Tyrosine kinase inhibitory activity of dehydroabietylamine derivatives tested by homogeneous time-resolved fluorescence based high throughput screening model / 中国天然药物

Protein tyrosine kinases (PTKs) are attractive targets in searching for therapeutic agents against many diseases. In this study, a series of dehydroabietylamine derivatives were first determined to show PTK inhibitory activity using a high-throughput screening (HTS) method based on homogeneous time-resolved fluorescence (HTRF) technology. The structure-activity relationships of the dehydroabietylamine derivatives were established, and it was found that the compounds with a nitrogen-containing side chain had better inhibitory activity. Further studies showed that the compounds substituted with halogen in the phenyl ring resulted in higher inhibitory activity on the epidermal growth factor receptor (EGFR), and can be a guide to modify the structure of dehydroabietylamine derivatives. Dehydroabietylamine derivatives might be a new class of multi-targeted and effective PTK inhibitors with structure modifications.

Protective effects of glutamine on the intestinal mucosal barrier in young rabbits under hemorrhagic shock / 中国当代儿科杂志

<p><b>OBJECTIVE</b>Glutamine (Gln) is now considered as conditionally essential amino acid with many biological activities. This study aimed to investigate whether it has protective effects on the intestinal mucosal barrier in young rabbits under hemorrhagic shock.</p><p><b>METHODS</b>Eighteen young rabbits aged 26 +/- 3 days were randomly assigned into 3 groups: Control (no treatment), Low-dose Gln (L-Gln, 0.5 g/kg daily) and High-dose Gln (H-Gln, 1.0 g/kg daily) treatment groups. Gln was administered by gastric tube daily for 7 days and then hemorrhagic shock was induced by blood withdrawing from femoral artery. Plasma levels of diamine oxidase (DAO) and serum levels of interleukin-8 (IL-8) were measured before shock, and at 2, 6 and 24 hrs after resuscitation. Ileum tissues located approximately 5 cm away from the ileocecal valve was removed for histological examination, lymphocyte distribution, polymorphonuclear (PMN) count and assessing the height, width and surface area of the villi.</p><p><b>RESULTS</b>Plasma levels of DAO and serum levels of IL-8 at 6 and 24 hrs after resuscitation in the L-Gln and the H-Gln groups decreased significantly compared with those of the Control group. L-Gln and H-Gln also resulted in a decrease in the PMN counts and the lymphocyte percentage in the ileum compared with the Control group. Exfoliation and atrophy of villous epithelial cells occurred and the height and surface area of villous were reduced in the Control group. The ileum morphology of the two Gln treatment groups was found to be nearly normal. There were no differences between the L-Gln and the H-Gln groups.</p><p><b>CONCLUSIONS</b>Gln within a therapeutic dose has protective effects on intestinal mucosal barrier in young rabbits under hemorrhagic shock.</p>