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Biomedical subjects

M Sala

Publications and source records attributed to M Sala.

At least 145 records · Page 8Linked to original sources
PubMed1985

Central pharmacological activities and opiate receptor binding studies of some dermorphin analogs.

A series of dermorphin-like compounds were injected intracerebroventricularly in the rat to assess in vivo their effects on intestinal motility and analgesia. In vitro they were tested by binding assay using 3H-naloxone as radioligand or by guinea pig ileum bioassay. The synthetic peptides were less potent than dermorphin in inhibiting intestinal transit and in producing analgesia, or even inactive up to doses 30 times the dermorphin ED50. This reduction in pharmacological activity was coupled with a decrease in binding potency. The 3H-naloxone binding studies in the absence or presence of Na+ indicated that Na+ reduced the interaction of dermorphin and its analogs with brain opiate receptors. Only the dibenzyl derivative was slightly affected by sodium, suggesting a dual action for this peptide, as confirmed by preliminary data from guinea pig ileum bioassay.

Amino Acid Sequence↗
PubMed1984

Glucocorticoids and catecholamines as mediators of acute-phase proteins, especially rat alpha-macrofoetoprotein.

Adrenal hormones were studied as possible triggering substances of the synthesis of acute-phase reactants in rats. alpha-Macrofoetoprotein, which rises sharply in concentration during inflammation, was used to monitor the acute-phase reaction. In normal rats glucocorticoids and catecholamines induce alpha-macrofoetoprotein synthesis; glucocorticoids only increase alpha-macrofoetoprotein to moderate levels in plasma, but catecholamines enhance alpha-macrofoetoprotein synthesis to very high levels, comparable with those observed in the post-injury phase. However, catecholamines in vivo also activate the adrenal cortex, suggesting a synergistic effect of both kinds of adrenal hormones. Our study showed that in adrenalectomized rats, the effect of catecholamines on alpha-macrofoetoprotein synthesis is greatly diminished, whereas the moderate effect of glucocorticoids remains. Combination of glucocorticoids and catecholamines induces extremely high alpha-macrofoetoprotein levels in both adrenalectomized and normal rats. With crossed immunoelectrophoresis it was shown that other acute-phase reactants, such as haptoglobin and alpha 1-major acute-phase protein, are affected differently by the hormones. Contrary to glucocorticoids, catecholamines give a pattern comparable with that found after surgical injury.

Acute-Phase Proteins↗
PubMed1984

Lack of effect of cimetidine on the renin-angiotensin-aldosterone system in man.

It is widely accepted that angiotensin II, ACTH and potassium are the major factors controlling the release of aldosterone. Conflicting results have been reported about the role of serotonin, dopamine and histamine. To evaluate the possible involvement of H2-histaminergic receptors, the effect of intravenous injection of 400 mg cimetidine on the renin-angiotensin-aldosterone system has been evaluated in 10 healthy volunteers. The administration of cimetidine did not induce a significant change in plasma aldosterone level or in its major controlling factors.

Adult↗
PubMed1984

Dermorphin interaction with peripheral opioid receptors.

The interaction of dermorphin with different peripheral opioid receptor subtypes was investigated in vitro, using the guinea pig ileum as representative tissue for mu, the mouse vas deferens for delta, the rabbit vas deferens for kappa and the rat vas deferens for epsilon. The effect of dermorphin on each tissue preparation was compared with that of selective mu, delta, kappa epsilon agonists respectively morphine, met-enkephalinamide, ethylketocyclazocine and camel beta-endorphin. Antagonism with naloxone was also tested and calculated as Ke. It is concluded that dermorphin mainly interacts with the mu receptors, although it also binds to epsilon receptors; the interaction with delta receptors is questionable, and the kappa receptors are unaffected.

Animals↗
PubMed1984

Globin evolution in some species of the genus Bufo.

The globins of 10 species of toads of the genus Bufo have been analysed. From the values of the reciprocal rates between their amino acid residues a 'dissimilarity matrix' was made. In this have been included the values related to Discoglossus pictus and Xenopus laevis. The numerical data, derived from a computer program, gave a dendrogram representing the evolution of the analysed globins. This appears correlated to the geographical distribution and to the metabolic adaptation of the corresponding species of Bufo more than their chronological appearance.

Amino Acids↗
PubMed1984

The lack of transformation activity of 9-hydroxybenzo[a]pyrene related to the absence of modified deoxyribonucleosides in DNA of C3H/10T1/2 cells.

Sephadex LH-20 chromatography of DNA digests of C3H/10T1/2 cells treated with [3H]9-hydroxybenzo[a]pyrene (9-OH-BaP) and [14C]BaP-7,8-diol showed: (i) the presence only of uncharacterized 3H radioactivity eluted in the early portion of the gradient; [3H]9-OH-BaP-4,5-oxide-modified deoxyribonucleosides were not observed. (ii) The total amount of [14C]-labelled radioactivity corresponded to nucleoside moieties which were modified by anti- and syn-benzo[a]pyrene diol-epoxide. The absence of nucleosides modified by 9-OH-BaP-4,5-oxide in C3H/10T1/2 cells observed in this study may account in part for the relative resistance of these cells to the mutagenic and transforming action of 9-OH-BaP.

Animals↗
PubMed1984

Different performance of two commercial nebulizers.

Two different nebulizers, the DeVilbiss 646 and the Mefar were tested for differences in output characteristics (air flow rate, amount of nebulized liquid and particle size) and it was found that there is a high variability between nebulizers of both brands. In the light of these findings, neither of these devices can be chosen as a standard nebulizer for bronchial provocation.

Aerosols↗
PubMed1984

Serotonergic regulation of cortisol secretion in dogs.

The role of serotonin (5-HT) in the control of serum cortisol secretion was studied in 50 conscious beagle dogs. A significant rise in corticosteroids was observed after 1.5 and 3 mg/kg (P less than 0.01) iv fenfluramine, an indirect serotonergic agonist, as well as after 2 (P less than 0.05) and 3 mg/kg (P less than 0.01) iv quipazine, a direct agonist of 5-HT receptors. Both drugs exhibited a dose-related effect. A lower dose of fenfluramine, 0.5 mg/kg, was ineffective when administered iv, but raised serum cortisol (P less than 0.05) after direct injection into a lateral cerebral ventricle, through a chronically implanted brain cannula. The marked increases in corticosteroid concentration produced by the highest fenfluramine and quipazine doses were completely abolished by pretreatment with ketanserin, an antagonist of 5-HT2 receptors, which did not affect cortisol secretion when administered alone. These data suggest that brain serotonergic system plays a role in the control of cortisol secretion in conscious dogs.

Animals↗
PubMed1984

Relationship between the chemical structure and the mutagenic and carcinogenic potentials of five naphthofurans.

We have analyzed the relationship between the biological activities and chemical structure of five naphthofurans. The compounds studied included 2-nitro-7-methoxynaphtho[2,1-b]-furan (R 7000) (Compound A), 2-nitro-8-methoxynaphtho[2,1-b]-furan (Compound B), 2-nitronaphtho[2,1-b]furan (Compound C), 2-nitro-7-bromonaphtho[2,1-b]furan (Compound D), and 7-methoxynaphtho[2,1-b]furan (Compound E), the nonnitrated analogue of Compound A. The genotoxic activities of the compounds were studied in V79 cells using the micronucleus, sister chromatid exchange, and hypoxanthine-guanine phosphoribosyltransferase locus mutation tests. This allowed us to classify their mutagenic properties in the following order: A congruent to B much greater than C greater than D greater than E. However, in the in vivo short-term skin tests, the order in activities of the first three compounds is reversed, and the five compounds can be classified in decreasing rank of potency: C greater than B greater than A greater than or equal to E congruent to D. The two compounds tested for in vitro transformation, Compounds A and B, demonstrated a positive effect in both the C3H10T1/2 and the Syrian hamster embryo cell systems. The biological activities of Compounds A, B, C, and D appeared to be strongly linked to the presence of a NO2 group in position 2. These activities were enhanced or decreased by a methoxy group in position 7 or 8. Almost all activities were suppressed if the methoxy group in position 7 was replaced by a bromine (Compound D). The positive results obtained in the cell transformation assays and in the short-term skin tests indicate that Compounds A, B, and C are probably carcinogenic. Therefore, further in vivo studies should be accomplished before using the 2-nitronaphthofuran derivatives in human and animal treatments.

Animals↗
PubMed1983

Involvement of periaqueductal gray matter in intestinal effect of centrally administered morphine.

Microinjections of morphine in the rat periaqueductal gray matter (PAG) inhibited intestinal transit in linear relation to the log of the dose administered (in the range from 5 to 20 micrograms/rat). This linear regression was parallel with that obtained on intracerebroventricular (i.c.v.) or intraperitoneal (i.p.) administration of morphine and the intracerebral (i.c.) route was calculated to be 4 times more potent than the i.c.v. route and 189 times more potent than the i.p. route. Monolateral electrolytic lesions into the PAG abolished the intestinal effect of i.c.v. morphine to a large extent. The relevance of other brain areas and the type of opiate receptors involved in this central effect of morphine are discussed.

Animals↗
PubMed1983

Changes in methylation pattern of albumin and alpha-fetoprotein genes in developing rat liver and neoplasia.

To determine whether methylation changes in specific DNA sequences of the albumin and AFP genes are implicated in the modulation of transcriptional activity during rat liver development and neoplasia we have analysed the methylation pattern of C-C-G-G sequences within these genes in DNA isolated from fetal and adult hepatocytes, from adult kidney and from a clonal hepatoma cell line which produces AFP but no albumin. We have assayed for methylation of the internal cytosine of this sequence by using the restriction enzyme isoschizomers HpaII and MspI. 32P-labelled cloned cDNA probes were used to reveal the albumin and AFP gene containing fragments. Genomic subclones of the albumin gene were also utilized as molecular probes to measure quantitatively the level of methylation of 6 specific sites within the albumin gene in the different DNA samples. The results indicate that methylation changes at the sites analysed are not responsible for the changes in gene activity during rat liver development. Further they demonstrate that: 1) extensively methylated genes can be actively transcribed; 2) prominent changes in methylation of specific genes during normal development are not necessarily related to alterations in gene activity.

Aging↗
PubMed1983

Loperamide: evidence of interaction with mu and delta opioid receptors.

Loperamide was tested on electrically-evoked contractions using a series of "in vitro" isolated preparations, in comparison with morphine, met-enkephalin, beta-endorphin, ethylketocyclazocine used as representative agonists of mu, delta, epsilon, kappa receptors respectively. The IC50 of loperamide on myenteric plexus longitudinal muscle of guinea pig ileum was found to be 1.90 X 10(-7)M and equal to that of morphine. The IC50 on mouse vas deferens was found to be 13.02 X 10(-7)M. In this tissue, loperamide resulted as active as morphine, but 54 times less active than met-enkephalin (IC50 0.24 X 10(-7)M). On the rat vas deferens where, as expected, beta-endorphin was strongly active (IC50 1.38 X 10(-7)M), morphine exerted a stimulatory action within the range 10(-5)M-10(-4)M and loperamide was only poorly depressive. The Ke value of naloxone, a specific mu receptor antagonist, against loperamide in the guinea pig ileum was 3.83 nM, and in the mouse vas deferens was 82.87 nM indicating that loperamide in the guinea pig ileum acts on mu receptors while in the mouse vas deferens on another opiate receptor.

Animals↗
PubMed1983

Effect on intestinal transit of neurotensin administered intracerebroventricularly to rats.

Neurotensin (NT) administered intracerebroventricularly (i.c.v.) to rats, blocks intestinal transit (tested by charcoal meal) in linear relation to the log of the doses within the range of 0.6-2.5 nmoles/rat. NT in this test is about 40 times more active than morphine (M) and 6 times less active than dermorphin (DM) on a molar basis. Within this dose range NT does not induce analgesia (tail-flick test) or hypothermia (tested at 22 degrees C). The intestinal effect can also be elicited by injecting the peptide into the periaqueductal gray matter (PAG). NT injected intraperitoneally (i.p.) is inactive up to doses 4 times the maximal active i.c.v. dose. Naloxone (Nx) and dynorphin 1-13 could not antagonize the intestinal effect of i.c.v. NT. The relationship between this central intestinal effect and many other central effects of NT is discussed.

Animals↗
PubMed1983

Developmental time of the hemoglobin transition in the anuran Bombina orientalis.

The electrophoretic pattern of the larval hemoglobin of the anuran Bombina orientalis presents two bands. In premetamorphic period gradually appear four other bands, corresponding to those of the adult hemoglobin; they substitute, within 15-16 days after metamorphosis, the larval pattern. The percentage of larval and adult fractions during the development is shown. In Bombina orientalis the change of the hemoglobinic fractions from larval to adult type is total as in most anurans. But it starts earlier than in other species studied and develops slower than most of the other species.

Animals↗
PubMed1982

Increase of plasma corticosterone induced by loperamide in rats.

Loperamide given intracerebroventricularly and intraperitoneally to rats provoked, like morphine, a plasma corticosterone increase 60 min after injection. Loperamide intracerebroventricularly was 3.73 times less active than morphine, while intraperitoneally it was 10.13 times more potent. This increase, associated with a significant elevation in the plasma ACTH concentration, was antagonized by naloxone (10 mg/kg i.p.) injected 30 min before loperamide. In hypophysectomized rats loperamide intraperitoneally did not affect the plasma corticosterone levels. We conclude that loperamide can stimulate corticosterone secretin from the adrenal gland via the opiate receptors and that this effect is mediated by a direct or indirect induction of ACTH release.

Adrenocorticotropic Hormone↗