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Biomedical subjects

M Rubio

Publications and source records attributed to M Rubio.

At least 19 recordsLinked to original sources
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

[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

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

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

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↗
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↗
PubMed1999

The vitronectin receptor and its associated CD47 molecule mediates proinflammatory cytokine synthesis in human monocytes by interaction with soluble CD23.

The vitronectin receptor, alphavbeta3 integrin, plays an important role in tumor cell invasion, angiogenesis, and phagocytosis of apoptotic cells. CD47, a member of the multispan transmembrane receptor family, physically and functionally associates with vitronectin receptor (VnR). Although vitronectin (Vn) is not a ligand of CD47, anti-CD47 and beta3 mAbs suppress Vn, but not fibronectin (Fn) binding and function. Here, we show that anti-CD47, anti-beta3 mAb and Vn, but not Fn, inhibit sCD23-mediated proinflammatory function (TNF-alpha, IL-12, and IFN-gamma release). Surprisingly, anti-CD47 and beta3 mAbs do not block sCD23 binding to alphav+beta3+ T cell lines, whereas Vn and an alphav mAb (clone AMF7) do inhibit sCD23 binding, suggesting the VnR complex may be a functional receptor for sCD23. sCD23 directly binds alphav+beta3+/CD47(-) cell lines, but coexpression of CD47 increases binding. Moreover, sCD23 binds purified alphav protein and a single human alphav chain CHO transfectant. We conclude that the VnR and its associated CD47 molecule may function as a novel receptor for sCD23 to mediate its proinflammatory activity and, as such, may be involved in the inflammatory process of the immune response.

Animals↗
PubMed1999

Drug glucuronidation and hepatic lipid microsomal membrane profile in cholestatic rats followed paracetamol intoxication.

The uridin-diphosphoglucuronyl-transferase (UDP-GT) is a membrane-bound enzyme responsible for glucuronidation of endogenous and exogenous compounds. This work established the UDP-GT activity and its lipid membrane microenvironment in two experimental models: acute paracetamol intoxication, and cholestasis followed by acute paracetamol intoxication. Cholestasis was performed by bile duct ligation. After 7 days animals were injected with paracetamol (BDL-APAP group). Sham-operated rats were injected at day 7 with paracetamol (APAP group). Cholestatic and sham-operated rats injected with vehicle (BDL and control groups). UDP-GT activity was measured by a kinetic method for different substrates. Microsomal membrane phospholipid composition, cholesterol content and ultrastructure were determined. BDL-APAP group showed an increment in the UDP-GT activity except for chloramphenicol, morphine and paracetamol if compared to controls and to BDL group. The same increment was observed when BDL-APAP was compared to APAP except for chloramphenicol and lorazepam. Between BDL and APAP groups similar levels of activity were detected except for paracetamol. Microsomal phospholipid profile: phosphatidylcholine showed the lowest content in the BDL group, with a significant recovery in the BDL-APAP and APAP groups. Phosphatidylserine was markedly decreased in the APAP group compared to the rest and phosphatidylinositol was decreased in all the groups if compared to control values. An increment of phosphatidylethanolamine was seen in the APAP and BDL-APAP groups if compared to BDL and control values. A significant increment of microsomal cholesterol content was seen in BDL. Under these conditions, a different lipid microenvironment is produced, resulting in an increment of the enzyme activity for a variety of substrates.

Acetaminophen↗
PubMed1999

Immunohistochemical evidence of the presence of aromatase P450 in the rat hypophysis.

In order to analyze whether aromatase is present in the hypophysis of adult rats, we have performed an immunohistochemical study in young adult male and female rats. Our study has revealed that the hypophysis of adult rats contains aromatase, although marked differences are found between the sexes. The hypophyses of male rats have cells immunoreactive for the enzyme, 34.40% of these hypophyseal cells showing reaction. By contrast, cells from female rats show very little reaction, only 0.84% of them being reactive. No significant differences in the percentage of immunoreactive cells between one phase and another are observed during the estrous cycle. Our results point to the immunohistochemical expression of aromatase in the hypophysis of adult rats and at the same time suggest that its expression is sex-dependent. The enzyme may therefore be involved in the regulation of adenohypophyseal cytology by androgens.

Amino Acid Sequence↗
PubMed1999

Lidocaine and monoethylglycinexylidide serum determinations to analyze liver function of cirrhotic patients after oral administration.

Our aim was to compare standard liver function tests (serum bilirubin, serum albumin and prothrombin concentration), with lidocaine and monoethylglycinexylidide pharmacokinetic parameters, after oral lidocaine administration, to assess hepatic function of cirrhotic individuals. Twenty-one consecutive cirrhotic patients, nine consecutive acute hepatitis patients, and nine healthy individuals received oral lidocaine. Lidocaine and monoethylglycinexylidide serum concentrations were determined by the TDx system. Cirrhotic patients had higher lidocaine and lower monoethylglycinexylidide serum concentrations and differences in its pharmacokinetic variables, compared to control and hepatitis groups (P < 0.05). Sensitivity of lidocaine serum determinations (100%) was greater than sensitivity of serum bilirubin (57%), serum albumin (62%), and prothrombin concentrations (43%) and monoethylglycinexylidide serum concentrations (57%) in differentiating cirrhotic individuals from controls. In conclusion, after oral administration, lidocaine and monoethylglycinexylidide pharmacokinetic parameters are significantly altered in cirrhotic patients compared to normal and acute hepatitis subjects. Lidocaine pharmacokinetic parameters would be better than those of monoethylglycinexylidide and standard liver function tests in the evaluation of liver function of cirrhotic patients.

Administration, Oral↗
PubMed1999

Bacteremic pneumonia due to Staphylococcus aureus: A comparison of disease caused by methicillin-resistant and methicillin-susceptible organisms.

We performed a prospective study of all patients with bacteremic pneumonia due to Staphylococcus aureus over a period of 6 years during an outbreak of methicillin-resistant S. aureus (MRSA). Patients with bacteremic pneumonia due to MRSA (32 cases) or methicillin-susceptible S. aureus (MSSA; 54 cases) were compared. The patients with MRSA pneumonia were older and were more likely than those with MSSA pneumonia to have predisposing factors for acquisition of the infection. There were no differences in clinical findings, radiological pattern, or complications in clinical evolution among patients with MRSA and MSSA pneumonia. Mortality was significantly higher among MSSA-infected patients treated with vancomycin than among those treated with cloxacillin (47% vs. none; P<.01). Multivariate analysis (stepwise logistic regression method) showed a relationship between mortality and the following variables: septic shock (odds ratio [OR], 61), vancomycin treatment (OR, 14), and respiratory distress (OR, 8).

Adult↗