OBJECTIVE To develop and validate a method for determination of dextromethorphan (DMT) and dextrorphan (DTP) in plasma samples using HPLC-FL and to apply it to CYP2D6 phenotyping of a population from the South of Brazil. METHODS Samples were prepared by hydrolysis and liquid-liquid extraction. Analysis was conducted in a reversed phase column, with isocratic elution and fluorescence detection...

The toxicity of abrin, modeccin, and ricin to Vero cells was maximal at neutral and slightly alkaline pH, and it was strongly reduced at pH 6.0 and below. Diphtheria toxin was most toxic at low pH. Binding and endocytosis of abrin, modeccin, and ricin did not vary much within the pH range tested. High concentrations of the carboxylic ionophore Br-X-537A, protected against all four toxins. Combi...

Two chemically induced, antigenically distinct guinea pig hepatoma cell lines, line 1 and line 10, which are resistant to killing by rabbit anti-Forssman or specific anti tumor antibody and complement, can be rendered susceptible when the cells are pretreated with metabolic inh~bitors and drugs commonly used for the treatment of cancer patients. The effect appears within 7 hr after initial cont...

DNA topoisomerases are important cellular enzymes found in almost all types of living cells (eukaryotic and prokaryotic). These enzymes are essential for various DNA metabolic processes e.g. replication, transcription, recombination, chromosomal decatenation etc. These enzymes are important molecular drug targets and inhibitors of these enzymes are widely used as effective anticancer and antiba...

Abstract:MYC is a critical growth regulatory gene that is commonly overexpressed in a wide range of cancers. Therapeutic targeting of MYC transcriptional activity has long been a goal, but it has been difficult to achieve with drugs that directly block its DNA-binding ability. Additional approaches that exploit oncogene addiction are promising strategies against MYC-driven cancers. Also, drugs ...

A microtest has been devised for the rapid preliminary assay in vitro of the effect of over 100 drugs and inhibitors on African trypanosomes (Trypanosoma brucei and T. rhodesiense). Parasite motility and infectivity for mice are indexes, respectively, of respiration and glycolysis and of cell division; trypanocidal titers based on these indexes can show primary metabolic areas of drug attack. V...

Cells derived from neonatal rat heart tissue may be cultured in vitro. These cells retain the ability to spontaneously beat or contract. As the cells age in vitro, the beating rate gradually decreases and eventually stops . This loss of function has been described as dedifferentiation (1) . In the intact, adult, mammalian heart, lipids are the primary source of metabolic energy (2) . Lipids are...

Characterizing new drugs and chemical probes of biological systems is hindered by difficulties in identifying the mechanism of action (MOA) of biologically active molecules. Here we present a metabolite suppression approach to explore the MOA of antibacterial compounds under nutrient restriction. We assembled an array of metabolites that can be screened for suppressors of inhibitory molecules. ...

To the Editor—In their commentary, Chan et al propose that angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) should be considered first-choice antihypertensive therapies for obese patients, given the favourable effects of these agents on glucose metabolism. We agree with this assertion and suggest that the antiinflammatory action of renin-angiotensin blocka...

The present study utilized a cultured myocardial cell model to evaluate the relationship between the release of arachidonate from membrane phospholipids, and the progression of cell injury during ATP depletion. High-energy phosphate depletion was induced by incubating cultured neonatal rat myocardial cells with various combinations of metabolic inhibitors (deoxyglucose, oligomycin, cyanide, and...