The effect of pentoxifylline and its metabolite-1 on inflammation and fibrosis in the TNBS model of colitis.

TNBS-induced colitis has characteristics resembling human Crohn's disease including transmural inflammation, ulceration, and fibrosis. Current treatments target acute symptoms but do not necessarily prevent fibrotic complications of the disease. The aim of this study was to determine the effect of pentoxifylline and its primary metabolite (M-1) on fibrosis in the TNBS-induced colitis model.

A novel drug interaction between the quinolone antibiotic ciprofloxacin and a chiral metabolite of pentoxifylline.

Pentoxifylline (PTX), a methylxanthine derivative, is metabolized to seven compounds in vivo, with metabolites 1 and 5 possessing biologic activity. Metabolite-1 is a chiral molecule and its S-enantiomer is selectively formed during PTX metabolism in vivo. We have developed a reproducible method of synthesizing a racemic mixture of the chiral metabolite-1 (M-1) of PTX.

Cytokines as therapeutic targets for the gastrointestinal manifestations of scleroderma.

Systemic sclerosis (SSc), or scleroderma, is a connective tissue disorder characterized by progressive fibrosis of the skin and internal organs. It has significance for gastroenterologists because the gastrointestinal tract is involved in 90% of SSc patients, who often present with esophageal dysfunction. Though the exact pathogenesis of SSc is unknown, there is increasing evidence supporting an immune mechanism.

Retention of transporter activities in cryopreserved, isolated rat hepatocytes.

The success of cryopreservation of isolated hepatocytes with existing methodologies is assessed with respect to the retentivity of cell integrity/viability (defined by trypan blue) and metabolic activities upon thawing in comparison to those of freshly prepared cells. But the ability of the cryopreserved cells to transport xenobiotics relative to that of freshly prepared cells has not been investigated. In this study, we optimized our previous methodology for cryopreservation and evaluated the metabolism and transport of thawed hepatocytes.