Reactive Oxygen Species-Responsive Polymer Nanoparticles to Improve the Treatment of Inflammatory Skin Diseases.

To improve the quality of life for people living with chronic inflammatory skin diseases, we propose a new treatment strategy by exploring a stimuli-responsive drug delivery system. Formulations designed by exploiting smart materials can be programmed to perform a specific action upon exposure to disease-related stimuli. For instance, increased levels of reactive oxygen species (ROS), especially the accumulation of hydrogen peroxide, can be utilized to differentiate between healthy and inflamed tissues.

Fragment-Based Discovery of 6-Arylindazole JAK Inhibitors.

Janus kinase (JAK) inhibitors are emerging as novel and efficacious drugs for treating psoriasis and other inflammatory skin disorders, but their full potential is hampered by systemic side effects. To overcome this limitation, we set out to discover soft drug JAK inhibitors for topical use. A fragment screen yielded an indazole hit that was elaborated into a potent JAK inhibitor using structure-based design.

PKPD model of interleukin-21 effects on thermoregulation in monkeys--application and evaluation of stochastic differential equations.

Purpose: To describe the pharmacodynamic effects of recombinant human interleukin-21 (IL-21) on core body temperature in cynomolgus monkeys using basic mechanisms of heat regulation. A major effort was devoted to compare the use of ordinary differential equations (ODEs) with stochastic differential equations (SDEs) in pharmacokinetic pharmacodynamic (PKPD) modelling.

Methods: A temperature model was formulated including circadian rhythm, metabolism, heat loss, and a thermoregulatory set-point.

Non-linear mixed effects modeling of sparse concentration data from rats: application to a glycogen phosphorylase inhibitor.

We investigated the use of non-linear mixed effects modeling in two preclinical studies of the glycogen phosphorylase inhibitor 1,4-dideoxy-1,4-imino-D-arabinitol (DAB). In a 28-day repeated-dose toxicity study rats were dosed once daily p.o.

EP3 receptors inhibit antidiuretic-hormone-dependent sodium transport across frog skin epithelium.

We examined the effect of prostaglandin E2 (PGE2) on antidiuretic hormone (ADH)-dependent Na+ transport and cAMP production in isolated frog skin epithelium. ADH caused an increase in transepithelial Na+ transport and a decrease in cellular potential, indicating an increase in apical Na+ permeability. Subsequent addition of PGE2 decreased Na+ transport and repolarised the cells.