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M Rubio

Publications and source records attributed to M Rubio.

At least 19 recordsLinked to original sources
PubMed2000

CD47 ligation selectively inhibits the development of human naive T cells into Th1 effectors.

The CD47 Ag, also named integrin-associated protein, was recently reported to regulate the production of IL-12 by human monocytes and dendritic cells. The present study shows that CD47 ligation by CD47 mAb in primary cultures of cord blood mononuclear cells inhibits IL-12-driven Th1 cell development, as revealed by the cytokine secretion profile at restimulation and IFN-gamma production at the single-cell level. F(ab')(2) fragments of CD47 mAb or the synthetic peptide 4N1K, corresponding to the CD47 binding site of thrombospondin, display the same activity. CD47 engagement does not change the phenotype of IL-12-primed cells from Th1 to Th2 or affect IL-4-induced Th2 cell development. Moreover, CD47 mAb inhibits IL-12- but not IL-4-induced IL-2 production as well as IFN-gamma in primary cultures, which was correlated with a decrease of the IL-12Rbeta2 chain expression. Inclusion of exogenous IL-2 at priming corrects IL-12R expression as well as the inhibition of Th1 cell development. The data thus underline the role of IL-2 in Th1 cell development and further suggest that targeting IL-2 and IL-12 simultaneously may have some therapeutic advantage in Th1 autoimmune diseases.

Adjuvants, Immunologic↗
PubMed2000

Human monocyte-derived dendritic cells induce naive T cell differentiation into T helper cell type 2 (Th2) or Th1/Th2 effectors. Role of stimulator/responder ratio.

The subset of dendritic cells (DCs) and the nature of the signal inducing DC maturation determine the capacity of DCs to generate polarized immune responses. In this study, we show that the ability of human monocyte-derived DCs (myeloid DC(1)) to promote T helper type 1 (Th1) or Th2 differentiation was also found to be critically dependent on stimulator/responder ratio. At a low ratio (1:300), mature DCs that have been differentiated after inflammatory (Staphylococcus aureus Cowan 1 or lipopolysaccharide) or T cell-dependent (CD40 ligand) stimulation induced naive T cells to become Th2 (interleukin [IL]-4(+), IL-5(+), interferon gamma) effectors. Th2 differentiation was dependent on B7-CD28 costimulation and enhanced by OX40-OX40 ligand interactions. However, high DC/T cell ratio (1:4) favored a mixed Th1/Th2 cell development. Thus, the fact that the same DC lineage stimulates polarized Th1 or Th2 responses may be relevant since it allows the antigen-presenting cells to initiate an appropriate response for the signal received at the peripheral sites. Controlling the number and the rate of DC migration to the T cell areas in lymphoid tissues may be important for the therapeutic use of DCs.

Animals↗
PubMed2000

A non-destructive method to determine the safranal content of saffron (Crocus sativus L.) by supercritical carbon dioxide extraction combined with high-performance liquid chromatography and gas chromatography.

A supercritical carbon dioxide extraction method to obtain selectively volatile compounds of saffron without sample destruction has been developed. The influence of both pressure and temperature was studied, 20 MPa and 100 degrees C being the best conditions to extract the total safranal content. A decrease in supercritical fluid density was shown to be a critical parameter for enhancing the extraction power of carbon dioxide. For all the assay conditions, the extracts mainly contained safranal and HTCC, as demonstrated by gas chromatography and high-performance liquid chromatography analyses. Both chromatographic methods were suitable for safranal quantification and showed excellent agreement. Supercritical extracts from five different saffron types were studied by high-performance liquid chromatography and their safranal contents were determined.

Chromatography↗
PubMed2000

Enhanced DNA binding and activation of transcription factors NF-kappa B and AP-1 by acetaldehyde in HEPG2 cells.

Because transcription factors NF-kappaB and activator protein-1 (AP-1) are known to regulate gene expression, we have analyzed the role of acetaldehyde in the activation of NF-kappaB and AP-1 in HepG2 cells. Binding activity and transactivation of NF-kappaB and AP-1 were determined by gel retardation assays and transfection of a luciferase reporter construct controlled by kappaB and AP-1 binding sites, respectively. Acetaldehyde enhanced the DNA binding of NF-kappaB and AP-1 by 1 and 4 h, respectively, increasing the kappaB- and AP-1-dependent luciferase expression. Supershift assays revealed the presence of NF-kappaB heterodimers p65/p50 and p50/p52, whereas nuclear c-Jun levels correlated with the DNA binding of AP-1. The enhanced binding of NF-kappaB to DNA by acetaldehyde in intact cells was accompanied by the proteolytic degradation of IkappaB-alpha. However, the addition of acetaldehyde to cytostolic extracts from untreated Hep G2 cells did not affect the DNA binding of AP-1 but activated the NF-kappaB heterodimer p65/p50 in the absence of IkappaB-alpha degradation. Preincubation of HepG2 cells with protein kinase C inhibitors abolished the enhanced DNA binding of NF-kappaB and AP-1 caused by acetaldehyde. Hence, these findings uncover a previously unrecognized role for acetaldehyde in the activation of NF-kappaB and AP-1, which may be of relevance in the alcohol-induced liver disease.

Acetaldehyde↗
PubMed2000

CD47 engagement inhibits cytokine production and maturation of human dendritic cells.

Upon encounter with bacterial products, immature dendritic cells (iDCs) release proinflammatory cytokines and develop into highly stimulatory mature DCs. In the present study, we show that human monocyte-derived DCs functionally express the CD47 Ag, a thrombospondin receptor. Intact or F(ab')2 of CD47 mAb suppress bacteria-induced production of IL-12, TNF-alpha, GM-CSF, and IL-6 by iDCs. 4N1K, a peptide derived from the CD47-binding site of thrombospondin, also inhibits cytokine release. The inhibition of IL-12 and TNF-alpha is IL-10-independent inasmuch as IL-10 production is down-modulated by CD47 mAb and blocking IL-10 mAb fails to restore cytokine levels. CD47 ligation counteracts the phenotypic and functional maturation of iDCs in that it prevents the up-regulation of costimulatory molecules, the loss of endocytic activity, and the acquisition of an increased capacity to stimulate T cell proliferation and IFN-gamma production. Interestingly, regardless of CD47 mAb treatment during DC maturation, mature DC restimulated by soluble CD40 ligand and IFN-gamma, to mimic DC/T interaction, produce less IL-12 and more IL-18 than iDCs. Finally, CD47 ligation on iDCs does not impair their capacity to phagocytose apoptotic cells. We conclude that following exposure to microorganisms, CD47 ligation may limit the intensity and duration of the inflammatory response by preventing inflammatory cytokine production by iDCs and favoring their maintenance in an immature state.

Antibodies, Monoclonal↗
PubMed2000

[Short-stay lung resection surgery].

We report a prospective study applying a short-stay lung resection program for all patients requiring such surgery with the aim of shortening mean hospital stay in our service (9.5 days) by half. All patients who underwent surgery from November 1998 to November 1999 requiring lung resection surgery were enrolled in the short-stay study, classified in two groups. Group A met the criteria for enrollment and a stay of 5 days was predicted. Group B were those who did not meet the criteria marked by the program and for whom a 5-day stay could not be predicted. Sixty-four patients were enrolled (25 in group A [39.1%] and 39 in group B [60.9%]). After application of the program, the mean stay for all 64 patients was 6.4 days, with group A patients staying a mean 5.3 days and group B patients staying a mean 7.1 days.

Aged↗
PubMed2000

[Features of patients with bronchial asthma seen at the emergency department of a referral hospital in a semirural area].

UNLABELLED: Bronchial asthma is a chronic disease whose prevalence and severity is increasing. Appropriate treatment of exacerbation seems to affect the subsequent course of disease. OBJECTIVES: To assess the extent of application of guidelines for treating exacerbations of asthma and to describe the clinical and epidemiological characteristics of patients. PATIENTS AND METHODS: All patients presenting with exacerbations to the emergency room of a referral hospital in a semi-rural area of Catalonia were enrolled consecutively. We recorded symptoms, function and treatment variables during the emergency and when the patient was stable, at which time we also administered the Asthma Quality of Life Questionnaire (AQLQ). RESULTS: Forty-seven percent of patients resided in rural villages. Seventy-one percent lived in the area served by our hospital. Of the remaining patients, 57% came from municipalities in the Baix Empordà area, 29% in Alt Empordà area and 14% in La Selva area. Seventy-one percent went to the hospital directly from home, 66% of them were in the province of Girona; 75% of those homes were within urban areas. Of the 29% who had been sent to the emergency room by a physician, 71% were from a rural area. The 119 asthma exacerbations treated (114 patients, 71 females, 42 +/- 23 years) accounted for 0.3% of all emergency room visits. The exacerbation was considered severe in 31%, moderate in 47% and mild in all remaining cases. Eighty-eight percent of patients had experienced an exacerbation before. Symptoms were often present before the attack, but nearly half the patients were receiving relatively inadequate medication. Peak expiratory flow and oxygen saturation were recorded in 70% of cases and both variables improved after initial treatment (250 +/- 97 to 349 +/- 92 l/min, p < 0.001; and 92 +/- 7 to 96 +/- 2%, p < 0.01, respectively). All patients received inhaled salbutamol, 44% inhaled corticosteroids and 73% intravenous corticosteroids. A quarter of the patients were admitted to the ward (0.4% of all admissions) and 4% were admitted to the intensive care unit. Patients stayed 8.8 +/- 1.4 h in the emergency room. When patients were stable, asthma was severe in 14%, moderate in 42%, mild but persistent in 27%, and occasional in 17%. The total score on the AQLQ was 13.8 +/- 11.1, with mood being the dimension with the highest score (5.1 +/- 4.9). This score, along with social restriction, were lowest in the group of patients with chronic airflow obstruction. CONCLUSIONS: Nearly half the patients were from rural villages most of which were located outside the zone served directly by our hospital. The preference for specialized medical attention would explain the percentage of patients seen who did not belong to the assigned area. Difficulty of access to the hospital from certain rural areas would account for the greater number of rural patients who had been referred by a physician. Clinical management and monitoring of asthmatic patients with exacerbation could be improved by greater diffusion and application of guidelines. It would be interesting to incorporate come sort of questionnaire on quality of life while taking a patient's history.

Adolescent↗
PubMed2000

Angiotensin-(1-7) does not affect norepinephrine neuronal uptake or catabolism in rat hypothalamus and atria.

1. Since we previously reported that angiotensin-(1-7) [Ang-(1-7)] increases or inhibits norepinephrine (NE) release in rat atria or hypothalamus, respectively, the present work was undertaken to investigate the effect of the heptapeptide on NE neuronal uptake and metabolism in atria and hypothalamus isolated from rats. 2. Ang II (1-10 microM) caused a decrease in neuronal NE uptake in both atria and hypothalami isolated from rats. On the contrary, tissues incubated with [3H]NE in the presence of 0.1-10 microM Ang-(1-7) showed no modification in [3H]NE content with respect to the control group, suggesting that the heptapeptide did not modify [3H]NE neuronal uptake. 3. To study the effect of the heptapeptide on NE catabolism, monoamine-oxidase (MAO) and catechol-O-methyltransferase (COMT) activities were determined. Pretreatment of the tissue with Ang-(1-7) (0.1-1.0 microM) showed a tendency to diminish MAO activity in rat atria, while no significant changes were observed in hypothalamic MAO activity. Moreover, the heptapeptide (0.1-1.0 microM) did not affect central COMT activity with respect to the control group. 4. Present results allow us to conclude that Ang-(1-7) interacts with noradrenergic neurotransmission by increasing or inhibiting NE release at the peripheral and central levels, respectively, without affecting either the neurotransmitter neuronal uptake or catabolism.

Angiotensin I↗
PubMed2000

The effect of a single intravenous dose of metamizol 2 g, ketorolac 30 mg and propacetamol 1 g on haemodynamic parameters and postoperative pain after heart surgery.

Although nonopiate analgesics may be particularly useful in the immediate postoperative period after major surgery, their use has been associated with haemodynamic adverse effects during postoperative pain treatment and in critically ill patients in intensive care. The effect of a single intravenous dose of metamizol (dipyrone) 2 g, ketorolac 30 mg and propacetamol 1 g on haemodynamic variables and pain control in the immediate postoperative period after heart surgery is compared. Seventy-two patients undergoing elective coronary and/or heart valve surgery, were included in a cohort study of 1-years duration (1998). After weaning from mechanical ventilation and extubation, haemodynamic variables and a 4-point verbal rating pain scale were asseseed at base-line and 60 min after the administration of a single doses of metamizol, ketorolac or propacetamol. The Student's t-test for paired samples was used to compare changes produced by the study medications. A significant, but small, decrease in radial artery blood pressure was observed in all treatment groups which had little clinical relevance; no vasodilator effects were observed and ventricular function showed only minor changes: propacetamol decreased cardiac index by 10% and a 15% decrease in right ventricular work was also observed. Metamizol and ketorolac produced a 10% decrease in the left ventricular work index. Pain scores showed a statistically significant decrease in all treatment groups. The analgesic effects of metamizol, ketorolac and propacetamol were not associated with a clinically significant impairment in haemodynamic function when administered to haemodynamically stable patients.

Acetaminophen↗
PubMed2000

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Journal Article↗
PubMed2000

Pleural SC5b-9: a test for identifying complicated parapneumonic effusions.

UNLABELLED: BACKGROUND AND OBJECTIVES We have tested whether the complement activation products SC5b-9 and C3a-desArg are useful to distinguish complicated (CPE) from uncomplicated parapneumonic effusions (UPE). DESIGN: A total of 66 patients were enrolled in the study: 5 with empyema, 19 with CPE, 12 with UPE, and 30 transudates who served as controls. SC5b-9 and C3a-desArg were measured by commercial ELISA tests, and their performances were evaluated using receiver operating characteristic (ROC) analysis. RESULTS: Patients with CPE had higher mean levels of pleural SC5b-9 (8,218 microg/l) and C3a-desArg (8,790 microg/l) than those with UPE (2,227 and 3,772 microg/l, respectively; p < 0.0001), whereas concentrations in the latter were comparable with controls for the SC5b-9 test. Empyemas had a wide range of pleural complement activation product values. Pleural SC5b-9 and C3a-desArg showed very high diagnostic accuracy in the diagnosis CPE (90.3 and 77.8%, respectively) when corresponding cutoff points of 2,000 and 4,000 microg/l were used. In a stepwise logistic regression analysis, the combination of SC5b-9 >/=2,000 microg/l, LDH >/=1,000 U/l and a pleural polymorphonuclear percentage >/=85% provided the highest discriminative power for the diagnosis of CPE (area under ROC curve 0.97). CONCLUSION: This pilot study suggests that measurement of pleural SC5b-9 can be useful in the workup of patients with a parapneumonic effusion in order to differentiate CPE from UPE.

Adult↗
PubMed2000

Habitually sleepy drivers have a high frequency of automobile crashes associated with respiratory disorders during sleep.

Sleepiness is a common cause of traffic crashes with a cost of billions of dollars per year. A recent study has found that 2 to 3% of drivers are habitually sleepy while driving. However, there has not been a controlled study to define the characteristics, driving performance, or automobile crash rate of habitually sleepy drivers. The prevalence of respiratory disorders during sleep, and whether these respiratory disorders contribute to the increased automobile crash frequency, is unknown in habitually sleepy drivers. We interviewed 4,002 randomly selected drivers to define the prevalence of drivers who are habitually sleepy while driving. We studied the habitually sleepy drivers and an age- and sex-matched control group of drivers. These studies included reporting of daytime sleepiness, automobile crashes, driving performance and sleep studies. Of the 4, 002 drivers interviewed, 145 (3.6%, confidence interval [CI] = 3.1 to 4.3) were habitually sleepy while driving. The habitually sleepy drivers reported a significantly higher frequency of auto crashes than control subjects (the adjusted odds ratio [OR] was 13.3, CI = 4. 1 to 43). The habitually sleepy drivers had a significantly higher prevalence of respiratory sleep disorders than control subjects. For a total respiratory events index (apneas, hypopneas, and other respiratory effort-related arousals) >/= 15 the adjusted OR was 6.0, CI = 1.1 to 32. In the habitually sleepy drivers group, the frequency of sleep apnea (apnea-hypopnea index) between subjects with or without auto crashes was not statistically different. However, if we consider total respiratory events index, this frequency of respiratory sleep disorders was significantly higher in subjects with automobile crashes (the adjusted OR for a total respiratory event index >/= 15 was 8.5, CI = 1.2 to 59). Habitually sleepy drivers are a large group of drivers (1 of 30 drivers) who are involved in several fold more automobile crashes than control subjects. As these excess auto crashes can be explained in part by the presence of respiratory disorders during sleep, which are treatable, many automobile crashes in these sleepy drivers may be preventable. Our findings suggest that asking about excessive sleepiness while driving may better predict which subjects with breathing disorders during sleep have crashes than asking about overall sleepiness.

Accidents, Traffic↗
PubMed2000

Usefulness of pleural complement activation products in differentiating tuberculosis and malignant effusions.

OBJECTIVE: To determine whether measurement of the complement activation products SC5b-9 and C3a-desArg in pleural fluid can reliably differentiate tuberculous from malignant pleural effusions. DESIGN: Twenty-four patients with tuberculous pleuritis, 29 with malignant pleural effusion, and 30 control subjects with transudates were enrolled in the study. SCSb-9 and C3a-desArg were measured in pleural fluid using commercial ELISA tests, and their performances were evaluated using receiver operating characteristic (ROC) analysis. RESULTS: Patients with tuberculous pleuritis had higher mean levels of pleural SC5b-9 (5052 microg/L) and C3a-desArg (7436 microg/L) than those with malignant effusions (1048 and 2835 microg/L, respectively), whereas only SC5b-9 concentrations in the latter were comparable with controls. The area under the ROC curve (AUC) was 0.84 for SC5b-9 and 0.81 for C3a-desArg. Pleural SC5b-9 showed an accuracy of 80.8%, compared with 78.8% for C3a-desArg, when cut-off points of 1500 and 4500 microg/L, respectively, were used. Using a stepwise logistic regression model, the combination of pleural SCSb-9 > or =1500 microg/L, age < or =35 years, and pleural monocyte percentage > or =90% provided the highest accuracy for tuberculous pleurisy (88.5%, AUC 0.95). CONCLUSION: This pilot study suggests that pleural SC5b-9 is clinically useful for differentiating tuberculous and malignant pleural effusions.

Adult↗
PubMed2000

S-adenosylmethionine prevents hepatic tocopherol depletion in carbon tetrachloride-injured rats.

In various experimental models, S-adenosylmethionine (SAMe) has been shown to reduce liver injury by preventing depletion of glutathione, one of the antioxidant systems that plays a critical role in defence against oxidative stress. On the other hand, alpha-tocopherol may be decreased in liver diseases, and treatment with this vitamin reduces liver injury in CCl(4)-treated rats. Since there is a close relationship among the different antioxidant systems (mainly glutathione, alpha-tocopherol and ascorbic acid), we have assessed whether, as well as restoring hepatic glutathione content, SAMe has any effect on liver alpha-tocopherol and ascorbic acid levels in CCl(4)-injured rats. Four groups of seven male Wistar rats treated for 9 weeks were studied: rats induced to cirrhosis with CCl(4), rats induced to cirrhosis plus SAMe administration (10 mg x kg(-1) x day(-1)) and their respective controls. Liver samples were obtained for measuring levels of glutathione, alpha-tocopherol, ascorbic acid and thiobarbituric acid-reactive substances (TBARS), and hydroxyproline concentration as an index of collagen content. The hydroxyproline content was higher in CCl(4)-injured rats than in the control group (4.4+/-1.8 and 1.1+/-0.3 micromol/g respectively; P<0.05). In CCl(4)-injured rats, SAMe administration decreased collagen content (2.7+/-1.0 microl/g; P<0.05) and TBARS, and corrected glutathione depletion. alpha-Tocopherol was significantly lower in CCl(4)-injured rats than in controls (17.3+/-4.9 and 23.0+/-4.0 micromol/g respectively; P<0.05). By contrast, alpha-tocopherol levels were similar (23.8+/-5.1 micromol/g) in CCl(4)-injured rats receiving SAMe and in controls. In CCl(4)-injured rats, liver ascorbic acid was decreased in comparison with controls (4.9+/-1.8 and 8.2+/-1.0 micromol/g respectively; P<0.05), levels which were not replenished by SAMe (4.6+/-0.4 micromol/g). In conclusion, SAMe not only decreases fibrosis and protects against hepatic glutathione depletion, but has a further antioxidant effect of preventing alpha-tocopherol depletion in CCl(4)-injured rats.

Animals↗
PubMed2000

Diagnosis of tuberculous pleuritis by the measurement of soluble interleukin 2 receptor in pleural fluid.

OBJECTIVE: As soluble interleukin-2 receptor (sIL-2R) is a marker of T-lymphocyte activation, we sought to determine whether its measurement in pleural fluid is diagnostically useful in tuberculous pleurisy. DESIGN: We compared the concentrations of sIL-2R in pleural samples of 23 patients with tuberculous pleurisy and 109 patients with non-tuberculous effusions (34 malignant, 34 parapneumonic, 27 transudates and 14 miscellaneous). sIL-2R was measured by a commercial ELISA test and its performance was evaluated using receiver operating characteristic (ROC) analysis. RESULTS: The mean values of pleural sIL-2R were 9179 U/mL in patients with tuberculous pleurisy vs 3664 U/mL in patients with malignancy, 2603 U/mL in patients with parapneumonic effusions, 1016 U/mL in patients with transudates, and 1906 U/mL in patients with miscellaneous diseases (P < 0.0001). A ROC curve identified the best cut-off at 4700 U/mL, yielding measures for sensitivity (0.91), specificity (0.94) and accuracy (0.94). CONCLUSIONS: The results of this pilot study suggest that pleural sIL-2R appears to be clinically useful for differentiating between tuberculous and non-tuberculous pleural effusions.

Adolescent↗
PubMed1999

CD47 ligation selectively downregulates human interleukin 12 production.

Interleukin (IL)-12 plays a key role not only in protective innate and adaptive T helper cell type 1 (Th1) responses but also in chronic inflammatory diseases. We report here that engagement of CD47 by either monoclonal antibody, its natural ligand thrombospondin (TSP), or 4N1K (a peptide of the COOH-terminal domain of TSP selectively binding CD47) inhibits IL-12 release by monocytes. The suppression occurred after T cell-dependent or -independent stimulation of monocytes and was selective for IL-12 inasmuch as the production of tumor necrosis factor (TNF)-alpha, IL-1, IL-6, and granulocyte/macrophage colony-stimulating factor was not inhibited. CD47 ligation did not alter transforming growth factor (TGF)-beta and IL-10 production, and the suppressive effect on IL-12 was not due to autocrine secretion of TGF-beta or IL-10. The IL-12 inhibition was not mediated by Fcgamma receptor ligation, did not require extracellular Ca(2+) influx, but was reversed by two phosphoinositide 3-kinase inhibitors (wortmannin and Ly294002). Thus, engagement of CD47 on monocytes by TSP, which transiently accumulates at the inflammatory site, is a novel and unexplored pathway to selectively downregulate IL-12 response. The pathway may be relevant in limiting the duration and intensity of the inflammatory response, and in developing novel therapeutic strategies for Th1-mediated diseases.

Androstadienes↗