Sea-blue or ceroid histiocytosis is a storage phenomena associated with a variety of conditions especially abnormal lipid metabolism and particularly hyperlipoproteinemia. It is characterized by histiocytic proliferation in the bone marrow and spleen, contain-ing sea-blue inclusions by Romanovsky stain. The present case is a 1 1/2 year-old Korean boy who had marked enlargement of the spleen which was eventually removed. Aspirates of the bone marrow and histology of the spleen disclosed an enormous proliferation of histiocytes containing numerous cytoplasmic inclusions which stained sea-blue with Wright stain, was strongly positive to PAS and weakly positive to oil red-O and Sudan black B in frozen and in paraffin embedded section. Ultrastructually histiocytes were marked1y hypertrophic and contained numerous cytoplasmic inclusions which showed three distinct types and conglomeration of all three types, presumably representing age or maturation steps of the inclusions. The ear1y type consisted of a high electron dense core or deposits within a low electron dense matrix, evolving into homogeneous moderately electron dense inclusion and finally a well developed finger print-like internal structure. Analysis of the plasma lipid disclosed type IIb hyperlipoproteinemia. Types of hyperlipoproteinemia previously reported in association with sea-blue histiocytosis were type-I, III, IV and V, and this is the first case of type IIb hyperlipoproteinemia.
Child, Preschool ; Human ; Hypercholesterolemia, Familial/complications* ; Hypercholesterolemia, Familial/pathology ; Male ; Sea-Blue Histiocyte Syndrome/complications* ; Sea-Blue Histiocyte Syndrome/pathology ; Spleen/pathology

Atherosclerosis is the most severe problem in the high-pressure systemic circulation and similar changes also occur in the high-pressure loading valve. This study was designed to test the hypothesis that early atherosclerosis, induced by a high cholesterol diet in rabbits, is characterized by significant ultrastructural change in the elastic laminae of the aortic valve. However, it is not known whether this process is also taking place in the cardiac valve at the early stage of atherosclerosis. Animals were fed either a high cholesterol diet (n = 5) or a control diet (n = 5) for 10-12 weeks. Histologic analysis demonstrated that subendothelial thickening and foam-cell infiltration were evident in the arterialis of aortic valves. Confocal microscopy revealed an altered pattern characterized by fragmentation and disorganization of the arterialis elastic laminae of hypercholesterolemic valves. Computerized digital analysis of the images obtained by confocal scanning microscopy demonstrated that compared to normal valves, the arterialis elastic laminae of hypercholesterolemic valves decreased in percentage of their elastin content (29.03 +/- 1.10% vs. 42.94 +/- 1.35%, p = 0.023). Immunohistochemical staining for matrix metalloproteinase-3 (MMP-3) revealed MMP-3 immunoreactivity was increased in hypercholesterolemic valves, predominantly in the arterialis. This study demonstrated that early atherosclerosis, induced by a high cholesterol diet in rabbits, is characterized by significant ultrastructural change in the elastic laminae of the aortic valve. The arterialis endothelium of the aortic valve may be a more atherosclerosis-prone area compared with the ventricularis. The presence of ultrastructural defect in the elastic laminae may play a role in chronic degenerative change and a resultant valvular dysfunction.
Animal ; Aortic Valve/ultrastructure* ; Elastic Tissue/ultrastructure* ; Hypercholesterolemia/pathology* ; Male ; Microscopy, Confocal ; Rabbits ; Stromelysin 1/metabolism

The external elastic lamina (EEL) serves as a barrier for cells and macromolecules between the media and adventitia in the vascular wall. We evaluated the morphological changes and quantitative assessments of the EEL architecture in the coronary circulation of pigs fed with a high cholesterol diet. Confocal microscopy analysis of the EEL from hypercholesterolemic coronary arteries revealed an altered pattern characterized by fragmentation and disorganization of the EEL associated with an increase in the thickness. Computerized digital analysis of the images obtained by confocal scanning microscopy demonstrated that compared to normal coronary arteries, the EEL of hypercholesterolemic coronary arteries decreased in the percentage of their elastin content (30.80 +/- 1.64% vs. 47.85 +/- 1.82%, p = 0.001). The percentage of elastin content was negatively correlated with the vessel wall area (r = -0.82, p = 0.001). The immunoreactivity for matrix metalloproteinase-3 (MMP-3) increased in cholesterol-fed coronary arteries, predominantly in the neointima and adventitia. This study demonstrates that experimental hypercholesterolemia induced ultrastructural changes of the EEL in coronary circulation. The EEL may also be an atherosclerosis-prone area compared with the intima. The EEL may play an important role in the development of structural changes which characterizes the early phase of coronary atherosclerosis and vascular remodeling.
Animal ; Arteries/ultrastructure ; Arteries/enzymology ; Coronary Vessels/ultrastructure* ; Coronary Vessels/enzymology ; Elastic Tissue/ultrastructure* ; Elastic Tissue/enzymology ; Female ; Hypercholesterolemia/pathology* ; Hypercholesterolemia/enzymology ; Stromelysin 1/metabolism ; Swine

OBJECTIVETo determine the effect of hypercholsterolemia induced by a high-lipid diet on glomerulosclerosis.

METHODSTwenty nephrotic syndrome (NS) Wistar rats administrated adriamycin (ADR) with a single intravenous dose of 5 mg/kg body weight, were divided into the standard and high-lipid chow groups. Another 20 weight-matched non-NS rats that received a vehicle alone were grouped as control. Urinary protein excretion and serum cholesterol were assayed; image analysis and techniques of pathology, immunohistochemistry, and molecular biology were used to determine morphological changes in glomeruli and the production of glomerular mesangial matrices in different groups.

RESULTSThe serum total cholesterol level was significantly higher in rats with high-lipid chow in both non-NS [(2.2 +/- 0.3) g/L vs. (0.9 +/- 0.1) g/L, P < 0.01] and NS [(9.5 +/- 0.2) g/L vs. (2.3 +/- 0.3) g/L, P < 0.01]. The urinary protein excretion was significantly higher in the high-lipid diet rats than in standard chow rats [(76.2 +/- 24.2) mg/24h vs. (44.8 +/- 13.6) mg/24h, P < 0.05] in NS rats. Although increases in the mesangial matrix and mesangial cells were observed in rats with high-lipid diet in both NS and non-NS group, more obvious pathological changes were found in NS group, such as lipid deposits and foam cell formation in mesangial areas, and progressing to focal and segmental glomerulosclerosis in some glomeruli. The immunohistochemical asay showed that the production of 3 major components (collagen IV, fibronectin, and laminin) was increased in NS group, especially in the rats with high-lipid chow. The increased expression of laminin mRNA was also detected with slot blotting in both NS and non-NS rats with high-lipid chow, and it was more obvious in the rats with NS.

CONCLUSIONOur findings indicated that diet-induced hyperlipidemia can lead to over-production of mesangial matrix components, and further aggravate glomerulosclerosis in ADR-induced nephrosis.

Animals ; Dietary Fats ; pharmacology ; Doxorubicin ; Fibronectins ; metabolism ; Glomerular Mesangium ; metabolism ; pathology ; Hypercholesterolemia ; metabolism ; Laminin ; metabolism ; Male ; Nephrotic Syndrome ; chemically induced ; metabolism ; pathology ; Proteinuria ; urine ; Rats ; Rats, Wistar

OBJECTIVETo study the effect of Lycium ruthenicum anthocyanins on atherosclerosis (AS) in mice.

METHODNormal mice were taken as the control group, and hyperlipemia mice were divided into the model group, Lycium ruthenicum anthocyanins low, medium and high dose groups, and the simvastatin drug control group. After the oral administration, blood lipid indicators were detected by enzymatic analysis. The histomorphological changes in aortas, hearts and livers were observed, and liver-related indicators were determined by using hematoxylin-eosin (HE) staining.

RESULTCompared with the high-fat group, L. ruthenicum anthocyanins low, medium and high dose groups showed significant decrease in total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and atherosclerotic index (AI) (P < 0.05). However, high-density lipoprotein cholesterol (HDL-C) level showed a trend of higher than the model group. Liver's total antioxidant capacity (T-AOC), Glutathione peroxidase (GSH-PX), lipoprotein lipase (LPL) were significantly increased (P < 0.05), malondialdehyde (MDA) was markedly decreased (P < 0.01); the percentage of aortic plaque area of each anthocyanins dose group in the total area was significantly lower than the model group (P < 0.05); severity of aorta, heart and liver were significantly lighter than the high-fat group. But the media dose group was similar with the simvastatin group.

CONCLUSIONL. ruthenicum anthocyanins can interfere the formation of AS, while lowering blood lipid levels in mice.

Animals ; Anthocyanins ; therapeutic use ; Atherosclerosis ; prevention & control ; Body Weight ; drug effects ; Glutathione Peroxidase ; metabolism ; Hypercholesterolemia ; blood ; drug therapy ; pathology ; Lipids ; blood ; Liver ; pathology ; Lycium ; chemistry ; Male ; Mice ; Phytotherapy

Lipid-lowering and antioxidant activities of a hydroalcoholic extract of Cyperus scariosus Linn. root (HCS) were evaluated in guinea pigs fed with a high cholesterol diet. Serum lipid profile (total cholesterol, triglycerides, LDL-C, VLDL-C, and HDL-C), atherogenic indices and serum enzymes (ALT, AST, ALP, LDH, and CK-MB) were performed in each group at 0 days and at the end of 60 days. Histological study of liver and kidney was done in groups 1, 2, 5, 6 and 7. The total phenolic and flavonoid content in HCS and its antioxidant activity were evaluated by the DPPH assay. Both doses of HCS decreased serum lipid profile and atherogenic indices (P < 0.05). HCS has lipid lowering, immunosuppressive and antioxidant properties, and mays have value in atherosclerosis prevention. The higher dose of HCS also reduced serum AST, ALP, and LDH levels and rosuvastatin increased AST and ALP levels (P < 0.05). Histology of the liver showed decreased lipid accumulation and improvement in hepatocytes in HCS-treated animals. The antioxidant activity of HCS may be responsible for its lipid lowering and cytoprotective action. HCS had significant lipid lowering and antioxidant activity, which; may be due to the phenolic compounds. HCS may be a safe and cost effective alternative to current statin therapy for patients with dyslipidaemia.
Animals ; Cyperus ; Female ; Guinea Pigs ; Hypercholesterolemia ; drug therapy ; Hypolipidemic Agents ; pharmacology ; therapeutic use ; Kidney ; pathology ; Liver ; pathology ; Male ; Mice ; Plant Extracts ; pharmacology ; therapeutic use ; Plant Roots ; chemistry

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 hypercholesterolemicrabbits. The genistein supplementation also suggests that it helps the stabilization of the atherosclerotic lesion by inhibition of MMP-3 expression.
Animals ; Aorta/pathology ; Arteriosclerosis/*drug therapy/pathology/*prevention & control ; Blotting, Western ; Diet, Atherogenic ; Genistein/*pharmacology ; Growth Inhibitors/*pharmacology ; Hypercholesterolemia/*drug therapy/pathology ; Macrophages/pathology ; Male ; Muscle, Smooth, Vascular/enzymology/pathology ; Rabbits ; Research Support, Non-U.S. Gov't ; Stromelysin 1/metabolism

AIMTo explore the prevention of atherosclerosis by PPARy agonist rosiglitazone.

METHODS24 male New Zealand white rabbits weighing 1.8 to 2.2 kg were randomly divided into 3 groups: control group, normal rabbit chow; cholesterol group, 1% cholesterol diet; rosiglitazone group, 1% cholesterol diet supplemented with rosiglitazone 0.5 mg x kg(-1) x d(-1) for 6 weeks. Rabbits in cholesterol group and rosiglitazone group were sequentially fed 1% cholesterol-containing diet for 16 weeks. At the end of the experiment, blood glucose, serum lipids levels, ratio of plaque area to aorta area and ratio of intima to media were determined.

RESULTSHypercholesterolemia was successfully reproduced in rabbits. Adnimistration of rosiglitazone significantly decreased serum TC and LDL-C. The ratio of intima to media and ratio of plaque area to aorta area were also reduced.

CONCLUSIONRosiglitazone could prevent atherosclerosis by decreasing levels of TC and LDL-C.

Animals ; Aorta ; pathology ; Atherosclerosis ; blood ; etiology ; pathology ; Cholesterol ; blood ; Cholesterol, Dietary ; Cholesterol, LDL ; blood ; Fibrinolytic Agents ; pharmacology ; Hypercholesterolemia ; blood ; etiology ; pathology ; Male ; PPAR gamma ; agonists ; Rabbits ; Random Allocation ; Thiazolidinediones ; pharmacology ; Tunica Intima ; pathology

Background and purpose : Striatocapsular infarction (SCI) has recently been described as a distinct type of stroke and forms an Important subgroup of sub-cortical infarction. The aims of this study were to define the clinical profile, pathogenesis and radiological features of the SCI. METHODS: Based on computed tomographic (CT) and magnetic resonance (MR) findings, 24 patients with SCI were selected from among 599 patients admitted consecutively to our Institute from January, 1993 to June, 1995 and reviewed with attention to clinical characteristics and radiological findings retrospectively. SCI defined as the following CT and MR imaging criteria :the area of infarction included the internal capsule and striatum, the maximum diameter of the lesion exceeded 20mm without cortical involvement Results : The study population consisted of 12 men and 12 women, aged 33 to 80 years. The most common clinical presentation was a stuttering progression of the motor weakness, sensory change and accompanying cortical dysfunction. Eight patients presented with a lacunar syndrome(3:pure motor syndrome and 5:sensory motor syndrome). The 13 patients had the sign of cortical dysfunction. Only one patients experienced TIA in ipsilateral carotid territory. Risk factors for atherosclerosis were hypertension in 10 (42%) patients, diabetes in 4(17%), smoking in 9(41%), and hypercholesterolemia in 2(8%). The presumed mechanism of stroke was large artery thrombosis in 15 (63%) patients (13 MCA, 4 ICA) :definite cardioembolism in 6(25%), (arterial fibrillation in 5, myocardial infarction in 2) : embolic infarction with tandem arterial pathology in1 : Moyamoya disease in 1 : undetermined cause in 1. Conclusions : We conclude that, SCI occurs mostly due to occlusive disease of cerebral large vessel and not due to a disseminated in situ occlusion of the long penetrating arteries as in lacunas. It is important because the different pathological mechanisms demand different therapeutic strategies.
Arteries ; Atherosclerosis ; Female ; Humans ; Hypercholesterolemia ; Hypertension ; Infarction* ; Internal Capsule ; Magnetic Resonance Imaging ; Male ; Moyamoya Disease ; Myocardial Infarction ; Pathology ; Retrospective Studies ; Risk Factors ; Smoke ; Smoking ; Stroke ; Stuttering ; Thrombosis

BACKGROUND: Endothelial dysfunction, the initial pathogenic factor in atherosclerosis, can be alleviated via transient limb ischemia. We observed the effects of regular transient limb ischemia (RTLI) on atherosclerosis in hypercholesterolemic rabbits. METHODS: Twenty-eight rabbits were randomized to control, cholesterol, sham, ischemia groups (n = 7 each) between October 2010 and March 2011. They were fed a normal diet in the control group and hypercholesterolemic diet in other groups for 12 weeks. Six cycles of RTLI were performed once per day on the ischemia group. Serum samples were prepared to measure the total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) before the experiment (W0), at the end of weeks 4, 8, 12 (W4, W8, W12). The whole aorta was harvested at W12 and stained using Sudan IV to identify the plaque. The plaque area was measured using Image J. Results were analyzed by analysis of variance or rank sum test. RESULTS: Concentrations of TC in the cholesterol group were higher than those in the control group at W4 (29.60 [23.75, 39.30] vs. 1.00 [0.80, 1.55], Z = -2.745, P = 0.006), W8 (41.78 [28.08, 47.37] vs. 0.35 [0.10, 0.68], Z = -2.739, P = 0.006), W12 (48.32 [40.04, 48.95] vs. 0.61 [0.50, 0.86], Z = -2.739, P = 0.006). Similar results were obtained for HDL-C and LDL-C. Serum concentrations of TC, HDL-C, and LDL-C in the hypercholesterolemic groups had no differences (all P > 0.05). The percentage of plaque area in the cholesterol group was higher than that in the control group (47.22 ± 23.89% vs. 0, Z = -2.986, P = 0.003). Square root of the percentage of plaque area was smaller in the ischemia group than that in the cholesterol (0.44 ± 0.13 vs. 0.67 ± 0.18, P = 0.014) or sham groups (0.44 ± 0.13 vs. 0.61 ± 0.12, P = 0.049). CONCLUSION In hypercholesterolemic rabbits, RTLI might prevent atherosclerosis progression by reducing the percentage of plaque area.
Animals ; Atherosclerosis ; blood ; prevention & control ; Cholesterol ; blood ; Cholesterol, HDL ; blood ; Cholesterol, LDL ; blood ; Extremities ; pathology ; Hypercholesterolemia ; blood ; Ischemic Attack, Transient ; blood ; Ischemic Postconditioning ; methods ; Male ; Rabbits ; Triglycerides ; blood