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R Cortés

Publications and source records attributed to R Cortés.

At least 37 records · Page 2Linked to original sources
PubMed1998

Basal and stimulated extracellular serotonin concentration in the brain of rats with altered serotonin uptake.

We examined the relationship between the density of serotonergic (5-hydroxytryptamine [5-HT]) uptake sites and extracellular 5-HT concentration in the rat brain using microdialysis with two different models, lesions with 5,7-dihydroxytryptamine (50 microg in the dorsal raphe nucleus (DRN) 15 days before) and sublines of rats genetically selected displaying extreme values of platelet 5-HT uptake. Compared to controls, lesioned rats had a reduced cortical concentration of 5-hydroxyindoles (45%), unchanged basal extracellular 5-HT in the DRN and ventral hippocampus (VHPC), and reduced basal 5-hydroxyindoleacetic acid (5-HIAA) concentrations (46%, DRN; 22%, VHPC). Yet the perfusion of 100 mmol/L KCl or 1 micromol/L citalopram elevated dialysate 5-HT significantly more in the DRN and VHPC of controls. In genetically selected rats, platelet 5-HT content and uptake were highly correlated (r2 = 0.9145). Baseline dialysate 5-HT (VHPC) was not different between high and low 5-HT rats and from normal Wistar rats. However, KCl or citalopram perfusion increased dialysate 5-HT significantly more in high 5-HT than in low 5-HT rats, and the former displayed a greater in vivo tissue 5-HT recovery. Significant but small differences in the same direction were noted in [3H]citalopram binding in several brain areas, as measured autoradiographically. Thus, basal extracellular 5-HT (but not 5-HIAA) concentrations are largely independent on the density of serotonergic innervation and associated changes in uptake sites. However, marked differences emerge during axonal depolarization or reuptake blockade. The significance of these findings for the treatment of mood disorders in patients with neurological disorders is discussed.

5,7-Dihydroxytryptamine↗
PubMed1998

Prospective comparative study with intracavernous sodium nitroprusside and prostaglandin E1 in patients with erectile dysfunction.

PURPOSE: To compare the effectiveness of intracavernous administration of sodium nitroprusside and prostaglandin E1 to induce penile erection in men with erectile dysfunction. MATERIAL AND METHODS: 100 patients with erectile dysfunction entered the study prospectively. As part of the diagnostic workup, each patient received an intracavernous injection of 20 microg prostaglandin E1 and a second injection of 600 microg sodium nitroprusside 1-7 days later. A tourniquet was placed at the base of the penis before each injection. The data recorded included time required to initiate tumescence, local and systemic side effects, objective and subjective quality of erections, duration of tumescence and patient satisfaction by means of a personal questionnaire. RESULTS: Prostaglandin E1 induced better overall responses than sodium nitroprusside, the difference being almost significant (p = 0.055). The overall duration of erections was also significantly longer with prostaglandin E1 (mean 81.3 min) than with sodium nitroprusside (mean 65.4 min; p < 0.04). 67% of the patients considered the erections induced with prostaglandin E1 to be of better quality than those with sodium nitroprusside, and only 11% stated that sodium nitroprusside was superior. Side effects were minimal with both drugs, the most frequent side effect being systemic hypotension, which was induced by sodium nitroprusside in 7% of the patients. CONCLUSIONS: The moderate risk of systemic hypotension and the lower potency of sodium nitroprusside to induce erections compared to prostaglandin E1 rules out sodium nitroprusside as a routine alternative intracavernous drug in men with erectile dysfunction at the doses employed. Sodium nitroprusside, however, could be used in patients who have intolerance or penile pain with intracavernous prostaglandin E1.

Adult↗
PubMed1997

Distribution of AMPA receptor subunit mRNAs in the human basal ganglia: an in situ hybridization study.

The distribution of AMPA receptor subunit mRNAs (spliced flip and flop variants of GluR-A to GluR-D) in the human post-mortem striatum, nucleus accumbens, globus pallidus and basal nucleus of Meynert was determined by in situ hybridization histochemistry. In the striatum and nucleus accumbens, for each subunit, the mRNA for the flop variant was more enriched than that for the corresponding flip variant. The GluR-C(flop) mRNA was most abundant, followed by the GluR-A(flop) mRNA. Transcripts for flop forms were evenly distributed in these regions, whereas those for flip forms showed a dorsoventral increasing gradient of the hybridization signals. The signals in these areas were found to originate mainly from medium-sized neurons. In the globus pallidus, mRNAs encoding GluR-A(flop) and GluR-C(flop) were also abundantly expressed. The basal nucleus of Meynert was enriched for mRNAs of flop forms. In conclusion, AMPA receptors in these areas of the human basal ganglia appeared to be mainly composed of flop variants, especially GluR-A(flop) and GluR-C(flop). However, the finding that flip transcripts were more abundant in the nucleus accumbens than in the striatum implies differences in functions of AMPA receptors between the two regions.

Aged↗
PubMed1996

Localization of 5-HT4 receptor mRNA in rat brain by in situ hybridization histochemistry.

Oligonucleotide probes that recognize two cloned splice variants (5-HT4S and 5-HT4L) of 5-HT4 receptors were used to study by in situ hybridization the localization in rat brain of mRNA encoding these receptors. A probe common to both variants reveals high levels of transcripts in olfactory tubercle, some components of the basal ganglia (caudate putamen, ventral striatum), medial habenula and hippocampal formation. Similar patterns of distribution are obtained with probes that recognize each splice variant individually, suggesting that no dramatic differences exist in their respective regional distribution. Comparison of mRNA distribution with receptor distribution as visualized with [125I]SB 207710 indicates that 5-HT4 receptors are localized both somatodendritically in e.g. caudate putamen and on axon terminals in e.g. substantia nigra and globus pallidus.

Animals↗
PubMed1996

Automated analysis of drugs in urine.

A totally automated procedure has been developed for the preparation and analysis of 34 basic and neutral drugs in urine samples using an integrated HP 7686 PrepStation-HP 6890 gas chromatographic system. The automated preparation of the sample consisted of a liquid-liquid extraction of 250 microliters urine at alkaline pH with 100 microliters of methyl tert.-butyl ether. After phase separation the organic solvent was automatically placed in the injector of the gas chromatograph and analysed. High recoveries of extraction were obtained. The limits of detection of most of the drugs were less than 0.5 microgram/ml. The method, which allows the preparation and analysis of the samples to be completely synchronised, showed good accuracy and precision.

Automation↗
PubMed1996

5-HT receptors in mammalian brain: receptor autoradiography and in situ hybridization studies of new ligands and newly identified receptors.

In recent years the family of mammalian serotonin receptors has grown to 14 different subtypes, characterized by pharmacological or molecular biological techniques. In parallel, new ligand molecules have been developed for their study. However, selective ligands are not yet available to study every one of them. In addition the degree of selectivity of ligands, hitherto regarded as specific for a particular receptor subtype has been called in question by their affinities for newly discovered receptors. Consequently, a re-evaluation of past ligand receptor autoradiography work is necessary in view of the redefined receptor profiles of these ligands, and the introduction of newly developed ligands. A further difficulty for the characterization of these receptors is the absence of selective antagonist ligands which, for some of the subtypes, have become available only recently. In an attempt to overcome these difficulties we have combined in situ hybridization histochemistry and receptor ligand autoradiography to study the regional and cellular localization of several serotonin receptors in the rodent brain. In addition, for some receptors, we have expanded these studies to primates, including humans. We have found that the distribution of 5-HT1A receptors in monkey brain, labelled with the agonist 3H-8-OH-DPAT and the antagonist 3H-WAY 100635 was very similar at the levels examined, and corresponded well with that observed for the cells containing mRNA coding for this receptor, confirming the somatodendritic localization of 5-HT1A receptors in monkey brain. The labelling conditions to visualize 5-HT1F receptors in guinea pig brain, namely 3H-sumatriptan in the presence of 10(-8) M 5-CT to block 5-HT1D receptors, are suitable for visualizing this receptor, since the results agreed with those observed by in situ hybridization. By using 3H-ketanserin and 3H-mesulergine in parallel with in situ hybridization using the corresponding oligonucleotides, we were able to show that these ligands label respectively 5-HT2A and 5-HT2C binding sites in monkey brain. 5-HT4 receptors were localized in the brain of several species including humans by using 125I-SB 207710. In situ hybridization experiments performed in guinea pig confirmed that 5-HT4 receptors are localized on the terminals of the striatopallidal and striatonigral projections. 5-HT7 binding sites were labelled in rat and guinea pig brains by incubating with 3H-5-CT in the presence of 100 microM WAY 100135 and 250 microM GR 127935; the distribution obtained in both species agreed, in general, with that of the corresponding mRNA coding for them. These results are an illustration of the understanding of our current knowledge of the chemical neuroanatomy of the mammalian 5-HT system.

Adult↗
PubMed1996

Autoradiographic analysis of 5-HT receptor subtypes labeled by [3H]5-CT ([3H]5-carboxamidotryptamine).

This work examines the autoradiographic distribution of serotonin (5-HT) receptor subtypes in rat, guinea pig and human brain, using [3H]5-HT and [3H]5-CT as ligands. Different displacers were used to mask radioligand binding to 5-HT1A, 5-HT1B/1D and 5-HT2C receptors, in an attempt to visualize other receptor populations, which presumably would correspond to 5-HT1E and 5-HT1F sites. Brain areas enriched in 5-HTnon1A/1B/1D sites in guinea pig were the hilus, dentate gyrus, striatum, claustrum, substantia nigra and superior colliculus, among others. In humans, however, the claustrum, a structure supposed to contain 5-HT1E sites, showed significant densities of [3H]5-CT binding. An interesting finding was that blockade [3H]5-CT binding to 5-HT1A receptors by 8-OH-DPAT could only be achieved at very high concentrations of the displacer. This could be due to differences in the affinity of ligands in intact tissue sections compared to membrane homogenates or cell lines. Another possibility would be that [3H]5-CT labels 5-HT1A receptors in the low-affinity state. These hypotheses remain to be investigated.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1996

Differential regional distribution of AMPA receptor subunit messenger RNAs in the human spinal cord as visualized by in situ hybridization.

The electrophysiological characteristics of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors vary with their subunit composition. The establishment of the subunit distribution is an essential step in the understanding of the function of these receptors. In the spinal cord, AMPA receptors are involved in normal and, possibly, pathological processes. Using in situ hybridization histochemistry with radiolabelled oligonucleotides as probes, we have studied the distribution of AMPA receptor subunit messenger RNAs (spliced flip and flop variants of glutamate receptor subunits A-D) in the human post mortem spinal cord. Transcripts for flip variants were preferentially expressed in the superficial dorsal horn, with a dorsoventral decreasing gradient of the signals. Transcripts for flop variants were also abundantly present in all layers of the gray matter, with the highest signal being observed for glutamate receptor subunit Bflop. Accordingly, flop forms were predominant in areas other than the superficial dorsal horn. This differential distribution of transcripts in the dorsal horn suggests that the subunit composition of AMPA receptors varies with the afferent inputs; AMPA receptors on neurons in the superficial dorsal horn, where terminals of thin primary afferents conducting noxious information are located, contain more flip forms, whereas neurons in the deep dorsal horn, where thick primary afferents mediating innocuous stimuli terminate, have AMPA receptors which are mainly composed of flop forms of glutamate receptor subunits A and B. The relatively high abundance of glutamate receptor subunit B transcripts in the superficial laminae of the dorsal horn indicates that AMPA receptors in these laminae have lower Ca2+ permeability. In addition, the relative abundance of glutamate receptor subunits Bflip and Dflop may show that AMPA receptors in the superficial dorsal horn have slow desensitization, while those of motor neurons have rapid desensitization.

Adult↗
PubMed1995

Determination of epitestosterone and testosterone in urine by high-performance liquid chromatography.

This paper describes an alternative HPLC method for the determination of testosterone and epitestosterone, which is simple, rapid, selective, sensitive and reproducible. Samples were prepared using a previous enzymatic hydrolysis with liquid-liquid extraction. The determination was carried out on a Hypersil BDS-C18 reversed-phase column with gradient elution and UV absorbance detection (240 nm). The limits of quantification (signal-to-noise ratio = 6) were 20 ng/ml for testosterone and 30 ng/ml for epitestosterone.

Chromatography, High Pressure Liquid↗
PubMed1994

Urine excretion of androgen hormones in professional racing cyclists.

This study was performed on 16 professional racing cyclists to examine changes in urine concentrations of androgen hormones (testosterone, epitestosterone, androsterone, etiocholanolone, 11-hydroxy-androsterone and 11-hydroxy-etiocholanolone) and plasma sex hormone binding globulin (SHBG) after training and after competition. The urinary concentrations of androgen hormones decreased during the period of training and increased during competition, this being the reverse of what happened to SHBG plasma concentrations. These changes would suggest that physical activity may have an influence on the elimination of androgen hormones and on the synthesis of its transporting protein SHBG.

Androgens↗
PubMed1994

Dopaminergic regulation of the serotonergic raphe-striatal pathway: microdialysis studies in freely moving rats.

Morphological evidence demonstrates the existence of dopaminergic afferent pathways and dopamine (DA)-containing neurons in the dorsal raphe nucleus (DRN). In a recent report, a DA D2-like receptor-mediated regulation of serotonin (5-HT) extracellular concentration in DRN has been found. Given the existence of somatodendritic 5-HT1A autoreceptors in the DRN, changes of the extracellular concentration of 5-HT in the vicinity of cell bodies and dendrites may be relevant for the control of the activity of ascending serotonergic pathways. In the present brain microdialysis study we have used a chromatographic method (HPLC) enabling the simultaneous measurement of DA, 5-HT, and their main metabolites dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindoleacetic acid (5-HIAA). The presence of a neuronal pool of DA within the DRN was revealed by the local infusion of amphetamine (10 microM), which significantly increased the extracellular concentration of both amines. The local striatal infusion (10 microM) of the selective DA D1-like agonist SKF-38393, the selective DA D2-like agonist quinpirole (LY 171,555), or the nonselective DA agonist apomorphine markedly decreased DA and DOPAC extracellular concentrations and failed to modify 5-HT or 5-HIAA in the striatum, indicating the lack of terminal (striatal) control of 5-HT release by dopaminergic transmission. In contrast, the systemic administration of apomorphine (2.8 mumol/kg, s.c.) significantly increased the extracellular concentration of 5-HT in the DRN and decreased it in the striatum. The reduction of striatal 5-HT extracellular concentration was prevented by the previous administration of the selective 5-HT1A receptor antagonist WAY 100135 (17.6 mumol/kg, s.c.), which by itself did not change extracellular 5-HT in striatum.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dihydroxyphenylacetic Acid↗
PubMed1993

p-chlorophenylalanine increases tryptophan-5-hydroxylase mRNA levels in the rat dorsal raphe: a time course study using in situ hybridization.

The effects of a single dose of p-chlorophenylalanine on the mRNA encoding tryptophan-5-hydroxylase (EC 1.14.16.4) in the rat dorsal raphe nucleus were analyzed using in situ hybridization. The levels of tryptophan-5-hydroxylase mRNA were markedly increased in cell bodies located in the ventromedial part of the dorsal raphe 1-2 days after p-chlorophenylalanine (300 mg/kg, i.p.) administration. This was followed by a decrease in the amount of tryptophan-5-hydroxylase mRNA, which returned to basal values by 5 days after treatment. An almost symmetric time course was observed for the midbrain serotonin concentration. Our results on the temporal pattern of changes in tryptophan-5-hydroxylase mRNA levels in the ventromedial part of the dorsal raphe are opposite to those reported for the enzyme activity and serotonin concentration after p-chlorophenylalanine treatment. These changes may result from modifications in enzyme mRNA expression, suggesting that tryptophan-5-hydroxylase gene transcription is involved in feedback mechanisms regulating serotonin synthesis.

Animals↗
PubMed1992

Evidence for upregulation of galanin synthesis in rat glial cells in vivo after colchicine treatment.

The localization of galanin (GAL) and GAL mRNA was studied in rat brain after colchicine or vinblastine treatment using in situ hybridization and immunohistochemistry. GAL-like immunoreactivity was found in glial cells, presumably activated microglia, in the cortex, caudate nucleus and septum, mainly on the injection side. GAL mRNA expression was found in small cells in the same areas with an overlapping distribution, including the adjacent white matter. The results suggest that the glial cells initiate synthesis of the peptide GAL in response to intraventricular injection of high doses of the 2 mitosis inhibitors.

Animals↗
PubMed1992

[Single oral dose of phosphomycin trometamol versus pipemidic acid and norfloxacin in treating uncomplicated low-level urinary tract infections].

OBJECTIVE: To make an assessment of the effectiveness and safety of a single oral dose compared with the conventional way of treating low-level Urinary Infections presenting no complications. DESIGN: This was an investigative and prospective study, using a control, a simple blind and randomised sample. SITE. Health Centres in Oviedo and Zaragoza. PATIENTS OR OTHERS PARTICIPANTS: We looked at 150 patients and included 106 females between the ages of 16 and 75 in the study. Their clinical symptoms were compatible with low-level urinary infections presenting no complications. INTERVENTIONS: 49 patients were given Trometamol Phosphomicine (TP) in a single oral dose; 36 took Pipemidic Acid (PA) and 21 Norfloxacine (NFX), both of these in a dose of 400 mg twice a day for 5 to 7 days. MAIN MEASUREMENTS AND RESULTS: Clinical and bacteriological assessments of the results were made 3, 7, and 28 days after treatment. A total of 75 gems were isolated: E. coli was the most common (68%). In all three groups, the main symptoms rapidly disappeared after the start of the treatment. CONCLUSIONS: Having considered the bacteriological and clinical findings, as well as tolerance levels, we are able to conclude that a single oral dose of Trometamol Phosphomicine is a good alternative to conventional therapy for the treatment of low-level Urinary Infections Which present no complications.

Administration, Oral↗
PubMed1991

Immunohistochemical study of cholecystokinin peptide in rat spinal motoneurons.

With the aid of indirect immunofluorescence histochemistry and sequence specific antibodies a possible localization of cholecystokinin (CCK) peptide in spinal motoneurons has been analyzed. To increase peptide levels, the sciatic nerve was ligated, and the area around the ligation was studied 24 hours later. For comparison, antisera raised against calcitonin gene-related peptide (CGRP) and substance P were employed. With CCK specific antisera (directed to the N-terminal portion of CCK-8 or the midportion of CCK-33) accumulation of peptide-like immunoreactivity (LI) was observed in large, dilated axonal swellings proximal to, but at some distance from, the ligature. Such accumulations were also observed with C-terminally directed CCK antiserum, but in addition numerous axons of smaller diameter extending up to the ligation contained this type of immunoreactivity. The latter antiserum is thought to cross-react with CGRP. In fact, this staining pattern was indistinguishable from the one seen after incubation with CGRP antiserum. In contrast substance P-LI could not be seen in the larger dilated axons but only in large numbers of thinner fibers close to the ligation. Double staining experiments revealed that the large dilations contained both CGRP- and CCK-specific LI. Distal to the ligation CGRP- and substance P- but no specific CCK-LI could be observed. The present findings support the view that CCK mRNA in spinal motoneurons is translated into CCK peptide, at least after axotomy, and that the peptide is transported into the motoneuron axon. However, compared to CGRP the CCK levels are presumably low, and the functional role of CCK peptide in motoneurons remains to be established.

Animals↗
PubMed1991

Distribution patterns of CCK and CCK mRNA in some neuronal and non-neuronal tissues.

Mutt and Jorpes (49) originally isolated cholecystokinin (CCK) from porcine intestine. Subsequently, it was recognized that CCK/gastrin-like material could be found in the rat brain (74), and it was later shown mainly to represent the C-terminal octapeptide (CCK-8) (2, 12-14, 48, 54, 55). These radioimmunoassay studies have been supplemented by numerous immunohistochemical investigations showing extensive CCK immunoreactive neuron systems in the brain and spinal cord (20, 26, 27, 31, 37, 40, 42, 44, 72, 75, 76). During recent years several groups have employed in situ hybridisation and radioactively labelled probes complementary to CCK mRNA and partly confirmed results from immunohistochemical studies but also revealed new interesting findings (3, 5, 6, 30, 41, 58, 64-66, 77). Several lines of evidence indicate that CCK-8 may act as a neurotransmitter or neuromodulator in many areas of the central nervous system. The development of new CCK antagonists has opened up new possibilities to understand the functional significance of CCK peptides in the neurons and other systems. The aim of the present article is to briefly review the distribution of some of the CCK systems and in this way define possible targets for these new types of drugs. Focus will be on cerebral cortex in view of the theme of the meeting, anxiety, on spinal cord as a basis for discussion of CCK and pain, and finally CCK/gastrin peptides in sperm will be discussed. The question of coexistence of CCK and dopamine in mesencephalic neurons is reviewed in a parallel article (28).

Animals↗
PubMed1991

Effect of reserpine and colchicine on neuropeptide mRNA levels in the rat hypothalamic paraventricular nucleus.

Using in situ hybridization and immunohistochemistry, we have studied mRNA and peptide levels in the hypothalamic paraventricular nucleus (PVN) 24 h after a single large dose of reserpine (10 mg/kg, i.p.) and 24 h after an intraventricular (i.c.v.) injection of colchicine (120 microliters/20 microliters saline). Sections of the PVN were hybridized using synthetic oligonucleotide probes complementary to mRNA for corticotropin-releasing hormone (CRH), neurotensin (NT), enkephalin (ENK), vasoactive intestinal polypeptide (VIP) and thyrotropin-releasing hormone (TRH). For immunohistochemistry rabbit antisera to CRH, NT, ENK, VIP and TRH were used. In situ hybridization showed a clear increase in CRH mRNA as compared to control rats after both treatments. Also NT and VIP mRNA could be seen in parvocellular neurons in reserpine and in colchicine-treated rats, whereas we so far have not been able to demonstrate these mRNAs in untreated rats. No changes in TRH mRNA could be detected after reserpine of colchicine. These results provide final evidence that subpopulations of parvocellular PVN neurons can synthesize not only CRH and ENK, but also NT and VIP, in agreement with earlier immunohistochemical results. With immunochemistry, after reserpine, many CRH-, but no NT- or VIP- positive neurons could be observed in the parvoecellular part of the PVN. The present results demonstrate that treatment with two drugs, the monoamine depleting drug reserpine and the mitosis inhibitor colchicine, causes increased levels of mRNA for several peptides in neurons of the PVN, located almost exclusively in its parvocellular part and being part of the hypothalamo-pituitary adrenal axis.

Animals↗