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Biomedical subjects

E Fontana

Publications and source records attributed to E Fontana.

At least 37 records · Page 2Linked to original sources
PubMed2001

Dual action of octopamine on glucose transport into adipocytes: inhibition via beta3-adrenoceptor activation and stimulation via oxidation by amine oxidases.

Octopamine, which is closely related to norepinephrine, acts as a neurotransmitter in invertebrates and is a trace amine with undefined properties in vertebrates. The octopaminergic receptors identified in insects are targets of various pesticides but are absent in vertebrates. We have established that octopamine stimulates fat cell lipolysis in mammals via activation of beta3-adrenoceptors (ARs), whereas this amine has been described elsewhere as an alpha2-AR agonist and as a substrate for monoamine oxidase (MAO) or semicarbazide-sensitive amine oxidase (SSAO). Because we have recently reported that amine oxidase substrates promote glucose transport in rat and human adipocytes, the in vitro octopamine effects on lipolysis and glucose uptake were reassessed by using adipocytes from beta3-AR-deficient mice. The lipolytic effect and the counter-regulation of insulin action on glucose transport provoked by 0.1 to 1 mM octopamine or by 1 microM beta3-AR agonists found in control animals disappeared in adipocytes from beta3-AR-deficient mice. This revealed an insulin-like effect of octopamine on glucose uptake, which was dependent on its oxidation by MAO or SSAO, as was the case for tyramine and benzylamine, devoid of beta3-adrenergic agonism. Similarly, octopamine promoted glucose transport in human adipocytes and exhibited a weaker lipolytic stimulation than in rodent adipocytes. These findings indicate that, besides its lipolytic activity, octopamine exerts, at millimolar dose, dual effect on glucose transport in adipocytes: counteracting insulin action via beta3-AR activation and stimulating basal transport via its oxidation by MAO or SSAO.

Adipocytes↗
PubMed2000

[Primary bilateral adrenal lymphoma].

When abdominal imaging reveals the existence of unsuspected adrenal masses, a diagnostic strategy is necessary. We report the case of a woman presenting with pulmonary embolism, in whom abdominal ultrasound revealed voluminous masses in both adrenals without clinical or biological signs of hormone hypersecretion, but with mild primary adrenal failure. From a CT scan-directed needle biopsy of the right adrenal mass and subsequent staging we were able to diagnose a primary bilateral adrenal lymphoma, diffuse large B-cell type (REAL/WHO). On CHOP chemotherapy both adrenal masses decreased dramatically and the patient is in remission 18 months later. Primary adrenal lymphoma is a rare condition, since 65 cases have been reported to date. Histological diagnosis is nevertheless important, in view of the excellent response to specific therapy observed in some cases.

Adrenal Gland Neoplasms↗
PubMed2000

Effects of octopamine on lipolysis, glucose transport and amine oxidation in mammalian fat cells.

Octopamine is known to exert adrenergic effects in mammals although specific octopamine receptors have been cloned only in invertebrates. It has been shown that octopamine can stimulate alpha(2)-adrenoceptors (ARs) in Chinese hamster ovary cells transfected with human alpha(2)-ARs. More recently, we reported that octopamine stimulates lipolysis through beta(3)-rather than beta(1)-or beta(2)-AR activation in white adipocytes from different mammalian species. The present study was thus undertaken to further characterize the adrenergic properties of octopamine. For this purpose, several biological processes known to be regulated by adrenergic stimulation were studied in response to octopamine, noradrenaline, adrenaline and tyramine in white adipocytes from different mammals. First, octopamine was fully lipolytic in garden dormouse and Siberian hamster while tyramine was ineffective. Although being around one hundred-fold less potent that noradrenaline, octopamine was slightly more potent in these hibernators known for their high sensitivity to beta(3)-AR agonists than in rat and chiefly more active than in human adipocytes known for their limited responses to beta(3)-AR agonists. Second, octopamine reduced insulin-dependent glucose transport in rat fat cells, a response also observed with noradrenaline and selective beta(3)-AR agonists but not with beta(1)-or beta(2)-agonists. Third, human adipocytes, which endogenously express a high level of alpha(2)-ARs, exhibited a clear alpha(2)-adrenergic antilipolytic response to adrenaline but not to octopamine. Moreover, octopamine exhibited only a very weak affinity for the alpha(2A)-ARs labeled by [3H]RX821002 in human adipocyte membranes. In Syrian hamster adipocytes, which also possess alpha(2)-ARs, octopamine induced only a weak antilipolysis. Finally, octopamine was a substrate of fat cell amine oxidases, with an apparent affinity similar to that of noradrenaline. All these results demonstrate that octopamine, tyramine noradrenaline and adrenaline can be degraded by adipocyte amine oxidases. However these biogenic amines interact differently with adipocyte adrenoceptors: tyramine is inactive, adrenaline and noradrenaline activate both beta- and alpha(2)-ARs while octopamine activates only beta(3)-ARs and is devoid of alpha(2)-adrenergic agonism. Thus, octopamine could be considered as an endogenous selective beta(3)-AR agonist.

Adipocytes↗
PubMed2000

Oral doxifluridine in advanced hepatocellular carcinoma: A phase II study.

Hepatocellular carcinoma (HCC) remains one of the most common neoplasms in the world. Doxifluridine is an oral fluoropyrimidine derivative activated to 5-fluorouracil by uridine phosphorylase which is more expressed in malignant cells. Therefore, we conducted a phase II study to evaluate the activity of oral doxifluridine in patients with advanced hepatocellular carcinoma. Twenty-five advanced hepatocellular carcinoma patients entered the study; doxifluridine was given orally at the initial daily total dose of 2,250 mg for 4 consecutive days every week. All patients are evaluable for toxicity: these included mainly grade 1-2 (WHO) diarrhea, stomatitis, nausea and vomiting; 4 patients (16%) experienced grade 3-4 diarrhea. Twenty-four patients are evaluable for response and 1 complete and 3 partial responses have been observed (response rat 17%, 95% confidence interval: 5-37). Oral doxifluridine at the dose and schedule we used, although having only modest activity in advanced HCC, may represent an alternative to other frequently used chemotherapeutic agents, because of its favorable toxicity profile and its simple route of administration.

Administration, Oral↗
PubMed1999

Selective activation of beta3-adrenoceptors by octopamine: comparative studies in mammalian fat cells.

Numerous synthetic agonists selectively stimulate beta3-adrenoceptors (ARs). The endogenous catecholamines, noradrenaline and adrenaline, however, stimulate all the beta-AR subtypes, and no selective physiological agonist for beta3-ARs has been described so far. The aim of this study was to investigate whether any naturally occurring amine can stimulate selectively beta3-ARs. Since activation of lipolysis is a well-known beta-adrenergic function, the efficacy and potency of various biogenic amines were compared with those of noradrenaline, isoprenaline, and beta3-AR agonists 4-(-{[2-hydroxy-(3-chlorophenyl)ethyl]-amino} propyl)phenoxyacetate (BRL 37,344) and (R,R)-5-(2-{[2-(3-chlorophenyl )-2-hydroxyethyl]-amino} propyl)-1,3-benzo-dioxole-2,2-dicarboxylate (CL 316,243) by testing their lipolytic action in white fat cells. Five mammalian species were studied: rat, hamster and dog, in which selective beta-AR agonists act as full lipolytic agents, and guinea-pigs and humans, in which beta3-AR agonists are less potent activators of lipolysis. Several biogenic amines were inefficient (e.g. dopamine, tyramine and beta-phenylethylamine) while others (synephrine, phenylethanolamine, epinine) were partially active in stimulating lipolysis in all species studied. Their actions were inhibited by all the beta-AR antagonists tested, including those selective for beta1- or beta2-ARs. Octopamine was the only amine fully stimulating lipolysis in rat, hamster and dog fat cells, while inefficient in guinea-pig or human fat cells, like the beta3-AR agonists. In rat white fat cells, beta-AR antagonists inhibited the lipolytic effect of octopamine with a relative order of potency very similar to that observed against CL 316,243. Competitive antagonism of octopamine effect resulted in the following apparent pA2 [-log(IC50), where IC50 is the antagonist concentration eliciting half-maximal inhibition] values: 7.77 (bupranolol), 6.48 [3-(2-ethyl-phenoxy)-1[(1 S)-1,2,3,4-tetrahydronaphth-1-ylaminol]-(2S)2-propanol oxalate, SR 59230A, a beta3-selective antagonist], 6.30[erythro-D,L-1(7-lethylindan-4-yloxy)-3-isopropylamino-+ ++butan-2-ol, ICI 118,551, a beta2-selective antagonist] and 4.71 [(+/-)-[2-(3-carbomyl-4-hydroxyphenoxy)-ethylamino]-3-[4-(1- methyl-4-trifluoromethyl-2-imidazolyl)-phenoxy]2-propanolmethane sulphonate, CGP 20712A, a beta1-selective antagonist]. Octopamine had other properties in common with beta3-AR agonists: stimulation of oxygen consumption in rat brown fat cells and very low affinity in displacing [3H]CGP 12,177 binding to [beta1- or beta2-ARs in dog and rat adipocyte membranes. In Chinese hamster ovary (CHO) cells expressing human beta3-ARs, octopamine inhibited [125I]ICYP binding with only twofold less affinity than noradrenaline while it exhibited an affinity around 200-fold lower than noradrenaline in CHO cells expressing human beta1- or beta2-ARs. These data suggest that, among the biogenic amines metabolically related to catecholamines, octopamine can be considered as the most selective for beta3-ARs.

Adipose Tissue↗
PubMed1998

[Epilepsy and disorders of cortical development in children with congenital cytomegalovirus infection].

INTRODUCTION: Neuroimaging and experimental studies have related cytomegalovirus (CMV) to certain neuronal migration disorders. MATERIAL AND METHODS: To define the electroclinical picture of children with epilepsy associated with disorders of cortical development (DCD) and congenital CMV infection, we conducted a clinical, electroencephalographic and neuroradiological study of 10 children with this condition. RESULTS: Eighty per cent of them had dismorphic traits, or malformations outside CNS. All showed other neuroradiological signs (cerebral calcification, white matter damage, porencephaly). Six patients with bihemispheric DCD (agyria-pachigyria, 2; 'poligyria', 1; schizencephaly, 1; bilateral opercular DCD, 2) showed: Tetraparesis, severe or profound mental deficiency, early onset epilepsy (mean age at onset: 11 months) with spasms, tonic seizures, partial seizures, and multifocal paroxysms or unusual diffuse sharp Alfa-Beta EEG activity. One child developed Epilepsia Partialis Continua. Children with bilateral opercular DCD evolved to a continuous spike and wave (SW) electrical status during wakefulness and sleep, linked to a worsening of psychomotor derangement. Four patients with unilateral hemispheric DCD (pachigyric or 'poligyric') showed: Congenital hemiparesis, mild intellectual deficiency, motor seizures (orofacial, hemiclonic, generalized) beginning in the third year of live, atypical absences with focal phenomena, frequent focal rhythmic SW discharges during wakefulness, and continuous SW status during sleep (CSWS). CONCLUSIONS: A wide spectrum of DCD due to congenital CMV infection is documented. Characteristic electroclinical pictures related to the extent and topographical distribution of the DCD are recognized, which may lead to an appropriate diagnosis and prognosis.

Basal Ganglia↗
PubMed1995

Docking of a human rhinovirus neutralizing antibody onto the viral capsid.

The structure of the complex between the Fab fragment of a human rhinovirus serotype 2 (HRV2) neutralizing antibody (8F5) and a cross-reactive synthetic peptide derived from the viral capsid protein VP2 has been recently determined by crystallographic methods. The conformation adopted by the peptide was very similar to and could be superimposed onto the corresponding region of the viral protein VP2 of human rhinovirus 1A (HRV1A) whose three-dimensional structure is known. The structure of the Fab fragment determined in the complex was docked onto the viral capsid using the superimposition transformation found for the peptide. In the resulting model the Fab protrudes almost radially to about 60 A from the surface of the virion without any major steric problem. The Fab fragment was then placed on each one of the 60 equivalent epitopes using the T = 1 icosahedral symmetry of the virus. The closest pairs of Fab fragments are related by viral 2-fold axes and run almost parallel to each other without clashing. These axes of symmetry from the viral particle could thus be coincident with the dyad axes of the antibodies. Furthermore, comparison of the three-dimensional structure of the Fab/peptide complex with the structure of the Fab fragment alone indicates that the flexibility of the antibody's elbow would facilitate bivalent attachment to the same viral particle. In accordance with the docking results, experimental determination of the stoichiometry of binding yielded a ratio of 30 IgG molecules per virion also suggesting bivalent attachment of antibody 8F5 onto the viral particle. The neutralization of viral infectivity, being neither aggregation (this paper) nor inhibition of receptor binding, might be mainly achieved by reducing viral spread from cell to cell and/or inhibition of uncoating.

Amino Acid Sequence↗
PubMed1995

Efficacy and tolerability of vigabatrin in children with refractory partial seizures: a single-blind dose-increasing study.

The efficacy and tolerability of vigabatrin (VGB) in children with refractory partial epilepsy were assessed in a single-blind, add-on, fixed-sequence, placebo-controlled trial. After 1-month observation, the patients entered a 7-month treatment period that involved administration of placebo for 1 month followed by VGB at the initial dosage of 40 mg/kg/day, to be increased to 60 and 80 mg/kg/day at 2-month intervals if seizures persisted. Of the 46 children enrolled in the study, 7 dropped out prematurely due to lack of efficacy of the drug (n = 6) or increased seizure frequency (n = 1). In 11 patients who either became seizure-free (n = 3) or improved markedly (n = 8), treatment was completed at a dose < 80 mg/kg/day. The average number of seizures per month in the 39 patients who completed the study decreased from 97 during placebo to 21, 12, and 9 after 2, 4, and 6 months of VGB treatments respectively (p < 0.0001 at each time). Response to VGB remained statistically significant when dropouts were included in the evaluation. The number of patients who had > 50% reduction in seizure frequency after 2, 4, and 6 months was 28, 33, and 35, respectively. Eight patients became seizure-free during the last 2 months of VGB treatment (3 at 40, 3 at 60, and 2 at 80 mg/kg/day, as compared with none during placebo treatment). Serum levels of associated antiepileptic drugs (AEDs) showed no significant changes, except for serum phenytoin (PHT) concentration, which significantly (p < 0.01) decreased after VGB treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Anticonvulsants↗
PubMed1994

High-performance liquid chromatographic determination of FCE 24928, a new aromatase inhibitor, in human plasma.

A sensitive and selective high-performance liquid chromatographic method for the determination of FCE 24928 (4-amino-androsta-1,4,6-triene-3,17-dione) in human plasma is reported. The drug was extracted from buffered (pH = 8) plasma samples with methylene chloride-isooctane, then analysed by reversed-phase liquid chromatography. Quantitation was achieved by ultraviolet detection of the eluate at 238 nm. Blank plasma samples from humans, dog and rat assayed as described showed no significant peak at the retention time of the compound of interest. The suitability of the method for in vivo samples was tested by measuring the plasma levels of FCE 24928 in rats that received oral doses of the test compound.

Androstatrienes↗
PubMed1994

Radioimmunoassay for the testosterone 5 alpha-reductase inhibitor turosteride in biological fluids.

An antiserum against turosteride (code name FCE 26073), a potent testosterone 5 alpha-reductase inhibitor, has been raised in rabbits by immunization with an immunogen produced by conjugation of a derivative of FCE 26073 (FCE 27424) to bovine serum albumin. The antiserum was able to distinguish FCE 26073 from its derivatives modified at the 17 beta position and from all the endogenous steroids tested. A radioimmunoassay for the determination of FCE 26073 in human plasma and urine was developed using this antiserum and tritium labeled turosteride. FCE 26073 was extracted from 50 microliters of plasma or 25 microliters of urine using ethyl-ether with a recovery greater than 90%. Using this procedure it was possible to achieve a final limit of quantitation of 142 pg/ml in plasma and 284 pg/ml in urine. The assay was validated in terms of reproducibility, accuracy and precision in the range 3.9-250 pg/50 microliters of plasma and 25 microliters of urine. The plasma concentration of FCE 26073 in a healthy male volunteer who received 0.2 mg of the drug was measured using the radioimmunoassay.

5-alpha Reductase Inhibitors↗
PubMed1994

Freeze-dried dura mater for guided tissue regeneration in post-extraction dental implants: a clinical and histologic study.

Soft membranes were used in 69 patients for bone regeneration around implants (blades and screws, submerged and non-submerged) placed into extraction sockets. In about 10% of the patients a prosthetic restoration was completed immediately, while in the remaining patients the prostheses were connected after a healing period of 3 to 6 months; follow-up ranged from 6 to 30 months. In 22 patients a re-entry procedure was done to evaluate the membrane and in 4 patients a bone biopsy was taken from 3 to 6 months after the placement of the membrane. In all cases the peri-implant tissues appeared clinically healthy and it was possible to see radiographically that the newly formed bone closely adapted to the implants. In most cases it was possible at 6 months re-entry to see the membrane and detach it from the underlying tissues. There was a partial dehiscence of the membrane in only 4% of the cases. After 3 months the tissue under the membrane presented macroscopical features similar to mature bone, and bone biopsies in all cases showed a spongious lamellar bone with a high level of activity and a wide band of osteoid tissue.

Adult↗
PubMed1992

Metabolic fate of FCE 22716, a new antihypertensive agent, and of its N-oxide (FCE 24220) in the rat.

[3H]-FCE 22716 and [3H]-FCE 24220 were given both orally and intravenously to the rat. Radioactivity was mainly eliminated by the faecal route after oral administration in both cases. After intravenous administration, renal excretion was twice the faecal one in the case of FCE 22716, whereas for FCE 24220 the two routes were equal. In urine FCE 22716 was eliminated almost completely unchanged after both oral and intravenous administration. FCE 24220 was extensively reduced to FCE 22716 after oral administration, whereas after intravenous treatment, this reduction, although important, was not complete.

Administration, Oral↗
PubMed1991

Sleep and benign partial epilepsies of childhood: EEG and evoked potentials study.

The electroclinical picture and nosological limits of benign partial epilepsy of childhood with rolandic spikes (BERS) have been better defined by nocturnal sleep records. In all stages of sleep, there is a significant increase in frequency and amplitude of rolandic spikes (RS) without change of their morphology. Another interesting observation is the appearance of independent spike foci in sleep, or brief subclinical spike wave discharges which are limited to the state of drowsiness. More recently, other types of partial epilepsy of childhood with benign evolution have been identified: (a) partial epilepsy with induced spike representing somatosensory evoked potentials; (b) benign psychomotor epilepsy; (c) partial epilepsy with occipital spike waves. In all these forms, the sleep records are essentially similar to those in BERS and have been very helpful in the nosological identification of these forms of epilepsy. For this reason, the sleep records of these special forms are truly informative for the clinician from the diagnostic and prognostic viewpoint. On the other hand, some investigators, have pointed out that, in the initial stage of these benign forms of partial epilepsy, there may be more or less significant intellectual impairment and behavioral disorder, sometimes accompanied by frequent brief absences. From the EEG viewpoint, this condition is characterized by brief discharges of slow spike wave complexes amounting to a pattern of "electrical status epilepticus". This special electroclinical condition mimics the Lennox-Gastaut syndrome but is generally self-limited. Thus, a correct differential diagnosis is very important from the diagnostic viewpoint. There is good evidence that sleep records permit an earlier identification of these conditions and strongly contribute to a correct differential diagnosis. In the benign partial epilepsy the SEPs, during awake and sleep, morphology and latency are normal, while the N60 amplitude is increased. A group of children with benign partial epilepsy shows EEG spikes evoked by tapping, and giant N60 component. This giant component persists during sleep and is not specific for any type of benign partial epilepsy. In conclusion, the results of sleep recordings are conducive to a correct diagnosis and better definition of the nosological delineation of partial epilepsies in childhood; they also provide a better comprehension of their evolution, and thus of their prognosis. The Evoked Potentials seem be a useful tool in the study of benign partial epilepsy.

Adolescent↗
PubMed1989

Determination of the enantiomeric composition of salsolinol in biological samples by high-performance liquid chromatography with electrochemical detection.

The enantiomers of salsolinol were completely separated as diastereoisomeric derivatives, after reaction with S-1-(1-naphthyl)ethyl isothiocyanate, by reversed-phase high-performance liquid chromatography and quantified by electrochemical detection. Good calibration curves were obtained for the quantification and determination of the enantiomeric composition of salsolinol in human urine. The sensitivity and specificity to the assay also permit the determination of the enantiomeric composition of salsolinol in food such as dried bananas and chocolate.

Cacao↗