Receptor–receptor interactions: A novel concept in brain integration

A brief historical presentation of the hypothesis on receptor–receptor interactions as an important integrative mechanism taking place at plasma membrane level is given. Some concepts derived from this integrative mechanism especially the possible assemblage of receptors in receptor mosaics (high-order receptor oligomers) and their relevance for the molecular networks associated with the plasma membrane are discussed. In particular, the Rodbell's disaggregation theory for G-proteins is revisited in the frame of receptor mosaic model.     

2型DR患者同型半胱氨酸和胱抑素C水平的变化及相关性研究

目的:探讨同型半胱氨酸(Hcy)与胱抑素C(Cystatin C)及超敏C反应蛋白(hs-CRP)在2型糖尿病视网膜病变(DR)发病机制中的改变及其相关性。方法:选择经诊断为2型糖尿病患者无视网膜病变组45例;背景期DR组42例;增殖期DR组46例。同时选择40例健康正常人做对照组。Hcy,CysC采用酶联免疫分析法、hs-CRP采用颗粒增强免疫比浊法进行检测。双变量相关分析采用直线相关分析。结果:患者各组胱抑素C及同型半胱氨酸、超敏C反应蛋白含量明显高于对照组P<0.01,组间有非常显著差异P<0.01,且随着病程的进展升高明显P<0.01。Hcy与Cystatin C水平均有一定增长趋势,且两指标呈正相关(无视网膜病变组r=0.675,背景期DR组r=0.823,增殖期DR组r=0.756,P<0.01)。结论:2型糖尿病视网膜病变患者血浆胱抑素C、同型半胱氨酸、超敏C反应蛋白含量远高于正常对照,表明检测各指标在2型糖尿病视网膜病变的早期诊断、治疗等方面有很重要的临床意义,联合检测可推断糖尿病视网膜病变的进程,更全面的评价早期糖尿病视网膜病变,为临床早期干预血同型半胱氨酸及胱抑素C等提供理论基础。     

Dietary intake of S-(α-carboxybutyl)-dl-homocysteine induces hyperhomocysteinemia in rats

Betaine homocysteine S-methyltransferase (BHMT) catalyzes the transfer of a methyl group from betaine to homocysteine (Hcy), forming dimethylglycine and methionine. We previously showed that inhibiting BHMT in mice by intraperitoneal injection of S-(α-carboxybutyl)-dl-homocysteine (CBHcy) results in hyperhomocysteinemia. In the present study, CBHcy was fed to rats to determine whether it could be absorbed and cause hyperhomocysteinemia as observed in the intraperitoneal administration of the compound in mice. We hypothesized that dietary administered CBHcy will be absorbed and will result in the inhibition of BHMT and cause hyperhomocysteinemia. Rats were meal-fed every 8 hours an l-amino acid–defined diet either containing or devoid of CBHcy (5 mg per meal) for 3 days. The treatment decreased liver BHMT activity by 90% and had no effect on methionine synthase, methylenetetrahydrofolate reductase, phosphatidylethanolamine N-methyltransferase, and CTP:phosphocholine cytidylyltransferase activities. In contrast, cystathionine β-synthase activity and immunodetectable protein decreased (56% and 26%, respectively) and glycine N-methyltransferase activity increased (52%) in CBHcy-treated rats. Liver S-adenosylmethionine levels decreased by 25% in CBHcy-treated rats, and S-adenosylhomocysteine levels did not change. Furthermore, plasma choline decreased (22%) and plasma betaine increased (15-fold) in CBHcy-treated rats. The treatment had no effect on global DNA and CpG island methylation, liver histology, and plasma markers of liver damage. We conclude that CBHcy-mediated BHMT inhibition causes an elevation in total plasma Hcy that is not normalized by the folate-dependent conversion of Hcy to methionine. Furthermore, metabolic changes caused by BHMT inhibition affect cystathionine β-synthase and glycine N-methyltransferase activities, which further deteriorate plasma Hcy levels.     

Dl-3-n-butylphthalide can improve the cognitive function of patients with acute ischemic stroke: a prospective intervention study

Objectives: The present study investigated the effects of dl-3-n-butylphthalide on cognitive function of patients with acute ischemic stroke (AIS).

Methods: A total of 104 patients with AIS admitted between October 2012 and June 2013 were assigned to either the Treatment (standardized treatment plus dl-3-n-butylphthalide) or Control (standardized treatment alone) groups. Cognitive function was assessed by the Beijing version of the Montreal Cognitive Assessment (MoCA-BJ) and Mini-Mental State Examination (MMSE) before and 1 month after treatment, when high-sensitivity C-reactive protein (hs-CRP) and homocysteine (Hcy) were also detected. A multivariate logistic regression analysis was done for explore the independent risk factors for vascular dementia (VD).

Results: The proportion of cognitive impairment was significantly lower after treatment than before in both the Treatment (88% vs. 64%, P = 0.023) and Control (87% vs. 70%, P = 0.047) groups. Vascular dementia dropped from 30 to 10% in the Treatment (P = 0.035) and from 25.9 to 16.7% in the Control (P = 0.027) groups. Total cognitive improvement was more significant in the Treatment Group (P = 0.018); naming, memory, attention, and linguistic abilities were significantly improved (all P < 0.05). Serum Hcy and hs-CRP levels were significantly lower in the Treatment Group than in the Control Group 1 month after treatment (P < 0.05).

Discussion: Dl-3-n-butylphthalide could significantly improve the cognitive function of AIS patients 1 month after stroke. Hcy was involved in the incidence of VD 1 month after AIS. However, further studies are necessary because of differences between groups at baseline.     

冠心病伴心房颤动患者hs-CRP、Hcy及颈动脉粥样硬化与房颤发生的关系

目的：探讨冠心病伴心房颤动患者hs-CRP、Hcy及颈动脉粥样硬化与房颤发生的关系。方法：选取2013年11月-2015年6月我院收治的60例冠心病伴房颤患者为A组,60例冠心病伴窦性心律患者为B组,60例窦性心律非冠心病患者为对照组。对三组患者的hs-CRP、Hcy及颈动脉粥样硬化的状况进行比较分析。结果：A组患者的hs-CRP、Hcy、颈总动脉内膜中层厚度以及颈动脉粥样硬化指标明显高于B组;A组和B组患者的hs-CRP、Hcy、颈总动脉内膜中层厚度以及颈动脉粥样硬化指标均高于对照组,差异具有统计学意义(P<0.05)。除此之外,A组中永久性房颤患者其hs-CRP、Hcy、颈总动脉内膜中层厚度以及颈动脉粥样硬化指标明显高于持续性房颤患者及阵发性房颤患者,两组差异具有统计学意义(P<0.05)。结论：冠心病伴房颤患者具有氧化、炎症等反应,在检测下具有颈动脉粥样硬化的表现,除此之外,冠心病伴房颤患者hs-CRP、Hcy水平越高将会加重患者房颤的持续时间以及病情。     

恶性血液病患者的血浆同型半胱氨酸和血清叶酸水平的临床研究

目的 探讨血浆同型半胱氨酸(Hcy)和血清叶酸(FA)水平与恶性血液病患者的关系.方法 采用电化学发光法检测86名恶性血液病患者血浆中Hcy浓度、血浆叶酸、维生素B12的浓度.其中急性白血病63例,恶性淋巴瘤8例,多发性骨髓瘤8例;慢性粒细胞白血病慢性期(CML-CP)7例.并同时检查健康成人30名作为正常对照.结果 急性白血病、恶性淋巴瘤、多发性骨髓瘤、慢性白血病患者组中血浆Hcy水平显著高于健康对照组(P＜0.05),而FA水平明显降低(P＜0.05).结论 高同型半胱氨酸血症可能是恶性血液病患者的危险因素.     

稳心颗粒对冠心病合并血脂紊乱患者血清Cys-c和Hcy水平的影响及其临床意义

目的:观察稳心颗粒对冠心病合并血脂紊乱患者血清Cys-c和Hcy水平的影响,并探讨其临床指导意义。方法:选择本院心血管科2013年10月至2014年10月的120例冠心病合并血脂紊乱患者作为研究对象,采用随机数字法,随机分为2组,治疗组(n=60例)对照组(n=58例)。对照组采用西医常规基础治疗,治疗组在对照组治疗的基础上加用口服稳心颗粒治疗,9 g/次,冲服,3次/d,2组均治疗4周为1疗程,共治疗2个疗程后比较2组患者治疗前后血清Cys-c和Hcy水平变化及冠脉狭窄程度变化的差异。结果:经2个疗程治疗后,治疗组总有效率93.33%明显高于对照组的81.67%,差异具有统计学意义(P0.05);并且2组患者的血清Cys-c和Hcy水平亦均有不同程度所下降,而以治疗组下降更为显著,差异具有统计学意义(P0.05);此外2组患者的冠脉狭窄程度与治疗前比较,总体上也均有不同程度改善(P0.05),而治疗组的冠脉狭窄改善程度明显优于对照组(P0.05)试验过程中2组均未见到明显的不良反应。结论:稳心颗粒治疗冠心病合并血脂紊乱能够有效改善患者的冠脉狭窄程度,降低血清Cys-C和Hcy的水平,临床疗效高,不良反应发生率低,值得临床推广应用。     

Hyperhomocysteinemia and the presence of cardiovascular disease are associated with kynurenic acid levels and carotid atherosclerosis in patients undergoing continuous ambulatory peritoneal dialysis

Introduction

Hyperhomocysteinemia and the activation of kynurenine (KYN) pathway have been reported as the factors participated in atherosclerosis in uraemic patients. The objective of this study was to verify whether hyperhomocysteinemia may be involved in atherosclerotic cardiovascular disease (CVD) in patients undergoing continuous ambulatory peritoneal dialysis (CAPD).

Materials and methods

We determined the plasma concentrations of KYN, KYNA, KYNA/KYN ratio, homocysteine (Hcy) and intima-media thickness (IMT) - an early reflection of the systemic atherosclerosis in CAPD patients both with and without CVD and healthy controls.

Results

KYNA concentrations and KYNA/KYN ratio were about 3 times higher in the patients with hyperhomocysteinemia (Hcy > 15 μM) compared to those with normal Hcy levels (< 15 μM), and they were significantly lower in CVD[+] than in CVD[−] patients in these studied groups. The presence of CVD was associated with higher Hcy levels only in the patients with Hcy > 15 μM. The positive association was between Hcy and KYNA, KYNA/KYN ratio in all CAPD patients and in CVD[+] patients with hyperhomocysteinemia. IMT was positively associated with Hcy levels in patients with hyperhomocysteinemia, whereas there was no relationship between IMT and KYNA concentrations in the studied groups.

Conclusions

These results showed the association between hyperhomocysteinemia and carotid atherosclerosis as well as the possible role of hyperhomocysteinemia in the activation of KYNA production in CAPD patients. The elevated KYNA levels observed in patients with hyperhomocysteinemia seem to be protective against Hcy-mediated atherosclerosis in these patients.     

血清同型半胱氨酸水平与颈动脉粥样硬化的关系探讨

目的 探讨血清同型半胱氨酸水平(Hcy)与颈动脉粥样硬化程度的关系.方法 选择住院治疗的82例缺血性脑卒中患者,经彩色多普勒B超检查的结果分为颈动脉正常组、颈动脉内膜-中层增厚组、颈动脉粥样硬化斑块组,并测定血清同型半胱氨酸水平,进行组间比较.结果 颈动脉粥样硬化斑块组的血清同型半胱氨酸水平明显高于颈动脉正常组及颈动脉内膜-中层增厚(IMT)组,差异有统计学意义(P＜0.05);颈动脉内膜-中层增厚组与颈动脉正常组血清同型半胱氨酸水平比较,差异有统计学意义(P＜0.05).结论 血清同型半胱氨酸水平高低与颈动脉粥样硬化程度呈正相关,血清同型半胱氨酸水平(Hcy)越高,颈动脉粥样硬化斑块、狭窄越严重.     

影响冠心病病人同型半胱氨酸水平的主要非遗传因素分析

目的 分析影响冠心病人血浆同型半胱氨酸水平的主要非遗传因素.方法 164例住院冠心病患者,测定血浆同型半胱氨酸水平并分析其与全血叶酸、血浆维生素B12、血清雌二醇浓度以及冠心病传统危险因素之间的关系.结果 血浆同型半胱氨酸水平与叶酸、维生素B12水平呈负相关,男性血浆同型半胱氨酸浓度高于女性[（20.74±13.42）×10-6mol/L比（15.56±8.16） ×10-6mol/L,P〈0.05],吸烟者高于不吸烟者[（22.29±15.18）×10-6mol/L比（17.21±9.54） ×10-6mol/L,P〈0.05].结论 叶酸、维生素B12、性别和吸烟是影响冠心病患者血浆同型半胱氨酸水平的主要非遗传因素.