The potency-insolubility conundrum in pharmaceuticals: Mechanism and solution for hepatitis C protease inhibitors.

As compounds are optimized for greater potency during pharmaceutical discovery, their aqueous solubility often decreases, making them less viable as orally-administered drugs. To investigate whether potency and insolubility share a common origin, we examined the structural and thermodynamic properties of telaprevir, a sparingly soluble inhibitor of hepatitis C virus protease. Comparison of the hydrogen bond motifs in crystalline telaprevir with those present in the protease-telaprevir complex revealed striking similarities.

Protein Z Plasma Levels are Not Elevated in Patients with Non-Arteritic Anterior Ischemic Optic Neuropathy.

Background: Protein Z is a glycoprotein that acts as a co-factor for the inhibition of activated coagulation factor X. Protein Z circulating in abnormal levels has been associated with increased risk for acute ischemic events. Non-arteritic Anterior Ischemic Optic Neuropathy (N-AION) is caused by acute ischemic infarction of the optic nerve head, supplied by the posterior ciliary arteries.

Genetic risk factors associated with thrombosis in children with congenital neurologic disorders.

Thromboembolic events during the perinatal period are responsible for irreversible brain damage owing to cerebral hypoxia and neuronal necrosis. We investigated the presence of thrombophilia risk factors in children with congenital neurologic disorders. Nineteen children (9 males and 10 females), aged 1 to 14 years (median 4.

Genetic background of osteonecrosis: associated with thrombophilic mutations?

Intravascular coagulation is considered a major pathogenetic mechanism for nontraumatic osteonecrosis. The aim of our study was to evaluate the association of thrombophilic factor V G1691A mutation (factor V Leiden) and G20210A prothrombin mutation with the disease. Mutation presence was investigated by polymerase chain reaction techniques in a study population of 72 adult Caucasian patients with osteonecrosis of the femoral head and 300 healthy Caucasian control subjects.

Effect of Gravity on Colloidal Deposition Studied by Atomic Force Microscopy.

Atomic force microscopy (AFM) was used to study the effect of gravitational forces on the deposition of submicrometer colloidal particles onto solid surfaces to test the usual assumption that the contribution of gravity to the behavior of particles with diameters <1 &mgr;m is negligible. The effects of both particle size and density were examined using polystyrene sulfate latex, silica, and colloidal gold particles of several sizes ranging from 10 nm to 1 &mgr;m. The results show that significant differences are observed in the deposition of colloidal particles onto horizontal and vertical surfaces, under identical suspension conditions and exposure times, showing that gravitational forces can have a considerable effect.