Endoscopic measurements of canine colonic mucosal blood flow using hydrogen gas clearance.

We have examined the feasibility of hydrogen (H2) clearance for endoscopic measurements of colonic mucosal blood flow in anesthetized dogs. In 6 animals, measurements of H2 clearance did not differ significantly in different regions of the sigmoid colon and they were highly reproducible (p less than 0.001) on different days.

Protective effect of exogenous phospholipid on aspirin-induced gastric mucosal injury.

The protective effects of exogenous phospholipid on aspirin-induced gastric mucosal injury were examined in a canine chamber model which provided two separate segments of mucosa supplied by a single vascular pedicle. In each dog, one segment was treated with a suspension of surface-active phospholipid, similar in composition to that normally present in the gastric mucosa, whereas the other segment served as the control. Pretreatment of the test segments significantly prevented aspirin-induced disruption of the mucosal barrier as evidenced by an increase in potential difference and a decrease in acid back-diffusion and sodium ion and potassium ion flux.

Simultaneous determination of cytosine arabinoside, its nucleotides and metabolites by ion-pair high-performance liquid chromatography.

Currently available high-performance liquid chromatographic assays for cytosine arabinoside (ara-C) and its metabolites suffer from two major shortcomings: inability to resolve both ara-C and its nucleotides in a single chromatographic step and/or inadequate sensitivity to allow quantitation of intracellular cytosine arabinofuranoside-5'-triphosphate (ara-CTP) without the use of radiolabelled drug. In this paper, we describe a new ion-pairing high-performance liquid chromatographic assay for ara-C in biological samples that can separate ara-C from its nucleotides, metabolites, and naturally occurring ribonucleotides in a single chromatographic step with a lower limit of quantitation of 5 pmol for ara-C and 10 pmol for ara-CTP. Examples of the utility of this assay are shown in studies of intracellular pharmacokinetics of ara-C in cultured human breast cancer cells and in analysis of plasma nucleoside levels in patients receiving high-dose thymidine chemotherapy.

Insulin effects on methotrexate polyglutamate synthesis and enzyme binding in cultured human breast cancer cells.

Previous studies have demonstrated that insulin augments methotrexate transport and enhances its cytotoxicity to human breast cancer cells. We therefore investigated the effects of insulin on methotrexate polyglutamate synthesis and binding to dihydrofolate reductase (DHFR) in two human breast cancer cell lines, MCF-7 and MDA-MB-231. Cells were exposed to 2 microM [3H]MTX and varying insulin concentrations for the desired time before determination of the polyglutamate content by high-performance liquid chromatography (HPLC).