Copper Influences the Antibacterial Outcomes of a β-Lactamase-Activated Prochelator against Drug-Resistant Bacteria.

The unabated rise in bacterial resistance to conventional antibiotics, coupled with collateral damage to normal flora incurred by overuse of broad-spectrum antibiotics, necessitates the development of new antimicrobials targeted against pathogenic organisms. Here, we explore the antibacterial outcomes and mode of action of a prochelator that exploits the production of β-lactamase enzymes by drug-resistant bacteria to convert a nontoxic compound into a metal-binding antimicrobial agent directly within the microenvironment of pathogenic organisms. Compound PcephPT (phenylacetamido-cephem-pyrithione) contains a cephalosporin core linked to 2-mercaptopyridine N-oxide (pyrithione) via one of its metal-chelating atoms, which minimizes its preactivation interaction with metal ions and its cytotoxicity.

Fertility and cancer: psychological support in young women who contemplate emergency assisted reproductive technologies (ART) prior to chemo- and/or radiation-therapy.

Principles: Women of reproductive age with cancer fear for their childbearing potential as a result of the cancer itself and chemo- and/or radiation-therapy.

Methods: Starting in 2006, a dedicated task force was set up at Lausanne University Hospital (CHUV) to handle all cancer and fertility issues and, in certain cases, offer access to emergency assisted reproductive technologies (ART) to preserve further childbearing options. Help provided by the task force was offered within a multidisciplinary framework encompassing psychological counselling offered to each patient or couple.

Discovery and development of 5-[(5S,9R)-9-(4-cyanophenyl)-3-(3,5-dichlorophenyl)-1-methyl-2,4-dioxo-1,3,7-triazaspiro[4.4]non-7-yl-methyl]-3-thiophenecarboxylic acid (BMS-587101)--a small molecule antagonist of leukocyte function associated antigen-1.

LFA-1 (leukocyte function-associated antigen-1), is a member of the beta2-integrin family and is expressed on all leukocytes. This letter describes the discovery and preliminary SAR of spirocyclic hydantoin based LFA-1 antagonists that culminated in the identification of analog 8 as a clinical candidate. We also report the first example of the efficacy of a small molecule LFA-1 antagonist in combination with CTLA-4Ig in an animal model of transplant rejection.

De novo design, synthesis, and in vitro activity of LFA-1 antagonists based on a bicyclic[5.5]hydantoin scaffold.

LFA-1 (leukocyte function-associated antigen-1), is a member of the beta(2)-integrin family and is expressed on all leukocytes. The LFA-1/ICAM interaction promotes tight adhesion between activated leukocytes and the endothelium, as well as between T cells and antigen-presenting cells. Evidence from both animal models and clinical trials provides support for LFA-1 as a target in several different inflammatory diseases.