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N Marín

Publications and source records attributed to N Marín.

12 recordsLinked to original sources
PubMed2002

[Chronic ethanol feeding induces oxidative stress in the optic nerve of rats].

PURPOSE: To assess the involvement of oxidative stress in optic nerves after chronic intake of ethanol in adult rats, when compared to animals fed with an ethanol-free isocaloric diet. METHODS: Male Sprague-Dawley rats were used throughout the study. They were fed an ethanol-containing liquid diet, whereas the pair-fed group was given an ethanol-free isocaloric diet. After six weeks of the experiment, optic nerves were extracted and markers of oxidative stress were assayed, i.e., antioxidants such as glutathione and lipid peroxidation products such as malondialdehyde (MDA). RESULTS: The GSH content in the optic nerves of ethanol-fed animals was significantly reduced, and the concentration of MDA was significantly higher in this group when compared with the pair-fed group. Time-course of body weight of animals in both groups varied identically throughout the six weeks of the experiment. CONCLUSION: The increase in lipid peroxidation products (MDA), together with the decrease in cellular antioxidants (GSH) confirm, in this experimental model, the involvement of oxidative stress in ethanol-induced toxicity of the optic nerves of rats. In view of the body weight time course, the influence of nutritional status on the parameters studied could also be discarded (Arch Soc Esp Oftalmol 2002; 77: 263-268).

Animals↗
PubMed2000

Beta-amyloid-induced activation of caspase-3 in primary cultures of rat neurons.

It is known that beta-amyloid peptide (Abeta) contributes to the neurodegeneration in Alzheimer's disease (AD) and operates through activation of an apoptotic pathway. Apoptotic signal is driven by a family of cysteine proteases called caspases. The beta-amyloid precursor protein (APP) is directly and efficiently cleaved by caspases during apoptosis, resulting in elevated beta-amyloid peptide formation. Cerebellar neurons from rat pups were treated with the aged Abeta(25-35) at 1 and 5 microM and fluorescence assays of caspase activity performed over 4 days. We observed an increase in caspase activity after 48 h treatment in both 1 and 5 microM treated cells, then (72-96 h) caspase activity decreased to control values. The data presented support the hypothesis that Abeta(25-35)-induced apoptosis is mediated by the activation of Caspase-3 and that this is a transient effect.

Amyloid beta-Peptides↗
PubMed1999

4-Hydroxynonenal inhibits glutathione peroxidase: protection by glutathione.

4-Hydroxy-2,3-trans-nonenal, a lipid peroxidation product, inhibits glutathione peroxidase in a concentration-dependent manner. The concentration providing 50% inhibition is 0.12 mM. This inhibition can be almost completely (89%) prevented by 1 mM glutathione added to the incubation mixture 30 min before 4-hydroxy-2,3-trans-nonenal or 2,3-trans-nonenal, but not by other thiol-containing antioxidants such as 0.5 mM dithiothreitol or beta-mercaptoethanol. Again the addition of 1 mM glutathione, and not of 0.5 mM dithiothreitol or beta-mercaptoethanol, to the enzyme 30 min after incubation with 4-hydroxy-2,3-trans-nonenal restores activity to the same extent as does the preincubation with GSH. In view of the known reactivity of 4-hydroxy-2,3-trans-nonenal with lysine residues and the reversibility of the inhibition, the involvement of a lysine residue in GSH binding to glutathione peroxidase is proposed. The potential relevance of the inhibition of glutathione peroxidase by 4-hydroxy-nonenal to oxidative tissue damage is discussed with particular emphasis on neurological disorders.

Aldehydes↗
PubMed1999

Efficacy of the antioxidant ebselen in experimental uveitis.

Inflammation results in the production of free radicals. In a model of experimental uveitis upon subcutaneous injection of endotoxin to Lewis rats, i.e., endotoxin-induced experimental uveitis (EIU), we have evaluated the status of the antioxidant capacity of ocular tissues. EIU results in a decrease of glutathione (GSH) content and glutathione peroxidase (GPx) activity in whole eye homogenates 24-h after endotoxin administration. Furthermore, an increase in malondialdehyde (MDA) content was observed in these same samples, thus confirming the involvement of oxidative stress in the pathophysiology of the process. In view of the ability of the antioxidant ebselen as GPx enzyme mimic, we tested the effect of the oral treatment with two doses of 100 mg/kg body weight of ebselen (first dose administered at the same time of endotoxin, and the second after 12 h). Ebselen administration normalized the GSH and MDA contents and protected the GPx activity of the EIU rat eyes. The GPx activity in the eye homogenate of the treated rats could be completely acounted for by the ebselen-dependent GPx-like activity, i.e., GPx activity measured in the acidic supernatant of the homogenate after neutralization. Unmodified ebselen was detected in whole eye homogenates, thus it shows for the first time the penetration of ebselen through the blood-aqueous and blood-retina barrier. The results herein may allow the proposal of ebselen as a suitable antiinflammatory agent in ocular tissues.

Animals↗
PubMed1999

Glycemic control and not protein kinase C inhibition prevents the early decrease of glutathione peroxidase activity in peripheral nerve of diabetic mice.

Experimental diabetes promotes changes in biochemical activities of peripheral nervous tissue. Glutathione peroxidase activity decreases in sciatic nerve of diabetic mice very early after onset of experimental diabetes. Effective glycemic control with insulin restores the early lost glutathione peroxidase activity in peripheral nerve of diabetic mice to control values. Data are also presented demonstrating that glutathione peroxidase activity in diabetic mouse peripheral nerve is not modified by the constant delivery of calphostin C, a protein kinase C inhibitor, therefore this decrease seems to be independent on a protein kinase C mediated mechanism. Thus, the early glutathione peroxidase activity decrease in peripheral nerve of diabetic mice is closely related to hyperglycemia, and a tight glycemic control is rather effective in restoring the control levels of this enzymatic activity. The results herein do not rule out the benefits of antioxidant adjuvant therapies in diabetes to help recover the overall decrease in antioxidant defense in peripheral nerve elicited by the decrease of glutathione peroxidase activity.

Animals↗
PubMed1998

Lipid peroxidation products and antioxidants in human disease.

Lipid peroxidation (LPO) is a free radical-related process that in biologic systems may occur under enzymatic control, e.g., for the generation of lipid-derived inflammatory mediators, or nonenzymatically. This latter form is associated mostly with cellular damage as a result of oxidative stress, which also involves cellular antioxidants in this process. This article focuses on the relevance of two LPO products, malondialdehyde (MDA) and 4-hydroxynonenal (HNE), to the pathophysiology of human disease. The former has been studied in human serum samples of hepatitis C virus-infected adults and human immunodeficiency virus-infected children. In these two cases it is shown that the specific assay of serum MDA is useful for the clinical management of these patients. The presence of MDA in subretinal fluid of patients with retinal detachment suggests the involvement of oxidative stress in this process. Moreover, we were able to report the dependence of this involvement on the degree of myopia in these patients. The assay of MDA contents in the peripheral nerves of rats fed a chronic alcohol-containing diet or diabetic mice also confirms the pathophysiologic role of oxidative stress in these experimental models. In these two cases, associated with an increase in tissue LPO products content, we detected a decrease of glutathione peroxidase (GSHPx) activity in peripheral nerve, among other modifications. We have demonstrated that in vitro HNE is able to inhibit GSHPx activity in an apparent competitive manner, and that glutathione may partially protect and/or prevent this inactivation. The accumulation of LPO products in the brain of patients with Alzheimer's disease has also been described, and it is on the basis of this observation that we have tried to elucidate the role of oxidative stress and cellular antioxidants in beta-amyloid-induced apoptotic cell death of rat embryo neurons. Finally, we discuss the possible role of the observed vascular effects of HNE on human arteries.

Adult↗
PubMed1997

[Socioeconomic determinants and utilization of emergency hospital services].

BACKGROUND: Socioeconomic level is a key determinant for health status. It may also influence on the utilization of hospital emergency services, although the factor responsible for that is not known. The main objective of the present report is to assess whether patients using frequently hospital emergency services have one or more variables related to low socioeconomic level. PATIENTS AND METHODS: A standardized questionnaire was applied to 800 patients randomly selected from those attending the emergency services of a provincial reference hospital. It was gathered information on: income, education level, employment, loneliness, domestic violence, occupational accidents, and life style. Odds ratios (OR) and their 95% confidence intervals (CI) were estimated. Stepwise logistic regression analysis was used to ascertain the independent predictors for attending for than once to the emergency services. RESULTS: In crude analysis, low income and low educational level were significantly related to the use of emergency services (both chi 2 for a trend < 0.05). Alcoholism (OR = 2.3, 95% CI = 1.2-4.7) and domestic violence (OR = 2.6, 95% CI = 0.9-8.1) were also related. Stepwise logistic regression analysis selected income (OR for intermediate level = 1.6, 95% CI = 1.0-2.7, and OR for low level = 2.3, 95% CI = 1.4-3.7) and alcoholism (OR = 2.9, 95% CI = 1.3-6.4) as independent predictors. CONCLUSIONS: Patients with low income and/or alcoholism use emergency hospital services more frequently.

Adult↗
PubMed1997

Bronchodilator and anti-inflammatory activities of SCA40: studies in human isolated bronchus, human eosinophils, and in the guinea-pig in vivo.

There is currently interest in the use of inhibitors of cyclic nucleotide phosphodiesterases (PDE) as potential anti-asthma agents. In this study we examined the effects of SCA40 (6-bromo-8-methylaminoimidazol-[1,2-a] pyrazine-2-carbonitrile), a preferential inhibitor of PDE 3 also endowed with PDE 4 and 5 inhibitory activities, on isolated bronchus and eosinophil functions and in an animal model of asthma. SCA40 (1 nM-0.1 mM) produced concentration-dependent inhibition of spontaneous and stimulated tone of human isolated bronchus and reached a maximal relaxation similar to that of theophylline (3 mM). The potency (-log EC50 values) of SCA40 against spontaneous tone (6.52 +/- 0.10) was greater than against tone raised by equieffective concentrations (approximately 70%) of histamine (5.76 +/- 0.06), leukotriene C4 (5.44 +/- 0.11), and acetylcholine (4.98 +/- 0.09). In the presence of cytochalasin B, the chemotactic peptide N-formyl-L-methionyl-L-leucyl-L-phenylalanine (FMLP; 0.5 microM) induced leukotriene C4 production in human eosinophils isolated in discontinuous metrizamide gradients. The production of leukotriene C4 was inhibited by SCA40 in a concentration-related fashion (-log IC50 = 6.04 +/- 0.20; n = 6). Rolipram, a selective PDE 4 inhibitor, was also effective (-log IC50 = 7.29 +/- 0.32) but the selective PDE 3 inhibitor SKF94120 was scarcely effective (< 10% inhibition for 10 microM). In ovalbumin sensitized guinea-pigs, SCA40 (1 mg kg(-1), i.p.) given 30 min before antigen challenge significantly inhibited the acute bronchoconstriction produced by aerosol antigen (5 mg ml(-1), 30 s) (antigen response was 185 +/- 13 and 91 +/- 21 cmH2O l(-1) s(-1) in control and SCA40-treated animals, respectively, P < 0.05). Pretreatment with SCA40 (1 mg kg(-1), i.p., 30 min pre- and 3 h post-antigen exposure) prevented airway hyperreactivity to histamine which developed 24 h after exposure of conscious guinea-pigs to aerosol antigen. Eosinophil lung accumulation that accompanied airway hyperreactivity was also inhibited by SCA40 (from 6.15 +/- 0.86 in control to 1.27 +/- 0.27 in treated animals; expressed as eosinophils x 10(6); P < 0.05). SCA40 (1 mg kg(-1), i.p.) also inhibited the microvascular leakage produced after inhaled antigen (5 mg ml(-1), 30 s) at all airway levels. The haemodynamic effects of SCA40 (1 mg kg(-1), i.p.) consisted of a rapid decrease (peak at 5 min) in mean arterial blood pressure (-39.4 +/- 2.4%) and tracheal mucosal blood flow (-13.5 +/- 2.0%) that slowly recovered with time. These data support previous work showing that PDE inhibition results in antispasmogenic and anti-inflammatory effects. SCA40 was effective in vitro and in vivo and these effects are probably related to its activity as a mixed PDE inhibitor.

Animals↗
PubMed1994

[An epidemiological analysis of insomnia at a primary care center].

OBJECTIVE: To evaluate the real problems of insomnia, analysing its prevalence and its characteristic presentation, within the clinics using an appointment system at a Primary Care Centre. DESIGN: Observation study of a crossover type, by means of a personal interview. SETTING: Primary Care context. PATIENTS: The survey was on the basis of a sample population calculated for qualitative variables (N = 470; a = 0.05; p = 0.50; i = 0.05). A total of 490 patients, taken from the appointment lists of on-demand clinics by means of systematic sampling (K = 4), were studied. MEASUREMENTS AND RESULTS: The reply index was 100%. Out of a sample study population of 490, 278 patients with insomnia were recorded. 65.83% had proximal insomnia (difficulty in getting to sleep); 49.28%, interrupted sleep (intermittent insomnia); and 16.5% of cases, late insomnia (premature waking). Insomnia was persistent in 69.1% of cases and transitory in 30.9%. Regarding the aetiological factors linked to insomnia, non-organic mental disorder (64.29%); known organic Pathology (25%). CONCLUSIONS: 57% (CI 0.53 divided by 0.61) of the population under study had suffered insomnia at some time. 61.9% of these were suffering it at the time of the survey; and only 44% of these sought medical advice for the problem. We found that a significant relationship existed between suffering insomnia and age, civil status and socio-economic level. It is important to manage and have sufficient knowledge of insomnia, as it is a common health problem in Primary Care.

Adolescent↗
PubMed1990

Hemodynamic effects of long-term converting-enzyme inhibition in renal hypertensive rats.

The hemodynamic effects of a converting-enzyme inhibitor (CEI) given during 12 consecutive hours were studied in severe chronic renal hypertensive and normotensive Wistar rats. Hemodynamic parameters were obtained by thermodilution method in conscious unrestrained animals twenty-four hours after surgery. A bolus of CEI induced a significant decrease of mean arterial pressure (MAP) (from 192.2 +/- 8.2 to 163.3 +/- 5.9 mmHg, p less than 0.001) and total peripheral resistance (TPR) (from 7.69 +/- 0.53 to 5.83 +/- 0.33 mmHg.min/ml 100 g) in hypertensive animals. Cardiac index (CI) and heart rate increased significantly (p less than 0.05). Infusion of CEI to hypertensive animals during 12 consecutive hours produced a further progressive decrease in MAP and TPR (p less than 0.05) and an increase in CI (p less than 0.05). Heart rate did not change. Acute and prolonged infusions of CEI to normotensive group induced less but similar effect to those observed in hypertensive group. These results suggest that an increase of the renin-angiotensin system activity is the principal mechanism involved in the maintenance of high blood pressure during chronic phase of renal hypertension on the rats.

Angiotensin-Converting Enzyme Inhibitors↗
PubMedDate not supplied

[Consumption and cost of antipsychotic drugs].

INTRODUCTION: In recent years, new atypical antipsychotic drugs have been marketed. This study aims to analyze the evolution of the consumption pattern and pharmaceutical cost of the antipsychotic drugs during the last years and the impact that the new atypical antipsychotic drugs have had. METHODS: Based on the ECOM database of the Ministry of Health and Consumer Affairs of Spain, the sales data of the antipsychotic drugs in Catalonia during the 1990-2001 period have been chosen. The drugs have been classified into typical or classical and atypical. Consumption data have been expressed in daily defined dose (DDD) per 1,000 inhabitants and per day of treatment (DID), and cost data in constant euros. RESULTS: Antipsychotic consumption increased from 3.31 DID in 1990 to 6.04 DID in 2001. Typical drugs consumption decreased (from 100 % consumption in 1990 to 46 % in 2001) and that of the atypical ones increased (from 1% consumption in the year 1993 to 54% in the year 2001). A change in the use pattern of different drugs is verified. In the year 1990, the most consumed drugs were flupenthixol (0.86 DID) and haloperidol (0.67 DID), and in the year 2001 olanzapine (1.69 DID) and risperidone (1.30 DID). The drugs with a greater increase in consumption were olanzapine, which multiplied its consumption five fold from 1997 to 2001 and risperidone, which multiplied it by 20 from 1994 to 2001. During the study period, the cost increased 13 times, above all due to increase in cost of atypical antipsychotics (from less than 1 % of the total cost in 1993 to 92 % of the total cost in 2001). The DDD cost of antipsychotics increased (6.48 euros in 1990 and 20.31 euros in 2001). However, that of the typical antipsychotics decreased (6.48 euros in 1990 and 4.62 euros in 2001) and that of the atypical ones increased (2.06 euros in 1993 and 15.69 euros in 2001). CONCLUSION: The marketing of the new atypical antipsychotic drugs has had an extraordinary impact on antipsychotic drug consumption and cost. The cost/effectiveness ratio of the new atypical antipsychotic drugs in the clinical practice should be evaluated to determine the economic resources aimed at costs of the different antipsychotic drugs.

Antipsychotic Agents↗