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Biomedical subjects

R Porta

Publications and source records attributed to R Porta.

12 recordsLinked to original sources

A novel insight into the mechanism of the antithrombotic action of defibrotide.

Defibrotide is a polydeoxyribonucleotide sodium salt with antithrombotic properties. These properties have been attributed to its profibrinolytic activity [increase of tissue plasminogen activator (t-PA) activity, concomitant decrease of that of plasminogen activator inhibitor (PAI)], but there could conceivably be other factor(s). To look for these, we studied Defibrotide in a thrombosis model (pulmonary thromboembolism in mice) in which free radicals play a pivotal role. Defibrotide was found to be active after both intravenous and oral administration. Defibrotide behaved in vitro like a scavenger of H2O2 but not of O2.- in cell-free systems. Defibrotide added in vitro to cellular systems decreased the stimulated release of beta-glucuronidase from polymorphonuclear cells (PMNs), the luminol chemiluminescence induced by oxygen species generated by stimulated PMNs and the generation of O2.- from stimulated macrophages. We think that the antithrombotic activity of Defibrotide is based on other factor(s) in addition to profibrinolytic activity, i.e., some scavenger activity and desensitization of cells involved in thrombus formation must also be taken into account.

Animals

Interocular transfer of a visual aftereffect in early-onset esotropia.

The interocular transfer of the tilt aftereffect was studied in strabismic patients with early-onset esotropia and in controls. Squinting subjects were divided into a microtropia subgroup with anomalous binocular vision and a large-angle esotropia subgroup with total suppression of the deviated eye. Patients with alternating microtropia and large-angle esotropia showed normal or moderately reduced interocular transfer of the aftereffect. Patients with monocular microtropia with medium- or low-degree amblyopia showed a reduced monocular visual aftereffect in the dominant eye and practically no transfer to the nondominant eye. Adaptation of the nondominant eye and transfer of the aftereffect to the dominant eye was normal. The interocular transfer of the tilt aftereffect is a poor indicator of the state of binocularity of a squinting subject, and the clinical usefulness of this test is limited.

Adolescent

Polyamine quantitative analysis in the developing chick embryo.

1. An improved specific and sensitive method for the separation and detection of polyamines, based on an automated ion exchange chromatography, is described. 4. The mean contents of polyamines in embryos at different stages of development are reported. The data show a direct correlation between the cellular polyamine content and the growth rate of the embryo.

Animals

Absorption, distribution and excretion of a dihydroxydibutyl ether labelled with 14C in animals.

Kinetic studies were performed in rats, dogs and monkeys after oral administration of 14C-labelled dihydroxy-dibutyl ether (DHBE; Discinil), a known choleretic agent. The data presented indicate that the compound was intirely and readily absorbed and that it was excreted mainly with the urine in all the three species. The complete distribution pattern was investigated in rats. In most tissues high levels of radioactivity were already present after 10 min and the peak concentration was reached within the first 30 min. The decay was rapid and at the fourth hour only traces of radioactivity could be still detected in the tissues. Liver and kidney were the target organs for the radioactive material (which is in accordance with the activity and the excretory route of DHBE). The blood levels paralleled the general tissue distribution. The excretion of radioactivity was completed within 24 h in the three animal species and it took place by the urinary route, mainly witin the first 7--8 h.

Animals

Arginase from human full-term placenta.

Arginase was purified about 1800-fold from extracts of human full-term placenta; the enzyme appeared to be homogenous by disc electrophoresis and molecular-sieve chromatography. The mol. wt. determination by gel filtration and sodium dodecyl sulphate/polyacrylamide-gel electrophoresis yielded a value of 70000 for the most pure and the partially purified enzyme. The human placenta arginase is a metalloenzyme with an optimum pH of 9.1. The Km for L-arginine is 27 mM. L-Ornithine and L-lysine show competitive inhibition with Ki values of 6.3 and 14 mM respectively.

Arginase

Pharmacology of dihydroxy-dibutylether, a specific choleretic drug.

The choleretic and the general pharmacological properties of dihydroxy-dibutyl ether (Discinil) were investigated in several animal species. Discinil (DHBE) increased the bile flow in conscious rats and dogs, after both oral and i.v. administration. A choleretic effect was also observed after i.v. injection into anaesthetized rats and guinea pigs. A dose-response relationship was always obtained, the threshold dose being 25--100 mg/kg. No evidence of tachyphylaxis was observed in rats after repeated treatments. The bile hyperflow was generally accompanied by an increased excretion of the total dry residue in guinea pigs and dogs. The choleretic effect in rats was still present after pretreatment with either DL-ethionine (causing parenchymal liver damage) or atropine (blocking the cholinergic control of bile production). At low doses (25--100 mg/kg i.v.) eliciting a definite choleretic response, DHBE did not show spasmogenic and spasmolytic effects in vivo on the smooth muscles of the gallbladder of guinea pigs and dogs, neither on the stomach and intestine of mice and dogs; while it constricted the pylorus sphincter of rats. At larger doses (200--400 mg/kg i.v.) the compound showed a mild relaxing activity on Oddi's sphincter of guinea pigs and a weak spasmogenic activity either on gall bladder or on small intestine. In vitro, it caused an unspecific antagonism against the spasm induced by acetylcholine, barium chloride, histamine, 5-hydroxytryptamine and norepinephrine. In anaesthetized rats, rabbits and dogs, DHBE caused a moderate and short-lasting hypotension, and tachycardia. The threshold doses for these effects were 2--4 times superior to those being choleretic. In conscious dogs, the compound was slightly hypertensive. DHBE did not provoke important respiratory and ECG changes, neither showed diuretic nor antiphlogistic effects.

Administration, Oral