ABSTRACT
OBJECTIVE: Controlling outbreaks of nosocomial infections is a priority for public healthcare in France. This study concerned the incidence of multidrug-resistant bacteria (MDRB) in Lorraine and the impact of the national guidelines for the prevention of MDRB. METHODS: A multicenter incidence study was conducted for 5 months, in volunteer hospitals. Samples collected for the clinical diagnostic were included. The bacteria studied were: methicillin-resistant Staphylococcus aureus (MRSA), Klebsiella sp., Enterobacter sp., and other Enterobacteriaceae producing extended-spectrum beta-lactamase (ESBL), and vancomycin resistant Enterococci sp. RESULTS: A total of 30 hospitals were included in the surveillance of MDRB. During the study period (2001-2003), 17874 strains were identified. MRSA reached 29.3% of the 4038 strains of S. aureus, 20.9%, 1.23% and 1.21% of ESBL, respectively, for Enterobacter sp., Klebsiella sp., and other Enterobacteriaceae (for 895, 1061 and 9419 strains). Overall, the incidence of MRSA reached 0.55 per 1000 hospital-days and 0.087 for Enterobacter sp. The incidence increased during the 3 years, from 3.36 to 4.84 per 1000 new patients for MRSA, and from 0.43 to 0.90 for Enterobacter sp. CONCLUSION: Despite guidelines on isolation, MRSA remains poorly controlled and requires more efficient measures. Surveillance of ESBL should be improved.
Subject(s)
Bacteria/drug effects , Bacterial Infections/drug therapy , Bacterial Infections/epidemiology , Drug Resistance, Multiple , Population Surveillance , Bacteria/pathogenicity , Cross Infection , France , Hospitals/statistics & numerical data , Humans , IncidenceABSTRACT
A 644-membered library of chalcones was prepared by parallel synthesis using the Claisen-Schmidt base-catalyzed aldol condensation of substituted acetophenones and benzaldehydes. The cytotoxicity of these chalcones was conveniently determined upon the crude products directly in 96-well microtiter test plates by the conventional MTT assay. This method revealed seven chalcones of IC(50) less than 1 microM of which 4'-hydroxy-2,4,6,3'-tetramethoxychalcone (5a) was the most active [IC(50) (K562), 30 nM]; it causes cell cycle arrest at the G(2)/M point and binds to tubulin at the colchicine binding site.
Subject(s)
Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/pharmacology , Chalcone/chemical synthesis , Chalcone/pharmacology , Tetrazolium Salts , Thiazoles , Acetophenones/chemical synthesis , Acetophenones/chemistry , Combinatorial Chemistry Techniques , Drug Screening Assays, Antitumor , Humans , Magnetic Resonance Spectroscopy , Reproducibility of Results , Tumor Cells, CulturedABSTRACT
The chalcone 3,4,3',4',5'-pentamethoxychalcone is a potent cytotoxic agent. A series of chalcones and (E)-4-(4'-hydroxyphenyl)but-3-en-2-one were prepared and assessed for their ability to inhibit cell growth in vitro. The cytotoxicity correlates with their ability to bind to tubulin as measured by immunofluorescence, cell cycle analysis and disruption of microtubule assembly. Some of the chalcones were shown to bind to the type II oestrogen receptor.
Subject(s)
Antineoplastic Agents/chemistry , Cell Cycle/drug effects , Chalcone/analogs & derivatives , Chalcone/chemistry , Propiophenones/chemistry , Tubulin/drug effects , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/toxicity , Cell Division/drug effects , Cell Survival/drug effects , Chalcone/toxicity , Chlorocebus aethiops , Drug Design , Humans , Indicators and Reagents , K562 Cells , Microtubules/drug effects , Microtubules/ultrastructure , Molecular Structure , Propiophenones/chemical synthesis , Propiophenones/toxicity , Structure-Activity Relationship , Swine , Vero CellsABSTRACT
A new and efficient synthesis of the (+)-pancratistatin phosphate prodrug (2a) has been accomplished. Selective protection (tetraacetate 4) of (+)-pancratistatin (la) was followed by phosphorylation (to 5) with dibenzyl chlorophosphite (prepared in situ from dibenzyl phosphite). Cleavage of the acetate (with sodium methoxide) and benzyl (by hydrogenolysis) protecting groups followed by concomitant reaction with two equivalents of sodium methoxide afforded a good yield of disodium (+)-pancratistatin phosphate (2a). Further increases in yields of the prodrug (2a) were realized by avoiding heat in the final purification steps. Fourteen (2b-o) additional metal and ammonium cation derived phosphate prodrugs were also synthesized.
Subject(s)
Amaryllidaceae Alkaloids , Antineoplastic Agents, Phytogenic/chemical synthesis , Isoquinolines/chemical synthesis , Prodrugs/chemical synthesis , Antineoplastic Agents, Phytogenic/chemistry , Isoquinolines/chemistry , Magnetic Resonance Spectroscopy , Molecular Structure , Prodrugs/chemistry , Spectrometry, Mass, Fast Atom Bombardment , Spectrophotometry, InfraredABSTRACT
A series of substituted chalcones was synthesised and screened for cytotoxic activity against the K562 human leukaemia cell line. (E)-3-(3"-Hydroxy-4"-methoxyphenyl)-2-methyl-1-(3',4',5'- trimethoxyphenyl)-prop-2-en-1-one [IC50 (K562) 0.21 nM] was found to be the most active. A relationship between the conformation and cytotoxicity of the chalcones is discussed.
Subject(s)
Antineoplastic Agents/chemistry , Antineoplastic Agents/toxicity , Chalcone/analogs & derivatives , Chalcone/toxicity , Antineoplastic Agents/chemical synthesis , Cell Cycle/drug effects , Cell Division/drug effects , Cell Survival/drug effects , Chalcone/chemical synthesis , Chalcone/chemistry , Crystallography, X-Ray , Drug Design , Humans , K562 Cells , Models, Molecular , Molecular Conformation , Molecular Structure , Structure-Activity RelationshipABSTRACT
Aurantiamide acetate (N-benzoyl-1-phenylalanyl-1-pheylalaninol acetate) has been isolated by chromatographic separation of a methanol extract of Arisaema erubescens and its structure confirmed by synthesis.
