The future of proteomics in the study of alcoholism

This article represents the proceedings of a workshop at the 2003 annual meeting of the Research Society on Alcoholism in Fort Lauderdale, FL. The workshop organizers/chairpersons were Chinnaswamy Kasinathan and Paul Manowitz. The presentations were (1) Introduction to the field of proteomics, by Kent Vrana; (2) Use of proteomics in the identification of urinary biomarkers for alcohol intake, by Chinnaswamy Kasinathan, Paul Thomas, and Paul Manowitz; (3) Proteomics screening illuminates ethanol-mediated induction of HDL proteins in macaques, by Kent Vrana, Randy Gooch, Travis Worst, Stephen Walker, Aaron Xu, Peter Pierre, Heather Green, and Kathleen Grant; and (4) Proteomics applied to the study of the liver, by Laura Beretta.     

Familial homozygous hypobetalipoproteinemia

An apparently new form of abetalipoproteinemia, homozygous hypobetalipoproteinemia, was studied in progeny of a mating of two parents each heterozygous for familial hypobetalipoproteinemia, which was characterized by three-generation vertical transmission on both maternal and paternal sides of the family. The two children, with an apparent homozygous form of hypobetalipoproteinemia, had, in addition to abetalipoproteinemia, acanthocytosis, intestinal etpithelial and hepatic steatosis and steatorrhea. No low desity lipoprotein (LDL) was detected by immunodiffusion with antisera to LDL or apoLDL. The defects in apolipoproteins in these two children were the same as those reported in children with abetalipoproteinemia inherited as an autosomal recessive trait. The genetic defect of hypobetalipoproteinemia, when homozygous, can lead to all of the known clinical and biochemical features of abetalipoproteinemia.     

Association of Epicardial Adipose Tissue With Progression of Coronary Artery Calcification Is More Pronounced in the Early Phase of Atherosclerosis: Results From the Heinz Nixdorf Recall Study

ObjectivesThis study sought to determine whether epicardial adipose tissue (EAT) volume predicts the progression of coronary artery calcification (CAC) score in the general population.BackgroundEAT predicts coronary events and is suggested to influence the development of atherosclerosis.MethodsWe included 3,367 subjects (mean age 59 ± 8 years; 47% male) from the population-based Heinz Nixdorf Recall study without known coronary artery disease at baseline. CAC was quantified from noncontrast cardiac electron beam computed tomography at baseline and after 5 years. EAT was defined as fat volume inside the pericardial sac and was quantified from axial computed tomography images. Association of EAT volume with CAC progression (log[CAC(follow-up) + 1] − log[CAC(baseline) + 1]) was depicted as percent progression of CAC + 1 per SD of EAT.ResultsSubjects with progression of CAC above the median had higher EAT volume than subjects with less CAC change (101.1 ± 47.1 ml vs. 84.4 ± 43.4 ml; p < 0.0001). In regression analysis, 6.3% (95% confidence interval [CI]: 2.3% to 10.4%; p = 0.0019) of progression of CAC + 1 was attributable to 1 SD of EAT, which persisted after adjustment for risk factors (6.1% [95% CI: 1.2% to 11.2%]; p = 0.014). For subjects with a CAC score of >0 to ≤100, progression of CAC + 1 by 20% (95% CI: 11% to 31%; p < 0.0001) was attributable to 1 SD of EAT. Effect sizes decreased with CAC at baseline, with no relevant link for subjects with a CAC score ≥400 (0.2% [95% CI: −3.5% to 4.2%]; p = 0.9). Likewise, subjects age <55 years at baseline showed the strongest association of EAT with CAC progression (20.6% [95% CI: 9.7% to 32.5%]; p < 0.0001). Interestingly, the effect of EAT on CAC progression was more pronounced in subjects with low body mass index (BMI), and decreased with degree of adiposity (BMI ≤25 kg/m²: 19.8% [95% CI: 9.2% to 31.4%]; p = 0.0001, BMI >40 kg/m²: 0.8% [95% CI: −26.7% to 38.9%]; p = 0.96).ConclusionsEAT is associated with the progression of CAC, especially in young subjects and subjects with low CAC score, suggesting that EAT may promote early atherosclerosis development.     

2017年北京市成年人睡眠与血清TG/HDL-C的关联性研究

背景　血清三酰甘油（TG）与高密度脂蛋白胆固醇（HDL-C）的比值（TG/HDL-C）是系统性反映血脂水平的指标,不良的睡眠状况可能是血脂异常的危险因素,探索睡眠问题对TG/HDL-C的影响并识别危险人群,有助于有针对性地通过改善睡眠减少血脂异常的发生。目的　了解2017年北京市成年人睡眠问题现状及其与血清TG/HDL-C的关联,旨在为改善睡眠质量及控制血脂水平提供依据。方法　数据来源于2017年北京市成年人慢性病与危险因素监测,在北京市16区采用多阶段分层整群抽样方法抽取18~79岁常住居民,收集调查对象年龄、性别、婚姻状况、受教育程度等人口学信息,高血压、糖尿病、血脂异常等慢性病患病情况,吸烟、饮酒等生活行为方式,睡眠时长及打鼾/窒息、入睡困难、中间觉醒≥2次、早醒、服用安眠药等睡眠问题,测量身高、体质量、腰围、血压,抽取空腹静脉血进行血脂四项检测。采用t检验、非参数Kruskal-Wallis H检验、Mann-Whitney U检验、χ2检验、多因素Logistic回归分析睡眠与TG/HDL-C的关联。结果　13 240例调查对象平均年龄为（44.79±15.47）岁,平均睡眠时长为（7.47±1.30）h/d,中位TG/HDL-C为0.99（0.84）,6 490例（49.02%）30 d内存在睡眠问题。睡眠处于9 h/d者TG/HDL-C水平最低,中位数为0.95（0.82）,不同睡眠时长的女性人群TG/HDL-C比较,差异有统计学意义（χ2=37.14,P<0.01）。按是否存在睡眠问题进行分组,组间TG/HDL-C水平比较,差异有统计学意义（P<0.01）。在控制性别、年龄、婚姻状况、城乡、受教育程度、现在吸烟、30 d内饮酒、身体活动不足、高血压、糖尿病、BMI等协变量之后,多因素Logistic回归分析结果显示,存在≥1种睡眠问题是TG/HDL-C升高的影响因素〔OR（95%CI）=1.05（1.01,1.08）〕;相比于无睡眠问题的人群,男性或18~44岁人群存在≥1种睡眠问题是高TG/HDL-C的影响因素〔OR男（95%CI）=1.05（1.01,1.09）;OR18~44岁（95%CI）=1.06（1.01,1.10）〕。结论　北京市18~79岁成年人睡眠时长过长或过短,打鼾/窒息/入睡困难、服用安眠药等睡眠问题可能影响血清TG/HDL-C,男性及45岁以下人群作为高危人群应采取改善睡眠的措施。     

Phloroglucinol averts isoprenaline hydrochloride induced myocardial infarction in rats

Myocardial infarction (MI) is indicated by the symptoms like sharp chest pain, sweating, palpitations, and nervousness finally leading to heart attack. MI occurs mainly due to the risk factors like smoking, elevated blood pressure, diabetes, hypercholesterolemia, obesity, decreased HDL level, elevated LDL level, hyperlipoproteinemia and aging consequently leads to demandable coronary blood supply, oxidative stress, and acute necrosis of the myocardium. Cardioprotective potential of the phloroglucinol (PG) was assessed by treating isoprenaline hydrochloride (ISO; 85 mg/kg b.w., s.c.) induced MI model in rats. Pretreatment with PG in a dose of 30 mg/kg was done for 28 days and followed by ISO (for MI induction) on 29th and 30th days, exhibited decline in the abnormalities in the ECG patterns, cardiac marker enzymes, enzymic and nonenzymic antioxidants, lipid peroxidation, lipid profiles, and histopathological investigations compared to isoprenaline alone treated group. On the whole, the present investigations elucidate the significance of PG in alleviating the pathological process and appreciably prevent the induction of MI in experimental rats.     

D-dimer relates positively with increased blood pressure in black South Africans: The SABPA study

Introduction

Hypertension is highly prevalent in black South Africans in which morbidity and mortality from stroke are on the increase. Elevated blood pressure and haemostatic markers can induce changes in blood rheology and endothelial function which could result in a procoagulant state that increases the risk for cerebrovascular disease. Information about the coagulation and fibrinolytic systems of people from African descent are limited. We therefore, investigated the haemostatic profile and its relationships with blood pressure in black South Africans.

Materials and methods

We measured ambulatory blood pressure and haemostatic markers of 201 black and 208 white school teachers. The haemostatic markers included measurements representing coagulation and fibrinolysis (von Willebrand factor, fibrinogen, plasminogen activator inhibitor-1, fibrin D-dimer and clot lysis time).

Results

Black participants displayed significantly higher blood pressure, von Willebrand factor, fibrinogen, plasminogen activator inhibitor-1 and D-dimer levels and longer clot lysis times (p ≤ 0.001). Single, partial and multiple regression analyses showed that systolic (p ≤ 0.011) and diastolic blood pressure (p = 0.010) correlated positively with D-dimer in black participants, while systolic (p ≤ 0.001) and daytime diastolic blood pressure (p = 0.011) correlated negatively with clot lysis time in white participants.

Conclusion

The black population had a more prothrombotic profile, with higher levels of coagulation markers and inhibited fibrinolysis, than the white study participants. The positive association between blood pressure and elevated D-dimer in the blacks may contribute to the high prevalence of hypertension and related increased cardiovascular and cerebrovascular risk in this group.     

A case for immediate-release niacin

Niacin is currently a favored drug for increasing high-density lipoprotein, especially in patients with ischemic heart disease or at high risk of developing it. In addition, niacin further decreases low-density lipoprotein in statin-treated patients and has been shown to reduce morbidity and mortality. Among the available niacin preparations, crystalline, immediate-release niacin is the most effective for increasing high-density lipoprotein and is relatively free of hepatic toxicity. We present the case of a patient who had an excellent clinical and laboratory response to 3 g daily of immediate-release niacin, but who later developed clinical hepatitis when he inadvertently switched to the same dose of slow-release niacin. We encourage the use of niacin in general, immediate-release niacin in particular, and caution that niacin is a drug and not a dietary supplement. We also present practical steps for starting niacin, including close patient contact and support, and beginning with a therapeutic dose of 2 g per day right from the start.