Impact of calcium entry blockers on glomerular injury in experimental hypertension

Summary A major problem for patients with kidney disease and their physicians is that most chronic renal diseases progress to global glomerular sclerosis and end-stage renal failure. Studies in experimental models of hypertension and renal insufficiency have advanced our understanding of the pathogenesis of progressive kidney damage. In a number of settings, sclerosis has been related to the presence of intrarenal hypertension, a consequence of the hemodynamic adaptation to a reduction in the number of functioning nephrons. A growing body of evidence also supports the hypothesis that kidney and glomerular hypetrophy constitute an independent risk factor for glomerular sclerosis. Recent studies suggest that calcium antagonists can reduce glomerular injury in experimental hypertension. Renal protection may be related to the ability of these agents to inhibit compensatory renal growth.     

Serum lipoproteins and cholesterol metabolism in two hypercholesterolaemic rabbit models

Summary Serum lipoproteins and key hepatic and intestinal enzymes regulating cholesterol synthesis, esterification and catabolism, namely 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase, acyl coenzyme A: cholesterol-o-acyltransferase (ACAT) and cholesterol 7-hydroxylase respectively, were compared in two hypercholesterolaemic rabbit models — the cholesterol-fed animal and the hypercholesterolaemic diabetic animal. Hypercholesterolaemia in the cholesterol-fed animals was reflected in the VLDL and LDL fractions, whereas VLDL and HDL₂ cholesterol levels were elevated in the diabetic animals. The lipoproteins of the cholesterol-fed animals were enriched with cholesterol but the lipoprotein fractions in the diabetic animals were enriched with triacylglycerol. While hepatic HMGCoA reductase activity was significantly reduced in both groups, the activities of hepatic ACAT and cholesterol 7-hydroxylase were significantly increased in the cholesterol-fed animals and significantly reduced in the diabetic animals compared with controls. In the intestine, the activity of HMGCoA reductase was increased and ACAT reduced in the diabetic animals. By contrast, in the cholesterol-fed group, HMGCoA reductase activity was lower and ACAT activity was higher in comparison with the control group. These differences in lipoproteins and cellular cholesterol metabolism between the hypercholesterolaemic rabbit models may explain the differences in susceptibility to atherosclerosis, previously reported in these two animal models.     

Evaluation of a new equation for LDL-c estimation and prediction of death by cardiovascular related events in a German population-based study cohort

A simple equation established by Cordova &; Cordova (LDL-COR) was developed to provide an improved estimation of LDL-cholesterol in a large Brazilian laboratory database. We evaluated this new equation in a general population cohort in Pomerania, north-eastern Germany (SHIP Study) compared to other existing formulas (Anandaraja, Teerakanchana, Chen, Hattori, Martin, Friedewald and Ahmadi), and its power in the prediction of death by atherosclerosis related events as the primary outcome. Analysis was conducted on a cohort of 4075 individuals considering age, gender, use of lipid lowering therapy and associated co-morbidities such as diabetes, hepatic, kidney and thyroid disease. LDL-COR values had a lower standard deviation compared to the previously published equations: 0.92 versus 1.02, 1.02, 1.03, 1.04, 1.09, 1.10 and 1.74?mmol/L, respectively. All of the factors known to affect the results obtained by the Friedewald’s equation (LDL-FW), except fibrate use, were associated with the difference between LDL-COR and LDL-FW (p?p?=?.06). LDL-COR determined a higher hazard ratio (1.23 versus 1.12, 1.19, 1.21, 1.19, 1.21 and 1.19) for cardiovascular disease related mortality, incident stroke or myocardial infarction compared to the other evaluated formulas, except for Ahmadi’s (1.24), and the same adjusted predictive power considering all confounding factors. The proposed simple equation was demonstrated to be suitable for a more precise LDL-c estimation in the studied population. Since LDL-c is a parameter frequently requested by medical laboratories in clinical routine, and will probably remain so, precise methods for its estimation are needed when direct measurement is not available.     

One Egg per Day Improves Inflammation when Compared to an Oatmeal-Based Breakfast without Increasing Other Cardiometabolic Risk Factors in Diabetic Patients

There is concern that egg intake may increase blood glucose in patients with type 2 diabetes mellitus (T2DM). However, we have previously shown that eggs reduce inflammation in patients at risk for T2DM, including obese subjects and those with metabolic syndrome. Thus, we hypothesized that egg intake would not alter plasma glucose in T2DM patients when compared to oatmeal intake. Our primary endpoints for this clinical intervention were plasma glucose and the inflammatory markers tumor necrosis factor (TNF)-α and interleukin 6 (IL-6). As secondary endpoints, we evaluated additional parameters of glucose metabolism, dyslipidemias, oxidative stress and inflammation. Twenty-nine subjects, 35–65 years with glycosylated hemoglobin (HbA1c) values <9% were recruited and randomly allocated to consume isocaloric breakfasts containing either one egg/day or 40 g of oatmeal with 472 mL of lactose-free milk/day for five weeks. Following a three-week washout period, subjects were assigned to the alternate breakfast. At the end of each period, we measured all primary and secondary endpoints. Subjects completed four-day dietary recalls and one exercise questionnaire for each breakfast period. There were no significant differences in plasma glucose, our primary endpoint, plasma lipids, lipoprotein size or subfraction concentrations, insulin, HbA1c, apolipoprotein B, oxidized LDL or C-reactive protein. However, after adjusting for gender, age and body mass index, aspartate amino-transferase (AST) (p < 0.05) and tumor necrosis factor (TNF)-α (p < 0.01), one of our primary endpoints were significantly reduced during the egg period. These results suggest that compared to an oatmeal-based breakfast, eggs do not have any detrimental effects on lipoprotein or glucose metabolism in T2DM. In contrast, eggs reduce AST and TNF-α in this population characterized by chronic low-grade inflammation.     

Intestinally derived lipoprotein particles in non-insulin-dependent diabetic patients with and without hypertriglyceridaemia

We have previously demonstrated alterations in apolipoprotein B-48 metabolism in the post-prandial state in patients with non-insulin-dependent diabetes mellitus. This study investigates the relationship between hypertriglyceridaemia and post-prandial lipoprotein metabolism. Four groups of patients were examined: non-insulin-dependent diabetic patients, with normal serum triglyceride levels (serum triglyceride <2.1 mmol l⁻¹; haemoglobin HbA_1c 5.5%±0.4%); poorly controlled, non-insulin-dependent diabetic patients with hypertriglyceridaemia (serum triglyceride >2.1 mmol 1⁻¹; HbA_1c 8.8%±0.9%); nondiabetic subjects with serum triglycerides <2.1 mmoll⁻¹; and non-diabetic subjects with hypertriglyceridaemia (serum triglyceride>2.1 mmol l⁻¹). Subjects were studied fasting and following a high-fat meal (1300 kcal). The triglyceride-rich lipoprotein fraction was isolated by ultracentrifugation (d<1.006 g ml⁻¹). Apoprotein B-48, apoprotein B-100 and apoprotein E were separated on 4%–15% gradient gels and quantified as a percentage of the fasting concentration by densitometric scanning. Triglyceride-rich lipoprotein apolipoprotein B-48 and apolipoprotein B-100 post-prandial profiles demonstrated a maximum increase either at 2 h or rising still further to a peak at 6 h before falling in the diabetic groups and hypertriglyceridaemic non-diabetic subjects when compared with the normotriglyceridaemic control subjects whose levels decreased after 2 h (P<0.05). A significantly different triglyceride-rich lipoprotein apolipoprotein E profile was also exhibited by the diabetic patients (P<0.05). Levels of triglyceride-rich lipoprotein, cholesterol, triglyceride, total protein and apoprotein B were elevated in the hypertriglyceridaemic subjects, both diabetic and non-diabetic. These results indicate that hypertriglyceridaemia is associated with altered metabolism and composition of post-prandial triglyceride-rich lipoprotein particles in both poorly controlled diabetic and non-diabetic subjects.     

Effect of exercise training and diet modification on serum lipids and lipoproteins in coronary artery disease patients treated with thiazides

The effects of chronic exercise training and diet modification on serum lipids and lipoproteins were measured in 17 hypertensive males and 41 normotensive males with documented coronary artery disease (CAD). Exercise consisted of aerobic activities which were performed at approximately 75-85% of the symptom-limited maximum heart rate for 30-40 minutes, three times weekly for 3 months. Each participant's diet was also controlled, the recommended daily intake of fat and cholesterol was no more than 40 g/day and 200 mg/day, respectively. Significant increases in estimated VO2max and total cholesterol/high density lipoprotein (HDL) and a significant decrease in serum triglycerides were documented after training. Significant differences in serum cholesterol and triglycerides between the nondiuretic and diuretic patients were also noted. No significant changes were found in low density lipoprotein (LDL), HDL, or body weight. Vigorous aerobic training and diet modification can favorably modify the deleterious effects of diuretic medications on serum triglycerides and total cholesterol/HDL in patients with documented CAD.     

Abnormalities in apo B-containing lipoproteins in diabetes and atherosclerosis

Atherosclerosis is the major cause of death in patients with diabetes. Low-density lipoprotein (LDL) being the most important cholesterol-carrying lipoprotein has been studied extensively in both diabetes and non-diabetes. This paper reviews the literature but also focuses on the precursors of LDL and in particular the postprandial apo B-containing lipoproteins. Abnormalities in the postprandial lipoproteins and alteration in chylomicron assembly and clearance are discussed and the evidence presented suggesting the importance of dysregulation of these lipoproteins in atherosclerotic progression. The relationship between chylomicron production in the intestine and hepatic release of very low-density lipoproteins (VLDL) is explored, as is the interrelationship between clearance rates of these lipoproteins. The size of LDL influences its atherogenicity. VLDL composition and size in relation to its influence on LDL is discussed. The effect of diet on the composition of lipoproteins and the relationship between fatty acid composition and clearance is reviewed. Evidence that diabetic control beneficially alters lipoprotein composition is presented suggesting how improved diabetic control may reduce atherosclerosis. The review concludes with a discussion on the effect of the apo B-containing lipoproteins and their modification through glycation and oxidation on macrophage and endothelial function.     

老年冠心病患者脂蛋白谱剖析

目的探讨老年冠心病患者的脂蛋白谱特点。方法以诊断明确的老年男性冠心病１４３例为观察对象，以年龄与生活水平相匹配的健康老年男性１４３名为对照，两组中均排除与脂代谢有关的其它疾病。以同一份血清用优选方法作１４项检查，包括总胆固醇（ＴＣ），甘油三酯（ＴＧ），高密度脂蛋白胆固醇及其亚类（ＨＤＬ－Ｃ、ＨＤＬ２－Ｃ、ＨＤＬ３－Ｃ），低密度脂蛋白胆固醇（ＬＤＬ－Ｃ），脂蛋白（ａ）〔Ｌｐ（ａ）〕，载脂蛋白（ａｐｏ）ＡⅠ、ＡⅡ、Ｂ、ＣⅠ、ＣⅡ、ＣⅢ和Ｅ。结果除ａｐｏＣⅠ、ＣⅢ两项外，其它１２项均值在冠心病组与对照组之间的差异均有显著性。逐步回归分析中顺次选入ａｐｏＡⅠ、ＬＤＬ－Ｃ与ＴＧ３项为优选指标，相关分析示Ｌｐ（ａ）是一项独立变量。结论在ＴＣ水平接近正常时，老年冠心病组最突出的改变是代表ＨＤＬ的５项参数均明显低下，其中以ａｐｏＡⅠ为最明显。临床上选用检验指标仍应以ＴＣ、ＴＧ、ＨＤＬ－Ｃ和ＬＤＬ－Ｃ为主，如果采用ａｐｏＡⅠ、Ｂ及Ｌｐ（ａ）测定，必须注意所用商品试剂的质量。     

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.