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Vascular calcification is major source of cardiovascular disease in patients with chronic kidney disease. Hyperphosphatemia leads to increased intracellular phosphorus influx, which leads to an increase in osteoblast-like cells in vascular smooth muscle cell. PiT-1 transports phosphate in vascular smooth muscle cell. However, the mechanism of vascular calcification is not completely understood. This study investigated candidate phosphorus-related molecules other than PiT-1. We hypothesized that phosphorus-related molecules belonging to the solute-carrier (SLC) superfamily would be involved in vascular calcification. As a result of DNA microarray analysis, we focused on SLC37A2 and showed that mRNA expression of these cells increased on calcified aotic smooth muscle cells (AoSMC). SLC37A2 has been reported to transport both glucose-6-phosphate/phosphate and phosphate/phosphate exchanges. In vitro analysis showed that SLC37A2 expression was not affected by inflammation on AoSMC. The expression of SLC37A2 mRNA and protein increased in calcified AoSMC. In vivo analysis showed that SLC37A2 mRNA expression in the aorta of chronic kidney disease rats was correlated with osteogenic marker genes. Furthermore, SLC37A2 was expressed at the vascular calcification area in chronic kidney disease rats. As a result, we showed that SLC37A2 is one of the molecules that increase with vascular calcification in vitro and in vivo.
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Vascular calcification progresses under hyperphosphatemia, and represents a risk factor for cardiovascular disease in chronic kidney disease (CKD) patients. We recently indicated that phosphorus (P) fluctuations also exacerbated vascular calcification in early-stage CKD rats. Dietary fiber intake is reportedly associated with cardiovascular risk. This study investigated the effects of dietary fiber on vascular calcification by repeated P fluctuations in early-stage CKD rats. Unilateral nephrectomy rats were used as an early-stage CKD model. For 36 days, a P fluctuation (LH) group was fed low-P (0.02% P) and high-P (1.2% P) diets alternating every 2 days, and a P fluctuation with dietary fiber intake (LH + F) group was fed low-P and high-P diets containing dietary fiber alternating every 2 days. The effect on vascular calcification was measured calcium content. Effects on uremic toxin were measured levels of indoxyl sulfate (IS) and investigated gut microbiota. The LH + F group showed significantly reduced vessel calcium content compared to the LH group. Further, dietary fiber inhibited increases in blood levels of IS after intake of high-P diet, and decreased uremic toxin-producing intestinal bacteria. Dietary fiber may help suppress progression of vascular calcification due to repeated P fluctuations in early-stage CKD rats by decreasing uremic toxin-producing intestinal bacteria.
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Cardiovascular disease is a major cause of death among hemodialysis patients. Hyperphosphatemia induces cardiovascular disease through vascular endothelial dysfunction and calcification. Repetition of a short-term excessive-phosphorus (P) diet causes transient elevations in plasma P and subsequent vascular endothelial dysfunction in normal rats. The purpose of this study was to investigate the effects of the P fluctuation on vascular calcification and inflammation in rats after unilateral nephrectomy as an early-stage chronic kidney disease (CKD) model. Rats were bred for 36 days; CP group, fed a control P (0.6%) diet; HP group, fed a high-P (1.2%) diet; and P fluctuation group, fed low-P (0.02%) and high-P diets alternately every 2 days. Influences on vascular calcification were analyzed using Von Kossa staining and measurement of vessel Ca content. The influence on inflammation was measured as urinary levels of 8-hydroxy-2'-deoxyguanosine. We demonstrated that the P fluctuation group showed similar vascular calcification and inflammation to the HP group, despite having the same total P intake as the CP group. A diet avoiding P fluctuations may be important for patients with early-stage CKD.
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7-Ketocholesterol is a major dietary cholesterol oxidation product found in high concentrations in atherosclerotic plaques, which contribute to the development of atherosclerosis. This study aimed to investigate the effects of 7-ketocholesterol on endothelial inflammation, as well as the underlying mechanisms. Pretreatment of human umbilical vein endothelial cells (HUVEC) with 7-ketocholesterol significantly enhanced the total interactions between human monocytic cells (THP-1 cell line) and TNFα-activated HUVECs under physiological flow conditions, compared to pretreatment with cholesterol (TNFα+50 µM cholesterol: 13.1 ± 0.54 cells/CPF, TNFα+50 µM 7-ketocholesterol: 18.9 ± 0.35 cells/CPF, p < 0.01). 7-Ketocholesterol enhanced the expression of E-selectin, ICAM-1, and VCAM-1 proteins. It also activated p38 mitogen-activated protein kinase (MAPK), and treatment with a p38 MAPK inhibitor inhibited both E-selectin expression via ATF-2 activation and 7-ketocholesterol-induced THP-1 adhesion to HUVECs. These findings suggest that 7-ketocholesterol enhances leukocyte-endothelial interactions by upregulating the expression of adhesion molecules, presumably via the p38 MAPK-dependent pathway.
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Adhesión Celular , Células Endoteliales/citología , Cetocolesteroles/farmacología , Leucocitos/citología , Sistema de Señalización de MAP Quinasas , Selectina E/metabolismo , Células Endoteliales de la Vena Umbilical Humana , Humanos , Molécula 1 de Adhesión Intercelular/metabolismo , Monocitos/citología , Oxiesteroles/química , Factores de Riesgo , Factor de Necrosis Tumoral alfa/metabolismo , Molécula 1 de Adhesión Celular Vascular/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismoRESUMEN
Phosphorus management through dietetic therapy is vital for the prevention of cardiovascular disease in chronic kidney disease patients. There are two main sources of phosphorus in the diet, organic phosphorus from protein and inorganic phosphorus from food additives. The adverse effects of high phosphorus intake on vascular-endothelium function have been reported; however, the differences in the effects of organic phosphorus versus inorganic phosphorus are not clear. In this study, we examined an acute effect of these high phosphorus meals intake on vascular-endothelium function. This was a randomized, double-blind, cross-over test study design targeting healthy young men. We conducted a food intake test using two test meals, one high in organic phosphorus from organic food sources, and one high in inorganic phosphorus from food additives. Endothelium-dependent vasodilation, phosphorus and calcium in the urine and blood, and phosphorus-related hormones were measured preprandial to 120 min postprandial. The results showed higher serum and urine phosphorus values after the high inorganic phosphorus meal, and a significant reduction in endothelium-dependent vasodilation at 30 min postprandial. These findings are evidence that inorganic phosphorus has a stronger influence on vascular-endothelium function than organic phosphorus.
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Refeeding syndrome (RFS) is characterized by the metabolic and clinical changes that occur following aggressive nutritional supplementation in malnourished patients. Hypophosphatemia is the hallmark of RFS and is key to its prevention and treatment in clinical practice. However, the mechanism of hypophosphatemia during RFS is unclear because of the lack of an animal model. In this study, we developed a rat RFS model as a first step to clarifying the molecular mechanism. After establishing the parenteral route, rats were fasted for 5 days and refeeding was started using total parenteral nutrition. The animals were infused with a high calorie solution with or without insulin administration. Results showed that plasma phosphate levels did not decrease in rats infused with the high calorie solution alone;in contrast, a 20% reduction compared to baseline was observed in rats administered insulin. In addition, rats infused with the high calorie solution containing added phosphate did not present with hypophosphatemia. Thus, we developed a rat RFS model with hypophosphatemia by tube feeding and insulin administration, and demonstrated the importance of phosphate in preventing refeeding hypophosphatemia. J. Med. Invest. 65:50-55, February, 2018.
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Hipofosfatemia/etiología , Insulina/administración & dosificación , Nutrición Parenteral Total/efectos adversos , Síndrome de Realimentación/etiología , Animales , Modelos Animales de Enfermedad , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND AND AIMS: Our aim was to gain insight into the role that lipoprotein lipase (LPL) and hepatic lipase (HL) plays in HDL metabolism and to better understand LPL- and HL-deficiency states. METHODS: We examined the apolipoprotein (apo) A-I-, A-II-, A-IV-, C-I-, C-III-, and E-containing HDL subpopulation profiles, assessed by native 2-dimensional gel-electrophoresis and immunoblotting, in 6 homozygous and 11 heterozygous LPL-deficient, 6 homozygous and 4 heterozygous HL-deficient, and 50 control subjects. RESULTS: LPL-deficient homozygotes had marked hypertriglyceridemia and significant decreases in LDL-C, HDL-C, and apoA-I. Their apoA-I-containing HDL subpopulation profile was shifted toward small HDL particles compared to controls. HL-deficient homozygotes had moderate hypertriglyceridemia, modest increases in LDL-C and HDL-C level, but normal apoA-I concentration. HL-deficient homozygotes had a unique distribution of apoA-I-containing HDL particles. The normally apoA-I:A-II, intermediate-size (α-2 and α-3) particles were significantly decreased, while the normally apoA-I only (very large α-1, small α-4, and very small preß-1) particles were significantly elevated. In contrast to control subjects, the very large α-1 particles of HL-deficient homozygotes were enriched in apoA-II. Homozygous LPL- and HL-deficient subjects also had abnormal distributions of apo C-I, C-III, and E in HDL particles. Values for all measured parameters in LPL- and HL-deficient heterozygotes were closer to values measured in controls than in homozygotes. CONCLUSIONS: Our data are consistent with the concept that LPL is important for the maturation of small discoidal HDL particles into large spherical HDL particles, while HL is important for HDL remodeling of very large HDL particles into intermediate-size HDL particles.
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Lipasa/sangre , Lipasa/deficiencia , Lipoproteína Lipasa/sangre , Lipoproteínas HDL/sangre , Adulto , Apolipoproteína A-I/sangre , Apolipoproteína A-II/sangre , Apolipoproteína C-I/sangre , Estudios de Casos y Controles , Colesterol/química , Femenino , Heterocigoto , Homocigoto , Humanos , Modelos Lineales , Masculino , Tamaño de la Partícula , Adulto JovenRESUMEN
Polyphenols are widely distributed in leaves, seeds, bark, and flowers and considered to have beneficial effects on cardiovascular health. We hypothesized that the potent antioxidant properties of pine bark extract (PBE) are exerted by its ability to scavenge free radicals and induce antioxidant enzymes. Therefore, we investigated the effects of PBE on low-density lipoprotein (LDL) oxidation and the antioxidant defense system in monocytes. Oxidative susceptibility of LDL was determined by lag time assay in vitro and by using a human umbilical vein endothelial cell-mediated oxidation model. THP-1 monocytic cells were treated with PBE, and the expression of antioxidant enzymes was measured by real-time polymerase chain reaction and Western blot. Pine bark extract showed radical scavenging ability and significantly inhibited free radical-induced and endothelial cell-mediated LDL oxidation in vitro. Pine bark extract treatment resulted in increases in the expressions of antioxidant enzymes, glutathione peroxidase-1, catalase, and heme oxygenase-1 in THP-1 cells. In addition, PBE induced nuclear factor-erythroid-2-related factor 2 activation, which was accompanied by the activation of extracellular signal-regulated kinase and Akt despite a down-regulation of reactive oxygen species. After the monocyte investigations, we further examined the antioxidant effect after the intake of PBE by 10 healthy male volunteers. Pine bark extract significantly prolonged the lag time of LDL oxidation. Based on our findings, it appears that PBE enhances the antioxidant defense capacity of LDL and monocytes and may play a preventive role in atherosclerosis progression.
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Antioxidantes/farmacología , Lipoproteínas LDL/metabolismo , Monocitos/efectos de los fármacos , Pinus/química , Extractos Vegetales/farmacología , Adulto , Antioxidantes/química , Aterosclerosis/prevención & control , Catalasa/genética , Línea Celular , Regulación hacia Abajo , Quinasas MAP Reguladas por Señal Extracelular/genética , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Glutatión Peroxidasa/genética , Glutatión Peroxidasa/metabolismo , Voluntarios Sanos , Hemo-Oxigenasa 1/genética , Hemo-Oxigenasa 1/metabolismo , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Monocitos/metabolismo , Factor 2 Relacionado con NF-E2/genética , Factor 2 Relacionado con NF-E2/metabolismo , Corteza de la Planta/química , Extractos Vegetales/química , Especies Reactivas de Oxígeno/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Glutatión Peroxidasa GPX1RESUMEN
BACKGROUND: Reactive oxygen species are known to mediate skin photoaging, which results in the formation of pigmented spots and wrinkles. Coffee is the largest source of polyphenols, which supplies a large number of antioxidants in one's daily life. However, little is known about how much coffee and polyphenol consumption influences skin health. In this study, a cross-sectional survey of the diet, environmental factors, and skin conditions was conducted in healthy Japanese females to explore the influence of coffee and polyphenol consumption on skin conditions. MATERIALS AND METHODS: Non-smoking, healthy female subjects with moderate sun exposure in their daily lives were recruited for this study (n = 131, age range: 30-60 years old) and recorded their food and beverage intake and life circumstances using questionnaires. The skin water content, transepidermal water loss, and elasticity were measured on the cheek of each subject using non-invasive methods: a Corneometer, a Tewameter, and a Cutometer, respectively. Wrinkles and pigmented spots were evaluated using digital photograph images. RESULTS: Consumption of coffee and total polyphenols from all sources and from coffee showed a statistically significant correlation towards a decrease in pigmented spot scores (P < 0.05). Subjects with high total polyphenol consumption from coffee or chlorogenic acids (the third tertile group) showed the lowest score of ultraviolet pigmented spots (P < 0.05). CONCLUSION: Coffee and polyphenol consumption was associated with low facial pigmented spots in Japanese middle-aged females. We speculated that coffee helps protect human skin from photoaging, and polyphenols, including chlorogenic acids, may contribute to the decreased hyperpigmentation of pigmented spots.
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Café , Polifenoles , Envejecimiento de la Piel , Piel , Adulto , Pueblo Asiatico , Estudios Transversales , Encuestas sobre Dietas , Femenino , Humanos , Persona de Mediana Edad , Luz Solar , Protectores SolaresRESUMEN
OBJECTIVE: As apoE(-/-) and LDL-Receptor(-/-) mice are commonly used in atherosclerosis research; our objective was to point out the differences in HDL metabolism between mice and humans regarding the roles of apoE and LDLR. METHODS: We examined HDL particles obtained from wild type (WT), LDLR(-/-), and apoE(-/-) mice, as well as from normal, homozygous familial hypercholesterolemic (FH), and apoE-deficient human subjects by 2-dimensional non-denaturing PAGE followed by immunoblot and image analysis. RESULTS: In WT mice, the majority of apoA-I was in large (9.0-12.0 nm), α-mobility HDL with trace amounts of apoA-I in small, preß-1 HDL. In LDL(-/-) mice, both apoA-I- and apoE-containing HDL looked normal. About one-third of apoE was associated with large apoA-I-containing HDL (LpA-I:E) and two-thirds formed large HDL without apoA-I (LpE). In apoE(-/-) mice, apoA-I was detected in multiple, ß-preß-mobility, tightly-packed bands (7.0-13.0 nm) indicating that apoA-I in these animals was present only in poorly-lipidated, discoidal particles. Neither FH nor apoE-deficient humans showed significant alterations in apoA-I-containing HDL particles as compared to non-carriers. CONCLUSIONS: Our data indicate that apoE is necessary for the formation of spherical, lipidated HDL particles in mice, but not in humans, probably because mice lack CETP. Based on our data, we hypothesize that apoE(-/-) mice have little or no functional HDL, therefore results from apoE(-/-) mice cannot be extrapolated to humans without taking this significant difference into consideration.
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Apolipoproteínas E/deficiencia , Receptores de LDL/deficiencia , Animales , Apolipoproteínas E/genética , Proteínas de Transferencia de Ésteres de Colesterol/deficiencia , Humanos , Errores Innatos del Metabolismo Lipídico/fisiopatología , Ratones , Modelos AnimalesRESUMEN
We describe a higher magnifying power operating microscope system to improve one method of high-quality microsurgical clipping for cerebral aneurysm in some cases. This higher magnification is achieved by a new lens design in the optical system, which makes the image of the object very clear at high magnifications (distinctiveness of 7 µm). This higher-resolution operating microscope system provides the surgeon with higher-magnified images (at the maximum of more than 30× magnifications as each working distance) in the operating field. The magnifications can be changed from low power (2.9×) to high power (62.0×) depending on the circumstances in a given procedure. We have used this operating microscope system on 11 patients with microsurgical clipping for cerebral aneurysms. Microsurgical treatment could be performed safely and precisely. All aneurysms were treated without any technical complications. We think that the use of this microscope would have potential benefits for microsurgical treatment for cerebral aneurysms because of better visualization.
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Revascularización Cerebral/instrumentación , Aneurisma Intracraneal/cirugía , Microscopía/instrumentación , Anciano , Aneurisma Roto/complicaciones , Aneurisma Roto/cirugía , Hemorragia Cerebral/etiología , Hemorragia Cerebral/cirugía , Craneotomía , Diseño de Equipo , Femenino , Humanos , Aneurisma Intracraneal/complicaciones , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
OBJECTIVES: HIV-positive patients have an increased risk for CVD; however, the underlying mechanisms are not well understood. Our goal was to assess traditional and emerging CVD-risk factors in the CARE Study, a well-described cohort of HIV-infected adults. METHODS: We analyzed demographic and clinical (viral load, CD4 count, ART regimen, cIMT) data including markers of lipid and glucose homeostasis in 176 HIV-positive subjects receiving regular care for HIV infection. RESULTS: No significant association between cIMT and LDL-C level was observed. HIV patients had significantly lower level of the large α-1 HDL particles and about 3-fold higher level of the small pre ß-1 HDL particles than the normal population, but these parameters were not significantly associated with cIMT. Components of the metabolic syndrome, high TG/low HDL-C, insulin resistance and high BMI, as well as viral load were significant but moderate contributors to increased cIMT. CONCLUSION: The major lipid disorder was low HDL-C and high TG level in this HIV-positive cohort. LDL-C was not elevated. These and previously published data indicate that HIV infection and HIV medications influence CVD risk by impairing cholesterol removal (efflux) via ABCA1 from macrophages. Decreasing CVD risk in HIV patients, with impaired cholesterol efflux from macrophages, may require a lower LDL-C goal than recommended for HIV-negative patients and also a better control of TG level.
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Food and beverages rich in polyphenols have been shown to reduce the risk of non-communicable diseases. The present study estimated polyphenol levels and consumption from food and beverages in Japanese women. Randomly recruited housewives living in the area around Tokyo (n 109; aged 21-56 years; Group 1) recorded all beverages and foods they ingested for 7 d, and the total polyphenol (TP) consumption was estimated based on the TP content of each item measured with a modified Folin-Ciocalteu method. For Group 1, TP was consumed at 841 (sd 403) mg/d (range 113-1759 mg/d), and beverages were a larger source of TP (79 %) than food (21 %). The largest single source of TP was coffee at 47 %, followed by green tea, black tea, chocolate, beer and soya sauce, at 16, 5·7, 3·3, 3·2 and 3·1 %, respectively. In terms of food groups, cereals/noodles, vegetables, fruits, beans and seeds, and seasonings (except for soya sauce) contributed 5·0, 4·0, 1·4, 1·8 and 2·4 %, respectively. Another group of housewives who consumed at least one cup of coffee per d were separately recruited (n 100; Group 2) in the same area. Their consumption of TP was higher at 1187 (sd 371) mg/d (range 440-2435 mg/d) than Group 1 (P < 0·001), and the difference mostly came from the coffee consumption. We conclude that not food but beverages, especially coffee, may be the major contributor to TP consumption in Japanese women.
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Perilla (Perilla frutescens (L.) Britt.) is a popular food as well as a traditional medicine in Japan, China, and other Asian countries. The aim of this study was to investigate the inhibitory effects of perilla on low-density lipoprotein (LDL) oxidation in vitro and in human subjects. We compared the antioxidant activities of red perilla and green perilla. Both green and red perilla had high 1,1-diphenyl-2-picrylhydrazyl radical scavenging activities and were abundant in polyphenol compounds. In addition, the radical scavenging activity and polyphenol content of red perilla were higher than those of green perilla. Perilla dramatically inhibited azo-radical-induced LDL oxidation and endothelial-cell-mediated LDL oxidation in vitro. Moreover, red perilla significantly increased mRNA and protein expression levels of antioxidant enzymes in endothelial cells. We further examined the antioxidant effects against LDL in human subjects after the consumption of perilla extracts. After oral intake of red perilla, the subjects' LDL oxidation lag times were significantly longer than those before the intake. Furthermore, lipid peroxide formation and the electrophoretic mobility of LDL decreased markedly. These results suggested that perilla, especially the red variety, had high antioxidant activity and prevented the oxidation of LDL, which is a process strongly related to the development of atherosclerosis.
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Antioxidantes/farmacología , Lipoproteínas LDL/metabolismo , Perilla frutescens/química , Extractos Vegetales/farmacología , Adulto , Femenino , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Células Endoteliales de la Vena Umbilical Humana/enzimología , Humanos , Oxidación-Reducción/efectos de los fármacos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Factores de Tiempo , Adulto JovenRESUMEN
PURPOSE OF REVIEW: Our purpose is to review recent findings highlighting the metabolic and functional diversity of HDL subspecies. RECENT FINDINGS: HDL heterogeneity - both structural and functional - is the main focus of this review. Recent work indicates that the metabolism and functionality of HDL particles differ greatly among HDL subspecies. With the introduction of new and improved methodology (e.g., proteomics), new aspects of the structural complexity and functionality of HDL have been revealed. It has been confirmed that HDL functions - including, but not limited to decreasing inflammation, apoptosis, macrophage adhesion to the endothelium and insulin resistance - are due to HDL's ability to remove cholesterol from cells (reverse cholesterol transport). A new level of HDL complexity has recently been revealed by investigating the lipid composition of HDL with gas chromatography, gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry. There are about 100 different HDL-associated proteins; however, there are many more lipid species potentially associated with HDL particles. SUMMARY: The most important recent findings disclose that HDL is more complex than previously thought. HDL subclasses differ in physical-chemical properties, protein and lipid composition, metabolism, physiological functions and pathophysiological significance. The staggering complexity of HDL demands significantly more investigation before we can truly begin to understand HDL metabolism and function in humans.
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Lipoproteínas HDL/metabolismo , Animales , Apolipoproteínas/metabolismo , Aterosclerosis/metabolismo , Aterosclerosis/patología , Colesterol/metabolismo , Proteínas del Sistema Complemento/metabolismo , Humanos , Lipoproteínas HDL/química , Lipoproteínas HDL/clasificación , Oxidación-Reducción , Tamaño de la Partícula , Terminología como AsuntoRESUMEN
Sweet potato (Ipomoea batatas L.) leaves are consumed as vegetables around the world, especially in Southeast Asia. The aim of this study was to investigate the inhibitory effect of sweet potato leaves on low-density lipoprotein oxidation in vitro and in human subjects. We compared the antioxidant activity of 8 kinds of sweet potato leaves. Every sweet potato leaf had high radical scavenging activity and prolonged a lag time for starting low-density lipoprotein oxidation in vitro. We found that sweet potato leaves contained abundant polyphenol compounds and the radical scavenging activity and prolongation rate of lag time were highly correlated with total polyphenol content. We also confirmed that thiobarbituric acid reactive substances production was increased in endothelial cell-mediated low-density lipoprotein oxidation, which was decreased by treatment with sweet potato leaves. We further measured the low-density lipoprotein oxidizability in 13 healthy volunteers after their intake of 18 g of "Suioh", raw sweet potato leaves. "Suioh" prolonged a lag time for starting low-density lipoprotein oxidation and decreased low-density lipoprotein mobility. These results suggest that sweet potato leaves have antioxidant activity leading to the suppression of low-density lipoprotein oxidation.
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AIM: Increased levels of small dense low-density lipoproteins (sd-LDL) have been reported more atherogenic compared to total low-density lipoprotein (LDL); however, no definitive experiments using macrophages have examined this concept in vitro. METHOD AND RESULT: In this study, we isolated fractions of total LDL (density 1.019-1.063 g/ml) and sd-LDL (density 1.044-1.063 g/ml) from the plasma of subjects with modest hypertriglycidemia. Oxidizabilty as assessed by copper-induced generation (1.6 µmol/L CuSO(4),12 h) of thiobarbituric acid reactive substances (TBARS) was significantly greater (7-fold higher, p < 0.01) for sd-LDL (4.3 ± 1.1 nmol/mg) than for total LDL (0.6 ± 0.2 nmol/mg) at the same cholesterol concentrations. Moreover, oxidized sd-LDL induced more lipid staining in macrophages than oxidized total LDL. When non-oxidized sd-LDL were incubated with THP1 macrophages, there was much greater lipid accumulation as assessed by oil red O staining, and more than a 2-fold increase (p < 0.05) in intracellular triglyceride content as compared to non-oxidized total LDL. Furthermore, non-oxidized sd-LDL in contrast to non-oxidized total LDL enhanced macrophage lectin-like oxidized LDL receptor-1 (LOX-1) protein expression and significantly LOX-1 mRNA levels (+158%, p < 0.05), with no effect on scavenger receptor A or CD36 gene expression. These effects of non-oxidized sd-LDL on LOX-1 gene expression were suppressed when Toll-like receptor 4 was inactivated either by RNAi or antibody. CONCLUSION: Our data indicate for the first time that sd-LDL is much more effective in promoting macrophage triglyceride accumulation and LOX-1 gene expression than total LDL.
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Células Espumosas/citología , Lipoproteínas LDL/metabolismo , Macrófagos/citología , Antígenos CD36/biosíntesis , Línea Celular , Cobre/química , Relación Dosis-Respuesta a Droga , Humanos , Lectinas/metabolismo , Lípidos/química , Macrófagos/metabolismo , Interferencia de ARN , Receptores Depuradores de Clase A/metabolismo , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo , Factores de Tiempo , Receptor Toll-Like 4/metabolismoRESUMEN
Here, we report the case of a patient successfully treated by a series of electroconvulsive therapy (ECT) who had implanted skull fixation devices made of titanium alloy. The patient was a 57-year-old man with bipolar I disorder. He was hospitalized for the treatment of manic symptoms of bipolar I disorder with pharmacotherapy and ECT. He sustained a fall and hit his head hard on the ground. Acute subdural hematoma developed, and emergent surgery to remove the hematoma was carried out. Cranioplasty was performed using fixation devices made of titanium alloy (Ti 6Al-4V). In order to control his manic symptoms, a series of ECT was readministered from 1 week after surgery. No adverse effects occurred. Devices must be investigated and chosen very carefully for permanent implantation, especially in patients during a course of ECT.
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Aleaciones/normas , Trastorno Bipolar/terapia , Terapia Electroconvulsiva , Prótesis e Implantes/normas , Cráneo , Titanio/normas , Terapia Electroconvulsiva/instrumentación , Humanos , Masculino , Persona de Mediana Edad , SeguridadRESUMEN
Oxidized low-density lipoprotein (LDL) is believed to contribute to atherosclerosis in part by being taken up into macrophages via scavenger receptors, thus accounting for foam cells. Balsamic vinegar is made from grapes and generally consumed in the Mediterranean region. In this study, we investigated the preventive effects of balsamic vinegar on LDL oxidation and foam cell formation. Balsamic vinegar had stronger 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging abilities and higher polyphenol concentrations than rice vinegar. Balsamic vinegar dramatically inhibited LDL oxidation by azoradicals and endothelial cell-mediated oxidation in vitro. Further, we assessed the anti-oxidative effect against LDL after balsamic vinegar consumption in human subjects. Balsamic vinegar prolonged the LDL oxidation lag time and decreased lipid peroxide (LPO) and lyso-phosphatidylcholine (LPC) in LDL particles. We next examined the effect of balsamic vinegar on foam cell formation. Oil red O staining showed that balsamic vinegar inhibited oxidized LDL-induced foam cell formation in THP-1 macrophages. The concentrations of intracellular triglycerides and total cholesterols were reduced in the presence of balsamic vinegar. In addition, balsamic vinegar decreased the mRNA and protein expression level of scavenger receptors in THP-1 macrophages. These results showed that balsamic vinegar contained abundant polyphenols and inhibited LDL oxidation and oxidized LDL-induced foam cell formation by decreasing the expression of scavenger receptors.
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Ácido Acético/farmacología , Antioxidantes/farmacología , LDL-Colesterol/metabolismo , Metabolismo de los Lípidos/efectos de los fármacos , Peroxidación de Lípido/efectos de los fármacos , Macrófagos/efectos de los fármacos , Adulto , Compuestos de Bifenilo/metabolismo , Colesterol/metabolismo , Células Endoteliales/metabolismo , Femenino , Humanos , Macrófagos/metabolismo , Oryza , Fosfatidilcolinas/metabolismo , Picratos/metabolismo , ARN Mensajero/metabolismo , Receptores Depuradores/genética , Receptores Depuradores/metabolismo , Triglicéridos/metabolismo , Vitis , Adulto JovenRESUMEN
BACKGROUND: Astaxanthin is a red carotenoid pigment which has significant potential for antioxidant activity. The macrophages in atherosclerotic lesions, known as activated macrophages, express scavenger receptors responsible for the clearance of pathogenic lipoproteins. In addition, the expression and secretion of proteolytic enzymes, matrix metalloproteinases (MMPs), and pro-inflammatory cytokines are remarkably promoted in activated macrophages. AIM OF THE STUDY: In this study, we investigated the effects of astaxanthin on the expression of scavenger receptors, MMPs, and pro-inflammatory cytokines in macrophages. METHODS: THP-1 macrophages were incubated with 5-10 microM astaxanthin for 24 h. The expression levels of scavenger receptors, MMPs, and pro-inflammatory cytokines were determined by Western blot analysis or real-time RT-PCR. The MMP-9 and -2 activities were examined by gelatin zymography and total MMP activity was measured by fluorometry. RESULTS: We found that astaxanthin remarkably decreased the class A scavenger receptor and CD36 expression in the protein and mRNA levels. Astaxanthin also reduced MMP-1, -2, -3, -9, -12, and -14 activity and expression. The mRNA expression of tumor necrosis factor-alpha, interleukin-1beta, interleukin-6, inducible nitric oxide synthase, and cyclooxygenase-2 were significantly suppressed by astaxanthin. Furthermore, astaxanthin inhibited the phosphorylation of nuclear factor-kappaB. CONCLUSIONS: These results indicate that astaxanthin has inhibitory effects on macrophage activation, such as scavenger receptors up-regulation, MMPs activation, and pro-inflammatory cytokines secretion.