Electron Microscopic Characterization of Lipoproteins from Patients with Familial Type III Hyperlipoproteinaemia

The lipoproteins of very low density, low density and intermediate density were isolated by zonal ultracentrifugation from the plasma of subjects with familial type III hyperlipoproteinaemia and studied by electron microscopy. Each of these lipoproteins exhibited a spherical shape when free-standing. The very low density, low density and intermediate density lipoproteins ranged in diameter from 31 - 80, 17 - 23, and 21 - 35 nm, respectively. These results are consistent with, our previous findings that the intermediate density lipoprotein particles characteristic of plasma from type III subjects exhibit properties which are intermediate between those of very low density and low density lipoproteins.     

慢性阻塞性肺疾病患者IGF-1水平变化及其与肺功能、骨密度的关系

目的:探讨慢性阻塞性肺疾病患者血清胰岛素样生长因子1(IGF-1)、生长激素(GH)水平变化并分析IGF-1水平与肺功能、骨密度之间的关系。方法:选择病情稳定的COPD患者70例,健康体检者35例,检测所有受试者血清IGF-1水平、GH水平及肺功能,同时测定COPD患者的骨密度(BMD)。COPD组进一步根据肺功能结果分为轻中度、重度、极重度三组,根据骨密度结果分为骨质疏松、低骨量、正常骨密度组。结果:COPD患者血清IGF-1水平明显低于对照组(P0.01﹚,GH水平与对照组比较差异无统计学意义。肺功能分组比较中,仅极重度组与健康对照组IGF-1水平比较差异具有统计学意义(P0.01),GH水平各组间两两比较均无显著性差异(P均0.05)。骨密度分组比较中,各组间IGF-1水平差异无统计学意义(P均0.05)。在相关分析中,COPD患者log IGF-1与L_1、L_2、L_3、L_4、左侧股骨干的BMD值呈直线正相关。结论 :COPD患者血清IGF-1水平降低,但其水平下降主要发生在极重度患者中,GH水平则无明显变化,IGF-1水平可能与气流受限程度有关;COPD患者血清IGF-1水平与L_1、L_2、L_3、L_4、左侧股骨干的BMD值存在相关性。     

定量CT评估1型糖尿病患者股骨骨密度和骨强度

[目的] 采用定量CT评估1型糖尿病患者股骨骨密度和骨强度,并探讨其与胰岛素样生长因子-1(IGF-1)的相关性.[方法] 选择本院收治的25例1型糖尿病患者为观察组,选择同期在本院健康体检的25例健康者为对照组.通过三维定量CT计算股骨不同部位体积骨密度(vBMD)和骨强度,检测血清IGF-1、骨特异性碱性磷酸酶(B-ALP)、骨钙素(sOC)、Ⅰ型前胶原氨基端肽(PⅠNP),分析1型糖尿病患者股骨骨密度和骨强度与IGF-1之间的相关性.[结果] 与对照组比较,观察组股骨颈皮质vBMD明显降低[(582.5±27.7) mg/cm3 vs (558.1± 31.9) mg/cm3,P<0.05] ;股骨粗隆总vBMD、皮质厚度和皮质横截面积显著降低[(258.4 ± 42.9) mg/cm3 vs(223.7± 27.3)mg/cm3;(3.3 ± 0.7)mm vs(2.8 ± 0.5)mm;(5.3 ± 1.2)cm2 vs (4.3 ± 0.5)cm2;均P<0.01] .与对照组比较,观察组屈曲比(BR)显著增加[(10.8 ±1.8) vs(12.9±1.9), P<0.01] .观察组和对照组血清B-ALP、sOC、PⅠNP水平比较,差异无统计学差异(P>0.05).血清IGF-1与1型糖尿病患者股骨颈总vBMD呈显著正相关性(r=0.48;P<0.05).[结论] 定量CT发现1型糖尿病患者股骨粗隆间vBMD、皮质横截面积和皮质厚度较低,血清IGF-1水平可显著影响1型糖尿病患者股骨颈总vBMD.     

Variation in serum type III procollagen peptide with age in healthy subjects and its comparative value in the assessment of disease activity in children and adults with chronic active hepatitis

To determine the comparative value of serum Type III procollagen peptide (PIIIP) in paediatric and adult liver disease we have measured PIIIP in 201 healthy subjects (aged 1 day-77 years) and twenty-one children and five adults with chronic active hepatitis (CAH). Healthy children had significantly higher PIIIP levels than adults (P less than 0.001), with highest values of 298 +/- 88 ng ml-1 (s.d.) in the neonatal period. PIIIP fell to 30.9 +/- 7.0 by 1 year, 19.1 +/- 4.5 by 3 years and rose significantly (P less than 0.01) at puberty. Adult levels (8.3 +/- 3.2) occurred by 16 years of age. Serum PIIIP levels were significantly elevated (P less than 0.001) in adults when they had biochemical and histological evidence of active liver disease but were consistently within the normal range for age in 70% of children with similar hepatic pathology. The minor elevations in PIIIP in the other children were unrelated to clinical, biochemical or histological evidence of active liver disease. While raised PIIIP may be a non-invasive marker of liver disease activity in adults, its value in childrens' disorders appears to be limited by the high levels of PIIIP which occur during growth.     

2型糖尿病合并非酒精性脂肪性肝病患者血浆脂肪细胞特异性脂肪酸结合蛋白水平的分析

目的研究2型糖尿病（type 2diabetes mellitus,T2DM）合并非酒精性脂肪性肝病（non-alcoholic fattyliver disease,NAFLD）患者血浆脂肪细胞特异性脂肪酸结合蛋白（adipocyte-specific fatty acid-binding protein,A-FABP）的水平及其相关因素。方法 2009年10月～2010年10月选取T2DM合并NAFLD组（A组）60例,未合并NAFLD组56例（B组）为研究对象。测定体质量指数（body mass index,BMI）,检测血脂、糖化血红蛋白（hemoglobinA1c,HbA1c）等生化指标。放射免疫法测定空腹胰岛素（fasting insulin,FINS）,空腹C肽水平（fasting C-peptide,FCP）,计算胰岛素抵抗指数（homeostasis model of assessment-insulin resistance,HOMA-IR）、胰岛素敏感指数（insulin sensitivity index,ISI）,测定A-FABP、C反应蛋白（C-reaction protein,CRP）及肿瘤坏死因子-α（tumor necrosisfactor-α,TNF-α）。结果与B组患者相比,A组患者其血浆A-FABP水平、BMI、腰围、腰臀比、丙氨酸氨基转移酶、门冬氨酸氨基转移酶、CRP、TNF-α、FCP、FINS、总胆固醇、甘油三酯、Ln（HOMA-IR）升高,Ln（ISI）降低,差异有统计学意义（P〈0.05）;两组HbA1c差异无统计学意义（P〉0.05）。A-FABP水平变化与TNF-α、HOMA-IR、CRP呈正相关,与ISI呈负相关。结论 T2DM伴NAFLD中,A-FABP升高与胰岛素抵抗是并存的,且存在明显相关关系,二者在疾病的发生发展中均可能具有重要的作用。     

2型糖尿病患者糖化血红蛋白水平与红细胞变形能力的相关性研究

目的 探讨2型糖尿病患者不同糖化血红蛋白水平与红细胞变形能力的相关性.方法 选取2型糖尿病患者90例为实验组,根据糖化血红蛋白水平分为≤6.5%、6.5%～8.5%、≥8.5%三组;选取体检健康者30名为对照组.测定不同糖化血红蛋白水平的红细胞变形指数及红细胞聚集指数,以红细胞变形指数表示红细胞变形能力.结果 2型糖尿病患者糖化血红蛋白〉6.5%时红细胞变形指数显著降低（P＜0.05）,红细胞聚集指数显著升高（P＜0.05）,红细胞变形指数随着糖化血红蛋白的升高逐步降低（P＜0.05）,红细胞聚集指数随着糖化血红蛋白的升高逐步升高（P＜0.05）.结论 2型糖尿病患者红细胞变形能力在糖化血红蛋白＞6.5%时开始下降,并随着糖化血红蛋白的升高逐步降低.     

Diagnostic Power of Longitudinal Strain at Rest for the Detection of Obstructive Coronary Artery Disease in Patients with Type 2 Diabetes Mellitus

Global longitudinal strain (GLS) measured by 2-D speckle-tracking echocardiography (2-D STE) at rest has been recognized as a sensitive parameter in the detection of significant coronary artery disease (CAD). However, the diagnostic power of 2-D STE in the detection of significant CAD in patients with diabetes mellitus is unknown. Two-dimensional STE features were studied in total of 143 consecutive patients who underwent echocardiography and coronary angiography. Left ventricular global and segmental peak systolic longitudinal strains (PSLSs) were quantified by speckle-tracking imaging. In the presence of obstructive CAD (defined as stenosis ≥75%), global PSLS was significantly lower in patients with diabetes mellitus than in patients without (16.65 ± 2.29% vs. 17.32 ± 2.27%, p < 0.05). Receiver operating characteristic analysis revealed that global PSLS could effectively detect obstructive CAD in patients without diabetes mellitus (cutoff value: –18.35%, sensitivity: 78.8%, specificity: 77.5%). However, global PSLS could detect obstructive CAD in diabetic patients at a lower cutoff value with inadequate sensitivity and specificity (cutoff value: –17.15%; sensitivity: 61.1%, specificity: 52.9%). In addition, the results for segmental PSLS were similar to those for global PSLS. In conclusion, global and segmental PSLSs at rest were significantly lower in patients with both obstructive CAD and diabetes mellitus than in patients with obstructive CAD only; thus, PSLSs at rest might not be a useful parameter in the detection of obstructive CAD in patients with diabetes mellitus.     

2型糖尿病患者左室整体舒缩功能与HbA1c的相关性研究

【目的】应用实时三平面定量组织速度成像技术（Triplane‐QTVI）评价2型糖尿病（T2DM）患者左室功能,并探讨T2DM患者左室功能与糖化血红蛋白（HbA1c）的相关性。【方法】选取单纯T2DM患者50例（T2DM组）和正常体检者50例（对照组）,采用常规超声心动图、Triplane‐QTVI技术检测左室纵轴收缩、舒张功能;检测T2DM患者的HbA1c ,并探讨超声心动图参数与 HbA1c的相关性。【结果】两组左室射血分数（EF％）、左室短轴缩短率（FS％）、二尖瓣环收缩期均值速度（Sm ）及二尖瓣口舒张早期最大血流速率（E ）比较无统计学意义（ P ＞0．05）;T2DM组左房收缩期最大血流速率（A）、二尖瓣环舒张晚期均值速度（Am）、E／二尖瓣环舒张早期均值速度（Em）高于对照组,E／A、Em、Em／Am明显低于对照组（ P ＜0．01）。HbA1c与E／A呈线形负相关（ P ＜0．05）,与E／Em呈线形正相关（ P＜0．05）,与EF、FS、E、A、Sm、Am不相关性。【结论】Triplane‐QTVI能够准确评价T2DM患者左室纵轴收缩、舒张功能,T2DM患者左室舒张功能障碍早于收缩功能,HbA1c与左室舒张功能障碍相关。     

Plasma Concentrations of the Urate-Binding Alpha1–2-Globulin in Patients with Different Types of Primary Gout as Compared to Healthy Control Subjects

Abstract. The relationship between the plasma concentrations of the urate-binding alpha_1–2, globulin in patients with different types of primary gout and in healthy control subjects has been studied by an immuno-assay method based on diffusion in antibody-agar plates. Plasma from 33 different individuals was investigated including healthy control subjects, asymptomatic, normouraemic subjects from a gouty kindred previously shown to have reduced plasma urate-binding capacities, patients with and without an incomplete hypoxanthine-guanine-phosphoribosyl-transferase (PRT) deficiency associated with gout, as well as one case of LeschNyhan syndrome and one case of xanthinuria. In gouty subjects previously demonstrated to have a reduced urate-binding capacity and in their asymptomatic relatives with this defect the plasma concentrations of the urate-binding alpha_1–2 globulin were reduced to 25% of the values found in healthy control subjects. This protein deficiency could hardly result from hyperuricaemia as protein concentrations within normal limits were found in three subjects with gout associated with an incomplete PRT-deficiency as well as in the case of LeschNyhan syndrome. The finding of a normal protein concentration in these last cases further indicates that the urate-binding alpha_1–2 globulin deficiency may represent an additional modality in which the pathogenetic heterogeneity in primary gout can be expressed.     

糖尿病、冠心病患者ABCA1基因R219K多态性的频率分布特点

目的旨在探讨我国北方地区汉族人ABCA1基因R219K多态性的频率分布特点,对血脂水平的影响,及其与冠心病、糖尿病和糖尿病合并冠心病的关系。方法采用改良碘化钠法提取基因组DNA,聚合酶链反应限制性片段长度多态性（PCR-RFLP）法分析ABCA1基因R219K多态性。结果正常对照组ABCA1基因R219K多态性RR、RK、KK基因型频率、R等位基因频率、K等位基因频率分别为28.5%、48.6%、22.9%、52.8%、47.2%;糖尿病组分别为29.6%、63.9%、6.5%、61.5%、38.5%;冠心病组分别为44.7%、44.7%、10.6%、67.0%、33.0%;糖尿病合并冠心病组分别为30.5%、61.9%、7.6%、61.4%、38.6%。疾病组ABCA1基因R219K多态性基因型分布与对照组有显著差异。结论 ABCA1基因R219K多态性极大的影响了血清HDL-C水平,K等位基因携带者HDL-C水平明显高于RR基因型。糖尿病组、冠心病组和糖尿病合并冠心病组ABCA1基因R219K多态性基因型分布与正常对照组有显著差异。K等位基因与冠心病的患病风险有一定关系。     

Studies on the Metabolic Clearance Rate, Apparent Distribution Space and Plasma Half-Disappearance Time of Unlabelled Human Growth Hormone in Normal Subjects and in Patients with Liver Disease, Renal Disease, Thyroid Disease and Diabetes Mellitus

Abstract. The metabolic clearance rate (MCR), half-disappearance time (T½ and apparent distribution space (DS) of unlabelled human growth hormone (HGH) have been studied using the priming dose – constant infusion technique. In 11 normal subjects MCR averaged 2.99 ml/kg/min., T½ 19.0 min. and DS 79.3 ml/kg. There were no differences between males and females and MCR was constant at HGH levels ranging from 5 to 50 ng/ml. In 10 out of 17 patients with chronic liver disease of varying severity MCR/kg was reduced below the lower limit of normal. TV₂ was prolonged in 15 of these patients. There was a very close correlation between MCR/kg and DS/kg in liver disease (r = 0.8219). Increased DS/kg accounted for the normal MCR/kg seen in some patients with severe hepatocellular failure. MCR/kg was markedly reduced in three patients'with chronic renal failure. T7₂ and DS/kg were both significantly increased in this group (48.0 min. and 117.0 ml/kg, respectively). MCR/kg and T7₂ were normal in one patient with the nephrotic syndrome but normal glomerular filtration rate. MCR/kg was not significantly different from normal in patients with thyrotoxicosis, myxoedema and uncontrolled diabetes mellitus, despite the fact that T½ shorter than normal in thyrotoxicosis and longer than normal in myxoedema. It is suggested that HGH does not normally diffuse freely from the vascular to extravascular extracellular fluid, and that normally a substantial concentration gradient exists between the vascular and extravascular compartments; under these circumstances, the liver and kidneys are the major sites of HGH metabolism. In hepatic and renal failure, this gradient is reduced and extravascular degradation sites may assume more importance in the metabolism of growth hormone. Acute fluctuations in the peripheral blood concentrations of growth hormone indicate alterations in secretion rate and not alterations in metabolism.     

The PRIMAVERA study protocol design: Evaluating the effect of continuous erythropoiesis receptor activator (C.E.R.A.) on renal function in non-anemic patients with chronic kidney disease

Erythropoiesis stimulating agents (ESA) are widely used for hemoglobin correction in patients suffering from renal anemia. However, their beneficial non-hematopoietic effects on renal deterioration have not been adequately assessed. The Primavera study is the first prospective, controlled trial to assess whether ESA treatment could ameliorate progression of chronic kidney disease (CKD) in non-anemic patients. Primavera is a single-blind, 24-month trial in which patients are randomized to placebo or to C.E.R.A., a continuous erythropoietin receptor activator. Patients with type 2 diabetes or who have undergone kidney transplantation are eligible to enter the study if they have CKD stage III (estimated GFR [eGFR] 30–59 mL/min/1.73 m²), urinary albumin to creatinine ratio (UACR) ≥ 50 g/g and ≤ 1500 g/g, or total urine protein ≥ 50 mg/24 h and ≤ 1500 mg/24 h, and hemoglobin 11–14 g/dL. The primary efficacy endpoint is the change in eGFR from baseline to month 24. Secondary efficacy endpoints are the changes in UACR, serum cystatin C and serum creatinine from baseline. Safety endpoints include adverse events and discontinuation due to pre-specified adverse events. An interim analysis will be performed after all patients have completed the first year. The planned sample size is 400 patients (200 type 2 diabetics, 200 transplant recipients) conferring 90% power to detect a prespecified significant difference of 1.5 mL/min/1.73 m² in the annual reduction in eGFR between treatment groups. The results of Primavera are expected in 2013.