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21.
Calcium antagonists (CA) exert an anti-atherosclerotic effect in cholesterol-fed rabbits through reduction of cholesterol accumulation in the arterial wall. Further studies in our Institute indicate that verapamil-like compounds and diltiazem stimulate receptor-mediated LDL uptake by human fibroblasts in culture, while nifedipine-like compounds and flunarizine are inactive. Verapamil and diltiazem stimulated LDL-receptor activity also in cells from a heterozygous FH patient, while they were inactive in a receptor defective homozygous FH patient. A basic group needs to be present on the CA molecule to modulate the LDL receptor expression. Preliminary data in our laboratory suggest that some CA can achieve concentrations in the aortic wall likely to exert effects on LDL receptors. This stimulatory activity may improve lipid metabolism in the arterial wall.Corresponding author 相似文献
22.
重症肌无力病人乙酰胆碱受体抗体的测定及临床意义 总被引:7,自引:0,他引:7
用ELISA(固相酶联免疫吸附)法测定172例MG病人血清乙酰胆碱受体抗体(AchRab),结果显著高于健康献血员组和非MG病人组。不同性别、病程及临床类型与AchRab无相关性,但41~50岁组的显著高于其他年龄组。67例类固醇激素治疗组、22例大剂量两种球蛋白治疗组、12例胸腺切除术组及3例MG危象病人24次血浆交换疗法(PE)组,治疗后伴随肌无力症状的好转,AchRab均显著低于治疗前。结果表明:AchRab测定为MG诊断提供了可靠的实验依据,为类固醇激素、大剂量丙种球蛋白、胸腺切除术和PE等治疗MG提供理论依据和疗效评定的实验指标,进一步证实了MG免疫学发病机理。 相似文献
23.
Avasimibe is a novel orally bioavailable ACAT inhibitor, currently under clinical development (phase III trials). It was safe when administered to rats, dogs, and humans. In vitro studies in human macrophages demonstrated that avasimibe reduces foam cell formation not only by enhancing free cholesterol efflux, but also by inhibiting the uptake of modified LDL. The concentration‐dependent reduction in cellular cholesteryl ester content in these cells was not accompanied by an increase in intracellular free cholesterol, which is in agreement with a good safety profile for avasimibe. In the liver, avasimibe caused a significant reduction in the secretion of apo B and apo B‐containing lipoproteins into plasma. Avasimibe induced cholesterol 7α‐hydroxylase and increased bile acid synthesis in cultured rat hepatocytes, and its administration to rats did not produce an increase in lithogenicity index of the bile. The hypolipidemic efficacy of the compound was demonstrated in cholesterol‐fed as well as in non‐cholesterol‐fed animals. In these models, plasma cholesterol levels were reduced, mainly due to the decrease in the non‐HDL cholesterol fraction. Clinical data are scarce, but in a study performed in 130 men and women with combined hyperlipidemia and hypoalphalipoproteinemia, avasimibe, 50–500 mg/day, significantly reduced plasma total triglyceride and VLDL‐cholesterol. Although total cholesterol, LDL‐cholesterol, and HDL‐cholesterol were unchanged, it must be stressed that animal data suggest that avasimibe may have direct antiatherosclerotic activity in addition to its cholesterol‐lowering effect. Avasimibe treatment can also contribute to increase plaque stability, as it reduces the accumulation of lipids in the arterial wall, inhibits macrophage infiltration into the media and reduces matrix metalloproteinase expression and activity. Moreover, avasimibe and statins have been shown to have synergistic effects, and the combination therapy may not only inhibit atherosclerotic lesion progression but also induce lesion regression, independently of changes in plasma cholesterol. 相似文献
24.
高分辨MRI对颈动脉粥样硬化斑块成分显示的病理对照研究 总被引:3,自引:0,他引:3
目的分析和评价高分辨MRI对颈动脉粥样硬化斑块不同成分的显示效果,为颈动脉内膜切除术术前判断斑块稳定性提供参考。方法对26例行颈动脉内膜切除术的颈动脉粥样硬化性狭窄患者术前高分辨MRI 4种不同序列的影像(T1WI、T2WI、PDWI和3D TOF)与斑块标本病理进行逐层对照,分析斑块内不同成分的MRI影像特点。结果获得斑块28块,切为238段,主要分布于颈总动脉和颈内动脉,以复杂斑块为特征的Ⅳ~Ⅴ型58段(24.37%)和Ⅵ型79段(33.19%)为主;斑块内纤维帽主要表现为TOF序列的带状低信号,钙化和纤维化组织分别表现为在各序列影像上的不规则低信号和不特定信号,脂质池和坏死核呈T1WI、PDWI和3D TOF序列的等至稍高信号,近期出血表现为T1WI、T2WI和PDWI序列的明显高信号。结论高分辨MRI不仅可以清晰显示动脉粥样硬化斑块,进行动脉管腔狭窄程度的测定,通过多序列影像联合分析还可以分辨斑块内部不同成分,有助于术前对斑块稳定性的判断。 相似文献
25.
Characterization and autoradiographic distribution of hemicholinium-3 high-affinity choline uptake sites in mammalian brain 总被引:4,自引:0,他引:4
R Quirion 《Synapse (New York, N.Y.)》1987,1(4):293-303
[3H]hemicholinium-3 (HC-3) binding characteristics have been investigated using membrane binding assays and in vitro receptor autoradiography. In rat brain membrane preparations, [3H]HC-3 binds with high affinity to an apparent single class of sites. [3H]HC-3 binding is Na+-dependent. The ligand selectivity pattern strongly suggests that [3H]HC-3 selectivity labels the high affinity choline uptake (HACU) in brain membranes (HC-3 greater than choline greater than carbamylcholine greater than acetylcholine). This hypothesis is also supported by quantitative autoradiographic data which demonstrate that the discrete distribution of [3H]HC-3 binding sites correlates very well with the known distribution of other cholinergic markers such as choline acetyltransferase (ChAT), acetylcholinesterase (AChE), HACU, and [3H]AH-5183 (blocker of the vesicular transport of acetylcholine). For example, high densities of labelling are observed for these different markers in the interpeduncular nucleus, anteroventral nucleus of the thalamus, striatum, basolateral nucleus of the amygdala, and an exquisite laminar distribution in the hippocampus. Similar autoradiographic distributions of [3H]HC-3 binding sites are observed in other mammalian species such as guinea pig and monkey. Finally, 7-day unilateral kainic acid lesions of the nucleus basalis magnocellularis (nbm) decrease cortical [3H]HC-3 binding and ChAT activity, although not to a similar extent. In summary, these results demonstrate that [3H]HC-3 is a selective ligand of the HACU in mammalian brain. Thus, it is now possible to characterize precisely various structural components of the cholinergic synapses using markers such as [3H]HC-3, ChAT, HACU, [3H]AH-5183, and selective muscarinic and nicotinic receptor radioligands. 相似文献
26.
Quisqualate lesions of rat NBM: Selective effects on working memory in a double Y-maze 总被引:8,自引:0,他引:8
S.L. Biggan R.J. Beninger J. Cockhill K. Jhamandas R.J.Boegman 《Brain research bulletin》1991,26(4):613-616
Some authors have reported that quisqualic acid lesions of the nucleus basalis magnocellularis (NBM), although producing large cortical cholinergic losses, have little effect on memory. The purpose of the present study was to investigate the effects of quisqualic acid lesions of the NBM on working and reference memory in a double Y-maze. Each trial started with placement into one of the two end arms of the first Y-maze, and the correct response was to go down the stem (reference memory). Access was then given to the second Y-maze, the correct response being conditional upon the side of the first Y-maze from which that trial had begun (working memory). Rats were trained to an 88% correct criterion and were then given either bilateral quisqualic acid (60 nM, 0.5 microliters) or sham lesions (0.9% saline, 0.5 microliters) of the NBM. One week postsurgery, rats were tested on the double Y-maze task with delays of 0, 5 or 30 seconds being introduced prior to both the working and reference memory choice. NBM lesions produced a 63.2 +/- 6.2% decrease of cortical choline acetyltransferase (ChAT) compared to unoperated controls. Delays affected only the working memory of the sham group. Rats with lesions showed a significant impairment of working memory at all delays, but no change in reference memory. Results indicate that quisqualic acid lesions of the NBM that produce significant reductions in cortical ChAT selectively impair working memory. 相似文献
27.
Helen E. Savaki Jean-Antoine Girault Umberto Spampinato Ngog-An Truong Jacques Glowinski Marie-Jo Besson 《Brain research bulletin》1986,16(2)
The release of newly synthesized 3H-dopamine (3H-DA) was measured in the rat striatum superfused, through a push-pull cannula, with a physiological medium enriched in 3H-tyrosine. The level of spontaneous 3H-DA release was dependent on the topographical localisation of the cannula in the striatum (anterior parts displayed higher levels than posterior ones) and on the anesthetic state (halothane anesthetized rats demonstrated higher levels than awake ones). Inhibition of DA inactivation processes by local application of benztropine (a DA reuptake inhibitor, 10−6 M) or by IV administration of pargyline (a MAO inhibitor, 100 mg/kg) enhanced the detectable outflow of 3H-DA from the striatum in both halothane anesthetized and awake rats. Local application of D-amphetamine (10−5 M) or acetylcholine (5 × 10−5 M) in the presence of eserine (5 × 10−5 M) evoked respectively a fivefold and a 30% increase in spontaneous 3H-DA release in halothane anesthetized rats. Inhibition of the firing of dopaminergic neurons by IV injection of gamma-hydroxybutyrate (400 mg/kg) produced a 30% decrease in striatal 3H-DA release. The present results demonstrate that the push-pull cannula method is suitable for the study of DA release in both the anesthetized and the awake rat. 相似文献
28.
29.
应用酶标法测定58例脑梗塞患者和56例健康对照者血清脂蛋白(a)[LP(a)]含量,并同时测定了其他脂代谢指标,对其中26例脑梗塞患者还测定了血浆纤维蛋白溶解(简称纤溶)指标。结果表明脑梗塞组存在显著的脂代谢和纤溶功能紊乱。LP(a)含量增高,与所测脂代谢、纤溶指标无显著相关,是脑梗塞发病独立的危险因素。 相似文献
30.
抗体阴性重症肌无力发病与凝集素之间关系研究 总被引:2,自引:0,他引:2
借助研究抗体阴性重症肌无力(MG)发病与凝集素之间的关系,以阐明其发病过程是否与凝集素有关。方法观察伴刀豆球蛋白A(ConA)和麦胚凝集素(Triticum)及其凝集素-糖复合物对TE671细胞表达的乙酰胆碱受体(AChR)功能的作用,以及对α-BuTx结合试验的影响。结果有两种凝集素对AChR功能均有抑制作用,抑制率(%)分别为54±14(n=11)和47±16(n=10),此作用可被3种糖抑制,抑制率(%)分别为:95±5(n=5)和84±8(n=5);69±6(n=4)和65±5(n=4);39±4(n=5)和57±6(n=5);ConA抑制α-BuTx结合试验,而Triticum则不能。结论Triticum和抗体阴性MG患者非IgG部分对AChR功能和α-BuTx结合试验的作用类同或一致,表明抗体阴性MG患者非IgG部分中的内源性Triticum样糖蛋白在其发病过程中起重要作用。 相似文献