Risk Of Atherogenesis Research Articles

LIPID AND CARBOHYDRATE METABOLISM, AND ANTIOXIDANT STATUS IN CHILDREN AFTER LIVER TRANSPLANTATION

Organ transplantation is a risk factor of atherogenesis that may be related to immune suppression therapy. Increased free radical generation may even aggrevate atherogenesis. The aim of the study was to assess lipid metabolism in relation to risk factors of atherogenesis as well as carbohydrate metabolism and antioxidant status in children after liver transplantation. Material: We investigated 35 children 3-5 y after liver transplantation aged 10.6 ± 4.7. We did not observe major liver injury in the patients studied (normal bilirubin and INR). Results: 95% conf. interval of total cholesterol (150-191 mg/dl), LDL-C (83-111 mg/dl), VLDL-C (12-18 mg/dl), HDL-C (44-54 mg/dl), apo AI (1.27-1.49 g/l), apo B (0.6-0.89 g/l), alpha-tocopherol (7.8-8.83 μg/ml) serum concentrations were within the normal limits. GSH was decreased in transplanted children when compared to 28 aged matched healthy controls (527.6-606.6 μmol/ml vs. 667.5-763.5), whereas GPx activity was similar in the study and control group (28.3-32.8 U/gHb vs. 30.6-34.5). Kruskall Wallis analysis in subgroups of children treated with cyclosporine (Cs) only (n = 8), tacrolimus (Tac) only (n = 12) and mycophenolate mofetil (MMF; n = 8) showed differences only in total cholesterol (Cs: 131.6-285.6; Tac: 144.0-181.6l; MMF: 132.1-181.2) and LDL-C (Cs: 79.4-126.9; Tac: 42.2-118.8; MMF: 74.2-117.3). Conclusion: Lipid metabolism is not significantly disturbed in children after liver transplantation that does not point to the high risk of atherogenesis. Cyclosporine seems to have the strongest untoward effect on cholesterol metabolism. GSH concentration is decreased after liver transplantation that may be related to slightly impaired liver function, but GPx activity and alpha-tocopherol concentration remain normal.

Growth hormone therapy influences endothelial function in children with renal failure.

Endothelial dysfunction, an early step in atherogenesis, is prevalent in children with renal insufficiency. Endothelial dysfunction in growth hormone deficiency is reversed by growth hormone (rhGH) therapy. Renal failure induces growth hormone resistance at the receptor and post-receptor level, which can be overcome by rhGH therapy. This study investigates the influence of rhGH therapy in children with renal failure on flow-mediated dilation (FMD) of the brachial artery, a marker of endothelial function. We studied 8 patients, who were on rhGH for at least 6 months, and 8 healthy children for comparison. FMD of the brachial artery was measured non-invasively as the percentage increase in diameter during post-ischemic hyperemia. Patients were studied at baseline, after 4 weeks interruption of rhGH therapy, and 4 weeks after resumption of therapy. FMD was significantly lower in patients (4.7%) than healthy controls (13.8%) ( P=0.01). During the administration of rhGH, FMD was significantly higher (3.9%) than during interruption of the treatment (1.4%) ( P=0.04). Our data support the theory that a disturbance in the GH-IGF axis contributes to the endothelial dysfunction of renal failure. Treatment with rhGH not only improves growth but may also favorably influence the risk for atherogenesis.

Nitrogen dioxide air pollution near ambient levels is an atherogenic risk primarily in obese subjects: a brief communication.

Ambient exposure to nitrogen dioxide, a critical air pollutant in developed countries, is positively associated with cardiovascular mortality and morbidity. Although its cardiovascular effects are predominantly shown in patients with high risk of atherogenesis, no studies have elucidated whether daily exposure to nitrogen dioxide air pollution enhances atherogenic metabolisms, primarily in obese subjects who are susceptible to atherogenesis and subsequent cardiovascular diseases. We used male Otsuka Long-Evans Tokushima Fatty (OLETF) rats as obese subjects and Long-Evans Tokushima (LETO) rats as nonobese controls. The animals were continuously exposed to nitrogen dioxide at a concentration of 0, 0.16, 0.8, or 4.0 ppm from 8 weeks of age through 32 weeks. At 40 weeks of age, levels of body weight, triglyceride, and total cholesterol were significantly greater in the OLETF rats than in the LETO rats. A ratio of high-density lipoprotein (HDL) to total cholesterol was significantly smaller in the former than in the latter. In the LETO rats, nitrogen dioxide exposure significantly decreased only the levels of HDL as compared with clean air exposure. In the OLETF rats, however, nitrogen dioxide exposure at a concentration of 0.16 ppm significantly elevated triglyceride concentration and decreased the ratio of HDL to total cholesterol as well as the levels of HDL. Nitrogen dioxide air pollution near ambient levels is an atherogenic risk primarily in obese subjects.

Enhanced lipoprotein lipase secretion and foam cell formation by macrophages of patients with growth hormone deficiency: possible contribution to increased risk of atherogenesis?

GH deficiency is associated with increased prevalence of atherosclerosis, and recent data indicate a proatherogenic role for macrophage lipoprotein lipase (LPL) in the arterial wall. In this pilot study, we determined LPL expression and foam cell formation in monocyte-derived macrophages of 12 control subjects and nine patients with GH deficiency without GH replacement therapy. LPL mRNA levels, mass, and activity were increased in macrophages of patients with GH deficiency. In these subjects, macrophage LPL activity correlated with body mass index and fat mass. Incubation of patient macrophages with IGF-I for 24 h or differentiation of monocytes isolated from GH-deficient patients into macrophages in the presence of this growth factor decreased the amount of LPL mass. Compared with control cells, macrophages derived from GH-deficient patients took up and stored increased amounts of proatherogenic lipoproteins and were more easily converted to foam cells. In the supernatants of these cells, increased levels of free fatty acids and TNFalpha were also documented. These results demonstrate that macrophages of patients with GH deficiency secrete increased amounts of proatherogenic cytokines and are more susceptible to foam cell formation. These alterations may contribute to the increased cardiovascular risk in patients with GH deficiency.

Tocotrienols and Atherosclerosis

The adherence of monocytes to the vascular endothelial cells is an important early event in atherogenesis. Monocyte adherence to endothelial cells is induced by oxidized low density lipoprotein (LDL) and mediated by multiple cell adhesion molecules including vascular cell-adhesion molecule 1 (VCAM-1). Enhanced endothelial expression of these molecules by oxidized LDL has been shown to be a critical step in foam cell formation and the development of atherosclerosis. Recent studies have demonstrated that vitamin E inhibited the expression of mRNA and protein for VCAM-1 by endothelial cells in response to stimulation with oxidized LDL or inflammatory cytokines. Compared to α- tocopherol, α-tocotrienol displayed a more profound inhibitory effect on adhesion molecule expression and monocytic cell adherence. Among the isomers of tocotrienol, δ-tocotrienol was a potent and effective agent for the reduction of cellular VCAM-1 expression and monocytic cell adherence. The inhibitory effects of vitamin E analogs on the adhesiveness of endothelial cells correlated with their intracellular concentrations. Anti-atherogenic effects of tocotrienols may be derived from their properties of cholesterol-lowering effect, protein kinase C inhibition, and modulation of cyclooxygenase cascade. Although recent human studies have raised some doubts on the efficacy of vitamin E in the prevention of progression of atherosclerotic lesions, the experimental studies using tocotrienol strongly support its positive effect on the reduction of risk of atherogenesis. Further studies will be necessary for clarifying the anti-atherogenic effect of tocotrienol and its bioavailability after oral administration.

Postprandial lipemia and cardiovascular disease.

Postprandial lipemia, characterized by a rise in triglyceride-rich lipoproteins after eating, is a dynamic, nonsteady-state condition in which humans spend the majority of time. There are several lines of evidence suggesting that postprandial lipemia increases risk of atherogenesis. Clinical data show a correlation between postprandial lipoproteins and the presence/progression of coronary artery disease and carotid intimal thickness. Mechanistic studies demonstrate that triglyceride-rich lipoprotein remnants may have adverse effects on endothelium and can penetrate into the subendothelial space. Exchange of core lipids between postprandial lipoproteins and low-density lipoprotein (LDL)/high-density lipoprotein (HDL) is increased during prolonged lipemia, resulting in small, dense LDL particles and reduced HDL cholesterol levels. Hemostatic variables, including clotting factors, platelet reactivity, and monocyte cytokine expression, may be increased during postprandial lipemia. Collectively, these data suggest that assessment and treatment of atherosclerosis should include parameters related to postprandial lipemia.

Study 1: unexpected high incidence of coronary artery disease and abnormal platelet reactivity in long-term pediatric kidney transplant recipients

L ong-term outcomes of children who undergo renal transplantation are unknown. However, as they enter adulthood, many will have risk factors for developing coronary artery disease (CAD). Certain noninvasive tests may detect early CAD. Electron-beam computed tomography (EBCT) can measure the amount of coronary artery calcification (CAC), which correlates with the presence of atherosclerotic CAD. In addition, abnormal platelet function has been linked to increased risk for atherogenesis and CAD. The purpose of this study was to determine the incidence of CAD by using EBCT in adults who underwent renal transplantation as children and determine whether presence of accelerated atherogenesis is associated with enhanced platelet reactivity. Eight pediatric kidney transplant recipients with good long-term allograft function ( 10 years) underwent evaluation by EBCT. The CAC score was determined by standardized technique. Platelet reactivity was assessed by measures of dense granule secretory rate, metabolic content, and spontaneous microaggregate formation. Results were compared with those in age-matched controls. The mean age at transplantation was 14 years (range, 10-16). Mean age at evaluation was 45 years (range, 23-48). Mean follow-up in this group was 17 years (range, 10-23). All received cyclosporine-based immunosuppression. Seven had 2 or more clinical risk factors for CAD. All were asymptomatic at the time of evaluation. Seven out of 8 patients had significant CAC detected on EBCT. When compared with ageand gender-matched controls, study patients had CAC scores 99% (n 4), 95% to 99% (n 2), and 75% to 95% (n 1). Platelets from those with CAC were significantly more likely to form microaggregates after mild stimulation compared with those without CAC (P .02). Also, they were more likely to form microaggregates (P .03), had slower dense granule secretion (P .04), and had lower metabolic stores (P .03) compared with controls. Conclusion: The incidence of CAC by EBCT in long-term pediatric kidney transplant recipients is much higher than expected compared with the general population. Besides clinical risk factors, it appears that platelets from these patients are more reactive, which may place them at further increased risk for thrombotic complications of atherosclerosis. Our data suggest that measures to decrease risk factors for CAD should be undertaken as children approach young adulthood. From the William J. von Liebig Transplant Center, Mayo Clinic; and the Department of Radiology; and Division of Cardiovascular Medicine, Mayo Clinic, Rochester, MN. © 2004 Elsevier Inc. All rights reserved. 0955-470X/04/1704-0000$30.00/0 doi:10.1016/j.trre.2003.10.006

Serum glucose and insulin response to mango and papaya in type 2 diabetic subjects

To rank Bangladeshi Mango and Papaya in terms of their Glycemic Index (GI) and Insulinemic Index (II), which are useful measures of glucose and insulin responses to a dietary component, thirteen type 2 diabetic subjects consumed, under a cross-over design, equi-carbohydrate amounts of mango (250 g), papaya (602 g) and white bread (the reference food, 63 g). Blood sample was drawn 5 times between 0h and 3h. Serum C-peptide was measured to evaluate Insulinemic status. Mango and Papaya showed higher serum glucose responses compared to that of bread. The similar glycemic responses of Papaya and Mango were reflected in their GI values. Papaya showed higher insulin response compared to both Mango and Bread ( p < 0.001). Papaya also showed significantly higher C-peptide–glucose ratio in comparison to that of Mango and Bread. The data suggest that equi-carbohydrate amount of Papaya and Mango produce higher glycemic response as compared to bread, but the two fruits are comparable regarding this property. The higher insulin response of papaya needs to be considered in case of therapeutic management of diabetic patients and in assessing the risk of atherogenesis due to hyperinsulinemia.

Wine Polyphenols and Optimal Nutrition

One of the key elements of Mediterranean diet is the use of wine, usually taken with foods. Besides the evidence from human experience and ancient medicine, modern experimental data support the notion that the most striking effect of wine in protecting against cardiovascular disease involves the reduction of oxidative damage to plasma lipoproteins. This oxidative damage is thought to be mediated by eating foods containing oxidized lipids. In fact, eating a meal containing oxidized lipids increases the plasma level of lipid hydroperoxides and increases the susceptibility to oxidation of LDL. The postprandial increase of LDL-, an oxidatively modified form of LDL, where apoB is unfolded and sinking in the core of the particle, is a valuable biomarker for this food-derived oxidative stress in plasma. Wine, taken with foods minimizes the postprandial rise of lipid hydroperoxides and LDL- and abolishes the increase of LDL oxidability. Among wine antioxidants, the best candidates for providing an antioxidant effect are procyanidins. These compounds are considered better antioxidants than the corresponding monomers containing catechol groups. This is due to the hydrogen transfer mechanism for the radical-scavenging reaction, which renders the reaction more specific for peroxyl radicals and pH independent. Moreover, the fast intramolecular disproportion among aroxyl radicals pulls the antioxidant reaction by both decreasing the oxidation potential and increasing the rate of the reaction. Apparently, wine procyanidins are active in preventing lipid oxidation of foods while in the digestive tract, thus preventing the postprandial plasma rise in oxidants. The likely limited bioavailability of these compounds, therefore, does not affect their relevance as key elements for optimizing nutrition and reducing risk of atherogenesis. Accordingly, studies with rabbits fed a high cholesterol diet show that grapeseed procyanidins are strongly protective not only in terms of reducing plasma lipid peroxides, but they also markedly inhibit lipid-laden foam-cell deposition. Drinking wine at meals provides this kind of protection, and the final benefits are realized by the prevention of the development of atheromatous lesions even under conditions of hypercholesterolemia.

Triacylglycerol-rich lipoproteins alter the secretion, and the cholesterol-effluxing function, of apolipoprotein E-containing lipoprotein particles from human (THP-1) macrophages

Elevated plasma levels of triacylglycerol-rich lipoproteins (TGRLP) are associated with increased risk of atherogenesis and abnormal reverse cholesterol transport, as illustrated in Type II diabetes. Here we examine the effect of plasma triacylglycerol-rich or cholesteryl ester-rich lipoproteins on the secretion of nascent apolipoprotein E (apoE)-containing lipoprotein E (LpE) particles by human (THP-1) macrophages. As expected, preincubation with low-density lipoprotein (LDL) yielded small but significant increases in total cellular cholesterol content and also the secretion of apoE by macrophages. By contrast, preincubation with TGRLP resulted in higher, dose-dependent, increases in apoE secretion that reflected, but were not dependent on, cellular triacylglycerol accumulation. Secreted apoE was incorporated into a pre-β migrating LpE fraction that differed in lipid composition and flotation density depending on preincubation conditions. Specifically, the LpE-containing lipoprotein fraction produced by macrophages preincubated with TGRLP was cholesterol-poor, markedly heterogeneous and of higher peak flotation density (d 1.14–1.18) when compared with particles produced after preincubation with LDL. Both the conditioned medium and the isolated (d &amp;lt; 1.21) LpE-containing fraction, yielded by macrophages preincubated with TGRLP, seemed poorer at inducing cholesterol efflux than the equivalent fractions from cells preincubated with LDL, as judged by [3H]cholesterol efflux from untreated ‘naïve’ macrophages. Thus, although the interaction of TGRLP with macrophages can enhance apoE output from these cells, the LpE particles produced seem to be relatively inefficient mediators of cholesterol efflux. These factors might contribute to the increased risk of atherosclerosis in individuals with Type II diabetes.

Triacylglycerol-rich lipoproteins alter the secretion, and the cholesterol-effluxing function, of apolipoprotein E-containing lipoprotein particles from human (THP-1) macrophages

Elevated plasma levels of triacylglycerol-rich lipoproteins (TGRLP) are associated with increased risk of atherogenesis and abnormal reverse cholesterol transport, as illustrated in Type II diabetes. Here we examine the effect of plasma triacylglycerol-rich or cholesteryl ester-rich lipoproteins on the secretion of nascent apolipoprotein E (apoE)-containing lipoprotein E (LpE) particles by human (THP-1) macrophages. As expected, preincubation with low-density lipoprotein (LDL) yielded small but significant increases in total cellular cholesterol content and also the secretion of apoE by macrophages. By contrast, preincubation with TGRLP resulted in higher, dose-dependent, increases in apoE secretion that reflected, but were not dependent on, cellular triacylglycerol accumulation. Secreted apoE was incorporated into a pre-beta migrating LpE fraction that differed in lipid composition and flotation density depending on preincubation conditions. Specifically, the LpE-containing lipoprotein fraction produced by macrophages preincubated with TGRLP was cholesterol-poor, markedly heterogeneous and of higher peak flotation density (d 1.14-1.18) when compared with particles produced after preincubation with LDL. Both the conditioned medium and the isolated (d<1.21) LpE-containing fraction, yielded by macrophages preincubated with TGRLP, seemed poorer at inducing cholesterol efflux than the equivalent fractions from cells preincubated with LDL, as judged by [(3)H]cholesterol efflux from untreated 'naïve' macrophages. Thus, although the interaction of TGRLP with macrophages can enhance apoE output from these cells, the LpE particles produced seem to be relatively inefficient mediators of cholesterol efflux. These factors might contribute to the increased risk of atherosclerosis in individuals with Type II diabetes.

Reduced oxidized low-density lipoprotein after weight reduction in obese premenopausal women.

Several studies support the hypothesis that oxidation of low-density lipoprotein (LDL) promotes atherogenesis. Obesity is one of the risk factors of atherosclerosis, but it is not known whether obesity is related to LDL oxidation. We investigated the effect of weight reduction and subsequent weight maintenance program on LDL oxidation in 77 obese premenopausal women (BMI 29-46 kg/m(2)). Another group of seven obese women served as a control group. Oxidized LDL was measured as baseline concentration of conjugated dienes in LDL lipids (ox-LDL). The weight reduction was performed in 12 weeks, using a very-low-energy diet. The mean weight loss was 13 kg (92 vs 79 kg). During weight reduction, the concentration of LDL cholesterol decreased by 11%, the concentration of ox-LDL decreased by 40%, and the ratio of ox-LDL to LDL by 33%. The concentration of LDL antioxidant capacity (LDL-TRAP) decreased by 8%, but the decrease was caused by the decrease in LDL. The concentration of LDL, ox-LDL or LDL-TRAP did not change in the control group. The weight reduction correlated with the decrease of ox-LDL. During the subsequent 9 month weight maintenance programme, the concentrations of serum LDL (10%), ox-LDL (11%), LDL-TRAP (29%), and the ratio of LDL-TRAP to LDL (21%) decreased. This study strengthens the evidence that the risk of atherogenesis is influenced favourably by weight reduction in obese women. This risk reduction is associated with a reduced oxidation of LDL.

The effect of pharmacological doses of different antioxidants on oxidation parameters and atherogenesis in hyperlipidaemic rabbits

The oxidation hypothesis of atherosclerosis implies that antioxidants are able to inhibit lipoprotein oxidation in the arterial wall and thereby retard atherogenesis. Since most of the animal studies performed have used very high doses of antioxidants, it is to date unknown whether antioxidants are effective antiatherosclerotic agents when given in pharmacological doses. Here we addressed this question using homozygous Watanabe heritable hyperlipidaemic (WHHL) rabbits as an animal model of atherosclerosis. The rabbits were divided into four groups, each consisting of ten animals. They received either a standard diet or a diet containing 4.3 mg ubiquinone-10, or 4.3 mg vitamin E or 15 mg probucol/kg body weight daily. After 12 months, the extent of aortic atherosclerosis was assessed as the intima thickness, media thickness and intima-to-media ratio in 14 cross sections equally distributed over the whole aorta. To evaluate the antioxidant effects of the diet, lipophilic and hydrophilic antioxidants, lipids, fatty acids and plasma oxidizability were measured after 0, 3 and 6 months of feeding. We found that supplementation with probucol significantly decreased aortic intima-to-media ratio compared to controls. The antiatherosclerotic action of probucol was accompanied by its beneficial action on plasma oxidizability and some plasma antioxidants. No decrease in aortic atherosclerosis was measured in ubiquinone-10- and vitamin E-supplemented rabbits, despite the fact that both antioxidants decreased plasma oxidizability and ubiquinone-10 increased the plasma levels of antioxidants. Taken together, these data suggest that pharmacological doses of probucol retard atherogenesis in WHHL rabbits by an antioxidant mechanism, while ubiquinone-10 and vitamin E at these dosages are ineffective in this highly hyperlipidaemic model. The measurement of some oxidation-related parameters in plasma, such as lipophilic antioxidants, polyunsaturated fatty acids and lipoprotein oxidizability, may be useful in assessing the risk of atherogenesis in humans.

Thyroid and lipid metabolism.

Thyroid hormones influence all major metabolic pathways. Their most obvious and well-known action is an increase in basal energy expenditure obtained acting on protein, carbohydrate and lipid metabolism. With specific regard to lipid metabolism, thyroid hormones affect synthesis, mobilization and degradation of lipids, although degradation is influenced more than synthesis. The main and best-known effects on lipid metabolism include: (a) enhanced utilization of lipid substrates; (b) increase in the synthesis and mobilization of triglycerides stored in adipose tissue; (c) increase in the concentration of non-esterified fatty acids (NEFA); and (d) increase of lipoprotein-lipase activity. While severe hypothyroidism is usually associated with an increased serum concentration of total cholesterol and atherogenic lipoproteins, the occurrence of acute myocardial infarction (AMI) in hypothyroid patients is not frequent. However, hypothyroid patients appear to have an increased incidence of residual myocardial ischemia following AMI. Even in subclinical hypothyroidism, which is characterized by raised serum TSH levels with normal serum thyroid hormone concentrations, mild hyperlipidemia is present and may contribute to an increased risk of atherogenesis. Prudent substitution therapy with L-thyroxine is indicated in patients with both overt and subclinical hypothyroidism, with or without angina, to counteract the cardiovascular risk resulting from hyper-dyslipidemia.

Restenosis after Percutaneous Coronary Interventions and Infection

Infectious agents may directly or indirectly (through the response of the host's immune system) modulate the growth of vascular cells. Local and/or systemic increase of cytokines could influence the extent of (re-)stenosis in the vascular tree. Further studies in this field may identify patients at a high risk for atherogenesis and restenosis. Their results should be helpful in treating restenosis after percutaneous coronary interventions.

Is an atherogenic lipoprotein profile in the fetus a prerequisite for placental vascular disease?

To measure the blood apolipoprotein A-1 and apolipoprotein B in the fetal circulation in normal pregnancy and in pregnancy with evidence of vascular disease in the fetal umbilical placental circulation defined in the antenatal period by Doppler ultrasound study. An observational study to compare fetal plasma apolipoprotein levels in normal and complicated pregnancy. A university hospital tertiary referral obstetric unit. Umbilical vein blood was collected at delivery from 22 normal fetuses delivered by elective caesarean section for non fetal reasons and 30 fetuses with evidence of umbilical placental vascular disease identified antenatally by Doppler ultrasound study. Plasma apolipoprotein A-1 and B were determined using an enzyme-linked immunosorbent assay (ELISA) methods. Fetal plasma levels of apolipoprotein A-1 and B were measured. There was a significantly lower level of fetal plasma apolipoprotein A-1 in placental insufficiency [placental insufficiency vs normal pregnancy, median 0.30 g/L (interquartile range 0.24, 0.39 g/L) vs 0.35 g/L (0.31, 0.42 g/L), P = 0.045]. In contrast, the levels of fetal plasma apolipoprotein B in placental insufficiency [0.20 g/L (0.17, 0.26 g/L)] were significantly increased compared with normal pregnancy [0.16 g/L (0. 14, 0.20 g/L), P = 0.03]. The ratio of fetal plasma apolipoprotein B to A-1 was also substantially higher in placental insufficiency [0.68 (0.55, 0.83)] than in normal pregnancy [0.45 (0.36, 0.60), P = 0.0003]. Our study has demonstrated that levels of fetal plasma apolipoprotein A-1, apolipoprotein B and the ratio of apolipoprotein B to A-1 were altered in the fetuses who are victims of umbilical placental insufficiency in the same direction as in adults associated with a high risk of atherogenesis.

Large variations in human foam cell formation in individuals: a fully autologous in vitro assay based on the quantitative analysis of cellular neutral lipids

The transformation of monocyte-derived macrophages into lipid-laden foam cells constitutes a characteristic and crucial event in the development of the earliest atherosclerotic lesions. We investigated whether the propensity to form foam cells varies among individuals. We developed a fully autologous foam cell assay based on a recently developed novel culture technique for human monocyte-derived macrophages (Wintergerst ES, Jelk J, Asmis, R. Differential expression of CD14, CD36 and the LDL receptor on human monocyte-derived macrophages. A novel cell culture system to study macrophage differentiation and heterogeneity, Histochem. Cell Biol. 1998;110:231–241). Thin layer chromatography and laser densitometry were used to determine cholesterol, triglyceride and cholesteryl ester levels in human macrophages. Aggregated LDL obtained by vortexing was found to be a reproducible stimulus of foam cell formation in human macrophages. In our hands, Cu 2+-oxidized LDL also induced cholesteryl ester accumulation, but only when vortexed. We found that foam cell formation in an individual varied by less than 25% over a 10-month period. In contrast, we observed a sevenfold difference in foam cell formation among eight male volunteers. The transfer of foam cells into culture medium with freshly thawed autologous serum resulted in a 75% regression within 1 week, independent of the amount of cellular cholesteryl esters accumulated. Foam cell formation correlated neither to serum nor to cellular cholesterol and triglyceride levels. The propensity to form foam cells could therefore represent a novel indicator of individual risk of atherogenesis.

Juvenile rheumatoid arthritis.

The heterogeneous nature of juvenile rheumatoid arthritis is further defined in publications from the past year. Decreased IL-10 production, an anti-inflammatory cytokine, and soluble IL-6 receptor are associated with systemic juvenile rheumatoid arthritis (JRA). IL-4 may have an anti-inflammatory role in the pathogenesis of pauciarticular JRA and may protect, along with IL-10, against the development of joint erosions. Active JRA is associated with lower levels of platelet activating factor acetylhydrolase, which may contribute to the loss of anti-inflammatory activity and increased risk of atherogenesis. The phase 3 clinical trial of etanercept confirmed its efficacy and safety in JRA. Intra-articular steroids are safe and effective in the treatment of JRA. Methotrexate does have disease-modifying effects. The risk of hepatotoxicity with methotrexate use increases with serial transaminase abnormalities and with obesity. Osteoclasts are responsible for joint erosions. Cyclosporine A, mycophenolate mofetil, and methotrexate are effective in the treatment of refractory uveitis. During the past year a number of scientific publications have contributed significantly to our understanding and treatment of juvenile rheumatoid arthritis.

Trans fatty acid isomers in human health and in the food industry

Trans fatty acids are unsaturated fatty acids with at least one double bond in the trans configuration. These fatty acids occur naturally in dairy and other natural fats and in some plants. However, industrial hydrogenation of vegetable or marine oils is largely the main source of trans fatty acids in our diet. The metabolic effect of trans isomers are today a matter of controversy generating diverse extreme positions in light of biochemical, nutritional, and epidemiological studies. Trans fatty acids also have been implicated in the etiology of various metabolic and functional disorders, but the main concern about its health effects arose because the structural similarity of these isomers to saturated fatty acids, the lack of specific metabolic functions, and its competition with essential fatty acids. The ingestion of trans fatty acids increases low density lipoprotein (LDL) to a degree similar to that of saturated fats, but it also reduces high density lipoproteins (HDL), therefore trans isomers are considered more atherogenic than saturated fatty acids. Trans isomers increase lipoprotein(a), a non-dietary-related risk of atherogenesis, to levels higher than the corresponding chain-length saturated fatty acid. There is little evidence that trans fatty acids are related to cancer risk at any of the major cancer sites. Considerable improvement has been obtained with respect to the metabolic effect of trans fatty acids due the development of analytical procedures to evaluate the different isomers in both biological and food samples. The oleochemical food industries have developed several strategies to reduce the trans content of hydrogenated oils, and now margarine and other hydrogenated-derived products containing low trans or virtually zero trans are available and can be obtained in the retail market. The present review provides an outline of the present status of trans fatty acids including origin, analytical procedures, estimated ingestion, metabolic effects, efforts to reduce trans isomers in our diet, and considerations for future prospects on trans isomers.

Effects of Acetate or Bicarbonate Dialysis Solutions on Serum HDL and HDL Subfractions of Patients Undergoing Haemodialysis

SummaryThe aim of this study was to compare the effect of acetate- and bicarbonate-containing dialysis solutions (buffers) on serum lipid (triglyceride and total cholesterol) and lipoprotein (LDL, HDL and its subfractions as HDL, and HDL., Apolipoprotein A1 and Apolipoprotein B) values in patients undergoing haemodialysis. Lipid concentrations in 16 patients on bicarbonate and in 18 patients on acetate haemodialysis were investigated initially and after four weeks of dialysis treatment. Over four weeks of treatment both acetate and bicarbonate dialysis treatments had no negative effects on either HDL or HDL subfractions, and these buffering systems were indistinguishable from each other. We confirm that HDL is the major factor that is changed in the lipid profile in haemodialysis patients undergoing acetate or bicarbonate dialysis and suggest that the relation between LDL and HDL subfractions may be useful for monitoring the lipid changes in haernodialysis patients at risk ofatherogenesis.