Disseminated xanthosiderohistiocytosis with cardiac involvement and monoclonal gammapathy

Xanthosiderohistiocytosis is a rare non-Langerhans histiocytosis (4 reported cases). The clinical characteristics include diffuse, sometimes deep, dark-brown infiltrations of the skin. Histological examination reveals abundant deposits of haemosiderin within the histiocyte proliferation. This entity is a clinical form of Montgomery's disease (xanthoma disseminatum) which has been reported in over 100 cases. Our case of disseminated xanthosiderohistiocytosis was particular because it involved the heart and was associated with a monoclonal gammapathy. Five cases have been reported associating xanthoma disseminatum and monoclonal gammapathy, including one case of xanthosiderohistiocytosis. In our case, rapidly increasing levels of monoclonal immunoglobulin suggested an evolution towards a myeloma. A monoclonal gammapathy should be looked for and monitored in cases of xanthosiderohistiocytosis, and more generally xanthoma disseminatum because of the risk of developing lymphoma or myeloma.     

Effect of intensive glycemic control on fibrinogen, lipids, and lipoproteins: Veterans Affairs Cooperative Study in Type II Diabetes Mellitus

BACKGROUND: The Veterans Affairs Cooperative Study in Type II Diabetes Mellitus prospectively studied insulin-treated patients with type 2 (non-insulin-dependent) diabetes mellitus, achieving 2.1% glycosylated hemoglobin separation between intensive- and standard-treatment arms (P<.001) for 2 years. OBJECTIVE: To assess the effect of intensive therapy on serum fibrinogen and lipid levels, compared with standard treatment. METHODS: One hundred fifty-three male subjects with type 2 diabetes mellitus and who required insulin treatment were recruited from 5 Veterans Affairs medical centers. The subjects were divided into intensive- and standard-treatment arms for a randomized prospective study. Dyslipidemia was managed identically in both arms (diet, drugs). Fibrinogen levels and lipid fractions were measured in the full cohort. Lipid fractions are separately reported in patients not treated with hypolipidemic agents. RESULTS: There were no baseline differences between arms. Fibrinogen levels rose in the intensive-treatment arm at 1 year (from 3.34+/-0.12 to 3.75+/-0.15 g/L; P<.001) but returned to baseline at 2 years (3.47+/-0.12 g/L). There was no change in the standard-treatment arm. Triglyceride levels decreased in the intensive-treatment arm from 2.25+/-0.27 to 1.54+/-0.14 mmol/L (199+/-24 to 136+/-12 mg/ dL) at 1 year (P = .004) and to 1.74+/-0.18 mmol/L (154+/-16 mg/dL) at 2 years (P = .03); there was no change in the standard-treatment arm. Cholesterol levels decreased in the intensive-treatment arm at 1 year from 5.4+/-0.21 to 4.99+/-0.13 mmol/L (207+/-8 to 193+/-5 mg/dL) (P = .02); there was no change in the standard-treatment arm. Levels of low- and high-density lipoprotein cholesterol decreased in the standard-treatment arm only by 2 years, from 3.44+/-0.13 to 3.16+/-0.10 mmol/L (133+/-5 to 122+/-4 mg/ dL) (P =.02) and from 1.10+/-0.03 to 1.00+/-0.03 mmol/L (42+/-1 to 38+/-1 mg/dL) (P<.001) for low-density and high-density lipoprotein cholesterol, respectively. Levels of apolipoprotein B decreased in both treatment arms (P<.001), and apolipoprotein A1 levels decreased in the standard-treatment arm (P<.01). Lipoprotein (a) levels did not change in either treatment arm. Lipid results were essentially identical whether examined in the full cohort or excluding those patients receiving hypolipidemic agents. CONCLUSIONS: Intensive insulin therapy led to a potentially beneficial reduction in serum triglyceride levels and preservation of high-density lipoprotein cholesterol and apolipoprotein A1 levels. However, it caused transient elevation in plasma fibrinogen levels, a possible thrombogenic effect.     

Fatty acid composition of plasma phosphatidylcholine and levels of lipids and lipoproteins in hyperlipoproteinemia. II. Relation with B lipoproteins

BACKGROUND: Epidemiological trials provided evidence that the cholesterol concentration in lipoproteins B, i.e. VDL, IDL and LDL, correlate significantly with the incidence of ischaemic heart disease (IHD). The objective of the present study was to assess how the fatty acid composition in plasma phosphatidyl choline affects the total and LDL cholesterol, triglyceride and apolipoprotein B concentrations in subjects with primary hyperlipoproteinaemia and dyslipidaemia. METHODS AND RESULTS: In a group of 142 subjects with primary hyperlipoproteinaemia and dyslipidaemia the concentrations of plasma lipids, lipoproteins apolipoproteins and fatty acids in plasma phosphatidyl choline (PC) were assessed. The authors provided evidence by discriminant analysis where the dependent variables were the lower quintiles (Q1 + Q2) and the upper quintiles (Q4 + Q5) of concentrations of total cholesterol, triglycerides, LDL-cholesterol and apolipoprotein B and the independent variables were FA concentrations in plasma PC, that the total cholesterol concentration was inversely associated with the concentration of docosahexaenic acid (22:6n-3). The concentration of LDL-cholesterol correlated inversely with the concentration of palmitoleic acid (16:1n-7). Triglyceridaemia was inversely associated with the linoleic acid concentration (18:2n-6). The concentration of apolipoprotein B correlated positively with myristic acid (14:0) and negatively with concentrations of oleic acid (18:1n-9) and linoleic acid (18:2n-6). CONCLUSIONS: The submitted results indicate that the fatty acid concentrations of PC in plasma are significantly and markedly correlated with concentrations of total cholesterol, triglycerides, LDL-cholesterol and apolipoprotein B. It is possible that atherogenic lipoproteins may be favourably influenced not only by the amount of fat but also by a suitable fatty acid composition.     

Apolipoprotein AI-CIII, B, and CII gene polymorphisms in patients with non-insulin dependent diabetes mellitus. Association with hyperlipemia

BACKGROUND: Dislipidaemia is an usual feature in patients affected by non insulin dependent diabetes mellitus. Several studies show that this disease could be genetically determined. The aim of this study was to ascertain whether any of the genetic polymorphism remaining in three apolipoprotein loci (apolipoprotein AI-CIII, B100 and CII) is related with the presence of dislipidaemia in non insulin dependent diabetes mellitus patients. PATIENTS AND METHODS: 53 non insulin dependent diabetes mellitus patients with less than 5 years evolution and treated only with diet, were included. 86 healthy persons were included as the control group. The lipidic parameters analyzed were: cholesterol, LDL cholesterol, HDL cholesterol, triglycerides, apolipoprotein AI, B and lipoprotein (a). The following polymorphic variants were analyzed: RFLP-Sacl of the apolipoprotein AI-CIII-AIV cluster, RFLP-Xbal of the apolipoprotein B100 region and the RFLP-Taql of the apolipoprotein E-CI-CII cluster. RESULTS: There were no genetic nor allelic differences in the distribution of the genes, between controls and diabetic patients. Regarding the apolipoprotein CII gen, the diabetic patients with the T2T2 genotype had higher triglyceride levels (p < 0.01) compared with the remaining genotypes and compared with the control group having the same genotype (p < 0.01) matched for sex, age and body mass index. There was no difference in the metabolic parameters' distribution related to the genotypic distribution of the apolipoproteins AI-CIII and B100 genes. CONCLUSIONS: The apolipoprotein CII can be related with the presence of hypertriglyceridaemia in non insulin dependent diabetes mellitus patients.     

Asymmetrical hemispheric activation and behavioral persistence: effects of unilateral muscle contractions

OBJECTIVE: To compare pubertal maturation, sex steroid hormones, and lipoproteins and their interrelationships in male offspring of parents with premature coronary heart disease (cases) and a control group. DESIGN: This was a cross-sectional comparison of cases and members of a control group 10 to 15 years of age. SUBJECTS AND METHODS: Offspring were recruited from patient lists of area physicians. Members of the control group were recruited from area schools. Body mass (kg/m2), serum lipids, lipoproteins, apolipoproteins, estradiol, and free testosterone were measured. RESULTS: Differences in age were not significant, but offspring were taller, heavier, and more mature. Offspring had higher total and low density lipoprotein cholesterol. Offspring had lower estradiol levels in early puberty but higher levels in late puberty. With family history and body mass in the regression models for lipid parameters, free testosterone was a significant explanatory factor for total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein, and estradiol was a significant predictor for apolipoprotein B. The percent of the variance in the lipid parameters explained by testosterone and estradiol was small. CONCLUSION: Sex hormone concentrations appear to be modest but significant predictors of lipoprotein and apolipoprotein concentrations in offspring and a control group in cross-sectional analysis. After controlling for pubertal maturation, hormone and lipid concentrations differed in offspring and the control group.     

Effect of increasing the plasma oxygen diffusivity on experimental cryogenic edema

Xanthelasma palpebrarum is the most common xanthoma and is associated with other xanthomas or hyperlipemia syndromes in only 5 percent of the patients--even though one third of the affected patients have an elevated serum cholesterol level. Surgical excision is simple, safe, leaves minimal scarring, and will be definitive in more than half of the patients being treated for the first time. Reexcision may still be worthwhile if the xanthelasma recurs. However, recurrence is to be anticipated if all 4 eyelids are involved, if there is an underlying hyperlipemia syndrome, or if there has been more than one previous recurrence.     

Alterations in lipoprotein metabolism in peroxisome proliferator-activated receptor alpha-deficient mice

The peroxisome proliferator-activated receptor-alpha (PPARalpha) controls gene expression in response to a diverse class of compounds collectively referred to as peroxisome proliferators. Whereas most known peroxisome proliferators are of exogenous origin and include hypolipidemic drugs and other industrial chemicals, several endogenous PPARalpha activators have been identified such as fatty acids and steroids. The latter finding and the fact that PPARalpha modulates target genes encoding enzymes involved in lipid metabolism suggest a role for PPARalpha in lipid metabolism. This was investigated in the PPARalpha-deficient mouse model. Basal levels of total serum cholesterol, high density lipoprotein cholesterol, hepatic apolipoprotein A-I mRNA, and serum apolipoprotein A-I in PPARalpha-deficient mice are significantly higher compared with wild-type controls. Treatment with the fibrate Wy 14,643 decreased apoA-I serum levels and hepatic mRNA levels in wild-type mice, whereas no effect was detected in the PPARalpha-deficient mice. Administration of the fibrate Wy 14,643 to wild-type mice results in marked depression of hepatic apolipoprotein C-III mRNA and serum triglycerides compared with untreated controls. In contrast, PPARalpha-deficient mice were unaffected by Wy 14,643 treatment. These studies demonstrate that PPARalpha modulates basal levels of serum cholesterol, in particular high density lipoprotein cholesterol, and establish that fibrate-induced modulation in hepatic apolipoprotein A-I, C-III mRNA, and serum triglycerides observed in wild-type mice is mediated by PPARalpha.     

Hyperhomocysteinemia. A risk factor for the development of vascular diseases not associated with lipid levels

BACKGROUND: Elevated total homocysteine plasma levels are considered a significant factor of vascular damage. As they are encountered in more than half the patients with atherosclerotic vascular damage the importance as a lipid-dependent or lipid-independent risk factor in the promotion of pathophysiological processes is discussed. METHODS AND RESULTS: In a group of 100 healthy subjects and 529 patients with indication for an aortocoronary or peripheral arterial bypass and in patients from the lipid clinic the mutual relation between total plasma homocysteine levels and selected indicators of the lipid metabolism was investigated. The following results more obtained: for total cholesterol a correlation coefficient of r = 0.26, for HDL-cholesterol r = 0.20, for LDL-cholesterol r = 0.21, for triacylglycerols r = 0.29, apolipoprotein A-I r = 0.06, apolipoprotein B r = -0.12 and for Lp(a) r = -0.03. To ensure correct evaluation of the homocysteine levels simultaneously also folate levels were examined (correlation coefficient r = 0.28), vitamin B12 r = (0.03) and fibrinogen r = (0.09). CONCLUSIONS: The authors did not detect an unequovical relationship between the total homocysteine level and selected lipid indicators in any of the patient groups (p < 0.05).     

Endoscopic projectile extraction in treatment of a gunshot injury to the head

HISTORY AND CLINICAL FINDINGS: A 14-year-old boy had in war-torn Bosnia sustained a transcranial gunshot wound from a 7.65 mm bullet. After primary medical care with craniotomy and the removal of bony fragments and cerebral debris followed by a duraplasty, he was transported to the French-German Field Hospital. On arrival he was breathing spontaneously and in stable cardiovascular state but with impaired responsiveness and somnolent. His pupils were moderately dilated with slight anisocoria (right > left). His gaze was deviated to the left and he had vertical gaze paralysis as well as right central facial nerve paresis. In addition he had a mild diencephalic syndrome, right hemiplegia and a right hemihypaesthesia with increased muscle tone, especially of the leg, paratonia and right positive Babinski reflex. There also was a marked ciliospinal reflex and he had a bulbar speech as well as cognitive and memory abnormalities. INVESTIGATIONS: Haemoglobin and haematocrit were below normal (12.1 g/dl and 35.0%, respectively), while biochemical tests were normal. Cranial computed tomography localized the bullet in the pineal recess of the 3rd ventricle and the lamina quadrigemina. DIAGNOSIS, TREATMENT AND COURSE: These findings indicated endoscopic transcranial removal of the bullet, achieved with a rigid endoscope and forceps along the entry track. Subsequent intensive care proceeded without complication. On discharge the boy was normal oriented and ready to make contact. The neurological defects were regressing. CONCLUSION: Endoscopic transcranial removal of a bullet wedged in the brain is a relatively sparing neurological procedure which, under unusual circumstances and conditions, can achieve a satisfactory result even with limited facilities.     

Retinoic acid enhances fibrinolytic activity in-vivo by enhancing tissue type plasminogen activator (t-PA) activity and inhibits venous thrombosis

BACKGROUND: Simvastatin and pravastatin are both competitive inhibitors of the rate limiting enzyme for cholesterol biosynthesis (HMG CoA) reductase, but data from individual clinical trials suggest significant differences in potency for cholesterol reduction between the two drugs. AIM: To assess any differences in efficacy and safety between simvastatin and pravastatin in a direct, comparative study. METHODS: A double-blind, double-dummy, randomised study design was used, involving 48 patients with primary hypercholesterolaemia. Following a 6 week placebo baseline period, patients were randomly allocated to treatment with either simvastatin or pravastatin, commencing at a dose of 10 mg daily. The dose levels were titrated up to the recommended maximum effective dose of 40 mg daily at 6 weekly intervals if LDL cholesterol levels remained > or = 3.4 mmol/L. After 18 weeks of therapy, all patients were transferred to simvastatin therapy for a further 6 weeks, continuing at their week 18 dose level. Patients complied with a standard lipid lowering diet (containing < 30% of energy as total fat) throughout the study period. RESULTS: Over the 18 week direct comparison of the two drugs, there was a significant difference (p < 0.001) in response between simvastatin and pravastatin for reduction in levels of total cholesterol (32% vs 21% respectively), LDL cholesterol (38% vs 27%) and apolipoprotein B levels (34% vs 23%). No significant difference in drug effect was seen for the small reduction in levels of apolipoprotein AI (5% vs 6% respectively), nor for the increased levels of apolipoprotein AII (14% vs 11%) and HDL cholesterol (11% vs 7%). Lp(a) levels remained unchanged. When pravastatin was replaced with simvastatin for the final 6 weeks of the study in the 23 patients initially randomised to pravastatin, there were further reductions (p < 0.01) in total and LDL cholesterol, and apolipoprotein B. These results establish the advantage of simvastatin over pravastatin in terms of efficacy, for the treatment of primary hypercholesterolaemia.     

Unravelling high density lipoprotein-apolipoprotein metabolism in human mutants and animal models

Apolipoprotein A-I plays an essential structural and functional role in HDL metabolism and apolipoprotein A-II has important effects on HDL metabolism and function. Kinetic studies in humans have established that variation in plasma HDL-cholesterol and apolipoprotein A-I concentrations is primarily determined by variation in the rate of apolipoprotein A-I catabolism. In contrast, plasma apolipoprotein A-II levels are primarily determined by the rate of apolipoprotein A-II production. Genetic factors play an important role in modulating the plasma levels of HDL-cholesterol and apolipoproteins A-I and A-II. Studies in humans have established that mutations in genes encoding enzymes that esterify cholesterol (lecithin : cholesterol acyltransferase), transfer cholesterol (cholesteryl ester transfer protein) and hydrolyze lipids (hepatic lipase, lipoprotein lipase) regulate HDL-cholesterol and apolipoprotein A-I levels by modifying the lipid content (and therefore the size) of HDL particles. Recent studies in transgenic and knockout animals have confirmed the key role of HDL lipid-modifying proteins in HDL, apolipoprotein A-I and apolipoprotein A-II metabolism and have expanded our understanding of the role of lipid modification in determining plasma concentrations of HDL-cholesterol and apolipoprotein A-I, as well as the potential functional roles of apolipoprotein A-II.     

Decreased postprandial high density lipoprotein cholesterol and apolipoproteins A-I and E in normolipidemic smoking men: relations with lipid transfer proteins and LCAT activities

We have previously reported that normolipidemic smokers are lipid intolerant due to increased responses of triglyceride-rich lipoproteins (TRL) apolipoprotein B-48, triglyceride (TG), and retinyl esters to a mixed meal compared to non-smokers. To investigate whether postprandial high density lipoprotein (HDL), apolipoprotein A-I (apoA-I), apolipoprotein A-II (apoA-II), and apolipoprotein E (apoE) concentrations or lipid transfer protein activities are affected by cigarette smoking, we investigated 12 male smokers and 12 non-smokers with comparable fasting lipoprotein profile, BMI, and age. Plasma samples obtained after an overnight fast and postprandially were separated by density gradient ultracentrifugation. Postprandial apoA-I, lipoprotein AI-particles (LpA-I), HDL-cholesterol, and HDL apoE concentrations decreased in smokers, but remained unchanged in controls. Concomitantly, cholesterol and apoE concentrations increased significantly in TRL fractions in smokers. Fasting lecithin:cholesterol acyltransferase (LCAT) and phospholipid transfer protein (PLTP) activity levels, as well as esterification rates (EST) and phospholipid transfer rates were comparable between the groups. Cholesteryl ester transfer protein (CETP) activity levels were lower in the smokers. Postprandially EST increased, but CETP and PLTP activities deceased in smokers as compared to controls. We conclude, that even healthy, normolipidemic smokers have altered postprandial high density lipoprotein (HDL) cholesterol and apolipoprotein composition, as well as lipid transfer protein activities. The shift of cholesterol and apoE from HDL to the triglyceride-rich lipoprotein (TRL) fraction, together with decreased plasma apoA-I and LpA-I concentrations during alimentary lipemia may indicate impaired reverse cholesterol transport. Both the postprandial increase in TRL and the lowering of HDL may promote atherogenesis in smokers.     

African American-white differences in lipids, lipoproteins, and apolipoproteins, by educational attainment, among middle-aged adults: the Atherosclerosis Risk in Communities Study

Measures of socioeconomic status have been shown to be related positively to levels of high density lipoprotein (HDL) cholesterol in white men and women and negatively in African American men. However, there is little information regarding the association between educational attainment and HDL fractions or apolipoproteins. The authors examined these associations in 9,407 white and 2,664 African American men and women aged 45-64 years who participated in the Atherosclerosis Risk in Communities Study baseline survey, and they found racial differences. A positive association for HDL cholesterol, its fractions HDL2 and HDL3 cholesterol, and its associated apolipoprotein A-I was found in white men and white women, but a negative association was found in African American men, and there was no association in African American women. In whites, there was also an inverse association of low density lipoprotein (LDL) cholesterol and apolipoprotein B with educational attainment. With the exception of African American men, advanced education was associated with a more favorable cardiovascular lipid profile, which was strongest in white women. Racial differences in total cholesterol (women only), plasma triglycerides, LDL cholesterol, apolipoprotein B (women only), HDL cholesterol, HDL2 and HDL3 cholesterol, and apolipoprotein A-I were reduced at higher levels of educational attainment. Apart from triglycerides in men and HDL3 cholesterol in women, these African American-white lipid differences associated with educational attainment remained statistically significant after multivariable adjustment for lifestyle factors. Lipoprotein(a) showed no association with educational attainment. These findings confirm African American-white differences in lipids, lipoproteins, and apolipoproteins across levels of educational attainment that were not explained by conventional nondietary lifestyle variables. Understanding these differences associated with educational attainment will assist in identifying measures aimed at prevention of cardiovascular disease.     

Cholestyramine and a fat-free diet lower apolipoprotein A-IV mRNA in jejunum and cholestyramine lowers apolipoprotein A-I mRNA in ileum of rats

To investigate the effect of bile acids or dietary lipid on the expression of intestinal apolipoproteins, the mRNA levels of apolipoprotein A-I and A-IV in the intestine from rats fed a diet containing cholestyramine or a fat-free diet were compared with those from rats fed a control diet containing 25% casein and 5% corn oil. Plasma total cholesterol concentration was lower after 16 h in rats fed a diet containing cholestyramine or a fat-free diet than in rats fed a control diet. In rats fed the fat-free diet, HDL cholesterol concentration also was lower than in those fed the control diet. The pool of bile acid in intestinal contents was significantly lower in rats fed cholestyramine than in both other groups. The relative abundance of jejunal apolipoprotein A-I mRNA did not differ between groups. Jejunal apolipoprotein A-IV mRNA abundance was significantly lower than in controls in rats fed the fat-free and cholestyramine-containing diets. Abundance of apolipoprotein A-I mRNA in ileal mucosa was comparable to controls in rats fed a fat-free diet but was significantly lower in rats fed cholestyramine. Ileal apolipoprotein A-IV mRNA tended to be lower in rats fed cholestyramine and a fat-free diet than in controls. We propose that decreased absorption of dietary lipid may modulate changes in jejunal apolipoprotein A-IV mRNA level and low levels of bile acids in the lumen may modulate changes in ileal apolipoprotein A-I mRNA level.     

Biological variability in serum vitamin E concentrations: relation to serum lipids

The components of biological variation in serum vitamin E in relation to serum cholesterol, triglycerides, high- and low-density lipoprotein cholesterol (HDL-C, LDL-C), apolipoprotein A-I (apo A-I), and apo B were examined in 26 healthy volunteers who had monthly blood samplings during one calendar year. The estimated CVs for vitamin E were: interindividual, 19.9%, and intraindividual, 11.9%; the index of individuality (I-index) was 0.59. The I-indices for all lipid variables were < 0.51. Serum concentrations of vitamin E, cholesterol, triglycerides, HDL-C, LDL-C, and apo B were lower in spring than in the other seasons. The peak-trough differences in the yearly variations, expressed as a percentage of the mean, were for vitamin E 14.5%, cholesterol 16.2%, triglycerides 14.5%, and LDL-C 24.3%. A significant common annual rhythm was expressed in vitamin E or lipid variables and in the changes in ambient temperature the weeks before blood sampling (inverse relations). There were highly significant positive time relations between serum vitamin E and cholesterol, triglycerides, and apo B. Subjects with higher homeostatic setpoints of cholesterol showed higher homeostatic setpoints of vitamin E, triglycerides, LDL-C, and apo B.     

The compositional abnormalities of lipoproteins in diabetic renal failure

BACKGROUND: Diabetic nephropathy (DN) is a common cause of chronic renal failure (CRF). Patients with DN have abnormal lipoprotein metabolism that can be influenced by both the impairment of renal function and the metabolic control of diabetes. The aim of the study was to explore the specific compositional lipoprotein abnormalities in patients with insulin-dependent DN in comparison with diabetic patients without nephropathy and non-diabetic CRF patients. METHODS: The lipid and apolipoprotein (apo) composition of major lipoprotein density classes was determined in 20 patients with insulin-dependent diabetes mellitus and nephropathy and compared with that in seven diabetic patients without nephropathy, 20 patients with non-diabetic CRF, and nine healthy control subjects. Lipoproteins isolated by preparative ultracentrifugation were very-low-density lipoproteins (VLDL), intermediate-density lipoproteins (IDL), low-density lipoproteins (LDL), and high-density lipoproteins (HDL). RESULTS: Patients with DN had a plasma lipid and apolipoprotein profile characteristic of renal dyslipoproteinaemia with increased concentrations of triglycerides and cholesterol, reduced levels of apoA-I and apoA-II and increased levels of apoB, apoC-II, apoC-III and apoE. These changes were more pronounced in diabetic than in non-diabetic patients with comparable degrees of renal failure. All density classes were characterized by abnormal concentration and composition of some lipid and apolipoprotein constituents. DN patients had a more than four-fold increase of VLDL mass, a three-fold increase of IDL mass, and a significant reduction of HDL mass compared to control subjects. They also had significantly higher concentrations of apoB, apoC-peptides and apoE particularly in VLDL and IDL, and to some extent in LDL. In HDL, DN patients had lower cholesterol, apoA-I, apoA-II and apoC-II levels than controls. The major compositional change in DN patients was a significant increase in the relative content of apoC-peptides in IDL and LDL. The lipoprotein abnormalities were more pronounced in patients with high HbA1c values. In addition, lower GFR and increased proteinuria were associated with higher concentrations of triglycerides and apoC peptides in VLDL, IDL, and LDL in DN patients. CONCLUSIONS: The results indicate that patients with DN share the characteristic features of dyslipidaemia of CRF with accumulation of intact or partially delipidized apoB-containing lipoproteins enriched in apoC-peptides and apoE, which are present not only in VLDL and IDL but also in LDL density range. The alterations are more marked in DN than in nondiabetic CRF patients reflecting the additional impact of metabolic control. Increased levels of these lipoproteins may represent risk factors for the accelerated development of atherosclerotic vascular disease in these patients.     

Helium-oxygen improves Clinical Asthma Scores in children with acute bronchiolitis

Sprague-Dawley rats (n = 32) were fed diets without fiber (control) or containing 1 or 5% chicory extract or 5% inulin for 4 wk; 0.2% cholesterol was added to all diets. Rats fed chicory extract and inulin diets had significantly higher serum high density lipoprotein (HDL) cholesterol and generally lower low density lipoprotein (LDL) cholesterol concentrations, thus significantly greater ratios of HDL/LDL cholesterol compared with the controls (P < 0.05). The serum apolipoprotein B/apolipoprotein A-1 ratio was significantly lower in rats fed diets containing chicory extract or inulin than that in rats fed fiber-free diets, due to significant reductions in apolipoprotein B concentration (P < 0.05). Greater liver lipid and triglyceride concentrations were observed in rats fed chicory extract or inulin diets compared with the controls (P < 0.05). However, liver phospholipid and cholesterol concentrations were not significantly different among groups (P > 0.05). Addition of 5% inulin to the diet resulted in greater cecal weight, whereas both 5% chicory extract and 5% inulin resulted in greater cecal propionic acid concentration compared with the controls (P < 0.05). Rats fed chicory extract and inulin had significantly greater fecal lipid, cholesterol and bile acid excretions than those fed fiber-free diets (P < 0.05). The results of this study suggest that the improved lipid metabolism observed in rats fed chicory extract (mainly inulin component) may be caused by an alteration in the absorption and/or synthesis of cholesterol, which might result from the changes in cecal fermentation, and by an increase in the fecal excretion of lipid, cholesterol and bile acid.     

The relationship between serum lipids, apolipoproteins level and bile lipids level, chemical type of stone

To pick up serum high risk lithogenic factors predisposing one to gallstone formation and protective factors against gallstone formation in gallbladder. We compared serum lipid and apolipoprotein level of patients with gallbladder stone (stone group) with that of patients without gallbladder stone (control group). The correlation between serum lipid, apolipoprotein level and bile lipid level, cholesterol saturated index (CSI), characteristics of lipidemia in different kinds of gallbladder stones were studied. The results showed that the increase of serum Apo A1, C2 and E level in the stone group was more significant than in the control group. But there was no statistical significance in TC, TG, LDL-C, HDL-C, Apo A2, B, C3 level between the stone and control groups. These results suggested that serum apolipoproteins perhaps are more sensitive parameters than serum lipids in distinguishing patients with stones from those without stones. There were different profiles of serum lipid and apolipoproteins in different chemical types of gallbladder stones. Increased level in serum LDL-C, Apo B and ratio of LDL-C/HDL-C were characterized by an index for cholesterol stone, otherwise that in serum TG and Apo C2 an index for pigment stones. There was a positive correlation between serum total cholesterol (TC) or Apo B, C2, C3 and cholesterol amount or CSI in gallbladder bile. Therefore, TC, Apo B, C2, C3 could be considered as high risk lithogenic factors. A positive correlation existed between serum HDL-C and lecithin in gallbladder or common bile duct (CBD) bile as well as between HDL-C and bile acids in CBD bile. Thus, HDL-C might be a protective factor against gallstone formation in gallbladder.     

Systemic vasculitis: classification and serologic diagnosis

Cardiovascular morbidity and mortality in hemodialyzed patients are increased due to the frequently abnormal lipid metabolism. It has been reported that this abnormal lipid metabolism could be partially corrected by some highly permeable membranes, such as polysulfone or cellulose triacetate. We investigated the influence of 4 months of dialysis with a polyamide membrane upon the course of lipid parameters in 6 patients presenting a hypertriglyceridemia > 2 mmol/l while on bicarbonate dialysis with a cellulose membrane. Lipid parameters improved after 4 months of hemodialysis with a polyamide membrane. Serum triglyceride and cholesterol levels decreased, while HDL cholesterol and HDL levels rose significantly (p < 0.05). Apolipoprotein B decreased significantly (p < 0.05). Following heparin administration, lipoprotein lipase activity improved (p < 0.02), associated with a decrease apolipoprotein C3 (p < 0.05). The fractional clearance rate of triglycerides rose significantly (p < 0.01). The use of highly permeable polyamide membranes results in a significant improvement in lipid disturbances of dialysis patients due to an increased lipoprotein lipase activity, induced perhaps by the removal of circulating inhibitors such as apolipoprotein C3.     

Surface composition regulates clearance from plasma and triolein lipolysis of lipid emulsions

Sphingomyelin (SM) and cholesterol (Chol) are major surface lipid constituents of plasma lipoproteins. We investigated the effects of SM and Chol on the plasma clearance of lipid emulsions as a model for lipoprotein particles in rats. The presence of Chol facilitated the removal of emulsion particles from plasma, whereas SM delayed particle removal. Preinjection of lactoferrin, an inhibitor of the apolipoprotein E (apoE) receptor, revealed that the differences in clearance of emulsions were due to the differences in affinity for the apoE receptor. Measurement of apolipoprotein binding suggested that the balance of apoE and apoC (apoC-II and apoC-III) bound to emulsions caused the difference in plasma clearance of emulsion particles. That is to say, SM in the emulsion surface decreased binding of apoE, which led to a longer circulation of emulsion particles in plasma. Chol, on the other hand, decreased the ratio of apoC to apoE, which may have promoted emulsion uptake through the apoE receptor. We also examined in vitro lipolysis using immobilized lipoprotein lipase (LPL) in a heparin affinity column. Lipolysis rates were significantly reduced by the incorporation of SM into the emulsion surface, but not by the incorporation of Chol, indicating that SM in the lipoprotein surface is an important lipid component regulating LPL-mediated lipolysis. Our results suggest that the presence of SM and Chol in the lipoprotein surface plays an important role in the circulation behavior and LPL-mediated lipolysis of lipid emulsions through their effect on the selectivity of plasma protein binding.