[Zebrafish as a Model Animal for the Study of Blood-Brain Barrier Permeability by Biomolecules].

[Zebrafish as a model animal for the study of blood-brain barrier permeability by biomolecules].

Filed under: Drug and Alcohol Rehabilitation

Yao Xue Xue Bao. 2012 Nov; 47(11): 1447-51
Fu AL, Chen HY, Xu XR, Zhao BQ

Blood-brain barrier (BBB) is the major obstacle for drug delivery into the central nervous system (CNS). However, there is no ideal model animal for the study of BBB permeability till now. Currently zebrafish (Danio rerio) has emerged as a powerful model organism for the study of vertebrate biology. In this study, the feasibility of using zebrafish as model animal was investigated for BBB permeability by comparing the results of administration of BBB-penetrating peptide and protein to mouse and zebrafish. The results showed that the BBBs of mouse and zebrafish were similar in molecular permeability. Additionally, zebrafish has advantageous features as a model animal, such as small size, fertile and easy to breed. Therefore, it is suggested that zebrafish may be a favored model for the study of BBB permeability.
HubMed – drug

[Effects of angiotensin II and its receptor blockers on migration and endothelin-1 expression of rat vascular adventitial fibroblast subpopulations].

Filed under: Drug and Alcohol Rehabilitation

Yao Xue Xue Bao. 2012 Nov; 47(11): 1428-33
Lu HG, Liu P, Shao TM, Chai XQ, Gao WJ, An SJ

The study is to investigate the effect of angiotensin II (Ang II) and its receptor blockers on migration and endothelin-1 (ET-1) expression of rat vascular adventitial fibroblast subpopulations. Vascular adventitial fibroblasts were individually expanded by using cloning rings, and the effects of Ang II on the migration of adventitial fibroblast subpopulations were evaluated by Transwell. Fluorescence quantitative-PCR detected the expression of preproET-1 mRNA induced by Ang II, and its receptor antagonists losartan and PD-123319. The concentration of ET-1 was determined by ELISA. It showed that spindle shaped and epithelioid shaped cells were isolated by using cloning rings, named as spindle cells and round cells. RT-PCR showed that fibroblast subpopulations did not have leukocytes, endothelial cells and smooth muscle cells, namely pure cell lines. Compared with respective control cells, two subpopulations had transferring ability. Ang II significantly improved round cells migration in a concentration-dependent manner, and had no obvious influence on spindle cells migration. Ang II (1 x 10(-8) – 1 x 10(-6) mol x L(-1)) significantly increased the expression of preproET-1 mRNA in round cells (P < 0.01), and had no significant effect on the expression of preproET-1 mRNA in spindle cells. Losartan blocked the expression of preproET-1 mRNA induced by Ang II in round cells, and had no significant effect on the expression of preproET-1 mRNA in spindle cells. The effects of Ang II and ET-1 receptor inhibitors on the release of ET-1 were similar to the expression of preproET-1 mRNA. The results indicate that there are two cell subpopulations: round cells and spindle cells in rat vascular adventitial fibroblasts. Ang II significantly improved cells migration, and increased the expression of ET-1 in round cell subpopulation. It suggested that there may be different migratory mechanisms in two cell subpopulations, and the two subpopulations may play a different role in vascular remodeling and reparative process. HubMed – drug

[Inspirations from natural products based drug research and development for Chinese medicine research–analysis of natural products recoded in TTD].

Filed under: Drug and Alcohol Rehabilitation

Yao Xue Xue Bao. 2012 Nov; 47(11): 1423-7
Chen XP, Lu JJ, Guo JJ, Bao JL, Xu WS, Ding Q, Wang YT

Natural product is an important source of new drug research and development (R&D). Traditional Chinese medicine (TCM) innovation is the key step for its modernization and internationalization. However, due to the complexity of TCM, there are many difficulties and confusions in this process. Target-based drug discovery is the mainstream model and method of R&D. TTD, short for therapeutic target database, is developed by National University of Singapore. Besides a large amount of information on drug targets, the database also contains considerable information related to natural products. This paper briefly introduces the TTD, analyzes the natural products derived drugs/compounds recorded in TTD, which we think might provide some inspiration for the innovation of TCM.
HubMed – drug

[The application of structural optimization strategies in drug design of HIV NNRTIs].

Filed under: Drug and Alcohol Rehabilitation

Yao Xue Xue Bao. 2012 Nov; 47(11): 1409-22
Wang L, Zhan P, Liu XY

Nonnucleoside reverse transcriptase inhibitors (NNRTIs) play an important roles in the prevention and treatment of AIDS. NNRTIs can specifically target at HIV reverse transcriptase (RT) and have the advantages of high potency and low toxicity, which make them a research focus for a long time. In the guidance of structural optimization strategies (bioisosterism, molecular hybridization and scaffold hopping) in medicinal chemistry, structural modification to lead compounds can be carried out to design new compounds with different levels, which will improve the efficiency of drug discovery and decrease the cost of drug development. It is an effective way to find new NNRTIs. In this review, we will expatiate on the application of different levels of structural optimization strategies in the NNRTIs structural modification with concrete examples.
HubMed – drug

[TREK1 potassium channels and depression].

Filed under: Drug and Alcohol Rehabilitation

Yao Xue Xue Bao. 2012 Nov; 47(11): 1403-8
Ye DQ, Zhang ZJ, Li Y

Major depression disorder is an increasing heavy burden in modem society, but its pathological mechanism is still vague. Recent evidence indicated that two pore potassium channel, TREK1, is one of the important drug targets of antidepressants. The structural and functional research progress of TREK1 potassium channel were reviewed with an emphasis on its roles in anti-depression, neuronal protection, and neuronal plasticity. The complicated interactions between TREK1 potassium channel and monoamine transmitters-receptors were also reviewed and future directions to explore the underline mechanism were also discussed.
HubMed – drug

More Drug And Alcohol Rehabilitation Information…