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Biomedical subjects

R Cacabelos

Publications and source records attributed to R Cacabelos.

At least 91 records · Page 5Linked to original sources
PubMed1990

Effects of GRF (1-29) NH2 on short-term memory: neuroendocrine and neuropsychological assessment in healthy young subjects.

Recent studies seem to indicate that the somatotropinergic system (STS) (GRF-SS-GH-SM axis) may be involved in the neuromodulation of higher activities of the central nervous system (CNS). In an attempt to demonstrate the influence of the STS on memory functions in humans, we have investigated the effects of acute administration of exogenous GRF vs. placebo on short-term memory (STM) in healthy young subjects. We gave GRF(1-29)NH2 (150 micrograms; i.v.) to a group of subjects (EG) (N = 17) and placebo (0.9% saline, 1 ml; i.v.) to a different group of subjects (CG) (N = 6). Prior to testing we presented a list of 20 neutral words (A1), and 2 hours after injection the same list (A2) and another list (B) of similar characteristics were presented in order to evaluate cognitive performance (CP). Basal CP (A1 list) was similar in EG and CG. Differences between EG and CG were found for both A2 (EG = 14.76 +/- 1.55 words vs. CG = 11.83 +/- 1.34 words, p less than 0.01) and B lists (EG = 12.17 +/- 1.68 words, p less than 0.005). According to the basal serum GH levels, EG subjects were divided into 2 subgroups: EG1 (N = 6), with high basal GH levels (11.57 +/- 4.47 ng/ml) and EG2 (N = 11), with low basal GH levels (1.55 +/- 1.71 ng/ml), similar to CG (1.3 +/- 1.53 ng/ml). GRF-induced GH response showed maxima 15 (28.15 +/- 11.71 ng/ml) and 30 min (28.09 +/- 17.07 ng/ml) after injection in EG1 and at 45 min (15.52 +/- 14.45 ng/ml) in EG2.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Effect of histamine depletion on circadian variations of corticotropin and corticosterone in rats.

The effects of cerebral histamine depletion induced by alpha-fluoromethylhistidine (FMH) on corticotropin (ACTH) and corticosterone secretions were examined. Neither acute nor chronic FMH treatment altered the corticoadrenal responses to three types of stress: transposition, immobilization and water immersion. And exposure to stress did not affect the hypothalamic content of histamine. However, chronic intracerebral treatment with FMH had a significant effect on the circadian rhythm of the plasma corticosterone (CS) level in rats. Namely, it caused a marked attenuation of the amplitude of the peaks of the CS level resulting in an almost arrhythmic state. The maximum differences between FMH treated and untreated groups were seen at 8.00 and 20.00 h, the times when the illumination condition changed (light onset 8.00 h). This treatment with FMH also had a similar effect on the plasma ACTH concentration; namely the plasma ACTH level in the saline treated group was lower than that of the FMH-treated group at light onset and higher than the latter at dark onset, but was similar to the latter at other sampling points. These results indicate the histaminergic modulation of the circadian rhythm of hormonal secretion of the adrenal cortex and show that this phenomenon is mediated through the central nervous system by an influence on the rhythm of hypophyseal ACTH secretion possibly through alteration in the concentration of corticotropin-releasing factor.

Adrenocorticotropic Hormone↗
PubMed1989

Brain histamine in Alzheimer's disease.

The concentration of histamine (HA) has been determined by high-performance liquid chromatography (HPLC) with fluorometric detection in 21 different regions of brains from patients with senile dementia of the Alzheimer type (SDAT) and subjects (CB) whose causes of death were not related to neuropsychiatric, neurological and/or neurodegenerative diseases. The highest levels of HA in the central nervous system (CNS) of both control (CB) and SDAT samples were found in the posterior hypothalamus (CB = 3.13 +/- 0.63 pmol/mg; SDAT = 7.75 +/- 1.43 pmol/mg, p less than 0.005), where the HA neurons are located, and in the anterior hypothalamus (CB = 1.77 +/- 0.33 pmol/mg; SDAT = 2.82 +/- 0.45 pmol/mg, p less than 0.005). The lowest HA levels were detected in the cerebellum (CB = 0.12 +/- 0.04 pmol/mg; SDAT = 0.24 +/- 0.09 pmol/mg, p less than 0.01) and medulla oblongata. HA levels were significantly higher in SDAT than in CB in the following areas: motor cortex (Brodmann's area 4) (A4), premotor cortex (A6), postcentral gyrus (A1,2), posterior parietal cortex (A5,7), superior temporal gyrus (A41,42), temporal pole (A38), primary and secondary visual cortices (A17,18), anterior and posterior regions of the hypothalamus, putamen, caudate nucleus, nucleus accumbens, thalamus, hippocampus, pons, medulla oblongata and cerebellum. No changes were seen in globus pallidus and corpus callosum. Since the origin of HA in the brain is dependent upon three main compartments (neuronal, mast cell, vascular smooth muscle), with approximately 60-80% of the total HA belonging to the neuronal pool, on the basis of neurochemical data we postulate that the increase in the levels of HA in SDAT might account for or be associated with alterations in neuroendocrine, cognitive, neurovascular and sleep-wakefulness functions.

Aged↗
PubMed1988

Effect of neurotoxic lesions in the mammillary bodies on the distribution of brain histamine.

Unilateral lesions with ibotenic acid in the vicinity of the mammillary bodies where the histamine (HA)-secreting neurons are located induced bilateral reductions in the levels of HA in the posterior hypothalamus (40-60%), anterior hypothalamus (45%), and frontal cortex (30%) as well as in the ipsilateral hippocampus (40%) 7 days after injection. Changes in the concentration of HA in the median eminence and adenohypophysis were not significant, but in the neurohypophysis the content of HA increased by 80%. These results seem to indicate that intrahypothalamic and cortical HA pathways are bilateral in origin while hippocampal HA pathways are predominantly ipsilateral.

Animals↗
PubMed1988

Influence of somatostatin and growth hormone-releasing factor on behavior. Clinical and therapeutic implications in neuropsychiatric disorders.

Administration of hypothalamic peptides has been reported to induce behavioral changes and to modify neurological functions such as locomotor activity and learning. Somatostatin (SS) and growth hormone-releasing factor (GRF) exert opposite effects on anterior pituitary secretion. Similarly, at the central nervous system (CNS) level, SS and GRF display antagonistic actions on behavioral parameters. The authors were able to confirm these effects in male Wistar rats by means of a computerized electronic maze measuring locomotor activity and learning. SS concentration is reduced in specific areas of the CNS in patients with late onset of senile dementia of the Alzheimer's type (SDAT). In early onset SDAT a GRF test elicits a growth hormone response much greater than that observed in normal controls of the same age or in patients with late onset SDAT. Thus, administration of GRF to patients with early onset SDAT has been followed by a significant improvement in locomotion, appetite, mental performance and social interaction. A possible therapeutic role of GRF in the management of patients with dementia remains to be explored.

Animals↗
PubMed1988

Antagonistic effects of growth hormone-releasing factor and somatostatin on brain histamine.

Studies on the morphological distribution of histamine (HA)-secreting neurons and their hypothalamic projections suggest that HA may play a key role in regulating neuroendocrine functions, some of which have been recently elucidated. To investigate possible interactions between the somatotropinergic and histaminergic systems in the brain, the effects of GRF-44 [0.1-10 micrograms intracerebroventricular (icv)] and somatostatin (SS-14; 0.1-10 micrograms, icv) on HA in five different parts of the hypothalamo-hypophyseal system, and in the hippocampus and frontal cortex, were studied using a highly sensitive HPLC system for determination of HA. GRF-44 (1 microgram, icv) elicited significant (P less than 0.005) increases in the concentration of HA in the anterior hypothalamus, posterior hypothalamus, median eminence, adenohypophysis, neurohypophysis, frontal cortex, and, to a lesser extent, in the hippocampus, after a clear time-dependent pattern with maxima 15 min after injection. In contrast, SS-14 (1 microgram, icv) significantly (P less than 0.005) decreased the levels of HA in all areas studied, except in the neurohypophysis. The SS-induced HA levels reached minima 30 min after injection. The antagonistic effects of GRF-44 and SS-14 on the release of brain HA were dose dependent, showing an inverse linear correlation within the range 0.1-10 micrograms in the anterior hypothalamus (r = -0.59) and posterior hypothalamus (r = -0.75). Responses of HA to GRF-44 and SS-14 (range: 0.1-10 micrograms) also exhibited an inverse linear correlation in the median eminence (r = -0.90) and adenohypophysis (r = -0.58), while in the hippocampus and frontal cortex the antagonistic effects of GRF and SS displayed an inverse curvilinear correlation. SS-14 ED50 values ranged from 0.6 to 1.75 nmol with Emax of 0.65-6.10 nmol. GRF-44 ED50 values ranged from 0.02-0.3 nmol and the Emax values oscillated between 0.2 and 1.90 nmol in the regions studied. The greatest responses of HA to GRF-44 and SS-14 were obtained in the hypothalamo-hypophyseal system. Although brain HA is present in both the neuronal and the mast cell compartments, changes induced in the concentration of HA by centrally administered GRF-44 and SS-14 appear to occur mostly in the neuronal compartment. Therefore, it is likely that the somatotropinergic and histaminergic systems reciprocally interact at the central level to regulate still unknown neuroendocrine functions.

Animals↗
PubMed1988

GHRH-induced GH response in patients with senile dementia of the Alzheimer type.

To clarify the functional state of the somatotropinergic system at the hypothalamo-hypophyseal level in senile dementia of the Alzheimer type, the GHRH test was performed in three groups of subjects: a) healthy elderly subjects; b) early onset senile dementia patients; and c) late onset senile dementia patients. Intravenous administration of GHRH(1-44)NH2 (100 micrograms) elicited a marked plasma GH response with a maximum peak (709.54 +/- 259.0 pmol/l; P less than 0.005) 60 min after injection in patients with early onset senile dementia, but no significant response was detected in the other two groups. Electroencephalographic recording showed that GHRH modifies brain bioelectrical activity, decreasing frequency (0.52 +/- 0.15 Hz) and increasing amplitude (8.25 +/- 4.5 microV) of the electroencephalogram basic rhythm. The evaluation of mental performance and behaviour with a battery of different tests for mental assessment revealed that GHRH induces transient clinical changes in psychomotor behaviour. According to these results, it seems likely that the somatostatin deficiency reported in senile dementia of the Alzheimer type may account for the enhanced GHRH-induced GH response observed in patients with early onset senile dementia. In consequence, the GHRH test might constitute a useful antemortem marker for senile dementia of the Alzheimer type if the present results can be replicated in early stages of the disease.

Aged↗
PubMed1987

Histaminergic neuromodulation of the release of vasopressin.

In an attempt to clarify the nature of histaminergic neuromodulation of the vasopressinergic system, several studies under different experimental paradigms were carried out. L-Histidine loads (8 mmol/kg, i.p.) induced a marked increase in histamine (HA) in the anterior (AHR) and posterior (PHR) hypothalamic regions, the median eminence (ME) and adenohypophysis (Ah) with no apparent effect on the concentration of HA in the neurohypophysis (Nh), as measured by high-performance liquid chromatography. These findings correlated with decreases in vasopressin (VP) levels in the AHR and ME, accompanied by increases of the neuropeptide in the PHR and Ah. Intraperitoneal injections of HA (6 mumol/kg), resulted in a significant (p less than 0.005) rise in VP levels in the PHR, ME and Ah. HA induced an elevation of VP in the prefrontal cortex (PFC) from 6.23 +/- 2.02 to 43 +/- 4.05 microU/mg, as well as a 60% reduction in neurohypophyseal VP. These HA-induced VP responses were abolished by both mepyramine (3 mumol/kg) and famotidine (4 mumol/kg) in the PHR and PFC. Mepyramine suppressed the HA-induced VP response in the Ah and enhanced it in the Nh, while famotidine did the opposite. When alpha-fluoromethylhistidine (FMH), an irreversible inhibitor of histidine decarboxylase, was administered at doses of 100 mg/kg/day (i.p.), hypothalamic HA levels fell by 40-45% after 1 h, by 50% after 3 h, and by 65-80% after 24 h in adrenalectomized rats. In the same conditions, but after a week of treatment with FMH, the VP response to adrenalectomy was clearly impaired.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Time- and dose-dependent responses of brain histamine to intracerebroventricular and intraperitoneal administrations of growth hormone-releasing factor (GRF1-44).

Changes in the level of histamine (HA) in rat brain induced by intracerebroventricular (i.c.v.) and intraperitoneal (i.p.) administrations of growth hormone-releasing factor (GRF1-44) were studied. HA was determined by high-performance liquid chromatography (HPLC) in the anterior hypothalamic region, posterior hypothalamic region, median eminence, adenohypophysis, neurohypophysis, hippocampus and prefrontal cortex. GRF1-44 (1-10 micrograms, i.c.v.) induced significant time- and dose-dependent increases in the concentration of HA in the hypothalamo-hypophyseal system and time-dependent decrease of HA in the hippocampus. In contrast, after i.p. administration of GRF1-44 (10 micrograms) the level of HA in the hypothalamus tended to decrease but the total amount of H-1 receptors in the hypothalamo-hypophyseal system did not change. Circadian variations in the GRF-induced HA and growth hormone responses were also observed, responses being lower in the evening than in the morning. It is concluded that GRF interacts with HA at the central level to optimize the function of the somatotropinergic system.

Animals↗
PubMed1987

Somatostatin-induced histamine response in the rat central nervous system.

The effects of somatostatin (SS-14) (0.1-10 micrograms, i.c.v.) on brain histamine (HA) in male Wistar rats were investigated. HA was measured by HPLC with a cation exchanger and an automated fluorometric detection system. SS-14 induced time- and dose-dependent changes in the levels of HA in the anterior hypothalamus, posterior hypothalamus, median eminence, adenohypophysis, hippocampus, and frontal cortex. In the anterior hypothalamus, posterior hypothalamus and hippocampus, SS-14 (1 microgram, i.c.v.) significantly (p less than 0.01) decreased the levels of HA from 5 to 30 min. This response was delayed by 5 min in the frontal cortex and adenohypophysis. Only in the neurohypophysis, SS-14 increased the concentration of HA 10 min after injection, but this response was not dose-related. These results seem to indicate that SS-14 influences neuronal HA probably modifying HA release, it leading to a decrease of the levels of the biogenic amine in specific areas of the brain. Since this effect is opposite to that developed by growth hormone-releasing factor (GRF) in identical conditions, HA seems to fulfil the criteria by which a neuroendocrine modulator should currently respond in a specific time- and dose-dependent manner to those neuropeptides which modulate. Therefore, HA is likely to play a key role as a neuromodulator of the somatotropinergic system in the rat.

Animals↗