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Biomedical subjects

A Carvajal

Publications and source records attributed to A Carvajal.

At least 19 recordsLinked to original sources
PubMed2005

Progesterone pre-treatment potentiates EGF pathway signaling in the breast cancer cell line ZR-75.

Progesterone in hormone replacement therapy (HRT) preparations increases, while hysterectomy greatly reduces, the incidence of breast cancer. Cross-talk between the progesterone and growth factor signaling pathways occurs at multiple levels and this maybe a key factor in breast cancer survival and progression. To test this hypothesis, we characterized the effect of progesterone pre-treatment on the sensitization of the epidermal growth factor (EGF) signaling pathway to EGF in the breast cancer cell line ZR-75. For the first time in ZR-75 cells and in agreement with previous work using synthetic progestins, we demonstrate that pre-treatment with the natural ligand progesterone increases EGF receptor (EGFR) levels and subsequent ligand-dependent phosphorylation. Downstream we demonstrate that progesterone alone increases erk-1 + 2 phosphorylation, potentiates EGF-phosphorylated erk-1 + 2 and maintains these levels elevated for 24 h; over 20 h longer than in vehicle treated cells. Additionally, progesterone increased the levels of STAT5, another component of the EGF signaling cascade. Progesterone increased EGF mediated transcription of a c-fos promoter reporter and the nuclear localization of the native c-fos protein. Furthermore, progesterone and EGF both alone and in combination, significantly increase cell proliferation. Several results presented herein demonstrate the conformity between the action of the natural ligand progesterone with that of synthetic progestins such as MPA and R5020 and allows the postulation that the progestin/progesterone-dependent increase of EGF signaling provides a survival advantage to burgeoning cancer cells and may contribute to the breast cancer risk associated with endogenous progesterone and with progestin-containing HRT.

Breast Neoplasms↗
PubMed2003

Large changes in Pluto's atmosphere as revealed by recent stellar occultations.

Pluto's tenuous nitrogen atmosphere was first detected by the imprint left on the light curve of a star that was occulted by the planet in 1985 (ref. 1), and studied more extensively during a second occultation event in 1988 (refs 2-6). These events are, however, quite rare and Pluto's atmosphere remains poorly understood, as in particular the planet has not yet been visited by a spacecraft. Here we report data from the first occultations by Pluto since 1988. We find that, during the intervening 14 years, there seems to have been a doubling of the atmospheric pressure, a probable seasonal effect on Pluto.

Journal Article↗
PubMed2003

Antimigraine drug consumption in Spain (1990-2000).

OBJECTIVES: New marketed antimigraine drugs (triptans) are promising in the management of migraine pain. The impact of these new drugs on the overall consumption of the antimigraine drugs merits an analysis. MATERIAL AND METHODS: The package units of antimigraine drugs, sold and reimbursed by the Spanish National Health System, are used for estimations. Data are presented as defined daily doses per 10,000 inhabitants/day. RESULTS: During the 1990-2000 period, antimigraine drug utilization as a whole decreased by more than 25%; triptan use increased while ergot alkaloids' declined. CONCLUSIONS: The pattern of antimigraine drug utilization in Spain has changed noticeably in accordance with recent recommendations.

Adrenergic Agonists↗
PubMed2002

Isotype-specific antibody-secreting cells in systemic and mucosal associated lymphoid tissues and antibody responses in serum of conventional pigs inoculated with PEDV.

An enzyme-linked immunospot (ELISPOT) has been developed to detect porcine epidemic diarrhea virus (PEDV)-specific antibody secreting cells (ASC) in gut associated lymphoid tissues (duodenum and ileum lamina propria and mesenteric lymph nodes) and systemic locations (spleen and blood) of conventional pigs so as to characterise the mucosal and systemic antibody response generated by the infection with PEDV. A total number of 28 eleven-day-old conventional pigs were orally inoculated with the field isolate of the PEDV strain CV-777. Diarrhea was observed in 32% of the pigs and virus shedding was demonstrated in 100% between postinoculation day (PID) 1 and 8. Serum IgG and IgA antibodies to PEDV were detected by isotype ELISA from PID 12 and 15, respectively, reaching maximum values at PID 32 (IgG) and 21 (IgA). PEDV specific IgM ASC occurred in all the tissues between PID 4 and 7, with the strongest response in the intestinal lamina propria. IgA and IgG ASC responses were evident in the intestinal lymphoid tissues from PID 21, the highest number of specific ASC corresponded to the duodenum lamina propria. In the systemic lymphoid tissues the number of IgG and IgA ASC detected were lower than in the mucosal tissues, however, in the blood, presence of IgA ASC was constantly detected from PID 14 until the end of the experiment. Memory antibody response to the PEDV was also studied by secondary in vitro stimulation of the mononuclear cells (MNC) isolated from mesenteric lymph nodes, spleen and blood. The memory B cell response was prominent at PID 21 and 25 and consisted in IgG and IgA ASC. To our knowledge, this is the first report to research into the presence and distribution of specific ASC in different locations of the systemic and the gut associated lymphoid tissues after a PEDV infection as well as the presence of memory B cells.

Animals↗
PubMed2002

Mucosal and systemic isotype-specific antibody responses and protection in conventional pigs exposed to virulent or attenuated porcine epidemic diarrhoea virus.

Eleven-day-old conventionally reared piglets were inoculated orally with two different doses of the cell-culture adapted strain CV-777 of the porcine epidemic diarrhoea virus (PEDV) or the virulent isolate of the same strain and challenged with the same virulent PEDV 3 weeks later. Pigs inoculated with the two doses of the attenuated virus did not show any typical sign of the disease, and virus shedding was not frequent. In contrast, 31% of pigs exposed to the virulent PEDV developed diarrhoea and virus shedding was demonstrated in 100%. At different postinoculation day (PID) and postchallenge day (PCD) virus-specific antibody-secreting cells (ASC) in gut associated lymphoid tissues (duodenum and ileum lamina propria and mesenteric lymph nodes) and systemic locations (blood and spleen) were assessed by enzyme-linked immunospot (ELISPOT). Only a small response was detected in the groups inoculated with attenuated PEDV, whereas in the group previously exposed to the virulent virus on PID 21 a large number of IgG and IgA ASC was detected. Isotype-specific antibody responses in serum were investigated by ELISA. IgG responses were detected in all groups, although the highest response corresponded to the group inoculated with virulent virus and only this group showed an IgA response. The pigs exposed to virulent PEDV were completely protected against the challenge with a higher dose of the same virulent virus on PID 21 and none of them shed the virus. The pigs inoculated with the attenuated strain were partially protected against the challenge, and 25% of the low dose- and 50% of the high dose-exposed pigs did not shed virus after challenge. All the pigs from a control group, not previously exposed to the virus, excreted the virus in faeces. A strong positive correlation was established between protection and the ASC responses detected in gut associated lymphoid tissues and blood at the challenge day and also between protection and serum isotype-specific antibody titers on that day. In addition, the IgA and IgG ASC responses detected in the blood on PID 21 also correlated with the responses found in the gut associated lymphoid tissues. The ASC and serum antibody responses after the challenge corresponded to a secondary immune response in the groups inoculated with attenuated virus, whereas a primary response was evident in the control group. No increase was seen in any of the parameters studied in the pigs inoculated with virulent PEDV.

Animals↗
PubMed2002

Lymphoproliferative responses and protection in conventional piglets inoculated orally with virulent or attenuated porcine epidemic diarrhoea virus.

Lymphocyte proliferative responses were evaluated in mucosal (mesenteric lymph nodes) and systemic (spleen and blood) lymphoid tissues of conventional piglets inoculated with the virulent or attenuated isolates of porcine epidemic diarrhoea virus (PEDV) strain CV-777 and challenged 21 days later with the virulent isolate of the same virus. A lymphoproliferative assay was developed in which mononuclear cells isolated from lymphoid tissues at different postinoculation and postchallenge days underwent a secondary in vitro stimulation with semipurified antigen obtained from PEDV-infected cell cultures. Vigorous lymphocyte proliferative responses were detected in the pigs inoculated with the virulent PEDV at postinoculation days 4-21, especially in the mesenteric lymph nodes and the blood; however, in the spleen this response was lower and less regular. The pigs inoculated with the attenuated virus showed a less intense response, the higher lymphocyte proliferation also corresponded to the mononuclear cells from mesenteric lymph nodes. Lymphocyte proliferation responses showed high correlations with protection against homologous challenge with virulent PEDV, and this correlation was higher in the gut associated lymphoid tissues (mesenteric lymph nodes). The cell proliferation response detected in blood mirrored that detected in the mesenteric lymph nodes, and showed also good correlation with protection. The results confirm that T-cell-helper function, assessed by lymphocyte proliferation responses, contributes to establishing a protective immune response against PEDV infections.

Animals↗
PubMed2002

Lactic acidosis, potassium, and the heart rate deflection point in professional road cyclists.

OBJECTIVE: To determine the influence of lactic acidosis, the Bohr effect, and exercise induced hyperkalaemia on the occurrence of the heart rate deflection point (HRDP) in elite (professional) cyclists. METHODS: Sixteen professional male road cyclists (mean (SD) age 26 (1) years) performed a ramp test on a cycle ergometer (workload increases of 5 W/12 s, averaging 25 W/min). Heart rate (HR), gas exchange parameters, and blood variables (lactate, pH, P(50) of the oxyhaemoglobin dissociation curve, and K(+)) were measured during the tests. RESULTS: A HRDP was shown in 56% of subjects at about 88% of their maximal HR (HRDP group; n = 9) but was linear in the rest (No-HRDP group; n = 7). In the HRDP group, the slope of the HR-workload regression line above the HRDP correlated inversely with levels of K(+) at the maximal power output (r = -0.67; p<0.05). CONCLUSIONS: The HRDP phenomenon is associated, at least partly, with exercise induced hyperkalaemia.

Acidosis, Lactic↗
PubMed2001

Availability of medicines in the European Union: results from the EURO-Medicines project.

OBJECTIVE: There is at present no comprehensive directory of medicines available in European countries. Such a directory would be valuable to policy analysts, clinicians, regulatory agencies, pharmaceutical companies and consumer groups. The aim of this project was to compile such a directory of all medicines marketed in each of the European Union member countries. METHODS: Lists of medicines for each country, compiled from several national sources, classified by Anatomical-Chemical-Therapeutic (ATC) code. Census date was late 1998. RESULTS: A comprehensive directory was created using data from 14 of the 15 European Union countries. Numbers of trade names and of active ingredients varied widely, from Germany with 18,554 and 1,973, respectively, to Denmark with 1,915 and 1,016, respectively. In individual therapeutic areas, there were variations in the numbers of active ingredients available: the least variation between countries was in antineoplastic medicines (ATC code L, maximum number available in any country 101, minimum 60) and wider variation in alimentary (ATC code A, maximum 256. minimum 103) or cardiovascular (ATC code C, maximum 269, minimum 112). Only 7% of all the active ingredients were available in all the countries studied. The Scandinavian countries had the greatest proportion of active ingredients (60%) available in all other countries. Each country had a number of active ingredients available only in that country Italy had the largest number of these. CONCLUSIONS: The directory illustrates the wide variations in the availability of medicines across the European Union. The range of drugs available in each country represents differences in regulatory and market policies, as well as cultural and historic differences. This directory lends itself to many further analyses.

Data Collection↗
PubMed2000

Effect of nicorandil upon different guinea-pig and rat isolated organ preparations in vitro.

A study of the effect of nicorandil (N-2-(hydroxyethyl)nicotinamide nitrate, CAS 65141-46-0), a potassium channel and guanylatecyclase activator, upon preparations of rat was deferens and uterus, and guinea pig ileum was performed. Nicorandil does not modify rat isolated was deferens responses to noradrenaline (norepinephrine) and potassium. The drug exerts a non-competitive antagonist effect upon rat isolated uterus response to serotonin, histamine, oxytocin, and, at high concentrations, inhibits guinea-pig isolated ileum responses to acetylcholine, histamine, 4-aminopyridine and potassium.

Acetylcholine↗
PubMed2000

Efficacy of fenfluramine and dexfenfluramine in the treatment of obesity: a meta-analysis.

A meta-analysis was conducted to estimate the difference of weight loss among patients treated with placebo and with fenfluramine or dexfenfluramine after 1, 2, 3, 6, and 12 months of treatment. Placebo-controlled, double-blind, randomized clinical trials, whose results were presented as weight loss by the placebo group and the drug-treated patient group, were selected for the analysis. For the pooled estimations, the method of the weighted means by the inverse of the variance was used. The association between the difference of means and several predictive variables was studied by means of weighted linear regression. Patients treated with fenfluramine or dexfenfluramine achieved a higher weight loss than those receiving placebo in all the periods studied. The greatest efficacy was observed after 3 months of treatment. Beyond this time, there is a decline in the effectiveness. Based on the efficacy data, treatments longer than 3 months would not be justified.

Appetite Depressants↗
PubMed2000

Heart rate response during incremental exercise in master runners.

We analyzed the kinetics of heart rate (HR) response during incremental treadmill exercise in thirteen master runners (62 +/- 1 yr). The HR/running speed (HR/S) relationship showed the existence of a point of downward deflection (HR(d)) in only approximately 31% of the subjects. Resting echocardiographic evaluations showed similar heart dimensions in all of the subjects. In conclusion, HR does not seem to show a curvilinear response (downward deflection) in most aged athletes.

Aged↗