Increased endothelin-1 reactivity and endothelial dysfunction in carotid arteries from rats with hyperhomocysteinemia

Background and purpose:

There are interactions between endothelin-1 (ET-1) and endothelial vascular injury in hyperhomocysteinemia (HHcy), but the underlying mechanisms are poorly understood. Here we evaluated the effects of HHcy on the endothelin system in rat carotid arteries.

Experimental approach:

Vascular reactivity to ET-1 and ET_A and ET_B receptor antagonists was assessed in rings of carotid arteries from normal rats and those with HHcy. ET_A and ET_B receptor expression was assessed by mRNA (RT-PCR), immunohistochemistry and binding of [¹²⁵I]-ET-1.

Key results:

HHcy enhanced ET-1-induced contractions of carotid rings with intact endothelium. Selective antagonism of ET_A or ET_B receptors produced concentration-dependent rightward displacements of ET-1 concentration response curves. Antagonism of ET_A but not of ET_B receptors abolished enhancement in HHcy tissues. ET_A and ET_B receptor gene expressions were not up-regulated. ET_A receptor expression in the arterial media was higher in HHcy arteries. Contractions to big ET-1 served as indicators of endothelin-converting enzyme activity, which was decreased by HHcy, without reduction of ET-1 levels. ET-1-induced Rho-kinase activity, calcium release and influx were increased by HHcy. Pre-treatment with indomethacin reversed enhanced responses to ET-1 in HHcy tissues, which were reduced also by a thromboxane A₂ receptor antagonist. Induced relaxation was reduced by BQ788, absent in endothelium-denuded arteries and was decreased in HHcy due to reduced bioavailability of NO.

Conclusions and implications:

Increased ET_A receptor density plays a fundamental role in endothelial injury induced by HHcy. ET-1 activation of ET_A receptors in HHcy changed the balance between endothelium-derived relaxing and contracting factors, favouring enhanced contractility.British Journal of Pharmacology (2009) 157, 568–580; doi:10.1111/j.1476-5381.2009.00165.x; published online 9 April 2009This article is part of a themed section on Endothelium in Pharmacology. For a list of all articles in this section see the end of this paper, or visit: http://www3.interscience.wiley.com/journal/121548564/issueyear?year=2009     

青钱柳甜味成分的研究

从青钱柳[Cyclocarya paliurus(Batal.)Iljinsk]嫩叶中分离得到3个(Ⅰ～Ⅲ)有强甜味的化合物。根据理化性质和光谱数据,确定化合物Ⅰ的结构为20,24-环氧-达玛烷-(3β,12β,20S,24R)-12-O-β-D-吡喃鸡纳糖基-3-O-α-L-呋喃阿拉伯糖甙,为一新化合物,命名为青钱柳甙I(cyclocariosideI)。     

小百部的甾体皂甙成分

从云南产小百部(Asparagus filicinus Buch.-Ham)的根中分离到四个甾体皂甙,经光谱分析和化学降解,确定了结构,其中三个为新化合物,分别命名为小百部甙A(Ⅰ),小百部甙B(Ⅱ)和小百部甙C(Ⅲ)。另一个为已知皂甙Asp-Ⅳ的22-甲氧基化物(Ⅳ)。此外还分离到β-蜕皮甾酮(β-ecdysone,Ⅴ)。     

青钱柳酸A的结构研究

青钱柳酸Ａ的结构研究钟瑞建，舒任庚，倪小兰，徐昌瑞，黎莲娘（江西中医学院，南昌３３０００６；中国医学科学院，中国协和医科大学药物研究所，北京１０００５０）胡桃科植物青钱柳（ＣｙｃｌｏｃａｒｙａＰａｌｉａｒｕｓＩｌｊｉｎｓｋ为我国特产，民间用其叶制成保...     

A study on BMI among the Bhotia of Uttaranchal,India

ObjectiveTo investigate the nutritional status of the males and females in two subgroups of the Bhotia tribe (Marcha and Tolcha) inhabiting in three different altitudes in Uttaranchal, India.MethodsData were collected from the Tolcha and Marcha, two sub-groups of the Bhotia, inhabiting in Chamoli district of Uttaranchal. Bhotia adults of both sexes were considered. Field investigation was conducted in three ecological zones (high, middle and low altitude) of the district during April-August, in the years 2002-2004. Anthropometric measurements were obtained in accordance with the techniques recommended by Weiner and Lourie (1981). The variables like height, weight, waist circumference, hip circumference, waist-hip ratio and blood pressure were studied in relation to BMI.ResultsRelatively higher value of mean BMI is recorded among the females than that of the males, which is true for different altitudes, in both subgroups. The BMI also indicates an inverse relationship with altitude, except for the Tolcha males in high altitude. Lowest mean BMI is recorded in middle altitude among the Tolcha subgroup. Chronic energy deficient (CED) individuals are much more than twice the number among the males of both the subgroups inhabiting in different altitudes. Interestingly, the percentage of CED individuals increases with the altitude.ConclusionsRegression analysis indicates that height, weight, hip circumference and waist circumference are dependent on body mass index in the studied populations. Probable reason for poor nutrition status among the Tolcha and Marcha of high altitude might be due to the fact that the Tolcha and Marcha of high altitude consume lesser amount of proteins, fat, milk and milk products in general than their counterpart inhabit in lower and middle altitude.     

Novel PLA/Chitosan Composite Materials Prepared by SCF-CO2 Technique

Because of the incomparable merits （nontoxicity, non-remainder, fast transfer mass） of supercritical carbon dioxide fluid technique（SC-CO2）, it was used to developed a series of novel biodegradable tissue engineering scaffold materials in this research. The novel PLA/chitosan composite materials could be molded to different shapes, and the porosity of the materials were over 200 lam and connected. Chondrocyte cultivation, subcutaneous and intramuscular implantation were mainly discussed this paper. The results showed that the cells could well adhere, grow and multiplicate on the surface of the materials, which indicated good biocompatibility of the composite materials. The plantation test revealed that the PLA materials had already dismissed 2 month late in the body, while the composite materials could still keep certain strength and shape, and the most important things is the response of the tissue toward the implanted PLA/chitosan composite materials was mild and had far less inflammation than PLA materials. 8 to 16 weeks later, fiber membrane was stable; degradation of the materials was seen clear and tissue had already spread into it.     

Inhibition of leukemic HL60 cell growth by transferrin-gallium: effects on ribonucleotide reductase and demonstration of drug synergy with hydroxyurea [see comments]

Cellular requirements for iron during DNA synthesis are related to the increased activity of the iron-containing M2 subunit of ribonucleotide reductase, the enzyme responsible for the reduction of ribonucleotides to deoxyribonucleotides. We have previously shown that transferrin- gallium (Tf-Ga) inhibits cellular iron incorporation. In the present study, Tf-Ga-induced inhibition of HL60 cell growth and upregulation of Tf receptor density was reversed with hemin. Cells exposed to 2 mumol/L Tf-Ga for six hours or longer displayed a diminution in the electron spin resonance (ESR) spectroscopy signal of the tyrosyl radical of the M2 subunit of ribonucleotide reductase. The effect of Tf-Ga on the ESR signal was reversed by hemin. Tf-Ga decreased the incorporation of 14C- adenosine into DNA and decreased intracellular deoxyribonucleotide pools, with the maximum diminution seen in deoxyadenosine triphosphate (dATP) and deoxycytidine triphosphate (dCTP) pools. Exposure of cells to combinations of Tf-Ga and hydroxyurea (a known inhibitor of ribonucleotide reductase) resulted in a marked inhibition of cell growth that was consistent with drug synergy. Our studies suggest that Tf-Ga inhibits DNA synthesis through action on the M2 subunit of ribonucleotide reductase and that combinations of Ga and hydroxyurea should be further evaluated in in vivo tumor models.