Piracetam Inhibits The Lipid-Destabilising Effect Of The Amyloid Peptide A Beta C-Terminal Fragment

in Biochimica et Biophysica Acta-Biomembranes (2003), 1609(1), 28-38

Amyloid peptide (Abeta) is a 40/42-residue proteolytic fragment of a precursor protein (APP), implicated in the pathogenesis of Alzheimer's disease. The hypothesis that interactions between Abeta ... [more ▼]

Amyloid peptide (Abeta) is a 40/42-residue proteolytic fragment of a precursor protein (APP), implicated in the pathogenesis of Alzheimer's disease. The hypothesis that interactions between Abeta aggregates and neuronal membranes play an important role in toxicity has gained some acceptance. Previously, we showed that the C-terminal domain (e.g. amino acids 29-42) of Abeta induces membrane permeabilisation and fusion, an effect which is related to the appearance of non-bilayer structures. Conformational studies showed that this peptide has properties similar to those of the fusion peptide of viral proteins i.e. a tilted penetration into membranes. Since piracetam interacts with lipids and has beneficial effects on several symptoms of Alzheimer's disease, we investigated in model membranes the ability of piracetam to hinder the destabilising effect of the Abeta 29-42 peptide. Using fluorescence studies and 31P and 2H NMR spectroscopy, we have shown that piracetam was able to significantly decrease the fusogenic and destabilising effect of Abeta 29-42, in a concentration-dependent manner. While the peptide induced lipid disorganisation and subsequent negative curvature at the membrane-water interface, the conformational analysis showed that piracetam, when preincubated with lipids, coats the phospholipid headgroups. Calculations suggest that this prevents appearance of the peptide-induced curvature. In addition, insertion of molecules with an inverted cone shape, like piracetam, into the outer membrane leaflet should make the formation of such structures energetically less favourable and therefore decrease the likelihood of membrane fusion. [less ▲]

Piracy prevention and the pricing of information goods

in Information Economics and Policy (2009), (21), 34-42

This paper studies the effects of piracy on prices and welfare and determines the optimal enforcement policy. A monopolist sells an information good at a non-linear price in two versions designed for two ... [more ▼]

This paper studies the effects of piracy on prices and welfare and determines the optimal enforcement policy. A monopolist sells an information good at a non-linear price in two versions designed for two types of consumers with different willingness to pay. Consumers with low willingness to pay consumers can copy the good at some cost and with some quality loss. High valuation customers cannot engage in full-fledged piracy. However, they can consume the version designed for the other customer type. We show that copying or piracy may be welfare enhancing because it enables a good to be provided to individuals with a low willingness to pay without undermining the producing firm’s ability to finance the development cost via the pricing scheme applied to high valuation consumers. There are then three levels of piracy control. The highest is that chosen by the private monopoly. The next level is the one chosen by a welfare-maximizing monopoly. The lowest level, which can be zero, is the level of control chosen by the public authority when the good is sold (and priced) by a profit-maximizing monopoly. ! 2008 Elsevier B.V. All rights reserved. [less ▲]

Pirates informatiques et mathématique modulaire

Learning material (2007)

De nos jours, l'envoi de messages secrets requiert la manipulation de nombres ayant plus de cent chiffres décimaux. Nous illustrons une technique cryptographique standard (le RSA) dont la sécurité réside ... [more ▼]

De nos jours, l'envoi de messages secrets requiert la manipulation de nombres ayant plus de cent chiffres décimaux. Nous illustrons une technique cryptographique standard (le RSA) dont la sécurité réside dans le fait qu'il est "rapide", sur le plus banal des ordinateurs personnels, de calculer le produit de deux "grands" nombres (cela se compte au pire en secondes), alors que le temps nécessaire pour effectuer l'opération inverse de factorisation prend, dans l'état actuel des connaissances mathématiques, énormément plus de temps (que l'on pourrait estimer en milliards d'années même pour un super-calculateur !). [less ▲]

PIRENE : Programme intégré de recherche environnement - eau - Partim caractérisation et modélisation hydrauliques des cours d'eau

Report (2004)

Pirlindole: a selective reversible inhibitor of monoamine oxidase A. A review of its preclinical properties.

in Pharmacological Research (1997), 36(1), 23-33

Pirlindole is a tetracyclic compound that has been characterized as a potential antidepressant drug. It has pharmacological characteristics in common with both tricyclic antidepressants and classical ... [more ▼]

Pirlindole is a tetracyclic compound that has been characterized as a potential antidepressant drug. It has pharmacological characteristics in common with both tricyclic antidepressants and classical irreversible monoamine oxidase inhibitors. Its main mechanism of action consists of a selective and reversible inhibition of monoamine oxidase A. Secondarily, it exerts an inhibitory effect on noradrenaline and 5-hydroxytryptamine reuptakes. It has no effect on the dopaminergic and cholinergic systems. It has only a low potential for amplifying tyramine and noradrenaline pressor effect, which makes one expect that it will not be at the basis of a 'cheese effect'. Pirlindole has an absolute bioavailability of between 20 and 30% due to an extensive first-pass effect. Orally, the Tmax varies between 2.5 and 6 h in the rat and 0.8 and 2 h in the dog. Two phases of elimination (7.5 and 34-70 h) are measured in the rat and three phases in the dog (1.3, 10.8 and 185 h); it is extensively metabolized. The rat eliminates mainly unconjugated products while the dog eliminates mostly conjugated products. Acute and chronic toxicological studies have not revealed potentially dangerous effects of the drug at the usual doses. It does not present measurable mutagenic, clastogenic or carcinogenic properties. Thus, pirlindole shows pharmacological, pharmacokinetic and toxicological properties which make it suitable for the management of depression. [less ▲]

Piroxicam fails to reduce myocellular enzyme leakage and delayed onset muscle soreness induced by isokinetic eccentric exercise

in Pflügers Archiv : European Journal of Physiology (1996), 431

Piroxicam-Beta-Cyclodextrin in the Treatment of Acute Pain of Rheumatic Disease

in European Journal of Rheumatology and Inflammation (1993), 12(4), 38-46

Analgesics continue to be the mainstay of therapy in osteoarthritis. Non-steroidal anti-inflammatory drugs (NSAIDs) play an important role, particularly where there is a significant inflammatory component ... [more ▼]

Analgesics continue to be the mainstay of therapy in osteoarthritis. Non-steroidal anti-inflammatory drugs (NSAIDs) play an important role, particularly where there is a significant inflammatory component to the osteoarthritis. Piroxicam-beta-cyclodextrin (PBC) is a new formulation in which piroxicam has been complexed with beta-cyclodextrin, a cyclic oligosaccharide. This results in an increase in the rate of absorption of the active compound and, consequently, in an earlier onset of analgesic action. PBC, like piroxicam, is administered once daily. PBC has been used in the treatment of osteoarthritis. In comparison with piroxicam, PBC showed a more rapid analgesic-anti-inflammatory action after the first administration in patients with active osteoarthritis. Subsequent evaluations at the second, fifth and last day of treatment demonstrated a comparable efficacy of the two drugs. The efficacy and tolerability of PBC was compared with other NSAIDs given intramuscularly, such as diclofenac and ketoprofen. The three compounds provided marked pain relief within thirty minutes and this increased progressively until the third to fourth hour. The efficacy of oral PBC was comparable to that of intramuscular diclofenac or ketoprofen. In comparison with metamisole PBC achieved a more rapid and sustained reduction in pain intensity during the first twelve hours of treatment. This rapid and marked reduction in pain intensity with PBC was also observed in patients with low-back pain when compared with etodolac. In view of its efficacy, tolerability and rapid onset of action, piroxicam-beta-cyclodextrin appears to be an useful analgesic and a prominent progress in the treatment of acute rheumatic pain. [less ▲]

PISA 2000 : Programme international pour le Suivi des Acquis des élèves : présentation de l'enquête

Report (2002)

PISA 2003 : en moyenne, des résultats moyens mais trop de jeunes en situation critique

in TRACeS de ChanGements (2006), 10

PISA 2003 Data Analysis Manual : sas users

Book published by OECD (2005)