, in 1974. Determinations were made for the socioeconomical level each child belonged (NES) and clinical and anthropometric examinations. Nutritional inquests were carried out in 414 of these children, psychological examinations in 51, and biochemical inquests in 61 children.

Argentina↗