Has resistance to chlorhexidine increased among clinically-relevant bacteria? A systematic review of time course and subpopulation data.

Chlorhexidine (CHX) was introduced for use as an antimicrobial more than 70 years ago. CHX has been and continues to be used broadly for disinfecting surfaces in medical and food service facilities as well as directly on skin of humans and animals. Considering its widespread use over many decades, questions of resistance to CHX have been raised.

Use of mixture distributions to deconvolute the behavior of "hits" and controls in high-throughput screening data.

The stochastic nature of high-throughput screening (HTS) data indicates that information may be gleaned by applying statistical methods to HTS data. A foundation of parametric statistics is the study and elucidation of population distributions, which can be modeled using modern spreadsheet software. The methods and results described here use fundamental concepts of statistical population distributions analyzed using a spreadsheet to provide tools in a developing armamentarium for extracting information from HTS data.

Calculating the probability of detection for inhibitors in enzymatic or binding reactions in high-throughput screening.

In high-throughput screening (HTS) for drug candidates from a library containing tens of thousands to millions of chemical compounds, one problem is assessing the sensitivity of an assay for detecting compounds with a particular potency. For example, when looking for inhibitors of an enzyme, what is the potency of an inhibitor that will be readily detected by an enzyme inhibition assay? Similarly, when assessing compounds that inhibit binding between receptors and ligands or similar molecule-to-molecule interactions, what potency of an inhibitor will be readily detected? In this article, the well-established concepts of Michaelis-Menten kinetics and Langmuir binding isotherms are combined with fundamental statistical principles to yield a measure of assay sensitivity. The approach is general and can be modified to accommodate situations where the reaction kinetics is known to be more complicated than situations described by the Michaelis-Menten and Langmuir equations.

Pharmacokinetic properties, induction of interferon, and efficacy of selected 5-halo-6-phenyl pyrimidinones, bropirimine analogues, in a model of severe experimental autoimmune encephalomyelitis.

We showed previously that a 5-halo-6-phenyl-pyrimidinone, bropirimine (PNU-54461), inhibited progression of severe experimental autoimmune encephalomyelitis (EAE), an animal model of human multiple sclerosis. In the work presented here, we examined the activity of a group of chemically-related bropirimine analogues. First, the pharmacokinetic properties of the bropirimine analogues were examined in normal mice following oral dosing.

Effects of membrane partitioning and other physical chemical properties on the apparent potency of "membrane active" compounds evaluated using red blood cell lysis assays.

The membrane-destabilizing properties of Amphotericin B and Zwittergent were used as benchmark compounds for examining in detail their membrane-altering effects in a series of human red blood cell lysis assays. The procedures included examining dose responses and the effects of different cell concentrations on potency in rbc lysis assays. In order to enhance detection of subtle membrane effects, we also used a range of NaCl concentrations to osmotically stress the rbc's.