Background: Metabolic syndrome (MetS) prevalence in rheumatoid arthritis (RA) patients is known to vary considerably across the world. This study aimed to determine the prevalence of MetS in RA patients from western Mexico and to analyze the interrelation of the MetS components with the clinical variables of RA.

Methods: This case-control study included 216 RA patients and 260 control subjects (CS). MetS prevalence was determined according to the NCEP/ATP III and the Latin American Consensus of the Latin American Diabetes Association (ALAD) criteria.

Results: MetS was observed in 30.6% RA patients and 33.3% of controls (p > 0.05) according to NCEP/ATP III and 28.7% in RA patients and 31.1% for controls using ALAD criteria. Total cholesterol, LDL-C, and Castelli's I-II indexes were lower in RA (p < 0.001) than in CS. The RA patients with MetS had more swollen joints than those without MetS (p = 0.018). In RA patients with MetS, DAS-28 score correlated with smoking index (rho = 0.4601, p = 0.0004) and VLDL-C (rho = 0.3108, p = 0.0056); similarly, rheumatoid factor (RF) correlated with age (rho = 0.2031, p = 0.0027), smoking index (rho = 0.3404, p < 0.0001), triglycerides (rho = 0.1958, p = 0.0039), and VLDL-C (rho = 0.1761, p = 0.0162).

Conclusions: The MetS prevalence in RA patients from western Mexico is not higher than controls; however, in RA patients with MetS, some inflammatory markers are associated with MetS components; thus, the control of MetS in RA could be beneficial to regulate disease activity.

Keywords: Castelli's index; disease activity; lipid profiles; metabolic syndrome; rheumatoid arthritis; rheumatoid factor.

Objective: To assess the expression and significance of proprotein convertase subtilisin kexin 9 (PCSK9) in patients with rheumatoid arthritis (RA). Methods: Sixty-five RA patients and forty-seven healthy controls were recruited in this study. The body mass index (BMI) and serum total cholesterol(TC), triglyceride(TG), high density lipoprotein(HDL), lipoprotein a, low density lipoprotein(LDL), very low density lipoprotein(VLDL), apolipoprotein A(ApoA), apolipoprotein B(ApoB) and the ratio of LDL-C/HDL-C were tested. Other parameters included disease activity score 28(DAS28), rheumatoid factor (RF), anti-cyclic citrullinated peptide (CCP) antibody, erythrocyte sedimentation rate (ESR), c-reactive protein (CRP). Serum PCSK9 level was measured by ELISA and compared between RA patients and healthy controls. Results: (1) The serum PCSK9 levels in RA patients were higher than those in healthy controls[(409.36±223.52) μg/L vs (292.19±109.79) μg/L, P<0.05]. (2) Compared with subgroup of moderate and low active disease and patients in remission, PCSK9 was significantly higher in patients with highly active disease (P<0.05). (3) The serum PCSK9 levels were positively correlated with RF, TC, TG, LDL, very low density lipoprotein (VLDL), ApoB, with r values as 0.303, 0.490, 0.320, 0.451, 0.319, 0.463, respectively (P<0.05). (4) Multiple stepwise regression analysis showed that DAS28, RF, TC and LDL-C/HDL-C were relevant factors for PCSK9 in RA patients. Conclusions: The serum PCSK9 level is elevated in RA patients, which is related to RF, disease activity, TC, TG, LDL, VLDL, ApoB. This suggests that PCSK9 is potentially linked to inflammatory reaction and lipid metabolism in rheumatoid arthritis.

Tightly regulated iron metabolism prevents oxidative stress. Hepcidin is a hormone that regulates iron flow in plasma; its production is induced by an iron overload and by inflammation. It inhibits iron entry into the circulation by blocking dietary absorption in the duodenum, the release of recycled iron from macrophages and the exit of stored iron from hepatocytes. Varied signals responding to iron stores, erythropoietic activity and host defense converge to regulate hepcidin production and thereby affect iron homeostasis. Although it is known that hepcidin increases when interleukin 6 (IL-6) increases, the relationship between hepcidin, dyslipidemia, insulin resistance (IR) and visceral adiposity index (VAI) in adolescents with obesity is unclear. In this cross-sectional study of 29 obese adolescents and 30 control subjects, we explored the difference of hepcidin, iron metabolism markers and IL-6 between obese and non-obese adolescents, and identified associations with inflammation, atherogenic dyslipidemia and IR. As compared to lean controls, obese participants showed 67% higher hepcidin: 14,070.8 ± 7213.5 vs. 8419.1 ± 4826.1 pg/mL^c; 70% higher ferritin: 94.4 ± 82.4 vs. 55.1 ± 39.6 pg/mL^a and 120% higher IL-6: 2.0 (1.1-4.9) vs. 0.9 (0.5-1.3) pg/mL^d. Transferrin, soluble transferrin receptor and total body iron (as measured by sTFR/ferritin, log10 sTFR/ferritin ratio and sTFR/log ferritin ratios) were not different between the two cohorts. In the whole cohort, hepcidin correlated with VAI (r = 0.29^a), sd-LDL (r = 0.31^b), HOMA-IR (r = 0.29^a) and IL-6 (r = 0.35^c). In obese adolescents hepcidin correlated with TG (r = 0.47^b), VLDL-C (r = 0.43^b) and smaller LDL2 (r = 0.39^a). Hepcidin elevation in adolescents with obesity is linked more to inflammation and metabolic alterations than to iron metabolism since the other markers of iron metabolism were not different between groups, except for ferritin. Studies addressing the long-term effects of higher hepcidin levels and their impact on subclinical anemia and iron status are warranted. ^a&nbsp;p < 0.05; ^b&nbsp;p < 0.01, ^c&nbsp;p < 0.001 ^dp < 0.0001.

<st<em>r</em>ong class="sub-title"> Keywo<em>r</em>ds: </st<em>r</em>ong> athe<em>r</em>oscle<em>r</em>osis; dyslipidemia; fe<em>r</em><em>r</em>itin; hepcidin; metabolic synd<em>r</em>ome; obesity.

The most electronegative constituents of human plasma LDL (i.e., L5) and VLDL (i.e., V5) are highly atherogenic. We determined whether the combined electronegativity of L5 and V5 (i.e., L5 + V5) plays a role in coronary heart disease (CHD). In 33 asymptomatic individuals (ages 32-64), 10-year hard CHD risk correlated with age (r = 0.42, p = 0.01). However, in age-adjusted analyses, 10-year hard CHD risk correlated with L5 + V5 plasma concentration (r = 0.43, p = 0.01) but not age (p = 0.74). L5 + V5 plasma concentration was significantly greater in the group with high CHD risk (39.4 ± 22.0 mg/dL; n = 17) than in the group with low CHD risk (16.9 ± 14.8 mg/dL; n = 16; p = 0.01). In cultured human aortic endothelial cells, L5 + V5 treatment induced significantly more senescence-associated-β-Gal activity than did equal concentrations of L1 + V1 (n = 4, p < 0.001). To evaluate the in vivo relevance of these findings, we fed ApoE^-/- and wild-type mice with a high-fat diet and found that plasma LDL, VLDL, and LDL + VLDL from ApoE^-/- mice exhibited significantly greater electrophoretic mobility than did wild-type counterparts (n = 6, p < 0.01). The increased electronegativity of LDL and VLDL in ApoE^-/- mice was accompanied by increased aortic lipid accumulation and cellular senescence (n = 6, p < 0.05). Clinical trials are warranted to test the predictive value of L5 + V5 concentration in patients with CHD.

BACKGROUND

Recent data suggest that in addition to glucose, fetal growth is related to maternal triglycerides (TG). To reach the fetus, TG must be hydrolyzed to free fatty acids (FFA) and transported across the placenta, but regulation is uncertain. Placental lipoprotein lipase (pLPL) hydrolyzes TG, both dietary chylomicron TG (CM-TG) and very-low density lipoprotein TG (VLDL-TG), to FFA. This may promote fetal fat accretion by increasing the available FFA pool for placental uptake. We tested the novel hypothesis that pLPL activity, but not maternal adipose tissue LPL activity, is associated with newborn adiposity and higher maternal TG.

METHODS

Twenty mothers (n = 13 normal-weight; n = 7 obese) were prospectively recruited. Maternal glucose, insulin, TG (total, CM-TG, VLDL-TG), and FFA were measured at 14-16, 26-28, and 36-37 weeks, and adipose tissue LPL was measured at 26-28 weeks. At term delivery, placental villous biopsies were immediately analyzed for pLPL enzymatic activity. Newborn percent body fat (newborn %fat) was assessed by skinfolds.

RESULTS

Placental LPL activity was positively correlated with birthweight (r = 0.48;P = 0.03) and newborn %fat (r = 0.59;P = 0.006), further strengthened by correcting for gestational age at delivery (r = 0.75;P = 0.0001), but adipose tissue LPL was not. Maternal TG and BMI were not correlated with pLPL activity. Additionally, pLPL gene expression, while modestly correlated with enzymatic activity (r = 0.53;P < 0.05), was not correlated with newborn adiposity.

CONCLUSIONS

This is the first study to show a positive correlation between pLPL activity and newborn %fat. Placental lipase regulation and the role of pLPL in pregnancies characterized by nutrient excess and fetal overgrowth warrant further investigation.

The total fraction of low and very low density lipoproteins (LDL, VLDL), total cholesterol (TCS) and high density lipoprotein cholesterol (CS HDL) in arterial and venous blood was determined in 42 patients with atherosclerosis affecting predominantly arteries of the pelvis and the lower extremities. The mean concentration of the above-mentioned substances in the in-flowing and outflowing blood in the affected vascular region did not practically differ. At normal blood lipid level there exists a significant negative correlation between the absolute and relative CS HDL content on the one hand and, on the other hand, the arteriovenous difference in TCS content (r = -0.414 and -0.531 respectively). At hyperlipoproteinaemia, the CS HDL content correlates with the arteriovenous LDL and VLDL difference (r = -0.511). The findings attest to the fact that a decrease in the CS HDL level is accompanied by increased uptake of atherogenic substances in the peripheral vessels.

A 58-year-old patient with heterozygous familial hypercholesterolemia (FH) showed normal levels of serum cholesterol (193 mg/dL) in coexistence with hyperthyroidism. After hyperthyroidism therapy with radioiodine and methimazole, the patient's lipid profile showed high concentrations of cholesterol (whole serum 318 mg/dL, VLDL 35 mg/dL, LDL 217 mg/dL, HDL 44 mg/dL). There was a significant inverse correlation between serum cholesterol levels and serum thyroxine levels (r = -0.815, p less than 0.01). Effects of triiodothyronine on LDL degradation and cholesterol synthesis from 14C-labeled acetate were studied in cultured skin fibroblasts. Triiodothyronine (T3) stimulated both LDL degradation and cholesterol synthesis in the cells from normal subjects and patients with heterozygous FH. The T3 increased cellular cholesterol synthesis markedly in the cells from patients with homozygous FH but did not increase LDL receptor activity. These results suggest that normal serum cholesterol levels in our case result in part from an enhancement of LDL receptors by thyroid hormone.

The epsilon4 allele of apolipoprotein E (ApoE) is a risk factor in late-onset Alzheimer's disease (AD). As a receptor for ApoE, very-low-density lipoprotein receptor (VLDLR) might be involved in AD pathogenesis. A Japanese study [Okuizimi, K., et al., Nature Genet., 11 (1995) 207-209] has shown an increased 5 and decreased 8 CGG-repeat allele frequency in the 5' untranslated region of VLDLR in Japanese AD versus normal controls (N). Subsequent studies in Caucasian Americans failed to duplicate the result. We examined this polymorphism in pathologically- or clinically-diagnosed Chinese late-onset AD. Our data did not show a significant increase in the 5 CGG-repeat in AD, thus suggesting no association to VLDLR. However, our data did show that the allele frequencies for each CGG-repeat were similar in both Chinese and Japanese.

Probucol demonstrated a profound metabolic effect on the metabolism of plasma lipoproteins by lowering the levels of circulating low-density lipoproteins (LDL). This main metabolic phenomenon was usually accompanied with other substantial events in lipoprotein patterns. Their significance ought to be confirmed by more than one analytical method. Our primary analytic system used for the basic analysis of plasma lipoproteins consisted of analytical ultracentrifugation, highly standardized agarose-gel electrophoresis and molecular separation of lipoproteins according to their molecular sizes. This paper refers to an attempt to endorse electrophoresis as a supporting technique for ultracentrifugal studies. Correlation between corresponding ultracentrifugal classes and electrophoretic fractions, declared by their coefficients, were therefore studied in order to further examine the usefulness and applicability of agarose-gel electrophoresis in the research, as well as in determining and monitoring patient therapy. Close correlations were found between the group of chylomicrons (CHY), very-very-low-density lipoproteins (VVLDL), very-low-density lipoproteins (VLDL), intermediate-density lipoproteins (IDL), their remnants and the entire pre-beta-electrophoretic complex of plasma lipoproteins (r=0.91). CHY, VVLDL and VLDL were also well related to the alpha 2- and pre-beta 2-electrophoretic fraction (r=0.95). However, if we consider concentration units for comparison of the relation between pre-beta 1- and beta-electrophoretic fractions versus all sub-classes of LDL, such correlation was found weaker (r=0.77); results were similar when such correlation was made with HDL2,3 classes versus alpha electrophoretic fractions (r=0.78). On the contrary, when the relative percentage in the spectra of the same classes and fractions were correlated, the correlation coefficients were different: CHY and all subclasses and remnants of VLDL, versus the entire pre-beta-electrophoretic complex demonstrated r=0.87, versus the alpha 2- and pre-beta 2-electrophoretic fraction r=0.73. The electrophoretic pre-beta 1-beta-complex correlated weakly (r=0.50) with low and medium density lipoproteins (MDL). Unexpectedly tight (r=0.89) was the correlation between relative percentages of the electrophoretic alpha 1-fraction and the high-density lipoproteins (HDL).

The primary metabolic effect of probucol is characterized by significant lowering of plasma low-density lipoproteins (LDL2) (p less than 0.01), frequently connected with a decrease in concentration of very-low density lipoproteins (VLDL) (p less than 0.05). This main effect is correlated (r = 0.84-0.75) with a decrease of chylomicrons (CHY) and macromolecular very, very-low density lipoproteins (VVLDL). High density lipoproteins (HDL2,3) tended to decrease in the majority of cases, although a restoration of their levels was observed after the therapy. The strong significance of probucol's lowering action of LDL2 does not statistically relate to any other metabolic phenomenon, confirming its relative independence on remaining pathways.

<st<em>r</em>ong class="sub-title"> Backg<em>r</em>ound: </st<em>r</em>ong> Studies investigating cognitive dysfunction in pso<em>r</em>iatic patients <em>r</em>emain inconclusive.

<st<em>r</em>ong class="sub-title"> Objective: </st<em>r</em>ong> To investigate the <em>r</em>isk of cognitive decline in plaque-type pso<em>r</em>iasis patients.

<st<em>r</em>ong class="sub-title"> Methods: </st<em>r</em>ong> Se<em>r</em>um neu<em>r</em>ofilament light chain (NFL) and tau p<em>r</em>otein concent<em>r</em>ations in 45 patients with plaque-type pso<em>r</em>iasis and fo<em>r</em>ty-five healthy cont<em>r</em>ols we<em>r</em>e measu<em>r</em>ed by enzyme-linked immunoso<em>r</em>bent assay (ELISA).

<st<em>r</em>ong class="sub-title"> Results: </st<em>r</em>ong> Mean homeostasis model assessment (HOMA-IR) values (6.82 vs 3.25) and se<em>r</em>um levels of insulin (28.19 vs 15.71), NFL (5.74 vs 1.98), and tau (348.17 vs 207.30) in patients with pso<em>r</em>iasis we<em>r</em>e found to be significantly highe<em>r</em> than those of in healthy cont<em>r</em>ols. The<em>r</em>e was a significant positive co<em>r</em><em>r</em>elation between NFL and tau (<em>r</em> = .257, P = .015). The<em>r</em>e was significant co<em>r</em><em>r</em>elation between NFL, tau and PASI (<em>r</em> = .310, P = .040) and (<em>r</em> = .383, P = .010), <em>r</em>espectively. Significant co<em>r</em><em>r</em>elations between NFL and insulin, TC, HDL-C, TG, <em>VLDL</em>-C, and BMI we<em>r</em>e found. NFL (9.38 vs 3.08) and tau (439.28 vs 281.58) concent<em>r</em>ations and PASI values (23.94 vs 14.18) in patients with disease onset befo<em>r</em>e 40 yea<em>r</em>s we<em>r</em>e significantly highe<em>r</em> than that of the patients with disease onset afte<em>r</em> 40 yea<em>r</em>s. C-<em>r</em>eactive p<em>r</em>otein (CRP) was significantly co<em>r</em><em>r</em>elated with BMI (<em>r</em> = .449, P < .001), LDL-C (<em>r</em> = .240, P = .026), TG (<em>r</em> = .244, P = .024), and <em>VLDL</em>-C (<em>r</em> = .241, P = .025) in patients with pso<em>r</em>iasis.

<st<em>r</em>ong class="sub-title"> Conclusions: </st<em>r</em>ong> Inc<em>r</em>eased se<em>r</em>um NFL and tau p<em>r</em>otein levels and the p<em>r</em>esence of positive co<em>r</em><em>r</em>elations between NFL, tau p<em>r</em>otein and PASI sco<em>r</em>e show cognitive decline <em>r</em>isk may be highe<em>r</em> in mode<em>r</em>ate-to-seve<em>r</em>e pso<em>r</em>iasis.

<st<em>r</em>ong class="sub-title"> Keywo<em>r</em>ds: </st<em>r</em>ong> PASI; cognition; insulin <em>r</em>esistance; neu<em>r</em>ofilament light chain; pso<em>r</em>iasis; total tau p<em>r</em>otein.

BACKGROUND

This study aimed to evaluate the Quetelet Body Mass Index (BMI), and specific anthropometric indexes of the distribution of body fat, with glycemia, insulinemia, uricemia, and the lipid profile in 124 hypertensives and 124 normotensives, selected according to age and sex.

METHODS

We preset an observational case and control study, referring to a population attending health care centers. The inclusion criteria for the cases were: to be 25 years or older, having been diagnosed with essential hypertension. Incident and prevalent cases of an evolution of less than 2 years are selected.

RESULTS

The hypertensives studied, presented levels which were statistically significant and higher than those seen in the normotensive, of all anthropometric indexes used, in insulinemia, glycemia, uricemia, and in the total cholesterolemia. In the cases, the waist hip ratio (WHR) presents a greater number of correlations with biochemical parameters such as uricemia (r = 0.376, p = 0.00), triglyceridemia (r = 0.252, p = 0.00), and the VLDL-cholesterol fraction (r = 0.263, p = 0.00). On the other hand, the BMI, only correlates, in the cases, with the insulinemia. In turn, insulinemia correlates with the majority of the anthropometric measures, with a similar behavior in cases and controls.

CONCLUSIONS

The WHR is presented as a complementary index to the classic BMI in the evaluation of obesity and its metabolic alterations, especially in women, but also, the WHR correlates with an adverse lipid profile in hypertensives.

To determine the most frequent dyslipidemias among first-degree relatives of NIDDM patients, and its association with their glucose-tolerance status and hyperinsulinemia, we have started to examine members of NIDDM pedigrees, according to American Diabetes Association guidelines for nuclear family studies. In a large family with 2 NIDDM siblings in the 2nd generation, and 4 siblings with NIDDM in the 3rd generation, we have evaluated 14 first degree relatives and also 15 sex and aged matched healthy control subjects without family history of diabetes. The NIDDM relative group presented BMI = 31.8 +/- 3.9 kg/m2, SBP = 128 +/- 18.2 mmHg, DBP = 84 +/- 12.7 mmHg. Both relatives and controls were subjected to a 2h 75g OGTT for glucose and insulin determinations. Although none of NIDDM relatives has IGT, both Glycemic Area (GA) and Insulin Area (IA) were greater (p < 0.01) in the NIDDM relative group. The Insulin/Glucose ratio was also higher (p < 0.01) at 0 and 120 min of OGTT, this might be indirect evidence of Insulin- Resistance. Fasting serum lipids in the NIDDM relatives were TG = 148 +/- 24mg/dl, T-Chol = 244 +/- 10.7mg/dl, HDL-C = 34.2 +/- 2.5mg/dl; lipids in the control group were TG = 84.8 +/- 10.1mg/dl, T-Chol = 167 +/- 10.2mg/dl, HDL-C = 44.4 +/- 2.6mg/dl. Electrophoretic pattern showed type IIa (30.7%) and IIb (61.5%) hyperlipidemias in the NIDDM relatives. In this group, there was a positive and significant association between basal insulin and DBP (r = 0.67; p < 0.01), and between DBP and both TG (r = 0.74; p < 0.01)) and VLDL-C (r = 0.58; p < 0.05). It was also obtained a negative association between basal insulin and HDL-C (r = -0.89; p < 0.001). These data suggest that hyperinsulinemia in association with lipid abnormalities could appear early (before the development of Impaired Glucose Tolerance and Diabetes) in first degree relatives of NIDDM patients.

Serum lathosterol concentration in rabbits was assessed as a possible indicator of whole-body cholesterol synthesis. In random-bred New Zealand White (NZW) rabbits fed a control diet or a diet containing either cholesterol, simvastatin, or cholestyramine, neither serum lathosterol concentration nor the serum lathosterol:total cholesterol ratio systematically corresponded with the anticipated rate of cholesterol synthesis. In control rabbits and those fed simvastatin or cholestyramine, whole-body cholesterol synthesis, which was calculated from the sterol balance, was correlated with serum lathosterol concentration when expressed relative to cholesterol in very low, intermediate, and low density lipoproteins (VLDL + IDL + LDL) (r = 0.61; n = 23; P = 0.002). The low correlation coefficient indicates that the predictive value of the lathosterol: (VLDL + IDL + LDL) cholesterol ratio is limited when applied to individual rabbits. Cholesterol and simvastatin feeding reduced the group mean serum lathosterol:(VLDL + IDL + LDL) cholesterol ratio, whereas cholestyramine in the diet raised the group mean ratio in the NZW rabbits. We conclude that the serum lathosterol:(VLDL + IDL + LDL) cholesterol ratio may be an indicator of group mean rates of whole-body cholesterol synthesis in rabbits but may not yield reliable information on individual rabbits. The lathosterol:(VLDL + IDL + LDL) cholesterol ratio predicted that in hyperresponsive inbred rabbits, showing an excessive hypercholesterolemia after cholesterol feeding, baseline whole-body cholesterol synthesis is lower than in hyporesponsive rabbits. Addition of cholesterol to the diet caused a reduction of predicted cholesterol synthesis in hypo- but not in hyper-responsive rabbits.

OBJECTIVE

To examine whether lipoprotein subfractions are associated with age-related changes in visceral obesity and maximal aerobic fitness in women athletes.

METHODS

Body composition was measured using dual energy X-ray absorptiometry (DEXA) and a single slice computed tomography (CT) scan of the abdomen of 39 women athletes (age: 18-69y, body mass index (BMI): 19-24 kg/m2). Lipoprotein lipids were measured in plasma drawn after a 12 h fast using nuclear magnetic resonance (NMR) spectroscopy, which quantifies lipoprotein subfractions by the spectroscopic differences exhibited by lipoprotein particles of various sizes.

RESULTS

Total cholesterol (r=0.42; P<0.01) and low-density lipoprotein cholesterol (LDL-C) (r=0.32; P=0.05) correlated positively with age, even after adjustment for age-related decreases in maximal aerobic fitness (VO2 max) and increases in the intra-abdominal fat area. There were no relationships between any of the lipoprotein subfractions or sizes with age. Very-low-density lipoprotein (VLDL) size and VLDLrrelated with total fat mass (r = 0.40 and r= -0.43, respectively; P < 0.05) and with intra-abdominal fat area (r = -0.47 and r = 0.43, respectively; P < 0.01), but not independently of total fat mass. Total cholesterol and LDL-C were negatively related to maximal aerobic fitness (VO2max) (r = -0.37 and r = -0.33, respectively; P < 0.05), while low-density-lipoprotein (LDL) size was positively related to VO2max (r = 0.35, P < 0.05).

CONCLUSIONS

These results suggest that age-associated changes in lipoprotein concentrations are probably, in part, due to primary aging, rather than age-related changes in abdominal obesity and aerobic fitness.

We often observe nutritional disturbances in children and adolescents leading to obesity or cachexy. For evaluating the state of nutrition or the degree of obesity anthropometrics indices are used such as Body Mass Index (BMI). The aim of the study was analysed the concentration of selected indices of lipid metabolism in serum in children and adolescents with relation to BMI.

METHODS

The examined children were divided into 3 groups: BMI between 10-90 percentiles (186 children), BMI>95 percentiles (27 obese children) and BMI <5 percentiles (17 anorectic girls). In all the studied children concentration of triacyloglycerol, total and HDL cholesterol were assayed in the serum. The level of LDL and VLDL cholesterol was determined with an indirect method. The apolipoproteins:apo-AI and apo-B were assayed in obese children and anorectic girls.

RESULTS

No significant relationship between triacyloglycerol, total cholesterol and cholesterol fractions concentrations and BMI, was found in the group of 186 children (BMI between 10-90 percentiles). Significant positive correlation between BMI and cholesterol LDL in obese children (BMI >95 percentiles) was confirmed (r=0.38, p<0.05). No significant relationship between the lipid parameters and BMI was found in the anorectic girls (BMI< 5 percentiles).

CONCLUSIONS

Children with BMI above 95 centile may constitute a group particularly predisposed for early development of atherosclerosis.

The importance of overall diet in modifying circulating lipoprotein particles and fatty acids during pregnancy is unclear. We examined the relationships of diet quality as assessed by the validated Healthy Food Intake Index (HFII) with serum HDL, LDL and VLDL particle concentrations and sizes and proportions of serum fatty acids in pregnant women at high risk for gestational diabetes mellitus (GDM). Overall, 161 women with a BMI of ≥30 kg/m2 and/or a history of GDM were drawn from the Finnish Gestational Diabetes Prevention Study, which is a dietary and exercise intervention trial to prevent GDM. At baseline, the HFII score was inversely related to concentrations of HDL particles (P=0·010) and MUFA (P=0·010) and positively related to concentrations of n-3 (P<0·001) and n-6 (P=0·003) PUFA. The significance for MUFA disappeared after adjustments. An increase in the HFII score from the first to second trimester of pregnancy correlated with reduced VLDL particle size (r -0·16, 95 % CI -0·31, -0·01), decreased MUFA concentrations (r -0·17, 95 % CI -0·31, -0·01) and elevated n-6 PUFA concentrations (r 0·16, 95 % CI 0·01, 0·31). In the maximum-adjusted model, the results remained significant except for VLDL particle size. These findings suggest that higher diet quality as defined by the HFII is related to a more favourable serum fatty acid profile, whereas the relationship with serum lipoprotein profile is limited in pregnant women at increased GDM risk.

Objective: This study tested whether substrate concentrations or fatty acid storage proteins predict storage of endogenous lipids in visceral adipose tissue (VAT) and upper body subcutaneous adipose tissue (UBSQ) fat.

Methods: The day prior to surgery, 25 patients undergoing bariatric procedures received an infusion of autologous [1-¹⁴ C]triolein-labeled very low-density lipoprotein (VLDL) particles, and during surgery, they received a continuous [U-¹³ C]palmitate infusion/bolus [9,10-³ H]palmitate tracer. VAT and UBSQ fat were collected to measure VLDL-triglyceride (TG) storage, direct free fatty acid (FFA) storage rates, CD36 content, lipoprotein lipase (LPL), acyl-CoA synthetase, diacylglycerol acetyl-transferase, and glycerol-3-phosphate acyltransferase activities.

Results: Storage of VLDL-TG and FFA-palmitate in UBSQ and VAT was not different. Plasma palmitate concentrations correlated with palmitate storage rates in UBSQ and VAT (r = 0.46, P = 0.02 and r = 0.46, P = 0.02, respectively). In VAT, VLDL-TG storage was correlated with VLDL concentrations (r = 0.53, P < 0.009) and LPL (r = 0.42, P < 0.05). In UBSQ, VLDL-TG storage was correlated with LPL (r = 0.42, P < 0.05). CD36, acyl-CoA synthetase, glycerol-3-phosphate acyltransferase, and diacylglycerol acetyl-transferase were not correlated with VLDL-TG or palmitate storage.

Conclusions: Adipose storage of VLDL-TG is predicted by VLDL-TG concentrations and LPL; FFA concentrations predict direct adipose tissue FFA storage rates.

Utilizing the polyvinyl sponge-implant model in the rabbit we have previously demonstrated modification in low density lipoproteins (LDL) of interstitial tissue fluid obtained in association with a cellular inflammatory response. In order to examine the interaction between the inflammatory response and lipoproteins from hypercholesterolemic rabbits, 30 male, New Zealand White rabbits were fed standard chow supplemented with 0.5% cholesterol for 4 weeks prior to sponge implantation. Lipoproteins were prepared from interstitial inflammatory fluid (IF) as well as homologous whole plasma (WP). Total IF cholesterol was positively correlated with plasma cholesterol (459 +/- 43 vs. 1485 +/- 130 mg/dl, means +/- SEM, r = 0.81, P less than 0.01). Distribution of lipoproteins in IF was similar to WP in both particle size and density. Beta-migrating VLDL were the predominant particles in both WP and IF, containing 43.7 +/- 3.4 and 42.2 +/- 5.1% of WP and IF cholesterol, respectively. IF-VLDL were similar to WP-VLDL in lipid and apoprotein composition, morphology and particle size distribution. We conclude from these data that the observed dramatic alterations in lipoprotein distribution in response to a dietary cholesterol challenge in rabbit plasma is essentially unaltered in interstitial inflammatory fluid obtained from these animals.

BACKGROUND

Remnant-like particle-cholesterol (RLP-C) is recognized as a risk factor for cardiovascular disease. As an alternative to the immunoseparation assay widely used for the measurement of RLP-C, a new remnant lipoprotein-C homogenous assay (RemL-C) is available. In light of its homogeneity as an assay method, we speculated that this homogeneous assay (RemL-C) is closely associated with very-low-density lipoprotein(VLDL) remnant including intermediate-density lipoprotein(IDL). We examined the characteristics of the homogeneous assay for reacting with VLDL remnants.

RESULTS

<em>VLDL</em>1, <em>VLDL</em>2, and IDL were separated by ultracentrifugation in the fasting serum of subjects including hypertriglyceridemia and uremic patients usually having higher levels of remnants. While RemL-C and RLP-C were mainly recovered in <em>VLDL</em>1 and both assays were strongly correlated with serum TG and <em>VLDL</em>1, the RemL-C assay was more closely correlated with <em>VLDL</em>2 and IDL levels than the RLP-C assay. RemL-C levels were significantly correlated with IDL-C, whereas RLP-C levels had only borderline associations with IDL-C (r= 0.56 Vs. 0.31).

CONCLUSIONS

The remnant lipoprotein cholesterol homogenous assay is more closely associated with <em>VLDL</em>2 and IDL than the immunoseparation assay.

The apolipoproteins (Apos) of human very low-density lipoprotein (VLDL) were investigated by an optimized cyclodextrin-micellar electrokinetic chromatography (CD-MEKC) method. The separation buffer consisted of 20 mM sodium phosphate, 40 mM bile salts (50% sodium cholate and 50% sodium deoxycholate), 25 mM carboxymethyl-β-cyclodextrin (CM-β-CD) (pH 7.0). For CD-MEKC separation, a sample injection time of 12 s, a separation voltage of 15 kV and a capillary temperature of 15 °C were chosen. The optimal CD-MEKC method showed good resolution and repeatability for VLDL Apos. Identification and quantitation of VLDL Apos CI, CIII and E were based on comparison with human Apo standards. Good linear relationships with correlation coefficient (R² ) 0.99 were obtained for Apos CI, CIII and E standards. For these three Apos, the linear ranges were within 0.01 - 0.54 mg/mL, and the concentration limits of detection (LODs) were lower than 0.02 mg/mL. Moreover, VLDL Apos from four uremic patients and four healthy subjects were compared. The uremic and healthy CD-MEKC profiles showed dramatic difference. The levels of Apo CIII were significantly higher for two patients, and the level of Apo E was significantly higher for one patient. This study might be helpful for following the disease development of uremia and cardiovascular disease (CVD) in the future. This article is protected by copyright. All rights reserved.

Small (Sf 20-100) very low density lipoprotein (VLDL) particles were prepared by density gradient ultracentrifugation of plasma from normolipidemic and type IV hypertriglyceridemic post-infarction patients and healthy controls. The small VLDL separated from the plasma of severely hypertriglyceridemic post-infarction patients were found to contain twice the amount of cholesteryl esters per particle, compared with small VLDL from normolipidemic patients and healthy controls. There was a linear increase in the percentage of cholesterol that was esterified in the small VLDL with the serum VLDL triglyceride concentration (r = 0.66). When incubated for two hours with bovine lipoprotein lipase in excess and bovine albumin as a free fatty acid acceptor at one and the same triglyceride concentration in the medium, the end-product isolated by ultracentrifugation varied as a function of the serum VLDL triglyceride level. The amount of glyceride-glycerol recovered after two hours of incubation with lipoprotein lipase was 13.3 +/- 1.3% (mean +/- SEM) of the initial values and did not correlate with the VLDL triglyceride level. With rising serum VLDL triglyceride concentration, the product isolated in the low density lipoprotein (LDL) density region (1.006 less than d less than 1.063 kg/l) contained more total cholesterol and phospholipids. The linear correlation coefficients for these relations were 0.65 and 0.58 for cholesterol and phospholipids respectively. The ratio of total cholesterol to insoluble protein in the LDL density range after lipolysis rose with increasing serum VLDL triglyceride level (r = 0.68). The end-product was further characterized by density gradient ultracentrifugation of the incubate. In vitro LDL derived by lipolysis of normolipidemic small VLDL was denser than in vitro LDL of hypertriglyceridemic small VLDL. A significant relation was found between the percentage of cholesteryl esters of total cholesterol in the substrate and the relative amount of total cholesterol recovered in the LDL density fraction after lipolysis (r = 0.69). We suggest that the enrichment with cholesteryl esters of small VLDL from type IV hypertriglyceridemic patients is caused by lipid transfer from LDL and high density lipoprotein (HDL) and that the change in VLDL particle composition influences the precursor-product relationship to LDL.

Rauwolfia serpentina is well-reported in traditional medicines for the treatment of hypertensive and neurological disorders. However, its antidiabetic potential has been currently described in both alloxan-treated and normoglycemic mice. Present effort was carried out to investigate the effect of methanol root extract (MREt) of R.serpentina in fructose-induced type 2 diabetic mice. Experimental mice were grouped into normal control (distilled water 1ml/kg) and fructose-induced type 2 diabetic groups (10% fructose 1 ml/kg).The second group sub-divided into negative (0.05% DMSO 1ml/kg) control, positive (pioglitazone 15mg/kg) control and three test groups (MREt 10, 30 & 60 mg/kg). Each treatment was given orally for 14 days consecutively then mice were sacrificed in order to collect serum and liver samples to analyze physical, biochemical as well as hematological markers. MREt significantly improved percent body weight and glycemic change along with serum insulin, total cholesterol (TC), triglycerides (TG), low density lipoprotein (LDL-c), very low-density lipoprotein (VLDL-c), high-density lipoprotein-cholesterols (HDL-c), total hemoglobin, glycosylated hemoglobin, hepatic glycogen, coronary risk and fasting insulin resistance indices while suppressed down the activity of 3-hydroxy-3-methylglutaryl Coenzyme A reductase enzyme in test groups when compared with diabetic controls. The present findings conclude that MREt of R. serpentina can effectively betters the carbohydrate and lipid homeostasis by either inhibiting fructose absorption in intestine or decreasing insulin resistance in fructose-induced type 2 diabetic mice.

Present work seeks to investigate the biochemical parameters in terms of hypoglycemic and hypolipidemic effects of hydro-methanolic roots extract (HyMREt) of Rauwolfia serpentina in type 1 (alloxan induced) diabetic mice. Animals were divided into seven groups, four control groups, and three were test groups (HyMREt at 50, 100, & 150mg/kg). Each treatment was repeated for 14 days regularly in all seven respective groups and afterwards the body weights, fasting blood glucose (FBG), insulin, and serum lipid levels were determined. Total body weights of diabetic mice treated with HyMREt extract were dose dependently (p<0.05) improved. FBG of test groups were significantly (p<0.0001) reduced in comparison with diabetic controls which displayed elevated fasting blood glucose level. The insulin levels of HyMREt treated groups were significantly (p<0.0001) higher than those of diabetic controls. Lower triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-c) and very low density lipoprotein cholesterol (VLDL-c) whereas elevated level of high density lipoprotein cholesterol (HDL-c) were observed in test dose treated groups. In comparison with diabetic controls, the converse levels of serum lipid were observed. Significant improvement in cardio-protective indices and coronary risk index was also observed. Findings of present study support the hypoglycemic and hypolipidemic potential of HyMREt of R. serpentina.