Prevalence of hyperhomocysteinemia in healthy Indian doctors

Currently, hyperhomocysteinemia is a well-known risk factor for variety of vascular diseases. Prevalence of hyperhomocysteinemia increases with age. Hence, the present study was aimed to investigate the prevalence of hyperhomocysteinemia in healthy upper socio-economic class population in India. Total homocysteine (tHcy) concentration was determined in 1243 (906 men & 337 women) healthy Indian doctors with different age group. Using Third National Health and Nutrition Examination Survey (NHANES III) study criteria, the prevalence of hyperhomocysteinemia was 92.85% among men (>11.4 µmol/L) and 81.60% among women (>10.4 µmol/L). The prevalence of hyperhomocysteinemia was higher among men with mean tHcy concentration (21.96 ± 0.38 µmol/L) significantly higher (P<0.0001) than women (15.90 ± 0.39 µmol/L) (95% CI, 4.733- 7.376). Our study showed very high prevalence of hyperhomocysteinemia which may point to the future risk for various pathologies in the present subset of population. Further studies to look at the plasma levels of homocysteine lowering vitamins are warranted to prevent the future risk of vascular diseases.     

二甲双胍联合津力达颗粒治疗妊娠期糖尿病的临床效果及对患者血清VEGF、APN、Hcy水平的影响

目的:探讨二甲双胍联合津力达颗粒治疗妊娠期糖尿病的临床效果及对患者血清血管内皮生长因子(VEGF)、脂联素(APN)、同型半胱氨酸(Hcy)水平的影响。方法:选择2014年7月至2016年7月我院接诊的94例妊娠期糖尿病患者并通过随机数表法分为观察组(n=47)和对照组(n=47)。对照组使用二甲双胍治疗,观察组在对照组的基础上联合津力达颗粒治疗,均治疗至胎儿娩出。比较两组治疗前后血糖、血脂及血清VEGF、APN和Hcy水平的变化及产妇并发症和新生儿不良结局的发生情况。结果:与治疗前比较,两组治疗后血糖、血脂指标均显著改善(P0.05),观察组空腹血糖(FBG)、餐后2 h血糖(2h PG)、糖化血红蛋白(Hb A1c)、总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)水平均明显低于对照组,血清高密度脂蛋白胆固醇(HDL-C)水平明显高于对照组(P0.05)。两组治疗后血清VEGF、APN、Hcy水平较治疗前均显著改善(P0.05),且观察组血清VEGF、Hcy均明显低于对照组,血清APN水平明显高于对照组(P0.05)。观察组妊娠期高血压、羊水过多、剖宫产、早产、巨大儿、新生儿黄疸、新生儿呼吸窘迫的发生率均明显低于对照组(P0.05)。结论:二甲双胍联合津力达颗粒治疗妊娠期糖尿病的临床效果显著,可有效控制血糖、血脂水平,降低不良母婴结局的发生率,可能与其有效调节血清VEGF、APN、Hcy水平有关。     

Homocysteine Induces Iron-Catalyzed Lipid Peroxidation of Low-Density Lipoprotein that is Prevented by Alpha-Tocopherol

Homocystinuria is an inborn error of methionine metabolism that is characterized by the premature development of arteriosclerosis. As one of the major factors in the pathogenesis of arteriosclerosis, modification of low-density lipoprotein (LDL) has received widespread attention by many investigators. In this study, to elucidate the relationship between elevated homocysteine levels and premature arteriosclerosis, we investigated the role of homocysteine in the iron-catalyzed oxidative modification of LDL. When LDL isolated from a healthy subject was incubated with homocysteine and ferric ion, a gradual decrease of polyunsaturated fatty acids (PUFA), formation of thiobarbituric acid-reactive substances (TBARS) and fluorescent substances, and the fragmentation of apoprotein B (apoB) were observed. The extent of oxidative modification was dependent on the concentration of homocysteine. Modification of LDL was suppressed until the remaining α-tocopherol concentration reached a critical level. When the α-tocopherol content of LDL was increased by 2.6-fold, both the formation of TBARS and the fragmentation of apoB were suppressed. These results suggest that homocysteine might promote iron-catalyzed oxidation of LDL and imply its role for the development of premature arteriosclerosis.     

硫化氢减轻同型半胱氨酸诱导大鼠海马CA1区神经元损伤

目的探讨硫化氢(H2S)对同型半胱氨酸(Hcy)诱导大鼠海马CA1区神经元损伤的改善作用。方法以侧脑室注射同型半胱氨酸的SD大鼠为同型半胱氨酸神经毒性动物模型,采用Tunel染色法分析大鼠海马CA1区神经元的凋亡情况,采用Elisa法分析大鼠海马组织MDA含量。结果 0.6μmol和2.0μmol的同型半胱氨酸使大鼠海马CA1区神经元发生大量的凋亡(P0.01),而NaHS(100μmol/kg)显著抑制同型半胱氨酸(0.6μmol)诱导大鼠海马CA1区神经元的凋亡(P0.05);同型半胱氨酸(0.2,0.6μmol)可增加大鼠海马CA1区丙二醛含量(P0.001),而NaHS(100μmol/kg)可抑制同型半胱氨酸(0.6μmol/L)诱导大鼠海马CA1区丙二醛水平的增加(P0.001)。结论硫化氢可减轻同型半胱氨酸诱导大鼠海马CA1区神经元的损伤。     

Induction of betaine: Homocysteine methyltransferase in some murine cells cultured in vitro

Betaine when present in the culture medium could induce the activity of betaine: homocysteine methyltransferase (EC 2.1.1.5) in mouse L-cells, and leukemic L1210 cells, as well as in mouse embryo fibroblasts grown in vitro. We found this process to be time- and concentration-dependent. A persisting contact of the cells with betaine was indispensible for expressing and maintaining the enzyme activity. The treatment of cells with cycloheximide or actinomycin D abolished the process of induction. Methionine as well as homocysteine, when present either in the culture medium or in the reaction mixture, strongly depressed the activity of this enzyme. The L-cells with the induced betaine: homocysteine methyltransferase survived but did not multiply in the methionine-deficient medium, therefore, they did not become prototrophs with respect to methionine.     

Higher serum homocysteine and lower thyroid hormone levels in pregnant women are associated with neural tube defects

BackgroundThis study tested the hypothesis that abnormal maternal metabolism of both homocysteine and thyroid hormone network in pregnant women is associated with neural tube defects (NTDs) in a part of China with high NTD prevalence.MethodsA case–control study was performed between 2007 and 2009 in Lüliang Mountains, Shanxi Province. This study included 83 pregnant women who had fetuses with NTDs (cases) and 90 pregnant women with normal fetuses (controls). In addition, a cell model to illustrate the epidemiological findings was established.ResultsFetuses of mother who had both high total homocysteine (tHcy) and inadequate free thyroxine were 3 times more at risk of developing NTDs (adjusted odds ratio = 3.5; 95 % confidence interval = 1.2–10.4; cases vs. controls) using multivariate logistic regression models. Furthermore, biological interaction between metabolisms of Hcy and thyroid hormones was demonstrated in vitro. In homocysteine thiolactone of a metabolite of Hcy-treated mouse embryonic neural stem NE4C cells, genes (Bmp7, Ctnnb1, Notch 1, Gli2, and Rxra) related to both neural tube closure and thyroid hormone network were shown to be regulated by H3K79 homocysteinylation, which increased their expression levels.ConclusionsThe effect of maternal serum high tHcy on risk of developing NTDs is depended on maternal serum level of thyroxine. Meanwhile, a higher level of tHcy might also affect both maternal metabolism of thyroid hormone and neural tube closure in embryogenesis through homocysteinylation of histones.     

Allosteric Communication between the Pyridoxal 5′-Phosphate (PLP) and Heme Sites in the H2S Generator Human Cystathionine β-Synthase

Human cystathionine β-synthase (CBS) is a unique pyridoxal 5′-phosphate (PLP)-dependent enzyme that has a regulatory heme cofactor. Previous studies have demonstrated the importance of Arg-266, a residue at the heme pocket end of α-helix 8, for communication between the heme and PLP sites. In this study, we have examined the role of the conserved Thr-257 and Thr-260 residues, located at the other end of α-helix 8 on the heme electronic environment and on activity. The mutations at the two positions destabilize PLP binding, leading to lower PLP content and ∼2- to ∼500-fold lower activity compared with the wild-type enzyme. Activity is unresponsive to PLP supplementation, consistent with the pyridoxine-nonresponsive phenotype of the T257M mutation in a homocystinuric patient. The H₂S-producing activities, also impacted by the mutations, show a different pattern of inhibition compared with the canonical transsulfuration reaction. Interestingly, the mutants exhibit contrasting sensitivities to the allosteric effector, S-adenosylmethionine (AdoMet); whereas T257M and T257I are inhibited, the other mutants are hyperactivated by AdoMet. All mutants showed an increased propensity of the ferrous heme to form an inactive species with a 424 nm Soret peak and exhibited significantly reduced enzyme activity in the ferrous and ferrous-CO states. Our results provide the first evidence for bidirectional transmission of information between the cofactor binding sites, suggest the additional involvement of this region in allosteric communication with the regulatory AdoMet-binding domain, and reveal the potential for independent modulation of the canonical transsulfuration versus H₂S-generating reactions catalyzed by CBS.     

Improving the endothelial dysfunction in type 2 diabetes with chromium and vitamin D3 byreducing homocysteine and oxidative stress: A randomized placebo-controlled trial

BackgroundChromium picolinate (CrPic) and vitamin D3 are known as two antioxidant micronutrients. Through inducing endothelial dysfunction, oxidants such as homocysteine (Hct) and malondialdehyde (MDA) lead to cardiovascular disease in type 2 diabetes mellitus (T2DM). No published data has directly examined the effects of these two antioxidants on improving the endothelial dysfunction in T2DM throughreducing homocysteine and oxidative stress.MethodsSubjects (n = 92) in this randomized, double blind, placebo-control study were randomly assigned to receive oral placebo (group I), D₃ (group II: 50,000 IU/ week), chromium picolinate (CrPic) (group III: 500 μg/day), and both vitamin D₃ and CrPic (group IV) for four months. Fasting blood samples were drawn at study baseline and following intervention to determine Hct, MDA, total antioxidant capacity (TAC), total thiol groups (SHs), vascular cell adhesion molecule- 1 (VCAM-1), and plasminogen activator inhibitor-1 (PAI-1).ResultsAfter intervention, MDA significantly decreased in groups II and IV; TAC significantly increased in group IV, and SHs significantly augmented in group III; Hct was significantly reduced in groups II, III, and IV; and VCAM-1 significantly decreased in groups III and IV and PAI-1 was significantly reduced in groups II, III, and IV.ConclusionOur findings suggest that through reducing homocysteine and oxidative stress and improving endothelial dysfunction, chromium and vitamin D₃ co-supplementation might be predictive and preventive of cardiovascular diseasesassociated with T2DM.IRCT, IRCT20190610043852N1, registered 21 October 2019, https://fa.irct.ir/user/trial/42293/view     

利伐沙班用于急性肺栓塞的抗凝效果及对血清Hcy、BNP、TnI与D-D水平的影响

目的:探讨利伐沙班用于急性肺栓塞的抗凝效果及对血清脑钠肽(Brain natriuretic peptide,BNP)、肌钙蛋白I (Troponin I,TnI)、D-二聚体(D-Dimer,D-D)、同型半胱氨酸(homocysteine,Hcy)水平的影响。方法:选择2014年2月至2017年12月在我院进行治疗的(高)中危组急性肺栓塞患者106例,并将其随机分为观察组和对照组。对照组皮下注射低分子肝素钙搭配华法林治疗,观察组予以利伐沙班治疗,观察和比较两组患者的临床疗效、治疗前后血清BNP、TnI、D-D、Hcy水平的变化及不良反应的发生情况。结果:治疗后,观察组患者总有效率为94.37%,显著高于对照组(42.10%,P0.05);观察组患者血清BNP、TnI、D-D、Hcy及肺动脉收缩压水平均显著低于对照组(P0.05),而动脉收缩压、动脉血氧分压水平较对照组水平显著升高(P0.05)。结论:利伐沙班应用于治疗急性肺栓塞的抗凝效果显著优于低分子肝素钙搭配华法林治疗,其可有效降低患者血清BNP、TnI、D-D、Hcy水平以及肺动脉收缩压。     

吡拉西坦联合鼠神经生长因子对急性缺血性脑卒中患者的疗效及Hcy、PCT和皮质醇水平的影响

目的:探讨吡拉西坦联合鼠神经生长因子对急性缺血性脑卒中患者的疗效及对同型半胱氨酸(Hcy)、降钙素原(PCT)和皮质醇水平的影响。方法:回顾性分析我院2017年2月～2018年11月收治的73例急性缺血性脑卒中患者为研究对象,依据入院先后顺序分为对照组(n=35)和观察组(n=38)。对照组患者采用吡拉西坦治疗,观察组基于对照组加以鼠神经生长因子治疗。观察并比较两组临床疗效,治疗前后美国国立卫生研究院卒中量表(NIHSS)、日常生活能力(ADL),治疗前及治疗2周结束时用全自动生化分析仪测定血浆Hcy水平,用放射免疫学分析法测定PCT水平,用化学发光法测定皮质醇水平,用超声多普勒诊断仪测定基底动脉、左右大脑中动脉血流。结果:治疗后,观察组NIHSS评分低于对照组(8.96±1.21)vs(11.27±1.59)分,ADL评分高于对照组(74.21±9.75)vs(66. 04±8.03)分(P0.05)。观察组总有效率高于对照组89.47%vs 68.57%(P0.05)。治疗后,观察组Hcy、PCT及皮质醇水平低于对照组(14.27±2.01)vs (18.51±2.84)μmol/L、(0.25±0.03)vs (0.31±0.04)μg/L、(171.93±23.86)vs(228.75±30.27)nmol/L(P0.05)。治疗后,观察组脑血流学指标高于对照组基底动脉(43.81±6.84)vs(39.62±5.27)mL/min、左大脑中动脉血流(64.27±9.95)vs(57.03±7.52)mL/min、右大脑中动脉血流(62.85±9.01)vs(56.64±7.42)mL/min(P0.05)。结论:吡拉西坦联合鼠神经生长因子能够提高急性缺血性脑卒中的疗效,降低Hcy、PCT及皮质醇水平,促进神经功能的恢复。