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Biomedical subjects

F Mora

Publications and source records attributed to F Mora.

At least 19 recordsLinked to original sources

Dopamine-glutamic acid interaction in the anterior hypothalamus: modulatory effect of melatonin.

The aim of the present study was to investigate the role of melatonin as neuromodulator. For that, the effects of melatonin on the extracellular concentrations of excitatory amino acids, glutamic and aspartic acids, were investigated in the anterior hypothalamus and parieto-temporal cortex of the conscious rat using an intracerebral perfusion system. Melatonin at doses of 250 nM and 1 microM produced no effects on extracellular glutamate and aspartate concentrations in these two areas of the brain. Since amphetamine releases dopamine we perfused melatonin into the anterior hypothalamus and parieto-temporal cortex after a previous injection of amphetamine. Interestingly, we found a release of glutamic acid (p < 0.01) and aspartic acid (p < 0.01) produced by melatonin only when the increase (157%) of the extracellular dopamine concentration evoked by amphetamine was inhibited by melatonin in the anterior hypothalamus. The possibility is discussed of melatonin exerting its effects when the dopaminergic system is activated.

Animals

Structural characterization by affinity cross-linking of glucagon-like peptide-1(7-36)amide receptor in rat brain.

Specific binding of glucagon-like peptide (GLP)-1(7-36)amide was detected in several rat brain areas, with the highest values being found in hypothalamic nuclei and the nucleus of the solitary tract. In hypothalamus and brainstem homogenate binding of 125I-GLP-1(7-36)amide was time, temperature, and protein content dependent and was inhibited by unlabeled proglucagon-derived peptides. The rank order of potency was GLP-1(7-36)amide >> GLP-1(1-36)amide > GLP-1(1-37) approximately equal to GLP-2 > glucagon. Scatchard analysis of the steady-state binding data was consistent with the presence of both high- and low-affinity binding sites in hypothalamus and brainstem. Brain 125I-GLP-1(7-36)amide-binding protein complexes were covalently cross-linked using disuccinimidyl suberate and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A single radiolabeled band of M(r) 56,000 identified in both hypothalamus and brainstem homogenates was unaffected by reducing agents. An excess of unlabeled GLP-1(7-36)amide abolished the band labeling, whereas glucagon had no effect. Other unlabeled GLPs inhibited M(r) 56,000 complex labeling with the following order of potency: GLP-1(1-36)amide > GLP-1(1-37) > GLP-2. The binding of 125I-GLP-1(7-36)amide and the intensity of the cross-linked band were similarly inhibited in a dose-response manner by increasing concentrations of unlabeled GLP-1(7-36)amide. Covalent M(r) 56,000 125I-GLP-1(7-36)amide-binding protein complexes solubilized by Triton X-100 were adsorbed onto wheat germ agglutinin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Dopamine receptor blockade inhibits the amphetamine-induced release of diadenosine polyphosphates, diadenosine tetraphosphate and diadenosine pentaphosphate, from neostriatum of the conscious rat.

The diadenosine polyphosphates diadenosine tetraphosphate (Ap4A) and diadenosine pentaphosphate (Ap5A) are costored with ATP and released in a calcium-dependent manner from neural preparations in vitro. By means of a push-pull perfusion system, samples from conscious rat were collected from the caudate putamen area, and nucleotide compounds were analyzed by HPLC. The adenine dinucleotides were not detectable before systemic amphetamine injection. The maximal levels were reached 20 min after injection, independently of the dose. The EC50 values for amphetamine-induced release of dinucleotides were 2.04 +/- 0.15 and 2.43 +/- 0.36 mg/kg for Ap4A and Ap5A, respectively. Amphetamine doses higher than 5 mg/kg did not increase the dinucleotide release, the maximal values being 12.9 +/- 0.9 and 11.5 +/- 0.9 pmol/fraction for Ap4A and Ap5A, respectively, which corresponds with 64.5 and 57.5 nM in the samples. Adenosine and AMP were present in push-pull samples from rat brain under basal conditions. Their levels were 15 pmol/fraction (75 nM) and 50 pmol/fraction (250 nM) for adenosine and AMP, respectively. A significant increase was obtained for both compounds after amphetamine injection. The adenosine increase reached 45 pmol/sample (225 nM), which was 200% of the basal value 20 min after the stimulant administration. The increase at other times was not significant. The AMP levels increased significantly from 10 to 50 min. The maximal level was reached 20 min after amphetamine injection, with 150 pmol/fraction (750 nM), which represents a 200% increase with respect to the basal level. The adenine dinucleotide release was blocked by the dopamine receptor antagonist haloperidol, which returned the levels to the control basal values.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine

Effects of a nitric oxide donor on glutamate and GABA release in striatum and hippocampus of the conscious rat.

The effects of intracerebral perfusion of the nitric oxide (NO) donor 3-morpholino-sydnonimine (SIN-1) and the nitric oxide synthase inhibitor N-nitroarginine (NARG) on the extracellular concentrations of glutamate (GLU) and gamma-aminobutyric acid (GABA) in striatum and CA1 area of the hippocampus were studied. Continuous push-pull perfusions at a flow rate of 20 microliters min-1 were performed in the conscious rat. SIN-1 (100, 200, and 400 microM) and NARG (100 microM) were perfused over 20 min. In both striatum and CA1 SIN-1 increased extracellular concentrations of GLU (maximal increase 150% and 197% of baseline, respectively) and GABA (maximal increase 202% and 204% of baseline, respectively). NARG had no effects on extracellular levels of GLU and GABA in either area. These results are consistent with the hypothesis that NO acts as a modulator of GLU and GABA release in both striatum and hippocampus. This study is the first to report the potentiation of GLU and GABA release by NO in CA1 area of the hippocampus in the conscious rat.

Amino Acid Oxidoreductases

Effects of apomorphine and L-methionine sulphoximine on the release of excitatory amino acid neurotransmitters and glutamine in the striatum of the conscious rat.

The effects of apomorphine, a D1-, D2-dopamine receptor agonist, on the extracellular concentrations of excitatory amino acids, glutamic and aspartic acids, and on that of their precursor, glutamine, were investigated using an intracerebral perfusion system. Apomorphine produced a concentration-related rise in glutamic acid concentration in cerebral perfusates (P < 0.01) whereas only the highest concentration of apomorphine (3 x 10(-3) micrograms/microliters) increased the concentration of aspartic acid (P < 0.05). These effects were seen in the sample taken at the same time as the apomorphine injection. The rise in glutamine concentration (P < 0.01) produced by apomorphine continued for 10 min beyond perfusion with apomorphine. These effects were attenuated by previous injections of D1-, D2-dopamine receptor blocker. To investigate further the release of glutamine, the glutamine synthetase inhibitor L-methionine sulphoximine (MSO) was injected intracerebrally before apomorphine perfusion. After MSO pre-injection, the extracellular concentration of glutamine decreased (P < 0.01) to near zero concentrations. In MSO-treated animals, apomorphine did not induce the release of glutamic acid, aspartic acid or glutamine. These results indicate a role for dopamine in the release of excitatory amino acids and glutamine in the neostriatum of the rat. A possible volumetric interaction between dopamine and glutamic acid as well as the hypothesis of a striato-pallido-thalamo-cortico-striatal feedback loop are discussed.

Analysis of Variance

Active microglia, sick astroglia and Alzheimer type dementias.

We propose that Alzheimer's disease is initiated by failure of axonal transport. After the neurodegeneration cascade is initiated, microglial and astroglial cells have major roles in directly and indirectly promoting self-sustaining neurodegeneration cycles. This hypothesis makes testable predictions and suggests logical therapies.

Alzheimer Disease

Unchanged exocytotic release of glutamic acid in cortex and neostriatum of the rat during aging.

The Ca(2+)-dependent release of glutamate induced by 4-aminopyridine in synaptosomes prepared both from the cerebral cortex and basal ganglia was unchanged in aged rats (27-30 months) when compared to adults rats (3 months). Consistent with the absence of changes in glutamate exocytosis during aging, the rise in the cytosolic free Ca2+ concentration, [Ca2+]c, induced by depolarization in synaptosomes from aged rats was similar to that found in control adult rats. The results suggest that during aging the nerve terminals from the cerebral cortex and basal ganglia maintain an intact ability to release glutamate by exocytosis.

4-Aminopyridine

Fixed versus removable microdialysis probes for in vivo neurochemical analysis: implications for behavioral studies.

The levels of several neurochemicals, i.e., uric acid (UA), dopamine (DA), dihydroxyphenylacetic acid, and 5-hydroxyindoleacetic acid, collected daily from the rat striatum with either fixed or removable microdialysis probes for 7 days after surgery were compared. The implantation of the fixed cannula was followed by a 10-fold increase in the UA content in the dialysates collected from the first day after surgery onward and by a steady decrease in dihydroxyphenylacetic acid levels, whereas those of DA remained fairly stable. With the removable cannula system, only a smaller, transient increase in UA during the first 3 days after surgery was observed, with no change in DA or monoamine metabolites. The glial reaction around the cannula tracks was assessed by both quantitative histological techniques and measuring the glutamine levels in the dialysates collected at the time of surgery and 7 days later. Both the glial cell number and nuclear size, as well as the glutamine outflow, were considerably larger in the animals implanted with the fixed probes. It is, therefore, likely that the UA levels in the dialysate reflect the glial reaction to the probe. The suitability of the removable probe system for behavioral experiments involving repeated microdialysis sampling was illustrated in an experiment showing that the DA release in the nucleus accumbens of male rats assessed daily at postsurgery days 5-10 was virtually identical in three alternating sessions of sexual behavior as was the smaller release of this neurotransmitter detected during intervening nonsexual social interactions.

3,4-Dihydroxyphenylacetic Acid

Effects of neurotensin on the release of glutamic acid in the prefrontal cortex and striatum of the rat.

The effects of neurotensin (NT) on the extracellular concentrations of excitatory amino acids (EAA) glutamic acid (GLU) and aspartic acid (ASP) in the medial prefrontal cortex (MPC) and striatum (ST) of the conscious rat have been studied. NT was infused directly into these two structures for 10 min at doses of 10, 100 and 1000 nM. In the MPC, NT produced a dose-related increase of GLU. Also, NT produced a delayed increase of ASP at the highest dose. In ST, NT at doses of 10, 100 and 1000 nM produced no effect on GLU and ASP. It is suggested that the increase of GLU and ASP in the MPC could be due to a direct effect of NT on pyramidal cortical neurones. On the contrary, it is suggested that a direct interaction NT-GLU does not exist in the ST of the rat.

Animals

[Value of long-term ambulatory pH-metry in the assessment of patients with reflux esophagitis].

The aim of this study is to analyze different reflux-patterns by 24-hour ambulatory pH-metry and to correlate them with clinical symptoms and intensity of esophagitis. 115 patients (50 males/65 females) with a median age of 47 +/- 16 years, typical reflux symptoms have been studied and classified attending to the grade of esophagitis microscopically only 17 cases and endoscopically (grade I = 29, grade II = 44 and grade III/IV = 25 patients). Demeester's score has been used for clinical evaluation. Ambulatory pH-metry has been done with a Holter Synectics Digitrapper MK II, which registered intraesophageal pH-variations every 4 seconds during 24 hours. 28 normal subjects (13 males/15 females) with a median age of 51 +/- 16 years are referred as the control group. Clinical symptoms became more intensified when pH-metric alterations resulted more evident. Thoracic pain was noted in 12 from 115 patients, increasing its frequency in parallel fashion to that of the degree of esophagitis (6% in grade 0, 9% in grades I/II and 20% in grades II/IV). With increasing grades of esophagitis all parameters departed from normality, with significant differences between median values of the different parameters (to the exception of reflux episodes) when comparing patients with low-grade esophagitis (O/I) and high-grade esophagitis (II/III/IV). There is an excellent correlation between severity of esophagitis and % of time to acid exposure (Spearman's correlation coefficient). Only 5% of the patients with esophagitis presented normal pH-metry values and corresponded to esophagitis grade O/I. No patient had only a night reflux pattern, but 10% of our patients had only a day reflux pattern, the mixed pattern being the most frequent one (85%). The fact that 82% of our patients with microscopical esophagitis had a pathological pH-metry recommends the use this method in patients with clinical reflux symptoms and with normal endoscopy.

Adult

[Metoclopramide versus cinitapride in the treatment of functional dyspepsia].

In 20 patients with diagnosis of functional dyspepsia due to dysmotility and/or reflux, the effectivity and tolerance of two prokinetic drugs--metochlopramide (MCP) (10 mg. three daily doses, vo) and cinitrapide (CTP) (1 mg., 3 daily doses, vo)--were assessed using a protocol of a propective and cross-sectional study after a blank period. Following the treatment with MCP and CTP, statistically significant improvements were observed in the intensity/severity of postprandial epigastric fullness, flatulence, epigastralgia, pyrosis, active regurgitations and anorexia. The MCP was more effective for the improvement of vomiting in these patients; however, the number of defecations per week increased significantly only after the CTP therapy. The therapeutical effectivity of both drugs, according to a subjective and objective global assessment was similar, with good results of 60-65% for MCP and 55-60% for CTP. Tolerance of both drugs was good. None of the patients spontaneously referred to the presence of side effects and only 3 patients (15%) treated with MCP and 2 patients (10%) treated with CTP mentioned some of the suggested side effects, which were absent before the onset of treatment. Both drugs produced an increase in the levels of Prolactine, but their average values were within the normal range. Only in two patients treated with MCP and in one patient treated with CTP, values slightly higher than the upper normal limit were observed. No significant differences were observed when comparing the results obtained with MCP therapy and CTP therapy.

Adult

[Colonic transit time (segmental and total) in healthy subjects and patients with chronic idiopathic constipation].

BACKGROUND: The efficacy of the treatment of patients with chronic idiopathic constipation not responding to normal therapeutic measures depends on correct functional diagnosis. The study of the segmentary and total colonic transit time with radioopaque markers is the most economic technique in everyday clinic ambience for functionally evaluating these patients. METHODS: Segmental and total colonic transit time was calculated with the use of radioopaque markers in 23 healthy subjects (12 men and 11 women) and in 13 women with severe idiopathic constipation. Twenty markers were administered daily for three consecutive days and simple x-rays of the abdomen were made on the fourth, seventh and in some cases on the tenth day. In addition, the symptomatology of 9 patients was collected by means of a 30 day diary. RESULTS: The maximum values of transit time (mean + 2SD) obtained in the healthy subjects were 17, 25, 26, and 49 hours for the right colon, left colon, rectosigmoid and the whole colon, respectively. The time of left colon transit was significantly lower in the women. The transit time in constipated patients permitted the differentiation of three functional patients: a) slowing of the right and left colon possibly associated to rectosigmoid slowing in 5 patients; b) isolated slowing in the left colon in 4 patients and c) isolated rectosigmoid slowing in 4 patients. Group a) was characterized by long total colonic transit times while these were normal in 2 patients of group b) and in one patient of group c). No differences were seen in the symptomatology of the groups. CONCLUSIONS: The calculation of segmentary and total colonic transit time with radioopaque markers is a simple technique which permits the detection of different subgroups of patients with chronic idiopathic constipation refractory to normal treatment. The exact typification of the functional anomaly is an important basis for the individualization of treatment.

Adult

[Oropharyngeal functional assessment in patients with Zenker's diverticulum. Manometric and isotopic study].

Twenty patients with the diagnosis of Zenker's diverticulum were studied clinically and manometrically. In 8 patients oropharyngeal clearance of liquid isotopic markers was done. In three, esophageal emptying of a marked meal was also studied. Clinically, sixteen patients had oropharyngeal dysphagia, while for remained asymptomatic. Dysphagia was severe in only five patients. In half of the patients there were signs of hiatus hernia and/or reflux. Pharyngo-sphincteric incoordination was present in 70% of cases with a mean resting pressure of the LES significantly lower than in controls. There were no differences among patients with or without reflux. Isotopic esophageal clearance was not useful as a test, as there were no significant differences with the control group. On the other hand, esophageal emptying of solid isotopic meals may show the persistence of food in the diverticular sac long time after the meal.

Deglutition Disorders

[Oropharyngeal dysphagia due to a primary change in the pharyngeal musculature. A manometric and isotopic study].

Twenty-five patients with oropharyngeal dysphagia due to a variety of disorders (4 with muscular dystrophy, 4 with myasthenia gravis and 13 with inflammatory myopathies) were studied clinically by esophageal manometry and isotopic clearance. Clinically patients had moderate dysphagia and 45% other symptoms such as nasal regurgitation, bronchial aspiration, etc. The most important manometric abnormality was the feeble contractions of the pharyngeal musculature, more pronounced in patients with severe dysphagia (grade II). Isotopic clearance of the oropharynx showed slowing of the pharyngeal emptying curve and an increased residual activity in this area. Isotopic oropharyngeal clearance is a useful, comfortable and noninvasive test for determining the clinical improvement which accompanies the manometric recovery of the pharyngeal muscular contraction.

Deglutition Disorders

Chronic idiopathic constipation: the importance of transit time studies.

Chronic idiopathic constipation includes a very heterogeneous group of alterations which cannot be correctly defined only by their clinical appearance and require an examination of the colonic transit time. This test is performed by using a specific number of radiopaque markers and a fixed number of X-ray observations. By means of transit time study, we can classify the constipated patients into 4 groups: a) patients with stasis in the right colon (17-53% of cases) which implies an alteration of propulsive forces or absence of mass movements and segmentary motor activity; b) stasis in the left colon (13-27% of cases) which could be due to a "reflux" of colonic contents or to a hyperactive sigmoid; c) rectosigmoid stasis (20-33% of cases) which is secondary to a megarectum. Internal anal sphincter (IAS) and/or external anal sphincter (EAS) function failure and d) normal transit time (greater than 40 of cases) which is commonly due to psychological problems or to a low-fiber-content diet. We can conclude that transit time study is not necessary in mild constipation, but it is advised for those patients who do not respond to standard medical therapy or when surgery is being contemplated.

Anal Canal

Alteration of recto-anal motility in chronic idiopathic constipation.

We studied anorectal function in 10 controls and 13 constipated patients (chronic idiopathic constipation, outlet obstruction and inertia coli). We did not find any difference among the 3 groups as regards the internal anal sphincter (IAS) basal tone, the recto-anal inhibitory reflex (RAIR) and the maximal voluntary contraction, whereas some significant differences were observed in the sensitivity threshold. In fact, we observed that all patient groups required larger volumes in order to perceive the minimum sensation. Moreover, the patients with distal obstruction showed higher threshold for a permanent defecation stimulus. The reduction of rectal sensitivity in these patients was confirmed by the infusion of 1500 cc of saline solution. On the basis of our experience constipated patients are characterized by both normal IAS tone, RAIR appearance, squeezing capacity, and lower rectal sensitivity.

Adult