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Biomedical subjects

M Cross

Publications and source records attributed to M Cross.

At least 127 records · Page 7Linked to original sources
PubMed1996

Absence of effect of sertraline on the pharmacokinetics and pharmacodynamics of phenytoin.

UNLABELLED: A double-blind, randomized, placebo-controlled study assessed the effects of sertraline on the pharmacokinetics and pharmacodynamics of phenytoin in 30 healthy male volunteers. METHOD: All subjects received phenytoin throughout the study. The dose of phenytoin was 100 mg three times daily; steady-state trough plasma phenytoin concentrations were determined on Day 6. Concurrent treatment with sertraline (16 subjects) or placebo (13 subjects) was initiated on Day 8 and continued throughout the study in those subjects whose trough plasma phenytoin concentrations were between 5 and 20 micrograms/mL. The dose of sertraline was increased from 50 to 200 mg/day over 7 days; the 200-mg dose was then administered for 10 days. The plasma phenytoin concentration-time profile was determined on Day 7 before the start of sertraline or placebo dosing and at the end of dosing on Day 24. Psychometric testing was done before and after dosing on Days 0, 7, and 24. RESULTS: There were no significant differences between the sertraline group and the placebo group in the pharmacokinetic parameters of phenytoin. In addition, there was no indication that administration of phenytoin alone or concomitant administration of phenytoin and sertraline impaired cognitive function. Treatment-related side effects, primarily headache and nausea, were reported in 8 of 16 sertraline subjects and in 5 of 13 placebo subjects. Two subjects in the sertraline group withdrew because of side effects (rash), and 3 subjects in the placebo group withdrew because of side effects (rash and headache). CONCLUSION: High dosages of setraline did not affect the pharmacokinetics or the pharmacodynamics of phenytoin in ths study performed in healthy volunteers.

1-Naphthylamine↗
PubMed1996

Antigenic variation in trypanosomes.

We review here antigenic variation in African trypanosomes with emphasis on genetic mechanisms and on the expression sites in which the genes for Variant Surface Glycoproteins (VSGs) are expressed. There are multiple expression sites in a trypanosome, but only one of these is active at a time. We discuss recent experiments that provide new information on expression site regulation, i.e., how inactive sites are kept inactive and how the trypanosome switches from expression of one site to expression of another one. Trypanosomes can also change the gene expressed by replacing the gene in an active expression site by another VSG gene. This replacement involves the duplicative transposition of a silent VSG gene into the expression site. We present a model for the mechanism of this transposition that incorporates new features and that explains several unusual characteristics of the transposition process. We also discuss how new knowledge of nutrient uptake, notably uptake of host transferrin by trypanosomes, might be used for vaccine development.

Animals↗
PubMed1995

Hydroxyl radical generation following ischaemia-reperfusion in cell-free perfused rat kidney.

The difficulty in direct detection of oxygen-derived free radicals (OFR) in the intact kidney has left uncertain the role of OFR in renal hypoperfusion injury. Salicylate hydroxylation was used as a sensitive method of estimating the extent of production of highly reactive hydroxyl radicals in renal ischaemia-reperfusion injury in the intact rat kidney perfused with recirculating cell-free medium. The reaction products were detected and quantified by HPLC with electrochemical detection. Hydroxyl radicals were detected as 2,5-dihydroxybenzoic acid (2,5-DHBA). Ischaemia for 15 min followed by reperfusion for 15 min caused more than a twofold increase in 2,5-DHBA concentration (to 2279 +/- 225 pg/g tissue weight) compared to controls (933 +/- 103, P < 0.001). Addition of 15 mM dimethylthiourea (DMTU) before induction of ischaemia prevented this increase. Induction of hypoxia for 15 min with continued perfusion (as a model of low-flow ischaemia) had no significant effect on hydroxyl radical formation. We conclude that significant quantities of hydroxyl radicals form in the absence of circulating leucocytes during reperfusion following ischaemia, but not during hypoxia in the perfused rat kidney.

Animals↗
PubMed1995

The roles of multiple pathways in regulating bombesin-stimulated phospholipase D activity in Swiss 3T3 fibroblasts.

The regulation of bombesin-stimulated phospholipase D (PLD) activity in Swiss 3T3 fibroblasts was examined. Increasing protein-tyrosine phosphorylation by using pervanadate to inhibit tyrosine phosphatases was found to stimulate protein kinase C (PKC)-independent [3H]phosphatidylbutanol ([3H]PtdBut) accumulation within 5 min, which continued to increase up to 30 min. The stimulation of PLD activity in response to submaximal [bombesin] could be decreased by approx. 50% by the tyrosine kinase inhibitor genistein, whereas pretreatment with genistein and the PKC inhibitor Ro-31-8220 completely abolished the generation of [3H]PtdBut in response to a maximal concentration of bombesin. The addition of guanosine 5'-[gamma-thio]triphosphate (GTP[S]) into permeabilized cells resulted in an increase in [3H]PtdBut, which was abolished by depletion of cellular ATP. The additional presence of 30 microM GTP[S] did not increase the stimulation of PLD activity by any [bombesin] tested, whereas it was synergistic with that stimulated in response to phorbol 12-myristate 13-acetate. These findings suggest that bombesin-stimulated PLD activity is indirectly regulated by G-proteins, possibly through a kinase intermediate. Furthermore, activation of protein tyrosine kinases is proposed to account for the PKC-independent arm of bombesin-stimulated PLD activity. No evidence was obtained for a form of PLD directly regulated by tyrosine phosphorylation.

3T3 Cells↗