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Biomedical subjects

T J Lenehan

Publications and source records attributed to T J Lenehan.

6 recordsLinked to original sources
PubMed1986

Interaction of antimicrobial agents with human peripheral blood leucocytes: uptake and intracellular localization of certain sulphonamides and trimethoprims.

The uptake of sulphamethoxazole, sulphadiazine, sulphamerazine, sulphanilamide, trimethoprim and brodimoprim by human peripheral blood leucocytes, has been investigated. High performance liquid chromatography (HPLC) was used to assay drug concentrations before and after incubation with leucocyte suspensions. Using radiolabelled material the intracellular localization of two of these compounds was also determined. The results indicated that all the investigated drugs were taken up by leucocytes. Differential studies demonstrated that mononuclear cells accumulated higher drug concentrations (0.13-0.55 microgram/10(7) cells), than resting neutrophils (0.02-0.26 microgram/10(7) cells) with the exception of sulphanilamide, which was taken up to a greater extent by neutrophils (0.75 microgram/10(7) cells). During neutrophil phagocytosis intracellular levels of all the drugs except brodimoprim increased from 3 to 130-fold as compared to resting neutrophils. The uptake of 14C-sulphanilamide and 14C-trimethoprim, in neutrophils and mononuclear blood cells, as assessed by measurement of the cell-associated radioactivity, correlated well with that determined by the HPLC procedure. In the intracellular localization studies 14C-sulphanilamide and 14C-trimethoprim exhibited similar distribution profiles. In neutrophils, 35-40% of radiolabelled drug was located in both the microsome and cytosol fractions whereas in peripheral blood mononuclear cells 40-60% was found in the cytosol and 10-20% in the microsome fraction. The results of this study suggest that, following activation, leucocytes may actively transport these drugs and release them locally at sites of infection. The ability of neutrophils to further concentrate the drugs during phagocytosis may result in reduced survival time of some ingested bacteria. These concepts may be important in designing treatment stratagems for intracellular pathogens.

Chromatography, High Pressure Liquid↗
PubMed1983

Platelet uptake of serotonin following repeated administration of 3-cyano-imipramine to healthy volunteers.

In a double blind, placebo-controlled study the effects of daily oral administration of 3-cyano-imipramine on the 3H-serotonin uptake capacity of platelets were investigated in healthy volunteers. The initial dose was 1 mg, rising to 3 mg daily for 7 days. A rapid and profound inhibition of 3H-serotonin uptake was observed in platelets isolated from the treated subjects. During repeated administration, uptake was reduced to less than 10% of pre-drug values. Five days after the final dose uptake had only partially recovered, to 53% of pre-drug values. A similar inhibition profile was observed when serum from the treated subjects was incubated with normal platelets and 3H-serotonin. The results establish 3-cyano-imipramine as a potent inhibitor of platelet serotonin uptake in humans.

Adolescent↗
PubMed1983

Effects of a single oral dose of 3-cyano-imipramine on serotonin uptake and content of platelets in healthy volunteers.

Changes in platelet serotonin uptake and content were investigated following administration of a single oral dose of 3-cyano-imipramine to healthy volunteers. The uptake of 3H-serotonin by platelets harvested from these subjects was almost completely inhibited 4 h after dose administration. This inhibition continued for at least 24 h. Plasma taken from the subjects inhibited the uptake of 3H-serotonin by platelets isolated from non-treated subjects. A small but significant reduction in platelet serotonin content was observed 3.75 h after dosing and was still evident after 24 h.

Administration, Oral↗