The authors compared three different indices, of atherogenicity in 120 men with ischaemic heart disease, type stable angina pectoris (mean age 35.9 +/- 7.54 years) with 30 men of a control group--mean age 42.1 +/- 8.89 years). They evaluated relationship between the atherogenicity index and coronary score by the Spearman correlation coefficient. They consider the index HDL-cholesterol: total cholesterol the best index for evaluation of the coronary risk. This index differentiates men with ischaemic heart disease, type stable angina pectoris with a positive coronary score from the control group of men with a negative coronary score (r = -0.54, p less than 0.001). The index VLDL-cholesterol + LDL-cholesterol: HDL-cholesterol is the best index for evaluation of the severity of atherosclerotic stenosis of the coronary arteries in men with ischaemic heart disease, type stable angina. This index differentiated probands with a different score (r = 0.24, p less than 0.05).

OBJECTIVE

To investigate the correlation between blood concentrations of tacrolimus (FK506) and cystatin C (Cys C) and the effect of FK506 on glycolipid metabolism in renal transplant recipients.

METHODS

A total of 325 patients <em>r</em>eceiving <em>r</em>enal t<em>r</em>ansplantation between August, 2014 and Septembe<em>r</em>, 2015 in Nanfang Hospital we<em>r</em>e divided into 4 g<em>r</em>oups acco<em>r</em>ding to the postope<em>r</em>ative time (1 month g<em>r</em>oup, 1-3 months g<em>r</em>oup, 4-6 months g<em>r</em>oup, and 7-12 months g<em>r</em>oup). FK506 blood t<em>r</em>ough concent<em>r</em>ation was measu<em>r</em>ed at the time of postope<em>r</em>ative follow-up, and c<em>r</em>eatinine (Sc<em>r</em>) and Cys C levels we<em>r</em>e also detected. Results Plasma FK506 concent<em>r</em>ation dec<em>r</em>eased with age in the <em>r</em>ecipients and showed a positive co<em>r</em><em>r</em>elation with Cys C (<em>r</em>=0.985, P=0.015) but no obvious co<em>r</em><em>r</em>elation with Sc<em>r</em> (<em>r</em>=0.259, P=0.741). FK506 had no effect on blood glucose (5.53-5.59 mmol<L) o<em>r</em> blood lipids (TG 1.47-1.55 mmol<L, TC 5.04-5.17 mmol<L, LDL-C 3.00-3.07 mmol<L, and <em>VLDL</em> 0.73-0.76 mmol<L) in patients 1-6 months afte<em>r</em> <em>r</em>enal t<em>r</em>ansplantation.

CONCLUSIONS

FK506 does not affect the level of glycolipid metabolism in patients after renal transplantation. Cys C is positively related to blood concentration of FK506 in the renal transplantation recipients. The rational use of FK506 can improve the effectiveness and safety of the treatment in the recipients.

In this study we compare various methods for h;igh-density-lipoprotein cholesterol quantitation: ultracentrifugation; electrophoresis either on cellulose acetate or on agarose gel; precipitation methods with polyanions-bivalent cations; adsorption procedure using concanavalin A (Con A). quantification by electrophoresis is slow and not precise. Except heparin-Mn++ and dextran (MM 5 X 10(5) and 2 X 10(6)) - CaCl2 procedures, precipitation and Con A methods own a good repeatability (VC 2%) and give a linear response after VLDL or LDL-VLDL addition to tested sera. Regression analysis of the data obtained using these methods in pairs demonstrate a correct accuracy (r>> 0.95). The Student t-test shows that the usual values must be evaluated for each method. We suggest to use either phosphotungstate - Mg++ or Con A procedure as method for HDL cholesterol quantitation.

<Abst<em>r</em>actText>Int<em>r</em>oduction: Small intestinal bacte<em>r</em>ial ove<em>r</em>g<em>r</em>owth may cause the hype<em>r</em>lipidemia appea<em>r</em>ance by ente<em>r</em>ohepatic ci<em>r</em>culation distu<em>r</em>bance which evolves on the backg<em>r</em>ound of the ea<em>r</em>ly bile acids deconjugation with fu<em>r</em>the<em>r</em> endotoxin p<em>r</em>oduction and oxidative st<em>r</em>ess in the live<em>r</em> with hype<em>r</em>p<em>r</em>oduction of choleste<em>r</em>ol and athe<em>r</em>ogenic lipop<em>r</em>oteins. The aim: the dete<em>r</em>mination of p<em>r</em>evalence and featu<em>r</em>es of SIBO in a se<em>r</em>ies of patients with hype<em>r</em>lipidemia and in cont<em>r</em>ol subjects.</Abst<em>r</em>actText><Abst<em>r</em>actText>Mate<em>r</em>ials and methods: Nineteen patients with hype<em>r</em>lipidemia and ten cont<em>r</em>ol subjects we<em>r</em>e studied. Small intestinal bacte<em>r</em>ial ove<em>r</em>g<em>r</em>owth was assessed by a lactulose b<em>r</em>eath test. Such biochemical ma<em>r</em>ke<em>r</em>s as CRP, ALT, AST, GGTP, apolipop<em>r</em>otein B, bili<em>r</em>ubin, choleste<em>r</em>ol and lipid p<em>r</em>ofile we<em>r</em>e dete<em>r</em>mined. Except the <em>r</em>outine inte<em>r</em>p<em>r</em>etation of lactulose b<em>r</em>eath test, which contains the SIBO detection, small intestinal t<em>r</em>ansit time and hyd<em>r</em>ogen level evaluation with next compa<em>r</em>ison between g<em>r</em>oups of patients was <em>r</em>ealized.</Abst<em>r</em>actText><Abst<em>r</em>actText>Results: Small intestinal bacte<em>r</em>ial ove<em>r</em>g<em>r</em>owth was p<em>r</em>esent in 78.9% of patients with hype<em>r</em>lipidemia and 40% in cont<em>r</em>ol subjects. The maximal dose of H2 was pa<em>r</em>ticula<em>r</em>ly highe<em>r</em> in patients with hype<em>r</em>lipidemia in compa<em>r</em>ison with cont<em>r</em>ol g<em>r</em>oup (94,7±13,69 vs. 36,13±5,4). The<em>r</em>e was a st<em>r</em>ong co<em>r</em><em>r</em>elation between AST level and SIBO existence in both g<em>r</em>oups (<em>r</em>=1). Positive connection between LDL, TG, <em>VLDL</em> and the dose of exhaled hyd<em>r</em>ogen on 120 minute (<em>r</em>=0.6, <em>r</em>= 0.62, <em>r</em>=0.7 <em>r</em>espectively) and st<em>r</em>ong negative co<em>r</em><em>r</em>elation between HDL and 120 minute dose (<em>r</em>=-0.74) in main g<em>r</em>oup was ma<em>r</em>ked.</Abst<em>r</em>actText><Abst<em>r</em>actText>Conclusions: Patients with hype<em>r</em>lipidemia have a highe<em>r</em> p<em>r</em>evalence of small intestinal bacte<em>r</em>ial ove<em>r</em>g<em>r</em>owth and the<em>r</em>e is a <em>r</em>elationship between H2 <em>r</em>ate and LDL, TG, <em>VLDL</em>.</Abst<em>r</em>actText>

Leprosy reduces quality of life of affected persons. Oxidative stress caused by reactive oxygen species may play a vital role in the pathogenesis of leprosy. This study evaluated anthropometric indices, fasting plasma glucose (FPG), lipid profile, total antioxidant capacity (TAC), total plasma peroxide (TPP), oxidative stress index (OSI), malondialdehyde (MDA), glutathione (GSH) and 8-hydroxy-2-deoxyguanosine (8-OHdg) in leprosy patients. Sixty test participants of both genders, aged 18-65years and diagnosed of multibacillary leprosy and 30 apparently healthy controls were consecutively recruited for this study. The test participants comprised of 30 patients on multidrug therapy (MDT) and 30 patients relieved from therapy (RFT). Body mass index (BMI), Waist-hip ratio (WHR), FPG, lipid profile, TAC, TPP, OSI, MDA, GSH and 8-OHdg were determined using appropriate methods. Data were analyzed using Analysis of variance; p<0.05 was considered statistically significant. The MDT group had significantly lower BMI (p = 0.0001), Total cholesterol (p = 0.001), HDL-C (p = 0.019), LDL-C (p = 0.005), TAC (p = 0.0001) and higher TPP (p = 0.001), MDA (p = 0.0001), OSI (p = 0.005) and 8-OHdg (p = 0.035) compared to the controls. The RFT group had significantly lower BMI (p = 0.001) Total cholesterol (0.0001), HDL-C (p = 0.006) LDL-C (p = 0.0001), TAC (p = 0.001) and higher WHR (p = 0.010), VLDL-C (p = 0.035), TG (p = 0.023) Atherogenic index of plasma (p = 0.0001) and TPP (p = 0.001), MDA (p = 0.0001) compared to the control group. GSH levels correlated negatively with duration of treatment (r = -0.401, p = 0.028). This study has shown that there is oxidative stress in multibacillary leprosy patients irrespective of drug treatment status. This study also shows that leprosy patients relieved from treatment may be susceptible to cardiovascular events. Antioxidants supplementation may be beneficial in the treatment of leprosy and clinical follow up on patients relieved from treatment may also be necessary to monitor health status and prevent development of cardiovascular events.

<st<em>r</em>ong class="sub-title"> Backg<em>r</em>ound: </st<em>r</em>ong> Fib<em>r</em>oblast G<em>r</em>owth Facto<em>r</em> 21 (FGF21) se<em>r</em>um levels a<em>r</em>e associated with insulin <em>r</em>esistance and metabolic synd<em>r</em>ome in HIV patients.

<st<em>r</em>ong class="sub-title"> Objective: </st<em>r</em>ong> To quantify FGF21 levels in HIV patients using anti<em>r</em>et<em>r</em>ovi<em>r</em>al the<em>r</em>apy (ART) and to analyze a possible association between se<em>r</em>um FGF21 levels and lipid p<em>r</em>ofile, levels of p<em>r</em>o-inflammato<em>r</em>y cytokines, and athe<em>r</em>ogenic <em>r</em>isk facto<em>r</em>s.

<st<em>r</em>ong class="sub-title"> Mate<em>r</em>ials and methods: </st<em>r</em>ong> Twenty patients with HIV infection, who <em>r</em>eceived ART in a scheme consisting of Tenofovi<em>r</em>/Emt<em>r</em>icitabine+Lopinavi<em>r</em>/Ritonavi<em>r</em>, we<em>r</em>e en<em>r</em>olled in this study. The se<em>r</em>um levels of FGF21, inflammato<em>r</em>y pa<em>r</em>amete<em>r</em>s (IL-6 and IL-1β), glucose, choleste<em>r</em>ol, t<em>r</em>iglyce<em>r</em>ides, and insulin we<em>r</em>e dete<em>r</em>mined at baseline and afte<em>r</em> 36 weeks of t<em>r</em>eatment. The homeostatic model assessment fo<em>r</em> insulin <em>r</em>esistance (HOMA-IR) and the athe<em>r</em>ogenic <em>r</em>isk facto<em>r</em> we<em>r</em>e also calculated.

<st<em>r</em>ong class="sub-title"> Results: </st<em>r</em>ong> Afte<em>r</em> 36 weeks, se<em>r</em>um FGF21 levels dec<em>r</em>eased significantly (p=0.011), whe<em>r</em>eas IL-6 levels (<em>r</em>=0.821, p=0.0001) and the CD4+ T cell count (<em>r</em>=0.446, p=0.048), showed a positive co<em>r</em><em>r</em>elation with the dec<em>r</em>ease in FGF21 levels. The<em>r</em>e was an inc<em>r</em>ease in total choleste<em>r</em>ol (<em>r</em>=-0.483, p=0.031), LDL (<em>r</em>=-0.496, p=0.026), <em>VLDL</em> (<em>r</em>=-0.320, p=0.045), and the athe<em>r</em>ogenic index facto<em>r</em> (<em>r</em>=-0.539, p=0.014), these values showed a negative co<em>r</em><em>r</em>elation with FGF21 levels.

<st<em>r</em>ong class="sub-title"> Conclusions: </st<em>r</em>ong> The dec<em>r</em>ease of se<em>r</em>um FGF21 levels due to ART is associated with the alte<em>r</em>ation in lipid p<em>r</em>ofile and an inc<em>r</em>eased <em>r</em>isk fo<em>r</em> ca<em>r</em>diovascula<em>r</em> diseases. These va<em>r</em>iations a<em>r</em>e p<em>r</em>edicto<em>r</em>s of inflammato<em>r</em>y status in HIV patients using anti<em>r</em>et<em>r</em>ovi<em>r</em>al the<em>r</em>apy.

<st<em>r</em>ong class="sub-title"> Keywo<em>r</em>ds: </st<em>r</em>ong> AIP; Anti<em>r</em>et<em>r</em>ovi<em>r</em>al the<em>r</em>apy; FGF21; Human Immunodeficiency Vi<em>r</em>us; IL-6; Inflammato<em>r</em>y and Metabolic Pa<em>r</em>amete<em>r</em>s.

Binding of apoB-containing lipoproteins from unfractionated human blood sera to the immobilized bovine receptor of low density lipoproteins (LDL receptor) was studied. Peroxidase-labeled anti-human apoB antibodies were used to evaluate the lipoprotein binding. The equilibrium dissociation constant (Kd) of the interaction between apoB-containing lipoproteins from unfractionated human sera from healthy donors and the immobilized LDL receptor varied from 1 to 20 microg apoB/ml. To describe the binding of lipoproteins to the LDL receptor, a parameter of relative binding affinity (RBA) was used. RBA is inversely related to value of Kd and equal to unity for the standard serum. The RBA values for the binding of apoB-containing lipoproteins from unfractionated sera to the immobilized LDL receptor were found to correlate with the RBA values for the binding of isolated VLDL (r = 0.76, p < 0.001) and fail to correlate with the RBA values for the binding of isolated LDL. The RBA values for the binding of apoB-containing lipoproteins from unfractionated sera correlated with the RBA values for the binding of apoE-containing lipoproteins from unfractionated sera (r = 0.92, p < 0.001) and with values of triglyceride concentration in the sera (r = 0.93, p < 0.001). The RBA values for the binding of apoB-containing lipoproteins from sera of patients with FDB whose LDL were unable to bind to the LDL receptor did not significantly differ from the RBA values for the normal sera. However, the removal of VLDL from the normal sera significantly decreased the RBA values for the binding of apoB-containing lipoproteins from unfractionated sera. The results indicate that the different binding of apoB-containing lipoproteins to the immobilized LDL receptor mainly depended on the different binding of VLDL and not of LDL.

Remnant lipoprotein can be measured by immunoseparation assay and polyacrylamide gel disc electrophoresis; however, these methods have some problems, such as a lack of specificity and being technically complicated. Recently, a new method, the remnant lipoprotein cholesterol homogeneous assay(RemL-C), has been established. In this study, we evaluated the basal performance of RemL-C assay. One hundred and fifty patients with diabetes mellitus were enrolled in this study. RemL-C level was higher in the midband (+) group than in the midband (-) group (p<0.01), and a strong correlation was observed between RemL-C level and remnant lipoprotein level measured by conventional method (r=0.89, p<0.01). RemL-C level correlated positively with triglyceride(TG) (r=0.94, p<0.01) and total cholesterol(TC) (r=0.39, p<0.01), negatively with high density lipoprotein(HDL-C) (r=-0.35, p<0.01) and positively with apolipoprotein (apo) CII, and apoE (apoCII: r=0.59, p<0.01, apoE: r=0.71, p<0.01). In particular, RemL-C level correlated strongly with TG and apoE. RemL-C level was significantly higher in patients with combined hyperlipidemia compared to patients with other hyperlipidemias (p<0.01). When the serum of a patient with combined hyperlipidemia was separated by sepharose 4B gel filtration, the fraction showing peak RemL-C level was observed between the fraction corresponding to VLDL and the fraction corresponding to LDL. Furthermore, the peak of RemL-C corresponded to the peak of apoE. Moreover RemL-C level correlated negatively with preheparin serum lipoprotein lipase mass that is a marker of metabolic syndrome (r=-0.30, p<0.01). These results suggest that the measurement of remnant lipoprotein by RemL-C assay reflects the quantity of intermediate-density lipoprotein. Since RemL-C measurement can be run on an automated clinical analyzer permitting quick and high throughput measurement, RemL-C levels may be useful in the screening of hyperlipidemia.

The effect of Pravastatin sodium (CS-514), a new inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA R) on very-low-density lipoprotein (VLDL) composition and kinetics was studied in normal and experimental nephrotic rats under fasting conditions. Nephrotic rats, induced by a single intraperitoneal injection of puromycin aminonucleoside (100 mg/kg body weight), had significantly higher plasma lipids and apoprotein (apo) B concentrations than controls. The hypertriglyceridemia associated with nephrosis was mainly due to a markedly elevated VLDL-triglyceride (TG) concentration. Pravastatin sodium was administrated as a 0.04% solution in drinking water for 7 days to normal control and nephrotic rats. Plasma TG concentration in both control and nephrotic rats was significantly reduced by the treatment with Pravastatin, but plasma cholesterol levels were not reduced by the treatment in either group of rats. TG, cholesterol, phospholipid, and apo B concentrations in nephrotic VLDL were significantly reduced by Pravastatin treatment, whereas only TG was decreased in control VLDL. Pravastatin reduced the apo B 100 + 95/48 ratio in nephrotic VLDL. Pravastatin did not alter the lipid concentration of low-density lipoprotein (LDL) and high-density lipoprotein (HDL) in control and nephrotic rats. VLDL-TG turnover studies showed that TG secretion rate was significantly suppressed by Pravastatin administration without affecting its removal in both groups of rats. These suggested that Pravastatin, an inhibitor of cholesterol biosynthesis, can reduce VLDL concentration by rectifying the overproduction of VLDL exhibited in nephrotic rats.

Male Sprague-Dawley IVA-SIV rats were compared to male Sprague-Dawley Charles River rats of the same age, body weight, and daily food intake. The IVA-SIV rats demonstrated hypertriglyceridemia (182 +/- 9.4 v 131 +/- 9.4 mg/dL, P less than 0.001), associated with increased fasting plasma glucose (115 +/- 3 v 84 +/- 2 mg/dL, P less than 0.001), and plasma insulin (35 +/- 5 v 19 +/- 2 microU/mL, P less than 0.001) levels. Furthermore, IVA-SIV rats responded to an oral glucose load with higher plasma glucose and insulin levels. Very-low-density lipoprotein (VLDL)-triglyceride (TG) turnover studies were performed, documenting a higher TG production rate, which correlated with the plasma TG concentrations, (r = 0.58, P less than 0.01) in the IVA-SIV rats. Since lipoprotein lipase activity in both adipose tissue and muscle was not significantly different in the two groups of rats, it appears that the hypertriglyceridemia in IVA-SIV rats is due to increased VLDL-TG secretion, associated with hyperglycemia, hyperinsulinemia, and increased plasma FFA levels. The IVA-SIV rats provide a model of endogenous hypertriglyceridemia, independent of obesity.

OBJECTIVE

To evaluate whether apolipoproteins A-I (Apo A-I) and B (Apo B) have, higher ensitivity (SN), specificity (SP) and positive predictive value (PPV) than lipoproteins (LP), total cholesterol (TC), high density lipoprotein (HDL), low density lipoprotein (LDL), very low density lipoprotein (VLDL), and triglycerides (TGL) in assessing the risk of coronary heart disease (CHD).

METHODS

This is a transversal case-control study of 241 patients, who were divided into two groups: 1) 145 patients with CHD, and 2) 96 patients without coronary disease. A model of logistic regression to evaluate the relation between the LPs and CHD was developed in which variables with a p-alpha < 0.1 were included.

RESULTS

Apo A-I levels were higher in the patients without CHD, (OR 2.08, CI 1.20-3.57). There were no statistical differences between the values of Apo A-I and the remaining lipid fractions (Apo A-I: 67%; Apo B: 100%; PPV: TC = 71%; TGC = 71%; HDL = 71%; LDL = 71%). The costs of the tests in Reais were as follows: Apo A-I: R$ 56.60; Apo B-100: R$ 56.60; TC: R$ 9.94; HDL: R$ 21.30; LDL: R$ 28.40; TGL: R$ 14.20.

CONCLUSIONS

Levels of Apo A-I and Apo B have no advantage over conventional lipoproteins in predicting the risk of CHD, despite the statistical association between Apo A-I and CHD; in addition, their costs are higher than those of the conventional lipoproteins.

OBJECTIVE

To evaluate a single step electrophoresis for quantitative determination of cholesterol of high-, low-, very-low-density lipoprotein(HDL, LDL, VLDL) and fast pre-beta lipoprotein [lipoprotein (a), Lp(a)].

METHODS

Quantification of lipoprotein cholesterol was performed by enzymatic staining of cholesterol in a new agarose gel electrophoresis method that allows the separation of LDL, VLDL, HDL, and Lp(a) by Helena REP system. The results of electrophoresis method were compared with those by traditional method like PTA-Mg2+ precipitation method for HDL-C, PVS precipitation method for LDL-C, and Immunoturbidimetric assay(ITA) method for Lp(a).

RESULTS

Within-runs CV were 5.16%-7.46%, 1.26%-3.28% and 3.78%-5.86% for VLDL-C, LDL-C and HDL-C, respectively. Between-runs CV were 8.35%-11.25%, 2.78%-4.08% and 4.23%-6.36%, respectively. The linearity of this method was up to 10.35 mmol/L total cholesterol. The recoveries were 90.3%, 94.3% and 89.6%, respectively. No interference were observed when bilirubin(< 342 mumol/L), hemoglobin(< 20 g/L) or triglyceride(< 11.0 mmol/L) were added to pooled serum, respectively. There was good agreement between methods, with r = 0.9557 for HDL-C(electrophoresis method vs PTA-Mg2+ precipitation method), r = 0.9609 for LDL-C(electrophoresis method vs PVS precipitation method) and r = 0.9235 for Lp(a)-C (electrophoresis method) vs Lp(a) (ITA method).

CONCLUSIONS

The electrophoresis method offers a simple and inexpensive means of simultaneously measuring HDL-C, VLDL-C, Lp(a)-C and LDL-C.

Background Abdominal obesity (AO) is linked to inflammation and insulin resistance (IR). However, there is limited information on whether preschoolers with AO present these risk factors. We evaluated the association between AO and cardiovascular risk factors in preschoolers. Methods We enrolled 232 children (2-5 years), of whom 50% had AO. Serum total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-c), high-density lipoprotein-cholesterol (HDL-c), triglycerides (TG), apolipoprotein B (Apo-B) and apolipoprotein A-1 (Apo-A1), glucose, insulin, high-sensitivity C-reactive protein (hs-CRP), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, IL-1β, monocyte chemoattractant protein (MCP-1/CCL2), leptin, adiponectin, vascular cell adhesion molecule (VCAM-1/CD106) and intercellular adhesion molecule (ICAM-1/CD54) were measured. The homeostatic model assessment of IR (HOMA-IR) was calculated. We analyzed these variables according to the presence of AO and other metabolic syndrome (MetS) components. Results A total of 75.8% of children with AO had one or more risk factors for MetS. Children with AO had significantly higher body mass indexes (BMIs), insulin, HOMA-IR, TG, very low-density lipoprotein-cholesterol (VLDL-c) and TC/HDL-c ratio and lower HDL-c, compared to children without AO; but there were no differences in inflammatory markers. After adjusting for BMI, sex and age, the differences between groups were not significant for any variable. Waist circumference (WC) was correlated with insulin (r=0.547; p<0.001), TG (r=0.207; p=0.001), ICAM-1 (r=0.213; p=0.039), hs-CRP (r=0.189; p=0.015) and glucose (r=0.187; p=0.004). After adjusting for BMI, age and sex, AO plus one MetS component contributed to individual variation in glucose, insulin, HOMA-IR and TG. Conclusions AO in preschool children is associated with greater IR and atherogenic lipid profiles, although these findings seem to be more related to general obesity than just central obesity. In addition, our data suggest that IR may precede the elevation of systemic cytokines in obese children, unlike findings in adults. More studies in pediatric populations are needed to elucidate these associations.

Microalbuminuria (MAU) is a strong predictor of diabetic nephropathy (DN), which is the main cause of morbidity and mortality in patients with diabetes mellitus (DM). Dyslipidemia exists in the majority of patients with DM and contributes to micro- and macrovascular complications associated with DM. Apolipoprotein CIII (apoCIII) is an inhibitor of the activity of lipoprotein lipase, which metabolizes triglyceride (TG) in very low-density lipoprotein (VLDL) and facilitates its clearance from plasma. The aim of the present study was to investigate the associations between apoCIII and MAU and the effects of atorvastatin in type 2 diabetes. In total, 120 subjects were divided into type 2 diabetes and type 2 DN groups, while 60 healthy subjects were selected as controls. The patients with DN were administered 20 mg atorvastatin daily for 16 weeks. Blood pressure, body mass index (BMI) and levels of HbA1c, FBG, TG, VLDL-cholesterol (VLDL-C), apoCIII and MAU were markedly elevated in the type 2 diabetes and type 2 DN groups compared with those in the control group (P<0.01), while high-density lipoprotein-cholesterol (HDL-C) levels were decreased significantly (P<0.01). All patients with type 2 DN showed significantly elevated blood pressure, apoCIII levels, MAU, course of the disease and rate of stroke and retinopathy compared with the patients with type 2 diabetes (P<0.01). MAU was significantly positively correlated with the course of the disease, systolic blood pressure, diastolic blood pressure, BMI and HbA1c, FBG, TG, total cholesterol, low-density lipoprotein-cholesterol, VLDL-C and apoCIII levels (P<0.05), whereas negatively correlated with HDL-C levels (r=-0.194, P=0.020). Logistic regression analysis showed that apoCIII levels were independently associated with MAU (odds ratio, 1.100; 95% confidence interval, 1.037-1.153; P<0.001). Atorvastatin improved the lipid profile and MAU in patients with type 2 DN (P<0.01). Therefore, the present study demonstrated that an independent positive correlation exists between the levels of apoCIII and MAU in patients with type 2 diabetes. Furthermore, atorvastatin may be used to improve the lipid profile and MAU in type 2 DN.

BACKGROUND

Serum triacylglycerols (TG), VLDL, HDL, fatty acid and eicosanoid spectrum are among the factors determining the risk of cardiovascular complications in NIDDM. N-3 polyunsaturated fatty acids (PUFA) are expected to have beneficial effects on these factors. In NIDDM patients there have however been previously reported (late 1980s) some adverse effects.

OBJECTIVE

Our aim was to verify the effects of n-3 PUFA in NIDDM patients using relatively low dosage.

METHODS

The investigated group included 21 NIDDM patients with dyslipoproteinemia type IV. The patients were treated for 28 days with 1.7 g EPA (eicosapentaenoic acid) + 1.15 g DHA (docosahexaenoic acid)/day (10 capsules/day of MAXEPA, Seven Seas U.K.). The lipoproteins were measured using the BIO-LACHEMA kits, the fatty acid spectrum in phospholipids was determined by gas chromatography and prostanoids (after their separation) were measured by RIA methods.

CONCLUSIONS

After the MAXEPA treatment there has been a strong decrease in TG (p < 0.005) and VLDL (p < 0.002) serum levels, accompanied by a significant increase in HDL (p < 0.02). The final-to-baseline TG ratio in individual patients negatively correlated with the relative percentage of EPA in phospholipids after the treatment (p < 0.03; r = -0.474). There was no significant change in serum total cholesterol, fasting glycaemia and glycosylated hemoglobin. There was a slight, but statistically already significant (p < 0.05), rise in LDL. The relative percentage of EPA, docosapentaenoic acid and DHA in serum phospholipids increased sharply (p < 0.001, p < 0.001, p < 0.001). The increase of n-3 PUFA in individual patients was linked with the decrease in n-6 PUFA (p < 0.001; r = -0.686). The spectrum of the latter has changed also very markedly. The prostacyclin PGI2-to-thromboxane TxA2 ratio increased significantly (p < 0.001). Beneficial effects of n-3 fatty acids have prevailed and this kind of treatment seems very encouraging also in NIDDM patients. The results are logically compatible with other authors' results pattern formed in 1990s. A slight rise in serum LDL needs a more detailed discussion since only its phenotype B ("small dense LDL particles") has been recently found to be atherogenic. (Tab. 2, Fig. 5, Ref. 15.)

Rabbit very low density lipoproteins (VLDL) have been fractionated by heparin sepharose chromatography into two subpopulations: an unretained fraction (UR) and a retained fraction (R). The separation profiles of VLDL from cyclophosphamide treated rabbits differed from those obtained in normal animals: UR fraction was far more important in treated rabbits than in control animals. Comparative studies of the two VLDL subfractions isolated from treated rabbits have been performed. Polyacrylamide gel electrophoresis in presence of urea showed a similar distribution in both fractions of apolipoproteins X, a group of low molecular weight apolipoproteins detected after antimitotic therapy. SDS - polyacrylamide electrophoresis revealed the presence of one form of apolipoprotein B: apo B100 in the VLDL from treated rabbits giving evidence of their hepatic origin. Relative to the R-fraction, the UR-fraction was characterized by an increased triacylglycerol content and a larger diameter as observed by electron microscopy. In vitro incubations with lipoprotein lipase and reisolation of postlipolysis particles suggest that both VLDL fractions can undergo metabolic conversion to LDL. A decrease of lipoprotein lipase activity after treatment, as previously observed, may thus explain the accumulation of the large VLDL.

The biological role of the very low density lipoprotein receptor (VLDL-R) in humans is not yet elucidated. This cellular receptor binds apolipoprotein E (apoE)-containing lipoparticles and is mainly expressed in peripheral tissues. The VLDL-R gene contains a polymorphic triplet (CGG) repeat located 19 bp upstream of the initiation codon. We explored the allelic distribution of this repeat in 1384 subjects of European Caucasian origin, 609 of them surviving a myocardial infarction. Six alleles corresponding to 5, 6, 7, 8, 9, and 11 repeats were detected in this population. The alleles 5, 8, and 9 were the most frequent, with frequencies of 0.413, 0.275, and 0.292, respectively. No association was found between the VLDL-R polymorphism and myocardial infarction. In controls without lipid lowering treatment, a statistically significant interaction between VLDL-R genotype and apoE phenotype was found for plasma triglycerides (P < .04), suggesting a gene-gene interaction. There was also a main effect of the VLDL-R polymorphism on LpE:B and LpA-I. The VLDL-R 9 allele was associated with lower levels of plasma LpE:B (P < .05) and higher concentrations of plasma LpA-I (P < .01) than the other alleles. These results suggest that VLDL-R has a modest influence on circulating lipoproteins in humans.

We investigated the effects of the severity of the hypertriglyceridemic state on lipolysis of very-low-density lipoproteins (VLDLs) in vivo. In six patients with mild (Mild, fasting triglyceride 2.54 +/- 0.27 mmol/L) and six with moderate hypertriglyceridemia (Mod, fasting triglyceride 4.63 +/- 0.47 mmol/L), heparin infusion decreased plasma triglycerides in direct correlation with the baseline triglyceride (r = 0.92 in Mild, r = 0.96 in Mod) concentration. Fasting VLDL-triglyceride correlated inversely with postheparin lipoprotein lipase (LPL) (r = -0.85). A decrease in VLDL-triglyceride correlated with baseline VLDL-triglyceride (r = 0.93), but not with postheparin LPL. In the Mild group, low-density-lipoprotein (LDL) cholesterol steadily increased (baseline, 2.90 +/- 0.18 mmol/L; 30 min, 3.03 +/- 0.23 mmol/L; 2 h, 3.15 +/- 0.18 mmol/L) in correlation with the decrease in VLDL-triglyceride (r = 0.89). In the Mod group, LDL cholesterol initially decreased (baseline, 2.51 +/- 0.34 mmol/L; 30 min, 2.30 +/- 0.23 mmol/L) and then increased (2 h, 2.82 +/- 0.28 mmol/L). These results demonstrate a delay in conversion of VLDLs into LDLs in pronounced hypertriglyceridemia, which may contribute to the etiology of low plasma LDL cholesterol.

<Abst<em>r</em>actText>A total of 120 ove<em>r</em>weight subjects pa<em>r</em>ticipated in this study. The ci<em>r</em>culating PCSK9 and vitamin D we<em>r</em>e measu<em>r</em>ed by ELISA technique. The se<em>r</em>um vitamin A and vitamin E amounts we<em>r</em>e simultaneously measu<em>r</em>ed by HPLC method. The se<em>r</em>um small dense LDL-Choleste<em>r</em>ol (sdLDL-C) values we<em>r</em>e evaluated using hepa<em>r</em>in-Mg2+ p<em>r</em>ecipitation technique. The lipid p<em>r</em>ofile was measu<em>r</em>ed by <em>r</em>outine labo<em>r</em>ato<em>r</em>y techniques.</Abst<em>r</em>actText><Abst<em>r</em>actText>The se<em>r</em>um vitamin E values co<em>r</em><em>r</em>elated significantly to vitamin A (<em>r</em>=0.47, P= 0.0001), <em>VLDL</em>-C (<em>r</em>= 0.30, P= 0.002), total choleste<em>r</em>ol (<em>r</em>=0.309, P= 0.001), PCSK9 (<em>r</em>=0.233, P=0.01) and total t<em>r</em>iglyce<em>r</em>ide (<em>r</em>= 0.61, P= 0.0001) values. The ci<em>r</em>culating PCSK9 values co<em>r</em><em>r</em>elated significantly to LDL-C (<em>r</em>=0.17, P=0.05) and total choleste<em>r</em>ol (<em>r</em>=0.23, P=0.009) values. Howeve<em>r</em>, the<em>r</em>e we<em>r</em>e not co<em>r</em><em>r</em>elations between the levels of se<em>r</em>um D and A vitamins, the se<em>r</em>um LDL-C, sdLDL-C and total choleste<em>r</em>ol values.</Abst<em>r</em>actText><Abst<em>r</em>actText>The data showed the co<em>r</em><em>r</em>elations between se<em>r</em>um vitamin E and PCSK9-<em>r</em>elated LDL-C values lowe<em>r</em> than the no<em>r</em>mal <em>r</em>ange. Fu<em>r</em>the<em>r</em>mo<em>r</em>e, the <em>r</em>esults suggested a nut<em>r</em>itional need on the patents conside<em>r</em>ing supplementation o<em>r</em> fo<em>r</em>tification of vitamin E fo<em>r</em> the ove<em>r</em>weight subjects with highe<em>r</em> LDL-C levels.</Abst<em>r</em>actText>

The changes in body composition and in serum levels of total cholesterol (T-chol), triglycerides (TG), high density lipoprotein cholesterol (HDL-C), very low plus low density lipoprotein cholesterol (VLDL + LDL-C), the ratio T-chol/HDL-C and non esterified fatty acid (NEFA) were studied in nineteen obese male adolescents after 28 days of slimming treatment which consisted in hypoenergetic diet and exercise. Relative fat body weight (%BF) was calculated by Parizková and Roth's regression equations for five fatfolds and lean body weight was obtained as the difference between body weight and fat body weight. Significant reductions in %BF, T-chol and T-chol/HDL-C ratio were found. The decrease in TG was not significant but had a better correlation with the reduction of adiposity (delta %BF) than the previously mentioned two variables. The increase of lipolysis during the four weeks of study is expressed in the significant rise of NEFA and its correlation (r = -0.714) with delta %BF. A tendency to increase in HDL-C could be observed, and a significant inverse correlation (r = -.804) with delta %BF was found. The results obtained showed that the combination of diet and exercise for treating obesity in adolescents influences favourably the risk factors of ischaemic heart disease related to serum lipid and lipoprotein profiles and does not significantly affect lean body mass, at least up to four weeks.

Forty male cynomolgus monkeys were fed a nutritionally complete diet containing butter and 0.5% cholesterol for 18 months to ensure development of atherosclerosis. Timefurone was administered daily at 10 mg/kg/day. Lipoprotein cholesterol parameters were measured every 4 weeks and clinical chemistries were done at approximately 8-week intervals. Low density lipoprotein cholesterol [LDL-C] was significantly reduced 24-45% at all time periods and total-C was lowered 17-23% at weeks 12, 16, and 24-40 in the timefurone group. Very low density lipoprotein cholesterol [VLDL-C] was increased 68-156% from weeks 40-78 and triglycerides [TG] were significantly elevated 52-220% on weeks 4-16, 24, 28, and 36-78 by timefurone. Timefurone caused small but significant changes in several clinical chemistry parameters including: creatinine, total bilirubin, albumin, glucose, serum glutamic-oxalacetic transaminase, and serum glutamic-pyruvic transaminase during the test. Significant reductions in arterial cholesterol were observed in thoracic aorta (-24%) and carotid arteries (-29%) in treated monkeys when compared to placebo. Arterial cholesterol in treated monkeys was positively correlated to LDL-C (R = 0.54, p less than or equal to 0.05). Timefurone, therefore, appears to have a significant beneficial effect against the development of atherosclerosis in cholesterol-fed male monkeys and possesses excellent potential for clinical experimentation.

We previously found an inverse correlation between platelet ionized magnesium concentration ((Mg2+)i) and serum total cholesterol concentration in normal male but not female subjects. In the present study, we determined the platelet (Mg2+)i by using a fluorescent ionized magnesium (Mg2+) indicator, FURAPTRA, and measured the serum concentrations of the following: total cholesterol; very-low-density lipoprotein cholesterol (VLDL-C); low-density lipoprotein cholesterol (LDL-C); high-density lipoprotein cholesterol (HDL-C); antioxidized low-density lipoprotein (LDL) autoantibodies; lipoprotein(a); apolipoproteins A-I (apo A-I) and B (apo B); triglycerides; estradiol-17 (E2); ceruloplasmin (Cp); and selected electrolytes, including total and ionized magnesium and calcium and total protein and albumin. In men, but not in women, platelet (Mg2+)i significantly inversely correlated with serum total cholesterol (r = -0.52, p < 0.02), LDL-C (r = -0.54, p < 0.009 by a "direct" method; r = -0.40, p < 0.05 by an electrophoretic method), and apo B (r = -0.42, p < 0.04). We found no significant correlations between platelet (Mg2+)i and any other variables, including serum total and ionized magnesium, antioxidized LDL autoantibodies, Cp, and E2. We speculate that decreased platelet (Mg2+)i is a possible marker for platelet membrane alterations that may affect platelet involvement in thrombosis and atherogenesis.

Triglyceride-rich lipoproteins increase net transport of cell cholesterol to postprandial plasma from healthy subjects after a meal rich in fat and cholesterol. The aim of the present study was to determine the effect of meals rich in polyunsaturated fats (PUFA) and monounsaturated fats (MUFA) and low in cholesterol on net in vitro transport of cholesterol from red blood cells (RBCs) to postprandial plasma from 21 men with mild to moderate hypercholesterolemia in a randomized, crossover trial. Cholesterol concentration increased by 12% due to accumulation of cell cholesterol in fasted hypercholesterolemic plasma incubated with a 2/1 (vol/vol) excess of RBCs at 37 degrees C for 18 hours. The increase in cell cholesterol in plasma was mainly localized in the low-density lipoprotein (LDL) fraction (64%) and the remainder was approximately equally divided between the very-low-density lipoprotein (VLDL) and high-density lipoprotein (HDL) fractions. Accumulation of cell cholesterol in the LDL fraction prevented the significant decrease in LDL cholesterol in plasma incubated alone. When RBCs were incubated with postprandial plasma isolated 4 hours and 6 hours after liquid meals rich in safflower and olive oils, the accumulation of cell cholesterol in plasma increased significantly (11%, P <.004) above values for fasted plasma and irrespective of the type of fat in the meal. Also, the content of cell cholesterol increased significantly (70%, P <.001) in triglyceride (TG)-rich lipoproteins and decreased significantly (P =.006) in the LDL fraction, which remained the main ultimate destination of cell cholesterol in postprandial plasma. The increased loss of cell cholesterol to fasted and postprandial plasma was closely correlated (r>> 0.823, P <.001) with the concomitant increase in plasma cholesteryl esters (CE) generated by lecithin cholesterol acyltransferase (LCAT) activity. There was a small (5%), significant (P <.001) increase in plasma cholesterol esterification in postprandial plasma. These data suggest that high-fat meals rich in MUFA and PUFA and low in cholesterol may produce a small postprandial increase in the capacity of plasma to accept cell membrane cholesterol that is limited by a concomitant small increase in plasma cholesterol esterification, in hypercholesterolemic subjects. Thus, low-fat, lipid-lowering diets may have a minimal effect on this capacity but will reduce levels of atherogenic LDL cholesterol that appear to be maintained by diffusion of cell cholesterol to plasma.

The measurement of CHO and TG concentrations in three lipoprotein subfractions (VLDL, LDL, and HDL) are useful to estimate qualitative change of lipoproteins. This method, CHO and TG dual staining using agarose gel electrophoresis (AG-CHO, TG staining), is conventional and the results correlated highly with ultracentrifugation. Using this method, we measured CHO and TG concentrations of VLDL, LDL, and HDL subfractions in 244 patients after an overnight fast. All cases were stratified to 4 groups, normolipidemia (LDL-CHO < 160 mg/dl, sTG < 150 mg/dl, n = 111), type IIa(n = 34), IIb(n = 39), and IV(n = 36), according to hyperlipidemia types. Furthermore, normolipidemia with low HDL cases (HDL-CHO < 45 mg/dl, n = 24) distinguished from HDL-CHO>> or = 45 mg/dl, normolipidemia cases(n = 111). Between serum TCHO and LDL-CHO, serum TG and VLDL-CHO, TG showed positive correlation(n = 0.895, 0.971), particularly serum TG and VLDL-TG showed strong positive in all lipidemia types. However, serum TG and VLDL-CHO was strongly positive in type IIb and IV(r = 0.825, 0.823), but weakly positive in type IIa(r = 0.459). HDL-CHO showed no correlation with sTCHO and sTG. The correlation of CHO and TG with each subfraction was strongly positive in VLDL(r = 0.910), weakly positive(r = 0.49) in LDL, and showed the no correlation in HDL in all cases. These correlation varied in lipidemia types, IIb and IV were strongly positive(r = 0.886, 0.838) in VLDL subfraction, but nomolipidemia cases(r = 0.555) showed significant weaker correlation(p < 0.0001). In the LDL subfraction, IIb and IV showed no correlation(r = 0.009, 0.163) between CHO and TG. The CHO/TG ratio of three subfractions were widely distributed, and type IIb and IV distributed to lower range than normolipidemia and/or type IIa lipidemia in three subfractions. From these results, dual measurement of LDL-CHO and LDL-TG are useful to estimate qualitative change in the LDL subfraction. For instance, in high LDL-CHO or LDL-TG with low CHO/TG cases, we could suspect the presence of IDL-rich particles in the LDL subfraction or small particle LDL cases. HDL-CHO and CHO/TG show positive(r = 0.714), HDL-CHO and VLDL-TG, VLDL-CHO showed weakly negative correlations(r = 0.500, 0.487), showing that high HDL-CHO level cases tended to have a CHO rich, and low VLDL-TG concentration. These results indicated that qualitative change in lipoproteins could be clarified by measurement of the TG concentration, in addition to CHO concentrations in three subfractions. We conclude that AG-CHO, TG staining method is useful for diagnosis and monitoring of dyslipidemia.