新型齐墩果酸衍生物的合成及抗肿瘤活性

以齐墩果酸（OA）为先导化合物,经C28位羧基保护、C3位乙酰化、C12位氧化、C11位溴代后消除等7步连续反应合成了具有α,β-不饱和酮结构的OA衍生物;再以甘氨酸为连接基团,将不同取代的呋咱氮氧化物类一氧化氮供体与其偶联,获得新型OA衍生物,其结构经IR、MS及¹H NMR确证。采用MTT法测定目标物和部分中间体对4种人肿瘤细胞的增殖抑制活性。结果表明,所有目标物的抗肿瘤活性均显著优于OA,其中10a-10e和10i对人肝癌HepG2细胞的增殖抑制活性与阳性对照药2-氰基-3,12-二氧代齐墩果烷-1,9（11）-二烯-28-羧酸甲酯（CDDO-Me）相当。     

柱前衍生HPLC-UV同时测定人工牛黄中胆酸及猪去氧胆酸的含量

目的建立柱前衍生HPLC-UV同时测定人工牛黄中胆酸及猪去氧胆酸的含量。方法以2-萘基溴甲基酮为衍生试剂,三乙胺为催化剂,60℃水浴条件下对胆酸及猪去氧胆酸进行衍生,考察衍生试剂用量、催化剂用量及反应时间等对衍生产物的影响,确定衍生反应的条件,然后考察建立HPLC-UV分离检测方法对人工牛黄中胆酸及猪去氧胆酸含量进行测定。结果当衍生试剂的摩尔量与胆酸及猪去氧胆酸的摩尔总量的比大于30∶1,催化剂的摩尔量与两者的摩尔总量的比在5∶1~60∶1范围内,在60℃水浴条件下反应50 min时,胆酸及猪去氧胆酸的衍生物反应完全。方法学验证:胆酸在0.4~5.0μg范围内线性关系良好(r=0.999 5);猪去氧胆酸在0.12~1.5μg范围内线性关系良好(r=0.999 8)。胆酸的平均回收率(n=6)为100%,RSD为2.40%;猪去氧胆酸的平均回收率(n=6)为101%,RSD为1.33%。此批次人工牛黄样品中胆酸的含量为5.55%,猪去氧胆酸的含量为2.55%。结论本方法灵敏度高、准确可靠、稳定性和重复性好,可用于测定人工牛黄中胆酸及猪去氧胆酸的含量。     

3-溴甲基头孢烯酸二苯甲酯S-氧化物的合成

3-溴甲基头孢烯酸二苯甲酯S-氧化物是研制C_(10)-取代头孢菌素的关键中间体。本文对合成比中间体的方法进行了研究。实验采用青霉素扩环路线,以(牙卡)基青霉素为原料经由去乙酰氧头孢烯酸及其二苯甲酯S-氧化物转化成3-溴甲基头孢烯酸二苯甲酯S-氧化物,总收率为40—50％。     

齐墩果酸酯的合成研究（I）

齐墩果酸(Oleanolic acid, OLA)是一种齐墩果烷型五环三萜类化合物,具有保肝、抗炎、降血脂和降血糖等生理活性,是治疗慢性肝炎和黄疸型肝炎的常用药物,临床上应用的有齐墩果酸片等,但其治疗不够理想[1].为此,我们以齐墩果酸为先导化合物合成了一系列衍生物,目的是经药理研究筛选出活性更好的化合物.3-位为游离羟基的齐墩果酸酯类是合成中所需的重要中间体,因齐墩果酸的28位羧基酸性较弱,位阻较大,一般的酯化反应较难进行.     

五环三萜含氮衍生物的合成及糖原磷酸化酶抑制活性

以五环三萜化合物科罗索酸为原料,经乙酰化保护、酰胺化、水解等反应,合成了8个科罗索酸C-28位酰胺衍生物;以齐墩果酸为原料,经酰化、烷基化、催化氢化等反应合成了6个齐墩果酸C-3位含氮衍生物,所有目标化合物进行了糖原磷酸化酶抑制活性测试。结果表明:11个化合物表现出不同程度的抑酶活性,其中4个化合物活性强于其先导化合物,其中目标化合物6的糖原磷酸化酶抑制活性最强,IC50为11.2μmol/L。     

胆汁酸类药物的紫外检测HPLC测定法

采用1-溴乙酰基对硝基苯为衍生试剂,18-冠醚-6为催化剂,对胆汁酸进行衍生反应,然后用HPLC法进行分离。254nm紫外检测器检测,测定了合成药物熊去氧胆酸以及它的差向异构体鹅去氧胆酸的含量,选用胆酸为内标,色谱柱YWG C_(18) 10μm,5mm×150mm,流动相甲醇醇-水(81:19),流速1ml/min,熊去氧胆酸和鹅去氧胆酸的加样回收率分别为100.1%和99.7%,变异系数分别为0.9%和1.1%同时对人工牛黄中的胆酸,猪去氧胆酸,去氧酸和鹅去氧胆酸进行分离定性。     

噻吩酮,醛缩氨硫脲衍生物的合成

采用A,B两法合成2-乙酰噻吩缩氨硫脲、2-甲酰噻吩缩氨硫脲(Ⅴ)及3-取代-4-氧噻唑烷-2叉-(2′-乙酰噻吩)腙(Ⅵ)等化合物,计31个。A法:以肼基二硫代羧酸甲酯与乙酰噻吩或噻吩醛缩合,再与各种胺反应制得化合物Ⅴ。B法:N~4取代的氨基硫脲中间体,与乙酰噻吩或噻吩醛缩合得化合物Ⅴ,再与氯乙酸环合而成化合物Ⅵ。对上述化合物进行伯氏鼠疟的抑制性治疗作用和约氏鼠疟的病因性予防作用筛选,未发现有明显的抗疟活性。对其中13个化合物及两个中间体进行体外抑菌试验,中间体3-[1-(2-噻吩)甲叉]肼基二硫代酸甲酯(Ⅳ_2)对革兰氏阳性菌有较好的抑制作用,对革兰氏阴性菌仅有中度以上的敏感性。     

4-羟基-3-甲氧基苯甲醛木糖苷的合成

目的:香草醛(Vanlillin)作为一种重要的天然产物,具有镇静、抗惊厥、抗癫痫、治疗神经性头痛,抗菌等生物活性.通过分析了解香草醛的化学结构,改善香草醛中苯酚基易被氧化,易受空气影响的缺陷.方法:以天然D-木糖为原料经过乙酰化和溴代反应生成2,3,4-三- O -乙酰-a-D-溴代吡喃木糖.再与香草醛反应生成4-甲酰基-2-甲氧基-苯基-2,3,4-三-O-乙酰-β-D-吡喃木糖苷,通过熔点及薄层鉴定确定该化合物的结构.结论:此化合物提高了香草醛的稳定性和生物活性,且合成利于筛选更高抗菌活性的药物.     

木瓜齐墩果酸和熊果酸等三萜酸类薄层色谱分离鉴别

目的建立木瓜齐墩果酸、熊果酸等三萜酸薄层色谱分离鉴别方法。方法将点于硅胶G板上的样品点浸入1%碘-二氯甲烷溶液中预处理,以环己烷-丙酮-乙酸乙酯-甲酸(9∶2∶1∶0.2)为展开剂。结果木瓜中熊果酸、齐墩果酸以及3-O-乙酰熊果酸能够被很好地分离和检识。结论薄层色谱法简便、可靠,使木瓜鉴别更具客观性和专属性。     

黄花败酱的化学成分研究

目的 研究黄花败酱Patrinia scabiosaefolia的化学成分。方法 采用甲醇提取、溶剂萃取、硅胶柱色谱法、Sephadex LH-20凝胶柱色谱法、中压快速制备及半制备高效液相色谱等方法分离纯化;通过化学方法及核磁共振谱、质谱等光谱数据鉴定化合物结构。结果 分离得到14个化合物,分别鉴定为3-羟基-11-氧代齐墩果酸（1）、3, 11-二氧代齐墩果酸（2）、3-O-木糖-齐墩果酸-28-葡萄糖酯苷（3）、3-氧代-29-羟基齐墩果酸（4）、3β, 12α-二羟基-13β, 28-内酯齐墩果酸（5）、3-鼠李糖-(1→2)-木糖-齐墩果酸-28-葡萄糖酯苷（6）、愈创木-6(7)-烯-4, 10-二醇（7）、3α-乌苏酸（8）、豆甾醇（9）、麦角甾- 6, 22-二烯-3β, 5α, 8α-三醇（10）、齐墩果酸-3-O-β-D-吡喃木糖苷（11）、齐墩果酸-3-O-鼠李糖-(1→2)-木糖苷（12）、3-O-木糖- (1→3)-鼠李糖-(1→2)-阿拉伯糖-齐墩果酸-28-葡萄糖酯苷（13）、齐墩果酸-28-O-葡萄糖-(1→6)-葡萄糖酯苷（14）。结论 化合物1～8均为首次从本属植物中分离得到。     

Role of vitamin K2 in the development of hepatocellular carcinoma in women with viral cirrhosis of the liver

Context  Previous findings indicate that vitamin K₂ (menaquinone) may play a role in controlling cell growth. Objective  To determine whether vitamin K₂has preventive effects on the development of hepatocellular carcinoma in women with viral cirrhosis of the liver. Design, Setting, and Participants  Forty women diagnosed as having viral liver cirrhosis were admitted to a university hospital between 1996 and 1998 and were randomly assigned to the treatment or control group. The original goal of the trial was to assess the long-term effects of vitamin K₂ on bone loss in women with viral liver cirrhosis. However, study participants also satisfied criteria required for examination of the effects of such treatment on the development of hepatocellular carcinoma. Interventions  The treatment group received 45 mg/d of vitamin K₂ (n = 21). Participants in the treatment and control groups received symptomatic therapy to treat ascites, if necessary, and dietary advice. Main Outcome Measure  Cumulative proportion of patients with hepatocellular carcinoma. Results  Hepatocellular carcinoma was detected in 2 of the 21 women given vitamin K₂ and 9 of the 19 women in the control group. The cumulative proportion of patients with hepatocellular carcinoma was smaller in the treatment group (log-rank test, P = .02). On univariate analysis, the risk ratio for the development of hepatocellular carcinoma in the treatment group compared with the control group was 0.20 (95% confidence interval [CI], 0.04-0.91; P = .04). On multivariate analysis with adjustment for age, alanine aminotransferase activity, serum albumin, total bilirubin, platelet count, -fetoprotein, and history of treatment with interferon alfa, the risk ratio for the development of hepatocellular carcinoma in patients given vitamin K₂ was 0.13 (95% CI, 0.02-0.99; P = .05). Conclusion  There is a possible role for vitamin K₂ in the prevention of hepatocellular carcinoma in women with viral cirrhosis.      

肌苷衍生物的碱基核糖化研究

目的研究N1-核糖肌苷衍生物的合成反应。方法用丙叉保护肌苷2′,3′-OH,单甲氧基三苯甲基保护5′-OH,在碳酸钾、18-冠醚-6作用下与2,3,5-O-三苄基-1-溴代核糖反应。结果反应得到N1-核糖肌苷衍生物。结论用酰基做保护基易发生酰基重排反应,改用丙叉保护肌苷2′,3′-OH,再用单甲氧基三苯甲基保护5′-OH与2,3,5-O-三苄基-1-溴代核糖在碳酸钾18-冠醚-6作用下得到目的物N1-(2,3,5-O-三苄基-D-核糖)-2′,3′-O-异亚丙基-5′-O-单甲氧基三苯甲基肌苷。     

胆碱能抗炎通路对内毒素复合油酸致大鼠急性肺损伤的影响

目的研究胆碱能抗炎通路(cholinergic anti-inflammatory pathway,CAP)对内毒素复合油酸2次打击致大鼠急性肺损伤(acute lung injury,ALI)的影响及其可能的作用机制。方法 24只雄性Wistar大鼠,体质量250±20g。按数字表法将大鼠随机分为4组,每组6只。①对照组(control group,C组):腹腔注射生理盐水10 mL.kg-1;②急性肺损伤(ALI)组:腹腔注射1%内毒素(lipopolysaccharide,LPS)10 mg.kg-1,30 min后静脉注射油酸(oleic acid,OA)0.15 mL.kg-1;③电刺激(stimulation,ST)组:右颈迷走神经干连接刺激电极,以5 V、2 ms、1 Hz强度持续刺激神经10 min,腹腔注射1%LPS 10 mg.kg-1,再持续刺激神经10 min,20min后静脉注射OA 0.15 mL.kg-1;④他克林(tetrahydroaminoacridine,THA)组:静脉注射胆碱酯酶抑制剂THA 1.5 mg.kg-1,10min后行急性肺损伤操作。各组动物均于130 min后从颈总动脉采血1 mL行血气分析,处死动物采集标本,分别检测肺组织Toll-样受体-2(Toll-like receptor-2,TLR2)和TLR4 mRNA、核转录因子κB(nuclear factor kappa-B,NF-κB)p65、血清白介素-6(interleukin-6,IL-6)、肺组织髓过氧化物酶(mycloperoxidase,MPO)含量和肺组织湿质量-干质量比(wet weight/dry weight,W/D),HE染色观察左肺组织病理学改变。结果 ALI组与C组比较,pH和动脉氧分压(partial pressure of oxygen,PaO2)均显著下降,二氧化碳分压(partial pressure of carbon dioxide,PaCO2)显著升高;肺泡破坏严重,有大量组织液渗出;肺组织W/D及MPO活性均显著增高;肺组织NF-κB p65蛋白表达明显增强;血清IL-6浓度显著升高;与C组相比,其余3个实验组肺组织TLR2和TLR4mRNA表达均显著增加,组间比较差异无统计学意义;ST组和THA组与ALI组比较,pH和PaO2均显著升高,PaCO2显著下降;肺组织病理改变明显改善;肺组织W/D及MPO活性均显著降低;肺组织NF-κB p65蛋白表达及血清IL-6浓度显著下降。结论电刺激迷走神经或者静脉注射他克林可通过激活CAP,减轻LPS复合油酸2次打击致大鼠ALI时的炎性反应;其可能的机制是抑制NF-κB途径活化,在转录前水平发挥抗炎作用,但是不影响ALI时TLR2和TLR4mRNA的活化。     

HEK293细胞内源性电压门控钾离子通道电生理学特性研究

目的探讨人胚胎肾细胞(HEK293细胞)内源性电压门控钾通道的电生理特性,避免HEK293细胞上内源性离子通道对外源性离子通道表达时的干扰。方法利用全细胞膜片钳技术分析了HEK293细胞内源性电压门控钾通道的电生理特性。结果在HEK293细胞上去极化电压从-80 mV开始可触发1个外向电流。在+100 mV时电流为(422.78±68.87)pA,电流密度为(21.91±3.20)pA/pF。钾通道阻断剂四乙胺(tetraethylammonium,TEA)、4-氨基吡啶(4-aminopyri-dine,4-AP),在将细胞外液钾浓度由4 mmol/L提高到40 mmol/L时,对外向电流有影响。结论正常培养的HEK293细胞本身有内源性的钾通道。该外向电流可能包括了IK、IK1、IKur和Ito。     

Effect of homocysteine-lowering therapy with folic acid,vitamin B12, and vitamin B6 on clinical outcome after percutaneous coronary intervention: the Swiss Heart study: a randomized controlled trial

Context  Plasma homocysteine level has been recognized as an important cardiovascular risk factor that predicts adverse cardiac events in patients with established coronary atherosclerosis and influences restenosis rate after percutaneous coronary intervention. Objective  To evaluate the effect of homocysteine-lowering therapy on clinical outcome after percutaneous coronary intervention. Design, Setting, and Participants  Randomized, double-blind placebo-controlled trial involving 553 patients referred to the University Hospital in Bern, Switzerland, from May 1998 to April 1999 and enrolled after successful angioplasty of at least 1 significant coronary stenosis (50%). Intervention  Participants were randomly assigned to receive a combination of folic acid (1 mg/d), vitamin B₁₂ (cyanocobalamin, 400 µg/d), and vitamin B₆ (pyridoxine hydrochloride, 10 mg/d) (n = 272) or placebo (n = 281) for 6 months. Main Outcome Measure  Composite end point of major adverse events defined as death, nonfatal myocardial infarction, and need for repeat revascularization, evaluated at 6 months and 1 year. Results  After a mean (SD) follow-up of 11 (3) months, the composite end point was significantly lower at 1 year in patients treated with homocysteine-lowering therapy (15.4% vs 22.8%; relative risk [RR], 0.68; 95% confidence interval [CI], 0.48-0.96; P = .03), primarily due to a reduced rate of target lesion revascularization (9.9% vs 16.0%; RR, 0.62; 95% CI, 0.40-0.97; P = .03). A nonsignificant trend was seen toward fewer deaths (1.5% vs 2.8%; RR, 0.54; 95% CI, 0.16-1.70; P = .27) and nonfatal myocardial infarctions (2.6% vs 4.3%; RR, 0.60; 95% CI, 0.24-1.51; P = .27) with homocysteine-lowering therapy. These findings remained unchanged after adjustment for potential confounders. Conclusion  Homocysteine-lowering therapy with folic acid, vitamin B₁₂, and vitamin B₆ significantly decreases the incidence of major adverse events after percutaneous coronary intervention.      

Effect of folic acid and B vitamins on risk of cardiovascular events and total mortality among women at high risk for cardiovascular disease: a randomized trial

Christine M. Albert, MD, MPH; Nancy R. Cook, ScD; J. Michael Gaziano, MD, MPH; Elaine Zaharris, BA; Jean MacFadyen, BA; Eleanor Danielson, MIA; Julie E. Buring, ScD; JoAnn E. Manson, MD, DrPH

JAMA. 2008;299(17):2027-2036.

Context  Recent randomized trials among patients with preexisting cardiovascular disease (CVD) have failed to support benefits of B-vitamin supplementation on cardiovascular risk. Observational data suggest benefits may be greater among women, yet women have been underrepresented in published randomized trials.

Objective  To test whether a combination of folic acid, vitamin B₆, and vitamin B₁₂ lowers risk of CVD among high-risk women with and without CVD.

Design, Setting, and Participants  Within an ongoing randomized trial of antioxidant vitamins, 5442 women who were US health professionals aged 42 years or older, with either a history of CVD or 3 or more coronary risk factors, were enrolled in a randomized, double-blind, placebo-controlled trial to receive a combination pill containing folic acid, vitamin B₆, and vitamin B₁₂ or a matching placebo, and were treated for 7.3 years from April 1998 through July 2005.

Intervention  Daily intake of a combination pill of 2.5 mg of folic acid, 50 mg of vitamin B₆, and 1 mg of vitamin B₁₂.

Main Outcome Measures  A composite outcome of myocardial infarction, stroke, coronary revascularization, or CVD mortality.

Results  Compared with placebo, a total of 796 women experienced a confirmed CVD event (406 in the active group and 390 in the placebo group). Patients receiving active vitamin treatment had similar risk for the composite CVD primary end point (226.9/10 000 person-years vs 219.2/10 000 person-years for the active vs placebo group; relative risk [RR], 1.03; 95% confidence interval [CI], 0.90-1.19; P = .65), as well as for the secondary outcomes including myocardial infarction (34.5/10 000 person-years vs 39.5/10 000 person-years; RR, 0.87; 95% CI, 0.63-1.22; P = .42), stroke (41.9/10 000 person-years vs 36.8/10 000 person-years; RR, 1.14; 95% CI, 0.82-1.57; P = .44), and CVD mortality (50.3/10 000 person-years vs 49.6/10 000 person-years; RR, 1.01; 95% CI, 0.76-1.35; P = .93). In a blood substudy, geometric mean plasma homocysteine level was decreased by 18.5% (95% CI, 12.5%-24.1%; P < .001) in the active group (n = 150) over that observed in the placebo group (n = 150), for a difference of 2.27 µmol/L (95% CI, 1.54-2.96 µmol/L).

Conclusion  After 7.3 years of treatment and follow-up, a combination pill of folic acid, vitamin B₆, and vitamin B₁₂ did not reduce a combined end point of total cardiovascular events among high-risk women, despite significant homocysteine lowering.

Trial Registration  clinicaltrials.gov Identifier: NCT00000541

     

积雪草中积雪草酸的分离、纯化及其含量测定

目的分离纯化积雪草中积雪草酸,并建立高效液相色谱法(high-performance liquid chromatography,HPLC)测定积雪草酸的含量。方法超声提取积雪草中积雪草酸,将粗提物用石油醚-丙酮体系在硅胶柱上梯度洗脱,HPLC法测定积雪草酸的含量。色谱条件:采用Waters Symmetry C18色谱柱(4.6 mm×250 mm,5μm),流动相为乙腈-10 mmol.L-1乙酸铵溶液(38∶62,V/V),检测波长为210 nm,流速为1.0 mL.min-1,柱温25℃,进样体积为20μL。结果积雪草酸在浓度10～200 mg.L-1线性关系良好(R2=0.999 5),其日内、日间RSD均小于5.4%,回收率为100.5%。积雪草中积雪草酸含量为0.99 g.kg-1。经提取、分离、纯化得到积雪草酸白色粉末,纯度为79.0%。结论本实验所用分析方法简便、准确、重复性好,可用于积雪草酸的含量测定;所用提取分离及纯化积雪草酸的方法可使中药中积雪草酸得到有效富集。     

Respiration during snow burial using an artificial air pocket

Context  Asphyxia is the most common cause of death after avalanche burial. A device that allows a person to breathe air contained in snow by diverting expired carbon dioxide (CO₂) away from a 500-cm³ artificial inspiratory air pocket may improve chances of survival in avalanche burial. Objective  To determine the duration of adequate oxygenation and ventilation during burial in dense snow while breathing with vs without the artificial air pocket device. Design  Field study of physiologic respiratory measures during snow burial with and without the device from December 1998 to March 1999. Study burials were terminated at the subject's request, when oxygen saturation as measured by pulse oximetry (SpO₂) dropped to less than 84%, or after 60 minutes elapsed. Setting  Mountainous outdoor site at 2385 m elevation, with an average barometric pressure of 573 mm Hg. Participants  Six male and 2 female volunteers (mean age, 34.6 years; range, 28-39 years). Main Outcome Measures  Burial time, SpO₂, partial pressure of end-tidal CO₂ (ETCO₂), partial pressure of inspiratory CO₂(PICO₂), respiratory rate, and heart rate at baseline (in open atmosphere) and during snow burial while breathing with the device and without the device but with a 500-cm³ air pocket in the snow. Results  Mean burial time was 58 minutes (range, 45-60 minutes) with the device and 10 minutes (range, 5-14 minutes) without it (P=.001). A mean baseline SpO₂ of 96% (range, 90%-99%) decreased to 90% (range, 77%-96%) in those buried with the device (P=.01) and to 84% (range, 79%-92%) in the control burials (P=.02). Only 1 subject buried with the device, but 6 control subjects buried without the device, decreased SpO₂ to less than 88% (P=.005). A mean baseline ETCO₂ of 32 mm Hg (range, 27-38 mm Hg) increased to 45 mm Hg (range, 32-53 mm Hg) in the burials with the device (P=.02) and to 54 mm Hg (range, 44-63 mm Hg) in the control burials (P=.02). A mean baseline PICO₂ of 2 mm Hg (range, 0-3 mm Hg) increased to 32 mm Hg (range, 20-44 mm Hg) in the burials with the device (P=.01) and to 44 mm Hg (range, 37-50 mm Hg) in the control burials (P=.02). Respiratory and heart rates did not change in burials with the device but significantly increased in control burials. Conclusions  In our study, although hypercapnia developed, breathing with the device during snow burial considerably extended duration of adequate oxygenation compared with breathing with an air pocket in the snow. Further study will be needed to determine whether the device improves survival during avalanche burial.      

Effects of arotinoid acid on induction of apoptosis and differentiation and telomerase activity and cell cycle in the HL-60 cell line

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Distribution of and factors associated with serum homocysteine levels in children: Child and Adolescent Trial for Cardiovascular Health

Context  Although evidence suggests that homocysteine is a risk factor for cardiovascular disease in adults, little information exists on homocysteine levels in children. Objectives  To describe the distribution of serum homocysteine concentrations among children and to examine the association between homocysteine levels and several characteristics, including serum levels of folic acid and vitamins B₁₂ and B₆. Design  Cross-sectional analysis. Setting  School-based cohort from California, Louisiana, Minnesota, and Texas. Participants  A total of 3524 US schoolchildren, aged 13 and 14 years, from the Child and Adolescent Trial for Cardiovascular Health (completed in 1994). Measurement was conducted in 1997. Main Outcome Measure  Nonfasting serum total homocysteine concentration. Results  The distribution of homocysteine values ranged from 0.1 to 25.7 µmol/L (median, 4.9 µmol/L). Geometric mean homocysteine concentration was significantly higher in boys (5.22 µmol/L) than girls (4.84 µmol/L); blacks (5.51 µmol/L) than whites (4.96 µmol/L) or Hispanics (4.93 µmol/L); nonusers of multivitamins (5.09 µmol/L) than users (4.82 µmol/L); and smokers (5.19 µmol/L) than nonsmokers (5.00 µmol/L). Serum homocysteine was significantly inversely correlated with serum levels of folic acid (r=-0.36; P=.001), vitamin B₁₂ (r=-0.21; P=.001), and vitamin B₆ (r=-0.18; P=.001). Serum homocysteine was not significantly associated with serum lipid levels or family history of cardiovascular disease and was only weakly related to body mass index and systolic blood pressure. After multivariate adjustment, homocysteine remained independently associated with sex, race, serum folic acid and vitamin B₁₂ levels, and systolic blood pressure. Conclusions  The distribution of homocysteine levels in children is substantially lower than that observed for adults; however, a small percentage of children are still potentially at elevated risk for future cardiovascular disease. Serum folic acid may be an important determinant of homocysteine levels in children.