Industrial platforms--a unique feature of the European Commission's biotechnology R&D programme.

The European Commission's research, technological development and demonstration programmes aim to strengthen European research and technological development, and to increase the competitiveness of European industries. The creation and development of Industrial Platforms play an important role in these processes by improving the transition from research to commercial application. Industrial Platforms are technology-based industrial groupings established by industry with the aims of enabling the exploitation or dissemination of research results, encouraging academic-industrial collaborations and providing their members with a means of voicing their opinion on present and future research policies.

Development of a novel series of (2-quinolinylmethoxy)phenyl-containing compounds as high-affinity leukotriene receptor antagonists. 1. Initial structure-activity relationships.

This series of reports describes the development of orally active, highly potent, specific antagonists of the peptidoleukotrienes containing a (2-quinolinylmethoxy)phenyl moiety. Described in this first report are the structure-activity relationships that led to a more than a 20-fold improvement of the potency and selectivity of the initial chemical lead (RG 5901). From this series of compounds, RG 7152 (16) was identified and selected for further evaluation in the clinic as an antiasthmatic agent. Compound 16 competitively inhibits [3H]LTD4 binding to membranes from guinea pig lung (Ki = 38 +/- 6 nM) and the spasmogenic activity of LTC4, LTD4, and LTE4 in parenchymal lung strips from guinea pigs. Unlike the original lead (RG 5901), compound 16 does not inhibit 5-lipoxygenase from guinea pig PMNs. Following oral administration to guinea pigs, 16 blocks LTD4-induced dermal permeability (ED50 = 6.9 mg/kg), LTD4-induced bronchoconstriction (ED50 = 1.1 mg/kg), antigen-induced bronchoconstriction (ED50 = 2.5 mg/kg), and anaphylactic-induced mortality (ED50 = 16 mg/kg). These studies on structure-activity relationships indicate that there is a requirement for an acidic function and the presence of the (2-quinolinylmethoxy)phenyl moiety in a specific geometric arrangement.

[Treatment of opiate weaning by clonidine in prison (evaluation based on 36 patients)]. / Traitement du sevrage aux opiacés par clonidine en milieu carcéral (bilan pour 36 patients).

The authors have used Clonidine for withdrawal from opiates of prisoners. About detoxification of 36 men entering into prison and published studies, they show that Clonidine is an efficacy and safe treatment. Clonidine induced hypotensia is not considered problematic.

Dose--effect relationships, r.b.e. and split-dose effects after gamma-ray and fast neutron irradiation of protoplasts from wild Nicotiana species.

Protoplasts from a diploid Nicotiana species were used to investigate the effects of gamma-rays and fast neutrons. The damage was assessed by scoring the relative plating efficiencies. The effects of single acute doses, as well as fractionated doses, are described for both qualities of radiation. The dose--r.b.e. relationship, expressing the effectiveness of fast neutrons relative to gamma-rays as a function of dose, appears similar to that of most animal systems, with higher values in the region of lower doses. The fractionation of gamma-ray doses, with sufficiently long time intervals between split doses, allowed a substantial recovery, as known also for X-rays. On the other hand, the fractionation of a fast neutron dose into low single fractions markedly increased the biological effectiveness of the total dose. This could not be explained by cell progression during resting time intervals and necessitated an additional hypothesis, possibly involving other mechanisms in the specific action of low doses of radiation.

The pharmacodynamics of bucainide (RHC G233): pharmacokinetic parameters and relationship between plasma levels and the effect on the electrocardiogram in the dog.

The pharmacodynamic profile of bucainide dimaleate (RHC G-233) in dogs has been studied. The first observed pharmacologic effect was a change in the ECG pattern (T-wave duration and amplitude) that occurred after an average intravenous dose of 2.7 mg/kg. The average plasma concentration of bucainide was approximately 350 ng/ml. Analysis of data from dogs that received a dual infusion of bucainide indicated that bucainide has an extensive volume of distribution, with an average value of approximately 26 l/kg. An average terminal half-life of 89 minutes was observed. Studies with the radiolabeled drug in rats and dogs also demonstrated the drug's large volume of distribution, and its initial rapid disappearance from the blood. Tissue distribution studies in the rat after administration of the radiolabeled drug showed that bucainide is rapidly taken up by the tissues.