PubMed Health⌕ Search

Biomedical subjects

M Rubio

Publications and source records attributed to M Rubio.

At least 37 records · Page 2Linked to original sources

Cellular senescence, cancer and aging: the telomere connection.

Telomeres are the repetitive DNA sequences and specialized proteins that form the distinctive structure that caps the ends of linear chromosomes. Telomeres allow cells to distinguish the chromosome ends from double strand DNA breaks. The telomeric structure prevents the degradation or fusion of chromosome ends, and thus is essential for maintaining the integrity and stability of eukaryotic genomes. In addition, and perhaps less widely appreciated, telomeres may also indirectly influence gene expression. The length, structure and organization of telomeres are regulated by a host of telomere-associated proteins, and can be influenced by basic cellular processes such as cell proliferation, differentiation, and DNA damage. In mammalian cells, telomere length and/or telomere structure have been linked to both cancer and aging. Here, we briefly review what is known about mammalian telomeres and the proteins that associate with them, and discuss the cellular and organismal consequences of telomere dysfunction and the evidence that cells with dysfunctional telomeres can contribute to cancer and aging phenotypes.

Aging↗

Anisakis simplex-sensitized patients: should fish be excluded from their diet?

BACKGROUND: Anisakis simplex (A.s.) allergy is an emerging disease. The third-stage larvae of this nematode are a source of hidden allergens in fish. There are no clear guidelines concerning dietary restrictions for patients with serum-specific IgE to this parasite. OBJECTIVE: To follow up the clinical data and immunological parameters of patients sensitized to A.s. during 6 to 23 months. METHODS: The clinical symptoms and serologic status of 17 patients with specific IgE and positive skin prick test results to A.s. were studied prospectively. Six of these had anaphylaxis (ANA) attributed to A.s. and 11 patients experienced concomitant chronic urticaria (CU). All patients were advised not to eat fish for 6 months. RESULTS: Four patients from the ANA group excluded fish, and ANA did not recur. Two other patients with ANA refused to exclude fish; one remained free of symptoms and the other experienced several urticarial episodes. During this 6-month period total IgE levels decreased in all six ANA patients; specific IgE for A.s. decreased in four patients and increased in two. Two patients from the CU group did not exclude fish, and symptoms persisted in these two patients. Clinical improvement was observed in 78% of the patients with CU who excluded fish. Total and specific IgE levels decreased in all the patients with CU. CONCLUSIONS: Because ANA symptoms are very severe, patients should always be advised to exclude fish until specific food allergens are identified. However, in patients with CU and specific IgE to A.s., only the clinical response to fish ingestion will determine the need for strict fish avoidance.

Adult↗

Evaluation of three methods to measure anti-Brucella IgM antibodies and interference of IgA in the interpretation of mercaptan-based tests.

The results of a dipstick assay for the detection of immunoglobulin M (IgM) to Brucella smooth lipopolysaccharide (S-LPS) correlated with those of an enzyme-linked immunosorbent assay (ELISA) for IgM and of the serum agglutination test (SAT) performed with and without dithiothreitol. Two sera which were dithiothreitol-sensitive and were dipstick negative were shown to contain specific IgA. The dipstick assay is recommended as a simple method for detecting specific IgM antibodies in acute-phase brucellosis patients.

Agglutination Tests↗

Useful tests on pleural fluid that distinguish transudates from exudates.

We aimed to compare the classic Light's criteria with different testing strategies in an effort to improve the accuracy of pleural fluid (PF) categorization. Thirty-two patients with transudates and 140 with exudates on the basis of their clinical diagnosis were entered into the study. We examined the discriminative properties of 10 analytes in the identification of PF, both singly and in combination with an 'or' rule, to see which was best in distinguishing a transudate from an exudate. A combination of PF lactate dehydrogenase (LD) > 307 U/L (two-thirds of the upper limit of the serum LD reference range) with either PF cholesterol > 1.55 mmol/L or PF to serum protein ratio > 0.5 had a diagnostic accuracy similar to that of Light's criteria. We suggest the use of PF LD and cholesterol in combination as an alternative method for distinguishing pleural transudates from exudates. This test combination avoids the need for venepuncture and the simultaneous collection of a blood sample.

Adult↗

Characterization of GFAP expression and cell proliferation in the rat median eminence following hypophysectomy.

To analyze whether the reorganization of the rat median eminence after hypophysectomy might be related to changes in glial fibrillary acidic protein (GFAP)- and cellular proliferation, the distribution of cells immunoreactive for GFAP and the proliferation rate of such cells were analyzed at 20, 40 and 60 days posthypophysectomy. For this study, four rostro-caudal regions of the median eminence were differentiated: the retrochiasmatic, preinfundibular, infundibular and postinfundibular regions. In each of these regions, three layers were studied: the ependymal, the internal and the external. At 20 and 40 days after hypophysectomy, significant increases in cellular proliferation affecting all three layers studied in the preinfundibular and infundibular regions were found. At the same time points, increases in GFAP expression were also observed. However, after 60 days, GFAP and proliferative cellular nuclear antigen (PCNA) expression decreased. Although variations of PCNA and GFAP levels were evident, no colocalisation of PCNA and GFAP was found in the cells of the median eminence in untreated or hypophysectomized rats when sections were analyzed by double immunohistochemical staining. Our results suggest that reorganization of median eminence involves alterations (or modulation) of GFAP-immunoreactive cells together with a proliferation of cells that are not GFAP-immunoreactive. This study also demonstrates that this reorganization is completed within the first two months after hypophysectomy.

Animals↗

Bezafibrate-induced anaphylactic shock: unusual clinical presentation.

We report a case of a patient who suffered generalized urticaria, chest tightness, wheezing, nausea, vomiting, hypotension, and loss of consciousness. Two hours earlier she had taken Eulitop Retard following lunch. She had tolerated all the implicated food after the reaction. Allergy evaluation revealed intense positive responses to intradermal tests with bezafibrate active component and Eulitop Retard (skin tests in control subjects were negative). Specific IgE tests (RAST) to Eulitop Retard were negative. An IgE mechanism is suggested to be responsible for this adverse reaction on the basis of the positive skin tets. The delayed onset (two hours) of this anaphylactic shock is unusual. Although infrequent, it may be caused by the specific pharmacokinetic characteristics of this drug, which is a slow releasing agent, mainly absorbed in the gut. The drug was taken just after lunch, and this concomitant food ingestion could also have produced a delay in gastric drainage and a retarded drug absorption. An IgE-mediated accelerated type reaction could also explain this delay. Apparently the patient reacted after the first contact to the drug, and the absence of a sensitization period is not usual in this type of immune reponse. Finally, we recommend the performance of prick and intradermal skin tests prior to any systemic challenge when allergic reactions to fibric acid derivatives are suspected.

Anaphylaxis↗

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↗

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↗

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↗

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↗

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↗

[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↗

[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↗

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↗

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↗