Ethanol inhibits triglyceride synthesis and secretion by human small intestinal mucosa

We studied the effect of ethanol on human intestinal lipid absorption and on triglyceride synthesis and secretion. Human duodenojejunal biopsy specimens were incubated in a micellar lipid solution containing carbon 14-labeled oleate in the presence of ethanol 0.1%, 1.0%, and 5.0% (vol/vol). Tissue triglyceride synthesis was significantly decreased by 52.0% +/- 7.7%, 57.0% +/- 9.0%, and 81.3% +/- 4.0% (mean +/- SEM), respectively, when compared with triglyceride synthesis by control biopsy specimens incubated in the absence of ethanol. Tissue levels of oleate were increased in biopsy specimens incubated in the presence of ethanol by 90% +/- 30% and 115% +/- 5% for ethanol concentrations of 1.0% and 5.0% (vol/vol), respectively (P less than 0.02). At ethanol concentration of 0.01%, no change in tissue oleate or triglyceride levels was noted. The effect of 1.0% and 5.0% ethanol on triglyceride synthesis may reflect in large part their significant increase of the medium osmolarity. However, the osmolarity of the medium containing 0.1% ethanol was similar to that of the ethanol-free medium, and its effect is therefore probably specific. Duodenojejunal biopsy specimens were also preincubated for 30 minutes in a micellar lipid solution containing 14C-oleate, and subsequently were organ cultured in micellar-free medium in the presence or absence of ethanol 1.0% (vol/vol). During organ culture, the decrease in tissue oleate levels was similar in biopsy tissue cultured in the presence or absence of ethanol. However, in the presence of ethanol, triglyceride secretion to the organ culture medium was reduced by 49.9% +/- 11.1% (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Lipoprotein profiles in plasma and interstitial fluid analyzed with an automated gel-filtration system

BACKGROUND: High-quality methods for lipoprotein characterization are warranted in studies on various metabolic diseases. MATERIALS AND METHODS: An automated system for size-exclusion chromatography (SEC) of lipoproteins using commercially available components is described. Cholesterol or triglyceride content in separated lipoproteins from plasma and interstitial fluid (IF) was continuously determined on-line using microlitre sample volumes. RESULTS: The lipoprotein assay showed a good concordance with the classic ultra-centrifugation/precipitation technique using fresh or frozen samples. Determination of lipoproteins in IF obtained from vacuum-induced skin blisters from 18 healthy subjects revealed that very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol levels were 18%, 19% and 25%, respectively, of concomitant plasma concentrations. The size-exclusion chromatography (SEC) system also allows for triglyceride determination on-line and it could be shown that the system is advantageous for an accurate determination of triglycerides in conditions when there are high levels of glycerol, e.g. in mice and in patients with hyperglycerolaemia (pseudo-hypertriglyceridaemia). CONCLUSIONS: The described system should be of value in studies where detailed lipoprotein analysis is warranted and particularly when significant sample series with small volumes are available. Our data also suggest that there is a 4-5.5-fold concentration gradient between plasma and IF for the three major plasma lipoproteins.     

Regulation of sterol synthesis in human intestinal mucosa

Abstract The effect of dietary factors and experimental manipulations designed to perturb the entero-hepatic circulation on the rate of sterol synthesis were studied in freshly isolated human jejunal mucosa from normal subjects.
Fasting significantly reduced the rate of sterol synthesis from [¹⁴C] acetate in jejunal mucosa obtained from normolipaemic obese subjects. A high cholesterol diet had no consistent effect on the synthesis in normal subjects. Administration of cholestyramine resulted in a marked rise in the incorporation of [^l4C] acetate into sterols, while the administration of chenodeoxycholic acid did not significantly reduce basal sterol synthesis in normal subjects.
These results demonstrate that in man the rate of sterol synthesis in intestinal mucosa is altered in response to physiological variables. Although these findings indicate that sterol synthesis in this tissue is subject to regulation, no difference was observed in basal sterol synthesis between normal subjects and patients heterozygous for familial hypercholesterolaemia.     

丙二酰二醛修饰的低密度脂蛋白与冠心病的相关性研究

目的探讨丙二酰二醛修饰的低密度脂蛋白(MDALDL)与冠心病及其他血脂之间的关系。方法选择冠心病患者组68例,正常对照组74名。采用酶联免疫吸附分析(ELISA)的方法检测人血清中MDALDL,同时对受检者的血脂水平进行检测,结果进行统计学分析。结果冠心病患者血清氧化低密度脂蛋白(oxLDL)水平为(115.62±53.4)U/L,明显高于正常对照组(86.7±27.6)U/L(P<0.05);MDALDL与低密度脂蛋白胆固醇(LDLC)水平的比值在冠心病患者组为(43.25±2.64)mmol/U,明显高于正常对照组(33.74±1.58)mmol/U(P<0.01)。血清总胆固醇(TG)、LDLC与MDALDL水平呈显著正相关,相关系数r=0.486,而高密度脂蛋白胆固醇(HDLC)与MDALDL水平呈负相关,相关系数r=0.402。结论MDALDL与冠心病有着非常密切的关系,参与冠心病的发生发展过程。     

脑梗死患者中的血清总胆固醇、低密度脂蛋白及非高密度脂蛋白胆固醇的含量分析

目的:探讨总胆固醇(TC)、低密度脂蛋白(LDL-C)及非高密度脂蛋白胆固醇(non-HDL-C)与脑梗死关系,为预防和临床治疗提供参考。方法:153例脑梗死患者分为单纯脑梗死组(57例)、合并糖尿病组(43例)、合并高血压组(53例),另设67例健康体检者为对照组,各组均测定血清三酰甘油(TG),TC和HDL-C,同时根据Friedewald公式计算出LDL-C,按Frost法计算出non-HDL-C含量,数据输入计算机进行分析。结果:脑梗死各组血清TC、LDL-C及non-HDL-C含量均高于对照组,有显著差异(P<0.01);脑梗死各组间比较,LDL-C无显著差异,但糖尿病组TC及non-HDL-C含量高于单纯脑梗死组和合并高血压组,有显著差异(P<0.01)。结论:TC及non-HDL-C与脑梗死的发生有关,应重视合并糖尿病的脑梗死患者血清non-HDL-C含量。     

Lipoprotein disorder in brain infarction and hemorrhage

The cholesterol, triglyceride, and apolipoprotein B content of very low-, intermediate-, low-, and highdensity lipoprotein fractions (separated by ultracentrifugation) and plasma were measured in healthy controls and patients with atherothrombotic infarction (26), lacunar infarction (26), and brain hemorrhage (14). In both atherothrombotic and lacunar infarction, increased plasma and low-density lipoprotein apolipoprotein B and a decreased low-density lipoprotein cholesterol/apolipoprotein B ratio were noted. In brain hemorrhage patients, a decreased ratio was also observed. These findings suggest that increased small dense low-density lipoprotein is a characteristic risk factor for atherothrombotic and lacunar infarction.     

原代培养人嗜铬细胞瘤细胞的生长和分泌特征

目的观察体外培养的人嗜铬细胞瘤细胞生长和分泌的特征。方法连续分次消化人嗜铬细胞瘤组织，进行细胞原代培养；用细胞计数方法测定生长曲线，同时收集细胞液，用高效液相色谱分析法测定其中儿茶酚胺的水平，绘制时间-分泌曲线。结果在培养的第3天，原代培养的人嗜铬细胞瘤细胞数目开始逐渐增多，第6天达高峰，第7天后细胞数目减少；在细胞培养第1～2天，细胞液中去甲肾上腺素（NE）、肾上腺素（E）浓度明显下降，第2～8天无明显变化，多巴胺（DA）浓度在1～8天无明显变化。结论人嗜铬细胞瘤在体外培养时，增殖不显著，但分化明显，其儿茶酚胺的水平，在培养最初明显下降。     

Metabolism of heme and bilirubin in rat and human small intestinal mucosa.

Formation of heme, bilirubin, and bilirubin conjugates has been examined in mucosal cells isolated from the rat upper small intestine. Intact, viable cells were prepared by enzymatic dissociation using a combined vascular and luminal perfusion and incubated with an isotopically labeled precursor, delta-amino-[2,3-3H]levulinic acid. Labeled heme and bile pigment were formed with kinetics similar to those exhibited by hepatocytes. Moreover, the newly formed bilirubin was converted rapidly to both mono- and diglucuronide conjugates. In addition, cell-free extracts of small intestinal mucosa from rats or humans exhibited a bilirubin-UDP-glucuronyl transferase activity that was qualitatively similar to that present in liver. The data suggest that the small intestinal mucosa normally contributes to bilirubin metabolism.     

Lecithin:Cholesterol Acyl Transfer in Plasma of Normal Persons in Relation to Lipid and Lipoprotein Concentration

Gimsing, P. &; Nexö, E. The Metabolism in Man of Intravenously Injected Iodine-Labelled Transcobalamin I Not Saturated with Cobalamin. Scand. J. clin. Lab. Invest. 36, 669–672, 1976.

Transcobalamin I not saturated with cobalamin was purified. After iodine-labelling, a fraction of approximately 0.6 retained its cobalamin-binding capacity. Iodinated protein was used for turnover studies in three healthy subjects. The plasma curves obtained were identical to those of iodinated transcobalamin I saturated with cyanocobalamin. The cobalamin-binding capacity of the iodinated protein was determined on microcolumns containing insolubilized cobalamin. The binding capacity decreased rapidly, only 50% of the initial unsaturated cobalamin-binding capacity remaining after 0.2 to 0.3 days. It is concluded that the turnover of transcobalamin I not saturated with cobalamin does not differ from the turnover of transcobalamin I saturated with cyanocobalamin, and that transcobalamin I saturated with cobalamin in vivo is metabolized at the same rate as is transcobalamin I saturated with cyanocobalamin in vitro.     

Lipoprotein apheresis reduces biomarkers of plaque destabilization and cardiovascular risk

Lipoprotein apheresis (LA) is believed to exert anti‐atherosclerotic effects beyond LDL‐cholesterol reduction. We investigated 22 patients undergoing regular LA on a weekly basis (group A) before (AP) and after LA procedure (EP), 15 healthy individuals (group B), and 22 hyperlipoproteinemic patients with concomitant cardiovascular end organ damage treated without LA therapy (group C). Biomarkers of endothelial inflammation (hsCRP), plaque destabilization, and rupture (sVCAM, MMP‐9, PAPP‐A, ADMA) were quantified. Intergroup comparison revealed a statistically significant lower MMP‐9 level in group A (AP and EP) compared with group C (P < 0.01), whereas PAPP‐A levels were lower in group B compared with group A and C (P = 0.04). EP ADMA‐levels and EP sVCAM levels in group A were statistically lower compared with group B and C. AP and EP values comparison revealed a significant reduction for hsCRP (mean 41.0 ± 16.7%, P < 0.01), sVCAM (mean 69.6 ± 14.0%, P < 0.01), PAPP‐A (mean 88.7 ± 20.4%, P < 0.01), ADMA (mean 69.7 ± 18.4% P < 0.01). In conclusion, we observed a transient decrease in the plasma concentrations of several biomarkers expressed during plaque destabilization and elevated cardiovascular risk after a single LA treatment. J. Clin. Apheresis 29:235–242, 2014. © 2013 Wiley Periodicals, Inc.     

低频交变高压电磁场对脂蛋白代谢及血液流变学的影响

为探讨低频交变高压电磁场对脂蛋白代谢及血液流变学的影响,应用交变高压电磁场治疗心脑血管疾病３２０例,对比分析治疗前后５５例血清脂蛋白及春亚组分和３０例血液流变学指标的变化。结果显效１２５例,好转１６６例,无效２９例,治疗后血清ＴＧ、ＴＣ、ＬＤＬ－Ｃ降低,ＨＤＬ－Ｃ浓度升高,ＴＣ／ＨＤＬ－Ｃ、ＬＤＬ－Ｃ／ＨＤＬ－Ｃ比率降低;降低了全血和血浆粘度。提示：低频交变高压电磁场能改善脂蛋白代谢,发迹血液流变     

In vitro studies upon the release of γ-glutamyltransferase from human liver

Samples of human liver have been incubated in different fluids for up to 48 h and the released γ-glutamyltransferase studied by gel chromatography on Sephacryl S-300 and polyacrylamide gradient gel electrophoresis. When human liver is incubated in serum, most of the released enzyme is of high M_r (greater than 1 000 000). Incubation in hepatic bile, or in a solution of glycochenodeoxycholate, results in the release of enzyme that is hydrophobic in nature and which reaggregates to a varying extent after the removal of bile salts. In contrast, incubation in saline, or in a solution of human albumin results in the release of a hydrophilic low M_r (about 120 000) form of the enzyme. These observations are discussed in relation to possible mechanisms for the release of these multiple forms.     

Free cholesterol distribution during in vitro lipolysis of rat plasma very low density lipoprotein: lack of a role for blood and heart cells

Abstract. In the present study, an attempt was made to quantify free cholesterol transfer from lipolyzed VLDL to HDL, blood cells and heart cells. The experiments were carried out in vitro or in the isolated perfused rat heart with rat plasma VLDL labelled biosynthetically with [¹⁴C]-palmitic acid and [³H]cholesterol, and with bovine milk lipoprotein lipase, human blood cells (erythrocytes, leucocytes and platelets) or rat plasma HDL. Exchange and transfer of free cholesterol was followed by radioactivity and specific activity determinations. The study demonstrated an exchange of free cholesterol between VLDL and blood cells (6–10 h) and VLDL and HDL (120 min). However, none of the blood cells tested served as acceptor for lipolysis-generated free cholesterol, whereas HDL did. In the isolated perfused rat heart, a maximum of 25% of the free cholesterol radioactivity lost from VLDL was found in the tissue. Since exchange must have contributed to this process, the transfer of free cholesterol molecules to the heart is necessarily lower. The study thus demonstrated minimal or possibly no net transport of free cholesterol from VLDL to cells and cell membranes.