Biomedical subjects

S Ramos

Publications and source records attributed to S Ramos.

At least 19 recordsLinked to original sources

PubMed2006

X-ray and neutron scattering studies of the hydration structure of alkali ions in concentrated aqueous solutions.

The presence of ions in water provides a rich and varied environment in which many natural processes occur with important consequences in biology, geology and chemistry. This article will focus on the structural properties of ions in water and it will be shown how the 'difference' methods of neutron diffraction with isotopic substitution (NDIS) and anomalous X-ray diffraction (AXD) can be used to obtain direct information regarding the radial pair distribution functions of many cations and anions in solution. This information can subsequently be used to calculate coordination numbers and to determine ion-water conformation in great detail. As well as enabling comparisons to be made amongst ions in particular groups in the periodic table, such information can also be contrasted with results provided by molecular dynamics (MD) simulation techniques. To illustrate the power of these 'difference' methods, reference will be made to the alkali group of ions, all of which have been successfully investigated by the above methods, with the exception of the radioactive element francium. Additional comments will be made on how NDIS measurements are currently being combined with MD simulations to determine the structure around complex ions and molecules, many of which are common in biological systems.

Ions↗

PubMed2006

Thermoluminescence behaviour of KCL(1-x)Br(x):Pb2+ exposed to gamma radiation.

The thermoluminescence (TL) behaviour of solid solutions of lead doped KCl(1-x)Br(x) (X = 0.02, 0.35, 0.50, 0.65, 0.85, 1) mixed crystals exposed to gamma radiation at different doses from 60Co is reported. The TL glow curves of KCl(1-x)Br(x):Pb2+ crystal exposed in the range of 0-140 Gy is strongly dependent on composition X. The maximum temperature of the main TL glow peak was found to shift towards lower temperatures as composition X increased and a significant enhancement of the TL efficiency in KCl(1-x)Br(x):Pb2+ was found for X = 0.50 which is attributed to an increase in the vacancy concentration of the mixed halides at middle composition. The participation of the F-centre in the TL phenomenon particularly related to the main TL glow peak observed in mixed samples was also confirmed.

Bromides↗

PubMed2006

Spontaneous symmetry-breaking vortex lattice transitions in pure niobium.

We report an extensive investigation of magnetic vortex lattice (VL) structures in single crystals of pure niobium with the magnetic field applied parallel to a fourfold symmetry axis, so as to induce frustration between the cubic crystal symmetry and hexagonal VL coordination expected in an isotropic situation. We observe new VL structures and phase transitions; all the VL phases observed (including those with an exactly square unit cell) spontaneously break some crystal symmetry. One phase even has the lowest possible symmetry of a two-dimensional Bravais lattice. This is quite unlike the situation in high-Tc or borocarbide superconductors, where VL structures orient along particular directions of high crystal symmetry. The causes of this behavior are discussed.

Journal Article↗

PubMed2006

Pinning-depinning of the contact line on nanorough surfaces.

We study the pinning-depinning phenomenon of a contact line on a solid surface decorated by a random array of nanometric structures. For this purpose, we have investigated the contact angle hysteresis behaviour of six different wetting and non-wetting fluids with surface tensions varying from 25 to 72mN m(-1). For low values of the areal density of defects phi(d), the hysteresis H increases linearly with phi(d) indicating that "individual" defects pin the contact line. Then, from a given value of phi(d), the hysteresis H becomes to decrease with increasing phi(d), indicating a new kind of collective depinning. These two regimes were observed for all fluids used. In both cases, our experimental results are compared with the theoretical predictions for contact angle hysteresis induced by single or multiple topographical defects. We ascribe the decrease of H to the formation of cavities along the wetting front.

Computer Simulation↗

PubMed2006

Melatonin inhibits both ER alpha activation and breast cancer cell proliferation induced by a metalloestrogen, cadmium.

Cadmium (Cd) is a heavy metal affecting human health both through environmental and occupational exposure. There is evidence that Cd accumulates in several organs and is carcinogenic to humans. In vivo, Cd mimics the effect of estrogens in the uterus and mammary gland. In estrogen-responsive breast cancer cell lines, Cd stimulates proliferation and can also activate the estrogen receptor independent of estradiol. The ability of this metalloestrogen to increase gene expression in MCF7 cells is blocked by anti-estrogens suggesting that the activity of these compounds is mediated by ER alpha. The aims of this work were to test whether melatonin inhibits Cd-induced proliferation in MCF7 cells, and also to study whether melatonin specifically inhibits Cd-induced ER alpha transactivation. We show that melatonin prevents the Cd-induced growth of synchronized MCF7 breast cancer cells. In transient transfection experiments, we prove that both ER alpha- and ER beta-mediated transcription are stimulated by Cd. Melatonin is a specific inhibitor of Cd-induced ER alpha-mediated transcription in both estrogen response elements (ERE)- and AP1-containing promoters, whereas ER beta-mediated transcription is not inhibited by the pineal indole. Moreover, the mutant ER alpha-(K302G, K303G), unable to bind calmodulin, is activated by Cd but becomes insensitive to melatonin treatment. These results proved that melatonin inhibits MCF7 cell growth induced by Cd and abolishes the stimulatory effect of the heavy metal in cells expressing ER alpha at both ERE-luc and AP1-luc sites. We can infer from these experiments that melatonin regulates Cd-induced transcription in both ERE- and AP1 pathways. These results also reinforce the hypothesis of the anti-estrogenic properties of melatonin as a valuable tool in breast cancer therapies.

Breast Neoplasms↗

PubMed2006

Adolescents anticipated experience of screening for genital herpes.

Screening asymptomatic adolescents for genital herpes will require sensitivity to adolescents' developmental needs. Twenty-four adolescents (age range 1619 years) were interviewed to explore their perceptions of screening. In general, adolescents thought screening for genital herpes would be viewed as taking care of themselves, although there were concerns that their peers might view getting screened as implying that the adolescent was infected or sexually promiscuous. Most adolescents expected their parents to respond positively, but typically thought that younger adolescents should obtain parental consent for screening, and that adolescents should inform their parents of positive test results. Adolescents wanted to be screened in settings that provided confidentiality and by non-judgemental care providers, but they differed on the setting which they believed would accomplish this. Some recommended mass screening (for example, screening all of those in a certain year at school), presumably as a way to reduce embarrassment and/or stigma. Screening programmes that are adolescent-friendly and accessible, and address adolescents' specific concerns regarding managing the information, can be created.

Adolescent↗

PubMed2005

An anomalous x-ray diffraction study of the hydration structures of Cs+ and I- in concentrated solutions.

Anomalous x-ray diffraction experiments were carried out on concentrated aqueous solutions of sodium iodide (6 molal) and cesium iodide (3 molal). Data were gathered at two energies below the absorption edges of the Cs+ and I- ions in order to avoid contributions from fluorescence. The statistics and quality of the raw data were improved by the use of a focusing analyzer crystal. Differences were taken between the data sets and used to calculate the hydration structures of Cs+ and I-. The structures found are more complex than anticipated for such large ions with relatively low charge densities and show evidence of ion-pair formation in both solutions. A two-Gaussian fit to the Cs+ data gives information about the Cs+-O and Cs+-I- correlations. The central position of the Gaussian representing the Cs+-O was fixed at 3.00 A, that is, the maximum of this contribution. The other parameters were allowed to vary freely, giving a Cs+-I- distance of 3.84+/-0.05 A and coordination numbers of 7.9 and 2.7, respectively, for the Cs+-O and Cs+-I- correlations. The results on the structure of I- in the 6 molal NaI aqueous solution were also fitted to a model based on Gaussians; this gives correlations for I- -O and I- -Na+ at 3.17+/-0.06 and 3.76+/-0.06 A with respective coordination numbers of 8.8 and 1.6. The structure of I- in the 3 molal CsI solution shows overlapping contributions due to I- -H, I- -O, and I- -Cs+. The best Gaussian fit gives two peaks centered at 3.00+/-0.08 and 3.82+/-0.04 A and shows that the latter two correlations are unresolved. The hydration structures are compared with those of other alkali and halide ions. The results are also found to be in good agreement with those obtained from standard x-ray diffraction and computer simulation.

Cesium↗

PubMed2005

Polyglycine expansions in eRF3/GSPT1 are associated with gastric cancer susceptibility.

Gastric cancer remains a major cause of death in the developed countries, and a large percentage is still genetically unexplained. Because of their major role in cell survival, mutations in translation factors and altered expression of these genes have been associated with cancer development. Apart from its role in translation termination, the eukaryotic translation release factor 3 (eRF3) is involved in several critical cellular processes, such as cell cycle regulation, cytoskeleton organization and apoptosis. The aim of this study was to evaluate eRF3/GSPT1 gene as a potential genetic susceptibility associated locus for gastric cancer, analysing a stable GGC expansion in exon 1 encoding a polyglycine tract in the N-terminal domain of the protein. DNA was obtained from 139 patients with gastric cancer and from 100 individuals of a healthy control population. The GGC expansion was amplified by PCR and the number of repeats determined by genotyping in an automatic sequencer. There are five known alleles encoding from 8 to 12 glycines. The most common allele encodes 10 glycines. The 12-Gly allele was detected exclusively in the cancer patients (allelic frequency = 5%). Regardless of the genotype, patients with the 12-Gly allele had a 20-fold increased risk for gastric cancer. We also detected a single-base alteration in the gene (G274T) although no correlation with cancer development has been found. Thus, our results show that the GGC expansion may have a potential role in regulating eRF3/GSPT1 expression and/or changing the protein function that can lead to gastric cancer development.

Adenocarcinoma↗

PubMed2005

Polyinosinic acid induces TNF and NO production as well as NF-kappaB and AP-1 transcriptional activation in the monocytemacrophage cell line RAW 264.7.

OBJECTIVE: This study evaluates the poly inosinic acid (poly I)-induced activation in the murine monocytemacrophage cell line RAW 264.7, which led to an inflammatory phenotype. MATERIAL: RAW 264.7, and WEHI 164 cell lines were used. RESULTS: The activation process is characterized by the acquisition of a mature macrophage morphology and the production of inflammatory mediators tumor necrosis factor (TNF) and nitric oxide (NO). The activation by poly I has distinctive features. Thus, poly I induced an increase in nuclear factor kappaB (NF-kappaB) transcriptional activity due to a long-term degradation of inhibitory NF-kappaB (IkappaB) beta while lipopolysaccharide (LPS) induced the degradation of both IkappaBalpha and IkappaBbeta. Poly I also induced an increase in activator protein 1 (AP-1) transcriptional activity, possibly due to the activation of the mitogen activated protein kinases (MAPKs) ERK, Jun N terminal kinase (JNK) and p38. Dextran sulphate (DS) efficiently inhibited the activation induced by poly I including the production of the inflammatory mediators. Dextran sulphate also inhibited AP-1 and NF-kappaB transcriptional activities in poly I-stimulated cells. RAW 264.7 cells express macrophage scavenger receptor 1 (Msr1) type I and Msr1 type II that are differently up-regulated upon treatment with poly I. CONCLUSIONS: The results presented demonstrate that the well-known blocker of scavenger receptors poly I activates macrophages to produce TNF and NO, triggering specific signal transduction pathways.

Animals↗

PubMed2005

Benefits of omalizumab as add-on therapy in patients with severe persistent asthma who are inadequately controlled despite best available therapy (GINA 2002 step 4 treatment): INNOVATE.

BACKGROUND: Patients with severe persistent asthma who are inadequately controlled despite Global Initiative for Asthma (GINA) 2002 step 4 therapy are a challenging population with significant unmet medical need. We determined the effect of omalizumab on clinically significant asthma exacerbations (requiring systemic corticosteroids) in the first omalizumab study to exclusively enrol patients from this difficult-to-treat patient population. METHODS: Following a run-in phase, patients (12-75 years) inadequately controlled despite therapy with high-dose inhaled corticosteroids (ICS) and long-acting beta(2)-agonists (LABA) with reduced lung function and a recent history of clinically significant exacerbations were randomized to receive omalizumab or placebo for 28 weeks in a double-blind, parallel-group, multicentre study. RESULTS: A total of 419 patients were included in the efficacy analyses. The clinically significant asthma exacerbation rate (primary efficacy variable), adjusted for an observed relevant imbalance in history of clinically significant asthma exacerbations, was 0.68 with omalizumab and 0.91 with placebo (26% reduction) during the 28-week treatment phase (P = 0.042). Without adjustment, a similar magnitude of effect was seen (19% reduction), but this did not reach statistical significance. Omalizumab significantly reduced severe asthma exacerbation rate (0.24 vs 0.48, P = 0.002) and emergency visit rate (0.24 vs 0.43, P = 0.038). Omalizumab significantly improved asthma-related quality of life, morning peak expiratory flow and asthma symptom scores. The incidence of adverse events was similar between treatment groups. CONCLUSIONS: In patients with inadequately controlled severe persistent asthma, despite high-dose ICS and LABA therapy, and often additional therapy, omalizumab significantly reduced the rate of clinically significant asthma exacerbations, severe exacerbations and emergency visits. Omalizumab is effective and should be considered as add-on therapy for patients with inadequately controlled severe persistent asthma who have a significant unmet need despite best available therapy.

Administration, Inhalation↗

PubMed2005

Differential expression of the eukaryotic release factor 3 (eRF3/GSPT1) according to gastric cancer histological types.

BACKGROUND: There are now several lines of evidence to suggest that protein synthesis and translation factors are involved in the regulation of cell proliferation and cancer development. AIMS: To investigate gene expression patterns of eukaryotic releasing factor 3 (eRF3) in gastric cancer. METHODS: RNA was prepared from 25 gastric tumour biopsies and adjacent non-neoplastic mucosa. Real time TaqMan reverse transcription polymerase chain reaction (RT-PCR) was performed to measure the relative gene expression levels. DNA was isolated from tumour and normal tissues and gene dosage was determined by a quantitative real time PCR using SYBR Green dye. RESULTS: Different histological types of gastric tumours were analysed and nine of the 25 tumours revealed eRF3/GSPT1 overexpression; moreover, eight of the 12 intestinal type carcinomas analysed overexpressed the gene, whereas eRF3/GSPT1 was overexpressed in only one of the 10 diffuse type carcinomas (Kruskal-Wallis Test; p < 0.05). No correlation was found between ploidy and transcript expression levels of eRF3/GSPT1. Overexpression of eRF3/GSPT1 was not associated with increased translation rates because the upregulation of eRF3/GSPT1 did not correlate with increased eRF1 levels. CONCLUSIONS: Overexpression of eRF3/GSPT1 in intestinal type gastric tumours may lead to an increase in the translation efficiency of specific oncogenic transcripts. Alternatively, eRF3/GSPT1 may be involved in tumorigenesis as a result of its non-translational roles, namely (dis)regulating the cell cycle, apoptosis, or transcription.

Adult↗

PubMed2004

Protein-caloric food restriction affects insulin-like growth factor system in fetal Wistar rat.

We have previously shown that fetuses from protein-caloric undernourished pregnant rats (35% of control diet during the last week of pregnancy) at 21.5 d post coitum exhibit increased beta-cell mass. This alteration is correlated with increased insulinemia and total pancreatic insulin content, a pattern similar to that reported in infants of mild diabetic mothers. In this work, we investigated in undernourished fetuses: 1) whether availability of growth factors such as insulin, GH, and IGFs and their binding proteins (IGFBPs) could be implicated in this alteration, and 2) the beta-cell mitogenic response to IGFs in vitro. The results show that maternal undernutrition increases pancreatic IGF-I expression and islet IGF-I receptor content in undernourished fetuses, whereas hepatic IGF-I expression and serum IGF-I levels were decreased. No changes were observed in serum IGF-II, and its expression was diminished in undernourished pancreases and unchanged in the liver, compared with control fetuses. Serum levels and liver and pancreatic mRNA expression of IGFBP-1 were found to be normal in undernourished fetuses, whereas the serum concentration and abundance of IGFBP-2 mRNA in pancreas were increased. Finally, the beta-cell mitogenic response to IGFs in vitro was significantly increased in undernourished fetal islets, compared with controls. In conclusion, in undernourished fetuses the increased beta-cell mass can be related to the stimulation of replicative beta-cell response due to locally increased pancreatic IGF-I mRNA; this effect is perhaps potentiated or favored by the enhanced islet IGF-I receptor content and pancreatic IGFBP-2 gene expression.

Animals↗

PubMed2004

[DNA extraction using Chelex resin for oncogenic amplification analysis in head and neck tumours].

DNA extraction from tissues can be the most laborious and complex step in amplifying DNA by PCR when phenol-choroform procedure is used. We compare this lengthy, slow and expensive extraction method with other two based in the use of Chelex-100 resin. This chelating resin has been applied for extracting DNA from different tissues to use with the PCR. These procedures are simple, rapid and do not require multiple steps. In this study we compared DNA extraction from 30 head and neck squamous cell carcinomas (HNSCC) using organic solvent precipitation, Chelex 100 resin with and without proteinase K pretreatment. The results show that proteinase K-Chelex 100 procedure is as efficient as the phenol-chloroform one.

Carcinoma, Squamous Cell↗

PubMed2003

Age-dependent adaptation of the liver thyroid status and recovery of serum levels and hepatic insulin-like growth factor-I expression in neonatal and adult diabetic rats.

The effect of treatment with thyroxine (T(4)) on the hepatic deiodinase (5'D-I) activity and triiodothyronine (T(3)) content and on insulin-like growth factor-I (IGF-I) secretion and mRNA hepatic expression were studied in neonatal and adult diabetic (D) rats and compared with 4 thyroidectomized (Tx) groups: neonatal and adult Tx rats treated or not with T(4). Serum T(3) and T(4) decreased by 92% in both Tx populations and by 80% to 70% in D adults according to the severity of diabetes: -70 mg/kg body weight (BW) (D(70)) or 50 mg/kg BW (D(50)) of streptozotocin (STZ) injected, whereas only a 30% to 33% decrease was found in D neonates. A similar decrease of liver 5'D-I activity and T(3) concentrations was found in neonatal and adult Tx rats, whereas a significant reduction in those parameters was observed only in adult diabetics, either D(70) or D(50), but not in D neonates. Serum levels and liver mRNA expression of IGF-I determined by ribonuclease protection assay, plasma and pituitary growth hormone (GH), plasma insulin, and glycemia were also measured in both D populations. A decrease in circulating IGF-I, previously reported for Tx adult rats, was also found in both D populations. T(4) treatment recovered IGF-I and liver T(3) in both Tx groups and D neonates, but not in D adults. These results show an age-dependent adaptation of the liver thyroid economy in diabetes, as hepatic 5'D-I does not respond to diabetes in neonates and IGF-I is insensitive to T(4) treatment in adult diabetics and suggest a positive correlation between hepatic T(3) content and IGF-I expression in conditions of diabetes and Tx.

Adaptation, Physiological↗

PubMed2002

Effects of early undernutrition on the brain insulin-like growth factor-I system.

Undernutrition reduces circulating concentrations of insulin-like growth factor (IGF)-I, but how it affects the brain IGF system, especially during development, is largely unknown. We have studied IGF-I, IGF-II, IGF receptor and IGF binding protein (BP)-2 mRNA expression in the hypothalamus, cerebellum and cerebral cortex of neonatal rats that were food restricted beginning on gestational day 16. One group was refed starting on postnatal day 14. Rats were killed on postnatal day 8 or 22. Undernutrition did not produce an overall reduction in brain weight at either age but, at 22 days, both the cerebellum and hypothalamus weighed significantly less. At 8 days, no change was detected in the central IGF axis in response to undernutrition. However, in 22-day-old undernourished rats, IGF-I and IGF receptor mRNA expression were increased in both the hypothalamus and cerebellum, while IGFBP-2 was decreased, but only in the hypothalamus. Refeeding had no effect on any of these parameters. These results suggest that the hypothalamus and cerebellum respond to malnutrition and the decrease in circulating IGF-I, a peptide fundamental for growth and development, by increasing the local production of both the growth factor and its receptor in attempt to maintain normal development.

Animals↗

PubMed2002

The importance of educational and psychological factors in Parkinson's disease quality of life.

OBJECTIVE: To define the factors correlated with quality of life (QoL) in patients with idiopathic Parkinson's disease (PD). BACKGROUND: PD has a substantial impact on QoL. Although several clinical factors have been associated with QoL in PD, the influence of patient's education still remains controversial. METHODOLOGY: A consecutive series of patients with PD were examined using the unified Parkinson's Disease Rating Scale (UPDRS part I, II, III), Schwab and England (SE), and Hoehn and Yahr stage (H&Y). QoL was rated with the PDQ-39, cognition with the Mini-Mental State examination (MMSE), and the presence of depressive symptoms with the geriatric depression scale (GDS). Patient's characteristics, estimated cumulative levodopa dose (CLD), UPDRS, H&Y, MMSE and GDS were correlated with the PDQ-39 using univariate and multiple regression analysis. RESULTS: A total of one hundred 58 patients (68 men, 90 women) with a mean age of 65.6 +/- 9.3 years, PD duration of 8.1 +/- 10.6 years, and education of 6.6 +/- 3.9 years were included. The mean PDQ-39 was 48.8 +/- 27.8, mean MMSE was 25.7 +/- 4, and mean GDS was 11.7 +/- 6.8. Using stepwise multiple regression analysis, the most important predictive factors were depression, UPDRS part I, UPDRS part II, and educational background, which accounted for a 61% of the variability of the PDQ-39 scores. CONCLUSIONS: In our PD sample, educational, behavioural, and psychological factors influenced life satisfaction more than physical ones.

Aged↗

PubMed2002

Influence of hypothyroidism on circulating concentrations and liver expression of IGF-binding proteins mRNA from neonatal and adult rats.

The aim of this work was to study the influence of the endocrine balance between thyroid hormones, insulin and growth hormone (GH) on the regulation of insulin-like growth factor binding proteins (IGFBPs), complementing a study previously reported for insulin-like growth factors (IGFs) in similar populations. Serum concentrations of IGFBPs-1 to -3 were assayed by Western ligand blot and their mRNA expression in the liver assayed by RNase protection assay in the hypothyroid populations: thyroidectomized and mercapto-1-methylimidazole (MMI)-treated neonates, and thyroidectomized adult rats at different periods after thyroidectomy. Serum concentrations of insulin, GH and IGF-I were increased in thyroidectomized neonates and decreased in the other populations. IGFBPs-1 and -2 increased 79% and 50% respectively in thyroidectomized neonatal rats compared with control at 15 days after thyroidectomy, whereas only IGFBP-2 increased (87%) in MMI-treated neonates, which had low serum insulin and GH compared with control on the same days. In thyroidectomized adult rats, IGFBPs-1 and -2 decreased 60% compared with controls on all days studied. Furthermore, when streptozotocin was administered to thyroidectomized neonates and insulin was given to thyroidectomized adult rats to restore insulin to control values in both groups, a differential regulation was found for IGFBPs-1 and -2. The transcriptionally induced decrease in IGFBP-3 (20-25% compared with control in neonates and 50% in adult rats), however, seemed to be regulated by GH and IGF-I. The similarity of changes in IGFBPs found in hypothyroid, undernourished and streptozotocin-induced diabetic neonatal rats suggests that the regulatory effect of insulin or GH on the IGFBPs requires the reduced biologically active thyroid hormone that is found in these three populations.

Animals↗

PubMed2001

The need for youth-oriented policies and programmes on responsible sexuality in Argentina.

Since the mid-1990s, several provincial bills have been passed in Argentina mandating the creation of programmes for family planning and sexual health services and education. A National Plan for Integrated Health Care for Adolescents was also passed but resources and actual programmes remain limited. The policy process has been fraught with difficulties, owing to a strong alliance between the State and the Catholic church. Provision of contraceptives to adolescents has been one of the most contentious issues, as adolescents are legally minors and need parental permission to use family planning. NGOs are working with young people to help them to voice their perspectives and demands. The Programme for Responsible Sexuality was launched by the Province of Buenos Aires in 1999, in response to concrete demands on the part of poor communities for sexual and reproductive health services, including for young people. This Programme came to an abrupt end with the change of governor in that same year, illustrating the complexity of the policy-making process. These experiences demonstrate the urgency to develop strategies and set up task forces for effective advocacy of health and social programmes, and to make political leaders more aware of the social costs of refusing to support these.

Adolescent↗