The effect of Probucol on serum lipids, lipoproteins and the apoproteins A1, A2 and B was studied in 27 patients with primary hypercholesterolemia. After 3 months of dietary treatment and a 6 week placebo period the patients received 4 X 250 mg of Probucol or placebo per day for 4 months in a double blind design. Total and LDL-cholesterol were significantly reduced with Probucol (13% and 16% respectively) in addition to the diet. Apo B showed a 12% decrease. The HDL cholesterol concentration as well as the serum triglycerides and triglyceride-rich lipoproteins were not significantly altered. Both apo A1 and apo A2 were markedly reduced under Probucol treatment. In general the subjective and objective tolerance of the drug was good.

Simvastatin (synvinolin MK-733) is a potent inhibitor of 3-HMG-CoA-reductase, the key enzyme for cholesterol biosynthesis. To investigate the efficiency and safety of this new drug on a long term basis, simvastatin was administered for 3 years to ten patients with type II hyperlipoproteinemia. Daily dosages were 20 or 40 mg. The drug therapy produced a significant reduction in serum levels of total cholesterol (19-34%), LDL-cholesterol (26-44%) and Apo B (19-33%). Triglycerides decreased moderately (2-23%) while HDL-cholesterol and Apo A1 changed only slightly (-3 to 6% and 5-13% respectively). Simvastatin was well tolerated. No consistent adverse clinical or biochemical effects were observed during the three-year therapy. The results indicate that simvastatin is a promising new therapy for high risk hypocholesterolemic patients.

The clearance of particulate triglyceride from the plasma of cholesterol-fed rats with appreciable stores of hepatic cholesterol ester produces a substantial increment in plasma cholesterol. Most of this plasma cholesterol increment arises from existing tissue sources. The increment begins from 4 to 6 h after clearance and is due to the appearance of larger cholesterol-rich, triglyceride-poor, beta migrating lipoproteins, which are isolated in the d < 1.063 fraction with an apoprotein (Apo) content consisting primarily of Apo E and smaller amounts of Apo B. A concurrent decrease in alpha lipoproteins occurs with the beta lipoprotein increment. Within 1 d of clearance the beta lipoproteins fall and alpha lipoproteins increase. The increase in total plasma Apo E and Apo B initially parallels that of the cholesterol, but it persists even when cholesterol falls. A modest decrease in plasma Apo A1 was observed during the time alpha lipoproteins declined. A significant increase in plasma lecithin cholesterol acyl transferase preceded the increase in beta lipoprotein cholesterol. This enzyme increment was absent in rats with little lipoprotein response despite increased hepatic cholesterol. In vivo inhibition of this enzyme with dithionitrobenzoic acid virtually eliminated the postclearance hypercholesterolemia. Plasma particulate triglyceride clearance induces an increase in beta lipoproteins. Coupling of this clearance and hepatic lipoprotein secretion occurs by an unknown mechanism modulated by lecithin cholesterol acyl transferase.

The effect of 2 to 3 weeks of 73% sucrose feeding and intestinal sucrose infusion upon intestinal lipoprotein formation was studied in mesenteric lymph cannulated female rats. Lymph lipoprotein fractions were analyzed for lipid and apoprotein content and were compared to chow-fed control rats. The sucrose regimen increased mesenteric lymph triglyceride output by 54%, the increase being confined to the very low-density lipoprotein fraction. Sucrose infusion in chow-fed control rats did not increase lymph triglyceride transport when compared to infusion of a glucose polymer. Unesterified cholesterol output in whole lymph was stimulated by sucrose by 76%. Both the d greater than 1.006 and d less than 1.006 g/ml fractions of lymph were found to have an increase in unesterified cholesterol output. Since no difference in the chemical composition of very low-density lipoproteins in the two groups of animals was detected, sucrose appeared to increase the number of very low-density lipoprotein particles secreted by the intestine. Sucrose did not alter the relative proportions of apo A1, apo A4, apo ARP, and total C peptides present in very low-density lipoproteins. However, differences in the proportion of apo C subunits after sucrose were detected by isoelectric focusing with a pronounced increase in the apo CIII0 peak. The present studies demonstrate that the intestine participates in changes in lipoprotein formation and metabolism that accompany experimental sucrose induced hyperlipidemia.

OBJECTIVE

In renal transplant recipients, cyclosporine treatment appears to cause more frequent hyperlipidemia than tacrolimus usage. In this study, hyperlipidemic renal transplant recipients who use cyclosporine were investigated for changes in high-density lipoprotein (HDL)-2/3, apolipoprotein (Apo) A1/B, other lipid and biochemical parameters, and body mass index after prospective cyclosporine to tacrolimus switching.

METHODS

Fifteen patients, including 9 females of overall mean age of 33.2 +/- 10.7 years and posttransplantation time of 78.06 +/- 42.93 months with a mean body mass index of 23.77 +/- 3.34 kg/m(2), were included if they were nondiabetic, hyperlipidemic, and had undergone renal transplantation between 1992 and 2000, using cyclosporine and candidates for a switch to tacrolimus due to hyperlipidemia. Before switching to tacrolimus and at 12 months of tacrolimus use we studied fasting blood samples for creatinine, uric acid, glucose, triglyceride, Apo A1, Apo B, low-density lipoprotein (LDL), HDL2, HDL3, and total cholesterol.

RESULTS

There were no significant differences in creatinine, uric acid, glucose levels, or body mass index before tacrolimus versus 12 months thereafter. It was observed that tacrolimus significantly decreased triglyceride, <em>Apo</em> <em>A1</em>, <em>Apo</em> B, LDL, HDL, and total cholesterol levels (P < .001; P = .006; P = .01; P < .001; P = .03; P </= .001, respectively), but had no effect on homocysteine, <em>Apo</em> <em>A1</em>/B, HDL 2, HDL 3, or HDL 2/3 levels (P>> .05).

CONCLUSIONS

Switching from cyclosporine to tacrolimus was associated with a more favorable cardiovascular risk profile by improving hyperlipidemia.

BACKGROUND

Blood lipid profile of French men and women obtained from the general population is not well known. Furthermore, the association between these lipids, as a function of other potential risk factors for cardiovascular disease, and sociodemographic factors such as age, educational level, and region of residence is not well studied in large samples in Europe.

METHODS

Data on French healthy volunteers, aged between 40 and 65 years for men (n = 5141) and 35 and 65 years for women (n = 7876) were obtained from the "Supplementation en Vitamines et Mineraux Antioxydants" (SU.VI.MAX) study, a primary prevention trial. Baseline blood samples were collected in 1994-1995 and analyzed for cholesterol, triglyceride, apolipoproteins (apo)-B and -A1. The results were analyzed separately for men and women as a function of age, educational level, and area of residence.

RESULTS

Overall, blood lipid levels for men and women did not differ significantly from those reported in other Western industrialized countries. Except for triglyceride in men, all blood lipids were statistically different among ages. In women, cholesterol, apo-A1, and apo-B showed a significant decrease with educational level. Statistical differences were found in both genders between blood lipids and lipoproteins among regions of residence.

CONCLUSIONS

Even if differences between region of residence were found in blood lipid levels, this cannot explain the North-East to South gradient in the prevalence of cardiovascular disease in France nor differences between France and other industrialized Western countries.

OBJECTIVE

Regular aerobic exercise leads to changes in plasma lipids, lipoprotein and apoprotein levels. The aim of this study was to examine the training effects of the intervention program consisted of regular exercise and low fat diet on plasma lipid profile.

METHODS

The effects of the four weeks intervention programme which consisted of walking and dietary restriction on lipid profile in sedentary subjects were investigated. Subjects, who had dyslipidemia or obesity, were instructed to walk (consecutive 60 minutes, one times daily) and to consume no more than 20% total fat and 300 mg/d of cholesterol for four weeks. At the end of fourth week, 41 subjects who had implemented exercise-diet programme, were assigned to study (intervention) group; 21 subjects who had remained sedentary, nondieting, were included into the control group. Total-C, triglycerides, LDL-C, HDL-C, Lp (a), apo A1 and apo B100 were measured in fasting blood samples before and after 4 weeks of intervention programme.

RESULTS

At the end of four weeks, subjects in the exercise-diet group, as compared with the control group, showed a significant reduction in body weight (respectively 1.67 +/- 2.36 kg versus -0.21 +/- 1.36 kg, p = 0.001), total cholesterol (35 +/- 37 mg/dl vs -20 +/- 25 mg/dl, p < 0.001), triglycerides (30 +/- 68 mg/dl vs -10 +/- 52 mg/dl, p = 0.024) and LDL-C (29 +/- 41 mg/dl vs -18 +/- 25 mg/dl, p < 0.001) levels. However, at the end of programme, in the exercise-diet group, as compared with the control group, the changes in HDL-C (respectively -0.85 +/- 7.30 mg/dl vs 1.05 +/- 5.64 mg/dl, p = 0.302), Lp (a) (1.59 +/- 3.06 mg/dl vs -0.09 +/- 3.96 mg/dl, p = 0.069), apo A1 (0.61 +/- 22.69 mg/dl vs -0.66 +/- 17.27 mg/dl, p = 0.822) and apo B100 (5.41 +/- 19.33 mg/dl vs -4.00 +/- 20.51 mg/dl, p = 0.080) were not significant.

CONCLUSIONS

The data of this study demonstrate that the four weeks programme based on regular daily aerobic exercise and low fat diet is capable of decreasing total cholesterol, triglycerides and LDL-C levels and that this short-term intervention is insufficient in increasing HDL-C, in decreasing Lp (a) and improving apoprotein levels.

This study examines the effects of extracellular albumin on hepatic apo B-100 metabolism. To do so, a transformed human liver cell line, HepG2, was used as a hepatocyte model and the concentration of albumin in the medium was varied between 0 and 5 g%. Apo B-100 and apo A1 concentrations in the medium were determined by specific enzyme-linked immunoassay (ELISA) and intracellular synthesis of cholesterol ester and triglyceride were determined by addition of appropriate radiolabels to the medium. The data demonstrate that the reduction of extracellular albumin concentration resulted in increased apo B-100 concentration in the medium. Apo A1 secretion, however, was unaffected. While the differences in apo B-100 concentration in the medium were statistically significant (33% +/- 7%, P < 0.0025, 0 g% albumin compared to 5 g% albumin in the medium), the absolute magnitude of the effect under these conditions was relatively modest. Nevertheless, the changes were consistent and evident over incubation periods as long as 8 days. Of interest, although triglyceride synthesis was unaffected, cholesterol ester synthesis changed such that as albumin concentration decreased, synthesis of cholesterol ester increased paralleling the changes in apo B-100 (170% +/- 9%, P < 0.005). These findings were extended by studying interventions which altered cholesterol ester synthesis. Addition of the compound 58-035 (5 micrograms/ml, a specific inhibitor of acylcholesterol acyltransferase activity) resulted in substantial inhibition of cholesterol ester synthesis (39% to 66%, P < 0.025 and P < 0.005, respectively) and apo B-100 concentrations in the medium which decreased by 20% to 28%, P < 0.025. Triglyceride synthesis, in contrast, increased significantly by 32% P < 0.025. Therefore, addition of 58-035 confirmed the previous findings of a parallel relation between cholesterol ester synthesis and apo B-100 concentration in the medium. Nonetheless, albumin still had an additional inhibitory effect on cholesterol ester and apo B-100 secretion. Of interest, when chylomicron remnants (25 micrograms/ml cholesterol), which cause apo B-100 secretion to increase by more than threefold, were added to the medium, albumin now had a more pronounced absolute effect on apo B-100 secretion with a 48% inhibition observed as albumin was increased from 0 to 5 g% in the medium (P < 0.0125). The effect of extracellular albumin on the low density lipoprotein (LDL) pathway was also examined. No differences in non-specific cell association component were detected.(ABSTRACT TRUNCATED AT 400 WORDS)

The effect of 10 day-low dosage of n-3 long chain fatty acids (390 mg/day of EPA and 252 mg/day of DHA) on lipid and apolipoprotein (Apo) concentrations has been studied in nine normolipidaemic women aged 28.9 +/- 4.2 years. n-3 fatty acid supplementation did not significantly decrease total cholesterol and triglyceride levels but markedly decreased the Apo A1 and Apo B concentrations (12.7%, p < 0.01 and 23.1%, p < 0.001, respectively), while the Apo A1/Apo B ratio significantly increased (14.8%, p < 0.02). In contrast to the individual variations found for triglycerides and cholesterol, Apo changes indicate a fairly homogeneous response to the fish oil supplement. In seven women Apo A1 decreased >> 10%), whereas Apo B decreased >> 10%) in all of them. The Apo A1/Apo B ratio increased >> 10%) in five of these nine women. Changes in Apo A-1 and Apo B did not significantly correlate with changes in serum lipids. These findings suggest that short-term supplementation with low amount of n-3 long chain fatty acids, EPA and DHA, influences the serum Apo content more than the lipid levels in normolipidaemic women.

BACKGROUND

The role of lipids in atherogenesis is now well established. However, the exact mechanisms by which different lipoproteins affect endothelial function and induce atherogenesis are still not well understood. In the present study we examined the effect of lipid profile on forearm vasodilatory response to reactive hyperemia, an index of endothelial function, in a cohort of young, low-risk adults.

METHODS

One hundred sixty seven healthy subjects were included in the study. The effect of total cholesterol, high density lipoprotein (HDL), low density lipoprotein (LDL), triglycerides, apolipoprotein (apo)-A1, apo-B and apo-E on endothelial function and inflammatory process was examined. Endothelial function was evaluated by determining forearm vasodilatory response to reactive hyperemia (RH%) using gauge-strain plethysmography. RH% was defined as the % change of forearm blood flow from baseline to the maximum flow during post-ischemic hyperemia. Endothelium independent dilatation in response to nitroglycerin (NTG%) was defined as the % change of forearm blood flow from baseline to the maximum flow after sublingual nitroglycerin administration.

RESULTS

RH% was correlated with HDL (r = 0.267, p = 0.001), LDL (r = 0.355, p = 0.0001), triglycerides (rho = -0.366, p = 0.0001), apo-Al (r = 0.240, p = 0.004) and apo-B (r = -0.277, p = 0.005). NTG% was not affected by serum lipid levels. In multivariate linear regression, LDL (beta = -0.217 [SE: 0.098], p = 0.028), apo-A1 (beta = 0.277 [SE: 0.124], p = 0.027) and age (beta = 0.916 [SE:0.369], p = 0.015) were independent predictors for RH% in this population (R2 for the model: 0.243, p = 0.0001).

CONCLUSIONS

Elevated lipid levels decrease forearm vasodilatory response to reactive hyperemia. Apolipoproteins, and especially apo-Al, are important determinants of endothelial function in these subjects, independently of LDL, HDL and triglycerides, implying that full measurement of the lipid profile may be of great importance in risk stratification of young individuals.

BACKGROUND

We tested the hypothesis that serum apolipoprotein H (apo H) concentration increases after an oral fat load. Such a study would give valuable insight into whether apo H was influenced by the postprandial state.

METHODS

Ten male subjects aged 24-48 years were fed 62.5 g of total fat (saturates 12 g, monounsaturates 35.3 g, polyunsaturates 12.5 g). Venous blood was sampled hourly for 5 h post-oral fat load.

RESULTS

No significant change in serum apo H concentration occurred following the oral fat load. However, serum apo H in the baseline samples correlated significantly with subject body mass index (r = 0.683, P < 0.05), body fat mass (r = 0.778, P < 0.01), lean body mass (r = 0.693, P < 0.05), serum triglyceride (r = 0.732, P < 0.02), serum insulin (r = 0.808, P < 0.01) and insulin resistance index (r = 0.794, P < 0.01). In stepwise multiple linear regression model, with serum apo A1, apo B, lipoprotein(a), total cholesterol, triglyceride, HDL-cholesterol, LDL-cholesterol, plasma glucose and insulin and apo H as the dependent variable, insulin remained in the model (r = 0.81, P < 0.01). Conversely, with body mass index, body fat mass, lean body mass and waist/hip ratio in the model and apo H as dependent variable, only body fat mass remained in the model (r = 0.78, P < 0.01).

CONCLUSIONS

Serum apo H may be involved in insulin resistance and relates to various indices of adipose tissue, including body fat mass. However, serum apo H concentrations do not significantly change postprandially.

OBJECTIVE

The aims of the present study were to determine if metabolic abnormalities and cytokine derangements are modified in HIV-1-infected patients after 12 months on treatment interruption (TI).

METHODS

The design of this study was prospective randomized study.

METHODS

Longitudinal multicenter study in HIV-1-infected patients with a 12-month follow-up. Patients on stable highly active antiretroviral therapy, with CD4 count >600/microL and HIV RNA <50 copies/mL for at least 6 months, were randomized to interrupt therapy or continue ongoing highly active antiretroviral therapy. Lipids (total cholesterol, triglycerides), apoproteins (A1, B, and E), and adipocytokines (leptin, adiponectin, plasminogen activator inhibitor-1, monocyte chemotactic protein-1, Interleukin-6, Interleukin-8, and tumor necrosis factor-alpha) were measured at baseline and at month 12. Multiplex suspension bead array immunoassay was performed using the Luminex 100 analyzer to identify protein expression in plasma.

RESULTS

Patients who underwent TI (n = 19) had a significant decrease in median cholesterol levels (P < 0.001), while median triglyceride levels remained unchanged. There was a significant decrease in Apo-A1 levels (P = 0.048) and Apo-B levels (P < 0.001) and an increase in tumor necrosis factor-alpha levels (P = 0.034). Given the greater decrease in Apo-B, the ratio Apo-A1/Apo-B increased after 12 months of TI (from 3.4 to 5.1, P = 0.008). We did not find significant variations in leptin or adiponectin levels. In patients who continued on highly active antiretroviral therapy (n = 18), there were no significant changes in any of the measured parameters.

CONCLUSIONS

The lipid profile and apoproteins levels change toward a less atherogenic profile after TI, arguing against a lipid-mediated mechanism to explain the increased cardiovascular risk in patients who interrupt treatment.

BACKGROUND

Icosabutate is a structurally enhanced omega-3 fatty acid molecule developed with the aim of achieving improved triglyceride (TG)-lowering efficacy, increased potency, and preserved safety compared with conventional prescription omega-3 fatty acid.

OBJECTIVE

To evaluate the efficacy and safety of icosabutate 600 mg once daily in patients with very high TGs.

METHODS

After a 6-8 week run-in period, men and women with TG levels ≥ 500 mg/dL and ≤ 1500 mg/dL were randomized to double-blind treatment with placebo or icosabutate 600 mg for 12 weeks. The primary end point was % change from baseline in TGs at 12 weeks.

RESULTS

A total of 87 subjects were randomized. At baseline, median TG (interquartile range) levels were 611 (543-878) and 688 (596-892) mg/dL, and the median change after 12 weeks of treatment was -51% and -17%, respectively, for a placebo-corrected change of -33% (P < .001). Adjusted for placebo, icosabutate significantly reduced very low-density lipoprotein cholesterol (-36%, P < .001), remnant lipoprotein cholesterol (-34%, P < .001), apolipoprotein (Apo) C-III (-35%, P < .001), trended toward reduced non-high-density lipoprotein cholesterol (-7%, P = .064); significantly increased high-density lipoprotein cholesterol (18%, P < .001) and low-density lipoprotein cholesterol (28%, P < .001), with a trend of an increased lipoprotein (a; 10%, P = .054). No changes were observed in total cholesterol, apolipoprotein B, or apolipoprotein A1. Fasting plasma glucose was unchanged, whereas fasting plasma insulin was reduced (P = .001) with icosabutate. Icosabutate was generally well tolerated.

CONCLUSIONS

Treatment with icosabutate once daily significantly reduced TG, very low-density lipoprotein cholesterol, and Apo C-III levels in patients with very high TG levels. This trial was registered at www.clinicaltrials.gov as NCT01893515.

Blood collected from 62 fetuses aged 20-38 weeks of gestation was studied. The values of ten lipid parameters were determined: cholesterol (TC), triglycerides (TGs), apolipoprotein A1 (apo A1), apolipoprotein B (apo B), apolipoprotein E (apo E), total apolipoprotein CIII (apo CIII), apolipoprotein CIII present in particles containing apo B (apo CIII LpB) or not (apo CIII Lp non-B), lipoparticles A1 (LpA1), and lipoprotein a (Lp(a)). The results show that, except for apo E, all the studied parameters were present in lower concentrations than in adults and newborns, and that Lp(a) is not detectable at that stage in life.

Peroxisome proliferator-activated receptors (PPARs) and liver X receptor alpha are ligand-activated transcription factors that belong to nuclear receptors superfamily and are involved in the regulation of lipid metabolism. PPAR, especially PPAR-alpha, PPAR-gamma agonists and liver X receptor alpha agonists can regulate the expression or biosynthesis of some factors involved in the formation and function of HDL, such as apolipoprotein (apo) A-I and ATP binding cassette transporter A1 (ABCA1). It is well known that HDL plays an important role in the treatment of hyperlipidemia as the carrier of reverse cholesterol transport. In the present study, the anti-hyperlipidemic properties of CM108, a derivative of flavone, 9-Hydroxy-2-mercapto-6-phenyl-2-thioxo-1,3,5-trioxa-2lambda(5)-phospha-cyclopenta[b]naphthalen-8-one, were studied. Through the transactivation assays of in vitro study, it was discovered that CM108 could activate PPAR-alpha PPAR-gamma and liver X receptor alpha at 40-150 microg/ml, which subsequently resulted in activating ABCA1 promoter and enhancing apoA-I and apoA-II production, whereas reducing apoC-III production significantly. Furthermore, after in vivo study that the hyperlipidemic rats were treated with CM108 for 4 weeks, a significant increase was found in HDL cholesterol levels (26.7%, P<0.05) and a significant decrease was also noticed in triglyceride levels (26.3%, P<0.01) at 100 mg/kg CM108 group compared with that of control animals. Meanwhile, the atherogenicity index, represented by total cholesterol/HDL ratio, was significantly reduced (P<0.01). In conclusion, CM108 can effectively elevate HDL levels and lower triglyceride levels in hyperlipidemic rats maybe by regulating a series of genes, receptors and proteins related to HDL.

OBJECTIVE

Recent data indicate that oral medroxyprogesterone acetate (MPA) has limited unfavourable, neutral or even favourable effects on serum lipid fractions when added to oestrogen replacement therapy. The purpose of this study was to evaluate the serum lipid fractions at the beginning and at the end of each phase of a sequentially combined replacement cycle comparing the oral and the transdermal routes of oestrogen administration.

METHODS

Randomized study with a matched control group. Oral conjugated oestrogens (OCE, 0.625 mg) or transdermal oestradiol (TE 50 micrograms) was taken from day 1 to day 25 and MPA (5 mg) added on days 14 to 25. Serum lipids were evaluated on days 1, 14 and 25 of monthly replacement cycles.

METHODS

The early post-menopausal women in the control group (n = 11) and in the treatment groups (OCE/MPA, n = 15; TE/MPA, n = 17) were evaluated every 3 months for 12 months and every 6 months for another 12 months.

METHODS

Serum levels of triglycerides (TG), cholesterol (C) fractions and apolipoproteins (Apo) and their respective ratios were measured at months 1, 3, 6, 9, 12, 18, 24. Menopausal symptoms and uterine bleedings were evaluated in parallel and an endometrial biopsy was performed at the end of the 12th and 24th months of treatment.

RESULTS

After 14 days of OCE, C, LDL-C, and Apo B were decreased and TG, HDL-C and Apo A1 were increased. The sequential addition of MPA accentuated the reduction of LDL-C and Apo B but attenuated the elevation of TG, HDL-C and Apo A1. These changes tended to revert toward baseline during the period free of medication. By contrast, at the end of 14 days of TE there was a non-significant reduction in TG and LDL components and a limited increase in HDL-C and Apo A1. During the subsequent addition of MPA there was no significant decrease in TG, LDL-C or Apo B but an elimination of the increase in HDL components. These combined changes resulted in a significant reduction in the LDL-C/HDL-C ratio and a significant elevation in the Apo A1/Apo B ratio only in the OCE/MPA group.

CONCLUSIONS

Overall, oral conjugated oestrogens induced favourable intragroup changes in cholesterol fractions whereas transdermal oestradiol maintained serum lipids at levels not different from baseline. The sequential addition of oral medroxyprogesterone acetate attenuated the beneficial elevation of HDL, did not affect the beneficial effect of oestrogens on ratios of cholesterol fractions and attenuated the unfavourable effect of oral conjugated oestrogens on triglycerides. The partial loss of beneficial effects on lipoproteins during cyclical interruption of hormone therapy would be an argument in favour of the evaluation of continuous regimens of oestrogen/progestagen replacement.

Recombinant mouse IL-1receptor antagonist protein (rmIL-1ra) was expressed in Escherichia coli. In vivo administration of rmIL-1ra, in a casein-induced murine model of acute inflammation, completely abolished the hepatic induction of the mRNAs specifying serum amyloid A1 (A-SAA1) and A-SAA2 for up to 12 h, indicating that hepatic A-SAA mRNA synthesis is totally IL-1 driven. A-SAA protein, however, was present in the serum of rmIL-1ra-treated casein-stimulated mice (although at lower levels than in untreated casein-stimulated mice) at 12 h indicating that extrahepatic A-SAA synthesis is driven in part by factors acting independently of IL-1. Hepatic mRNA levels of the other mouse acute phase reactants (APRs), serum amyloid P component, C-reactive protein, alpha1-acid glycoprotein, and C3 were also induced with casein after 12 h, as were serum protein levels of SAP and C3. These inductions were only partially inhibited by rmIL-1ra, indicating that hepatic expression of the latter APRs (unlike that of A-SAA) is driven partly by IL-1 and partly by factors acting independently of IL-1. Hepatic mRNA levels of the negative APRs apolipoprotein A-I and serum albumin were down-regulated 12 h after casein stimulation. rmIL-1ra partially restored serum albumin mRNA levels but not apo A-I mRNA levels, indicating differential regulation of these negative APRs. The rmIL-1ra will be useful in studies of IL-1-mediated gene regulation in murine models of inflammation.

Among high density lipoprotein particles, LpAI particles which contain apolipoprotein A1 alone, appear to be involved in cholesterol transport from peripheral tissues to the liver. The aim of this cross-sectional study was to examine serum LpAI particle concentrations in Type 1 and Type 2 diabetic patients with renal lesions of differing grades, in comparison with normal controls and with nondiabetic patients presenting with chronic renal failure. LpAI concentrations and LpAI-to-apo A1 ratios were increased in Type 1 diabetic patients with normal albumin excretion. In Type 1 and in Type 2 diabetic patients with increased urinary albumin excretion, LpAI concentrations and LpAI-to-apo A1 ratios were found to be not different from those of normal controls. In diabetic and in nondiabetic patients with chronic renal failure, LpAI concentrations were decreased. These abnormalities may contribute to the development of macrovascular complications.

BACKGROUND

Trace amounts of lipids are present in the urine of patients with glomerular disease, raising the possibility that the excess lipids reabsorbed by tubule cells may be toxic to these cells. In the present study, we assessed the prognostic value of micro-cholesterol (mCHO) levels in patients with chronic glomerular disease.

METHODS

The urinary mCHO levels of healthy subjects and patients with chronic kidney disease were measured by the enzymatic cholesterol cycling (ECC) method with a minimum detection level of 0.10 x 10(-3) mmol/L. First, the urinary mCHO levels of healthy subjects and 320 patients with various glomerular diseases with proteinuria >1000 mg/gCr were measured. Second, correlations of urinary mCHO levels with those of various other molecules, including albumin, IgG, IgM, transferrin, phospholipid, alpha1-microglobulin (alpha1MG), Apo A1, Apo A2, and Apo B, and urinary fatty body counts, were determined. Third, urinary mCHO, total protein (TP), albumin, and N-acetyl-beta-D-glucosaminidase (NAG) levels were measured longitudinally over 12 months (20.5 +/- 5.8 months) in 68 nondiabetic patients with impaired renal function [serum creatinine (Cr)>> or = 1.5 mg/dL]. Correlations of the concentrations of urinary parameters in the initial 3-month period with the slopes of the reciprocal of creatinine versus time for the entire follow-up period were assessed by the ROC method and multiple regression analysis.

RESULTS

Urinary mCHO levels of the healthy subjects were 0.06 to 0.72 mg/gCr for males and 0.16 to 2.34 mg/gCr for females. Urinary mCHO levels in subjects with minimal change nephrotic syndrome were significantly lower than those in the patients with other glomerular diseases with massive proteinuria. Urinary mCHO levels correlated significantly with Apo A1 and Apo A2 levels, but not with urinary Apo B levels, in the latter subjects. The correlation coefficient of urinary fatty body counts (a marker of lipoprotein loading tubulopathy) with mCHO was higher than those with TP, albumin, IgG, IgM, and alpha1MG. The urinary mCHO elevation was significantly greater in patients who had a nonselective index of proteinuria than in those with a highly or moderately selective index. In nondiabetic patients with impaired renal function, the urinary mCHO level had a higher predictive value for rapid decline of renal function than TP, albumin, or NAG.

CONCLUSIONS

The urinary cholesterol level corresponds to the magnitude of urinary HDL excretion, and correlates with the degree of lipoprotein loading tubulopathy. Measurement of urinary mCHO by the ECC method is a simple and useful tool for predicting progression of chronic glomerular disease.

Aims: To investigate the associations between Lp(a), Apo A1, Apo B, and Apo B/Apo A1 ratio with micro- and macrovascular complications of diabetes.

Methods and results: In this case-cohort study, 1057 patients with type 2 diabetes (T2DM) were followed in the diabetes clinic of Vali-Asr Hospital from 2014 to 2019. The association between serum Lp (a) and apolipoproteins with cardiovascular disease (CVD), neuropathy, and nephropathy were assessed by using binary regression analysis. The ROC curve analysis was used to evaluate the predictive properties of proteins. Youden index was used to calculate cutoff values. Among patients with T2DM, 242, 231, and 91 patients developed CVD, neuropathy, and nephropathy, respectively. The serum Lp (a) level was positively correlated with the development of all three. (P-values = 0.022, 0.042, and 0.038, respectively). The Apo A1 level was negatively correlated with nephropathy. Among the biomarkers, Lp(a) had the highest AUC for prediction of CVD, neuropathy, and nephropathy. Calculated cutoff values of Lp(a), and Apo A1 levels were higher than the standard cutoff values.

Conclusion: Serum level of Lp(a) is a predictor for CVD, neuropathy, and nephropathy. Based on the calculated cutoff values in patients with T2DM, we should consider diabetic complications at higher levels of Lp(a).

Keywords: Apolipoproteins; Cardiovascular complications; Diabetic nephropathy; Diabetic neuropathy; Lipoprotein(a) [Lp(a)]; Type 2 diabetes.

OBJECTIVE

To compare the safety and efficacy of lovastatin and simvastatin in patients with primary hypercholesterolemia.

METHODS

Fourteen Canadian centres participated in this double-blind, randomized, parallel-design study with a six-week screening period, a four-week placebo baseline period and an 18-week active treatment period. Patients were included in the study if their total cholesterol (TC) was at least 6.2 mmol/L and total triglycerides (TG) were 4.0 mmol/L or less at baseline. Half of the patients were in stratum I (TC 6.2 to 7.8 mmol/L at baseline and placebo period) and half in stratum II (TC greater than 7.8 mmol/L). The initial dose of lovastatin or simvastatin (20 and 10 mg/day, respectively) was doubled if the patient's cholesterol was greater than 5.2 mmol/L after six and/or 12 weeks, to a maximum of 80 mg/day lovastatin or 40 mg/day simvastatin. Of 298 randomized patients, two had baseline data only (and were excluded from the efficacy analysis), while 77 were treated with lovastatin and 74 with simvastatin in stratum I, and 72 were on lovastatin and 75 on simvastatin in stratum II.

RESULTS

In stratum I, both lovastatin and simvastatin lowered TC (-26.0% in both the lovastatin and simvastatin groups), low density lipoprotein (LDL) cholesterol (-33.4% in lovastatin and -34.4% in simvastatin), TG (-11.4% in lovastatin and -16.2% in simvastatin), apolipoprotein (apo)-B (-24.8% in lovastatin and -26.3% in simvastatin) and the TC:high density lipoprotein (HDL) cholesterol ratio (from 6.65 to 4.73 in lovastatin and from 6.45 to 4.46 in simvastatin), and increased HDL cholesterol (+3.6% in lovastatin and +7.8% in simvastatin) and apo-A1 (+6.3% in lovastatin and +9.0% in simvastatin) with P < 0.001 in all within-group tests except for HDL cholesterol (P < 0.05). Similar results were obtained in stratum II for TC (-30.7% in lovastatin and -30.3% in simvastatin), LDL cholesterol (-37.6% in lovastatin and -36.8% in simvastatin), TG (-21.9% in lovastatin and -16.9% in simvastatin), apo-B (-32.0% in lovastatin and -31.7% in simvastatin), TC:HDL cholesterol ratio (from 8.62 to 5.47 in lovastatin and from 8.96 to 5.77 in simvastatin), HDL cholesterol (+9.7% in lovastatin and +7.5% in simvastatin) and apo-A1 (+7.2% in lovastatin and +8.8% in simvastatin), with P < 0.001 in all within-group tests. Serious adverse events (clinical and laboratory) were reported in four patients in the lovastatin group and three in the simvastatin group. The most reported nonserious adverse effects were gastrointestinal tract (15 patients in the lovastatin group and 16 in the simvastatin group) and musculoskeletal (14 patients in the lovastatin group and 11 in the simvastatin group). Medication was withdrawn in eight patients.

CONCLUSIONS

Both lovastatin and simvastatin were found to be effective and well tolerated in each stratum. However, there were no significant differences between lovastatin and simvastatin in the treatment of moderate or severe primary hypercholesterolemia.

Serum concentrations of total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride (TG), apolipoprotein A1 (Apo A1), and apolipoprotein B (Apo B) were determined in mentally handicapped subjects (n = 87). 33 women were on lynestrenol 5-10 mg for therapeutic amenorrhea (TA). 18 of them were randomly allocated to continue on lynestrenol and 15 were switched to intramuscular administration of medroxyprogesterone (DMPA). The switch to DMPA resulted in significant increases in HDL-C (33%), Apo A1 (12%), as well as in the HDL-C/LDL-C (48%) and Apo A1/Apo B (22%) ratios. The concentrations of HDL-C and Apo A1 were significantly greater in patients receiving DMPA, than in patients continuing with lynestrenol therapy. The amenorrhea incidence, however, did not differ between the two therapy groups. It is concluded that therapy with DMPA may be associated with smaller atherosclerosis risk than with peroral lynestrenol, because of its weaker effect on HDL-C and A1 levels.

BACKGROUND

A relationship between asthma and obesity has been documented in children and adolescents. An alternate day calorie restriction diet has been reported to improve asthma symptoms by decreasing levels of serum cholesterol and triglycerides, reducing markers of oxidative stress and increasing levels of the antioxidant uric acid. Therefore, to investigate the lipid profile in asthmatic children may be important in asthma control treatment.

METHODS

One hundred and sixty newly diagnosed persistent asthmatic children were selected to participate in the study. They were divided into four groups based on their body mass index (BMI): Group I normal weight (BMI=20-24.9kg/m(2), n=30); Group II under-weight (BMI<20kg/m(2), n=30); Group III overweight (BMI=25-30kg/m(2), n=25); and Group IV obese (BMI>30kg/m(2), n=25). Fasting blood sugar, fasting insulin, and HbA1c were measured to exclude the possibility of pre-diabetes. Lipid profile measurements included total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), apo-A1, apo-B and triglycerides.

RESULTS

There were no significant differences in the levels of apo-A1, apo-B, triglycerides, cholesterol and LDL in all four groups. Only the level of HDL was higher in GIV>GIII>GII>GI (75.84±13.95, 68.56±15.28, 64.17±13.93, 63.17±14.34mg/dl, respectively). There were no cases of pre-diabetes in any of the four groups.

CONCLUSIONS

Hypercholesterolaemia and hypertriglyceridaemia were not found in any of the persistent asthmatic children, and thus they are not high risk factors for asthma. Similarly, there were no differences in apo-A1 and apo-B between any of the BMI groups. No differences were found in LDL levels, however HDL levels were increased in all four groups, indicating that allergic sensitisation may have occurred. Controlling body weight and restricting calorie intake may be as important as appropriate pharmacological management in controlling asthma.

We have elucidated the structures of N-linked sugar chains of human apolipoprotein (apo) B-100 (Arch Biochem Biophys 1989; 273:197-205). To investigate the role of the carbohydrate moieties of apolipoprotein B-100, we determined the structures of the N-linked sugar chains of apo B-100 purified from low density lipoprotein (LDL) of a Watanabe heritable hyperlipidemic (WHHL) rabbit and compared them with those of fasting Japanese White rabbits. The N-linked oligosaccharides of apo B-100 were liberated by hydrozinolysis, followed by NaB3H4 reduction, and were fractionated by paper electrophoresis and Bio-Gel P-4 column chromatography. These consisted of one neutral fraction (N) and two acidic fractions (A1 and A2) in both WHHL and fasting rabbits. N contained high mannose type oligosaccharides consisting of Man5GlcNAc2 to Man9GlcNAc2. A1 and A2 contained monosialylated and disialylated biantennary complex type oligosaccharides, respectively. The molar ratios of N, A1, and A2 were 5:2:2 in the WHHL rabbit and 4:2:5 in fasting rabbits. The content of sialic acid residues in the WHHL rabbit was calculated to be 0.64 by taking the value of that in fasting rabbits as 1.0. These results show the heterogeneity of N-linked sugar chains of apo B-100 in WHHL and fasting rabbits and suggest the possibility that the characteristics of LDL in WHHL rabbits may be altered by making the surface charge more positive than in fasting rabbits.