fully-human-tumor-based-matrix-three-dimensional-spheroid-invasion

Fully Human Tumor-based Matrix in Three-dimensional Spheroid Invasion Assay

Two-dimensional cell culture-based assays are commonly used in in vitro cancer research. However, they lack several basic elements that form the tumor ...

University of Helsinki

The human immunodeficiency virus protease inhibitor ritonavir is a potent inhibitor of the cytochrome P450 3A4 enzyme, and ritonavir's concomitant administration with the substrates of this enzyme may lead to dangerous drug interactions.

Ritonavir's role in reducing fentanyl clearance and prolonging its half-life.

We studied seven healthy volunteers given itraconazole 200 mg orally or placebo, once daily for 4 days, in a crossover study. On day 4, racemic bupivacaine 0.3 mg kg-1 was given i.v. over 60 min and venous plasma samples were collected for 23 h. Plasma concentrations of R- and S-bupivacaine, itraconazole and hydroxyitraconazole were measured. Itraconazole reduced the clearance of R-bupivacaine by 21% (P < 0.05) and that of S-bupivacaine by 25% (P < 0.05), while it had no significant effect on other pharmacokinetic variables of the enantiomers. Reduction of bupivacaine clearance by itraconazole probably increases the steady-state concentration of bupivacaine enantiomers by 20-25%. This should be taken into account in the concomitant use of bupivacaine and itraconazole, although the interaction seems to be of limited clinical significance.

Effect of itraconazole on the pharmacokinetics of bupivacaine enantiomers in healthy volunteers.

Preliminary pharmacological experiments have suggested that in the bovine retractor penis muscle there are relaxation-mediating endothelin ET(B) receptors, at least part of which are located on the inhibitory nitrergic nerves. The present work was undertaken to test this hypothesis by means of receptor autoradiography and additional pharmacological experiments. In the retractor penis muscle and the penile artery, specific binding of the ETB receptor-selective agonist [125I]BQ-3020 took place predominantly to nerve trunks and minor nerve branches. The situation was the same in the dorsal metatarsal artery, that was included as a reference because of its different innervation. Throughout the nerves the silver grains were evenly distributed over the nuclei of Schwann cells and the spaces between them. In the retractor penis there was also a small amount of specific binding to smooth muscle. No specific endothelial binding was observed in any of the tissues examined. The pharmacological studies confirmed that the relaxation of the retractor penis muscle induced by the ET(B) receptor-selective agonist, sarafotoxin S6c, is susceptible to tetrodotoxin as well as to inhibition of nitric oxide synthase. The relaxation was also characterized by inconsistency, weakness and tachyphylaxis. The electrical field stimulation-induced submaximal relaxation of the retractor penis was unaffected by stimulation or blockade of ET(B) receptors. The autoradiography suggests that in all the three bovine tissues studied there are ET(B) receptors located on nerves independently of the type of efferent nerve. The pharmacological experiments do not support the concept that in the bovine retractor penis muscle neuronal ET(B) receptors exert important immediate effects on the functioning of the penile erection-mediating nitrergic nerves.

Article	Year
Ritonavir's role in reducing fentanyl clearance and prolonging its half-life. Anesthesiology\| PubMed ID: 10485779	1999
Effect of itraconazole on the pharmacokinetics of bupivacaine enantiomers in healthy volunteers. British journal of anaesthesia\| PubMed ID: 10673888	1999
The endothelin ET(B) receptor agonist [125I]BQ-3020 binds predominantly to nerves in the bovine retractor penis muscle and penile artery. Pharmacology & toxicology\| PubMed ID: 11129504	2000

Miila Palkama

Biography

JoVE Journal Publications

Other Publications