Thermogravimetric studies on co-pyrolysis of raw/torrefied biomass and coal blends.

The pyrolysis and co-pyrolysis behaviours of cotton stalk (CS), torrefied cotton stalk (TCS) and mined coal, as single fuels, and their blends, have been examined through thermogravimetric analysis. Biomass has been torrefied at 250°C for 45 min to enhance physicochemical properties, and then mixed with mined coal for co-pyrolysis. Thermal degradation of CS and TCS is characterized by a reaction. However, this is not the case for mined coal, which shows a single-stage reaction. The thermal degradation of all blends was done in three stages: dehydration; biomass and small mined coal; and lignin or mined coal. A similar trend emerged for mass loss of individual fuels, which depended mainly on their ratios in the blend. The kinetics of pyrolysis and co-pyrolysis of all fuels were calculated at 20°Cmin-1 heating rate using the Coats-Redfern model-fitting method.

Hierarchization of animal teratology findings for improving the human risk evaluation of drugs.

The risk assessment of drugs in pregnancy can be improved through better knowledge and interpretation of significant experimental findings. Embryo-fetal effects can be considered as the endpoint of importance, after excluding that their occurrence is related to maternal toxicity. If embryo-fetal toxic effects occur in the presence of maternal toxicity, the dam influence should be clearly assessed, and can be taken into account in the determination of a safety margin. A determination of the lowest developmental toxic dose, if any, apart from any maternal toxicity, should be made. With positive animal developmental findings, interpretation should take into account various parameters including the incidence and the severity of the embryo-fetal insult, interspecies reproducibility, the level of exposure, metabolic pathways, and the results of possible mechanistic investigations. Hierarchization of the experimental findings should take into account all these parameters together to provide support for the risk assessment in humans.

[Toxicology of reproduction: predictive value of experimental models. Round Table No 1 at Giens XIII]. / Toxicologie de la reproduction: valeurs prédictives des modèles expérimentaux. Table Ronde No 1 de Giens XIII.

The carrying out of clinical trials with a view to the marketing of drugs for human use is directly related to results of some animal studies. This workshop was devoted to evaluation of the quality and interest of these experimental models in reproductive toxicology. The predictive ability of preclinical trials to make extrapolations from animals to man decreases from foetotoxic to tetratogenic risks respectively and from the effects on fertility in both sexes to postnatal risks. As a result of this workshop, we propose the following improvements: (1) standardization and generalization of fertility test evaluations, especially the spermogram, in order to improve animal and human correlations; (2) development of knowledge and standardization of the follow up of the oestral cycle; (3) improvement of standardization, harmonization and diffusion of postnatal tests that prove relevant in animals; (4) increase in initiatives aimed at better mutual understanding of all drug partners; (5) creation of registers for new drugs, as soon as possible during clinical trials, to study their effects on the whole reproductive process; (6) recommendations for the creation of guidelines for International Conference on Harmonisation (ICH) to enable classification of observed effects in experimental models. This could lead to specific (potentially for each phase of the reproductive cycle) guidelines, precautions for use and/or contraindications which are listed in the summary of product characteristics.

[Drug interactions: regulatory aspects]. / Interactions médicamenteuses: les aspects réglementaires.

The task of the Drug Interactions working party of the French Medicines Agency is to select the clinically relevant interactions. This selection is carried out on the basis of an analysis of published and unpublished observed cases (pharmacovigilance), a follow-up of interactions which could be subsequently selected in view of new data, and an update of the labelling of interactions which have been already selected. The conclusions of the working group are subjected to approval by the French Medicines Registration Committee. This leads mainly to: a harmonization of the Drug Interactions heading, in the Summary of Products Characteristics, for drugs of the same pharmacological class; the yearly publishing of an addendum to the Vidal relative to 'Drug Interactions', which reflects precisely the working group's conclusions; the acknowledgement, at Community level, of the above mentioned drug interactions labelling, i.e. clinically relevant adverse drug reactions, pharmacokinetic or pharmacodynamic mechanism of action (if known), recommendations (four levels), and corresponding co-prescription management, if necessary.

Defensive function of pigment granules in Blepharisma japonicum.

The defensive function of pigment granules in the red heterotrichous ciliate Blepharisma japonicum was studied by comparing normally-pigmented red cells, albino mutant cells and light-bleached cells (a phenocopy of the albino mutant) as prey for a carnivorous ciliate Dileptus margaritifer. Albino and bleached cells were eaten more readily than red cells by dilepti. Under certain conditions, dilepti were killed by red cells, but not by albino and light-bleached cells. The cell-free fluid of red cells, but not of albino and bleached cells, was toxic to dilepti. We conclude that one of the functions of pigment granules in B. japonicum is defense against predators. The offense-defense interaction between D. margaritifer and B. japonicum is, therefore, mediated by their extrusomes, toxicysts in the former and pigment granules in the latter. Other extrusomes of unknown function might also participate in offense-defense cell-cell interaction in protists.

No effect of roxithromycin on pharmacokinetic or pharmacodynamic properties of warfarin and its enantiomers.

The macrolide antibiotics are metabolized by cytochrome P-450 enzymes in the liver and interactions with similarly metabolized compounds have been described. Simultaneous treatment with erythromycin and warfarin is known to decrease warfarin clearance and prolong prothrombin time. Roxithromycin (RU 28965), a new erythromycin derivative with improved pharmacokinetic properties, might then, because of structure similarity, be expected to interact with warfarin. In 21 healthy volunteers, the effect of orally administered roxithromycin (150 mg b.i.d.) on warfarin steady-state kinetics, and the effects of warfarin on roxithromycin kinetics, were investigated in a double-blind, randomized study versus placebo. Since the warfarin enantiomers, R- and S-warfarin have both different potency and different metabolism, the ratio between the enantiomers with and without roxithromycin, was also determined. In this study, mean AUC for warfarin increased slightly from day 14 of warfarin treatment to day 28, but no difference was found between the roxithromycin group and the placebo group, and no change appeared in the ratio between the warfarin enantiomers. A moderate increase in dosage was needed to maintain hypocoagulability during warfarin medication, but there was no difference between the roxithromycin group and the placebo groups, respectively. In addition, roxithromycin kinetics appeared to be unaffected by warfarin treatment.

A study of the interaction of roxithromycin with theophylline and carbamazepine.

There have been reports of an interaction when theophylline and macrolides are given together, and also when carbamazepine is given with macrolides. We compared the kinetics of theophylline and carbamazepine, given alone and then in combination with roxithromycin. Roxithromycin had little effect on the pharmacokinetics of theophylline and none on carbamazepine, and roxithromycin can be given with either of the drugs without any need to alter the dose.

Pharmacokinetics of ofloxacin and theophylline alone and in combination.

The pharmacokinetic interactions of ofloxacin (2 X 200 mg) and theophylline (3 X 200 mg) were investigated in 12 healthy volunteers over a period of two weeks. In the first week, theophylline was given over five days to reach a steady state. In the second week, the combination of theophylline and ofloxacin was applied. Cmax, tmax, AUC0-8, the serum elimination constant and serum half-life of theophylline were not changed when theophylline was given alone or in combination with ofloxacin. The kinetic parameters of ofloxacin were in accordance with data from the literature.