Optically active β-ketoiminato manganese(III) complexes as efficient catalysts in enantioselective aerobic epoxidation of unfunctionalized olefins

A novel manganese(III) complex having an optically active N, N′-ethylenebis-β-ketoimine ligand was prepared and characterized crystallographically. The manganese(III) complexes behave as effective catalysts in enantioselective epoxidation of unfunctionalized olefins by combined use of molecular oxygen, an oxidant, and pivalaldehyde, a reductant. Dihydronaphthalene derivatives were converted into the corresponding optically active epoxides with good to high enantioselectivities.     

Clostridium difficile toxin and faecal lactoferrin assays in adult patients

Clostridium difficile is the primary aetiological agent of antibiotic-associated diarrhoea. The faecal lactoferrin (FL) assay is a simple in vitro test which is highly sensitive to the presence of a marker of polymorphonuclear cells. We evaluated the use of the FL assay in conjunction with the C. difficile toxin assay in faecal samples obtained from 231 adult patients. The relationship between C. difficile toxin and FL in both negative and positive status was highly significant statistically (P < 0.001). Therefore, the FL assay performed simultaneously with the C. difficile toxin assay can help rule out asymptomatic carriage of C. difficile.     

Incision at O6-methylguanine:thymine mispairs in DNA by extracts of human cells.

Human cell-free extracts were used to detect activities specifically incising O6-methylguanine (m6G) paired with C or T in DNA. A 45-bp double-stranded DNA containing one m6G across from a T (m6G:T) was the test substrate. Extracts from glioblastoma cell lines A172 and A1235 (lacking the m6G-specific repair protein m6G-DNA methyltransferase, MGMT) and colon carcinoma cell line HT29, containing MGMT, showed incision activities specific for the T strand of m6G:T [and G:T, as reported previously by Wiebauer and Jiricny (1989)] substrates, but did not cleave m6G:C (or G:C) substrates. Competition experiments showed that the activity was similar to, if not identical with, the activity in human cells that incises G:T mismatches. The incision sites were similar to those recognized by human G:T- or G:A-specific mismatch enzymes, i.e., the phosphodiester bonds both 3' and 5' to the poorly matched T, suggesting the glycolytic removal of the poorly matched T followed by backbone incisions by class I or II AP endonucleases. Three experiments in which MGMT was inactivated showed that the m6G:T incision activity was not simply due to a two-step mechanisms in which MGMT would first mediate conversion of the m6G:T substrate to a G:T substrate which would serve as a substrate for G:T incision. Extracts from HT29 contained a DNA-binding factor, possibly DNA sequence-specific, that inhibited incision of the m6G:T (but not the G:T) substrate, that was removed by the addition of synthetic DNA to the reaction.     

Metalloporphyrins as chemical mimics of cytochrome P-450 systems

Certain synthetic metalloporphyrins have been shown to mimic the in vivo metabolism of some pharmaceuticals. Oxidation, hydroxylation and N-demethylation yielded synthetic metabolites. If found to be general, this lays the foundation of a predictive basis to optimize analog desing of inhibitors with reduced oxidative reactivity, to determine the proclivity of drugs to form biological active metabolites, and provides a convenient methodology for their preparation.

Certain Synthetic metalloporphyrins have been shown to mimic the in vivo metabolism of some pharmaceuticals. Oxidation. hydroxylation and N-demethylation yielded synthetic metabolites. If found to be general, this lays the foundation of a predictive basis to optimize analog design of inhibitors with reduced oxidative reactivity, to determine the proclivity of drugs to form biologically active metabolites, and provides a convenient methodology for their preparation.     

In Vitro Potency Assay for Hepatitis A Vaccines: Development of a Unique Economical Test

Prior to the official release of each Hepatitis A vaccine lot to the market, a quality control performed by a National Control Authority requires an in vivo or an in vitro potency assay. At the beginning of our work, no standardised in vitro test common to all hepatitis A vaccines was available for both manufacturers and National Control Laboratories. In this study, a unique polyvalent enzyme-linked immunosorbent assay (ELISA) method was developed to appraise all commercially available HAV vaccines. After comparing a direct and an indirect sandwich method with commercial antibodies, the indirect assay was selected and an evaluation of sensitivity, linearity, accuracy and precision was performed before being applied to HAV antigen determination from four different manufacturers. The results are satisfactory and incline us to use routinely this method to release Hepatitis A vaccines.