Biomedical subjects

M Segura

Publications and source records attributed to M Segura.

At least 19 recordsLinked to original sources

PubMed2007

High prevalence of human papillomavirus 16 in penile carcinoma.

In order to analyze the incidence and prevalence of Human Papillomavirus (HPV) in penile carcinoma, we studied 49 patients with penile carcinoma. Formalin-fixed, paraffin-embedded tissue samples were collected from 64 samples of penile carcinoma from the Hospital General Universitario (Albacete, Spain). Cases were histologically classified and the polymerase chain reaction (PCR) method was used to detect the presence of HPV. Two sets of consensus primers were used, the My09/My11, and the GP5+/GP6+. All positive cases were sequenced in order to establish the implicated genotype. Our results showed that 38 of the 49 cases were positive for HPV (77,5%). HPV16 appeared in 32 (84,2 %) of the 38 positive cases and HPV18 in 4 (10,5%). Our data demonstrate that the My09/My11 primers are more sensitive than GP5+/GP6+ primers, although the combination of the two sets of primers notably increased the total number of HPV positive cases detected.

Carcinoma, Squamous Cell↗

PubMed2006

Cassini encounters Enceladus: background and the discovery of a south polar hot spot.

The Cassini spacecraft completed three close flybys of Saturn's enigmatic moon Enceladus between February and July 2005. On the third and closest flyby, on 14 July 2005, multiple Cassini instruments detected evidence for ongoing endogenic activity in a region centered on Enceladus' south pole. The polar region is the source of a plume of gas and dust, which probably emanates from prominent warm troughs seen on the surface. Cassini's Composite Infrared Spectrometer (CIRS) detected 3 to 7 gigawatts of thermal emission from the south polar troughs at temperatures up to 145 kelvin or higher, making Enceladus only the third known solid planetary body-after Earth and Io-that is sufficiently geologically active for its internal heat to be detected by remote sensing. If the plume is generated by the sublimation of water ice and if the sublimation source is visible to CIRS, then sublimation temperatures of at least 180 kelvin are required.

Extraterrestrial Environment↗

PubMed2006

Distribution of killer-cell immunoglobulin-like receptor (KIR) in Comoros and Southeast France.

Killer-cell immunoglobulin-like receptors (KIRs) expressed by natural killer cells are cell surface molecules able to recognize groups of HLA class I alleles. The number and distribution of KIR genes vary among individuals and populations. The aim of this study is to analyse the KIR gene content in a Comorian population in order to investigate genetic relationships with other populations and to reconstruct past migration events. The Comorian population consisted of 54 unrelated immigrants living in France and a control population consisted of 38 individuals from Southeast France. We investigated the presence or absence of 15 KIR genes, two pseudogenes expressed and non-expressed forms of KIR2DL5 and the two major subtype full-length and deleted forms of KIR2DS4. All individuals were typed positive for the framework genes, i.e. KIR2DL4, KIR3DL2 and KIR3DL3, and the two pseudogenes KIR3DP1 and KIR2DP1. The frequencies of full-length KIR2DS4 (*00101/00102/002) were lower in the French population (F = 29%) than in the Comorian population (F = 72%) (P(c) < 0.05). No significant differences were found for other KIR genes. A total of 11 genotypes were identified in the Southeast French population and 22 genotypes in the Comorian population. The most common genotype (2DL1, 2DL3, 2DL4, 3DL1, 3DL2, 3DL3 and 2DS4) accounted for 41% in the Comorian population and 34% in the Southeast French population. Principal component analysis using KIR gene data from 20 populations was performed to determine genetic differences and relations between populations. The Comorian population exhibited closest kinship with Africans and Asians. As KIR gene content is heterogeneous among ethnic groups, it can probably be used to assess the genetic relationships among populations from different geographic areas.

Comoros↗

PubMed2006

Efficacy and potential for resistance selection of antipseudomonal treatments in a mouse model of lung infection by hypermutable Pseudomonas aeruginosa.

Hypermutable Pseudomonas aeruginosa strains are found with high frequency in the lungs of patients with chronic infections and are associated with high antibiotic resistance rates. The in vivo consequences of hypermutation for treatment in a mouse model of lung infection using strain PAO1 and its hypermutable derivative PAOdeltamutS are investigated. Groups of 30 mice were treated for 3 days with humanized regimens of ciprofloxacin (CIP), tobramycin (TOB), CIP plus TOB, or placebo, and mortality, total lung bacterial load, and 4x- and 16x-MIC mutants were recorded. The rates of mutation and the initial in vivo frequencies of mutants (at the onset of treatment) were also estimated and the in vitro- and in vivo-selected mutants characterized. Since both strains had identical MICs, the same pharmacokinetic/pharmacodynamic (PK/PD) parameters were obtained: area under the 24-h concentration-time curve (fAUC)/MIC = 385 for CIP and maximum concentration of drug in serum (fC(max))/MIC = 19 for TOB. Despite adequate PK/PD parameters, persistence of high bacterial numbers and amplification (50,000-fold) of resistant mutants (MexCD-OprJ hyperexpression) were documented with CIP treatment for PAOdeltamutS, in contrast to complete resistance suppression for PAO1 (P < 0.01), showing that conventional PK/PD parameters may not be applicable to infections by hypermutable strains. On the other hand, the efficacy of TOB monotherapy in terms of mortality reduction and bacterial load was very low regardless of the strain but not due to resistance development, since mutants were not selected for PAO1 and were only modestly amplified for PAOdeltamutS. Finally, the CIP-plus-TOB combination was synergistic, further reducing mortality and bacterial load and completely preventing resistance even for PAOdeltamutS (P < 0.01 compared to monotherapy), showing that it is possible to suppress resistance selection in infections by hypermutable P. aeruginosa using appropriate combined regimens.

Animals↗

PubMed2003

Up-regulation of ICAM-1, CD11a/CD18 and CD11c/CD18 on human THP-1 monocytes stimulated by Streptococcus suis serotype 2.

Streptococcus suis serotype 2 is known to be a major pathogen of swine, causing mainly meningitis. It is also a zoonotic agent leading predominantly to meningitis in humans working in close contact with pigs. In this study, we investigated the ability of S. suis to up-regulate the expression of adhesion molecules involved in inflammation, using an enzyme-linked immunosorbent assay. S. suis serotype 2 stimulated the up-regulation of the expression of intercellular adhesion molecule-1 (ICAM-1, CD54), CD11a/CD18 and CD11c/CD18 on human THP-1 monocytes, but did not change that of ICAM-1, vascular cell adhesion molecule-1 (VCAM-1, CD106) and E-selectin (CD62E) on human endothelial cells. The up-regulation of adhesion molecules was time- and bacterial concentration-dependent, and cell wall components were largely responsible for such stimulation. To a lesser extent, purified haemolysin of S. suis also stimulated adhesion molecule expression. Stimulation of monocytes with strains of different origin showed that there was no clear tendency for human strains to induce a higher expression of adhesion molecules than strains from diseased pigs. Finally, monocytes stimulated with S. suis also showed an increase in adherence to endothelial cells. Hence, S. suis is capable of up-regulating important adhesion molecules involved in inflammation, which may result in an increased leucocyte recruitment into sites of infection, thus providing a possible mechanism for some of the inflammatory features of meningitis caused by this pathogen.

Antigens, CD↗

PubMed2002

High-performance liquid chromatography with electrochemical detection applied to the analysis of 3,4-dihydroxymethamphetamine in human plasma and urine.

Metabolic activation in the disposition of 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") has been implicated in some of its pharmacological and toxicological effects, with the major metabolite 3,4-dihydroxymethamphetamine (HHMA) as a putative toxicant through the formation of thioether adducts. We describe the first validated method for HHMA determination based on acid hydrolysis of plasma and urine samples, further extraction by a solid-phase strong cation-exchange resin (SCX, benzenesulfonic acid), and analysis of extracts by high-performance liquid chromatography with electrochemical detection. The chromatographic separation was performed in an n-butyl-silane (C4) column and the mobile phase was a mixture of 0.1 M sodium acetate containing 0.1 M 1-octanesulphonic acid and 4 mM EDTA (pH 3.1) and acetonitrile (82:18, v/v). Compounds were monitored with an electrochemical cell (working potentials 1 and 2, +0.05 and +0.35 V, respectively, gain 60 microA). A mobile phase conditioning cell with a potential set at +0.40 V was connected between the pumping system and the injector. Calibration curves were linear within the working concentration ranges of 50-1000 microg/L for urine and plasma. Limits of detection and quantification were 10.5 and 31.8 microg/L for urine and 9.2 and 28.2 microg/L for plasma. Recoveries for HHMA and DHBA (3,4-dihydroxybenzylamine, internal standard) were close to 50% for both biological matrices. Intermediate precision and inter-day accuracy were within 3.9-6.5% and 7.4-15.3% for urine and 5.0-10.8% and 9.2-13.4% for plasma.

Calibration↗

PubMed2002

CD14-dependent and -independent cytokine and chemokine production by human THP-1 monocytes stimulated by Streptococcus suis capsular type 2.

Streptococcus suis capsular type 2 is an important aetiologic agent of swine meningitis, and it has been highlighted as a cause of occupational disease leading to meningitis and fulminant sepsis in humans. The objective of the present work was to study the ability of S. suis type 2 to induce the release of tumour necrosis factor alpha (TNF-alpha), interleukin-1 (IL-1), IL-6, IL-8 and monocyte chemotactic protein one (MCP-1) by human monocytic THP-1 cells. The induction of these five cytokines was dose- and incubation time-dependent, and it was significantly enhanced by pre-treatment of cells with interferon gamma. IL-8 levels were markedly higher compared with those obtained with the other cytokines. However, elevated levels of MCP-1 and IL-6 were also observed. Levels of cytokine induced by heat-killed or live bacteria were similar. Pre-treatment of cells with anti-CD14 monoclonal antibodies suggested that this important host receptor is partially implicated in TNF, IL-1, IL-6 and MCP-1 production, while CD14-independent pathways seem to be responsible for IL-8 production after S. suis stimulation. In addition, blocking studies with anti-TNF and anti-IL-1 antibodies revealed that these cytokines are involved in amplification of the S. suis-induced cytokine cascade. When several different S. suis strains of human or porcine origin were compared, a very heterogeneous pattern of cytokine production was observed. Human strains did not exhibit a clear tendency to induce higher cytokine release by human THP-1 monocytes. The synergistic effect of the up-regulation of cytokines during S. suis meningitis may mediate many of the inflammatory reactions, including the sequestration of leucocytes at the site of infection.

Animals↗

PubMed2001

3,4-Dihydroxymethamphetamine (HHMA). A major in vivo 3,4-methylenedioxymethamphetamine (MDMA) metabolite in humans.

There is evidence that some heavy users of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) show signs of neurotoxicity (a cognitive dysfunction, a larger incidence of psychopathology). It has been postulated that the catechol intermediates of methylenedioxyamphetamines such as 3,4-dihydroxymethamphetamine (HHMA), a metabolite of MDMA, may play a role in their neurotoxicity by formation of thioether adducts. This study describes the first validated method for HHMA determination in plasma and urine by strong cation-exchange solid-phase extraction high-performance liquid chromatography/electrochemical detection (HPLC/ED) analysis. The method has been applied for the determination of HHMA in plasma and urine samples from a clinical study in healthy volunteers of MDMA and provides preliminary kinetic data on this metabolite. HHMA appeared to be a major MDMA metabolite with plasma concentrations as high as the parent compound. Thus, HHMA C(max) (154.5 microg/L) and AUC(0-24h)(1990.9 microg/L h) were similar to those obtained in previously published reports for MDMA (181.6 microg/L and 1465.9 microg/L h, respectively). The 24-h urinary recovery of HHMA accounted for 17.7% of the MDMA dose administered and increases the total 24 h recovery of MDMA and metabolites to 58% of the 100 mg dose administered. The determination of HHMA in plasma and urine samples is of interest in order to establish its relevance in MDMA metabolism and its possible contribution to MDMA neurotoxicity in humans. Its validation showed appropriate accuracy and precision for its use in pharmacokinetic studies.

Adult↗

PubMed2001

Analytical methodology for the detection of benzodiazepine consumption in opioid-dependent subjects.

Benzodiazepines are frequently abused by heroin users, but not all compounds have shown the same abuse liability. We developed an analytical method that was able to detect various benzodiazepine compounds in a single run. Enzymatically hydrolyzed urine underwent a liquid-liquid extraction procedure with chloroform/isopropanol (9:1) at pH 8-9 followed by a solid-liquid clean-up (Bond Elut TCA C18) to obtain appropriate extracts for HPLC analysis. Mobile phase composition was optimized by means of the linear solvation energy relationship methodology based on Reichardt's normalized solvatochromic parameter (E(T)N). The method was validated for the simultaneous detection and quantitation of alprazolam, alpha-hydroxyalprazolam, oxazepam, 7-aminoflunitrazepam, flunitrazepam, nordiazepam, lorazepam, and diazepam. The prevalence of benzodiazepine consumption in 229 opioid-dependent subjects on methadone-maintenance treatment was 48%. Oxazepam and nordiazepam were the benzodiazepines most frequently recoved in urine samples. The prevalence of alprazolam use (40%) was higher than that of flunitrazepam (10%).

Adult↗

PubMed2000

The pathogenesis of the meningitis caused by Streptococcus suis: the unresolved questions.

Streptococcus suis is one of the most important swine pathogens world-wide. Among the serotypes described, type 2 is the serotype most frequently associated with disease. Despite increasing research in recent years, knowledge of virulence factors and the pathogenesis of the infection remain limited. This review discusses the currently available information on S. suis serotype 2 virulence factors and the pathogenesis of the meningitis caused by this important bacterial species. In addition, some hypotheses on the critical steps of the infection, such as bacterial invasion from mucosal surfaces to the bloodstream, survival of bacteria in blood, and invasion from blood into the central nervous system, are presented. Finally, the role that the stimulation of the immune system of animals (inflammatory reaction) could play during infection is also discussed. A complete understanding of the cell-interacting pathways that S. suis may follow inside the host could give important insights into the progression of disease. Further studies to delineate the mechanisms through which S. suis induces meningitis will contribute to the development of potential therapies for S. suis infections.

Animals↗

PubMed2000

Immunohistochemical expression of Bcl-2, Bax and cytochrome c following focal cerebral ischemia and effect of hypothermia in rat.

Recent studies suggest that mild hypothermia significantly alleviate damage following cerebral ischemia though the precise mechanism is poorly defined. In the present study, middle cerebral artery occlusion (MCAo) was induced in Sprague-Dawley (SD) rats for 1 h followed by varying periods of reperfusion. Cerebral infarcts identified by hematoxylin & eosin (H&E) staining revealed extensive lesion in normothermic (NT) 37 degrees C and small lesion in hypothermic (HT) 33 degrees C group of rats. Immunohistochemical analysis revealed Bcl-2 was induced in many neurons of HT group, while Bax and cytochrome c was induced in few neurons. In situ detection of DNA fragmentation using 3'-OH end labeling method (terminal dUTP nick-end labelling (TUNEL)) indicated, higher number of TUNEL-positive cells in NT group, but significantly decreased in HT group. The expression pattern revealed many neurons at the penumbra region could survive in HT group whereas, many neurons are committed to die in NT group. Our results suggest that hypothermia is selectively interfering at more than one place and providing protection.

Animals↗

PubMed2000

A close-up look at Io from Galileo's near-infrared mapping spectrometer.

Infrared spectral images of Jupiter's volcanic moon Io, acquired during the October and November 1999 and February 2000 flybys of the Galileo spacecraft, were used to study the thermal structure and sulfur dioxide distribution of active volcanoes. Loki Patera, the solar system's most powerful known volcano, exhibits large expanses of dark, cooling lava on its caldera floor. Prometheus, the site of long-lived plume activity, has two major areas of thermal emission, which support ideas of plume migration. Sulfur dioxide deposits were mapped at local scales and show a more complex relationship to surface colors than previously thought, indicating the presence of other sulfur compounds.

Extraterrestrial Environment↗

PubMed2000

Feasibility study prior to the certification of trace elements in urban and industrial wastewater reference materials.

Reliable results for the determination of trace elements in urban and industrial wastewaters are of paramount importance for both checking the performance of sewage treatment and for detecting possible urban or industrial contamination sources. The quality control of measurements should in principle rely on external tools such as certified reference materials (CRM), which should represent, as closely as possible, the matrix of samples currently analysed, e.g., in the frame of environmental monitoring. To date, however, no CRM representatives of wastewater composition are available, which limits the possibility for control laboratories to check their QC externally. To fill this gap, the European Commission's Standards, Measurements and Testing Programme (formerly BCR) has started a European collaborative project of which the aim is to test the feasibility of preparation of wastewater reference materials and the analytical state-of-the-art to enable the certification of trace elements in such matrices. This paper presents the results of the first phase of this project, namely the feasibility study and the results of an interlaboratory trial.

Certification↗

PubMed1999

Heat-killed Streptococcus suis capsular type 2 strains stimulate tumor necrosis factor alpha and interleukin-6 production by murine macrophages.

Streptococcus suis capsular type 2 is an important etiological agent of swine meningitis, and it is also a zoonotic agent. Since mononuclear phagocytes have been suggested to play a central role in the pathogenesis of meningitis, the objective of the present study was to evaluate the capacity of whole killed S. suis type 2 organisms to induce the release of the proinflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and interleukin-6 (IL-6) by murine macrophages. Induction of cytokines was evaluated in the presence or absence of phorbol ester (phorbol 12-myristate 13-acetate [PMA]) costimulation. Results showed that S. suis type 2 stimulated the production of both cytokines in a concentration- and time-dependent fashion. Although large doses of bacteria were required for maximal cytokine release, titers were similar to those obtained with the lipopolysaccharide (LPS) positive control. An increase in cytokine release was observed with both S. suis and LPS with PMA costimulation. Experiments with cytochalasin-treated macrophages showed that the stimulation of cytokine production was phagocytosis independent. When macrophages were stimulated with an unencapsulated mutant, an increase in TNF production was observed, but the absence of the capsule had no effect on IL-6 production. In fact, whereas purified capsular polysaccharide of S. suis failed to induce cytokine release, purified S. suis cell wall induced both TNF and, to a lesser extent, IL-6. IL-6 secretion probably requires some distinct stimuli which differ from those of TNF. Finally, the S. suis putative virulence factors suilysin and extracellular protein EF showed no cytokine-stimulating activity. The ability of S. suis to trigger macrophages to produce proinflammatory cytokines may have an important role in the initiation and development of meningitis caused by this microorganism.

Animals↗

PubMed1999

Factors determining analgesic and sedative drug requirements during extracorporeal shock wave lithotripsy.

PURPOSE: The aim of this study was to determine what factors influence the analgesic and sedative requirements during extracorporeal shock wave lithotripsy (ESWL). MATERIALS AND METHODS: A retrospective study was carried out on 2,103 lithotripsy treatments performed over a 7-year period using an electromagnetic lithotriptor. Treatment with analgesics and anxiolytic drugs administered during ESWL was evaluated, and two new variables to determine the analgesic and sedative requirements were defined. A multivariant analysis model was established to determine which variables are related to or could predict the analgesic and/or sedative drug requirements. RESULTS: The most frequently used sedative drug was potassium chlorazepate which was used in 2,059 patients at a mean total dose of 25.6 mg. Pethidine was used in 2, 006 patients at a mean total dose of 56.3 mg, and fentanyl in 995 patients at a dose of 93.3 microg. In 52.4% of patients analgesic requirements were low, and in 76.6% sedative requirements were low. In 21.1% of patients analgesic drug requirements were high, and in 1. 8% of patients sedative drug requirements were high. The multivariant analysis showed that those requiring most analgesics were, the younger patients (p = 0.003), those who received a higher number of shock waves (p < 0.001) and those who needed more sedation (p < 0.001). Those who received the greatest amount of sedatives were women (p = 0.0026); younger patients (p < 0.001); those treated with higher voltages (p = 0.032), and patients with the highest analgesic requirements (p < 0.001). CONCLUSIONS: Predicting the analgesic drug requirements prior to ESWL is very difficult. The present study shows that young age, a greater discharge of shock waves and a high sedative drug requirement are factors clearly related to greater analgesic drug requirements. Higher sedative drug requirements are needed by women, younger patients, those receiving high discharge voltages and those with higher analgesic requirements.

Adult↗

PubMed1998

Avirulence and immunogenicity in mice of a bovine mastitis Staphylococcus aureus mutant.

An avirulent mutant, designated RC122, was derived from Staphylococcus aureus bovine mastitis strain RC108 after N-methyl-N'-nitro-N-nitrosoguanidine mutagenesis. Mutant RC122, which was isolated on the basis of reduced colony size, showed diminished virulence in mice (LD50 of RC122: 3.1 x 10(10) cfu vs LD50 of RC108: 2.3 x 10(7) cfu). Mutant RC122 grew more slowly than its parental strain and showed decreased production of several exoproteins, such as alpha- and beta-hemolysin, DNAse and coagulase. The production of its capsule was induced only under in vivo growth conditions. Clearance studies performed in the mouse kidney revealed that the kinetics of disappearance of the mutant was similar to that of its parental strain. Protection experiments carried out by intraperitoneal administration in mice showed that mutant RC122 conferred a good degree of protection from challenge with homologous and heterologous strains.

Animals↗

PubMed1997

Organics and other molecules in the surfaces of Callisto and Ganymede.

Five absorption features are reported at wavelengths of 3.4, 3.88, 4. 05, 4.25, and 4.57 micrometers in the surface materials of the Galilean satellites Callisto and Ganymede from analysis of reflectance spectra returned by the Galileo mission near-infrared mapping spectrometer. Candidate materials include CO2, organic materials (such as tholins containing C(triple bond)N and C-H), SO2, and compounds containing an SH-functional group; CO2, SO2, and perhaps cyanogen [(CN)2] may be present within the surface material itself as collections of a few molecules each. The spectra indicate that the primary surface constituents are water ice and hydrated minerals.

Carbon Dioxide↗

PubMed1997

Prevention of catheter sepsis: the hub.

The prevention of catheter sepsis lies in a sound understanding of the routes through which catheters get contaminated. The catheter hub has been recognized as a portal for microorganisms causing catheter sepsis, particularly in central venous catheters inserted for > 1 wk. Bacteria and fungi may reach the internal surface of the catheter connector during manipulation by hospital staff and then colonize the entire lumen of the catheter. Endoluminal contamination has diagnostic, therapeutic, and preventive implications. Some traditional preventive approaches (site care, subcutaneous cuffs and tunnels, maximal aseptic barriers at the time of catheter insertion, and external antiseptic or antibiotic coating) may fail because they focus solely on the skin as a source of bacteria. Hub-related catheter sepsis can be prevented by aseptic hub manipulation, appropriate junction protection, and by reducing the number of catheter lumens, side ports, three-way stopcocks, and changes of the infusion sets. Needleless systems must be evaluated in terms of their safety in preventing endoluminal contamination. A new disinfecting catheter hub incorporating an antiseptic barrier has been developed and reduced hub-related catheter sepsis by more than 90%. The endoluminal route of intravascular catheter contamination must be taken into account when designing strategies for the diagnosis and prevention of catheter-related sepsis.

Asepsis↗