The effect of P38 MAP kinase inhibition in a mouse model of influenza.

PURPOSE: Influenza viruses are a common cause of human respiratory infections, resulting in epidemics of high morbidity and mortality. We investigated the effect of a novel mitogen-activated protein kinase (MAPK) inhibitor in vitro and in a murine influenza model to further explore whether p38 MAPK inhibition could reduce viral replication. METHODS: In vitro, the antiviral effect of p38 MAPK inhibitor BCT194 was evaluated in differentiated human bronchial epithelial cells (HBECs); in vivo, female BALB/c mice were infected intranasally with 150 pfu of influenza H1N1 A/Puerto Rico/8/34 and treated with BCT197 (a closely related p38 MAPK inhibitor with an IC50 value of<1 µM, currently in clinical testing), dexamethasone or oseltamivir (Tamiflu) starting 24 h post infection. Body weight, bronchoalveolar lavage cells, cytokines, total protein and lactate dehydrogenase as well as serum cytokines were measured; a subset of animals was evaluated histopathologically.Results/Key findings. p38MAP kinase inhibition with BCT194 had no impact on influenza replication in HBECs. When examining BCT197 in vivo, and comparing to vehicle-treated animals, reduced weight loss, improvement in survival and lack of impaired viral control was observed at BCT197 concentrations relevant to those being used in clinical trials of acute exacerbations of chronic obstructive pulmonary disease; at higher concentrations of BCT197 these effects were reduced. CONCLUSIONS: Compared to vehicle treatment, BCT197 (administered at a clinically relevant concentration) improved outcomes in a mouse model of influenza. This is encouraging given that the use of innate inflammatory pathway inhibitors may raise concerns of negative effects on infection regulation.

[Simvastatin indused chylothorax]. / Chylothorax induit par la simvastatine.

Chylothorax is a rare disorder occurring most often in aftermath of a thoracic surgery or during cancer of mediastinum. We report the clinical history of the world's second case of chylothorax which appeared during treatment with simvastatin.

Antiplasmodial activity of plant extracts used in west African traditional medicine.

Five plants originating from Ivory Coast were selected after an ethnobotanical survey, Alchornea cordifolia, Mitragyna inermis, Nauclea diderrichii, Pterocarpus santalinoides, and Terminalia glaucescens. Traditional healers for the treatment of malaria commonly used these plants. Extracts of these plants were tested on three strains of Plasmodium falciparum, FcB1-Colombia and FcM29-Cameroon (chloroquine-resistant strains) and a Nigerian chloroquine-sensitive strain. Extracts were obtained by preparing decoction in water of the powdered plant, the technique used by most of the traditional healers. A radioactive micromethod allowed the evaluation of the in vitro activity of the extracts on P. falciparum. Concentrations inhibiting 50% of the parasite growth (IC(50)) ranged from 2.34 to more than 500 microg/ml according to the plant. For the most active plants (A. cordifolia and T. glaucescens) ethanol and pentane extracts were made and tested. The IC(50) values obtained for these extracts ranged from 0.35 to 43.40 microg/ml. The stage specificity of the ethanol extracts of A. cordifolia and T. glaucescens and pentane extract of T. glaucescens on the parasite erythrocytic cycle were determined. The ethanol extract of T. glaucescens showed its highest activity at the transition from the trophozoite to the schizont stages. Cytotoxicity was estimated on human fibroblasts (HeLa) cells and a cytotoxicity/antiplasmodial index was calculated, it ranged between 5 and 21, and the best antiplasmodial extract (T. glaucescens ethanol extract) had the higher index (>20).

Anti-Toxoplasma activity of vegetal extracts used in West African traditional medicine.

Both Toxoplasma gondii and Plasmodium are Apicomplexan protozoa that share common metabolic pathways and potential drug targets. The objective of this study was to examine the anti-Toxoplasma activity of nine West African plants with known activity against P. falciparum. The extracts were obtained from parts of plant commonly used, by most traditional healers, in the form of infusion or as water decoction. The in vitro activity of plant extracts on T. gondii was assessed on MRC5 tissue cultures and was quantified by enzyme-linked immunoassay. Aqueous extracts from Vernonia colorata were found to be inhibitory for Toxoplasma growth at concentrations > 10 mg/L, with an IC50 of 16.3 mg/L. A ten-fold gain in activity was obtained when organic solvents such as dichloromethane, acetone or ethanol were used to extract V. colorata's active principles. These extracts were inhibitory at concentrations as low as 1 mg/L, with IC50 of 1.7, 2.6 and 2.9 mg/L for dichloromethane, acetone and ethanol extracts respectively. These results indicate a promising source of new anti-Toxoplasma drugs from V. colorata and African medicinal plants.

In vitro antimalarial activity of vegetal extracts used in West African traditional medicine.

Among strategies for the development of new antimalarials, a study of plants traditionally used in Africa against malaria has been pursued. Extracts obtained from the plants Azadirachta indica, Cinnamonum camphora, Lippia multiflora, Vernonia colorata, Guiera senegalensis, Combretum micranthum, and Ximenia americana, commonly used in Cote d'Ivoire by native healers for the treatment of malaria, were tested on two strains of Plasmodium falciparum: FcB1-Colombia (chloroquine-resistant) and F32-Tanzania (chloroquine-sensitive). Extracts were obtained after infusion and decoction, both techniques being used by most native healers. The antimalarial activities of the extracts were tested first by parasite 3H-hypoxanthine incorporation and second by visual evaluation of the activities of plant extracts on thin blood smears, which also permitted the determination of parasitic stages and parasite alteration. Among the seven plants tested, some had an apparent inhibitory effect on P. falciparum growth in vitro, while other seemed to be less efficient.

Study of Caffein - Catechin Association in Lyophilized Fresh Seeds and in Stabilized Extract of Cola nitida.

Caffein-catechin association has been demonstrated in lyophilized fresh seeds and in stabilized extract of COLA NITIDA (Vent.) A. Chev. by using various analytical techniques which have made it possible to determine specifically the concentrations of free caffein versus associated caffein. Associated caffein varies from 0% in dried seeds to 91% in lyophilized fresh seeds and in stabilized extract of COLA. It was possible to simulate these quantitative variations of associated caffein by using an experimental model with a saturated aqueous solution of caffein and various amounts of catechin. Infrared spectrophotometric studies have shown the hydrogen bond type of the association. The differences of pharmacological effects of fresh and dried seeds may be due to the varying concentrations of associated and free caffein.