William Bains | PubMed Health

PubMed2003

Vasoprotective VEGF as a candidate for prevention of recurrence of fibrotic diseases such as Dupuytren's contracture.

Dupuytren's contracture is a disease caused by the proliferation of contractile, fibroblastic cells adjacent to the palmar fascia of the hand. Cellular proliferation is apparently related to similar 'fibroblast' proliferation in wound healing, but continues in the absence of wounding. I propose that this is a similar processes to that which happens in the vascular wall during vascular surgery, that the myofibroblasts are at least partially similar to smooth muscle cells in phenotype, and consequently that treatment with VEGF, either as protein or via gene therapy, which has proven successful in controlling aberrant, wounding-related cell proliferation in arterial grafting, may be valuable in preventing recurrence of Dupuytren's disease after surgery.

Dupuytren Contracture↗

PubMed2002

Evolutionary computational methods to predict oral bioavailability QSPRs.

This review discusses evolutionary and adaptive methods for predicting oral bioavailability (OB) from chemical structure. Genetic Programming (GP), a specific form of evolutionary computing, is compared with some other advanced computational methods for OB prediction. The results show that classifying drugs into 'high' and 'low' OB classes on the basis of their structure alone is solvable, and initial models are already producing output that would be useful for pharmaceutical research. The results also suggest that quantitative prediction of OB will be tractable. Critical aspects of the solution will involve the use of techniques that can: (i) handle problems with a very large number of variables (high dimensionality); (ii) cope with 'noisy' data; and (iii) implement binary choices to sub-classify molecules with behavior that are qualitatively different. Detailed quantitative predictions will emerge from more refined models that are hybrids derived from mechanistic models of the biology of oral absorption and the power of advanced computing techniques to predict the behavior of the components of those models in silico.

Animals↗