溃疡性结肠炎患者血浆同型半胱氨酸和叶酸及维生素B12的检测水平及其临床意义

目的探讨溃疡性结肠炎（UC）患者中血浆同型半胱氨酸（Hcy）、叶酸（FA）和维生素B12（VitB12）水平的改变及其临床意义。方法采用高效液相荧光检测法（HPLC—FD）检测112例UC患者和110名健康对照人群血浆Hcy水平．应用ELISA方法检测76例UC患者和12名健康对照人群血浆FA和VitB12水平。结果UC患者中血浆Hcy水平为（11．27±7．26）μmol／L,明显高于对照组的（8．19±4．81）μmol／L（P〈0．01）;UC患者中血浆Hcy水平与UC病情分度、病变范围及病程均无关（P〉0．05）。UC患者中血浆FA和VitB12水平分别为（7．64±1．95）nmol／L和（108．64±32．22）pmol／L,明显低于对照组[（9．14±1．23）nmol／L和（112．64±33．33）pmol／L,均P〈0．01]。高Hcy组患者血浆FA和VitB12水平显著低于低Hcy组（P〈0．05）。UC患者中血浆FA水平与UC病程呈负相关（P〈0．01）;而VitB12水平则与病程无相关性（P〉0．221）。结论UC患者血浆Hcy水平升高,可能与FA和VitB12水平下降有关。     

叶酸及维生素 B12联合应用对老年慢性肾衰血透患者 Hcy 的影响

目的观察外源性补充叶酸及维生素 B12对老年慢性肾衰血透患者血浆同型半胱氨酸（ Hcy）水平的影响。方法选取本院肾内科2012年10月～2014年10月收治的老年慢性肾衰血透患者,随机分为HD治疗组与对照组（每组48例）。 HD治疗组给予叶酸及维生素 B12治疗,治疗前及治疗8周后于早晨空腹采集肘静脉血液分别检测叶酸、维生素B12及同型半胱氨酸（ Hcy）水平;HD对照组不给予上述药物治疗,亦于入组时及8周后同上检测血浆叶酸、维生素B12及同型半胱氨酸（ Hcy）水平。同时选取48例健康人群作为健康对照组。比较三组检测结果及治疗组治疗前后各指标水平的变化。结果 HD治疗组及HD对照组入组时的血浆Hcy水平明显高于健康对照组,差异具有统计学意义（ P ＜0．05）,叶酸及维生素B12水平三组比较差异无统计学意义（ P ＞0．05）;HD治疗组患者治疗后的血浆 Hcy水平明显低于治疗前,且叶酸及维生素B12水平高于治疗前,差异具有统计学意义（ P ＜0．05）。结论老年慢性肾衰血透患者均存在较高血浆Hcy水平,患者服用叶酸以及维生素 B12可降低血浆 Hcy水平,可能减少心脑血管并发症发生,提高患者生活质量,值得临床应用推广。     

血浆同型半胱氨酸对糖尿病肾损伤的影响

目的观察血浆同型半胱氨酸水平与糖尿病肾脏病大鼠肾损伤的关系及替米沙坦对其影响。方法用链佐菌素（STZ）诱导糖尿病大鼠模型,成模18只后随机分为替米沙坦治疗组（A组）和实验对照组（B组）,每组各9只;另设空白对照组（C组）10只。于12周末收集24h尿,测定尿白蛋白排泄率（UAER）,并处死大鼠,心脏采血,ELISA法测血浆同型半胱氨酸（Hcy）水平,生化分析仪测血糖、血肌酐等生化指标。取肾脏称重,免疫组化法测。肾组织中纤溶酶原激活物抑制物-1（PAI-1）的表达水平。结果①与C组相比,B组肾肥大指数（肾质量／体质量）、UAER显著增加（P〈0．05）,血浆Hcy浓度明显升高（P〈0．01）,肾组织表达PAI-1明显增强（P〈0．05）。②与B组相比,A组血浆Hcy水平明显下降（P〈0．05）,肾组织表达PAI-1显著减少（P〈0．01）,肾肥大指数、UAER显著降低（P〈0．01,P％0．05）。③相关性分析显示,血浆Hcy浓度与肾组织表达PAI-1水平呈显著正相关（r=0．641,P〈0．01）,与UAER呈显著正相关（r=0．684,P〈0．01）。结论血浆Hcy参与糖尿病肾损伤的发生、发展,其机制可能与其引起纤溶系统失衡等因素有关;替米沙坦可通过减少PAI-1表达水平而降低血浆Hcy水平,恢复纤溶系统平衡,降低蛋白尿,保护肾功能。     

服用复合维生素和单一叶酸片达到红细胞叶酸阈值浓度的比较研究

目的观察服用含0.8mg叶酸的复合维生素或单一叶酸片(0.4mg叶酸)达到预防神经管畸形红细胞叶酸阈值浓度(906nmol/L)的时间和人数。方法采用单中心、随机对照的临床试验方法,将纳入的研究对象随机分为复合组(21例)和单一组(17例)。建议所有受试者维持原来的生活习惯。复合组给予含0.8mg叶酸的复合维生素片口服,单一组给予0.4mg单一叶酸片口服,两组用法及疗程相同。比较两组对象用药前、用药2周、4周、8周和12周时的血清叶酸、红细胞叶酸、血清同型半胱氨酸(Hcy)和血清维生素B12(VB12)水平。结果两组患者一般资料比较无显著性差异(P0.05)。复合组与单一组在用药4周时红细胞叶酸浓度比较有显著性差异(P0.05),复合组达到预防神经管畸形的红细胞叶酸阈值浓度(906nmol/L)者显著多于单一组(95.2%vs.58.8%,P0.01)。服药2周和8周时,两组达到红细胞叶酸阈值浓度者比较无显著性差异(P0.05)。复合组服药后血清VB12水平显著升高(P0.05),单一组各时间点VB12水平则无显著变化(P0.05)。两组均可使血清Hcy水平降低,复合组服药2周后血清Hcy水平较服药前下降,而单一组服药8周后才开始下降(P0.05)。结论服用复合维生素片能够更快地达到预防神经管畸形的红细胞叶酸阈值浓度,降低Hcy水平,同时增加血清VB12水平,有效预防出生缺陷。     

慢性肾脏病患者血浆同型半胱氨酸水平与左心室肥大的关系

目的探讨早期慢性肾脏病（CKD）血浆同型半胱氨酸（Hcy）水平及其与左心室肥大（LVH）的关系。方法64例早期CKD患者分为3组,即A组[eGFR≥90ml·min^-1·（1．73m^2）^-1]31例;B组[eGFR60～89ml·min^-1·（1．73m^2）^-1]22例;C组[eGFR30～60ml·min^-1（1．73m^2）^-1]11例。另设同期健康体检者25例为对照组（N组）。采用荧光偏振免疫分析法测定血浆Hcy浓度,心脏超声检测左室舒张末期内径（LVDd）、室间隔厚度（IVST）和左室后壁厚度（LVPWT）、左心室心肌质量指数（LVMI）。结果①A组血浆Hcy与N组比较无统计学差异（P〉0．05）;B组和C组血浆Hcy显著高于A组和N组（P〈0．01）;C组血浆Hcy显著高于B组（P〈0．01）。CKD组高Hcy（〉12μmol／L）比例为39．06％,是N组的3．26倍。②A组、B组和C组各期左室质量指数（LV—MI）、左室舒张末期内径（LVDd）、室间隔厚度（IVST）、左室后壁厚度（LVPWT）均较N组显著增加。③血浆Hcy与LVPWT显著正相关（r=0．400,P=0．000）,与LVMI、LVDd、IVST无相关性。结论早期CKD即出现高Hcy血症,随肾功能进展而加重;血浆Hcy与早期CKD的左心室肥厚有关。     

同型半胱氨酸、超敏C反应蛋白、低密度脂蛋白胆固醇、D-二聚体与脑梗死的关系

目的：探讨血清同型半胱氨酸（Hcy）、血脂、超敏c反应蛋白（hs—CRP）、凝血功能、D-二聚体的变化与脑梗死的关系。方法：收集2012年3月-2013年2月于我院住院治疗的急性脑梗死患者172例为观察组,并根据病灶大小分为大梗死组、小梗死组和腔隙性脑梗死组。分别对3组患者入院后次日晨测定血清Hcy、血脂、hs—CRP、凝血功能、D-二聚体。100例健康体检者作为正常对照。结果：脑梗死患者血清Hcy、血脂、hs—CRP、纤维蛋白原（Fib）、D-二聚体水平均高于正常对照组,APTT和TT均低于正常对照组（P〈0．05）。血清Hcy水平与LDL、hs—CRP和血浆胁二聚体水平有一定相关性（r值分别为0．739,0．681和0．803,P〈0．01）。大梗死组、小梗死组血清Hcy、hs—CRP、LDL和血浆D-二聚体水平明显高于腔隙性脑梗死组（P〈0．05）,大梗死组血浆Fib水平明显高于腔隙性脑梗死组和小梗死组（P〈0．05）。脑梗死面积大小与血清Hcy、hs—CRP、LDL和血浆胁二聚体水平具有良好的相关性（r值分别为0．604、0．587、0．515、0．333,P〈0．05或P-〈0．01）。结论：血清Hcy、hs—CRP、LDL和D-二聚体水平升高可能是脑梗死的危险因素。     

叶酸对血液透析患者动脉粥样硬化影响

目的通过比较维持性血液透析（maintenance hemodialysis,MHD）患者叶酸干预治疗前后的同型半胱氨酸（homocysteine,Hcy）及颈动脉动脉内膜-中层厚度（intima-media thickness, IMT）改变情况,旨在探讨叶酸对动脉粥样硬化的保护作用。方法选择 MHD治疗时间超过3个月患者60例,分为对照组和叶酸组,每组各30例。所有患者均进行普通低通量透析器透析,每周3次,每次4h,常规降压、纠正贫血、纠正酸碱失衡及电解质紊乱等处理,以及口服维生素 B121mg/d,叶酸组口服叶酸15mg/d,疗程为6个月,所有患者进入观察前及干预治疗半年后于透析前10 min,抽取空腹血10ml,比较治疗前后2组间Hcy值,并超声测量IMT的变化。结果①治疗半年后叶酸组 Hcy水平下降（P〈0.01）,对照组治疗前后 Hcy 水平变化不明显（P〉0.7）;且2组治疗半年后Hcy比较。②叶酸组治疗半年后颈动脉IMT值差异不明显（P〉0.05）,而对照组半年后IMT值明显升高（P〈0.05）,且半年后2组IMT值之间比较差异有统计学意义（P〈0.05）。结论叶酸组经干预治疗后 Hcy水平明显下降,而颈动脉 IMT值变化不明显;对照组 Hcy变化不明显,而颈动脉 IMT明显升高,提示 Hcy可能参与了动脉粥样硬化的发生和发展。推测叶酸可能通过下调 Hcy水平,起到延缓动脉粥样硬化病情发展的作用。     

维持性血液透析患者高同型半胱氨酸血症的影响因素和大剂量叶酸治疗的效果

目的 观察慢性肾功能衰竭（CRF）维持性血液透析（HD）患者血浆总同型半胱氨酸（tHcy)的影响因素和大剂量叶酸治疗是否可以纠正其高同型半胱氨酸血症（HHcy)。方法 77例稳定的HD患者被分为4组，分别口服叶酸0、5、15或30mg/d，3个月以上（所有患者均不使用维生素B12），用放射免疫分析法测定透析前血浆叶酸，全血叶酸和维生素B12，用高效液相法测定透析前和部分患者透析后血浆总同型半胱氨酸（tHcy)。用常规方法测定总胆固醇（TC），甘油三酯（TG），高密度脂蛋白（HDL），低密度脂蛋白（LDL），血清白蛋白（Alb)，肌酐（Scr），尿素（Urea)。观察不同剂量的叶酸治疗对血浆和全血叶酸的影响。以及血浆和全血叶酸与tHcy的关系。结果 叶酸治疗可以明显提高血疗对血浆和全血叶酸的影响，以及血浆和全血叶酸与tHcy的关系。结果 叶酸治疗可以明显提高血浆和全血叶酸水平。血浆和全血叶酸水平呈线性正相关。血浆和全血叶酸与tHcy均呈非线性负相关，口服叶酸5-15mg/d均可使血浆叶酸大于200ng/ml，此时血浆和全血叶酸的进一步上升不引起tHcy的进一步下降，结论 对HD患者，治疗HHcy的叶酸的合适剂量是5-15mg/d，进一步增大叶酸剂量并不能使tHcy水平进一步下降，口服叶酸结合HD治疗不能完全纠正HD患者HHcy。     

脑卒中患者血清Hcy、VitB12和FA水平变化的研究

自Mccully1969年提出高同型半胱氨酸（Hcy）血症可能与动脉粥样硬化（AS）有关的观点以来，血浆Hcy水平增高是导致动脉粥样硬化（AS）和冠心病的一种独立危险因素已得到一致认同。近来国外研究表明高Hcy血症与脑卒中的发生和发展关系十分密切。由此．本研究拟观察脑卒中病例中血清Hcy、维生素B12（VitB12）和叶酸（FA）水平变化。从而说明脑卒中与高Hcy血症的关系。     

MTHFR基因C677T和A1298C多态与中国部分人群非综合征性唇腭裂的相关研究

目的 探讨MTHFR基因C677T和A1298C多态与非综合征性唇腭裂（NSCL／P）发生的关系。方法 采用病例对照设计，应用聚合酶链式反应-限制性片段长度多态性（PCR—RFLP）方法，进行亚甲基四氢叶酸还原酶（MTHFR）基因C677T和A1298C多态性检测，并进行遗传统计分析。结果 对于MTHFR基因C677T，48个杂合子父母及患儿的核心家庭TDT检验（X^2=0．02，P〉0．05）；76例NSCL／P患儿和60例正常儿童基因型及等位基因频数病例对照研究（X^2=9．91，P〈0．05）。而MTHFR基因A1298C，27个杂合子父母及患儿的核心家庭TDT检验（X^2=4．00，P〈0．05）；76例NSCL／P患儿和60例正常儿童基因型及等位基因频数病例对照研究（X^2=4．42，P〈O．05）。结论 MTHFR基因C677T位点多态与NSCL／P的发生相关，MTHFR基因A1298C位点多态可能是NSCL／P的遗传易感因子。     

2型糖尿病大鼠血浆同型半胱氨酸与阴茎海绵体内NOS和内源性CO的相关性研究

目的:研究2型糖尿病性大鼠血浆同型半胱氨酸(Hcy)与阴茎海绵体内NOS和内源性CO的相关性。方法:选取3月龄雄性Wistar大鼠50只,随机选取10只为对照组(A组);高糖高脂饲料饲养4周后从其他40只大鼠中筛选出30只构建成功的糖尿病(DM)大鼠模型,随机分成3组:DM大鼠组(B组);胰岛素治疗组(C组)和叶酸+维生素B12治疗组(D组)。8周及12周后注射阿朴吗啡观察各组大鼠阴茎勃起情况。12周后测各组大鼠血浆总Hcy含量及阴茎海绵体内NOS活性和CO含量。结果:与A组比较,B组大鼠血浆Hcy浓度明显升高,阴茎勃起功能明显降低,阴茎海绵体NOS活性和CO含量均下降,差异有显著性(P<0.01)。2型DM大鼠中高Hcy血症发生率为55%。与B组比较,C组和D组中大鼠血浆Hcy浓度显著下降,阴茎勃起功能、阴茎海绵体NOS活性均升高(P<0.01),Hcy与NOS(rA=-0.89,rB=-0.76,rC=-0.91,rD=-0.91)及CO含量(rA=-0.82,rB=-0.77,rC=-0.93,rD=-0.81)均呈负相关。结论:2型DM大鼠血浆中的高Hcy可能是引起阴茎海绵体NOS活性下降、CO含量下降,进而导致DM ED发病的分子机制之一。胰岛素、叶酸和维生素B12可以改善DM大鼠的勃起功能,提高阴茎海绵体NOS活性和CO含量。     

Creatine supplementation decreases homocysteine in an animal model of uremia

BACKGROUND: Hyperhomocysteinemia is prevalent in more than 85% of patients with end-stage renal disease (ESRD) and is thought to contribute to the excess cardiovascular mortality and morbidity. Creatine is synthesized by methylation of guanidinoacetate with formation of S-adenosylhomocysteine and subsequently, homocysteine (Hcy). Creatine supplementation down-regulates its endogenous synthesis and, thus, may reduce Hcy production. The present study investigates the effect of creatine supplementation on Hcy concentrations in an animal model of uremia. METHODS: Male Wistar rats were either sham-operated and received a control diet (N = 8) or a 2% creatine-supplemented diet (N = 8), or underwent subtotal nephrectomy and received a control diet (N = 10) or a 2%-supplemented creatine diet (N = 10). After 2 weeks of treatment, total plasma Hcy, creatine, creatinine, folate, and vitamin B12 were determined, as well as hepatic folate and vitamin B12 concentrations. RESULTS: Plasma creatinine concentrations were higher in nephrectomized animals, but similar in creatine-supplemented and control diet-fed animals. Plasma Hcy was higher in nephrectomized animals but lower in creatine-supplemented nephrectomized animals compared to nephrectomized control diet-fed animals (12.1 +/- 2.4 micromol/L vs. 15.4 +/- 1.7 micromol/L; P < 0.01). Total plasma Hcy inversely correlated with plasma creatine concentrations (r =-0.39; P = 0.02). Plasma folate was higher in supplemented animals and hepatic tetrahydrofolate (THF) was higher in nephrectomized supplemented animals. Plasma vitamin B12 was similar in all groups, whereas hepatic vitamin B12 was higher in nephrectomized animals. CONCLUSION: Creatine supplementation can effectively lower plasma Hcy concentrations in an animal model of uremia and should be further investigated as a potential treatment for hyperhomocysteinemia in patients with ESRD.     

Hyperhomocysteinemia in children on renal replacement therapy

Hyperhomocysteinemia is an independent risk factor for the development of atherosclerosis in adult patients on dialysis or after kidney transplantation. There are few data on homocysteine (Hcy) concentrations in children under these circumstances. The aim of our study was to evaluate plasma Hcy levels and their determining factors in children on renal replacement therapy. In 29 children and adolescents on chronic dialysis therapy and in 34 children after renal transplantation (Tx) fasting total plasma Hcy, red blood cell (RBC) folate, and serum vitamin B(12) levels were measured. The plasma Hcy levels were expressed as number of standard deviations (SD) from mean level in age- and gender-matched controls. In dialysis patients the mean plasma Hcy level was elevated (4.4+/-0.8 SDs), without significant difference between patients on hemodialysis or continuous cycling peritoneal dialysis. In the dialysis patients a negative correlation ( r=-0.49) between plasma Hcy levels and RBC folate concentrations was found. Oral folate supplementation was given to 8 of 21 dialysis patients, resulting in high RBC folate levels (>800 micro g/ml) and normalization of the plasma Hcy levels (0.4+/-0.5 SDs). In Tx patients the mean plasma Hcy level was 5.6+/-1.4 SDs. Multivariate regression analysis revealed that the main factor determining Hcy level after kidney Tx was creatinine clearance. Patients with normal kidney function had a mean Hcy concentration of 1.69+/-0.86 compared with 10.0+/-2.2 in children with decreased function. Folate and cyclosporine levels had less significant effects on Hcy concentrations. Seven patients who were evaluated while on dialysis and after a successful kidney Tx demonstrated a significant reduction in Hcy levels. Children and adolescents on dialysis therapy and with impaired renal function after renal Tx have significant hyperhomocysteinemia. Oral folate supplementation normalizes the increased plasma Hcy levels and should be added to the medical treatment of all children with impaired renal function.     

Folate, vitamin B12, and sulfur amino acid levels in patients with renal failure

We examined the plasma profile of sulfur amino acids (SAA) in patients with chronic renal failure (CRF) and looked for any correlation with serum folate (FA) and/or vitamin B₁₂. Group 1 comprised 9 patients with CRF and glomerular filtration rate (GFR) >20 ml/min per 1.73 m², 9 patients with GFR<20 ml/min per 1.73 m² comprised group 2, and 14 patients on hemodialysis group 3. The control group comprised 16 healthy children. Homocysteine (Hcy), methionine (Met), cysteine (Cys), and serine (Ser) were measured with gas chromatography. FA and vitamin B₁₂ were measured using enzymatic immunoassay. Median SAA concentrations were significantly lower in controls than in the three groups of patients. Hcy concentrations were 0.8 μmol/l in controls versus 5 μmol/ (group 1), 9 μmol/l (group 2), and 20 μmol/l (group 3). Met concentrations were 26 μmol/l in controls versus 26 μmol/l (group 1), 66 μmol/l (group 2), and 281 μmol/l (group 3). Cys concentrations were 10 μmol/ in controls versus 98 μmol/l (group 1), 54 μmol/l (group 2), and 122 μmol/l (group 3). Ser concentrations were 88 μmol/ in controls versus 153 μmol/l (group 1), 239 μmol/l (group 2), and 240 μmol/l (group 3). The median concentrations of FA were lower in controls than in groups 2 and 3: 5.5 ng/ml versus 8 ng/ml and 15 ng/ml, respectively. Vitamin B₁₂ concentrations did not differ between groups. Vitamin levels did not correlate with SAA. The only difference between patients with Hcy levels in the lower and upper quartile was in Met concentration (38 vs. 263 μmol/l, P<0.02) and GFR (P<0.01). In conclusion, patients with CRF had higher SAA concentrations than healthy children. FA concentrations are higher in CRF patients than in healthy children but did not correlate with concentrations of SAA. Received: 3 January 2000 / Revised: 21 September 2000 / Accepted: 11 October 2000     

Novel roles of lipopolysaccharide and TLR4/NF-κB signaling pathway in inflammatory response to liver injury in Budd-Chiari syndrome

BACKGROUNDBudd-Chiari syndrome (BCS) is an uncommon disorder characterized by obstruction of hepatic venous outflow. To date, the exact mechanism underlying hepatic injury derived from the hepatic venous outflow obstruction in BCS remains largely unknown.AIMTo assess the role of NF-κB-mediated inflammation in BCS-induced liver injury in humans and rats.METHODSA total of 180 rats were randomly assigned into nine groups, including four BCS model groups (1, 3, 6 and 12 wk), four sham-operated groups (1, 3, 6 and 12 wk), and a control group. Lipopolysaccharide (LPS) levels in each group were detected by the Tachypleus Amebocyte Lysate assay. The mRNA and protein levels of TLR4, NF-κB, tumor necrosis factor (TNF)-α, interleukin (IL)-2 and interferon (IFN)-γ were quantified. In addition, 60 patients with BCS and 30 healthy controls were enrolled, and their blood samples were analyzed.RESULTSHepatic and plasma LPS levels were significantly increased in rats. The mRNA and protein expression levels of TLR4, NF-κB and inflammatory cytokines (TNF-α, IL-2 and IFN-γ) in liver tissues were significantly higher in the BCS model groups compared with the other two groups. In addition, the model groups (1, 3, 6 and 12 wk after BCS induction) showed significant differences in the levels of LPS, TLR4, NF-κB, TNF-α, IL-2 and IFN-γ. Notably, there was a significant correlation between the LPS concentrations and mRNA and protein levels of TLR4, NF-κB and inflammatory cytokines. Importantly, it was revealed that the levels of LPS, TLR4, NF-κB and inflammatory cytokines were significantly greater in chronic BCS patients than healthy controls and acute BCS patients.CONCLUSIONLPS level is markedly elevated in BCS, in turn activating the TLR4/NF-κB signaling pathway, leading to induction of inflammatory cytokines (TNF-α, IL-2 and IFN-γ) in response to BCS-induced liver injury.     

Factors involved in baseline hyperhomocysteinemia in renal transplantation

Hyperhomocysteinemia (hyperHcy) is one cardiovascular risk. The objective of this study was to establish the prevalence demographic, and clinical and analytical factors related to hyperhomocysteinemia among renal transplant patients. The mean Hcy level was 17.3 micromol/L; the prevalence of hyperHcy was 61.2%. The population was categorized as hyperHcy and normal-homocysteinemia (Hcy) patients. Those subjects with hyperHcy were mostly men, with lower intraerythrocyte folate and vitamin B(12) levels, higher fibrinogen levels, and poorer renal function. Multivariate evaluation showed that creatinine clearance, plasma intraerythrocyte folate and vitamin B(12) levels, and plasma fibrinogen levels were independently associated with Hcy levels. Even though the Hcy level was slightly higher among patients who suffered a posttransplantation cardiovascular event, this was statistically significant.     

Relationships between homocysteine and related amino acids in chronic hemodialysis patients.

AIMS: Homocysteine (Hcy) has emerged as an important risk factor for atherosclerotic disease. Elevated levels in chronic dialysis patients may contribute to high vascular mortality, but little is known about levels of related amino acids in this group. In an observational study in the clinical setting we sought to document these. METHODS: In 114 hemodialysis patients pre-dialysis total plasma homocysteine, vitamin B12 and red blood cell (RBC) folate concentrations were measured. In a subgroup of patients (n = 42), other plasma amino acids were measured pre- and post-dialysis. All patients were routinely taking oral folic acid supplements (1.2 mg per week). RESULTS: Elevated homocysteine concentrations were found in all patients (geometric mean 33.1 umol/l, range 13.8 - 69.2 umol/l, laboratory reference range (RR) 3-13 umol/l). RBC folate levels were high (1223 +/- 54.5 nmol/l mean +/- SE, RR 300 - 710 nmol/l) and inversely related to pre-dialysis plasma Hcy (r = -0.44, p < 0.001). Hcy levels were not related to vitamin B12 levels. A history of vascular disease was not associated with higher concentrations of Hcy. Hcy clearance on dialysis was substantial (mean Hcy reduction 33 +/- 14%). While plasma methionine levels were normal, serine levels were significantly lower than the reference range (59.3 +/- 2.39 umol/l (mean +/- SE, RR 70 - 195 umol/l)) and directly related to levels of glycine (r = 0.52, p < 0.001). Glycine levels were within normal range. Although overall levels were low, higher serine levels were related to elevated homocysteine (r = 0.42, p < 0.01). Dialytic loss of glycine, serine and methionine was moderate. CONCLUSION: An inverse association between RBC folate and homocysteine levels extended to 3 times the upper limit of normal for folate, suggesting a role for high dose folic acid supplementation in the treatment of renal-failure related hyperhomocysteinemia. Low serine levels are expected as it is primarily synthesized in the kidney. The direct relationship between serine and homocysteine is consistent with the reported lack of effect of serine supplements on high Hcy levels.     

Study of the homocysteine status in children with chronic renal failure

BACKGROUND/AIMS: Vascular diseases are a major cause of morbidity and mortality in end-stage renal disease (ESRD) patients and they cannot be explained entirely by the prevalence of traditional risk factors for atherosclerosis. The role of hyperhomocysteinemia as an additional risk factor in the development of accelerated atherosclerosis and/or thrombosis in these patients has been suggested possibly due to homocysteine (Hcy) induced endothelial cell injury. This study was aimed at evaluation of the Hcy status in children with chronic renal failure (CRF) especially in those suffering from ESRD and the possible role of folic acid and vitamin B12 therapy in the correction of hyperhomocysteinemia if present. METHODS: This study included 40 patients with CRF, 30 on regular hemodialysis (HD) treatment (group I) and 10 on conservative (medical) treatment (group II) in comparison to 20 healthy age- and sex-matched controls (group III). The basal serum levels of Hcy, folic acid and vitamin B12 as well as plasma level of activated protein C resistance (APC-R) were measured in patients and controls. RESULTS: The mean serum Hcy was significantly higher in those on regular HD (17.9 +/- 10.07 micromol/l) in comparison to those on conservative treatment (8.05 +/- 2.99 micromol/l) (p < 0.001) and controls (7.07 +/- 2.24 micromol/l) (p < 0.001), while there was no significant variation between the latter two groups. The mean values of APC-R, folic acid and vitamin B12 failed to show any significant difference in the three studied groups. No significant difference in the basal Hcy level between patients with previous history of vaso-occlusive disease and those without was found. Half of the patients on regular HD (group Ia) (n = 15) were given folic acid as 50 mg of 5-formyl-tetrahydrofolate (the active form of folic acid) intravenously once weekly after the dialysis session for 4 weeks. The other half (group Ib) (n = 15) received in addition to folic acid therapy, vitamin B12 1,000 microg hydroxycobalamine once intramuscularly. After therapy the mean Hcy decreased significantly in those who received folic acid and vitamin B12 (7.80 +/- 3.77 micromol/l) (p < 0.001) to a level comparable to the basal levels in conservative and control groups, whereas a non-significant decrease was found in those who received folic acid only (13.3 +/- 11.47 micromol/l) (p > 0.05). CONCLUSIONS: Hcy is high in children with ESRD on regular HD and combined therapy of the active form of folic acid and vitamin B12 is of value in decreasing Hcy values comparable to that in controls.     

同型半胱氨酸代谢异常与不明原因反复性自然流产相关性研究

目的　探讨同型半胱氨酸 ( Hcy)代谢异常对不明原因反复性自然流产( URSA)的发生及与叶酸、维生素 B12 缺乏和抗心磷脂抗体 ( ACA)的关系。　方法　非孕期 URSA患者 57例 ,非孕期正常妇女 50例为对照组。采用高压液相色谱法测空腹血清总 Hcy,放射免疫法测血清叶酸、维生素 B12 ,酶链免疫法测 ACA的 Ig G、Ig M。　结果　( 1 ) URSA组血清 Hcy水平显著高于对照组 ( P<0 .0 1 ) ;血清叶酸、维生素 B12 水平显著低于对照组 ;血清 Hcy水平与年龄明显相关 ,叶酸、维生素 B12 水平与年龄无相关性 ,三者与城乡、流产次数、流产时期及原发性或继发性流产均无明显关联。URSA患者血清 Hcy水平与血清叶酸、维生素 B12 浓度均呈负相关。 ( 2 ) URSA组 ACA阳性率显著高于对照组。URSA患者中 ACA( +)组 Hcy水平显著高于 ACA( -)组 ( P<0 .0 1 ) ;ACA与高 Hcy血症有一定的协同作用。　结论　高同型半胱氨酸血症 ( HHM)和低叶酸状态均系 URSA发生的独立危险因素。叶酸和维生素 B12 缺乏 ,是血清 Hcy增高的主要原因之一。 ACA也是 URSA的独立危险因素。 ACA与 HHM相互影响 ,可能存在协同作用。     

Homocysteine and C-reactive protein levels in Haemodialysis patients

Background: Mild to moderatehyperhomocysteinemia is very common amongpatients undergoing haemodialysis. There issufficient evidence that hyperhomocysteinemiais an independent risk factor forcardiovascular and or atheromatous disease inend stage renal failure patients. Vitaminsupplementation such as vitamin B6, B12 orfolate has been proposed to correct thismetabolic disturbance and it is to be proved ifthis intervention benefit these patients, butthere is no agreement whether oral folatesupplementation is capable to normalizehomocysteine levels in end stage renal failurepatients.Methods: In 53 patients, undergoinghaemodialysis, homocysteine levels (Hcy),folate, vitamin B12, ferritin and C-reactiveprotein (CRP) were estimated before and afterdialysis, without folate supplementation.Thirty voluntary blood donors were used ascontrols to compare homocysteine levels. Afterfour weeks of oral folate supplementation(10 mg/24 hours) the levels of homocysteine,serum folate and intra-erythrocyte folate wereestimated again. Eighteen months later thesurvival rate of our patients was recorded andanalyzed in relation to Hcy and CRP levels.Results: The results showed thathaemodialysis patients exhibited, almost,fourfold higher homocysteine levels thancontrols (27.39 ± 11.54 vs 7.38 ± 3.5, t = –8.2, p = 0.000000). Folate levels, vitamin B12 and CRP increase significantly afterhaemodialysis where as homocysteine levelsdecrease (Hcy1 vs. Hcy2: z = 2.08, p = 0.03).Fourteen (14) patients suffered from coronaryheart disease (CHD) and they exhibited thehigher levels of homocysteine (Hcy1 vs. CHD: z =–3.4, p = 0.0006). All estimations performedrevealed a negative correlation betweenhomocysteine levels and plasma orintra-erythrocyte folate. No other variableexhibited any significant influence uponhomocysteine levels. After folatesupplementation homocysteine levels in thewhole number of patients were unchanged(Hcy(before) vs. Hcy(after): 27.39 ± 11.54vs. 26.95 ± 8.22, z = 0.3, p = 0.7, NS). Whenpatients with homocysteine levels higher than24 µmol/L were selected, a significantdecrease was observed (34.77 ± 9.32 vs.30.0 ± 8.05, z = 2.09, p = 0.02). Forty-twopatients were treated with erythropoietin fortheir anemia and we found a positivecorrelation between C-reactive protein levelsand rhu-Epo dose (CRP vs. Epo: r = 0.45,p = 0.002). Homocysteine levels did not exhibitany significant influence upon short-termsurvival (U = –0.37, p = 0.3, NS) where as CRPlevels exhibit a significant influence uponshort-term survival (U = 2.15, p = 0.005).Conclusions: Homocysteine levels inhaemodialysis patients are fourfold higher thanhealthy controls. Folate, vitamin B12 and CRPincrease significantly after dialysis. Patientswith coronary heart disease exhibit the highestlevels of homocysteine. The homocysteine levelsare inversely related with the folate levels.The exogenous folate supplementation increasethe serum folate levels but decreaseshomocysteine only in patients with higher thanmild hyperhomocysteinemia. Hcy doesn't exertany significant effect upon the short-termsurvival of the haemodialysis patients but CRPlevel is a god predictor of the short-termsurvival of these patients.