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Biomedical subjects

L Pieri

Publications and source records attributed to L Pieri.

At least 37 records · Page 2Linked to original sources
PubMed1993

[National working team report on defecography].

A questionnaire concerning defecography was submitted to 5 national experts in order to: 1) quantify the demand and 2) develop a consensus report. The demand is currently 2-8 exams week and the most frequent indication (70%) is obstructed defection, with/without constipation. The highest discriminatory capabilities was exhibited by the following variables: a) the anorectal angle (ARA) on straining and b) the distance from the pubococcygeal line (PCL) on squeezing (101.2 degrees +/- 15 vs. 120.6 degrees +/- 13, p < 0.05 and 27.4 mm +/- 15 vs. 2.4 mm +/- 7, p = 0.005, respectively) in chronically constipated patients (mean age: 60 years) when compared to the control group; and c) PCL on squeezing and at rest (35.5 mm +/- 20 vs. 2.4 mm +/- 7, p = 0.005 and 38.9 mm +/- 18 vs 18.4 mm +/- 17, p < 0.05, respectively) in patients with severe incontinence with respect to healthy subjects. While sensitivity and positive predictive values of the test were highest (97 and 98% respectively) for rectocele, specificity ranked first (92%) in anal gaping.

Defecation↗
PubMed1991

[The continent perineal colostomy after abdominoperineal resection of the rectum. A digital defecographic study].

For 10 years, in the Surgery Dept. of the University of Pisa, perineal colostomies have been performed on patients who had undergone abdominoperineal rectal amputation. The gracilis muscles of the thighs, transposed to the perineum, are used for building a continent muscular apparatus. Seventeen of 40 patients operated with this procedure have been submitted to defecographic studies, by means of digital fluoroscopic image acquisition. This modality allowed the visualization of anastomotic colon morphology as well as of the functionality of the transposed gracilis muscles during the various phases of defecography. The muscle surrounding the colostomy acts as a sphincter and relaxes only during evacuation; the one positioned as a sling acts as the normal puborectalis muscle. In two patients a perineocele was documented, causing problems in the evacuation phase, which were solved after surgical intervention.

Colostomy↗
PubMed1990

Physical dependence induced in DBA/2J mice by benzodiazepine receptor full agonists, but not by the partial agonist Ro 16-6028.

Continuous administration of triazolam, alprazolam or diazepam for a 7-day period by means of minipumps or chronic (17 days) p.o. treatment with alprazolam induced clear physical dependence in DBA/2J mice as assessed by precipitation of a withdrawal syndrome with an i.v. injection of the benzodiazepine receptor partial inverse agonist Ro 15-3505. In contrast, no precipitated withdrawal signs were observed following chronic exposure to high doses of the benzodiazepine receptor partial agonist Ro 16-6028. The use of minipumps and precipitation with a benzodiazepine receptor antagonist permits a simple and rapid evaluation of the physical dependence liability of potent compounds acting at the benzodiazepine receptor. Furthermore, these results support the hypothesis that benzodiazepine receptor partial agonists are less likely to induce physical dependence than full agonists.

Administration, Oral↗
PubMed1990

In vitro and in vivo evaluation of iodine-123-Ro 16-0154: a new imaging agent for SPECT investigations of benzodiazepine receptors.

The flumazenil analogue, Ro 16-0154, a benzodiazepine partial inverse agonist, has been labeled by halogen exchange to enable SPECT investigations of central benzodiazepine receptors in the human brain. The purified 123I-Ro 16-0154 was found to be stable in rat brain preparations and to be metabolized in rat liver preparations. Its pharmacologic properties were comparable to those of flumazenil. The biodistribution in rats (1 hr postinjection) resulted in a high brain-to-blood ratio of 16. Clinical studies revealed images of the benzodiazepine receptor density in the brain. Since the receptor labeling was markedly reduced by injection of flumazenil, it was considered to be specific. Storage defects due to pathologic cerebral blood flow and changed receptor density were detected; this shows the potential usefulness of the substance for diagnostic purposes, e.g., the differential diagnosis of various forms of epilepsy.

Animals↗
PubMed1989

Convulsions induced by centrally administered NMDA in mice: effects of NMDA antagonists, benzodiazepines, minor tranquilizers and anticonvulsants.

1. Convulsions were induced reproducibly by intracerebroventricular injection of N-methyl-D-aspartic acid (NMDA) to conscious mice. 2. Competitive (carboxypiperazine-propylphosphonic acid, CPP; 2-amino-7-phosphonoheptanoic acid, AP7) and non-competitive (MK801; phencyclidine, PCP; thienylcyclohexylpiperidine, TCP; dextrorphan; dextromethorphan) NMDA antagonists prevented NMDA-induced convulsions. 3. Benzodiazepine receptor agonists and partial agonists (triazolam, diazepam, clonazepam, Ro 16-6028), classical anticonvulsants (diphenylhydantoin, phenobarbitone, sodium valproate) and meprobamate were also found to prevent NMDA-induced convulsions. 4. Flumazenil (a benzodiazepine receptor antagonist) and the GABA agonists THIP and muscimol (up to subtoxic doses) were without effect. 5. Flumazenil reversed the anticonvulsant action of diazepam, but not that of MK801. 6. Results obtained in this model differ somewhat from those described in a seizure model with systemic administration of NMDA. An explanation for this discrepancy is offered. 7. This model is a simple test for assessing the in vivo activity of NMDA antagonists and also expands the battery of chemically-induced seizure models for characterizing anticonvulsants not acting at NMDA receptors.

Animals↗
PubMed1989

[Digital videoradiography applied to the study of stress urinary incontinence in women].

A digital videofluoroscopic unit was employed to evaluate 42 female patients with urinary stress incontinence, cystocele or endometrial neoplasms, using either voiding cystourethrography or colpo-cysto-urethrorectography (CCURG), with or without urethral metallic bead chain. The digital subtraction technique allowed the direct visualization (on a single frame) of the lowering of both bladder base and other pelvic structures, and of the modification of urethral angles during Valsalva and micturition. The demonstration of contrasted urethra during micturition and Valsalva in incontinent patients allowed CCURG to be performed without urethral chain, with encouraging diagnostic accuracy. The advantages of digital CCURG are emphasized.

Algorithms↗
PubMed1988

Ro 15-4513: partial inverse agonism at the BZR and interaction with ethanol.

The imidazobenzodiazepinone derivative Ro 15-4513 has the activity profile of a partial inverse (low efficacy) agonist at the benzodiazepine receptor (BZR). It reverses central nervous depressant effects of diazepam, and, in part, of phenobarbitone and ethanol in mice, rats and cats in behavioural, electrophysiological, and neurochemical paradigms. The interaction of Ro 15-4513 with barbiturates and ethanol is due to its inverse agonistic (negative allosteric modulatory) property at the BZR, as it was reversed by the selective BZR blocker flumazenil (Ro 15-1788). In the present experiment situations, other BZR partial inverse agonists in subconvulsant or overt convulsant doses were less effective against ethanol effects than Ro 15-4513. Possible mechanisms for this differential activity of BZR inverse agonists are discussed.

Animals↗
PubMed1988

Effects of an intrathecally administered benzodiazepine receptor agonist, antagonist and inverse agonist on morphine-induced inhibition of a spinal nociceptive reflex.

1. The effects of an intrathecally administered benzodiazepine receptor (BZR) agonist (midazolam, up to 50 micrograms), antagonist (flumazenil, Ro 15-1788, 5 micrograms) and inverse agonist (Ro 19-4603, 15 micrograms) on nociception and on morphine-induced antinociception were studied in rats. 2. By themselves, none of these compounds significantly altered pain threshold. 3. The BZR agonist midazolam enhanced the morphine-induced antinociceptive effect whereas the antagonist flumazenil did not alter it. In contrast, the BZR inverse agonist Ro 19-4603 decreased the morphine-induced antinociceptive effect. 4. Naloxone (1 mg kg-1 i.p.) completely reversed all these effects. 5. These results demonstrate that BZR agonists and inverse agonists are able to affect, by allosteric up- or down-modulation of gamma-aminobutyric acidA (GABAA)-receptors, the transmission of nociceptive information at the spinal cord level, when this transmission is depressed by mu-opioid receptor activation.

Animals↗
PubMed1988

[Digital radiology in the study of the lacrimal ducts].

The authors emphasize the usefulness of digital dacryocystography (DCG), as compared with various current techniques. Utilizing a radiographic unit equipped with a video-fluoroscopic system and interfaced to a digital video-processor, several digitalized images are acquired before, during and after the injection of contrast medium. Final images are obtained by subtraction of suitable pairs of source frames. Twenty-six patients affected by epiphora have been examined so far. In 21 cases digital subtraction DCG allowed an accurate visualization of the lacrimal system; in the other five patients the amount of information was acceptable. This methodology allows the assessment of both the normal anatomy of the lacrimal passages and their pathological patterns, such as obstructions, stenoses, fistulas, chronic dacryocystitis, lacrimal stones. The examination is easy and quick to perform, with no discomfort for the patient. Digital subtraction DCG proves thus to be a very valuable technique thanks to its possible electronic elaboration--i.e. the subtraction and the magnification of images--to its better contrast resolution, and to the possibility it yields of dynamic studies under radioscopic control.

Humans↗
PubMed1986

L-cycloserine: behavioural and biochemical effects after single and repeated administration to mice, rats and cats.

L-Cycloserine dose-dependently inhibited the activity of gamma-aminobutyric acid (GABA)-transaminase (GABA-T) and elevated the level of GABA in whole mouse brain with a peak effect 3-4 hr after a single intraperitoneal injection. At a dose (30 mg/kg) which elevated the level of GABA almost 4-fold, L-cycloserine moderately increased the content of alanine and slightly reduced that of aspartate, glutamate and glycine in the brain. L-Cycloserine (10-30 mg/kg, p.o. or i.p.) prevented tonic seizures induced by 3-mercaptopropionic acid (3-MPA) and audiogenic seizures in DBA/2 mice, without affecting those evoked by pentylenetetrazol, bicuculline and electroshock. Similarly small doses of L-cycloserine reduced the level of cGMP in the cerebellum of rats, prevented its elevation by 3-MPA and attenuated the hypothalamically-elicited rage reaction in cats. Larger doses of L-cycloserine (greater than 30-100 mg/kg) impaired the performance of mice in the rotarod, chimney and horizontal wire tests, and reduced spontaneous locomotor activity of rats. Upon repeated administration the inhibitory effect of L-cycloserine on the activity of GABA-T and on seizures elicited by 3-MPA in mice increased. In contrast, the depressant action of L-cycloserine on motor performance and locomotion declined in subchronically-treated mice and rats. The levels of amino acids in brain after repeated administration did not differ markedly from those in acutely-treated mice. It is suggested that small doses of L-cycloserine, probably by increasing GABAergic inhibition, reduce hyperexcitability in the brain in acute- and subchronically-treated animals. Larger doses of L-cycloserine, possibly by inducing multiple neurochemical changes, evoke central depressant effects which diminish during subchronic treatment.

4-Aminobutyrate Transaminase↗
PubMed1985

Isoniazid-induced convulsions in rats: effects of Ro 15-1788 and beta-CCE.

Dose-response curves for the convulsant effect of isoniazid were determined in male rats. The specific benzodiazepine antagonist Ro 15-1788, at doses from 20 to 100 mg/kg i.v. or at 300 mg/kg p.o., failed to produce any relevant shift of the isoniazid dose-response curves to the left (proconvulsant) or to the right (anticonvulsant). In contrast, the benzodiazepine receptor ligand ethyl-beta-carboline-3-carboxylate (beta-CCE) 10 mg/kg i.v. produced a clear-cut shift to the left of the isoniazid dose-response curve. Ro 15-1788 was inactive up to high p.o. or i.v. doses, versus convulsions induced by a low supraliminal dose of isoniazid, whereas beta-CCE had a significant proconvulsant effect beginning at 5 mg/kg i.v. This effect of beta-CCE was dose dependently antagonized by Ro 15-1788. In conclusion, in the present experimental conditions Ro 15-1788 showed no inverse agonistic properties at benzodiazepine receptors, in contrast to beta-CCE.

Animals↗
PubMed1984

The pharmacology of Parkinson's disease: basic aspects and recent advances.

Basic aspects and recent advances in the understanding of the pharmacological mechanism of action of the clinically most used antiparkinson drugs are reviewed. Recent human and animal biochemical investigations clearly confirm and extend previous findings indicating that benserazide is much more potent than carbidopa as peripheral decarboxylase inhibitor. L-DOPA in combination with benserazide or carbidopa constitutes the best available therapy for Parkinson's disease (PD). To reduce peaks and rapid fluctuations of L-DOPA plasma levels (possibly responsible for peak-dose dyskinesias and end-of-dose deterioration) a slow-release formulation of L-DOPA in combination with benserazide or with benserazide plus catechol-O-methyltransferase inhibitors should be developed. In parkinsonian patients under long-term L-DOPA therapy monoamine oxidase inhibitors type B (MAO-B) e.g. (-)deprenyl and direct dopamine receptor agonists (bromocriptine, lisuride, pergolide etc.), due to their L-DOPA-sparing effects, alleviate in some cases L-DOPA-induced side-effects e.g. dyskinesias and on-off phenomena. However, since (-)deprenyl, due to its metabolism to (-)methamphetamine and (-)amphetamine, seem to have indirect sympathomimetic activity, new selective MAO-B inhibitors devoid of indirect sympathomimetic effects should be tested clinically to assess the functional role of pure MAO-B inhibition in the therapy of PD. The auxiliary therapy with direct dopamine receptor agonists of the D-2 subtype represents another valid approach which should be further investigated in order to find novel dopamine agonists, less expensive than bromocriptine, and strictly selective for D-2 receptor sites.

Animals↗
PubMed1983

Preclinical pharmacology of midazolam.

Midazolam, a new imidazobenzodiazepine, forms salts that are stable in water solution, and has an overall pharmacological potency similar to that of diazepam but a much shorter duration of action. It produces all the characteristic effects of the benzodiazepine class. Its metabolites account for only a negligible part, if any, of its pharmacological effects observed in the mouse. The time course of its anticonvulsant activity, studied with different experimental protocols and by different routes of administration, revealed an almost immediate onset of action. Midazolam was slightly more potent, and its duration of action was shorter than diazepam, in enhancing presynaptic inhibition in the spinal cord of cats and in depressing spontaneous activity of cerebellar Purkinje cells in the rat. Midazolam decreased spontaneous multiunit activity (MUA) in different nuclei of the brain in 'encéphale isolé' rats. This depression was reversed by Ro 15-1788, a recently discovered selective benzodiazepine antagonist. Midazolam and diazepam decreased the cyclic GMP level in the cerebellum of rats with about the same potency; the effect of midazolam was of much shorter duration than that of diazepam. Midazolam had one-third the potency of diazepam in displacing 3H-flunitrazepam in mouse brain in vivo, and also in this case the effect of midazolam was of brief duration, as compared with diazepam. Midazolam in therapeutic doses was virtually ineffective in the cardiovascular system of conscious dogs after p.o. or i.v. administration. No direct effects of the drug on autonomic functions were found. The animal data suggest the usefulness of midazolam as an oral sleep-inducer, as an agent for i.v. induction of anaesthesia and as an i.v. or i.m. anticonvulsant in status epilepticus or tetanus, because of its rapid onset of action and its excellent local tolerance as water-soluble injection form.

Animals↗
PubMed1982

Benzodiazepine antagonist Ro 15-1788: neurological and behavioral effects.

In neurological and behavioral studies in mice, rats, dogs and squirrel monkeys, the imidazobenzodiazepinone Ro 15-1788 acted as a potent benzodiazepine antagonist. The antagonistic activity was both preventive and curative and seen at doses at which no intrinsic effects were detected. It was highly selective in that it acted against CNS effects induced by benzodiazepines but not against those produced by other depressants, such as phenobarbitone, meprobamate, ethanol, and valproate. The onset of action was rapid even after oral administration. Depending on the animal species studied, the antagonistic effects lasted from a few hours to 1 day. The acute and subacute toxicity of Ro 15-1788 was found to be very low. Benzodiazepine-like effects were not seen.

Animals↗