Ileal adenocarcinoma in a mild phenotype of abetalipoproteinemia

Abetalipoproteinemia (ABL) is a rare autosomal recessive disorder that is characterized by defective assembly and secretion of plasma apolipoprotein (apo) B-containing lipoproteins. This disorder results from mutations in the MTP gene encoding the microsomal triglyceride transfer protein. We report a 58-year-old male homozygote for a missense mutation, S590I, in MTP. The patient had a lifelong history of fat malabsorption, but was only diagnosed with ABL at age 52, based upon such classic features as absence of apo B-containing lipoproteins, acanthocytosis, atypical retinitis pigmentosa and markedly depressed serum beta-carotene concentration. However, his presentation was notable not only by survival to the sixth decade of life without specific treatment, but also by the absence of neurological involvement and by normal serum vitamin E concentration. He subsequently developed adenocarcinoma of the ileum, which required ileal resection. Therefore, this missense mutation appears to be associated with a late-presenting and relatively mild ABL phenotype that lacks some classical features, particularly neuropathy, but appears to be associated with other atypical features, specifically small intestinal cancer.     

Smoking influences the atherogenic potential of low-density lipoprotein

Summary The possible influence of smoking on the low-density lipoprotein (LDL) and its biological activity was investigated. Plasma LDL was prepared from healthy male smokers and nonsmokers, and oxidized with Cu (11) as prooxidant. Oxidized LDL from smokers generated significantly more lipidperoxidation products, so-called thiobarbituric acid reactive substances (TBARS), when compared to oxidized nonsmoker LDL. Analysis of vitamin E levels in LDL obtained from both smokers and nonsmokers revealed that the vitamin E content of smoker LDL was significantly less than that of nonsmoker LDL. The amounts of cholesteryl esters formed in cultured P388. D.1 macrophages were greater in the presence of smoker LDL than with nonsmoker LDL. The data suggest that some of the proatherogenic effects of smoking may be related to oxidative modification of LDL and alteration of its biological activity.Abbreviations CE cholesterol ester - FC free cholesterol - FCS fetal calf serum - HPLC high performance liquid chromatography - LDL low-density lipoprotein - MDA malondialdehyde - PUFA polyunsaturated fatty acid - SD standard deviation - TBA thiobarbituric acid - TBARS thiobarbituric acid reactive substances - TLC thin-layer chromatography     

Effects of apoE gene polymorphism on Lp(a) concentrations depend on the size of apo(a): a study of 466 white men

 Polymorphisms in the genes for the low-density lipoprotein (LDL) receptor ligands, apolipoprotein E (apoE), and apolipoprotein B (apoB) are associated with variation in plasma levels of LDL cholesterol. Lp(a) lipoprotein(a) [Lp(a)] is LDL in which apoB is attached to a glycoprotein called apolipoprotein(a) [apo(a)]. Apo(a) has several genetically determined isoforms differing in molecular weight, which are inversely correlated with Lp(a) concentrations in blood. The interaction of apo(a) with triglyceride-rich lipoproteins differs with the size of apo(a), and therefore the effects of apoE gene polymorphism on Lp(a) levels could also depend on apo(a) size. We have investigated the possible effect of genetic variation in the apoE and apoB genes on plasma Lp(a) concentrations in 466 white men with different apo(a) phenotypes. Overall there was no significant association between the common apoE polymorphism and Lp(a), but in the subgroup with apo(a)-S4, concentrations of Lp(a) differed significantly among the apoE genotypes (P=0.05). Lp(a) was highest in the apoE genotypes ɛ₂ɛ₃ and ɛ₃ɛ₃ and lowest in genotype ɛ₃ɛ₄, and the apoE polymorphism was estimated to account for about 2.4% of the variation in Lp(a). In contrast, in the subgroup with apo(a)-S2 Lp(a) was significantly lower (P=0.04) in apoE genotype ɛ₂ɛ₃ than in genotype ɛ₃ɛ₃. Lp(a) concentrations did not differ among the XbaI (P=0.65) or SP 24/27 (P=0.26) polymorphisms of the apoB gene. The expected effects of both apoE and apoB polymorphism on LDL levels were significant in the whole population sample and in subjects with large-sized apo(a) isoforms (P<0.01), whereas no effect was seen in those with low molecular weight apo(a) isoforms. We conclude that the influence of apoE genotypes on Lp(a) concentrations depends on the size of the apo(a) molecule in Lp(a), possibly because both apo(a)-S4 and apoE4 have high affinity for triglyceride-rich lipoproteins and may be taken up and degraded rapidly by remnant receptors. Received: 12 January 1995 / Accepted: 12 July 1996     

郑州地区1180例儿童维生素A、D、E水平研究

目的 了解郑州地区儿童维生素的水平,为临床诊治提供参考.方法 以2016年3月至12月期间在郑州大学第三附属医院儿科门诊健康体检的儿童为研究对象,测量血清25羟维生素D[25(OH)D]、维生素A、E的水平.结果 1180名儿童中,男童755例,女童425例,维生素A平均水平0.22±0.07 mg/L,总体缺乏率为45.34％;维生素D平均水平为64.25±19.65 nmol/L,总体缺乏率为30.51％;维生素E平均水平为4.95±1.64 mg/L,总体缺乏率为51.10％.男童和女童血清维生素E水平差异具有统计学意义(P＜0.05);郑州市城乡儿童三种血清维生素水平差异均具有统计学意义(P＜0.05).结论 儿童维生素的水平缺乏情况,应引起我们的重视,尤其是维生素E,城乡儿童仍然需要进行及时的维生素补充,以预防儿童维生素缺乏症及其并发症的发生.     

Response of lipid, lipoprotein-cholesterol, and electrophoretic characteristics of lipoproteins following a single bout of aerobic exercise in women

The effects of a single session of moderate intensity (65% VO(2)max) aerobic exercise expending 500 kcal of energy on serum lipid and lipoprotein-cholesterol concentrations and the electrophoretic characteristics of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) particles were determined in 11 sedentary, eumenorrheic, premenopausal women immediately prior to, and 24 and 48 h following exercise. Repeated measures analysis of variance revealed significant reductions in triglyceride (25.0%), HDL-cholesterol (10.9%), and HDL(3)-cholesterol (11.9%) concentrations at 48 h post-exercise. Despite these changes in lipid and lipoprotein-cholesterol concentrations, no significant changes were observed in peak LDL or HDL particle sizes or in the distribution of cholesterol within the LDL and HDL subfractions. Accordingly, it appears that a single session of moderate intensity aerobic exercise expending 500 kcal (2,092 kJ) of energy promotes reductions in triglyceride, HDL-C, and HDL(3)-C concentrations without concomitantly affecting the electrophoretic characteristics of LDL and HDL particles in this sample of women.     

A lipidologist perspective of global lipid guidelines and recommendations,part 2: Lipid treatment goals

Having knowledge of worldwide areas of harmonization and consensus regarding lipid guidelines and recommendations may provide clinicians a more global perspective on lipid management. This review examines 8 international scientific/medical organizations that have issued lipid guidelines, recommendations, and position papers: the National Lipid Association (2014), National Institute for Health and Care Excellence (2014), International Atherosclerosis Society (2013), American College of Cardiology/American Heart Association (2013), Canadian Cardiovascular Society (2013), Japan Atherosclerosis Society (2012), European Society of Cardiology/European Atherosclerosis Society (2012), and Adult Treatment Panel III (2001/2004). Part 1 of this perspective focused on sentinel components of these lipid guidelines and recommendations as applied to the role of atherogenic lipoprotein cholesterol levels, primary lipid target of therapy, other primary and secondary lipid treatment targets, and assessment of atherosclerotic cardiovascular disease (ASCVD) risk. This part 2 examines goals of lipid-altering therapy. While lipid guidelines and recommendations may differ regarding ASCVD risk assessment and lipid treatment goals, lipid guidelines and recommendations generally agree on the need to reduce atherogenic lipoprotein cholesterol levels, with statins being the first-line treatment of choice.     

补充VA、VE对梭曼中毒大鼠体内抗氧化能力影响的初探

目的 研究梭曼对急性中毒大鼠的自由基损伤作用,探讨维生素A、E的抗氧化作用。方法 雄性大鼠,随机分为对照组、阳性组、VA组、VE组。灌胃10d,第11d除阴性组外其余各组大鼠均皮下注射0．9LD50梭曼,2h后取样,测定各组全血和肝组织的谷胱甘肽过氧化物酶（GSH－Px)、过氧化氢酶（CAT）、VE和总抗氧化力（T－AOC）。结果 梭曼中毒2h后,GSH－Px活性、T－AOC水平、VE含量降低。维生素A、E均有效的抑制其变化。结论 梭曼对大鼠有自由基损伤作用,维生素A、E对梭曼中毒大鼠过氧化损伤具有保护作用,提示维生素A、E对梭曼中毒有预防作用。     

Recurrent Pregnancy Loss and Apolipoprotein E Gene Polymorphisms: A Case–Control Study from North India

Citation Agarwal M, Parveen F, Faridi RM, Phadke SR, Das V, Agrawal S. Recurrent pregnancy loss and apolipoprotein E gene polymorphisms: a case–control study from North India. Am J Reprod Immunol 2010; 64: 172–178 Problem The role of apolipoprotein E gene polymorphisms in the etiology of recurrent pregnancy loss (RPL) is not clearly understood. We evaluated this polymorphism in unexplained pregnancy losses among North Indian women. Method of study In a retrospective case–control study, 200 well‐characterized RPL cases were examined for their APO‐E genotypes based on restriction fragment length polymorphism analysis of PCR‐amplified fragments including amino acid positions 112 and 158. The observed genotypes were compared with those obtained from an equal number of ethnically matched negative controls. Results We found similar APO‐E genotypes and E2, E3, and E4 allele frequency distribution among RPL patients and controls. The allele frequencies obtained in patients and controls respectively were as follows: E2 = 7.5% and 9.0% (P = 0.52; OR = 0.81; 95%CI = 0.49–1.35), E3 = 89.7% and 90% (P = 1.00; OR = 0.97; 95%CI = 0.61–1.54), and E4 = 2.8% and 1% (P = 0.12; OR = 2.79; 95%CI = 0.88–8.86). Conclusions Our data did not support the association of APO‐E gene polymorphisms with recurrent pregnancy loss as reported by some of the previous studies. We endorse adequate characterization of RPL cases, inclusion of appropriate negative controls, and adequate sample size prior to addressing such studies.     

孕妇血清维生素A、维生素E、25-羟基维生素D与 子痫前期的相关性研究

目的 探讨孕妇血清维生素A、维生素E、25-羟基维生素D水平与子痫前期的相关性。方法 选择2016年3月~2017年10月在我院产检的单胎孕妇为研究对象,其中子痫前期组72例,健康对照组30例。分析血清维生素A、维生素E、25-羟基维生素D水平与子痫前期的相关性及其诊断价值。结果 在孕10~14周时,两组孕妇孕血清维生素A、维生素E 、25-羟基维生素D水平比较,差异无统计学意义（P＞0.05）;孕24~28周时,子痫前期组血清维生素A、维生素E 、25-羟基维生素D水平低于对照组水平（P＜0.05）;多因素Logistic回归分析结果显示,孕24~28周血清维生素A、维生素E、25-羟基维生素D水平与子痫前期发病具有显著的相关性;回归模型显示,血清维生素A诊断子痫前期的AUC为0.976,95%CI为0.931~1.000,当界值为0.46时,预测子痫前期发病的灵敏度为95.70%,特异度为72.50%;维生素E诊断子痫前期的AUC为0.820,95%CI为0.725~0.914,当界值为0.28时,预测子痫前期发病的灵敏度为76.70%,特异度为77.80%;25-羟基维生素D诊断子痫前期的AUC为0.789,95%CI为0.681~0.898,当界值为0.33时,预测子痫前期发病的灵敏度为73.30%,特异度为81.90%;血清维生素A+维生素E+25-羟基维生素D诊断子痫前期的AUC为0.988,95%CI为0.966~1.000。当界值为0.55时,预测子痫前期发病的灵敏度为96.70%,特异度为95.80%。结论 在孕10~14周时,血清维生素A、维生素E、25-羟基维生素D水平下降与子痫前期发病无关;在孕24~28周时,血清维生素A、维生素E、25-羟基维生素D水平下降与子痫前期发病显著相关,孕晚期血清维生素A、维生素E、25-羟基维生素D可作为子痫前期的关键指标。     

LRP1 expression in cerebral cortex,choroid plexus and meningeal blood vessels: Relationship to cerebral amyloid angiopathy and APOE status

APOE genotype is a risk factor for Alzheimer's disease (AD) and cerebral amyloid angiopathy (CAA). The risk and severity of CAA increase with possession of APOE ?4, whereas APOE ?2 increases the risk of vessel rupture. Uptake of Aβ by cerebrovascular smooth muscle cells (CVSMCs) is mediated by low-density lipoprotein receptor-related protein-1 (LRP1). To determine whether APOE influences CAA by altering LRP1 expression, particularly by CVSMCs, we analysed APOE genotype, CAA severity, and LRP1 levels in post-mortem cerebral cortex, choroid plexus and meningeal vessels. LRP1 mRNA and protein were not related to CAA severity and presence. LRP1 mRNA was increased in meningeal vessels, but not cortex or choroid plexus, in AD and in association with APOE ?4, and was decreased in association with APOE ?3. In brains with CAA, APOE ?2 was associated with decreased LRP1 protein in meningeal vessels, and ?3 with increased LRP1 in choroid plexus. These findings suggest that APOE may influence the severity of CAA through altered expression of LRP1.     

Vitamin B12 deficiency presenting as an acute confusional state: a case report and review of literature

Background

Vitamin B12 deficiency is associated with a wide spectrum of neuro-psychiatric manifestations.

Results

We report a case of a 44 year old female patient referred to the haematology unit with vitamin B12 deficiency presenting as an acute confusional state or delirium. Total resolution of the psychiatric symptoms occurred following parenteral vitamin B12 replacement therapy.

Conclusion

This case report highlights one of the neuro-psychiatric presentations of vitamin B12 deficiency in a previously healthy individual.     

DLPME-HPLC法同时测定人血清中维生素A和维生素E含量

目的 建立分散液相微萃取（DLPME）-高效液相色谱（HPLC）同时测定人血清中维生素A、E含量的方法。方法 2018年5月随机抽取人血液样本50例,经DLPME技术处理后,采用HPLC对人血清中维生素A、E含量进行检测,使用标准曲线法进行定量分析。结果 维生素A标准曲线方程为y=13225x+410.03,相关系数为0.9998,检出限为0.042 μg/ml;维生素E标准曲线方程为y=1383.9x-458.27,相关系数为0.9997,检出限为0.096 μg/ml。维生素A和维生素E的加标回收率分别为90.12%~103.70%和81.09%~92.21%,含量范围分别为（0.62±0.04）μg/ml和（8.41±0.43）μg/ml。结论 DLPME-HPLC法操作简便,节约试剂,对样本富集效率高,通过该方法的研究,对微量血清中维生素A和维生素E的测定具很好的的应用价值。     

Mutational analysis in UK patients with a clinical diagnosis of familial hypercholesterolaemia: relationship with plasma lipid traits, heart disease risk and utility in relative tracing

As part of a randomised trial [Genetic Risk Assessment for Familial Hypercholesterolaemia (FH) Trial] of the psychological consequences of DNA-based and non-DNA-based diagnosis of FH, 338 probands with a clinical diagnosis of FH (46% with tendon xanthomas) were recruited. In the DNA-based testing arm (245 probands), using single-strand conformation polymorphism of all exons of the low-density lipoprotein receptor (LDLR) gene, 48 different pathogenic mutations were found in 62 probands (25%), while 7 (2.9%) of the patients had the R3500Q mutation in the apolipoprotein B (APOB) gene. Compared to those with no detected mutation, mean untreated cholesterol levels in those with the APOB mutation were similar, while in those with an LDLR mutation levels were significantly higher (None=9.15±1.62 vs LDLR=9.13±1.16 vs APOB=10.26±2.07 mmol/l p<0.001, respectively). Thirty seven percent of the detected mutations were in exon 3/4 of LDLR, and this group had significantly higher untreated cholesterol than those with other LDLR mutations (11.71±2.39 mmol/l vs 9.88±2.44 mmol/l, p=0.03), and more evidence of coronary disease compared to those with other LDLR or APOB mutations (36 vs 13% p=0.04). Of the probands with a detected mutation, 54 first-degree relatives were identified, of whom 27 (50%) had a mutation. Of these, 18 had untreated cholesterol above the 95th percentile for their age and gender, but there was overlap with levels in the non-carrier relatives such that 12% of subjects would have been incorrectly diagnosed on lipid levels alone. In the non-DNA-based testing arm (82 probands) only 19 of the 74 relatives identified had untreated cholesterol above the 95th percentile for their age and gender, which was significantly lower (p<0.0005) than the 50% expected for monogenic inheritance. These data confirm the genetic heterogeneity of LDLR mutations in the UK and the deleterious effect of mutations in exon 3 or 4 of LDLR on receptor function, lipids and severity of coronary heart disease. In patients with a clinical diagnosis of FH but no detectable mutation, there is weaker evidence for a monogenic cause compared with relatives of probands with LDLR mutations. This supports the usefulness of DNA testing to confirm diagnosis of FH for the treatment of hyperlipidaemia and for further cascade screening.     

Therapy of severe familial heterozygous hypercholesterolemia by low-density lipoprotein apheresis with immunoadsorption: effects of the addition of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors to therapy

Summary To establish whether additional therapy with 3-hydroxy-3-methylglutaryl (HMG) coenzyme A (CoA) reductase inhibitors enhances the low-density lipoprotein (LDL) cholesterol lowering effect of LDL apheresis with immunoadsorption in the treatment of patients with familial heterozygous hypercholesterolemia and coronary artery disease we studied eight patients initially on immunoadsorption therapy alone for 3 years. The adding of HMG CoA reductase inhibitors decreased pretreatment LDL cholesterol from 6.76±0.98 to 4.97±0.98 mmol/l and posttreatment LDL cholesterol from 2.33±0.80 to 1.94±0.67 mmol/l and increased pre- and posttreatment high-density lipoprotein (HDL) cholesterol by 0.08 and 0.13 mmol/l respectively. The LDL/HDL ratio was reduced from 4.0 to 2.8 (prior to any therapy the ratio was 13.4). The increase in LDL cholesterol between weekly treatments was less steep under the combined therapy. At the same time the treated plasma volume during LDL apheresis could be decreased from 5070±960 to 4370±1200 1200 ml. We conclude that in patients with severe familial heterozygous hypercholesterolemia LDL apheresis should be combined with HMG CoA reductase inhibitors.Abbreviations CoA coenzyme A - HDL high-density lipoprotein - HMG 3-hydroxy-3-methylglutaryl - LDL low-density lipoprotein Dedicated to Prof. Dr. G. Paumgartner on the occasion of his 60th birthday     

A lipidologist perspective of global lipid guidelines and recommendations,part 1: Lipid treatment targets and risk assessment

Having knowledge of worldwide lipid guidelines and recommendations may provide clinicians a more global perspective on lipid management. This perspective reviews 8 international scientific and/or medical organizations' lipid guidelines, recommendations, and position papers: the National Lipid Association (2014), National Institute for Health and Care Excellence (2014), International Atherosclerosis Society (2013), American College of Cardiology/American Heart Association (2013), Canadian Cardiovascular Society (2013), Japan Atherosclerosis Society (2012), European Society of Cardiology/European Atherosclerosis Society (2012), and Adult Treatment Panel III (2001/2004). Part 1 of this perspective focuses on sentinel components of these lipid guidelines and recommendations as applied to the role of atherogenic lipoprotein cholesterol levels, primary lipid target of therapy, other primary and secondary lipid treatment targets, and assessment of atherosclerotic cardiovascular disease (ASCVD) risk. Part 2 examines goals of lipid-altering therapy to reduce ASCVD events. Both parts 1 and 2 include the author's perspective on sentinel topics. In general, some guidelines and recommendations differ with regard to ASCVD risk assessment and lipid treatment goals. However, lipid guidelines and recommendations have significant concordance regarding the need to reduce atherogenic lipoprotein cholesterol levels, and are in general agreement on the primary lipid treatment targets. Finally, a substantial degree of agreement exists among guidelines and recommendations in their emphasis on the need for aggressive treatment of hypercholesterolemia, for which the predominance of ASCVD outcomes studies suggests statins as the first-line treatment of choice.