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Biomedical subjects

E Castro

Publications and source records attributed to E Castro.

At least 19 recordsLinked to original sources
PubMed2026

A spotlight on PTEN alterations in prostate cancer: A narrative review.

Among the molecular alterations observed in prostate cancer, PTEN loss represents a key event, functionally linked to aberrant activation of the PI3K/AKT/mTOR pathway. Loss of PTEN function contributes to disease progression, therapy resistance and poor prognosis. This review highlights the biological significance and the prognostic role of PTEN in prostate cancer, the biologically relevant crosstalk between the PI3K and androgen receptor pathways, and the implications of this interaction for tumour adaptation and treatment resistance. We also discuss current methodologies for PTEN assessment, including immunohistochemistry and genomic techniques, and provide an overview of clinical trials targeting the PI3K/AKT axis in prostate cancer. Understanding PTEN alterations is essential for improving prognostic stratification and guiding precision oncology approaches.

Humans↗
PubMed1999

Polymorphisms at the Werner locus: I. Newly identified polymorphisms, ethnic variability of 1367Cys/Arg, and its stability in a population of Finnish centenarians.

The Werner syndrome gene (WRN) encodes a novel helicase of 1,432 amino acids. Homozygous mutations, all of which result in the truncation of the protein, lead to Werner syndrome. However, little is known about the role of WRN in "normal" aging. We have identified four missense polymorphisms and four conservative polymorphsims in WRN gene. A single study showed that a polymorphism at amino acid 1367 Cys(TTG)/ Arg(CTG) is associated with a variation in risk of myocardial infarction among a Japanese population. The 1367 Cys/Arg polymorphism was examined during aging in three different populations: Finnish, Mexican, and North American. The frequencies of 1367 Cys were higher than those of 1367 Arg in all the populations examined, though the frequencies varied among populations. The frequency of the 1367 Arg allele, thought to be protective against myocardial infarction in a Japanese population, was approximately three times higher in the North American and Finnish adult populations. When newborns and centenarians were compared within the Finnish population, no differences were observed in the proportions of 1367 Cys/Arg across age groups. Within the Finnish population, we confirmed a significant decrease of the APOE epsilon2 allele and an increase in the epsilon4 allele in newborn infants compared with centenarians. Thus, unlike the APOE polymorphism, there is no evidence of an association of this WRN polymorphism with longevity.

Adult↗
PubMed1998

Potentiation of adenosine 5'-triphosphate calcium responses by diadenosine pentaphosphate in individual rat cerebellar astrocytes.

The calcium responses induced by adenosine 5'-triphosphate (ATP) were examined in single cerebellar type 1 astrocytes by fura-2 microfluorometry. ATP elicited fast and transient increases of intracellular calcium concentration ([Ca2+]i) even in the absence of extracellular calcium, indicating the involvement of metabotropic purinoceptors. The co-stimulation with P1P5-di(adenosine-5')pentaphosphate (Ap5A; 0.1 microM) potentiated ATP-metabotropic calcium responses. After this preincubation ineffective concentrations of ATP triggered 40% of maximal response. Co-stimulation with Ap5A and ATP was mandatory. The potentiated response to ATP was also independent of extracellular Ca2+ and was maintained for long periods of time (h). These results show a relevant interaction of purinoceptors that may imply a novel mechanism of action for diadenosine polyphosphates.

Adenosine Triphosphate↗
PubMed1998

Ca2+ signals mediated by P2X-type purinoceptors in cultured cerebellar Purkinje cells.

We have studied [Ca2+]i signals elicited by extracellular ATP in cultured cells from postnatal day 7-8 rat cerebellum using single-cell fluorescence microscopy and fura-2. Putative Purkinje cells selected under phase contrast by size and characteristic cytoplasm appearance were uniquely identified by selective labeling with anti-calbindin antibodies. Extracellularly applied ATP (50 microM) evoked fast [Ca2+]i rises revealed by a rapid and transient increase in fura-2 F340/F380 ratio in all Purkinje cells tested, whereas granule cells failed to show a response to ATP. The mean [Ca2+]i increase was approximately 400 nM, comparable to that obtained after glutamate stimulation. The response to ATP was completely abolished by removal of extracellular Ca2+ with EGTA. Conversely, an increased extracellular Mn2+ entry pathway was activated by ATP stimulation. These results indicate that the effect of ATP is mediated by an ionotropic P2X receptor. The action of ATP was mimicked by the analog 2-methylthio-adenosine 5'-triphosphate with similar efficacy but almost half its potency (EC50, 10.6 +/- 0.7 vs 21.7 +/- 1.9 microM). Other purinergic compounds tested, such as adenosine(5')-tetraphospho-(5')adenosine, adenosine(5')pentaphospho-(5')adenosine, adenosine 5'-(alpha, beta-methylene) triphosphate, UTP, and adenosine, were completely inactive in eliciting [Ca2+]i responses. The purinoceptor antagonists suramin and pyridoxalphosphate-6-azophenyl-2', 4'disulphonic acid effectively blocked the responses elicited by ATP. Our results demonstrate for the first time the presence of functional ionotropic P2X purinoceptors in the cerebellar Purkinje cells and indicate that their pharmacology is similar to receptors formed by P2X2 subunit oligomers.

Adenosine Triphosphate↗
PubMed1998

Segregation of nitric oxide synthase expression and calcium response to nitric oxide in adrenergic and noradrenergic bovine chromaffin cells.

Previous work has demonstrated that nitric oxide can be an important intracellular messenger in the regulation of neurosecretion in chromaffin cells. Since standard chromaffin cell cultures are mixed populations of noradrenaline and adrenaline producing cells, it would seem important to understand the functional differences between these individual components. The use of fluorescence imaging techniques for the recording of cytosolic calcium from single chromaffin cells together with the immunoidentification of individual cells with specific antibodies against tyrosine hydroxylase, N-phenyl ethanolamine methyl transferase and nitric oxide synthase, has allowed us to measure single-cell calcium responses in identified adrenergic, noradrenergic and nitrergic chromaffin cells, thus helping us to clarify the differential role of nitric oxide in the function of these chromaffin cell types. 53 +/- 2% of chromaffin cells were able to synthesize nitric oxide (nitric oxidesynthase-positive cells), these cells being mainly noradrenergic (82 +/-2%). Results indicate that nitric oxide donors such as sodium nitroprusside, molsidomine and isosorbide dinitrate evoke [Ca2+]i increases in a 62 +/- 4% of chromaffin cells, the response to nitric oxide donors being between 30 and 50% of that of 20 microM nicotine. Cells responding to nitric oxide donors were mainly adrenergic (68 +/- 5%) although 45 +/- 9% of noradrenergic cells also gave [Ca2+]i increasing responses. The distribution of nitric oxide responding cells between nitric oxide synthase-positive and negative was very similar in the whole population (63 +/- 5 and 60 +/- 7%, respectively), but these differences were more prominent when considering the distribution of nitric oxide response between noradrenergic and adrenergic nitric oxide synthase-positive cells; while 73 6% of adrenergic nitric oxide synthase-positive cells evoke [Ca2+]i increases by nitric oxide stimulation, only 35 +/- 11% of noradrenergic nitric oxide synthase-positive cells respond. Taken together these results seem to indicate that (i) nitric oxide could act within adrenal medulla as both an intracellular and intercellular messenger; and (ii) noradrenergic cells seem to be specialized in nitric oxide synthesis while adrenergic cells with an endocrine function could mainly act as a target of neurosecretory action of this second messenger.

Animals↗
PubMed1998

A purinergic component of the excitatory postsynaptic current mediated by P2X receptors in the CA1 neurons of the rat hippocampus.

The pyramidal neurons in the CA1 area of hippocampal slices from 17- to 19-day-old rats have been investigated by means of patch clamp. Excitatory postsynaptic currents (EPSCs) were elicited by stimulating the Schaffer collateral at a frequency below 0.2 Hz. It was found that inhibition of glutamatergic transmission by 20 microM 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and 100 microM 2-amino-5-phosphonovaleric acid (D-APV) left a small component of the EPSC uninhibited. The amplitude of this residual EPSC (rEPSC) comprised 25 +/- 11% of the total EPSC when measured at a holding potential of -50 mV. The rEPSC was blocked by selective P2 blocker pyridoxal phosphate-6-azophenyl-2'-4'-disulphonic acid (PPADS) 10 microM and bath incubation with non-hydrolysable ATP analogues, ATP-gamma-S and alpha, beta-methylene-ATP at 50 and 20 microM, respectively. The rEPSC was dramatically potentiated by external Zn2+ (10 microM). In another series of experiments exogenous ATP was applied to the CA1 neurons in situ. An inward current evoked by ATP was inhibited by PPADS to the same extent as the rEPSC. It is concluded that, depending on membrane voltage, about one-fifth to one-quarter of the EPSC generated by the excitatory synaptic input to the hippocampal CA1 neurons of rat is due to the activity of P2X receptors.

2-Amino-5-phosphonovalerate↗
PubMed1998

[Follow-up of partial seizure progression in an infant].

UNLABELLED: OBJECTIVE AND MATERIAL: We are carried out a retrospective study of 43 patients, 21 males and 22 women entered during the period of infancy in the Service of Neurology of our hospital and with diagnostic of any type of partial seizure, in an intent to correlate a series of clinical parameters, electroneurophysiologics and initial therapeutics with their factors follow-up periods. RESULTS: They are a half age of 7.11 months (1-19), consecutive being controlled for a period of time of 40 months (6-96). We have settled down a relationship between the drugs utilized in the first seizure and that other that they remained in their last revision, the current state of the critical manifestations, and the existence or not of an agreement between the e diagnosis emitted to the discharge and the development of the illness. CONCLUSION: After the present study, we thought that the current classification of the epileptic seizures is insufficient in the age of the infant, with presages much more complexes.

Anticonvulsants↗
PubMed1997

The influence of pH and aeration rate on the fermentation of D-xylose by Candida shehatae.

The effects of the initial pH and air supply on the production of ethanol from D-xylose using the yeast Candida shehatae in a batch reactor were investigated. The initial pH was altered within the range of 2.5-6.5 and the specific aeration rate from 0.0-0.3 vv-1 min-1. The results showed that the most favorable initial pH for ethanol production was 4.5 and aeration via the stirring vortex of the bioreactor was sufficient. Under these conditions, the maximum specific growth rate (mu(m)) was 0.329 h-1; biomass production rate (b), 0.024 kg m-3 h-1; overall biomass yield (YGx/s), 0.036 kg kg-1; the specific uptake rate of D-xylose (qs), 2.0 kg kg-1 h-1; and the specific ethanol production rate (qE), 0.72 kg kg-1 h-1 (both at 20 h culture time). The average xylitol yield (Yxy/s) was 0.078 kg kg-1 and the overall ethanol yield (YGE/s), 0.41 kg kg-1. Both qs and qE diminished once the exponential growth phase was over.

Aerobiosis↗
PubMed1997

[Monotherapy with vigabatrin in the treatment of West's syndrome].

INTRODUCTION: Vigabatrin (VGB) was specifically synthesized to enhance inhibitory GABAergic transmission by elevating GABA levels via irreversible inhibition of GABA transaminase. MATERIAL AND METHODS: This study was conducted to determine the efficacy of VGB introduced as monotherapy in 26 children fulfilled the criteria for diagnosis of West syndrome. Duration of follow-up was 24 months. RESULTS: Following the introduction of VGB, 13 patients became seizure free, a special efficacy in one case of tuberous sclerosis. Relapses of infantile spasms occurred in 8 infants, generalized seizures developed in 4 infants, and partial seizures in 3, of whom 2 were eventually rendered seizure-free by increasing the dose. EEG features and age affecting the response rate. VGB has been well tolerated in children with agitation being the most commonly reported side effects, and one case required discontinuation of therapy. CONCLUSIONS: VGB seems to be an effective an safe antiepileptic drug as primary monotherapy for West syndrome.

Adrenocorticotropic Hormone↗
PubMed1996

The diadenosine polyphosphate receptors: P2D purinoceptors.

Diadenosine polyphosphates-Ap4A, Ap5A and Ap6A-are co-stored in neurosecretory vesicles together with ATP and aminergic compounds. They are released from neural cells and synaptic terminals in a Ca(2+)-dependent process. Ligand binding and displacement experiments carried out with [3H]Ap4A on isolated chromaffin cells and synaptosomal preparations result in curvilinear Scatchard plots with Kd values close to 0.1 nM for the high-affinity binding sites. Displacement curves with two steps are obtained for homologous and heterologous nucleotide ligands; the lowest-affinity step exhibits Ki values in the micromolar range for ApnA compounds. The high-affinity binding sites were named P2D purinoceptors on the basis of their binding characteristics. Single-cell studies in neurochromaffin cells indicate the presence of P2X purinoceptors in noradrenergic cells that do not respond to Ap4A and in which noradrenaline secretion can be induced by influx of extracellular Ca2+. P2Y receptors that respond to ATP analogues and ApnAs are present in endothelial cells from adrenal medulla. Those cells that express P2U purinoceptors are unresponsive to ApnAs. Ectodiadenosine polyphosphate hydrolases with Km values of 0.3 to 2 microM are present in both neural and endothelial cells from adrenal medulla. In midbrain synaptic terminals diadenosine polyphosphates induce Ca2+ entry from the extracellular medium. The fact that the synaptic response is not cross-desensitized by ATP and its non-hydrolysable analogues, the non-blocking effect of suramin, and the differential effect of Ca2+ channel blockers, together suggest that there are different receptors for nucleotides and dinucleotides in rat brain synaptosomes, which we have called P4 purinoceptors on the basis of functional studies.

Adrenal Medulla↗
PubMed1996

Experience with transvaginal ultrasound-guided aspiration of supernumerary follicles for the prevention of multiple pregnancies after ovulation induction and intrauterine insemination.

OBJECTIVE: To avoid multiple pregnancies caused by ovulation induction. SETTING: Infertile couples treated in the Women's Hospital and the Institute of Reproductive Medicine of the University of Münster, Münster, Germany. DESIGN: The outcome of ovulation induction in patients in whom supernumerary ovarian follicles were aspirated transvaginally was compared with the outcome in patients in whom this intervention was not necessary. In a second randomized prospective study, the efficacy of a low dosage of gonadotropins was compared with a higher dosage. PATIENTS: Two hundred twenty-seven couples suffering from male infertility, unexplained infertility, incipient ovarian failure, and polycystic ovaries. INTERVENTIONS: Aspirations were performed if more than three follicles were sized > 14 mm. MAIN OUTCOME MEASURE: Number of (multiple) pregnancies. RESULTS: During 232 ovulation inductions, 127 aspirations of supernumerary follicles were performed (54.7%). The pregnancy rate (PR) in these cycles was similar to cycles in which aspirations were unnecessary (24.4% versus 21.9%). The efficacy of 75 units of FSH administered daily during the recruitment phase of follicular development was equivalent to 150 units of FSH (PR: 32.4% versus 31.6%), but supernumerary follicles were fewer (26.5% versus 76.3%). Six twins, two triplets (multiple PR: 10.4%), and no ovarian hyperstimulation syndrome occurred. CONCLUSIONS: Transvaginal aspiration of supernumerary follicles does not reduce the PR in ovulation induction. Supernumerary follicles can be avoided by low-dose administration of gonadotropins without compromising the PR.

Female↗
PubMed1996

Structure and function of the Bacillus SpoIIE protein and its localization to sites of sporulation septum assembly.

Functioning of the spoIIE locus of Bacillus subtilis is required for formation of a normal polar septum during sporulation and for activation of the transcription factor sigma F, which directs early forespore-specific gene expression. We have determined the DNA sequence of the wild type and several mutant alleles of the spoIIE gene of B. subtilis and sequenced a substantial portion of its presumptive homologue in Bacillus megaterium. We show that the spoIIE locus encodes a single large protein with a predicted molecular mass of 92 kDa. Each of five point-mutation alleles, which have traditionally defined the locus, and two transposon-generated mutations were shown to fall within the coding sequence for the 92 kDa gene product or within sequences expected to be required for its expression. The amino-terminal portion of the predicted SpoIIE gene product, comprising approximately 40% of the protein, is extremely hydrophobic and is expected to contain up to 12 membrane-spanning segments. The remainder of the protein contains no hydrophobic segments long enough to span a lipid bilayer and is therefore presumed to comprise one or more globular, aqueous-phase exposed domains. An in-frame fusion joining the 3' end of the B. megaterium spoIIE coding sequence to the 5' end of gfp, a gene encoding the green fluorescent protein (GFP) of Aquorea victoria, resulted in a strong, sporulation-specific fluorescent signal localized to the sites of sporulation septum assembly. We speculate that SpoIIE plays a role in assembling the sporulation septum, perhaps determining the special properties of the structure that permit intercompartment signalling during development.

Alleles↗
PubMed1996

Autoradiographic distribution of [3H]sumatriptan-binding sites in post-mortem human brain.

The anatomical distribution of [3H]sumatriptan-binding sites was analysed in brain tissue sections from 11 subjects. Relevant concentrations of [3H]sumatriptan-binding sites were seen in areas such as visual cortex > locus niger > globus pallidus > layers IV-V of the frontal cortex > subiculum > entorhinal cortex > nucleus tractus solitarius > nucleus trigeminalis caudalis. This distribution of [3H]sumatriptan-binding sites in the human brain shows some differences when compared with that of 5HT1D receptors, confirming that, besides 5HT1D, sumatriptan also binds to 5HT1F receptor subtype. Some species differences are evident between the distribution of [3H]sumatriptan-binding sites in the human brain and that reported for guinea-pig and rat brains, emphasizing that caution is needed in extrapolating experimental data from animals to humans. Furthermore, these data help to explain some of the therapeutic actions of sumatriptan. The remarkable levels of binding found in areas as nucleus tractus solitarius and nucleus trigeminalis caudalis suggest that in migraine attacks sumatriptan could exert its specific anti-emetic effects and, partly at least, induce analgesia by directly acting over these brain nuclei.

Adult↗
PubMed1996

Two components of glutamate exocytosis differentially affected by presynaptic modulation.

The total Ca(2+)-dependent release of glutamate induced by depolarization of cerebrocortical nerve terminals with KCl was analyzed into a fast and a slow component. The fast component exhibited a decay time of < 1 s and accounted for 0.95 +/- 0.10 nmol of glutamate, whereas the slow component, which exhibited a decay time of 52 +/- 7 s, accounted for the release of 2.48 +/- 0.19 nmol of glutamate. These two components were differentially affected by the Ca2+ chelator BAPTA, the divalent cation Sr2+, or the botulinum neurotoxin A. The adenosine A1 receptor agonist N6-cyclohexyladenosine strongly reduced the fast component without altering the slow component. In contrast, the inhibitory effect of arachidonic acid and the facilitatory action of the metabotropic glutamate receptor agonist (1S, 3R)-1-aminocyclopentane-1, 3-dicarboxylic acid were observed as a decrease and an increase, respectively, in the two components. It is concluded, first, that the fast and slow components correspond to the release of docked and mobilized vesicles, respectively, and second, that presynaptic modulation more significantly alters the fast component of release.

Animals↗