The effect of local anaesthesia of the airway on respiratory reflexes in the rabbit.
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Biomedical subjects
Publications and source records attributed to F Reynolds.
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The rabbit placenta perfused in itu was used to investigate the factors determining the placental transfer of drugs used in labour. Each doe was given an intravenous infusion of pethidine, lignocaine, bupivacaine and antipyrine concurrently, and the umbilical circulation was artificially perfused with Mammalian Krebs' bicarbonate buffer. The umbilical flow rate was varied between 0.25 and 4.0 ml/min. Drugs were analysed in maternal plasma and umbilical effluent by gas liquid chromatography . Maternal protein binding and lipid solubilities were also determined, and were high for bupivacaine, low for antipyrine and intermediate for pethidine and lignocaine. The Cuv /Cma (mean +/- s.e.) at 1.0 ml/min for antipyrine was 0.74 +/- 0.036; for pethidine, 0.64 +/- 0.04; for lignocaine, 0.5 +/- 0.026; and for bupivacaine 0.072 +/- 0.006. This is the same rank order as is observed for the drugs in humans. The placental clearance increased with flow rates up to 2.0 ml/min for antipyrine and up to 4.0 ml/min and probably more for pethidine, lignocaine and bupivacaine. Transfer rate is therefore reduced by maternal protein binding, is flow-dependent at low flows, and permeability-dependent at high flows for the less lipid-soluble compounds.
The fetal-to-maternal ratios of carbamazepine, antipyrine and phenytoin are principally determined by maternal protein binding, though greater lipid solubility may enhance the transfer of valproate compared to that of other drugs at high flows. Placental clearance of all anticonvulsants showed flow-dependent characteristics. This is in line with our findings for basic drugs.
The ability to use magnetic nanoparticles for cell tracking, or for the delivery of nanoparticle-based therapeutic agents, requires a detailed understanding of probe metabolism and transport. Here we report on the development and metabolism of a dual fluorochrome version of our tat-CLIO nanoparticle termed Tat(FITC)-Cy3.5-CLIO. The nanoparticle features an FITC label on the tat peptide and a Cy3.5 dye directly attached to the cross-linked coating of dextran. This nanoparticle was rapidly internalized by HeLa cells, labeling 100% of cells in 45 min, with the amount of label per cell increasing linearly with time up to 3 h. Cells loaded with nanoparticles for 1 h retained 40-60% of their FITC and Cy3.5 labels over a period of 72 h in label-free media. Over a period of 144 h, or approximately 3.5 cell divisions, the T2 spin-spin relaxation time of cells was not significantly changed, indicating retention of the iron oxide among the dividing cell population. Using confocal microscopy and unfixed cells, both dyes were nuclear and perinuclear (broadly cytoplasmic) after Tat(FITC)-Cy3.5-CLIO labeling. Implications of the rapid labeling and slow excretion of the Tat(FITC)-Cy3.5-CLIO nanoparticle are discussed for cell tracking and drug delivery applications.
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