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Biomedical subjects

A Tabernero

Publications and source records attributed to A Tabernero.

At least 19 recordsLinked to original sources
PubMed2004

Probability of prostate cancer as a function of the percentage of free prostate-specific antigen in patients with a non-suspicious rectal examination and total prostate-specific antigen of 4-10 ng/ml.

Our aim was to assess the usefulness of measuring the percentage of free prostate specific antigen (PSA) in serum in relation to reducing the number of prostate biopsies in men with benign prostate examinations and serum PSA levels between 4 and 10 ng/ml. The percentage of free PSA (Immulite) in serum was analyzed prospectively in 500 men, all of whom underwent ultrasound-guided sextant prostate biopsies. Cancer was detected in 21.4% (107/500) of the patients. Using a free PSA cutoff of < or = 23% as a criterion for performing prostate biopsy would have detected 94.4% of cancers, avoided 18.8% of benign biopsies and yielded a positive predictive value of 25.3%. The percentage of free PSA increased with prostate volume. Mean total PSA and mean free percent PSA values increased as patient age increased, influencing the calculation of cutoff values, sensitivity and specificity. PSA density had a sensitivity and specificity not significantly different than the percentage of free PSA. Measurement of the percentage of free serum PSA improves the specificity of prostate cancer detection in patients with elevated total serum PSA levels and benign prostate examinations.

Aged↗
PubMed2001

Proliferation of C6 glioma cells is blunted by the increase in gap junction communication caused by tolbutamide.

We have previously reported that tolbutamide prevents the inhibition of gap junction communication in astrocytes. Here, we show that tolbutamide increases gap junction communication and connexin 43 expression in poorly coupled C6 glioma cells. The increase in communication is concurrent with the inhibition of the rate of proliferation due to a block of the progression of C6 glioma cells through the S phase of the cell cycle. The effects of tolbutamide were quantitatively similar to that found after the elevation of intracellular cAMP. Furthermore, the effects of tolbutamide and cAMP were additive. The possible beneficial effect of tolbutamide on gene therapy for gliomas is discussed.

Animals↗
PubMed2001

Oligodendrocytes use lactate as a source of energy and as a precursor of lipids.

Lactate is an important metabolic substrate for the brain during the postnatal period and also plays a crucial role in the traffic of metabolites between astrocytes and neurons. However, to date there are no clues with regard to lactate utilization by oligodendrocytes, the myelin-forming cells in the brain. In the present work, lactate utilization by oligodendrocytes in culture was investigated and compared with its utilization by cultured neurons, type 1 and type 2 astrocytes. Our results clearly indicate that oligodendrocytes readily use lactate both as a metabolic fuel and as a precursor to build carbon skeletons. Oligodendrocytes oxidize lactate at a higher rate than that observed for neurons and astrocytes, and their rate of lipid synthesis from lactate was at least 6-fold higher than that found in astrocytes or neurons. The rate of glucose utilization through different pathways was also investigated. The flux of glucose through the pentose phosphate pathway and the rate of lipid synthesis were at least 2-fold higher in oligodendrocytes than in astrocytes or neurons. These findings indicate that oligodendrocyte metabolism is designed specifically for the synthesis of lipids, presumably those of myelin.

Aging↗
PubMed2001

Different alpha1-adrenoceptor-induced inositol phosphate formation in the two portions of rat vas deferens.

The two portions of rat vas deferens differed in the postjunctional sensitivity to noradrenaline. Alpha1-adrenoceptor-linked phosphoinositide breakdown was analysed in this tissue. The noradrenaline-induced [3H]inositol phosphate accumulation was similar in both ends although the pEC50 was higher in the epididymal (5.97+/-0.07) than in the prostatic (5.47+/-0.15, P<0.01) portion. [3H]Prazosin showed similar density of binding sites in both portions. Tissue pretreated with pertussis toxin did not change [3H]inositol phosphate accumulation. Finally, Western blot analysis indicated a smaller concentration of Gq/11 protein in the prostatic half (-29+/-5%, P<0.01). These results suggest that the different sensitivity to noradrenaline could be due to the higher availability of this sort of G protein in the epididymal portion.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed2001

The enhancement of glucose uptake caused by the collapse of gap junction communication is due to an increase in astrocyte proliferation.

We have previously shown that several gap junction uncouplers increase the uptake of glucose in astrocytes. The aim of the present work was to study whether the increase in glucose uptake was a consequence of the inhibition of gap junction communication and the purpose of this effect. Our results show that alpha-glycyrrhetinic acid and endothelin-1 increase the uptake of glucose in highly, but not in poorly, coupled astrocytes. This effect depended on connexin 43 levels and was abolished when the inhibition of gap junction communication was prevented by tolbutamide or ouabain. The inhibition of gap junctions increased the rate of glucose incorporation into DNA and RNA, which was inhibited by treatment with dehydroepiandrosterone, an inhibitor of glucose-6-phosphate dehydrogenase, the regulatory enzyme of the pentose phosphate pathway. The inhibition of gap junctions significantly increased astrocyte proliferation, which was counteracted by tolbutamide. These effects were not observed in poorly coupled astrocytes expressing low levels of connexin 43. The increase in astrocyte proliferation caused by gap junction inhibition was prevented when either glucose uptake or the pentose phosphate pathway were inhibited. We conclude that the inhibition of gap junction communication induces astrocyte proliferation, resulting in an enhancement of glucose uptake and its utilization through the pentose phosphate pathway to provide ribose-5-phosphate for the synthesis of nucleic acids.

Administration, Topical↗
PubMed2001

Neuronal differentiation is triggered by oleic acid synthesized and released by astrocytes.

Unlike in the adult brain, the newborn brain specifically takes up serum albumin during the postnatal period, coinciding with the stage of maximal brain development. Here we report that albumin stimulates oleic acid synthesis by astrocytes from the main metabolic substrates available during brain development. Oleic acid released by astrocytes is used by neurons for the synthesis of phospholipids and is specifically incorporated into growth cones. Oleic acid promotes axonal growth, neuronal clustering, and expression of the axonal growth-associated protein-43, GAP-43; all these observations indicating neuronal differentiation. The effect of oleic acid on GAP-43 synthesis is brought about by the activation of protein kinase C, since it was prevented by inhibitors of this kinase, such as H-7, polymyxin or sphingosine. The expression of GAP-43 was significantly increased in neurons co-cultured with astrocytes by the presence of albumin indicating that neuronal differentiation takes place in the presence of oleic acid synthesized and released by astrocytes in situ. In conclusion, during brain development the presence of albumin could play an important role by triggering the synthesis and release of oleic acid by astrocytes, which induces neuronal differentiation.

Albumins↗
PubMed2000

Effects of chronic and acute aminoguanidine treatment on tail artery vasomotion in ageing rats.

1. This study was designed to evaluate the effects of aminoguanidine, a selective inhibitor of the inducible isoform of nitric oxide synthase (iNOS), on the reactivity and intracellular calcium ([Ca(2+)](i)) mobilization induced by noradrenaline in the perfused tail artery from aged WAG/Rij rats. Global mean internal diameter was 350+/-15 microns and wall thickness 161+/-3 microns. The influence of the endothelium on these responses was also analysed. The intracellular dye fura-2 for [Ca(2+)](i) measurements was used. 2. Noradrenaline-induced vasoconstriction decreased progressively from 3 to 20 and 30 months. Removal of the endothelium attenuated vasoconstriction in 20 and 30 month-old rats (P<0.05) but not in young rats. 3. Chronic administration of aminoguanidine (50 mg kg(-1) day(-1), p.o.) to WAG/Rij rats from 20 to 30 months enhanced (P<0. 01) the [Ca(2+)](i)-sensitivity of noradrenaline-induced vasoconstriction. 4. Aminoguanidine (300 microM) in vitro significantly shifted the concentration-vasoconstriction curve to noradrenaline to the left (P<0.01) in denuded vessels from both 20 and 30 month-old rats. The acute inhibitory effect of aminoguanidine was also observed after chronic aminoguanidine treatment. Aminoguanidine failed to modify vasoconstriction in the presence of the endothelium. 5. Acute aminoguanidine (300 microM) treatment did not modify vasoconstriction induced by noradrenaline in young rats. 6. Quantification of iNOS mRNA expression in tail arteries from 3 and 20 month-old WAG/Rij rats showed that expression was enhanced (x2.1, P<0.01) with age. 7. These results suggest that an inflammatory process develops in the media of the rat tail artery with age and that the subsequent increase in non-endothelial iNOS activity attenuates noradrenaline-induced vasoconstriction.

Age Factors↗
PubMed2000

ATP-sensitive potassium channel regulates astrocytic gap junction permeability by a Ca2+-independent mechanism.

Using the scrape-loading technique in cultured astrocytes, we show that sulfonylureas such as tolbutamide and glybenzcyclamide, which inhibit the ATP-sensitive K+ channel, prevent the inhibition of gap junction permeability caused by several structurally unrelated uncouplers such as oleic acid, arachidonic acid, endothelin-1, octanol, and alpha-glycyrrhetinic acid. When the intracellular level of Ca2+ was diminished, all the uncouplers tested were still able to inhibit gap junction communication, indicating that their inhibitory effect was not mediated by Ca2+. In addition, tolbutamide and glybenzcyclamide prevented the inhibitory effect of these uncouplers in Ca(2+)-depleted astrocytes, suggesting that the inhibition of the ATP-sensitive K+ channel increases gap junction permeability through a Ca(2+)-independent mechanism. The activation of the ATP-sensitive K+ channel caused by potassium channel openers such as diazoxide and pinacidil led to the inhibition of gap junction communication and overcame the effect of sulfonylureas. These results suggest that the ATP-sensitive K+ channel regulates gap junctional permeability.

Adenosine Triphosphate↗
PubMed2000

Determination of the percentage of free prostate-specific antigen helps to avoid unnecessary biopsies in men with normal rectal examinations and total prostate-specific antigen of 4-10 ng/ml.

OBJECTIVE: To assess the usefulness of measuring the percentage of free prostate-specific antigen (PSA) in serum to reduce the number of prostate biopsies in men with serum PSA levels between 4 and 10 ng/ml and benign prostate examinations. MATERIALS AND METHODS: The percentage of free PSA (Immulite((R))) in serum was analyzed prospectively in 180 men with benign digital rectal examinations and total PSA serum levels of between 4 and 10 ng/ml. All patients underwent ultrasound-guided sextant prostatic biopsies. Sensitivity, specificity and positive and negative predictive values were calculated as well as the percent of patients in which biopsies could have been avoided for various cutoff values of the percentage of free PSA as an indicator for biopsy. Influence of age in the determination of cut points was evaluated. RESULTS: Cancer was detected in 22.2% (40/180) of the patients. Mean percentage of free PSA was 13.4% in patients with cancer and 18.9% in patients with benign prostatic hyperplasia (p = 0.001). Using a percentage of free PSA cutoff of 22% or less as a criterion for performing prostatic biopsy would have detected 95% of cancers, avoided 25% of benign biopsies and yielded a positive predictive value of 29% in patients who underwent biopsy. Mean percent of free PSA values increased as mean subject age increased, influencing the calculation of cut points, sensitivity and specificity. Leaving the cut point constant across all age groups will oblige older patients to undergo an increased number of unnecessary biopsies, although allowing for higher sensitivity in younger men. CONCLUSIONS: Measurement of the percentage of free serum PSA improves specificity of prostate cancer detection in patients with elevated total serum PSA levels and benign prostate examinations. Subject age seemed to influence the determination of optimal cut points.

Aged↗
PubMed1999

Modelling the changes due to the endothelium and hypertension in the alpha-adrenoreceptor-mediated responses of rat aorta.

The present study focuses on the role of endothelium on alpha1-adrenoceptor-mediated vasoconstriction in aorta from Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR). To define and quantify changes in the parameters governing agonism at alpha1-adrenoceptor by hypertension and/or endothelium, the operational model of analysis was used. In either endothelium intact or denuded aorta, the sensitivity (P < 0.001) and the maximum contraction (P < 0.05) to phenylephrine were smaller in SHR than in WKY. However, in each strain of rats, removal of endothelium increased the sensitivity (P < 0.001) to phenylephrine but reduced (P < 0.05) KCl-evoked vasoconstriction, suggesting a modulation of these responses by the endothelium. The observed differences in sensitivity and maximum contraction are interpreted in terms of the operational parameters: Em, the maximum possible effect; pK(A), the agonist affinity; alpha, the agonist efficacy and n, the slope for the function relating receptor occupancy to pharmacological effect. The estimated parameters reflected differences, between strains, in the signal transduction processes linked to alpha1-adrenoceptor stimulation ascribed to the presence of the endothelium. N(G)-nitro-L-arginine methyl ester (L-NAME), enhanced to a similar extend in both rat strains the sensitivity (P < 0.001) and the maximum contraction to phenylephrine. Indomethacin reduced the maximum contraction to phenylephrine by 56.85% in SHR and by 11.80% in WKY suggesting that contracting prostanoids play a more major role in this response in SHR than in WKY. Nevertheless, these inhibitors were without effect on denuded vessels from both strains suggesting that NO and cyclooxygenase products from the media or the adventitia do not play a role on the phenylephrine-mediated responses. The studied endothelial factors partially explain the observed differences in modulation of alpha1-adrenoceptor responses by the endothelium but suggest the participation of other compounds released by the endothelium.

Adrenergic alpha-Agonists↗
PubMed1999

The effect of albumin on astrocyte energy metabolism is not brought about through the control of cytosolic Ca2+ concentrations but by free-fatty acid sequestration.

Albumin is an important serum protein that under normal circumstances is not present in the brain. However, during development, under hypoxia, or after breakdown of the blood-brain barrier, albumin is found in the brain, where it is able to regulate energy metabolism. In this work the mechanism through which albumin regulates astrocyte metabolism was investigated. Our results show that albumin strongly increases (more than 100%) the flux of glucose and lactate through the pyruvate dehydrogenase-catalyzed reaction in astrocytes from primary culture. However, albumin only slightly stimulated other metabolic pathways, such as the tricarboxylic acid cycle or the pentose phosphate shunt, indicating that it exerts its effect specifically on the reaction catalyzed by pyruvate dehydrogenase. Although albumin increased cytosolic Ca2+ concentrations in astrocytes, our results show that the increase in pyruvate dehydrogenase activity promoted by albumin is not due to the enhancement of Ca2+ concentrations. Indeed, highly purified albumins failed to increase the Ca2+ concentration but did enhance lactate oxidation. In agreement with this, the effect of albumin on lactate oxidation was not abolished after Ca2+ depletion. Instead, the presence of fatty acids inhibited lactate oxidation and counteracted the effect of albumin, suggesting that albumin activates pyruvate dehydrogenase by binding free fatty acids and/or their CoA-derivatives.

Albumins↗
PubMed1998

The K-ATP channel regulates the effect of Ca2+ on gap junction permeability in cultured astrocytes.

Using the scrape-loading technique we show that tolbutamide and glybenzcyclamide, two inhibitors of the K+ channel sensitive to ATP (K-ATP channel), partially prevent the inhibition of gap junction permeability promoted by Ca2+ in cultured astrocytes. This effect was dose-dependent, reaching a maximum at 400 microM and 1 microM of tolbutamide and glybenzcyclamide, respectively. The presence of the Ca2+ ionophore A-23187 strongly reduced the concentration of Ca2+ required to block gap junction permeability but did not abolish the effect of tolbutamide and glybenzcyclamide. These results suggest that the effect of these two compounds are not brought about by control of the intracellular concentration of Ca2+ but probably by the promotion of plasma membrane depolarization.

ATP-Binding Cassette Transporters↗
PubMed1998

The neuron-glia signal beta neuregulin induces sustained CREB phosphorylation on Ser-133 in cultured rat Schwann cells.

beta neuregulins (also called NDF, GGF, ARIA, and heregulins) are neuron-derived molecules that are likely to be responsible for Schwann cell precursor survival, proliferation, and maturation in vivo and in vitro. Although the receptors to which beta neuregulins bind have been defined, little is known about the transcription factors these important ligands activate. Using antibodies, quantitative imaging methods and Western blotting, we show that beta neuregulin induces a high level of phosphorylation of the transcription factor cyclic AMP response element binding protein (CREB) on Ser-133 in cultured rat Schwann cells and that the phosphorylation is prolonged over several hours. In contrast, neurotrophins, CNTF, FGF-2, EGF, and TGF beta induce little or no phosphorylation of CREB despite the fact that receptors for these factors are present on Schwann cells. As expected CREB phosphorylation was detected following cAMP elevation, and it was also induced by elevation of cytoplasmic Ca2+, endothelin 1, and PDGF-BB. The signal was lower than that seen in response to beta neuregulin, and transient, unlike the sustained CREB activation induced by beta neuregulin. Our results suggest that the sustained phosphorylation of CREB on Ser-133 may contribute to the broad spectrum of effects that beta neuregulins have on cells of the Schwann cell lineage and that the CREB pathway may be important for transduction of neuregulin signals in Schwann cells.

Animals↗
PubMed1998

The Neuron-Glia Signal beta Neuregulin Induces Sustained CREB Phosphorylation on Ser-133 in Cultured Rat Schwann Cells.

beta neuregulins (also called NDF, GGF, ARIA, and heregulins) are neuron-derived molecules that are likely to be responsible for Schwann cell precursor survival, proliferation, and maturation in vivo and in vitro. Although the receptors to which beta neuregulins bind have been defined, little is known about the transcription factors these important ligands activate. Using antibodies, quantitative imaging methods and Western blotting, we show that beta neuregulin induces a high level of phosphorylation of the transcription factor cyclic AMP response element binding protein (CREB) on Ser-133 in cultured rat Schwann cells and that the phosphorylation is prolonged over several hours. In contrast, neurotrophins, CNTF, FGF-2, EGF, and TGFbeta induce little or no phosphorylation of CREB despite the fact that receptors for these factors are present on Schwann cells. As expected CREB phosphorylation was detected following cAMP elevation, and it was also induced by elevation of cytoplasmic Ca2+, endothelin 1, and PDGF-BB. The signal was lower than that seen in response to beta neuregulin, and transient, unlike the sustained CREB activation induced by beta neuregulin. Our results suggest that the sustained phosphorylation of CREB on Ser-133 may contribute to the broad spectrum of effects that beta neuregulins have on cells of the Schwann cell lineage and that the CREB pathway may be important for transduction of neuregulin signals in Schwann cells. Copyright 1998 Academic Press.

Journal Article↗
PubMed1998

[Substitution urethroplasties with free graft buccal mucosa].

OBJECTIVE: To present our experience with free graft buccal mucosa substitution urethroplasties. METHODS: Between June, 1992 and December, 1997, we performed 18 urethroplasties with buccal mucosa in 17 patients (double urethroplasty in the same stage in one): 8 for the repair of urethral strictures, 9 for the repair of hypospadias cripples and one for epispadias repair, in an exstrophic boy. Only 3 patients had not undergone previous reconstructive operations. The mean age was 26.2 years (range 10-69). In 8 cases we harvested the graft from the inner cheek and in another 8 cases from the inner lower lip; in two cases we combined mucosa from the cheek and from the lip. In 14 patients we managed to preserve the urethral roof and the buccal mucosa was grafted as an onlay patch; 4 patients underwent full circumference tube replacement. The median follow-up of the series was 17.8 months, ranging from 1 month to 5.5 years. RESULTS: In 15 out of 18 repairs (83.3%) the final outcome was satisfactory, while in three cases the graft failed and reoperation was necessary. In 10 of the 15 successful urethroplasties the end result was excellent: first intention healing no complications or sequelae; in the other 5, although the end result was good, fistulae requiring surgery for closure developed in 2 and meatal stenosis requiring autodilations in three patients. The best results were obtained in strictures of the bulbar urethra secondary to trauma with 100% success rate. In hypospadias the success rate was 77.7%. Onlay patch grafts never failed, with 10 out of 14 excellent results. Three out of 4 tubed grafts failed. CONCLUSIONS: At short and medium term, the free grafts of buccal mucosa yield results comparable to those of other epitheliums in use for urethral repair, thus increasing the choice of techniques at our disposal for one-stage repairs. We consider that it is best suited for long strictures of the bulbar urethra.

Adolescent↗
PubMed1997

P0 is constitutively expressed in the rat neural crest and embryonic nerves and is negatively and positively regulated by axons to generate non-myelin-forming and myelin-forming Schwann cells, respectively.

We show that in the rat, the major gene of PNS myelin, P0, is expressed long before myelination in the neural crest, Schwann cell precursors, and embryonic Schwann cells irrespective of whether they will myelinate or not. This myelin-independent P0 expression is constitutive and likely to serve as a specific marker for the Schwann cell lineage. The much higher P0 expression accompanying myelination is therefore not new gene expression but strong up-regulation of preexisting basal levels. We provide new evidence that the up-regulation to myelination-related levels depends on positive extrinsic signals and therefore does not represent a constitutive phenotype. P0 mRNA is not detectable in mature non-myelin-forming Schwann cells of the sympathetic trunk, but is detectable after transection, indicating that there is a P0-inhibitory signal associated with mature unmyelinated axons. Thus, the regulation of the P0 gene is complex, encompassing extrinsically signaled amplification superimposed on a highly lineage-specific and constitutive basal expression.

Animals↗
PubMed1997

Use of the operational model of agonism and [3H]prazosin binding to assess altered responsiveness of alpha1-adrenoceptors in the vas deferens of spontaneously hypertensive rat.

Changes in functional responsiveness to alpha1-adrenoceptor activation with noradrenaline and in [3H]prazosin binding in the epididymal portion of vas deferens from normotensive Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR) were investigated. The operational model fitting and the nested hyperbolic method were used to analyze the effects of irreversible receptor alkylation by phenoxybenzamine (0.1 microM) on the alpha1-adrenoceptor mediated contractile responses to noradrenaline of vasa deferentia from SHR and WKY rats. Saturation isotherms for [3H]prazosin revealed a significant increase (P < 0.05) in the Bmax in SHR vas deferens (145 +/- 19 fmol/mg protein) compared with vas deferens from normotensive controls (75 +/- 12 fmol/mg protein) without changes in the K(D). No differences in the proportion of high and low affinity binding sites for WB-4101 and 5-methylurapidil were observed. The maximum contractile response, alpha, (P < 0.001) and the pEC50 (P < 0.05) values for noradrenaline were greater for SHR than for WKY rat tissues. The apparent affinity (pK(A)) determined by the nested hyperbolic method and by the operational model of agonism was found to be similar in the two strains. In agreement with relative pEC50, the efficacy (tau) value for SHR was greater than for WKY rats. However, the difference in the tau estimates did not reach statistical significance. In summary, in the epididymal portion of SHR vas deferens, the increased maximum contractile response to noradrenaline is due to an increase of Em. Taken together, the tau values and the results from binding experiments lead to the assumption that the transducer constant K(E) must be greater in SHR than in WKY rats, suggesting a deterioration in the transduction of the stimulus provided by the agonist in hypertensive animals.

Adrenergic alpha-Agonists↗