Pharmacokinetics of bound and unbound telaprevir in cirrhotic patients with moderate and severe hepatic impairment.

This study aimed to characterize the pharmacokinetic parameters of telaprevir (TVR) in patients with moderate and severe hepatic impairment, measure the unbound (pharmacologically active) plasma concentrations of TVR, and determine if any changes in TVR exposure were of clinical relevance. Ten patients with moderate (Child-Pugh B) hepatic impairment, 10 matched healthy control volunteers, and 4 nonmatched patients with severe (Child-Pugh C) hepatic impairment received 750 mg TVR every 8 hours for 6 days. Venous blood samples were collected at various times throughout the study.

NO-induced activation of cyclic GMP-dependent pathway down regulates ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1) protein in rat C6 glioma.

In rat C6 glioma cells, the ecto-nucleotide pyrophosphatase/phosphodiesterase-1 (NPP1), a modulator of purinergic receptor signaling, is down regulated after an increase in intracellular cAMP by addition of dibutyryl cAMP, a membrane-permeable cAMP-analog, or by activation of the β-adrenoceptor receptor with (-)-isoproterenol (Aerts et al., 2011, Eur. J.

The expression of ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (E-NPP1) is correlated with astrocytic tumor grade.

Objective: Astrocytic brain tumors are subdivided in four grades. The most aggressive and invasive one is grade IV or glioblastoma multiforme (GBM). Ecto-nucleotide pyrophosphatase/phosphodiesterase-1 (E-NPP1), a membrane-bound enzyme, is involved in many cellular processes such as modulation of purinergic signalling, nucleotide recycling, regulation of extracellular pyrophosphate levels and stimulation of cell motility.

Cyclic AMP-dependent down regulation of ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1) in rat C6 glioma.

In this communication, we demonstrate that an increase in intracellular cAMP by 1) addition of dibutyrylic cAMP (dbcAMP), a membrane-permeable cAMP-analogue, or 2) activation of the β-adrenoceptor with (-)-isoproterenol, down regulates the levels of ecto-nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1) mRNA, NPP1 protein and ecto-NPPase activity in rat C6 glioma cells. DbcAMP and (-)-isoproterenol inhibit NPP1 expression in a time and dose-dependent manner. After 48h of stimulation, 1mM dbcAMP or 5μM (-)-isoproterenol decreases the amount of NPP1 protein by 75±3% and 81±1% respectively.