Relative bioavailability and food effect study of an oral suspension of alectinib in healthy volunteers using venipuncture and capillary microsampling.

Alectinib, approved as 150 mg capsules for the treatment of adults with advanced ALK-positive non-small cell lung cancer, is being assessed in children with ALK-positive solid and central nervous system tumors. An ad hoc pediatric-friendly suspension of alectinib, prepared from capsule contents, is under investigation as an alternative formulation for children who cannot swallow capsules. This randomized, crossover, relative bioavailability, and food effect study evaluated alectinib administered as an oral suspension versus capsule formulation following conventional venipuncture and capillary microsampling.

Focal degeneration of astrocytes in amyotrophic lateral sclerosis.

Astrocytes emerge as key players in motor neuron degeneration in Amyotrophic Lateral Sclerosis (ALS). Whether astrocytes cause direct damage by releasing toxic factors or contribute indirectly through the loss of physiological functions is unclear. Here we identify in the hSOD1(G93A) transgenic mouse model of ALS a degenerative process of the astrocytes, restricted to those directly surrounding spinal motor neurons.

Defective tumor necrosis factor-alpha-dependent control of astrocyte glutamate release in a transgenic mouse model of Alzheimer disease.

The cytokine tumor necrosis factor-alpha (TNFalpha) induces Ca2+-dependent glutamate release from astrocytes via the downstream action of prostaglandin (PG) E2. By this process, astrocytes may participate in intercellular communication and neuromodulation. Acute inflammation in vitro, induced by adding reactive microglia to astrocyte cultures, enhances TNFalpha production and amplifies glutamate release, switching the pathway into a neurodamaging cascade (Bezzi, P.

Cinnamamide analogs as inhibitors of protein tyrosine kinases.

Protein tyrosine kinases (PTK) are important signal transducing enzymes involved in the modulation of normal cellular growth and differentiation and have been associated with the etiology of various human cancers. The development of properly designed inhibitors, which block their function by interfering with the substrate binding, may therefore offer an unique target for selective anticancer chemotherapy. Here we describe synthesis and biochemical testing of a novel series of non-peptide PTK inhibitors which have as characteristic active pharmacophore the cinnamamide moiety.

The in vivo biodegradation of nylon 6 utilized in a particular IUD.

The particular IUD of this study was composed of a plastic shield and a nylon 6 coated filament tail string. This IUD was unique, in the fact that its tail string was the only one (and has been to date) that consisted of a coated multifilament arrangement. Studies on the tail string have revealed bacteria and debris existing between the outer filaments that are underneath the coating.