Juan Rodriguez - Academia.edu (original) (raw)

Papers by Juan Rodriguez

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Revista española de quimioterapia : publicación oficial de la Sociedad Española de Quimioterapia, 2014

Introduction. The marA, soxS, ramA, acrB and ompF genes have been studied in order to characteriz... more Introduction. The marA, soxS, ramA, acrB and ompF genes have been studied in order to characterize mechanisms of AcrAB-TolC active efflux pumps and membrane permeability alterations that reduce fluoroquinolones susceptibility in Salmonella spp. Methods. Mutations in marA, soxS, ramA, acrB and ompF genes were detected, as well as their expression levels in presence and absence of ciprofloxacin, calculating the level of change between them by qPCR. Data were analysed by using SPSS 19.0. Results. No mutations in these genes were found, but both AcrAB-TolC regulatory genes and structural acrB gene expression were affected by ciprofloxacin in both mutant strains and wild type bacterial strains (WT). The activation of the marA gene in presence of drug was higher in WT strains (level of change 0.823) than in mutants strains (level of change 0.158; p=0.049). In gyrA mutants, a reduction in ompF gene expression in presence of ciprofloxacin was found (level of change -0.949 p=0.017). Conclusion. The reduction of fluoroquinolones susceptibility in Salmonella spp is a complex process, in which several different bacterial mechanisms are involved. This study has found a high difference in the degree of participation among studied mechanisms, between bacterial strains with and without gyrA mutation. Whereas WT strains activated efflux pumps especially through marA gene, mutants supressed ompF gene expression related to porins.

The European respiratory journal, 2014

Revista Espanola De Medicina Nuclear, 2003

Resumen.-Objetivo: Cuantificar el contenido del receptor del factor de crecimiento epidérmico (EG... more Resumen.-Objetivo: Cuantificar el contenido del receptor del factor de crecimiento epidérmico (EGFR) mediante técnica de radioligando en el cáncer de mama, y analizar su relación con las características de las pacientes y de sus tumores así como su significado pronóstico.

Journal of Craniofacial Surgery, 1998

Surgical treatment for glossoptosis-micrognathic association is indicated in the most severe case... more Surgical treatment for glossoptosis-micrognathic association is indicated in the most severe cases. Usually, complications occur. We used mandibular distraction to pull the tongue away from the posterior pharyngeal wall. This procedure, used in 3 patients, was effective.

Expert Opinion on Pharmacotherapy, 2004

Gastroenteritis, caused by Salmonella spp. is usually a self-limiting infection and does not requ... more Gastroenteritis, caused by Salmonella spp. is usually a self-limiting infection and does not require treatment. However, in some immunosuppressed patients (such as the newborn, the elderly, those with AIDS or neoplasms), there is a greater risk of developing a severe systemic infection, and in these cases, antibiotic treatment is recommended. Third-generation cephalosporins and fluoroquinolones are the most useful antibiotics in the treatment of these infections, although resistant strains are sometimes isolated. Therapeutic failures have been reported with fluoroquinolones in extra-intestinal infections caused by nalidixic acid resistant strains.

Journal of Empirical Finance, 2007

This paper models dependence with switching-parameter copulas to study financial contagion. Using... more This paper models dependence with switching-parameter copulas to study financial contagion. Using daily returns from five East Asian stock indices during the Asian crisis, and from four Latin American stock indices during the Mexican crisis, it finds evidence of changing dependence during periods of turmoil. Increased tail dependence and asymmetry characterize the Asian countries, while symmetry and tail independence describe the Latin American case. Structural breaks in tail dependence are a dimension of the contagion phenomenon. Therefore, the rejection of the correlation breakdown hypothesis should not be considered, without further investigation, as evidence of a stable dependence structure.

Se realizaron 2 estudios aleatorios para evaluar por ELISA los niveles de antitoxina tetánica y d... more Se realizaron 2 estudios aleatorios para evaluar por ELISA los niveles de antitoxina tetánica y diftérica inducidos por vacunación, así como para detectar poblaciones no protegidas. El primer estudio se realizó en 1 356 niños preescolares entre 1 y 5 años de edad de todas las provincias de Cuba, y el segundo en 311 recién nacidos de Ciudad de La Habana. Niveles no adecuados de antitoxina tetánica y diftérica (< 0,1 UI/mL) fueron encontrados solo en 23 (1,70 %) y 239 niños (17,62 %), respectivamente. En ambos casos, los menores valores se observaron a los 4 y 5 años de edad antes del refuerzo con la vacuna difteria-tétanos. Se pudo concluir que los niveles de antitoxina tetánica y diftérica en niños preescolares cubanos eran apropiados para la prevención de estas enfermedades. Se observaron niveles excelentes de antitoxina tetánica en los recién nacidos, 87,78 % con valores de larga duración (> 1,0 UI/mL), lo que avala el programa cubano de vacunación para la eliminación del tétanos neonatal. Sin embargo, niveles de antitoxina diftérica inferiores a 0,1 UI/mL fueron detectados en 51,12 % de los recién nacidos evaluados, esto los hace susceptibles a la difteria.

La apolipoproteína D (Apo D) es una lipoprote ína componente del sistema de transporte de lípidos... more La apolipoproteína D (Apo D) es una lipoprote ína componente del sistema de transporte de lípidos en el plasma humano. Se ha demostrado que en l íneas celulares de cáncer de mama y pr óstata su expresión esta regulada por andrógenos. Objetivo: Evaluar la expresi ón de ApoD en cáncer de próstata resecable así como su posible relaci ón con parámetros clínico-patológicos de los pacientes y sus tumores, además de su posible importancia pronóstica.

The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG, 2003

The purpose of the study was to calculate gentamicin, tobramycin, and amikacin pharmacokinetic pa... more The purpose of the study was to calculate gentamicin, tobramycin, and amikacin pharmacokinetic parameters in HIV-infected children and compare conventional multiple daily aminoglycoside dosing to once-daily aminoglycoside (ODA) dosing in attaining peak serum aminoglycoside concentrations (SACs) to minimum inhibitory concentration for 90% of isolates (MIC(90)) ratios ≥8 against selected pathogens. Patients (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;13yrs) receiving an aminoglycoside (15 patients/drug) in the treatment of gram-negative infection were studied. Intravenous gentamicin/ tobramycin were administered at a dose of 6-7.5 mg/kg/day and amikacin at 20-30 mg/kg/d divided every 8 hrs. Peak and trough serum concentrations were obtained and pharmacokinetic parameters were calculated utilizing a one-compartment steady-state model. SACs for gentamicin/tobramycin dosed at 7.5 mg/kg and amikacin at 22.5 mg/kg once daily were simulated using the calculated pharmacokinetic parameters. Peak SAC:MIC(90) ratios were calculated for each dosing method. Mean pharmacokinetic parameters were within 1 standard deviation of reported literature values. Mean peak:MIC(90) ratio of ≥8 was attained only for Klebsiella species (MIC90 1 μg/mL) using conventional gentamicin/tobramycin dosing whereas mean amikacin peak:MIC(90) ratios ≥8 were reached for Klebsiella, Enterobacter, and Citrobacter species (MIC(90) 4 μg/mL). ODA simulations predicted gentamicin/tobramycin peak:MIC(90) ratios ≥8 in 100% of patients with an organism-MIC(90) of 1 μcg/mL and in 80% of patients with an organism-MIC(90) of 2 μg/mL. Amikacin peak:MIC(90) ratio ≥8 was predicted for 93% of patients with an organism-MIC(90) of 4 μg/mL but in only 27% if the MIC(90) was 8 μg / mL. Optimal peak SAC:MIC90 ratios using conventional aminoglycoside dosing were predicted only for organisms with low MIC(90) values. ODA dosing represents an option for improving pharmacodynamic outcomes.

Journal of AOAC International

Multivariate experimental design has been used to optimize 2 flow-injection spectrophotometric me... more Multivariate experimental design has been used to optimize 2 flow-injection spectrophotometric methods for the determination of indapamide in pharmaceutical dosage forms, both pure and commercial tablets. The methods are based on the oxidation of this drug with iron (III) in acidic medium and the subsequent formation of an intensive orange-red complex between the liberated iron (II) and 2,2&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;-bipyridyl or 1,10-phenanthroline reagents. Plackett-Burman designs were applied as a screening method to evaluate the most significant factors with few experiments. Central composite 2(3)+ star designs were performed to evaluate the response surfaces. The methods have been fully validated and were applied successfully to the determination of indapamide in pure and pharmaceutical forms with good accuracy and precision. Therefore, the 2 proposed procedures are simple, inexpensive, and rapid flow methods for the routine determination of indapamide in pharmaceutical preparations.

SSRN Electronic Journal, 2000

Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine, Jan 17, 2014

The impact of hospitalization on sleep in late-life is underexplored. The current study examined ... more The impact of hospitalization on sleep in late-life is underexplored. The current study examined patterns of sleep quality before, during, and following hospitalization, investigated predictors of sleep quality patterns, and examined predictors of classification discordance between two suggested clinical cutoffs used to demarcate poor/good sleep. This study included older adults (n = 163; mean age 79.7±6.9 years, 31% female) undergoing inpatient post-acute rehabilitation. Upon admission to inpatient post-acute rehabilitation, patients completed the Pittsburgh Sleep Quality Index (PSQI) retrospectively regarding their sleep prior to hospitalization. They subsequently completed the PSQI at discharge, and 3- months, 6- months, 9- months, and 1 year post discharge. Patient demographic and clinical characteristics (pain, depression, cognition, comorbidity) were collected upon admission. Using latent class analysis methods, older adults could be classified into (1) Consistently Good Sleepers and (2) Chronically Poor Sleepers based on patterns of self-reported sleep quality pre-illness, during, and up to 1 year following inpatient rehabilitation. This pattern was maintained regardless of the clinical cutoff employed (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;5 or…

An indirect solid-phase enzyme-linked immunosorbent assay (ELISA) was developed for the quantitat... more An indirect solid-phase enzyme-linked immunosorbent assay (ELISA) was developed for the quantitation of antidiphtheria antibodies in human sera on the basis of a calibrated antibody standard. Intra-and inter-assay imprecision was around 10%. This assay showed an excellent accuracy (97.06% average recovery). Parallelism deviations were below 10%, which were evaluated with dilutions covering the working range of the standard curve. The detection limit of 0.0044 international units per milliliter (IU/mL) was sufficient for determining the immunological protection against diphtheria. In a preliminary study, a good correlation was found between the ELISA and the neutralization test in guinea pigs (R 2 = 0.992). A wide range of diphtheria antitoxin quantitation made possible to classify 81 adults prior and four weeks after revaccination against diphtheria as: unprotected subjects (≤ 0.01 U/mL), relatively protected (> 0.01-0.1 IU/mL), satisfactorily protected (> 0.1-1.0 IU/mL), and long-lasting protected (>1.0 IU/ mL).

British Journal of Cancer, 2007

An immunohistochemical study was performed using tissue microarrays and specific antibodies again... more An immunohistochemical study was performed using tissue microarrays and specific antibodies against matrix metalloproteinase (MMP)-1, -2, -7, -9, -11, -13 and -14, tissular inhibitors of metalloproteinase (TIMP)-1, -2 and -3. More than 2600 determinations on cancer specimens from 131 patients with primary ductal invasive tumours of the breast were performed. To identify specific groups of tumours with distinct expression profiles the data were analysed by unsupervised hierarchical cluster analysis by each cellular type. We did not find well-defined cluster of cases for tumour cells or fibroblastic cells. However, for mononuclear inflammatory cells the dendogram shows a first-order division of the tumours into two distinct MMP/TIMP molecular profiles, designated group 1 (n ¼ 89) and group 2 (n ¼ 42). Matrix metalloproteinase-7, -9, -11, -13 and -14, and TIMP-1 and -2, were identified as showing significant high expression in group 2 compared with group 1. Multivariate analysis demonstrated that clustering for mononuclear inflammatory cells was the most potent independent factor associated with distant relapse-free survival (group 2: 5.6 (3.5 -9.6), Po0.001). We identify a phenotype of mononuclear inflammatory cells infiltrating tumours, which is associated with the development of distant metastasis. Therefore, this finding suggests that these host inflammatory cells could be a possible target for inhibition of metastasis.

Breast Cancer Research and Treatment, 2005

Background. Tissue-type plasminogen activator (tPA) is a serine protease primarily involved in th... more Background. Tissue-type plasminogen activator (tPA) is a serine protease primarily involved in the intravascular dissolution of blood clots. High intratumoral tPA levels are associated with prognosis in several human tumors. In addition, tPA has been shown to be an estrogen-inducible protein in human breast cancer cell lines. The aim of the present study was to analyze the cytosolic tPA content in primary breast carcinomas and its potential clinical value. Materials and methods. tPA was measured by a solid-phase enzyme immunoassay in tumor cytosol samples obtained from 800 patients with breast cancer. The median follow-up period was of 49.2 months. Results. Cytosolic tPA levels ranged widely in breast carcinomas (median: 3.9; range: 0.1– 315.3 ng/mg protein). tPA levels were significantly lower in large tumors, as well as in those showing poor differentiation, estrogen (ER) or PgR-negativity, aneuploidy, or a high S-phase fraction. In addition, low tPA intratumoral levels were associated with a high probability of both shortened relapse-free and overall survival in all patients and in the subgroup with node-negative tumors. However, our results did not show any significant relationship between intratumoral tPA levels and prognosis in the different subgroups of patients, stratified according to the type of systemic adjuvant therapy received (chemotherapy, tamoxifen or chemotherapy plus sequential tamoxifen). Conclusion. The results of the present investigation indicate that low intratumoral tPA levels are associated with aggressiveness and poor prognosis in breast cancer patients. However, the study suggests that tPA levels do not predict response to systemic adjuvant therapy.

Cheminform, 2003

For Abstract see ChemInform Abstract in Full Text.

Chemotherapy, 2005

We studied the importance of the efflux pump mechanisms in Salmonella spp. mutants with reduced f... more We studied the importance of the efflux pump mechanisms in Salmonella spp. mutants with reduced fluoroquinolone susceptibility generated in vitro. The efflux pump was studied using MC-207,110 as an inhibitor of these systems. Wild strains with mutations in gyrA exhibit greater activity of the efflux pump systems than nalidixic-acid-susceptible strains (30-fold). When we evaluate the respective mutants, in those of susceptible strains there is seen to be greater elimination of the antibiotic (13-fold), whereas in mutants of nalidixic-acid-resistant strains these systems are not modified. When evaluating the influence of the antibiotic generating the mutants, ciprofloxacin is seen to be the quinolone that activates the efflux pump systems the most. Repeated exposure to low concentrations of all the fluoroquinolones studied leads to activation of the efflux pump systems and a reduction in susceptibility, even when there are no mutations in gyrA. Activation of these mechanisms is greatly influenced by the chemical structure of the antibiotic. The capacity of these systems to eliminate fluoroquinolones is limited and therefore, for the microorganism to acquire high-level fluoroquinolone resistance, they must be complemented by other mechanisms.

PloS one, 2015

CD56 + cells have been recognized as being involved in bridging the innate and acquired immune sy... more CD56 + cells have been recognized as being involved in bridging the innate and acquired immune systems. Herein, we assessed the effect of two major classes of immunostimulatory oligonucleotides (ODNs), PyNTTTTGT and CpG, on CD56 + cells. Incubation of human peripheral blood mononuclear cells (hPBMC) with some of these ODNs led to secretion of significant amounts of interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α) and granulocyte/monocyte colony-stimulating factor (GM-CSF), but only if interleukin 2 (IL2) was present. IMT504, the prototype of the PyNTTTTGT ODN class, was the most active. GM-CSF secretion was very efficient when non-CpG ODNs with high T content and PyNTTTTGT motifs lacking CpGs were used. On the other hand, CpG ODNs and IFNα inhibited this GM-CSF secretion. Selective cell type removal from hPBMC indicated that CD56 + cells were responsible for GM-CSF secretion and that plasmacytoid dendritic cells (PDCs) regulate this process. In addition, PyNTTTTGT ODNs inhibited the IFNα secretion induced by CpG ODNs in PDCs by interference with the TLR9 signaling pathway. Since IFNα is essential for CD56 + stimulation by CpG ODNs, there is a reciprocal interference of CpG and PyNTTTTGT ODNs when acting on this cell population. This suggests that these synthetic ODNs mimic different natural alarm signals for activation of the immune system.