Lipoprotein(a)

Fibrinogen IS an important risk factor for atherosclerosis, stroke and cardiovascular heart disease (CHD). This risk is increased when associated with a high serum cholesterol. Furthermore, it is also believed that not only fibrinogen concentration, but also the quality of fibrin networks may bean important risk factor for the development of CHD. CHD and stroke as a result of atherosclerosis, plus the related problems of hyperinsulinaemia,hyperlipidaemia and hypertensionare strongly related to diet. The "western" diet, defined by low fibre and high fat, sucrose and animal protein intakes, appears to be a major factor leading to death. It has been established that the water-soluble dietary fibre, pectin, significantly decrease the concentration of serum cholesterol levels. Evidence is also accumulating that a diet rich in fibre may protect against diseases associated with raised clotting factors. This investigation studied the possible effects of pectin on fibrinogenlevels and fibrin network architecture. Two groups of 10 male hyperlipidaemicvolunteerseach, received a pectin supplement ( 15g/day)or placebo ( 15rg/day) for 4 weeks. Lipid and fibrin network structure variables were measured at baseline and the end of supplementation. Pectin supplementation caused significant decreases in total cholesterol, low-density lipoproteincholesterol, , apolipoproteinA & B and lipoprotein (a). Significant changes in the characteristics of fibrin networks developed in the plasma of the pectin supplemented group indicated that networks were more permeable and had lower tensile strength. These network structures are believed to be less atherogenic. It is suspected that pectin modified network characteristics by a combinationof its effects on metabolism and altered fibrin conversion. This confirms the therapeutic possibilities of dietary intervention. Furthermore, this stud} also showed that changes in plasma fibrinogen need not be present to induce alterations in fibrin network architecture. 01997Elsevier

Background  High-quality methods for lipoprotein characterization are warranted in studies on various metabolic diseases.Materials and methods  An automated system for size-exclusion chromatography (SEC) of lipoproteins using commercially available components is described. Cholesterol or triglyceride content in separated lipoproteins from plasma and interstitial fluid (IF) was continuously determined on-line using microlitre sample volumes.Results  The lipoprotein assay showed a good concordance with the classic ultra-centrifugation/precipitation technique using fresh or frozen samples. Determination of lipoproteins in IF obtained from vacuum-induced skin blisters from 18 healthy subjects revealed that very low density lipoprotein (VLDL), low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol levels were 18%, 19% and 25%, respectively, of concomitant plasma concentrations. The size-exclusion chromatography (SEC) system also allows for triglyceride determination on-line and it could be shown that the system is advantageous for an accurate determination of triglycerides in conditions when there are high levels of glycerol, e.g. in mice and in patients with hyperglycerolaemia (pseudo-hypertriglyceridaemia).Conclusions  The described system should be of value in studies where detailed lipoprotein analysis is warranted and particularly when significant sample series with small volumes are available. Our data also suggest that there is a 4–5·5-fold concentration gradient between plasma and IF for the three major plasma lipoproteins.

Human lecithin:cholesterol acyltransferase (LCAT) is a key enzyme in the metabolism of cholesterol and is postulated to participate in the physiological process called reverse cholesterol transport. We have used transgenic mice (Tgm) expressing either both human apolipoprotein AI (apo AI) and human LCAT genes or only the human apo AI gene (HuAILCAT or HuAI Tgm, respectively) to assess the consequences of LCAT overexpression on serum lipid and lipoprotein profiles and on the ability of each serum to promote bidirectional flux of cholesterol between serum and Fu5AH hepatoma cells. Mean serum LCAT activity of HuAILCAT Tgm was 2-fold increased compared to the HuAI group (48 9 9 vs. 24 9 5 nmol/ml per h, PB 0.01 for HuAILCAT and HuAI Tgm, respectively) and the cholesterol esterification rates were not significantly different between the two groups of animals (66911 vs. 74918 nmol/ml per h for HuAILCAT and HuAI Tgm, respectively). HuAILCAT Tgm exhibited higher total cholesterol serum values (2.3-fold) due to an increase in both HDL-cholesterol (1.9-fold) and non-HDL-cholesterol (3-fold). The HDL particles from HuAILCAT Tgm were relatively phospholipid depleted and cholesterol enriched compared to HuAI mice. When cells were incubated for six hours with the mouse serum, the fractional efflux of radiolabeled cholesterol was slightly increased with the HuAILCAT Tgm (1.2-fold) but the increase in intracellular cholesterol content was also 2-fold higher than with the HuAI Tgm. Fu5AH can be viewed as a model for the evaluation of bidirectional flux of cholesterol in SR-BI-rich cells. In this model LCAT overexpression in mice, by increasing both HDL and non-HDL-cholesterol, mostly enhances the uptake of cholesterol by the cells, which would be of benefit for the last step of reverse cholesterol transport in hepatocytes.

The effects of the administration of 50 mg of guggulipid or placebo capsules twice daily for 24 weeks were compared as adjuncts to a fruit- and vegetable-enriched prudent diet in the management of 61 patients with hypercholesterolemia (31 in the guggulipid group and 30 in the placebo group) in a randomized, double-blind fashion. Guggulipid decreased the total cholesterol level by 11.7%, the low density lipoprotein cholesterol (LDL) by 12.5%, triglycerides by 12.0%, and the total cholesterol/high density lipoprotein (HDL) cholesterol ratio by 11.1% from the postdiet levels, whereas the levels were unchanged in the placebo group. The HDL cholesterol level showed no changes in the two groups. The lipid peroxides, indicating oxidative stress, declined 33.3% in the guggulipid group without any decrease in the placebo group. The compliance of patients was greater than 96%. The combined effect of diet and guggulipid at 36 weeks was as great as the reported lipid-lowering effect of modern drugs. After a washout period of another 12 weeks, changes in blood lipoproteins were reversed in the guggulipid group without such changes in the placebo group. Side effects of guggulipid were headache, mild nausea, eructation, and hiccup in a few patients.

All, but no tendency to precocious atherosclerosis is present. To elucidate this paradox, the structure of HDL, the potential of serum to promote cholesterol effiux from cultured cells, and the in vivo metabolism of HDL were examined in a 53-year-old Woman with a FED syndrome in association with a markedly decreased lecithin:cholesterol acyltransferase (LCAT) activity in HDL due to a mutation of the LCAT gene (Arglse -~ Cys). HDLs isolated by uitracentrifugation were small and enriched in unesterified cholesterol and phospholipids at the expense of cholesteryl esters and proteins, The apolipoprotein content showed an enrichment in apo E and apo AIV, whereas apo AI and apo All were dramatically reduced. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE} and immunoblotting using specific antibodies showed that the apo E was free or covalently bound to apo All. These particles analyzed by electron microscopy were small and round lipoproteins with a size similar to the smallest fraction of normal HDL3. The potential capacity of the serum to promote efflux from the cells was approximately 40% of control serum levels, but FED HDLs were as efficient as control HDLs in promoting cholesterol efflux from cells. To assess the metabolism of HDL apolipoproteins, in vivo apolipoprotein kinetic studies were performed using endogenous labeling techniques in the patient with FED and three control subjects. All subjects were administered D3-1abeled leucine by primed constant infusion for up to 10 hours. The fractional synthetic rates (FSRs) of apo AI and apo All in the patient were 0.674 and 0,594 per day, clearly higher than in controls, 0.210 +-0.053 and 0.148 +-0.014 per day for apo AI and apo All, respectively. Apo AI and apo All production rates in the patient with FED were normal, 11.32 and 2.62 mgJkg • d, respectively, as compared with those in normal subjects, 11.45 + 1.23 and 2.68 -+ 0.17 mg/kg • d. These data established that hypoalphalipoproteinemia in FED was caused by marked hypercatabolism of apo AI and apo All. This hypercatabolism could be the consequence of structural abnormalities due to the selective LCAT deficiency, in conclusion, two steps of reverse cholesterol transport, cholesterol efflux and apo-HDL metabolism, appeared particularly efficient. This efficiency could participate in the absence of premature atherosclerosis in FED patients as regards the low HDL level.

in life when bone catabolism supersedes anabolism, the significant loss of bone mass (osteoporosis) becomes a common medical problem ). tures (NIH Consensus Development Panel on Osteopo-Shauna Heeger, George Sabatakos, Suneel Apte, rosis Prevention, 2001). The worldwide annual incidence William N. Adkins, Jeremy Allgrove, of osteoporotic hip fracture exceeds 1.7 million cases Mine Arslan-Kirchner, Jennifer A. Batch, (http://www.who.int/inf-pr-1 999/en/pr99-58.html). Peter Beighton, Graeme C. M. Black, Numerous factors have been implicated in the develop-Richard G. Boles, Laurence M. Boon, ment of osteoporosis. Family and epidemiological stud-Carla Borrone, Han G. Brunner, Georges F. Carle, ies indicate that the peak bone mass attained during Bruno Dallapiccola, Anne De Paepe, Barbara Floege, growth is an important risk factor (NIH Consensus Devel-Melissa Lees Halfhide, Bryan Hall, opment Panel on Osteoporosis Prevention, 2001; See-Raoul C. Hennekam, Tatsuo Hirose, Ab Jans, man et al., 1994). Harald Jü ppner, Chong Ae Kim, Kim Keppler-Noreuil, Two principal cell types are responsible for the depo-Alfried Kohlschuetter, Didier LaCombe, sition and degradation of bone matrix. The bone-forming Marie Lambert, Emmanuelle Lemyre, cells, osteoblasts, differentiate from mesenchymal stem Tom Letteboer, Leena Peltonen, cells at sites of membranous bone formation, in perios-Rajkumar S. Ramesar, Marta Romanengo, teum of endochondral bones, and in bone marrow Hannu Somer, Elisabeth Steichen-Gersdorf, stroma (Aubin, 1998). The bone-degrading cells, osteo-Beat Steinmann, Beth Sullivan, clasts, differentiate from hematopoietic mononuclear Andrea Superti-Furga, Walter Swoboda, cells present in peripheral blood and bone marrow Marie-José van den Boogaard, Wim Van Hul, (Roodman, 1996). In order for bone mass to accrue dur-Miikka Vikkula, Marcela Votruba, Bernhard Zabel, ing the growth and maturation of the skeleton, bone Teresa Garcia, Roland Baron, Bjorn R. Olsen, formation by osteoblasts must exceed bone degradaand Matthew L. Warman 1 tion by osteoclasts. The Osteoporosis-Pseudoglioma Syndrome Children with the autosomal recessive disorder osteo-Collaborative Group 3 porosis-pseudoglioma syndrome (OPPG) (Gong et al., 1996) have very low bone mass and are prone to developing fractures and deformation ( .

The prawn Macrobrachium borellii has lecithotrophic eggs with highly-abbreviated development. The major yolk component is lipovitellin (LV), a lipoprotein with 30% lipids (by weight). LV consumption during embryogenesis was followed by ELISA and Western blot analysis using an anti-LV polyclonal antibody. No cross-reacting proteins were observed and LV-like lipoproteins were strongly recognized by the antibody in hemolymph (vitellogenin), yolk (LV) and embryos (LVe), as determined by Western Blot analysis. LV decreased significantly along development from 9.4 to 1.1 µg/mg egg. Consumption rate of LV was slow in early embryogenesis, followed by a rapid utilization in late embryonic stages. Significant LVe amounts were still present at hatching. LV apolipoproteins were selectively degraded during embryo development, being the highest molecular weight subunit the most affected. Comparison among in vitro, in vivo and theoretical proteolysis suggested that trypsin may be involved in LV degradation during late embryogenesis. Embryo lipoprotein (HDLe) synthesis was first detected at stage 6. HDLe shared the same density, MW and subunit composition as adult hemolymph HDL 1 and did not cross-react with LV-like lipoproteins. Though expressed at low concentration, it fulfilled embryo needs for lipid transport among organs.

This study evaluates the impact of obesity on coronary endothelial function in patients with normal or mild coronary artery disease. BACKGROUND The American Heart Association (AHA) has recently classified obesity as a modifiable risk factor for coronary heart disease.

A battery of histological and histochemical techniques was applied on the lead intranuclear bodies that have resuted in the kidneys of adult Wistar male rats receiving lead acetate in their diet to determine their nature. The intranuclear inclusion bodies have stained strongly with xanthene, anthraquinone, and trisulfonated basophilic dyes and weakly with dyes containing both positive and negative radicals, and they have responded negatively to acidophilic cationic dyes. They have also reacted positively to proteins and lead stains, but weakly to lipid stains, and negatively to Feulgen and methyl green pyronin techniques. The intranuclear bodies proved to be lead lipoprotein complexes containing sulfyhydryl groups and are basic in nature with orthochromatic, eosinophilic, argyrophilic, osmophilic, fuchsinophilic, and sudanophilic characteristics.

Surface associated pneumococcal proteins ␣-enolase (Eno), immunoglobulin A1 protease (Iga), streptococcal lipoprotein rotamase A (SlrA), and putative proteinase maturation protein A (PpmA) have potential as candidates for future protein-based anti-pneumococcal vaccines. The immunogenicity of these proteins were studied in a cohort of 329 children during their first two years of life. During the first recorded episode of otitis media, acute and convalescent phase sera were available from 151 children. Concentrations of antibodies against Eno, Iga, SlrA and PpmA were measured by EIA and detected in 99% (300/302), 95% (288/302), 95% (288/302), and 83% (251/302) of the sera, respectively. There were no statistically significant differences between the groups of children with and without a history of pneumococcal contact or with respect to the type of pneumococcal contact. Despite a mean overall decrease in the antibody titers in the convalescent sera following AOM, several children were able to respond with a more than twofold increase in antibody titer in response to AOM. The majority of the children with increased antibody concentrations appeared in the groups, which were colonized with pneumococci at the time of serum collection, but were recorded as having no prior contact with pneumococci. In conclusion, SlrA, PpmA, Eno and Iga are immunogenic proteins that elicit antibody responses early in life. No significant correlation between antibody titers to these proteins and pneumococcal carriage or infection was found. Presumably, this results from the presence of cross-reactive epitopes on commensal bacteria.

Hyperhomocysteinemia is an independent risk factor for ischemic cardiovascular diseases, but its causal role in atherothrombosis remains controversial. Proatherogenic and/or prothrombotic effects may underlie the potential causal relation between hyperhomocysteinemia and cardiovascular events. Here, the effects of selective lowering of plasma homocysteine, plasma cholesterol, or both on endothelial function and on atherogenesis in male hyperlipidemic and hyperhomocysteinemic C57BL/6 lowdensity lipoprotein receptor (LDLr) −/− /cystathionine-β-synthase (CBS) +/− -deficient mice were investigated. Second, we evaluated whether selective homocysteine lowering has anti-thrombotic effects in a model of arterial thrombosis. A hyperhomocysteinemic and atherogenic diet was started at the age of 12 weeks. Three weeks later, gene transfer was performed with E1E3E4-deleted adenoviral vectors for hepatocyte-restricted overexpression of CBS (AdCBS) or of the LDLr (AdLDLr), or with the control vector Adnull. In a fourth group, AdCBS and AdLDLr were coadministered. Selective homocysteine lowering but not selective cholesterol lowering restored endothelial function at 6 weeks after gene transfer. Intimal area in the aortic root and in the brachiocephalic artery at 13 weeks was more than 100-fold (p<0.001) smaller in AdLDLr and AdCBS/ AdLDLr mice than in control mice and AdCBS mice. No differences in intimal area were observed between control mice and AdCBS mice. In a model of carotid artery thrombosis, the average time to first occlusion and to stable occlusion were 1.9-fold (p <0.01) and 2.1-fold longer (p<0.01), respectively, in AdCBS-treated mice than in control mice. Taken together, these data show that correction of endothelial dysfunction following selective homocysteine lowering has anti-thrombotic but no antiatherogenic effects.

Peripheral arterial disease (PAD) is a common manifestation of atherosclerosis that affects more than 10 million people in the United States. The risk factors associated with PAD are similar to those found in patients with coronary artery disease and cerebrovascular disease. Medical therapy of PAD must include modification of cardiovascular risk factors with application of strict secondary prevention guidelines. For improvement in quality of life, a structured exercise rehabilitation program remains the most effective noninterventional treatment strategy, but it is difficult to employ from economic and patient-compliance perspectives. Newer pharmacologic therapies have demonstrated efficacy in patients with intermittent claudication. Emerging strategies for management of these patients include revascularization and maximal medical therapy for improvement of physical function as well as reduction in risk for subsequent major cardiovascular events. This article will review the clinical data supporting aggressive medical interventions for patients with PAD.

Summary  We used a new and remarkably simple method to examine the extent of in vivo lipoprotein glycation in type II diabetic patients with atherosclerosis and diabetic patients with no complications. Serum glycated lipoprotein levels were determined by agarose gel film electrophoresis in 48 non-diabetic control subjects and 39 diabetic patients, of whom 26 had no complications and 13 had atherosclerotic

Background: Risk of cardiovascular disease is assessed, in part, by laboratory measurement of the concentra- tions of several lipoproteins. b-Quantification is a method of lipoprotein measurement that uses ultracen- trifugation to partially separate lipoprotein classes. Al- though b-quantification is used largely in clinical and basic research, methods have not been described to allow the analysis of a large number of

To determine the prevalence of insulin resistance, impaired fasting glycaemia, impaired glucose tolerance, and diabetes mellitus in a rural Maori community, and to compare different methods for identifying individuals with insulin resistance.

This metabolic study was designed to investi- gate the effects of mycoprotein on blood lipids. Mycoprotcin is a food produced by continuous fermentation of Fusarium graminearum (Schwabe) on a carbohydrate substrate. Iwo groups of subjects with slightly raised cholesterol concentra- tions took part in the 3-wk study. The experimental group was fed mycoprotein in place of meat and the control

The goal of this study was to examine the association between paraoxonase-1 (PON1) activity and concentration and the severity and extent of coronary artery disease (CAD). Paraoxonase-1, a high-density lipoprotein-associated enzyme, is proposed to have an antiatherogenic effect by protecting low-density lipoproteins against oxidation. We studied PON1 activity and concentration in 107 patients with known or suspected CAD referred for cardiac catheterization. Based on visual estimation of coronary angiograms, subjects were classified as having no or mild CAD (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;50% stenosis) and significant CAD (&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt; or =50% stenosis). Quantitative coronary angiography (QCA) was used to estimate the indexes of severity, extent, and overall atheroma burden of CAD. We found lower values of PON1 activity and concentration (p = 0.003 and p = 0.016, respectively) in the group with significant CAD as compared with the group with no or mild CAD. The PON1 activity was significantly inversely correlated with CAD severity (r = -0.364, p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001), extent (r = -0.221, p = 0.022), and atheroma burden (r = -0.277, p = 0.004). Similarly, PON1 concentration correlated with CAD severity (r = -0.306, p = 0.001) and atheroma burden (r = -0.229, p = 0.017). In multiple regression analysis, gender and PON1 activity were significant determinants of the severity of CAD independently of age, hypertension, smoking, abnormal glucose regulation, and high-density lipoprotein cholesterol. Our results indicate that PON1 activity and concentration are lower in subjects with significant CAD, and that there is a significant relationship between PON1 activity and concentration and CAD assessed by QCA.

In this work we describe the ability of living Trypanosoma rangeli to hydrolyze extracellular ATP. In these intact parasites whose viability was assessed before and after the reactions by motility and by Trypan blue dye exclusion, there was a low level of ATP hydrolysis in the absence of any divalent metal (1.53 § 0.12 nmol Pi/h £ 10 7 cells). The ATP hydrolysis was stimulated by MgCl 2 and the Mg-dependent ecto-ATPase activity was 5.24 § 0.64 nmol Pi/h £ 10 7 cells. The Mg-dependent ecto-ATPase activity was linear with cell density and with time for at least 60 min. This stimulatory eVect on the ATP hydrolysis was also observed when MgCl 2 was replaced by MnCl 2 , but not by CaCl 2 , SrCl 2 , and ZnCl 2 . The apparent K m for Mg-ATP2-was 0.53 § 0.11 mM. The optimum pH for the T. rangeli Mg-dependent ecto-ATPase activity lies in the alkaline range. This ecto-ATPase activity was insensitive to inhibitors of other ATPase and phosphatase activities, such as oligomycin, sodium azide, baWlomycin A1, ouabain, furosemide, vanadate, molybdate, sodium Xuoride, tartrate, and levamizole. To conWrm that this Mg-dependent ATPase was an ecto-ATPase, we used an impermeant inhibitor, DIDS (4, 4Ј-diisothiocyanostylbene 2Ј-2Ј-disulfonic acid) as well as suramin, an antagonist of P2 purinoreceptors and inhibitor of some ecto-ATPases. These two reagents inhibited the Mg 2+ -dependent ATPase activity in a dose-dependent manner. This ecto-ATPase activity was stimulated by carbohydrates involved in the attachment/invasion of salivary glands of Rhodnius prolixus and by lipophorin, an insect lipoprotein circulating in the hemolymph. 

Recentemente, indicadores associados à aptidão física relacionada à saúde vêm sendo interpretados mediante informações referenciadas por critério. Informações referenciadas por critério direcionadas à saúde representam níveis desejáveis consistentes com reduzido risco de aparecimento e desenvolvimento de disfunções orgânicas que deverão ser alcançados pelos adolescentes. Objetivo do estudo foi analisar a validade de pontos de corte associados às informações referenciadas por critério preconizados pela proposta Physical Best na identificação de adolescentes portadores e não-portadores de fatores de risco predisponentes às doenças cardiovasculares. A amostra foi constituída por 281 adolescentes (157 moças e 124 rapazes) com idades entre 15 e 18 anos. Informações acerca da aptidão física relacionada à saúde foram obtidas mediante indicadores morfológicos (índice de massa corporal e somatório de espessuras das dobras cutâneas tricipital e subescapular) e resultados de testes motores (sentar-e-alcançar, abdominal modificado e caminhada/corrida de 1600 metros). Quanto aos fatores de risco predisponentes às doenças cardiovasculares, recorreu-se ao conteúdo de gordura corporal, ao consumo máximo de oxigênio, aos níveis de pressão arterial e às concentrações de lipídios-lipoproteínas plasmáticas. Estimativas quanto aos índices de sensibilidade, especificidade, valor preditivo positivo e eficiência foram utilizados para descrever a validade relativa. Os resultados mostraram que os índices de sensibilidade se apresentaram entre 20% e 70% e os de especificidade entre 30% e 85%. Os indicadores morfológicos demonstraram que podem identificar corretamente três em cada quatro adolescentes com fatores de risco predisponentes às doenças cardiovasculares. Os pontos de corte associados aos resultados dos testes motores demonstraram baixos níveis de sensibilidade e elevada proporção de casos falso-positivos. Como conclusão, os achados sugerem que, independentemente dos pontos de corte utilizados, o índice de massa corporal e o somatório das espessuras das dobras cutâneas caracterizam-se como razoável alternativa para identificar a presença de fatores de risco predisponentes às doenças cardiovasculares em adolescentes.

The methanol extract of Costus pictus (C. pictus) D.DON (Family: Zingiberaceae) leaf was investigated for its anti-diabetic effect in Wistar Albino rats. Diabetes was induced in Albino rats by administration of single doses of alloxan monohydrate (120 mg/kg, i.p.). The methanol extract of C. pictus (MECP) at a dose of 120 mg/kg, p.o. was administered as single dose per day to diabetes-induced rats for a period of 21 days. The effect of MECP leaf extract on blood glucose, plasma insulin, serum lipid profile [cholesterol, triglycerides, phospholipids, very lowdensity lipoprotein (VLDL), low-density lipoprotein (LDL), and high-density lipoprotein (HDL)], serum enzymes [serum glutamate oxaloacetate transaminases (SGOT), serum glutamate pyruvate transaminases (SGPT), alkaline phosphatase (ALP)], total protein, and liver glycogen were measured in the diabetic rats. Histopathological studies of liver, pancreas and kidney were also carried out. MECP elicited significant (p < 0.001) reductions of blood glucose, lipid parameters except HDL, and serum enzymes and significantly (p < 0.001) increased HDL level. MECP also caused significant (p < 0.001) increases in plasma insulin levels in the diabetic rats. Furthermore, MECP significantly (p < 0.05), (p < 0.001) increased total protein and liver glycogen in diabetic rats. Histopathological observations revealed that leaf is non-toxic and regenerates the toxic effect of alloxan. From the above results, it is concluded that MECP possesses significant anti-diabetic effects in alloxan-induced diabetic rats.

Emerging data suggest that acute presentations of coronary artery disease may involve a complex interplay between the vessel wall, inflammatory cells, and the coagulation cascade. Although a culprit thrombotic lesion may be treated effectively by antithrombotic therapy and revascularization, this will have little effect on the global processes that determine recurrent events at non-culprit sites. Thus, additional systemic treatment is required to modulate the adverse biological features that are the hallmark of acute coronary syndromes (ACS). Statins possess multiple beneficial effects that are independent of low-density-lipoprotein cholesterol (LDL-C) lowering and that have favorable effects on inflammation, the endothelium, and the coagulation cascade. In the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22 (PROVE IT-TIMI 22) trial, differences were seen based on achieved LDL-C that could be further discriminated by the achieved C-reactive protein level. Studies of non-vascular disease such as multiple sclerosis have shown that statins reduce inflammation, supporting the presence of lipid-independent effects of statins. This review focuses on the potential importance of these effects in the management of ACS. (J Am Coll Cardiol 2005;46:1425-33)

A simple and reproducible method of determining the quality and quantity of neutral lipids in human saliva was tested. Parotid, submandibular and whole stimulated saliva were collected from l0 healthy adults. The lipids were extracted by the Folch method. A special method for extraction of glycolipids was also tested but gave no additional recovery. Thin-layer chromatography was used for separating the different lipid classes. The concentrations of total lipids in parotid, submandibular and whole stimulated saliva were 0.2, 0.9 and 1.3 mg/dl, respectively. Cholesteryl esters, cholesterol, triglycerides, diglycerides, monoglycerides and free fatty acids accounted for 96-99% of the total salivary lipids. Thus, polar lipids such as phospholipids contributed only a minor fraction, indicating that the lipids are not primarily of membrane origin. Ultracentrifugation of saliva samples at d = 1.21 g rnl -L showed that the salivary lipids did not float like blood plasma lipoproteins. Therefore, they must be in a different state of aggregation from lipids in blood or lymph. No significant lipase activity of the type that acts on plasma lipoproteins was found in parotid or submandibular saliva. The content of free fatty acids and partial glycerides was high.

Experimentally, we demonstrated the beneficial effects of L-arginine on regulation of hyperglycemia and dyslipidemia in experimental diabetes, in addition to a positive anti-aggregating effect in platelets in animals and humans. Here, the effect of L-arginine on foot ulcers from diabetic patients was studied. Three groups of diabetic patients were included: 11 patients without ulcer received neither treatment and served as controls. Eleven patients with diabetic ulcer received the standard treatment, this group served as diabetic control with diabetic ulcer. Eleven remain patients with diabetic ulcer received 10 mM L-arginine subcutaneously on the site of the wound. Biopsy with punch number 5 on wound site comprising both ulcerative and contiguous undamaged skin were performed in all patients with ulcerative lesions before any treatment. Patients with intact skin had biopsy performed with punch number 5 on external malleolar region of right lower limb. Biopsies were examined by light and confocal microscopy utilizing histochemical and immunohistochemical methods. Initial and final blood samples were collected to determine glucose, triglycerides, total cholesterol, glycated hemoglobin (HbA 1c ), low (LDL), and high density lipoproteins (HDL). Significant differences (P < 0.05) were observed between initial and final serum glucose levels for treated patients, and initial serum glucose levels between treated and control patients without diabetic ulcer. Glycated hemoglobin, triglycerides, cholesterol, and lipoprotein levels showed no significant changes. Eight patients treated with L-arginine reached total wound healing and the remaining three who abandoned the study because of change of residence showed relevant improvement. Histochemistry and immunohistochemistry methods have shown vascular impairment in both patients with diabetic ulcer (prior to treatment) and control patients without diabetic ulcer. Our observations strongly support efficacy of L-arginine for successful wound healing of diabetic ulcers.

membrane-bound states of the peptide. 15 N relaxation rates were measured to obtain the effective rotational correlation time of the Aam-I molecule. The obtained value (~40 nsec at 45°C) is indicative of additional peptide motions within the Aam-I/LPN complex.

Background: n-3 Polyunsaturated fatty acids (n-3 PUFA) convey several health benefits, including a reduction of serum concentration of triglycerides (TG). Aim: To examine the effect on blood lipids, particularly TG, of a diet with n-3 PUFA enriched eggs in healthy volunteers in the Seychelles (Indian Ocean). Methods: Double-blind crossover trial with one group of volunteers fed with 5 normal eggs per week during 3 weeks followed by 5 enriched eggs per week during the next 3 weeks while the other group received eggs in the inverse sequence. Hen feed was supplemented at 5% with tuna oil. Enriched eggs contained nine times more n-3 PUFA than usual eggs (mainly docosahexaenoic acid). Results: Twenty-five healthy volunteers participated in the study. Based on pooled results observed during the two 3-week periods, consumption of enriched eggs was associated with a significant 16e18% decrease in serum triglycerides (P < 0.01) but with no significant difference in serum LDL-cholesterol and HDL-cholesterol. Serum LDL-cholesterol increased during the first 3-week period and decreased during the second 3-week period with both normal and enriched eggs. Participants did not report a systematic preference for either type of eggs.

Hyaluronic acid (HA) and tissue inhibitor of metalloproteinase 1 (TIMP-1) are reliable markers of liver fibrosis and are closely linked to the proinflammatory status. In this pilot cohort study, we attempted to identify a clinical score that would predict the severity of nonalcoholic fatty liver disease (NAFLD) based on clinical variables and serum markers of fibrosis and inflammation. The cohort included 46 patients with histologically confirmed NAFLD (76.1% male; mean age, 43 6 13 years; mean body mass index [BMI], 27.8 6 3.5). Serum transforming growth factor beta (TGF-b), HA, TIMP, and matrix metalloproteinase (MMP) levels were measured with commercial enzyme-linked immunoassay (ELISA) kits. Demographic features and clinical and laboratory findings were subjected to univariate and multivariate binary logistic regression analysis to construct the mathematical model. Receiver operating characteristic curve (ROC) analysis was used to identify a threshold value for diagnosis of NASH and to assess its sensitivity and specificity. Serum levels of HA and TIMP-1 were statistically different in patients with nonalcoholic steatohepatitis (NASH) (P , 0.05). Logistic regression analysis of several clinical variables indicated patient age as the only independent predictor of NASH (odds ratio [OR], 1.129, 95% confidence interval [CI], 1.019-1.251, P 5 0.020). The mathematical model constructed on the basis of these results included age, TIMP-1, and HA levels. A value of 148.27 or more identified patients with NASH with 85.7% sensitivity, 87.1% specificity, and negative and positive predictive values of 96.4% and 60%, respectively. This model seems to represent a reliable noninvasive tool for excluding the presence of NASH. If validated in larger prospective cohort studies, it might be useful for determining when a liver biopsy is actually warranted in patients with NAFLD. (Translational Research

. The performance of microdiets MDs for larvae of marine fish is frequently improved when they are co-fed with Artemia. This suggests that nutritional factors in the live food are positively influencing the ingestion, digestion and assimilation of the MD. This paper reviews recent advances in MD development on the gilthead seabream with special emphasis on studies that isolated, identified and tested these live food factors in MD with the aim of improving their performance.

The primary objective of this 6-week, parallel-group, open-label, randomized, multicenter trial was to compare rosuvastatin with atorvastatin, pravastatin, and simvastatin across dose ranges for reduction of lowdensity lipoprotein (LDL) cholesterol. Secondary objectives included comparing rosuvastatin with comparators for other lipid modifications and achievement of National Cholesterol Education Program Adult Treatment Panel III and Joint European Task Force LDL cholesterol goals. After a dietary lead-in period, 2,431 adults with hypercholesterolemia (LDL cholesterol >160 and <250 mg/dl; triglycerides <400 mg/dl) were randomized to treatment with rosuvastatin 10, 20, 40, or 80 mg; atorvastatin 10, 20, 40, or 80 mg; simvastatin 10, 20, 40, or 80 mg; or pravastatin 10, 20, or 40 mg. At 6 weeks, across-dose analyses showed that rosuvastatin 10 to 80 mg reduced LDL cholesterol by a mean of 8.2% more than atorvastatin 10 to 80 mg, 26% more than prava-statin 10 to 40 mg, and 12% to 18% more than simvastatin 10 to 80 mg (all p <0.001). Mean percent changes in high-density lipoprotein cholesterol in the rosuvastatin groups were ؉7.7% to ؉9.6% compared with ؉2.1% to ؉6.8% in all other groups. Across dose ranges, rosuvastatin reduced total cholesterol significantly more (p <0.001) than all comparators and triglycerides significantly more (p <0.001) than simvastatin and pravastatin. Adult Treatment Panel III LDL cholesterol goals were achieved by 82% to 89% of patients treated with rosuvastatin 10 to 40 mg compared with 69% to 85% of patients treated with atorvastatin 10 to 80 mg; the European LDL cholesterol goal of <3.0 mmol/L was achieved by 79% to 92% in rosuvastatin groups compared with 52% to 81% in atorvastatin groups. Drug tolerability was similar across treatments. ᮊ2003

Aronia melanocrpa fruit juice (AMFJ) used in our experiment was very rich in phenolic substances (709.3 mg gallic acid equivalents/100 ml juice). Anthocyanins (106.8 mg cyanidin-3-glucoside equivalents/100 ml juice) were the main flavonoid group. The aim of this study was to assess the influence of AMFJ on plasma lipids and lipoprotein profile, and histopathology of liver and aorta in rats with dietary-induced hyperlipidemia. AMFJ was administered by gavage for 30 days at doses of 5, 10 and 20 ml/kg body weight to rats fed a standard diet (SD) or a 4% cholesterol-containing diet (4% ChD). The 4% ChD caused a significant elevation of plasma total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG). AMFJ did not significantly influence plasma lipids in rats fed the SD and significantly hindered the elevation of plasma TC, LDL-C and TG in rats fed the 4% ChD. High-density lipoprotein cholesterol (HDL-C) levels were not significantly influenced either by...

Cardiovascular disease is a leading cause of mortality in the United States, and is a significant cause of death worldwide. In 2002, it accounted for 38.0% of all deaths in the US, and approximately one-third of all global deaths. It has a significant economic impact, with an estimated cost in the US of $393.5 billion for 2005. The most common form of heart disease is coronary heart disease (CHD) 1 /coronary artery disease (CAD) resulting from atherosclerosis. Thirteen million Americans are affected by CHD annually, with 7.1 million of these experiencing a myocardial infarction (MI). Five to ten percent of new MI's occur in individuals younger than age 50, and the lifetime risk of developing CAD after age 40 ranges from 32% in women to 49% in men. Because of its major impact on morbidity and mortality, as well as its contribution to annual health care costs, it is of the utmost importance that improved strategies for preventing and treating CAD be developed. A promising, but inherently difficult, area of study is the identification of genes that predispose to or directly cause CAD. The identification of these genes may lead to screening tests that will allow persons at risk for developing CAD to be identified early enough that prevention/intervention strategies can be implemented to prevent or ameliorate the disease process, and may also lead to the development of gene therapy mechanisms useful in the treatment of ischemic heart disease (IHD). Because an exhaustive review of all the genes being studied in relation to CAD and MI is difficult within the confines of a review article, this review will focus on describing representative studies investigating the genes considered most likely to potentially contribute toward an increased risk for CAD and MI. Genes resulting in inherited disorders with which an increased risk of CAD and MI is associated will be discussed, as well as a number of candidate genes that may play a role in the multifactorial inheritance of CHD risk. convertase subtilisin/kexin type 9; RFLP, restriction fragment length polymorphism; VLDL, very lowdensity lipoprotein.

Serum lipoprotein(a) (Lp(a)) was serially determined after acute attacks of myocardial infarction and after surgical operations. Acute phase proteins, such as C-reactive protein, cw,-acid glycoprotein, cy,-antitrypsin and haptoglobin, increased rapidly and markedly after the episodes. Initial values of serum Lp(a) concentrations were almost the same in both groups. Increases in serum Lp(a) levels were also observed during the first few days, with a return to the initial levels after more than 1 month. The periods for reaching maximal levels of acute phase proteins were similar in both groups of patients. On the contrary, the period required for Lp(a) to reach the maximal level in the myocardial infarction group was significantly longer than in the post-operative group. The present study suggests that Lp(a) has the characteristics of an acute phase reactant and may play an important role in recovery from tissue damage.

Macrophages isolated from a variety of organs in several animal species exhibit high affinity binding sites that recognize chemically modified proteins. One of these binding sites recognizes human plasma low density lipoprotein (LDL) in which the positive charges on the epsilon-amino groups of lysine have been removed or neutralized by chemical modification, thus giving the protein an enhanced negative charge. Effective treatments include reaction of LDL with organic acid anhydrides (acetylation or maleylation) and reaction with aldehydes, such as treatment with malondialdehyde. After the negatively-charged LDL binds to the surface receptor sites, it is rapidly internalized by the macrophages by endocytosis and hydrolyzed in lysosomes. The liberated cholesterol is reesterified in the cytoplasm, producing massive cholesteryl ester deposition. The binding site for negatively-charged LDL has been demonstrated so far only on macrophages and other scavenger cells. It is not expressed in cultured fibroblasts, smooth muscle cells, lymphocytes, or adrenal cells. In addition to its affinity for acetylated LDL and malondialdehyde-treated LDL, the macrophage site binds a variety of polyanions. It exhibits a particularly high affinity for certain sulfated polysaccharides (dextran sulfate and fucoidin), certain polynucleotides (polyinosinic acid and polyguanylic acid), polyvinyl sulfate, and maleylated albumin. It is possible that the site that binds negatively-charged LDL may be responsible for the massive accumulation of cholesteryl esters that occurs in vivo in macrophages and other scavenger cells in patients with high levels of circulating plasma LDL.

The aim of this study was to investigate the adhesive phenotype of the human intestinal isolate Bifidobacterium bifidum MIMBb75 to human colon carcinoma cell lines. We have previously shown that the adhesion of this strain to Caco-2 cells is mediated by an abundant surface lipoprotein named BopA. In this study, we found that this strain adheres to Caco-2 and HT-29 cells, and that its adhesion strongly depends on the environmental conditions, including the presence of sugars and bile salts and the pH. Considerably more adhesion to a Caco-2 monolayer occurred in the presence of fucose and mannose and less when MIMBb75 grew in Oxgall bile salts compared to standard environmental conditions. In particular, growth in Oxgall bile salts reduced the adhesion ability of MIMBb75 and modified the SDS-PAGE profile of the cell wall associated proteins of the strain. The pH markedly affected both adhesion to Caco-2 and bacterial autoaggregation. Finally, experiments with sodium metaperiodate suggested that not only proteinaceous determinants are involved in the adhesion process of B. bifidum. In conclusion, it seems that the colonization strategy of this bacterium can be influenced by factors varying along the gastrointestinal tract, such as the presence of specific sugars and bile salts and the pH, possibly limiting the adhesion of B. bifidum to only restricted distal sites of the gut.

Background: Coronary artery disease (CAD) is one of the major causes of morbidity and mortality in the world. The disease is determined by many risk factors such as age, gender, diabetes, dyslipidemia, smoking, as well as elevated serum levels of lipoprotein (a) (Lp(a)), homocysteine, C-reactive protein (CRP) and uric acid. In this study, we evaluated the association of biologic and metabolic parameters with CAD in a group of Lebanese patients. Methods: Three hundred patients were recruited for the study. Biologic and blood metabolic parameters were measured. Patients were then divided into 3 groups according to their catheterization result: 0% stenosis (controls), b 50% stenosis and z 50% stenosis. Results: Hyperlipidemias, CRP, homocysteine and uric acid levels in CAD patients were not different from those of the controls. However, age, elevated fasting blood glucose (FBG) and elevated serum Lp(a) levels were found to be strong independent predictors of CAD in our study population. Association with CAD was also shown for gender, hypertension, diabetes and family history of CAD. Conclusion: We report the importance of serum Lp(a) levels and FBG in the prediction and prevention of CAD in our population. D

The Human Genome Project and subsequent identification of single nucleotide polymorphisms (SNPs) within populations has played a major role in predicting individual response to drugs (pharmacogenetics) leading to the concept of "personalized medicine." Nutritional genomics is a recent off-shoot of this genetic revolution that includes (1) nutrigenomics: the study of interaction of dietary components with the genome and the resulting proteonomic and metabolomic changes; and (2) nutrigenetics: understanding the gene-based differences in response to dietary components and developing nutraceuticals that are most compatible with health based on individual genetic makeup. Despite the extensive data on genetic polymorphisms in humans, its translation into medical practice has been slow because of the time required to accumulate population data on SNP incidence, understand the significance of a given SNP in disease, and develop suitable diagnostic tests. Nutrigenomics revitalized the field by showing that nutrients and botanicals can interact with the genome and modify subsequent gene expression, which has provided a great impetus for nutrigenetic research and nutraceutical development based on nutrigenetics. Polymorphisms in methlyene tetrahydrofolate reductase (MTHFR) (involved in folate metabolism), apolipoprotein E (Apo E) and ApoA1 (in cardiovascular disease), and leptin/leptin receptor (obesity) genes are some good examples for understanding basic nutrigenetics. Developing nutraceuticals to prevent and manage thrombosis risk in women with thrombophilic gene mutations are discussed in the context of the opportunities that exist at the nutrigenetic/pharmacogenetic interphase leading to "personalized nutrition." Further research on individual differences in genetic profiles and nutrient requirements will help establish nutrigenetics as an essential discipline for nutrition and dietetics practice. (Translational Research 2007;149:55-61) Abbreviations: Apo E ϭ apolipoprotein E; CAM ϭ complimentary and alternative medicine; CHD ϭ coronary heart disease; HDL ϭ high-density lipoprotein; HRT ϭ horomone replacement therapy; LDL ϭ low-density lipoprotein; MTHFR ϭ methlyene tetrahydrofolate reductase; PAI-1 ϭ plasminogen activator inhibitor; SNP ϭ single nucleotide polymorphism; WHI ϭ Women's Health Initiative T he completion of the Human Genome Project 1 has sparked a great deal of research on individual variation in gene sequences, particularly in single nucleotide polymorphisms (SNPs), their role in chronic diseases, and in predicting individual responses to drugs (pharmacogenetics). Nutritional genomics is a recent offshoot of this genetic revolution 2,3 that includes (1) nutrigenomics: The study of interaction of dietary components with the genome, the resulting changes in proteins, and other metabolites; and (2) nutrigenetics: Understanding

In this study, we synthesized and characterized two methoxy poly(ethylene glycol)-block-poly(caprolactone) (MePEG-b-PCL) amphiphilic diblock copolymers, both based on MePEG with a molecular weight of 5000 g/mol (114 repeat units) and PCL block lengths of either 19 or 104 repeat units. Nanoparticles were formed from these copolymers by a nanoprecipitation and dialysis technique. The MePEG 114 -b-PCL 19 copolymer was water soluble and formed micelles that had a hydrodynamic diameter of 40 nm at all copolymer concentrations tested, and displayed a relatively low core microviscosity. The practically water insoluble MePEG 114 -b-PCL 104 copolymer formed nanoparticles with a larger hydrodynamic diameter, which was dependent on copolymer concentration, and possessed a higher core microviscosity than the MePEG 114 -b-PCL 19 micelles, characteristic of nanospheres. The micelles solubilized a maximum of 1.6% w/w of the hydrophobic anticancer agent, paclitaxel (PTX), and released 92% of their drug payload over 7 days, as compared to the nanospheres, which solubilized a maximum of 3% w/w of PTX and released 60% over the same period of time. Both types of nanoparticles were found to be hemocompatible, causing only minimal hemolysis and no changes in plasma coagulation times as compared to control. Upon in vitro incubation in human plasma, PTX solubilized by micelles had a plasma distribution similar to free drug. The majority of PTX was associated with the lipoprotein deficient plasma (LPDP) fraction, which primarily consists of albumin and alpha-1glycoprotein. In contrast, nanospheres were capable of retaining more of the encapsulated drug with significantly less PTX partitioning into the LPDP fraction.

Track 4. Basic Resealnh S381 was used to detect apoptosis. Flow cytometric analysis of bovine retinal capillary endothelial cells and pericytes quiesced in serum-free medium for 24 hr then treated with different concentrations of either unmodified or glycoxidized LDL for 24 hr showed apoptotic and non-apoptotic populations. At 300 &ml lipoprotein, percentage of apoptotic cells in endothelial cells was 2.33 f 0.72 SD fold higher using glycoxidized compared to unmodified LDL (n = 4 experiments, P -z 0.01). Preliminary data in pericytes showed that percentage of apoptotic cells was 4 fold higher using glycoxidized LDL than unmodified LDL at 200 &ml lipoprotein. At 300 &ml glycoxidized LDL, massive cell death was observed microscopically in the cultured pericytes. Our results suggest that exposure of retinal capillary cells to modified LDL in diabetic patients may lead to premature (apoptotic) death of these cells, and could contribute to some of the features of diabetic retinopathy.

To review the effectiveness of exercise-based cardiac rehabilitation in patients with coronary heart disease. METHODS: A systematic review and meta-analysis of randomized controlled trials was undertaken. Databases such as MEDLINE, EMBASE, and the Cochrane Library were searched up to March 2003. Trials with 6 or more months of follow-up were included if they assessed the effects of exercise training alone or in combination with psychological or educational interventions. RESULTS: We included 48 trials with a total of 8940 patients. Compared with usual care, cardiac rehabilitation was associated with reduced all-cause mortality (odds ratio [OR] ϭ 0.80; 95% confidence interval [CI]: 0.68 to 0.93) and cardiac mortality (OR ϭ 0.74; 95% CI: 0.61 to 0.96); greater reductions in total cholesterol level (weighted mean difference, -0.37 mmol/L [-14.3 mg/dL]; 95% CI: -0.63 to -0.11 mmol/L [-24.3 to -4.2 mg/dL]), triglyceride level (weighted mean difference, -0.23 mmol/L [-20.4 mg/dL]; 95% CI: -0.39 to -0.07 mmol/L [-34.5

The quantity and quality of fats consumed in the diet influence the risk of cardiovascular disease (CVD). Although the effect of diet on plasma lipids and lipoproteins is well documented, less information exists on the role of fats on blood pressure (BP). Objective: The objective was to evaluate the effects of different types of dietary fat on BP in healthy subjects. Design: Healthy subjects (n ҃ 162) were randomly assigned for 3 mo to follow 1 of 2 isoenergetic diets: 1 rich in monounsaturated fatty acids (MUFA diet) and the other rich in saturated fatty acids (SFA diet). Each group was further randomly assigned to receive supplementation with fish oil (3.6 g nҀ3 fatty acids/d) or placebo. Results: Systolic BP (SBP) and diastolic BP (DBP) decreased with the MUFA diet [Ҁ2.2% (P ҃ 0.009) and Ҁ3.8% (P ҃ 0.0001), respectively] but did not change with the SFA diet [Ҁ1.0% (P ҃ 0.2084) and Ҁ1.1% (P ҃ 0.2116)]. The MUFA diet caused a significantly lower DBP than did the SFA diet (P ҃ 0.0475). Interestingly, the favorable effects of MUFA on DBP disappeared at a total fat intake above the median (37% of energy). The addition of nҀ3 fatty acids influenced neither SBP nor DBP. Conclusions: Changing the proportions of dietary fat by decreasing SFAs and increasing MUFAs decreased diastolic BP. Interestingly, the beneficial effect on BP induced by fat quality was negated by the consumption of a high total fat intake. The addition of nҀ3 fatty acids to the diet had no significant effect on BP.

Vitamin K is a group name for K 1 (phylloquinone) and K 2 (menaquinones). Both forms contribute to the tissue vitamin K status. Following intestinal absorption, the serum transport of these lipophilic compounds to their target tissues takes place via lipoproteins. In previous studies we have found that K 1 is preferentially accumulated in the liver, whereas menaquinones have a more widespread distribution pattern. Here we have tested whether these differences may be explained by the different liposolubility of the various Kvitamers, resulting in their association with different lipoprotein particles. Six healthy male volunteers received a mixture containing 2 Wmol of each of three K vitamers (K 1 , MK-4, and MK-9) dissolved in corn oil. Blood was obtained at baseline and at different time intervals after intake for the measurement of vitamin K in serum and in the lipoprotein fractions. During the first 4 h after intake all Kvitamins were found to be associated predominantly with the triacylglycerol-rich lipoprotein (TGRLP) fraction. Since the TGRLP fraction is mainly cleared by the liver, this suggests that initially most of the K-vitamins are transported to the liver. In contrast to K 1 , however, both menaquinones investigated were also found in TGRLP and low-density lipoprotein, whereas MK-4 was even present in high-density lipoprotein. This explains why menaquinones may have a different distribution profile and suggests a relatively large impact of menaquinones on extra-hepatic vitamin K status than generally assumed. Moreover, the very long half-life time of MK-9 in the circulation indicates that it may form a more constant source of vitamin K than are either K 1 or MK-4. ß

L'endothélium vasculaire joue un rôle primordial notamment dans la régulation du tonus vasculaire, en réponse à différents stimuli tels que la prostacycline, l'endothéline et surtout le monoxyde d'azote (NO • ). Le stress oxydant, caractérisé par une augmentation relative des espèces réactives de l'oxygène (ERO), peut diminuer la biodisponibilité du NO • , ce qui conduit à un dysfonctionnement vasculaire. En outre, les ERO (produites notamment par la NADPH oxydase) participent soit directement, soit par le biais des lipoprotéines de basse densité oxydées, à la transduction du signal dans les cellules vasculaires. Elles sont ainsi impliquées dans les phénomènes d'apoptose, la prolifération des cellules musculaires lisses, l'adhésion des monocytes aux cellules endothéliales et l'agrégation plaquettaire. Des perspectives thérapeutiques visant par exemple à moduler la production radicalaire au niveau des cellules endothéliales pourraient être envisagées pour restaurer la fonction endothéliale. © 2002 É ditions scientifiques et médicales Elsevier SAS. Tous droits réservés.

Over the past 10 years, capillary electrophoresis (CE) is an analytical tool that has shown great promise in replacing many conventional clinical laboratory methods, especially electrophoresis and high performance liquid chromatography (HPLC). The main attraction of CE was that it was fast, used small amounts of sample and reagents, and was extremely versatile, being able to separate large and small analytes, both neutral and charged. Because of this versatility, numerous methods for clinically relevant analytes have been developed. However, with the exception of the molecular diagnostic and forensic laboratories CE has not had a major impact. A possible reason is that CE is still perceived as requiring above-average technical expertise, precluding its use in a laboratory workforce that is less technically adept. With the introduction of multicapillary instruments that are more automated, less technique-dependent, in addition to the availability of commercial and cost effective test kit methods, CE may yet be accepted as a instrument routinely used in the clinical laboratories. Thus, this review will focus on the areas where CE shows the most potential to have the greatest impact on the clinical laboratory. These include analysis of proteins found in serum, urine, CSF and body fluids, immunosubstraction electrophoresis, hemoglobin variants, lipoproteins, carbohydrate-deficient transferrin (CDT), forensic and therapeutic drug screening, and molecular diagnostics. D

Profiles of fatty acids in lipid classes of plasma and ultracentrifugally separated lipoproteins were analyzed by capillary gas chromatography. Contribution of individual steps of the whole procedure was calculated on the basis of the multiple analyses. GC contributes to the overall error by the smallest part. Contribution of the extraction, thin-layer chromatography separation and methylation processes might be comparable. The value of relative standard deviation is indirectly proportional to the amount of analyzed component. Comparison of FA profiles in lipid classes of very low density lipoproteins and low density lipoproteins revealed highly individual differences. Increased content of arachidonic and docosahexaenoic acids in triglycerides of low density lipoproteins are in agreement with formerly published results. Duplicate analyses are recommended for the evaluation of differences between FA composition in individual lipoproteins.