Etoposide phosphate, the water soluble prodrug of etoposide

An elevated plasma homocysteine level may result from various enviromental and genetic factors. Hereditary causes of severe hyperhomo-cysteinaemia are very rare and usually lead to disease in childhood or adolescence. Common pathology consists of early atherosclerotic vascular changes, arterioocclusive complications and venous thrombosis. Mildly elevated genetically determined plasma homocysteine levels are observed in 5% of the general population. In the last two decades research has shown mild hyperhomocysteinaemia to be linked to an increased risk of premature atherosclerosis, pregnancies complicated by neural tube defects and early pregnancy loss, and venous thrombosis. Homozygosity for thermolabile MTHFR deficiency has been identified as one important genetic factor, which expression is modified by dietary folate intake. Although mild hyperhomocysteinaemia can easily be treated by vitamin supplementation the beneficial effects of such treatment remains to be shown.     

Hyperhomocysteinaemia and chronic venous ulcers

Chronic venous ulceration (CVU) is the major cause of chronic wounds of lower extremities, and is a part of the complex of chronic venous disease. Previous studies have hypothesised that several thrombophilic factors, such as hyperhomocysteinaemia (HHcy), may be associated with chronic venous ulcers. In this study, we evaluated the prevalence of HHcy in patients with venous leg ulcers and the effect of folic acid therapy on wound healing. Eighty‐seven patients with venous leg ulcers were enrolled in this study to calculate the prevalence of HHcy in this population. All patients underwent basic treatment for venous ulcer (compression therapy ± surgical procedures). Patients with HHcy (group A) received basic treatment and administered folic acid (1·2 mg/day for 12 months) and patients without HHcy (group B) received only basic treatment. Healing was assessed by means of computerised planimetry analysis. The prevalence of HHcy among patients with chronic venous ulcer enrolled in this study was 62·06%. Healing rate was significantly higher (P < 0·05) in group A patients (78·75%) compared with group B patients (63·33%). This study suggests a close association, statistically significant, between HHcy and CVU. Homocysteine‐lowering therapy with folic acid seems to expedite wound healing. Despite these aspects, the exact molecular mechanisms between homocysteine and CVU have not been clearly defined and further studies are needed.     

Association of cardiometabolic risk profile with prehypertension accompany hyperhomocysteinaemia

Abstract

Background: Study suggested that elevated homocysteine showed a multiplicative effect on cardiovascular diseases in hypertensive subjects. It was reported that elevated homocysteine level was independently associated with increased arterial stiffness in prehypertensives. It remains unclear whether prehypertensives combined with elevated homocysteine have adverse cardiovascular risk factors. We aimed to compare cardiometabolic risk profile between prehypertensives with hyperhomocysteinaemia and those without either condition. Methods: Plasma total homocysteine and risk profile were determined among 874 Chinese non-hypertension individuals in Tianjin. They were subdivided into four groups: prehypertension with hyperhomocysteinaemia (≥10?μmol/L), prehypertension with normal homocysteine (<10?μmol/L), normotension with hyperhomocysteinaemia, normotension with normol homocysteine, respectively. Results: In 874 participants, 22.5% of them were male, mean age was 56.8 years. In multiple comparisons, after adjustment for age, gender, smoking, alcohol, exercise, education prehypertensives had higher body mass index (BMI) and high sensitive C reactive protein (hs-CRP) than normotensives (p?<?0.05, respectively); Only prehypertensive subjects with hyperhomocysteinaemia had higher triglyceride and serum uric acid compared to normotensive subjects, and lower HDL cholesterol than normotensives with normal homocysteine (p?<?0.05, respectively). However, the significance of higher hs-CRP, uric acid and lower HDL cholesterol were abolished when further adjustment was made for BMI. Conclusion: The combination of prehypertension and hyperhomocusteinaemia increases the likelihood of having adverse cardiometabolic risk profile. Strict lipid management and weigh control may be needed in prehypertensives with elevated homocysteine.     

血浆同型半胱氨酸水平对老年高血压患者轻度认知功能障碍的预测价值

目的探讨血浆同型半胱氨酸水平对老年高血压患者发生轻度认知功能障碍的预测价值。方法入选符合标准的老年高血压合并轻度认知功能障碍患者104例,并选取同期认知功能正常的老年高血压患者102例作为对照组,分析各组患者血浆同型半胱氨酸水平,并通过Logistic回归分析明确老年高血压患者发生轻度认知功能障碍的相关因素。结果老年高血压合并轻度认知功能障碍组与单纯高血压组的临床资料比较,在血浆同型半胱氨酸水平及高密度脂蛋白胆固醇水平上差异有统计学意义（t=4.251,P=0.006;t=3.302,P=0.015）;高同型半胱氨酸者轻度认知功能障碍的发病率明显升高（P〈0.05）;经Logistic回归分析显示高同型半胱氨酸血症是老年高血压患者发生轻度认知功能障碍的独立危险因素（OR=2.32,95%CI=1.31~4.16）,P〈0.05。结论高同型半胱氨酸血症对老年高血压患者发生轻度认知功能障碍具有预测价值。     

Evidence for sex differences in the determinants of homocysteine concentrations

A high homocysteine phenotype, often accompanied by low folate, is associated with several pathologies including cardiovascular disease and birth defects. This phenotype appears to be influenced by both genetic and environmental factors, which may act in a sex-dependent manner. The present analyses were undertaken to identify the determinants of homocysteine concentrations in young men and women, and are based on data from a cohort of young, reproductive age (20–26 years old) individuals in Northern Ireland. Multivariate modeling indicated that homocysteine concentrations are associated with red blood cell (RBC) folate, vitamin B₁₂, MTHFR 677C>T genotype and smoking status in both males and females. However, the inter-relationships between these variables appear to differ between the sexes. Specifically, homocysteine levels in males were significantly associated with interactions between MTHFR 677C>T genotype and both RBC folate and smoking status. In contrast, homocysteine levels in females were significantly associated with interactions between smoking status and RBC folate. These results suggest that the characteristics of individuals who are at the highest risk for a high homocysteine phenotype differ for males and females. Among males, those with the MTHFR 677TT genotype appear to be at the highest risk and to be the most vulnerable to factors (e.g. smoking, low RBC folate) that are associated with homocysteine raising effects. Among females, smokers (regardless of MTHFR genotype) appear to be at the highest risk, and to be the most vulnerable to a single factor (i.e. RBC folate) that is associated with homocysteine raising effects.     

Anti-Epileptic drug treatment in children: Hyperhomocysteinaemia, B-Vitamins and the 677C→T Mutation of the Methylenetetrahydrofolate Reductase Gene

The aim of the study was to observe the influence of carbamazepine and valproic acid on plasma total homocysteine and B-vitamin status and the gene-drug interaction with the 677C-->T mutation of the methylenetetrahydrofolate reductase (MTHFR) gene. Plasma total homocysteine concentrations were determined in 136 epileptic children taking anti-epileptic drugs as monotherapy. Nutritional (folate, B12 and B6 vitamins) and genetic (MTHFR 677 C-->T) determinants of plasma homocysteine were studied in a random sample of 59 of the 136 epileptic children. Total homocysteine concentrations were significantly increased (p < 0.05) and folate and vitamin B6 levels were significantly decreased (p < 0.01) in the children taking anti-epileptic drugs compared with our reference ranges. In the carbamazepine-treated group, significantly positive correlation was found between duration of treatment and homocysteine concentration (p < 0.01). Homocysteine concentrations showed a significantly negative correlation with vitamin levels (folate: p = 0.002, and vitamin B12: p = 0.017) only in the carbamazepine treated group. In children treated with carbamazepine up to 3 years, total homocysteine concentration correlated negatively only with folate (p = 0.003), while in patients treated for more than 3 years, total homocysteine correlated negatively only with vitamin B12 values (p = 0.007). The lowering action of carbamazepine treatment on folate levels seems to be associated with hyperhomocysteinaemia, which seems to be related to the homozygous condition for the MTHFR 677C-->T mutation. Valproic acid treatment, although also associated with hyperhomocysteinaemia, only shows a lowering effect on vitamin B6 levels, which seems to be independent of the MTHFR genotype.     

甜菜碱药理作用的研究进展

甜菜碱是广泛存在于动植物体内的天然维生素物质,有许多优良的药理作用。甜菜碱具有渗透调节作用,保护细胞抵抗外界高渗等的影响;甜菜碱是一种比蛋氨酸或胆碱更为有效的甲基供体,参与蛋氨酸循环及卵磷脂合成,在高同型半胱氨酸血症的治疗中安全而有效,同时对多种肝脏疾病有很好的治疗作用;此外,还有抑瘤抗癌、降压镇静、解热镇痛等多种药理作用。     

Hyperhomocysteinaemia; with reference to its neuroradiological aspects

Severe or even mild hyperhomocysteinaemia can cause a wide range of neurological problems. In recent years its vascular complications, including cerebral stroke, in children and young adults have gained special interest, because hyperhomocysteinaemia is treatable and recurrence of vascular incidents may be preventable. Current knowledge about biochemical mechanisms leading to hyperhomocysteinaemia, the pathogenesis of vascular pathology and neurological disfunction, and the various patterns of cerebral damage are reviewed. The significance of MRI in diagnosis, follow-up and research on hyperhomocysteinaemia is discussed.     

叶酸治疗短暂性脑缺血发作伴高半胱氨酸血症疗效观察

目的 观察叶酸治疗对合并高半胱氨酸血症(Hcy)的短暂性脑缺血发作(TIA)患者血浆高半胱氨酸(HCA)水平及预后的影响.方法 将129例合并Hcy的TIA患者应用随机数字法随机分为2组,对照组(n=64)只给予常规治疗,观察组(n=65)在常规治疗的基础上给予叶酸治疗,对比分析2组患者治疗前及治疗后3个月HCA水平的变化及其1年内完全缓解率及完全性脑卒中发生率.结果 初发TIA患者Hcy的发生率高达41.4%.治疗3个月后,观察组血浆HCA显著降低[(14.27±6.13)μmol/L,(24.99±6.87)μmol/L,t=2.799,P＜0.01],而对照组血浆HCA无明显变化[(24.68±6.89)μmol/L,(25.68±7.11)μmol/L,t=2.735,P＜0.01].1年后,观察组完全性脑卒中发生率显著低于对照组(9.8%,25.0%,x2=4.849,P＜0.05),TIA症状完全缓解率高于对照组(73.8%,50.0%,x2=7.253,P＜0.01),且无明显不良反应.结论 叶酸治疗可有效降低TIA患者的血浆HCA水平,改善患者的预后.

Abstract：

Objective To observe the therapeutic effect of folic acid on transient ischemic attack(TIA)patients with homocysteinaemia (Hcy ). Methods 129 patients of primary TIA with Hcy were divided into two groups randomly. The observation group ( n = 65 )was administered with conventional therapy and folic acid, and the control group ( n=64 ) was only given conventional therapy. The variances of the plasma HCA level three months later were compared, and remission rate of TIA and complete stroke incidence one year later were analyzed between two groups. Results The Hcy incidence rate of TIA patients was up to 41.4%. Three months later, the plasma HCA level of observation group was lower than control group( ( 14.27 ± 6. 13 ) μmol/L vs (24.99 ± 6.87 )μmol/L, t=2.799, P＜0. 01 ) ,and much lower than that of the control group post-treatment ( ( 14. 27 ±6. 13)μmol/L vs (24.68 ± 6.89) μmol/L, t = 2.735, P ＜ 0.01 ). One year later, the complete stroke incidence of TIA in observation group was lower than that of the control group(9.8% vs 25.0%, P＜0.05 ) ,and complete remission rate was higher than the latter(73.8% vs 50.0%, P ＜ 0. 01 ). Conclusion Folic acid can decrease the plasma HCA level of TIA patients with Hcy efficiently,and improve the prognosis of such patients.     

2型糖尿病合并高同型半胱氨酸血症患者血浆CRP水平的变化及临床意义

[目的]探讨血浆C-反应蛋白(CRP)水平的变化在2型糖尿病合并高同型半胱氨酸血症患者发病中的临床意义. [方法]2型糖尿病患者100例,其中合并高同型半胱氨酸血症组50例,单纯糖尿病组50例,正常对照组100例.比较各组间血浆CRP,血脂及同型半胱氨酸. [结果]2型糖尿病组CRP水平明显高于对照组(P＜0.05),2型糖尿病合并高同型半脱氨酸血症组CRP水平明显高于无高同型半胱氨酸血症组(P＜0.05). [结论]2型糖尿病合并高同型半胱氧病血症患者CRP水平明显升高,炎症可能是2型糖尿病和高同型半胱氨酸血症的共同危险因子.