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J Pineda

Publications and source records attributed to J Pineda.

At least 19 recordsLinked to original sources
PubMed2004

E-MSD: an integrated data resource for bioinformatics.

The Macromolecular Structure Database (MSD) group (http://www.ebi.ac.uk/msd/) continues to enhance the quality and consistency of macromolecular structure data in the Protein Data Bank (PDB) and to work towards the integration of various bioinformatics data resources. We have implemented a simple form-based interface that allows users to query the MSD directly. The MSD 'atlas pages' show all of the information in the MSD for a particular PDB entry. The group has designed new search interfaces aimed at specific areas of interest, such as the environment of ligands and the secondary structures of proteins. We have also implemented a novel search interface that begins to integrate separate MSD search services in a single graphical tool. We have worked closely with collaborators to build a new visualization tool that can present both structure and sequence data in a unified interface, and this data viewer is now used throughout the MSD services for the visualization and presentation of search results. Examples showcasing the functionality and power of these tools are available from tutorial webpages (http://www. ebi.ac.uk/msd-srv/docs/roadshow_tutorial/).

Algorithms↗
PubMed2004

A novel marker for traumatic brain injury: CSF alphaII-spectrin breakdown product levels.

Currently, there is no definitive diagnostic test for traumatic brain injury (TBI) to help physicians determine the seriousness of injury or the extent of cellular pathology. Calpain cleaves alphaII-spectrin into breakdown products (SBDP) after TBI and ischemia. Mean levels of both ipsilateral cortex (IC) and cerebral spinal fluid (CSF) SBDP at 2, 6, and 24 h after two levels of controlled cortical impact (1.0 mm and 1.6 mm of cortical deformation) in rats were significantly elevated by injury. CSF and IC SBDP levels were significantly higher after severe (1.6 mm) injury than mild (1.0 mm) injury over time. The correlation between CSF SBDP levels and lesion size from T2-weighted magnetic resonance images 24 hours after TBI as well as correlation of tau and S100beta was assessed. Mean levels of CSF SBDP (r = 0.833) and tau (r = 0.693) significantly correlated with lesion size while levels of CSF S100beta did not (r = 0.188). Although levels of CSF and IC SBDP and lesion size are all significantly higher after 1.6 mm than 1.0 mm injury, the correlation between CSF SBDP and lesion size was not significant following the removal of controls from the analysis. This indicates CSF SBDP is a reliable marker of the presence or absence of injury. Furthermore, larger lesion sizes 24 h after TBI were negatively correlated with motor performance on days 1-5 after TBI (r = -0.708). Based on these data, evaluation of CSF SBDP levels as a biomarker of TBI is warranted in clinical studies.

Animals↗
PubMed2003

E-MSD: the European Bioinformatics Institute Macromolecular Structure Database.

The E-MSD macromolecular structure relational database (http://www.ebi.ac.uk/msd) is designed to be a single access point for protein and nucleic acid structures and related information. The database is derived from Protein Data Bank (PDB) entries. Relational database technologies are used in a comprehensive cleaning procedure to ensure data uniformity across the whole archive. The search database contains an extensive set of derived properties, goodness-of-fit indicators, and links to other EBI databases including InterPro, GO, and SWISS-PROT, together with links to SCOP, CATH, PFAM and PROSITE. A generic search interface is available, coupled with a fast secondary structure domain search tool.

Animals↗
PubMed2003

Low serum carnitine in HIV-infected children on antiretroviral treatment.

OBJECTIVE: HIV-infection and antiretroviral therapies are associated with energy dysfunction and lipid metabolism in adults. Our aim was to detect a possible carnitine deficiency in HIV-infected children on antiretroviral treatments. We analysed the relation among serum carnitine, its amino-acid precursors (methionine and lysine), clinical evaluation and antiretroviral therapy. DESIGN AND SETTING: Cross-sectional study performed in a tertiary care hospital. SUBJECTS: A total of 79 HIV-infected children on antiretroviral therapy, monitored prospectively in our hospital. INTERVENTIONS: Antiretroviral therapy included nucleoside analogues plus protease inhibitors and/or non-nucleoside analogues. Carnitine was analysed by an enzymatic-spectrometric procedure, and amino acids by ion exchange chromatography. Reference values of carnitine and amino acids were established in apparently healthy children who underwent presurgical analysis for minor surgery. RESULTS: Serum free and total carnitine, acylcarnitines, methionine and lysine were significantly lower in HIV-infected children compared with our reference values for similar ages (P<0.0001; Student's t-test). Low carnitine values were observed in 37% of our HIV-infected children. A significantly positive correlation was observed between serum total carnitine and methionine or lysine (P<0.0001 and P=0.005, respectively; Pearson test). No relation was observed between serum carnitine and clinical stage of HIV infection, immunological or nutritional status or lipodystrophy. Free and total carnitine were significantly lower (P=0.002 and 0.033, respectively) in HIV-infected patients on protease inhibitors (N=56) compared with those on other treatments (N=23). CONCLUSIONS: Low serum carnitine concentration was observed in 37% of our HIV-infected children on antiretroviral therapy. Malabsorption or defective synthesis may also account for the low serum carnitine values detected in these patients.

Adolescent↗
PubMed2003

[Secondary osteoporosis].

Secondary osteoporosis is caused by pathologies or medications, differing from the bone loss explainable by the post-menopausal stage or by ageing. The possible pathologies that can condition the loss of bone mass are very varied: endocrinological, digestive, genetic, haematological, rheumatic, post-transplant, pharmacological and a wide miscellaneous group. This article essentially reviews the endocrinological causes, with special emphasis on the more controversial aspects, followed by a clinical approach for the systematic diagnosis of these pathologies, which are frequent in cases initially labelled as primary osteoporosis

Endocrine System Diseases↗
PubMed2001

Stimulatory effect of harmane and other beta-carbolines on locus coeruleus neurons in anaesthetized rats.

Harmane, harmaline and norharmane are beta-carboline related compounds which have been proposed to be endogenous ligands for imidazoline receptors. The effect of these compounds on the activity of locus coeruleus (LC) neurons was studied by extracellular recordings techniques. Intracerebroventricular administration of harmane and harmaline increased the firing rate of LC neurons. Systemic administration of efaroxan, a mixed alpha(2)-adrenoceptor/I(1)-imidazoline antagonist or vagotomy failed to modify the harmane effect. Furthermore, local applications of harmane and harmaline increased the firing rate of LC neurons in a dose-related manner. Finally, intravenous administration of norharmane also increased the activity of LC neurons. Our results demonstrate that beta-carbolines stimulate LC neuron activity and indicate that this stimulation occurs directly in the LC by a mechanism independent of I(1)- and I(2)-imidazoline receptors.

Anesthesia↗
PubMed2001

NO synthase inhibitors reduce opioid desensitization in rat locus coeruleus neurons in vitro.

The aim of this study was to examine by electrophysiological techniques whether nitric oxide (NO) is involved in the development of desensitization to the opioid agonist Met5-enkephalin (ME) in locus coeruleus neurons from rat brain slices. Bath perfusion with ME (0.05-1.6 microM) caused a concentration-dependent reduction in the firing rate of locus coeruleus cells, whereas perfusion with a high concentration of ME (10 microM) desensitized the inhibitory effect of subsequent ME (0.8 microM) applications. However, in slices perfused with the NO synthase inhibitors 7-NI (100 microM), L-NAME (100 microM) or L-NA (100 microM) the ME (10 microM)-induced opioid desensitization was strongly attenuated. The effect of L-NAME was prevented by administration of L-arginine (100 microM). These results suggest that nitric oxide may contribute to opioid desensitization in locus coeruleus neurons.

Animals↗
PubMed2001

Tissue factor/tissue factor pathway inhibitor system and long-term prognosis after acute myocardial infarction.

UNLABELLED: The tissue factor and tissue factor pathway inhibitor (TFPI) system has been studied in the acute phase of coronary disease but its prognostic importance has been less well assessed. We evaluated its association with recurrent coronary events during long-term follow-up after a myocardial infarction. METHODS: We studied 55 consecutive patients with the following criteria for inclusion: (1) first myocardial infarct; (2) aged < 70 years; (3) non-complicated infarct; (4) low risk effort-test. Blood samples were taken 60-80 days after infarction. Tissue factor, total and free-TFPI were measured. A 4-year follow-up was carried out. Death, unstable angina and new myocardial infarction were considered as poor prognosis. RESULTS: There were no statistical differences in tissue factor/TFPI levels between patients and controls. Total-TFPI showed statistical correlation with total cholesterol (r = 0.59), triglycerides (r = 0.34), LDL-cholesterol (r = 40) and Lipoprotein(a) (r = 0.48). Patients with high levels of cholesterol, LDL-cholesterol and triglycerides showed elevated levels of total-TFPI with no differences in free-TFPI. During follow-up, 8 patients showed poor prognosis. There were no statistical associations between tissue factor/TFPI levels and prognosis. CONCLUSIONS: After acute myocardial infarction, we did not find any differences in the tissue factor/TFPI system between controls and patients. The tissue factor/TFPI system showed little value as a prognostic factor.

Aged↗
PubMed2001

Effect of cyclic 3',5'-adenosine monophosphate, glucocorticoids, and insulin on leptin messenger RNA levels and leptin secretion in cultured human trophoblast.

Leptin is a polypeptide hormone originally thought to be produced exclusively by adipocytes. However, both leptin mRNA and leptin protein were identified in human placental trophoblast cells, suggesting a potential role in human pregnancy. In the present report, we examined the regulation of leptin mRNA levels and secretion by cAMP, glucocorticoids, and insulin in term human placental tissue. Placentae were obtained immediately after delivery from mothers with uncomplicated pregnancies. Leptin concentrations were measured by ELISA in the cultured media of trophoblast maintained in monolayer culture for 24, 48, and 72 h. Likewise leptin mRNA levels in these cultured human trophoblast cells were determined by reverse transcription-polymerase chain reaction. Treatment with forskolin and (Bu)(2) cAMP led to a time- and dose-dependent increase in leptin release, significant after 48 and 72 h. Moreover, incubation with forskolin for 48 h also clearly increased leptin mRNA concentration. Leptin secretion and mRNA levels were also assessed after treatment with insulin or dexamethasone. We found a time- and dose-dependent increase in leptin release, significant after 48 and 72 h. Leptin mRNA levels were also increased after these treatments. All this supports a stimulatory role of cAMP pathway, insulin and dexamethasone in the leptin mRNA levels, and leptin release in trophoblast cells in vitro.

Bucladesine↗
PubMed2001

Cardiopulmonary bypass induces neurologic and neurocognitive dysfunction in the rat.

BACKGROUND: Neurocognitive dysfunction is a common complication of cardiac surgery using cardiopulmonary bypass (CPB). Elucidating injury mechanisms and developing neuroprotective strategies have been hampered by the lack of a suitable long-term recovery model of CPB. The purpose of this study was to investigate neurologic and neurocognitive outcome after CPB in a recovery model of CPB in the rat. METHODS: Fasted rats (n = 10) were subjected to 60 min of normothermic (37.5 degrees C) nonpulsatile CPB using a roller pump and a membrane oxygenator. Sham-operated controls (n = 10) were not subjected to CPB. Neurologic outcome was assessed on days 1, 3, and 12 after CPB using standardized functional testing. Neurocognitive outcome, defined as the time (or latency) to finding a submerged platform in a Morris water maze (an indicator of visual-spatial learning and memory), was evaluated daily from post-CPB days 3-12. Histologic injury in the hippocampus was also evaluated. RESULTS: Neurologic outcome was worse in the CPB versus the sham-operated controls at all three measurement intervals (P < 0.001). The CPB group also had longer water maze latencies compared with the sham-operated controls (P = 0.004), indicating significant neurocognitive dysfunction after CPB. No difference in histologic injury between groups was observed. CONCLUSIONS: CPB caused both neurologic and neurocognitive impairment in a rodent recovery model. This model could potentially facilitate the investigation of CPB-related injury mechanisms and possible neuroprotective interventions.

Anesthesia↗
PubMed2000

Inhibition of 5-hydroxytryptamine reuptake by the antidepressant citalopram in the locus coeruleus modulates the rat brain noradrenergic transmission in vivo.

The in vivo effect of the serotonin (5-HT) reuptake inhibitor antidepressant citalopram, administered in the locus coeruleus (LC), on noradrenergic transmission was evaluated in the rat brain. In dual-probe microdialysis assays, citalopram (0.1-100 microM), in a concentration-dependent manner, increased extracellular noradrenaline (NA) in the LC and simultaneously decreased extracellular NA in the cingulate cortex (Cg). These effects of citalopram were abolished by pretreatment with the 5-HT synthesis inhibitor p-chlorophenylalanine (400 mg/kg, i.p.). When the alpha(2)-adrenoceptor antagonist RS79948 (1 microM) was perfused in the LC, local citalopram increased NA dialysate in the LC but no longer modified NA dialysate in the Cg. In electrophysiological experiments, the administration of citalopram (100 microM) in the LC by reversal dialysis, decreased the firing rate of LC neurones. The results demonstrate in vivo that local administration of citalopram in the LC leads to a decreased release of NA in the Cg. This modulation seems to be the result of an increase in NA concentration in the LC and the subsequent inhibition of LC neurones via alpha(2)-adrenoceptors. The effects of citalopram are dependent on the presence of endogenous 5-HT in the LC.

Animals↗
PubMed2000

Anesthetic effects on cerebral metabolic rate predict histologic outcome from near-complete forebrain ischemia in the rat.

BACKGROUND: Although reduction of cerebral metabolic rate is thought to contribute to anesthetic neuroprotection, histologic evidence to support this concept has not been provided. In this study, histologic outcome was evaluated in rats subjected to different durations of severe forebrain ischemia while anesthetized with volatile anesthetics that have substantially different effects on cerebral metabolic rate. METHODS: Normothermic rats that underwent fasting were anesthetized with 0.75 minimum alveolar concentration (MAC) isoflurane-60% nitrous oxide (N2O) or 0.75 MAC halothane-60% N2O. Ischemia was induced with use of a combination of bilateral carotid occlusion and controlled hypotension. Rats in the isoflurane group were subjected to 6.5 min or 8.0 min ischemia, whereas the halothane group received 6.5 min ischemia. Histologic damage was assessed 4 days later. RESULTS: With 6.5 min ischemia, mean +/- SD, hippocampal CA1 percent of dead (% dead) neurons was reduced with isoflurane-N2O (45 +/- 18) versus halothane-N2O (60 +/- 23, P = 0. 023). Eight minutes of ischemia increased % dead neurons in the isoflurane-N2O group (60 +/- 17, P = 0.017). There was no difference between the isoflurane 8.0-min and halothane 6.5-min groups (P = 0. 935). A similar pattern was observed in hippocampal CA4 and the neocortex. Striatal damage was not affected by anesthetic or ischemic duration. CONCLUSIONS: At 6.5 min ischemia, isoflurane provided improved outcome versus halothane. Previous research has shown that 0.75 MAC isoflurane-N2O increases the time to onset of ischemic depolarization by 1.5 min and reduces cerebral metabolic rate by 42% versus 0.75 MAC halothane-N2O. In the current study, when the duration of ischemia was increased by 1.5 min in the isoflurane-N2O group, histologic outcome became similar to that in halothane-N2O-anesthetized rats. These results provide evidence that cerebral metabolic rate reduction has an advantageous effect on outcome from severe brain ischemia, but also suggest that such benefit is likely to be small.

Anesthetics, Inhalation↗
PubMed1999

Pilocarpine treatments differentially affect alpha2-adrenoceptors which modulate the firing rate of locus coeruleus neurones and the synthesis and release of noradrenaline in rat brain.

We have investigated the effect of treatments with the muscarinic acetylcholine receptor agonist, pilocarpine, on the sensitivity of central alpha2-adrenoceptors that regulate the firing activity of rat locus coeruleus, the tyrosine hydroxylase activity in the rat cortex, hippocampus and hypothalamus, and the K(+)-evoked release of [3H]noradrenaline from rat cortical and hippocampal synaptosomes. Short-term (4 days), but not acute, treatment with pilocarpine caused a small but statistically significant increase in the inhibitory effect of the alpha2-adrenoceptor agonist clonidine on the firing rate of locus coeruleus neurones, with a decrease in the ED50 of 290% (P<0.001). However, no change in the effect of clonidine on the locus coeruleus was observed after longer pilocarpine (11 days) treatment. In the rat cerebral cortex, but not in hippocampus or hypothalamus, chronic (19 days) treatment with pilocarpine caused a decrease in the inhibitory effect of clonidine on tyrosine hydroxylase activity (55%, P<0.05), but did not change the stimulatory effect of the alpha2-adrenoceptor antagonist idazoxan. Moreover, treatments (4, 11 and 19 days) with pilocarpine did not alter the inhibitory effect of clonidine [10(-8)-10(-5) M] on the K(+)-evoked release of [3H]noradrenaline from rat cortical and hippocampal synaptosomes. These results indicate that administration of pilocarpine slightly potentiates some but not all the functional responses mediated by brain presynaptic alpha2-adrenoceptors. In conclusion, these results do not support the hypothesis that chronic treatments with pilocarpine lead to a suitable model of alpha2-adrenoceptor supersensitivity.

Animals↗
PubMed1998

Attenuation of withdrawal-induced hyperactivity of locus coeruleus neurones by inhibitors of nitric oxide synthase in morphine-dependent rats.

Electrophysiological, biochemical, and behavioural studies have suggested that opiate withdrawal is mediated, at least in part, by a hyperactivity of locus coeruleus (LC) neurones. The aim of this study was to evaluate, using single-unit extracellular recordings, the role of NO in the opiate withdrawal-induced hyperactivity of LC neurones in anaesthetized rats. In animals chronically treated with morphine (5 days), administration of naloxone caused an increase in the spontaneous firing rate of LC cells. Acute pretreatment with the nitric oxide synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (30 mg kg(-1) i.p.) attenuated some signs of opiate withdrawal (total score reduced by 55%), and also the withdrawal-induced hyperactivity of LC neurones (hyperactivity reduced by approximately 50%). Acute pretreatment with 7-nitro indazole (50 mg kg(-1) i.p.), a selective inhibitor of neuronal NOS, caused a complete blockade of the withdrawal-induced hyperactivity of LC neurones. Application of 7-nitro indazole (30 microM) in the vicinity of the LC also caused a reduction (of approximately 60%) in the withdrawal-induced hyperactivity of LC cells. Intravenous administration of these NOS inhibitors (after naloxone challenge) did not produce comparable changes in the LC cell firing activity. 7-Nitro indazole failed to affect the development of tolerance of the LC to the morphine effect in opiate-dependent rats (i.e. morphine dose-effect curves were shifted to the right by morphine treatments to a similar degree in vehicle- and 7-nitro indazole-pretreated rats). The present data suggest that opiate withdrawal might be mediated by nitric oxide acting as an intermediate messenger in the LC.

Animals↗
PubMed1998

Stimulation of locus coeruleus neurons by non-I1/I2-type imidazoline receptors: an in vivo and in vitro electrophysiological study.

1. Imidazoline binding sites have been reported to be present in the locus coeruleus (LC). To investigate the role of these sites in the control of LC neuron activity, we studied the effect of imidazolines using in vivo and in vitro single-unit extracellular recording techniques. 2. In anaesthetized rats, local (27 pmoles) and systemic (1 mg kg(-1), i.v.) administrations of 2-(2-benzofuranyl)-2-imidazoline (2-BFI), a selective I-imidazoline receptor ligand, increased the firing rate of LC cells (maximal increase: 22+/-5%, P<0.001 and 16+/-7%, P<0.001 respectively). Chronic pretreatment with the irreversible monoamine oxidase inhibitor clorgyline (3 mg kg(-1), i.p., every 12 h for 14 days) abolished this effect. 3. In rat midpontine brain slices containing the LC, bath application (1 mM) of the imidazolines 2-BFI, 2-(4,5-dihydroimidaz-2-yl)-quinoline (BU224), idazoxan, efaroxan, phentolamine and (2-2-methoxy-1,4-benzodioxan-2-yl)-2-imidazoline (RX821002) reversibly stimulated LC cells. The maximal effect was approximately 90% except for RX821002 and efaroxan which induced smaller maximal effects (approximately 58% and approximately 35% respectively). Simultaneous application of idazoxan and 2BFI did not lead to additive effects. 4. Bath application of the alpha2-adrenoceptor antagonists, yohimbine (1 - 10 microM) and N-ethoxycarbonyl-1,2-dihydroquinoline (EEDQ) (10 microM), failed to modify LC activity. The irreversible blockade of alpha2-adrenoceptors with EEDQ (10 microM) did not alter the effect of idazoxan or that of efaroxan. Previous application of clorgyline (10 microM) did not modify the excitatory effect of 2-BFI or efaroxan. 5. Changes in the pH of the bathing solution (6.84-7.84) did not influence the effect caused by idazoxan. Bath application of 2-BFI (1 mM) reversed the inhibition induced by diazoxide (300 microM), an ATP-sensitive K+ channel opener, whereas application of glibenclamide (3 microM), an ATP-sensitive K+ channel blocker, partially blocked the effect of 2-BFI. 6. This study shows that imidazoline compounds stimulate the firing rate of LC neurons. This effect is not mediated by alpha2-adrenoceptors nor by I1 or I2-imidazoline receptors but involves a different subtype of imidazoline receptor. Our results indicate that this receptor is located extracellularly and modulates ATP-sensitive K+ channels.

Adenosine Triphosphate↗
PubMed1998

Somatodendritic alpha2-adrenoceptors in the locus coeruleus are involved in the in vivo modulation of cortical noradrenaline release by the antidepressant desipramine.

The effect of the antidepressant and selective noradrenaline reuptake blocker desipramine (DMI) on noradrenergic transmission was evaluated in vivo by dual-probe microdialysis. DMI (1, 3, and 10 mg/kg, i.p.) dose-dependently increased extracellular levels of noradrenaline (NA) in the locus coeruleus (LC) area. In the cingulate cortex (Cg), DMI (3 and 10 mg/kg, i.p.) also increased NA dialysate, but at the lowest dose (1 mg/kg, i.p.) it decreased NA levels. When the alpha2-adrenoceptor antagonist RX821002 (1 microM) was perfused in the LC, DMI (1 mg/kg, i.p.) no longer decreased but rather increased NA dialysate in the Cg. In electrophysiological experiments, DMI (1 mg/kg, i.p.) inhibited the firing activity of LC neurons by a mechanism reversed by RX821002. Local DMI (0.01-100 microM) into the LC increased concentration-dependently NA levels in the LC and simultaneously decreased NA levels in the Cg. This decrease was abolished by local RX821002 administration into the LC. The results demonstrate in vivo that DMI inhibits NA reuptake at somatodendritic and nerve terminal levels of noradrenergic cells. The increased NA dialysate in the LC inhibits noradrenergic activity, which in part counteracts the effects of DMI on the Cg. The modulation of cortical NA release by activity of DMI at the somatodendritic level is mediated through alpha2-adrenoceptors located in the LC.

Adrenergic alpha-Antagonists↗
PubMed1998

Development of gastric slow waves in preterm infants measured by electrogastrography.

The aim of this study was to investigate the developmental process of gastric myoelectrical activity (GMA) in preterm infants. Nineteen healthy preterm infants were studied. GMA was recorded using surface electrogastrography, and six follow-up studies were performed in each subject. Spectral analysis methods were applied to compute the parameters of the electrogastrogram (EGG). The results showed that there was a developmental process of GMA with age during the first 6 mo of life. 1) The percentage of normal slow waves showed a progressive increase after birth (36.7 +/- 6.1, 37.8 +/- 6.2, 47.0 +/- 10.0, 52.2 +/- 12.2, 55.2 +/- 9.7, and 65.8 +/- 13.5% at 1 and 2 wk and 1, 2, 4, and 6 mo, respectively); 2) there was a significant postprandial increase in the percentage of normal slow waves during the first 2 mo after birth; and 3) the percentages of normal slow waves for different gestation ages were not statistically significant. In conclusion, the percentage of normal slow waves is low at birth and there is a developmental process that may be stimulated by enteral feeding.

Electromyography↗