Plasma choline metabolites associate with metabolic stress among young overweight men in a genotype-specific manner

OBJECTIVES:

We aimed to test the hypotheses that (i) plasma choline metabolites differ between normal (body mass index (BMI)<25 kg m⁻²) and overweight (BMI ⩾25 kg m⁻²) men, and (ii) an elevated BMI alters associations between plasma choline metabolites and indicators of metabolic stress.

DESIGN:

This was a cross-sectional study. A one-time fasting blood sample was obtained for measurements of the choline metabolites and metabolic stress indicators (that is, serum alanine aminotransferase (ALT), glucose, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides and homocysteine), and for genotype determination.

SUBJECTS:

The analysis was conducted with 237 Mexican American men with a median age of 22 years.

RESULTS:

Compared with men with a normal BMI (n=98), those with an elevated BMI (n=139) had 6% lower (P=0.049) plasma betaine and an 11% lower (P=0.002) plasma betaine to choline ratio. Among men with an elevated BMI, plasma betaine and the plasma betaine to choline ratio positively associated (P⩽0.044) with a favorable serum cholesterol profile, and inversely associated (P=0.001) with serum ALT, a marker of liver dysfunction. The phosphatidylethanolamine N-methyltransferase (PEMT) 5465G→A (rs7946) genotype interacted (P⩽0.007) with the plasma betaine to choline ratio to modulate indicators of metabolic stress with stronger inverse associations observed among overweight men with the PEMT 5465GG genotype.

CONCLUSIONS:

Plasma choline metabolites predict metabolic stress among overweight men often in a genotype-specific manner. The diminished betaine among overweight men coupled with the inverse association between betaine and metabolic stress suggest that betaine supplementation may be effective in mitigating some of the metabolic insults arising from lipid overload.     

An indirect response model of homocysteine suppression by betaine: optimising the dosage regimen of betaine in homocystinuria

AIMS: To investigate the pharmacokinetics (PK) and pharmacodynamics (PD) of betaine in the treatment of classical homocystinuria due to cystathionine beta-synthase (CbetaS) deficiency with a view to optimizing the dosage regimen. METHODS: Betaine was given as a single oral dose of 100 mg kg(-1) to six patients (age range 6-17 years) who normally received betaine but whose treatment had been suspended for 1 week prior to the study. Plasma betaine and total homocysteine concentrations were measured by high performance liquid chromatography (h.p.l.c.) at frequent intervals over 24 h. The best-fit PK model was determined using the PK-PD program Win-Nonlin and the concentration-time-effect data analysed by an indirect PD model. Using the PK and PD parameters, simulations were carried out with the aim of optimizing betaine dosage. RESULTS: Betaine PK was described by both mono- and bi-exponential disposition functions with first order absorption and a lag time. The correlation coefficient between betaine oral clearance and body weight was 0.6. Mean betaine clearance was higher in males than in females (P=0.03). PK-PD simulation indicated minimal benefit from exceeding a twice-daily dosing schedule and a 150 mg kg(-1) day(-1) dosage for betaine. CONCLUSIONS: PK-PD modelling allows recommendations for optimal dosage of betaine in the treatment of homocystinuria, that have the potential for improved patient compliance and both therapeutic and pharmacoeconomic benefit.     

枸杞子粉碎前几种预处理方法的比较研究

目的研究3种预处理方法,比较并筛选适合枸杞子对照药材的预处理方法,以提高其粉碎和分装效率。方法采用减压干燥法、液氮冻干法、冻干法3种预处理方法处理枸杞子;测定并比较3种预处理方法得到的枸杞子原料与未经预处理的枸杞子原料特性量值(水分、指标含量)的差异。结果直接粉碎的枸杞子原料水分为6.4%,3种预处理方法得到的枸杞子原料的水分分别为4.6%、5.0%、5.2%;直接粉碎的枸杞子原料的枸杞多糖质量分数为2.5%,3种预处理方法得到的枸杞子原料的枸杞多糖质量分数分别为2.6%、2.8%、2.6%;直接粉碎的枸杞子原料甜菜碱质量分数为0.98%,3种预处理方法得到的枸杞子原料的甜菜碱质量分数分别为0.94%、1.00%、0.87%。特性量值的测定结果表明,3种预处理方法得到的枸杞子原料的质量无显著差异。因此从经济角度出发,推荐使用更加实惠的减压干燥法处理枸杞子对照药材。经预处理后的枸杞子原料应尽快粉碎、分装,并严格控制粉碎和分装环境的湿度在20%～30%,以提高粉碎和分装效率。结论基于成本考虑,3种预处理方法中减压干燥法最为经济实惠,在实际工作中推荐使用减压干燥法最佳。     

重组人甜菜碱高半胱氨酸甲基转移酶的表达纯化和鉴定

目的对重组人甜菜碱高半胱氨酸甲基转移酶（recombinant human betaine-homocysteine S-methyltrans-ferase,rhBHMT）进行表达纯化和鉴定。方法采用基因重组技术在原核系统表达BHMT蛋白,镍螯合亲和层析和Sephacryl S200层析进行纯化。产物经SDS-PAGE、HPLC、N端氨基酸序列检测与活性验证。结果终产物rhBHMT纯度达97.9%。相对分子质量为45 000,N端氨基酸序列与理论序列一致。结论从工程菌中获得具有活性的高纯度rhBHMT,产物均一,工艺稳定,为中试放大提供可靠依据。     

Betaine—The dark knight of the brain

The role of betaine in the liver and kidney has been well documented, even from the cellular and molecular point of view. Despite literature reporting positive effects of betaine supplementation in Alzheimer's, Parkinson's and schizophrenia, the role and function of betaine in the brain are little studied and reviewed. Beneficial effects of betaine in neurodegeneration, excitatory and inhibitory imbalance and against oxidative stress in the central nervous system (CNS) have been collected and analysed to understand the main role of betaine in the brain. There are many ‘dark’ aspects needed to complete the picture. The understanding of how this osmolyte is transported across neuron and glial cells is also controversial, as the expression levels and functioning of the known protein capable to transport betaine expressed in the brain, betaine-GABA transporter 1 (BGT-1), is itself not well clarified. The reported actions of betaine beyond BGT-1 related to neuronal degeneration and memory impairment are the focus of this work. With this review, we underline the scarcity of detailed molecular and cellular information about betaine action. Consequently, the requirement of detailed focus on and study of the interaction of this molecule with CNS components to sustain the therapeutic use of betaine.     

Variation of Sweet Chemicals in Different Ripening Stages of Wolfberry Fruits

Objective To evaluate the variation of sweet chemicals(sugars and betaine) in fruits of six species in genus Lycium L. i.e. Lycium truncatum, L. cylindricum, L. dasystemum, L. dasystemum var. rubricaulium, L. chinense, and L. barbarum harvested at three different ripening stages. Methods A simple and effective method based on UPLC-ELSD was developed for the simultaneous determination of two monosaccharides(glucose and fructose), two disaccharides(sucrose and maltose), one sugar alcohol(xylitol), and betaine in wolfberry fruits(goji berries) of genus Lycium L. Results The six species of wolfberry fruits harvested at the three different ripening stages were evaluated in sugars and betaine contents. Fructose and glucose were the predominant sugars in mature wolfberry fruits. Fructose, glucose, and betaine, as well as total sugar contents, increased continually over the ripening process. L. truncatum and L. dasystemum had higher contents of sugars and betaine than the other species. Conclusion UPLC-ELSD is a simple, reliable and effective method for analysis of the sweet chemicals in wolfberries. Wolfberry fruits at the different ripening stages were significant different in sweetness. L. truncatum and L. dasystemum could be the potential sources of wolfberry fruit sources.     

Cost-Effectiveness of PHMB & betaine wound bed preparation compared with standard care in venous leg ulcers: A cost-utility analysis in the United Kingdom

BackgroundWounds cost £8.3 billion per year in the United Kingdom (UK) annually. Venous leg ulcers (VLUs) account for 15% of wounds and can be complicated to heal, increasing nurse visits and resource costs. Recent wound bed preparation consensus recommends wound cleansing and biofilm disrupting agents. However, inert cleansers such as tap water or saline are inexpensive, an evaluation of evidence is required to justify the higher upfront costs of treatment with active cleansers. We undertook a cost-effectiveness analysis of the use of a biofilm disrupting and cleansing solution and gel, Prontosan® Solution and Gel X, (PSGX) (B Braun Medical), as compared to the standard practice of using saline solution, for treating VLUs.MethodsA Markov model was parameterised to one-year costs and health-related quality of life consequences of treating chronic VLUs with PSGX versus saline solution. Costs are viewed from a UK healthcare payer perspective, include routine care and management of complications. A systematic literature search was performed to inform the clinical parameters of the economic model. Deterministic univariate sensitivity analysis (DSA) and probabilistic sensitivity analysis (PSA) were undertaken.ResultsFor PSGX an Incremental Net Monetary Benefit (INMB) of £1,129.65 to £1,042.39 per patient (with a Maximum Willingness to Pay of £30k and £20k per QALY respectively), of which cost savings are £867.87 and 0.0087 quality-adjusted life years (QALYs) gain per patient. PSA indicates a 99.3% probability of PSGX being cost-effective over saline.ConclusionsPSGX for the treatment of VLUs is dominant compared with saline solution in the UK with expected cost-savings within a year and improved patient outcomes.     

基于植物代谢组学方法的天竺黄天然品与合成品间化学成分差异研究

目的应用超高效液相色谱-四级杆串联飞行时间质谱(UPLC-Q-TOF-MS)研究天竺黄天然品与合成品间化学成分差异。方法结合在线数据库、二级碎片裂解规律等进行化学成分定性分析;并采用PeakView软件Enhance Peak Find功能进行差异性分析;将转换后数据导入SIMCA-P软件,建立OPLS-DA统计模型,进行差异性次生代谢产物分析。结果天竺黄的成分类别主要包括氨基酸、有机酸、生物碱、糖苷类等,其中11个已知成分被检出,未曾报道的化合物达43个;分析鉴定出2,5-二甲基-1,3-氧唑-4-羧酸、蔗糖等14个显著差异性成分及4-(庚氧基)苯基-4-(己氧基)苯甲酸酯、N-十二烷基乙醇胺等12个生物标志物。结论研究发现天竺黄天然品与合成品间化学差异明显,甜菜碱和蔗糖可作为区分两者的鉴别指标,为天竺黄质量控制及药效物质阐明提供新的思路和数据参考。