Lipid storage disease: Part I. Ultrastructure of xanthoma cells in various xanthomatous diseases

The fundamental ultrastructure of lipid storage in the xanthoma cells of various xanthomatous diseases, including familial hyperlipoproteinemia type IIa, III, and V, cerebrotendinous xanthomatosis, Wolman's disease, Tangier disease, Hand-Schüller-Christian disease, and normolipidemic cutaneous xanthomatosis, revealed lipid vacuoles, either membrane-bound or with no single unit membrane, cholesterol crystals, multivesicular or multilocular lipid bodies, myelin-like bodies, and ceroid granules (residual bodies). According to the presence or absence of such a single unit membrane and enzyme cytochemical demonstration of acid phosphatase activity, these lipid storage inclusions were largely classified into lysosomal and non-lysosomal ones; the former included membrane-bound lipid vacuoles, cholesterol crystals, multivesicular or multilocular lipid bodies, myelin-like bodies, and ceroid granules and the latter was lipid vacuoles with no limiting membrane. The ultrastructural relationship on formation of these lysosomal and non-lysosomal lipid storage inclusions and pathogenesis of the lipid storage in the xanthoma cells of the disorders were presented. As for the origin of the xanthoma cells, the majority of them were considered to be derived from macrophages in many of the disease; however, transformation of fibroblasts into xanthoma cells was confirmed in xanthomatous diseases, such as Hand-Schüller-Christian disease.     

Acute myelomonocytic leukaemia presenting as xanthomatous skin eruption

A case of acute myelomonocytic leukaemia (AMMOL) is reported in which skin infiltration with xanthomatous nodules was the presenting feature. The histological, including ultrastructural, appearances are described.     

Lipid metabolism in cholelithiasis

The results of studies of the blood and bile lipid metabolism in normal subjects and cholelithiasis patients and the findings of guinea pig experiments indicate that lipid levels decrease with age. The time course of the blood and bile lipids and the relationship thereof reflect the depression of cholesterol hydroxylation processes and reduction with age of cholic and deoxycholic acids synthesis and conjugation intensities in the patients with cholelithiasis, as well as a reduction of deoxycholic acid synthesis in normal subjects.     

实验性高胆固醇血症家兔血液流变性改变在微循环障碍中的作用

本文利用实验性高胆固醇血症家兔模型,研究了微循环灌流和血液流变性改变间关系。结果表明,微循环流量、流态、流速,微血管形态有明显改变,而这些变化与血清中胆固醇浓度,血浆粘度,全血粘度,红细胞聚集性及红细胞变形有着明显相关性。血液流变性变化构成此模型微循环障碍的基础。     

Antiatherosclerotic effects of antioxidants are lesion-specific when evaluated in hypercholesterolemic New Zealand white rabbits.

Oxidative modification of LDL may represent an initiating event in the formation of monocyte-macrophage foam cells, a major cell present in fatty streaks and atherosclerotic fibrous plaques. Therefore, we studied the effect of such antioxidants as probucol (500 mg/kg) and vitamins E and C (500 mg/kg each) on the regression of induced iliac-femoral lesions and progression of naturally occurring thoracic aortic fatty streak lesions in hypercholesterolemic New Zealand White rabbits. Following an initial 9-week lesion induction phase, both therapies were evaluated for 8 weeks. Probucol lowered plasma cholesterol 47% while vitamins E and C had no effect on plasma cholesterol. Probucol decreased the cholesteryl ester (CE) content of the thoracic aorta by 31% without changing the thoracic aortic lesion coverage. Vitamins E and C decreased thoracic aortic CE content by 40% and lesion coverage by 46%. Neither probucol nor vitamins E and C altered the CE content, lesion size, or macrophage/lesion ratio of the iliac-femoral artery. Thus, we conclude that the effects of antioxidants are specific to the stage of atherosclerotic lesion development. Antioxidant therapy alters the progression and cholesteryl ester enrichment of diet-induced thoracic aortic fatty streaks but has no effect on the progression and/or regression of more complicated injury-induced iliac-femoral lesions.     

蒲黄对家兔实验性高胆固醇血症血液流变性的影响

心脑血管病是中老年人最常见的病症,而血脂的升高是其主要危害因素之一。本文用血液流变学的方法,观察蒲黄对实验性高胆固醇血症家兔的影响,以期在分子水平及细胞水平上探讨蒲黄对高胆固醇血症的作用。结果表明,蒲黄具有降低血清胆固醇浓度和降低红细胞膜胆固醇与磷脂克分子比值(ch/pl),从而改善红细胞膜流动性、增大红细胞变形性、降低全血粘度及血浆粘度的作用。由此可见,蒲黄可望成为降血脂及活血的良药。     

Lipid metabolism in anaerobic ecosystems

In anaerobic ecosystems, acyl lipids are initially hydrolyzed by microbial lipases with the release of free fatty acids. Glycerol, galactose, choline, and other non-fatty acid components released during hydrolysis are fermented to volatile fatty acids by the fermentative bacteria. Fatty acids are not degraded further in the rumen or other parts of the digestive tract but are subjected to extensive biohydrogenation especially in the rumen. However, in environments such as sediments and waste digestors, which have long retention times, both long and short chain fatty acids are beta-oxidized to acetate by a special group of bacteria, the H2-producing syntrophs. Long chain fatty acids can also be degraded by alpha-oxidation. Biotransformation of bile acids, cholesterol, and steroids by intestinal microorganisms is extensive. Many rumen bacteria have specific growth requirements for fatty acids such as n-valeric, iso-valeric, 2-methylbutyric, and iso-butyric acids. Some species have requirements for C13 to C18 straight-chain saturated or monoenoic fatty acids for growth.     

Genistein supplementation inhibits atherosclerosis with stabilization of the lesions in hypercholesterolemic rabbits

The effect of genistein on aortic atherosclerosis was studied by immunohistochemistry with RAM-11 and HHF-35 antibodies and western blotting for matrix metalloproteinase-3 (MMP-3) in New Zealand White rabbits. After provocation of atherosclerosis with hyperlipidemic diet, the rabbits were divided as hyperlipidemic diet group (HD), normal diet group (ND) and hyperlipidemic plus genistein diet group (HD+genistein) for 4 and half months. The average cross sectional area of atherosclerotic lesion was 0.269 mm2 after provocation. The lesion was progressed by continuous hyperlipidemic diet (10.06 mm2) but was increased mildly by genistein (0.997 mm2), and decreased by normal diet (0.228 mm2). The ratio of macrophages to smooth muscle cells in the lesion was not changed by genistein supplementation. The western blotting showed reduction of MMP-3 expression in HD+genistein and ND groups than HD group. The inhibition of atherogenesis by genistein was might be due to improve the endothelial dysfunction rather than direct action on macrophages and/or smooth muscle cells in the lesion, since endothelial dysfunction by lipid peroxidation was the main atherogenic factor in the hypercholesterolemic rabbits. The genistein supplementation also suggests that it helps the stabilization of the atherosclerotic lesion by inhibition of MMP-3 expression.     

l-Arginine supplementation enhances eNOS expression in experimental model of hypercholesterolemic rabbits aorta

Introduction: Diminished bioavailability of nitric oxide is crucial in endothelial dysfunction and the development of atherosclerosis. Several studies have found that l-arginine as a nitric oxide (NO) donor has beneficial effect in prevention of atherosclerosis, but the mechanism is not completely known. We hypothesized that increased endothelial nitric oxide synthase (eNOS) and/or decreased inducible NOS (iNOS) expressions might be involved in the preventive effects of l-arginine in hypercholesterolemic rabbits. Methods: Seventeen male rabbits were divided randomly in two groups. They received rabbits chow supplemented with 1% cholesterol (group 1, n = 8) and the other group received also l-arginine (3% in drinking water) (group 2, n = 9) for 1 month. Blood samples were obtained before and after the experiment. At the end of experiment, the aortas were harvested. The serum levels of cholesterol and low-density lipoproteins (LDL) were measured. The intima/media thickness (IMT) ratio was measured and the determination of fatty streak formation was done with the aid of light microscopy. eNOS and iNOS expression in aorta were studied with immuohistochemistery. Results: The IMT ratio in first group having fatty streaks was 0.287 ± 0.15. No fatty streak lesion was detected in l-arginine-treated group. The results also indicated that eNOS expression (intensity) in aortas was significantly higher in l-arginine-treated group (group 1: 13.62 ± 2.7 and group 2: 21.77 ± 2.8; p < 0.05), but no significant difference was observed for iNOS expression between the groups. Conclusion: The expression of eNOS plays an important role in the protection of the vessel wall from atherosclerosis. l-Arginine in drinking water has a beneficial effect in the enhancement of eNOS protein expression.     

Effects of lipid peroxides on prostacyclin and thromboxane generation in hypercholesterolemic rabbits

Rabbits fed an atherogenic diet for 60 days resulted in high levels of plasma lipid peroxides as well as extreme hypercholesterolemia. Both levels stayed high until 35 days after the atherogenic diet stopped. At the same time, plasma PGI2 level was remarkably decreased while TXA2 and platelet aggregability were increased. Atherosclerotic aortas contain high levels of lipid peroxides associated with decreased PGI2 and increased TXA2 generation. Atherosclerotic plaques had the highest level of lipid peroxides and TXA2 while PGI2 production was the least, as compared with nonplaque tissue of the same artery and the normal arteries. The condition of normal arteries was just the reverse. There was a negative correlation between lipid peroxides and prostacyclin production, and a positive correlation between lipid peroxides and TXA2, in both plasma and aorta of rabbits. These results suggest that there is a close correlation between atherosclerosis, elevated lipid peroxides, and disturbances in PGI2/TXA2 balances.     

Effect of early feed restriction in broilers. II. Lipid metabolism

Three experiments were conducted with broiler chicks to evaluate the effect of dietary energy restrictions on in vitro lipid metabolism. In Experiment 1, chicks were restricted from either 6 to 12 or 6 to 18 days of age and then fed ad libitum until day 27. In Experiment 2, both male and female chicks were restricted from 5 to 11 days of age and then were refed until 27 or 54 days of age. Glutamic:oxaloacetic aminotransferase (GOT), isocitrate dehydrogenase (ICD), malic enzyme (ME) and the fatty acid synthetase complex (FAS) were assayed at 27 days (Experiment 1) and at 27 and 54 days (Experiment 2). In Experiment 3, male chicks were restricted from days 6 to 12 and then were refed until day 27. In vitro lipogenesis and enzyme activities were determined during the 12 to 18-day period as the chicks were refed following the restriction. Both restriction regimes decreased (P less than .05) ME and FAS at the conclusion of the respective restriction intervals (Experiments 1 & 2). The 6 to 12-day restriction decreased (P less than .05) in vitro lipogenesis in the 12 day old chick when compared to controls. When restricted chicks were refed, in vitro lipogenesis exceeded that of the controls at both 14 and 16 days, but was less than that of the controls at 27 days.     

Lipid metabolism and aging

Lipids have important biochemical functions, but their excess in plasma is a risk factor for atherosclerotic disease. After puberty, the plasma total and low-density lipoprotein (LDL) cholesterol concentrations increase with age as a consequence of an increase in production and a decrease in catabolism mediated by LDL receptors. On the other hand, the plasma high-density lipoprotein (HDL) cholesterol concentrations remain constant. The correlation between serum cholesterol and coronary risk becomes weak with age but also exists in the elderly, while low levels of HDL cholesterol remain to be a risk. The rise in serum triglycerides with age results mainly from the increase in body weight and the decrease in physical activity. Dietary polyunsaturated fatty acids (PUFAs) such as linoleic acid protect against progression of atherosclerosis in part by their hypocholesterolemic effect. The proportion of linoleic acid in serum phospholipids decreases with age. This change also is a separate risk factor for cardiac and cerebral infarction. Among many prostanoids, prostaglandin I2 has antiaggregatory and vasodilatory effects and thromboxane A2 has the opposite effects. Lipid peroxides which are produced inevitably from PUFAs may damage biomembranes and might accelerate cellular aging. The questions of whether dietary manipulation can reduce the age-related changes in lipid metabolism and can improve cellular functions are of major importance.     

Lipid metabolism during exercise

Summary Seven physically fit (well-trained, maximal oxygen uptake 69.6±4.4 ml×kg^–1×min^–1) and eight less fit (moderately trained, maximal oxygen uptake 56.1±5.7 ml×kg^–1×min^–1) healthy male subjects were exercised for 4 h by bicycle ergometry against a pedalling resistance calculated to cause oxygen consumption corresponding to approximately 30% of each individual's maximal oxygen uptake value. Respiratory exchange ratio was estimated at 1 h and blood glucose and lactate concentrations and muscle glycogen content at 2 h intervals. Muscle glycogen content decreased markedly during the first 2 h of exercise in the well-trained group but was similar after 4 h exercise in both groups. No major differences were observed between the two subject groups in blood variable concentrations. Calculations based on respiratory exchange ratio showed that the proportion of carbohydrates utilized in the total energy consumption was 14% in the physically fit group and 25% in the less fit group, thus supporting previous observations that more energy is derived by fat oxidation in well-trained than in less-trained individuals during submaximal work at relatively similar oxygen consumption levels.This study was supported by grant no. 9791/79/73 from the Research Council for Physical Education and Sports (Ministry of Education, Finland)It is deeply regretted that our honoured friend and mentor, Professor Esko Karvinen, PhD, MD, died during the preparation of this paper     

Lipid spectrum of the skin in psoriasis

Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 116, N ^o 9, pp. 271–272, September, 1993     

Lipid A dependence of the ocular response to circulating endotoxin in rabbits.

The effects of bacterial lipopolysaccharides on ocular vascular permeability were measured after their intravenous injection in rabbits. Alterations in ocular vascular permeability were quantitated by the accumulation of 125I-labeled albumin in the enucleated eye compared with that in heart blood (ocular albumin space). Two lipopolysaccharides extracted from Escherichia coli O111:B4, one with high lipid A content and one with high polysaccharide content, were tested initially, and the one with greater lipid A was 200 times more effective in producing an alteration in ocular vascular permeability. Lipopolysaccharide from a rough strain, Salmonella minnesota (R595), containing lipid A primarily, as well as a purified lipid A extracted from +595, were also effective. But an extract of the protein associated with lipid A was without significant effect. In vitro pretreatment of the lipopolysaccharides with polymyxin B, an inhibitor of the biological activity of lipid A through direct binding, could abrogate the ocular response. These results indicate the paramount importance of the lipid A moiety in the ocular response to circulating endotoxin.