Biomedical subjects

E Fernandez-Alvarez

Publications and source records attributed to E Fernandez-Alvarez.

9 recordsLinked to original sources

PubMed1992

Kinetic and inhibition studies on catechol-O-methyltransferase affinity labelling by N-(3,4-dihydroxyphenyl)maleimide.

Initial velocity and product inhibition studies have been performed on soluble catechol-O-methyltransferase which has been partially purified from pig liver. The results are consistent with an ordered reaction mechanism, in which S-adenosyl-L-methionine (AdoMet) is the leading substrate. The enzyme is irreversibly inhibited by maleimide derivatives in a biphasic manner, which suggests a differential reaction with two thiol groups. N-(3,4-Dihydroxyphenyl)maleimide, which has a reactive moiety (maleimide ring) and an affinity moiety (catechol ring), acts as an affinity labelling compound on the more reactive SH group; AdoMet and Mg2+ protect against this modification. Total protection of this SH group results in a pseudo-first-order inhibition of the enzyme, with the apparent rate constant being proportional to the inhibitor concentration. All the other maleimide derivatives studied inhibited the enzyme by reacting with one of the two SH groups in a non-specific manner. The reaction of the other, more reactive, SH group was either specific (active-site-directed) or non-specific, depending on the substituent present in the affinity moiety and also on the length of an intermediate chain of methylene groups present between this moiety and the reactive maleimide ring. In the presence of both AdoMet and Mg2+, 3,5-dinitrocatechol, a reversible inhibitor of the enzyme which is competitive with respect to the catechol substrate, protects the enzyme from inactivation by any of the maleimide derivatives. The adducts of these maleimide derivatives formed with dithiothreitol inhibit the enzyme reversibly, showing inhibition patterns that are consistent with the mechanism deduced from the initial velocity and product inhibition studies.

Affinity Labels↗

PubMed1991

New 5H-pyridazino[4,5-b]indole derivatives. Synthesis and studies as inhibitors of blood platelet aggregation and inotropics.

Some fused 5H-pyridazino[4,5-b]indoles (7-10), substituted in positions 1 and 4 by hydrazine and/or amino groups, have been synthesized. These new compounds present a planar topography, a dipole with an adjacent acidic proton, and a basic hydrogen-acceptor site opposite the dipole. These compounds have some resemblance to carbazeram and other pyridazino agents with cardiotonic activity. Some of the new compounds here described possess inotropic activity (Table I and II), with a complementary effect as inhibitors of platelet aggregation (Table III and IV). 1-Hydrazino-4-(3,5-dimethyl)-1-pyrazolyl-5H-pyridazino[4,5-b ]indole hydrochloride (7a.HCl) is the first compound described in the literature with activities as inhibitor of PDE-IV and as selective inhibitor of TXA2 synthetase (Table V).

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed1990

Inhibition of MAO by substituted tryptamine analogues.

Three different acetylenic analogues of tryptamine, in which the side chain is attached at the 2 position of the heterocyclic ring, were studied as inhibitors of MAO-A and MAO-B. IC50 values were determined after 30 min preincubation of the enzyme and inhibitor, at 37 degrees C before assay. Irreversibility and time-dependence of the inhibition were also established in each case. The kinetic parameters defining non-covalent complex formation and covalent adduct formation were calculated for the mechanism-based inhibition of both MAO-A and MAO-B by these compounds.

Animals↗

PubMed1990

New 5H-[1,3]thiazolo[3,2-a]pyrido[3,2-e]pyrimidine derivatives as diuretics.

New 5H-[1,3]thiazolo[3,2-a]pyrido[3,2-e]pyrimidines 1 and 6,10-dihydro-5H-pyrido[3',2':5,6]pyrimido[2,1-c] [1,2,4]triazines 4 with 5-one, 5-thione or 5-hydrazono substituents and in some cases 1,2,3,4 or 8,9 hydrogenated are synthetized. The diuretic, natriuretic and kaliuretic activities of these compounds in Wistar rats at a dose of 24 mg/kg were estimated. A series of 24 possible derivatives of 1 and 4 possessing diuretic and saliuretic activities are investigated for structure-activity relationships in light of Fujita-Ban model. The Fujita-Ban group contributions have been calculated for different structural variations on the parent ring 1a. It is observed that the hydrogenation of pyridine, [1,3]thiazole or [1,2,4]triazine rings on 1 or 4 decrease the diuretic and saliuretic activities.

Animals↗

PubMed1986

Effects of 2-indolecarbohydrazides on thromboxane synthetase activity and on in vitro and ex vivo blood platelet aggregation. New selective inhibitors.

Platelet antiaggregatory action of 42 synthetic 2-indolecarbohydrazides was studied observing their actions on arachidonic acid (AA) and adenosine-5-diphosphate (ADP) induced platelet aggregation. Radioimmunoassay studies, following AA induced aggregation, measuring thromboxane B2 (TXB2) and prostaglandin E2 (PGE2) were carried out on those compounds whose previous activities included inhibition of AA induced platelet aggregation and inhibition of the second wave of aggregation using ADP as the aggregating agent. Those compounds which demonstrated inhibition of TXB2 with increased PGE2 were subsequently tested with PGH2 as the aggregating agent. Results of this work demonstrate that 3 of the 42 compounds have specific inhibitory activity for thromboxane synthetase. The most active compounds were 1-methyl-5-hydroxyindole derivatives.

Arachidonic Acid↗

PubMed1985

[Episodes of apnea in an infant: unusual forms of epileptic seizures].

The authors report the observation of an infant who begins at the age of 7 months to present episodes of epileptic apnea with cyanosis, lost of consciousness, hypotony and sometimes ocular revulsion and distal myoclonia. From their onset there are several a day, more frequent during sleep than when awake. From the EEG point of view they are characterized by a 5-7 c/sec large and diffuse rhythm. The infant also presents epileptic myoclonias, tonic and partial seizures. She has a very slight evolutive encephalopathy, disclosed at the age of 4 months by a psychomotor retardation. No etiology has been proved. The CT scan shows during the evolution a cortico-subcortical atrophy. Every type of seizure was very resistant to different treatments. The apneas disappeared after ACTH therapy. The authors demonstrate the epileptic nature of these apneas which are very rarely observed after the neonatal period.

Adrenocorticotropic Hormone↗

PubMed1979

Uncommon case of type II glycogenosis.

The authors report an uncommon case of type II glycogenosis. An 8-year-old boy developed a slow progressive myopathy. Biopsy of skeletal muscle showed scarce lesions under the optic microscope but in 50% of the fibers the presence of vacuoles filled with glycogen under the electron microscope. Ultrastructural analysis of fibroblasts in culture showed numerous vacuoles filled with glycogen, characteristic of type II glycogenosis. Enzymatic analysis revealed that acid-alpha-glucosidase activity was normal in muscle tissues but deeply deficient in leukocytes and fibroblasts in culture. This is, as far as we know, the first case with such a discrepancy in the distribution of the enzymatic activity, and it underlines the necessity of investigating several tissues in atypical cases.

Biopsy↗

PubMed1979

"Moya-moya' disease caused by cranial trauma.

A case of "moya-moya" disease of a 12-year-old boy is reported. The clinical history started at 3 years 2 months after cranial trauma. The patient developed mental retardation, hemiparesis and seizures.

Arterial Occlusive Diseases↗

PubMed1977

[Lissencephaly: agyria. A study using the Golgi technic].

A case of lissencephaly (agyria) is reported in which the Golgi stain was used to study the fronto-parietal cortex. The external cellular layer, the so-called true cortex, was shown to be made up of neurons from the 5th and 6th layers of the normal cortex. The neurons in the much less cellular layer were shown to be large pyramidal cells with well-developed dendritic branching and spines. The deeper cellular layer was a neuronal pool without well-defined layering. All the neural forms from the normal cortex were represented. In this layer the inner neurons showed a less advanced stage of development than did those in the outer groups. In the external cellular layer there was a disorganization of neuronal disposition as well. Otherwise typical large and medium-sized pyramidal cells from the outer third showed apical dendrites directed towards deeper structures, and the basal dendrites ran through the marginal layer. Neurons with doulbe dendritic branching and fusiform neurons were present in an abnormal rotated position. In both cases, the axons always showed a descending direction. These findings add to existing knowledge concerning the anatomy of the lissencephalic cortex, although the exact interpretation of the abnormalities found in the external cellular layer remains speculative.

Cerebral Cortex↗