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Biomedical subjects

S Velasco

Publications and source records attributed to S Velasco.

At least 19 recordsLinked to original sources
PubMed2006

Density functional theory of fluids in nanopores: analysis of the fundamental measures theory in extreme dimensional-crossover situations.

Two density functional theories, the fundamental measures theory of Rosenfeld [Phys. Rev. Lett. 63, 980 (1989)] and a subsequent approximation by Tarazona [Phys. Rev. Lett. 84, 694 (2000)] are applied to the study of the hard-sphere fluid in two situations: the cylindrical pore and the spherical cavity. The results are compared with those obtained with grand canonical ensemble Monte Carlo simulations. The differences between both theories are evaluated and interpreted in the terms of the dimensional crossover from three to one and zero dimensions.

Algorithms↗
PubMed2006

Environmental factors influencing growth of and exopolysaccharide formation by Pediococcus parvulus 2.6.

Natural exopolysaccharides (EPSs) from food-grade lactic acid bacteria have potential for development and exploitation as food additives and functional food ingredients with both health and economic benefits. In this study, we have examined the physiological capacity of EPS production in Pediococcus parvulus 2.6. EPS formation by P. parvulus 2.6 was found to be linked to biomass yields, provided that glucose was not limiting. Higher biomass yields and EPS productions were obtained when cultures were pH-controlled at pH 5.2. Various compounds have been tested for their influence on growth rate and EPS formation. Of those, only glucose (up to 75 g l(-1)), ethanol (up to 4.9%, w/v) and glycerol (up to 6.6%, w/v) had positive effects on EPS production. EPS production was not directly linked to growth, because its production continued in the stationary phase provided that glucose was present. According to an empirical model, the growth of P. parvulus 2.6 was completely inhibited by 58.9+/-18.1 g l(-1) lactate. Lactate, the sole fermentation product, was suggested to affect growth by chelation of manganese. The organism grew in an apparent linear fashion due to this imposed manganese limitation. This could be overcome by increasing the manganese concentration to at least 2 mg l(-1) in the medium. The excretion of Mn(2+) upon depletion of glucose indicated that maintenance of the high Mn(2+) gradient over the cell membrane is an energy requiring process. EPS production was increased from 0.12 g l(-1) to 4.10 g l(-1) in an improved medium that is based on the results from this study.

Colony Count, Microbial↗
PubMed2006

TGF-beta1 induces COX-2 expression and PGE2 synthesis through MAPK and PI3K pathways in human mesangial cells.

Transforming growth factor-beta1 (TGF-beta1) plays a fundamental role in the progression of renal diseases. Accumulating evidence has suggested that eicosanoids derived from cyclooxygenase-2 (COX-2) participate in a number of pathological processes in immune-mediated renal diseases. Mesangial cells (MC) play a major role in physiological and pathophysiological renal processes. MC express receptors for TGF-beta1, and COX-2 expression can be induced in MC. However, to date, there are no published data on the possible role of TGF-beta1 in COX-2 expression in human mesangial cells (HMC). We designed studies to determine (1) whether TGF-beta1 stimulates COX-2 expression in primary HMC, (2) whether mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) cascades are involved in TGF-beta1-induced COX-2 expression, and (3) whether prostaglandin (PG)E2 synthesis is affected by TGF-beta1 and MAP kinases and PI3K activation. Studies were performed in primary cultures of HMC and in an immortalized line of HMC. TGF-beta1 induces COX-2 promoter activity and COX-2 mRNA and protein expression in HMC. COX-2 induction is accompanied by increased PGE2 synthesis. Extracellular signal-regulated kinase (ERK)1/2, p38 MAPK, and PI3K pathway inhibition blunted TGF-beta1-induced COX-2 overexpression. We demonstrate that TGF-beta1 regulates COX-2 expression in HMC through the activation of ERK1/2, p38 MAPK, and PI3K. These results can help to elucidate the molecular mechanisms underlying the regulation of COX-2 and open up specific strategies for the treatment of glomerular disease.

Cell Proliferation↗
PubMed2006

Finite-size effects in the microscopic structure of a hard-sphere fluid in a narrow cylindrical pore.

We examine the microscopic structure of a hard-sphere fluid confined to a small cylindrical pore by means of Monte Carlo simulation. In order to analyze finite-size effects, the simulations are carried out in the framework of different statistical mechanics ensembles. We find that the size effects are specially relevant in the canonical ensemble where noticeable differences are found with the results in the grand canonical ensemble (GCE) and the isothermal isobaric ensemble (IIE) which, in most situations, remain very close to the infinite system results. A customary series expansion in terms of fluctuations of either the number of particles (GCE) or the inverse volume (IIE) allows us to connect with the results of the canonical ensemble.

Journal Article↗
PubMed2006

[Improvement of Darier's disease on treatment with topical 5-fluorouracil].

BACKGROUND: Darier's disease is an inherited genodermatosis with autosomal dominant transmission characterized by hyperkeratotic papules of seborrheic regions in the axillae, groin or submammary skin in women. Current therapeutic alternatives are poor, encouraging recourse to alternatives treatments such as topical 5-fluorouracil (Efudix) used until now for pre-epitheliomatous keratosis. CASE REPORT: A 55-year-old man presenting severe Darier's disease refractory to therapy for more than twenty years was treated with topical 5-fluorouracil. The cream was applied at a concentration of 1% every second day for five months, alternating with clobetasol ointment in order to improve tolerability. After one month of treatment, clinical signs of hyperkeratosis had virtually disappeared from the patient's face and neck. This dramatic improvement persisted for 2 months after the end of the treatment with 5-fluorouracil. No local or systemic side-effects have been observed to date. DISCUSSION: Darier's disease is caused by mutations of the ATP2A2 gene, which codes for the SERCA2 endoplasmic reticulum calcium pump. This pump is rendered non-functional through decreased ATP and calcium affinity and blockade of phosphorylation-dephosphorylation. We propose a new hypothesis according to which the action of 5-fluorouracil results from restoration of normal intracytoplasmic calcium concentrations, leading to renewed keratinization. Thanks to its mode of activation, this prodrug can compensate for failure of the ATP phosphorylation-dephosphorylation mechanisms necessary for calcium pump activity by releasing phosphoric acids. Thus, topical 5-fluorouracil appears to constitute an effective alternative therapy. Long-term studies in a larger population are needed to clarify the optimal dosage and identify potential side effects.

Administration, Topical↗
PubMed2006

[Erythema multiforme majus and Chlamydia pneumoniae infection].

BACKGROUND: Erythema multiforme majus of infectious origin is an acute eruptive syndrome seen more commonly in young subjects and characterised by an appearance of round target lesions. In most cases, it is associated with infection involving Herpes simplex virus or Mycoplasma pneumoniae. We report an original case of erythema multiforme majus subsequent to infection with Chlamydia pneumoniae. CASE REPORT: An 18 year-old man was hospitalised for management of generalised skin rash comprising lesions in rings, associated with bullous and post-bullous lesions, chiefly in the oral (preventing eating) and genital areas in a setting of febrile cough. Various bacterial agents (Mycoplasma pneumoniae, Chlamydia pneumoniae) and viral agents were suspected, but serological testing for Chlamydia pneumoniae alone was positive with IgM of 128 IU and IgG of 64 IU. The outcome was favourable within several days following administration of symptomatic treatment (rehydration, mouthwashes, etc.) and aetiological treatment (acyclovir: 30 mg/kg/d, ofloxacine: 400 mg/d). At D15, serologic tests for Mycoplasma pneumoniae continued to be negative. Anti-Chlamydia pneumoniae IgM and IgG were 256 IU. At D30, IgM was 128 IU while IgG remained at 256 IU. DISCUSSION: The existence of a systematic skin rash comprising typical target lesions and mucosal lesions in the oral and genital areas suggested to us a diagnosis of erythema multiforme majus. Screening for the agents generally responsible was negative and drug-induced rash was ruled out. Serological tests for Chlamydia pneumoniae were positive at various times, resulting in diagnosis of erythema multiforme majus secondary to infection with Chlamydia pneumoniae. Following demonstration of the presence of Chlamydia pneumoniae using reliable methods and the elimination of other causes of erythema multiforme majus, dermatologists should opt for this aetiology in order to optimise treatment.

Acyclovir↗
PubMed2005

Dynamical characterization of rotationally hindered species in liquids.

The rotational dynamics of HCl in liquid Ar has been studied by means of molecular-dynamics simulations. We calculate the lifetimes of weakly bound HCl-Ar dimers induced by the anisotropic pair interaction. It is shown that, although lifetimes are small with respect to the reorientational decorrelation, the time interval between the breaking down and formation of the next dimer is negligibly small. Thus, with respect to the rotational dynamics of the probe, the effect is similar to that and eventually would cause a time-stable complex. This provokes a peculiar hindered rotation of the diatomic in the liquid which is macroscopically embodied in the infrared spectrum of the solution as a Q-branch nonexistent otherwise.

Journal Article↗
PubMed2005

On the universal behavior of some thermodynamic properties along the whole liquid-vapor coexistence curve.

When thermodynamic properties of a pure substance are transformed to reduced form by using both critical- and triple-point values, the corresponding experimental data along the whole liquid-vapor coexistence curve can be correlated with a very simple analytical expression that interpolates between the behavior near the triple and the critical points. The leading terms of this expression contain only two parameters: the critical exponent and the slope at the triple point. For a given thermodynamic property, the critical exponent has a universal character but the slope at the triple point can vary significantly from one substance to another. However, for certain thermodynamic properties including the difference of coexisting densities, the enthalpy of vaporization, and the surface tension of the saturated liquid, one finds that the slope at the triple point also has a nearly universal value for a wide class of fluids. These thermodynamic properties thus show a corresponding apparently universal behavior along the whole coexistence curve.

Journal Article↗
PubMed2004

Infrared spectral profiles in liquids and atom-diatom interactions.

Molecular dynamics simulations of the infrared spectrum of a generic simple polar diatomic in a liquid nonpolar solvent allow to reproduce the different prototypical experimental line shapes of this kind of systems. This is feasible by using different solute-solvent anisotropic potentials at fixed thermodynamic conditions. In the limit cases, the rotation of the diatomic is explained in terms of a quasifree motion or a rotational diffusion evolution and the spectra show a doublet structure formed by P and R branches or a unique collapsed branch, respectively. When the profile contains three branches, including an intense Q branch in the vicinity of the center of the band, rotational evolution presents a particular hindering that can be understood by studying the influence on rotational spectral densities of the different time scales involved in rotational relaxation. Cancellation/enhancement effects among spectral density terms arising from intermediate and long times (0.4-1 ps) are essential to understand rotational hindering.

Journal Article↗
PubMed2004

Density functional theory of fluids in the isothermal-isobaric ensemble.

We present a density functional theory for inhomogeneous fluids at constant external pressure. The theory is formulated for a volume-dependent density, n(r,V), defined as the conjugate variable of a generalized external potential, nu(r,V), that conveys the information on the pressure. An exact expression for the isothermal-isobaric free-energy density functional is obtained in terms of the corresponding canonical ensemble functional. As an application we consider a hard-sphere system in a spherical pore with fluctuating radius. In general we obtain very good agreement with simulation. However, in some situations a peak develops in the center of the cavity and the agreement between theory and simulation becomes worse. This happens for systems where the number of particles is close to the magic numbers N=13, 55, and 147.

Journal Article↗
PubMed2001

Regulation of endothelial nitric oxide synthase expression in the vascular wall and in mononuclear cells from hypercholesterolemic rabbits.

BACKGROUND: We recently obtained evidence demonstrating that cultured bovine endothelial cells contain cytosolic proteins that form complexes with the 3'-untranslated region of endothelial nitric oxide synthase (eNOS) mRNA and are associated with its destabilization. The aim of this study was to determine the presence of such proteins and eNOS expression in hypercholesterolemic rabbits as an in vivo model of endothelial dysfunction. METHODS AND RESULTS: Endothelium-dependent relaxation to acetylcholine and the calcium ionophore A23187 was reduced in aortic segments from hypercholesterolemic rabbits compared with controls. Treatment of hypercholesterolemic rabbits with cerivastatin (0.1 mg. kg body wt(-1). d(-1)) restored endothelium-dependent relaxation. Aortic eNOS expression was reduced in hypercholesterolemic rabbits and was accompanied by enhanced binding activity of a 60-kDa cytosolic protein and reduced stability of eNOS mRNA. Cerivastatin treatment upregulated eNOS expression and reduced the interaction of the cytosolic protein with the 3'-untranslated region of eNOS mRNA. Mononuclear cells from hypercholesterolemic rabbits also showed a marked reduction of eNOS expression and eNOS mRNA stability and an increase in binding activity of the cytosolic protein, which were also prevented by cerivastatin treatment. CONCLUSIONS: These results demonstrate the presence of a 60-kDa protein that binds to eNOS mRNA and reductions in eNOS expression in both vascular wall and mononuclear cells that are prevented by cerivastatin.

3' Untranslated Regions↗
PubMed2001

Unified optimization criterion for energy converters.

We propose a unified optimization criterion for energy converters. It represents the best compromise between energy benefits and losses for a specific job and neither an explicit evaluation of entropies nor the consideration of environmental parameters are required. For all considered systems the criterion predicts a performance regime laying between those of maximum efficiency and maximum useful energy. Such regime has been invoked as optimum not only in macroscopic heat engines but also in some molecular motors.

Journal Article↗
PubMed2001

Cerivastatin prevents tumor necrosis factor-alpha-induced downregulation of endothelial nitric oxide synthase: role of endothelial cytosolic proteins.

Cardiovascular disease is accompanied by an impaired endothelium-dependent vasodilatory response. Loss of endothelial nitric oxide synthase (eNOS) expression may contribute to endothelial dysfunction. The aim of the present study was to analyze the effect of cerivastatin, a novel HMG CoA reductase inhibitor, on tumor necrosis factor-alpha (TNF-alpha)-induced downregulation of eNOS protein expression in bovine aortic endothelial cells (BAEC). TNF-alpha (10 ng/ml)- incubated BAEC showed a reduced expression of eNOS protein and decreased eNOS mRNA stabilization. This effect was associated with an increased binding activity of BAEC cytosolic proteins to the 3'-untranslated region (3'UTR) of eNOS mRNA. Cerivastatin prevented TNF-alpha-induced downregulation of eNOS protein expression in a concentration-dependent manner (10(-8) to 10(-5) M). Cerivastatin also prevented the binding of the cytosolic proteins to 3'-UTR of eNOS mRNA and was associated with eNOS mRNA stabilization. The reduced expression of eNOS protein by TNF-alpha was also prevented by coincubation with cycloheximide. In addition cycloheximide inhibited the binding activity of the cytosolic proteins to 3'-UTR of eNOS mRNA, suggesting the inducible character of the mentioned-cytosolic proteins. TNF-alpha stimulated the translocation of nuclear factor-kappaB (NF-kappaB), an effect that was not modified by cerivastatin. Furthermore, an inhibitor of NF-kappaB translocation, pyrrolidine dithiocarbamate failed to modify both the downregulation of eNOS expression and the increased binding activity of the cytosolic proteins to 3'-UTR of eNOS mRNA by TNF-alpha. The effect of cerivastatin on eNOS expression and the binding activity of the cytosolic proteins were reversed by coincubation with L-mevalonate. In conclusion, cerivastatin stabilized eNOS mRNA and upregulated eNOS expression in the endothelium, and this was associated with a decreased binding activity of cytosolic proteins to 3'-UTR of eNOS mRNA. The effect of cerivastatin on the regulation of eNOS expression was independent of NF-kappaB mobilization by TNF-alpha. These findings suggest that cerivastatin may have beneficial effects on the endothelial dysfunction associated with cardiovascular diseases beyond its effect on lowering cholesterol.

Animals↗
PubMed2001

Expression of inducible nitric oxide synthase in the liver of bile duct-ligated Wistar rats with modulation by lymphomononuclear cells.

BACKGROUND: The current study evaluated whether biliary tract obstruction stimulates inducible nitric oxide synthase (iNOS) protein expression in the liver and analyzed the implication of lymphomononuclear cells and interleukin-4 (IL-4). METHODS: Male Wistar rats were used. Bile flow interruption was achieved by a complete division of the extrapancreatic common bile duct. iNOS expression was determined by both the Western blot technique and immunohistochemistry. RESULTS: iNOS protein was markedly expressed in the liver 7 days after bile duct obstruction. Treatment with thymostimulin (TP-1), a partially purified thymic extract, reduced the intensity of the expression of iNOS protein in the liver after bile duct ligation. Recent data have suggested that IL-4 attenuates iNOS protein expression. We then analyzed the involvement of this anti-inflammatory cytokine on the modulation of iNOS expression in the liver. The liver from rats that underwent bile duct ligation (BDL) showed a lower content of IL-4 than that of sham-operated (SO) rats. TP-1 treatment increased the content of IL-4 in the liver. Liver slices incubated in vitro with Escherichia coli lipopolysaccharide (LPS, 10 microg/mL) stimulated the expression of iNOS protein. The level of LPS-induced iNOS expression was reduced by lymphomononuclear cells obtained from sham-operated animals. However, lymphomononuclear cells isolated from BDL rats potentiated the induction of iNOS expression by LPS-stimulated liver. However, lymphomononuclear cells from TP-1-treated BDL rats failed to modify LPS-stimulated iNOS expression. The different effect of lymphomononuclear cells on the modulation of iNOS expression in the liver was associated with their ability to generate IL-4. CONCLUSIONS: The liver of jaundiced rats markedly expressed iNOS protein, which was associated to modifications in the content of IL-4 in the liver. Furthermore, lymphomononuclear cells modulate iNOS protein expression in the liver by a mechanism in which IL-4 is involved.

Animals↗
PubMed2000

Density-functional theory of inhomogeneous fluids in the canonical ensemble

We present a density-functional approach for dealing with inhomogeneous fluids in the canonical ensemble. A general relation is proposed between the free-energy functionals in the canonical and the grand canonical ensembles. The minimization of the canonical-ensemble free-energy functional gives rise to Euler-Lagrange equations which involve averaged Ornstein-Zernike equations of second and third order. The theory is especially appropriate for systems with a small, fixed number of particles. As an example of application we obtain accurate results for the density profile of a hard-sphere fluid in a closed spherical cavity that contains only a few particles.

Journal Article↗
PubMed2000

(AC)23 [Z-2] polymorphism of the aldose reductase gene and fast progression of retinopathy in Chilean type 2 diabetics.

A recent case-control study suggests that the allele (AC)23 of a variable number tandem repeat (VNTR) associated to the aldose reductase (ALR2) gene could be related to early retinopathy in Type 2 diabetics. By means of a longitudinal-retrospective study, we aimed to seek for a relationship between the rate of progression of retinopathy and the (AC)23 allele of the VNTR associated to the ALR2 gene. A random sample was obtained of 27 Type 2 diabetics (aged 68.1 +/- 10.6 years, diabetes duration = 20.7 +/- 4.8 years, mean HbA1 = 10.6 +/- 1.6%). The mean HbA1 was the arithmetic average of 2.2 measurements per patient per year of total glycosilated hemoglobin (Gabbay method, normal range: 4.2-7.5%). Retinopathy was graded by an Ophthalmologist in a scale from zero to four score points. The genotype of the (AC), VNTR was determined by 32P-PCR plus sequenciation in a Perkin-Elmer laser device. The Mann-Whitney test and either chi2 or Fisher's exact test were used. A P < 0.05 was considered as statistically significant. The retinopathy progression rate (RPR, points x year(-1)) was calculated by dividing the increment of retinopathy score (delta Retinopathy Score, [points]), by the duration of the follow up [years]. The 12 diabetics having the (AC)23 allele had a mean RPR 8.9 times higher (0.40 +/- 0.61 points x year(-1)) than the 15 patients who had alleles other than (AC)23 (0.045 +/- 0.099 points x year(-1), P = 0.037). Both groups were similar with respect to: mean HbA1 (10.5 +/- 1.4 and 10.7 +/- 1.7%, P = 0.95), age at diagnosis (48.5 +/- 6.3 and 46.3 +/- 14.0 years, P = 0.81), diabetes' duration (21.3 +/- 4.7 and 20.2 +/- 4.9 years, P = 0.41) and serum creatinine (0.89 +/- 0.2 and 1.13 +/- 0.5 mg dl(-1), P = 0.35). We concluded that, in Type-2 diabetics having similar glycemic control, the (AC)23 allele of the VNTR associated to the ALR2 gene, is associated to a 8.9 times faster progression of retinopathy than in patients who have other alleles.

Age of Onset↗