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Biomedical subjects

J M Vega

Publications and source records attributed to J M Vega.

At least 19 recordsLinked to original sources

Pharmacodynamic and pharmacokinetic effects of TPA023, a GABA(A) alpha(2,3) subtype-selective agonist, compared to lorazepam and placebo in healthy volunteers.

TPA023, a GABA(A) alpha2,3 alphasubtype-selective partial agonist, is expected to have comparable anxiolytic efficacy as benzodiazepines with reduced sedating effects. The compound lacks efficacy at the alpha1 subtype, which is believed to mediate these effects. This study investigated the effects of 0.5 and 1.5 mg TPA023 and compared them with placebo and lorazepam 2 mg (therapeutic anxiolytic dose). Twelve healthy male volunteers participated in this placebo-controlled, double-blind, double-dummy, four-way, cross-over study. Saccadic eye movements and visual analogue scales (VAS) were used to assess the sedative properties of TPA023. The effects on posturaL stability and cognition were assessed using body sway and a standardized battery of neurophysiological memory tests. Lorazepam caused a significant reduction in saccadic peak velocity, the VAS alertness score and impairment of memory and body sway. TPA023 had significant dose dependent effects on saccadic peak velocity (85 deg/sec maximum reduction at the higher dose) that approximated the effects of lorazepam. In contrast to lorazepam, TPA023 had no detectabLe effects on saccadic latency or inaccuracy. Also unlike lorazepam, TPA023 did not affect VAS alertness, memory or body sway. These results show that the effect profile of TPA023 differs markedly from that of lorazepam, at doses that were equipotent with regard to effects on saccadic peak veLocity. Contrary to lorazepam, TPA023 caused no detectable memory impairment or postural imbalance. These differences reflect the selectivity of TPA023 for different GABA(A) receptor subtypes.

Adult↗

Radiological clinical telesession: a cooperative working environment for sharing clinical experience over the Internet.

We describe here a six-year-long project during which groups of radiologists belonging to various hospitals in Extremadura (one of Spain's regions) shared their clinical experience over the Internet in a process of continuing medical education. We designed a set of tools based on the most familiar Internet protocols (the WWW and e-mail) that make computer-mediated communication very straightforward. Periodically, each group put forward a clinical case of interest, presenting it on a Web page. The other participating groups discussed the case (in real or deferred time), describing the radiological findings, proposing a differential diagnosis, and making suggestions concerning the case. The clinical case was subsequently resolved by the proposing group on the basis of definitive diagnostic tests, and posted for public access on the Internet as a teaching file to form part of a cases-of-interest archive. As of present, more than 65 cases have been presented and discussed, and 55 posted as teaching files. At about halfway through the project, the participants were asked to respond to a questionnaire. In their responses, they indicated a high degree of acceptance of the system, finding no special difficulties in the use of the tools. They also reported having incorporated some of the procedures (consultation of clinical cases on Internet, access to information specifically targeted at radiologists, consulting specialist literature, etc.) into their work habits.

Cooperative Behavior↗

Enhancement of photorespiration in immobilized Chlamydomonas reinhardtii cells.

Immobilization of Chlamydomonas reinhardtii in alginate increases its photorespiration rate. In the immobilized cells, the photorespiratory enzyme, phosphoglycolate phosphatase, was 75% higher than in freely suspended cells. Thus, the immobilized cells produced glycolate at twice the rate than in freely suspended cells when treated with aminooxyacetate (a transaminase inhibitor). With immobilized cells in a batch reactor, 270 micromol glycolate mg(-1) Chl was produced after 12 h.

Animals↗

Influence of immobilization parameters on growth and lactic acid production by Streptococcus thermophilus and Lactobacillus bulgaricus co-immobilized in calcium alginate gel beads.

Streptococcus thermophilus and Lactobacillus bulgaricus were co-immobilized in different systems with varying calcium (0.1-1.5 M) and alginate (1-2%, w/v) concentrations. Highest lactic acid production was 35 g l(-1) when both bacteria were in high viscosity beads (1%, w/v alginate) hardened in 0.1 M CaCl2 . The gel bead composition affected size and distribution of entrapped lactic acid bacteria.

Alginates↗

Isolation and characterization of Tha p 1, a major allergen from the pine processionary caterpillar Thaumetopoea pityocampa.

BACKGROUND: Pine processionary caterpillars induce dermatitis by a toxic-irritative mechanism. The existence of true allergic reactions to allergens from these caterpillars has been recently demonstrated by positive immediate skin prick tests and specific IgE determination by immunoblotting using crude larval extracts. The aim of this work was to purify allergens from the crude larval extract in order to characterize IgE-binding proteins from these caterpillars. METHODS: Allergens were separated by ethanol gradient fractionation and reversed phase HPLC. The N-terminal amino acid sequence of a selected allergen was obtained after SDS-PAGE and transfer. The clinical relevance of this allergen was measured using sera from patients allergic to caterpillar. RESULTS: An allergen with a molecular weight close to 15 kDa was purified. It was recognized by 9 out of 11 allergic patients (82%). Its N-terminal amino acid sequence had no homologies to any other protein already described in data bases. For this reason, no information about its biological function could be obtained. CONCLUSIONS: This 15-kDa IgE-binding protein is a major caterpillar allergen and shows no homologies to other insect allergens already described.

Allergens↗

Cutaneous reactions to pine processionary caterpillar (Thaumetopoea pityocampa) in pediatric population.

Cutaneous lesions caused by pine processionary caterpillar (Thaumetopoea pityocampa, TP) are frequent in pinewood areas. However, no epidemiological studies have been performed so far in the pediatric population. In this study, we evaluated the relevance of reactions to pine processionary caterpillar in the pediatric population of our environment and determined the possible role of an IgE-mediated mechanism. A questionnaire was developed and given to 1,101 children and adolescents ranging from 3 to 17 years of age from rural areas with large pine forests. A total of 653 questionnaires were answered by the children or their parents. The search for immunoglobulin E (IgE)-mediated cases was based on the presence of a suspected reaction to caterpillar and confirmed by in vivo (skin prick) and in vitro (immunoblotting) tests. Sixty of the 653 people interviewed (9.18%) identified a cutaneous reaction from exposure to the processionary caterpillar. Within this group only four cases (6.7%) were because of an IgE-mediated mechanism. The predominant clinical feature of these patients with allergy to caterpillar was contact urticaria. We present the first study of cutaneous reactions to pine processionary caterpillar in a large pediatric population. This is a frequent pathology in pinery zones and only in a minority of the cases are because of an IgE-mediated allergic mechanism. This fact contrasts with studies in adults, where this percentage is much greater.

Adolescent↗

Pine processionary caterpillar allergenicity increases during larval development.

BACKGROUND: In European countries, pine processionary caterpillar (Thaumetopoea pityocampa) is one of the species of Lepidoptera able to affect humans. Its allergenicity has been demonstrated in previous studies. However, in all of them larval extract in the fifth stage of development has been used as antigen. Therefore, allergenicity of other larval stages was unknown. The objective of our study was to detect allergenic changes of pine processionary caterpillar during larval development. METHODS: Pine processionary caterpillar extracts in all larval stages were analyzed by SDS-PAGE. Immunoblotting was performed using patient sera with suggestive history of allergy and a positive prick test.

Allergens↗

Control of Rayleigh-Taylor instability by vertical vibration in large aspect ratio containers.

We consider a horizontal heavy fluid layer supported by a light, immiscible one in a wide (as compared to depth) container, which is vertically vibrated intending to counterbalance the Rayleigh-Taylor instability of the flat, rigid-body vibrating state. In the simplest case when the density and viscosity of the lighter fluid are small compared to their counterparts in the heavier fluid, we apply a long wave, weakly nonlinear analysis that yields a generalized Cahn-Hilliard equation for the evolution of the fluid interface. This equation shows that the stabilizing effect of vibration is like that of surface tension, and is used to analyze the linear stability of the flat state, the local bifurcation at the instability threshold and some global existence and stability properties concerning the steady states without dry spots. The analysis is extended to two cases of practical interest. Namely, (a) the viscosity of one of the fluids is much smaller than that of the other one, and (b) the densities and viscosities of both fluids are quite close to each other.

Journal Article↗

Assessment of a preclinical training system with indirect vision for dental education.

The aim of the present study is the evaluation of a pre-clinical training system using indirect vision for dental education purposes. The study population was undergraduate dental students between the ages of 18-20, at the beginning of their first dental course. From a total of 105 students, those presenting some condition that would have had influence on their manual skills and those who for some circumstance left the study after beginning it were excluded, resulting in 69 students (51 female and 18 male) taking part in the study. The study design involved two sessions separated by a 7-day interval in which the students used a reflection box to develop psychomotor skills in mirror use. In every session they performed an initial evaluation test, some training exercises and a final evaluation test. The evaluation tests and the training exercises consisted in following a curved, straight or convoluted shape in the reflection box. Four groups of students were used who trained in different ways using curved or straight lines. Evaluation of the tests was based on the number of errors made and the time to completion. All students showed an improvement in their performance of following curved and straight lines with indirect vision after this form of training. The results after the first training session were statistically significant, while the further improvement was not significant after the 2nd training session. Those students who trained first with curved lines and later with straight lines produced more errors than the other groups. Female students performed better than male students in this assessment.

Adolescent↗

Early introduction of cereals into children's diets as a risk-factor for grass pollen asthma.

BACKGROUND: The prevalence of asthma has increased from the 1950s to the 1990s. The relationship between diet and asthma is an area of controversy that has never been fully evaluated. Attempts at dietary prevention of asthma have produced conflicting results. We have recently identified allergens from cereals that show cross-reactivity with proteins in grass pollen. An early intake of cereals in the diet during early life might cause IgE sensitization to cereals. It is not known whether such sensitization predisposes the development of allergy to pollen. METHODS: To test this hypothesis, a cross-sectional study and an observational case-control analysis of reviewed data were carried out on 16381 patients who had been admitted to our Allergy Unit between 1989 and 1999. All the patients underwent allergy tests to identify asthma risk-factors. All information in our data base was analysed using the SPSS computer system. RESULTS: There has been an increase of 7.8% in incidences of allergic asthma and a 7.3% increase in asthma due to grass pollen in the last decade. Grass-pollen asthma was associated with sensitization to cereals. The early introduction of cereals in the diet of children was found to be a risk factor for grass-pollen asthma (OR = 5.95; 95% CI 3.89-9.10). CONCLUSIONS: These findings document the progression of allergic asthma during a decade in a large sample of people who were influenced by similar environmental conditions and studied with the same diagnostic methods. This study represents the largest database of patients in which a common food is shown to be a risk factor for asthma.

Adult↗

Interactions between simvastatin and troglitazone or pioglitazone in healthy subjects.

Two randomized, two-period crossover studies were conducted to evaluate the effects of repeat oral dosing of troglitazone (Study I) and pioglitazone (Study II) on the pharmacokinetics of plasma HMG-CoA reductase inhibitors following multiple oral doses of simvastatin and of simvastatin on the plasma pharmacokinetics of troglitazone (Study I) in healthy subjects. In both studies, each subject received two treatments. Treatment A consisted of once-daily oral doses of troglitazone 400 mg (Study I) or pioglitazone 45 mg (Study II) for 24 days with coadministration of once-daily doses of simvastatin 40 mg (Study I) or 80 mg (Study II) on Days 15 through 24. Treatment B consisted of once-daily oral doses of simvastatin 40 mg (Study I) or 80 mg (Study II) for 10 days. In Study I, the area under the plasma concentration-time profiles (AUC) and maximum plasma concentrations (Cmax) of HMG-CoA reductase inhibitors in subjects who received both troglitazone and simvastatin were decreased modestly (by approximately 30% for Cmax and approximately 40% for AUC), but time to reach Cmax (tmax) did not change, as compared with those who received simvastatin alone. Simvastatin, administered orally as a 40 mg tablet daily for 10 days, did not affect the AUC or tmax (p > 0.5) but caused a small but clinically insignificant increase (approximately 25%) in Cmax for troglitazone. In Study II, pioglitazone, at the highest approved dose for clinical use, did not significantly alter any of the pharmacokinetic parameters (AUC, Cmax, and tmax) of simvastatin HMG-CoA reductase inhibitory activity. For all treatment regimens, side effects were mild and transient, suggesting that coadministration of simvastatin with either troglitazone or pioglitazone was well tolerated. The modest effect of troglitazone on simvastatin pharmacokinetics is in agreement with the suggestion that troglitazone is an inducer of CYP3A. The insignificant effect of simvastatin on troglitazone pharmacokinetics is consistent with the conclusion that simvastatin is not a significant inhibitor for drug-metabolizing enzymes. The lack of pharmacokinetic effect of pioglitazone on simvastatin supports the expectation that this combination may be used safely.

Administration, Oral↗

The cytosolic O-acetylserine(thiol)lyase gene is regulated by heavy metals and can function in cadmium tolerance.

Regulation of the expression of the cytosolic O-acetylserine(thiol)lyase gene (Atcys-3A) from Arabidopsis thaliana under heavy metal stress conditions has been investigated. Northern blot analysis of Atcys-3A expression shows a 7-fold induction after 18 h of cadmium treatment. Addition of 50 microm CdCl(2) to the irrigation medium of mature Arabidopsis plants induces a rapid accumulation of the mRNA throughout the leaf lamina, the root and stem cortex, and stem vascular tissues when compared with untreated plants, as observed by in situ hybridization. High pressure liquid chromatography analysis of GSH content shows a transient increase after 18 h of metal treatment. Our results are compatible with a high cysteine biosynthesis rate under heavy metal stress required for the synthesis of GSH and phytochelatins, which are involved in the plant detoxification mechanism. Arabidopsis-transformed plants overexpressing the Atcys-3A gene by up to 9-fold show increased tolerance to cadmium when grown in medium containing 250 microm CdCl(2), suggesting that increased cysteine availability is responsible for cadmium tolerance. In agreement with these results, exogenous addition of cystine can, to some extent, also favor the growth of wild-type plants in cadmium-containing medium. Cadmium accumulates to higher levels in leaves of tolerant transformed lines than in wild-type plants.

Adaptation, Physiological↗

Glutathione biosynthesis in Arabidopsis trichome cells.

In Arabidopsis thaliana, trichome cells are specialized unicellular structures with uncertain functions. Based on earlier observations that one of the genes involved in cysteine biosynthesis (Atcys-3A) is highly expressed in trichomes, we have extended our studies in trichome cells to determine their capacity for glutathione (GSH) biosynthesis. First, we have analyzed by in situ hybridization the tissue-specific expression of the genes Atcys-3A and sat5, which encode O-acetylserine(thio)lyase (OASTL) and serine acetyltransferase (SAT), respectively, as well as gsh1 and gsh2, which encode gamma-glutamylcysteine synthetase and glutathione synthetase, respectively. The four genes are highly expressed in leaf trichomes of Arabidopsis, and their mRNA accumulate to high levels. Second, we have directly measured cytoplasmic GSH concentration in intact cells by laser-scanning microscopy after labeling with monochlorobimane as a GSH-specific probe. From these measurements, cytosolic GSH concentrations of 238+/-25, 80+/-2, and 144+/-19 microM were estimated for trichome, basement, and epidermal cells, respectively. Taking into account the volume of the cells measured using stereological techniques, the trichomes have a total GSH content more than 300-fold higher than the basement and epidermal cells. Third, after NaCl treatment, GSH biosynthesis is markedly decreased in trichomes. Atcys-3A, sat5, gsh1, and gsh2 mRNA levels show a decrease in transcript abundance, and [GSH](cyt) is reduced to 47+/-5 microM. These results suggest the important physiological significance of trichome cells related to GSH biosynthesis and their possible role as a sink during detoxification processes.

Arabidopsis↗