同型半胱氨酸与不同类型卒中的相关性研究

目的：探讨同型半胱氨酸（Hcy）与不同类型脑卒中的关系,并对高Hcy血症成因作初步分析。方法：测定225例缺血性脑卒中和40例出血性脑卒中患者以及85例同龄健康受试者的血浆Hcy水平以及叶酸、维生素B12的浓度,将缺血性卒中按照TOAST分型分为不同临床亚组--动脉粥样硬化性脑血栓形成组,腔隙性脑梗死组,心源性脑栓塞组以及其他或不明原因脑梗死组,并分别与健康组进行对照研究。结果：血浆同型半胱氨酸平均水平在动脉粥样硬化性脑梗死组患者为（16.19±4.35）μmol/L,腔隙性脑梗死患者为（16.89±6.41）μmol/L,心源性脑栓塞组为（18.23±4.83）μmol/L,其他或不明原因脑梗死患者为（17.31±2.56）μmol/L,脑出血组患者为（14.91±4.54）μmol/L,均高于对照组（7.20±7.91）μmol/L,P〈0.05;各缺血性卒中组间同型半胱氨酸水平差异无显著性（P〈0.05）;缺血性卒中组患者血浆同型半胱氨酸水平高于出血性卒中组（P〈0.05）。卒中各组叶酸和维生素B12浓度均显著低于对照组（P〈0.05）。结论：血浆同型半胱氨酸在不同类型卒中中均升高,高血浆Hcy水平可能是脑卒中的独立危险因素,叶酸和VitB12缺乏可能是导致高Hcy血症的重要原因。     

High-performance liquid chromatographic method for measuring total plasma homocysteine levels

We have modified a high-performance liquid chromatographic (HPLC) procedure based on SBD-F (ammonium-7-fluorobenzo-2-oxa-1,3-diazole-4-sulphonate) pre-column derivatization to obtain an assay that is useful for routine clinical total plasma homocysteine (tHcy) analysis. The introduction of easily handled sodium borohydride instead of the traditional tri-n-butylphosphine in dimethylformamide as a reductant and a 14-min run-time using basic isocratic HPLC equipment are the more notable advantages. The addition of mercaptopropionylglycine as an internal standard contributed to improvements in the reproducibility of the assay, yielding within- and between-run precisions of 1.9 and 4% (C.V.), respectively. Reference values for fasting tHcy were 7.65±2.3 and 8.9±2.4 μmol/l, while post-methionine load gave tHcy levels of 19.9±5.5 and 26.8±5.5 μmol/l, for women and men, respectively (n=40).     

急性脑梗死患者血浆同型半胱氨酸水平及其相关因素分析*

目的:探讨急性脑梗死患者血浆同型半胱氨酸水平及相关因素。方法:采用高效液相色谱法检测232例急性脑梗死患者血浆Hcy水平,并对其相关因素进行统计学分析。结果:急性脑梗死组患者血浆Hcy水平明显升高(P<0.05);并与叶酸及维生素B12水平显著相关。不同年龄段急性脑梗死患者血浆Hcy水平具有差异。并与颈动脉粥样硬化斑块相关联。结论:血浆Hcy水平增高是脑梗死的危险因素之一,并与患者年龄、血液中叶酸、维生素B12水平及脑梗死性质相关联。     

Evaluation of homocysteine,vitamin, and trace element levels in women with gallstones

ObjectiveIt was aimed to examine the changes in homocysteine, folic acid, and vitamin B12, which metabolize homocysteine from the body, and trace elements (zinc, copper, selenium, nickel) that affect the structure of tissues and epithelium in female patients with gallstone disease. Moreover, it was aimed to investigate the contribution of these selected parameters to the etiology of the disease and their usability in treatment according to the findings obtained.Materials and MethodsEighty patients, including 40 female patients (Group I) and 40 completely healthy female individuals (Group II) were included in this study. Serum homocysteine, vitamin B12, folate, zinc, copper, selenium, and nickel levels were evaluated. Electrochemiluminescence immunoassay was used in the analysis of vitamin B12, folic acid, and homocysteine levels, and the ICP-MS method was used in the analysis of trace element levels.ResultsHomocysteine levels in Group I were statistically significantly higher than in Group II. In terms of vitamin B12, zinc, and selenium, Group I levels were found to be statistically significantly lower than group II. There was no statistically significant difference between Group I levels and Group II in terms of copper, nickel, and folate.ConclusionIt was suggested that homocysteine, vitamin B12, zinc, and selenium levels should be determined in patients with gallstone disease and that vitamin B12, which is especially important in the excretion of homocysteine from the body, and zinc and selenium, which prevent the free radical formation and protect from its effects, should be added to the diets of these patients.     

血清Hcy、FA、VitB12水平及H.pylori感染与脑梗死的相关性研究

目的：探讨脑梗死（cerebral infarction,CI）患者血清同型半胱氨酸（homocysteine,Hcy）、叶酸（folate,FA）、维生素B12（Vitamin B12,VitBl2）水平及幽门螺杆菌（H_pylori）感染与脑梗死的关系,为预防和治疗脑梗死提供参考依据。方法：选择本科收治的132例脑梗死患者和同期81例健康对照者为研究对象,检测和比较其血清同型半胱氨酸（Hey）、叶酸（FA）、VitB12水平及HP-IgG抗体。结果：（1）脑梗死患者H．pylori的感染率为50．76％,显著高于健康对照组（35．80％）（X2=0．54,P〈0．05）;（2）脑梗死患者血清Hey[（20．02±8．84）μmol／L]和FA水平[（14．47±6．38）ng／mL）]与健康对照组[（12．36±4．97）μmol／L,（16．82±11．43）ng／mL）]比较,均具有显著差异（P〈0．01,P〈0．01）;而VitB12水平与健康对照组比较无统计学意义（P〉0．05）;（3）脑梗死患者中,HP-IgG阳性的患者Hey水平[（24．20±8．81）μmol／L]明显高于HP-IgG阴性的患者[（15．71±6．53）μmol／L]（P〈0．01）,血清FA水平[（14．59±7．54）ng／mL）]明显低于于HP-IgG阴性的患者[（14．43±4．98）ng／mL]（P〈0．05）,而两组之间VitBl2水平比较无明显差异（P〉0．05）;HP—IgG阳性的脑梗死患者Hey水平[（24．20±8．81）bLmol／L]与HP—IgG阳性的健康对照组[（13．25±5．24）μmol／L]相比,差异显著（P〈0．05）,FA,VitB12水平低于健康对照组,但并无显著差异（P〉0．05）.结论：脑梗死患者H．pylori的感染率高于健康人群;H．pylori感染可能影响脑梗死患者Hey的代谢,导致Hey水平升高,促进了脑梗死的发生和发展。     

Homocysteine concentrations in a German cohort of 500 individuals: Reference ranges and determinants of plasma levels in healthy children and their parents

Summary. Elevated plasma homocysteine is a risk factor for cardiovascular disease and a sensitive marker of inadequate vitamin B12 and folate status. We studied 257 pupils (120 boys, 137 girls, aged 6–17 years) and their parents (88 males, 172 females, aged 26–50 years). Our measurements were part of a national Bavarian health and nutrition examination survey evaluating cardiovascular risk factors. A mild hyperhomocysteinemia (Hcys >15 μmol/l) occurred in 7% of the adults, but in none of the children. Men had significantly higher Hcys levels than women (p < 0.0001), boys and girls had comparable concentrations. For adults and children, Hcys correlated inversely with vitamin B12 and folate and positively with the lean body mass and creatinine in serum, but not with cystatin C. Genetic and nutritional factors are determinants of Hcys metabolism. The correlation of Hcys and serum creatinine is dependent on the metabolic link between Hcys production and creatine synthesis. Received July 4, 1999 Accepted May 22, 2000     

Progressive DNA and RNA damage from oxidation after aneurysmal subarachnoid haemorrhage in humans

Free radical toxicity is considered as a key mechanism in the neuronal damage occurring after aneurysmal subarachnoid haemorrhage (SAH). We measured markers of DNA and RNA damage from oxidation (8-oxodG and 8-oxoGuo, respectively) in cerebrospinal fluid from 45 patients with SAH on day 1–14 after ictus and 45 age-matched healthy control subjects. At baseline, both markers were significantly increased in patients compared to controls (p values?20-fold above control levels) from day 5–14. None of the markers predicted the occurrence of vasospasms or mortality, although there was a trend that the 8-oxoGuo marker was more strongly associated with mortality than the 8-oxodG marker. We conclude that SAH leads to a massive increase in damage to nucleic acids from oxidative stress, which is likely to play a role in neuronal dysfunction and death. As only patients in need of a ventriculostomy catheter were included in the study, the findings cannot necessarily be extrapolated to all patients with SAH.     

Effect of nickel on red blood cell parameters and on serum vitamin B12, folate and homocysteine concentrations during pregnancy with and without anemia

BackgroundResearch to date suggests that nickel affects not only the metabolism of vitamin B12 but also folates and thus may affect hematopoiesis processes.ObjectiveThe aim of the study was to examine the relationship of nickel (Ni) status to red blood cell (RBC) parameters and serum vitamin B12, folate and homocysteine concentrations in the course of normal pregnancy and in pregnant women with anemia.MethodsThe study included fifty-three pregnant women recruited to the study from the Lower Silesia region of Poland, 17 % of whom developed anemia. Nickel concentration was determined in urine, whole blood and food samples by atomic absorption spectrometry. At the same time as the food and urine samples were taken, blood was also collected for the determination of RBC parameters and serum vitamin B12, homocysteine and folate concentrations.ResultsThe median reported Ni intake, and the urinary and whole blood nickel contents for the studied pregnant women for the first trimester were respectively – 162.46 μg/day, 3.98 μg/L and 3.32 μg/L; for the second trimester – 110.48 μg/day, 6.86 μg/L and 1.04 μg/L; and for the third trimester – 132.20 μg/day, 3.41 μg/L and 0.70 μg/L. With regard to Ni concentration in whole blood (p = 0.0204) and in urine (p = 0.0003), the differences in the values for individual trimesters were statistically significant. The whole blood Ni level was significantly higher (9.28 vs 3.62 μg/L, p = 0.0114), while the concentration of homosysteine was significantly lower (4.09 vs 5.04 μmol/L, p = 0.0165) in pregnant women with anemia compared to those without anemia. The whole blood Ni concentration was negatively correlated with almost all RBC parameters in non-anemic pregnant women.ConclusionsNi status changes with the development of normal pregnancy, and in the case of anemia, an increase in Ni concentration in whole blood is observed. The demonstrated correlations between the Ni status in pregnant women and RBC parameters as well as serum vitamin B12 and folate concentrations suggest that nickel is associated with the methionine–folate cycle, iron homeostasis and bacterial synthesis of vitamin B12 in humans.     

Source of Methyl Groups in Brain and Nerve Tissue in the Rat

Previous studies that demonstrated that mouse brain accumulated significantly more radioactivity from subcutaneously administered 5-methyltetrahydrofolate labelled in the methyl group compared to the label in the folate moiety are open to two interpretations. The methyl group could have been transferred to another compound (probably methionine) prior to its transport into the brain. Alternatively, if plasma 5-methyltetrahydrofolate per se is significantly involved in the provision of methyl groups to brain and nerve tissue it would be expected that the folate moiety would be returned to the plasma to complete the cycle and thus would appear not to have been taken up. In this article, using competition experiments that exploit the differences in the mechanism of transport of methionine and 5-methyltetrahydrofolate into brain and nerve, evidence is presented that in the rat the methyl group of 5-methyltetrahydrofolate is transported after its conversion to methionine.     

同型半胱氨酸与神经管畸形的相关病因学研究进展

神经管畸形(neural tube defects,NTDs)是一种最常见的严重中枢神经系统先天性畸形,在世界各地均有发生。它是造成流产、死产的主要原因之一,即便胎儿存活,也严重影响患儿的生长发育和生活质量,同时给家庭和社会带来沉重的精神压力和经济负担。神经管畸形的发生绝大多数是由遗传因素与环境因素相互作用的结果,若孕妇在孕早期缺乏叶酸、高热、接触射线、服用药物、感染或发生妊娠期糖尿病等条件下,结合遗传因素作用,均有可能导致神经管畸形的发生,但其目前其的确切病因及其发病机制仍有待深入研究。大量研究表明,在孕妇血清中低叶酸、低维生素B12水平及高血浆同型半胱氨酸(Hcy)水平,都与NTDs的发生密切相关。本文主要围绕同型半胱氨酸的代谢,从分子水平和基因水平对与神经管畸形相关的各因素做一综述。     

The effect of homocysteine thiolactone and its alpha methylated derivative on bone matrix in the mouse

Summary Homocysteine (HC) is a radiation protector but toxic to bone. Its derivative homocysteine thiolactone (HCTL) and the alpha-alkylated analogue (A-methyl-HCTL) was fed to mice for a period of six weeks in a daily dose of 50 mg/kg body weight. Parameters for bone matrix as collagen content, acid solubility of bone collagen, urinary bone collagen cross links (pyridinolines) and urinary acid glycosaminoglycans were determined. Urinary acid glycosaminoglycans were significantly reduced in the HCTL treated group but not in the alpha-methyl-homocysteine thiolactone (A-methyl-HCTL) group (controls: 45 ± 7 mg/mmol creatinine, homocysteine thiolactone 38 ± 5 mg/mmol creatinine, A-methyl HCTL 45 ± 6 mg/mmol creatinine).No differences were found for the parameters of bone collagen between the groups. The potent radiation protecting methylated derivative therefore did not change bone matrix and should be a candidate for further toxicological studies.     

Homocysteine in the context of cobalamin metabolism and deficiency states

It is becoming increasingly clear that serum vitamin B12 (cobalamin) concentration is a dubious indicator of functional B12 status and, in contrast to long-standing convention, correlates poorly with haematological indices. This, in turn, has led to poorly defined reference intervals for serum B12. Patients presenting with neurological disturbance due to B12 deficiency are at risk of not being diagnosed if total reliance is placed on serum B12 levels and haematological parameters. Plasma homocysteine remethylation is uniquely placed at the metabolic end-point of B12 metabolism such that plasma total homocysteine is proving to be a sensitive marker of functional B12 status. Studies also show that plasma homocysteine correlates better with holotranscobalamin than serum B12. It is suggested that clinicians should cease to be guided by surrogate haematological markers when more specific tests of B12 deficiency, such as holotranscobalamin and total homocysteine, exist. These tests demand greater prevalence in routine diagnostic use.     

Homocysteine, vitamins B6, B12, folate, and risk of coronary artery disease in patients undergoing diagnostic coronary angiography

Summary. Homocysteine and vitamins B were correlated with coronary artery disease in patients undergoing diagnostic coronary angiography. 160 patients having ≧1 stenosis (G1), 55 patients having normal coronary arteries (G2) and 171 healthy volunteers (G3) were prospectively recruited. Homocysteine levels were significantly higher in patients, particulary in those with normal coronary angiograms, than in healthy subjects (13.8 ± 6.3 μmol/L in G1 (p < 0.0001) and 15.2 ± 8.8 μmol/L in G2 (p < 0.0001) versus 10.1 ± 3.1 μmol/L in G3). Homocysteine levels were not related to the extent of coronary artery disease. In patients with normal angiogram, vitamin B12 and folate levels were significantly higher compared with the other groups (p < 0.05 and p < 0.001, respectively) showing that vitamin B deficiency was not involved in the hyperhomocysteinemia. In conclusion, homocysteine and vitamins B levels do not contribute to discriminate for the presence of coronary artery disease in patients undergoing diagnostic coronary angiography. Homocysteine levels, however, were higher in patients referred for coronary angiography than in healthy controls. Received November 7, 1998, Accepted February 20, 1999     

Methionine Recycling in Brain: A Role for Folates and Vitamin B-12

Abstract: The recycling of methionine via homocysteine was measured in vivo in brain. After constant intravenous infusions (5 h) of both [³H-methyl] methionine and [³⁵S]methionine into rats, the ratios of [³H-methyl]methionine to [³⁵S]methionine in liver, brain and plasma were determined, Similar experiments were performed in rabbits, except that the [³H-methyl]- and [³S]methionine were injected intraventricularly. If the methyl group of methionine was removed with the formation of homocysteine and then replaced by another (unlabeled) methyl group, the specific activity of the [³H-methyl]methionine would decrease more than that of [³⁵S]methionine; i.e., the ratio of [³H-methyl]- to [³⁵S]methionine in the tissue would decline. The results showed that the ratios of [³H-methyl]- to [³⁵S]methionine in liver and brain were less than the same ratio in plasma in the rats. The comparable ratios in the brain and CSF of rabbits were less than the ratio in the injectate. Since brain contains only one enzyme capable of remethylating homocysteine to methionine, the vitamin B-12–dependent methyltetrahydrofolate-homocysteine methyltransferase (EC 2.1.1.13), our results for methionine recycling via homocysteine in brain strongly support the activity of this enzyme in brain in vivo.     

Increased postprandial homocysteinemia in a group of depressed patients

Summary Elevated tissue and serum concentrations of homocysteine (HCY) are associated with neuropsychiatric disorders as well as with premature occlusive vascular disease, as seen in homocystinuria. In order to study dietary-related modifications in plasma HCY, total HCY was assayed in the fasted state and 2 hr after meals in 12 depressed female patients aged 54 to 81 yr and in 12 female controls aged 50 to 85 yr. Fasting HCY was also studied in 4 patients with dementia. Postprandial HCY varied only slightly in the controls compared with their fasting values, whereas a significant increase was noted in the depressives. To study the influence of normal and low protein diets on this abnormality, fasting and postprandial HCY were investigated in 4 of the depressives after one week of a normal diet, after a week on a diet without meat, fish or eggs, and then again after return to a normal diet for one week. Persistence of the abnormal increase in postprandial HCY in 2 of these 4 patients while on the low-protein diet may have been due to an inherited defect in HCY metabolism. Folate deficiency can also cause hyperhomocysteinemia, and as folate supplements constantly lower HCY concentrations, nutritional counseling and folate therapy might prove helpful in the treatment of depression.     

血清Hcy，叶酸和维生素B12在胃癌及其癌前疾病中的作用

目的:探讨血清同型半胱氨酸(Hcy)、叶酸以及维生素B12在胃癌及癌前疾病中的水平及临床意义。方法:收集2014年1月至2016年8月我院收治的100例胃癌患者(胃癌组),及100例胃良性病变患者包括41例胃炎、34例胃溃疡、25例胃息肉(癌前病变组),并于同期随机选择200例健康体检者为对照组,采用循环酶法测定三组的血清Hcy,电化学发光免疫分析法测定叶酸及维生素B12水平,并分析各指标与胃癌临床病理特征的关系。结果:胃癌组、癌前病变组血清Hcy水平均高于对照组,叶酸及维生素B12水平均低于对照组,并且胃癌组血清Hcy水平高于癌前病变组,叶酸及维生素B12水平低于癌前病变组,差异有统计学意义(P0.05)。Ⅲ+Ⅳ期胃癌患者Hcy水平高于Ⅰ+Ⅱ期,进展期患者Hcy水平高于早期,有淋巴结转移患者Hcy水平高于无转移者,差异有统计学意义(P0.05);Hcy表达与性别、年龄、病变位置以及分化程度无关,差异无统计学意义(P0.05)。叶酸、维生素B12的表达在胃癌患者中与各临床病理特征(性别、年龄、TNM分期、肿瘤浸润深度、病变位置、有无淋巴结转移、分化程度)无明显关系,差异无统计学意义(P0.05)。结论:血清Hcy在胃癌患者中呈高水平表达,而叶酸及维生素B12呈低水平表达,联合检测三种指标有助于早期区分胃癌及癌前病变,同时血清Hcy还可能参与了胃癌的发生发展过程。Hcy、叶酸及维生素B12可作为早期鉴别诊断胃癌及其癌前病变的重要指标。     

Plasma total homocysteine level and methylenetetrahydrofolate reductase 677C>T genetic polymorphism in Japanese patients with rheumatoid arthritis

Hyperhomocysteinemia is a known risk factor of cardiovascular disease. Homocysteine has been also linked to inflammation in rheumatoid arthritis (RA). In this study, we investigated the relationship between plasma homocysteine levels and single nucleotide polymorphism (SNP) of the gene coding for methylenetetrahydrofolate reductase (MTHFR), an enzyme involved in the biosynthesis of homocysteine, and the correlation between the plasma homocysteine levels and generally used inflammatory markers (C-reactive protein, erythrocyte sedimentation rate and matrix metalloproteinase-3) in 96 Japanese patients with RA. Plasma homocysteine levels in patients with the MTHFR 677TT genotype were significantly higher than in those with the 677CC genotype (p < 0.05). In addition, plasma homocysteine levels were increased along with the elevation of general inflammatory markers. Therefore, we conclude that homocysteine might affect the inflammatory status of patients, and the MTHFR 677C>T SNP could be a predictive factor of hyperhomocysteinemia in patients with RA.     

The vascular protective role of oestradiol: a focus on postmenopausal oestradiol deficiency and aneurysmal subarachnoid haemorrhage

The steroid hormone, oestradiol, has pleiotropic functions. The protective effects of oestradiol are attributed to its anti‐inflammatory, antioxidant, anti‐atherogenic, anti‐apoptotic, vasodilatory activities and regulation of micro RNA. Oestradiol upregulates endothelial nitric oxide synthase gene expression and increases the production of nitric oxide, an important vasodilator. It suppresses the renin–angiotensin system and monitors haemodynamic stress. The hormone maintains the integrity of blood vessels by reducing oxidative stress while upregulating the expression of antioxidant enzymes and prevents vascular inflammation by regulating pro‐ and anti‐inflammatory cytokines. Aneurysmal subarachnoid haemorrhage (aSAH) occurring as a consequence of the rupture of an intracranial aneurysm is a devastating cerebrovascular event, representing 5–7% of all strokes. Postmenopausal women are more susceptible to aSAH compared to men in the same age group. This gender disparity has been attributed to reduced levels of the vascular protective hormone oestradiol following menopause. This review is focused on the protective role of oestradiol on vasculature and how the drop in oestradiol levels after menopause dramatically increases the incidence of aSAH in women. During menopause, oestradiol deficiency may affect vascular integrity causing dysregulation of vascular homeostasis by affecting the renin–angiotensin–aldosterone system (RAAS) and inflammatory and apoptotic cascades, resulting in the weakening of the cerebral arterial wall and potentially to development of an aneurysm and its rupture. In view of the role of oestradiol in maintaining vascular integrity, treatments involving hormone replacement could be a promising approach in postmenopausal women who are at risk of developing or rupturing an intracranial aneurysm.