Biased small-molecule ligands for selective inhibition of HIV-1 cell entry via CCR5.

Since the discovery of HIV's use of CCR5 as the primary coreceptor in fusion, the focus on developing small-molecule receptor for inhibition hereof has only resulted in one single drug, Maraviroc. We therefore investigated the possibility of using small-molecule CCR5 as HIV-1 fusion inhibitors. A virus-free cell-based fusion reporter assay, based on mixing "effector cells" (expressing HIV and luciferase activator) with "target cells" (expressing CD4, CCR5 wild type or a selection of well-described mutations, and luciferase reporter), was used as fusion readout.

Intestinal alkaline phosphatase: selective endocytosis from the enterocyte brush border during fat absorption.

Absorption of dietary fat in the small intestine is accompanied by a rise of intestinal alkaline phosphatase (IAP) in the serum and of secretion of IAP-containing surfactant-like particles from the enterocytes. In the present work, fat absorption was studied in organ cultured mouse intestinal explants. By immunofluorescence microscopy, fat absorption caused a translocation of IAP from the enterocyte brush border to the interior of the cell, whereas other brush-border enzymes were unaffected.

Interaction between peripheral afferent activity and presynaptic inhibition of ia afferents in the cat.

It has been demonstrated in man that the H-reflex is more depressed by presynaptic inhibition than the stretch reflex. Here we investigated this finding further in the alpha-chloralose-anesthetized cat. Soleus monosynaptic reflexes were evoked by electrical stimulation of the tibial nerve or by stretch of the triceps surae muscle.