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Sample records for cholesterol gallstone formation

  1. Cholesterol gallstones and bile host diverse bacterial communities with potential to promote the formation of gallstones.

    Science.gov (United States)

    Peng, Yuhong; Yang, Yang; Liu, Yongkang; Nie, Yuanyang; Xu, Peilun; Xia, Baixue; Tian, Fuzhou; Sun, Qun

    2015-01-01

    The prevalence of cholesterol gallstones has increased in recent years. Bacterial infection correlates with the formation of gallstones. We studied the composition and function of bacterial communities in cholesterol gallstones and bile from 22 cholesterol gallstone patients using culture-dependent and culture-independent methods. Altogether fourteen and eight bacterial genera were detected in cholesterol gallstones and bile, respectively. Pseudomonas spp. were the dominant bacteria in both cholesterol gallstones and bile. As judged by diversity indices, hierarchical clustering and principal component analysis, the bacterial communities in gallstones were different from those in bile. The gallstone microbiome was considered more stable than that of bile. The different microbial communities may be partially explained by differences in their habitats. We found that 30% of the culturable strains from cholesterol gallstones secreted β-glucuronidase and phospholipase A2. Pseudomonas aeruginosa strains showed the highest β-glucuronidase activity and produced the highest concentration of phospholipase A2, indicating that Ps. aeruginosa may be a major agent in the formation of cholesterol gallstones. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Molecular Mechanisms Underlying the Link between Nuclear Receptor Function and Cholesterol Gallstone Formation

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    Mary Carmen Vázquez

    2012-01-01

    Full Text Available Cholesterol gallstone disease is highly prevalent in western countries, particularly in women and some specific ethnic groups. The formation of water-insoluble cholesterol crystals is due to a misbalance between the three major lipids present in the bile: cholesterol, bile salts, and phospholipids. Many proteins implicated in biliary lipid secretion in the liver are regulated by several transcription factors, including nuclear receptors LXR and FXR. Human and murine genetic, physiological, pathophysiological, and pharmacological evidence is consistent with the relevance of these nuclear receptors in gallstone formation. In addition, there is emerging data that also suggests a role for estrogen receptor ESR1 in abnormal cholesterol metabolism leading to gallstone disease. A better comprehension of the role of nuclear receptor function in gallstone formation may help to design new and more effective therapeutic strategies for this highly prevalent disease condition.

  3. CORRELATION OF GALLSTONE FORMATION WITH SERUM IRON LEVELS

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    Rohini Bipin Bhadre

    2016-07-01

    Full Text Available INTRODUCTION Gallstones are one of the most common problem associated with the gallbladder, affecting millions of people throughout the world. Bile is excreted from liver and gallbladder into Duodenum for digestion. After digestion, if the gallbladder is not emptied out completely, the Bile Juice that remains in the gallbladder can become too concentrated with cholesterol leading to gallstone formation. Cholesterol and calcium bilirubinate are the two main substances involved in gallstone formation. Gallstones derived from bile consists of mixture of cholesterol, bilirubin with or without calcium. Based on their chemical composition, gallstones found in the gallbladder are classified as cholesterol, pigmented or mixed stones. Iron deficiency has been shown to alter the activity of several hepatic enzymes, leading to increased gallbladder bile cholesterol saturation and promotion of cholesterol crystal formation. AIMS & OBJECTIVE Attempt to establish a correlation with gallstones and decreased serum iron levels. MATERIAL & METHODS This study was a prospective cohort study which included 100 consecutive patients with imaging studies suggestive of Cholelithiasis. The Gallstone surgically removed was crushed with mortar and pestle and then analysed for cholesterol, calcium, phosphate and bilirubin (pigment. Serum samples were analysed for Cholesterol, iron and iron binding capacity. RESULTS 86% patients had increased cholesterol levels (p=0.04 and 93% had decreased serum Iron levels (p=0.96. The most common type of gallstone was found to be Cholesterol type of gallstone followed by Mixed and Pigment gallstones. CONCLUSION Serum cholesterol levels were found to be raised in majority of the patients and serum iron was found to be low in these majority of the patients indicating iron deficiency may play a role in gallstone formation.

  4. Determinants for gallstone formation

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    Shabanzadeh, Daniel Monsted; Sorensen, Lars Tue; Jørgensen, Torben

    2016-01-01

    . Gallstone incidence was assessed through repeated ultrasound examinations. Body mass index (BMI), blood pressure, self-rated health, lifestyle variables, blood lipids, and use of female sex hormones were measured at the baseline examination. Statistical analyses included logistic regression. Based...... re-examination were followed-up completely (mean 11.6 years, N = 2848). The overall cumulative incidence of gallstones was 0.60% per year. Independent positive determinants for incident gallstones were age, female sex, non-high density lipoprotein (non-HDL) cholesterol, and gallbladder polyps...... associations were found for blood pressure, smoking, alcohol consumption, HDL cholesterol, or triglycerides in meta-analyses. Conclusions: Age, female sex, BMI, non-HDL cholesterol, and polyps are independent determinants for gallstone formation. Incident gallstones and the metabolic syndrome share common risk...

  5. Gallbladder filling and emptying during cholesterol gallstone formation in the prairie dog. A cholescintigraphic study

    International Nuclear Information System (INIS)

    Pellegrini, C.A.; Ryan, T.; Broderick, W.; Way, L.W.

    1986-01-01

    We studied gallbladder bile flow before, during, and after cholesterol gallstone formation in the prairie dog using infusion cholescintigraphy with /sup 99m/Tc-diethyl iminodiacetic acid. In 18 fasting animals partitioning of bile between gallbladder and intestine was determined every 15 min for 140 min, and gallbladder response to cholecystokinin (5 U/kg X h) was calculated from the gallbladder ejection fraction. Ten prairie dogs were then placed on a 0.4% cholesterol diet and 8 on a regular diet, and the studies were repeated 1, 2, and 6 wk later. The proportion of hepatic bile that entered the gallbladder relative to the intestine varied from one 15-min period to the next, and averaged 28.2% +/- 5.1% at 140 min. Partial spontaneous gallbladder emptying (ejection fraction 11.5% +/- 5.6%) was intermittently observed. Neither the number nor the ejection fraction of spontaneous gallbladder contractions changed during gallstone formation. By contrast, the percent of gallbladder emptying in response to cholecystokinin decreased from 72.1% +/- 5% to 25.9% +/- 9.3% (p less than 0.025) in the first week and was 14.3% +/- 5.5% at 6 wk (p less than 0.01 from prediet values, not significant from first week). Gallbladder filling decreased from 28.2% +/- 5.1% to 6.7% +/- 3% (p less than 0.01), but this change was only observed after 6 wk, when gallstones had formed. This study shows that bile flow into the gallbladder during fasting is not constant; the gallbladder contracts intermittently; gallbladder emptying in response to exogenous cholecystokinin is altered very early during gallstone formation; and gallbladder filling remains unaffected until later stages, when gallstones have formed

  6. Thyroid dysfunction, either hyper or hypothyroidism, promotes gallstone formation by different mechanisms*

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    Wang, Yong; Yu, Xing; Zhao, Qun-zi; Zheng, Shu; Qing, Wen-jie; Miao, Chun-di; Sanjay, Jaiswal

    2016-01-01

    We have investigated comprehensively the effects of thyroid function on gallstone formation in a mouse model. Gonadectomized gallstone-susceptible male C57BL/6 mice were randomly distributed into three groups each of which received an intervention to induce hyperthyroidism, hypothyroidism, or euthyroidism. After 5 weeks of feeding a lithogenic diet of 15% (w/w) butter fat, 1% (w/w) cholesterol, and 0.5% (w/w) cholic acid, mice were killed for further experiments. The incidence of cholesterol monohydrate crystal formation was 100% in mice with hyperthyroidism, 83% in hypothyroidism, and 33% in euthyroidism, the differences being statistically significant. Among the hepatic lithogenic genes, Trβ was found to be up-regulated and Rxr down-regulated in the mice with hypothyroidism. In contrast, Lxrα, Rxr, and Cyp7α1 were up-regulated and Fxr down-regulated in the mice with hyperthyroidism. In conclusion, thyroid dysfunction, either hyperthyroidism or hypothyroidism, promotes the formation of cholesterol gallstones in C57BL/6 mice. Gene expression differences suggest that thyroid hormone disturbance leads to gallstone formation in different ways. Hyperthyroidism induces cholesterol gallstone formation by regulating expression of the hepatic nuclear receptor genes such as Lxrα and Rxr, which are significant in cholesterol metabolism pathways. However, hypothyroidism induces cholesterol gallstone formation by promoting cholesterol biosynthesis. PMID:27381728

  7. Determination of cholesterol, calcium carbonate and bilirubinate of gallstone

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    Iqbal, Y.; Nazneen, B.I.

    2004-01-01

    Gallstones of seven patients were collected from different parts of North West Frontier and Punjab provinces. These stones were analyzed using Liebermann-Burchard method, estimation technique and Microlab-200 for cholesterol, calcium carbonate (CaCO/sub 3/) and bilirubinate respectively. The levels of cholesterol bilirubinate and CaCO/sub 3/ were found in the ranges of 50-81, 12-40 and 7-19% respectively. All of the stones were found to be mixed type stones that contain cholesterol, bilirubinate and calcium carbonate. The structures of the stones are also shown in the picture, which confirm our analysis data. Possible reasons, which cause formation of gallstones, are discussed in this paper. (author)

  8. Ursodeoxycholic Acid for the Treatment of Cholesterol Gallstones

    International Nuclear Information System (INIS)

    Zaater, M.K.

    2011-01-01

    Cholesterol is the principal constituent of more than three quarters of gallstones. Pure cholesterol crystals are quite soft, and protein contributes importantly to the strength of cholesterol stones. The risk of gallstones does not correlate with total serum cholesterol levels, but it does correlate with decreased high-density lipoprotein cholesterol and increased triglyceride levels. At least 10 percent of adults have gallstones where female: male ratio of about 2:1 in the younger age groups with increasing prevalence with age. Nine patients with gallstones (6 females and 3 males) were included in the study. Patients were treated with ursodeoxycholic acids tablets in two oral doses, one after breakfast, and the other after dinner for 9 months. Ultrasound examination was repeated every 3 months. Re-examination by abdominal ultrasonography revealed that gallstone 1 cm or less in diameter disappeared within 6 months, and the largest stone 3.06 cm in diameter disappeared within 9 months.

  9. The ABCG5/8 Cholesterol Transporter and Myocardial Infarction Versus Gallstone Disease

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    Stender, Stefan; Frikke-Schmidt, Ruth; Nordestgaard, Børge G

    2014-01-01

    OBJECTIVES: The study sought to test the hypothesis that genetic variation in ABCG5/8, the transporter responsible for intestinal and hepatobiliary cholesterol efflux, may simultaneously influence plasma and biliary cholesterol levels, and hence risk of myocardial infarction (MI) and gallstone...... disease in opposite directions. BACKGROUND: High plasma levels of low-density lipoprotein (LDL) cholesterol are a causal risk factor for MI, whereas high levels of biliary cholesterol promote gallstone formation. METHODS: A total of 60,239 subjects from Copenhagen were included, including 5,647 with MI...... and 3,174 with symptomatic gallstone disease. Subjects were genotyped for 6 common, nonsynonymous and functional variants in ABCG5/8, and a combined weighted genotype score was calculated. RESULTS: Combined, weighted genotype scores were associated with stepwise decreases in LDL cholesterol of up to 5...

  10. Activation of the Hypoxia Inducible Factor 1α Subunit Pathway in Steatotic Liver Contributes to Formation of Cholesterol Gallstones.

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    Asai, Yoichiro; Yamada, Tetsuya; Tsukita, Sohei; Takahashi, Kei; Maekawa, Masamitsu; Honma, Midori; Ikeda, Masanori; Murakami, Keigo; Munakata, Yuichiro; Shirai, Yuta; Kodama, Shinjiro; Sugisawa, Takashi; Chiba, Yumiko; Kondo, Yasuteru; Kaneko, Keizo; Uno, Kenji; Sawada, Shojiro; Imai, Junta; Nakamura, Yasuhiro; Yamaguchi, Hiroaki; Tanaka, Kozo; Sasano, Hironobu; Mano, Nariyasu; Ueno, Yoshiyuki; Shimosegawa, Tooru; Katagiri, Hideki

    2017-05-01

    Hypoxia-inducible factor 1α subunit (HIF1A) is a transcription factor that controls the cellular response to hypoxia and is activated in hepatocytes of patients with nonalcoholic fatty liver disease (NAFLD). NAFLD increases the risk for cholesterol gallstone disease by unclear mechanisms. We studied the relationship between HIF1A and gallstone formation associated with liver steatosis. We performed studies with mice with inducible disruption of Hif1a in hepatocytes via a Cre adenoviral vector (inducible hepatocyte-selective HIF1A knockout [iH-HIFKO] mice), and mice without disruption of Hif1a (control mice). Mice were fed a diet rich in cholesterol and cholate for 1 or 2 weeks; gallbladders were collected and the number of gallstones was determined. Livers and biliary tissues were analyzed by histology, quantitative reverse-transcription polymerase chain reaction, immunohistochemistry, and immunoblots. We measured concentrations of bile acid, cholesterol, and phospholipid in bile and rates of bile flow. Primary hepatocytes and cholangiocytes were isolated and analyzed. HIF1A was knocked down in Hepa1-6 cells with small interfering RNAs. Liver biopsy samples from patients with NAFLD, with or without gallstones, were analyzed by quantitative reverse-transcription polymerase chain reaction. Control mice fed a diet rich in cholesterol and cholate developed liver steatosis with hypoxia; levels of HIF1A protein were increased in hepatocytes around central veins and 90% of mice developed cholesterol gallstones. Only 20% of the iH-HIFKO mice developed cholesterol gallstones. In iH-HIFKO mice, the biliary lipid concentration was reduced by 36%, compared with control mice, and bile flow was increased by 35%. We observed increased water secretion from hepatocytes into bile canaliculi to mediate these effects, resulting in suppression of cholelithogenesis. Hepatic expression of aquaporin 8 (AQP8) protein was 1.5-fold higher in iH-HIFKO mice than in control mice. Under hypoxic

  11. ANALYSIS OF BILIARY CHOLESTEROL LEVELS IN IRON-DEFICIENT PATIENTS OPERATED FOR GALLSTONE DISEASE

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    R. Kannan

    2017-01-01

    Full Text Available BACKGROUND Gallstone disease is a common gastrointestinal problem in day-to-day practice. The old concept that a typical gallstone sufferer is fat, fertile, flatulent female of 50. This is partially true as the disease has been found in women soon after their first delivery who are thin and underweight and in males also. Conditions that favour the formation of cholesterol gallstones are super saturation of bile with cholesterol, kinetically favourable nucleation and presence of cholesterol crystals in the gallbladder long enough to agglomerate into a stone. Recent studies have defined the role of trace elements (Fe, Ca, Zn and Cu and defective pH in the formation of gallstones. The aim of the study is to determine the association of iron deficiency in super saturation of bile. This cross-sectional study of 50 patients was conducted over a period of 12 months in the Department of General Surgery, Kilpauk Medical College, Chennai, India. Biliary cholesterol and serum cholesterol were compared in iron deficient and non-iron deficient patients having gallstones. A low serum iron level is a factor in bile super saturation with respect to cholesterol leading to gallstone formation. MATERIALS AND METHODS This study was conducted over a period of 12 months in the Department of General Surgery, Kilpauk Medical College, Chennai, India. 50 patients suffering from cholelithiasis confirmed by USG were divided into two groups based on serum iron values. Group A consists of patients with normal serum iron (non-anaemic and Group B of patients with less than normal serum iron (anaemic. RESULTS Serum total cholesterol of the patients of cholelithiasis was not different among groups categorised based on serum iron levels. There were no significant variations in the serum cholesterol contents of both the groups. Also, there was no significant variation of the above parameter in the male and female patients. CONCLUSION Though, it is difficult to draw a causal

  12. Biliary lipid composition and gallstone formation in rabbits fed on soy protein, cholesterol, casein and modified casein.

    OpenAIRE

    Ozben, T

    1989-01-01

    In four experimental groups, rabbits were fed on diets containing soy beans, soy beans plus cholesterol (1%, w/w), casein and modified casein for 8 weeks. Biliary lipid levels, lithogenic-index values and the rate of gallstone formation were determined. The highest mean relative concentrations (mol%) of cholesterol and phospholipid were found in the soy bean + cholesterol group, and the highest mean relative bile acid concentration was in the soy bean group. The lowest mean relative cholester...

  13. Current Views on Genetics and Epigenetics of Cholesterol Gallstone Disease

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    Agostino Di Ciaula

    2013-01-01

    Full Text Available Cholesterol gallstone disease, one of the commonest digestive diseases in western countries, is induced by an imbalance in cholesterol metabolism, which involves intestinal absorption, hepatic biosynthesis, and biliary output of cholesterol, and its conversion to bile acids. Several components of the metabolic syndrome (e.g., obesity, type 2 diabetes, dyslipidemia, and hyperinsulinemia are also well-known risk factors for gallstones, suggesting the existence of interplay between common pathophysiological pathways influenced by insulin resistance, genetic, epigenetic, and environmental factors. Cholesterol gallstones may be enhanced, at least in part, by the abnormal expression of a set of the genes that affect cholesterol homeostasis and lead to insulin resistance. Additionally, epigenetic mechanisms (mainly DNA methylation, histone acetylation/deacetylation, and noncoding microRNAs may modify gene expression in the absence of an altered DNA sequence, in response to different lithogenic environmental stimuli, such as diet, lifestyle, pollutants, also occurring in utero before birth. In this review, we will comment on various steps of the pathogenesis of cholesterol gallstones and interaction between environmental and genetic factors. The epigenomic approach may offer new options for therapy of gallstones and better possibilities for primary prevention in subjects at risk.

  14. Relevance of hereditary defects in lipid transport proteins for the pathogenesis of cholesterol gallstone disease

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    vanBerge-Henegouwen, G. P.; Venneman, N. G.; Portincasa, P.; Kosters, A.; van Erpecum, K. J.; Groen, A. K.

    2004-01-01

    In the formation of cholesterol gallstones, cholesterol hypersecretion into bile causing cholesterol supersaturation and crystallization appears to be the primary factor, with disturbed gallbladder and intestinal motility as secondary factors. Although intestinal uptake mechanisms have not yet been

  15. Low-density lipoprotein cholesterol and risk of gallstone disease

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    Stender, Stefan; Frikke-Schmidt, Ruth; Benn, Marianne

    2013-01-01

    Drugs which reduce plasma low-density lipoprotein cholesterol (LDL-C) may protect against gallstone disease. Whether plasma levels of LDL-C per se predict risk of gallstone disease remains unclear. We tested the hypothesis that elevated LDL-C is a causal risk factor for symptomatic gallstone...

  16. Ursodeoxycholic acid lowers bile lithogenicity by regulating SCP2 expression in rabbit cholesterol gallstone models

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    Cui, Yunfeng; Li, Zhonglian; Zhao, Erpeng; Zhang, Ju; Cui, Naiqiang

    2012-01-01

    Aims: We designed this study to get insight into the disorder of lipid metabolism during cholesterol gallstone formation and evaluate the effect of ursodeoxycholic acid on the improvement of bile lithogenicity and on expression of lipid related genes. Methods: Rabbit cholesterol gallstone models were induced by high cholesterol diet. Bile, blood and liver tissues were obtained from rabbits after 0, 1, 2, 3, 4 and 5 weeks. Bile and blood lipids were measured enzymatically. 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), cytochrome P450, family 7, subfamily A, polypeptide 1 (CYP7A1) and sterol carrier protein 2 (SCP2) mRNA expressions were detected by using quantitative real-time RT-PCR. Cholesterol saturation index (CSI) was calculated by using Carey table to represent the bile lithogenicity. Results: Rates of gallstone formation of the 4 and 5 week treatment groups were 100 %, but that of the ursodeoxycholic acid treatment group was only 33.3 %. Expression of HMGCR and SCP2 mRNA in the 4 week group was upregulated and that of CYP7A1 mRNA decreased as compared with the 0 week group. Ursodeoxycholic acid could significantly extend nucleation time of bile and lower CSI. Ursodeoxycholic acid could reduce the expression of SCP2, but couldn't influence expression of HMGCR and CYP7A1. Conclusions: Abnormal expression of HMGCR, CYP7A1 and SCP2 might lead to high lithogenicity of bile. Ursodeoxycholic acid could improve bile lipids and lower bile lithogenicity, thereby reducing the incidence of gallstones. So it might be a good preventive drug for cholesterol gallstones. PMID:27847447

  17. Bile acid synthesis is increased in Chilean Hispanics with gallstones and in gallstone high-risk Mapuche Indians.

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    Gälman, Cecilia; Miquel, Juan Francisco; Pérez, Rosa Maria; Einarsson, Curt; Ståhle, Lars; Marshall, Guillermo; Nervi, Flavio; Rudling, Mats

    2004-03-01

    Gallstone disease is an important, costly health-care problem in Western societies. It is still unclear whether hepatic lipid regulatory enzymes play primary or secondary roles in gallstone formation. In this study, the aim was to investigate whether the synthesis of bile acids and cholesterol is increased in gallstone disease and to test whether such a metabolic change, if present, might occur before gallstone formation. A total of 125 Chilean Hispanic women (80 without gallstones and 45 with gallstones) matched for age and body mass index were investigated, along with 40 Chilean Mapuche Indian women (20 without gallstones and 20 with gallstones), a population group in which the prevalence for gallstone disease is very high. Fasting blood plasma samples were assayed for 7 alpha-hydroxy-4-cholesten-3-one and lathosterol, 2 strong indicators for hepatic bile acid and body cholesterol synthesis, respectively. Plasma 7 alpha-hydroxy-4-cholesten-3-one levels, corrected for plasma cholesterol, were significantly increased by 50% in Hispanic women with gallstones as compared with gallstone-free Hispanics (P or =100% (P Mapuche Indian women, independently of whether gallstones were present. Plasma lathosterol, corrected for plasma cholesterol, was significantly increased by 22% in Hispanic women with gallstones and in Mapuche Indian women compared with Hispanic women. The results indicate that the synthesis of bile acids and cholesterol is induced in gallstone disease and precedes gallstone development. These inductions presumably occur as a response to an increased intestinal loss of bile acids.

  18. Phytosterol and cholesterol precursor levels indicate increased cholesterol excretion and biosynthesis in gallstone disease.

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    Krawczyk, Marcin; Lütjohann, Dieter; Schirin-Sokhan, Ramin; Villarroel, Luis; Nervi, Flavio; Pimentel, Fernando; Lammert, Frank; Miquel, Juan Francisco

    2012-05-01

    In hepatocytes and enterocytes sterol uptake and secretion is mediated by Niemann-Pick C1-like 1 (NPC1L1) and ATP-binding cassette (ABC)G5/8 proteins, respectively. Whereas serum levels of phytosterols represent surrogate markers for intestinal cholesterol absorption, cholesterol precursors reflect cholesterol biosynthesis. Here we compare serum and biliary sterol levels in ethnically different populations of patients with gallstone disease (GSD) and stone-free controls to identify differences in cholesterol transport and synthesis between these groups. In this case-control study four cohorts were analyzed: 112 German patients with GSD and 152 controls; two distinct Chilean ethnic groups: Hispanics (100 GSD, 100 controls), and Amerindians (20 GSD, 20 controls); additionally an 8-year follow-up of 70 Hispanics was performed. Serum sterols were measured by gas chromatography / mass spectrometry. Gallbladder bile sterol levels were analyzed in cholesterol GSD and controls. Common ABCG5/8 variants were genotyped. Comparison of serum sterols showed lower levels of phytosterols and higher levels of cholesterol precursors in GSD patients than in controls. The ratios of phytosterols to cholesterol precursors were lower in GSD patients, whereas biliary phytosterol and cholesterol concentrations were elevated as compared with controls. In the follow-up study, serum phytosterol levels were significantly lower even before GSD was detectable by ultrasound. An ethnic gradient in the ratios of phytosterols to cholesterol precursors was apparent (Germans > Hispanics > Amerindians). ABCG5/8 variants did not fully explain the sterol metabolic trait of GSD in any of the cohorts. Individuals predisposed to GSD display increased biliary output of cholesterol in the setting of relatively low intestinal cholesterol absorption, indicating enhanced whole-body sterol clearance. This metabolic trait precedes gallstone formation and is a feature of ethnic groups at higher risk of cholesterol

  19. Gallstones

    Science.gov (United States)

    ... skin and the whites of your eyes High fever with chills Types of gallstones Types of gallstones that can form in the gallbladder include: Cholesterol gallstones. The most common type of gallstone, called a cholesterol gallstone, often appears yellow in color. These gallstones are composed mainly of ...

  20. Changes in Gallbladder Motility and Gallstone Formation Following Laparoscopic Gastric Banding for Morbid Obesity

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    Bilal O Al-Jiffry

    2003-01-01

    Full Text Available Morbid obesity is associated with cholesterol gallstone formation, a risk compounded by rapid weight loss. Laparoscopic gastric banding allows for a measured rate of weight loss, but the subsequent risk for developing gallstones is unknown.

  1. Alpinumisoflavone and abyssinone V 4'-methylether derived from Erythrina lysistemon (Fabaceae) promote HDL-cholesterol synthesis and prevent cholesterol gallstone formation in ovariectomized rats.

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    Mvondo, Marie A; Njamen, Dieudonné; Kretzschmar, Georg; Imma Bader, Manuela; Tanee Fomum, Stephen; Wandji, Jean; Vollmer, Günter

    2015-07-01

    Erythrina lysistemon was found to improve lipid profile in ovariectomized rats. Alpinumisoflavone (AIF) and abyssinone V 4'-methylether (AME) derived from this plant induced analogous effects on lipid profile and decreased atherogenic risks. To highlight the molecular mechanism of action of these natural products, we evaluated their effects on the expression of some estrogen-sensitive genes associated with cholesterol synthesis (Esr1 and Apoa1) and cholesterol clearance (Ldlr, Scarb1 and Cyp7a1). Ovariectomized rats were subcutaneously treated for three consecutive days with either compound at the daily dose of 0.1, 1 and 10 mg/kg body weight (BW). Animals were sacrificed thereafter and their liver was collected. The mRNA of genes of interest was analysed by quantitative real-time polymerase chain reaction. Both compounds downregulated the mRNA expression of Esr1, a gene associated with cholesterogenesis and cholesterol gallstone formation. AME leaned the Apoa1/Scarb1 balance in favour of Apoa1, an effect promoting high-density lipoprotein (HDL)-cholesterol formation. It also upregulated the mRNA expression of Ldlr at 1 mg/kg/BW per day (25%) and 10 mg/kg/BW per day (133.17%), an effect favouring the clearance of low-density lipoprotein (LDL)-cholesterol. Both compounds may also promote the conversion of cholesterol into bile acids as they upregulated Cyp7a1 mRNA expression. AIF and AME atheroprotective effects may result from their ability to upregulate mechanisms promoting HDL-cholesterol and bile acid formation. © 2015 Royal Pharmaceutical Society.

  2. Gallstones

    NARCIS (Netherlands)

    Lammert, Frank; Gurusamy, Kurinchi; Ko, Cynthia W.; Miquel, Juan Francisco; Méndez-Sánchez, Nahum; Portincasa, Piero; Van Erpecum, Karel J.; Van Laarhoven, Cees J.; Wang, David Q H

    2016-01-01

    Gallstones grow inside the gallbladder or biliary tract. These stones can be asymptomatic or symptomatic; only gallstones with symptoms or complications are defined as gallstone disease. Based on their composition, gallstones are classified into cholesterol gallstones, which represent the

  3. Antilithogenic influence of dietary capsaicin and curcumin during experimental induction of cholesterol gallstone in mice.

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    Shubha, Malenahalli C; Reddy, Raghunatha R L; Srinivasan, Krishnapura

    2011-04-01

    Spice bioactive compounds, capsaicin and curcumin, were both individually and in combination examined for antilithogenic potential during experimental induction of cholesterol gallstones in mice. Cholesterol gallstones were induced by feeding mice a high-cholesterol (0.5%) diet for 10 weeks. Groups of mice were maintained on a lithogenic diet that was supplemented with 0.015% capsaicin/0.2% curcumin/0.015% capsaicin + 0.2% curcumin. The lithogenic diet that contained capsaicin, curcumin, or their combination reduced the incidence of cholesterol gallstones by 50%, 66%, and 56%, respectively, compared with lithogenic control. This was accompanied by reduced biliary cholesterol and a marginal increase in phospholipid in these spice-fed groups. Increased cholesterol saturation index and cholesterol : phospholipid ratio in the bile caused by the lithogenic diet was countered by the dietary spice compounds. The antilithogenic influence of spice compounds was attributable to the cholesterol-lowering effect of these dietary spices in blood and liver, as well as a moderate increase in phospholipids. Decreased activities of hepatic glutathione reductase and glutathione-S-transferase caused by the lithogenic diet were countered by the combination of capsaicin and curcumin. The increased lipid peroxidation and the decreased concentration of ascorbic acid in the liver that was caused by the lithogenic diet was countered by the dietary spice compounds, individually or in combination. Thus, while the capsaicin and curcumin combination did not have an additive influence in reducing the incidence of cholesterol gallstones in mice, their combination nevertheless was more beneficial in enhancing the activity of hepatic antioxidant enzyme ─ glutathione reductase in the lithogenic situation. The antioxidant effects of dietary spice compounds are consistent with the observed reduction in cholesterol gallstones formed under lithogenic condition.

  4. Quantitative Analysis of Serum Lipid Profile in Gallstone Patients and Controls

    International Nuclear Information System (INIS)

    Channa, N.A.; Ghanghro, A.B.; Soomro, A.M.

    2010-01-01

    The present study was undertaken to explore the possible role of serum lipid profile in gallstone formation. For this serum lipid profile such as total, free and bound cholesterol, LDL cholesterol, HDL cholesterol, triacylglycerols and total lipids were determined in 109 gallstone patients and 100 controls (matched for age, sex and with negative personal or family history of gallstones) treated at Liaquat University Hospital, Jamshoro, Pakistan. Comparison for serum lipid profile between different groups of gallstone patients and controls revealed no significant variation except for the triacylglycerols and total lipids, which were differed significantly between females of up to 45 and above 45 years age. Comparison for serum lipid profile between pure cholesterol and mixed composition gallstone formers showed no significant difference (p>0.05) between the two groups. The serum lipid profile significantly varied between gallstone patients and controls except bound cholesterol level. Comparison of total cholesterol, free cholesterol, LDL cholesterol, HDL cholesterol, triacylglycerols and total lipids between gallstone patients and controls revealed that there was a significant difference between gallstone patients and controls for (a) females with or without gallstones, (b) females of up to 45 years age and (c) females having more than 3 children. HDL cholesterol is significantly decreased in all the groups of gallstone patients as compared to controls, whereas, bound cholesterol remained non significant in all the groups of gallstone patients when compared with controls. In conclusion, elevated serum total cholesterol, free cholesterol, LDL cholesterol, triacylglycerols and decreased levels of HDL cholesterol seem to play major contributing role in the pathogenesis of gallstones in females of up to 45 years age with more than three children. (author)

  5. New determinants for gallstone disease?


    DEFF Research Database (Denmark)

    Shabanzadeh, Daniel Mønsted

    2018-01-01

    screened for gallstone disease with multiple ultrasound examinations, it was possible to both confirm previously identified determinants and to identify new determinants for gallstone disease. Temporal associations for incident gallstone disease and female sex, BMI, non-HDL cholesterol, and inverse...... is the self-reported exposures which may cause misclassification bias. If explored in future studies, assessment of lifestyle habits should include objective measures in order to contribute any further to existing evidence on determinants for gallstone disease.
Associations for biomarkers of insulin...... formation have a long history and the most established include bile cholesterol saturation, gallbladder motor function, and the enterohepatic circulation of secondary bile salts produced by fecal microbiota. A small number of determinants that are believed to affect these mechanisms have been identified...

  6. Decreased Retinol Binding Protein 4 Concentrations are Associated With Cholesterol Gallstone Disease

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    Shen-Nien Wang

    2010-06-01

    Conclusion: Circulating RBP4 decreases in cholesterol gallstone disease independent of renal function. Further studies are needed to investigate the relationship between liver function and RBP4 levels in these patients.

  7. Analysis of human gallstones by FTIR

    International Nuclear Information System (INIS)

    Channa, Naseem A.; Khand, Fateh D.

    2008-01-01

    The present study was aimed at determining the composition of gallstones removed from patients in Southern Sindh, Pakistan. 109 gallstone samples surgically removed from as many patients (98 females and 11 males; age range 20 to 80 years) admitted for treatment in Liaquat University hospital, Jamshsoro during 2000 to 2003, were analyzed for composition by Fourier Transform Infrared (FTIR) spectroscopy. 74 (67.9%) of the 109 gallstone samples were found to be pure cholesterol stones, 5 (4.6%) pure calcium carbonate stones, 13 (11.9%) cholesterol + calcium carbonate, 10 (9.2%) cholesterol + bilirubin and 07 (6.4%) calcium bilirubinate stones. In mixed composition gallstones cholesterol was concentrated more at periphery than in the center of stone. Cholesterol either singly (67.9%) or in combination with either calcium carbonate (11.9%) or bilirubin (9.2%) was the most predominant component of gallstones. Analysis of gallstones based on FTIR suggests that cholesterol either singly or in combination with either calcium carbonate or bilirubin is the most predominant component of gallstones from Southern Sindh, Pakistan. (author)

  8. New determinants for gallstone disease?
.

    Science.gov (United States)

    Shabanzadeh, Daniel Mønsted

    2018-02-01

    Gallstone disease is highly prevalent in Denmark and other countries of northern Europe, and cholecystectomy for the treatment of clinical gallstone disease is one the most frequently performed surgical procedures. Research efforts for the identification of mechanisms involved in gallstone formation have a long history and the most established include bile cholesterol saturation, gallbladder motor function, and the enterohepatic circulation of secondary bile salts produced by fecal microbiota. A small number of determinants that are believed to affect these mechanisms have been identified until now. However, much of this research on determinants for gallstone disease has been hampered by insufficient study designs and by insufficient assessment of gallstone disease by only assessing the selected minority of people with clinical gallstone disease. 
In a Danish general-population cohort screened for gallstone disease with multiple ultrasound examinations, it was possible to both confirm previously identified determinants and to identify new determinants for gallstone disease. Temporal associations for incident gallstone disease and female sex, BMI, non-HDL cholesterol, and inverse associations for increasing alcohol consumption and cessation of hormone replacement therapy in females were confirmed. New determinants included testosterone and increase in SHBG in males which had directly and inverse associations with incident gallstone disease, respectively. All of the identified determinants for incident gallstone disease found in this thesis can be linked to the three biological mechanisms of gallstone formation.
Other modifiable factors such as tobacco smoking, coffee consumption, dietary habits, physical activity, and blood pressure were not identified as determinants of incident gallstone disease in this thesis. Previous findings from other studies may be hampered by study design without exploration of temporal associations or due to selective assessment of

  9. Genetics of gallstone disease.

    Directory of Open Access Journals (Sweden)

    Mittal B

    2002-04-01

    Full Text Available Gallstone disease is a complex disorder where both environmental and genetic factors contribute towards susceptibility to the disease. Epidemiological and family studies suggest a strong genetic component in the causation of this disease. Several genetically derived phenotypes in the population are responsible for variations in lipoprotein types, which in turn affect the amount of cholesterol available in the gall bladder. The genetic polymorphisms in various genes for apo E, apo B, apo A1, LDL receptor, cholesteryl ester transfer and LDL receptor-associated protein have been implicated in gallstone formation. However, presently available information on genetic differences is not able to account for a large number of gallstone patients. The molecular studies in the animal models have not only confirmed the present paradigm of gallstone formation but also helped in identification of novel genes in humans, which might play an important role in pathogenesis of the disease. Precise understanding of such genes and their molecular mechanisms may provide the basis of new targets for rational drug designs and dietary interventions.

  10. An extended chemical analysis of gallstone.

    Science.gov (United States)

    Chandran, P; Kuchhal, N K; Garg, P; Pundir, C S

    2007-09-01

    Chemical composition of gall stones is essential for aetiopathogensis of gallstone disease. We have reported quantitative chemical analysis of total cholesterol bilirubin, calcium, iron and inorganic phosphate in 120 gallstones from haryana. To extend this chemical analysis of gall stones by studying more cases and by analyzing more chemical constituents. A quantitative chemical analysis of total cholesterol, total bilirubin, fatty acids, triglycerides, phospholipids, bile acids, soluble proteins, sodium potassium, magnesium, copper, oxalate and chlorides of biliary calculi (52 cholesterol, 76 mixed and 72 pigment) retrieved from surgical operation of 200 patients from Haryana state was carried out. Total cholesterol as the major component and total bilirubin, phospholipids, triglycerides, bile acids, fatty acids (esterified), soluble protein, calcium, magnesium, iron, copper, sodium, potassium, inorganic phosphate, oxalate and chloride as minor components were found in all types of calculi. The cholesterol stones had higher content of total cholesterol, phospholipids, fatty acids (esterified), inorganic phosphate and copper compared to mixed and pigment stones. The mixed stones had higher content of iron and triglycerides than to cholesterol and pigment stones. The pigment stones were richer in total bilirubin, bile acids, calcium, oxalate, magnesium, sodium, potassium, chloride and soluble protein compared to cholesterol and mixed stones. Although total cholesterol was a major component of cholesterol, mixed and pigment gall stone in Haryana, the content of most of the other lipids, cations and anions was different in different gall stones indicating their different mechanism of formation.

  11. Genetic variation in the cholesterol transporter NPC1L1, ischaemic vascular disease, and gallstone disease

    DEFF Research Database (Denmark)

    Lauridsen, Bo Kobberø; Stender, Stefan; Frikke-Schmidt, Ruth

    2015-01-01

    developed IVD or symptomatic gallstone disease, respectively, during follow-up from 1977 to 2013. We genotyped four common NPC1L1 variants, previously associated with reduced LDL cholesterol levels, thus mimicking the effect of ezetimibe, and calculated a weighted genotype score. With increasing genotype...

  12. An extended chemical analysis of gallstone

    OpenAIRE

    Chandran, P.; Kuchhal, N. K.; Garg, P.; Pundir, C. S.

    2007-01-01

    Chemical composition of gall stones is essential for aetiopathogensis of gallstone disease. We have reported quantitative chemical analysis of total cholesterol bilirubin, calcium, iron and inorganic phosphate in 120 gallstones from haryana. To extend this chemical analysis of gall stones by studying more cases and by analyzing more chemical constituents. A quantitative chemical analysis of total cholesterol, total bilirubin, fatty acids, triglycerides, phospholipids, bile acids, soluble prot...

  13. New insights into the metal partitioning in different microphases of human gallstones.

    Science.gov (United States)

    Parviainen, Annika; Roman-Alpiste, Manuel Jesús; Marchesi, Claudio; Suárez-Grau, Juan Manuel; Pérez-López, Rafael

    2017-12-01

    Chronic metal exposure, e.g. from metal mining, may cause accumulation of metals in soft and hard tissues, and in developing biomineralizations in the human body. Gallstones are biomineralizations formed in the gallbladder which are able to trap trace elements from the bile. Laser Ablation-Inductively Coupled Plasma-Mass Spectrometry (LA-ICP-MS) was used to analyze gallstone cross-sections to trace the elemental abundances and correlate them with the principal phases constituting gallstones, namely cholesterol, Ca bilirubinate salts, Ca carbonate, and Ca phosphate. Five different types of gallstones (pure, mixed, and composite cholesterol stones, pigment stone, and carbonate stone) were chosen according to a previous classification based on phase characterization by different spectroscopic and microscopic techniques. These data were combined with bulk solution ICP-MS/OES analyses for total elemental concentrations. The results indicated that cholesterol has a zero capacity to retain elements except for Ca. Hence, pure cholesterol stones contained the lowest bulk metal concentrations, and the metals were found in the scarce carbonate and phosphate phases in these calculi. Calcium and trace element concentrations increased in other types of gallstones along with increasing amount of bilirubinate, carbonates and phosphates; pigment stones being the most enriched in metals. Phosphates were the principal carriers of Ca, P, Na, Mg, Mn, Fe, Pb, and Cd, whereas carbonate phases were enriched in Ca, Mg, Na, and Mn in order of decreasing abundance. Bilirubinate on the other hand was enriched in Ca, Cu, Ag, and Ni. The higher trace metal affinities of bilirubinate and phosphate explain the elevated metal concentrations observed in the pigment stones. These results give new insight to the trace metal behavior in the gallstone formation and the metal accumulation in the human body, validating the possible use of these biomineralizations as a proxy for exposure to metal

  14. Mucins and calcium phosphate precipitates additively stimulate cholesterol crystallization

    NARCIS (Netherlands)

    van den Berg, A. A.; van Buul, J. D.; Tytgat, G. N.; Groen, A. K.; Ostrow, J. D.

    1998-01-01

    Human biliary mucin and calcium binding protein (CBP) influence formation of both calcium salt precipitates and cholesterol crystals and colocalize in the center of cholesterol gallstones. We investigated how physiological concentrations of these proteins regulate cholesterol crystallization in

  15. Bile salt-induced cholesterol crystal formation from model bile vesicles: a time course study

    NARCIS (Netherlands)

    van de Heijning, B. J.; Stolk, M. F.; van Erpecum, K. J.; Renooij, W.; Groen, A. K.; vanBerge-Henegouwen, G. P.

    1994-01-01

    Precipitation of cholesterol crystals from vesicles is an important step in the pathogenesis of cholesterol gallstones. Little is known, however, about the kinetics and the mechanisms involved in cholesterol crystallization. Therefore, the time course of cholesterol crystal precipitation and lipid

  16. Genetic and functional identification of the likely causative variant for cholesterol gallstone disease at the ABCG5/8 lithogenic locus

    DEFF Research Database (Denmark)

    von Kampen, Oliver; Buch, Stephan; Nothnagel, Michael

    2013-01-01

    The sterolin locus (ABCG5/ABCG8) confers susceptibility for cholesterol gallstone disease in humans. Both the responsible variant and the molecular mechanism causing an increased incidence of gallstones in these patients have as yet not been identified. Genetic mapping utilized patient samples from...... Germany (2,808 cases, 2,089 controls), Chile (680 cases, 442 controls), Denmark (366 cases, 766 controls), India (247 cases, 224 controls), and China (280 cases, 244 controls). Analysis of allelic imbalance in complementary DNA (cDNA) samples from human liver (n = 22) was performed using pyrosequencing....... Transiently transfected HEK293 cells were used for [(3) H]-cholesterol export assays, analysis of protein expression, and localization of allelic constructs. Through fine mapping in German and Chilean samples, an ∼250 kB disease-associated interval could be defined for this locus. Lack of allelic imbalance...

  17. An experimental study on prediction of gallstone composition by ultrasonography and computed tomography

    International Nuclear Information System (INIS)

    Lee, Jong Beum; Chung, Sae Yul; Kim, Kun Sang; Lee, Yong Chul; Han, Man Chung; Kim, Jin Kyu

    1992-01-01

    Prediction of chemical composition of gallstones is a prerequisite in contemplating the chemical dissolution or extracorporeal shock wave lithotripsy of gallstones. The author retrospectively analysed the correlation between quantitative chemical composition of gallstones and their ultrasonographic and computed tomographic findings. The ultrasonography(US) and computed tomography(CT) of 100 consecutive stones obtained from 100 patients were performed under the in vitro condition. Their US and CT findings were grouped with certain pattern and each group was compared with the chemical composition of the stones. Stones with entirely discernible circumference and homogeneous internal echo on US had high bilirubin and low cholesterol content. Acoustic shadows were frequently absent with those stones. Stones with variable internal echo on US had relatively high cholesterol content but their distribution range were wide. There was no correlationship between the cholesterol content and the CT No. of the gallstones. There was positive correlationship between the calcium content and the CT No. of gallstones. The near totally calcified gallstones had very low cholesterol and high residue content. There was no relationship between the calcification type and the ultrasonographic pattern. In conclusion, those stones with entirely discernible circumference and homogeneous internal echo on US were pigment stones. On the contrary, stones with variable internal echo had relatively high cholesterol content. CT could predict the calcium content with CT No., but could not predict the cholesterol content

  18. Metastable and equilibrium phase diagrams of unconjugated bilirubin IXα as functions of pH in model bile systems: Implications for pigment gallstone formation

    Science.gov (United States)

    Berman, Marvin D.

    2014-01-01

    Metastable and equilibrium phase diagrams for unconjugated bilirubin IXα (UCB) in bile are yet to be determined for understanding the physical chemistry of pigment gallstone formation. Also, UCB is a molecule of considerable biomedical importance because it is a potent antioxidant and an inhibitor of atherogenesis. We employed principally a titrimetric approach to obtain metastable and equilibrium UCB solubilities in model bile systems composed of taurine-conjugated bile salts, egg yolk lecithin (mixed long-chain phosphatidylcholines), and cholesterol as functions of total lipid concentration, biliary pH values, and CaCl2 plus NaCl concentrations. Metastable and equilibrium precipitation pH values were obtained, and average pKa values of the two carboxyl groups of UCB were calculated. Added lecithin and increased temperature decreased UCB solubility markedly, whereas increases in bile salt concentrations and molar levels of urea augmented solubility. A wide range of NaCl and cholesterol concentrations resulted in no specific effects, whereas added CaCl2 produced large decreases in UCB solubilities at alkaline pH values only. UV-visible absorption spectra were consistent with both hydrophobic and hydrophilic interactions between UCB and bile salts that were strongly influenced by pH. Reliable literature values for UCB compositions of native gallbladder biles revealed that biles from hemolytic mice and humans with black pigment gallstones are markedly supersaturated with UCB and exhibit more acidic pH values, whereas biles from nonstone control animals and patients with cholesterol gallstone are unsaturated with UCB. PMID:25359538

  19. Characterization of free and bound fatty acids in human gallstones by capillary gas liquid chromatography

    International Nuclear Information System (INIS)

    Channa, N.A.; Khand, F.D.; Noorani, M.A.; Bhanger, M.I.

    2002-01-01

    Forty-four human gallstone samples either of pure cholesterol or cholesterol and bilirubin were randomly selected and analyzed by capillary gas liquid chromatography for the relative percentage composition of free and total fatty acids. The results showed that bound fatty acids were present in higher amounts than the free fatty acids. Amongst the bound fatty acids the percentage occurrence for palmitic acid was highest followed by stearic, oleic, linoleic and myristic acids. Fatty acids myristic, palmitic and linoleic were present in higher amounts in cholesterol gallstones, whereas stearic acid in cholesterol and bilirubin gallstones. When compared, no significant difference (p < 0.05) in the levels of free and bound fatty acids were seen in gallstones of males and females. The results suggest that bound fatty acids have a role to play in the structure of gallstones. (author)

  20. Preventing a Mass Disease: The Case of Gallstones Disease: Role and Competence for Family Physicians.

    Science.gov (United States)

    Portincasa, Piero; Di Ciaula, Agostino; Grattagliano, Ignazio

    2016-07-01

    Gallstone formation is the result of a complex interaction between genetic and nongenetic factors. We searched and reviewed the available literature to define how the primary prevention of gallstones (cholesterol gallstones in particular) could be applied in general practice. Electronic bibliographical databases were searched. Prospective and retrospective cohort studies and case-controlled studies were analyzed and graded for evidence quality. The epidemiological data confirmed that genetic factors are estimated to account for only approximately 25% of the overall risk of gallstones, while metabolic/environmental factors are at least partially modifiable in stone-free risk groups, and are thus modifiable by primary prevention measures related to diet, lifestyle, and environmental factors (i.e., rapid weight loss, bariatric surgery, somatostatin or analogues therapy, transient gallbladder stasis, and hormone therapy). There is no specific recommendation for the secondary prevention of recurrent gallstones. Family physicians can contribute to preventing gallstones due to their capability to identify and effectively manage several risk factors discussed in this study. Although further studies are needed to better elucidate the involvement of epigenetic factors that may regulate the effect of environment and lifestyle on gene expression in the primary prevention of gallstone formation, preventive interventions are feasible and advisable in the general practice setting.

  1. Relative measurement of heavy elements in the bile gallbladder and gallstone

    International Nuclear Information System (INIS)

    Moosavi, K.; Vatankhah, S.; Salimi, J.

    2006-01-01

    Particle Induced X-Ray Emission is a suitable method for the analysis of biological samples in which heavy trace elements are contained in light matrix elements. It is very important to know which factors or probably elements act as initial seed and lead to growing the sands. The goal of this study was to compare the relative values of Fe/K, Cu/K and Zn/K for gallstones, gallbladder, and bile of a specific patient for studying the origination of forming the gallstones. Materials and Methods Human gallbladder, bile, and gallstone samples were obtained by surgical operation from 15 patients and are bombarded by 2.0 MeV energy proton beams produced by van de Graaff accelerator in vacuum. All .. the gallstones were chosen of pigment type of stones and, all the patients were adults. In contrast with conventional methods, the shell and center of the sands has been analyzed separately. The PIXE spectrum analysis was performed using the nonlinear least square fitting code AXIL and GUPIX. Results: The results of detected minor and trace elements shows that the precipitation of calcium salt in the bile lead to reduction of crystals' formation. Elemental comparison of pigment type of gallstone and bile shows that the concentration of calcium in the shell of the stones is four times more than that in the bile. Conclusion: Precipitation of the calcium from the saturated bile on the cholesterols as a seed of gallstones led to reduced sands formation. Analysis of the gallbladder of the same patients revealed no relation between elemental concentrations of bile and gallstones

  2. Prevalence and risk factors of gallstones in adult health screening population

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Mi Hwa; Cho, Pyong Kon [Dept. of Radiological Science, Catholic University of Daegu, Daegu (Korea, Republic of); Kwon, Duck Moon [Dept. of Diagnostic Radiology, Daegu Health College, Daegu (Korea, Republic of)

    2014-12-15

    Gallstone is the most common disease of the biliary system. Korean has experienced an increase in the percentage of cholesterol gallstones. The major risk factors associated with cholesterol gallstones are age, gender as well as obesity. This study was designed to determine the prevalence of gallstones in the last three years and evaluate the associated risk factors in the population who underwent health screening. The study population consisted of 2,484 males and 2,212 females who visited the health promotion center in Dalseogu, Daegu in Korea from January 2011 to December 2013. Each participant in the study had their biliary system gallbladder examined using ultrasonography. Classified as underweight, normal weight or overweight using the population of obese according to the body mass index, and classified according to mood diagnosis of diabetes presented by the American Diabetes Association. Fasting blood glucose and number of liver function, the divided the control group by referring to the normal liver function values used herein. The geological map, I was classified as NCEP APT Ⅲ. A showed of total 148 people were found to have gallstones. The prevalence of sex among 148 patients (3.15%) 84 men (1.79%) and 64 women (1.36%) which shows significantly there is little difference. 1.84% 40 years and below, 3.38% 40's showed age prevalence was 4.66% in 50's and above. In addition, Total-cholesterol was at the most in 52 people, LDL-cholesterol in 398 people, Triglyceride in 36 people, HDL-cholesterol in 19 people. The abnormal group, was created from the total-cholesterol categories from a physical examination of a subject that has been found to be gallstones in the gallbladder. A result of conducting the univariate analysis shows the prevalence of gallstones, a correlation that is meaningful. The logistic regression analysis of multiple ages was chosen to show risk factors age independent cholelithiasis. In spite of the conclusion, gallstones are not

  3. Prevalence and risk factors of gallstones in adult health screening population

    International Nuclear Information System (INIS)

    Lee, Mi Hwa; Cho, Pyong Kon; Kwon, Duck Moon

    2014-01-01

    Gallstone is the most common disease of the biliary system. Korean has experienced an increase in the percentage of cholesterol gallstones. The major risk factors associated with cholesterol gallstones are age, gender as well as obesity. This study was designed to determine the prevalence of gallstones in the last three years and evaluate the associated risk factors in the population who underwent health screening. The study population consisted of 2,484 males and 2,212 females who visited the health promotion center in Dalseogu, Daegu in Korea from January 2011 to December 2013. Each participant in the study had their biliary system gallbladder examined using ultrasonography. Classified as underweight, normal weight or overweight using the population of obese according to the body mass index, and classified according to mood diagnosis of diabetes presented by the American Diabetes Association. Fasting blood glucose and number of liver function, the divided the control group by referring to the normal liver function values used herein. The geological map, I was classified as NCEP APT Ⅲ. A showed of total 148 people were found to have gallstones. The prevalence of sex among 148 patients (3.15%) 84 men (1.79%) and 64 women (1.36%) which shows significantly there is little difference. 1.84% 40 years and below, 3.38% 40's showed age prevalence was 4.66% in 50's and above. In addition, Total-cholesterol was at the most in 52 people, LDL-cholesterol in 398 people, Triglyceride in 36 people, HDL-cholesterol in 19 people. The abnormal group, was created from the total-cholesterol categories from a physical examination of a subject that has been found to be gallstones in the gallbladder. A result of conducting the univariate analysis shows the prevalence of gallstones, a correlation that is meaningful. The logistic regression analysis of multiple ages was chosen to show risk factors age independent cholelithiasis. In spite of the conclusion, gallstones are not

  4. Metastable and equilibrium phase diagrams of unconjugated bilirubin IXα as functions of pH in model bile systems: Implications for pigment gallstone formation.

    Science.gov (United States)

    Berman, Marvin D; Carey, Martin C

    2015-01-01

    Metastable and equilibrium phase diagrams for unconjugated bilirubin IXα (UCB) in bile are yet to be determined for understanding the physical chemistry of pigment gallstone formation. Also, UCB is a molecule of considerable biomedical importance because it is a potent antioxidant and an inhibitor of atherogenesis. We employed principally a titrimetric approach to obtain metastable and equilibrium UCB solubilities in model bile systems composed of taurine-conjugated bile salts, egg yolk lecithin (mixed long-chain phosphatidylcholines), and cholesterol as functions of total lipid concentration, biliary pH values, and CaCl2 plus NaCl concentrations. Metastable and equilibrium precipitation pH values were obtained, and average pKa values of the two carboxyl groups of UCB were calculated. Added lecithin and increased temperature decreased UCB solubility markedly, whereas increases in bile salt concentrations and molar levels of urea augmented solubility. A wide range of NaCl and cholesterol concentrations resulted in no specific effects, whereas added CaCl2 produced large decreases in UCB solubilities at alkaline pH values only. UV-visible absorption spectra were consistent with both hydrophobic and hydrophilic interactions between UCB and bile salts that were strongly influenced by pH. Reliable literature values for UCB compositions of native gallbladder biles revealed that biles from hemolytic mice and humans with black pigment gallstones are markedly supersaturated with UCB and exhibit more acidic pH values, whereas biles from nonstone control animals and patients with cholesterol gallstone are unsaturated with UCB. Copyright © 2015 the American Physiological Society.

  5. Postmenopausal Estrogen Therapy and Risk of Gallstone Disease

    DEFF Research Database (Denmark)

    Simonsen, Maja Hellfritzsch; Erichsen, Rune; Frøslev, Trine

    2013-01-01

    BACKGROUND: Female gender and increasing age are key risk factors for gallstone disease; therefore, postmenopausal women are at high risk. Estrogen increases cholesterol saturation of bile and may further increase gallstone risk, but population-based evidence is sparse. OBJECTIVE: Our objective......, and parity. RESULTS: We identified 16,386 cases with gallstone disease and 163,860 controls. A total of 1,425 cases (8.7 %) and 8,930 controls (5.4 %) were current estrogen users, yielding an adjusted OR for gallstone disease of 1.74 (95 % CI 1.64-1.85) compared with non-users. The corresponding adjusted...

  6. Ursodeoxycholic Acid in the Prevention of Gallstone Formation After Bariatric Surgery: an Updated Systematic Review and Meta-analysis.

    Science.gov (United States)

    Magouliotis, Dimitrios E; Tasiopoulou, Vasiliki S; Svokos, Alexis A; Svokos, Konstantina A; Chatedaki, Christina; Sioka, Eleni; Zacharoulis, Dimitris

    2017-11-01

    We aim to review the available literature on obese patients treated with ursodeoxycholic acid (UDCA) in order to prevent gallstone formation after bariatric surgery. A systematic literature search was performed in PubMed, Cochrane library, and Scopus databases, in accordance with the PRISMA guidelines. Eight studies met the inclusion criteria incorporating 1355 patients. Random-effects meta-analysis showed a lower incidence of gallstone formation in patients taking UDCA. Subgroup analysis reported fewer cases of gallstone disease in the UDCA group in relation to different bariatric procedures, doses of administered UDCA, and time from bariatric surgery. Adverse events were similar in both groups. Fewer patients required cholecystectomy in UDCA group. No deaths were reported. The administration of UDCA after bariatric surgery seems to prevent gallstone formation.

  7. Incidence of gallstone disease and complications

    DEFF Research Database (Denmark)

    Shabanzadeh, Daniel Mønsted

    2018-01-01

    PURPOSE OF REVIEW: The purpose of this review was to describe the epidemiology of gallstone disease in the era of ultrasound screening and laparoscopic cholecystectomy. RECENT FINDINGS: Recent general population cohorts, including ultrasound screenings, have contributed to our understanding...... of formation and clinical course of gallstone disease. Cohorts of symptomatic gallstone disease have been informative about symptom recurrence and need of treatment. Preventive targets for gallstone formation may include obesity and the associated metabolic changes. The presence of gallstone disease is best...... described as a continuum from asymptomatic to symptomatic disease, with the latter including both pain attacks and complicated disease. Symptomatic disease causes a persistent high risk of symptom recurrence and need of cholecystectomy. The majority of gallstone carriers will remain asymptomatic and about...

  8. A PROSPECTIVE STUDY OF HYPOTHYROIDISM IN DIAGNOSED CASE OF GALLSTONE DISEASE

    Directory of Open Access Journals (Sweden)

    P. Sundareswar

    2016-11-01

    Full Text Available BACKGROUND Disturbances in lipid metabolism, which occur during hypothyroidism lead to the formation of gallstones. This study aims to evaluate the thyroid function pattern in patients with gallstones. The aim of this study was to investigate the association between hypothyroidism and gallstone disease. MATERIALS AND METHODS 200 patients admitted as inpatients for management of gallstone disease in Department of General Surgery, GRH, Madurai, between September 2014 to August 2015 were evaluated with details of cases, full history, clinical examination, symptoms and signs of hypothyroidism (loss of appetite, gaining weight, tiredness, constipation, cold intolerance, menstrual disturbances, bradycardia, presence or absence of goiter, etc. and investigations (USG abdomen, USG neck, thyroid function test (T3, T4, TSH. Patients are divided according to history, clinical examination, USG neck and lab estimation of T3, T4 and TSH. 1. Subclinical Hypothyroidism: Symptom free patient with TSH concentration above upper limit of normal range and T3/T4 or both decrease below normal limit. 2. Clinical Hypothyroidism: In which, there are symptoms of hypothyroidism with TSH level above the upper limit and T3/T4 or both decrease below normal limit. 3. Euthyroid Group: Where clinical and lab tests are within normal range (all these groups may present with or without goiter. RESULTS This study included 200 gallstone patients who were studied prospectively over a period of 1 year from September 2014 to August 2015. Among them, 18 patients had subclinical hypothyroidism and 6 patients had clinical hypothyroidism. A total of 12% of gallstone patients were diagnosed to have hypothyroidism showing that there is association of hypothyroidism with gallstone disease. CONCLUSION Thyroid dysfunction is more common among patients with gallstones and it maybe a risk factor for biliary stone formation. This may be attributed to the absence of the pro-relaxing effects of

  9. Indications for Laparoscopic Cholecystectomy or Oral Dissolution Therapy with Ursodeoxycholic Acid in Symptomatic Gallstone Disease

    Directory of Open Access Journals (Sweden)

    Andrea Cariati

    2014-06-01

    A large Danish study has shown that high bilirubin plasma levels and the genetic variant rs6742078 TT of the enzyme bilirubin glucuronidase UGT1A1 are associated with an increased risk of developing symptomatic gallstone disease. Recent reports regarding the significant association between bilirubin levels and symptomatic gallstone disease open a new chapter about the indication and exclusion criteria for oral dissolution therapy of symptomatic gallstone disease. A highly select subgroup of patients with small, single, radiolucent cholesterol gallstones who received oral dissolution therapy with ursodeoxycholic acid (UDCA had a reported recurrence of symptomatic gallstone disease of 50% over five years. This is probably related to the persistence of other causal risk factors for gallstones in addition to that of cholesterol suprasaturation. A subgroup of patients with high plasma bilirubin levels and the UGT1A1 genetic variant rs6742078 have a greater risk of recurrence. In conclusion, oral dissolution therapy with UDCA might still be appropriate for patients that refuse laparoscopic cholecystectomy provided they have small (< 0.5 cm, radiolucent cholesterol gallstones and a functioning gallbladder, and have mean plasma bilirubin levels below 1.33 mg/dL and are not homozygous for the UGT1A1 rs6742078 TT genotype. [Arch Clin Exp Surg 2014; 3(3.000: 161-165

  10. Chemical nature and distribution of calcium compounds in radiolucent gallstones

    International Nuclear Information System (INIS)

    Agarwal, D.K.; Choudhuri, G.; Kumar, J.

    1993-01-01

    A high failure rate for radiolucent cholesterol gallstones to dissolve with oral bile acids may be due to the presence of insoluble calcium compounds. Twenty sets of radiolucent gallstones, 7-20 mm in diameter, obtained from 20 patients undergoing cholecystectomy, were cut, and the outer surface, outer rim, middle portion, and central core areas were scanned for calcium by energy-dispersive X-ray microanalysis (EDX) and scanning electron microscopy (SEM). Scrapings from the four areas of each stone were analysed by infrared spectroscopy. A sample of the crushed stone was used for chemical estimation of cholesterol. 11 of the 20 cholesterol stones showed presence of calcium by EDX; the distribution was peripheral in 5, homogeneous in 4, and central in 2. The chemical compound was calcium bilirubinate in 10 and calcium carbonate in 8 stones. Calcium compounds are present in a high proportion of radiolucent gallstones considered suitable for chemodissolution by conventional criteria. Their unrecognized presence may explain the high failure rate of such stones to respond to medical therapy. 20 refs., 3 figs

  11. Serum lipids coupled with menopausal status may be used as biomarkers in female gallstone patients

    International Nuclear Information System (INIS)

    Awan, A.Y.; Channa, N.A.; Solangi, D.A.; Tabassum, N.

    2017-01-01

    Objective: Females with different menopausal status are compared for serum lipids to explore the role of menopausal status in developing gallstones. Methodology: This study was conducted at Institute of Biochemistry, University of Sindh Jamshoro, Pakistan. A total number of 135 female gallstone patients admitted at Liaquat University Hospital, Wali Bhai Rajputana Hospital, Hyderabad and other hospitals of Hyderabad, Pakistan and 170 age and gender matched control subjects were selected for the study. The serum samples of patients of different menopausal status and control group were analyzed for the lipid contents. Gallstones recovered from the patients were also analyzed for the composition by FTIR. Results: Serum total cholesterol (TC) and serum high density lipoprotein cholesterol (HDL-C) were significantly varied among all age groups while serum triglycerides (TG), serum very low density lipoprotein cholesterol (VLDL-C) and serum total lipids (TL) were found to be significantly differed among four different types of gallstone formers. Consumers of non-branded oil and non-branded ghee were found with significant lipid alterations in comparison to control group. Major lipid alterations were found in female gallstone patients with pre and peri-menopause. Conclusion: Raised serum TC, serum TG and decreased serum HDL-C in addition to pre- and peri-menopausal status may be considered as biomarkers for female gallstone patients.

  12. The analogy in the formation of hardness salts and gallstones according to the EPR study

    Science.gov (United States)

    Pichugina, Alina; Tsyro, Larisa; Unger, Felix

    2017-11-01

    The article shows that the hardness salts contain the same crystalline phases as the bile stone pigment. The identity of EPR spectra of hardness salts and pigment of gallstones containing calcium carbonate was established. An analogy between the processes of formation of hardness salts and gallstones is played, in which particles with open spin-orbitals (fermions) play a decisive role.

  13. Analysis of micellar and vesicular lecithin and cholesterol in model bile using 1H- and 31P-NMR

    NARCIS (Netherlands)

    de Graaf, M. P.; Groen, A. K.; Bovée, W. M.

    1995-01-01

    The distribution of phospholipid and cholesterol between the vesicular and micellar phases in bile plays an important role in the formation of cholesterol gallstones. Conventional analytical procedures to determine the distribution are potentially unreliable because they disturb the distribution of

  14. Nuclear magnetic resonance imaging characteristics of gallstones in vitro

    International Nuclear Information System (INIS)

    Moon, K.L. Jr.; Hricak, H.; Margulis, A.R.; Bernhoft, R.; Way, L.W.; Filly, R.A.; Crooks, L.E.

    1983-01-01

    The nuclear magnetic resonance (NMR) imaging characteristics of gallstones of various composition from 36 patients were studied in vitro using a spin-echo imaging technique. The majority of gallstones (83%) produced no measurable NMR signal despite having a mean water content of 12% and a mean cholesterol content of 61%. Six (17%) of the stones had a weak but measurable signal in the center of the stone, which was thought to represent signal from water in clefts or pores within the stones. The mean water and cholesterol content of the stones with measurable signal did not differ significantly from that of stones with no signal. A possible explanation for these findings, based on the known NMR characteristics of solid materials, is offered

  15. Radiation absorption, water content and contrast medium impregnation of gallstones

    International Nuclear Information System (INIS)

    Schmitt, W.G.H.

    1982-01-01

    Gallstones extracted by surgery were examined for CT density, which was compared with the X-ray film, floating performance and chemical analysis of the stones. So far, the water content of the biliary concrements - 14% on the average - has not been given much attention. Drying will considerably reduce the density; examination of the dried gallstones yields a false picture of direct ray absorption. Pure cholesterol stones do not float in water, and they show positive values on Hounsfield's scale (+30 - +60). The article discusses the question whether CT is suitable for effecting a better selection of gallstone patients who can be treated by drug therapy. (orig.) [de

  16. Gallbladder contractility and mucus secretion after cholesterol feeding in the prairie dog

    NARCIS (Netherlands)

    Li, Y. F.; Moody, F. G.; Weisbrodt, N. W.; Zalewsky, C. A.; Coelho, J. C.; Senninger, N.; Gouma, D.

    1986-01-01

    The purpose of our study was to evaluate changes in gallbladder contractility and mucus secretion in vitro during the early stages of gallstone formation in prairie dogs. Thirty-two animals were divided into five groups. Control animals were fed a trace cholesterol diet. Experimental animals were

  17. Percutaneous Dissolution of Gallstones using Methyl Tert-Butyl Ether

    OpenAIRE

    1990-01-01

    Radiolucent cholesterol gallstones can be dissolved rapidly by methyl terc-buryl ether (MTBE) introduced directly into the gallbladder. Percutaneous transhepatic catheter placement is a well established interventional radiology procedure and is the preferred route for MTBE administration. A small number of patients have been treated using nasobiliary placement of a gallbladder catheter. Rapid stirring automatic pump systems allow dissolution of most cholesterol stones, but s...

  18. Gallstone disease and type-2 diabetes mellitus-the link

    International Nuclear Information System (INIS)

    Olokoba, A.B.; Bojuwoye, B.J.; Olokoba, K.B.; Braimoh, K.T.; Inikori, A.K.

    2007-01-01

    To determine the factors predisposing patients with type-2 diabetes mellitus to gallstone disease. One hundred type 2 diabetic patients and 100 age and gender-matched controls underwent real time ultrasonography to study factors predisposing patients with type 2 diabetes mellitus to gallstone disease. The age, gender, body mass index (BMI), duration of diabetes mellitus and serum lipids were determined in the individuals enrolled for the study. Fifteen percent of the diabetic patients had ultrasound evidence of gallstone disease as compared to 7% in non-diabetic controls. There was a steady increase in the incidence of gallstone disease in diabetic patients with age with a peak incidence in the seventh decade i.e. 60-69 years, and a decline in the eighth decade i.e. 70 - 79 years. The average age of the diabetic patients with gallstone disease - 59.1+ 9.5 years was significantly higher than in those without gallstone disease - 51.8 + 10.5 years (p 0.014). The mean duration of disease in the diabetic patients with gallstone disease was 5.0 + 4.9 years compared with 4.5 + 3.8 years in the diabetic patients without gallstone disease (p=0.772). The mean serum cholesterol and triglyceride levels - 4.3 + 1.3 mmol/L and 1.5 + 0.8 mmol/L respectively in the diabetic patients with gallstone disease was higher than in those without gallstone disease - 3.4 + 0.5 mmol/L (p=0.0941) and 1.4 + 0.7 mmol/L (p=0.712) respectively. The mean body mass index for the diabetic patients with gallstone disease was 26.2 + 5.5 kg /m 2 compared with 25.7 + 6.7 kg/m2 in those without gallstone disease (p=0.755) . Increasing age is a risk factor for gallstone disease in diabetic patients. Hyperlipidaemia, female gender, heavier weight and a longer duration of diabetes mellitus appear to be associated risk factors. (author)

  19. Impact of ursodeoxycholic acid on a CCK1R cholesterol-binding site may contribute to its positive effects in digestive function.

    Science.gov (United States)

    Desai, Aditya J; Dong, Maoqing; Harikumar, Kaleeckal G; Miller, Laurence J

    2015-09-01

    Dysfunction of the type 1 cholecystokinin (CCK) receptor (CCK1R) as a result of increased gallbladder muscularis membrane cholesterol has been implicated in the pathogenesis of cholesterol gallstones. Administration of ursodeoxycholic acid, which is structurally related to cholesterol, has been shown to have beneficial effects on gallstone formation. Our aims were to explore the possible direct effects and mechanism of action of bile acids on CCK receptor function. We studied the effects of structurally related hydrophobic chenodeoxycholic acid and hydrophilic ursodeoxycholic acid in vitro on CCK receptor function in the setting of normal and elevated membrane cholesterol. We also examined their effects on a cholesterol-insensitive CCK1R mutant (Y140A) disrupting a key site of cholesterol action. The results show that, similar to the impact of cholesterol on CCK receptors, bile acid effects were limited to CCK1R, with no effects on CCK2R. Chenodeoxycholic acid had a negative impact on CCK1R function, while ursodeoxycholic acid had no effect on CCK1R function in normal membranes but was protective against the negative impact of elevated cholesterol on this receptor. The cholesterol-insensitive CCK1R mutant Y140A was resistant to effects of both bile acids. These data suggest that bile acids compete with the action of cholesterol on CCK1R, probably by interacting at the same site, although the conformational impact of each bile acid appears to be different, with ursodeoxycholic acid capable of correcting the abnormal conformation of CCK1R in a high-cholesterol environment. This mechanism may contribute to the beneficial effect of ursodeoxycholic acid in reducing cholesterol gallstone formation. Copyright © 2015 the American Physiological Society.

  20. Biliary cholesterol secretion : More than a simple ABC

    NARCIS (Netherlands)

    Dikkers, Arne; Tietge, Uwe J. F.

    2010-01-01

    Biliary cholesterol secretion is a process important for 2 major disease complexes, atherosclerotic cardiovascular disease and cholesterol gallstone disease With respect to cardiovascular disease, biliary cholesterol secretion is regarded as the final step for the elimination of cholesterol

  1. Successful topical dissolution of cholesterol gallbladder stones using ethyl propionate.

    Science.gov (United States)

    Hofmann, A F; Amelsberg, A; Esch, O; Schteingart, C D; Lyche, K; Jinich, H; Vansonnenberg, E; D'Agostino, H B

    1997-06-01

    Topical dissolution of cholesterol gallbladder stones using methyl tert-butyl ether (MTBE) is useful in symptomatic patients judged too ill for surgery. Previous studies showed that ethyl propionate (EP), a C5 ester, dissolves cholesterol gallstones rapidly in vitro, but differs from MTBE in being eliminated so rapidly by the liver that blood levels remain undetectable. Our aim was to test EP as a topical dissolution agent for cholesterol gallbladder stones. Five high-risk patients underwent topical dissolution of gallbladder stones by EP. In three patients, the solvent was instilled via a cholecystostomy tube placed previously to treat acute cholecystitis; in two patients, a percutaneous transhepatic catheter was placed in the gallbladder electively. Gallstone dissolution was assessed by chromatography, by gravimetry, and by catheter cholecystography. Total dissolution of gallstones was obtained in four patients after 6-10 hr of lavage; in the fifth patient, partial gallstone dissolution facilitated basketing of the stones. In two patients, cholesterol dissolution was measured and averaged 30 mg/min. Side effects were limited to one episode of transient hypotension and pain at the infusion site; no patient developed somnolence or nausea. Gallstone elimination was associated with relief of symptoms. EP is an acceptable alternative to MTBE for topical dissolution of cholesterol gallbladder stones in high-risk patients. The lower volatility and rapid hepatic extraction of EP suggest that it may be preferable to MTBE in this investigational procedure.

  2. The Ability of Bile to Scavenge Superoxide Radicals and Pigment Gallstone Formation in Guinea Pigs

    Directory of Open Access Journals (Sweden)

    Cong Lin

    1996-01-01

    Full Text Available After partial ligation of the common bile duct (CBD of guinea pigs, 14 of 16 animals developed pigment gallstones within one week (S group. Intraperitoneal injection of Vit. E and C, each 10 mg/kg daily from 3 days before CBD ligation to one week after the operation (S+V group, decreased the gallstone incidence to 5/14 (exact probability0.05, but Vit. E and C normalized the SR, and the difference between S group and S+V group was significant (p<0.05. These results suggested that Vit. E and C, known as antioxidants, enhanced the ability to scavenge oxygen radical in S+V group; and that in addition to the increases of UCB and Ca2+ concentrations, the participation of oxygen radicals might be of importance for pigment gallstone formation induced by bile duct obstruction.

  3. Comparative studies of trace elements in two kinds of human gallstones

    International Nuclear Information System (INIS)

    Vatankhah, S.; Moosavi, K.; Peyrovan, H.; Salimi, J.

    2003-01-01

    Structural composition of 11 trace elements with Z greater than 13 (Al, P, Si, K, Ca, Mn, Fe, Cu, Zn, Mo, I) was analyzed for the two main groups of human gallstones according to their cholesterol and pigment types by PIXE (Proton Induced X-ray Emission). In both types of stones, the shell and the center were analyzed separately. The gallstones were obtained from 12 patients in wide age group from 22 to 78 years of age during surgical operation. The results show relatively higher values of heavy elements for ages greater than 40. The values of phosphorus in cholesterol type stones are significantly higher than in those of pigment stones. The concentration of calcium in the center of stones is large in comparison with that in the shells. In this paper, a correlation between stone structure and trace elemental concentration has been presented. Comparison of the two essential types of stones (cholesterol and pigment) shows that the center of the pigment stones is very similar to that of the cholesterol type. (author)

  4. Compound analysis of gallstones using dual energy computed tomography-Results in a phantom model

    Energy Technology Data Exchange (ETDEWEB)

    Bauer, Ralf W., E-mail: ralfwbauer@aol.co [Department of Diagnostic and Interventional Radiology, Clinic of the Goethe University Frankfurt, Theodor-Stern-Kai 7, 60596 Frankfurt (Germany); Schulz, Julian R., E-mail: julian.schulz@t-online.d [Department of Diagnostic and Interventional Radiology, Clinic of the Goethe University Frankfurt, Theodor-Stern-Kai 7, 60596 Frankfurt (Germany); Zedler, Barbara, E-mail: zedler@em.uni-frankfurt.d [Department of Forensic Medicine, Clinic of the Goethe University Frankfurt, Kennedyallee 104, 60596 Frankfurt (Germany); Graf, Thomas G., E-mail: thomas.gt.graf@siemens.co [Siemens AG Healthcare Sector, Computed Tomography, Physics and Applications, Siemensstrasse 1, 91313 Forchheim (Germany); Vogl, Thomas J., E-mail: t.vogl@em.uni-frankfurt.d [Department of Diagnostic and Interventional Radiology, Clinic of the Goethe University Frankfurt, Theodor-Stern-Kai 7, 60596 Frankfurt (Germany)

    2010-07-15

    Purpose: The potential of dual energy computed tomography (DECT) for the analysis of gallstone compounds was investigated. The main goal was to find parameters, that can reliably define high percentage (>70%) cholesterol stones without calcium components. Materials and methods: 35 gallstones were analyzed with DECT using a phantom model. Stone samples were put into specimen containers filled with formalin. Containers were put into a water-filled cylindrical acrylic glass phantom. DECT scans were performed using a tube voltage/current of 140 kV/83 mAs (tube A) and 80 kV/340 mAs (tube B). ROI-measurements to determine CT attenuation of each sector of the stones that had different appearance on the CT images were performed. Finally, semi-quantitative infrared spectroscopy (FTIR) of these sectors was performed for chemical analysis. Results: ROI-measurements were performed in 45 different sectors in 35 gallstones. Sectors containing >70% of cholesterol and no calcium component (n = 20) on FTIR could be identified with 95% sensitivity and 100% specificity on DECT. These sectors showed typical attenuation of -8 {+-} 4 HU at 80 kV and +22 {+-} 3 HU at 140 kV. Even the presence of a small calcium component (<10%) hindered the reliable identification of cholesterol components as such. Conclusion: Dual energy CT allows for reliable identification of gallstones containing a high percentage of cholesterol and no calcium component in this pre-clinical phantom model. Results from in vivo or anthropomorphic phantom trials will have to confirm these results. This may enable the identification of patients eligible for non-surgical treatment options in the future.

  5. Compound analysis of gallstones using dual energy computed tomography-Results in a phantom model

    International Nuclear Information System (INIS)

    Bauer, Ralf W.; Schulz, Julian R.; Zedler, Barbara; Graf, Thomas G.; Vogl, Thomas J.

    2010-01-01

    Purpose: The potential of dual energy computed tomography (DECT) for the analysis of gallstone compounds was investigated. The main goal was to find parameters, that can reliably define high percentage (>70%) cholesterol stones without calcium components. Materials and methods: 35 gallstones were analyzed with DECT using a phantom model. Stone samples were put into specimen containers filled with formalin. Containers were put into a water-filled cylindrical acrylic glass phantom. DECT scans were performed using a tube voltage/current of 140 kV/83 mAs (tube A) and 80 kV/340 mAs (tube B). ROI-measurements to determine CT attenuation of each sector of the stones that had different appearance on the CT images were performed. Finally, semi-quantitative infrared spectroscopy (FTIR) of these sectors was performed for chemical analysis. Results: ROI-measurements were performed in 45 different sectors in 35 gallstones. Sectors containing >70% of cholesterol and no calcium component (n = 20) on FTIR could be identified with 95% sensitivity and 100% specificity on DECT. These sectors showed typical attenuation of -8 ± 4 HU at 80 kV and +22 ± 3 HU at 140 kV. Even the presence of a small calcium component (<10%) hindered the reliable identification of cholesterol components as such. Conclusion: Dual energy CT allows for reliable identification of gallstones containing a high percentage of cholesterol and no calcium component in this pre-clinical phantom model. Results from in vivo or anthropomorphic phantom trials will have to confirm these results. This may enable the identification of patients eligible for non-surgical treatment options in the future.

  6. Analysis of Carcinogenic Heavy Metals in Gallstones and its Role in Gallbladder Carcinogenesis.

    Science.gov (United States)

    Mondal, Bikash; Maulik, Dhrubajyoti; Mandal, Mousumi; Sarkar, Gautam Narayan; Sengupta, Sanjay; Ghosh, Debidas

    2017-12-01

    Gallstone is a high-risk factor for gallbladder pre-malignancy or malignancy (GB PM-M) but which substances of gallstones definitely assist to turn out in to GB PM-M, remains unclear. This study aimed to find out the presence of carcinogenic heavy metals in gallstones and to explore the aetiopathogenesis of gallbladder pre-malignancy and malignancy. Presence of elements in gallstones was detected by energy dispersive X-ray spectroscopy (EDS) with scanning electron microscopy (SEM) and then level of carcinogenic heavy metals was estimated in gallstones using atomic absorption spectroscopy (AAS). The experiment was carried out in gallstone samples of 46 patients with gallbladder pre-malignant and malignant condition (PM-M group) and 65 sex and age-matched patients with chronic cholecystitis (C-C group). Gallstones were also classified in to three types such as cholesterol stone, mixed stone, and black pigment stone. EDS analysis detected presence of mercury, lead, and cobalt elements in all types of gallstones of both PM-M and C-C groups. AAS analysis revealed significantly higher amount of mercury (p heavy metals also varied among stone types of both groups. EDS phase analysis showed 'dense deposits' of these metals in gallstones. Presence of significantly higher amount of mercury, lead, cobalt, and cadmium in gallstones may play a pivotal role as risk factors in the development of gallbladder malignancy or pre-malignancy. 'Dense deposits' of these metals in the gallstones which is the first observation, may act as crucial doses of carcinogens.

  7. A case-control study of gallstones: a major risk factor for biliary tract cancer.

    Science.gov (United States)

    Kato, I; Kato, K; Akai, S; Tominaga, S

    1990-01-01

    Because of the strong association between gallstones and biliary tract cancer, we conducted a case-control study of gallstones at Niigata Cancer Center Hospital. Eighty-six cases with gallstones (33 males and 53 females) and 116 hospital controls (56 males and 60 females) were surveyed by means of a self-administered questionnaire. Gallstones were categorized into cholesterol stones (25 cases) and pigment stones (30 cases) based on the appearance of the stones. In multivariate analyses based on an unconditional logistic regression model, the risk of total gallstones was positively associated with a taste for salty food (relative risk (RR) = 2.31, 95% confidence interval (CI): 1.10-4.84), an intake of lettuce and cabbage (RR = 2.98, 95% CI: 1.47-6.06) and a family history of biliary diseases (RR = 5.63, 95% CI: 1.76-17.95), and inversely associated with an intake of salted and dried fish (RR = 0.16, 95% CI: 0.04-0.64). When analyzed by type of stones, cholesterol stones were associated with a taste for oily food (RR = 3.87, 95% CI: 1.36-11.03) and pigment stones were positively associated with professional or administrative occupation (RR = 4.74, 95% CI: 1.35-16.68) and inversely associated with a taste for less greasy food (RR = 0.28, 95% CI: 0.10-0.83). Some of these results are consistent with the results of our previous study on biliary tract cancer.

  8. Cholesterol and Health

    Indian Academy of Sciences (India)

    fats and oil in the diet on the other hand. Gallstones result from ... such factors as high levels of estrogens, multiple pregnancies, obesity, genetic factors and certain ... protein with an inner core of cholesterol and triglycerides. Lipoproteins are ...

  9. Gallstones

    Science.gov (United States)

    ... in the abdomen, back, or just under the right arm. Gallstones are most common among older adults, women, overweight people, Native Americans and Mexican Americans. Gallstones are often found during imaging tests ...

  10. Protein content in gallstone patients can be a contributing factor in cholelithiasis

    International Nuclear Information System (INIS)

    Channa, N.A.; Memon, A.H.; Awan, A.Y.; Noorani, L.

    2017-01-01

    To find out the protein contents as contributing factor in the cholelithiasis patients. Methodology: The study was conducted during January 2016 to December 2016 at Institute of Biochemistry, University of Sindh, Jamshoro, Pakistan. A total number of 109 cholelithiasis patients admitted at Liaquat University Hospital, Jamshoro, Wali Bhai Rajputana Hospital, Hyderabad and Memon Charitable Hospital, Hyderabad, Pakistan and 294 age and gender matched control subjects were selected for the study. The serum samples of gallstone patients and control subjects were analyzed for the total protein contents by biuret kit method, gallstones recovered from the patients were also analyzed for the protein contents by Bradford method. Results: Cholelithiasis patients showed that gallstone protein contents increased with increasing age. We found increased amount of protein contents in mixed composition of gallstones as compared to pure cholesterol gallstones. Serum protein contents were increased in patients with age group 31-45 years, followed by age group 16-30 years. Female cholelithiasis patients were found with increased serum protein contents (but within normal limits) as compared to male cholelithiasis patients. Increased protein contents were also observed in serum as well as in gallstone samples recovered from multiparous female patients in comparison to triparous female patients. Conclusion: Protein may play a role in the pathogenesis of cholelithiasis. (author)

  11. Concanavalin A-binding cholesterol crystallization inhibiting and promoting activity in bile from patients with Crohn's disease compared to patients with ulcerative colitis.

    Science.gov (United States)

    Keulemans, Y C; Mok, K S; Slors, J F; Brink, M A; Gouma, D J; Tytgat, G N; Groen, A K

    1999-10-01

    Crohn's disease is a risk factor for gallstone formation. In contrast, patients with ulcerative colitis have an incidence of gallstone formation comparable to the general population. The reason for this difference is not known. The aim of this study was to elucidate the factors controlling cholesterol crystallization in gallbladder bile of Crohn's disease and ulcerative colitis patients. Gallbladder bile was obtained by aspiration during bowel resections (26 Crohn's disease patients, 20 ulcerative colitis patients). Biliary lipid composition, crystal detection time and the effect of extraction of the concanavalin A-binding fraction on crystal formation were determined. Cholesterol crystals were present in seven of the 26 bile samples of Crohn's disease-patients and one of the 20 ulcerative colitis patients. Four of the bile samples of Crohn's disease patients were fast nucleating. None of the 20 ulcerative colitis patients had fast nucleating bile. Lipid composition, total lipid concentration and CSI were not significantly different between the two groups. In Crohn's disease patients extraction of concanavalin A-binding fraction decreased crystallization in 10 bile samples but accelerated crystallization in one bile sample. In eight bile samples from ulcerative colitis patients crystallization increased after concanavalin A-binding fraction extraction. Compared to ulcerative colitis patients, gallbladder bile of Crohn's disease patients showed increased cholesterol crystallization despite comparable lipid composition and cholesterol saturation index. This difference is caused by increased cholesterol crystallization-promoting activity. Bile from ulcerative colitis patients contains a Con A-binding factor which inhibits cholesterol crystallization.

  12. Gallstone disease and mortality

    DEFF Research Database (Denmark)

    Shabanzadeh, Daniel Mønsted; Sørensen, Lars Tue; Jørgensen, Torben

    2017-01-01

    OBJECTIVES: The objective of this cohort study was to determine whether subjects with gallstone disease identified by screening of a general population had increased overall mortality when compared to gallstone-free participants and to explore causes of death. METHODS: The study population (N...... built. RESULTS: Gallstone disease was present in 10%. Mortality was 46% during median 24.7 years of follow-up with 1% lost. Overall mortality and death from cardiovascular diseases were significantly associated to gallstone disease. Death from unknown causes was significantly associated to gallstone...... disease and death from cancer and gastrointestinal disease was not associated. No differences in mortality for ultrasound-proven gallstones or cholecystectomy were identified. CONCLUSIONS: Gallstone disease is associated with increased overall mortality and to death from cardiovascular disease. Gallstones...

  13. Correlation between chemical components of billary calculi and bile & sera and bile of gallstone patients

    OpenAIRE

    Chandran, Prasheeda; Garg, Pradeep; Pundir, Chandra S.

    2005-01-01

    Total cholesterol, total bilirubin, calcium, oxalate, inorganic phosphate, magnesium, iron, copper, sodium and potassium were analyzed quantitatively in gallstones, bile of gall bladder and sera of 200 patients of cholelithiasis (52 cholesterol, 76 mixed and 72 pigment stone patients) and their contents were correlated between calculi and bile and sera and bile in these three type of stone patients. A significant positive correlation was observed between total cholesterol, total bilirubin of ...

  14. Limitations of CT in the prediction of gallstone composition

    International Nuclear Information System (INIS)

    Brink, J.A.; Mueller, P.R.; Simeone, J.F.; Prien, E.L.; Saini, S.; Tung, G.; Ferrucci, J.T.

    1989-01-01

    Gallstones from 87 patients were harvested at cholecystectomy and selected for thin-section specimen CT and crystallographic analysis. A peripheral rim of density different from the center of the stone was noted in 32 (37%) of 87. The relative attenuations (HU) of the stone rim and stone core were recorded as the difference in attenuation from that of the distilled water bath. The correlation of these measurements with the percent cholesterol content in both the rim and core were poor (r = .57, 0.34, respectively). This paper reports the predictive ability of CT examined by defining predominantly cholesterol stones as having a relative core HV ≥ (62 of 87) and core cholesterol content ≥ 80% (59 of 87). Ct correctly predicted the composition as predominantly cholesterol or pigment in 68 of 87 (78%)

  15. Development of a duodenal gallstone ileus with gastric outlet obstruction (Bouveret syndrome four months after successful treatment of symptomatic gallstone disease with cholecystitis and cholangitis: a case report

    Directory of Open Access Journals (Sweden)

    Winnekendonk Guido

    2010-11-01

    Full Text Available Abstract Introduction Cases of gallstone ileus account for 1% to 4% of all instances of mechanical bowel obstruction. The majority of obstructing gallstones are located in the terminal ileum. Less than 10% of impacted gallstones are located in the duodenum. A gastric outlet obstruction secondary to a gallstone ileus is known as Bouveret syndrome. Gallstones usually enter the bowel through a biliary enteral fistula. Little is known about the formation of such fistulae in the course of gallstone disease. Case presentation We report the case of a 72-year-old Caucasian woman born in Germany with a gastric outlet obstruction due to a gallstone ileus (Bouveret syndrome, with a large gallstone impacted in the third part of the duodenum. Diagnostic investigations of our patient included plain abdominal films, gastroscopy and abdominal computed tomography, which showed a biliary enteric fistula between the gallbladder and the duodenal bulb. Our patient was successfully treated by laparotomy, duodenotomy, extraction of the stone, cholecystectomy, and resection of the fistula in a one-stage surgical approach. Histopathological examination showed chronic and acute cholecystitis, with perforated ulceration of the duodenal wall and acute purulent inflammation of the surrounding fatty tissue. Four months prior to developing a gallstone ileus our patient had been hospitalized for cholecystitis, a large gallstone in the gallbladder, cholangitis and a small obstructing gallstone in the common biliary duct. She had been treated with endoscopic retrograde cholangiopancreatography, endoscopic biliary sphincterotomy, balloon extraction of the common biliary duct gallstone, and intravenous antibiotics. At the time of her first presentation, abdominal ultrasound and endoscopic examination (including esophagogastroduodenoscopy and endoscopic retrograde cholangiopancreatography had not shown any evidence of a biliary enteral fistula. In the four months preceding the

  16. Nanoscale Membrane Domain Formation Driven by Cholesterol

    DEFF Research Database (Denmark)

    Javanainen, Matti; Martinez-Seara, Hector; Vattulainen, Ilpo

    2017-01-01

    Biological membranes generate specific functions through compartmentalized regions such as cholesterol-enriched membrane nanodomains that host selected proteins. Despite the biological significance of nanodomains, details on their structure remain elusive. They cannot be observed via microscopic...... dipalmitoylphosphatidylcholine and cholesterol - the "minimal standard" for nanodomain formation. The simulations reveal how cholesterol drives the formation of fluid cholesterol-rich nanodomains hosting hexagonally packed cholesterol-poor lipid nanoclusters, both of which show registration between the membrane leaflets....... The complex nanodomain substructure forms when cholesterol positions itself in the domain boundary region. Here cholesterol can also readily flip-flop across the membrane. Most importantly, replacing cholesterol with a sterol characterized by a less asymmetric ring region impairs the emergence of nanodomains...

  17. Combined microstructural and mineralogical phase characterization of gallstones in a patient-based study in SW Spain - Implications for environmental contamination in their formation.

    Science.gov (United States)

    Parviainen, Annika; Suárez-Grau, Juan Manuel; Pérez-López, Rafael; Nieto, José Miguel; Garrido, Carlos J; Cobo-Cárdenas, Gema

    2016-12-15

    This study explores the environmental impact of metal exposure on humans through detailed phase and structural characterization of gallstones from two environmentally contrasting populations in Huelva Province (SW Spain). A total of 42 gallstone samples, obtained after surgical intervention at the Riotinto Hospital, were studied by powder X-ray diffraction (XRD), Fourier Transformed Infra-Red spectroscopy (FTIR), FTIR-μ-ATR (Attenuated Total Reflection) coupled with an optical microscope, and by Environmental Scanning Electron Microscope with Energy Dispersive X-ray Spectroscopy (ESEM-EDS), and subsequently classified according to their phase composition and structure. Additionally, the patients were enquired for their living habits in order to analyze the source of possible exposure to metal contamination. The gallstones were classified into pure, mixed and composite cholesterol stones, black and brown pigment stones, and carbonate stones. The patients from the study group residing in a region with acknowledged metal contamination of both natural and anthropogenic origin have a higher risk of metal exposure through contaminated soil, particle matter in the air, and consumption of local water and food products. According to our findings, the metal exposure is related to a higher tendency of forming black pigment stones in the study group in comparison to the control group residing in a natural park with nearly pristine environmental conditions. Moreover, the gallstones from the study group showed to contain more abundant metal components, such as Cu, Fe, Ni, and Zn, than those from the control group. To our knowledge this is the first study to examine the regional environmental impact of metal exposure on human gallstones. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Rapid formation of cholesterol crystals in gallbladder bile is associated with stone recurrence after laparoscopic cholecystotomy.

    Science.gov (United States)

    Jüngst, D; del Pozo, R; Dolu, M H; Schneeweiss, S G; Frimberger, E

    1997-03-01

    Laparoscopic cholecystotomy (LCT) with subsequent extraction of gallstones and primary closure of the gallbladder has been introduced as an alternative therapy for patients with cholecystolithiasis and preserved gallbladder function. However, stone recurrence has to be considered as a major drawback that might be related to lithogenic factors of gallbladder bile or the composition of gallbladder stones. Therefore, these were studied in relation to stone recurrence within an observation period of 1 to 5 years (median, 3.6 years) in 50 patients after LCT. The concentrations of total and individual bile acids, phospholipids, cholesterol, total lipids, mucin, protein, and the cholesterol saturation indices in gallbladder bile were not significantly different between 10 patients with and 40 patients without stone recurrence. However, the crystal observation time was significantly (P < .02) shorter (range, 1-2 days; median, 1.5) in the bile of patients with stone recurrence compared to those without (range, 1-21 days, median 3.5). Moreover, all 10 stone recurrences were observed in the 28 patients with a crystal observation time in the bile of less than or equal to 2 days (approximate annual risk: 12%-15%), and no recurrences were observed in the 22 patients with a crystal observation time greater than 2 days (P < .0001) or in patients with pigment stones. The rapid formation of cholesterol monohydrate crystals in bile seems to be the major risk factor for recurrent stones after LCT. These are most likely cholesterol stones and, therefore, are amenable to oral bile-acid prevention or treatment.

  19. The association between gallstone disease and plaque in the abdominopelvic arteries

    Directory of Open Access Journals (Sweden)

    Halil Ibrahim Serin

    2017-01-01

    Full Text Available Background: The aim of this study was to assess the atheromatous plaque, in the abdominopelvic arteries as a marker of cardiac risk in patients with or without gallstone disease (GD. Materials and Methods: A total of 136 patients were enrolled in this cross-sectional study. Forty-eight patients had GD and the remaining 88 patients did not. The presence or absence of gallstones was noted during abdominal ultrasonography while vascular risk factors such as plaque formation, intima-media thickness, plaque calcification, mural thrombus, stenosis, aneurysm, and inflammation were recorded during an abdominopelvic computed tomography scan. In addition, percentage of the abdominopelvic aorta surface covered by atheromatous plaque was calculated. Results: The mean age of patients with GD and without GD was 50.81 ± 16.20 and 50.40 ± 12.43, respectively. Patients with GD were more likely to have diabetes mellitus, a higher body mass index (BMI (P < 0.001, and higher cholesterol (P < 0.01, and low-density lipoprotein-cholesterol (P < 0.02 levels. No significant differences were found between the groups regarding other atherosclerotic risk factors. Patients with GD had significantly higher rates of the vascular risk factors as intima-media thickness, plaque formation, calcification, aneurysm, mural thrombosis, stenosis, and inflammation in all abdominal arterial segments other than aneurysm in the femoral arteries. In addition, patients with GD had severe atheromatous plaques in the abdominal aorta, common iliac, external iliac, and common femoral artery (CFA. In patients with GD, parameters of age, BMI, and systolic and diastolic blood pressure were all correlated with the severity of the atheromatous plaque in abdominal aorta, common iliac, external iliac, and CFA. Conclusion: We demonstrated a direct relationship between GD and abdominopelvic atheromatous plaque, which is a marker for increased cardiovascular risk, for the first time in the literature

  20. Gallstone Ileus Caused by Cholecystocolonic Fistula and Gallstone Impaction in the Sigmoid Colon: Review of the Literature and Novel Surgical Treatment with Trephine Loop Colostomy

    Directory of Open Access Journals (Sweden)

    James W. O’Brien

    2017-03-01

    Full Text Available Gallstone ileus is an uncommon cause of intestinal obstruction and occurs following the formation of a cholecystoenteric fistula, permitting passage of gallstones into the gastrointestinal tract. Impaction of a gallstone in the sigmoid colon is rare and is usually at sites of previous colonic disease. Definitive management can be challenging due to the advanced age and co-morbidity usually seen in this group of patients. We describe a patient successfully managed with on-table endoscopy and, under local anaesthetic, the formation of a left iliac fossa trephine loop colostomy, permitting an enterolithotomy to deliver the stone whilst accommodating for severe pre-existing distal sigmoid diverticular disease. A review of the literature identified various endoscopic and surgical treatments that, depending on local expertise and patient characteristics, can be considered on a case-by-case basis. We advocate the management described in this case for patients presenting with large bowel obstruction due to gallstone ileus, with a background of diverticular disease and who are not fit for general anaesthetic or formal bowel resection, as an alternative to medical palliation alone.

  1. Gallstones and colorectal cancer

    DEFF Research Database (Denmark)

    Jørgensen, Torben; Rafaelsen, Søren Rafael

    1992-01-01

    The prevalence of gallstone disease in 145 consecutive patients with colorectal cancer was compared with gallstone prevalence in 4,159 subjects randomly selected from a population. The group of patients had a significantly higher prevalence of gallstone disease than the population (odds ratio = 1...... substantial evidence for an association between gallstones and colorectal cancer, an association which is not due to cholecystectomy being a predisposing factor to colorectal cancer. Sporadic findings of an association between cholecystectomy and colorectal cancer can be explained by the above relationship........59; 95 percent confidence limits 1.04-2.45), whereas cholecystectomies occurred with equal frequency in the two groups. There was a nonsignificant trend toward more right-sided cancers in patients with gallstones than in patients without. These results, together with available literature, give...

  2. Randomized, Prospective Comparison of Ursodeoxycholic Acid for the Prevention of Gallstones after Sleeve Gastrectomy.

    Science.gov (United States)

    Adams, Lindsay B; Chang, Craig; Pope, Janet; Kim, Yeonsoo; Liu, Pei; Yates, Amy

    2016-05-01

    Several studies have examined the role of ursodeoxycholic acid (UDCA) for the prevention of cholelithiasis (gallstones) following rapid weight loss from restrictive diets, vertical band gastroplasty, and Roux-en-Y gastric bypass. However, to date, there have been no prospective, controlled studies examining the role of UDCA for the prevention of gallstones following sleeve gastrectomy (SG). This study was conducted to identify the effectiveness of UDCA for prevention of gallstones after SG. Following SG, eligible patients were randomized to a control group who did not receive UDCA treatment or to a group who were prescribed 300 mg UDCA twice daily for 6 months. Gallbladder ultrasounds were performed preoperatively and at 6 and 12 months postoperatively. Patients with positive findings preoperatively were excluded from the study. Compliance with UDCA was assessed. Between December 2011 and April 2013, 37 patients were randomized to the UDCA treatment arm and 38 patients were randomized to no treatment. At baseline, the two groups were similar. At 6 months, the UDCA group had a statistically significant lower incidence of gallstones (p = 0.032). Analysis revealed no significant difference in gallstones between the two groups at 1 year (p = 0.553 and p = 0.962, respectively). The overall gallstone formation rate was 29.8%. The incidence of gallstones is higher than previously estimated in SG patients. UDCA significantly lowers the gallstone formation rate at 6 months postoperatively.

  3. Influence of gallstones and ursodeoxycholic acid therapy on gallbladder emptying

    International Nuclear Information System (INIS)

    Forgacs, I.C.; Maisey, M.N.; Murphy, G.M.; Dowling, R.H.

    1984-01-01

    Altered gallbladder motility could predispose to, or result from, gallstone formation and could also explain the alleged relief of biliary colic seen during bile acid therapy. Therefore, in 14 controls, 25 patients with radiolucent gallstones, and 14 patients with radiopaque gallstones, the authors used two techniques to measure gallbladder contraction--radionuclide imaging and real-time ultrasound--in response to one of two stimuli--a Lundh meal or intravenous cholecystokinin-octapeptide. Using the radionuclide technique, postprandial gallbladder emptying (t1/2) was prolonged both in patients with radiopaque and radiolucent gallstones when compared with controls. In patients with radiolucent stones, the t1/2 of gallbladder emptying became further prolonged after 1 mo of therapy with ursodeoxycholic acid. A similar pattern of results was seen after cholecystokinin-octapeptide and also with real-time ultrasound. Thus, after both stimuli and using two independent techniques, gallbladder contraction was reduced in patients with gallstones. The slower and less complete gallbladder emptying with ursotherapy might explain the reduction in biliary colic noted during treatment

  4. Comparative study of sodium and potassium in different types of gallstones and in serum of subjects with gallstones and controls

    International Nuclear Information System (INIS)

    Channa, N.A.; Ghanghro, A.B.; Soomro, A.M.

    2008-01-01

    The study comprises evaluation of sodium and potassium in the pathogenesis of human gallstones as well as measurement of the concentration of these elements in gallstones and in sera of 109 gallstone subjects and 100 controls (age and sex matched with no personal or family history of gallstone disease). It was observed that serum concentrations for both sodium and potassium were comparable (p<0.05) between gallstone subjects and control subjects. In gallstones the concentration of sodium was significantly higher as compared to potassium (p<0.5). Normal sodium to potassium ratio was seen in serum of gallstone subject, whereas, low sodium to potassium ratio was seen in gallstone carriers. Amongst the different types of gallstones, significantly high (p<0.05) concentrations of sodium and potassium were seen in calcium bilirubinate gallstones. The levels for these mineral elements were also raised in serum of pure calcium carbonate gallstone subjects. The results demonstrate that the higher concentration of sodium and potassium in gallstones may involve in both calcium bilirubinate gallstones and in serum of calcium carbonate gallstone subjects, which indicate their association with calcium in the precipitation of calcium bilirubinate and calcium carbonate in bile. Furthermore, low sodium to potassium ratio in gallstones indicates low ratio in bile of gallstone subjects. (author)

  5. Comparative Study of Sodium and Potassium in Different Types of Gallstones and in Serum of Subjects with Gallstones and Controls

    Directory of Open Access Journals (Sweden)

    Ali Mohammad Soomro

    2008-06-01

    Full Text Available The study comprises evaluation of sodium and potassium in the pathogenesis of human gallstones as well as measurement of the concentration of these elements in gallstones and in sera of 109 gallstone subjects and 100 controls (age and sex matched with no personal or family history of gallstone disease. It was observed that serum concentrations for both sodium and potassium were comparable (p>0.05 between gallstone subjects and control subjects. In gallstones the concentration of sodium was significantly higher as compared to potassium (p<0.05. Normal sodium to potassium ratio was seen in serum of gallstone subjects, whereas, low sodium to potassium ratio was seen in gallstone carriers. Amongst the different types of gallstones, significantly high (p<0.05 concentrations of sodium and potassium were seen in calcium bilirubinate gallstones. The levels for these mineral elements were also raised in serum of pure calcium carbonate gallstone subjects.The results demonstrate that the higher concentration of sodium and potassium in gallstones may involve in both calcium bilirubinate gallstones and in serum of calcium carbonate gallstone subjects, which indicate their association with calcium in the precipitation of calcium bilirubinate and calcium carbonate in bile. Furthermore, low sodium to potassium ratio in gallstones indicates low ratio in bile of gallstone subjects.

  6. Analysis of heterogeneous gallstones using laser-induced breakdown spectroscopy (LIBS) and wavelength dispersive X-ray fluorescence (WD-XRF).

    Science.gov (United States)

    Jaswal, Brij Bir S; Kumar, Vinay; Sharma, Jitendra; Rai, Pradeep K; Gondal, Mohammed A; Gondal, Bilal; Singh, Vivek K

    2016-04-01

    Laser-induced breakdown spectroscopy (LIBS) is an emerging analytical technique with numerous advantages such as rapidity, multi-elemental analysis, no specific sample preparation requirements, non-destructiveness, and versatility. It has been proven to be a robust elemental analysis tool attracting interest because of being applied to a wide range of materials including biomaterials. In this paper, we have performed spectroscopic studies on gallstones which are heterogeneous in nature using LIBS and wavelength dispersive X-ray fluorescence (WD-XRF) techniques. It has been observed that the presence and relative concentrations of trace elements in different kind of gallstones (cholesterol and pigment gallstones) can easily be determined using LIBS technique. From the experiments carried out on gallstones for trace elemental mapping and detection, it was found that LIBS is a robust tool for such biomedical applications. The stone samples studied in the present paper were classified using the Fourier transform infrared (FTIR) spectroscopy. WD-XRF spectroscopy has been applied for the qualitative and quantitative analysis of major and trace elements present in the gallstone which was compared with the LIBS data. The results obtained in the present paper show interesting prospects for LIBS and WD-XRF to study cholelithiasis better.

  7. Different responsiveness to a high-fat/cholesterol diet in two inbred mice and underlying genetic factors: a whole genome microarray analysis

    Directory of Open Access Journals (Sweden)

    Jin Gang

    2009-10-01

    Full Text Available Abstract Background To investigate different responses to a high-fat/cholesterol diet and uncover their underlying genetic factors between C57BL/6J (B6 and DBA/2J (D2 inbred mice. Methods B6 and D2 mice were fed a high-fat/cholesterol diet for a series of time-points. Serum and bile lipid profiles, bile acid yields, hepatic apoptosis, gallstones and atherosclerosis formation were measured. Furthermore, a whole genome microarray was performed to screen hepatic genes expression profile. Quantitative real-time PCR, western blot and TUNEL assay were conducted to validate microarray data. Results After fed the high-fat/cholesterol diet, serum and bile total cholesterol, serum cholesterol esters, HDL cholesterol and Non-HDL cholesterol levels were altered in B6 but not significantly changed in D2; meanwhile, biliary bile acid was decreased in B6 but increased in D2. At the same time, hepatic apoptosis, gallstones and atherosclerotic lesions occurred in B6 but not in D2. The hepatic microarray analysis revealed distinctly different genes expression patterns between B6 and D2 mice. Their functional pathway groups included lipid metabolism, oxidative stress, immune/inflammation response and apoptosis. Quantitative real time PCR, TUNEL assay and western-blot results were consistent with microarray analysis. Conclusion Different genes expression patterns between B6 and D2 mice might provide a genetic basis for their distinctive responses to a high-fat/cholesterol diet, and give us an opportunity to identify novel pharmaceutical targets in related diseases in the future.

  8. Ursodeoxycholic acid improves gastrointestinal motility defects in gallstone patients

    Science.gov (United States)

    Colecchia, A; Mazzella, G; Sandri, L; Azzaroli, F; Magliuolo, M; Simoni, P; Bacchi-Reggiani, ML; Roda, E; Festi, D

    2006-01-01

    AIM: To simultaneously evaluate the presence of defects in gallbladder and gastric emptying, as well as in intestinal transit in gallstone patients (GS) and the effect of chronic ursodeoxycholic acid (UDCA) administration on these parameters and on serum bile acids and clinical outcome in GS and controls (CTR). METHODS: After a standard liquid test meal, gallbla-dder and gastric emptying (by ultrasound), oroileal transit time (OITT) (by an immunoenzymatic technique) and serum bile acids (by HPLC) were evaluated before and after 3 mo of UDCA (12 mg/kg bw/d) or placebo administration in 10 symptomatic GS and 10 matched healthy CTR. RESULTS: OITT was longer in GS than in CTR (P < 0.0001); UDCA significantly reduced OITT in GS (P < 0.0001), but not in CTR. GS had longer gastric half-emptying time (t1/2) than CTR (P < 0.0044) at baseline; after UDCA, t1/2 significantly decreased (P < 0.006) in GS but not in CTR. Placebo administration had no effect on gastric emptying and intestinal transit in both GS and CTR. CONCLUSION: The gallstone patient has simultaneous multiple impairments of gallbladder and gastric emptying, as well as of intestinal transit. UDCA administration restores these defects in GS, without any effect in CTR. These results confirm the pathogenetic role of gastrointestinal motility in gallstone disease and suggest an additional mechanism of action for UDCA in reducing bile cholesterol supersaturation. PMID:16981264

  9. Potentiation of anti-cholelithogenic influence of dietary tender cluster beans (Cyamopsis tetragonoloba) by garlic (Allium sativum) in experimental mice.

    Science.gov (United States)

    Raghavendra, Chikkanna K; Srinivasan, Krishnapura

    2015-10-01

    Dietary fibre-rich tender cluster beans (Cyamopsis tetragonoloba; CB) are known to exert beneficial cholesterol lowering influence. We examined the influence of a combination of dietary tender CB and garlic (Allium sativum) in reducing the cholesterol gallstone formation in mice. Cholesterol gallstones were induced in Swiss mice by feeding a high-cholesterol diet (HCD) for 10 wk. Dietary interventions were made with 10 per cent CB and 1 per cent garlic included individually or together along with HCD. A total of 100 mice were divided into five groups of 20 mice each. Dietary CB, garlic and CB+garlic reduced the formation of cholesterol gallstones by 44, 25 and 56 per cent, respectively, lowered cholesterol by 23-48, 16-24, and 24-58 in bile, serum, and liver, respectively. Cholesterol saturation index in bile and cholesterol: phospholipid ratio in circulation and hepatic tissue were significantly lowered by these dietary interventions, with highest beneficial effect from CB+garlic. Activities of hepatic cholesterol metabolizing enzymes were modulated by CB, garlic and CB+garlic. Elevation in lipid peroxides caused by HCD was also countered by these dietary interventions, the combination producing the highest effect. The results showed that the prevention of experimentally induced formation of cholesterol gallstones by dietary CB and garlic was due to decreased biliary cholesterol secretion and increased cholesterol saturation index. In addition of anti-lithogenic effect, dietary CB and garlic in combination had a beneficial antioxidant effect.

  10. Gallstone ileus - the double challenge: case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Petrişor Banu

    2016-05-01

    Full Text Available Gallstone ileus is a rare condition which occurs as an evolutive complication of biliary lithiasis. It occurs after stone migration from extrahepatic biliary tree to the digestive lumen, mostly through a biliary-enteric fistula. This condition involves repeated inflammatory relapses with the formation of local adhesions and generally requires a long evolution. The vast majority of patients with biliary ileus are third aged women who often have concomitant medical illnesses. Gallstone ileus surgery deals with the two components: bowel obstruction and biliary pole. Obstruction solving is approached as a surgical emergency and it requires an attitude adapted to the local situation. The attitude towards biliary surgery for gallstone ileus is a matter in debate. It could be one-stage surgery, elective surgery or expectancy and its choice is imposed by both local and general condition of the patient. We report the case of a middle-age woman whose first symptom of cholelithiasis was the gallstone ileus. Plain upright abdominal radiography revealed air-fluid levels with distended loops of the small bowel and pneumobilia. Laparotomy was decided and exploration revealed an impacted gallstone into the ileum and dense adhesions were found under the liver region. Enterolithotomy for gallstone removal was made. Postoperative evolution was uneventful with discharge on 7th day.

  11. Recreational physical activity is inversely associated with asymptomatic gallstones in adult Mexican women.

    Science.gov (United States)

    Henao-Morán, Santiago; Denova-Gutiérrez, Edgar; Morán, Segundo; Duque, Ximena; Gallegos-Carrillo, Katia; Macías, Nayeli; Salmerón, Jorge

    2014-01-01

    Epidemiologic research suggests that physical activity (PA) reduces the risk of chronic diseases including gallstones. This study explores the association between recreational physical activity (RPA) and risk of asymptomatic gallstones (AG) in adult Mexican women. We performed a cross-sectional analysis of women from the Health Workers Cohort Study. The study population included Mexican women aged 17-94 years, with no history of gallstone (GS) or cholecystectomy. A self-administered questionnaire was used to collect information on weight change, gynecological health history, cholesterol-lowering medications and diuretics, history of diabetes mellitus type 2 (DM2), PA and diet. PA was calculated in minutes/day, minutes/week and Metabolic Equivalents (METs)/week. Gallstone diagnosis was performed using real-time ultrasonography. The association between RPA and risk of AG was evaluated using multivariate logistic regression models. Results. Of the 4,953 women involved in the study, 12.3% were diagnosed with AG. The participants with AG were significantly older, had a higher body mass index, and had a higher prevalence of DM2 than those without AG. The participants with > 30 min/day of RPA had lower odds of AG (OR = 0.80; 95% CI: 0.65-0.97; P = 0.03), regardless of other known risk factors for gallstone disease. Furthermore, we observed an inverse relationship between RPA time and AG risk, especially in women doing more than 150 min a week of RPA (OR = 0.76; 95%CI: 0.61- 0.95; P = 0.02). These findings support the hypothesis that RPA may protect against AG, although further prospective investigations are needed to confirm this association.

  12. Cholesterol inhibits entotic cell-in-cell formation and actomyosin contraction.

    Science.gov (United States)

    Ruan, Banzhan; Zhang, Bo; Chen, Ang; Yuan, Long; Liang, Jianqing; Wang, Manna; Zhang, Zhengrong; Fan, Jie; Yu, Xiaochen; Zhang, Xin; Niu, Zubiao; Zheng, You; Gu, Songzhi; Liu, Xiaoqing; Du, Hongli; Wang, Jufang; Hu, Xianwen; Gao, Lihua; Chen, Zhaolie; Huang, Hongyan; Wang, Xiaoning; Sun, Qiang

    2018-01-01

    Cell-in-cell structure is prevalent in human cancer, and associated with several specific pathophysiological phenomena. Although cell membrane adhesion molecules were found critical for cell-in-cell formation, the roles of other membrane components, such as lipids, remain to be explored. In this study, we attempted to investigate the effects of cholesterol and phospholipids on the formation of cell-in-cell structures by utilizing liposome as a vector. We found that Lipofectamine-2000, the reagent commonly used for routine transfection, could significantly reduce entotic cell-in-cell formation in a cell-specific manner, which is correlated with suppressed actomyosin contraction as indicated by reduced β-actin expression and myosin light chain phosphorylation. The influence on cell-in-cell formation was likely dictated by specific liposome components as some liposomes affected cell-in-cell formation while some others didn't. Screening on a limited number of lipids, the major components of liposome, identified phosphatidylethanolamine (PE), stearamide (SA), lysophosphatidic acid (LPA) and cholesterol (CHOL) as the inhibitors of cell-in-cell formation. Importantly, cholesterol treatment significantly inhibited myosin light chain phosphorylation, which resembles the effect of Lipofectamine-2000, suggesting cholesterol might be partially responsible for liposomes' effects on cell-in-cell formation. Together, our findings supporting a role of membrane lipids and cholesterol in cell-in-cell formation probably via regulating actomyosin contraction. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Shock-wave lithotripsy of gallstones

    International Nuclear Information System (INIS)

    Torres, W.E.; Baumgartner, B.R.; Nelson, R.C.; Morris, S.J.

    1990-01-01

    This paper evaluates the American Dornier MPL-9000 gallstone study on the effectiveness and safety of biliary extracorporeal shock wave lithotripsy (ESWL) and, in a prospective double blind manner, the need for ursodeoxycholic acid (UDCA). At our institution, 174 symptomatic patients with gallstones (149 with noncalcified stones and 25 with calcified stones) were randomized to receive UDCA or placebo for 6 months. The gallstones were fragmented in 171/174 patients (98%). Evaluation by ultrasound was done at 6 weeks following ESWL; retreatment was done on 42/174 patients for fragments larger than 5 mm. Cholecystectomy was done in 6/174 patients. The 6- and 12- month stone-free rates were noncalcified stones + UDCA, 31% and 41%; noncalcified stones + placebo, 24% and 15%; calcified gallstones, 8% and 8%

  14. Effect of Processing Methods on Cholesterol Contents and Cholesterol Oxides Formation in Some Dairy Products

    International Nuclear Information System (INIS)

    AlRowaily, Meshref A

    2008-01-01

    The effects of pasteurization, boiling, microwaving, processing and storage of milk and some locally produced dairy products on cholesterol contents and cholesterol oxides formation were studied and evaluated. The 7-ketocholesterol were not detected (ND) in all raw milk samples. On the contrary, heating of milk led to formation of cholesterol oxidation products (COPs), mostly, 7- ketocholesterol in different quantities. No significant effect of heating of milk on cholesterol level was observed with the exception of the ultra-high temperature (UHT) milk prepared from milk powder heated at 140 + - 1.0 degree C for 4 sec showed the highest value of 7-ketocholesterol (80.97 mgg-1), followed by microwave heated milk for 5 min (31.29 mgg-1), whereas the lowest value was in milk pasteurized at 85 + - 1.0 degree C for 16 sec (3.125 mgg-1). Commercial storage showed no significant effect on cholesterol and 7-ketocholestrol but lowered cholesterol concentration and increased 7-ketocholestrol level of UHT reconstituted milk. Cholesterol content of both yogurt and labaneh strained by centrifugal separator showed significant decrease while 7-ketochostrol level was increased significantly with refrigerated storage. The findings are discussed in the context with the results of previous similar studies. (author)

  15. Gallstones in Patients with Chronic Liver Diseases

    Directory of Open Access Journals (Sweden)

    Xu Li

    2017-01-01

    Full Text Available With prevalence of 10–20% in adults in developed countries, gallstone disease (GSD is one of the most prevalent and costly gastrointestinal tract disorders in the world. In addition to gallstone disease, chronic liver disease (CLD is also an important global public health problem. The reported frequency of gallstone in chronic liver disease tends to be higher. The prevalence of gallstone disease might be related to age, gender, etiology, and severity of liver disease in patients with chronic liver disease. In this review, the aim was to identify the epidemiology, mechanisms, and treatment strategies of gallstone disease in chronic liver disease patients.

  16. Gallstones

    African Journals Online (AJOL)

    Publications in English language on gallstones up to 2012 were obtained .... spinal cord injury[43] or with the use of the somatostatin analogue octreotide ... in the Scandinavian countries and Chile and among Native ..... weeks of disability.

  17. Correlation between chemical components of billary calculi and bile & sera and bile of gallstone patients.

    Science.gov (United States)

    Chandran, Prasheeda; Garg, Pradeep; Pundir, Chandra S

    2005-07-01

    Total cholesterol, total bilirubin, calcium, oxalate, inorganic phosphate, magnesium, iron, copper, sodium and potassium were analyzed quantitatively in gallstones, bile of gall bladder and sera of 200 patients of cholelithiasis (52 cholesterol, 76 mixed and 72 pigment stone patients) and their contents were correlated between calculi and bile and sera and bile in these three type of stone patients. A significant positive correlation was observed between total cholesterol, total bilirubin of calculi and bile, copper of bile and sera of cholesterol stone patients, copper of calculi and bile, total bilirubin, oxalate, magnesium, potassium of sera and bile of pigment stone patients and oxalate and iron of stone and bile, total bilirubin, oxalate, sodium of sera and bile of mixed stone patients. A significant negative correlation was found between magnesium of serum and bile of cholesterol stone patients, oxalate of calculi and bile of pigment stone patients and magnesium of serum and bile of mixed stone patients.

  18. Bouveret syndrome: gallstone ileus of the duodenum.

    Science.gov (United States)

    Englert, Zachary P; Love, Katie; Marilley, Mark D; Bower, Curtis E

    2012-10-01

    This is a case of a 59-year-old woman with Bouveret syndrome. An initial endoscopic approach to management is described. Gallstone ileus occurs when a gallstone passes from a cholecystoduodenal fistula or a choledochoduodenal fistula into the gastrointestinal tract and causes obstruction, usually at the ileocecal valve. Bouveret syndrome is a variant of gallstone ileus where the gallstone lodges in the duodenum or pylorus causing a gastric outlet obstruction. The endoscopic and surgical management of this process are important to keep in mind and may be evolving as endoscopic therapies improve.

  19. The rotary gallstone lithotrite to aid gallbladder extraction in laparoscopic cholecystectomy.

    Science.gov (United States)

    Sackier, J M; Hunter, J G; Paz-Partlow, M; Cuschieri, A

    1992-01-01

    During laparoscopic cholecystectomy, a large stone burden may cause difficulty when extracting the gallbladder through the abdominal wall. Currently, the alternatives available to the surgeon include increasing the incision, removing stones singly, or utilizing complex fragmentation techniques like the pulsed dye laser. We have employed an electromechanical rotary gallstone lithotrite (RGL) to fragment stones to an aspiratable size. Initially, cholesterol spheres were pulverized in a latex balloon to demonstrate the efficacy of the device. Then, human gallstones were placed in the balloon and reduced to fragments less than or equal to 1 mm from initial sizes of 4-24 mm. Human stones were then inserted in ex vivo porcine gallbladders in a controlled experiment and treated with the device. Ten out of 12 tests were completed within 30 s; one test required 49 s and one 105 s to achieve complete fragmentation. Blinded histological evaluation demonstrated that tissue abrasion caused by use of the device would not interfere with the diagnosis of unsuspected malignancy. Clinical trials have now commenced under the auspices of the hospital ethical committee.

  20. Screen-detected gallstone disease and cardiovascular disease

    DEFF Research Database (Denmark)

    Shabanzadeh, Daniel Mønsted; Skaaby, Tea; Sørensen, Lars Tue

    2017-01-01

    Knowledge about temporal associations for screen-detected gallstone disease and cardiovascular disease is limited. The objective of this study was to determine if screen-detected gallstones or cholecystectomy was associated with development of cardiovascular disease. A cohort study of three...... of cardiovascular disease through nationwide registers until December 2014. Multivariable Cox regression analyses were performed including traditional cardiovascular disease risk factors and apolipoprotein E genotype. Gallstone disease was identified in 10% (591/5928) of participants at baseline of whom 6.8% had...... gallstones and 3.2% had cholecystectomy. The study population was followed for a period of 32 years with only 1% lost to follow-up. Gallstone disease was associated with all cardiovascular disease (hazard ratio (HR) 1.36, 95% confidence interval (CI) [1.17;1.59]) and to the subgroups coronary artery (HR 1...

  1. Vitamin D and gallstone disease-A population-based study

    DEFF Research Database (Denmark)

    Shabanzadeh, Daniel Mønsted; Jørgensen, Torben; Linneberg, Allan

    2016-01-01

    sample. Determinants of vitamin D status were also explored. A random sample of 4130 people from the population of Copenhagen with ages 41–71 years were invited (N = 4130) and 2650 participants were included. Ultrasound examinations were performed to assess gallstone status and blood samples were drawn...... to assess 25-hydroxyvitamin D and biomarkers of renal and hepatic function. Gallstone disease was found in 422 participants. Associations were estimated by logistic regression models. Levels of 25-hydroxyvitamin D was not significantly associated with gallstone disease. Time of birth during low vitamin D....... Findings suggest gallstones to be associated to low vitamin D exposure in utero and to renal failure suggesting that vitamin D might have an impact on gallstone disease. Future studies should explore associations for vitamin D and gallstone disease prospectively....

  2. Gallstones | Njeze | Nigerian Journal of Surgery

    African Journals Online (AJOL)

    Gallstone disease is a worldwide medical problem, but the incidence rates show substantial geographical variation, with the lowest rates reported in African populations. Publications in English language on gallstones which were obtained from reprint requests and PubMed database formed the basis for this paper.

  3. Bile anaerobic bacteria detection and antibiotic susceptibility in patients with gallstone.

    Science.gov (United States)

    Lu, Yun; Xiang, Ting-Hai; Shi, Jing-Sen; Zhang, Bing-Yuan

    2003-08-01

    To detect bile anaerobic bacteria and antibiotic susceptibility in 59 patients with gallstones who had had cholecystectomy. BACT/ALERT 120 microbe detection system and SCEPTOR microbe detection system were used to detect bile anaerobic bacteria, antibiotic susceptibility. The ratio of anaerobic bacteria to the patients examined was 52.5% (31/59). Obligate anaerobe bile culture showed positive results in 4 patients. B. fragilis (37.8%) was the major type of anaerobic bacteria in bile. Most (81.8%) of anaerobic bacteria were sensitive to metronidazole, and imipenem was suitable for beta-lactamase bacteria. Culture of anaerobic bacteria in logarithmic phase can improve the positive rate of the culture. There are some relations between anaerobic infection and gallstone formation.

  4. Stereoselective formation of a cholesterol ester conjugate from fenvalerate by mouse microsomal carboxyesterase(s).

    Science.gov (United States)

    Miyamoto, J; Kaneko, H; Takamatsu, Y

    1986-06-01

    In accordance with in vivo findings, of the four chiral isomers of fenvalerate (S-5602 Sumicidin, Pydrin, [RS]-alpha-cyano-3-phenoxybenzyl [RS]-2-(4-chlorophenyl)isovalerate), only the [2R, alpha S]-isomer (B-isomer) yielded cholesteryl [2R]-2-(4-chlorophenyl)isovalerate (CPIA-cholesterol ester) in the in vitro study using several tissue homogenates of mice, rats, dogs, and monkeys. There were species differences in the extent of CPIA-cholesterol-ester formation, with mouse tissues showing relatively higher activity than those of other animals. The kidney, brain, and spleen of mice showed relatively higher capacities to form this ester compared to other tissues, and the enzyme activity was mainly localized in microsomal fractions. The CPIA-cholesterol ester did not seem to be produced by three known biosynthetic pathways of endogenous cholesterol esters--acyl-CoA:cholesterol O-acyltransferase (ACAT), lecithin:cholesterol O-acyltransferase (LCAT), and cholesterol esterase. Carboxyesterase(s) of mouse kidney microsomes solubilized by digitonin hydrolyzed only the B alpha-isomer of fenvalerate, yielding CPIA, whereas they yielded the corresponding cholesterol ester in the presence of artificial liposomes containing cholesterol. Thus, it appears that the stereoselective formation of the CPIA-cholesterol ester results from the stereoselective formation of the CPIA-carboxyesterase complex only from the B alpha-isomer, which subsequently undergoes cleavage by cholesterol to yield the CPIA-cholesterol ester.

  5. Study of different concentric rings inside gallstones with LIBS.

    Science.gov (United States)

    Pathak, Ashok Kumar; Singh, Vivek Kumar; Rai, Nilesh Kumar; Rai, Awadhesh Kumar; Rai, Pradeep Kumar; Rai, Pramod Kumar; Rai, Suman; Baruah, G D

    2011-07-01

    Gallstones obtained from patients from the north-east region of India (Assam) were studied using laser-induced breakdown spectroscopy (LIBS) technique. LIBS spectra of the different layers (in cross-section) of the gallstones were recorded in the spectral region 200-900 nm. Several elements, including calcium, magnesium, manganese, copper, silicon, phosphorus, iron, sodium and potassium, were detected in the gallstones. Lighter elements, including carbon, hydrogen, nitrogen and oxygen were also detected, which demonstrates the superiority of the LIBS technique over other existing analytical techniques. The LIBS technique was applied to investigate the evolution of C(2) swan bands and CN violet bands in the LIBS spectra of the gallstones in air and an argon atmosphere. The different layers (dark and light layers) of the gallstones were discriminated on the basis of the presence and intensities of the spectral lines for carbon, hydrogen, nitrogen, oxygen and copper. An attempt was also made to correlate the presence of major and minor elements in the gallstones with the common diet of the population of Assam.

  6. Vegetarian diet as a risk factor for symptomatic gallstone disease.

    Science.gov (United States)

    McConnell, T J; Appleby, P N; Key, T J

    2017-06-01

    Previous small studies have shown either no difference or a lower risk of symptomatic gallstone disease in vegetarians than in non-vegetarians. This study examined the incidence of symptomatic gallstone disease in a cohort of British vegetarians and non-vegetarians, and investigated the associations between nutrient intake and risk of symptomatic gallstone disease. The data were analysed from 49 652 adults enroled in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Oxford study, one-third of whom were vegetarian. The linked databases of hospital records were used to identify incident cases. Risk by diet group was estimated using Cox proportional hazards models. Further analysis quantified risk by intakes of selected macronutrients. There were 1182 cases of symptomatic gallstone disease during 687 822 person-years of follow-up (mean=13.85 years). There was a large significant association between increasing body mass index (BMI) and risk of developing symptomatic gallstone disease (overall trend Pvegetarians had a moderately increased risk compared with non-vegetarians (HR: 1.22; 95% CI: 1.06-1.41; P=0.006). Although starch consumption was positively associated with gallstones risk (P=0.002 for trend), it did not explain the increased risk in vegetarians. There is a highly significant association of increased BMI with risk of symptomatic gallstone disease. After adjusting for BMI, there is a small but statistically significant positive association between vegetarian diet and symptomatic gallstone disease.

  7. Effect of Ursodeoxycholic Acid Alone and Ursodeoxycholic Acid Plus Domperidone on Radiolucent Gallstones and Gallbladder Contractility in Humans

    Directory of Open Access Journals (Sweden)

    Ilyas Tuncer

    2012-01-01

    Full Text Available Background/Aims. The aim of this study was to compare the effects of ursodeoxycholic acid (UDCA alone and UDCA plus domperidone on dissolution of solitary or multiple gallstones. Methods. Fifty-three patients with cholesterol gallstones were randomized into three treatment groups: group I (=22 was given UDCA (15 mg/kg/day alone and group II (=18 was treated with domperidone (30 mg/day in addition to UDCA. The control group (=13 was followed without a medical treatment. Gallbladder volumes and ejection fractions were measured sonographically in all patients before and after treatment. Results. After 12 months of treatment, stone dissolution was found in 9 (40.9% of the patients in group I and 7 (38.8% of the patients in group II. The difference was statistically significant compared to controls in both treatment groups (0.05. All the patients that achieved dissolution had multiple gallstones except for one patient with a solitary stone in group I. Neither monotherapy of UDCA nor the combination with domperidone affected the ejection fraction of gallbladder. Conclusions. Combination with domperidone did not potentiate the efficacy of UDCA. It has been observed that both UDCA alone and UDCA plus domperidone treatment did not affect ejection fraction of gallbladder.

  8. Association Between Screen-Detected Gallstone Disease and Cancer in a Cohort Study

    DEFF Research Database (Denmark)

    Shabanzadeh, Daniel Mønsted; Sørensen, Lars Tue; Jørgensen, Torben

    2017-01-01

    , sigmoid colon, and rectal cancers were not associated with gallstone disease. Breast cancer had a weak association with gallstone disease depending on other factors (10.6% of patients with gallstone disease vs 7.41% without; hazard ratio, 1.44; 95% confidence interval, 0.99-2.11). Pooled...... ratio, 1.50; 95% confidence interval, 1.12-2.01). Right-side colon cancer was also associated with gallstone disease (2.57% of patients with gallstone disease vs 0.96% without; hazard ratio, 2.04; 95% confidence interval, 1.10-3.78). Pancreatic, esophageal, gastric, pooled colorectal, left-side colon...... nongastrointestinal and prostate cancers were not associated with gallstone disease. Conclusions: Screen-detected gallstone disease in the general population is associated with pooled gastrointestinal and right-side colon cancers. These associations are not due to detection bias or cholecystectomy. Further studies...

  9. The prevalence and risk factors for cholelithiasis and asymptomatic gallstones in adults with congenital heart disease.

    Science.gov (United States)

    Shiina, Yumi; Toyoda, Tomohiko; Kawasoe, Yasutaka; Tateno, Shigeru; Shirai, Takeaki; Matsuo, Kozo; Mizuno, Yoshiko; Ai, Toshiji; Niwa, Koichiro

    2011-10-20

    Cyanosis is considered to be a risk factor for cholelithiasis which is an important complication of cyanotic congenital heart disease (CCHD) in adults. In this study, the prevalence of cholelithiasis and asymptomatic calcium bilirubinate gallstones was evaluated in adults with congenital heart disease (CHD). Furthermore, risk factors for this potentially high risk complication were assessed. Subjects were derived from 114 consecutive congenital patients who visited our center from May 2008 to January 2009. For analyses of risk factors, we divided them into 4 groups: group A, 15 CCHD patients without reparative surgery (7 men, 31.8 ± 7.0 years old); group B, 41 CCHD patients rendered acyanotic by reparative surgery (21 men, 32.5 ± 11.8 years old); group C, 23 unoperated acyanotic CHD patients (11 men, 42.4 ± 16.4 years old); and group D, 35 patients who were acyanotic before and after operation (18 men, 36.3 ± 14.8 years old). Gallstones were identified by abdominal ultrasound and risk factors were analyzed by a multivariate logistic regression model. Cholecystectomy was performed in 5/114 (4.3%), asymptomatic gallstones were seen in 16/114 (14%), and symptomatic gallstones except for patients after cholecystectomy were seen in 7/114 (6.1%). In group A, 4 (27%) with gallstones underwent cholecystectomy (pnobody in group C, and 3 patients (8.6%) in group D. By a multivariate logistic regression model, CCHD by nature regardless of repair, prolonged cyanosis periods, higher frequency of cardiopulmonary bypass (CPB), and lower platelet counts were significant factors predicting gallstones (odds ratio 4.48, 1.08, 3.96, and 0.87, 95% CI, 1.14-17.5, 1.00-1.18, 1.65-9.54, and 0.75-0.99, respectively). The prevalence of cholelithiasis and asymptomatic gallstones is significantly high in CCHD patients regardless of cardiac repairs. CCHD by nature, prolonged cyanosis durations, high frequency of CPB and low platelet counts have influences on gallstone formation in adults

  10. New strategies for the treatment of gallstone disease

    NARCIS (Netherlands)

    Keulemans, Y. C. A.; Venneman, N. G.; Gouma, D. J.; van Berge Henegouwen, G. P.

    2002-01-01

    Background: Symptomatic gallstones are generally accepted as being the indication for cholecystectomy. Generally, severe abdominal pain in epigastrium and in the right upper abdominal quadrant, and lasting for more than 15 min, is thought to be caused by gallstones. However, many patients with other

  11. Kinetics of 25-hydroperoxycholesterol formation during photo-oxidation of crystalline cholesterol.

    Science.gov (United States)

    Medina-Meza, Ilce Gabriela; Rodriguez-Estrada, Maria Teresa; Lercker, Giovanni; Barnaba, Carlo; García, Hugo Sergio

    2014-06-01

    25-Hydroxycholesterol (25-OH), a side-chain product of cholesterol oxidation, has emerged as one of the important issues in food chemistry and biochemistry, because of its involvement in several human pathologies. This oxysterol is derived from both enzymatic and non-enzymatic pathways. However, the latter mechanism has been scarcely studied in either food or model systems. In this work, a kinetic model was developed to evaluate the formation of 25-OH and its precursor 25-hydroperoxycholesterol (25-OOH) during photo-oxidation of cholesterol for 28 days under fluorescent light. 25-OOH was estimated by an indirect method, using thin-layer chromatography coupled with gas chromatography-mass spectrometry. Peroxide value (POV) and cholesterol oxidation products (COPs) were determined. POV showed a hyperbolic behavior, typical of a crystalline system in which the availability of cholesterol is the limiting factor. Further reactions of hydroperoxides were followed; in particular, after photo-oxidation, 25-OOH (0.55 mg g(-1) ) and 25-OH (0.08 mg g(-1) ) were found in cholesterol, as well as seven other oxysterols, including 7-hydroxy and 5,6-epoxy derivatives. The application of kinetic models to the data showed good correlation with theoretical values, allowing derivation of the kinetic parameters for each oxidation route. The results of this work confirm that cholesterol in the crystalline state involves different oxidation patterns as compared to cholesterol in solution. Moreover, the numerical fit proved that hydroperoxidation is the rate-limiting step in 25-OH formation. © 2013 Society of Chemical Industry.

  12. Gallstone fragmentation by control electrohydraulic lithotripsy

    International Nuclear Information System (INIS)

    Tung, G.A.; Mueller, P.R.; Brink, J.A.; Saini, S.; Picus, D.; Simeone, J.F.; Ferrucci, J.T.

    1989-01-01

    The authors have performed in vitro contact electrohydraulic lithotripsy (EHL) of 100 gallstones > 10 mm in diameter to identify physical and technical factors that affect fragmentation success. Ninety-one of 100 stones were fragmented with a 3-F electrode (average, seven shocks; range, 1--42); only 12 stones were fragmented with a single shock. Of the nine stones refractory to 50 shocks, four were > 30 mm in diameter and five stones were densely calcified. The most important variable determining power requirements for fragmentation was gallstone size (R = .58), but radiographic calcification of gallstones was also important (R = .47). Stones < 15 mm tended to produce fragments of left-angle 2 mm; stones right-angle 20 mm tended to produce two to five large discrete fragments (P , .05). In addition, lithotripsy could be conducted equally well in 1:1 dilute diatrizoate contrast agent as in 1:6 normal saline, suggesting that contact EHL could be performed under fluoroscopy

  13. Sonographic demonstration of a gallstone ileus

    International Nuclear Information System (INIS)

    Uebel, H.E.; Wilhelm, F.

    1987-01-01

    A woman of 60 years of age with acute abdominal pain, vomiting, constipation and radiological signs of small bowel obstruction was subjected to sonographic examination. Careful examination of the entire abdomen demonstrated a hyperechoic object within the distended terminal ileum with an intensive acoustic shadow. The gallbladder was not visible. This strongly suggested gallstone ileus, especially since the patient had a history of gallbladder disease. She was treated immediately by enterotomy and extraction of a noncalcified obstructing stone. The value of ultrasound in detecting gallstones causing small bowel obstruction is discussed. (orig.) [de

  14. Sonographic demonstration of a gallstone ileus

    Energy Technology Data Exchange (ETDEWEB)

    Uebel, H.E.; Wilhelm, F.

    1987-04-01

    A woman of 60 years of age with acute abdominal pain, vomiting, constipation and radiological signs of small bowel obstruction was subjected to sonographic examination. Careful examination of the entire abdomen demonstrated a hyperechoic object within the distended terminal ileum with an intensive acoustic shadow. The gallbladder was not visible. This strongly suggested gallstone ileus, especially since the patient had a history of gallbladder disease. She was treated immediately by enterotomy and extraction of a noncalcified obstructing stone. The value of ultrasound in detecting gallstones causing small bowel obstruction is discussed.

  15. Optimal timing of cholecystectomy in children with gallstone pancreatitis.

    Science.gov (United States)

    Badru, Faidah; Saxena, Saurabh; Breeden, Robert; Bourdillon, Maximillan; Fitzpatrick, Colleen; Chatoorgoon, Kaveer; Greenspon, Jose; Villalona, Gustavo

    2017-07-01

    Little data exist regarding the recurrence of pancreatitis in pediatric patients with gallstone pancreatitis awaiting cholecystectomy. This study evaluates the recurrence rate of pancreatitis after acute gallstone pancreatitis based on the timing of cholecystectomy in pediatric patients. A retrospective chart review of all patients admitted with gallstone pancreatitis from 2007 to 2015 was performed. Children were divided into the following five groups. Group 1 had surgery during the index admission. Group 2 had surgery within 2 wk of discharge. Group 3 had surgery between 2 and 6 wk postdischarge. Group 4 had surgery 6 wk after discharge, and group 5 patients had no surgery. The recurrence rates of pancreatitis were calculated for all groups. Forty-eight patients with gallstone pancreatitis were identified in this study. The 19 patients in group 1 had no recurrence of their pancreatitis. Of the remaining 29 patients, nine (31%) had recurrence of pancreatitis or required readmission for abdominal pain prior to their cholecystectomy. In group 2, two of the eight patients (25%) had recurrent pancreatitis. In group 3, three of eight patients (37.5%) developed recurrent pancreatitis. In group 4, three of five patients (60%), and in group 5, one of eight. No children in group 5 had demonstrable gallstones at presentation, only sludge in their gallbladder. Cholecystectomy during the index admission is associated with no recurrence or readmission for pancreatitis. Therefore, we recommend that cholecystectomy be performed after resolution of an episode of gallstone pancreatitis during index admission. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Lifestyle and gallstone disease: Scope for primary prevention

    Directory of Open Access Journals (Sweden)

    Sandeep Sachdeva

    2011-01-01

    Full Text Available Objective : To study the antecedent risk factors in the causation of gallstone disease in a hospital-based case control study. Materials and Methods: Cases (n = 150 from all age groups and both sexes with sonographically proven gallstones were recruited over a duration of 3 months from the surgical wards of a tertiary care teaching hospital. Modes of presentation were also noted among cases. Age- and sex-matched controls (n = 150 were chosen from among ward inmates admitted for other reasons. Univariate and multivariate logistic regression analyses were performed for selected sociodemographic, dietary, and lifestyle-related variables. Results : Females had a higher prevalence of gallstone disease than males (P 60 years was relatively more susceptible (28%. Prepubertal age group was least afflicted (3.3%. Univariate analysis revealed multiparity, high fat, refined sugar, and low fiber intakes to be significantly associated with gallstones. Sedentary habits, recent stress, and hypertension were also among the significant lifestyle-related factors. High body mass index and waist hip ratios, again representing unhealthy lifestyles, were the significant anthropometric covariates. However, only three of these, viz., physical inactivity, high saturated fats, and high waist hip ratio emerged as significant predictors on stepwise logistic regression analysis (P < 0.05. Conclusion : Gallstone disease is frequent among females and elderly males. Significant predictor variables are abdominal adiposity, inadequate physical activity, and high intake of saturated fats; thus representing high risk lifestyles and yet amenable to primary prevention.

  17. Intra-Hepatic Spillage of Gallstones as a Late Complication of Laparoscopic Cholecystectomy: MR Imaging Findings

    International Nuclear Information System (INIS)

    Ragozzino, Alfonso; Puglia, Marta; Romano, Federica; Imbriaco, Massimo

    2016-01-01

    Spillage of gallstones in the abdominal cavity may rarely occur during the course of laparoscopic cholecystectomy. Dropped gallstones in the peritoneal and extra-peritoneal cavity are usually asymptomatic. However, they may lead to abscess formation with an estimated incidence of about 0.3%. Common locations of the abscess are in the abdominal wall followed by the intra-abdominal cavity, usually in the sub-hepatic or retro-peritoneum inferior to the sub-hepatic space. We hereby describe an unusual case of infected spilled gallstones in the right sub-phrenic space, prospectively detected on abdominal MRI performed two years after laparoscopic cholecystectomy, in a patient with only a mild right-sided abdominal complaint. This case highlights the role of MRI in suggesting the right diagnosis in cases with vague or even absent symptomatology. In our case the patient’s history together with high quality abdomen MRI allowed the correct diagnosis. Radiologists should be aware of this rare and late onset complication, even after many years from surgery as an incidental finding in almost asymptomatic patients

  18. Formation of 3D cholesterol crystals from 2D nucleation sites in lipid bilayer membranes: implications for atherosclerosis.

    Science.gov (United States)

    Varsano, Neta; Fargion, Iael; Wolf, Sharon G; Leiserowitz, Leslie; Addadi, Lia

    2015-02-04

    Atherosclerosis is the major precursor of cardiovascular disease. The formation of cholesterol crystals in atherosclerotic plaques is associated with the onset of acute pathology. The cholesterol crystals induce physical injury in the plaque core, promoting cell apoptosis and triggering an increased inflammatory response. Herein we address the question of how cholesterol crystal formation occurs in atherosclerosis. We demonstrate that three-dimensional (3D) cholesterol crystals can undergo directed nucleation from bilayer membranes containing two-dimensional (2D) cholesterol crystalline domains. We studied crystal formation on supported lipid bilayers loaded with exogenous cholesterol and labeled using a monoclonal antibody that specifically recognizes ordered cholesterol arrays. Our findings show that 3D crystals are formed exclusively on the bilayer regions where there are segregated 2D cholesterol crystalline domains and that they form on the domains. This study has potentially significant implications for our understanding of the crucial step in the mechanism by which atherosclerotic lesions form.

  19. Clinical, ultrasonographic, and roentgenographic study in 134 asymptomatic gallstone carriers

    International Nuclear Information System (INIS)

    Lirussi, F.; Passera, D.; Iemmolo, R.M.; Nassuato, G.; Okolicsanyi, L.

    1993-01-01

    The authors investigated retrospectively the ultrasonographic and roentgenographic characteristics of the gallstones and the gallbladder in 134 symtom-free carriers and evaluated prospectively the outcome and side effects of 6 to 24 months' ursodeoxycholic acid (UDCA) therapy in 36 individuals with silent stones. Two-thirds of the 134 subjects had multiple stones, and 71 to 75% had stones less than 15 mm in diameter. Gallstone calcification was detected in 13%. A non-functioning gallbladder was observed in 19%, whereas gallbladder contraction was normal in 64 of 76 gallstone carriers. With regard to oral bile acid treatment, complete and partial dissolutions were achieved in 7 and 9 of 33 subjects, respectively (48.5%). Development of a non-functioning gallbladder occurred in 9%, and acquired gallstone calcification was seen in another 15%. It is concluded that: i) the characteristics of the gallstones and the gallbladder are similar to those observed in symptomatic patients, and ii) UDCA therapy may be given in selected symptom-free carriers for no more than 6 to 12 months. Thereafter, it does not appear to be cost-effective. 23 refs., 2 figs., 3 tabs

  20. Influence of dietary tender cluster beans (Cyamopsis tetragonoloba) on biliary proteins, bile acid synthesis and cholesterol crystal growth in rat bile.

    Science.gov (United States)

    Raghavendra, Chikkanna K; Srinivasan, Krishnapura

    2015-02-01

    Tender cluster beans (CBs; Cyamopsis tetragonoloba) are observed to possess anti-lithogenic potential in experimental mice. Formation of cholesterol gallstones in gallbladder is controlled by procrystallizing and anticrystallizing factors present in bile in addition to supersaturation of cholesterol. This study aimed at evaluating the influence of CB on biliary glycoproteins, low molecular weight (LMW) and high molecular weight (HMW) proteins, cholesterol nucleation time, and cholesterol crystal growth in rat hepatic bile. Groups of rats were fed for 10 weeks with 0.5% cholesterol to render the bile lithogenic. Experimental dietary interventions were: 10% freeze-dried CB, 1% garlic powder or their combination. Incorporation of CB into HCD decreased the cholesterol saturation index in bile, increased bile flow and biliary glycoproteins. Dietary CB prolonged cholesterol nucleation time in bile. Electrophoresis of biliary proteins showed the presence of high concentration of 27 kDa protein which might be responsible for the prolongation of cholesterol nucleation time in the CB fed group. Proteins of 20 kDa and 18 kDa were higher in CB treated animals, while the same were less expressed in HCD group. Biliary proteins from CB fed animals reduced cholesterol crystal growth index which was elevated in the presence of proteins from HCD group. Cholesterol-7α-hydroxylase and cholesterol-27-hydroxylase mRNA expression was increased in CB treated animals contributing to the bile acid synthesis. Thus, the beneficial anti-lithogenic effect of dietary CB which primarily is due to reduced cholesterol saturation index was additionally affected through a modulation of the nucleating and anti-nucleating proteins that affect cholesterol crystallization. Copyright © 2014 Elsevier Inc. All rights reserved.

  1. Gallstone Ileus: An Unlikely Cause of Mechanical Small Bowel Obstruction

    Directory of Open Access Journals (Sweden)

    Estela Abich

    2017-06-01

    Full Text Available Gallstone ileus is a rare disease that accounts for 1–4% of intestinal obstructions. Almost exclusively a condition in the older female population, it is a difficult diagnosis to make. We report the case of gallstone ileus in a 94-year-old Caucasian female, who presented to the emergency department with acute-onset nausea, coffee-ground emesis, lack of bowel movement, and abdominal distension. On CT scan, the diagnosis of gallstone ileus was made by the presence of a cholecystoduodenal fistula, pneumobilia, and small bowel obstruction. Emergent laparotomy with a one-stage procedure of enterolithotomy and stone removal by milking the bowel distal to the stone were performed. The postoperative course was uneventful until postoperative day 4 when the patient was found tachycardic, lethargic, and unresponsive. We reviewed the literature on the diagnosis and treatment of gallstone ileus.

  2. Concanavalin A-binding cholesterol crystallization inhibiting and promoting activity in bile from patients with Crohn's disease compared to patients with ulcerative colitis

    NARCIS (Netherlands)

    Keulemans, Y. C.; Mok, K. S.; Slors, J. F.; Brink, M. A.; Gouma, D. J.; Tytgat, G. N.; Groen, A. K.

    1999-01-01

    BACKGROUND/AIMS: Crohn's disease is a risk factor for gallstone formation. In contrast, patients with ulcerative colitis have an incidence of gallstone formation comparable to the general population. The reason for this difference is not known. The aim of this study was to elucidate the factors

  3. Effect of fat intake on cholesterol turnover and bile acid formation

    International Nuclear Information System (INIS)

    Iritani, Nobuko; Fukuda, Eiko; Ibamoto, Kazuko

    1977-01-01

    Three groups of male rats were maintained on diets containing different amounts of fat. After one week on such regimens, they were injected intraperitoneally with cholesterol- 3 H. During the following 28 days, the radioactivity and quantity of fecal cholesterol and its metabolites were determined. The coprostanol excretion was the about same in all groups and the bile acids excretion increased with increasing fat intake; however, compared to the fat-free group, the excretion of the injected cholesterol- 3 H was greater in the 3% fat group and less in the 10% fat group. Consequently, the specific radioactivity of bile acids was lower in the 10% group than in the others. The half-life of labelled cholesterol was 12.6, 16.0 and 22.2 days for the 3%, 10% fat and fat-free groups, respectively. Rather than a fat-free diet, a low-fat diet of 3% or so, would be of more advantage in eliminating cholesterol by increasing the formation of bile acids to emulsify the fat. In the 10% fat group, however, the enlarged pool size of bile acid probably delayed cholesterol metabolism to bile acids. (auth.)

  4. Increased Risk of Gallstone Disease Following Colectomy for Ulcerative Colitis

    DEFF Research Database (Denmark)

    Mark-Christensen, Anders; Brandsborg, Søren; Laurberg, Søren

    2017-01-01

    Objectives:Biochemical studies suggest that patients who have had a colectomy or restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) are at an increased risk of developing gallstone disease, but epidemiological studies are lacking. We evaluated the risk of gallstone disease follo...

  5. Four Susceptibility Loci for Gallstone Disease Identified in a Meta-analysis of Genome-Wide Association Studies

    DEFF Research Database (Denmark)

    Joshi, Amit D; Andersson, Charlotte; Buch, Stephan

    2016-01-01

    discovery studies (8720 cases and 55,152 controls). We performed an inverse variance weighted, fixed-effects meta-analysis of study-specific estimates to identify single-nucleotide polymorphisms that were associated independently with gallstone disease. Associations were replicated in 6489 cases and 62...... in TM4SF4 (OR, 1.12; 95% CI, 1.08-1.16; P = 6.09 × 10(-11)), rs2547231 in SULT2A1 (encodes a sulfoconjugation enzyme that acts on hydroxysteroids and cholesterol-derived sterol bile acids) (OR, 1.17; 95% CI, 1.12-1.21; P = 2.24 × 10(-10)), rs1260326 in glucokinase regulatory protein (OR, 1.12; 95% CI, 1...

  6. Cholesterol is essential for mitosis progression and its deficiency induces polyploid cell formation

    International Nuclear Information System (INIS)

    Fernandez, Carlos; Lobo, Maria del Val T.; Gomez-Coronado, Diego; Lasuncion, Miguel A.

    2004-01-01

    As an essential component of mammalian cell membranes, cells require cholesterol for proliferation, which is either obtained from plasma lipoproteins or synthesized intracellularly from acetyl-CoA. In addition to cholesterol, other non-sterol mevalonate derivatives are necessary for DNA synthesis, such as the phosphorylated forms of isopentane, farnesol, geranylgeraniol, and dolichol. The aim of the present study was to elucidate the role of cholesterol in mitosis. For this, human leukemia cells (HL-60) were incubated in a cholesterol-free medium and treated with SKF 104976, which inhibits cholesterol biosynthesis by blocking sterol 14α-demethylase, and the expression of relevant cyclins in the different phases of the cell cycle was analyzed by flow cytometry. Prolonged cholesterol starvation induced the inhibition of cytokinesis and the formation of polyploid cells, which were multinucleated and had mitotic aberrations. Supplementing the medium with cholesterol completely abolished these effects, demonstrating they were specifically due to cholesterol deficiency. This is the first evidence that cholesterol is essential for mitosis completion and that, in the absence of cholesterol, the cells fail to undergo cytokinesis, entered G1 phase at higher DNA ploidy (tetraploidy), and then progressed through S (rereplication) into G2, generating polyploid cells

  7. The development of Gallstone solvent temperature adaptive PID control system

    Institute of Scientific and Technical Information of China (English)

    MA; BING; QIAO; BO; YAN

    2012-01-01

    The paper expatiated the work principle,general project,and the control part of the corresponding program of the temperature system in the gallstone dissolving instrument.Gallstone dissolving instrument adopts automatic control solvent cycle of direct solution stone treatment,replacing the traditional external shock wave rock row stone and gallblad-der surgery method.PID control system to realize the gall stone solvent temperature intelligent control,the basic principle of work is as solvent temperature below the set temperature,the relay control heater to solvent to be heated,conversely,no heating,achieve better able to dissolve the the rapeutic effect of gallstones.

  8. Update on dissolution of gallstones with methyl-tert-butyl ether

    International Nuclear Information System (INIS)

    van Sonnenberg, E.; D'Agostino, H.B.; Hofmann, A.F.; Casola, G.; Varney, R.R.; Jinich, H.; Steingart, C.; McQuade, K.; Hoyt, D.

    1989-01-01

    The authors have studied 50 patients who underwent percutaneous MTBE dissolution of gallstones with or without supplemental basketing. All patients had symptomatic gallbladder or ductal stones. Five patients underwent emergency gallbladder drainage for acute calculous cholecystitis; after recovery, their gallstones were dissolved or removed. The other 45 patients had elective gallstone dissolution; preliminary studies on these patients included plain film, US, oral cholecystography, and CT. Follow-up studies were chromatography, US, and cholecystography. Three patients underwent cholecystectomy after MTBE treatment; no averse effects of MTBE were seen histologically. Three patients had stone recurrence. The majority of patients were placed on ursodeoxycholic acid after stone dissolution

  9. Systematic review with meta-analysis: coffee consumption and the risk of gallstone disease.

    Science.gov (United States)

    Zhang, Y-P; Li, W-Q; Sun, Y-L; Zhu, R-T; Wang, W-J

    2015-09-01

    Epidemiologic evidence on coffee consumption reducing the risk of gallstone disease has been contradictory. To perform a meta-analysis of observational studies, to investigate an association and dose-response of coffee consumption with gallstone disease. We used PubMed and EMBASE databases to identify all published studies before June 2015. A random-effects model was used to compute a pooled relative risk (RR) and corresponding 95% confidence intervals (CIs). One case-control study and five prospective cohort studies (with seven cohorts) involving 227,749 participants and 11,477 gallstone disease cases were included. Coffee consumption was significantly associated with a reduced risk of gallstone disease (RR, 0.83; 95% CI, 0.76 to 0.89; I(2) = 35.9%), based on prospective studies; specifically, we observed an inverse relation in females, but not in males. The case-control study did not reveal any association between coffee and gallstone disease (OR, 0.99; 95% CI, 0.64 to 1.53). In a dose-response analysis, the RR of gallstone disease was 0.95 (95% CI, 0.91 to 1.00; P = 0.049) per 1 cup/day of coffee consumption. A significant nonlinear dose-response association was also identified (P for nonlinearity = 0.0106). For people who drank 2, 4 and 6 cups of coffee per day, the estimated RRs of gallstone disease were 0.89 (95% CI, 0.79 to 0.99), 0.81 (95% CI, 0.72 to 0.92) and 0.75 (95% CI, 0.64 to 0.88), respectively, compared with the lowest level drinkers. This study suggests that coffee consumption is related to a significantly decreased risk of gallstone disease. © 2015 John Wiley & Sons Ltd.

  10. High Prevalence of Gallstone Disease in Rheumatoid Arthritis: A New Comorbidity Related to Dyslipidemia?

    Science.gov (United States)

    García-Gómez, María Carmen; de Lama, Eugenia; Ordoñez-Palau, Sergi; Nolla, Joan Miquel; Corbella, Emili; Pintó, Xavier

    2017-08-01

    To assess the prevalence of gallstone disease and identify associated risk factors in rheumatoid arthritis (RA) patients compared to the general population. Eighty-four women with rheumatoid arthritis were included in the study. Each patient was assessed via a structured interview, physical examination, abdominal ultrasound and blood test including lipid profile. The prevalence of gallstone disease in rheumatoid arthritis was compared with data from a study of the Spanish population matched by age groups. Twenty-eight of the 84 women had gallstone disease (33.3%). RA women with and without gallstone disease were similar in most of the variables assessed, except for older age and menopausal status in the former. A greater prevalence of gallstone disease was seen in rheumatoid arthritis patients compared to the general population of the same age; however, the differences were significant only in women aged 60 or older (45.5% versus 23.1% respectively, P-value .008). The age-adjusted OR of developing gallstone disease in RA women compared with general population women was 2,3 (95% CI: 1.3-4.1). A significantly higher HDL3-c subfraction and higher apoA-I/HDL and HDL3-c/TC ratios were observed in patients with gallstone disease. Women with rheumatoid arthritis may have a predisposition to gallstones that can manifest in middle or older age compared with women in the general population. This situation could be related to chronic inflammation and HDL metabolism. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  11. Are incident gallstones associated to sex-dependent changes with age? A cohort study

    DEFF Research Database (Denmark)

    Shabanzadeh, D M; Holmboe, S A; Sørensen, L T

    2017-01-01

    Age and female sex have repeatedly been identified as gallstone determinants but the underlying mechanisms are not clarified. The objectives of this study were to determine if changes with age in physiology, lifestyle, or reproductive hormones were associated with incident gallstones. A cohort...... pressure, blood lipids, self-rated health), lifestyle (smoking, alcohol and coffee consumption, dietary habits, physical activity level), and indices of reproductive function (number of births, oral contraceptive use, hormone replacement therapy, male reproductive hormones) were explored in females...... (OR) 0.94, 95% confidence interval (CI) [0.90; 0.98]) and the cessation of hormone replacement therapy (OR 0.29, 95% CI [0.10; 0.83]) inversely determined incident gallstones. In males, increasing levels of SHBG (OR 0.97, 95% CI [0.94; 0.998]) inversely determined incident gallstones. Other changes...

  12. Determinants for Clinical Events in Gallstone Carriers Unaware of their Gallstones

    DEFF Research Database (Denmark)

    Mønsted Shabanzadeh, Daniel; Sørensen, Lars Tue; Jørgensen, Torben

    2017-01-01

    , vocational training, and inversely association to a higher physical activity level when compared to being sedentary. Multiple adjusted models confirmed association for total events and body mass index and for complicated events and physical activity. No significant associations were identified for alcohol......, coffee, diet, smoking, or visits to general practitioner and clinical events. CONCLUSIONS: Body mass index, vocational training, and physical activity level were associated to clinical events in long-term follow-up of unaware gallstone carriers. Future trials should investigate clinical effects...

  13. Known risk factors do not explain disparities in gallstone prevalence between Denmark and northeast Germany

    DEFF Research Database (Denmark)

    Friedrich, Nele; Völzke, Henry; Hampe, Jochen

    2009-01-01

    OBJECTIVES: Gallstones are a common disease worldwide, with disparities in the prevalence of the disease in different settings. The aim of the present study was to assess if different distributions of risk factors could explain the disparities in the prevalence of gallstone disease between Denmark...... and northeast Germany. METHODS: Data of 5,559 subjects from the Danish MONICA survey and of 3,647 subjects of the German Study of Health in Pomerania were investigated. Gallstone disease was defined as a prior history of cholecystectomy or the presence of sonographically diagnosed gallstones. Logistic...... regression models were performed to assess the confounding effect of selected risk factors on regional disparities in gallstone disease. RESULTS: After adjustment for age and vocational training, German subjects (women: Odds ratio, OR, 2.46 (95% confidence interval, CI: 2.07-2.91); men: OR, 1.89 (95% CI: 1...

  14. Influence of packaging atmosphere on the formation of cholesterol oxides in [gamma]-irradiated egg powder

    Energy Technology Data Exchange (ETDEWEB)

    Lebovics, V.K.; Gaal, O. (National Inst. of Food Hygiene and Nutrition, Budapest (Hungary)); Farkas, J.; Somogyi, L. (University of Horticulture and Food Industry, Budapest (Hungary))

    1993-09-01

    In the present work the influence of aerobic and anoxic conditions have been comparatively investigated to study the chemical changes of cholesterol in [gamma]-irradiated egg powder. The irradiation treatment was carried out with powdered egg packed under air and also under vacuum in polyethylene (PE) bags and in laminated, oxygen impermeable three-layer (polyester-aluminium-polyethylene) foil to dosage levels 2 and 4 kGy at room temperature. The cholesterol oxidation is demonstrated by thin-layer chromatograms. In the egg powder wrapped in Pe bags the predominant cholesterol derivatives -7-hydroxycholesterol isomers ([alpha] and [beta]) - accumulated in significant amounts (increasing with dose) while vacuum-packaging in laminated foil considerably suppressed the quantity of these products and prevented the formation of cholesterol 5[alpha], 6[alpha]-epoxide as well as 7-ketocholesterol. Little or no change was observed in non-irradiated (control) vacuum-packed egg powder stored at approximately 22[sup o]C for up to 5 months. Peroxide values showed changes parallel to the formation of COPs. (author).

  15. Microbiology of bile in symptomatic uncomplicated gallstone disease

    International Nuclear Information System (INIS)

    Ahmad, M.; Akhtar, M.R.; Akhtar, M.R.

    2015-01-01

    To determine the microbiology of the bile culture and antimicrobial susceptibility in patients with symptomatic gallstone disease in our setup. Study Design: A descriptive study. Place and Duration of Study: Surgical Department Combined Military Hospital (CMH) Kharian from Oct, 2010 to Jun, 2011. Patients and Methods: A total of 106 patients underwent cholecystectomy due to symptomatic gallstones and their bile was cultured for aerobic and anaerobic bacteria and culture sensitivity was performed. Data was analysed by using statistical package for social sciences (SPSS) version 13. Results: Bile culture was negative in 81 patients (76.4%) and was positive in only 25 patients (23.6%). Escheria Coli was the most common cultured organism in 10 (40%) patients, Klebsiella in 5 (20%) patients, Pseudomonas in 5 (20%) patients, Proteus in 2 (8%) patients, Staphlococcus aureus in 2 (8%) patients and mixed organisms were cultured in 1 patient (4%). Cefoperazone with sulbactum and Amikacin were the most effective prophylactic antibiotics. Conclusion: Bile in majority of patients with symtomatic uncomplicated gallstone disease is sterile. E. coli is the most commonly cultured organism and cefoperazone with sulbactum and amikacin are the most appropriate antibiotics in our setup. (author)

  16. Abdominal wall sinus due to impacting gallstone during laparoscopic cholecystectomy: an unusual complication.

    Science.gov (United States)

    Pavlidis, T E; Papaziogas, B T; Koutelidakis, I M; Papaziogas, T B

    2002-02-01

    During laparoscopic cholecystectomy, perforation of the gallbladder can occurs in extraction of the gallbladder. The fate of such lost gallstones, which can lead to the formation of an abscess, an abdominal wall mass, or a persistent sinus, has not been studied adequately. Herein we report the case of a persistent sinus of the abdominal wall after an emergent laparoscopic cholecystectomy in an 82-year-old woman with gangrenous cholecystitis and perforation of the friable wall in association with an empyema of the gallbladder. The culture of the obtained pus was positive for Escherichia coli. After a small leak of dirty fluid from the wound of the epigastric port site of 4 months' duration, surgical exploration under local anesthesia revealed that the sinus was caused by spilled gallstones impacting into the abdominal wall between the posterior sheath and left rectus abdominalis muscle. The removal of the stones resulted in complete healing. Long-term complications after laparoscopic cholecystectomy involving the abdominal wall are rare but important possible consequences that could be avoided.

  17. Antilithiasic and Hypolipidaemic Effects of Raphanus sativus L. var. niger on Mice Fed with a Lithogenic Diet

    Science.gov (United States)

    Castro-Torres, Ibrahim Guillermo; Naranjo-Rodríguez, Elia Brosla; Domínguez-Ortíz, Miguel Ángel; Gallegos-Estudillo, Janeth; Saavedra-Vélez, Margarita Virginia

    2012-01-01

    In Mexico, Raphanus sativus L. var. niger (black radish) has uses for the treatment of gallstones and for decreasing lipids serum levels. We evaluate the effect of juice squeezed from black radish root in cholesterol gallstones and serum lipids of mice. The toxicity of juice was analyzed according to the OECD guidelines. We used female C57BL/6 mice fed with a lithogenic diet. We performed histopathological studies of gallbladder and liver, and measured concentrations of cholesterol, HDL cholesterol and triglycerides. The juice can be considered bioactive and non-toxic; the lithogenic diet significantly induced cholesterol gallstones; increased cholesterol and triglycerides levels, and decreased HDL levels; gallbladder wall thickness increased markedly, showing epithelial hyperplasia and increased liver weight. After treatment with juice for 6 days, cholesterol gallstones were eradicated significantly in the gallbladder of mice; cholesterol and triglycerides levels decreased too, and there was also an increase in levels of HDL (P < 0.05). Gallbladder tissue continued to show epithelial hyperplasia and granulocyte infiltration; liver tissue showed vacuolar degeneration. The juice of black radish root has properties for treatment of cholesterol gallstones and for decreasing serum lipids levels; therefore, we confirm in a preclinical study the utility that people give it in traditional medicine. PMID:23093836

  18. Andrographolide Inhibits Oxidized LDL-Induced Cholesterol Accumulation and Foam Cell Formation in Macrophages.

    Science.gov (United States)

    Lin, Hung-Chih; Lii, Chong-Kuei; Chen, Hui-Chun; Lin, Ai-Hsuan; Yang, Ya-Chen; Chen, Haw-Wen

    2018-01-01

    oxLDL is involved in the pathogenesis of atherosclerotic lesions through cholesterol accumulation in macrophage foam cells. Andrographolide, the bioactive component of Andrographis paniculata, possesses several biological activities such as anti-inflammatory, anti-oxidant, and anticancer functions. Scavenger receptors (SRs), including class A SR (SR-A) and CD36, are responsible for the internalization of oxLDL. In contrast, receptors for reverse cholesterol transport, including ABCA1 and ABCG1, mediate the efflux of cholesterol from macrophage foam cells. Transcription factor liver X receptor [Formula: see text] (LXR[Formula: see text] plays a key role in lipid metabolism and inflammation as well as in the regulation of ABCA1 and ABCG1 expression. Because of the contribution of inflammation to macrophage foam cell formation and the potent anti-inflammatory activity of andrographolide, we hypothesized that andrographolide might inhibit oxLDL-induced macrophage foam cell formation. The results showed that andrographolide reduced oxLDL-induced lipid accumulation in macrophage foam cells. Andrographolide decreased the mRNA and protein expression of CD36 by inducing the degradation of CD36 mRNA; however, andrographolide had no effect on SR-A expression. In contrast, andrographolide increased the mRNA and protein expression of ABCA1 and ABCG1, which were dependent on LXR[Formula: see text]. Andrographolide enhanced LXR[Formula: see text] nuclear translocation and DNA binding activity. Treatment with the LXR[Formula: see text] antagonist GGPP and transfection with LXR[Formula: see text] siRNA reversed the ability of andrographolide to stimulate ABCA1 and ABCG1 protein expression. In conclusion, inhibition of CD36-mediated oxLDL uptake and induction of ABCA1- and ABCG1-dependent cholesterol efflux are two working mechanisms by which andrographolide inhibits macrophage foam cell formation, which suggests that andrographolide could be a potential candidate to prevent

  19. Extreme Bilirubin Levels as a Causal Risk Factor for Symptomatic Gallstone Disease

    DEFF Research Database (Denmark)

    Stender, Stefan; Frikke-Schmidt, Ruth; Nordestgaard, Børge G

    2013-01-01

    In individuals without blockage of their bile ducts, levels of plasma bilirubin likely reflect levels of biliary bilirubin; higher biliary bilirubin levels may increase the risk of gallstone disease.......In individuals without blockage of their bile ducts, levels of plasma bilirubin likely reflect levels of biliary bilirubin; higher biliary bilirubin levels may increase the risk of gallstone disease....

  20. Beneficial effect of sulphate-bicarbonate-calcium water on gallstone risk and weight control.

    Science.gov (United States)

    Corradini, Stefano Ginanni; Ferri, Flaminia; Mordenti, Michela; Iuliano, Luigi; Siciliano, Maria; Burza, Maria Antonella; Sordi, Bruno; Caciotti, Barbara; Pacini, Maria; Poli, Edoardo; Santis, Adriano De; Roda, Aldo; Colliva, Carolina; Simoni, Patrizia; Attili, Adolfo Francesco

    2012-03-07

    To investigate the effect of drinking sulphate-bicarbonate-calcium thermal water (TW) on risk factors for atherosclerosis and cholesterol gallstone disease. Postmenopausal women with functional dyspepsia and/or constipation underwent a 12 d cycle of thermal (n = 20) or tap (n = 20) water controlled drinking. Gallbladder fasting volume at ultrasound, blood vitamin E, oxysterols (7-β-hydroxycholesterol and 7-ketocholesterol), bile acid (BA), triglycerides, total/low density lipoprotein and high density lipoprotein cholesterol were measured at baseline and at the end of the study. Food consumption, stool frequency and body weight were recorded daily. Blood lipids, oxysterols and vitamin E were not affected by either thermal or tap water consumption. Fasting gallbladder volume was significantly (P water group (19.0 ± 1.4 mL vs 19.4 ± 1.5 mL). Total serum BA concentration was significantly (P water group (3.41 ± 0.46 μmol vs 2.91 ± 0.56 μmol). The increased BA concentration after TW consumption was mainly accounted for by glycochenodeoxycholic acid. The number of pasta (P water group. Body weight did not change at the end of the study as compared to baseline in both groups. Sulphate-bicarbonate-calcium water consumption has a positive effect on lithogenic risk and intestinal transit and allows maintenance of a stable body weight despite a high food intake.

  1. Cholesterol: a novel regulatory role in myelin formation.

    Science.gov (United States)

    Saher, Gesine; Quintes, Susanne; Nave, Klaus-Armin

    2011-02-01

    Myelin consists of tightly compacted membranes that form an insulating sheath around axons. The function of myelin for rapid saltatory nerve conduction is dependent on its unique composition, highly enriched in glycosphingolipids and cholesterol. Cholesterol emerged as the only integral myelin component that is essential and rate limiting for the development of CNS and PNS myelin. Experiments with conditional mouse mutants that lack cholesterol biosynthesis in oligodendrocytes revealed that only minimal changes of the CNS myelin lipid composition are tolerated. In Schwann cells of the PNS, protein trafficking and myelin compaction depend on cholesterol. In this review, the authors summarize the role of cholesterol in myelin biogenesis and myelin disease.

  2. The effect of extracorporeal shock wave lithotripsy in the management of idiopathic gallstones in children

    Science.gov (United States)

    Mousavi, Seyed Abdollah; Karami, Hasan; Barzegarnejad, Ayub

    2014-01-01

    Objective: The most common etiology for gallstones in children is hemolytic diseases; however, the prevalence of nonhemolytic gallstones, which are mostly idiopathic, is increasing. Several studies concerning the treatment of gallstones with respect to the influence of extracorporeal shock wave lithotripsy (ESWL) have been conducted in adults, but not to the same extent in children. Therefore, this study attempted to examine the effects of lithotripsy on idiopathic gallstones in children. Materials and Methods: In this study, 12 children, all of whom were under 12 years of age and diagnosed with idiopathic gallstones, were treated with ESWL. The average age of the children examined in this study was 6.5 years (range 3-11 years). Patients were treated with 2500-3000 shockwaves per session. The number of shockwaves was 90 shocks/min and the impulse intensity ranged from 10 to 12 kV. The final goal was the fragmentation of stones in pieces with less than 3 mm in dimension. Patients were followed up for 6-30 months. Results: A total of 12 patients were treated with ESWL for 14 rounds. In three patients, complete fragmentation occurred within the first trial and was cleared. The nine remaining patients underwent ESWL 10 times in which an acceptable change in the gallstone's condition was not observed. Five of the patients underwent surgery. The chemical composition of the gallstones showed that the dominant element in them was calcium. Conclusions: Our findings show that performing ESWL can be effective in some children. Further studies with larger population are recommended. Furthermore, it seems increasing the voltage intensity and frequency as conducted in adults accompanied with biliary acids prescription can be effective in children. PMID:25336804

  3. Methods of chemical and phase composition analysis of gallstones

    Science.gov (United States)

    Suvorova, E. I.; Pantushev, V. V.; Voloshin, A. E.

    2017-11-01

    This review presents the instrumental methods used for chemical and phase composition investigation of gallstones. A great body of data has been collected in the literature on the presence of elements and their concentrations, obtained by fluorescence microscopy, X-ray fluorescence spectroscopy, neutron activation analysis, proton (particle) induced X-ray emission, atomic absorption spectroscopy, high-resolution gamma-ray spectrometry, electron paramagnetic resonance. Structural methods—powder X-ray diffraction, infrared spectroscopy, Raman spectroscopy—provide information about organic and inorganic phases in gallstones. Stone morphology was studied at the macrolevel with optical microscopy. Results obtained by analytical scanning and transmission electron microscopy with X-ray energy dispersive spectrometry are discussed. The chemical composition and structure of gallstones determine the strategy of removing stone from the body and treatment of patients: surgery or dissolution in the body. Therefore one chapter of the review describes the potential of dissolution methods. Early diagnosis and appropriate treatment of the disease depend on the development of clinical methods for in vivo investigation, which gave grounds to present the main characteristics and potential of ultrasonography (ultrasound scanning), magnetic resonance imaging, and X-ray computed tomography.

  4. Duodenal Obstruction by a Gallstone (Bouveret's Syndrome Managed by Endoscopic Stone Extraction: A Case Report and Review

    Directory of Open Access Journals (Sweden)

    Franzjosef Schweiger

    1997-01-01

    Full Text Available Gastric outlet obstruction caused by a large gallstone in the duodenum or pylorus (Bouveret's syndrome is a rare complication of gallstone disease. The presenting symptoms are often nonspecific and include nausea, vomiting, epigastric pain and a history of gallbladder disease. Although the diagnosis is established only at surgery in many cases, preoperative recognition by imaging techniques and endoscopy is desirable. Surgical treatment aims at removal of the ectopic gallstone, closure of the fistula and cholecystectomy. A case of Bouveret's syndrome is presented where endoscopic extraction of the duodenal gallstone was accomplished providing definitive treatment for this patient.

  5. YouTube as a source of patient information on gallstone disease.

    Science.gov (United States)

    Lee, Jun Suh; Seo, Ho Seok; Hong, Tae Ho

    2014-04-14

    To investigate the quality of YouTube videos on gallstone disease and to assess viewer response according to quality. A YouTube search was performed on September 18, 2013, using the keywords ''gallbladder disease'', ''gallstone disease'', and ''gallstone treatment''. Three researchers assessed the source, length, number of views, number of likes, and days since upload. The upload source was categorised as physician or hospital (PH), medical website or TV channel, commercial website (CW), or civilian. A usefulness score was devised to assess video quality and to categorise the videos into ''very useful'', ''useful'', ''slightly useful'', or ''not useful''. Videos with misleading content were categorised as ''misleading''. One hundred and thirty-one videos were analysed. Seventy-four videos (56.5%) were misleading, 36 (27.5%) were slightly useful, 15 (11.5%) were useful, three (2.3%) were very useful, and three (2.3%) were not useful. The number of mean likes (1.3 ± 1.5 vs 17.2 ± 38.0, P = 0.007) and number of views (756.3 ± 701.0 vs 8910.7 ± 17094.7, P = 0.001) were both significantly lower in the very useful group compared with the misleading group. All three very useful videos were PH videos. Among the 74 misleading videos, 64 (86.5%) were uploaded by a CW. There was no correlation between usefulness and the number of views, the number of likes, or the length. The "gallstone flush" was the method advocated most frequently by misleading videos (25.7%). More than half of the YouTube videos on gallstone disease are misleading. Credible videos uploaded by medical professionals and filtering by the staff of YouTube appear to be necessary.

  6. The number of metabolic abnormalities associated with the risk of gallstones in a non-diabetic population.

    Directory of Open Access Journals (Sweden)

    Chung-Hung Tsai

    Full Text Available AIM: To evaluate whether metabolic syndrome is associated with gallstones, independent of hepatitis C infection or chronic kidney disease (CKD, in a non-diabetic population. MATERIALS AND METHODS: A total of 8,188 Chinese adult participants that underwent a self-motivated health examination were recruited into the final analysis after excluding the subjects who had a history of cholecystectomy, diabetes mellitus, or were currently using antihypertensive or lipid-lowering agents. Gallstones were defined by the presence of strong intraluminal echoes that were gravity-dependent or that attenuated ultrasound transmission. RESULTS: A total of 447 subjects (5.5% had gallstones, with 239 (5.1% men and 208 (6.0% women. After adjusting for age, gender, obesity, education level, and lifestyle factors, included current smoking, alcohol drinking, regular exercise, hepatitis B, hepatitis C, and CKD, there was a positive association between metabolic syndrome and gallstones. Moreover, as compared to subjects without metabolic abnormalities, subjects with one, two, and three or more suffered from a 35, 40, and 59% higher risk of gallstones, respectively. CONCLUSIONS: Non-diabetic subjects with metabolic syndrome had a higher risk of gallstones independent of hepatitis C or CKD, and a dose-dependent effect of metabolic abnormalities also exists.

  7. Gallbladder microbiota variability in Colombian gallstones patients.

    Science.gov (United States)

    Arteta, Ariel Antonio; Carvajal-Restrepo, Hernan; Sánchez-Jiménez, Miryan Margot; Diaz-Rodriguez, Sergio; Cardona-Castro, Nora

    2017-03-31

    Gallbladder stones are a very frequently occurring condition. Despite bile bactericidal activity, many bacteria have been detected inside the gallbladder, and gallstones facilitate their presence. Between 3% and 5% of the patients with Salmonella spp. infection develop the carrier stage, with the bacteria persisting inside the gallbladder, shedding bacteria in their feces without signs of infection. The aim of this study was to isolate bacteria from Colombian patients with gallstones, using standard culturing methods, and to identify Salmonella spp. carriers by molecular techniques. A total of 149 patients (120 female and 29 male) diagnosed with gallstones who underwent cholecystectomy and who did not have symptoms of acute inflammation were included. Gallbladder tissue and bile were cultured and used for DNA extraction and Salmonella spp. hilA gene detection. Of the 149 patients 28 (19%) had positive cultures. Twenty-one (75%) patients with positive cultures were from Medellin's metropolitan area. In this geographical location, the most frequent isolations were Pseudomonas spp. (38%), Klebsiella spp. (23%), and Proteus spp. (9%) in addition to unique cases of other bacteria. In Apartado, the isolates found were Enterobacter cloacae (50%), Raoultella terrigena (32%), and both Enterobacter cloacae and Raoultella terrigena were isolated in one (18%) male patient. Five (3.3%) of the 149 patients had positive polymerase chain reaction (PCR) results for the hilA gene of Salmonella spp., all of whom were female and residents of the Medellín metropolitan area. The gallbladder microbiota variability found could be related to geographical, ethnic, and environmental conditions.

  8. Same-admission versus interval cholecystectomy for mild gallstone pancreatitis (PONCHO): a multicentre randomised controlled trial

    NARCIS (Netherlands)

    Costa, D.W. da; Bouwense, S.A.; Schepers, N.J.; Besselink, M.G.; Santvoort, H.C. van; Brunschot, S. van; Bakker, O.J.; Bollen, T.L.; Dejong, C.H.; Goor, H. van; Boermeester, M.A.; Bruno, M.J.; Eijck, C.H. van; Timmer, R.; Weusten, B.L.; Consten, E.C.; Brink, M.A.; Spanier, B.W.; Bilgen, E.J.; Nieuwenhuijs, V.B.; Hofker, H.S.; Rosman, C.; Voorburg, A.M.; Bosscha, K.; Duijvendijk, P. van; Gerritsen, J.J.; Heisterkamp, J.; Hingh, I.H. de; Witteman, B.J.; Kruyt, P.M.; Scheepers, J.J.; Molenaar, I.Q.; Schaapherder, A.F.; Manusama, E.R.; Waaij, L.A. van der; Unen, J. van; Dijkgraaf, M.G.; Ramshorst, B. van; Gooszen, H.G.; Boerma, D.

    2015-01-01

    BACKGROUND: In patients with mild gallstone pancreatitis, cholecystectomy during the same hospital admission might reduce the risk of recurrent gallstone-related complications, compared with the more commonly used strategy of interval cholecystectomy. However, evidence to support same-admission

  9. Same-admission versus interval cholecystectomy for mild gallstone pancreatitis (PONCHO): a multicentre randomised controlled trial

    NARCIS (Netherlands)

    da Costa, David W.; Bouwense, Stefan A.; Schepers, Nicolien J.; Besselink, Marc G.; van Santvoort, Hjalmar C.; van Brunschot, Sandra; Bakker, Olaf J.; Bollen, Thomas L.; Dejong, Cornelis H.; van Goor, Harry; Boermeester, Marja A.; Bruno, Marco J.; van Eijck, Casper H.; Timmer, Robin; Weusten, Bas L.; Consten, Esther C.; Brink, Menno A.; Spanier, B. W. Marcel; Bilgen, Ernst Jan Spillenaar; Nieuwenhuijs, Vincent B.; Hofker, H. Sijbrand; Rosman, Camiel; Voorburg, Annet M.; Bosscha, Koop; van Duijvendijk, Peter; Gerritsen, Jos J.; Heisterkamp, Joos; de Hingh, Ignace H.; Witteman, Ben J.; Kruyt, Philip M.; Scheepers, Joris J.; Molenaar, I. Quintus; Schaapherder, Alexander F.; Manusama, Eric R.; van der Waaij, Laurens A.; van Unen, Jacco; Dijkgraaf, Marcel G.; van Ramshorst, Bert; Gooszen, Hein G.; Boerma, Djamila

    2015-01-01

    Background In patients with mild gallstone pancreatitis, cholecystectomy during the same hospital admission might reduce the risk of recurrent gallstone-related complications, compared with the more commonly used strategy of interval cholecystectomy. However, evidence to support same-admission

  10. Same-admission versus interval cholecystectomy for mild gallstone pancreatitis (PONCHO) : A multicentre randomised controlled trial

    NARCIS (Netherlands)

    Da Costa, David W.; Bouwense, Stefan A.; Schepers, Nicolien J.; Besselink, Marc G.; van Santvoort, Hjalmar C.; Van Brunschot, Sandra; Bakker, Olaf J.; Bollen, Thomas L.; Dejong, Cornelis H.; Van Goor, Harry; Boermeester, Marja A.; Bruno, Marco J.; Van Eijck, Casper H.; Timmer, Robin; Weusten, Bas L.; Consten, Esther C.; Brink, Menno A.; Spanier, B. W Marcel; Bilgen, Ernst Jan Spillenaar; Nieuwenhuijs, Vincent B.; Hofker, H. Sijbrand; Rosman, Camiel; Voorburg, Annet M.; Bosscha, Koop; Van Duijvendijk, Peter; Gerritsen, Jos J.; Heisterkamp, Joos; De Hingh, Ignace H.; Witteman, Ben J.; Kruyt, Philip M.; Scheepers, Joris J.; Molenaar, I. Quintus; Schaapherder, Alexander F.; Manusama, Eric R.; Van Der Waaij, Laurens A.; Van Unen, Jacco; Dijkgraaf, Marcel G.; Van Ramshorst, Bert; Gooszen, Hein G.; Boerma, Djamila

    2015-01-01

    Background In patients with mild gallstone pancreatitis, cholecystectomy during the same hospital admission might reduce the risk of recurrent gallstone-related complications, compared with the more commonly used strategy of interval cholecystectomy. However, evidence to support same-admission

  11. Black bile of melancholy or gallstones of biliary colics: historical perspectives on cholelithiasis.

    Science.gov (United States)

    Bielefeldt, Klaus

    2014-11-01

    Barely 130 years after its first description, cholecystectomies are among the most commonly performed surgeries in the USA. The success of this operation with subsequent technical improvements, such as laparoscopic approaches, caused a paradigm shift in the management of gallstone disease. However, symptoms persist in 10-40 % of successfully operated patients. Reviewing monographs, textbooks, and articles published during the last 300 years, several important factors emerge as likely contributors to limited or poor treatment responses. Early on, clinicians recognized that cholelithiasis is quite common and thus often an incidental finding, especially if patients present with vague or atypical symptoms. Consistent with these observations, patients with such atypical symptoms are less likely to benefit from cholecystectomy. Similarly, lasting improvements are more reliably seen in patients with symptoms of presumed biliary origin and documented gallstones compared to individuals without stones, an important point in view of increasing rates of surgery for biliary dyskinesia. While cholelithiasis can cause serious complications, the overall incidence of clinically relevant problems is so low that prophylactic cholecystectomy cannot be justified. This conclusion corresponds to epidemiologic data showing that the rise in elective cholecystectomies decreased hospitalizations due to gallstone disease, but was associated with a higher volume of postoperative complications, ultimately resulting in stable combined mortality due to gallstone disease and its treatment. These trends highlight the tremendous gains in managing gallstone disease, while at the same time reminding us that the tightening rather than expanding indications for cholecystectomy may improve outcomes.

  12. Electrochemical oxidation of cholesterol in acetonitrile leads to the formation of cholesta-4,6-dien-3-one

    International Nuclear Information System (INIS)

    Hosokawa, Yu-Ya; Hakamata, Hideki; Murakami, Tomonori; Aoyagi, Sakae; Kuroda, Minpei; Mimaki, Yoshihiro; Ito, Ayumi; Morosawa, Sayaka; Kusu, Fumiyo

    2009-01-01

    Cholesterol was shown to be oxidized at the glassy carbon electrode in an acetonitrile-2-propanol mixture and this oxidation reaction was applied to the determination of serum total cholesterol by high-performance liquid chromatography with electrochemical detection (K. Hojo, H. Hakamata, A. Ito, A. Kotani, C. Furukawa, Y.Y. Hosokawa, F. Kusu, J. Chromatogr. A 1166 (2007) 135-141). To gain insight into the detection mechanisms of cholesterol, an electrolytic product of cholesterol was collected and characterized by infrared spectroscopy, one- and two-dimensional nuclear magnetic resonance, and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The three techniques, together with comparisons of literature spectral data, confirmed the formation of cholesta-4,6-dien-3-one. The conversion of cholesterol to cholesta-4,6-dien-3-one, a four-electron, four-proton electrochemical process, has been proposed as an electrochemical oxidation mechanism of cholesterol in acetonitrile.

  13. Inhibitory activities of some vitamins on the formation of cholesterol oxidation products in beef patties.

    Science.gov (United States)

    Wong, Daniel; Wang, Mingfu

    2013-09-04

    The capacities of 15 vitamins to inhibit the formation of 7α-hydroxycholesterol, 7β-hydroxycholesterol, and 7-ketocholesterol were examined in beef patties. Their inhibitory activities were tested at a concentration of 0.4 mmol in 30 g of beef. Among them, L-ascorbic acid, retinoic acid, and α-(±)-tocopherol were found to exert a potent inhibitory effect (30-50%) on 7-ketocholesterol formation and (~20%) on 7α-hydroxycholesterol and 7β-hydroxycholesterol formations. Pyridoxamine inhibited 7-ketocholesterol formation by 60% with a statistically significant difference (p cholesterol oxidation, a chemical model with pyridoxamine added in the cholesterol oxidation system (heated at 140 °C for 240 min in dimethyl sulfoxide) was employed. It was demonstrated that pyridoxamine could directly react with 7-ketocholesterol via the addition reaction. The reaction involved a nucleophilic attack of the free amine group of pyridoxamine on 7-ketocholesterol (an α,β-unsaturated carbonyl compound). This type of reaction was also found to occur in beef patties by chromatographic and spectral analyses.

  14. Analysis of minor and trace elements in gallstones by induction of characteristic ionising radiation

    International Nuclear Information System (INIS)

    Al-Kinani, A.T.; Watt, D.E.

    1984-01-01

    Samples from five patients were analysed using three different techniques for cross-verification: NAA, PIXE, and XRF. In addition, certified standards of bovine liver and oyster tissue from the NBS, Washington, were re-analysed using the different techniques to confirm the accuracy of the experimental procedures. NAA of five gallstones was used for the quantitative analysis of 19 elements with Z>11. The concentrations of Cl, K+Ca, Mn, Fe and Cu+Zn were determined by PIXE and those of Mg, P, S, K and Ca by XRF. In most cases the concentrations were in the range of a few PPB to a few hundred PPM. The spatial distribution of the component elements was obtained using XRF with a scanning electron microscope and the results demonstrated that calcium was present centrally in all the stones. The analysis of gallbladder bile from four patients showed that the calcium concentration was much greater than normal, indicating that calcium and other elements play an important role in stone formation. Infrared spectroscopy showed that the calcium salts were present in gallstones in three compound forms: calcium carbonate, calcium phosphate and calcium bilirubinate. Reasons for the cause of calcium precipitation are discussed. (author)

  15. Prevalência e fisiopatologia da litíase biliar em pacientes submetidos a transplante de órgãos Prevalence and physiopathology of gallstone in transplant patients

    Directory of Open Access Journals (Sweden)

    Júlio Cesar Uili Coelho

    2009-06-01

    Full Text Available INTRODUÇÃO: O objetivo do presente estudo é apresentar revisão da prevalência e dos principais mecanismos fisiopatológicos que levam a formação da litíase biliar em pacientes submetidos a transplante de órgãos. MÉTODOS: Revisão da literatura abrangendo 29 publicações obtidas das bases Medline/Pubmed, Scielo e Lilacs com cruzamento dos unitermos "transplante, transplante renal, transplante hepático, cálculo biliar, colecistite.". Vários estudos que utilizaram a ultrassonografia demonstraram aumento na prevalência da litíase biliar em pacientes submetidos a transplante de órgãos. A taxa de formação de cálculos novos após o transplante variou de 10 a 55% e a total (cálculos formados antes e após o transplante de 17 a 68%. Tanto o ganho como a perda de peso rápida, que podem ocorrer após o transplante, predispõem à formação de cálculos biliares. O uso do imunossupressor ciclosporina é considerado como o principal fator que aumenta a incidência de litíase biliar após o transplante. CONCLUSÃO: A prevalência de litíase biliar é maior nos pacientes submetidos a transplante de órgãos do que na população geral. As principais alterações que ocorrem no paciente transplantado que predispõem a formação dos cálculos são as alterações do peso corporal, uso de imunossupressores, diabete melito e hiperlipidemia.INTRODUCTION: The objective of the present study is to review the prevalence and the main physiopathologic mechanisms that result in gallstone formation in transplant patients. METHODS: Literature review with 29 papers included in Medline/Pubmed, Scielo and Lilacs database, crossing key-words "transplantation; kidney transplantation; liver transplantation; gallstone; cholecystitis". Several ultrasonographic studies have demonstrated an increase in gallstone prevalence in transplant patients. The formation rate of new stones after transplantation varied from 10 to 55% and the rate of total stones

  16. A Prediction Rule for Risk Stratification of Incidentally Discovered Gallstones

    DEFF Research Database (Denmark)

    Shabanzadeh, Daniel Mønsted; Sørensen, Lars Tue; Jørgensen, Torben

    2016-01-01

    % confidence interval [CI], 1.45-3.69), acute cholecystitis (HR, 9.49; 95% CI, 2.05-43.92), and uncomplicated events (HR, 2.55; 95% CI, 1.38-4.71), including cholecystectomy (HR, 2.69; 95% CI, 1.29-5.60). Multiple stones were associated with all events (HR, 1.68; 95% CI, 1.00-2.81), complicated events (HR, 2...... the highest risk for events (HR, 11.05; 95% CI, 3.76-32.44; unadjusted absolute risk, 0.0235 events/person-years). CONCLUSIONS: Fewer than 20% of subjects with gallstones develop clinical events. Larger, multiple, and older gallstones are associated with events. Further studies are needed to confirm...

  17. Clinical, ultrasonographic, and roentgenographic study in 134 asymptomatic gallstone carriers; Is oral ursodeoxycholic acid treatment worhtwhile

    Energy Technology Data Exchange (ETDEWEB)

    Lirussi, F.; Passera, D.; Iemmolo, R.M.; Nassuato, G.; Okolicsanyi, L. (Inst. of Medicine, Univ. of Parma (Italy))

    1993-03-01

    The authors investigated retrospectively the ultrasonographic and roentgenographic characteristics of the gallstones and the gallbladder in 134 symtom-free carriers and evaluated prospectively the outcome and side effects of 6 to 24 months' ursodeoxycholic acid (UDCA) therapy in 36 individuals with silent stones. Two-thirds of the 134 subjects had multiple stones, and 71 to 75% had stones less than 15 mm in diameter. Gallstone calcification was detected in 13%. A non-functioning gallbladder was observed in 19%, whereas gallbladder contraction was normal in 64 of 76 gallstone carriers. With regard to oral bile acid treatment, complete and partial dissolutions were achieved in 7 and 9 of 33 subjects, respectively (48.5%). Development of a non-functioning gallbladder occurred in 9%, and acquired gallstone calcification was seen in another 15%. It is concluded that: (i) the characteristics of the gallstones and the gallbladder are similar to those observed in symptomatic patients, and (ii) UDCA therapy may be given in selected symptom-free carriers for no more than 6 to 12 months. Thereafter, it does not appear to be cost-effective. 23 refs., 2 figs., 3 tabs.

  18. Increased Risk of Clinically Significant Gallstones following an Appendectomy: A Five-Year Follow-Up Study.

    Directory of Open Access Journals (Sweden)

    Shiu-Dong Chung

    Full Text Available Although the vermiform appendix is commonly considered a vestigial organ, adverse health consequences after an appendectomy have garnered increasing attention. In this study, we investigated the risks of gallstone occurrence during a 5-year follow-up period after an appendectomy, using a population-based dataset. We used data from the Taiwan Longitudinal Health Insurance Database 2005. The exposed cohort included 4916 patients who underwent an appendectomy. The unexposed cohort was retrieved by randomly selecting 4916 patients matched with the exposed cohort in terms of sex, age, and year. We individually tracked each patient for a 5-year period to identify those who received a diagnosis of gallstones during the follow-up period. Cox proportional hazard regressions were performed for the analysis. During the 5-year follow-up period, the incidence rate per 1000 person-years was 4.71 for patients who had undergone an appendectomy, compared to a rate of 2.59 for patients in the unexposed cohort (p<0.001. Patients who had undergone an appendectomy were independently associated with a 1.79 (95% CI = 1.29~2.48-fold increased risk of being diagnosed with gallstones during the 5-year follow-up period. We found that among female patients, the adjusted hazard ratio of gallstones was 2.25 (95% CI = 1.41~3.59 for patients who underwent an appendectomy compared to unexposed patients. However, for male patients, we failed to observe an increased hazard for gallstones among patients who underwent an appendectomy compared to unexposed patients. We found an increased risk of a subsequent gallstone diagnosis within 5 years after an appendectomy.

  19. gallstone disease: a call to awareness in subsaharan africa

    African Journals Online (AJOL)

    Gallstone disease (GSD) is a major global health problem that causes high ... common causes of upper gastrointestinal morbidity and may mimic / be associated ... gastroesophageal reflux disease, duodenitis; acute and chronic pancreatitis, ...

  20. The outcome of unretrieved gallstones in the peritoneal cavity during laparoscopic cholecystectomy. A prospective analysis.

    Science.gov (United States)

    Memon, M A; Deeik, R K; Maffi, T R; Fitzgibbons, R J

    1999-09-01

    Gallbladder perforation during laparoscopic cholecystectomy (LC) with spillage of bile and gallstones occurs in a substantial number of patients (up to 40%). Most surgeons believe that free intraperitoneal stones are not a justification for conversion to laparotomy even if a large number of stones are left in situ. There are, however, a number of reports demonstrating that, on occasion, these unretrieved gallstones may cause infection or abscess, inflammation, fibrosis, adhesions, cutaneous sinuses, small bowel obstruction, or generalized septicemia. The aim of this study was to determine the outcome of unretrieved gallstones in the peritoneal cavity after gallbladder perforation during LC. In a 7-year period between 1989 and 1996, prospective data were maintained on 856 patients who underwent LCs by a single surgeon (R. J.F.). Of the 856 patients, 165 (16%) had gallbladder perforations resulting in lost gallstones in the peritoneal cavity. A concerted attempt was made to remove the lost stones using a variety of extraction devices. Of these 165 patients, 106 (64%) were available for follow-up through mail (76%) and by telephone (24%). The mean age of these patients was 64.9 years (range, 18 to 98 years), and the mean follow-up was 44.8 months (range 4.9 to 92.3 months). Of the 106 patients with unretrieved gallstones, we identified four patients with short-term complications and one patient with a long-term complication. The first patient with a short-term complication had pyrexia for 10 days postoperatively. Diagnostic evaluation, which included computed tomography (CT) scan, failed to reveal any abnormality. The patient was treated conservatively with a course of oral antibiotics. In the second patient, cellulitis developed at a drain site after its removal, which resolved with oral antibiotics. The third patient acquired an umbilical wound abscess, which drained spontaneously, requiring no treatment. A sterile subphrenic collection developed in the fourth

  1. The changes of bile dynamics in patients with gallstones by quantitative hepatobiliary scintigraphy

    International Nuclear Information System (INIS)

    Xu Wei'na; Yu Shupeng

    2004-01-01

    The gold standard of diagnosing SOD is endoscopic sphincter of Oddi manometry, but it is not widely used because it is invasive, expensive and there are more complicateds after examination. Hepatobiliary scintigraphy can give us quantitative parameters of bile emptying and it is a noninvasive, sensitive and accurate method in diagnosing SOD. The bile dynamics after cholecystectomy was seldom studied, the aim of this study is to obtain the normal changes of bile emptying after cholecystectomy by hepatobiliary scintigraphy and provide basis for diagnosing SOD. Objective: Quantitative hepatobiliary scintigraphy, a noninvasive method used to diagnose dysfunction of bile duct, can show bile secretion and outflow in bile duct. The goal of this study was to examine the dynamics of bile secretion and outflow by quantitative hepatobiliary scintigraphy in patients with gallstones, postcholecystectomy and normal groups, got the parameters of normal changes of bile emptying in postcholecystectomy patients and to help diagnosing SOD. Methods: 1 Patients. 31 patients with gallstones, demonstrated single or multiple gallstones by abdominal ultrasonography; 12 normal controls and 12 patients after cholecystectomy. They were all rulled out liver diseases and bile duct stones by liver function tests and US respectively, the diameter of common bile duct were normal, liver functions were normal and there were not symptoms of bile duct diseases. 2 Methods. All the patients were examined by fatty meal * hepatobiliary scintigraphy according to the same method. after fasting over 4 hours, 740 MBq 99m Tc-EHIDA was injected intravenously. Images were recorded continuously at one frame per minute for 100 minutes, at 60th minute two fry eggs were taken. Then the parameters of of bile emptying (Tmax in liver and common bile duct, T1/2 in liver and common bile duct, time of duodenal appeared (DAT), transit time from liver to duodenol(HDTT) and half-emptying time in common bile duct after fatty

  2. Alcohol, smoking and benign hepato-biliary disease

    DEFF Research Database (Denmark)

    Shabanzadeh, Daniel Mønsted; Novovic, Srdan

    2017-01-01

    through effects on bile cholesterol metabolism, the enterohepatic circulation, and gallbladder function. The impact of smoking on gallstone formation seems minor. Both alcohol intake and smoking do not alter the clinical course of gallstone disease carriers. Cholecystectomy is the preferred treatment...... for symptomatic gallstone disease. Studies about the impact of alcohol and smoking on the post-cholecystectomy state are few and future studies should be performed. Pancreatitis is associated with both excessive alcohol intake and smoking in observational studies. Interpretation of associations with pancreatitis...... is hampered by an incomplete understanding of underlying mechanisms and by the co-existence of excessive alcohol intake and smoking. Smoking cessation and alcohol abstinence is recommended in the treatment of pancreatitis, but higher-level evidence is needed....

  3. Elimination of C-6-hydrogen during the formation of ecdysteroids from cholesterol in Locusta migratoria ovaries

    International Nuclear Information System (INIS)

    Fujimoto, Y.; Hiramoto, M.; Kakinuma, K.; Ikekawa, N.

    1989-01-01

    Being administered to Locusta migratoria adult females, [6- 3 H, 4- 14 C]cholesterol was incorporated into ecdysone and 2-deoxyecdysone. The ratio of 3 H/ 14 C of the two ecdysteroids isolated from newly laid eggs revealed that C-6-hydrogen of cholesterol was eliminated during the conversion to ecdysteroids in the ovaries of the insects. Thus, a hypothetical mechanism involving migration of the C-6-hydrogen to the C-5 position in the formation of A/B cis junction turned out to be less likely

  4. Inhibition of the NLRP3 inflammasome attenuates foam cell formation of THP-1 macrophages by suppressing ox-LDL uptake and promoting cholesterol efflux.

    Science.gov (United States)

    Chen, Liang; Yao, Qiying; Xu, Siwei; Wang, Hongyan; Qu, Peng

    2018-01-01

    The NOD-like receptor family, pyrin domain-containing protein 3 (NLRP3) inflammasome plays an important role in the development of atherosclerosis. The activated NLRP3 inflammasome has been reported to promote macrophage foam cell formation, but not all studies have obtained the same result, and how NLRP3 inflammasome is involved in the formation of foam cells remains elusive. We used selective NLRP3 inflammasome inhibitors and NLRP3-deficient THP-1 cells to assess the effect of NLRP3 inflammasome inhibition on macrophage foam cell formation, oxidized low-density lipoprotein (ox-LDL) uptake, esterification, and cholesterol efflux, as well as the expression of associated proteins. Inhibition of the NLRP3 inflammasome attenuated foam cell formation, diminished ox-LDL uptake, and promoted cholesterol efflux from THP-1 macrophages. Moreover, it downregulated CD36, acyl coenzyme A: cholesterol acyltransferase-1 and neutral cholesterol ester hydrolase expression; upregulated ATP-binding cassette transporter A1 (ABCA1) and scavenger receptor class B type I (SR-BI) expression; but had no effect on the expression of scavenger receptor class A and ATP-binding cassette transporter G1. Collectively, our findings show that inhibition of the NLRP3 inflammasome decreases foam cell formation of THP-1 macrophages via suppression of ox-LDL uptake and enhancement of cholesterol efflux, which may be due to downregulation of CD36 expression and upregulation of ABCA1 and SR-BI expression, respectively. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Antibiotic activity and synergistic effect of antimicrobial peptide against pathogens from a patient with gallstones

    International Nuclear Information System (INIS)

    Park, Yoonkyung; Park, Soon Nang; Park, Seong-Cheol; Park, Joon Yong; Park, Yong Ha; Hahm, Joon Soo; Hahm, Kyung-Soo

    2004-01-01

    HP (2-20) is a peptide derived from the N-terminus of Helicobacter pylori ribosomal protein L1 that has been shown to have antimicrobial activity against various species of bacteria. When we tested the effects of HP (2-20), we found that this peptide displayed strong activity against pathogens from a patient with gallstones, but it did not have hemolytic activity against human erythrocytes. We also found that HP (2-20) had potent activity against cefazolin sodium-resistant bacterial cell lines, and that HP (2-20) and cefazolin sodium had synergistic effects against cell lines resistant to the latter. To investigate the mechanism of action of HP (2-20), we performed fluorescence activated flow cytometry using pathogens from the patient with gallstones. As determined by propidium iodide (PI) staining, pathogenic bacteria treated with HP (2-20) showed higher fluorescence intensity than untreated cells, similar to melittin-treated cells, and that HP (2-20) acted in an energy- and salt-dependent manner. Scanning electron microscopy showed that HP (2-20) caused significant morphological alterations in the cell surface of pathogens from the patient with gallstones. By determining their 16S rDNA sequences, we found that both the pathogens from the patient with gallstones and the cefazolin sodium-resistant cell lines showed 100% homology with sequences from Pseudomonas aeruginosa. Taken together, these results suggest that HP (2-20) has antibiotic activity and that it may be used as a lead drug for the treatment of acquired pathogens from patients with gallstones and antibiotic-resistant cell lines

  6. Design and application of a new series of gallbladder endoscopes that facilitate gallstone removal without gallbladder excision

    Science.gov (United States)

    Qiao, Tie; Huang, Wan-Chao; Luo, Xiao-Bing; Zhang, Yang-De

    2012-01-01

    In recent years, some Chinese doctors have proposed a new concept, gallstone removal without gallbladder excision, along with transition of the medical model. As there is no specialized endoscope for gallstone removal without gallbladder excision, we designed and produced a new series of gallbladder endoscopes and accessories that have already been given a Chinese invention patent (No. ZL200810199041.2). The design of these gallbladder endoscopes was based on the anatomy and physiology of the gallbladder, characteristics of gallbladder disease, ergonomics, and industrial design. This series of gallbladder endoscopes underwent clinical trials in two hospitals appointed by the State Administration of Traditional Chinese Medicine. The clinical trials showed that surgeries of gallstones, gallbladder polyps, and cystic duct calculus could be smoothly performed with these products. In summary, this series of gallbladder endoscopes is safe, reliable, and effective for gallstone removal without gallbladder excision. This note comprehensively introduces the research and design of this series of gallbladder endoscopes.

  7. Variation of calcium, copper and iron levels in serum, bile and stone samples of patients having different types of gallstone: A comparative study.

    Science.gov (United States)

    Khan, Mustafa; Kazi, Tasneem Gul; Afridi, Hassan Imran; Sirajuddin; Bilal, Muhammad; Akhtar, Asma; Khan, Sabir; Kadar, Salma

    2017-08-01

    Epidemiological data among the human population has shown a significantly increased incidence of gallstone (GS) disease worldwide. It was studied that some essential (calcium) and transition elements (iron and copper) in bile play an important role in the development of GS. The estimation of calcium, copper and iron were carried out in the serum, gall bladder bile and different types of GS (cholesterol, mixed and pigmented) of 172 patients, age ranged 20-55years. For comparative purpose age matched referents not suffering from GS diseases were also selected. Biliary concentrations of calcium (Ca), iron (Fe) and copper (Cu) were correlated with their concentrations in serum and different types of GS samples. The ratio of Ca, Fe and Cu in bile with serum was also calculated. Understudy metals were determined by flame atomic absorption spectroscopy after acid decomposition of matrices of selected samples. The Ca concentrations in serum samples were significantly higher in patients with pigmented GS as compared to controls (p0.001). The contents of Cu and Fe in serum and bile of all patients (except female cholesterol GS patient have low serum iron concentration) were found to be higher than control, but difference was significant in those patients who have pigmented GS. The concentration of Ca, Fe and Cu in different types GS were found in the order, Pigmented>mixed>cholesterol. The bile/serum ratio for Ca, Cu and Fe was found to be significantly higher in pigmented GS patients. Gall bladder bile was slightly alkaline in patients as compared to referents. The density of bile was found to be higher in patients as compared to the referents. Various functional groups present in different types of GS samples were confirmed by Fourier transform infra-red spectroscopy. The higher density and pH of bile, elevated concentrations of transition elements in all types of biological samples (serum, bile and GS), could be an important factor for the formation of different types of

  8. High Cholesterol/Low Cholesterol: Effects in Biological Membranes: A Review.

    Science.gov (United States)

    Subczynski, Witold K; Pasenkiewicz-Gierula, Marta; Widomska, Justyna; Mainali, Laxman; Raguz, Marija

    2017-12-01

    Lipid composition determines membrane properties, and cholesterol plays a major role in this determination as it regulates membrane fluidity and permeability, as well as induces the formation of coexisting phases and domains in the membrane. Biological membranes display a very diverse lipid composition, the lateral organization of which plays a crucial role in regulating a variety of membrane functions. We hypothesize that, during biological evolution, membranes with a particular cholesterol content were selected to perform certain functions in the cells of eukaryotic organisms. In this review, we discuss the major membrane properties induced by cholesterol, and their relationship to certain membrane functions.

  9. Diagnostic value of CT features of the gallbladder in the prediction of gallstone pancreatitis

    Energy Technology Data Exchange (ETDEWEB)

    Yie, Miyeon [Department of Radiology, Hallym University College of Medicine, 896 Pyungchon-dong, Dongan-gu, Anyang-city, Kyungki-do 431-070 (Korea, Republic of); Jang, Kyung Mi, E-mail: jkm7290@empal.com [Department of Radiology, Hallym University College of Medicine, 896 Pyungchon-dong, Dongan-gu, Anyang-city, Kyungki-do 431-070 (Korea, Republic of); Department of Radiology and Center for Imaging Science, Sungkyunkwan University School of Medicine, 50, Ilwon-Dong, Kangnam-Ku, Seoul 135-710 (Korea, Republic of); Kim, Min Jeong; Lee, Yul [Department of Radiology, Hallym University College of Medicine, 896 Pyungchon-dong, Dongan-gu, Anyang-city, Kyungki-do 431-070 (Korea, Republic of); Choi, Dongil [Department of Radiology and Center for Imaging Science, Sungkyunkwan University School of Medicine, 50, Ilwon-Dong, Kangnam-Ku, Seoul 135-710 (Korea, Republic of)

    2011-11-15

    Purpose: The aim of this retrospective study was to evaluate the diagnostic value of CT features of the gallbladder in the prediction of gallstone pancreatitis. Materials and methods: Eighty-six patients who underwent a diagnostic computed tomography (CT) scan for acute pancreatitis were included. The readers assessed the presence of pericholecystic increased attenuation of the liver parenchyma, enhancement of gallbladder (GB) and common bile duct (CBD) wall, pericholecystic fat strands, GB wall thickening, stone in the GB or CBD, and focal or diffuse manifestations of pancreatitis on abdominal CT scans. In addition, the maximal transverse luminal diameters of the GB and CBD were measured. Results: The presence of pericholecystic increased attenuation of the liver parenchyma, GB wall enhancement and thickening, pericholecystic fat strands, stone in the GB or CBD, and diffuse manifestations of pancreatitis achieved statistical significance for differentiation of gallstone induced pancreatitis from non-biliary pancreatitis (p < 0.05). The mean values of maximal transverse luminal diameter of GB and CBD were significantly higher in gallstone induced pancreatitis group (39.67 {+-} 7.26 mm, 10.20 {+-} 4.13 mm) than non-biliary pancreatitis group (27.01 {+-} 6.14 mm, 3.85 {+-} 2.51 mm, p < 0.0001). Conclusion: Gallbladder features of CT in patients with pancreatitis could be the valuable clues for the diagnosis of gallstone induced pancreatitis.

  10. Association between thyroid function and gallstone disease

    Institute of Scientific and Technical Information of China (English)

    Henry V(o)lzke; Daniel M Robinson; Ulrich John

    2005-01-01

    AIM: To investigate those associations using data of the population-based Study of Health in Pomerania.METHODS: A study population of 3 749 residents aged 20-79 years without previously diagnosed thyroid disease was available for analyses. Serum TSH was used to assess thyroid function. Cholelithiasis was defined by either a prior history of cholecystectomy or the presence of gallstones on ultrasound. Logistic regression was performed to analyze independent associations between thyroid function and cholelithiasis.RESULTS: There were 385 persons (10.3%) with low (<0.3 mIU/L), 3 321 persons (88.6%) with normal and 43 persons (1.2%) with high serum TSH levels (>3 mIU/L).The proportion of cholelithiasis among males and females was 14.4% and 25.3%, respectively. Among males, there was an independent relation between high serum TSH and cholelithiasis (OR 3.77; 95%-CI 1.06-13.41; ,P<0.05). zAlso among males, there was a tendency towards an elevated risk of cholelithiasis in persons with low serum TSH (OR 1.40; 95%-CI 0.96-2.02; P = 0.07). In the female population, no such relation was identified.CONCLUSION: There is an association between thyroid and gallstone disease with a gender-specific relation between hypothyroidism and cholelithiasis.

  11. [Correlation of retinol binding protein 4 with 
metabolic indexes of glucose and 
lipid, bile cholesterol saturation index].

    Science.gov (United States)

    Wang, Wen; Li, Nianfeng

    2015-06-01

    To measure retinol binding protein 4 (RBP4) levels in serum and bile and to analyze their relationship with insulin resistance, dyslipidemia or cholesterol saturation index (CSI).
 A total of 60 patients with gallstone were divided into a diabetes group (n=30) and a control group (n=30). The concentrations of RBP4 in serum and bile were detected by enzyme-linked immunosorbent assay (ELISA). Enzyme colorimetric method was used to measure the concentration of biliary cholesterol, bile acid and phospholipid. Biliary CSI was calculated by Carey table. Partial correlation and multiple linear regression analysis were used to evaluate the correlation between the RBP4 levels in serum or bile and the above indexes.
 The RBP4 concentrations in serum and bile in the diabetes group were significantly elevated compared with those in the control group (both Ptriglyceride (TG), serum high-density lipoprotein (HDL), bile TBA, bile total cholesterol (TC) , bile phospholipids and bile CSI between the 2 groups (all P>0.05); but the serum TC, low density lipoprotein (LDL), fasting blood glucose (FBG), fasting insulin (FINS), and homeostasis model assessment for insulin resistance (HOMA-IR) in the diabetes group were significantly increased compared to those in the control group (all Pindex (BMI), waist circumference (WC), FINS, FBG, TC, LDL and HOMA-IR (r=0.283, 0.405, 0.685, 0.667, 0.553, 0.424 and 0.735, respectively), and the serum RBP4 was also positively correlated with the WC, FINS, FBG, TC, LDL and HOMA-IR (r=0.317, 0.734, 0.609, 0.528, 0.386 and 0.751, respectively). Stepwise multivariate linear regression analysis suggested that the HOMA-IR, BMI and WC were independently correlated with the level of bile RBP4 (multiple regression equation: Ybile RBP4=2.372XHOMA-IR+0.420XBMI+0.178XWC-26.813), and the serum RBP4 level was correlated with the HOMA-IR and WC independently (multiple regression equation: Yserum RBP4=2.832XHOMA-IR +0.235XWC-20.128). Multiple regression equations

  12. Early definitive treatment rate as a quality indicator of care in acute gallstone pancreatitis.

    Science.gov (United States)

    Green, R; Charman, S C; Palser, T

    2017-11-01

    Early definitive treatment (cholecystectomy or endoscopic sphincterotomy in the same admission or within 2 weeks after discharge) of gallstone disease after a biliary attack of acute pancreatitis is standard of care. This study investigated whether compliance with early definitive treatment for acute gallstone pancreatitis can be used as a care quality indicator for the condition. A retrospective cohort study was conducted using the Hospital Episode Statistics database. All emergency admissions to National Health Service hospitals in England with a first time diagnosis of acute gallstone pancreatitis in the financial years 2008, 2009 and 2010 were examined. Trends in early definitive treatment between hospital trusts were examined and patient morbidity outcomes were determined. During the study interval there were 19 510 patients with an overall rate of early definitive treatment at 34·7 (range 9·4-84·7) per cent. In the 1-year follow-up period, 4661 patients (23·9 per cent) had one or more emergency readmissions for complications related to gallstone pancreatitis. Of these, 2692 (57·8 per cent) were readmissions for acute pancreatitis; 911 (33·8 per cent) were within the first 2 weeks of discharge, with the remaining 1781 (66·2 per cent) occurring after the point at which definitive treatment should have been received. Early definitive treatment resulted in a 39 per cent reduction in readmission risk (adjusted risk ratio (RR) 0·61, 95 per cent c.i. 0·58 to 0·65). The risk was further reduced for acute pancreatitis readmissions to 54 per cent in the early definitive treatment group (adjusted RR 0·46, 0·42 to 0·51). In acute gallstone pancreatitis, compliance with recommended early definitive treatment varied considerably, with associated variation in outcomes. Compliance should be used as a quality indicator to improve care. © 2017 BJS Society Ltd Published by John Wiley & Sons Ltd.

  13. Plasma cholecystokinin in obese patients before and after jejunoileal bypass with 3:1 or 1:3 jejunoileal ratio--no role in the increased risk of gallstone formation

    DEFF Research Database (Denmark)

    Sørensen, T I; Toftdahl, D B; Højgaard, L

    1994-01-01

    BACKGROUND AND AIM: Jejunoileal bypass surgery for obesity increases the risk of gallstone formation, and, contrary to expectations, the incidence is greater in patients with a long as compared to a short ileum left in continuity. Impaired gallbladder motility due to reduced cholecystokinin (CCK...... bypass surgery with either a 1:3 jejunoileal ratio (n = 14) or a 3:1 ratio (n = 15), and in unoperated obese patients (n = 7). Plasma CCK levels were determined during fasting and during 150 min following ingestion of a liquid test meal. RESULTS: There were no significant changes over time following......) stimulation could be an explanation. The aim of this study was to investigate the CCK levels in such patients. SETTING: The randomized trial of bypass surgery named The Danish Obesity Project. DESIGN AND METHODS: We compared plasma levels of CCK in obese patients at three, nine or 15 months after jejunoileal...

  14. Sludge and stone formation in the gallbladder in bedridden elderly patients with cerebrovascular disease: influence of feeding method.

    Science.gov (United States)

    Onizuka, Y; Mizuta, Y; Isomoto, H; Takeshima, F; Murase, K; Miyazaki, M; Ogata, H; Otsuka, K; Murata, I; Kohno, S

    2001-05-01

    The incidence of gallbladder sludge or gallstone formation in bedridden patients with cerebrovascular disease (CVD) remains obscure. The aim of this study was to determine the incidence, relationship to feeding method, and mechanisms of gallbladder sludge and gallstone formation in elderly patients with CVD. Using ultrasonography, we determined the development of gallbladder sludge and gallstone over a 12-month period, the area of the gallbladder, the gallbladder contractile response to cerulein, and fasting levels of plasma cholecystokinin (CCK) in 40 bedridden elderly patients with CVD. The patients were divided into three groups based on the feeding method: oral ingestion (OI), nasogastric feeding (NF), and total parenteral nutrition (TPN). Gallbladder sludge and gallstone were not observed in any of the 14 OI patients, but occurred in 6 and 1 of the 11 NF patients, and in 14 and 3 of the 15 TPN patients, respectively. Fasting gallbladder areas were significantly larger in the TPN group than in the other two groups. The TPN group showed a marked decrease in cerulein-induced gallbladder contractility. Fasting plasma CCK levels were lower in the TPN group than in the OI group. Our results indicate that elderly patients with CVD confined to bed over long periods are not necessarily at risk of gallbladder sludge or gallstone formation, and the development of these features may be associated with the feeding method. The predisposition of CVD patients on TPN to gallbladder disease is probably caused by failure of gallbladder contraction, resulting from insufficient secretion of CCK and impaired sensitivity of the gallbladder to CCK.

  15. Making the invisible visible: improving conspicuity of noncalcified gallstones using dual-energy CT.

    Science.gov (United States)

    Uyeda, Jennifer W; Richardson, Ian J; Sodickson, Aaron D

    2017-12-01

    To determine whether virtual monochromatic imaging (VMI) increases detectability of noncalcified gallstones on dual-energy CT (DECT) compared with conventional CT imaging. This retrospective IRB-approved, HIPAA-compliant study included consecutive patients who underwent DECT of the abdomen in the Emergency Department during a 30-month period (July 1, 2013-December 31, 2015), with a comparison US or MR within 1-year. 51 patients (36F, 15M; mean age 52 years) fulfilled the inclusion criteria. All DECT were acquired on a dual-source 128 × 2 slice scanner using either 80/Sn140 or 100/Sn140 kVp pairs. Source images at high and low kVp were used for DE post-processing with VMI. Within 3 mm reconstructed images, regions of interest of 0.5 cm 2 were placed on noncalcified gallstones and bile to record hounsfield units (HU) at VMI energy levels ranging between 40 and 190 keV. Noncalcified gallstones uniformly demonstrated lowest HU at 40 keV and increase at higher keV; the HU of bile varied at higher keV. Few of the noncalcified stones are visible at 70 keV (simulating a conventional 120 kVp scan), with measured contrast (bile-stone HU difference) 20 HU in 2%. Contrast was maximal at 40 keV, where 100% demonstrated >20 HU difference from surrounding bile, 75% >44 HU difference, and 50% >60 HU difference. A paired t test demonstrated a significant difference (p < 0.0001) between this stone-bile contrast at 40 vs. 70 keV and 70 vs. 190 keV. Low keV virtual monochromatic imaging increased conspicuity of noncalcified gallstones, improving their detectability.

  16. Ursodeoxycholic acid therapy in gallbladder disease, a story not yet completed

    Science.gov (United States)

    Guarino, Michele Pier Luca; Cocca, Silvia; Altomare, Annamaria; Emerenziani, Sara; Cicala, Michele

    2013-01-01

    Gallstone disease represents an important issue in the healthcare system. The principal non-invasive non-surgical medical treatment for cholesterol gallstones is still represented by oral litholysis with bile acids. The first successful and documented dissolution of cholesterol gallstones was achieved in 1972. Since then a large number of investigators all over the world, have been dedicated in biochemical and clinical studies on ursodeoxycholic acid (UDCA), demonstrating its extreme versatility. This editorial is aimed to provide a brief review of recent developments in UDCA use, current indications for its use and, the more recent advances in understanding its effects in terms of an anti-inflammatory drug. PMID:23964136

  17. Metformin Use Correlates with Reduced Risk of Gallstones in Diabetic Patients: A 12-Year Follow-up Study

    OpenAIRE

    Liao, Kuan-Fu; Chuang, Hsun-Yang; Lai, Shih-Wei

    2017-01-01

    Objective: Few studies are available on the association between gallstones and metformin use. The objective of the study was to determine whether metformin use is associated with gallstones. Methods: A population-based retrospective cohort study was conducted using the database of the Taiwan National Health Insurance Program. Subjects of newly diagnosed diabetes mellitus were included from 2002 to 2013. The metformin-exposure group was defined as ≥29 cumulative defined daily dose (DDD) of met...

  18. Metformin Use Correlates with Reduced Risk of Gallstones in Diabetic Patients: A 12-Year Follow-up Study

    OpenAIRE

    Kuan-Fu Liao; Kuan-Fu Liao; Hsun-Yang Chuang; Shih-Wei Lai; Shih-Wei Lai

    2017-01-01

    Objective: Few studies are available on the association between gallstones and metformin use. The objective of the study was to determine whether metformin use is associated with gallstones.Methods: A population-based retrospective cohort study was conducted using the database of the Taiwan National Health Insurance Program. Subjects of newly diagnosed diabetes mellitus were included from 2002 to 2013. The metformin-exposure group was defined as ≥29 cumulative defined daily dose (DDD) of metf...

  19. Apolipoprotein E4 genotype and gallbladder motility influence speed of gallstone clearance and risk of recurrence after extracorporeal shock-wave lithotripsy

    NARCIS (Netherlands)

    Portincasa, P.; van Erpecum, K. J.; van de Meeberg, P. C.; Dallinga-Thie, G. M.; de Bruin, T. W.; van Berge-Henegouwen, G. P.

    1996-01-01

    Extracorporeal shock-wave lithotripsy (ESWL) is an effective treatment in selected gallstone patients, but stone recurrence is a major drawback, Factors potentially influencing gallstone clearance and recurrence were studied in 84 patients in whom stone dissolution was diagnosed after ESWL plus bile

  20. Association of three common single nucleotide polymorphisms of ATP binding cassette G8 gene with gallstone disease: a meta-analysis.

    Directory of Open Access Journals (Sweden)

    Zhao-Yan Jiang

    Full Text Available In this study, we evaluated the association between these polymorphisms and gallstone disease using meta-analysis and compared the hepatic ABCG5/G8 mRNA expression and biliary lipids composition in patients with different genotypes of T400K and Y54C.Data were analyzed using the Stata/SE 11.0 software and a random- effects model was applied irrespective of between-study heterogeneity. Hepatic mRNA expression of ABCG5/G8 genes in 182 patients with gallstone disease and 35 gallstone-free patients who underwent cholecystectomy were determined using real-time PCR. Genotypes of Y54C and T400K in the ABCG8 gene were determined by allelic discrimination using either genomic DNA or hepatic cDNA as template by Taqman assays. Biliary compostion in gallbladder bile was assayed in these patients as well.Ten papers including 13 cohorts were included for the final analysis. In the genotype model, the overall association between genotype with gallstone was significant for D19H (OR = 2.43, 95%CI: 2.23-2.64, P<0.001, and for Y54C (OR = 1.36, 95%CI: 1.01-1.83, P = 0.044, or T400K (OR = 1.17, 95%CI: 0.96-1.43. P = 0.110. In allele model, minor alleles of D19H polymorphism (allele D: OR = 2.25, 95%CI: 2.10-2.42, P<0.001 and of T400K polymorphism (allele K: OR = 1.18, 95%CI: 1.06-1.31, P<0.001 were related with an increased risk of gallstone disease. However, minor allele of Y54C polymorphism (allele Y, OR = 1.08, 95%CI: 0.96-1.21, P = 0.146 was not related with gallstone disease. I(2 statistics indicated no significant between-study heterogeneity for all genetic models for any of the three polymorphisms. Funnel plot and Egger's test suggested the absence of publication bias as well. However, no association of T400K and Y54C polymorphism with hepatic ABCG8/G5 mRNA expression or biliary lipids composition was found.Our study showed strong association of D19H polymorphism with gallstone disease. T400K and Y54C polymorphism, though to

  1. Changes in gallbladder bile composition and crystal detection time in morbidly obese subjects after bariatric surgery.

    Science.gov (United States)

    Gustafsson, Ulf; Benthin, Lisbet; Granström, Lars; Groen, Albert K; Sahlin, Staffan; Einarsson, Curt

    2005-06-01

    The aim of the present study was to elucidate the mechanisms of development of cholesterol crystals and gallstones during weight reduction in obese subjects. Twenty-five morbidly obese, gallstone-free subjects underwent vertical-banded gastroplasty. Gallbladder bile was collected at the time of the operation via needle aspiration and 1.1-7.3 months after the operation via ultrasound-guided transhepatic puncture of the gallbladder. The mean weight loss was 17 kg. Two patients developed gallstones and 10 patients displayed cholesterol crystals in their bile. In patients with a follow-up time of less than 2 months (n = 13), cholesterol saturation increased from 90% to 114% but tended to decrease in the patients with a follow-up time of more than 2 months. The extraction of the concanavalin-A-binding fraction from gallbladder bile obtained after weight reduction in 7 patients prolonged crystallization detection time from 6 to 10 days. The hexosamine concentration, a marker for mucin, was increased by about 100% in bile obtained in 6 of 7 patients after weight reduction. In conclusion, the results indicate that crystallization-promoting compounds (mucin) are of great importance in the development of cholesterol crystals and gallstones in obese subjects during weight reduction, probably because of defective gallbladder emptying.

  2. Impact of heme oxygenase-1 on cholesterol synthesis, cholesterol efflux and oxysterol formation in cultured astroglia.

    Science.gov (United States)

    Hascalovici, Jacob R; Song, Wei; Vaya, Jacob; Khatib, Soliman; Fuhrman, Bianca; Aviram, Michael; Schipper, Hyman M

    2009-01-01

    Up-regulation of heme oxygenase-1 (HO-1) and altered cholesterol (CH) metabolism are characteristic of Alzheimer-diseased neural tissues. The liver X receptor (LXR) is a molecular sensor of CH homeostasis. In the current study, we determined the effects of HO-1 over-expression and its byproducts iron (Fe(2+)), carbon monoxide (CO) and bilirubin on CH biosynthesis, CH efflux and oxysterol formation in cultured astroglia. HO-1/LXR interactions were also investigated in the context of CH efflux. hHO-1 over-expression for 3 days ( approximately 2-3-fold increase) resulted in a 30% increase in CH biosynthesis and a two-fold rise in CH efflux. Both effects were abrogated by the competitive HO inhibitor, tin mesoporphyrin. CO, released from administered CORM-3, significantly enhanced CH biosynthesis; a combination of CO and iron stimulated CH efflux. Free iron increased oxysterol formation three-fold. Co-treatment with LXR antagonists implicated LXR activation in the modulation of CH homeostasis by heme degradation products. In Alzheimer's disease and other neuropathological states, glial HO-1 induction may transduce ambient noxious stimuli (e.g. beta-amyloid) into altered patterns of glial CH homeostasis. As the latter may impact synaptic plasticity and neuronal repair, modulation of glial HO-1 expression (by pharmacological or other means) may confer neuroprotection in patients with degenerative brain disorders.

  3. Solution of a gallstone with methyl-tertiary butyl ether

    Energy Technology Data Exchange (ETDEWEB)

    Brambs, H J; Roeren, T; Holstege, A; Raedecke, J

    1987-08-01

    Methyl-t-butyl ether is a new agent to dissolve gallstones. The substance proves to be very successful and acts very rapidly. A percutaneous transhepatic drainage supplies an adequate access route to dissolve calculi within the bile ducts. We report the case of a patient where before insertion of an internal stent a stone in the common bile duct was dissolved within 3 1/2 hours.

  4. Absolute requirement of cholesterol binding for Hedgehog gradient formation in Drosophila

    Directory of Open Access Journals (Sweden)

    Antoine Ducuing

    2013-05-01

    How morphogen gradients are shaped is a major question in developmental biology, but remains poorly understood. Hedgehog (Hh is a locally secreted ligand that reaches cells at a distance and acts as a morphogen to pattern the Drosophila wing and the vertebrate neural tube. The proper patterning of both structures relies on the precise control over the slope of Hh activity gradient. A number of hypotheses have been proposed to explain Hh movement and hence graded activity of Hh. A crux to all these models is that the covalent binding of cholesterol to Hh N-terminus is essential to achieve the correct slope of the activity gradient. Still, the behavior of cholesterol-free Hh (Hh-N remains controversial: cholesterol has been shown to either increase or restrict Hh range depending on the experimental setting. Here, in fly embryos and wing imaginal discs, we show that cholesterol-free Hh diffuses at a long-range. This unrestricted diffusion of cholesterol-free Hh leads to an absence of gradient while Hh signaling strength remains uncompromised. These data support a model where cholesterol addition restricts Hh diffusion and can transform a leveled signaling activity into a gradient. In addition, our data indicate that the receptor Patched is not able to sequester cholesterol-free Hh. We propose that a morphogen gradient does not necessarily stem from the active transfer of a poorly diffusing molecule, but can be achieved by the restriction of a highly diffusible ligand.

  5. Cholesterol autoxidation in phospholipid membrane bilayers

    International Nuclear Information System (INIS)

    Sevanian, A.; McLeod, L.L.

    1987-01-01

    Lipid peroxidation in unilamellar liposomes of known cholesterol-phospholipid composition was monitored under conditions of autoxidation or as induced by a superoxide radical generating system, gamma-irradiation or cumene hydroperoxide. Formation of cholesterol oxidation products was indexed to the level of lipid peroxidation. The major cholesterol oxidation products identified were 7-keto-cholesterol, isomeric cholesterol 5,6-epoxides, isomeric 7-hydroperoxides and isomeric 3,7-cholestane diols. Other commonly encountered products included 3,5-cholestadiene-7-one and cholestane-3 beta, 5 alpha, 6 beta-triol. Superoxide-dependent peroxidation required iron and produced a gradual increase in 7-keto-cholesterol and cholesterol epoxides. Cholesterol oxidation was greatest in liposomes containing high proportions of unsaturated phospholipid to cholesterol (4:1 molar ratio), intermediate with low phospholipid to cholesterol ratios (2:1) and least in liposomes prepared with dipalmitoylphosphatidylcholine and cholesterol. This relationship held regardless of the oxidizing conditions used. Cumene hydroperoxide-dependent lipid peroxidation and/or more prolonged oxidations with other oxidizing systems yielded a variety of products where cholesterol-5 beta,6 beta-epoxide, 7-ketocholesterol and the 7-hydroperoxides were most consistently elevated. Oxyradical initiation of lipid peroxidation produced a pattern of cholesterol oxidation products distinguishable from the pattern derived by cumene hydroperoxide-dependent peroxidation

  6. A single centre case series of gallstone sigmoid ileus management

    Directory of Open Access Journals (Sweden)

    Nicholas Farkas

    2017-01-01

    Conclusions: This is the first case series highlighting the differing strategies and challenges faced by clinicians managing gallstone sigmoid ileus. Conservative measures (including manual evacuation, endoscopy, lithotripsy and surgery all play important roles in relieving large bowel obstruction. It is essential to tailor care to individual patients’ needs given the complexities of this potentially life threatening condition.

  7. Laparoscopic cholecystectomy in acute gallstone pancreatitis in index hospital admission: feasibility and safety.

    Science.gov (United States)

    Sangrasi, Ahmed Khan; Syed, Bm; Memon, Amir Iqbal; Laghari, Abdul Aziz; Talpur, K Altaf Hussain; Qureshi, Jawaid Naeem

    2014-05-01

    Acute gallstone pancreatitis is quite common throughout the globe. Conventionally definitive cholecystectomy has been delayed in index hospital admission. Since the last decade timing of cholecystectomy is gradually shifting towards the earlier phase of disease and currently gallstone pancreatitis is being evaluated as a further indication for laparoscopic cholecystectomy. There is also great concern regarding compliance of patients for definitive surgery due to poverty, ignorance and illiteracy in developing countries. The aim of this study was to assess the feasibility and safety of laparoscopic cholecystectomy as a definitive treatment in patients with mild and resolving gall stone pancreatitis. This was a prospective study from July 2009 to June 2012. Patients were diagnosed by clinical examination, biochemical tests, ultrasonography and contrast enhanced CT. Patients with mild form of the disease (Ranson Score ≤3) and who showed clinical improvement were offered laparoscopic cholecystectomy in index hospital admission. Those who were unfit for surgery were referred for endoscopic sphincterotomy. Common bile duct stones were excluded preoperatively. A total of 38 patients were admitted with acute gallstone pancreatitis in the study period. The mean age of patients was 46.3 years with male to female ratio of 11/27. 22 (57.8%) patients were selected for laparoscopic cholecystectomy and procedure was completed successfully. Ten (26.3%) patients were referred for ERCP and endoscopic sphincterotomy and 11 (28.9%) were managed by conservative treatment and went without any definitive treatment. Mean duration of time from onset of symptoms and laparoscopic cholecystectomy was 7 days (range 4-10). Mean duration of operative time was 45 minutes and hospital stay was 7 days. There was no operative mortality. No major intra-operative or post-operative complication was recorded. two patients (9%) had minor complications. Laparoscopic cholecystectomy can be safely

  8. Molecular interactions between bile salts, phospholipids and cholesterol : relevance to bile formation, cholesterol crystallization and bile salt toxicity

    NARCIS (Netherlands)

    Moschetta, Antonio

    2001-01-01

    Cholesterol is a nonpolar lipid dietary constituent, absorbed from the small intestine, transported in blood and taken up by the liver. In bile, the sterol is solubilized in mixed micelles by bile salts and phospholipids. In case of supersaturation, cholesterol is kept in vesicles with phospholipid

  9. Preparation of cholesterol oxidase nanoparticles and their application in amperometric determination of cholesterol

    Energy Technology Data Exchange (ETDEWEB)

    Chawla, Sheetal; Rawal, Rachna; Sonia; Ramrati; Pundir, C. S., E-mail: pundircs@rediffmail.com [M. D. University, Department of Biochemistry (India)

    2013-09-15

    The nanoparticle (NP) aggregates of commercial cholesterol oxidase (ChOx) were prepared by desolvation method. The formation and characterization of ChOxNP aggregates were studied by transmission electron microscopy and scanning electron microscopy. NP aggregates were more stable, active and had a higher shelf life than that of free enzyme. An amperometric cholesterol biosensor was constructed by immobilizing ChOxNPs onto Au electrode. The biosensor showed optimum response within 8 s at pH 6.0 and 35 Degree-Sign C, when polarized at +0.27 V versus Ag/AgCl. The biosensor possesses high sensitivity and measures cholesterol concentrations as low as 1.56 mg/dl. The working linear range was 12.5-700 mg/dl for cholesterol. The biosensor was evaluated and employed for measurement of total cholesterol in human serum. The enzyme electrode lost 50 % of its initial activity during its regular use for 180 times over a period of 90 days when stored in 0.1 M sodium phosphate buffer, pH 7.0 at 4 Degree-Sign C.

  10. Preparation of cholesterol oxidase nanoparticles and their application in amperometric determination of cholesterol

    International Nuclear Information System (INIS)

    Chawla, Sheetal; Rawal, Rachna; Sonia; Ramrati; Pundir, C. S.

    2013-01-01

    The nanoparticle (NP) aggregates of commercial cholesterol oxidase (ChOx) were prepared by desolvation method. The formation and characterization of ChOxNP aggregates were studied by transmission electron microscopy and scanning electron microscopy. NP aggregates were more stable, active and had a higher shelf life than that of free enzyme. An amperometric cholesterol biosensor was constructed by immobilizing ChOxNPs onto Au electrode. The biosensor showed optimum response within 8 s at pH 6.0 and 35 °C, when polarized at +0.27 V versus Ag/AgCl. The biosensor possesses high sensitivity and measures cholesterol concentrations as low as 1.56 mg/dl. The working linear range was 12.5–700 mg/dl for cholesterol. The biosensor was evaluated and employed for measurement of total cholesterol in human serum. The enzyme electrode lost 50 % of its initial activity during its regular use for 180 times over a period of 90 days when stored in 0.1 M sodium phosphate buffer, pH 7.0 at 4 °C

  11. The origin of cholesterol in chyle demonstrated by nuclear indicator methods; Origines du cholesterol du chyle mises en evidence par la methode des indicateurs nucleaires

    Energy Technology Data Exchange (ETDEWEB)

    Vyas, M

    1962-07-01

    In order to obtain information about the mechanism of the intestinal absorption of cholesterol, rats having a lymphatic abdominal fistula are used. The animals receive either 4-{sup 14}C- cholesterol subcutaneously or orally, or the 1-{sup 14}C acetate. The study of the specific radio-activities of the cholesterol in chyle, in serum, in the lining, and in the intestinal contents makes it possible to define the roles played by the transfer cholesterol from the serum, by the cholesterol synthesised intestinally, and by the absorption cholesterol, in the formations of the lymph and of the chylomicrons. A new theory is proposed for the mechanism of cholesterol absorption. (author) [French] Pour obtenir des renseignements concernant le mecanisme de l'absorption intestinale du cholesterol, on utilise des rats porteurs d'une fistule lymphatique abdominale. Les animaux recoivent soit du cholesterol 4-{sup 14}C par voie sous-cutanee ou par voie orale, soit de l'acetate 1-{sup 14}C. L'etude des radioactivites specifiques du cholesterol du chyle, du serum, de la paroi et du contenu intestinal permet de preciser les roles joues par le cholesterol de transfert d'origine serique, par le cholesterol de synthese intestinale et par le cholesterol d'absorption, dans la formation de la lymphe et des chylomicrons. Une theorie nouvelle concernant le mecanisme de l'absorption du cholesterol est proposee. (auteur)

  12. Bouveret's syndrome complicated by distal gallstone ileus after laser lithotropsy using Holmium: YAG laser

    Directory of Open Access Journals (Sweden)

    Rodgers John B

    2002-06-01

    Full Text Available Abstract Background Bouveret's syndrome is an unusual presentation of duodenal obstruction caused by the passage of a large gallstone through a cholecystoduodenal fistula. Endoscopic therapy has been used as first-line treatment, especially in patients with high surgical risk. Case presentation We report a 67-year-old woman who underwent an endoscopic attempt to fragment and retrieve a duodenal stone using a Holmium: Yttrium-Aluminum-Garnet Laser (Ho:YAG which resulted in small bowel obstruction. The patient successfully underwent enterolithotomy without cholecystectomy or closure of the fistula. Conclusion We conclude that, distal gallstone obstruction, due to migration of partially fragmented stones, can occur as a possible complication of laser lithotripsy treatment of Bouveret's syndrome and might require urgent enterolithotomy.

  13. Changes in gallbladder bile composition and crystal detection time in morbidly obese subjects after bariatric surgery

    NARCIS (Netherlands)

    Gustafsson, Ulf; Benthin, Lisbet; Granström, Lars; Groen, Albert K.; Sahlin, Staffan; Einarsson, Curt

    2005-01-01

    The aim of the present study was to elucidate the mechanisms of development of cholesterol crystals and gallstones during weight reduction in obese subjects. Twenty-five morbidly obese, gallstone-free subjects underwent vertical-banded gastroplasty. Gallbladder bile was collected at the time of the

  14. Spiromastixones Inhibit Foam Cell Formation via Regulation of Cholesterol Efflux and Uptake in RAW264.7 Macrophages

    Directory of Open Access Journals (Sweden)

    Chongming Wu

    2015-10-01

    Full Text Available Bioassay-guided evaluation shows that a deep sea-derived fungus, Spiromastix sp. MCCC 3A00308, possesses lipid-lowering activity. Chromatographic separation of a culture broth resulted in the isolation of 15 known depsidone-based analogues, labeled spiromastixones A–O (1–15. Each of these compounds was tested for its ability to inhibit oxidized low-density lipoprotein (oxLDL-induced foam cell formation in RAW264.7 macrophages. Spiromastixones 6–8 and 12–14 significantly decreased oxLDL-induced lipid over-accumulation, reduced cell surface area, and reduced intracellular cholesterol concentration. Of these compounds, spiromastixones 6 and 14 exerted the strongest inhibitory effects. Spiromastixones 6 and 14 dramatically inhibited cholesterol uptake and stimulated cholesterol efflux to apolipoprotein A1 (ApoA1 and high-density lipoprotein (HDL in RAW264.7 macrophages. Mechanistic investigation indicated that spiromastixones 6, 7, 12 and 14 significantly up-regulated the mRNA levels of ATP-binding cassette sub-family A1 (ABCA1 and down-regulated those of scavenger receptor CD36, while the transcription of ATP-binding cassette sub-family A1 (ABCG1 and proliferator-activated receptor gamma (PPARγ were selectively up-regulated by 6 and 14. A transactivation reporter assay revealed that spiromastixones 6 and 14 remarkably enhanced the transcriptional activity of PPARγ. These results suggest that spiromastixones inhibit foam cell formation through upregulation of PPARγ and ABCA1/G1 and downregulation of CD36, indicating that spiromastixones 6 and 14 are promising lead compounds for further development as anti-atherogenic agents.

  15. SIRT6 reduces macrophage foam cell formation by inducing autophagy and cholesterol efflux under ox-LDL condition.

    Science.gov (United States)

    He, Jiangping; Zhang, Guangya; Pang, Qi; Yu, Cong; Xiong, Jie; Zhu, Jing; Chen, Fengling

    2017-05-01

    SIRT6 is a pivotal regulator of lipid metabolism. It is also closely connected to cardiovascular diseases, which are the main cause of death in diabetic patients. We observed a decrease in the expression of SIRT6 and key autophagy effectors (ATG5, LC3B, and LAMP1) in ox-LDL-induced foam cells, a special form of lipid-laden macrophages. In these cells, SIRT6 WT but not SIRT6 H133Y overexpression markedly reduced foam cell formation, as shown by Oil Red O staining, while inducing autophagy flux, as determined by both mRFP-GFP-LC3 labeling and transmission electron microscopy. Silencing the key autophagy initiation gene ATG5, reversed the autophagy-promoting effect of SIRT6 in ox-LDL-treated THP1 cells, as evidenced by an increase in foam cells. Cholesterol efflux assays indicated that SIRT6 overexpression in foam cells promoted cholesterol efflux, increased the levels of ABCA1 and ABCG1, and reduced miR-33 levels. By transfecting miR-33 into cells overexpressing SIRT6, we observed that reduced foam cell formation and autophagy flux induction were largely reversed. These data imply that SIRT6 plays an essential role in protecting against atherosclerosis by reducing foam cell formation through an autophagy-dependent pathway. © 2017 Federation of European Biochemical Societies.

  16. Is the loss of gallstones during laparoscopic cholecystectomy an underestimated complication?

    Science.gov (United States)

    Gerlinzani, S; Tos, M; Gornati, R; Molteni, B; Poliziani, D; Taschieri, A M

    2000-04-01

    Laparoscopic cholecystectomy entails an increased risk of gallbladder rupture and consequent loss of stones in the abdominal cavity. Herein we report the case of a 51-year-old male patient, who underwent laparoscopic cholecystectomy 2 years before presentation to our hospital. He had experienced tension sensation and epigastric pain since 4 months postoperatively. A well-defined epigastric mass, which was hard and painful on palpation, was detected and later confirmed by ultrasonography and CT scan. Explorative laparotomy revealed a mass in the area of the gastrocolic ligament,resulting from biliary gallstones in conjunction with a perimetral inflammatory reaction. A review of the literature showed that the incidence of gallbladder lesions during laparoscopy is 13-40%. In order to prevent this complication, meticulous isolation of the gallbladder, proper dissection of the cystic duct and artery, and careful extraction through the umbilical access are required. Ligation after the rupture or use of an endo-bag may be helpful. The loss of gallstones and their retention in the abdominal cavity should be noted in the description of the surgical procedure.

  17. New conception concerning the dynamical state of cholesterol in rat; Conception nouvelle concernant l'etat dynamyque du cholesterol chez le rat

    Energy Technology Data Exchange (ETDEWEB)

    Chevallier, F [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1956-03-15

    It presents the study of the cholesterol metabolism in rats. This thesis has been divided in three chapters. In a first part, it will discuss about the dynamic state of biological constituents in organism and in particular the dynamic state of cholesterol. This matter will be considered, firstly under its theoretical aspect and secondly under an experimental point of view with isotopic techniques. The current data on the dynamic state of cholesterol will allow to identify the essential points which are the subject of this research. In particular, the full understanding of the different cholesterol origins (diet, biosynthesis or formation of cholesterol from degradation or transformation of precursors as acetate or butyric acid for example) and the different cholesterol disappearance way (excretion, destruction, transformation or esters formation) is necessary to further research. In a second part, the experimental techniques and methods are described. A brief presentation of the methods for the study of the cholesterol transport and synthesis will be given as well as the experimental conditions and in particular the animal diet and cholesterol ingestion, the administration of acetate and {gamma}-phenyl {alpha}-aminobutyric. The different preparations of the {sup 14}C labelled cholesterol are also described as well as the extraction and measuring of the specific {sup 14}C radioactivity in the animal tissues extract, carbon dioxide gas and sodium acetate. Finally, the results will be given and discussed according to the way of intake: a radioactive cholesterol ingestion or an acetate intraperitoneal injection. (M.P.)

  18. Exploration of molecular interactions in cholesterol superlattices: effect of multibody interactions.

    Science.gov (United States)

    Huang, Juyang

    2002-08-01

    Experimental evidences have indicated that cholesterol may adapt highly regular lateral distributions (i.e., superlattices) in a phospholipid bilayer. We investigated the formations of superlattices at cholesterol mole fraction of 0.154, 0.25, 0.40, and 0.5 using Monte Carlo simulation. We found that in general, conventional pairwise-additive interactions cannot produce superlattices. Instead, a multibody (nonpairwise) interaction is required. Cholesterol superlattice formation reveals that although the overall interaction between cholesterol and phospholipids is favorable, it contains two large opposing components: an interaction favoring cholesterol-phospholipid mixing and an unfavorable acyl chain multibody interaction that increases nonlinearly with the number of cholesterol contacts. The magnitudes of interactions are in the order of kT. The physical origins of these interactions can be explained by our umbrella model. They most likely come from the requirement for polar phospholipid headgroups to cover the nonpolar cholesterol to avoid the exposure of cholesterol to water and from the sharp decreasing of acyl chain conformation entropy due to cholesterol contact. This study together with our previous work demonstrate that the driving force of cholesterol-phospholipid mixing is a hydrophobic interaction, and multibody interactions dominate others over a wide range of cholesterol concentration.

  19. Chronic skin inflammation accelerates macrophage cholesterol crystal formation and atherosclerosis

    Science.gov (United States)

    Ng, Qimin; Sanda, Gregory E.; Dey, Amit K.; Teague, Heather L.; Sorokin, Alexander V.; Dagur, Pradeep K.; Silverman, Joanna I.; Harrington, Charlotte L.; Rodante, Justin A.; Rose, Shawn M.; Varghese, Nevin J.; Belur, Agastya D.; Goyal, Aditya; Gelfand, Joel M.; Springer, Danielle A.; Bleck, Christopher K.E.; Thomas, Crystal L.; Yu, Zu-Xi; Winge, Mårten C.G.; Kruth, Howard S.; Marinkovich, M. Peter; Joshi, Aditya A.; Playford, Martin P.; Mehta, Nehal N.

    2018-01-01

    Inflammation is critical to atherogenesis. Psoriasis is a chronic inflammatory skin disease that accelerates atherosclerosis in humans and provides a compelling model to understand potential pathways linking these diseases. A murine model capturing the vascular and metabolic diseases in psoriasis would accelerate our understanding and provide a platform to test emerging therapies. We aimed to characterize a new murine model of skin inflammation (Rac1V12) from a cardiovascular standpoint to identify novel atherosclerotic signaling pathways modulated in chronic skin inflammation. The RacV12 psoriasis mouse resembled the human disease state, including presence of systemic inflammation, dyslipidemia, and cardiometabolic dysfunction. Psoriasis macrophages had a proatherosclerotic phenotype with increased lipid uptake and foam cell formation, and also showed a 6-fold increase in cholesterol crystal formation. We generated a triple-genetic K14-RacV12–/+/Srb1–/–/ApoER61H/H mouse and confirmed psoriasis accelerates atherogenesis (~7-fold increase). Finally, we noted a 60% reduction in superoxide dismutase 2 (SOD2) expression in human psoriasis macrophages. When SOD2 activity was restored in macrophages, their proatherogenic phenotype reversed. We demonstrate that the K14-RacV12 murine model captures the cardiometabolic dysfunction and accelerates vascular disease observed in chronic inflammation and that skin inflammation induces a proatherosclerotic macrophage phenotype with impaired SOD2 function, which associated with accelerated atherogenesis. PMID:29321372

  20. Can macular xanthophylls replace cholesterol in formation of the liquid-ordered phase in lipid-bilayer membranes?

    Science.gov (United States)

    Subczynski, Witold K; Wisniewska-Becker, Anna; Widomska, Justyna

    2012-01-01

    Lateral organization of membranes made from binary mixtures of dimyristoylphosphatidylcholine (DMPC) or dipalmitoylphosphatidylcholine (DPPC) and macular xanthophylls (lutein or zeaxanthin) was investigated using the saturation-recovery (SR) EPR spin-labeling discrimination by oxygen transport (DOT) method in which the bimolecular collision rate of molecular oxygen with the nitroxide spin label is measured. This work was undertaken to examine whether or not lutein and zeaxanthin, macular xanthophylls that parallel cholesterol in its function as a regulator of both membrane fluidity and hydrophobicity, can parallel other structural functions of cholesterol, including formation of the liquid-ordered phase in membranes. The DOT method permits discrimination of different membrane phases when the collision rates (oxygen transport parameter) differ in these phases. Additionally, membrane phases can be characterized by the oxygen transport parameter in situ without the need for separation, which provides information about the dynamics of each phase. In gel-phase membranes, two coexisting phases were discriminated in the presence of macular xanthophylls - namely, the liquid-ordered-like and solid-ordered-like phases. However, in fluid-phase membranes, xanthophylls only induce the solitary liquid-ordered-like phase, while at similar concentrations, cholesterol induces coexisting liquid-ordered and liquid-disordered phases. No significant differences between the effects of lutein and zeaxanthin were found.

  1. [DYNAMIC OF CLINICAL, LABORATORY AND SONOGRAPHIC PARAMETERS AFTER SUCCESSFUL LITHOLITIC THERAPY AT PATIENTS WITH GALLSTONE DISEASE IN ASSOCIATION WITH METABOLIC SYNDROME].

    Science.gov (United States)

    Gaus, O V; Akhmedov, V A

    2015-01-01

    The aim of study was to determine the leading clinical, immunological and sonographic pararneters, reflecting the efficiency of Ursodeoxycholic acid (UDCA) at the rate of 10 mg per 1 kg of body weight in the treatment of gallstone disease in patients with metabolic syndrome (MS). An assessment of clinical, biochemical immunological and sonographic parameters in 54 patients with gallstone disease associated with the metabolic syndrome before and after the six-month treatment UDCA were made. In accordance with our results the significant predictors, reflecting successful litholitic therapy at patients with gallstone disease in association with metabolic syndrome are decrease the serum concentration of gamma-glutamyltranspeptidase (P = 0.003), matrix metalloproteinase-9 (P = 0.001), increase the serum concentration of tissue inhibitor of metalloproteinases-1 (P = 0.02), decrease the left liver lobe thickness (P = 0,003) and the thickness of gallbladder wall (P = 0.0002). The results of our study have shown that the therapy with ursodesoxycholic acid of patients with metabolic syndrome leads to decrease of factors of gallstone progression (elevated levels of gamma-glutamyltranspeptidase, matrix metalloproteinase-9 and increased thickness of the left lobe liver and gallbladder wall).

  2. New conception concerning the dynamical state of cholesterol in rat; Conception nouvelle concernant l'etat dynamyque du cholesterol chez le rat

    Energy Technology Data Exchange (ETDEWEB)

    Chevallier, F. [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1956-03-15

    It presents the study of the cholesterol metabolism in rats. This thesis has been divided in three chapters. In a first part, it will discuss about the dynamic state of biological constituents in organism and in particular the dynamic state of cholesterol. This matter will be considered, firstly under its theoretical aspect and secondly under an experimental point of view with isotopic techniques. The current data on the dynamic state of cholesterol will allow to identify the essential points which are the subject of this research. In particular, the full understanding of the different cholesterol origins (diet, biosynthesis or formation of cholesterol from degradation or transformation of precursors as acetate or butyric acid for example) and the different cholesterol disappearance way (excretion, destruction, transformation or esters formation) is necessary to further research. In a second part, the experimental techniques and methods are described. A brief presentation of the methods for the study of the cholesterol transport and synthesis will be given as well as the experimental conditions and in particular the animal diet and cholesterol ingestion, the administration of acetate and {gamma}-phenyl {alpha}-aminobutyric. The different preparations of the {sup 14}C labelled cholesterol are also described as well as the extraction and measuring of the specific {sup 14}C radioactivity in the animal tissues extract, carbon dioxide gas and sodium acetate. Finally, the results will be given and discussed according to the way of intake: a radioactive cholesterol ingestion or an acetate intraperitoneal injection. (M.P.)

  3. Lipoprotein cholesterol uptake mediates upregulation of bile acid synthesis by increasing cholesterol 7a-hydroxylase but not sterol 27- hydroxylase gene expression in cultured rat hepatocytes.

    NARCIS (Netherlands)

    Post, S.M.; Twisk, J.W.R.; van der Fits, L.T.E.; Wit, E.C.M.; Hoekman, M.F.M.; Mager, W.H.; Princen, H.M.G.

    1999-01-01

    Lipoproteins may supply substrate for the formation of bile acids, and the amount of hepatic cholesterol can regulate bile-acid synthesis and increase cholesterol 7α-hydroxylase expression. However, the effect of lipoprotein cholesterol on sterol 27-hydroxylase expression and the role of different

  4. Microwave assisted direct saponification for the simultaneous determination of cholesterol and cholesterol oxides in shrimp.

    Science.gov (United States)

    Souza, Hugo A L; Mariutti, Lilian R B; Bragagnolo, Neura

    2017-05-01

    A novel microwave-assisted direct saponification method for the simultaneous determination of cholesterol and cholesterol oxides in shrimp was developed and validated. Optimal saponification conditions, determined by means of an experimental design, were achieved using 500mg of sample and 20mL of 1mol/L KOH ethanol solution for 16min at 45°C at maximum power at 200W and magnetic stirring at 120rpm. Higher extraction of cholesterol oxides in a reduced saponification time (∼75 times) was achieved in comparison with the direct cold saponification method. The new method showed low detection (≤0.57μg/mL) and quantification (≤1.73μg/mL) limits, good repeatability (≤10.50% intraday and ≤8.56% interday) and low artifact formation (evaluated by using a deuterated cholesterol-D6 standard). Raw, salted and dried-salted shrimps were successfully analyzed by the validated method. The content of cholesterol oxides increased after salting and decreased after drying. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Efficacy of Magnesium Trihydrate of Ursodeoxycholic Acid and Chenodeoxycholic Acid for Gallstone Dissolution: A Prospective Multicenter Trial.

    Science.gov (United States)

    Hyun, Jong Jin; Lee, Hong Sik; Kim, Chang Duck; Dong, Seok Ho; Lee, Seung-Ok; Ryu, Ji Kon; Lee, Don Haeng; Jeong, Seok; Kim, Tae Nyeun; Lee, Jin; Koh, Dong Hee; Park, Eun Taek; Lee, In-Seok; Yoo, Byung Moo; Kim, Jin Hong

    2015-07-01

    Cholecystectomy is necessary for the treatment of symptomatic or complicated gallbladder (GB) stones, but oral litholysis with bile acids is an attractive alternative therapeutic option for asymptomatic or mildly symptomatic patients. This study was conducted to evaluate the efficacy of magnesium trihydrate of ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA) on gallstone dissolution and to investigate improvements in gallstone-related symptoms. A prospective, multicenter, phase 4 clinical study to determine the efficacy of orally administered magnesium trihydrate of UDCA and CDCA was performed from January 2011 to June 2013. The inclusion criteria were GB stone diameter ≤15 mm, GB ejection fraction ≥50%, radiolucency on plain X-ray, and asymptomatic/mildly symptomatic patients. The patients were prescribed one capsule of magnesium trihydrate of UDCA and CDCA at breakfast and two capsules at bedtime for 6 months. The dissolution rate, response rate, and change in symptom score were evaluated. A total of 237 subjects were enrolled, and 195 subjects completed the treatment. The dissolution rate was 45.1% and the response rate was 47.2% (92/195) after 6 months of administration of magnesium trihydrate of UDCA and CDCA. Only the stone diameter was significantly associated with the response rate. Both the symptom score and the number of patients with symptoms significantly decreased regardless of stone dissolution. Adverse events necessitating discontinuation of the drug, surgery, or endoscopic management occurred in 2.5% (6/237) of patients. Magnesium trihydrate of UDCA and CDCA is a well-tolerated bile acid that showed similar efficacy for gallstone dissolution and improvement of gallstone-related symptoms as that shown in previous studies.

  6. Inhibition of cholesterol oxidation products (COPs) formation in emulsified porcine patties by phenolic-rich avocado (Persea americana Mill.) extracts.

    Science.gov (United States)

    Rodríguez-Carpena, Javier-Germán; Morcuende, David; Petrón, María Jesus; Estévez, Mario

    2012-03-07

    The effect of phenolic-rich extracts from avocado peel on the formation of cholesterol oxidation products (COPs) in porcine patties subjected to cooking and chill storage was studied. Eight COPs (7α-hydroxycholesterol, 7β-hydroxycholesterol, 7-ketocholesterol, 20α-hydroxycholesterol, 25-hydroxycholesterol, cholestanetriol, 5,6β-epoxycholesterol, and 5,6α-epoxycholesterol) were identified and quantified by GC-MS. The addition of avocado extracts (∼600 GAE/kg patty) to patties significantly inhibited the formation of COPs during cooking. Cooked control (C) patties contained a larger variety and greater amounts of COPs than the avocado-treated (T) counterparts. COPs sharply increased in cooked patties during the subsequent chilled storage. This increase was significantly higher in C patties than in the T patties. Interestingly, the amount of COPs in cooked and chilled T patties was similar to those found in cooked C patties. The mechanisms implicated in cholesterol oxidation in a processed meat product, the protective effect of avocado phenolics, and the potential implication of lipid and protein oxidation are thoroughly described in the present paper.

  7. Physical Chemistry of Bile: Detailed Pathogenesis of Cholelithiasis.

    Science.gov (United States)

    Itani, Malak; Dubinsky, Theodore J

    2017-09-01

    Despite the overwhelming prevalence of cholelithiasis, many health care professionals are not familiar with the basic pathophysiology of gallstone formation. This article provides an overview of the biochemical pathways related to bile, with a focus on the physical chemistry of bile. We describe the important factors in bile synthesis and secretion that affect the composition of bile and consequently its liquid state. Within this biochemical background lies the foundation for understanding the clinical and sonographic manifestation of cholelithiasis, including the pathophysiology of cholesterol crystallization, gallbladder sludge, and gallstones. There is a brief discussion of the clinical manifestations of inflammatory and obstructive cholestasis and the impact on bile metabolism and subsequently on liver function tests. Despite being the key modality in diagnosing cholelithiasis, ultrasound has a limited role in the characterization of stone composition.

  8. Cholesterol in unusual places

    Energy Technology Data Exchange (ETDEWEB)

    Kucerka, N; Nieh, M P; Marquardt, D; Harroun, T A; Wassail, S R; Katsaras, J, E-mail: John.Katsaras@nrc.gc.ca, E-mail: Norbert.Kucerka@nrc.gc.ca

    2010-11-01

    Cholesterol is an essential component of mammalian cells, and is required for building and maintaining cell membranes, regulating their fluidity, and possibly acting as an antioxidant. Cholesterol has also been implicated in cell signaling processes, where it has been suggested that it triggers the formation of lipid rafts in the plasma membrane. Aside from cholesterol's physiological roles, what is also becoming clear is its poor affinity for lipids with unsaturated fatty acids as opposed to saturated lipids, such as sphingomyelin with which it forms rafts. We previously reported the location of cholesterol in membranes with varying degrees of acyl chain unsaturation as determined by neutron diffraction studies (Harroun et al 2006 Biochemistry 45, 1227; Harroun et al 2008 Biochemistry 47, 7090). In bilayers composed of phosphatidylcholine (PC) molecules with a saturated acyl chain at the sn-1 position or a monounsaturated acyl chain at both sn-1 and sn-2 positions, cholesterol was found in its much-accepted 'upright' position. However, in dipolyunsaturated 1,2-diarachidonyl phosphatidylcholine (20:4-20:4PC) membranes the molecule was found sequestered in the center of the bilayers. In further experiments, mixing l-palmitoyl-2-oleoyl phosphatidylcholine (16:0-18:1 PC) with 20:4-20:4PC resulted in cholesterol reverting to its upright orientation at approximately 40 mol% 16:0-18:1 PC. Interestingly, the same effect was achieved with only 5 mol% 1,2-dimyristoyl phosphatidylchoile (14:0-14:0PC).

  9. Cholesterol in unusual places

    International Nuclear Information System (INIS)

    Kucerka, N; Nieh, M P; Marquardt, D; Harroun, T A; Wassail, S R; Katsaras, J

    2010-01-01

    Cholesterol is an essential component of mammalian cells, and is required for building and maintaining cell membranes, regulating their fluidity, and possibly acting as an antioxidant. Cholesterol has also been implicated in cell signaling processes, where it has been suggested that it triggers the formation of lipid rafts in the plasma membrane. Aside from cholesterol's physiological roles, what is also becoming clear is its poor affinity for lipids with unsaturated fatty acids as opposed to saturated lipids, such as sphingomyelin with which it forms rafts. We previously reported the location of cholesterol in membranes with varying degrees of acyl chain unsaturation as determined by neutron diffraction studies (Harroun et al 2006 Biochemistry 45, 1227; Harroun et al 2008 Biochemistry 47, 7090). In bilayers composed of phosphatidylcholine (PC) molecules with a saturated acyl chain at the sn-1 position or a monounsaturated acyl chain at both sn-1 and sn-2 positions, cholesterol was found in its much-accepted 'upright' position. However, in dipolyunsaturated 1,2-diarachidonyl phosphatidylcholine (20:4-20:4PC) membranes the molecule was found sequestered in the center of the bilayers. In further experiments, mixing l-palmitoyl-2-oleoyl phosphatidylcholine (16:0-18:1 PC) with 20:4-20:4PC resulted in cholesterol reverting to its upright orientation at approximately 40 mol% 16:0-18:1 PC. Interestingly, the same effect was achieved with only 5 mol% 1,2-dimyristoyl phosphatidylchoile (14:0-14:0PC).

  10. Apolipoprotein M promotes mobilization of cellular cholesterol in vivo

    DEFF Research Database (Denmark)

    Elsøe, Sara; Christoffersen, Christina; Luchoomun, Jayraz

    2013-01-01

    The HDL associated apolipoprotein M (apoM) protects against experimental atherosclerosis but the mechanism is unknown. ApoM increases prebeta-HDL formation. We explored whether plasma apoM affects mobilization of cholesterol from peripheral cells in mice.......The HDL associated apolipoprotein M (apoM) protects against experimental atherosclerosis but the mechanism is unknown. ApoM increases prebeta-HDL formation. We explored whether plasma apoM affects mobilization of cholesterol from peripheral cells in mice....

  11. Diagnostic imaging for preparation of extracorporeal shockwave lithotripsy of gallbladder stones

    International Nuclear Information System (INIS)

    Brandstetter, K.; Golder, W.; Neuhaus, H.

    1991-01-01

    Extracorporeal shockwave lithotripsy can be applied as a non-invasive treatment of patients with predominantly cholesterol-type gallstones. As for this treatment, gall bladder contractility and patency of the ductus cysticus must be guaranteed, CT and sonography are applied to check these conditions, and also to determine the size and number of gallstones. (DG) [de

  12. Cholesterol transfer at endosomal-organelle membrane contact sites.

    Science.gov (United States)

    Ridgway, Neale D; Zhao, Kexin

    2018-06-01

    Cholesterol is delivered to the limiting membrane of late endosomes by Niemann-Pick Type C1 and C2 proteins. This review summarizes recent evidence that cholesterol transfer from endosomes to the endoplasmic reticulum and other organelles is mediated by lipid-binding proteins that localize to membrane contact sites (MCS). LDL-cholesterol in the late endosomal/lysosomes is exported to the plasma membrane, where most cholesterol resides, and the endoplasmic reticulum, which harbors the regulatory complexes and enzymes that control the synthesis and esterification of cholesterol. A major advance in dissecting these cholesterol transport pathways was identification of frequent and dynamic MCS between endosomes and the endoplasmic reticulum, peroxisomes and plasma membrane. Positioned at these MCS are members of the oxysterol-binding protein (OSBP) and steroidogenic acute regulatory protein-related lipid-transfer family of lipid transfer proteins that bridge the opposing membranes and directly or indirectly mediate cholesterol transfer. OSBP-related protein 1L (ORP1L), ORP5 and ORP6 mediate cholesterol transfer to the endoplasmic reticulum that regulates cholesterol homeostasis. ORP1L and STARD3 also move cholesterol from the endoplasmic reticulum-to-late endosomal/lysosomes under low-cholesterol conditions to facilitate intraluminal vesicle formation. Cholesterol transport also occurs at MCS with peroxisomes and possibly the plasma membrane. Frequent contacts between organelles and the endo-lysosomal vesicles are sites for bidirectional transfer of cholesterol.

  13. Fluoroscopy-Guided Percutaneous Gallstone Removal Using a 12-Fr Sheath in High-Risk Surgical Patients with Acute Cholecystitis

    International Nuclear Information System (INIS)

    Kim, Young Hwan; Kim, Yong Joo; Shin, Tae Beom

    2011-01-01

    To evaluate the technical feasibility and clinical efficacy of percutaneous transhepatic cholecystolithotomy under fluoroscopic guidance in high-risk surgical patients with acute cholecystitis. Sixty-three consecutive patients of high surgical risk with acute calculous cholecystitis underwent percutaneous transhepatic gallstone removal under conscious sedation. The stones were extracted through the 12-Fr sheath using a Wittich nitinol stone basket under fluoroscopic guidance on three days after performing a percutaneous cholecystostomy. Large or hard stones were fragmented using either the snare guide wire technique or the metallic cannula technique. Gallstones were successfully removed from 59 of the 63 patients (94%). Reasons for stone removal failure included the inability to grasp a large stone in two patients, and the loss of tract during the procedure in two patients with a contracted gallbladder. The mean hospitalization duration was 7.3 days for acute cholecystitis patients and 9.4 days for gallbladder empyema patients. Bile peritonitis requiring percutaneous drainage developed in two patients. No symptomatic recurrence occurred during follow-up (mean, 608.3 days). Fluoroscopy-guided percutaneous gallstone removal using a 12-Fr sheath is technically feasible and clinically effective in high-risk surgical patients with acute cholecystitis

  14. Fluoroscopy-Guided Percutaneous Gallstone Removal Using a 12-Fr Sheath in High-Risk Surgical Patients with Acute Cholecystitis

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Young Hwan [Keimyung University, College of Medicine, Daegu (Korea, Republic of); Kim, Yong Joo [Andong General Hospital, Andong (Korea, Republic of); Shin, Tae Beom [Gyeonsang National University, College of Medicine, Jinju (Korea, Republic of)

    2011-04-15

    To evaluate the technical feasibility and clinical efficacy of percutaneous transhepatic cholecystolithotomy under fluoroscopic guidance in high-risk surgical patients with acute cholecystitis. Sixty-three consecutive patients of high surgical risk with acute calculous cholecystitis underwent percutaneous transhepatic gallstone removal under conscious sedation. The stones were extracted through the 12-Fr sheath using a Wittich nitinol stone basket under fluoroscopic guidance on three days after performing a percutaneous cholecystostomy. Large or hard stones were fragmented using either the snare guide wire technique or the metallic cannula technique. Gallstones were successfully removed from 59 of the 63 patients (94%). Reasons for stone removal failure included the inability to grasp a large stone in two patients, and the loss of tract during the procedure in two patients with a contracted gallbladder. The mean hospitalization duration was 7.3 days for acute cholecystitis patients and 9.4 days for gallbladder empyema patients. Bile peritonitis requiring percutaneous drainage developed in two patients. No symptomatic recurrence occurred during follow-up (mean, 608.3 days). Fluoroscopy-guided percutaneous gallstone removal using a 12-Fr sheath is technically feasible and clinically effective in high-risk surgical patients with acute cholecystitis

  15. Cholesterol biosynthesis in polychlorinated biphenyl-treated rats

    International Nuclear Information System (INIS)

    Kling, D.; Gamble, W.

    1982-01-01

    After administration of polychlorinated biphenly (PCB) at 0.055 (w/w) of the diet to Wistar rats for 30 days, followed by intraperitioneal injection of tritiated water, [ 14 C]mevalonate, and [ 14 C]acetate, there was a decrease in cholesterol biosynthesis in rat liver. No significant change in cholesterol formation was observed when PCB was administered at 0.01% (w/w) of the diet. In vitro inhibition of cholesterol synthesis by rat liver microsomes was observed with PCB. Squalene 2,3-oxidocyclase activity of rat liver microsomes was not significantly altered. Desmosterol delta 24 reductase activity was inhibited only at relatively high concentrations of PCB. There was increased incorporation of radioactivity into squalene and lanosterol, in vitro, in the presence of PCB. The primary inhibition of cholesterol biosynthesis appears to be at the demethylation and rearrangement reactions between lanosterol and cholesterol in the biosynthetic pathway

  16. High-fat diet reduces the formation of butyrate, but increases succinate, inflammation, liver fat and cholesterol in rats, while dietary fibre counteracts these effects.

    Directory of Open Access Journals (Sweden)

    Greta Jakobsdottir

    Full Text Available Obesity is linked to type 2 diabetes and risk factors associated to the metabolic syndrome. Consumption of dietary fibres has been shown to have positive metabolic health effects, such as by increasing satiety, lowering blood glucose and cholesterol levels. These effects may be associated with short-chain fatty acids (SCFAs, particularly propionic and butyric acids, formed by microbial degradation of dietary fibres in colon, and by their capacity to reduce low-grade inflammation.To investigate whether dietary fibres, giving rise to different SCFAs, would affect metabolic risk markers in low-fat and high-fat diets using a model with conventional rats for 2, 4 and 6 weeks.Conventional rats were administered low-fat or high-fat diets, for 2, 4 or 6 weeks, supplemented with fermentable dietary fibres, giving rise to different SCFA patterns (pectin - acetic acid; guar gum - propionic acid; or a mixture - butyric acid. At the end of each experimental period, liver fat, cholesterol and triglycerides, serum and caecal SCFAs, plasma cholesterol, and inflammatory cytokines were analysed. The caecal microbiota was analysed after 6 weeks.Fermentable dietary fibre decreased weight gain, liver fat, cholesterol and triglyceride content, and changed the formation of SCFAs. The high-fat diet primarily reduced formation of SCFAs but, after a longer experimental period, the formation of propionic and acetic acids recovered. The concentration of succinic acid in the rats increased in high-fat diets with time, indicating harmful effect of high-fat consumption. The dietary fibre partly counteracted these harmful effects and reduced inflammation. Furthermore, the number of Bacteroides was higher with guar gum, while noticeably that of Akkermansia was highest with the fibre-free diet.

  17. Key molecular requirements for raft formation in lipid/cholesterol membranes.

    Directory of Open Access Journals (Sweden)

    Davit Hakobyan

    Full Text Available The lipid mixture of DPPC (saturated lipid/DUPC (unsaturated lipid/CHOL (cholesterol is studied with respect to its ability to form liquid-ordered and liquid-disordered phases. We employ coarse-grained simulations with MARTINI force field. All three components are systematically modified in order to explore the relevant molecular properties, leading to phase separation. Specifically, we show that the DPPC/DUPC/CHOL system unmixes due to enthalpic DPPC-DPPC and DPPC-CHOL interactions. The phase separation remains unchanged, except for the formation of a gel phase at long times after decreasing the conformational degrees of freedom of the unsaturated DUPC. In contrast, the phase separation can be suppressed by softening the DPPC chains. In an attempt to mimic the ordering and unmixing effect of CHOL the latter is replaced by a stiff and shortened DPPC-like lipid. One still observes phase separation, suggesting that it is mainly the rigid and planar structure of CHOL which is important for raft formation. Addition of an extra bead to the head of CHOL has no notable impact on the phase separation of the system, supporting the irrelevance of the Umbrella model for the phase separation. Reduction of the conformational entropy of CHOL by stiffening its last bead results in a significant increase of the order of the DPPC/CHOL domain. This suggests that the conformational entropy of CHOL is important to prohibit the gelation process. The interleaflet interactions as mediated by the terminal molecular groups seem to have a strong impact on the possibility of a subsequent gelation process after phase separation.

  18. The origin of cholesterol in chyle demonstrated by nuclear indicator methods

    International Nuclear Information System (INIS)

    Vyas, M.

    1962-01-01

    In order to obtain information about the mechanism of the intestinal absorption of cholesterol, rats having a lymphatic abdominal fistula are used. The animals receive either 4- 14 C- cholesterol subcutaneously or orally, or the 1- 14 C acetate. The study of the specific radio-activities of the cholesterol in chyle, in serum, in the lining, and in the intestinal contents makes it possible to define the roles played by the transfer cholesterol from the serum, by the cholesterol synthesised intestinally, and by the absorption cholesterol, in the formations of the lymph and of the chylomicrons. A new theory is proposed for the mechanism of cholesterol absorption. (author) [fr

  19. The response of the prostate to circulating cholesterol: activating transcription factor 3 (ATF3 as a prominent node in a cholesterol-sensing network.

    Directory of Open Access Journals (Sweden)

    Jayoung Kim

    Full Text Available Elevated circulating cholesterol is a systemic risk factor for cardiovascular disease and metabolic syndrome, however the manner in which the normal prostate responds to variations in cholesterol levels is poorly understood. In this study we addressed the molecular and cellular effects of elevated and suppressed levels of circulating cholesterol on the normal prostate. Integrated bioinformatic analysis was performed using DNA microarray data from two experimental formats: (1 ventral prostate from male mice with chronically elevated circulating cholesterol and (2 human prostate cells exposed acutely to cholesterol depletion. A cholesterol-sensitive gene expression network was constructed from these data and the transcription factor ATF3 was identified as a prominent node in the network. Validation experiments confirmed that elevated cholesterol reduced ATF3 expression and enhanced proliferation of prostate cells, while cholesterol depletion increased ATF3 levels and inhibited proliferation. Cholesterol reduction in vivo alleviated dense lymphomononuclear infiltrates in the periprostatic adipose tissue, which were closely associated with nerve tracts and blood vessels. These findings open new perspectives on the role of cholesterol in prostate health, and provide a novel role for ATF3, and associated proteins within a large signaling network, as a cholesterol-sensing mechanism.

  20. Pancreatic Pseudocyst Pleural Fistula in Gallstone Pancreatitis

    Directory of Open Access Journals (Sweden)

    Sala Abdalla

    2016-01-01

    Full Text Available Extra-abdominal complications of pancreatitis such as pancreaticopleural fistulae are rare. A pancreaticopleural fistula occurs when inflammation of the pancreas and pancreatic ductal disruption lead to leakage of secretions through a fistulous tract into the thorax. The underlying aetiology in the majority of cases is alcohol-induced chronic pancreatitis. The diagnosis is often delayed given that the majority of patients present with pulmonary symptoms and frequently have large, persistent pleural effusions. The diagnosis is confirmed through imaging and the detection of significantly elevated amylase levels in the pleural exudate. Treatment options include somatostatin analogues, thoracocentesis, endoscopic retrograde cholangiopancreatography (ERCP with pancreatic duct stenting, and surgery. The authors present a case of pancreatic pseudocyst pleural fistula in a woman with gallstone pancreatitis presenting with recurrent pneumonias and bilateral pleural effusions.

  1. Cholesterol esterification by mouse liver homogenate. Contribution to the study of ACYL-CoA: Cholesterol ACYL transferase in mammalian liver

    International Nuclear Information System (INIS)

    Soares, M.G.C.B.

    1976-01-01

    A cholesterol- esterifying enzyme from mouse liver has been partially characterized. The enzyme which showed optimum activity at pH 7,1 and required ATP and CoA, was identified as an acyl CoA: cholesterol acyl transferase (E.C.2.3.1.26). As a fuction of time the percentage of esterified cholesterol increased linearly during the first hour of incubation and continued to increase but not linearly with 4 hours, after which time no further net esterefication was observed. The relative concentration of esterified cholesterol remained constant between the fourth and twelveth hours of incubation but afterwards decreased when the incubation continued until 24 hours. The cholesterol- esterifying activity was 24,0+- 2,9 nmoles cholesterol esterified per gram tissue wet weight per minute. The mean percentages of free cholesterol esterified in and 24 hours respectively were 14,8+- 1,6 e 21,9+- 4,5. The subfractionation of labelled cholesteryl esters after one hour incubation of liver homogenate with 4-C 14 -Cholesterol showed the order of preference for the formation of the different ester classes to be monounsatured > diunsatured ≥ saturated >> polyunsaturated. The properties of the enzyme frommouse liver do not markedly differ from those of the previously recorded ACAT activity of rat liver. (Author) [pt

  2. The efficacy of extracorporeal shock wave lithotripsy on single dense calcified gallstones according to computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Mori, Takao (Mie Univ., Tsu (Japan). School of Medicine); Shimono, Kazuko; Moriyama, Shigeru; Masuda, Touru; Ikeda, Tetsuya; Umegae, Satoru; Nagata, Norikazu

    1993-05-01

    The efficacy and complications of extracorporeal shock wave lithotripsy (ESWL) for single gallstones were compared between 15 patients with a CT-lucent stone and 18 patients with a dense calcified stone. In all of five patients with a stone smaller than 10 mm in diameter, complete or sufficient clearance was observed, regardless of calcification. However, in 28 patients with a stone larger than 11 mm in diameter, the rates of complete or sufficient clearance were lower in those with a dense calcified stone (64%) than in those with a computed tomography (CT) lucent stone (93%). There was no difference in the rate of complications between patients with a CT-lucent stone and those with a dense calcified stone. These results thus suggest that extracorporeal shock wave lithotripsy may be safely employed for patients with a single calcified gallstone. (author).

  3. The ABCG5 ABCG8 sterol transporter and phytosterols: implications for cardiometabolic disease

    Science.gov (United States)

    Sabeva, Nadezhda S.; Liu, Jingjing; Graf, Gregory A.

    2014-01-01

    Purpose of review This review summarizes recent developments in the activity, regulation, and physiology of the ABCG5 ABCG8 (G5G8) transporter and the use of its xenobiotic substrates, phytosterols, as cholesterol lowering agents in the treatment of cardiovascular disease. Recent progress has significant implications for the role of G5G8 and its substrates in complications associated with features of the metabolic syndrome. Recent findings Recent reports expand the clinical presentation of sitosterolemia to include platelet and adrenal dysfunction. The G5G8 sterol transporter is critical to hepatobiliary excretion of cholesterol under nonpathological conditions and has been linked to the cholesterol gallstone susceptibility. Finally, the cardiovascular benefits of cholesterol lowering through the use of phytosterol supplements were offset by vascular dysfunction, suggesting that alternative strategies to reduced cholesterol absorption offer greater benefit. Summary Insulin resistance elevates G5G8 and increases susceptibility to cholesterol gallstones. However, this transporter is critical for the exclusion of phytosterols from the absorptive pathways in the intestine. Challenging the limits of this protective mechanism through phytosterol supplementation diminishes the cardioprotective benefits of cholesterol lowering in mouse models of cardiovascular disease. PMID:19306529

  4. Transcriptional profiling uncovers a network of cholesterol-responsive atherosclerosis target genes.

    Directory of Open Access Journals (Sweden)

    Josefin Skogsberg

    2008-03-01

    Full Text Available Despite the well-documented effects of plasma lipid lowering regimes halting atherosclerosis lesion development and reducing morbidity and mortality of coronary artery disease and stroke, the transcriptional response in the atherosclerotic lesion mediating these beneficial effects has not yet been carefully investigated. We performed transcriptional profiling at 10-week intervals in atherosclerosis-prone mice with human-like hypercholesterolemia and a genetic switch to lower plasma lipoproteins (Ldlr(-/-Apo(100/100Mttp(flox/flox Mx1-Cre. Atherosclerotic lesions progressed slowly at first, then expanded rapidly, and plateaued after advanced lesions formed. Analysis of lesion expression profiles indicated that accumulation of lipid-poor macrophages reached a point that led to the rapid expansion phase with accelerated foam-cell formation and inflammation, an interpretation supported by lesion histology. Genetic lowering of plasma cholesterol (e.g., lipoproteins at this point all together prevented the formation of advanced plaques and parallel transcriptional profiling of the atherosclerotic arterial wall identified 37 cholesterol-responsive genes mediating this effect. Validation by siRNA-inhibition in macrophages incubated with acetylated-LDL revealed a network of eight cholesterol-responsive atherosclerosis genes regulating cholesterol-ester accumulation. Taken together, we have identified a network of atherosclerosis genes that in response to plasma cholesterol-lowering prevents the formation of advanced plaques. This network should be of interest for the development of novel atherosclerosis therapies.

  5. Novel Apo E-Derived ABCA1 Agonist Peptide (CS-6253 Promotes Reverse Cholesterol Transport and Induces Formation of preβ-1 HDL In Vitro.

    Directory of Open Access Journals (Sweden)

    Anouar Hafiane

    Full Text Available Apolipoprotein (apo mimetic peptides replicate some aspects of HDL function. We have previously reported the effects of compound ATI-5261 on its ability to replicate many functions of native apo A-I in the process of HDL biogenesis. ATI-5261 induced muscle toxicity in wild type C57Bl/6 mice, increased CPK, ALT and AST and increase in triglyceride (Tg levels. Aromatic phenylalanine residues on the non-polar face of ATI-5261, together with positively charged arginine residues at the lipid-water interface were responsible for these effects. This information was used to create a novel analog (CS-6253 that was non-toxic. We evaluated this peptide designed from the carboxyl terminus of apo E, in its ability to mimic apo A-I functionality. Our data shows that the lipidated particles generated by incubating cells overexpressing ABCA1 with lipid free CS-6253 enhances the rate of ABCA1 lipid efflux with high affinity interactions with native ABCA1 oligomeric forms and plasma membrane micro-domains. Interaction between ABCA1 and lipid free CS-6253 resulted in formation of nascent HDL-CS-6253 particles that are actively remodeled in plasma. Mature HDL-CS-6253 particles deliver cholesterol to liver cells via SR-BI in-vitro. CS-6253 significantly increases cholesterol efflux in murine macrophages and in human THP-1 macrophage-derived foam cells expressing ABCA1. Addition of CS-6253 to plasma dose-dependently displaced apo A-I from α-HDL particles and led to de novo formation of preβ-1 HDL that stimulates ABCA1 dependent cholesterol efflux efficiently. When incubated with human plasma CS-6253 was also found to bind with HDL and LDL and promoted the transfer of cholesterol from HDL to LDL predominantly. Our data shows that CS-6253 mimics apo A-I in its ability to promote ABCA1-mediated formation of nascent HDL particles, and enhances formation of preβ-1 HDL with increase in the cycling of apo A-I between the preβ and α-HDL particles in-vitro. These

  6. Dietary and biliary cholesterol absorption in rats. Effect of dietary cholesterol level and cholesterol saturation of bile

    International Nuclear Information System (INIS)

    Wilson, M.D.

    1985-01-01

    The principal objective of this research was to determine if cholesterol introduced into the duodenum of rats in a micellar form as occurs with bile, is absorbed more efficiently than cholesterol presented in a nonmicellar form, as occurs with dietary cholesterol. Cholesterol absorption was measured during the constant intraduodenal infusion of liquid diets ([ 14 C] cholesterol) and artificial biles ([ 3 H] cholesterol) in thoracic lymph duct cannulated rats. Percentage absorption was calculated by dividing the rate of appearance of radiolabeled cholesterol in lymph by its rate of infusion when lymph cholesterol specific activity was constant. Results provide strong evidence that under certain conditions biliary cholesterol is more efficiently absorbed than is dietary cholesterol, and that this differential must be considered when evaluating the influence of diet or drug therapy on cholesterol absorption

  7. LDL Receptor-Related Protein-1 (LRP1 Regulates Cholesterol Accumulation in Macrophages.

    Directory of Open Access Journals (Sweden)

    Anna P Lillis

    Full Text Available Within the circulation, cholesterol is transported by lipoprotein particles and is taken up by cells when these particles associate with cellular receptors. In macrophages, excessive lipoprotein particle uptake leads to foam cell formation, which is an early event in the development of atherosclerosis. Currently, mechanisms responsible for foam cell formation are incompletely understood. To date, several macrophage receptors have been identified that contribute to the uptake of modified forms of lipoproteins leading to foam cell formation, but the in vivo contribution of the LDL receptor-related protein 1 (LRP1 to this process is not known [corrected]. To investigate the role of LRP1 in cholesterol accumulation in macrophages, we generated mice with a selective deletion of LRP1 in macrophages on an LDL receptor (LDLR-deficient background (macLRP1-/-. After feeding mice a high fat diet for 11 weeks, peritoneal macrophages isolated from Lrp+/+ mice contained significantly higher levels of total cholesterol than those from macLRP1-/- mice. Further analysis revealed that this was due to increased levels of cholesterol esters. Interestingly, macLRP1-/- mice displayed elevated plasma cholesterol and triglyceride levels resulting from accumulation of large, triglyceride-rich lipoprotein particles in the circulation. This increase did not result from an increase in hepatic VLDL biosynthesis, but rather results from a defect in catabolism of triglyceride-rich lipoprotein particles in macLRP1-/- mice. These studies reveal an important in vivo contribution of macrophage LRP1 to cholesterol homeostasis.

  8. What's Cholesterol?

    Science.gov (United States)

    ... LDL. Most cholesterol is LDL (low-density lipoprotein) cholesterol. LDL cholesterol is more likely to clog blood vessels because ... Here's a way to remember the difference: the LDL cholesterol is the bad kind, so call it "lousy" ...

  9. Intensity of lipid oxidation and formation of cholesterol oxidation products during frozen storage of raw and cooked chicken

    OpenAIRE

    Conchillo, A. (Ana); Ansorena, D. (Diana); Astiasarán, I. (Iciar)

    2004-01-01

    Raw and cooked chicken breasts were stored at −18 °C for 3 months under aerobic and vacuum conditions, and the intensity of lipid oxidation and the formation of COP (cholesterol oxidation products) were studied. Raw samples showed low COP levels (4.60–7.40 µg g−1 fat), TBARS (thiobarbituric acid reactive substances) levels (0.01–0.03 mg kg−1) and peroxide values (not detected) under both aerobic and vacuum conditions. Cooked samples (grilled and roasted) showed TBARS levels of 0.36–0.99 mg kg...

  10. A new model for pore formation by cholesterol-dependent cytolysins.

    Directory of Open Access Journals (Sweden)

    Cyril F Reboul

    2014-08-01

    Full Text Available Cholesterol Dependent Cytolysins (CDCs are important bacterial virulence factors that form large (200-300 Å membrane embedded pores in target cells. Currently, insights from X-ray crystallography, biophysical and single particle cryo-Electron Microscopy (cryo-EM experiments suggest that soluble monomers first interact with the membrane surface via a C-terminal Immunoglobulin-like domain (Ig; Domain 4. Membrane bound oligomers then assemble into a prepore oligomeric form, following which the prepore assembly collapses towards the membrane surface, with concomitant release and insertion of the membrane spanning subunits. During this rearrangement it is proposed that Domain 2, a region comprising three β-strands that links the pore forming region (Domains 1 and 3 and the Ig domain, must undergo a significant yet currently undetermined, conformational change. Here we address this problem through a systematic molecular modeling and structural bioinformatics approach. Our work shows that simple rigid body rotations may account for the observed collapse of the prepore towards the membrane surface. Support for this idea comes from analysis of published cryo-EM maps of the pneumolysin pore, available crystal structures and molecular dynamics simulations. The latter data in particular reveal that Domains 1, 2 and 4 are able to undergo significant rotational movements with respect to each other. Together, our data provide new and testable insights into the mechanism of pore formation by CDCs.

  11. Cholesterol Balance in Prion Diseases and Alzheimer’s Disease

    Science.gov (United States)

    Hannaoui, Samia; Shim, Su Yeon; Cheng, Yo Ching; Corda, Erica; Gilch, Sabine

    2014-01-01

    Prion diseases are transmissible and fatal neurodegenerative disorders of humans and animals. They are characterized by the accumulation of PrPSc, an aberrantly folded isoform of the cellular prion protein PrPC, in the brains of affected individuals. PrPC is a cell surface glycoprotein attached to the outer leaflet of the plasma membrane by a glycosyl-phosphatidyl-inositol (GPI) anchor. Specifically, it is associated with lipid rafts, membrane microdomains enriched in cholesterol and sphinoglipids. It has been established that inhibition of endogenous cholesterol synthesis disturbs lipid raft association of PrPC and prevents PrPSc accumulation in neuronal cells. Additionally, prion conversion is reduced upon interference with cellular cholesterol uptake, endosomal export, or complexation at the plasma membrane. Altogether, these results demonstrate on the one hand the importance of cholesterol for prion propagation. On the other hand, growing evidence suggests that prion infection modulates neuronal cholesterol metabolism. Similar results were reported in Alzheimer’s disease (AD): whereas amyloid β peptide formation is influenced by cellular cholesterol, levels of cholesterol in the brains of affected individuals increase during the clinical course of the disease. In this review, we summarize commonalities of alterations in cholesterol homeostasis and discuss consequences for neuronal function and therapy of prion diseases and AD. PMID:25419621

  12. Cholesterol Balance in Prion Diseases and Alzheimer’s Disease

    Directory of Open Access Journals (Sweden)

    Samia Hannaoui

    2014-11-01

    Full Text Available Prion diseases are transmissible and fatal neurodegenerative disorders of humans and animals. They are characterized by the accumulation of PrPSc, an aberrantly folded isoform of the cellular prion protein PrPC, in the brains of affected individuals. PrPC is a cell surface glycoprotein attached to the outer leaflet of the plasma membrane by a glycosyl-phosphatidyl-inositol (GPI anchor. Specifically, it is associated with lipid rafts, membrane microdomains enriched in cholesterol and sphinoglipids. It has been established that inhibition of endogenous cholesterol synthesis disturbs lipid raft association of PrPC and prevents PrPSc accumulation in neuronal cells. Additionally, prion conversion is reduced upon interference with cellular cholesterol uptake, endosomal export, or complexation at the plasma membrane. Altogether, these results demonstrate on the one hand the importance of cholesterol for prion propagation. On the other hand, growing evidence suggests that prion infection modulates neuronal cholesterol metabolism. Similar results were reported in Alzheimer’s disease (AD: whereas amyloid β peptide formation is influenced by cellular cholesterol, levels of cholesterol in the brains of affected individuals increase during the clinical course of the disease. In this review, we summarize commonalities of alterations in cholesterol homeostasis and discuss consequences for neuronal function and therapy of prion diseases and AD.

  13. Thermodynamic studies of bilirubin/cholesterol mixtures at the air/water interface

    International Nuclear Information System (INIS)

    Xie Anjian; Shen Yuhua; Xia Bing; Chen Hongbo; Ouyang Jianming

    2005-01-01

    Mixed monolayers of cholesterol and bilirubin spread at the air/water interface were used as model systems to examine the cholesterol effect on bilirubin. Miscibility and interactions between cholesterol and bilirubin were studied based on the analysis of the surface pressure-molecular area isotherms. From the isotherm data differentiated with respect to area, the condensing effect of cholesterol on the mixed monolayers could be observed distinctly. By studying surface compressibility modulus of bilirubin/cholesterol binary system vs. molecule area, we show that the liquid expanded-condensed phase transition (LE-C) of bilirubin was eliminated by cholesterol. In monolayers, bilirubin and cholesterol were found to be miscible at low surface pressure and immiscible at high surface pressure by studying the excess molecular areas of bilirubin/cholesterol system vs. mole fraction of bilirubin. The results from excess free energy of bilirubin/cholesterol system vs. mole fraction of bilirubin (X BR ) show that the maximum negative value of ΔG exc appeared at X BR =0.6, which indicates the formation of a bilirubin/cholesterol complex (M B-C ) of 3:2 stoichiometry as a result of the strong hydrogen bond between the polar groups of cholesterol and bilirubin and the self-assembly characteristics of cholesterol

  14. Structural requirements of cholesterol for binding to Vibrio cholerae hemolysin.

    Science.gov (United States)

    Ikigai, Hajime; Otsuru, Hiroshi; Yamamoto, Koichiro; Shimamura, Tadakatsu

    2006-01-01

    Cholesterol is necessary for the conversion of Vibrio cholerae hemolysin (VCH) monomers into oligomers in liposome membranes. Using different sterols, we determined the stereochemical structures of the VCH-binding active groups present in cholesterol. The VCH monomers are bound to cholesterol, diosgenin, campesterol, and ergosterol, which have a hydroxyl group at position C-3 (3betaOH) in the A ring and a C-C double bond between positions C-5 and C-6 (C-C Delta(5)) in the B ring. They are not bound to epicholesterol and dihydrocholesterol, which form a covalent link with a 3alphaOH group and a C-C single bond between positions C-5 and C-6, respectively. This result suggests that the 3betaOH group and the C-CDelta(5) bond in cholesterol are required for VCH monomer binding. We further examined VCH oligomer binding to cholesterol. However, this oligomer did not bind to cholesterol, suggesting that the disappearance of the cholesterol-binding potential of the VCH oligomer might be a result of the conformational change caused by the conversion of the monomer into the oligomer. VCH oligomer formation was observed in liposomes containing sterols with the 3betaOH group and the C-C Delta(5) bond, and it correlated with the binding affinity of the monomer to each sterol. Therefore, it seems likely that monomer binding to membrane sterol leads to the assembly of the monomer. However, since oligomer formation was induced by liposomes containing either epicholesterol or dihydrocholesterol, the 3betaOH group and the C-C Delta(5) bond were not essential for conversion into the oligomer.

  15. Molecular View of Cholesterol Flip-Flop and Chemical Potential in Different Membrane Environments

    NARCIS (Netherlands)

    Bennett, W. F. Drew; MacCallum, Justin L.; Hinner, Marlon J.; Marrink, Siewert J.; Tieleman, D. Peter

    2009-01-01

    The relative stability of cholesterol in cellular membranes and the thermodynamics of fluctuations from equilibrium have important consequences for sterol trafficking and lateral domain formation. We used molecular dynamics computer simulations to investigate the partitioning of cholesterol in a

  16. Risk of peptic ulcer, oesophagitis, pancreatitis or gallstone in patients with unexplained chest/epigastric pain and normal upper endoscopy: a 10-year Danish cohort study

    DEFF Research Database (Denmark)

    Munk, E M; Drewes, A M; Gorst-Rasmussen, Anders

    2007-01-01

    BACKGROUND: No studies have examined the risk of upper gastrointestinal diseases among patients with unexplained chest/epigastric pain (UCEP) and a normal upper endoscopy. AIM: To examine the relative risk of peptic ulcer, oesophagitis, pancreatitis or gallstone in UCEP patients. METHODS...... for peptic ulcer, oesophagitis, pancreatitis or gallstone. RESULTS: Compared with controls, the adjusted relative risks among UCEP patients or = 1 year after upper endoscopy were for peptic ulcer 2.0 [95% confidence interval (CI) 0.2-18.4] and 1.7 (95% CI 0.9-3.4), for oesophagitis 8.2 (95% CI 1.......2-59.2) and 1.9 (95% CI 0.7-5.0), for pancreatitis 9.2 (95% CI 2.0-41.8) and 3.9 (95% CI 1.4-10.5), and for gallstone 14.1 (95% CI 5.4-37.2) and 3.3 (95% CI 1.9-5.8). CONCLUSIONS: UCEP is positively associated with all study outcomes especially in the first year after upper endoscopy, indicating that peptic...

  17. What Is Cholesterol?

    Science.gov (United States)

    ... of Cholesterol There are two main types of cholesterol: LDL and HDL. The cholesterol blood test tells how much of each kind you have. Most cholesterol is LDL (low-density lipoprotein) cholesterol. This type is most ...

  18. The influence of gallbladder function on the symptomatology in gallstone patients, and the outcome after cholecystectomy or expectancy

    DEFF Research Database (Denmark)

    Larsen, Thomas Kjaergaard; Qvist, Niels

    2007-01-01

    gallstone disease. Fifty-six patients had a functioning gallbladder and 44 had a nonfunctioning gallbladder. Patients with a nonfunctioning gallbladder had significantly more vomiting and received more pain-killing injections during pain attacks. Otherwise, there were no differences in pain patterns...

  19. Reference intervals for serum total cholesterol, HDL cholesterol and ...

    African Journals Online (AJOL)

    Reference intervals of total cholesterol, HDL cholesterol and non-HDL cholesterol concentrations were determined on 309 blood donors from an urban and peri-urban population of Botswana. Using non-parametric methods to establish 2.5th and 97.5th percentiles of the distribution, the intervals were: total cholesterol 2.16 ...

  20. Synthesis of the oxysterol, 24(S, 25-epoxycholesterol, parallels cholesterol production and may protect against cellular accumulation of newly-synthesized cholesterol

    Directory of Open Access Journals (Sweden)

    Brown Andrew J

    2007-04-01

    Full Text Available Abstract Aim The effects of 24(S,25-epoxycholesterol (24,25EC on aspects of cholesterol homeostasis is well-documented. When added to cells, 24,25EC decreases cholesterol synthesis and up-regulates cholesterol efflux genes, including ABCA1. Synthesis of 24,25EC occurs in a shunt of the mevalonate pathway which also produces cholesterol. Therefore, 24,25EC synthesis should be subject to the same negative feedback regulation as cholesterol synthesis. To date, no role has been ascribed to 24,25EC in light of the fact that increased accumulation of cholesterol should decrease formation of this oxysterol through feedback inhibition. This leads to the intriguing paradox: why inhibit production of an apparently important regulator of cholesterol homeostasis when it is needed most? Methods We used a combination of pharmacological and genetic approaches in Chinese Hamster Ovary cell-lines to investigate this paradox. Endogenous synthesis of 24,25EC was manipulated using partial inhibition of the enzyme, Oxidosqualene Cyclase. Changes in cholesterol and 24,25EC synthesis were determined using metabolic labelling with [1-14C]-acetate, thin-layer chromatography and phosphorimaging. Transcriptional effects mediated via SREBP and LXR were analysed by luciferase reporter assays. Results We showed that cholesterol addition to cells lead to a rapid and preferential inhibition of 24,25EC synthesis. Addition of 24,25EC resulted in parallel inhibition of 24,25EC and cholesterol synthesis. Furthermore, we used a variety of approaches to examine the relationship between cholesterol and 24,25EC synthesis, including cell-lines with different rates of cholesterol synthesis, varying cholesterol synthetic rates by pre-treatment with a statin, or lipoprotein cholesterol loading of macrophages. In all cases, we showed that 24,25EC synthesis faithfully tracked cholesterol synthesis. Moreover, changes in 24,25EC synthesis exerted downstream effects, reducing SREBP

  1. GABA and Topiramate Inhibit the Formation of Human Macrophage-Derived Foam Cells by Modulating Cholesterol-Metabolism-Associated Molecules

    Directory of Open Access Journals (Sweden)

    Ying Yang

    2014-04-01

    Full Text Available Aims: γ-aminobutyric acid (GABA, the principal inhibitory neurotransmitter, acts on GABA receptors to play an important role in the modulation of macrophage functions. The present study examined the effects of GABA and a GABA receptor agonist on modulating cholesterol-metabolism-associated molecules in human monocyte-derived macrophages (HMDMs. Methods: ORO stain, HPLC, qRT-PCR, Western blot and EMSA were carried out using HMDMs exposed to ox-LDL with or without GABAergic agents as the experimental model. Results: GABA and topiramate reduced the percentage of cholesterol ester in lipid-laden HMDMs by down-regulating SR-A, CD36 and LOX-1 expression and up-regulating ABCA1, ABCG1 and SR-BI expression in lipid-laden HMDMs. The production of TNF-a was decreased in GABA-and topiramate-treated lipid-laden HMDMs, and levels of interleukin (IL-6 did not change. The activation of two signaling pathways, p38MAPK and NF-γB, was repressed by GABA and topiramate in lipid-laden HMDMs. Conclusion: GABA and topiramate inhibit the formation of human macrophage-derived foam cells and may be a possibility for macrophage targeted therapy of atherosclerotic lesions.

  2. Morpho-functional gastric pre-and post-operative changes in elderly patients undergoing laparoscopic cholecystectomy for gallstone related disease

    Science.gov (United States)

    2012-01-01

    Background Cholecystectomy, gold standard treatment for gallbladder lithiasis, is closely associated with increased bile reflux into the stomach as amply demonstrated by experimental studies. The high prevalence of gallstones in the population and the consequent widespread use of surgical removal of the gallbladder require an assessment of the relationship between cholecystectomy and gastric mucosal disorders. Morphological evaluations performed on serial pre and post – surgical biopsies have provided new acquisitions about gastric damage induced by bile in the organ. Methods 62 elderly patients with gallstone related disease were recruited in a 30 months period. All patients were subjected to the most appropriate treatment (Laparoscopic cholecystectomy). The subjects had a pre-surgical evaluation with: • dyspeptic symptoms questionnaire, • gastric endoscopy with body, antrum, and fundus random biopsies, • histo-pathological analysis of samples and elaboration of bile reflux index (BRI). The same evaluation was repeated at a 6 months follow-up. Results In our series the duodeno-gastric reflux and the consensual biliary gastritis, assessed histologically with the BRI, was found in 58% of the patients after 6 months from cholecystectomy. The demonstrated bile reflux had no effect on H. pylori’s gastric colonization nor on the induction of gastric precancerous lesions. Conclusions Cholecystectomy, gold standard treatment for gallstone-related diseases, is practiced in a high percentage of patients with this condition. Such procedure, considered by many harmless, was, in our study, associated with a significant risk of developing biliary gastritis after 6 months during the postoperative period. PMID:23173777

  3. Preoperative prediction model of outcome after cholecystectomy for symptomatic gallstones

    DEFF Research Database (Denmark)

    Borly, L; Anderson, I B; Bardram, L

    1999-01-01

    and sonography evaluated gallbladder motility, gallstones, and gallbladder volume. Preoperative variables in patients with or without postcholecystectomy pain were compared statistically, and significant variables were combined in a logistic regression model to predict the postoperative outcome. RESULTS: Eighty...... and by the absence of 'agonizing' pain and of symptoms coinciding with pain (P model 15 of 18 predicted patients had postoperative pain (PVpos = 0.83). Of 62 patients predicted as having no pain postoperatively, 56 were pain-free (PVneg = 0.90). Overall accuracy...... was 89%. CONCLUSION: From this prospective study a model based on preoperative symptoms was developed to predict postcholecystectomy pain. Since intrastudy reclassification may give too optimistic results, the model should be validated in future studies....

  4. The cholesterol space of the rat; L'espace cholesterol du rat

    Energy Technology Data Exchange (ETDEWEB)

    Chevallier, F [Commissariat a l' Energie Atomique, Saclay (France).Centre d' Etudes Nucleaires

    1959-07-01

    The experiments consisted in feeding daily to rats the same mass of radioactive cholesterol, over variable time intervals. From the evolution of the specific radioactivity of cholesterol carbon-14 in the organs as a function of time, information relative to the transport of cholesterol in the organism may be obtained. 1) The cholesterol space, defined as the group of molecules capable of being transferred from the organs into the serum and vice versa, represents at the most 50 per cent of the total cholesterol of the adult rat. 2) The incessant interchange between the tissual and the serum cholesterol renews entirely or for the most part the cholesterol molecules contained in the following organs: spleen, heart, adipose tissue, suprarenal glands, lungs, bone marrow, liver, erythrocytes. For a second group of organs: skin, testicles, kidneys, colon, bones, muscles, only a fraction of their cholesterol is renewable by this process. No transfer can be detected at the level of the brain. 3) The relative speeds of the various means of appearance (absorption, synthesis) and disappearance (excretion, transformation) of the cholesterol from its space are such that a stationary isotopic state is established around the eighth day, when the animal absorbs 5 milligrams of radioactive cholesterol daily. (author) [French] Les experiences ont consiste a faire ingerer quotidiennement une meme masse de cholesterol radioactif a des rats, durant des laps de temps variables. L'evolution de la radioactivite specifique du carbone-14 du cholesterol des organes en fonction du temps permet d'obtenir des renseignements relatifs au transport du cholesterol dans l'organisme. 1) L'espace cholesterol defini comme l'ensemble des molecules susceptibles d'etre transferees des organes dans le serum, et vice-versa, represente au plus 50 pour cent du cholesterol total du rat adulte. 2) Le va et vient incessant entre le cholesterol tissulaire et le cholesterol serique renouvelle en totalite ou en

  5. Laparoscopic and ultrasound assisted management of gallstone ileus after biliointestinal bypass Case report and a review of literature.

    Science.gov (United States)

    Zago, Mauro; Bozzo, Samantha; Centurelli, Andrea; Giovanelli, Alessandro; Vasino, Michele Ciocca

    2016-05-24

    To report about an additional case of biliary ileus after bariatric surgery is reported and extensively reviewing the literature on this topic. We reviewed the literature and found three cases of gallstone ileus (GI) that occurred after bariatric surgery. A 41 year old patient presented a GI eight years after a biliointestinal bypass (BIB) for morbid obesity. The patient complained of abdominal pain for two weeks. Computed tomography (CT) and abdominal ultrasound (US) allowed a preoperative diagnosis of GI and planning of surgical strategy. Surgical treatment was carried out through laparoscopic-assisted enterolithotomy alone procedure. This choice is supported discussing the related issues: morbidity, potential recurrence, eventual developing of gallbladder carcinoma. It is the first reported case of GI after BIB preoperatively diagnosed through CT scan and US, and treated with a laparoscopic assisted approach. Additional considerations concerning preoperative diagnosis, surgical strategy, technical details and follow-up can be usefully applied even in non post-bariatric biliary ileus. Biliointestinal bypass, Gallstone ileus, Laparoscopy, Ultrasonography.

  6. Neurosteroids: oligodendrocyte mitochondria convert cholesterol to pregnenolone

    International Nuclear Information System (INIS)

    Hu, Z.Y.; Bourreau, E.; Jung-Testas, I.; Robel, P.; Baulieu, E.E.

    1987-01-01

    Oligodendrocyte mitochondria from 21-day-old Sprague-Dawley male rats were incubated with 100 nM [ 3 H]cholesterol. It yielded [ 3 H]pregnenolone at a rate of 2.5 +/- 0.7 and 5-[ 3 H]pregnene-3β,20α-diol at a rate of 2.5 +/- 1.1 pmol per mg of protein per hr. Cultures of glial cells from 19- to 21-day-old fetuses (a mixed population of astrocytes and oligodendrocytes) were incubated for 24 hr with [ 3 H]mevalonolactone. [ 3 H]Cholesterol, [ 3 H]pregnenolone, and 5-[ 3 H]pregnene-3β,20α-diol were characterized in cellular extracts. The formation of the 3 H-labeled steroids was increased by dibutyryl cAMP (0.2 mM) added to the culture medium. The active cholesterol side-chain cleavage mechanism, recently suggested immunohistochemically and already observed in cultures of C6 glioma cells, reinforces the concept of neurosteroids applied to Δ 5 -3β-hydroxysteroids previously isolated from brain

  7. Cholesterol testing and results

    Science.gov (United States)

    ... your cholesterol is in this normal range. LDL (Bad) Cholesterol LDL cholesterol is sometimes called "bad" cholesterol. ... to 3.3 mmol/l) are desired. VLDL (Bad) Cholesterol VLDL contains the highest amount of triglycerides. ...

  8. Cholesterol Facts and Statistics

    Science.gov (United States)

    ... Managing High Cholesterol Cholesterol-lowering Medicine High Cholesterol Statistics and Maps High Cholesterol Facts High Cholesterol Maps ... Deo R, et al. Heart disease and stroke statistics—2017 update: a report from the American Heart ...

  9. The Drosophila DHR96 nuclear receptor binds cholesterol and regulates cholesterol homeostasis

    OpenAIRE

    Horner, Michael A.; Pardee, Keith; Liu, Suya; King-Jones, Kirst; Lajoie, Gilles; Edwards, Aled; Krause, Henry M.; Thummel, Carl S.

    2009-01-01

    Cholesterol homeostasis is required to maintain normal cellular function and avoid the deleterious effects of hypercholesterolemia. Here we show that the Drosophila DHR96 nuclear receptor binds cholesterol and is required for the coordinate transcriptional response of genes that are regulated by cholesterol and involved in cholesterol uptake, trafficking, and storage. DHR96 mutants die when grown on low levels of cholesterol and accumulate excess cholesterol when maintained on a high-choleste...

  10. Relationship between plasma cholesterol levels and cholesterol esterification in isolated human mononuclear cells

    International Nuclear Information System (INIS)

    Dallongeville, J.; Davignon, J.; Lussier-Cacan, S.

    1990-01-01

    The authors studied the relationship between plasma lipoprotein concentrations and cholesterol esterification in freshly isolated human mononuclear cells from 27 normolipidemic and 32 hyperlipidemic individuals. Cells were either incubated for 5 hours with radiolabeled oleate immediately after isolation or were preincubated for 18 hours in the presence of exogenous cholesterol, and then incubated with [ 14 C]sodium-oleate-albumin complex. In the absence of exogenous cholesterol, control and hypercholesterolemic subjects had similarly low values of intracellular cholesterol esterification. In the presence of exogenous cholesterol, both hypertriglyceridemic and hypercholesterolemic subjects had higher cholesterol esterification than controls. There was a significant correlation between the rate of cholesterol esterification and plasma total cholesterol. These results suggest that plasma cholesterol levels may regulate mononuclear cell intra-cellular cholesterol esterification in humans

  11. Cholesterol Depletion from a Ceramide/Cholesterol Mixed Monolayer: A Brewster Angle Microscope Study

    KAUST Repository

    Mandal, Pritam; Noutsi, Bakiza Kamal; Chaieb, Saharoui

    2016-01-01

    to deplete cholesterol (Chol) from biomembranes. Here, we focus on the depletion of cholesterol from a C16 ceramide/cholesterol (C16-Cer/Chol) mixed monolayer using MβCD. While the removal of cholesterol by MβCD depends on the cholesterol concentration

  12. High blood cholesterol levels

    Science.gov (United States)

    Cholesterol - high; Lipid disorders; Hyperlipoproteinemia; Hyperlipidemia; Dyslipidemia; Hypercholesterolemia ... There are many types of cholesterol. The ones talked about most are: ... lipoprotein (HDL) cholesterol -- often called "good" cholesterol ...

  13. Cholesterol accumulation in Niemann Pick type C (NPC) model cells causes a shift in APP localization to lipid rafts

    International Nuclear Information System (INIS)

    Kosicek, Marko; Malnar, Martina; Goate, Alison; Hecimovic, Silva

    2010-01-01

    It has been suggested that cholesterol may modulate amyloid-β (Aβ) formation, a causative factor of Alzheimer's disease (AD), by regulating distribution of the three key proteins in the pathogenesis of AD (β-amyloid precursor protein (APP), β-secretase (BACE1) and/or presenilin 1 (PS1)) within lipid rafts. In this work we tested whether cholesterol accumulation upon NPC1 dysfunction, which causes Niemann Pick type C disease (NPC), causes increased partitioning of APP into lipid rafts leading to increased CTF/Aβ formation in these cholesterol-rich membrane microdomains. To test this we used CHO NPC1 -/- cells (NPC cells) and parental CHOwt cells. By sucrose density gradient centrifugation we observed a shift in fl-APP/CTF compartmentalization into lipid raft fractions upon cholesterol accumulation in NPC vs. wt cells. Furthermore, γ-secretase inhibitor treatment significantly increased fl-APP/CTF distribution in raft fractions in NPC vs. wt cells, suggesting that upon cholesterol accumulation in NPC1-null cells increased formation of APP-CTF and its increased processing towards Aβ occurs in lipid rafts. Our results support that cholesterol overload, such as in NPC disease, leads to increased partitioning of APP/CTF into lipid rafts resulting in increased amyloidogenic processing of APP in these cholesterol-rich membranes. This work adds to the mechanism of the cholesterol-effect on APP processing and the pathogenesis of Alzheimer's disease and supports the role of lipid rafts in these processes.

  14. Cholesterol Depletion from a Ceramide/Cholesterol Mixed Monolayer: A Brewster Angle Microscope Study

    KAUST Repository

    Mandal, Pritam

    2016-06-01

    Cholesterol is crucial to the mechanical properties of cell membranes that are important to cells’ behavior. Its depletion from the cell membranes could be dramatic. Among cyclodextrins (CDs), methyl beta cyclodextrin (MβCD) is the most efficient to deplete cholesterol (Chol) from biomembranes. Here, we focus on the depletion of cholesterol from a C16 ceramide/cholesterol (C16-Cer/Chol) mixed monolayer using MβCD. While the removal of cholesterol by MβCD depends on the cholesterol concentration in most mixed lipid monolayers, it does not depend very much on the concentration of cholesterol in C16-Cer/Chol monolayers. The surface pressure decay during depletion were described by a stretched exponential that suggested that the cholesterol molecules are unable to diffuse laterally and behave like static traps for the MβCD molecules. Cholesterol depletion causes morphology changes of domains but these disrupted monolayers domains seem to reform even when cholesterol level was low.

  15. Cholesterol IQ Quiz

    Science.gov (United States)

    ... Artery Disease Venous Thromboembolism Aortic Aneurysm More Cholesterol IQ Quiz Updated:Jul 5,2017 Begin the quiz ... What Your Cholesterol Levels Mean Common Misconceptions Cholesterol IQ Quiz • HDL, LDL, and Triglycerides • Causes of High ...

  16. Plasma cholesterol and endogenous cholesterol synthesis during refeeding in anorexia nervosa.

    Science.gov (United States)

    Feillet, F; Feillet-Coudray, C; Bard, J M; Parra, H J; Favre, E; Kabuth, B; Fruchart, J C; Vidailhet, M

    2000-04-01

    Normal or high levels of cholesterol have been measured in patients with anorexia nervosa (AN). Given that cholesterol intake in AN is usually very low, the reasons for this anomaly are not clearly understood. We studied lipid and lipoprotein profiles and endogenous cholesterol synthesis, estimated by serum lathosterol, in a population of 14 girls with AN, before and during a period of 30 days refeeding. The initial body mass index (BMI) of the patients was 13.41+/-1.62 kg/m(2). No changes were observed during refeeding in endocrine parameters (ACTH, cortisol and estradiol). At Day 0 the lipids data measured here showed normal levels of triglycerides, and total cholesterol at the upper limits of the normal range (5.44+/-1 mmol/l). At this time, total and LDL cholesterol were negatively correlated with transthyretin and BMI. Serum lathosterol (a precursor in cholesterol synthesis pathway) increased significantly (5.99+/-1.75 (Day 0) vs. 8.39+/-2.96 (Day 30); P=0.02) while there was a significant decrease in apo B (0.79+/-0.33 (Day 0) vs. 0. 60+/-0.17 g/l (Day 30), P=0.02) with refeeding. Thus, patients with initial high cholesterol levels have the worst nutritional status and high cholesterol levels are not related to a de novo synthesis. This profile returns to normal with refeeding. An increase of cellular cholesterol uptake may be responsible for this apparently paradoxical evolution with increase of cholesterol synthesis and decrease of apo B during renutrition.

  17. Cholesterol metabolism and serum non-cholesterol sterols: summary of 13 plant stanol ester interventions.

    Science.gov (United States)

    Hallikainen, Maarit; Simonen, Piia; Gylling, Helena

    2014-04-27

    The efficacy and safety of plant stanols added to food products as serum cholesterol lowering agents have been demonstrated convincingly, but their effects on cholesterol metabolism and on serum non-cholesterol sterols is less evaluated. The aim of this study was to assess the validity of serum non-cholesterol sterols and squalene as bioindices of cholesterol synthesis and absorption, and to examine how the individual serum non-cholesterol sterols respond to consumption of plant stanols. We collected all randomized, controlled plant stanol ester (STAEST) interventions in which serum cholestanol, plant sterols campesterol and sitosterol, and at least two serum cholesterol precursors had been analysed. According to these criteria, there was a total of 13 studies (total 868 subjects without lipid-lowering medication; plant stanol doses varied from 0.8 to 8.8 g/d added in esterified form; the duration of the studies varied from 4 to 52 weeks). Serum non-cholesterol sterols were assayed with gas-liquid chromatography, cholesterol synthesis with the sterol balance technique, and fractional cholesterol absorption with the dual continuous isotope feeding method. The results demonstrated that during the control and the STAEST periods, the serum plant sterol/cholesterol- and the cholestanol/cholesterol-ratios reflected fractional cholesterol absorption, and the precursor sterol/cholesterol-ratios reflected cholesterol synthesis. Plant sterol levels were dose-dependently reduced by STAEST so that 2 g of plant stanols reduced serum campesterol/cholesterol-ratio on average by 32%. Serum cholestanol/cholesterol-ratio was reduced less frequently than those of the plant sterols by STAEST, and the cholesterol precursor sterol ratios did not change consistently in the individual studies emphasizing the importance of monitoring more than one surrogate serum marker. Serum non-cholesterol sterols are valid markers of cholesterol absorption and synthesis even during cholesterol

  18. LDL: The "Bad" Cholesterol

    Science.gov (United States)

    ... There are two main types of cholesterol: LDL (bad) cholesterol and HDL (good) cholesterol: LDL stands for low-density lipoproteins. It is called the "bad" cholesterol because a high LDL level leads to ...

  19. Home-Use Tests - Cholesterol

    Science.gov (United States)

    ... Medical Procedures In Vitro Diagnostics Home Use Tests Cholesterol Share Tweet Linkedin Pin it More sharing options ... a home-use test kit to measure total cholesterol. What cholesterol is: Cholesterol is a fat (lipid) ...

  20. Impact of Dietary Cholesterol on the Pathophysiology of Infectious and Autoimmune Disease

    Directory of Open Access Journals (Sweden)

    Catherine J. Andersen

    2018-06-01

    Full Text Available Cellular cholesterol metabolism, lipid raft formation, and lipoprotein interactions contribute to the regulation of immune-mediated inflammation and response to pathogens. Lipid pathways have been implicated in the pathogenesis of bacterial and viral infections, whereas altered lipid metabolism may contribute to immune dysfunction in autoimmune diseases, such as systemic lupus erythematosus, multiple sclerosis, and rheumatoid arthritis. Interestingly, dietary cholesterol may exert protective or detrimental effects on risk, progression, and treatment of different infectious and autoimmune diseases, although current findings suggest that these effects are variable across populations and different diseases. Research evaluating the effects of dietary cholesterol, often provided by eggs or as a component of Western-style diets, demonstrates that cholesterol-rich dietary patterns affect markers of immune inflammation and cellular cholesterol metabolism, while additionally modulating lipoprotein profiles and functional properties of HDL. Further, cholesterol-rich diets appear to differentially impact immunomodulatory lipid pathways across human populations of variable metabolic status, suggesting that these complex mechanisms may underlie the relationship between dietary cholesterol and immunity. Given the Dietary Guidelines for Americans 2015–2020 revision to no longer include limitations on dietary cholesterol, evaluation of dietary cholesterol recommendations beyond the context of cardiovascular disease risk is particularly timely. This review provides a comprehensive and comparative analysis of significant and controversial studies on the role of dietary cholesterol and lipid metabolism in the pathophysiology of infectious disease and autoimmune disorders, highlighting the need for further investigation in this developing area of research.

  1. A study on the inhibitory mechanism for cholesterol absorption by α-cyclodextrin administration

    Directory of Open Access Journals (Sweden)

    Takahiro Furune

    2014-12-01

    Full Text Available Background: Micelle formation of cholesterol with lecithin and bile salts is a key process for intestinal absorption of lipids. Some dietary fibers commonly used to reduce the lipid content in the body are thought to inhibit lipid absorption by binding to bile salts and decreasing the lipid solubility. Amongst these, α-cyclodextrin (α-CD is reportedly one of the most powerful dietary fibers for decreasing blood cholesterol. However, it is difficult to believe that α-CD directly removes cholesterol because it has a very low affinity for cholesterol and its mechanism of action is less well understood than those of other dietary fibers. To identify this mechanism, we investigated the interaction of α-CD with lecithin and bile salts, which are essential components for the dissolution of cholesterol in the small intestine, and the effect of α-CD on micellar solubility of cholesterol.Results: α-CD was added to Fed-State Simulated Intestinal Fluid (FeSSIF, and precipitation of a white solid was observed. Analytical data showed that the precipitate was a lecithin and α-CD complex with a molar ratio of 1:4 or 1:5. The micellar solubility of cholesterol in the mixture of FeSSIF and α-CD was investigated, and found to decrease through lecithin precipitation caused by the addition of α-CD, in a dose-dependent manner. Furthermore, each of several other water-soluble dietary fibers was added to the FeSSIF, and no precipitate was generated.Conclusion: This study suggests that α-CD decreases the micellar solubility of cholesterol in the lumen of the small intestine via the precipitation of lecithin from bile salt micelles by complex formation with α-CD. It further indicates that the lecithin precipitation effect on the bile salt micelles by α-CD addition clearly differs from addition of other water-soluble dietary fibers. The decrease in micellar cholesterol solubility in the FeSSIF was the strongest with α-CD addition.

  2. Vesicle Origami and the Influence of Cholesterol on Lipid Packing.

    Science.gov (United States)

    Tanasescu, Radu; Lanz, Martin A; Mueller, Dennis; Tassler, Stephanie; Ishikawa, Takashi; Reiter, Renate; Brezesinski, Gerald; Zumbuehl, Andreas

    2016-05-17

    The artificial phospholipid Pad-PC-Pad was analyzed in 2D (monolayers at the air/water interface) and 3D (aqueous lipid dispersions) systems. In the gel phase, the two leaflets of a Pad-PC-Pad bilayer interdigitate completely, and the hydrophobic bilayer region has a thickness comparable to the length of a single phospholipid acyl chain. This leads to a stiff membrane with no spontaneous curvature. Forced into a vesicular structure, Pad-PC-Pad has faceted geometry, and in its extreme form, tetrahedral vesicles were found as predicted a decade ago. Above the main transition temperature, a noninterdigitated Lα phase with fluid chains has been observed. The addition of cholesterol leads to a slight decrease of the main transition temperature and a gradual decrease in the transition enthalpy until the transition vanishes at 40 mol % cholesterol in the mixture. Additionally, cholesterol pulls the chains apart, and a noninterdigitated gel phase is observed. In monolayers, cholesterol has an ordering effect on liquid-expanded phases and disorders condensed phases. The wavenumbers of the methylene stretching vibration indicate the formation of a liquid-ordered phase in mixtures with 40 mol % cholesterol.

  3. Cholesterol photosensitised oxidation of horse meat slices stored under different packaging films.

    Science.gov (United States)

    Boselli, Emanuele; Rodriguez-Estrada, Maria Teresa; Ferioli, Federico; Caboni, Maria Fiorenza; Lercker, Giovanni

    2010-07-01

    The effect of the type of packaging film (transparent vs. light-protecting red film) was evaluated on the formation of cholesterol oxidation products (COPs) in refrigerated horse meat slices stored in retail conditions under light exposure for 8h. In meat wrapped with a transparent film, COPs increased from 233 (control) to 317 microg/g of fat, whereas the red film delayed cholesterol oxidation and offered protection against COPs formation, since COPs decreased from 173 (control) to 139 microg/g of fat after 8h of light exposure. In addition, light opened the epoxy ring and led to the formation of triol, which was actually absent at T(0.) A proper packaging film may represent a useful strategy to retard oxidative degradation in a light-sensitive, high pigment- and fat-containing food, such as horse meat. Copyright 2010. Published by Elsevier Ltd.

  4. Cholesterol Transport Revisited : A New Turbo Mechanism to Drive Cholesterol Excretion

    NARCIS (Netherlands)

    de Boer, Jan Freark; Kuipers, Folkert; Groen, Albert K.

    A fine-tuned balance between cholesterol uptake and excretion by the body is pivotal to maintain health and to remain free from the deleterious consequences of cholesterol accumulation such as cardiovascular disease. The pathways involved in intracellular and extracellular cholesterol transport are

  5. Cholesterol (image)

    Science.gov (United States)

    Cholesterol is a soft, waxy substance that is present in all parts of the body including the ... and obtained from animal products in the diet. Cholesterol is manufactured in the liver and is needed ...

  6. Cholesterol efflux is differentially regulated in neurons and astrocytes: implications for brain cholesterol homeostasis

    Science.gov (United States)

    Chen, Jing; Zhang, Xiaolu; Kusumo, Handojo; Costa, Lucio G.; Guizzetti, Marina

    2012-01-01

    Disruption of cholesterol homeostasis in the central nervous system (CNS) has been associated with neurological, neurodegenerative, and neurodevelopmental disorders. The CNS is a closed system with regard to cholesterol homeostasis, as cholesterol-delivering lipoproteins from the periphery cannot pass the blood-brain-barrier and enter the brain. Different cell types in the brain have different functions in the regulation of cholesterol homeostasis, with astrocytes producing and releasing apolipoprotein E and lipoproteins, and neurons metabolizing cholesterol to 24(S)-hydroxycholesterol. We present evidence that astrocytes and neurons adopt different mechanisms also in regulating cholesterol efflux. We found that in astrocytes cholesterol efflux is induced by both lipid-free apolipoproteins and lipoproteins, while cholesterol removal from neurons is triggered only by lipoproteins. The main pathway by which apolipoproteins induce cholesterol efflux is through ABCA1. By upregulating ABCA1 levels and by inhibiting its activity and silencing its expression, we show that ABCA1 is involved in cholesterol efflux from astrocytes but not from neurons. Furthermore, our results suggest that ABCG1 is involved in cholesterol efflux to apolipoproteins and lipoproteins from astrocytes but not from neurons, while ABCG4, whose expression is much higher in neurons than astrocytes, is involved in cholesterol efflux from neurons but not astrocytes. These results indicate that different mechanisms regulate cholesterol efflux from neurons and astrocytes, reflecting the different roles that these cell types play in brain cholesterol homeostasis. These results are important in understanding cellular targets of therapeutic drugs under development for the treatments of conditions associated with altered cholesterol homeostasis in the CNS. PMID:23010475

  7. Cholesterol Test

    Science.gov (United States)

    ... artery disease. Other names for a cholesterol test: Lipid profile, Lipid panel What is it used for? If you ... Clinic [Internet]. Mayo Foundation for Medical Education and Research; c1998-2017.Cholesterol Test: Overview; 2016 Jan 12 [ ...

  8. Endogenous cholesterol synthesis, fecal steroid excretion and serum lanosterol in subjects with high or low response of serum cholesterol to dietary cholesterol

    NARCIS (Netherlands)

    Beynen, A.C.; Katan, M.B.; Gent, van C.M.

    1986-01-01

    In this study we addressed the question whether hypo- and hyper-responders to dietary cholesterol differ with regard to the flexibility of endogenous cholesterol synthesis after changes in cholesterol intake. Whole-body cholesterol synthesis was measured as faecal excretion of neutral steroids and

  9. Inhibitory action of conventional food-grade natural antioxidants and of natural antioxidants of new development on the thermal-induced oxidation of cholesterol.

    Science.gov (United States)

    Valenzuela, Alfonso; Sanhueza, Julio; Alonso, Pilar; Corbari, Alicia; Nieto, Susana

    2004-03-01

    Cholesterol is a molecule with an unsaturated bond; therefore, like polyunsaturated fatty acids, it is prone to oxidation. Cholesterol oxidation products (COPs) are found in many common foods and have been shown to be atherogenic, cytotoxic, mutagenic and possibly carcinogenic. Therefore, efforts to prevent or to avoid COPs formation during manufacture and/or processing of foods are of high priority. The effect of natural antioxidants on COPs formation has not been extensively studied. We assayed the effect of some widely applied natural antioxidants, such as tocopherol homologs (alpha-T, gamma-T, and delta-T) and rosemary extract, and of some natural products of newly developed as antioxidants, such as the flavonoids quercetin, catechin, morin, and rutin, and also of an alkaloid-derived product, boldine, to inhibit cholesterol oxidation of soybean oil, added of cholesterol, induced in the Rancimat test conditions (150 degrees C and air bubbling). Formation of six different COPs at the induction period and at the 100 microS conductivity value was monitored by gas chromatography. Under the experimental conditions gamma-T, quercetin, and rosemary extract prove effective to inhibit both soybean oil oxidation and COP formation. alpha-T, catechin, and morin are less efficient to prevent COP formation. delta-T, rutin and boldine are devoid of protective action against COP formation. gamma-T, quercetin and rosemary extract may inhibit COP formation from the nucleus and from the lateral chain of the cholesterol molecule.

  10. Dietary Factors Reduce Risk of Acute Pancreatitis in a Large Multiethnic Cohort.

    Science.gov (United States)

    Setiawan, Veronica Wendy; Pandol, Stephen J; Porcel, Jacqueline; Wei, Pengxiao C; Wilkens, Lynne R; Le Marchand, Loïc; Pike, Malcolm C; Monroe, Kristine R

    2017-02-01

    Pancreatitis is a source of substantial morbidity and health cost in the United States. Little is known about how diet might contribute to its pathogenesis. To characterize dietary factors that are associated with risk of pancreatitis by disease subtype, we conducted a prospective analysis of 145,886 African Americans, Native Hawaiians, Japanese Americans, Latinos, and whites in the Multiethnic Cohort. In the Multiethnic Cohort (age at baseline, 45-75 y), we identified cases of pancreatitis using hospitalization claim files from 1993 through 2012. Patients were categorized as having gallstone-related acute pancreatitis (AP) (n = 1210), AP not related to gallstones (n = 1222), or recurrent AP or suspected chronic pancreatitis (n = 378). Diet information was obtained from a questionnaire administered when the study began. Associations were estimated by hazard ratios and 95% confidence intervals using Cox proportional hazard models adjusted for confounders. Dietary intakes of saturated fat (P trend = .0011) and cholesterol (P trend = .0008) and their food sources, including red meat (P trend associated positively with gallstone-related AP. Fiber intake, however, was associated inversely with gallstone-related AP (P trend = .0005) and AP not related to gallstones (P trend = .0035). Vitamin D, mainly from milk, was associated inversely with gallstone-related AP (P trend = .0015), whereas coffee consumption protected against AP not related to gallstones (P trend factors were associated with recurrent acute or suspected chronic pancreatitis. Associations between dietary factors and pancreatitis were observed mainly for gallstone-related AP. Interestingly, dietary fiber protected against AP related and unrelated to gallstones. Coffee drinking protected against AP not associated with gallstones. Further studies are warranted to confirm our findings. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

  11. Intestinal cholesterol transport: Measuring cholesterol absorption and its reverse

    NARCIS (Netherlands)

    Jakulj, L.

    2013-01-01

    Intestinal cholesterol transport might serve as an attractive future target for cardiovascular disease reduction, provided that underlying molecular mechanisms are more extensively elucidated, combined with improved techniques to measure changes in cholesterol fluxes and their possible

  12. Biogenesis of plasma membrane cholesterol

    International Nuclear Information System (INIS)

    Lange, Y.

    1986-01-01

    A striking feature of the molecular organization of eukaryotic cells is the singular enrichment of their plasma membranes in sterols. The authors studies are directed at elucidating the mechanisms underlying this inhomogeneous disposition. Cholesterol oxidase catalyzes the oxidation of plasma membrane cholesterol in intact cells, leaving intracellular cholesterol pools untouched. With this technique, the plasma membrane was shown to contain 95% of the unesterified cholesterol of cultured human fibroblasts. Cholesterol synthesized from [ 3 H] acetate moved to the plasma membrane with a half-time of 1 h at 37 0 C. They used equilibrium gradient centrifugation of homogenates of biosynthetically labeled, cholesterol oxidase treated cells to examine the distribution of newly synthesized sterols among intracellular pools. Surprisingly, lanosterol, a major precursor of cholesterol, and intracellular cholesterol both peaked at much lower buoyant density than did 3-hydroxy-3-methylglutaryl-CoA reductase. This suggests that cholesterol biosynthesis is not taken to completion in the endoplasmic reticulum. The cholesterol in the buoyant fraction eventually moved to the plasma membrane. Digitonin treatment increased the density of the newly synthesized cholesterol fractions, indicating that nascent cholesterol in transit is associated with cholesterol-rich membranes. The authors are testing the hypothesis that the pathway of cholesterol biosynthesis is spatially organized in various intracellular membranes such that the sequence of biosynthetic steps both concentrates the sterol and conveys it to the plasma membrane

  13. Ceftriaxone-associated gallbladder sludge. Identification of calcium-ceftriaxone salt as a major component of gallbladder precipitate

    International Nuclear Information System (INIS)

    Park, H.Z.; Lee, S.P.; Schy, A.L.

    1991-01-01

    Ceftriaxone, a third-generation cephalosporin, is partially excreted into bile. With its clinical use, the formation of gallbladder sludge detected by ultrasonography has been reported. Four surgical specimens were examined and no gallstones were found. Instead, fine precipitates of 20-250 microns were present. Microscopically, there was a small number of cholesterol monohydrate crystals and bilirubin granules among an abundant amount of granular-crystalline material that was not morphologically cholesterol monohydrate crystals. The chemical composition of the precipitates (n = 4) was determined. There was a small amount of cholesterol (1.7% +/- 0.8%) and bilirubin (13.9% +/- 0.74%). The major component of the precipitate was a residue. On further analysis using thin-layer chromatography, high-performance liquid chromatography, and electron microprobe analysis, the residue was identified as a calcium salt of ceftriaxone. The residue also had identical crystal morphology and chromatographic elution profile as authentic calcium-ceftriaxone standards. It is concluded that ceftriaxone, after excretion and being concentrated in the gallbladder bile, can form a precipitate. The major constituent has been identified as a ceftriaxone-calcium salt

  14. Increased expression of RXRα in dementia: an early harbinger for the cholesterol dyshomeostasis?

    Directory of Open Access Journals (Sweden)

    Katsel Pavel

    2010-09-01

    Full Text Available Abstract Background Cholesterol content of cerebral membranes is tightly regulated by elaborate mechanisms that balance the level of cholesterol synthesis, uptake and efflux. Among the conventional regulatory elements, a recent research focus has been nuclear receptors, a superfamily of ligand-activated transcription factors providing an indispensable regulatory framework in controlling cholesterol metabolism pathway genes. The mechanism of transcriptional regulation by nuclear receptors such as LXRs involves formation of heterodimers with RXRs. LXR/RXR functions as a sensor of cellular cholesterol concentration and mediates cholesterol efflux by inducing the transcription of key cholesterol shuffling vehicles namely, ATP-binding cassette transporter A1 (ABCA1 and ApoE. Results In the absence of quantitative data from humans, the relevance of expression of nuclear receptors and their involvement in cerebral cholesterol homeostasis has remained elusive. In this work, new evidence is provided from direct analysis of human postmortem brain gene and protein expression suggesting that RXRα, a key regulator of cholesterol metabolism is differentially expressed in individuals with dementia. Importantly, RXRα expression showed strong association with ABCA1 and ApoE gene expression, particularly in AD vulnerable regions. Conclusions These findings suggest that LXR/RXR-induced upregulation of ABCA1 and ApoE levels may be the molecular determinants of cholesterol dyshomeostasis and of the accompanying dementia observed in AD.

  15. Shared decision-making during surgical consultation for gallstones at a safety-net hospital.

    Science.gov (United States)

    Mueck, Krislynn M; Leal, Isabel M; Wan, Charlie C; Goldberg, Braden F; Saunders, Tamara E; Millas, Stefanos G; Liang, Mike K; Ko, Tien C; Kao, Lillian S

    2018-04-01

    Understanding patient perspectives regarding shared decision-making is crucial to providing informed, patient-centered care. Little is known about perceptions of vulnerable patients regarding shared decision-making during surgical consultation. The purpose of this study was to evaluate whether a validated tool reflects perceptions of shared decision-making accurately among patients seeking surgical consultation for gallstones at a safety-net hospital. A mixed methods study was conducted in a sample of adult patients with gallstones evaluated at a safety-net surgery clinic between May to July 2016. Semi-structured interviews were conducted after their initial surgical consultation and analyzed for emerging themes. Patients were administered the Shared Decision-Making Questionnaire and Autonomy Preference Scale. Univariate analyses were performed to identify factors associated with shared decision-making and to compare the results of the surveys to those of the interviews. The majority of patients (N = 30) were female (90%), Hispanic (80%), Spanish-speaking (70%), and middle-aged (45.7 ± 16 years). The proportion of patients who perceived shared decision-making was greater in the Shared Decision-Making Questionnaire versus the interviews (83% vs 27%, P decision for operation was not associated with shared decision-making. Contributory factors to this discordance include patient unfamiliarity with shared decision-making, deference to surgeon authority, lack of discussion about different treatments, and confusion between aligned versus shared decisions. Available questionnaires may overestimate shared decision-making in vulnerable patients suggesting the need for alternative or modifications to existing methods. Furthermore, such metrics should be assessed for correlation with patient-reported outcomes, such as satisfaction with decisions and health status. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. [Trans-intestinal cholesterol excretion (TICE): a new route for cholesterol excretion].

    Science.gov (United States)

    Blanchard, Claire; Moreau, François; Cariou, Bertrand; Le May, Cédric

    2014-10-01

    The small intestine plays a crucial role in dietary and biliary cholesterol absorption, as well as its lymphatic secretion as chylomicrons (lipoprotein exogenous way). Recently, a new metabolic pathway called TICE (trans-intestinal excretion of cholesterol) that plays a central role in cholesterol metabolism has emerged. TICE is an inducible way, complementary to the hepatobiliary pathway, allowing the elimination of the plasma cholesterol directly into the intestine lumen through the enterocytes. This pathway is poorly characterized but several molecular actors of TICE have been recently identified. Although it is a matter of debate, two independent studies suggest that TICE is involved in the anti-atherogenic reverse cholesterol transport pathway. Thus, TICE is an innovative drug target to reduce -cardiovascular diseases. © 2014 médecine/sciences – Inserm.

  17. Intracellular cholesterol-binding proteins enhance HDL-mediated cholesterol uptake in cultured primary mouse hepatocytes.

    Science.gov (United States)

    Storey, Stephen M; McIntosh, Avery L; Huang, Huan; Landrock, Kerstin K; Martin, Gregory G; Landrock, Danilo; Payne, H Ross; Atshaves, Barbara P; Kier, Ann B; Schroeder, Friedhelm

    2012-04-15

    A major gap in our knowledge of rapid hepatic HDL cholesterol clearance is the role of key intracellular factors that influence this process. Although the reverse cholesterol transport pathway targets HDL to the liver for net elimination of free cholesterol from the body, molecular details governing cholesterol uptake into hepatocytes are not completely understood. Therefore, the effects of sterol carrier protein (SCP)-2 and liver fatty acid-binding protein (L-FABP), high-affinity cholesterol-binding proteins present in hepatocyte cytosol, on HDL-mediated free cholesterol uptake were examined using gene-targeted mouse models, cultured primary hepatocytes, and 22-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-amino]-23,24-bisnor-5-cholen-3β-ol (NBD-cholesterol). While SCP-2 overexpression enhanced NBD-cholesterol uptake, counterintuitively, SCP-2/SCP-x gene ablation also 1) enhanced the rapid molecular phase of free sterol uptake detectable in rate and maximal uptake of HDL free cholesterol and 2) differentially enhanced free cholesterol uptake mediated by the HDL3, rather than the HDL2, subfraction. The increased HDL free cholesterol uptake was not due to increased expression or distribution of the HDL receptor [scavenger receptor B1 (SRB1)], proteins regulating SRB1 [postsynaptic density protein (PSD-95)/Drosophila disk large tumor suppressor (dlg)/tight junction protein (ZO1) and 17-kDa membrane-associated protein], or other intracellular cholesterol trafficking proteins (steroidogenic acute response protein D, Niemann Pick C, and oxysterol-binding protein-related proteins). However, expression of L-FABP, the single most prevalent hepatic cytosolic protein that binds cholesterol, was upregulated twofold in SCP-2/SCP-x null hepatocytes. Double-immunogold electron microscopy detected L-FABP sufficiently close to SRB1 for direct interaction, similar to SCP-2. These data suggest a role for L-FABP in HDL cholesterol uptake, a finding confirmed with SCP-2/SCP-x/L-FABP null

  18. Statins increase hepatic cholesterol synthesis and stimulate fecal cholesterol elimination in mice

    NARCIS (Netherlands)

    Schonewille, Marleen; de Boer, Jan Freark; Mele, Laura; Wolters, Henk; Bloks, Vincent W.; Wolters, Justina C.; Kuivenhoven, Jan A.; Tietge, Uwe J. F.; Brufau, Gemma; Groen, Albert K.

    Statins are competitive inhibitors of HMG-CoA reductase, the rate-limiting enzyme of cholesterol synthesis. Statins reduce plasma cholesterol levels, but whether this is actually caused by inhibition of de novo cholesterol synthesis has not been clearly established. Using three different statins, we

  19. Statins increase hepatic cholesterol synthesis and stimulate fecal cholesterol elimination in mice

    NARCIS (Netherlands)

    Schonewille, Marleen; de Boer, Jan Freark; Mele, Laura; Wolters, Henk; Bloks, Vincent W.; Wolters, Justina C.; Kuivenhoven, Jan A.; Tietge, Uwe J. F.; Brufau, Gemma; Groen, Albert K.

    2016-01-01

    Statins are competitive inhibitors of HMG-CoA reductase, the rate-limiting enzyme of cholesterol synthesis. Statins reduce plasma cholesterol levels, but whether this is actually caused by inhibition of de novo cholesterol synthesis has not been clearly established. Using three different statins, we

  20. Dietary cholesterol from eggs increases the ratio of total cholesterol to high-density lipoprotein cholesterol in humans : a meta-analysis

    NARCIS (Netherlands)

    Weggemans, R.M.; Zock, P.L.; Katan, M.B.

    2001-01-01

    Several epidemiologic studies found no effect of egg consumption on the risk of coronary heart disease. It is possible that the adverse effect of eggs on LDL-cholesterol is offset by their favorable effect on HDL cholesterol. Objective: The objective was to review the effect of dietary cholesterol

  1. Cholesterol - what to ask your doctor

    Science.gov (United States)

    ... your doctor; What to ask your doctor about cholesterol ... What is my cholesterol level? What should my cholesterol level be? What are HDL ("good") cholesterol and LDL ("bad") cholesterol? Does my cholesterol ...

  2. Common Misconceptions about Cholesterol

    Science.gov (United States)

    ... Venous Thromboembolism Aortic Aneurysm More Common Misconceptions about Cholesterol Updated:Jan 29,2018 How much do you ... are some common misconceptions — and the truth. High cholesterol isn’t a concern for children. High cholesterol ...

  3. From blood to gut: Direct secretion of cholesterol via transintestinal cholesterol efflux

    NARCIS (Netherlands)

    Vrins, Carlos L. J.

    2010-01-01

    The reverse cholesterol transport pathway (RCT) is the focus of many cholesterol lowering therapies By way of this pathway, excess cholesterol is collected from peripheral tissues and delivered back to the liver and gastrointestinal tract for excretion from the body For a long time this removal via

  4. Quantification of mucin in human gallbladder bile: a fast, specific, and reproducible method

    NARCIS (Netherlands)

    Miquel, J. F.; Groen, A. K.; van Wijland, M. J.; del Pozo, R.; Eder, M. I.; von Ritter, C.

    1995-01-01

    It is generally accepted that gallbladder mucin (GBM) plays an important role in the pathogenesis of cholesterol gallstone (ChG) disease. However, it remains unclear whether ChG patients have higher GBM concentrations than controls. Discrepant findings regarding biliary mucin concentrations may be

  5. Covalent immobilization of cholesterol esterase and cholesterol oxidase on polyaniline films for application to cholesterol biosensor

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Suman [Biomolecular Electronics and Conducting Polymer Research Group, National Physical Laboratory, Dr. K. S. Krishnan Marg, New Delhi-110012 (India); Solanki, Pratima R. [Biomolecular Electronics and Conducting Polymer Research Group, National Physical Laboratory, Dr. K. S. Krishnan Marg, New Delhi-110012 (India); Pandey, M.K. [Biomolecular Electronics and Conducting Polymer Research Group, National Physical Laboratory, Dr. K. S. Krishnan Marg, New Delhi-110012 (India); Malhotra, B.D. [Biomolecular Electronics and Conducting Polymer Research Group, National Physical Laboratory, Dr. K. S. Krishnan Marg, New Delhi-110012 (India)]. E-mail: bansi@mail.nplindia.ernet.in

    2006-05-24

    Cholesterol esterase (ChEt) and cholesterol oxidase (ChOx) have been covalently immobilized on electrochemically prepared polyaniline (PANI) films. These PANI/ChEt/ChOx enzyme films have been characterized using UV-visible, Fourier transform infrared (FTIR) spectroscopy and scanning electron microscopy (SEM). Electrochemical behavior of these films has been studied using cyclic voltammetry (CV) and amperometric techniques, respectively. The PANI/ChEt/ChOx enzyme films show broad oxidation peak from 0.2 to 0.5 V. These PANI/ChEt/ChOx biosensing electrodes have a response time of about 40 s, linearity from 50 to 500 mg/dl of cholesterol oleate concentration. These PANI/ChEt/ChOx films are thermally stable up to 46 deg. C. This polyaniline based cholesterol biosensor has optimum pH in the range of 6.5-7.5, sensitivity as 7.5 x 10{sup -4} nA/mg dl and a lifetime of about 6 weeks.

  6. Cholesterol and ocular pathologies: focus on the role of cholesterol-24S-hydroxylase in cholesterol homeostasis

    Directory of Open Access Journals (Sweden)

    Fourgeux Cynthia

    2015-03-01

    Full Text Available The retina is responsible for coding the light stimulus into a nervous signal that is transferred to the brain via the optic nerve. The retina is formed by the association of the neurosensory retina and the retinal pigment epithelium that is supported by Bruch’s membrane. Both the physical and metabolic associations between these partners are crucial for the functioning of the retina, by means of nutrient intake and removal of the cell and metabolic debris from the retina. Dysequilibrium are involved in the aging processes and pathologies such as age-related macular degeneration, the leading cause of visual loss after the age of 50 years in Western countries. The retina is composed of several populations of cells including glia that is involved in cholesterol biosynthesis. Cholesterol is the main sterol in the retina. It is present as free form in cells and as esters in Bruch’s membrane. Accumulation of cholesteryl esters has been associated with aging of the retina and impairment of the retinal function. Under dietary influence and in situ synthesized, the metabolism of cholesterol is regulated by cell interactions, including neurons and glia via cholesterol-24S-hydroxylase. Several pathophysiological associations with cholesterol and its metabolism can be suggested, especially in relation to glaucoma and age-related macular degeneration.

  7. Interaction of bovine gallbladder mucin and calcium-binding protein: effects on calcium phosphate precipitation

    NARCIS (Netherlands)

    Afdhal, N. H.; Ostrow, J. D.; Koehler, R.; Niu, N.; Groen, A. K.; Veis, A.; Nunes, D. P.; Offner, G. D.

    1995-01-01

    Gallstones consist of calcium salts and cholesterol crystals, arrayed on a matrix of gallbladder mucin (GBM), and regulatory proteins like calcium-binding protein (CBP). To determine if interactions between CBP and GBM follow a biomineralization scheme, their mutual binding and effects on CaHPO4

  8. Taurine ameliorates cholesterol metabolism by stimulating bile acid production in high-cholesterol-fed rats.

    Science.gov (United States)

    Murakami, Shigeru; Fujita, Michiko; Nakamura, Masakazu; Sakono, Masanobu; Nishizono, Shoko; Sato, Masao; Imaizumi, Katsumi; Mori, Mari; Fukuda, Nobuhiro

    2016-03-01

    This study was designed to investigate the effects of dietary taurine on cholesterol metabolism in high-cholesterol-fed rats. Male Sprague-Dawley rats were randomly divided into two dietary groups (n = 6 in each group): a high-cholesterol diet containing 0.5% cholesterol and 0.15% sodium cholate, and a high-cholesterol diet with 5% (w/w) taurine. The experimental diets were given for 2 weeks. Taurine supplementation reduced the serum and hepatic cholesterol levels by 37% and 32%, respectively. Faecal excretion of bile acids was significantly increased in taurine-treated rats, compared with untreated rats. Biliary bile acid concentrations were also increased by taurine. Taurine supplementation increased taurine-conjugated bile acids by 61% and decreased glycine-conjugated bile acids by 53%, resulting in a significant decrease in the glycine/taurine (G/T) ratio. Among the taurine-conjugated bile acids, cholic acid and deoxycholic acid were significantly increased. In the liver, taurine supplementation increased the mRNA expression and enzymatic activity of hepatic cholesterol 7α-hydroxylase (CYP7A1), the rate-limiting enzyme for bile acid synthesis, by three- and two-fold, respectively. Taurine also decreased the enzymatic activity of acyl-CoA:cholesterol acyltransferase (ACAT) and microsomal triglyceride transfer protein (MTP). These observations suggest that taurine supplementation increases the synthesis and excretion of taurine-conjugated bile acids and stimulates the catabolism of cholesterol to bile acid by elevating the expression and activity of CYP7A1. This may reduce cholesterol esterification and lipoprotein assembly for very low density lipoprotein (VLDL) secretion, leading to reductions in the serum and hepatic cholesterol levels. © 2016 John Wiley & Sons Australia, Ltd.

  9. On the growth rate of gallstones in the human gallbladder

    Science.gov (United States)

    Nudelman, I.

    1993-05-01

    The growth rate of a single symmetrically oval shaped gallbladder stone weighing 10.8 g was recorded over a period of six years before surgery and removal. The length of the stone was measured by ultrasonography and the growth rate was found to be linear with time, with a value of 0.4 mm/year. A smaller stone growing in the wall of the gallbladder was detected only three years before removal and grew at a rate of ˜ 1.33 mm/year. The morphology and metallic ion chemical composition of the large stone and of a randomly selected small stone weighing about 1.1 g, extracted from another patient, were analyzed and compared. It was found that the large stone contained besides calcium also lead, whereas the small stone contained mainly calcium. It is possible that the lead causes a difference in mechanism between the growth of a single large and growth of multiple small gallstones.

  10. The role of serum non-cholesterol sterols as surrogate markers of absolute cholesterol synthesis and absorption.

    Science.gov (United States)

    Miettinen, T A; Gylling, H; Nissinen, M J

    2011-10-01

    To study the whole-body cholesterol metabolism in man, cholesterol synthesis and absorption need to be measured. Because of the complicated methods of the measurements, new approaches were developed including the analysis of serum non-cholesterol sterols. In current lipidologic papers and even in intervention studies, serum non-cholesterol sterols are frequently used as surrogate markers of cholesterol metabolism without any validation to the absolute metabolic variables. The present review compares serum non-cholesterol sterols with absolute measurements of cholesterol synthesis and absorption in published papers to find out whether the serum markers are valid indicators of cholesterol metabolism in various conditions. During statin treatment, during interventions of dietary fat, and in type 2 diabetes the relative and absolute variables of cholesterol synthesis and absorption were frequently but not constantly correlated with each other. In some occasions, especially in subjects with apolipoprotein E3/4 and E4/4 phenotypes, the relative metabolic markers were even more sensitive than the absolute ones to reflect changes in cholesterol metabolism during dietary interventions. Even in general population at very high absorption the homeostasis of cholesterol metabolism is disturbed damaging the validity of the serum markers. It is worth using several instead of only one precursor and absorption sterol marker for making conclusions of altered synthesis or absorption of cholesterol, and even then the presence of at least some absolute measurement is valuable. During consumption of plant sterol-enriched diets and in situations of interfered cholesterol homeostasis the relative markers do not adequately reflect cholesterol metabolism. Accordingly, the validity of the relative markers of cholesterol metabolism should not be considered as self-evident. Copyright © 2011 Elsevier B.V. All rights reserved.

  11. Kefiran reduces atherosclerosis in rabbits fed a high cholesterol diet.

    Science.gov (United States)

    Uchida, Masashi; Ishii, Itsuko; Inoue, Chika; Akisato, Yoshie; Watanabe, Kenta; Hosoyama, Saori; Toida, Toshihiko; Ariyoshi, Noritaka; Kitada, Mitsukazu

    2010-09-30

    Kefiran is an exopolysaccharide produced by Lactobacillus kefiranofaciens, and has been proposed to have many health-promoting properties. We investigated the antiatherogenic effect of kefiran on rabbits fed a high-cholesterol diet. Male New Zealand White rabbits were fed a 0.5% cholesterol diet without (control group, n = 7) or with kefiran (kefiran group, n = 8) for eight weeks. The aorta was analyzed by histochemistry and atherosclerotic lesions were quantified. Lipids and sugars in serum were measured. Foam cell formation of RAW264.7 by βVLDL derived from both groups of rabbits was also investigated. Cholesterol, triglyceride and phospholipids levels of serum and lipoprotein fractions were not significantly different between these groups. Atherosclerotic lesions of the aorta in the kefiran group were statistically lower than those of the control group, with marked differences in the abdominal aorta. T-lymphocytes were not detectable in the aorta of the kefiran group. Cholesterol contents in stools were almost identical in both groups. Cholesterol content in the liver of the kefiran group was statistically lower than in the control group. Galactose content of βVLDL derived from the kefiran group was higher, and the lipid peroxidation level was much lower than in the control group. RAW264.7 macrophages treated with βVLDL from the kefiran group showed a more spherical shape and accumulated statistically lower cholesterol than macrophages treated with βVLDL from the control group. Orally derived kefiran is absorbed in the blood. Kefiran prevents the onset and development of atherosclerosis in hypercholesterolemic rabbits by anti-inflammatory and anti-oxidant actions.

  12. Steady-state oxidation of cholesterol catalyzed by cholesterol oxidase in lipid bilayer membranes on platinum electrodes

    International Nuclear Information System (INIS)

    Bokoch, Michael P.; Devadoss, Anando; Palencsar, Mariela S.; Burgess, James D.

    2004-01-01

    Cholesterol oxidase is immobilized in electrode-supported lipid bilayer membranes. Platinum electrodes are initially modified with a self-assembled monolayer of thiolipid. A vesicle fusion method is used to deposit an outer leaflet of phospholipids onto the thiolipid monolayer forming a thiolipid/lipid bilayer membrane on the electrode surface. Cholesterol oxidase spontaneously inserts into the electrode-supported lipid bilayer membrane from solution and is consequently immobilized to the electrode surface. Cholesterol partitions into the membrane from buffer solutions containing cyclodextrin. Cholesterol oxidase catalyzes the oxidation of cholesterol by molecular oxygen, forming hydrogen peroxide as a product. Amperometric detection of hydrogen peroxide for continuous solution flow experiments are presented, where flow was alternated between cholesterol solution and buffer containing no cholesterol. Steady-state anodic currents were observed during exposures of cholesterol solutions ranging in concentration from 10 to 1000 μM. These data are consistent with the Michaelis-Menten kinetic model for oxidation of cholesterol as catalyzed by cholesterol oxidase immobilized in the lipid bilayer membrane. The cholesterol detection limit is below 1 μM for cholesterol solution prepared in buffered cyclodextrin. The response of the electrodes to low density lipoprotein solutions is increased upon addition of cyclodextrin. Evidence for adsorption of low density lipoprotein to the electrode surface is presented

  13. Isotope dilution/mass spectrometry of serum cholesterol with [3,4-13C]cholesterol: proposed definitive method

    International Nuclear Information System (INIS)

    Pelletier, O.; Wright, L.A.; Breckenridge, W.C.

    1987-01-01

    We describe a new gas-chromatographic/mass-spectrometric (GC/MS) isotope-dilution method for determination of serum cholesterol. The method has been fully optimized and documented to provide the high accuracy and precision expected for a Definitive Method. In the presence of [3,4- 13 C]cholesterol, cholesteryl esters in serum are hydrolyzed under optimum conditions and the entire cholesterol pool is extracted and derivatized to silyl ethers. The cholesterol derivatives are resolved from other sterols by gas-liquid chromatography on a fused silica column, and selected ions characteristic of cholesterol and the [3,4- 13 C]cholesterol are monitored with a GC/MS quandrupole system. We estimated the cholesterol content of samples by bracketing each sample with standards of comparable cholesterol concentration that also contained the [3,4- 13 C]cholesterol. The procedure was highly reproducible (CV less than 0.5%), better accuracy and precision being obtained with [3,4- 13 C]cholesterol than with heptadeuterated cholesterol. Mean values per gram of dry serum for one serum pool assayed by this method and that of the National Bureau of Standards differed by 0.5%. We conclude that the method satisfies the criteria for a Definitive Method

  14. Cholesterol - drug treatment

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/patientinstructions/000314.htm Cholesterol - drug treatment To use the sharing features on ... treatment; Hardening of the arteries - statin Statins for Cholesterol Statins reduce your risk of heart disease, stroke, ...

  15. Free cholesterol and cholesterol esters in bovine oocytes: Implications in survival and membrane raft organization after cryopreservation.

    Directory of Open Access Journals (Sweden)

    Jorgelina Buschiazzo

    Full Text Available Part of the damage caused by cryopreservation of mammalian oocytes occurs at the plasma membrane. The addition of cholesterol to cell membranes as a strategy to make it more tolerant to cryopreservation has been little addressed in oocytes. In order to increase the survival of bovine oocytes after cryopreservation, we proposed not only to increase cholesterol level of oocyte membranes before vitrification but also to remove the added cholesterol after warming, thus recovering its original level. Results from our study showed that modulation of membrane cholesterol by methyl-β-cyclodextrin (MβCD did not affect the apoptotic status of oocytes and improved viability after vitrification yielding levels of apoptosis closer to those of fresh oocytes. Fluorometric measurements based on an enzyme-coupled reaction that detects both free cholesterol (membrane and cholesteryl esters (stored in lipid droplets, revealed that oocytes and cumulus cells present different levels of cholesterol depending on the seasonal period. Variations at membrane cholesterol level of oocytes were enough to account for the differences found in total cholesterol. Differences found in total cholesterol of cumulus cells were explained by the differences found in both the content of membrane cholesterol and of cholesterol esters. Cholesterol was incorporated into the oocyte plasma membrane as evidenced by comparative labeling of a fluorescent cholesterol. Oocytes and cumulus cells increased membrane cholesterol after incubation with MβCD/cholesterol and recovered their original level after cholesterol removal, regardless of the season. Finally, we evaluated the effect of vitrification on the putative raft molecule GM1. Cholesterol modulation also preserved membrane organization by maintaining ganglioside level at the plasma membrane. Results suggest a distinctive cholesterol metabolic status of cumulus-oocyte complexes (COCs among seasons and a dynamic organizational structure

  16. C-Kit expression in the gallbladder of guinea pig with chronic calculous cholecystitis and the effect of Artemisia capillaris Thunb on interstitial cells of Cajal.

    Science.gov (United States)

    Feng, Hua; Wang, Fang; Wang, Changmiao

    2016-07-01

    To study the c-Kit expression in the gallbladder of cholesterol lithogenic guinea pig model and the effect of Artemisia capillaris Thunb on interstitial cells of Cajal (ICCs). A total of 45 guinea pigs were randomly assigned into three groups: the control group (guinea pigs fed a standard diet, normal group); the model group (guinea pigs fed a cholesterol gallstone-inducing diet); and the Chinese medicine group (guinea pigs fed the cholesterol gallstone-inducing diet and treated with A. capillaris through intragastric administration, therapy group). Each group had 15 guinea pigs. The gallbladders of the guinea pigs were harvested after 8 weeks. C-Kit expression was detected using an immunohistochemistry staining, real-time PCR, and Western blot analyses. The effect of A. capillaris on ICCs was evaluated by muscle strip contraction experiments. C-Kit expression significantly decreased in the gallbladder of model group, but increased in the Chinese medicine group. The Contractility of guinea pig gallbladder muscle strip significantly improved in the Chinese medicine group. Our results indicated that A. capillaris improves gallbladder impairment by up-regulating c-Kit expression, and it also can improve the contractile response of in vitro guinea pig gallbladder muscle strips.

  17. Remnant cholesterol and ischemic heart disease

    DEFF Research Database (Denmark)

    Varbo, Anette; Nordestgaard, Børge G

    2014-01-01

    PURPOSE OF REVIEW: To review recent advances in the field of remnant cholesterol as a contributor to the development of ischemic heart disease (IHD). RECENT FINDINGS: Epidemiologic, mechanistic, and genetic studies all support a role for elevated remnant cholesterol (=cholesterol in triglyceride......-rich lipoproteins) as a contributor to the development of atherosclerosis and IHD. Observational studies show association between elevated remnant cholesterol and IHD, and mechanistic studies show remnant cholesterol accumulation in the arterial wall like LDL-cholesterol (LDL-C) accumulation. Furthermore, large...... genetic studies show evidence of remnant cholesterol as a causal risk factor for IHD independent of HDL-cholesterol levels. Genetic studies also show that elevated remnant cholesterol is associated with low-grade inflammation, whereas elevated LDL-C is not. There are several pharmacologic ways of lowering...

  18. Ursodeoxycholic acid impairs atherogenesis and promotes plaque regression by cholesterol crystal dissolution in mice.

    Science.gov (United States)

    Bode, Niklas; Grebe, Alena; Kerksiek, Anja; Lütjohann, Dieter; Werner, Nikos; Nickenig, Georg; Latz, Eicke; Zimmer, Sebastian

    2016-09-09

    Atherosclerosis is a chronic inflammatory disease driven primarily by a continuous retention of cholesterol within the subendothelial space where it precipitates to form cholesterol crystals (CC). These CC trigger a complex inflammatory response through activation of the NLRP3 inflammasome and promote lesion development. Here we examined whether increasing cholesterol solubility with ursodeoxycholic acid (UDCA) affects vascular CC formation and ultimately atherosclerotic lesion development. UDCA mediated intracellular CC dissolution in macrophages and reduced IL-1β production. In ApoE(-/-) mice, UDCA treatment not only impaired atherosclerotic plaque development but also mediated regression of established vascular lesions. Importantly, mice treated with UDCA had decreased CC-depositions in atherosclerotic plaques compared to controls. Together, our data demonstrate that UDCA impaired CC and NLRP3 dependent inflammation by increasing cholesterol solubility and diminished atherosclerosis in mice. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. MicroRNA-20a/b regulates cholesterol efflux through post-transcriptional repression of ATP-binding cassette transporter A1.

    Science.gov (United States)

    Liang, Bin; Wang, Xin; Song, Xiaosu; Bai, Rui; Yang, Huiyu; Yang, Zhiming; Xiao, Chuanshi; Bian, Yunfei

    2017-09-01

    ATP-binding cassette transporter A1 (ABCA1) plays a crucial role in reverse cholesterol transport and exhibits anti-atherosclerosis effects. Some microRNAs (miRs) regulate ABCA1 expression, and recent studies have shown that miR-20a/b might play a critical role in atherosclerotic diseases. Here, we attempted to clarify the potential contribution of miR-20a/b in post-transcriptional regulation of ABCA1, cholesterol efflux, and atherosclerosis. We performed bioinformatics analysis and found that miR-20a/b was highly conserved and directly bound to ABCA1 mRNA with low binding free energy. Luciferase-reporter assay also confirmed that miR-20a/b significantly reduced luciferase activity associated with the ABCA1 3' untranslated region reporter construct. Additionally, miR-20a/b decreased ABCA1 expression, which, in turn, decreased cholesterol efflux and increased cholesterol content in THP-1 and RAW 264.7 macrophage-derived foam cells. In contrast, miR-20a/b inhibitors increased ABCA1 expression and cholesterol efflux, decreased cholesterol content, and inhibited foam-cell formation. Consistent with our in vitro results, miR-20a/b-treated ApoE -/- mice showed decreased ABCA1expression in the liver and reductions of reverse cholesterol transport in vivo. Furthermore, miR-20a/b regulated the formation of nascent high-density lipoprotein and promoted atherosclerotic development, whereas miR-20a/b knockdown attenuated atherosclerotic formation. miR-20 is a new miRNA capable of targeting ABCA1 and regulating ABCA1 expression. Therefore, miR-20 inhibition constitutes a new strategy for ABCA1-based treatment of atherosclerosis. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Usefulness of CT-scan in the diagnosis and therapeutic approach of gallstone ileus: report of two surgically treated cases

    OpenAIRE

    Michele, Danzi; Luciano, Grimaldi; Massimiliano, Fabozzi; Stefano, Reggio; Roberta, Danzi; Ernesto, Soscia; Bruno, Amato

    2013-01-01

    Background Gallstone ileus is a rare cause of gastrointestinal obstruction, more frequent in elderly patients, whose treatment is essentially surgical, although some para-surgical and mini-invasive possibilities exist, allowing the solution of such obstructive condition in a completely non-invasive way. Description In our study, after reporting two cases of biliary ileus managed by our surgical division, we will analyze the most suitable diagnostic procedures and the therapeutic approaches to...

  1. Purple perilla extracts with α-asarone enhance cholesterol efflux from oxidized LDL-exposed macrophages.

    Science.gov (United States)

    Park, Sin-Hye; Paek, Ji Hun; Shin, Daekeun; Lee, Jae-Yong; Lim, Soon Sung; Kang, Young-Hee

    2015-04-01

    The cellular accumulation of cholesterol is critical in the development and progression of atherosclerosis. ATP-binding cassette (ABC) transporters play an essential role in mediating the efflux of excess cholesterol. In the current study, we investigated whether purple Perilla frutescens extracts (PPE) at a non-toxic concentration of 1-10 µg/ml stimulate the induction of the ABC transporters, ABCA1 and ABCG1, and cholesterol efflux from lipid-laden J774A.1 murine macrophages exposed to 50 ng/ml oxidized low-density lipoprotein (LDL). Purple perilla, an annual herb in the mint family and its constituents, have been reported to exhibit antioxidant and cytostatic activity, as well as to exert anti-allergic effects. Our results revealed that treatment with oxidized LDL for 24 h led to the accumulation of lipid droplets in the macrophages. PPE suppressed the oxidized LDL-induced foam cell formation by blocking the induction of scavenger receptor B1. However, PPE promoted the induction of the ABC transporters, ABCA1 and ABCG1, and subsequently accelerated cholesterol efflux from the lipid-loaded macrophages. The liver X receptor (LXR) agonist, TO-091317, and the peroxisome proliferator-activated receptor (PPAR) agonist, pioglitazone, increased ABCA1 expression and treatment with 10 µg/ml PPE further enhanced this effect. PPE did not induce LXRα and PPARγ expression per se, but enhanced their expression in the macrophages exposed to oxidized LDL. α-asarone was isolated from PPE and characterized as a major component enhancing the induction of ABCA1 and ABCG1 in macrophages exposed to oxidized LDL. α-asarone, but not β-asarone was effective in attenuating foam cell formation and enhancing cholesterol efflux, revealing an isomeric difference in their activity. The results from the present study demonstrate that PPE promotes cholesterol efflux from macrophages by activating the interaction of PPARγ-LXRα-ABC transporters.

  2. Cellular Cholesterol Regulates Ubiquitination and Degradation of the Cholesterol Export Proteins ABCA1 and ABCG1*

    Science.gov (United States)

    Hsieh, Victar; Kim, Mi-Jurng; Gelissen, Ingrid C.; Brown, Andrew J.; Sandoval, Cecilia; Hallab, Jeannette C.; Kockx, Maaike; Traini, Mathew; Jessup, Wendy; Kritharides, Leonard

    2014-01-01

    The objective of this study was to examine the influence of cholesterol in post-translational control of ABCA1 and ABCG1 protein expression. Using CHO cell lines stably expressing human ABCA1 or ABCG1, we observed that the abundance of these proteins is increased by cell cholesterol loading. The response to increased cholesterol is rapid, is independent of transcription, and appears to be specific for these membrane proteins. The effect is mediated through cholesterol-dependent inhibition of transporter protein degradation. Cell cholesterol loading similarly regulates degradation of endogenously expressed ABCA1 and ABCG1 in human THP-1 macrophages. Turnover of ABCA1 and ABCG1 is strongly inhibited by proteasomal inhibitors and is unresponsive to inhibitors of lysosomal proteolysis. Furthermore, cell cholesterol loading inhibits ubiquitination of ABCA1 and ABCG1. Our findings provide evidence for a rapid, cholesterol-dependent, post-translational control of ABCA1 and ABCG1 protein levels, mediated through a specific and sterol-sensitive mechanism for suppression of transporter protein ubiquitination, which in turn decreases proteasomal degradation. This provides a mechanism for acute fine-tuning of cholesterol transporter activity in response to fluctuations in cell cholesterol levels, in addition to the longer term cholesterol-dependent transcriptional regulation of these genes. PMID:24500716

  3. Bile acid sequestrants for cholesterol

    Science.gov (United States)

    ... ency/patientinstructions/000787.htm Bile acid sequestrants for cholesterol To use the sharing features on this page, ... are medicines that help lower your LDL (bad) cholesterol . Too much cholesterol in your blood can stick ...

  4. FEL induced molecular operation on cultured fibroblast and cholesterol ester

    International Nuclear Information System (INIS)

    Awazu, Kunio; Ogino, Seiji; Nishimura, Eiichi; Tomimasu, Takio; Yasumoto, Masato.

    1997-01-01

    Free Electron Lasers can be used to molecular operation such as the delivery of a number of molecules into cells or the separation of cholesterol ester. First, cultured NIH3T3 cells are exposed to high-intensity short pulse Free Electron Laser (FEL). The FEL is tuned to an absorption maximum wavelength, 6.1 μm, which was measured by microscopic FTIR. A fluorescence dye in the cell suspension is more absorbed into the cell with the FEL exposure due to the FEL-induced mechanical stress to the cell membrane. A quantitative fluorescence microscopy is used to determine the efficiency of delivery. Second, as a compound in a lipid cell, cholesterol ester was exposed to 5.75 μm FEL. FTIR measurement was done to evaluate the modification of the cholesterol ester. The result showed that the fluorescence intensity of sample cells were higher than that of control cells, and there was significant difference between the control and the sample group. Blebbing and the colony formation of the cells were observed for cells with mechanical stress. As for the cholesterol ester, it can be modified by the FEL irradiation. These results showed that FEL can be used as a molecular operational tool by photo-chemical and photo-mechanical interaction. (author)

  5. to HDL-cholesterol functionality

    Directory of Open Access Journals (Sweden)

    Malara Marzena

    2016-05-01

    Full Text Available The purpose of this study was to analyse the scientific evidence concerning the effects of two enzymes – paraoxonase 1 and myeloperoxidase – on the functions of HDL-cholesterol. It is well documented that disturbed circulating lipoproteins (a high total and high LDL-cholesterol, and low HDL-cholesterol bring about atherosclerosis and an increased risk of cardiovascular disease (CVD which is recognised as the main cause of death all around the world. In consequence, numerous studies have focused on procedures which will improve the plasma lipoproteins profile by decreasing the total cholesterol and the LDL-cholesterol (LDL-C and increasing the HDL-cholesterol (HDL-C. However, the anti-atherogenic role of HDL-C has been challenged in studies showing that genetically elevated HDL-cholesterol does not offer protection against CVD. Moreover, it has been found that raising the circulating HDL-cholesterol fails to reduce atherosclerosis. The doubts concerning the protective role of HDL-C have been supported by in vitro studies which indicate that the HDL-C from patients with atherosclerosis does not have a protective action, but does stimulate inflammation and free radical synthesis. The above data suggests that HDL-C, commonly recognised as protective against atherosclerosis, in some circumstances becomes pro-atherogenic, and is thus dysfunctional. Our review focuses on two enzymes – paraoxonase 1 (PON1 and myeloperoxidase (MPO – which markedly affect the properties of HDL-C and contribute to its anti – or pro-atherogenic activity. Moreover, the effects of the diet and physical activity on PON1 and MPO are summarised with respect to the HDL-C functionality.

  6. Effect of dietary cholesterol and plant sterol consumption on plasma lipid responsiveness and cholesterol trafficking in healthy individuals.

    Science.gov (United States)

    Alphonse, Peter A S; Ramprasath, Vanu; Jones, Peter J H

    2017-01-01

    Dietary cholesterol and plant sterols differentially modulate cholesterol kinetics and circulating cholesterol. Understanding how healthy individuals with their inherent variabilities in cholesterol trafficking respond to such dietary sterols will aid in improving strategies for effective cholesterol lowering and alleviation of CVD risk. The objectives of this study were to assess plasma lipid responsiveness to dietary cholesterol v. plant sterol consumption, and to determine the response in rates of cholesterol absorption and synthesis to each sterol using stable isotope approaches in healthy individuals. A randomised, double-blinded, crossover, placebo-controlled clinical trial (n 49) with three treatment phases of 4-week duration were conducted in a Manitoba Hutterite population. During each phase, participants consumed one of the three treatments as a milkshake containing 600 mg/d dietary cholesterol, 2 g/d plant sterols or a control after breakfast meal. Plasma lipid profile was determined and cholesterol absorption and synthesis were measured by oral administration of [3, 4-13C] cholesterol and 2H-labelled water, respectively. Dietary cholesterol consumption increased total (0·16 (sem 0·06) mmol/l, P=0·0179) and HDL-cholesterol (0·08 (sem 0·03) mmol/l, P=0·0216) concentrations with no changes in cholesterol absorption or synthesis. Plant sterol consumption failed to reduce LDL-cholesterol concentrations despite showing a reduction (6 %, P=0·0004) in cholesterol absorption. An over-compensatory reciprocal increase in cholesterol synthesis (36 %, P=0·0026) corresponding to a small reduction in absorption was observed with plant sterol consumption, possibly resulting in reduced LDL-cholesterol lowering efficacy of plant sterols. These data suggest that inter-individual variability in cholesterol trafficking mechanisms may profoundly impact plasma lipid responses to dietary sterols in healthy individuals.

  7. Lack of Abcg1 results in decreased plasma HDL cholesterol levels and increased biliary cholesterol secretion in mice fed a high cholesterol diet

    NARCIS (Netherlands)

    Wiersma, Harmen; Nijstad, Niels; de Boer, Jan Freark; Out, Ruud; Hogewerf, Wytse; Van Berkel, Theo J.; Kuipers, Folkert; Tietge, Uwe J. F.

    Objective: The ATP Binding Cassette transporter G1 (ABCG1) has been implicated in cholesterol efflux towards HDL and reverse cholesterol transport (RCT). Biliary cholesterol secretion is considered as an important step in RCT. The aim of the present study was to determine the consequences of Abcg1

  8. [Lipids and cerebrovascular disease - New therapeutic options in lowering LDL-cholesterol].

    Science.gov (United States)

    Lovadi, Emese; Csécsei, Péter; Lovig, Csenge; Karádi, Zsófia; Szapáry, László

    2016-12-01

    Stroke is the third most common cause of death worldwide following myocardial infaction and malignancies, furthermore, its functional outcome is the worst of all conditions. Cholesterol, especially LDL-cholesterol plays a key role in the formation of atherosclerotic plaques. It has been verified recently that escalating incidence and mortality of cerebrovascular diseases are proportional to increased levels of LDL-cholesterol. Statin therapy undeniably reduces the risk of stroke, however other methods for decreasing lipid levels have not been proved significantly effective. Preventive effect of high-dose statin treatment is without doubt, although administration of such high dosage might require special precautions for patients with prior intracerebral hemorrhage and it also risks development of incident diabetes. The recently published IMPROVE-IT study is the first to prove that the addition of ezetimibe as a non-statin type drug, to statin treatment contributes to further reduction of LDL-cholesterol. The combination treatment results in additional decrease in the incidence and mortality of cerebrovascular events, without any expansion in the number or adverse effects. These results confirm the importance of any further reduction of LDL-cholesterol levels. Achieving target values with statin-ezetimibe combination allows administration of low to moderate dose of statin, which decreases risks of adverse effects related to high-dose statin therapy. Orv. Hetil., 2016, 157(52), 2059-2065.

  9. HDL cholesterol, very low levels of LDL cholesterol, and cardiovascular events

    NARCIS (Netherlands)

    Barter, Philip; Gotto, Antonio M.; LaRosa, John C.; Maroni, Jaman; Szarek, Michael; Grundy, Scott M.; Kastelein, John J. P.; Bittner, Vera; Fruchart, Jean-Charles

    2007-01-01

    BACKGROUND: High-density lipoprotein (HDL) cholesterol levels are a strong inverse predictor of cardiovascular events. However, it is not clear whether this association is maintained at very low levels of low-density lipoprotein (LDL) cholesterol. METHODS: A post hoc analysis of the recently

  10. Use of 1H-NMR to determine the distribution of lecithin between the micellar and vesicular phases in model bile

    NARCIS (Netherlands)

    Groen, A. K.; Goldhoorn, B. G.; Egbers, P. H.; Chamuleau, R. A.; Tytgat, G. N.; Bovée, W. M.

    1990-01-01

    Biliary cholesterol/phospholipid vesicles play an important role in the pathogenesis of gallstone disease. A prerequisite for the study of the lipid composition and stability of these vesicles is a reliable method to quantify the amount of vesicular lipid. In the present report we show that NMR can

  11. The synthesis and biological activity of some bile acid derivatives

    International Nuclear Information System (INIS)

    Kadirov, A.Kh.; Khaydarov, K.Kh.; Giyosov, A.Sh.

    2000-01-01

    In this monograph authors present the modified technologic scheme of receiving of 3α, 7α, 12α-three hydro xi cholanic acid with using of available raw materials for the synthesis products and for receiving on its base drugs diluent cholesterol gallstones of gall-bladder and bile-ducts

  12. Triglycerides, total cholesterol, high density lipoprotein cholesterol and low density lipoprotein cholesterol in rats exposed to premium motor spirit fumes.

    Science.gov (United States)

    Aberare, Ogbevire L; Okuonghae, Patrick; Mukoro, Nathaniel; Dirisu, John O; Osazuwa, Favour; Odigie, Elvis; Omoregie, Richard

    2011-06-01

    Deliberate and regular exposure to premium motor spirit fumes is common and could be a risk factor for liver disease in those who are occupationally exposed. A possible association between premium motor spirit fumes and plasma levels of triglyceride, total cholesterol, high density lipoprotein cholesterol and low density lipoprotein cholesterol using a rodent model could provide new insights in the pathology of diseases where cellular dysfunction is an established risk factor. The aim of this study was to evaluate the possible effect of premium motor spirit fumes on lipids and lipoproteins in workers occupationally exposed to premium motor spirit fumes using rodent model. Twenty-five Wister albino rats (of both sexes) were used for this study between the 4(th) of August and 7(th) of September, 2010. The rats were divided into five groups of five rats each. Group 1 rats were not exposed to premium motor spirit fumes (control group), group 2 rats were exposed for 1 hour daily, group 3 for 3 hours daily, group 4 for 5 hours daily and group 5 for 7 hours daily. The experiment lasted for a period of 4 weeks. Blood samples obtained from all the groups after 4 weeks of exposure were used for the estimation of plasma levels of triglyceride, total cholesterol, high density lipoprotein- cholesterol and low density lipoprotein- cholesterol. Results showed significant increase in means of plasma total cholesterol and low density lipoprotein levels (P<0.05). The mean triglyceride and total body weight were significantly lower (P<0.05) in the exposed group when compared with the unexposed. The plasma level of high density lipoprotein, the ratio of low density lipoprotein to high density lipoprotein and the ratio of total cholesterol to high density lipoprotein did not differ significantly in exposed subjects when compared with the control group. These results showed that frequent exposure to petrol fumes may be highly deleterious to the liver cells.

  13. Ezetimibe Increases Endogenous Cholesterol Excretion in Humans.

    Science.gov (United States)

    Lin, Xiaobo; Racette, Susan B; Ma, Lina; Wallendorf, Michael; Ostlund, Richard E

    2017-05-01

    Ezetimibe improves cardiovascular outcomes when added to optimum statin treatment. It lowers low-density lipoprotein cholesterol and percent intestinal cholesterol absorption, but the exact cardioprotective mechanism is unknown. We tested the hypothesis that the dominant effect of ezetimibe is to increase the reverse transport of cholesterol from rapidly mixing endogenous cholesterol pool into the stool. In a randomized, placebo-controlled, double-blind parallel trial in 24 healthy subjects with low-density lipoprotein cholesterol 100 to 200 mg/dL, we measured cholesterol metabolism before and after a 6-week treatment period with ezetimibe 10 mg/d or placebo. Plasma cholesterol was labeled by intravenous infusion of cholesterol-d 7 in a lipid emulsion and dietary cholesterol with cholesterol-d 5 and sitostanol-d 4 solubilized in oil. Plasma and stool samples collected during a cholesterol- and phytosterol-controlled metabolic kitchen diet were analyzed by mass spectrometry. Ezetimibe reduced intestinal cholesterol absorption efficiency 30±4.3% (SE, P <0.0001) and low-density lipoprotein cholesterol 19.8±1.9% ( P =0.0001). Body cholesterol pool size was unchanged, but fecal endogenous cholesterol excretion increased 66.6±12.2% ( P <0.0001) and percent cholesterol excretion from body pools into the stool increased 74.7±14.3% ( P <0.0001), whereas plasma cholesterol turnover rose 26.2±3.6% ( P =0.0096). Fecal bile acids were unchanged. Ezetimibe increased the efficiency of reverse cholesterol transport from rapidly mixing plasma and tissue pools into the stool. Further work is needed to examine the potential relation of reverse cholesterol transport and whole body cholesterol metabolism to coronary events and the treatment of atherosclerosis. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01603758. © 2017 American Heart Association, Inc.

  14. Trapping crystal nucleation of cholesterol monohydrate

    DEFF Research Database (Denmark)

    Solomonov, I.; Weygand, M.J.; Kjær, K.

    2005-01-01

    Crystalline nucleation of cholesterol at the air-water interface has been studied via grazing incidence x-ray diffraction using synchrotron radiation. The various stages of cholesterol molecular assembly from monolayer to three bilayers incorporating interleaving hydrogen-bonded water layers......, at least initially, an intralayer cholesterol rearrangement in a single-crystal-to-single-crystal transition. The preferred nucleation of the monoclinic phase of cholesterol . H2O followed by transformation to the stable monohydrate phase may be associated with an energetically more stable cholesterol...... bilayer arrangement of the former and a more favorable hydrogen-bonding arrangement of the latter. The relevance of this nucleation process of cholesterol monohydrate to pathological crystallization of cholesterol from cell biomembranes is discussed....

  15. Characterization of placental cholesterol transport

    DEFF Research Database (Denmark)

    Lindegaard, Marie L; Wassif, Christopher A; Vaisman, Boris

    2008-01-01

    Patients with Smith-Lemli-Opitz syndrome (SLOS) are born with multiple congenital abnormalities. Postnatal cholesterol supplementation is provided; however, it cannot correct developmental malformations due to in utero cholesterol deficit. Increased transport of cholesterol from maternal to fetal...... circulation might attenuate congenital malformations. The cholesterol transporters Abca1, Abcg1, and Sr-b1 are present in placenta; however, their potential role in placental transport remains undetermined. In mice, expression analyses showed that Abca1 and Abcg1 transcripts increased 2-3-fold between...... embryonic days 13.5 and 18.5 in placental tissue; whereas, Sr-b1 expression decreased. To examine the functional role of Abca1, Abcg1 and Sr-b1 we measured the maternal-fetal transfer of (14)C-cholesterol in corresponding mutant embryos. Disruption of either Abca1 or Sr-b1 decreased cholesterol transfer...

  16. Increased hepatic cholesterol esterification with essential fatty acid deficiency (EFAD): relationship to plasma lipoprotein (LP) cholesterol content

    International Nuclear Information System (INIS)

    Ney, D.M.; Ziboh, V.A.; Schneeman, B.O.

    1986-01-01

    EFAD in the rat is associated with hepatic accumulation of esterified cholesterol and altered distribution of cholesterol between plasma and hepatic tissue. Little is known regarding the impact of EFAD on LP composition. To determine the relationship between hepatic cholesterol esterification and plasma lP composition in control (C) and EFAD male Wistar rats, the authors induced EFAD with continuous intragastric (IG) infusion of EFA-free solutions containing 3.5% of calories as triolein for 7 and 14 days. C animals received IG infusion of solutions containing 3.5% of calories as linoleic acid. Data in the EFAD groups reveal: (i) marked decreases in hepatic EFAs and increases in monoenoic acids; (ii) progressive increases in hepatic content of triglyceride and esterified cholesterol with 7 and 14 days of feeding; (iii) assay of acyl CoA:cholesterol acyltransferase activity in hepatic tissue using 14 C-cholesterol demonstrates an increase in hepatic cholesterol esterification when compared to C animals. Increased hepatic cholesterol esterification correlates with elevated levels of esterified cholesterol in plasma VLDL and HDL particles. These data indicate that the elevated levels of cholesterol esters in LP particles is due, at least in part, to increased hepatic cholesterol esterification with EFAD

  17. Biliary Microbiota, Gallstone Disease and Infection with Opisthorchis felineus.

    Directory of Open Access Journals (Sweden)

    Irina V Saltykova

    2016-07-01

    Full Text Available There is increasing interest in the microbiome of the hepatobiliary system. This study investigated the influence of infection with the fish-borne liver fluke, Opisthorchis felineus on the biliary microbiome of residents of the Tomsk region of western Siberia.Samples of bile were provided by 56 study participants, half of who were infected with O. felineus, and all of who were diagnosed with gallstone disease. The microbiota of the bile was investigated using high throughput, Illumina-based sequencing targeting the prokaryotic 16S rRNA gene. About 2,797, discrete phylotypes of prokaryotes were detected. At the level of phylum, bile from participants with opisthorchiasis showed greater numbers of Synergistetes, Spirochaetes, Planctomycetes, TM7 and Verrucomicrobia. Numbers of > 20 phylotypes differed in bile of the O. felineus-infected compared to non-infected participants, including presence of species of the genera Mycoplana, Cellulosimicrobium, Microlunatus and Phycicoccus, and the Archaeans genus, Halogeometricum, and increased numbers of Selenomonas, Bacteroides, Rothia, Leptotrichia, Lactobacillus, Treponema and Klebsiella.Overall, infection with the liver fluke O. felineus modified the biliary microbiome, increasing abundance of bacterial and archaeal phylotypes.

  18. Effect of feeding garlic (allium sativum) on body weight and serum cholesterol levels in rats

    International Nuclear Information System (INIS)

    Farnaz, S.; Qamar, M.Z.; Karim, S.

    2011-01-01

    Background: Oral garlic supplementation may be effective in decreasing serum cholesterol levels as much as 15% to 20%. Garlic indirectly effect atherosclerosis by reduction of hyperlipidaemia, hypertension and probably diabetes mellitus and prevents thrombus formation. This study was undertaken to test the hypothesis that garlic powder with a prolonged mode of action promises potent biological effects into hypercholesterolaemia. Methods: Fifty albino rats were randomly divided into 5 equal groups (n=10). All rats were initially fed normal diet for at least 7 days. Then Group A was control and was fed a normal diet + 0.5% cholesterol, Group B was fed normal diet and 3 mg garlic per 10 g of feed and Group C was fed normal diet and 10 mg garlic per 10 g of feed. The experiment lasted for 12 weeks. Body weight and serum cholesterol were noted before and after giving garlic + cholesterol. Results: Effect of serum cholesterol level was significantly decreased after taking 3 and 10 mg of garlic. However it was observed that the body weight was increased after taking garlic. Conclusion: Garlic consumption although can decrease the level of serum cholesterol but it increases the body weight. Garlic consumption alone can decrease serum cholesterol level, but it cannot be used as the main therapeutic agent for hyperlipidaemia. (author)

  19. Recovery and purification of cholesterol from cholesterol-β-cyclodextrin inclusion complex using ultrasound-assisted extraction.

    Science.gov (United States)

    Li, Yong; Chen, Youliang; Li, Hua

    2017-01-01

    Response surface methodology was used to optimize ultrasound-assisted ethanol extraction (UAE) of cholesterol from cholesterol-β-cyclodextrin (C-β-CD) inclusion complex prepared from duck yolk oil. The best extraction conditions were solvent-solid ratio 10mL/g, ultrasonic power 251W, extraction temperature 56°C and sonication time 36min. Under these conditions, the highest cholesterol extraction yield and cholesterol content obtained 98.12±0.25% and 43.38±0.61mg/g inclusion complex, respectively. As compared with Reflux extraction and Soxhlet extraction, the UAE was more efficient and economical. To increase the purity of crude cholesterol extraction, silica gel column chromatography and crystallization were carried out. Finally, cholesterol was obtained at 95.1% purity, 71.7% recovery and 22.0% yield. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Cholesterol Medicines: MedlinePlus Health Topic

    Science.gov (United States)

    ... heart diseases . There are two main types of cholesterol. LDL is the "bad" cholesterol. A high LDL level leads to a buildup of cholesterol in ... 75 years old, you have diabetes, and your LDL cholesterol level is 70 mg/dL or higher You ...

  1. The cholesterol space of the rat

    International Nuclear Information System (INIS)

    Chevallier, F.

    1959-01-01

    The experiments consisted in feeding daily to rats the same mass of radioactive cholesterol, over variable time intervals. From the evolution of the specific radioactivity of cholesterol carbon-14 in the organs as a function of time, information relative to the transport of cholesterol in the organism may be obtained. 1) The cholesterol space, defined as the group of molecules capable of being transferred from the organs into the serum and vice versa, represents at the most 50 per cent of the total cholesterol of the adult rat. 2) The incessant interchange between the tissual and the serum cholesterol renews entirely or for the most part the cholesterol molecules contained in the following organs: spleen, heart, adipose tissue, suprarenal glands, lungs, bone marrow, liver, erythrocytes. For a second group of organs: skin, testicles, kidneys, colon, bones, muscles, only a fraction of their cholesterol is renewable by this process. No transfer can be detected at the level of the brain. 3) The relative speeds of the various means of appearance (absorption, synthesis) and disappearance (excretion, transformation) of the cholesterol from its space are such that a stationary isotopic state is established around the eighth day, when the animal absorbs 5 milligrams of radioactive cholesterol daily. (author) [fr

  2. Conversion of Exogenous Cholesterol into Glycoalkaloids in Potato Shoots, Using Two Methods for Sterol Solubilisation

    Science.gov (United States)

    Petersson, Erik V.; Nahar, Nurun; Dahlin, Paul; Broberg, Anders; Tröger, Rikard; Dutta, Paresh C.; Jonsson, Lisbeth; Sitbon, Folke

    2013-01-01

    Steroidal glycoalkaloids (SGA) are toxic secondary metabolites naturally occurring in the potato, as well as in certain other Solanaceous plant species, such as tomato, eggplant and pepper. To investigate the steroidal origin of SGA biosynthesis, cut potato shoots were fed cholesterol labelled with deuterium (D) in the sterol ring structure (D5- or D6-labelled), or side chain (D7-labelled), and analysed after three or five weeks. The labelled cholesterol and presence of D-labelled SGA were analysed by GC-MS and LC-MS/MS, respectively. When feeding D-labelled cholesterol solubilised in Tween-80, labelled cholesterol in free form became present in both leaves and stems, although the major part was recovered as steryl esters. Minor amounts of D-labelled SGA (α-solanine and α-chaconine) were identified in cholesterol-treated shoots, but not in blank controls, or in shoots fed D6-27-hydroxycholesterol. Solubilising the labelled cholesterol in methyl-β-cyclodextrin instead of Tween-80 increased the levels of labelled SGA up to 100-fold, and about 1 mole% of the labelled cholesterol was recovered as labelled SGA in potato leaves. Both side chain and ring structure D labels were retained in SGA, showing that the entire cholesterol molecule is converted to SGA. However, feeding side chain D7-labelled cholesterol resulted in D5-labelled SGA, indicating that two hydrogen atoms were released during formation of the SGA nitrogen-containing ring system. Feeding with D7-sitosterol did not produce any labelled SGA, indicating that cholesterol is a specific SGA precursor. In conclusion, we have demonstrated a superior performance of methyl-β-cyclodextrin for delivery of cholesterol in plant tissue feeding experiments, and given firm evidence for cholesterol as a specific sterol precursor of SGA in potato. PMID:24349406

  3. Transintestinal cholesterol excretion in humans

    NARCIS (Netherlands)

    Reeskamp, Laurens F.; Meessen, Emma C. E.; Groen, Albert K.

    2018-01-01

    Purpose of review To discuss recent insights into the measurement and cellular basis of transintestinal cholesterol excretion (TICE) in humans and to explore TICE as a therapeutic target for increasing reverse cholesterol transport. Recent findings TICE is the net effect of cholesterol excretion by

  4. Cholesterol Absorption and Synthesis in Vegetarians and Omnivores.

    Science.gov (United States)

    Lütjohann, Dieter; Meyer, Sven; von Bergmann, Klaus; Stellaard, Frans

    2018-03-01

    Vegetarian diets are considered health-promoting; however, a plasma cholesterol lowering effect is not always observed. We investigate the link between vegetarian-diet-induced alterations in cholesterol metabolism. We study male and female omnivores, lacto-ovo vegetarians, lacto vegetarians, and vegans. Cholesterol intake, absorption, and fecal sterol excretion are measured as well as plasma concentrations of cholesterol and noncholesterol sterols. These serve as markers for cholesterol absorption, synthesis, and catabolism. The biliary cholesterol secretion rate is estimated. Flux data are related to body weight. Individual vegetarian diet groups are statistically compared to the omnivore group. Lacto vegetarians absorb 44% less dietary cholesterol, synthesized 22% more cholesterol, and show no differences in plasma total and LDL cholesterol. Vegan subjects absorb 90% less dietary cholesterol, synthesized 35% more cholesterol, and have a similar plasma total cholesterol, but a 13% lower plasma LDL cholesterol. No diet-related differences in biliary cholesterol secretion and absorption are observed. Total cholesterol absorption is lower only in vegans. Total cholesterol input is similar under all vegetarian diets. Unaltered biliary cholesterol secretion and higher cholesterol synthesis blunt the lowered dietary cholesterol intake in vegetarians. LDL cholesterol is significantly lower only in vegans. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Effect of 17alpha-ethinylestradiol on activity of rat liver enzymes for synthesis and hydrolysis of cholesterol esters

    International Nuclear Information System (INIS)

    Nikitin, Yu.P.; Dushkin, M.I.; Dolgov, A.V.; Gordienko, I.A.

    1987-01-01

    Administration of estrogens is known to lower the concentration of cholesterol esters in the blood vessel wall and may delay the development of arteriosclerosis. It is also known that under the influence of estrogens the redistribution of concentrations of free cholesterol and cholesterol esters takes place in rats between the blood and liver as a result of the intensification of receptor-dependent uptake of low-density lipoproteins by the hepatocytes. The mechanisms of this intracellular redistribution, however, have been inadequately studied. The purpose of this paper is to study the effects of 17alpha-ethinylestradiol on the activity of lysosomal and cytoplasmic cholesterol esterases, acyl-CoA-cholesterol-O-acyltransferase, lysosomal acid phosphatase, and beta-D-galactosidase. The activity was measured by using cholesterol [1-C 14]-oleate as the substrate. The influence of the estradiol is found to be based on cholesterol redistribution between the blood and liver. Accumulation of free cholesterol in the liver under these conditions stimulates bile acid formation. Depression of cholesterol ester synthesis as a result of direct inhibition of the acyltransferase by the estradiol is found to possibly contribute to the fall in the cholesterol level in the body. Liquid scintillation counting was used to measure distribution and accumulation

  6. Relative variations of gut microbiota in disordered cholesterol metabolism caused by high-cholesterol diet and host genetics.

    Science.gov (United States)

    Bo, Tao; Shao, Shanshan; Wu, Dongming; Niu, Shaona; Zhao, Jiajun; Gao, Ling

    2017-08-01

    Recent studies performed provide mechanistic insight into effects of the microbiota on cholesterol metabolism, but less focus was given to how cholesterol impacts the gut microbiota. In this study, ApoE -/- Sprague Dawley (SD) rats and their wild-type counterparts (n = 12) were, respectively, allocated for two dietary condition groups (normal chow and high-cholesterol diet). Total 16S rDNA of fecal samples were extracted and sequenced by high-throughput sequencing to determine differences in microbiome composition. Data were collected and performed diversity analysis and phylogenetic analysis. The influence of cholesterol on gut microbiota was discussed by using cholesterol dietary treatment as exogenous cholesterol disorder factor and genetic modification as endogenous metabolic disorder factor. Relative microbial variations were compared to illustrate the causality and correlation of cholesterol and gut microbiota. It turned out comparing to genetically modified rats, exogenous cholesterol intake may play more effective role in changing gut microbiota profile, although the serum cholesterol level of genetically modified rats was even higher. Relative abundance of some representative species showed that the discrepancies due to dietary variation were more obvious, whereas some low abundance species changed because of genetic disorders. Our results partially demonstrated that gut microbiota are relatively more sensitive to dietary variation. Nevertheless, considering the important effect of bacteria in cholesterol metabolism, the influence to gut flora by "genetically caused cholesterol disorder" cannot be overlooked. Manipulation of gut microbiota might be an effective target for preventing cholesterol-related metabolic disorders. © 2017 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.

  7. Cholesterol and related sterols autoxidation.

    Science.gov (United States)

    Zerbinati, Chiara; Iuliano, Luigi

    2017-10-01

    Cholesterol is a unique lipid molecule providing the building block for membranes, hormones, vitamin D and bile acid synthesis. Metabolism of cholesterol involves several enzymes acting on the sterol nucleus or the isooctyl tail. In the recent years, research interest has been focused on oxysterols, cholesterol derivatives generated by the addition of oxygen to the cholesterol backbone. Oxysterols can be produced enzymatically or by autoxidation. Autoxidation of cholesterol proceeds through type I or type II mechanisms. Type I autoxidation is initiated by free radical species, such as those arising from the superoxide/hydrogen peroxide/hydroxyl radical system. Type II autoxidation occurs stoichiometrically by non-radical highly reactive oxygen species such as singlet oxygen, HOCl, and ozone. The vulnerability of cholesterol towards high reactive species has raised considerable interest for mechanistic studies and for the potential biological activity of oxysterols, as well as for the use of oxysterols as biomarkers for the non-invasive study of oxidative stress in vivo. Copyright © 2017. Published by Elsevier Inc.

  8. High Cholesterol in Children and Teens

    Science.gov (United States)

    ... dairy products. The body needs some cholesterol to work properly. But if your child or teen has high cholesterol (too much cholesterol in the blood), he or she has a higher risk of coronary artery disease and other heart diseases. What causes high cholesterol in children and teens? Three main ...

  9. Histone deacetylase inhibition decreases cholesterol levels in neuronal cells by modulating key genes in cholesterol synthesis, uptake and efflux.

    Directory of Open Access Journals (Sweden)

    Maria João Nunes

    Full Text Available Cholesterol is an essential component of the central nervous system and increasing evidence suggests an association between brain cholesterol metabolism dysfunction and the onset of neurodegenerative disorders. Interestingly, histone deacetylase inhibitors (HDACi such as trichostatin A (TSA are emerging as promising therapeutic approaches in neurodegenerative diseases, but their effect on brain cholesterol metabolism is poorly understood. We have previously demonstrated that HDACi up-regulate CYP46A1 gene transcription, a key enzyme in neuronal cholesterol homeostasis. In this study, TSA was shown to modulate the transcription of other genes involved in cholesterol metabolism in human neuroblastoma cells, namely by up-regulating genes that control cholesterol efflux and down-regulating genes involved in cholesterol synthesis and uptake, thus leading to an overall decrease in total cholesterol content. Furthermore, co-treatment with the amphipathic drug U18666A that can mimic the intracellular cholesterol accumulation observed in cells of Niemman-Pick type C patients, revealed that TSA can ameliorate the phenotype induced by pathological cholesterol accumulation, by restoring the expression of key genes involved in cholesterol synthesis, uptake and efflux and promoting lysosomal cholesterol redistribution. These results clarify the role of TSA in the modulation of neuronal cholesterol metabolism at the transcriptional level, and emphasize the idea of HDAC inhibition as a promising therapeutic tool in neurodegenerative disorders with impaired cholesterol metabolism.

  10. Controlling Cholesterol with Statins

    Science.gov (United States)

    ... For Consumers Home For Consumers Consumer Updates Controlling Cholesterol with Statins Share Tweet Linkedin Pin it More ... not, the following tips can help keep your cholesterol in check: Talk with your healthcare provider about ...

  11. Simplified procedure for the in vitro assay of the initial linear rate of the reaction of lecithin-cholesterol acyltransferase in human serum

    International Nuclear Information System (INIS)

    Mahadevan, V.; Soloff, L.A.

    1985-01-01

    A simple sensitive method for the determination of the initial rate of the reaction of lecithin-cholesterol acyltransferase by equilibrating [ 3 H]cholesterol with unesterified cholesterol of human serum is described. The resulting serum is incubated for various time periods at 37 degrees C and the increase of the label in the cholesterol ester fraction is measured. The labeling is effected by a fids at 37 degrees C and the increase of the label in the cholesterol ester fraction is measured. The labeling is effected by a filter paper method in which a paper strip containing the labeled cholesterol is placed in serum at 4 degrees C, thereby preventing the formation of labeled cholesterol esters by the action of the enzyme. The rate of the reaction was linear up to 30 min

  12. The Interpretation of Cholesterol Balance Derived Synthesis Data and Surrogate Noncholesterol Plasma Markers for Cholesterol Synthesis under Lipid Lowering Therapies

    Directory of Open Access Journals (Sweden)

    Frans Stellaard

    2017-01-01

    Full Text Available The cholesterol balance procedure allows the calculation of cholesterol synthesis based on the assumption that loss of endogenous cholesterol via fecal excretion and bile acid synthesis is compensated by de novo synthesis. Under ezetimibe therapy hepatic cholesterol is diminished which can be compensated by hepatic de novo synthesis and hepatic extraction of plasma cholesterol. The plasma lathosterol concentration corrected for total cholesterol concentration (R_Lath as a marker of de novo cholesterol synthesis is increased during ezetimibe treatment but unchanged under treatment with ezetimibe and simvastatin. Cholesterol balance derived synthesis data increase during both therapies. We hypothesize the following. (1 The cholesterol balance data must be applied to the hepatobiliary cholesterol pool. (2 The calculated cholesterol synthesis value is the sum of hepatic de novo synthesis and the net plasma—liver cholesterol exchange rate. (3 The reduced rate of biliary cholesterol absorption is the major trigger for the regulation of hepatic cholesterol metabolism under ezetimibe treatment. Supportive experimental and literature data are presented that describe changes of cholesterol fluxes under ezetimibe, statin, and combined treatments in omnivores and vegans, link plasma R_Lath to liver function, and define hepatic de novo synthesis as target for regulation of synthesis. An ezetimibe dependent direct hepatic drug effect cannot be excluded.

  13. Intracellular transport of cholesterol in mammalian cells

    International Nuclear Information System (INIS)

    Brasaemle, D.L.

    1989-01-01

    The erythrocyte was selected as a simple cell for the study of transbilayer movement of cholesterol. Cholesterol oxidase was used to measure the distribution of [ 3 H]cholesterol across the erythrocyte membrane. Cholesterol oxidase was also used to estimate the rate of transport of low density lipoprotein (LDL) cholesterol to the plasma membrane of cultured Chinese hamster ovary (CHO) fibroblasts; the half-time of this process was 42 minutes. The rate of transport of LDL cholesterol to the plasma membrane was confirmed by a second procedure using amphotericin B. Amphotericin B was also used to estimate the rate of transport of endogenously synthesized cholesterol to the plasma membrane of CHO cells. New methodology was developed including improvements of the previously published cholesterol oxidase assay for plasma membrane cholesterol. A new method for detecting transport of cholesterol to the plasma membrane in cultured cells was developed using amphotericin B. Preliminary studies investigated the use of fluorescent polyenes, pimaricin and etruscomycin, as probes for plasma membrane cholesterol in transport studies. Finally, a modification of a previously published cell staining protocol yielded a simple, quantitative assay for cell growth

  14. [Extracorporeal shock-wave lithotripsy of gallstones].

    Science.gov (United States)

    Freund, H R; Lebensart, P D; Muggia-Sullam, M; Durst, A L

    1989-08-01

    We performed 16 extracorporeal shock-wave lithotripsies (ESWL) to fragment gallstones in 11 women and 2 men, aged 19 to 57 (mean 41 +/- 10) years, during the past 10 months. Criteria for selection included a history of biliary colic, not more than 3 stones with a total diameter of not more than 30 mm, and a functioning gallbladder. 210 patients were examined, of whom 98 were referred for additional screening by combined ultrasonography and oral cholecystography. This resulted in rejection of another 71 patients due to multiple stones (38%), nonfunctioning gallbladder (22%), calcified stones (12%), stones not visualized in the prone position (9%), excessively large stones (3%) and other reasons (16%). Only 27 patients fulfilled all the criteria. Under epidural or general anesthesia (11 and 2 patients, respectively), we administered 1200-3500 (mean 2250 +/- 750) shock waves at 20-24 KV with the Tripter X1 (Direx, Israel-USA). This is an ultrasound-guided, modular portable, shock-wave generator utilizing underwater high energy spark discharge. Chenodeoxycholic or ursodeoxycholic acid, 10 mg/kg/day, was started 1 week prior to ESWL and continued for 3 months after disappearance of fragments and debris. We encountered skin petechiae in all patients, transient hematuria in 8, mild biliary colic in 1 and a small liver hematoma in 1. To date, 3 patients are free of stones, while in 7 only sludge and tiny fragments are present which we expect to disappear as a result of the litholytic therapy. 3 patients had fragments larger than 5 mm and required a second ESWL. Thus ESWL, which was indicated in only 13% of screened patients, proved to be safe and can be expected to be successful in 75% of selected candidates.

  15. [Cholesterol reducing food certainly is useful].

    Science.gov (United States)

    Stalenhoef, A F

    1997-12-27

    The effect of a low-cholesterol diet in open intervention studies depends in the long run on motivation, knowledge and dedication. The mean decrease of the serum cholesterol level is 10% (range: 0-20). Epidemiological and cohort studies clearly prove a connection between the intake of saturated fat, the serum cholesterol level and the risk of coronary heart disease and death. High-fat food slows down the clearance of the degradation products rich in cholesterol which appear in the blood after a meal and which are highly atherogenic (these products are not found at a fasting cholesterol assay). Cholesterol-reducing nutrition has additional useful effects, for instance on the blood pressure and the coagulation. The recommendations for healthy, low-cholesterol nutrition for the population as a whole apply particularly to patients with a high risk of coronary heart disease. Although advice given to individuals often has a disappointing effect, influencing the life pattern should be included in the strategy to reduce the risk of coronary heart disease.

  16. Gly[14]-humanin inhibits ox-LDL uptake and stimulates cholesterol efflux in macrophage-derived foam cells.

    Science.gov (United States)

    Zhu, Wa-Wa; Wang, Shu-Rong; Liu, Zhi-Hua; Cao, Yong-Jun; Wang, Fen; Wang, Jing; Liu, Chun-Feng; Xie, Ying; Xie, Ying; Zhang, Yan-Lin

    2017-01-01

    Foam cell formation, which is caused by imbalanced cholesterol influx and efflux by macrophages, plays a vital role in the occurrence and development of atherosclerosis. Humanin (HN), a mitochondria-derived peptide, can prevent the production of reactive oxygen species and death of human aortic endothelial cells exposed to oxidized low-density lipoprotein (ox-LDL) and has a protective effect on patients with in early atherosclerosis. However, the effects of HN on the regulation of cholesterol metabolism in RAW 264.7 macrophages are still unknown. This study was designed to investigate the role of [Gly14]-humanin (HNG) in lipid uptake and cholesterol efflux in RAW 264.7 macrophages. Flow cytometry and live cell imaging results showed that HNG reduced Dil-ox-LDL accumulation in the RAW 264.7 macrophages. A similar result was obtained for lipid accumulation by measuring cellular cholesterol content. Western blot analysis showed that ox-LDL treatment upregulated not only the protein expression of CD36 and LOX-1, which mediate ox-LDL endocytosis, but also ATP-binding cassette (ABC) transporter A1 and ABCG1, which mediate ox-LDL exflux. HNG pretreatment inhibited the upregulation of CD36 and LOX-1 levels, prompting the upregulation of ABCA1 and ABCG1 levels induced by ox-LDL. Therefore we concluded that HNG could inhibit ox-LDL-induced macrophage-derived foam cell formation, which occurs because of a decrease in lipid uptake and an increase in cholesterol efflux from macrophage cells. Copyright © 2016 Elsevier Inc. All rights reserved.

  17. Phospholipase A2-treated human high-density lipoprotein and cholesterol movements: exchange processes and lecithin: cholesterol acyltransferase reactivity.

    Science.gov (United States)

    Chollet, F; Perret, B P; Chap, H; Douste-Blazy, L

    1986-02-12

    Human HDL3 (d 1.125-1.21 g/ml) were treated by an exogenous phospholipase A2 from Crotalus adamenteus in the presence of albumin. Phosphatidylcholine hydrolysis ranged between 30 and 90% and the reisolated particle was essentially devoid of lipolysis products. (1) An exchange of free cholesterol was recorded between radiolabelled erythrocytes at 5-10% haematocrit and HDL3 (0.6 mM total cholesterol) from 0 to 12-15 h. Isotopic equilibration was reached. Kinetic analysis of the data indicated a constant rate of free cholesterol exchange of 13.0 microM/h with a half-time of equilibration around 3 h. Very similar values of cholesterol exchange, specific radioactivities and kinetic parameters were measured when phospholipase-treated HDL replaced control HDL. (2) The lecithin: cholesterol acyltransferase reactivity of HDL3, containing different amounts of phosphatidylcholine, as achieved by various degrees of phospholipase A2 treatment, was measured using a crude preparation of lecithin: cholesterol acyltransferase (the d 1.21-1.25 g/ml plasma fraction). The rate of esterification was determined between 0 and 12 h. Following a 15-30% lipolysis, the lecithin: cholesterol acyltransferase reactivity of HDL3 was reduced about 30-40%, and then continued to decrease, though more slowly, as the phospholipid content was further lowered in the particle. (3) The addition of the lecithin: cholesterol acyltransferase preparation into an incubation medium made of labelled erythrocytes and HDL3 promoted a movement of radioactive cholesterol out of cells, above the values of exchange, and an accumulation of cholesteryl esters in HDL. This reflected a mass consumption of free cholesterol, from both the cellular and the lipoprotein compartments upon the lecithin: cholesterol acyltransferase action. As a consequence of a decreased reactivity, phospholipase-treated HDL (with 2/3 of phosphatidylcholine hydrolyzed) proved much less effective in the lecithin: cholesterol acyltransferase

  18. The expression of cholesterol metabolism genes in monocytes from HIV-infected subjects suggests intracellular cholesterol accumulation.

    Science.gov (United States)

    Feeney, Eoin R; McAuley, Nuala; O'Halloran, Jane A; Rock, Clare; Low, Justin; Satchell, Claudette S; Lambert, John S; Sheehan, Gerald J; Mallon, Patrick W G

    2013-02-15

    Human immunodeficiency virus (HIV) infection is associated with increased cardiovascular risk and reduced high-density lipoprotein cholesterol (HDL-c). In vitro, HIV impairs monocyte-macrophage cholesterol efflux, a major determinant of circulating HDL-c, by increasing ABCA1 degradation, with compensatory upregulation of ABCA1 messenger RNA (mRNA). We examined expression of genes involved in cholesterol uptake, metabolism, and efflux in monocytes from 22 HIV-positive subjects on antiretroviral therapy (ART-Treated), 30 untreated HIV-positive subjects (ART-Naive), and 22 HIV-negative controls (HIV-Neg). HDL-c was lower and expression of ABCA1 mRNA was higher in ART-Naive subjects than in both ART-Treated and HIV-Neg subjects (both P ART-Treated and ART-Naive subjects than in HIV-Neg controls. In vivo, increased monocyte ABCA1 expression in untreated HIV-infected patients and normalization of ABCA1 expression with virological suppression by ART supports direct HIV-induced impairment of cholesterol efflux previously demonstrated in vitro. However, decreased expression of cholesterol sensing, uptake, and synthesis genes in both untreated and treated HIV infection suggests that both HIV and ART affect monocyte cholesterol metabolism in a pattern consistent with accumulation of intramonocyte cholesterol.

  19. Oxidized cholesterol as the driving force behind the development of Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Paola eGamba

    2015-06-01

    Full Text Available Alzheimer’s disease (AD, the most common neurodegenerative disorder associated with dementia, is typified by the pathological accumulation of amyloid β peptides and neurofibrillary tangles within the brain. Considerable evidence indicates that many events contribute to AD progression, including oxidative stress, inflammation, and altered cholesterol metabolism.The brain’s high lipid content makes it particularly vulnerable to oxidative species, with the consequent enhancement of lipid peroxidation and cholesterol oxidation, and the subsequent formation of end products, mainly 4-hydroxynonenal and oxysterols, respectively from the two processes. The chronic inflammatory events observed in the AD brain include activation of microglia and astrocytes, together with enhancement of inflammatory molecule and free radical release. Along with glial cells, neurons themselves have been found to contribute to neuroinflammation in the AD brain, by serving as sources of inflammatory mediators. Oxidative stress is intimately associated with neuroinflammation, and a vicious circle has been found to connect oxidative stress and inflammation in AD. Alongside oxidative stress and inflammation, altered cholesterol metabolism and hypercholesterolemia also significantly contribute to neuronal damage and to progression of AD. Increasing evidence is now consolidating the hypothesis that oxidized cholesterol is the driving force behind the development of AD, and that oxysterols are the link connecting the disease to altered cholesterol metabolism in the brain and hypercholesterolemia; this is because of the ability of oxysterols, unlike cholesterol, to cross the blood brain barrier. The key role of oxysterols in AD pathogenesis has been strongly supported by research pointing to their involvement in modulating neuroinflammation, Aβ accumulation, and cell death.This review highlights the key role played by cholesterol and oxysterols in the brain in AD pathogenesis.

  20. Cholesterol photo-oxidation: A chemical reaction network for kinetic modeling.

    Science.gov (United States)

    Barnaba, Carlo; Rodríguez-Estrada, Maria Teresa; Lercker, Giovanni; García, Hugo Sergio; Medina-Meza, Ilce Gabriela

    2016-12-01

    In this work we studied the effect of polyunsaturated fatty acids (PUFAs) methyl esters on cholesterol photo-induced oxidation. The oxidative routes were modeled with a chemical reaction network (CRN), which represents the first application of CRN to the oxidative degradation of a food-related lipid matrix. Docosahexaenoic acid (DHA, T-I), eicosapentaenoic acid (EPA, T-II) and a mixture of both (T-III) were added to cholesterol using hematoporphyrin as sensitizer, and were exposed to a fluorescent lamp for 48h. High amounts of Type I cholesterol oxidation products (COPs) were recovered (epimers 7α- and 7β-OH, 7-keto and 25-OH), as well as 5β,6β-epoxy. Fitting the experimental data with the CRN allowed characterizing the associated kinetics. DHA and EPA exerted different effects on the oxidative process. DHA showed a protective effect to 7-hydroxy derivatives, whereas EPA enhanced side-chain oxidation and 7β-OH kinetic rates. The mixture of PUFAs increased the kinetic rates several fold, particularly for 25-OH. With respect to the control, the formation of β-epoxy was reduced, suggesting potential inhibition in the presence of PUFAs. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Inhibition of HMG CoA reductase reveals an unexpected role for cholesterol during PGC migration in the mouse

    Directory of Open Access Journals (Sweden)

    Ewing Andrew G

    2008-12-01

    Full Text Available Abstract Background Primordial germ cells (PGCs are the embryonic precursors of the sperm and eggs. Environmental or genetic defects that alter PGC development can impair fertility or cause formation of germ cell tumors. Results We demonstrate a novel role for cholesterol during germ cell migration in mice. Cholesterol was measured in living tissue dissected from mouse embryos and was found to accumulate within the developing gonads as germ cells migrate to colonize these structures. Cholesterol synthesis was blocked in culture by inhibiting the activity of HMG CoA reductase (HMGCR resulting in germ cell survival and migration defects. These defects were rescued by co-addition of isoprenoids and cholesterol, but neither compound alone was sufficient. In contrast, loss of the last or penultimate enzyme in cholesterol biosynthesis did not alter PGC numbers or position in vivo. However embryos that lack these enzymes do not exhibit cholesterol defects at the stage at which PGCs are migrating. This demonstrates that during gestation, the cholesterol required for PGC migration can be supplied maternally. Conclusion In the mouse, cholesterol is required for PGC survival and motility. It may act cell-autonomously by regulating clustering of growth factor receptors within PGCs or non cell-autonomously by controlling release of growth factors required for PGC guidance and survival.

  2. Niacin to Boost Your HDL "Good" Cholesterol

    Science.gov (United States)

    Niacin can boost 'good' cholesterol Niacin is a B vitamin that may raise your HDL ("good") cholesterol. But side effects might outweigh benefits for most ... been used to increase high-density lipoprotein (HDL) cholesterol — the "good" cholesterol that helps remove low-density ...

  3. [THE SPIRIT CHOLESTEROL, BIOLOGICA L ROLE AT STAGES OF PHYLOGENESIS, MECHANISMS OF INHIBITION OF SYNTHESIS OF STEROL BY STATINS, FACTORS OF PHARMACOGENOMICS AND DIAGNOSTIC SIGNIFICANCE OF CHOLESTEROL OF LIPOPROTEINS OF LOW DENSITY].

    Science.gov (United States)

    Titov, V N; Kotlovskii, M Yu; Pokrovskii, A A; Kotlovskaia, O S; Osedko, A V; Titova, N M; Kotlovskii, Yu V; Digaii, A M

    2015-04-01

    The hypolipidemic effect of statins is realized by inhibition of synthesis of local pool of cholesterol spirit in endoplasmic net of hepatocytes. The cholesterol spirit covers all hydrophobic medium of triglycerides with polar mono layer of phosphatidylcholines and cholesterol spirit prior to secretion of lipoproteins of very low density into hydrophilic medium. The lesser mono layer between lipase enzyme and triglycerides substrate contains of cholesterol spirit the higher are the parameters of hydrolysis of palmitic and oleic lipoproteins of very low density. The sequence of effect of statins is as follows: blocking of synthesis in hepatocytes and decreasing of content of unesterified cholesterol spirit in blood plasma; activation of hydrolysis of triglycerides in palmitic and oleic lipoproteins of very low density; formation of ligand lipoproteins of very low density and their absorption by cells by force of apoB-100 endocytosis; decreasing in blood of content of polyenoic fatty acids, equimolar esterified by cholesterol spirit, polyethers of cholesterol spirit and decreasing of level of cholesterol spirit-lipoproteins of very low density. There is no way to eliminate aphysiological effect of disordered biological function of trophology (nutrition) on metabolism of fatty acids in population by means of pharmaceuticals intake. It is necessary to eliminate aphysiological effect of environment. To decrease rate of diseases of cardiovascular system one has to decrease in food content of saturated fatty acids and in the first instance palmitic saturated fatty acid, trans-form fatty acid, palmitoleic fatty acids up to physiological values and increase to the same degree the content of polyenoic fatty acids. The saturated fatty acids block absorption of polyenoic fatty acids by cells. The atherosclerosis is a deficiency of polyenoic fatty acids under surplus of palmitic saturated fatty acid.

  4. Lecithin-cholesterol acyltransferase (LCAT) catalyzes transacylation of intact cholesteryl esters. Evidence for the partial reversal of the forward LCAT reaction

    International Nuclear Information System (INIS)

    Sorci-Thomas, M.; Babiak, J.; Rudel, L.L.

    1990-01-01

    Lecithin-cholesterol acyltransferase (LCAT) catalyzes the intravascular synthesis of lipoprotein cholesteryl esters by converting cholesterol and lecithin to cholesteryl ester and lysolecithin. LCAT is unique in that it catalyzes sequential reactions within a single polypeptide sequence. In this report we find that LCAT mediates a partial reverse reaction, the transacylation of lipoprotein cholesteryl oleate, in whole plasma and in a purified, reconstituted system. As a result of the reverse transacylation reaction, a linear accumulation of [3H]cholesterol occurred during incubations of plasma containing high density lipoprotein labeled with [3H]cholesteryl oleate. When high density lipoprotein labeled with cholesteryl [14C]oleate was also included in the incubation the labeled fatty acyl moiety remained in the cholesteryl [14C]oleate pool showing that the formation of labeled cholesterol did not result from hydrolysis of the doubly labeled cholesteryl esters. The rate of release of [3H]cholesterol was only about 10% of the forward rate of esterification of cholesterol using partially purified human LCAT and was approximately 7% in whole monkey plasma. Therefore, net production of cholesterol via the reverse LCAT reaction would not occur. [3H]Cholesterol production from [3H]cholesteryl oleate was almost completely inhibited by a final concentration of 1.4 mM 5,5'-dithiobis(nitrobenzoic acid) during incubation with either purified LCAT or whole plasma. Addition of excess lysolecithin to the incubation system did not result in the formation of [14C]oleate-labeled lecithin, showing that the reverse reaction found here for LCAT was limited to the last step of the reaction. To explain these results we hypothesize that LCAT forms a [14C]oleate enzyme thioester intermediate after its attack on the cholesteryl oleate molecule

  5. Mechanisms of foam cell formation in atherosclerosis.

    Science.gov (United States)

    Chistiakov, Dimitry A; Melnichenko, Alexandra A; Myasoedova, Veronika A; Grechko, Andrey V; Orekhov, Alexander N

    2017-11-01

    Low-density lipoprotein (LDL) and cholesterol homeostasis in the peripheral blood is maintained by specialized cells, such as macrophages. Macrophages express a variety of scavenger receptors (SR) that interact with lipoproteins, including SR-A1, CD36, and lectin-like oxLDL receptor-1 (LOX-1). These cells also have several cholesterol transporters, including ATP-binding cassette transporter ABCA1, ABCG1, and SR-BI, that are involved in reverse cholesterol transport. Lipids internalized by phagocytosis are transported to late endosomes/lysosomes, where lysosomal acid lipase (LAL) digests cholesteryl esters releasing free cholesterol. Free cholesterol in turn is processed by acetyl-CoA acetyltransferase (ACAT1), an enzyme that transforms cholesterol to cholesteryl esters. The endoplasmic reticulum serves as a depot for maintaining newly synthesized cholesteryl esters that can be processed by neutral cholesterol ester hydrolase (NCEH), which generates free cholesterol that can exit via cholesterol transporters. In atherosclerosis, pro-inflammatory stimuli upregulate expression of scavenger receptors, especially LOX-1, and downregulate expression of cholesterol transporters. ACAT1 is also increased, while NCEH expression is reduced. This results in deposition of free and esterified cholesterol in macrophages and generation of foam cells. Moreover, other cell types, such as endothelial (ECs) and vascular smooth muscle cells (VSMCs), can also become foam cells. In this review, we discuss known pathways of foam cell formation in atherosclerosis.

  6. Intestinal cholesterol secretion : future clinical implications

    NARCIS (Netherlands)

    Jakulj, L.; Besseling, J.; Stroes, E. S. G.; Groen, A. K.

    2013-01-01

    Together with the liver, the intestine serves as a homeostatic organ in cholesterol metabolism. Recent evidence has substantiated the pivotal role of the intestine in reverse cholesterol transport (RCT). RCT is a fundamental antiatherogenic pathway, mediating the removal of cholesterol from tissues

  7. Intestinal cholesterol secretion: future clinical implications

    NARCIS (Netherlands)

    Jakulj, L.; Besseling, J.; Stroes, E. S. G.; Groen, A. K.

    2013-01-01

    Together with the liver, the intestine serves as a homeostatic organ in cholesterol metabolism. Recent evidence has substantiated the pivotal role of the intestine in reverse cholesterol transport (RCT). RCT is a fundamental antiatherogenic pathway, mediating the removal of cholesterol from tissues

  8. DIETARY-CHOLESTEROL INDUCED DOWN-REGULATION OF INTESTINAL 3-HYDROXY-3-METHYLGLUTARYL COENZYME-A REDUCTASE-ACTIVITY IS DIMINISHED IN RABBITS WITH HYPERRESPONSE OF SERUM-CHOLESTEROL TO DIETARY-CHOLESTEROL

    NARCIS (Netherlands)

    MEIJER, GW; SMIT, MJ; VANDERPALEN, JGP; KUIPERS, F; VONK, RJ; VANZUTPHEN, BFM; BEYNEN, AC

    Key enzymes of cholesterol metabolism were studied in two inbred strains of rabbits with hyper- or hyporesponse of serum cholesterol to dietary cholesterol. Baseline 3-hydroxy-3-methylglutaryl (HMG)CoA reductase activity in liver was similar in hypo- and hyperresponders, but that in intestine was

  9. Dietary cholesterol and fats at a young age : do they influence cholesterol metabolism in adult life?

    NARCIS (Netherlands)

    Temmerman, A.M.; Vonk, R.J.; Niezen-Koning, K.; Berger, R.; Fernandes, J.

    1989-01-01

    The effects of dietary cholesterol and fats on cholesterol metabolism later in life were studied in Mongolian gerbils. Three groups were given a basic diet with soybean oil, palm kernel oil amounting to 8.75% (w/w), or the basic diet only. In three other groups, cholesterol (0.05%) was added to the

  10. Imaging appearances of cholesterol pneumonia

    International Nuclear Information System (INIS)

    Miao Yanwei; Zhang Jingwen; Wu Jianlin; Zhou Yong; Li Mingwu; Lei Zhen; Shi Lifu

    2006-01-01

    Objection: To analyze the imaging appearances of cholesterol pneumonia. Methods We retrospectively analyzed the X-ray and CT findings of 3 patients with cholesterol pneumonia confirmed pathologically and reviewed correlative literature. Results: Lesions similar to mass were found in X-ray and CT imaging of three cases. Two of them appeared cavity with fluid-level and one showed multiple ring enhancement after CT contrast. The course of disease was very. long and it had no respond to antibiotic therapy. Amounts of foam cells rich in cholesterol crystal were detected in pathological examination. Conclusions: Cholesterol pneumonia is a rare chronic pulmonary idiopathic disease, and the radiological findings can do some help to its diagnosis. (authors)

  11. Interaction of bovine gallbladder mucin and calcium-binding protein: effects on calcium phosphate precipitation.

    Science.gov (United States)

    Afdhal, N H; Ostrow, J D; Koehler, R; Niu, N; Groen, A K; Veis, A; Nunes, D P; Offner, G D

    1995-11-01

    Gallstones consist of calcium salts and cholesterol crystals, arrayed on a matrix of gallbladder mucin (GBM), and regulatory proteins like calcium-binding protein (CBP). To determine if interactions between CBP and GBM follow a biomineralization scheme, their mutual binding and effects on CaHPO4 precipitation were studied. Binding of CBP to GBM was assessed by inhibition of the fluorescence of the complex of GBM with bis-1,8-anilinonaphthalene sulfonic acid (bis-ANS). The effects of the proteins on precipitation of CaHPO4 were assessed by nephelometry and gravimetry. Precipitates were analyzed for calcium, phosphate, and protein. CBP and bis-ANS competitively displaced each other from 30 binding sites on mucin, with a 1:1 stoichiometry and similar affinity. The rate of precipitation of CaHPO4 was retarded by mucin and CBP. Precipitate mass was unaffected by GBM alone but decreased with the addition of CBP. Complexing CBP with GBM abolished or moderated this latter effect, altered precipitate morphology, and changed the stoichiometric ratios of Ca to PO4 in the precipitates from 1:1 to 3:2. Mucin and CBP were incorporated into the precipitates. These studies suggest that the formation of calcium-containing gallstones is a biomineralization process regulated by both GBM and CBP.

  12. The influence of saponins on cell membrane cholesterol.

    Science.gov (United States)

    Böttger, Stefan; Melzig, Matthias F

    2013-11-15

    We studied the influence of structurally different saponins on the cholesterol content of cellular membranes. Therefore a cell culture model using ECV-304 urinary bladder carcinoma cells was developed. To measure the cholesterol content we used radiolabeled (3)H-cholesterol which is chemically and physiologically identical to natural cholesterol. The cells were pre-incubated with (3)H-cholesterol and after a medium change, they were treated with saponins to assess a saponin-induced cholesterol liberation from the cell membrane. In another experiment the cells were pre-incubated with saponins and after a medium change, they were treated with (3)H-cholesterol to assess a saponin-induced inhibition of cholesterol uptake into the cell membrane. Furthermore, the membrane toxicity of all applied saponins was analyzed using extracellular LDH quantification and the general cytotoxicity was analyzed using a colorimetric MTT-assay and DNA quantification. Our results revealed a correlation between membrane toxicity and general cytotoxicity. We also compared the results from the experiments on the saponin-induced cholesterol liberation as well as the saponin-induced inhibition of cholesterol uptake with the membrane toxicity. A significant reduction in the cell membrane cholesterol content was noted for those saponins who showed membrane toxicity (IC50 saponins either liberated (3)H-cholesterol from intact cell membranes or blocked the integration of supplemented (3)H-cholesterol into the cell membrane. Saponins with little influence on the cell membrane (IC50 >100 μM) insignificantly altered the cell membrane cholesterol content. The results suggested that the general cytotoxicity of saponins is mainly dependent on their membrane toxicity and that the membrane toxicity might be caused by the loss of cholesterol from the cell membrane. We also analyzed the influence of a significantly membrane toxic saponin on the cholesterol content of intracellular membranes such as those

  13. Cholesterol-conjugated supramolecular assemblies of low generations polyamidoamine dendrimers for enhanced EGFP plasmid DNA transfection

    Energy Technology Data Exchange (ETDEWEB)

    Golkar, Nasim; Samani, Soliman Mohammadi; Tamaddon, Ali Mohammad, E-mail: amtamadon@gmail.com [Shiraz University of Medical Sciences, Department of Pharmaceutics, School of Pharmacy (Iran, Islamic Republic of)

    2016-05-15

    Aimed to prepare an enhanced gene delivery system with low cytotoxicity and high transfection efficiency, various cholesterol-conjugated derivates of low generation polyamidoamine (PAMAM) dendrimers were prepared. The conjugates were characterized by TNBS assay, FTIR, and {sup 1}H-NMR spectroscopy. Self-assembly of the dendrimer conjugates (G1-Chol, G2-Chol, and G3-Chol) was investigated by pyrene assay. Following formation of the complexes between enhanced green fluorescence protein plasmid and the dendrimer conjugates at various N (primary amine)/P (phosphate) mole ratios, plasmid condensation, biologic stability, cytotoxicity, and protein expression were investigated. The conjugates self-assembled into micellar dispersions with the critical micelle concentration values (<50 µg/ml) depending on the dendrimer generation and cholesterol/amine mole ratio. Cholesterol conjugation resulted in higher resistance of the condensed plasmid DNA in a competition assay with heparin sulfate. Also, the transfection efficiency was determined higher for the cholesterol conjugates than unmodified dendrimers in HepG2 cells, showing the highest for G2-Chol at 40 % degree of cholesterol modification (G2-Chol{sub 40 %}) among various dendrimer generations. Interestingly, such conjugate showed a complete protection of plasmid against serum nucleases. Our results confirmed that the cholesterol conjugation to PAMAM dendrimers of low generations bearing little cytotoxicity improves their several physicochemical and biological characteristics required for an enhanced delivery of plasmid DNA into cells.

  14. Caveolin-1-mediated apolipoprotein A-I membrane binding sites are not required for cholesterol efflux.

    Directory of Open Access Journals (Sweden)

    Soazig Le Lay

    Full Text Available Caveolin-1 (Cav1, a structural protein required for the formation of invaginated membrane domains known as caveolae, has been implicated in cholesterol trafficking and homeostasis. Here we investigated the contribution of Cav1 to apolipoprotein A-I (apoA-I cell surface binding and intracellular processing using mouse embryonic fibroblasts (MEFs derived from wild type (WT or Cav1-deficient (Cav1(-/- animals. We found that cells expressing Cav1 have 2.6-fold more apoA-I binding sites than Cav1(-/- cells although these additional binding sites are not associated with detergent-free lipid rafts. Further, Cav1-mediated binding targets apoA-I for internalization and degradation and these processes are not correlated to cholesterol efflux. Despite lower apoA-I binding, cholesterol efflux from Cav1(-/- MEFs is 1.7-fold higher than from WT MEFs. Stimulation of ABCA1 expression with an LXR agonist enhances cholesterol efflux from both WT and Cav1(-/- cells without increasing apoA-I surface binding or affecting apoA-I processing. Our results indicate that there are at least two independent lipid binding sites for apoA-I; Cav1-mediated apoA-I surface binding and uptake is not linked to cholesterol efflux, indicating that membrane domains other than caveolae regulate ABCA1-mediated cholesterol efflux.

  15. Effect of emodin on mobility signal transduction system of gallbladder smooth muscle in Guinea pig with cholelithiasis.

    Science.gov (United States)

    Fang, Bang-Jiang; Shen, Jun-Yi; Zhang, Hua; Zhou, Shuang; Lyu, Chuan-Zhu; Xie, Yi-Qiang

    2016-10-01

    To study the effect of emodin on protein and gene expressions of the massagers in mobility signal transduction system of cholecyst smooth muscle cells in guinea pig with cholesterol calculus. The guinea pigs were randomly divided into 4 groups, such as control group, gall-stone (GS) group, emodin group and ursodeoxycholic acid (UA) group. Cholesterol calculus models were induced in guinea pigs of GS, emodin and UA groups by lithogenic diet, while emodin or UA were given to the corresponding group for 7 weeks. The histomorphological and ultrastructure change of gallbladder were detected by microscope and electron microscope, the content of plasma cholecystokinin (CCK) and [Ca 2+ ] i were analyzed successively by radioimmunoassay and flow cytometry. The protein and mRNA of Gsα, Giα and Cap in cholecyst cells were determined by western blotting and real time polymerase chain reaction (RT-PCR). Emodin or UA can relieve pathogenic changes in epithelial cells and muscle cells in gallbladder of guinea pig with cholesterol calculus by microscope and transmission electron microscope. In the cholecyst cells of GS group, CCK levels in plasma and [Ca 2+ ] i decreased, the protein and mRNA of GS were down-regulated, the protein and mRNA of Gi and Cap were up-regulated. Emodin significantly decreased the formative rate of gallstone, improved the pathogenic change in epithelial cells and muscle cells, increased CCK levels in plasma and [Ca 2+ ] i in cholecyst cells, enhanced the protein and mRNA of Gs in cholecyst cells, reduced the protein and mRNA of Gi and Cap in cholecyst cells in guinea pig with cholesterol calculus. The dysfunction of gallbladder contraction gives rise to the disorders of mobility signal transduction system in cholecyst smooth muscle cells, including low content of plasma CCK and [Ca 2+ ] i in cholecyst cells, abnormal protein and mRNA of Gs, Gi and Cap. Emodin can enhance the contractibility of gallbladder and alleviate cholestasis by regulating plasma

  16. Phytosterol glycosides reduce cholesterol absorption in humans

    Science.gov (United States)

    Lin, Xiaobo; Ma, Lina; Racette, Susan B.; Anderson Spearie, Catherine L.; Ostlund, Richard E.

    2009-01-01

    Dietary phytosterols inhibit intestinal cholesterol absorption and regulate whole body cholesterol excretion and balance. However, they are biochemically heterogeneous and a portion is glycosylated in some foods with unknown effects on biological activity. We tested the hypothesis that phytosterol glycosides reduce cholesterol absorption in humans. Phytosterol glycosides were extracted and purified from soy lecithin in a novel two-step process. Cholesterol absorption was measured in a series of three single-meal tests given at intervals of 2 wk to each of 11 healthy subjects. In a randomized crossover design, participants received ∼300 mg of added phytosterols in the form of phytosterol glycosides or phytosterol esters, or placebo in a test breakfast also containing 30 mg cholesterol-d7. Cholesterol absorption was estimated by mass spectrometry of plasma cholesterol-d7 enrichment 4–5 days after each test. Compared with the placebo test, phytosterol glycosides reduced cholesterol absorption by 37.6 ± 4.8% (P lecithin are bioactive in humans and should be included in methods of phytosterol analysis and tables of food phytosterol content. PMID:19246636

  17. Potassium-doped carbon nanotubes toward the direct electrochemistry of cholesterol oxidase and its application in highly sensitive cholesterol biosensor

    Energy Technology Data Exchange (ETDEWEB)

    Li Xiaorong [State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093 (China); Xu Jingjuan, E-mail: xujj@nju.edu.cn [State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093 (China); Chen Hongyuan [State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093 (China)

    2011-10-30

    We demonstrate herein a newly developed serum total cholesterol biosensor by using the direct electron transfer of cholesterol oxidase (ChOx), which is based on the immobilization of cholesterol oxidase and cholesterol esterase (ChEt) on potassium-doped multi-walled carbon nanotubes (KMWNTs) modified electrodes. The KMWNTs accelerate the electron transfer from electrode surface to the immobilized ChOx, achieving the direct electrochemistry of ChOx and maintaining its bioactivity. As a new platform in cholesterol analysis, the resulting electrode (ChOx/KMWNTs/GCE) exhibits a sensitive response to free cholesterol, with a linear range of 0.050-16.0 {mu}mol L{sup -1} and a detection limit of 5.0 nmol L{sup -1} (S/N = 3). Coimmobilization of ChEt and ChOx (ChEt/ChOx/KMWNTs/GCE) allows the determination of both free cholesterol and esterified cholesterol. The resulting biosensor shows the same linear range of 0.050-16.0 {mu}mol L{sup -1} for free cholesterol and cholesteryl oleate, with the detection limit of 10.0 and 12.0 nmol L{sup -1} (S/N = 3), respectively. The concentrations of total (free and esterified) cholesterol in human serum samples, determined by using the techniques developed in the present study, are in good agreement with those determined by the well-established techniques using the spectrophotometry.

  18. Acyl Chain Preference in Foam Cell Formation from Mouse Peritoneal Macrophages.

    Science.gov (United States)

    Fujiwara, Yuko; Hama, Kotaro; Tsukahara, Makoto; Izumi-Tsuzuki, Ryosuke; Nagai, Toru; Ohe-Yamada, Mihoko; Inoue, Keizo; Yokoyama, Kazuaki

    2018-01-01

    Macrophage foam cells play critical roles in the initiation and development of atherosclerosis by synthesizing and accumulating cholesteryl ester (CE) in lipid droplets. However, in analyzing lipid metabolism in foam cell formation, studies have focused on the sterol group, and little research has been done on the acyl chains. Therefore, we adapted a model system using liposomes containing particular acyl chains and examined the effect of various acyl chains on foam cell formation. Of the phosphatidylserine (PS) liposomes tested containing PS, phosphatidylcholine, and cholesterol, we found that unsaturated (C18:1), but not saturated (C16:0 and C18:0), PS liposomes induced lipid droplet formation, indicating that foam cell formation depends on the nature of the acyl chain of the PS liposomes. Experiments on the uptake and accumulation of cholesterol from liposomes by adding [ 14 C]cholesterol suggested that foam cell formation could be induced only when cholesterol was converted to CE in the case of C18:1 PS liposomes. Both microscopic observations and metabolic analysis suggest that cholesterol incorporated into either C16:0 or C18:0 PS liposomes may stay intact after being taken in by endosomes. The [ 14 C]C18:1 fatty acyl chain in the C18:1 PS liposome was used to synthesize CE and triacylglycerol (TG). Interestingly, the [ 14 C]C16:0 in the C18:1 PS liposome was metabolized to sphingomyelin rather than being incorporated into either CE or TG, which could be because of enzymatic acyl chain selectivity. In conclusion, our results indicate that the acyl chain preference of macrophages could have some impact on their progression to foam cells.

  19. Intracellular Cholesterol Trafficking and Impact in Neurodegeneration

    Directory of Open Access Journals (Sweden)

    Fabian Arenas

    2017-11-01

    Full Text Available Cholesterol is a critical component of membrane bilayers where it plays key structural and functional roles by regulating the activity of diverse signaling platforms and pathways. Particularly enriched in brain, cholesterol homeostasis in this organ is singular with respect to other tissues and exhibits a heterogeneous regulation in distinct brain cell populations. Due to the key role of cholesterol in brain physiology and function, alterations in cholesterol homeostasis and levels have been linked to brain diseases and neurodegeneration. In the case of Alzheimer disease (AD, however, this association remains unclear with evidence indicating that either increased or decreased total brain cholesterol levels contribute to this major neurodegenerative disease. Here, rather than analyzing the role of total cholesterol levels in neurodegeneration, we focus on the contribution of intracellular cholesterol pools, particularly in endolysosomes and mitochondria through its trafficking via specialized membrane domains delineated by the contacts between endoplasmic reticulum and mitochondria, in the onset of prevalent neurodegenerative diseases such as AD, Parkinson disease, and Huntington disease as well as in lysosomal disorders like Niemann-Pick type C disease. We dissect molecular events associated with intracellular cholesterol accumulation, especially in mitochondria, an event that results in impaired mitochondrial antioxidant defense and function. A better understanding of the mechanisms involved in the distribution of cholesterol in intracellular compartments may shed light on the role of cholesterol homeostasis disruption in neurodegeneration and may pave the way for specific intervention opportunities.

  20. Cholesterol asymmetry in synaptic plasma membranes.

    Science.gov (United States)

    Wood, W Gibson; Igbavboa, Urule; Müller, Walter E; Eckert, Gunter P

    2011-03-01

    Lipids are essential for the structural and functional integrity of membranes. Membrane lipids are not randomly distributed but are localized in different domains. A common characteristic of these membrane domains is their association with cholesterol. Lipid rafts and caveolae are examples of cholesterol enriched domains, which have attracted keen interest. However, two other important cholesterol domains are the exofacial and cytofacial leaflets of the plasma membrane. The two leaflets that make up the bilayer differ in their fluidity, electrical charge, lipid distribution, and active sites of certain proteins. The synaptic plasma membrane (SPM) cytofacial leaflet contains over 85% of the total SPM cholesterol as compared with the exofacial leaflet. This asymmetric distribution of cholesterol is not fixed or immobile but can be modified by different conditions in vivo: (i) chronic ethanol consumption; (ii) statins; (iii) aging; and (iv) apoE isoform. Several potential candidates have been proposed as mechanisms involved in regulation of SPM cholesterol asymmetry: apoE, low-density lipoprotein receptor, sterol carrier protein-2, fatty acid binding proteins, polyunsaturated fatty acids, P-glycoprotein and caveolin-1. This review examines cholesterol asymmetry in SPM, potential mechanisms of regulation and impact on membrane structure and function. © 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry.

  1. Dairy products and plasma cholesterol levels

    Directory of Open Access Journals (Sweden)

    Lena Ohlsson

    2010-08-01

    Full Text Available Cholesterol synthesized in the body or ingested is an essential lipid component for human survival from our earliest life. Newborns ingest about 3–4 times the amount per body weight through mother's milk compared to the dietary intake of adults. A birth level of 1.7 mmol/L plasma total cholesterol will increase to 4–4.5 mmol/L during the nursing period and continue to increase from adulthood around 40% throughout life. Coronary artery disease and other metabolic disorders are strongly associated with low-density lipoprotein (LDL and high-density lipoprotein (HDL cholesterol as well as triacylglycerol concentration. Milk fat contains a broad range of fatty acids and some have a negative impact on the cholesterol rich lipoproteins. The saturated fatty acids (SFAs, such as palmitic acid (C16:0, myristic acid (C14:0, and lauric acid (C12:0, increase total plasma cholesterol, especially LDL, and constitute 11.3 g/L of bovine milk, which is 44.8% of total fatty acid in milk fat. Replacement of dairy SFA and trans-fatty acids with polyunsaturated fatty acids decreases plasma cholesterol, especially LDL cholesterol, and is associated with a reduced risk of cardiovascular disease. Available data shows different effects on lipoproteins for different dairy products and there is uncertainty as to the impact a reasonable intake amount of dairy items has on cardiovascular risk. The aim of this review is to elucidate the effect of milk components and dairy products on total cholesterol, LDL, HDL, and the LDL/HDL quotients. Based on eight recent randomized controlled trials of parallel or cross-over design and recent reviews it can be concluded that replacement of saturated fat mainly (but not exclusively derived from high-fat dairy products with low-fat dairy products lowers LDL/HDL cholesterol and total/HDL cholesterol ratios. Whey, dairy fractions enriched in polar lipids, and techniques such as fermentation, or fortification of cows feeding can be used

  2. The cholesterol transporter ABCG1 links cholesterol homeostasis and tumour immunity.

    Science.gov (United States)

    Sag, Duygu; Cekic, Caglar; Wu, Runpei; Linden, Joel; Hedrick, Catherine C

    2015-02-27

    ATP-binding cassette transporter G1 (ABCG1) promotes cholesterol efflux from cells and regulates intracellular cholesterol homeostasis. Here we demonstrate a role of ABCG1 as a mediator of tumour immunity. Abcg1(-/-) mice have dramatically suppressed subcutaneous MB49-bladder carcinoma and B16-melanoma growth and prolonged survival. We show that reduced tumour growth in Abcg1(-/-) mice is myeloid cell intrinsic and is associated with a phenotypic shift of the macrophages from a tumour-promoting M2 to a tumour-fighting M1 within the tumour. Abcg1(-/-) macrophages exhibit an intrinsic bias towards M1 polarization with increased NF-κB activation and direct cytotoxicity for tumour cells in vitro. Overall, our study demonstrates that the absence of ABCG1 inhibits tumour growth through modulation of macrophage function within the tumour, and illustrates a link between cholesterol homeostasis and cancer.

  3. Can non-cholesterol sterols and lipoprotein subclasses distribution predict different patterns of cholesterol metabolism and statin therapy response?

    Science.gov (United States)

    Gojkovic, Tamara; Vladimirov, Sandra; Spasojevic-Kalimanovska, Vesna; Zeljkovic, Aleksandra; Vekic, Jelena; Kalimanovska-Ostric, Dimitra; Djuricic, Ivana; Sobajic, Sladjana; Jelic-Ivanovic, Zorana

    2017-03-01

    Cholesterol homeostasis disorders may cause dyslipidemia, atherosclerosis progression and coronary artery disease (CAD) development. Evaluation of non-cholesterol sterols (NCSs) as synthesis and absorption markers, and lipoprotein particles quality may indicate the dyslipidemia early development. This study investigates associations of different cholesterol homeostasis patterns with low-density (LDL) and high-density lipoproteins (HDL) subclasses distribution in statin-treated and statin-untreated CAD patients, and potential use of aforementioned markers for CAD treatment optimization. The study included 78 CAD patients (47 statin-untreated and 31 statin-treated) and 31 controls (CG). NCSs concentrations were quantified using gas chromatography- flame ionization detection (GC-FID). Lipoprotein subclasses were separated by gradient gel electrophoresis. In patients, cholesterol-synthesis markers were significantly higher comparing to CG. Cholesterol-synthesis markers were inversely associated with LDL size in all groups. For cholesterol homeostasis estimation, each group was divided to good and/or poor synthetizers and/or absorbers according to desmosterol and β-sitosterol median values. In CG, participants with reduced cholesterol absorption, the relative proportion of small, dense LDL was higher in those with increased cholesterol synthesis compared to those with reduced synthesis (p<0.01). LDL I fraction was significantly higher in poor synthetizers/poor absorbers subgroup compared to poor synthetizers/good absorbers (p<0.01), and good synthetizers/poor absorbers (p<0.01). Statin-treated patients with increased cholesterol absorption had increased proportion of LDL IVB (p<0.05). The results suggest the existence of different lipoprotein abnormalities according to various patterns of cholesterol homeostasis. Desmosterol/β-sitosterol ratio could be used for estimating individual propensity toward dyslipidemia development and direct the future treatment.

  4. Impaired cholesterol esterification in primary brain cultures of the lysosomal cholesterol storage disorder (LCSD) mouse mutant

    International Nuclear Information System (INIS)

    Patel, S.C.; Suresh, S.; Weintroub, H.; Brady, R.O.; Pentchev, P.G.

    1987-01-01

    Esterification of cholesterol was investigated in primary neuroglial cultures obtained from newborn lysosomal cholesterol storage disorder (LCSD) mouse mutants. An impairment in 3 H-oleic acid incorporation into cholesteryl esters was demonstrated in cultures of homozygous LCSD brain. Primary cultures derived from other phenotypically normal pups of the carrier breeders esterified cholesterol at normal levels or at levels which were intermediary between normal and deficient indicating a phenotypic expression of the LCSD heterozygote genotype. These observations on LCSD mutant brain cells indicate that the defect in cholesterol esterification is closely related to the primary genetic defect and is expressed in neuroglial cells in culture

  5. Synthesis of cholesterol 26. C{sup 14} (1961); Synthese du cholesterol {sup 14}C-26 (1961)

    Energy Technology Data Exchange (ETDEWEB)

    Herbert, M; Pichat, L [Commissariat a l' Energie Atomique, Saclay (France). Centre d' Etudes Nucleaires

    1961-07-01

    Cholesterol 26 {sup 14}C is synthesized from methylmagnesium iodide {sup 14}C with a 48 per cent overall yield. Cholesterol is purified by chromatography on alumina. The various intermediates of the synthesis are characterized by thin-layer chromatography according to Stahl. (authors) [French] Le cholesterol {sup 14}C-26 est synthetise a partir d'iodure de methyl magnesium {sup 14}C, avec un rendement de 48 pour cent par rapport a l'iodure de methyl {sup 14}C mis en jeu. Le cholesterol est purifie par chromatographie sur alumine. Les intermediaires de la synthese sont caracterises par chromatographie en couche mince, selon Stahl. (auteurs)

  6. Characteristics of human hypo- and hyperresponders to dietary cholesterol.

    Science.gov (United States)

    Katan, M B; Beynen, A C

    1987-03-01

    The characteristics of people whose serum cholesterol level is unusually susceptible to consumption of cholesterol were investigated. Thirty-two volunteers from the general population of Wageningen, the Netherlands, each participated in three controlled dietary trials in 1982. A low-cholesterol diet was fed during the first half and a high-cholesterol diet during the second half of each trial, and the change (response) of serum cholesterol was measured. The responses in the three trials were averaged to give each subject's mean responsiveness. Fecal excretion of cholesterol and its metabolites were measured in the second trial, and body cholesterol synthesis was calculated. Responsiveness showed a positive correlation with serum high density lipoprotein2 (HDL2) cholesterol (r = 0.41, p less than 0.05) and with serum total cholesterol level on a high-cholesterol diet (r = 0.31, p = 0.09). A negative relation was found with habitual cholesterol consumption (r = -0.62, p less than 0.01), with body mass index (r = -0.50, p less than 0.01), and with the rate of endogenous cholesterol synthesis (r = -0.40, p less than 0.05), but not with the reaction of endogenous cholesterol synthesis rate to an increased intake of cholesterol. No relation was found with age, sex, total caloric needs, or the ratio of primary to secondary fecal steroids. Upon multiple regression analysis, only habitual cholesterol intake and serum total and HDL2 cholesterol levels contributed significantly to the explanation of variance in responsiveness. Thus, a low habitual cholesterol intake, a high serum HDL2 cholesterol level, or a low body weight do not make one less susceptible to dietary cholesterol-induced hypercholesterolemia.

  7. National Cholesterol Education Month

    Centers for Disease Control (CDC) Podcasts

    2009-09-01

    Do you know your cholesterol numbers? Your doctor can do a simple test to check your cholesterol levels and help you make choices that lower your risk for heart disease and stroke.  Created: 9/1/2009 by National Center for Chronic Disease Prevention and Health Promotion (NCCDPHP).   Date Released: 9/9/2009.

  8. Communication: Orientational self-ordering of spin-labeled cholesterol analogs in lipid bilayers in diluted conditions

    Energy Technology Data Exchange (ETDEWEB)

    Kardash, Maria E.; Dzuba, Sergei A., E-mail: dzuba@kinetics.nsc.ru [Voevodsky Institute of Chemical Kinetics and Combustion, 630090 Novosibirsk, Russia, and Novosibirsk State University, 630090 Novosibirsk (Russian Federation)

    2014-12-07

    Lipid-cholesterol interactions are responsible for different properties of biological membranes including those determining formation in the membrane of spatial inhomogeneities (lipid rafts). To get new information on these interactions, electron spin echo (ESE) spectroscopy, which is a pulsed version of electron paramagnetic resonance (EPR), was applied to study 3β-doxyl-5α-cholestane (DCh), a spin-labeled analog of cholesterol, in phospholipid bilayer consisted of equimolecular mixture of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine and 1,2-dioleoyl-sn-glycero-3-phosphocholine. DCh concentration in the bilayer was between 0.1 mol.% and 4 mol.%. For comparison, a reference system containing a spin-labeled 5-doxyl-stearic acid (5-DSA) instead of DCh was studied as well. The effects of “instantaneous diffusion” in ESE decay and in echo-detected (ED) EPR spectra were explored for both systems. The reference system showed good agreement with the theoretical prediction for the model of spin labels of randomly distributed orientations, but the DCh system demonstrated remarkably smaller effects. The results were explained by assuming that neighboring DCh molecules are oriented in a correlative way. However, this correlation does not imply the formation of clusters of cholesterol molecules, because conventional continuous wave EPR spectra did not show the typical broadening due to aggregation of spin labels and the observed ESE decay was not faster than in the reference system. So the obtained data evidence that cholesterol molecules at low concentrations in biological membranes can interact via large distances of several nanometers which results in their orientational self-ordering.

  9. Phytosterol glycosides reduce cholesterol absorption in humans.

    Science.gov (United States)

    Lin, Xiaobo; Ma, Lina; Racette, Susan B; Anderson Spearie, Catherine L; Ostlund, Richard E

    2009-04-01

    Dietary phytosterols inhibit intestinal cholesterol absorption and regulate whole body cholesterol excretion and balance. However, they are biochemically heterogeneous and a portion is glycosylated in some foods with unknown effects on biological activity. We tested the hypothesis that phytosterol glycosides reduce cholesterol absorption in humans. Phytosterol glycosides were extracted and purified from soy lecithin in a novel two-step process. Cholesterol absorption was measured in a series of three single-meal tests given at intervals of 2 wk to each of 11 healthy subjects. In a randomized crossover design, participants received approximately 300 mg of added phytosterols in the form of phytosterol glycosides or phytosterol esters, or placebo in a test breakfast also containing 30 mg cholesterol-d7. Cholesterol absorption was estimated by mass spectrometry of plasma cholesterol-d7 enrichment 4-5 days after each test. Compared with the placebo test, phytosterol glycosides reduced cholesterol absorption by 37.6+/-4.8% (Pphytosterol esters 30.6+/-3.9% (P=0.0001). These results suggest that natural phytosterol glycosides purified from lecithin are bioactive in humans and should be included in methods of phytosterol analysis and tables of food phytosterol content.

  10. Topical cholesterol in clofazimine induced ichthyosis

    Directory of Open Access Journals (Sweden)

    Pandey S

    1994-01-01

    Full Text Available Topical application of 10% cholesterol in petrolatum significantly (P< 0.05 controlled the development of ichthyosis in 62 patients taking 100 mg clofazimine daily for a period of 3 months. However, topical cholesterol application did not affect the lowering of serum cholesterol induced by oral clofazimine. Probable mechanism of action is being discussed.

  11. Cholesterol depletion of enterocytes. Effect on the Golgi complex and apical membrane trafficking

    DEFF Research Database (Denmark)

    Hansen, Gert Helge; Niels-Christiansen, L L; Thorsen, Evy

    2000-01-01

    Intestinal brush border enzymes, including aminopeptidase N and sucrase-isomaltase, are associated with "rafts" (membrane microdomains rich in cholesterol and sphingoglycolipids). To assess the functional role of rafts in the present work, we studied the effect of cholesterol depletion on apical......, the rates of the Golgi-associated complex glycosylation and association with rafts of newly synthesized aminopeptidase N were reduced, and less of the enzyme had reached the brush border membrane after 2 h of labeling. In contrast, the basolateral Na(+)/K(+)-ATPase was neither missorted nor raft......-associated. Our results implicate the Golgi complex/trans-Golgi network in raft formation and suggest a close relationship between this event and apical membrane trafficking....

  12. Phytosterol glycosides reduce cholesterol absorption in humans

    OpenAIRE

    Lin, Xiaobo; Ma, Lina; Racette, Susan B.; Anderson Spearie, Catherine L.; Ostlund, Richard E.

    2009-01-01

    Dietary phytosterols inhibit intestinal cholesterol absorption and regulate whole body cholesterol excretion and balance. However, they are biochemically heterogeneous and a portion is glycosylated in some foods with unknown effects on biological activity. We tested the hypothesis that phytosterol glycosides reduce cholesterol absorption in humans. Phytosterol glycosides were extracted and purified from soy lecithin in a novel two-step process. Cholesterol absorption was measured in a series ...

  13. Analysis of Cholesterol Trafficking with Fluorescent Probes

    DEFF Research Database (Denmark)

    Maxfield, Frederick R.; Wustner, Daniel

    2012-01-01

    Cholesterol plays an important role in determining the biophysical properties of biological membranes, and its concentration is tightly controlled by homeostatic processes. The intracellular transport of cholesterol among organelles is a key part of the homeostatic mechanism, but sterol transport...... that can bind to cholesterol to reveal its distribution in cells. We also discuss the use of intrinsically fluorescent sterols that closely mimic cholesterol, as well as some minimally modified fluorophore-labeled sterols. Methods for imaging these sterols by conventional fluorescence microscopy...... and by multiphoton microscopy are described. Some label-free methods for imaging cholesterol itself are also discussed briefly....

  14. LCAT, HDL Cholesterol and Ischemic Cardiovascular Disease: A Mendelian Randomization Study of HDL Cholesterol in 54,500 Individuals

    DEFF Research Database (Denmark)

    Haase, Christiane L; Tybjærg-Hansen, Anne; Ali Qayyum, Abbas

    2012-01-01

    , S208T (rs4986970, allele frequency 4%), associated with HDL cholesterol levels in both the CCHS and the CGPS was used to study causality of HDL cholesterol using instrumental variable analysis.Results:Epidemiologically, in the CCHS, a 13% (0.21 mmol/liter) decrease in plasma HDL cholesterol levels...... was associated with an 18% increase in risk of MI. S208T associated with a 13% (0.21 mmol/liter) decrease in HDL cholesterol levels but not with increased risk of MI or other ischemic end points. The causal odds ratio for MI for a 50% reduction in plasma HDL cholesterol due to S208T genotype in both studies......Background:Epidemiologically, high-density lipoprotein (HDL) cholesterol levels associate inversely with risk of ischemic cardiovascular disease. Whether this is a causal relation is unclear.Methods:We studied 10,281 participants in the Copenhagen City Heart Study (CCHS) and 50,523 participants...

  15. The effects of cholesterol on learning and memory.

    Science.gov (United States)

    Schreurs, Bernard G

    2010-07-01

    Cholesterol is vital to normal brain function including learning and memory but that involvement is as complex as the synthesis, metabolism and excretion of cholesterol itself. Dietary cholesterol influences learning tasks from water maze to fear conditioning even though cholesterol does not cross the blood brain barrier. Excess cholesterol has many consequences including peripheral pathology that can signal brain via cholesterol metabolites, pro-inflammatory mediators and antioxidant processes. Manipulations of cholesterol within the central nervous system through genetic, pharmacological, or metabolic means circumvent the blood brain barrier and affect learning and memory but often in animals already otherwise compromised. The human literature is no less complex. Cholesterol reduction using statins improves memory in some cases but not others. There is also controversy over statin use to alleviate memory problems in Alzheimer's disease. Correlations of cholesterol and cognitive function are mixed and association studies find some genetic polymorphisms are related to cognitive function but others are not. In sum, the field is in flux with a number of seemingly contradictory results and many complexities. Nevertheless, understanding cholesterol effects on learning and memory is too important to ignore.

  16. What Are High Blood Cholesterol and Triglycerides?

    Science.gov (United States)

    ... Reduction Cholesterol What Are High Blood Cholesterol and Triglycerides? Cholesterol travels to the body’s cells through the ... doctor about medicines that can help. What are triglycerides? Triglycerides are the most common type of fat ...

  17. Photoaffinity labeling with cholesterol analogues precisely maps a cholesterol-binding site in voltage-dependent anion channel-1.

    Science.gov (United States)

    Budelier, Melissa M; Cheng, Wayland W L; Bergdoll, Lucie; Chen, Zi-Wei; Janetka, James W; Abramson, Jeff; Krishnan, Kathiresan; Mydock-McGrane, Laurel; Covey, Douglas F; Whitelegge, Julian P; Evers, Alex S

    2017-06-02

    Voltage-dependent anion channel-1 (VDAC1) is a highly regulated β-barrel membrane protein that mediates transport of ions and metabolites between the mitochondria and cytosol of the cell. VDAC1 co-purifies with cholesterol and is functionally regulated by cholesterol, among other endogenous lipids. Molecular modeling studies based on NMR observations have suggested five cholesterol-binding sites in VDAC1, but direct experimental evidence for these sites is lacking. Here, to determine the sites of cholesterol binding, we photolabeled purified mouse VDAC1 (mVDAC1) with photoactivatable cholesterol analogues and analyzed the photolabeled sites with both top-down mass spectrometry (MS), and bottom-up MS paired with a clickable, stable isotope-labeled tag, FLI -tag. Using cholesterol analogues with a diazirine in either the 7 position of the steroid ring (LKM38) or the aliphatic tail (KK174), we mapped a binding pocket in mVDAC1 localized to Thr 83 and Glu 73 , respectively. When Glu 73 was mutated to a glutamine, KK174 no longer photolabeled this residue, but instead labeled the nearby Tyr 62 within this same binding pocket. The combination of analytical strategies employed in this work permits detailed molecular mapping of a cholesterol-binding site in a protein, including an orientation of the sterol within the site. Our work raises the interesting possibility that cholesterol-mediated regulation of VDAC1 may be facilitated through a specific binding site at the functionally important Glu 73 residue. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  18. Ocimum basilicum ethanolic extract decreases cholesterol synthesis and lipid accumulation in human macrophages.

    Science.gov (United States)

    Bravo, Elena; Amrani, Souliman; Aziz, Mohammed; Harnafi, Hicham; Napolitano, Mariarosaria

    2008-12-01

    Macrophage lipid accumulation induced by low density lipoproteins (LDL) plays a pivotal role in atherosclerotic plaque development. Previous work showed that Ocimum basilicum extract, used as hypocholesterolemic agent by traditional medicine in Morocco, has hypolipidemic activity in rat acute hyperlipimidemia. This study investigated the effects of ethanolic extract of O. basilicum on lipid accumulation in human macrophages. As modification of LDL increase atherogenicity of the particles we evaluated the effects of the extract on LDL oxidation. The extract caused a dose-related increase of LDL-resistance to Cu(2+)-induced oxidation. Furthermore, at the dose of 60 microg/ml, significantly decreases the accumulation of macrophage lipid droplets induced by modified LDL evaluated as by red-oil staining. Cholesterol esterification and triacylglycerol synthesis in the cells were not affected. Macrophage treatment with 60 microg/ml, but not 20 microg/ml, of the extract reduced newly synthesized unesterified cholesterol by about 60% and decreased scavenger receptors activity by about 20-30%, evaluated by the internalization of cholesterol carried by [(3)H]CE-aggregated-LDL. The results suggest that O. basilicum ethanolic extract has the capability to reduce foam cell formation through the reduction of cholesterol synthesis and the modulation of the activity of surface scavenger receptors.

  19. Intestinal SR-BI does not impact cholesterol absorption or transintestinal cholesterol efflux in mice

    NARCIS (Netherlands)

    Bura, Kanwardeep S.; Lord, Caleb; Marshall, Stephanie; McDaniel, Allison; Thomas, Gwyn; Warrier, Manya; Zhang, Jun; Davis, Matthew A.; Sawyer, Janet K.; Shah, Ramesh; Wilson, Martha D.; Dikkers, Arne; Tietge, Uwe J. F.; Collet, Xavier; Rudel, Lawrence L.; Temel, Ryan E.; Brown, J. Mark

    Reverse cholesterol transport (RCT) can proceed through the classic hepatobiliary route or through the non-biliary transintestinal cholesterol efflux (TICE) pathway. Scavenger receptor class B type I (SR-BI) plays a critical role in the classic hepatobiliary route of RCT. However, the role of SR-BI

  20. Cholesterol Perturbs Lipid Bilayers Nonuniversally

    International Nuclear Information System (INIS)

    Pan Jianjun; Mills, Thalia T.; Tristram-Nagle, Stephanie; Nagle, John F.

    2008-01-01

    Cholesterol is well known to modulate the physical properties of biomembranes. Using modern x-ray scattering methods, we have studied the effects of cholesterol on the bending modulus K C , the thickness D HH , and the orientational order parameter S xray of lipid bilayers. We find that the effects are different for at least three classes of phospholipids characterized by different numbers of saturated hydrocarbon chains. Most strikingly, cholesterol strongly increases K C when both chains of the phospholipid are fully saturated but not at all when there are two monounsaturated chains

  1. Dietary cholesterol, heart disease risk and cognitive dissonance.

    Science.gov (United States)

    McNamara, Donald J

    2014-05-01

    In the 1960s, the thesis that dietary cholesterol contributes to blood cholesterol and heart disease risk was a rational conclusion based on the available science at that time. Fifty years later the research evidence no longer supports this hypothesis yet changing the dietary recommendation to limit dietary cholesterol has been a slow and at times contentious process. The preponderance of the clinical and epidemiological data accumulated since the original dietary cholesterol restrictions were formulated indicate that: (1) dietary cholesterol has a small effect on the plasma cholesterol levels with an increase in the cholesterol content of the LDL particle and an increase in HDL cholesterol, with little effect on the LDL:HDL ratio, a significant indicator of heart disease risk, and (2) the lack of a significant relationship between cholesterol intake and heart disease incidence reported from numerous epidemiological surveys. Over the last decade, many countries and health promotion groups have modified their dietary recommendations to reflect the current evidence and to address a now recognised negative consequence of ineffective dietary cholesterol restrictions (such as inadequate choline intake). In contrast, health promotion groups in some countries appear to suffer from cognitive dissonance and continue to promote an outdated and potentially hazardous dietary recommendation based on an invalidated hypothesis. This review evaluates the evidence for and against dietary cholesterol restrictions and the potential consequences of such restrictions.

  2. Immobilization of cholesterol esterase and cholesterol oxidase onto sol-gel films for application to cholesterol biosensor

    International Nuclear Information System (INIS)

    Singh, Suman; Singhal, Rahul; Malhotra, B.D.

    2007-01-01

    Cholesterol oxidase (ChOx) and cholesterol esterase (ChEt) have been covalently immobilized onto tetraethylorthosilicate (TEOS) sol-gel films. The tetraethylorthosilicate sol-gel/ChEt/ChOx enzyme films thus prepared have been characterized using scanning electron microscopic (SEM), UV-vis spectroscopic, Fourier-transform-infrared (FTIR) spectroscopic and amperometric techniques, respectively. The results of photometric measurements carried out on tetraethylorthosilicate sol-gel/ChEt/ChOx reveal thermal stability up to 55 deg. C, response time as 180 s, linearity up to 780 mg dL -1 (12 mM), shelf life of 1 month, detection limit of 12 mg dL -1 and sensitivity as 5.4 x 10 -5 Abs. mg -1 dL -1

  3. The molecular-scale arrangement and mechanical strength of phospholipid/cholesterol mixed bilayers investigated by frequency modulation atomic force microscopy in liquid

    Energy Technology Data Exchange (ETDEWEB)

    Asakawa, Hitoshi; Fukuma, Takeshi [Frontier Science Organization, Kanazawa University, Kakuma-machi, 920-1192 Kanazawa (Japan)], E-mail: hi_asa@staff.kanazawa-u.ac.jp, E-mail: fukuma@staff.kanazawa-u.ac.jp

    2009-07-01

    Cholesterols play key roles in controlling molecular fluidity in a biological membrane, yet little is known about their molecular-scale arrangements in real space. In this study, we have directly imaged lipid-cholesterol complexes in a model biological membrane consisting of dipalmitoylphosphatidylcholine (DPPC) and cholesterols by frequency modulation atomic force microscopy (FM-AFM) in phosphate buffer solution. FM-AFM images of a DPPC/cholesterol bilayer in the liquid-ordered phase showed higher energy dissipation values compared to those measured on a nanoscale DPPC domain in the gel phase, reflecting the increased molecular fluidity due to the insertion of cholesterols. Molecular-resolution FM-AFM images of a DPPC/cholesterol bilayer revealed the existence of a rhombic molecular arrangement (lattice constants: a = 0.46 nm, b = 0.71 nm) consisting of alternating rows of DPPC and cholesterols as well as the increased defect density and reduced molecular ordering. The mechanical strength of a DPPC/cholesterol bilayer was quantitatively evaluated by measuring a loading force required to penetrate the membrane with an AFM tip. The result revealed the significant decrease of mechanical strength upon insertion of cholesterols. Based on the molecular-scale arrangement found in this study, we propose a model to explain the reduced mechanical strength in relation to the formation of lipid-ion networks.

  4. The molecular-scale arrangement and mechanical strength of phospholipid/cholesterol mixed bilayers investigated by frequency modulation atomic force microscopy in liquid

    International Nuclear Information System (INIS)

    Asakawa, Hitoshi; Fukuma, Takeshi

    2009-01-01

    Cholesterols play key roles in controlling molecular fluidity in a biological membrane, yet little is known about their molecular-scale arrangements in real space. In this study, we have directly imaged lipid-cholesterol complexes in a model biological membrane consisting of dipalmitoylphosphatidylcholine (DPPC) and cholesterols by frequency modulation atomic force microscopy (FM-AFM) in phosphate buffer solution. FM-AFM images of a DPPC/cholesterol bilayer in the liquid-ordered phase showed higher energy dissipation values compared to those measured on a nanoscale DPPC domain in the gel phase, reflecting the increased molecular fluidity due to the insertion of cholesterols. Molecular-resolution FM-AFM images of a DPPC/cholesterol bilayer revealed the existence of a rhombic molecular arrangement (lattice constants: a = 0.46 nm, b = 0.71 nm) consisting of alternating rows of DPPC and cholesterols as well as the increased defect density and reduced molecular ordering. The mechanical strength of a DPPC/cholesterol bilayer was quantitatively evaluated by measuring a loading force required to penetrate the membrane with an AFM tip. The result revealed the significant decrease of mechanical strength upon insertion of cholesterols. Based on the molecular-scale arrangement found in this study, we propose a model to explain the reduced mechanical strength in relation to the formation of lipid-ion networks.

  5. CO2 Plant Extracts Reduce Cholesterol Oxidation in Fish Patties during Cooking and Storage.

    Science.gov (United States)

    Tarvainen, Marko; Quirin, Karl-Werner; Kallio, Heikki; Yang, Baoru

    2016-12-28

    Cholesterol oxidation products (COPs) in foods may pose risks for human health. Suitable antioxidants can reduce the formation of COPs in industrial products. Consumer awareness of food additives has brought a need for more natural alternatives. This is the first study on the effects of supercritical CO 2 extracts of rosemary, oregano, and an antimicrobial blend of seven herbs, tested at two levels (1 and 3 g/kg fish), against cholesterol oxidation in patties made of a widely consumed fish species, Atlantic salmon (Salmo salar), during baking and storage. Cholesterol oxidation was reduced by the extracts as indicated by lowered levels of 7α-hydroxycholesterol, 7β-hydroxycholesterol, and 7-ketocholesterol, which were quantified by GC-MS. The total amount of COPs was smaller in all of the cooked samples containing the plant extracts (<1 μg/g extracted fat) than in the cooked control (14 μg/g). Furthermore, the plant extracts exhibited protective effects also during cold storage for up to 14 days.

  6. The Role of Macrophage Lipophagy in Reverse Cholesterol Transport

    Directory of Open Access Journals (Sweden)

    Se-Jin Jeong

    2017-03-01

    Full Text Available Macrophage cholesterol efflux is a central step in reverse cholesterol transport, which helps to maintain cholesterol homeostasis and to reduce atherosclerosis. Lipophagy has recently been identified as a new step in cholesterol ester hydrolysis that regulates cholesterol efflux, since it mobilizes cholesterol from lipid droplets of macrophages via autophagy and lysosomes. In this review, we briefly discuss recent advances regarding the mechanisms of the cholesterol efflux pathway in macrophage foam cells, and present lipophagy as a therapeutic target in the treatment of atherosclerosis.

  7. Cholesterol-induced conformational changes in the sterol-sensing domain of the Scap protein suggest feedback mechanism to control cholesterol synthesis.

    Science.gov (United States)

    Gao, Yansong; Zhou, Yulian; Goldstein, Joseph L; Brown, Michael S; Radhakrishnan, Arun

    2017-05-26

    Scap is a polytopic protein of endoplasmic reticulum (ER) membranes that transports sterol regulatory element-binding proteins to the Golgi complex for proteolytic activation. Cholesterol accumulation in ER membranes prevents Scap transport and decreases cholesterol synthesis. Previously, we provided evidence that cholesterol inhibition is initiated when cholesterol binds to loop 1 of Scap, which projects into the ER lumen. Within cells, this binding causes loop 1 to dissociate from loop 7, another luminal Scap loop. However, we have been unable to demonstrate this dissociation when we added cholesterol to isolated complexes of loops 1 and 7. We therefore speculated that the dissociation requires a conformational change in the intervening polytopic sequence separating loops 1 and 7. Here we demonstrate such a change using a protease protection assay in sealed membrane vesicles. In the absence of cholesterol, trypsin or proteinase K cleaved cytosolic loop 4, generating a protected fragment that we visualized with a monoclonal antibody against loop 1. When cholesterol was added to these membranes, cleavage in loop 4 was abolished. Because loop 4 is part of the so-called sterol-sensing domain separating loops 1 and 7, these results support the hypothesis that cholesterol binding to loop 1 alters the conformation of the sterol-sensing domain. They also suggest that this conformational change helps transmit the cholesterol signal from loop 1 to loop 7, thereby allowing separation of the loops and facilitating the feedback inhibition of cholesterol synthesis. These insights suggest a new structural model for cholesterol-mediated regulation of Scap activity. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. Effect of incorporating cholesterol into DDA:TDB liposomal adjuvants on bilayer properties, biodistribution, and immune responses.

    Science.gov (United States)

    Kaur, Randip; Henriksen-Lacey, Malou; Wilkhu, Jitinder; Devitt, Andrew; Christensen, Dennis; Perrie, Yvonne

    2014-01-06

    Cholesterol is an abundant component of mammalian cell membranes and has been extensively studied as an artificial membrane stabilizer in a wide range of phospholipid liposome systems. In this study, the aim was to investigate the role of cholesterol in cationic liposomal adjuvant system based on dimethyldioctadecylammonium (DDA) and trehalose 6,6'-dibehenate (TDB) which has been shown as a strong adjuvant system for vaccines against a wide range of diseases. Packaging of cholesterol within DDA:TDB liposomes was investigated using differential scanning calorimetery and surface pressure-area isotherms of lipid monolayers; incorporation of cholesterol into liposomal membranes promoted the formation of a liquid-condensed monolayer and removed the main phase transition temperature of the system, resulting in an increased bilayer fluidity and reduced antigen retention in vitro. In vivo biodistribution studies found that this increase in membrane fluidity did not alter deposition of liposomes and antigen at the site of injection. In terms of immune responses, early (12 days after immunization) IgG responses were reduced by inclusion of cholesterol; thereafter there were no differences in antibody (IgG, IgG1, IgG2b) responses promoted by DDA:TDB liposomes with and without cholesterol. However, significantly higher levels of IFN-gamma were induced by DDA:TDB liposomes, and liposome uptake by macrophages in vitro was also shown to be higher for DDA:TDB liposomes compared to their cholesterol-containing counterparts, suggesting that small changes in bilayer mechanics can impact both cellular interactions and immune responses.

  9. Cholesterol metabolism in blood cells of irradiated rats

    International Nuclear Information System (INIS)

    Novoselova, E.G.; Kulagina, T.P.; Potekhina, N.I.

    1985-01-01

    Cholesterol metabolism in blood erythrocytes and lymphocytes of irradiated rats has been investigated. It has been found that at all terms and doses of irradiation, a suppression of the synthesis of erythrocyte cholesterol is observed. The increase of cholesterol quantiy in erythrocytes upon total gamma irradiation in the 10 Gr dose possibly is the result of growth of cholesterol transfer from plasma into erythrocyte cells. The study of the cholesterol synthesis in suspension of lymphocytes elminated from peripheral blood of control and irradiated rats has shown that at irradiation doses of 4 and 10 Gr in an hour acivation of cholesterol synthesis in vitro takes places

  10. PEG-lipid micelles enable cholesterol efflux in Niemann-Pick Type C1 disease-based lysosomal storage disorder

    Science.gov (United States)

    Brown, Anna; Patel, Siddharth; Ward, Carl; Lorenz, Anna; Ortiz, Mauren; Duross, Allison; Wieghardt, Fabian; Esch, Amanda; Otten, Elsje G.; Heiser, Laura M.; Korolchuk, Viktor I.; Sun, Conroy; Sarkar, Sovan; Sahay, Gaurav

    2016-08-01

    2-Hydroxy-propyl-β-cyclodextrin (HPβCD), a cholesterol scavenger, is currently undergoing Phase 2b/3 clinical trial for treatment of Niemann Pick Type C-1 (NPC1), a fatal neurodegenerative disorder that stems from abnormal cholesterol accumulation in the endo/lysosomes. Unfortunately, the extremely high doses of HPβCD required to prevent progressive neurodegeneration exacerbates ototoxicity, pulmonary toxicity and autophagy-based cellular defects. We present unexpected evidence that a poly (ethylene glycol) (PEG)-lipid conjugate enables cholesterol clearance from endo/lysosomes of Npc1 mutant (Npc1-/-) cells. Herein, we show that distearyl-phosphatidylethanolamine-PEG (DSPE-PEG), which forms 12-nm micelles above the critical micelle concentration, accumulates heavily inside cholesterol-rich late endosomes in Npc1-/- cells. This potentially results in cholesterol solubilization and leakage from lysosomes. High-throughput screening revealed that DSPE-PEG, in combination with HPβCD, acts synergistically to efflux cholesterol without significantly aggravating autophagy defects. These well-known excipients can be used as admixtures to treat NPC1 disorder. Increasing PEG chain lengths from 350 Da-30 kDa in DSPE-PEG micelles, or increasing DSPE-PEG content in an array of liposomes packaged with HPβCD, improved cholesterol egress, while Pluronic block copolymers capable of micelle formation showed slight effects at high concentrations. We postulate that PEG-lipid based nanocarriers can serve as bioactive drug delivery systems for effective treatment of lysosomal storage disorders.

  11. PEG-lipid micelles enable cholesterol efflux in Niemann-Pick Type C1 disease-based lysosomal storage disorder

    Science.gov (United States)

    Brown, Anna; Patel, Siddharth; Ward, Carl; Lorenz, Anna; Ortiz, Mauren; DuRoss, Allison; Wieghardt, Fabian; Esch, Amanda; Otten, Elsje G.; Heiser, Laura M.; Korolchuk, Viktor I.; Sun, Conroy; Sarkar, Sovan; Sahay, Gaurav

    2016-01-01

    2-Hydroxy-propyl-β-cyclodextrin (HPβCD), a cholesterol scavenger, is currently undergoing Phase 2b/3 clinical trial for treatment of Niemann Pick Type C-1 (NPC1), a fatal neurodegenerative disorder that stems from abnormal cholesterol accumulation in the endo/lysosomes. Unfortunately, the extremely high doses of HPβCD required to prevent progressive neurodegeneration exacerbates ototoxicity, pulmonary toxicity and autophagy-based cellular defects. We present unexpected evidence that a poly (ethylene glycol) (PEG)-lipid conjugate enables cholesterol clearance from endo/lysosomes of Npc1 mutant (Npc1−/−) cells. Herein, we show that distearyl-phosphatidylethanolamine-PEG (DSPE-PEG), which forms 12-nm micelles above the critical micelle concentration, accumulates heavily inside cholesterol-rich late endosomes in Npc1−/− cells. This potentially results in cholesterol solubilization and leakage from lysosomes. High-throughput screening revealed that DSPE-PEG, in combination with HPβCD, acts synergistically to efflux cholesterol without significantly aggravating autophagy defects. These well-known excipients can be used as admixtures to treat NPC1 disorder. Increasing PEG chain lengths from 350 Da-30 kDa in DSPE-PEG micelles, or increasing DSPE-PEG content in an array of liposomes packaged with HPβCD, improved cholesterol egress, while Pluronic block copolymers capable of micelle formation showed slight effects at high concentrations. We postulate that PEG-lipid based nanocarriers can serve as bioactive drug delivery systems for effective treatment of lysosomal storage disorders. PMID:27572704

  12. Serum starvation of ARPE-19 changes the cellular distribution of cholesterol and Fibulin3 in patterns reminiscent of age-related macular degeneration.

    Science.gov (United States)

    Rajapakse, Dinusha; Peterson, Katherine; Mishra, Sanghamitra; Wistow, Graeme

    2017-12-15

    Retinal pigment epithelium (RPE) has been implicated as key source of cholesterol-rich deposits at Bruch's membrane (BrM) and in drusen in aging human eye. We have shown that serum-deprivation of confluent RPE cells is associated with upregulation of cholesterol synthesis and accumulation of unesterified cholesterol (UC). Here we investigate the cellular processes involved in this response. We compared the distribution and localization of UC and esterified cholesterol (EC); the age-related macular degeneration (AMD) associated EFEMP1/Fibulin3 (Fib3); and levels of acyl-coenzyme A (CoA): cholesterol acyltransferases (ACAT) ACAT1, ACAT2 and Apolipoprotein B (ApoB) in ARPE-19 cells cultured in serum-supplemented and serum-free media. The results were compared with distributions of these lipids and proteins in human donor eyes with AMD. Serum deprivation of ARPE-19 was associated with increased formation of FM dye-positive membrane vesicles, many of which co-labeled for UC. Additionally, UC colocalized with Fib3 in distinct granules. By day 5, serum-deprived cells grown on transwells secreted Fib3 basally into the matrix. While mRNA and protein levels of ACTA1 were constant over several days of serum-deprivation, ACAT2 levels increased significantly after serum-deprivation, suggesting increased formation of EC. The lower levels of intracellular EC observed under serum-deprivation were associated with increased formation and secretion of ApoB. The responses to serum-deprivation in RPE-derived cells: accumulation and secretion of lipids, lipoproteins, and Fib3 are very similar to patterns seen in human donor eyes with AMD and suggest that this model mimics processes relevant to disease progression. Published by Elsevier Inc.

  13. Immobilization of cholesterol esterase and cholesterol oxidase onto sol-gel films for application to cholesterol biosensor

    Energy Technology Data Exchange (ETDEWEB)

    Singh, Suman [Central Mechanical Engineering Research Institute, G. Avenue, Durgapur 713209, West Bengal (India); Singhal, Rahul [Biomolecular Electronics and Conducting Polymer Research Group, National Physical Laboratory, Dr. K.S. Krishnan Marg, New Delhi 110012 (India); Malhotra, B.D. [Biomolecular Electronics and Conducting Polymer Research Group, National Physical Laboratory, Dr. K.S. Krishnan Marg, New Delhi 110012 (India)]. E-mail: bansi.malhotra@gmail.com

    2007-01-23

    Cholesterol oxidase (ChOx) and cholesterol esterase (ChEt) have been covalently immobilized onto tetraethylorthosilicate (TEOS) sol-gel films. The tetraethylorthosilicate sol-gel/ChEt/ChOx enzyme films thus prepared have been characterized using scanning electron microscopic (SEM), UV-vis spectroscopic, Fourier-transform-infrared (FTIR) spectroscopic and amperometric techniques, respectively. The results of photometric measurements carried out on tetraethylorthosilicate sol-gel/ChEt/ChOx reveal thermal stability up to 55 deg. C, response time as 180 s, linearity up to 780 mg dL{sup -1} (12 mM), shelf life of 1 month, detection limit of 12 mg dL{sup -1} and sensitivity as 5.4 x 10{sup -5} Abs. mg{sup -1} dL{sup -1}.

  14. Interaction of pathogens with host cholesterol metabolism.

    Science.gov (United States)

    Sviridov, Dmitri; Bukrinsky, Michael

    2014-10-01

    Pathogens of different taxa, from prions to protozoa, target cellular cholesterol metabolism to advance their own development and to impair host immune responses, but also causing metabolic complications, for example, atherosclerosis. This review describes recent findings of how pathogens do it. A common theme in interaction between pathogens and host cholesterol metabolism is pathogens targeting lipid rafts of the host plasma membrane. Many intracellular pathogens use rafts as an entry gate, taking advantage of the endocytic machinery and high abundance of outward-looking molecules that can be used as receptors. At the same time, disruption of the rafts' functional capacity, achieved by the pathogens through a number of various means, impairs the ability of the host to generate immune response, thus helping pathogen to thrive. Pathogens cannot synthesize cholesterol, and salvaging host cholesterol helps pathogens build advanced cholesterol-containing membranes and assembly platforms. Impact on cholesterol metabolism is not limited to the infected cells; proteins and microRNAs secreted by infected cells affect lipid metabolism systemically. Given an essential role that host cholesterol metabolism plays in pathogen development, targeting this interaction may be a viable strategy to fight infections, as well as metabolic complications of the infections.

  15. Annexins as organizers of cholesterol- and sphingomyelin-enriched membrane microdomains in Niemann-Pick type C disease.

    Science.gov (United States)

    Domon, Magdalena; Nasir, Mehmet Nail; Matar, Gladys; Pikula, Slawomir; Besson, Françoise; Bandorowicz-Pikula, Joanna

    2012-06-01

    Growing evidence suggests that membrane microdomains enriched in cholesterol and sphingomyelin are sites for numerous cellular processes, including signaling, vesicular transport, interaction with pathogens, and viral infection, etc. Recently some members of the annexin family of conserved calcium and membrane-binding proteins have been recognized as cholesterol-interacting molecules and suggested to play a role in the formation, stabilization, and dynamics of membrane microdomains to affect membrane lateral organization and to attract other proteins and signaling molecules onto their territory. Furthermore, annexins were implicated in the interactions between cytosolic and membrane molecules, in the turnover and storage of cholesterol and in various signaling pathways. In this review, we focus on the mechanisms of interaction of annexins with lipid microdomains and the role of annexins in membrane microdomains dynamics including possible participation of the domain-associated forms of annexins in the etiology of human lysosomal storage disease called Niemann-Pick type C disease, related to the abnormal storage of cholesterol in the lysosome-like intracellular compartment. The involvement of annexins and cholesterol/sphingomyelin-enriched membrane microdomains in other pathologies including cardiac dysfunctions, neurodegenerative diseases, obesity, diabetes mellitus, and cancer is likely, but is not supported by substantial experimental observations, and therefore awaits further clarification.

  16. Membrane Cholesterol Modulates Superwarfarin Toxicity

    Energy Technology Data Exchange (ETDEWEB)

    Marangoni, M. Natalia; Martynowycz, Michael W.; Kuzmenko, Ivan; Braun, David; Polak, Paul E.; Weinberg, Guy; Rubinstein, Israel; Gidalevitz, David; Feinstein, Douglas L.

    2016-04-26

    Superwarfarins are modified analogs of warfarin with additional lipophilic aromatic rings, up to 100-fold greater potency, and longer biological half-lives. We hypothesized that increased hydrophobicity allowed interactions with amphiphilic membranes and modulation of biological responses. We find that superwarfarins brodifacoum and difenacoum increase lactate production and cell death in neuroblastoma cells. In contrast, neither causes changes in glioma cells that have higher cholesterol content. After choleterol depletion, lactate production was increased and cell viability was reduced. Drug-membrane interactions were examined by surface X-ray scattering using Langmuir monolayers of dipalmitoylphosphatidylcholine and/or cholesterol. Specular X-ray reflectivity data revealed that superwarfarins, but not warfarin, intercalate between dipalmitoylphosphatidylcholine molecules, whereas grazing incidence X-ray diffraction demonstrated changes in lateral crystalline order of the film. Neither agent showed significant interactions with monolayers containing >20% cholesterol. These findings demonstrate an affinity of superwarfarins to biomembranes and suggest that cellular responses to these agents are regulated by cholesterol content.

  17. The effects of phytosterols present in natural food matrices on cholesterol metabolism and LDL-cholesterol: a controlled feeding trial.

    Science.gov (United States)

    Lin, X; Racette, S B; Lefevre, M; Spearie, C A; Most, M; Ma, L; Ostlund, R E

    2010-12-01

    Extrinsic phytosterols supplemented to the diet reduce intestinal cholesterol absorption and plasma low-density lipoprotein (LDL)-cholesterol. However, little is known about their effects on cholesterol metabolism when given in native, unpurified form and in amounts achievable in the diet. The objective of this investigation was to test the hypothesis that intrinsic phytosterols present in unmodified foods alter whole-body cholesterol metabolism. In all, 20 out of 24 subjects completed a randomized, crossover feeding trial wherein all meals were provided by a metabolic kitchen. Each subject consumed two diets for 4 weeks each. The diets differed in phytosterol content (phytosterol-poor diet, 126 mg phytosterols/2000 kcal; phytosterol-abundant diet, 449 mg phytosterols/2000 kcal), but were otherwise matched for nutrient content. Cholesterol absorption and excretion were determined by gas chromatography/mass spectrometry after oral administration of stable isotopic tracers. The phytosterol-abundant diet resulted in lower cholesterol absorption (54.2±2.2% (95% confidence interval 50.5%, 57.9%) vs 73.2±1.3% (69.5%, 76.9%), Pphytosterol-poor diet. Plasma lathosterol/cholesterol ratio rose by 82% (from 0.71±0.11 (0.41, 0.96) to 1.29±0.14 μg/mg (0.98, 1.53), Pphytosterols at levels present in a healthy diet are biologically active and have large effects on whole-body cholesterol metabolism not reflected in circulating LDL. More work is needed to assess the effects of phytosterol-mediated fecal cholesterol excretion on coronary heart disease risk in humans.

  18. Status of non-HDL-cholesterol and LDL-cholesterol among subjects with and without metabolic syndrome.

    Science.gov (United States)

    Khan, Sikandar Hayat; Asif, Naveed; Ijaz, Aamir; Manzoor, Syed Mohsin; Niazi, Najumusaquib Khan; Fazal, Nadeem

    2018-04-01

    To to compare non-high-density lipoprotein and low-density lipoprotein cholesterol among subjects with or without metabolic syndrome, glycation status and nephropathic changes. The comparative cross-sectional study was carried out from Dec 21, 2015, to Nov 15, 2016, at the department of pathology and medicine PNS HAFEEZ and department of chemical pathology and clinical endocrinology (AFIP), and comprised patients of either gender visiting the out-patient department for routine screening. They were evaluated for anthropometric indices, blood pressure and sampled for lipid profile, fasting plasma glucose, glycated haemoglobin, insulin, and urine albumin-to-creatinine ratio. Subjects were segregated based upon presence (Group1) or absence (Group2) of metabolic syndrome based upon criteria of National Cholesterol Education Programme and the International Diabetes Federation. Differences in high and low density lipoprotein cholesterols were calculated between the groups. Of the 229 subjects, 120(52.4%) were women and 109(47.6%) were men. Overall, there were 107(46.7%) subjects in Group 1, and 122(53.3%) in Group 2. Non-high-density lipoprotein cholesterol was significantly different between subjects with and without metabolic syndrome as per both the study criteria (p<0.05 each). . Non-high-density lipoprotein cholesterol levels were higher in subjects with metabolic syndrome.

  19. Is ketogenic diet treatment hepatotoxic for children with intractable epilepsy?

    Science.gov (United States)

    Arslan, Nur; Guzel, Orkide; Kose, Engin; Yılmaz, Unsal; Kuyum, Pınar; Aksoy, Betül; Çalık, Tansel

    2016-12-01

    Long-term ketogenic diet (KD) treatment has been shown to induce liver steatosis and gallstone formation in some in vivo and clinical studies. The aim of this retrospective study was to evaluate the hepatic side effects of KD in epileptic children. A total of 141 patients (mean age: 7.1±4.1years [2-18 years], 45.4% girls), receiving KD at least one year for intractable epilepsy due to different diagnoses (congenital brain defects, GLUT-1 deficiency, West syndrome, tuberous sclerosis, hypoxic brain injury, etc.) were included in the study. Serum triglyceride, cholesterol, aminotransferase, bilirubin, protein and albumin levels and abdominal ultrasonography were recorded before and at 1, 3, 6, and 12 months following after diet initiation. The mean duration of KD was 15.9±4.3months. At one month of therapy, three patients had elevated alanine and aspartate aminotransferase levels. These patients were receiving ketogenic diet for Doose syndrome, idiopathic epilepsy and GLUT-1 deficiency. Hepatosteatosis was detected in three patients at 6 months of treatment. Two of these patients were treated with KD for the primary diagnosis of tuberous sclerosis and one for Landau Kleffner syndrome. Cholelithiasis was detected in two patients at 12 months of treatment. They were receiving treatment for West syndrome and hypoxic brain injury sequelae. Long-term ketogenic diet treatment stimulates liver parenchymal injury, hepatic steatosis and gallstone formation. Patients should be monitored by screening liver enzymes and abdominal ultrasonography in order to detect these side effects. Copyright © 2016 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.

  20. Manipulation of Host Cholesterol by Obligate Intracellular Bacteria

    Directory of Open Access Journals (Sweden)

    Dhritiman Samanta

    2017-05-01

    Full Text Available Cholesterol is a multifunctional lipid that plays important metabolic and structural roles in the eukaryotic cell. Despite having diverse lifestyles, the obligate intracellular bacterial pathogens Chlamydia, Coxiella, Anaplasma, Ehrlichia, and Rickettsia all target cholesterol during host cell colonization as a potential source of membrane, as well as a means to manipulate host cell signaling and trafficking. To promote host cell entry, these pathogens utilize cholesterol-rich microdomains known as lipid rafts, which serve as organizational and functional platforms for host signaling pathways involved in phagocytosis. Once a pathogen gains entrance to the intracellular space, it can manipulate host cholesterol trafficking pathways to access nutrient-rich vesicles or acquire membrane components for the bacteria or bacteria-containing vacuole. To acquire cholesterol, these pathogens specifically target host cholesterol metabolism, uptake, efflux, and storage. In this review, we examine the strategies obligate intracellular bacterial pathogens employ to manipulate cholesterol during host cell colonization. Understanding how obligate intracellular pathogens target and use host cholesterol provides critical insight into the host-pathogen relationship.

  1. [Phytosterols: another way to reduce LDL cholesterol levels].

    Science.gov (United States)

    Bitzur, Rafael; Cohen, Hofit; Kamari, Yehuda; Harats, Dror

    2013-12-01

    Phytosterols are sterols found naturally in various oils from plants. Phytosterols compete with cholesterol for a place in the mixed micelles, needed for cholesterol absorption by the small intestine. As a result, cholesterol absorption, either from food or from bile salts is lowered by about 50%, leading to a towering of about 10% of blood cholesterol level, despite an increase in hepatic cholesterol synthesis. This reduction is achieved when phytosterols are given both as monotherapy, and in addition to statin therapy. The average Western diet contains about 400-800 mg of phytosterols per day, while the dose needed for lowering the blood cholesterol level is about 2-3 grams per day. Therefore, for the purpose of reducing blood cholesterol, they should be given either as phytosterol-enriched food or as supplements. The reduction in the level of LDL-choLesterol achieved with phytosterols may reduce the risk of coronary disease by about 25%. Hence, the American Heart Association recommended the consumption of phytosterols, as part of a balanced diet, for towering blood cholesterol levels.

  2. Transport of cholesterol autoxidation products in rabbit lipoproteins

    International Nuclear Information System (INIS)

    Peng, Shi-Kaung; Phillips, G.A.; Xia, Guang-Zhi; Morin, R.J.

    1987-01-01

    Radiolabeled pure [4- 14 C] cholesterol was kept at 60 0 C under air to autoxidize for 5 weeks, after which approximately 12% cholesterol oxidation products were formed. The mixture, suspended in gelatin, was given to rabbits by gastric gavage. Rabbits were killed 4, 24 and 48 h after treatment. Cholesterol and its autoxidation products were separated by thin-layer chromatography into 5 fractions and radioactivities of each fraction were measured. Percentages of each fraction of cholesterol oxidation products and cholesterol in the original mixture before administration and in the rabbit sera after administration were similar, suggesting that the rates of absorption of cholesterol oxidation products are not significantly different from that of cholesterol. Lipoproteins were fractioned by ultracentrifugation into VLDL, LDL and HDL. Radioactivities of each fraction in lipoproteins separated by thin layer chromatography showed that fractions containing cholestane-3β, 5α, 6β-triol, 7α- and 7β-hydroxycholesterol and 7-ketocholesterol were more selectively transported in VLDL, whereas most of the 25-hydroxycholesterol was present in LDL. HDL contained only minute amounts of cholesterol oxidation products. 22 refs

  3. HDL cholesterol: atherosclerosis and beyond

    NARCIS (Netherlands)

    Bochem, A.E.

    2013-01-01

    Cardiovascular disease (CVD) is the leading cause of death in the Western world. Myocardial infarction and stroke are the result of a compromised blood flow which may result from cholesterol accumulation in the vessel wall due to high plasma levels of LDL cholesterol. High plasma levels of HDL

  4. Very low levels of HDL cholesterol and atherosclerosis, a variable relationship – a review of LCAT deficiency

    Directory of Open Access Journals (Sweden)

    Savel J

    2012-06-01

    Full Text Available Julia Savel,1,2 Marianne Lafitte,1 Yann Pucheu,1,3 Vincent Pradeau,1 Antoine Tabarin,2,3 Thierry Couffinhal1,3,41Centre d'Exploration, de Prévention et de Traitement de l'Athérosclérose, Hôpital Cardiologique, 2Service d'endocrinologie, CHU Bordeaux, Université Bordeaux Segalen, Bordeaux, France; 3Université de Bordeaux Adaptation cardiovasculaire à l'ischémie, 4INSERM, Adaptation cardiovasculaire à l'ischémie, U1034, Pessac, FranceAbstract: A number of epidemiological and clinical studies have demonstrated that plasma high-density lipoprotein (HDL level is a strong inverse predictor of cardiovascular events. HDL is believed to retard the formation of atherosclerotic lesions by removing excess cholesterol from cells and preventing endothelial dysfunction. Lecithin cholesterol acyltransferase (LCAT plays a central role in the formation and maturation of HDL, and in the intravascular stage of reverse cholesterol transport: a major mechanism by which HDL modulates the development and progression of atherosclerosis. A defect in LCAT function would be expected to enhance atherosclerosis, by interfering with the reverse cholesterol transport step. As such, one would expect to find more atherosclerosis and cardiovascular events in LCAT-deficient patients. But this relationship is not always evident. In this review, we describe contradictory reports in the literature about cardiovascular risks in this patient population. We discuss the paradoxical finding of severe HDL deficiency and an absence of subclinical atherosclerosis in LCAT-deficient patients, which has been used to reject the hypothesis that HDL level is important in the protection against atherosclerosis. Furthermore, to illustrate this paradoxical finding, we present a case study of one patient, referred for evaluation of global cardiovascular risk in the presence of a low HDL cholesterol level, who was diagnosed with LCAT gene mutations.Keywords: atherosclerosis, LCAT function

  5. Cholesterol oxidation products and their biological importance

    DEFF Research Database (Denmark)

    Kulig, Waldemar; Cwiklik, Lukasz; Jurkiewicz, Piotr

    2016-01-01

    The main biological cause of oxysterols is the oxidation of cholesterol. They differ from cholesterol by the presence of additional polar groups that are typically hydroxyl, keto, hydroperoxy, epoxy, or carboxyl moieties. Under typical conditions, oxysterol concentration is maintained at a very low...... and precisely regulated level, with an excess of cholesterol. Like cholesterol, many oxysterols are hydrophobic and hence confined to cell membranes. However, small chemical differences between the sterols can significantly affect how they interact with other membrane components, and this in turn can have...

  6. Remnant cholesterol as a cause of ischemic heart disease

    DEFF Research Database (Denmark)

    Varbo, Anette; Benn, Marianne; Nordestgaard, Børge G

    2014-01-01

    This review focuses on remnant cholesterol as a causal risk factor for ischemic heart disease (IHD), on its definition, measurement, atherogenicity, and levels in high risk patient groups; in addition, present and future pharmacological approaches to lowering remnant cholesterol levels...... are considered. Observational studies show association between elevated levels of remnant cholesterol and increased risk of cardiovascular disease, even when remnant cholesterol levels are defined, measured, or calculated in different ways. In-vitro and animal studies also support the contention that elevated...... levels of remnant cholesterol may cause atherosclerosis same way as elevated levels of low-density lipoprotein (LDL) cholesterol, by cholesterol accumulation in the arterial wall. Genetic studies of variants associated with elevated remnant cholesterol levels show that an increment of 1mmol/L (39mg...

  7. High cholesterol level is essential for myelin membrane growth.

    Science.gov (United States)

    Saher, Gesine; Brügger, Britta; Lappe-Siefke, Corinna; Möbius, Wiebke; Tozawa, Ryu-ichi; Wehr, Michael C; Wieland, Felix; Ishibashi, Shun; Nave, Klaus-Armin

    2005-04-01

    Cholesterol in the mammalian brain is a risk factor for certain neurodegenerative diseases, raising the question of its normal function. In the mature brain, the highest cholesterol content is found in myelin. We therefore created mice that lack the ability to synthesize cholesterol in myelin-forming oligodendrocytes. Mutant oligodendrocytes survived, but CNS myelination was severely perturbed, and mutant mice showed ataxia and tremor. CNS myelination continued at a reduced rate for many months, and during this period, the cholesterol-deficient oligodendrocytes actively enriched cholesterol and assembled myelin with >70% of the cholesterol content of wild-type myelin. This shows that cholesterol is an indispensable component of myelin membranes and that cholesterol availability in oligodendrocytes is a rate-limiting factor for brain maturation.

  8. Effects of apolipoproteins on the kinetics of cholesterol exchange

    International Nuclear Information System (INIS)

    Letizia, J.Y.; Phillips, M.C.

    1991-01-01

    The effects of apolipoproteins on the kinetics of cholesterol exchange have been investigated by monitoring the transfer of [ 14 C]cholesterol from donor phospholipid/cholesterol complexes containing human apolipoproteins A, B, or C. Negatively charged discoidal and vesicular particles containing purified apolipoproteins complexed with lipid and a trace of [ 14 C]cholesterol were incubated with a 10-fold excess of neutral, acceptor, small unilamellar vesicles. The donor and acceptor particles were separated by chromatogrphy of DEAE-Sepharose, and the rate of movement of labeled cholesterol was analyzed as a first-order exchange process. The kinetics of exchange of cholesterol from both vesicular and discoidal complexes that contain apoproteins are consistent with an aqueous diffusion mechanism, as has been established previously for PC/cholesterol SUV. Apolipoproteins A-I, A-II, reduced and carboxymethylated A-11, and B-100 present in SUV at the same lipid/protein (w/w) ratio all enhance the rate of cholesterol exchange to about the same degree. Cholesterol molecules exchange more rapidly from discoidal complexes. Generally, as the diameter of apoprotein/phospholipid/cholesterol discs decreases, t 1/2 for cholesterol exchange decreases. Since small bilayer discs have a relatively high ratio of boundary to face surface area, cholesterol molecules desorb more rapidly than from larger discs. The modulation of lipid packing by the apoprotein molecules present at the surface of lipoprotein particles affects the rate of cholesterol exchange from such particles

  9. Monocytes of patients with familial hypercholesterolemia show alterations in cholesterol metabolism

    Directory of Open Access Journals (Sweden)

    Soufi Muhidien

    2008-11-01

    Full Text Available Abstract Background Elevated plasma cholesterol promotes the formation of atherosclerotic lesions in which monocyte-derived lipid-laden macrophages are frequently found. To analyze, if circulating monocytes already show increased lipid content and differences in lipoprotein metabolism, we compared monocytes from patients with Familial Hypercholesterolemia (FH with those from healthy individuals. Methods Cholesterol and oxidized cholesterol metabolite serum levels of FH and of healthy, gender/age matched control subjects were measured by combined gas chromatography – mass spectroscopy. Monocytes from patients with FH and from healthy subjects were isolated by antibody-assisted density centrifugation. Gene expression profiles of isolated monocytes were measured using Affymetrix HG-U 133 Plus 2.0 microarrays. We compared monocyte gene expression profiles from FH patients with healthy controls using a Welch T-test with correction for multiple testing (p Results Using microarray analysis we found in FH patients a significant up-regulation of 1,617 genes and a down-regulation of 701 genes compared to monocytes from healthy individuals. These include genes of proteins that are involved in the uptake, biosynthesis, disposition, and cellular efflux of cholesterol. In addition, plasma from FH patients contains elevated amounts of sterols and oxysterols. An increased uptake of oxidized as well as of native LDL by FH monocytes combined with a down-regulation of NPC1 and ABCA1 explains the lipid accumulation observed in these cells. Conclusion Our data demonstrate that circulating FH monocytes show differences in cell physiology that may contribute to the early onset of atherosclerosis in this disease.

  10. MooPoong (Gye Young Jeong) increases HDL-cholesterol but decreases LDL cholesterol and body-weight.

    Science.gov (United States)

    Chung, Hwan-Suck; Hong, Seung-Heon; Do, Keum-Rok; Rhee, Hyung-Koo; Jung, Sung-Ki; Hwang, Woo-Jun; Kim, Hyung-Min

    2004-05-01

    MooPoong (MP, Gye Young Jeong), a Korean traditional wine, has been used as a prevention and treatment agent of blood circulatory trouble. To evaluate such an effect of MP, we analyzed whether the plasma levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and body weight change after rats were fed on high fat diet with MP for 8 weeks. Plasma LDL cholesterol level decreased by 5.6% in 0.128% MP treated group and by 11.1% in 0.640% MP treated group. However, HDL cholesterol was increased by 6.7% in 0.128% MP diet group and 33.3% in 0.640% MP diet group. In addition, there was a significant weight loss in the MP treated group compared with the high-fat diet group (P < 0.05). Our findings indicate that MP may contain compounds with actions which can treat blood circulatory trouble as well as overweight.

  11. Cholesterol Levels: What You Need to Know: MedlinePlus Health Topic

    Science.gov (United States)

    ... lipoprotein ( LDL ) cholesterol and high-density lipoprotein ( HDL ) cholesterol. LDL (bad) cholesterol - the main source of cholesterol buildup ... Teens How to Lower Cholesterol How to Lower Cholesterol with Diet LDL: The "Bad" Cholesterol Nutrition Statins Triglycerides VLDL Cholesterol ...

  12. THE REDUCTION OF CHOLESTEROL WITH CUPPING THERAPY ON CHOLESTEROL REDUCTION IN PATIENTS WITH HYPERCHOLESTEROLEMIA

    Directory of Open Access Journals (Sweden)

    Zahid Fikri

    2017-04-01

    Full Text Available Introduction: Hypercholesterolemia is a risk factor causes of death at younger ages. Hypercholesterolemia may increase the risk of atherosclerosis, coronary heart disease, pancreatitis (pancreas inflammation in organs, diabetes mellitus, thyroid disorders, liver disease and kidney disease. Many patients with hypercholesterolemia using cupping therapy. Cupping therapy is alternative treatment process of throwing dirty blood from the body through the skin surface. The objective of this study was to determine the effect of cupping therapy to decrease cholesterol levels in patients with hypercholesterolemia. Method: Design used in this study was quasy experimental design. The population is all patients with hypercholesterolemia in the health center plaza Gresik. The total sample is 18 respondents, taken according to inclusion criteria. Independent variable is the cupping therapy. The dependent variable was the decrease in cholesterol levels. Data were collected using a questionnaire and observation of cholesterol. Data were analyzed using independent t-test and paired t tests with signi fi cance level α < 0.05. Result: The results show that cholesterol levels in patients with hypercholesterolemia treated groups decreased majority. Independent statistical analysis using t-test showed p = 0.001 and with the Paired t-test p value = 0.003. Discussion: This result means that there are significant effects of cupping therapy on cholesterol reduction in patients with hypercholesterolemia aged 45 years and over. Further research needs to be done in control diet, lifestyle and daily activities for the success of cupping therapy.

  13. Effect of ionizing radiation on the oxidation of cholesterol in frozen chicken and beef hamburgers

    International Nuclear Information System (INIS)

    Moura, Andrea Figueiredo Procopio de

    2004-01-01

    Several technologies have been developed to assure food quality. Among these technological processes, ionizing radiation has been described as a feasible alternative for food conservation, mainly for meat products, since it keeps their natural properties. In hamburgers, the use of irradiation has been studied due to the frequent implication of such products in outbreaks of food-borne diseases. Some of the outbreaks, which even killed consumers, were caused by E. coli O157:H7. But the use of ionizing radiation in hamburgers may form free radicals able to trigger lipid oxidation in the muscle tissue. As a component of the cell membrane lipids, cholesterol may also undergo oxidation and form biologically active compounds, with atherogenic, mutagenic, cytotoxic and cancerous properties. The aim of this work was to evaluate the occurrence of cholesterol oxidation products in chicken hamburgers and beef hamburgers submitted to irradiation and stored frozen, aerobically and under vacuum. The results showed that irradiation caused an increase of around 11% in the concentration of cholesterol oxides in frozen hamburgers. In chicken hamburgers, an increase in the levels of cholesterol oxides was observed ali over the storage period, while in beef hamburgers it was observed only in the final part of the storage period. Packaging itself did not have a significant effect on the concentrations of cholesterol oxides in either of the types of hamburgers studied. However, it showed a significant interaction with irradiation, that is, vacuum packaging prevented the formation of cholesterol oxides in irradiated beef hamburgers. (author)

  14. Particle size and cholesterol content of a mayonnaise formulated by OSA-modified potato starch

    Directory of Open Access Journals (Sweden)

    Shiva Ghazaei

    2015-03-01

    Full Text Available Egg yolk was partially replaced (0, 25, 50, 75, and 100% with octenyl succinic anhydride (OSA-modified potato starch in a reduced-fat mayonnaise formulation to curtail the problems associated with high cholesterol and induced allergic reactions. The physicochemical properties included parameters such as: pH, fat content, and emulsion stability of the formulations analyzed. The samples with 75% and 100% egg yolk substitute showed the maximum emulsion stability (>95% after two of months storage, and they were selected according to cholesterol content, particle size distributions, dynamic rheological properties, microstructure, and sensory characteristic. A significant reduction (84-97% in the cholesterol content was observed in the selected samples. Particle size analysis showed that by increasing the amount of OSA starch, the oil droplets with the peak size of 70 µm engulfed by this compound became larger. The rheological tests elucidated that in the absence of egg yolk, OSA starch may not result in a final product with consistent texture and that the best ratio of the two emulsifiers (OSA starch/egg yolk to produce stable reduced-fat, low cholesterol mayonnaise is 75/25. The microscopic images confirmed the formation of a stable cohesive layer of starch surrounding the oil droplets emulsified in the samples selected.

  15. Portulaca oleracea reduces triglyceridemia, cholesterolemia, and improves lecithin: cholesterol acyltransferase activity in rats fed enriched-cholesterol diet.

    Science.gov (United States)

    Zidan, Y; Bouderbala, S; Djellouli, F; Lacaille-Dubois, M A; Bouchenak, M

    2014-10-15

    The effects of Portulaca oleracea (Po) lyophilized aqueous extract were determined on the serum high-density lipoproteins (HDL2 and HDL3) amounts and composition, as well as on lecithin: cholesterol acyltansferase (LCAT) activity. Male Wistar rats (n = 12) were fed on 1% cholesterol-enriched diet for 10 days. After this phase, hypercholesterolemic rats (HC) were divided into two groups fed the same diet supplemented or not with Portulaca oleracea (Po-HC) (0.5%) for four weeks. Serum total cholesterol (TC) and triacylglycerols (TG), and liver TG values were respectively 1.6-, 1.8-, and 1.6-fold lower in Po-HC than in HC group. Cholesterol concentrations in LDL-HDL1, HDL2, and HDL3 were respectively 1.8, 1.4-, and 2.4-fold decreased in Po-HC group. HDL2 and HDL3 amounts, which were the sum of apolipoproteins (apos), TG, cholesteryl esters (CE), unesterified cholesterol (UC), and phospholipids (PL) contents, were respectively 4.5-fold higher and 1.2-fold lower with Po treatment. Indeed, enhanced LCAT activity (1.2-fold), its cofactor-activator apo A-I (2-fold) and its reaction product HDL2-CE (2.1-fold) were observed, whereas HDL3-PL (enzyme substrate) and HDL3-UC (acyl group acceptor) were 1.2- and 2.4-fold lower. Portulaca oleracea reduces triglyceridemia, cholesterolemia, and improves reverse cholesterol transport in rat fed enriched-cholesterol diet, contributing to anti-atherogenic effects. Copyright © 2014 Elsevier GmbH. All rights reserved.

  16. SR-BI: Linking Cholesterol and Lipoprotein Metabolism with Breast and Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Jorge L. Gutierrez-Pajares

    2016-10-01

    Full Text Available Studies have demonstrated the significant role of cholesterol and lipoprotein metabolism in the progression of cancer. The SCARB1 gene encodes the scavenger receptor class B type I (SR-BI, which is an 82-kDa glycoprotein with two transmembrane domains separated by a large extracellular loop. SR-BI plays an important role in the regulation of cholesterol exchange between cells and high-density lipoproteins. Accordingly, hepatic SR-BI has been shown to play an essential role in the regulation of the reverse cholesterol transport pathway, which promotes the removal and excretion of excess body cholesterol. In the context of atherosclerosis, SR-BI has been implicated in the regulation of intracellular signaling, lipid accumulation, foam cell formation, and cellular apoptosis. Furthermore, since lipid metabolism is a relevant target for cancer treatment, recent studies have focused on examining the role of SR-BI in this pathology. While signaling pathways have initially been explored in non-tumoral cells, studies with cancer cells have now demonstrated SR-BI’s function in tumor progression. In this review, we will discuss the role of SR-BI during tumor development and malignant progression. In addition, we will provide insights into the transcriptional and post-transcriptional regulation of the SCARB1 gene. Overall, studying the role of SR-BI in tumor development and progression should allow us to gain useful information for the development of new therapeutic strategies.

  17. Fermented inulin hydrolysate by Bifidobacterium breve as cholesterol binder in functional food application

    Science.gov (United States)

    Melanie, Hakiki; Susilowati, Agustine; Maryati, Yati

    2017-01-01

    Inulin hydrolysate is a result of inulin hydrolysis by inulinase enzyme of Scopulariopsis sp.-CBS1 fungi isolated from dahlia tuber skin in the formation of fructooligosaccharides (FOS) as dietary fiber. Inulin hydrolysate fermented by Bifidobacterium breve has a potential as cholesterol binder in digestive system due to dietary fiber content in inulin. This study was conducted to evaluate the best cholesterol binding capacity by the variation of lactic acid bacteria (LAB) culture concentration of 10%, 20% and 30% (v/v), respectively. Fermentation process were conducted with inulin hydrolysate concentration of 25% (w/v), skim milk 7,5% (w/v) and various LAB culture concentration at 40 °C for 0, 12, 24, 36 and 48 hours. The results showed that the variation of LAB culture concentrations affect the cholesterol binding ability in fermented inulin hydrolysate. The fermentation process with 10% LAB culture concentration at 40°C for 48 hours resulted in the highest cholesterol binding capacity (CBC) of 13,69 mg/g at pH 7and 14,44 mg/g at pH 2 with composition of total acids of 0,787%, soluble dietary fiber of 0,396%, insoluble dietary fiber of 5,47%, total solids of 14,476%, total sugars of 472,484 mg/mL, reducing sugar of 92 mg/mL and total plate count (TPC) of 7,278 log CFU/mL, respectively.

  18. Atorvastatin treatment lowers fasting remnant-like particle cholesterol and LDL subfraction cholesterol without affecting LDL size in type 2 diabetes mellitus: Relevance for non-HDL cholesterol and apolipoprotein B guideline targets

    NARCIS (Netherlands)

    Kappelle, Paul J. W. H.; Dallinga-Thie, Geesje M.; Dullaart, Robin P. F.

    2010-01-01

    The extent to which atorvastatin treatment affects LDL size, LDL subfraction levels and remnant-like particle cholesterol (RLP-C) was determined in type 2 diabetes. We also compared LDL size and RLP-C in relation to guideline cut-off values for LDL cholesterol, non-HDL cholesterol and apolipoprotein

  19. Atorvastatin treatment lowers fasting remnant-like particle cholesterol and LDL subfraction cholesterol without affecting LDL size in type 2 diabetes mellitus : Relevance for non-HDL cholesterol and apolipoprotein B guideline targets

    NARCIS (Netherlands)

    Kappelle, Paul J.W.H.; Dallinga-Thie, Geesje M.; Dullaart, Robin P. F.

    The extent to which atorvastatin treatment affects LDL size, LDL subfraction levels and remnant-like particle cholesterol (RLP-C) was determined in type 2 diabetes. We also compared LDL size and RLP-C in relation to guideline cut-off values for LDL cholesterol, non-HDL cholesterol and apolipoprotein

  20. Membrane cholesterol removal changes mechanical properties of cells and induces secretion of a specific pool of lysosomes.

    Science.gov (United States)

    Hissa, Barbara; Pontes, Bruno; Roma, Paula Magda S; Alves, Ana Paula; Rocha, Carolina D; Valverde, Thalita M; Aguiar, Pedro Henrique N; Almeida, Fernando P; Guimarães, Allan J; Guatimosim, Cristina; Silva, Aristóbolo M; Fernandes, Maria C; Andrews, Norma W; Viana, Nathan B; Mesquita, Oscar N; Agero, Ubirajara; Andrade, Luciana O

    2013-01-01

    In a previous study we had shown that membrane cholesterol removal induced unregulated lysosomal exocytosis events leading to the depletion of lysosomes located at cell periphery. However, the mechanism by which cholesterol triggered these exocytic events had not been uncovered. In this study we investigated the importance of cholesterol in controlling mechanical properties of cells and its connection with lysosomal exocytosis. Tether extraction with optical tweezers and defocusing microscopy were used to assess cell dynamics in mouse fibroblasts. These assays showed that bending modulus and surface tension increased when cholesterol was extracted from fibroblasts plasma membrane upon incubation with MβCD, and that the membrane-cytoskeleton relaxation time increased at the beginning of MβCD treatment and decreased at the end. We also showed for the first time that the amplitude of membrane-cytoskeleton fluctuation decreased during cholesterol sequestration, showing that these cells become stiffer. These changes in membrane dynamics involved not only rearrangement of the actin cytoskeleton, but also de novo actin polymerization and stress fiber formation through Rho activation. We found that these mechanical changes observed after cholesterol sequestration were involved in triggering lysosomal exocytosis. Exocytosis occurred even in the absence of the lysosomal calcium sensor synaptotagmin VII, and was associated with actin polymerization induced by MβCD. Notably, exocytosis triggered by cholesterol removal led to the secretion of a unique population of lysosomes, different from the pool mobilized by actin depolymerizing drugs such as Latrunculin-A. These data support the existence of at least two different pools of lysosomes with different exocytosis dynamics, one of which is directly mobilized for plasma membrane fusion after cholesterol removal.

  1. Survival of adult neurons lacking cholesterol synthesis in vivo.

    Science.gov (United States)

    Fünfschilling, Ursula; Saher, Gesine; Xiao, Le; Möbius, Wiebke; Nave, Klaus-Armin

    2007-01-02

    Cholesterol, an essential component of all mammalian plasma membranes, is highly enriched in the brain. Both during development and in the adult, brain cholesterol is derived from local cholesterol synthesis and not taken up from the circulation. However, the contribution of neurons and glial cells to total brain cholesterol metabolism is unknown. Using conditional gene inactivation in the mouse, we disrupted the squalene synthase gene (fdft1), which is critical for cholesterol synthesis, in cerebellar granule cells and some precerebellar nuclei. Mutant mice showed no histological signs of neuronal degeneration, displayed ultrastructurally normal synapses, and exhibited normal motor coordination. This revealed that these adult neurons do not require cell-autonomous cholesterol synthesis for survival or function. We conclude that at least some adult neurons no longer require endogenous cholesterol synthesis and can fully meet their cholesterol needs by uptake from their surrounding. Glia are a likely source of cholesterol in the central nervous system.

  2. Survival of adult neurons lacking cholesterol synthesis in vivo

    Directory of Open Access Journals (Sweden)

    Möbius Wiebke

    2007-01-01

    Full Text Available Abstract Background Cholesterol, an essential component of all mammalian plasma membranes, is highly enriched in the brain. Both during development and in the adult, brain cholesterol is derived from local cholesterol synthesis and not taken up from the circulation. However, the contribution of neurons and glial cells to total brain cholesterol metabolism is unknown. Results Using conditional gene inactivation in the mouse, we disrupted the squalene synthase gene (fdft1, which is critical for cholesterol synthesis, in cerebellar granule cells and some precerebellar nuclei. Mutant mice showed no histological signs of neuronal degeneration, displayed ultrastructurally normal synapses, and exhibited normal motor coordination. This revealed that these adult neurons do not require cell-autonomous cholesterol synthesis for survival or function. Conclusion We conclude that at least some adult neurons no longer require endogenous cholesterol synthesis and can fully meet their cholesterol needs by uptake from their surrounding. Glia are a likely source of cholesterol in the central nervous system.

  3. Aspirin Increases the Solubility of Cholesterol in Lipid Membranes

    Science.gov (United States)

    Alsop, Richard; Barrett, Matthew; Zheng, Sonbo; Dies, Hannah; Rheinstadter, Maikel

    2014-03-01

    Aspirin (ASA) is often prescribed for patients with high levels of cholesterol for the secondary prevention of myocardial events, a regimen known as the Low-Dose Aspirin Therapy. We have recently shown that Aspirin partitions in lipid bilayers. However, a direct interplay between ASA and cholesterol has not been investigated. Cholesterol is known to insert itself into the membrane in a dispersed state at moderate concentrations (under ~37.5%) and decrease fluidity of membranes. We prepared model lipid membranes containing varying amounts of both ASA and cholesterol molecules. The structure of the bilayers as a function of ASA and cholesterol concentration was determined using high-resolution X-ray diffraction. At cholesterol levels of more than 40mol%, immiscible cholesterol plaques formed. Adding ASA to the membranes was found to dissolve the cholesterol plaques, leading to a fluid lipid bilayer structure. We present first direct evidence for an interaction between ASA and cholesterol on the level of the cell membrane.

  4. Extreme nonfasting remnant cholesterol vs extreme LDL cholesterol as contributors to cardiovascular disease and all-cause mortality in 90000 individuals from the general population.

    Science.gov (United States)

    Varbo, Anette; Freiberg, Jacob J; Nordestgaard, Børge G

    2015-03-01

    Increased nonfasting remnant cholesterol, like increased LDL cholesterol, is causally associated with increased risk for ischemic heart disease (IHD). We tested the hypothesis that extreme concentrations of nonfasting remnant and LDL cholesterol are equal contributors to the risk of IHD, myocardial infarction (MI), and all-cause mortality. We compared stepwise increasing concentrations of nonfasting remnant and LDL cholesterol for association with risk of IHD, MI, and all-cause mortality in approximately 90 000 individuals from the Danish general population. During up to 22 years of complete follow-up, 4435 participants developed IHD, 1722 developed MI, and 8121 died. Compared with participants with nonfasting remnant cholesterol cholesterol of 0.5-0.99 mmol/L (19.3-38.2 mg/dL) to 2.4 (1.9-2.9) for remnant cholesterol of ≥1.5 mmol/L (58 mg/dL) (P for trend LDL cholesterol LDL cholesterol of 3-3.99 mmol/L (115.8-154 mg/dL) to 2.3 (1.9-2.8) for LDL cholesterol of ≥5 mmol/L (193 mg/dL) (P cholesterol (P LDL cholesterol (P cholesterol concentrations were associated stepwise with all-cause mortality ranging from hazard ratio 1.0 (0.9-1.1) to 1.6 (1.4-1.9) (P LDL cholesterol concentrations were associated with decreased all-cause mortality risk in a U-shaped pattern, with hazard ratios from 0.8 (0.7-0.8) to 0.9 (0.8-1.0) (P = 0.002). After mutual adjustment, LDL cholesterol best predicted MI, and remnant cholesterol best predicted all-cause mortality. Both lipoproteins were associated equally with risk of IHD and MI; however, only nonfasting remnant cholesterol concentrations were associated stepwise with increased all-cause mortality risk. © 2015 American Association for Clinical Chemistry.

  5. Cholesterol: the debate should be terminated.

    Science.gov (United States)

    Nathan, David G

    2017-07-01

    Here, I offer personal perspectives on cholesterol homeostasis that reflect my belief that certain aspects of the debate have been overstated.-Nathan, D. G. Cholesterol: the debate should be terminated. © FASEB.

  6. Cold labelled substrate and estimation of cholesterol esterification rate in lecithin cholesterol acyltransferase radioassay

    International Nuclear Information System (INIS)

    Dobiasova, M.; Schuetzova, M.

    1986-01-01

    A new method is described of cold labelling of blood serum, plasma and body fluids containing lecithin cholesterol acyltransferase (LCAT) and/or lipoproteins for radioassay to assess the cholesterol esterification rate. The method uses the principle of transfer, in refrigeration conditions, of 14 C-cholesterol from filter paper discs to the fluids. The preparation of the disc guarantees homogeneous labelling and high stability. The use of the labelling disc was shown to be reliable, easy and fast and suitable for accurate assessment of LCAT reaction, applicable in the widest possible enzyme concentration range. It was also, found suited for the measurement of the esterification rate of rabbit intraocular fluid which is a medium with the lowest contents of the substrate and LCAT. (L.O.)

  7. Isolation of Cholesterol from an Egg Yolk

    Science.gov (United States)

    Taber, Douglass F.; Li, Rui; Anson, Cory M.

    2011-01-01

    A simple procedure for the isolation of the cholesterol, by hydrolysis and extraction followed by column chromatography, is described. The cholesterol can be further purified by complexation with oxalic acid. It can also be oxidized and conjugated to cholestenone. The source of the cholesterol is one egg yolk, which contains about 200 mg of…

  8. Gallstones, a cholecystectomy, chronic pancreatitis, and the risk of subsequent pancreatic cancer in diabetic patients: a population-based cohort study.

    Science.gov (United States)

    Lai, Hsueh-Chou; Tsai, I-Ju; Chen, Pei-Chun; Muo, Chih-Hsin; Chou, Jen-Wei; Peng, Cheng-Yuan; Lai, Shih-Wei; Sung, Fung-Chang; Lyu, Shu-Yu; Morisky, Donald E

    2013-06-01

    The causal association between diabetes and pancreatic cancer remains unclear in Asian populations. This study examined whether gallstones, a cholecystectomy, chronic pancreatitis and the treatment of antidiabetic agents affect the risk of subsequent pancreatic cancer for patients with diabetes in a Taiwanese population. Using claims data from the universal health insurance program in Taiwan, 449,685 newly diagnosed diabetic cases among insured people from 2000 to 2003 were identified as the case group. The comparison group, matched for gender, age, and the index year of the diabetes cohort, consisted of 325,729 persons without diabetes. Pancreatic cancer incidence was measured in both groups until the end of 2008. Other risk factors associated with this cancer were also measured. The incidence of pancreatic cancer in the diabetic cohort was 2-fold greater than that in the comparison group (1.46 vs. 0.71 per 10,000 person-years) with an adjusted hazard ratio (HR) of 1.75 [95 % confidence interval (CI) 1.45-2.10]. The risk slightly increased for diabetic patients with gallstones, cholecystitis, and a cholecystectomy (HR 1.92, 95% CI 1.18-3.11), but greatly increased for those with comorbidity of chronic pancreatitis (HR 22.9, 95% CI 12.6-41.4). Pancreatic cancer risk also increased significantly for those patients who used more insulin for treating diabetes (OR 2.20, 95% CI 1.40-3.45). Our data suggest that the risk of pancreatic cancer is moderately increased in patients with diabetes, especially those using insulin therapy. The risk is greatly increased for diabetic patients with chronic pancreatitis.

  9. Combined laparoscopic cholecystectomy with ileostomy reversal: A method of delayed definitive management of postoperative gallstone pancreatitis

    Directory of Open Access Journals (Sweden)

    Gaurav V Kulkarni

    2014-01-01

    Full Text Available Traditional management of gallstone pancreatitis (GP has been to perform cholecystectomy during the same hospital admission after resolution. However, when GP develops in the immediate postoperative period from a major colorectal operation, cholecystectomy may be fraught with difficulty due to the inflammatory response that occurs. Thus, delaying cholecystectomy until the inflammatory response subsides may be worthwhile, and it maximizes the chances of completing the cholecystectomy laparoscopically. We have described our management of 2 patients with GP occurring after colorectal operations, which required proximal diverting ileostomy. In both cases, we deferred management of GP with either endoscopic retrograde cholangiopancreatography (ERCP or medical conservative measures during the acute attack and performed laparoscopic cholecystectomy during ostomy reversal surgery utilizing the existing ostomy takedown site for port placement. Both patients tolerated this management well.

  10. Impact of a public cholesterol screening program.

    Science.gov (United States)

    Fischer, P M; Guinan, K H; Burke, J J; Karp, W B; Richards, J W

    1990-12-01

    The National Cholesterol Education Program (NCEP) has endorsed physician case finding as the primary method to detect individuals with elevated cholesterol levels. Despite this recommendation, promotional and for-profit public screening programs have flourished. We surveyed participants of a mall-based cholesterol screening program 1 year after their screening. Sixty-four percent of those screened had not previously known their cholesterol levels. Those who were newly screened were less likely to benefit from this testing than the general public, since they were older (mean age, 55.3 years), more likely to be female (67.4%), and nonsmokers (88%). Screenees had excellent recall of their cholesterol level (mean absolute reporting error, 0.24 mmol/L [9 mg/dL]) and a good understanding of cholesterol as a coronary heart disease risk. Those with elevated cholesterol levels reported high distress from screening but no reduction in overall psychosocial well-being and an actual decrease in absenteeism. Only 53.7% of all who were advised to seek follow-up because of an elevated screening value had done so within the year following the screening program. However, of those with values greater than 6.2 mmol/L (240 mg/dL), 68% had sought follow-up. Many of those who participate in public screening programs have been previously tested, fall into low-benefit groups, or fail to comply with recommended follow-up. We therefore conclude that cholesterol screening programs of the type now commonly offered are unlikely to contribute greatly to the national efforts to further reduce coronary heart disease.

  11. Tuberculosis treatment raises total cholesterol level and restores ...

    African Journals Online (AJOL)

    aghomotsegin

    2013-10-09

    Oct 9, 2013 ... and restores high density lipoprotein cholesterol (HDL- ... cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) and triglycerides (TG) were determined .... However, we found a strong negative correlation (r = - 0.96,.

  12. Lack of P2Y(13) in mice fed a high cholesterol diet results in decreased hepatic cholesterol content, biliary lipid secretion and reverse cholesterol transport

    NARCIS (Netherlands)

    Lichtenstein, Laeticia; Serhan, Nizar; Annema, Wijtske; Combes, Guillaume; Robaye, Bernard; Boeynaems, Jean-Marie; Perret, Bertrand; Tietge, Uwe J. F.; Laffargue, Muriel; Martinez, Laurent O.

    2013-01-01

    Background: The protective effect of HDL is mostly attributed to their metabolic function in reverse cholesterol transport (RCT), a process whereby excess cellular cholesterol is taken up from peripheral cells, processed in HDL particles, and later delivered to the liver for further metabolism and

  13. Comparison of efficacy between choledochoscopic gallbladder-preserving cholelithotomy and laparoscopic cholecystectomy in treatment of gallstones: a meta-analysis

    Directory of Open Access Journals (Sweden)

    FAN Hua

    2015-10-01

    Full Text Available ObjectiveTo systematically evaluate the advantages and disadvantages of choledochoscopic gallbladder-preserving cholelithotomy (CGPC and laparoscopic cholecystectomy (LC in the treatment of gallstones. MethodsThe databases of CBM, CNKI, VIP, Wanfang Data, PubMed, EMBASE, the Cochrane Library, and Web of Science were searched for randomized controlled trials (RCTs related to CGPC and LC in the treatment of gallstones published up to June 2015. Data extraction and quality evaluation were performed for the literature included, and Review Manager 5.3 was used for the meta-analysis. ResultsFive RCTs involving 685 patients were included. The results of the meta-analysis showed that CGPC group and LC group had significant differences in operation time (OR=8.85, 95% CI: 049-17.21, P=0.04 and incidence of postoperative diarrhea (OR=0.24, 95% CI: 0.11-0.53, P=0.000 4. However, no significant differences were seen between the two groups in intraoperative bleeding volume (OR=-12.37, 95% CI: -29.73-4.99, P=0.16, time to postoperative intestinal function recovery (OR=-7.19, 95% CI: -24.28-9.90, P=0.41, hospitalization days (OR=-0.17, 95% CI: -1.98-1.63, P=0.85, and hospital costs (OR=-1.14, 95% CI: -2.57-0.28, P=0.12. ConclusionThe operation time and incidence of postoperative diarrhea in CGPC are superior to those in LC, while no significant differences are observed in intraoperative bleeding volume, time to postoperative intestinal function recovery, hospitalization days, and hospital costs. Due to a limited number of articles included and publication bias, RCTs with a large sample size and high quality are needed to provide more effective data.

  14. Atorvastatin increases HDL cholesterol by reducing CETP expression in cholesterol-fed APOE*3-Leiden.CETP mice

    NARCIS (Netherlands)

    Haan, W. de; Hoogt, C.C. van der; Westerterp, M.; Hoekstra, M.; Dallinga-Thie, G.M.; Princen, H.M.G.; Romijn, J.A.; Jukema, J.W.; Havekes, L.M.; Rensen, P.C.N.

    2008-01-01

    Objective: In addition to lowering low-density lipoprotein (LDL)-cholesterol, statins modestly increase high-density lipoprotein (HDL)-cholesterol in humans and decrease cholesteryl ester transfer protein (CETP) mass and activity. Our aim was to determine whether the increase in HDL depends on CETP

  15. Overexpression and deletion of phospholipid transfer protein reduce HDL mass and cholesterol efflux capacity but not macrophage reverse cholesterol transport[S

    Science.gov (United States)

    Kuwano, Takashi; Bi, Xin; Cipollari, Eleonora; Yasuda, Tomoyuki; Lagor, William R.; Szapary, Hannah J.; Tohyama, Junichiro; Millar, John S.; Billheimer, Jeffrey T.; Lyssenko, Nicholas N.; Rader, Daniel J.

    2017-01-01

    Phospholipid transfer protein (PLTP) may affect macrophage reverse cholesterol transport (mRCT) through its role in the metabolism of HDL. Ex vivo cholesterol efflux capacity and in vivo mRCT were assessed in PLTP deletion and PLTP overexpression mice. PLTP deletion mice had reduced HDL mass and cholesterol efflux capacity, but unchanged in vivo mRCT. To directly compare the effects of PLTP overexpression and deletion on mRCT, human PLTP was overexpressed in the liver of wild-type animals using an adeno-associated viral (AAV) vector, and control and PLTP deletion animals were injected with AAV-null. PLTP overexpression and deletion reduced plasma HDL mass and cholesterol efflux capacity. Both substantially decreased ABCA1-independent cholesterol efflux, whereas ABCA1-dependent cholesterol efflux remained the same or increased, even though preβ HDL levels were lower. Neither PLTP overexpression nor deletion affected excretion of macrophage-derived radiocholesterol in the in vivo mRCT assay. The ex vivo and in vivo assays were modified to gauge the rate of cholesterol efflux from macrophages to plasma. PLTP activity did not affect this metric. Thus, deviations in PLTP activity from the wild-type level reduce HDL mass and ex vivo cholesterol efflux capacity, but not the rate of macrophage cholesterol efflux to plasma or in vivo mRCT. PMID:28137768

  16. Effect of doxazosin on cholesterol synthesis in cell culture

    International Nuclear Information System (INIS)

    D'Eletto, R.D.; Javitt, N.B.

    1989-01-01

    The effect of doxazosin on cholesterol synthesis was determined by measuring the content of deuterium-enriched cholesterol in rabbit fibroblasts with and without receptors for low-density lipoproteins (LDL) and in hepatoma (Hep G2 cells). Doxazosin, at concentrations of 5-20 mumol/L, increased LDL binding to hepatic cells in a dose-related manner. Also, in these hepatic cells, doxazosin produced dose-related decreases in both newly synthesized cholesterol and cholesterol ester. In rabbit fibroblasts that were LDL receptor negative, de novo cholesterol synthesis was markedly reduced by increasing concentrations of doxazosin. Taken together, these results suggest that doxazosin may have a direct inhibitory effect on cholesterol synthesis independent of the LDL receptor. The inhibition of cholesterol synthesis by doxazosin may cause cells to compensate by upregulating the LDL receptor, thereby increasing the importation of lipoprotein cholesterol and reducing LDL cholesterol in the medium. This hypothesis supports findings in the clinical setting whereby doxazosin has a beneficial effect on the lipid profile, and suggests a useful additional property for this antihypertensive agent

  17. Cholesterol esterase activity of human intestinal mucosa

    International Nuclear Information System (INIS)

    Ponz de Leon, M.; Carubbi, F.; Di Donato, P.; Carulli, N.

    1985-01-01

    It has been suggested that cholesterol absorption in humans is dependent on bile acid pool composition and that expansion of the cholic acid pool size is followed by an increase of the absorption values. Similar observations were reported in rats. In the present study, therefore, the authors investigated some general properties of human intestinal cholesterol esterase, with particular emphasis on the effect of bile acids on this enzymatic activity. Twenty-nine segments of small intestine were taken during operations; the enzymatic activity was studied by using mucosal homogenate as a source of enzyme and oleic acid, cholesterol, and 14 C-labeled cholesterol as substrates. The time-activity relationship was linear within the first two hours; optimal pH for esterification ranged between 5 and 6.2. There was little difference between the esterifying activity of the jejunal and ileal mucosa. Esterification of cholesterol was observed with all the investigated fatty acids but was maximal with oleic acid. Bile acids did not affect cholesterol esterase activity when present in the incubation mixture at 0.1 and 1.0 mM; the enzymatic activity, however, was significantly inhibited when bile acids were added at 20 mM. In conclusion, this study has shown that the human intestinal mucosa possesses a cholesterol esterase activity; at variance with the rat, however, the human enzyme does not seem to be stimulated by trihydroxy bile acids

  18. Melanocortin signaling in the CNS directly regulates circulating cholesterol

    OpenAIRE

    Perez-Tilve, Diego; Hofmann, Susanna M; Basford, Joshua; Nogueiras, Ruben; Pfluger, Paul T; Patterson, James T; Grant, Erin; Wilson-Perez, Hilary E; Granholm, Norman A; Arnold, Myrtha; Trevaskis, James L; Butler, Andrew A; Davidson, William S; Woods, Stephen C; Benoit, Stephen C

    2010-01-01

    Cholesterol circulates in the blood in association with triglycerides and other lipids, and elevated blood low-density lipoprotein cholesterol carries a risk for metabolic and cardiovascular disorders, whereas high-density lipoprotein (HDL) cholesterol in the blood is thought to be beneficial. Circulating cholesterol is the balance among dietary cholesterol absorption, hepatic synthesis and secretion, and the metabolism of lipoproteins by various tissues. We found that the CNS is also an impo...

  19. Pectin penta-oligogalacturonide reduces cholesterol accumulation by promoting bile acid biosynthesis and excretion in high-cholesterol-fed mice.

    Science.gov (United States)

    Zhu, Ru-Gang; Sun, Yan-Di; Hou, Yu-Ting; Fan, Jun-Gang; Chen, Gang; Li, Tuo-Ping

    2017-06-25

    Haw pectin penta-oligogalacturonide (HPPS) has important role in improving cholesterol metabolism and promoting the conversion of cholesterol to bile acids (BA) in mice fed high-cholesterol diet (HCD). However, the mechanism is not clear. This study aims to investigate the effects of HPPS on cholesterol accumulation and the regulation of hepatic BA synthesis and transport in HCD-fed mice. Results showed that HPPS significantly decreased plasma and hepatic TC levels but increased plasma high-density lipoprotein cholesterol (HDL-C) and apolipoprotein A-I (apoA-I) levels, compared to HCD. BA analysis showed that HPPS markedly decreased hepatic and small intestine BA levels but increased the gallbladder BA levels, and finally decreased the total BA pool size, compared to HCD. Studies of molecular mechanism revealed that HPPS promoted hepatic ATP-binding cassette transporter A1 (ABCA1), ATP-binding cassette transporter G1 (ABCG1), and scavenger receptor BI (SR-BI) expression but did not affect ATB binding cassette transporter G5/G8 (ABCG5/8) expression. HPPS inactivated hepatic farnesoid X receptor (FXR) and target genes expression, which resulted in significant increase of cholesterol 7α-hydroxylase 1 (CYP7A1) and sterol 12α-hydroxylase (CYP8B1) expression, with up-regulations of 204.2% and 33.5% for mRNA levels, respectively, compared with HCD. In addition, HPPS markedly enhanced bile salt export pump (BSEP) expression but didn't affect the sodium/taurocholate co-transporting polypeptide (NTCP) expression. In conclusion, the study revealed that HPPS reduced cholesterol accumulation by promoting BA synthesis in the liver and excretion in the feces, and might promote macrophage-to-liver reverse cholesterol transport (RCT) but did not liver-to-fecal RCT. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. The cholesterol-lowering effect of coconut flakes in humans with moderately raised serum cholesterol.

    Science.gov (United States)

    Trinidad, Trinidad P; Loyola, Anacleta S; Mallillin, Aida C; Valdez, Divinagracia H; Askali, Faridah C; Castillo, Joan C; Resaba, Rosario L; Masa, Dina B

    2004-01-01

    This study investigated the effect of coconut flakes on serum cholesterol levels of humans with moderately raised serum cholesterol in 21 subjects. The serum total cholesterol of subjects differed and ranged from 259 to 283 mg/dL. The study was conducted in a double-blind randomized crossover design on a 14-week period, consisting of four 2-week experimental periods, with each experimental period separated by a 2-week washout period. The test foods were as follows: corn flakes as the control food, oat bran flakes as the reference food, and corn flakes with 15% and 25% dietary fiber from coconut flakes (made from coconut flour production). Results showed a significant percent reduction in serum total and low-density lipoprotein (LDL) cholesterol (in mg/dL) for all test foods, except for corn flakes, as follows: oat bran flakes, 8.4 +/- 1.4 and 8.8 +/- 6.0, respectively; 15% coconut flakes, 6.9 +/- 1.1 and 11.0 +/- 4.0, respectively; and 25% coconut flakes, 10.8 +/- 1.3 and 9.2 +/- 5.4, respectively. Serum triglycerides were significantly reduced for all test foods: corn flakes, 14.5 +/- 6.3%; oat bran flakes, 22.7 +/- 2.9%; 15% coconut flakes, 19.3 +/- 5.7%; and 25% coconut flakes, 21.8 +/- 6.0%. Only 60% of the subjects were considered for serum triglycerides reduction (serum triglycerides >170 mg/dL). In conclusion, both 15% and 25% coconut flakes reduced serum total and LDL cholesterol and serum triglycerides of humans with moderately raised serum cholesterol levels. Coconut flour is a good source of both soluble and insoluble dietary fiber, and both types of fiber may have significant role in the reduction of the above lipid biomarker. To our knowledge, this is the first study conducted to show a relationship between dietary fiber from a coconut by-product and a lipid biomarker. Results from this study serves as a good basis in the development of coconut flakes/flour as a functional food, justifying the increased production of coconut and coconut by-products.

  1. Remnant Cholesterol, Low-Density Lipoprotein Cholesterol, and Blood Pressure as Mediators From Obesity to Ischemic Heart Disease

    DEFF Research Database (Denmark)

    Varbo, Anette; Benn, Marianne; Smith, George Davey

    2015-01-01

    RATIONALE: Obesity leads to increased ischemic heart disease (IHD) risk, but the risk is thought to be mediated through intermediate variables and may not be caused by increased weight per se. OBJECTIVE: To test the hypothesis that the increased IHD risk because of obesity is mediated through...... variables and using genetic variants associated with these. During ≤22 years of follow-up 13 945 participants developed IHD. The increased IHD risk caused by obesity was partly mediated through elevated levels of nonfasting remnant cholesterol and low-density lipoprotein cholesterol, through elevated blood...... obesity were low-density lipoprotein cholesterol with 8%, systolic blood pressure with 7%, and remnant cholesterol with 7% excess risk of IHD. Corresponding observational excess risks using conventional body mass index were 21%, 11%, and 20%, respectively. CONCLUSIONS: The increased IHD risk because...

  2. Complexation of phospholipids and cholesterol by triterpenic saponins in bulk and in monolayers.

    Science.gov (United States)

    Wojciechowski, Kamil; Orczyk, Marta; Gutberlet, Thomas; Geue, Thomas

    2016-02-01

    The interactions between three triterpene saponins: α-hederin, hederacoside C and ammonium glycyrrhizate with model lipids: cholesterol and dipalmitoylphosphatidylcholine (DPPC) are described. The oleanolic acid-type saponins (α-hederin and hederacoside C) were shown to form 1:1 complexes with lipids in bulk, characterized by stability constants in the range (4.0±0.2)·10(3)-(5.0±0.4)·10(4) M(-1). The complexes with cholesterol are generally stronger than those with DPPC. On the contrary, ammonium glycyrrhizate does not form complexes with any of the lipids in solution. The saponin-lipid interactions were also studied in a confined environment of Langmuir monolayers of DPPC and DPPC/cholesterol with the saponins present in the subphase. A combined monolayer relaxation, surface dilational rheology, fluorescence microscopy and neutron reflectivity (NR) study showed that all three saponins are able to penetrate pure DPPC and mixed DPPC/cholesterol monolayers. Overall, the effect of the saponins on the model lipid monolayers does not fully correlate with the lipid-saponin complex formation in the homogeneous solution. The best correlation was found for α-hederin, for which even the preference for cholesterol over DPPC observed in bulk is well reflected in the monolayer studies and the literature data on its membranolytic activity. Similarly, the lack of interaction of ammonium glycyrrhizate with both lipids is evident equally in bulk and monolayer experiments, as well as in its weak membranolytic activity. The combined bulk and monolayer results are discussed in view of the role of confinement in modulating the saponin-lipid interactions and possible mechanism of membranolytic activity of saponins. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Cholesterol suppresses antimicrobial effect of statins

    Directory of Open Access Journals (Sweden)

    Mohammad Reza Haeri

    2015-12-01

    Full Text Available Objective(s:Isoprenoid biosynthesis is a key metabolic pathway to produce a wide variety of biomolecules such as cholesterol and carotenoids, which target cell membranes. On the other hand, it has been reported that statins known as inhibitors of isoprenoid biosynthesis and cholesterol lowering agents, may have a direct antimicrobial effect on the some bacteria. The exact action of statins in microbial metabolism is not clearly understood. It is possible that statins inhibit synthesis or utilization of some sterol precursor necessary for bacterial membrane integrity. Accordingly, this study was designed in order to examine if statins inhibit the production of a compound, which can be used in the membrane, and whether cholesterol would replace it and rescue bacteria from toxic effects of statins. Materials and Methods: To examine the possibility we assessed antibacterial effect of statins with different classes; lovastatin, simvastatin, and atorvastatin, alone and in combination with cholesterol on two Gram-positive (Staphylococcus aureus and Enterococcus faecalis and two Gram-negative (Pseudomonas aeruginosa and Escherichia coli bacteria using gel diffusion assay. Results: Our results showed that all of the statins except for lovastatin had significant antibacterial property in S. aureus, E. coli, and Enter. faecalis. Surprisingly, cholesterol nullified the antimicrobial action of effective statins in statin-sensitive bacteria. Conclusion: It is concluded that statins may deprive bacteria from a metabolite responsible for membrane stability, which is effectively substituted by cholesterol.

  4. The role of cholesterol metabolism and cholesterol transport in carcinogenesis; A review of scientific findings, relevant to future cancer therapeutics.

    Directory of Open Access Journals (Sweden)

    Pedro Miguel Cruz

    2013-09-01

    Full Text Available While the unique metabolic activities of malignant tissues as potential targets for cancer therapeutics has been the subject of several recent reviews, the role of cholesterol metabolism in this context is yet to be fully explored. Cholesterol is an essential component of mammalian cell membranes as well as a precursor of bile acids and steroid hormones. The hypothesis that cancer cells need excess cholesterol and intermediates of the cholesterol biosynthesis pathway to maintain a high level of proliferation is well accepted, however the mechanisms by which malignant cells and tissues reprogram cholesterol synthesis, uptake and efflux are yet to be fully elucidated as potential therapeutic targets. High and low density plasma lipoproteins, area the likely major suppliers of cholesterol to cancer cells and tumors, potentially via receptor mediated mechanisms. This review is primarily focused on the role(s of lipoproteins in carcinogenesis, and their future roles as drug delivery vehicles for targeted cancer chemotherapy.

  5. Cholesterol synthesis by human fetal hepatocytes: effect of lipoproteins

    International Nuclear Information System (INIS)

    Carr, B.R.; Simpson, E.R.

    1984-01-01

    The purpose of the present investigation was to determine the effect of various lipoproteins on the rate of cholesterol synthesis of human fetal liver cells maintained in culture. This was accomplished by measuring the rate of incorporation of tritium from tritiated water or carbon 14-labeled acetate into cholesterol in human fetal liver cells. Optimal conditions for each assay were determined. When human fetal liver cells were maintained in the presence of low-density lipoprotein, cholesterol synthesis was inhibited in a concentration-dependent fashion. Intermediate--density lipoprotein and very-low-density lipoprotein also suppressed cholesterol synthesis in human fetal liver cells. In contrast, high-density lipoprotein stimulated cholesterol synthesis in human fetal liver cells. The results of the present as well as our previous investigations suggest that multiple interrelationships exist between fetal liver cholesterol synthesis and lipoprotein-cholesterol utilization by the human fetal adrenal gland and that these processes serve to regulate the lipoprotein-cholesterol levels in fetal plasma

  6. Astragalus polysaccharides lowers plasma cholesterol through mechanisms distinct from statins.

    Directory of Open Access Journals (Sweden)

    Yunjiu Cheng

    Full Text Available To determine the efficacy and underlying mechanism of Astragalus polysaccharides (APS on plasma lipids in hypercholesterolemia hamsters. The effect of APS (0.25 g/kg/d on plasma and liver lipids, fecal bile acids and neutral sterol, cholesterol absorption and synthesis, HMG-CoA reductase activity, and gene and protein expressions in the liver and small intestine was investigated in twenty-four hypercholesterolemia hamsters. Treatment periods lasted for three months. APS significantly lowered plasma total cholesterol by 45.8%, triglycerides by 30%, and low-density lipoprotein-cholesterol by 47.4%, comparable to simvastatin. Further examinations revealed that APS reduced total cholesterol and triglycerides in the liver, increased fecal bile acid and neutral sterol excretion, inhibited cholesterol absorption, and by contrast, increased hepatic cholesterol synthesis and HMG-CoA reductase activity. Plasma total cholesterol or low-density lipoprotein-cholesterol levels were significantly correlated with cholesterol absorption rates. APS up-regulated cholesterol-7α-hydroxylase and LDL-receptor gene expressions. These new findings identify APS as a potential natural cholesterol lowering agent, working through mechanisms distinct from statins.

  7. A critical role for the cholesterol-associated proteolipids PLP and M6B in myelination of the central nervous system.

    Science.gov (United States)

    Werner, Hauke B; Krämer-Albers, Eva-Maria; Strenzke, Nicola; Saher, Gesine; Tenzer, Stefan; Ohno-Iwashita, Yoshiko; De Monasterio-Schrader, Patricia; Möbius, Wiebke; Moser, Tobias; Griffiths, Ian R; Nave, Klaus-Armin

    2013-04-01

    The formation of central nervous system myelin by oligodendrocytes requires sterol synthesis and is associated with a significant enrichment of cholesterol in the myelin membrane. However, it is unknown how oligodendrocytes concentrate cholesterol above the level found in nonmyelin membranes. Here, we demonstrate a critical role for proteolipids in cholesterol accumulation. Mice lacking the most abundant myelin protein, proteolipid protein (PLP), are fully myelinated, but PLP-deficient myelin exhibits a reduced cholesterol content. We therefore hypothesized that "high cholesterol" is not essential in the myelin sheath itself but is required for an earlier step of myelin biogenesis that is fully compensated for in the absence of PLP. We also found that a PLP-homolog, glycoprotein M6B, is a myelin component of low abundance. By targeting the Gpm6b-gene and crossbreeding, we found that single-mutant mice lacking either PLP or M6B are fully myelinated, while double mutants remain severely hypomyelinated, with enhanced neurodegeneration and premature death. As both PLP and M6B bind membrane cholesterol and associate with the same cholesterol-rich oligodendroglial membrane microdomains, we suggest a model in which proteolipids facilitate myelination by sequestering cholesterol. While either proteolipid can maintain a threshold level of cholesterol in the secretory pathway that allows myelin biogenesis, lack of both proteolipids results in a severe molecular imbalance of prospective myelin membrane. However, M6B is not efficiently sorted into mature myelin, in which it is 200-fold less abundant than PLP. Thus, only PLP contributes to the high cholesterol content of myelin by association and co-transport. Copyright © 2013 Wiley Periodicals, Inc.

  8. Cholesterol in myelin biogenesis and hypomyelinating disorders.

    Science.gov (United States)

    Saher, Gesine; Stumpf, Sina Kristin

    2015-08-01

    The largest pool of free cholesterol in mammals resides in myelin membranes. Myelin facilitates rapid saltatory impulse propagation by electrical insulation of axons. This function is achieved by ensheathing axons with a tightly compacted stack of membranes. Cholesterol influences myelination at many steps, from the differentiation of myelinating glial cells, over the process of myelin membrane biogenesis, to the functionality of mature myelin. Cholesterol emerged as the only integral myelin component that is essential and rate-limiting for the development of myelin in the central and peripheral nervous system. Moreover, disorders that interfere with sterol synthesis or intracellular trafficking of cholesterol and other lipids cause hypomyelination and neurodegeneration. This review summarizes recent results on the roles of cholesterol in CNS myelin biogenesis in normal development and under different pathological conditions. This article is part of a Special Issue entitled Brain Lipids. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. Regulation of direct transintestinal cholesterol excretion in mice

    NARCIS (Netherlands)

    van der Velde, Astrid E.; Vrins, Carlos L. J.; van den Oever, Karin; Seemann, Ingar; Elferink, Ronald P. J. Oude; van Eck, Miranda; Kuipers, Folkert; Groen, Albert K.

    2008-01-01

    Biliary secretion is generally considered to be an obligate step in the pathway of excess cholesterol excretion from the body. We have recently shown that an alternative route exists. Direct transintestinal cholesterol efflux ( TICE) contributes significantly to cholesterol removal in mice. Our aim

  10. Regulation of direct transintestinal cholesterol excretion in mice

    NARCIS (Netherlands)

    van der Velde, Astrid E.; Vrins, Carlos L. J.; van den Oever, Karin; Seemann, Ingar; Oude Elferink, Ronald P. J.; van Eck, Miranda; Kuipers, Folkert; Groen, Albert K.

    2008-01-01

    Biliary secretion is generally considered to be an obligate step in the pathway of excess cholesterol excretion from the body. We have recently shown that an alternative route exists. Direct transintestinal cholesterol efflux (TICE) contributes significantly to cholesterol removal in mice. Our aim

  11. Elevated Remnant Cholesterol Causes Both Low-Grade Inflammation and Ischemic Heart Disease, Whereas Elevated Low-Density Lipoprotein Cholesterol Causes Ischemic Heart Disease Without Inflammation

    DEFF Research Database (Denmark)

    Varbo, Anette; Benn, Marianne; Tybjærg-Hansen, Anne

    2013-01-01

    Elevated nonfasting remnant cholesterol and low-density lipoprotein (LDL) cholesterol are causally associated with ischemic heart disease (IHD), but whether elevated nonfasting remnant cholesterol and LDL cholesterol both cause low-grade inflammation is currently unknown....

  12. HDL Cholesterol and Risk of Type 2 Diabetes

    DEFF Research Database (Denmark)

    Haase, Christiane L; Tybjærg-Hansen, Anne; Nordestgaard, Børge G

    2015-01-01

    Observationally, low levels of HDL cholesterol are consistently associated with increased risk of type 2 diabetes. Therefore, plasma HDL cholesterol increasing has been suggested as a novel therapeutic option to reduce the risk of type 2 diabetes. Whether levels of HDL cholesterol are causally as...

  13. Potentiating the antitumour response of CD8+ T cells by modulating cholesterol metabolism

    Science.gov (United States)

    Yang, Wei; Bai, Yibing; Xiong, Ying; Zhang, Jin; Chen, Shuokai; Zheng, Xiaojun; Meng, Xiangbo; Li, Lunyi; Wang, Jing; Xu, Chenguang; Yan, Chengsong; Wang, Lijuan; Chang, Catharine C. Y.; Chang, Ta-Yuan; Zhang, Ti; Zhou, Penghui; Song, Bao-Liang; Liu, Wanli; Sun, Shao-cong; Liu, Xiaolong; Li, Bo-liang; Xu, Chenqi

    2016-01-01

    CD8+ T cells have a central role in antitumour immunity, but their activity is suppressed in the tumour microenvironment1–4. Reactivating the cytotoxicity of CD8+ T cells is of great clinical interest in cancer immunotherapy. Here we report a new mechanism by which the antitumour response of mouse CD8+ T cells can be potentiated by modulating cholesterol metabolism. Inhibiting cholesterol esterification in T cells by genetic ablation or pharmacological inhibition of ACAT1, a key cholesterol esterification enzyme5, led to potentiated effector function and enhanced proliferation of CD8+ but not CD4+ T cells. This is due to the increase in the plasma membrane cholesterol level of CD8+ T cells, which causes enhanced T-cell receptor clustering and signalling as well as more efficient formation of the immunological synapse. ACAT1-deficient CD8+ T cells were better than wild-type CD8+ T cells at controlling melanoma growth and metastasis in mice. We used the ACAT inhibitor avasimibe, which was previously tested in clinical trials for treating atherosclerosis and showed a good human safety profile6,7, to treat melanoma in mice and observed a good antitumour effect. A combined therapy of avasimibe plus an anti-PD-1 antibody showed better efficacy than monotherapies in controlling tumour progression. ACAT1, an established target for atherosclerosis, is therefore also a potential target for cancer immunotherapy. PMID:26982734

  14. Perilla Oil Supplementation Ameliorates High-Fat/High-Cholesterol Diet Induced Nonalcoholic Fatty Liver Disease in Rats via Enhanced Fecal Cholesterol and Bile Acid Excretion

    Directory of Open Access Journals (Sweden)

    Ting Chen

    2016-01-01

    Full Text Available Recent experimental studies and clinical trials have shown that hepatic cholesterol metabolic disorders are closely related to the development of nonalcoholic fatty liver disease (NAFLD. The main goal of this study was to investigate the efficacy of the perilla oil rich in alpha-linolenic acid (ALA against NASH and gain a deep insight into its potential mechanisms. Rats were fed a high-fat/high-cholesterol diet (HFD supplement with perilla oil (POH for 16 weeks. Routine blood biochemical tests and histological staining illustrated that the perilla oil administration improved HFD-induced hyperlipidemia, reduced hepatic steatosis, and inhibited hepatic inflammatory infiltration and fibrosis. Perilla oil also increased fecal bile acid and cholesterol excretion. Hepatic RNA-Seq analysis found that the long time perilla oil supplement notably modified the gene expression involved in cholesterol metabolism. Our results implicate that, after long-term high level dietary cholesterol feeding, rat liver endogenous synthesis of cholesterol and cholesterol-rich low density lipoprotein uptake was significantly inhibited, and perilla oil did not modulate expression of genes responsible for cholesterol synthesis but did increase cholesterol removed from hepatocytes by conversion to bile acids and increased fecal cholesterol excretion.

  15. 7-Dehydrocholesterol (7-DHC), But Not Cholesterol, Causes Suppression of Canonical TGF-β Signaling and Is Likely Involved in the Development of Atherosclerotic Cardiovascular Disease (ASCVD).

    Science.gov (United States)

    Huang, Shuan Shian; Liu, I-Hua; Chen, Chun-Lin; Chang, Jia-Ming; Johnson, Frank E; Huang, Jung San

    2017-06-01

    For several decades, cholesterol has been thought to cause ASCVD. Limiting dietary cholesterol intake has been recommended to reduce the risk of the disease. However, several recent epidemiological studies do not support a relationship between dietary cholesterol and/or blood cholesterol and ASCVD. Consequently, the role of cholesterol in atherogenesis is now uncertain. Much evidence indicates that TGF-β, an anti-inflammatory cytokine, protects against ASCVD and that suppression of canonical TGF-β signaling (Smad2-dependent) is involved in atherogenesis. We had hypothesized that cholesterol causes ASCVD by suppressing canonical TGF-β signaling in vascular endothelium. To test this hypothesis, we determine the effects of cholesterol, 7-dehydrocholesterol (7-DHC; the biosynthetic precursor of cholesterol), and other sterols on canonical TGF-β signaling. We use Mv1Lu cells (a model cell system for studying TGF-β activity) stably expressing the Smad2-dependent luciferase reporter gene. We demonstrate that 7-DHC (but not cholesterol or other sterols) effectively suppresses the TGF-β-stimulated luciferase activity. We also demonstrate that 7-DHC suppresses TGF-β-stimulated luciferase activity by promoting lipid raft/caveolae formation and subsequently recruiting cell-surface TGF-β receptors from non-lipid raft microdomains to lipid rafts/caveolae where TGF-β receptors become inactive in transducing canonical signaling and undergo rapid degradation upon TGF-β binding. We determine this by cell-surface 125 I-TGF-β-cross-linking and sucrose density gradient ultracentrifugation. We further demonstrate that methyl-β-cyclodextrin (MβCD), a sterol-chelating agent, reverses 7-DHC-induced suppression of TGF-β-stimulated luciferase activity by extrusion of 7-DHC from resident lipid rafts/caveolae. These results suggest that 7-DHC, but not cholesterol, promotes lipid raft/caveolae formation, leading to suppression of canonical TGF-β signaling and atherogenesis. J

  16. Hypercholesterolemia: The Role of Schools in Cholesterol Screening.

    Science.gov (United States)

    Price, James H.; Casler, Suzanne M.

    1997-01-01

    Examines the prevalence of cardiovascular disease risk factors among children and adolescents, the pros and cons of cholesterol screening among youth, cholesterol assessments of at-risk youth, and the role of schools in cholesterol education and screening (focusing on comprehensive school health education and services). (SM)

  17. Cholesterol and myelin biogenesis.

    Science.gov (United States)

    Saher, Gesine; Simons, Mikael

    2010-01-01

    Myelin consists of several layers of tightly compacted membranes wrapped around axons in the nervous system. The main function of myelin is to provide electrical insulation around the axon to ensure the rapid propagation of nerve conduction. As the myelinating glia terminally differentiates, they begin to produce myelin membranes on a remarkable scale. This membrane is unique in its composition being highly enriched in lipids, in particular galactosylceramide and cholesterol. In this review we will summarize the role of cholesterol in myelin biogenesis in the central and peripheral nervous system.

  18. EFFECTS OF DIETARY CORN AND OLIVE OIL VERSUS COCONUT FAT ON BILIARY CHOLESTEROL SECRETION IN RATS

    NARCIS (Netherlands)

    SMIT, MJ; WOLTERS, H; TEMMERMAN, AM; KUIPERS, F; BEYNEN, AC; VONK, RJ

    1994-01-01

    We have studied the effects of dietary corn and olive oil versus coconut fat on bile formation and fluidity of hepatic plasma membranes in rats. After 4 weeks of feeding the purified diets containing 9% (w/w) of the test fats, there was no difference in plasma cholesterol concentration between the

  19. Abdominal Hernias, Giant Colon Diverticulum, GIST, Intestinal Pneumatosis, Colon Ischemia, Cold Intussusception, Gallstone Ileus, and Foreign Bodies: Our Experience and Literature Review of Incidental Gastrointestinal MDCT Findings

    OpenAIRE

    Di Grezia, G.; Gatta, G.; Rella, R.; Donatello, D.; Falco, G.; Grassi, R.; Grassi, R.

    2017-01-01

    Incidental gastrointestinal findings are commonly detected on MDCT exams performed for various medical indications. This review describes the radiological MDCT spectrum of appearances already present in the past literature and in today’s experience of several gastrointestinal acute conditions such as abdominal hernia, giant colon diverticulum, GIST, intestinal pneumatosis, colon ischemia, cold intussusception, gallstone ileus, and foreign bodies which can require medical and surgical interven...

  20. Regulation of biliary cholesterol secretion and reverse cholesterol transport

    NARCIS (Netherlands)

    Dikkers, Arne

    2016-01-01

    According to the World Health Organization the number one cause of death throughout the world is cardiovascular disease. Therefore, there is an urgent need for new therapeutic strategies to prevent and treat cardiovascular disease. One possible way is to target the HDL-driven reverse cholesterol

  1. Cholesterol: Its Regulation and Role in Central Nervous System Disorders

    Directory of Open Access Journals (Sweden)

    Matthias Orth

    2012-01-01

    Full Text Available Cholesterol is a major constituent of the human brain, and the brain is the most cholesterol-rich organ. Numerous lipoprotein receptors and apolipoproteins are expressed in the brain. Cholesterol is tightly regulated between the major brain cells and is essential for normal brain development. The metabolism of brain cholesterol differs markedly from that of other tissues. Brain cholesterol is primarily derived by de novo synthesis and the blood brain barrier prevents the uptake of lipoprotein cholesterol from the circulation. Defects in cholesterol metabolism lead to structural and functional central nervous system diseases such as Smith-Lemli-Opitz syndrome, Niemann-Pick type C disease, and Alzheimer’s disease. These diseases affect different metabolic pathways (cholesterol biosynthesis, lipid transport and lipoprotein assembly, apolipoproteins, lipoprotein receptors, and signaling molecules. We review the metabolic pathways of cholesterol in the CNS and its cell-specific and microdomain-specific interaction with other pathways such as the amyloid precursor protein and discuss potential treatment strategies as well as the effects of the widespread use of LDL cholesterol-lowering drugs on brain functions.

  2. Critical time window of neuronal cholesterol synthesis during neurite outgrowth.

    Science.gov (United States)

    Fünfschilling, Ursula; Jockusch, Wolf J; Sivakumar, Nandhini; Möbius, Wiebke; Corthals, Kristina; Li, Sai; Quintes, Susanne; Kim, Younghoon; Schaap, Iwan A T; Rhee, Jeong-Seop; Nave, Klaus-Armin; Saher, Gesine

    2012-05-30

    Cholesterol is an essential membrane component enriched in plasma membranes, growth cones, and synapses. The brain normally synthesizes all cholesterol locally, but the contribution of individual cell types to brain cholesterol metabolism is unknown. To investigate whether cortical projection neurons in vivo essentially require cholesterol biosynthesis and which cell types support neurons, we have conditionally ablated the cholesterol biosynthesis in these neurons in mice either embryonically or postnatally. We found that cortical projection neurons synthesize cholesterol during their entire lifetime. At all stages, they can also benefit from glial support. Adult neurons that lack cholesterol biosynthesis are mainly supported by astrocytes such that their functional integrity is preserved. In contrast, microglial cells support young neurons. However, compensatory efforts of microglia are only transient leading to layer-specific neuronal death and the reduction of cortical projections. Hence, during the phase of maximal membrane growth and maximal cholesterol demand, neuronal cholesterol biosynthesis is indispensable. Analysis of primary neurons revealed that neurons tolerate only slight alteration in the cholesterol content and plasma membrane tension. This quality control allows neurons to differentiate normally and adjusts the extent of neurite outgrowth, the number of functional growth cones and synapses to the available cholesterol. This study highlights both the flexibility and the limits of horizontal cholesterol transfer in vivo and may have implications for the understanding of neurodegenerative diseases.

  3. Sex Differences in the Hepatic Cholesterol Sensing Mechanisms in Mice

    Directory of Open Access Journals (Sweden)

    Ingemar Björkhem

    2013-09-01

    Full Text Available Cholesterol is linked to many multifactorial disorders, including different forms of liver disease where development and severity depend on the sex. We performed a detailed analysis of cholesterol and bile acid synthesis pathways at the level of genes and metabolites combined with the expression studies of hepatic cholesterol uptake and transport in female and male mice fed with a high-fat diet with or without cholesterol. Lack of dietary cholesterol led to a stronger response of the sterol sensing mechanism in females, resulting in higher expression of cholesterogenic genes compared to males. With cholesterol in the diet, the genes were down-regulated in both sexes; however, males maintained a more efficient hepatic metabolic flux through the pathway. Females had higher content of hepatic cholesterol but this was likely not due to diminished excretion but rather due to increased synthesis and absorption. Dietary cholesterol and sex were not important for gallbladder bile acids composition. Neither sex up-regulated Cyp7a1 upon cholesterol loading and there was no compensatory up-regulation of Abcg5 or Abcg8 transporters. On the other hand, females had higher expression of the Ldlr and Cd36 genes. These findings explain sexual dimorphism of cholesterol metabolism in response to dietary cholesterol in a high-fat diet in mice, which contributes to understanding the sex-basis of cholesterol-associated liver diseases.

  4. Lack of Cholesterol Awareness among Physicians Who Smoke

    Directory of Open Access Journals (Sweden)

    Richard E. Scranton

    2009-02-01

    Full Text Available Cigarette use is a known risk factor for the development of coronary artery disease (CAD as it adversely affects HDL cholesterol levels and promotes thrombogenesis. Smoking may also be associated with behavioral characteristics that potentiate the risk of CAD. A lack of cholesterol knowledge would indicate an aversion to a prevention-oriented lifestyle. Thus, our goal was to determine the association between tobacco use and knowledge of self-reported cholesterol among male physicians. Using the 1982 and follow-up questionnaires from the physician health study, we report the changes in the frequencies of awareness of self-reported total cholesterol and cardiovascular risk factors among the 22,067 participants. We classified physicians as being aware of their cholesterol if they reported a cholesterol level and unaware if the question was left unanswered. In 1997, 207 physicians were excluded, as the recorded cholesterol was not interpretable, leaving 21,860 for our follow up analyses. Using unadjusted logistic models, we determined the odds ratios (OR and 95% confidence intervals (CI of not reporting a cholesterol level in either 1982 or 1997 for each specified risk factor. We then evaluated whether the lack of cholesterol awareness at both time points was associated with the use of tobacco throughout the study. After 14-years of follow up, cholesterol awareness increased from 35.9 to 58.6 percent. During this period, the frequency of hypertension and hyperlipidemia treatment increased (13.5 to 40.5% and 0.57% to 19.6% respectively, as did the diagnosis of diabetes (2.40 to 7.79%. Behavioral characteristics such as a sedentary lifestyle and obesity also increased (27.8 to 42% and 43.5 to 53.5%, respectively, however the proportion of current smokers deceased from 11.1 to 4.05%. The percentages of individuals being unaware of their cholesterol decreased in all risk factor groups. However, individuals were likely to be unaware of their cholesterol

  5. Impact of Air Frying on Cholesterol and Fatty Acids Oxidation in Sardines: Protective Effects of Aromatic Herbs.

    Science.gov (United States)

    Ferreira, Fernanda S; Sampaio, Geni R; Keller, Laura M; Sawaya, Alexandra C H F; Chávez, Davy W H; Torres, Elizabeth A F S; Saldanha, Tatiana

    2017-12-01

    The high temperatures used to fry fish may induce thermo-oxidation of cholesterol, forming cholesterol oxidation products (COPs). COPs have been associated to coronary heart diseases, atherosclerosis, and other chronic diseases. Air fryers are an alternative thermal process technology to fry foods without oil, and are considered a healthier cooking method. This study is the 1st to evaluate the formation of COPs and the degradation of polyunsaturated fatty acids (PUFAs) in air-fried sardine fillets. Furthermore, we evaluated the effect of fresh herbs added as natural antioxidants to sardines subjected to air frying. Parsley (Petroselinum crispum), chives (Allium schoenoprasum L.), and a mixture of both herbs (cheiro-verde) were added in quantities of 0%, 2%, and 4%. Air frying significantly decreased the content of essential PUFAs, and increased the levels of COPs from 61.2 (raw) to 283 μg/g (P addition of 4% of cheiro-verde in air-fried sardines presented the best protective effect against lipid oxidation. Fish is an important source of essential lipids. However, oxidized cholesterol products, which are formed during thermal processing, are potential hazards to human health. Air fryers present an alternative thermal process for frying food without oil, and this method of cooking is considered to be more convenient and healthier This study shows that the air frying increased the formation of cholesterol oxidation products and decreased the essential polyunsaturated fatty acids in sardine fillets. However, the lipid oxidation is significantly reduced by adding fresh herbs, such as parsley (Petroselinum crispum), chives (Allium schoenoprasum L.), or a mixture of both herbs (cheiro-verde) that are natural antioxidants. © 2017 Institute of Food Technologists®.

  6. Whole body and tissue cholesterol turnover in the baboon

    International Nuclear Information System (INIS)

    Dell, R.B.; Mott, G.E.; Jackson, E.M.; Ramakrishnan, R.; Carey, K.D.; McGill, H.C. Jr.; Goodman, D.S.

    1985-01-01

    Cholesterol turnover was studied in four baboons by injecting [ 14 C]cholesterol 186 days and [ 3 H]cholesterol 4 days before necropsy, and fitting a two- or three-pool model to the resulting specific activity-time data. At necropsy, cholesterol mass and specific activity were determined for the total body and for many tissues. The principal aim of this study was to estimate the extent of cholesterol synthesis in the side pools of the model, by computing the amount of side pool synthesis needed to equal the measured total body cholesterol. Central pool synthesis varied from 61 to 89% of the total cholesterol production rate. Moreover, the finding that the measured total body cholesterol fell within the range obtained from the kinetic analysis by using reasonable assumptions, provides evidence for the physiological validity of the model. A second aim of this study was to explore cholesterol turnover in various tissues. A pool model predicts that rapidly turning over tissues will have higher specific activities at early times and lower specific activities at later times after injection of tracer relative to slowly turning over tissues, except where significant synthesis occurs. Results in all four baboons were similar. Turnover rates for the different tissues loosely fell into three groups which were turning over at fast, intermediate, and slow rates. Finally, the magnitude of variation of cholesterol specific activity was moderate for several distributed tissues (fat, muscle, arteries, and the alimentary tract), but was small for liver. Cholesterol turnover in serial biopsies of skin, muscle, and fat could, however, be fitted with a single pool to estimate tissue turnover rates

  7. Cholesterol in the retina: the best is yet to come

    Science.gov (United States)

    Pikuleva, Irina A.; Curcio, Christine A.

    2014-01-01

    Historically understudied, cholesterol in the retina is receiving more attention now because of genetic studies showing that several cholesterol-related genes are risk factors for age-related macular degeneration (AMD) and because eye pathology studies showing high cholesterol content of drusen, aging Bruch's membrane, and newly found subretinal lesions. The challenge before us is determining how the cholesterol-AMD link is realized. Meeting this challenge will require an excellent understanding these genes’ roles in retinal physiology and how chorioretinal cholesterol is maintained. In the first half of this review, we will succinctly summarize physico-chemical properties of cholesterol, its distribution in the human body, general principles of maintenance and metabolism, and differences in cholesterol handling in human and mouse that impact on experimental approaches. This information will provide a backdrop to the second part of the review focusing on unique aspects of chorioretinal cholesterol homeostasis, aging in Bruch's membrane, cholesterol in AMD lesions, a model for lesion biogenesis, a model for macular vulnerability based on vascular biology, and alignment of AMD-related genes and pathobiology using cholesterol and an atherosclerosis-like progression as unifying features. We conclude with recommendations for the most important research steps we can take towards delineating the cholesterol-AMD link. PMID:24704580

  8. What Can We Learn about Cholesterol's Transmembrane Distribution Based on Cholesterol-Induced Changes in Membrane Dipole Potential?

    DEFF Research Database (Denmark)

    Falkovich, Stanislav G.; Martinez-Seara, Hector; Nesterenko, Alexey M.

    2016-01-01

    Cholesterol is abundant in the plasma membranes of animal cells and is known to regulate a variety of membrane properties. Despite decades of research, the transmembrane distribution of cholesterol is still a matter of debate. Here we consider this outstanding issue through atomistic simulations ...

  9. Cholesterol monohydrate nucleation in ultrathin films on water

    DEFF Research Database (Denmark)

    Rapaport, H.; Kuzmenko, I.; Lafont, S.

    2001-01-01

    The growth of a cholesterol crystalline phase, three molecular layers thick at the air-water interface, was monitored by grazing incidence x-ray diffraction and x-ray reflectivity. Upon compression, a cholesterol film transforms from a monolayer of trigonal symmetry and low crystallinity to a tri......The growth of a cholesterol crystalline phase, three molecular layers thick at the air-water interface, was monitored by grazing incidence x-ray diffraction and x-ray reflectivity. Upon compression, a cholesterol film transforms from a monolayer of trigonal symmetry and low crystallinity...... in pathological lipid deposits....

  10. 2013 Cholesterol Guidelines Revisited: Percent LDL Cholesterol Reduction or Attained LDL Cholesterol Level or Both for Prognosis?

    NARCIS (Netherlands)

    Bangalore, Sripal; Fayyad, Rana; Kastelein, John J.; Laskey, Rachel; Amarenco, Pierre; Demicco, David A.; Waters, David D.

    2016-01-01

    The 2013 American College of Cardiology (ACC)/American Heart Association (AHA) guideline on the treatment of blood cholesterol recommends moderate- to high-intensity statins for patients with atherosclerotic cardiovascular disease but departs from the traditional treat-to-target approach. Whether

  11. Inclusion of Almonds in a Cholesterol-Lowering Diet Improves Plasma HDL Subspecies and Cholesterol Efflux to Serum in Normal-Weight Individuals with Elevated LDL Cholesterol.

    Science.gov (United States)

    Berryman, Claire E; Fleming, Jennifer A; Kris-Etherton, Penny M

    2017-08-01

    Background : Almonds may increase circulating HDL cholesterol when substituted for a high-carbohydrate snack in an isocaloric diet, yet little is known about the effects on HDL biology and function. Objective: The objective was to determine whether incorporating 43 g almonds/d in a cholesterol-lowering diet would improve HDL subspecies and function, which were secondary study outcomes. Methods: In a randomized, 2-period, crossover, controlled-feeding study, a diet with 43 g almonds/d (percentage of total energy: 51% carbohydrate, 16% protein, and 32% total and 8% saturated fat) was compared with a similar diet with an isocaloric muffin substitution (58% carbohydrate, 15% protein, and 26% total and 8% saturated fat) in men and women with elevated LDL cholesterol. Plasma HDL subspecies and cholesterol efflux from J774 macrophages to human serum were measured at baseline and after each diet period. Diet effects were examined in all participants ( n = 48) and in normal-weight (body mass index: almond diet, compared with the control diet, increased α-1 HDL [mean ± SEM: 26.7 ± 1.5 compared with 24.3 ± 1.3 mg apolipoprotein A-I (apoA-I)/dL; P = 0.001]. In normal-weight participants, the almond diet, relative to the control diet, increased α-1 HDL (33.7 ± 3.2 compared with 28.4 ± 2.6 mg apoA-I/dL), the α-1 to pre-β-1 ratio [geometric mean (95% CI): 4.3 (3.3, 5.7) compared with 3.1 (2.4, 4.0)], and non-ATP-binding cassette transporter A1 cholesterol efflux (8.3% ± 0.4% compared with 7.8% ± 0.3%) and decreased pre-β-2 (3.8 ± 0.4 compared with 4.6 ± 0.4 mg apoA-I/dL) and α-3 (23.5 ± 0.9 compared with 26.9 ± 1.1 mg apoA-I/dL) HDL ( P almonds for a carbohydrate-rich snack within a lower-saturated-fat diet may be a simple strategy to maintain a favorable circulating HDL subpopulation distribution and improve cholesterol efflux in normal-weight individuals with elevated LDL cholesterol. This trial was registered at clinicaltrials.gov as NCT01101230. © 2017

  12. Nonlinear associations between plasma cholesterol levels and neuropsychological function.

    Science.gov (United States)

    Wendell, Carrington R; Zonderman, Alan B; Katzel, Leslie I; Rosenberger, William F; Plamadeala, Victoria V; Hosey, Megan M; Waldstein, Shari R

    2016-11-01

    Although both high and low levels of total and low-density lipoprotein (LDL) cholesterol have been associated with poor neuropsychological function, little research has examined nonlinear effects. We examined quadratic relations of cholesterol to performance on a comprehensive neuropsychological battery. Participants were 190 older adults (53% men, ages 54-83) free of major medical, neurologic, and psychiatric disease. Measures of fasting plasma total and high-density lipoprotein (HDL) cholesterol were assayed, and LDL cholesterol was calculated. Participants completed neuropsychological measures of attention, executive function, memory, visuospatial judgment, and manual speed and dexterity. Multiple regression analyses examined cholesterol levels as quadratic predictors of each measure of cognitive performance, with age (dichotomized as Reproduction II ( b = -.0020, p = .026) and log of the Trail Making Test, Part B (b = .0001, p = .044). Quadratic associations between HDL cholesterol and cognitive performance were nonsignificant. Results indicate differential associations between cholesterol and neuropsychological function across different ages and domains of function. High and low total and LDL cholesterol may confer both risk and benefit for suboptimal cognitive function at different ages. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

  13. Intestinal Farnesoid X Receptor Controls Transintestinal Cholesterol Excretion in Mice

    NARCIS (Netherlands)

    Boer, J.F. de; Schonewille, M.; Boesjes, M.; Wolters, H.; Bloks, V.W.; Bos, T.; Dijk, T.H. van; Jurdzinski, A.; Boverhof, R.; Wolters, J.C.; Kuivenhoven, J.A.; Deursen, J.M.A. van; Elferink, R.P.; Moschetta, A.; Kremoser, C.; Verkade, H.J.; Kuipers, F.; Groen, A.K.

    2017-01-01

    BACKGROUND & AIMS: The role of the intestine in the maintenance of cholesterol homeostasis increasingly is recognized. Fecal excretion of cholesterol is the last step in the atheroprotective reverse cholesterol transport pathway, to which biliary and transintestinal cholesterol excretion (TICE)

  14. Lymphatic vasculature mediates macrophage reverse cholesterol transport in mice.

    Science.gov (United States)

    Martel, Catherine; Li, Wenjun; Fulp, Brian; Platt, Andrew M; Gautier, Emmanuel L; Westerterp, Marit; Bittman, Robert; Tall, Alan R; Chen, Shu-Hsia; Thomas, Michael J; Kreisel, Daniel; Swartz, Melody A; Sorci-Thomas, Mary G; Randolph, Gwendalyn J

    2013-04-01

    Reverse cholesterol transport (RCT) refers to the mobilization of cholesterol on HDL particles (HDL-C) from extravascular tissues to plasma, ultimately for fecal excretion. Little is known about how HDL-C leaves peripheral tissues to reach plasma. We first used 2 models of disrupted lymphatic drainage from skin--1 surgical and the other genetic--to quantitatively track RCT following injection of [3H]-cholesterol-loaded macrophages upstream of blocked or absent lymphatic vessels. Macrophage RCT was markedly impaired in both models, even at sites with a leaky vasculature. Inhibited RCT was downstream of cholesterol efflux from macrophages, since macrophage efflux of a fluorescent cholesterol analog (BODIPY-cholesterol) was not altered by impaired lymphatic drainage. We next addressed whether RCT was mediated by lymphatic vessels from the aortic wall by loading the aortae of donor atherosclerotic Apoe-deficient mice with [2H]6-labeled cholesterol and surgically transplanting these aortae into recipient Apoe-deficient mice that were treated with anti-VEGFR3 antibody to block lymphatic regrowth or with control antibody to allow such regrowth. [2H]-Cholesterol was retained in aortae of anti-VEGFR3-treated mice. Thus, the lymphatic vessel route is critical for RCT from multiple tissues, including the aortic wall. These results suggest that supporting lymphatic transport function may facilitate cholesterol clearance in therapies aimed at reversing atherosclerosis.

  15. Differential effects of gemfibrozil and fenofibrate on reverse cholesterol transport from macrophages to feces in vivo.

    Science.gov (United States)

    Rotllan, Noemí; Llaverías, Gemma; Julve, Josep; Jauhiainen, Matti; Calpe-Berdiel, Laura; Hernández, Cristina; Simó, Rafael; Blanco-Vaca, Francisco; Escolà-Gil, Joan Carles

    2011-02-01

    Gemfibrozil and fenofibrate, two of the fibrates most used in clinical practice, raise HDL cholesterol (HDLc) and are thought to reduce the risk of atherosclerotic cardiovascular disease. These drugs act as PPARα agonists and upregulate the expression of genes crucial in reverse cholesterol transport (RCT). In the present study, we determined the effects of these two fibrates on RCT from macrophages to feces in vivo in human apoA-I transgenic (hApoA-ITg) mice. [(3)H]cholesterol-labeled mouse macrophages were injected intraperitoneally into hApoA-ITg mice treated with intragastric doses of fenofibrate, gemfibrozil or a vehicle solution for 17days, and radioactivity was determined in plasma, liver and feces. Fenofibrate, but not gemfibrozil, enhanced [(3)H]cholesterol flux to plasma and feces of female hApoA-ITg mice. Fenofibrate significantly increased plasma HDLc, HDL phospholipids, hApoA-I levels and phospholipid transfer protein activity, whereas these parameters were not altered by gemfibrozil treatment. Unlike gemfibrozil, fenofibrate also induced the generation of larger HDL particles, which were more enriched in cholesteryl esters, together with higher potential to generate preβ-HDL formation and caused a significant increase in [(3)H]cholesterol efflux to plasma. Our findings demonstrate that fenofibrate promotes RCT from macrophages to feces in vivo and, thus, highlight a differential action of this fibrate on HDL. Copyright © 2010 Elsevier B.V. All rights reserved.

  16. Nitric oxide, cholesterol oxides and endothelium-dependent vasodilation in plasma of patients with essential hypertension

    Directory of Open Access Journals (Sweden)

    P. Moriel

    2002-11-01

    Full Text Available The objective of the present study was to identify disturbances of nitric oxide radical (·NO metabolism and the formation of cholesterol oxidation products in human essential hypertension. The concentrations of·NO derivatives (nitrite, nitrate, S-nitrosothiols and nitrotyrosine, water and lipid-soluble antioxidants and cholesterol oxides were measured in plasma of 11 patients with mild essential hypertension (H: 57.8 ± 9.7 years; blood pressure, 148.3 ± 24.8/90.8 ± 10.2 mmHg and in 11 healthy subjects (N: 48.4 ± 7.0 years; blood pressure, 119.4 ± 9.4/75.0 ± 8.0 mmHg.Nitrite, nitrate and S-nitrosothiols were measured by chemiluminescence and nitrotyrosine was determined by ELISA. Antioxidants were determined by reverse-phase HPLC and cholesterol oxides by gas chromatography. Hypertensive patients had reduced endothelium-dependent vasodilation in response to reactive hyperemia (H: 9.3 and N: 15.1% increase of diameter 90 s after hyperemia, and lower levels of ascorbate (H: 29.2 ± 26.0, N: 54.2 ± 24.9 µM, urate (H: 108.5 ± 18.9, N: 156.4 ± 26.3 µM, ß-carotene (H: 1.1 ± 0.8, N: 2.5 ± 1.2 nmol/mg cholesterol, and lycopene (H: 0.4 ± 0.2, N: 0.7 ± 0.2 nmol/mg cholesterol, in plasma, compared to normotensive subjects. The content of 7-ketocholesterol, 5alpha-cholestane-3ß,5,6ß-triol and 5,6alpha-epoxy-5alpha-cholestan-3alpha-ol in LDL, and the concentration of endothelin-1 (H: 0.9 ± 0.2, N: 0.7 ± 0.1 ng/ml in plasma were increased in hypertensive patients. No differences were found for ·NO derivatives between groups. These data suggest that an increase in cholesterol oxidation is associated with endothelium dysfunction in essential hypertension and oxidative stress, although ·NO metabolite levels in plasma are not modified in the presence of elevated cholesterol oxides.

  17. The hedgehog receptor patched is involved in cholesterol transport.

    Directory of Open Access Journals (Sweden)

    Michel Bidet

    Full Text Available Sonic hedgehog (Shh signaling plays a crucial role in growth and patterning during embryonic development, and also in stem cell maintenance and tissue regeneration in adults. Aberrant Shh pathway activation is involved in the development of many tumors, and one of the most affected Shh signaling steps found in these tumors is the regulation of the signaling receptor Smoothened by the Shh receptor Patched. In the present work, we investigated Patched activity and the mechanism by which Patched inhibits Smoothened.Using the well-known Shh-responding cell line of mouse fibroblasts NIH 3T3, we first observed that enhancement of the intracellular cholesterol concentration induces Smoothened enrichment in the plasma membrane, which is a crucial step for the signaling activation. We found that binding of Shh protein to its receptor Patched, which involves Patched internalization, increases the intracellular concentration of cholesterol and decreases the efflux of a fluorescent cholesterol derivative (BODIPY-cholesterol from these cells. Treatment of fibroblasts with cyclopamine, an antagonist of Shh signaling, inhibits Patched expression and reduces BODIPY-cholesterol efflux, while treatment with the Shh pathway agonist SAG enhances Patched protein expression and BODIPY-cholesterol efflux. We also show that over-expression of human Patched in the yeast S. cerevisiae results in a significant boost of BODIPY-cholesterol efflux. Furthermore, we demonstrate that purified Patched binds to cholesterol, and that the interaction of Shh with Patched inhibits the binding of Patched to cholesterol.Our results suggest that Patched may contribute to cholesterol efflux from cells, and to modulation of the intracellular cholesterol concentration. This activity is likely responsible for the inhibition of the enrichment of Smoothened in the plasma membrane, which is an important step in Shh pathway activation.

  18. Lycopene from two food sources does not affect antioxidant or cholesterol status of middle-aged adults

    Directory of Open Access Journals (Sweden)

    Baker RA

    2004-09-01

    Full Text Available Abstract Background Epidemiological studies have reported associations between reduced cardiovascular disease and diets rich in tomato and/or lycopene. Intervention studies have shown that lycopene-containing foods may reduce cholesterol levels and lipid peroxidation, factors implicated in the initiation of cardiovascular disease. The objective of this study was to determine whether consumption of lycopene rich foods conferred cardiovascular protection to middle-aged adults as indicated by plasma lipid concentrations and measures of ex vivo antioxidants. Methods Ten healthy men and women consumed a low lycopene diet with no added lycopene (control treatment or supplemented with watermelon or tomato juice each containing 20 mg lycopene. Subjects consumed each treatment for three weeks in a crossover design. Plasma, collected weekly was analyzed for total cholesterol, high density lipoprotein cholesterol (HDL-C and triglyceride concentrations and for the antioxidant biomarkers of malondialdehyde formation products (MDA, plasma glutathione peroxidase (GPX and ferric reducing ability of plasma (FRAP. Data were analyzed using Proc Mixed Procedure and associations between antioxidant and lipid measures were identified by Pearson's product moment correlation analysis. Results Compared to the control diet, the lycopene-containing foods did not affect plasma lipid concentrations or antioxidant biomarkers. Women had higher total cholesterol, HDL-C and triglyceride concentrations than did the men. Total cholesterol was positively correlated to MDA and FRAP while HDL-C was positively correlated to MDA and GPX. GPX was negatively correlated to triglyceride concentration. Conclusions The inclusion of watermelon or tomato juice containing 20 mg lycopene did not affect plasma lipid concentrations or antioxidant status of healthy subjects. However, plasma cholesterol levels impacted the results of MDA and FRAP antioxidant tests.

  19. Lycopene from two food sources does not affect antioxidant or cholesterol status of middle-aged adults.

    Science.gov (United States)

    Collins, J K; Arjmandi, B H; Claypool, P L; Perkins-Veazie, P; Baker, R A; Clevidence, B A

    2004-09-15

    Epidemiological studies have reported associations between reduced cardiovascular disease and diets rich in tomato and/or lycopene. Intervention studies have shown that lycopene-containing foods may reduce cholesterol levels and lipid peroxidation, factors implicated in the initiation of cardiovascular disease. The objective of this study was to determine whether consumption of lycopene rich foods conferred cardiovascular protection to middle-aged adults as indicated by plasma lipid concentrations and measures of ex vivo antioxidants. Ten healthy men and women consumed a low lycopene diet with no added lycopene (control treatment) or supplemented with watermelon or tomato juice each containing 20 mg lycopene. Subjects consumed each treatment for three weeks in a crossover design. Plasma, collected weekly was analyzed for total cholesterol, high density lipoprotein cholesterol (HDL-C) and triglyceride concentrations and for the antioxidant biomarkers of malondialdehyde formation products (MDA), plasma glutathione peroxidase (GPX) and ferric reducing ability of plasma (FRAP). Data were analyzed using Proc Mixed Procedure and associations between antioxidant and lipid measures were identified by Pearson's product moment correlation analysis. Compared to the control diet, the lycopene-containing foods did not affect plasma lipid concentrations or antioxidant biomarkers. Women had higher total cholesterol, HDL-C and triglyceride concentrations than did the men. Total cholesterol was positively correlated to MDA and FRAP while HDL-C was positively correlated to MDA and GPX. GPX was negatively correlated to triglyceride concentration. The inclusion of watermelon or tomato juice containing 20 mg lycopene did not affect plasma lipid concentrations or antioxidant status of healthy subjects. However, plasma cholesterol levels impacted the results of MDA and FRAP antioxidant tests.

  20. Biochemical and Bioimaging Evidence of Cholesterol in Acquired Cholesteatoma

    DEFF Research Database (Denmark)

    Thorsted, Bjarne; Bloksgaard, Maria; Groza, Alexandra

    2016-01-01

    : The results show that the total lipid content of the cholesteatoma matrix is similar to that of stratum corneum from skin and that the cholesteatoma matrix unquestionably contains cholesterol. The cholesterol content in the cholesteatoma matrix is increased by over 30% (w/w dry weight) compared to the control....... The cholesterol sulfate content is below 1% of the total lipids in both the cholesteatoma and the control. Cholesterol ester was reduced by over 30% when compared to the control. CONCLUSIONS: The content of cholesterol in the cholesteatoma matrix is significantly different from that in stratum corneum from skin...

  1. Interactions between an anticancer drug - edelfosine - and cholesterol in Langmuir monolayers

    International Nuclear Information System (INIS)

    Wiecek, Agata; Dynarowicz-Latka, Patrycja; Minones, J.; Conde, Olga; Casas, Matilde

    2008-01-01

    Edelfosine (1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine, abbr. Et-18-OCH 3 ) is a new generation anticancer drug based on a phospholipids-like structure. Since its mechanism of action is believed to be related to the lipids of cellular membrane, we have investigated the interactions between edelfosine and main mammalian sterol: cholesterol, using the Langmuir monolayer technique. The interactions have been analyzed by comparing the experimental curves with theoretical ones, obtained basing on the additivity rule. The observed contraction together with negative deviations from ideality observed on the mean molecular area (A 12 ) vs film composition plots proves the existence of strong attractive forces between edelfosine and cholesterol, which have been quantified with the excess free energy of mixing (ΔG exc ) values, calculated from the surface pressure-area isotherms datapoints. The most negative values of ΔG exc have been found for the mixture of equimolar composition, proving its highest thermodynamic stability and the existence of the strongest interactions between film components. Thus, it has been postulated that at the surface edelfosine and cholesterol form stable complexes of 1:1 stoichiometry. The analysis of the collapse pressure values for the investigated mixed monolayers proves that films of edelfosine mole fraction ≤ 0.5 are miscible within the whole range of surface pressures, while monolayers richer in edelfosine mix in the pressure region below ca. 37.6 mN/m, which corresponds to the collapse of pure edelfosine monolayer. At this very surface pressure, edelfosine is expelled from the mixed monolayer and the remaining film is composed by surface complexes of high stability. The hypothesis of complex formation explains the results performed in vitro on cell cultures, indicating that the increase of cholesterol content significantly reduces the uptake of edelfosine

  2. Colorimetric detection of cholesterol based on enzyme modified gold nanoparticles

    Science.gov (United States)

    Nirala, Narsingh R.; Saxena, Preeti S.; Srivastava, Anchal

    2018-02-01

    We develop a simple colorimetric method for determination of free cholesterol in aqueous solution based on functionalized gold nanoparticles with cholesterol oxidase. Functionalized gold nanoparticles interact with free cholesterol to produce H2O2 in proportion to the level of cholesterol visually is being detected. The quenching in optical properties and agglomeration of functionalized gold nanoparticles play a key role in cholesterol sensing due to the electron accepting property of H2O2. While the lower ranges of cholesterol (lower detection limit i.e. 0.2 mg/dL) can be effectively detected using fluorescence study, the absorption study attests evident visual color change which becomes effective for detection of higher ranges of cholesterol (lower detection limit i.e. 19 mg/dL). The shades of red gradually change to blue/purple as the level of cholesterol detected (as evident at 100 mg/dL) using unaided eye without the use of expensive instruments. The potential of the proposed method to be applied in the field is shown by the proposed cholesterol measuring color wheel.

  3. Use of stable isotopes in the study of human cholesterol metabolism

    International Nuclear Information System (INIS)

    Virelizier, H.; Hagemann, R.

    1979-01-01

    An experimental procedure based on the use of stable isotopes spiked molecules of cholesterol, allows the measurement in faecal cholesterol of the relative parts coming from the plasma by transfer (deuterium spiked molecules), from the non absorbed alimentary cholesterol ( 13 C spiked molecules) and from the external intestinal secretion (not labelled way). The patient receive a dose of D 8 (2, 2', 3, 4, 4', 6, 7, 7') cholesterol intravenously and an oral dose of 3,4 13 C cholesterol. The plasmatic cholesterol transfer is calculated from the ratio of the measured dilutions of the faecal and plasmatic D 8 cholesterol. The non absorbed cholesterol is estimated from the percentage of 13 C cholesterol measured in the faecal sterols within the six days following the oral dose ingestion. The D 8 cholesterol dilutions are measured using the GC-MS technique on the trimethylsilyl derivatives of cholesterol. Dilutions up to 1/4000 can be measured. The 13 C enriched faecal cholesterol is converted into CO 2 and the 13 C/ 12 C ratios are measured on a dual collector mass spectrometer. Dilutions up to 1/5000 of the 3,4 13 C cholesterol can be detected. The details of the analytical procedure are given

  4. Remnant cholesterol, low-density lipoprotein cholesterol, and blood pressure as mediators from obesity to ischemic heart disease.

    Science.gov (United States)

    Varbo, Anette; Benn, Marianne; Smith, George Davey; Timpson, Nicholas J; Tybjaerg-Hansen, Anne; Nordestgaard, Børge G

    2015-02-13

    Obesity leads to increased ischemic heart disease (IHD) risk, but the risk is thought to be mediated through intermediate variables and may not be caused by increased weight per se. To test the hypothesis that the increased IHD risk because of obesity is mediated through lipoproteins, blood pressure, glucose, and C-reactive protein. Approximately 90 000 participants from Copenhagen were included in a Mendelian randomization design with mediation analyses. Associations were examined using conventional measurements of body mass index and intermediate variables and using genetic variants associated with these. During ≤22 years of follow-up 13 945 participants developed IHD. The increased IHD risk caused by obesity was partly mediated through elevated levels of nonfasting remnant cholesterol and low-density lipoprotein cholesterol, through elevated blood pressure, and possibly also through elevated nonfasting glucose levels; however, reduced high-density lipoprotein cholesterol and elevated C-reactive protein levels were not mediators in genetic analyses. The 3 intermediate variables that explained the highest excess risk of IHD from genetically determined obesity were low-density lipoprotein cholesterol with 8%, systolic blood pressure with 7%, and remnant cholesterol with 7% excess risk of IHD. Corresponding observational excess risks using conventional body mass index were 21%, 11%, and 20%, respectively. The increased IHD risk because of obesity was partly mediated through elevated levels of nonfasting remnant and low-density lipoprotein cholesterol and through elevated blood pressure. Our results suggest that there may be benefit to gain by reducing levels of these risk factors in obese individuals not able to achieve sustained weight loss. © 2014 American Heart Association, Inc.

  5. The surface pressure dynamics and appearance of mixed monolayers of cholesterol and different sized polystyrenes at an air-water interface.

    Science.gov (United States)

    Mudgil, Poonam; Dennis, Gary R; Millar, Thomas J

    2005-02-15

    Synthetic polymers are increasingly being used in situations where they are designed to interact with biological systems. As a result, it is important to investigate the interactions of the polymers with biochemicals. We have used cholesterol, as an example of an important biological surfactant component, to study its interactions with polystyrene. Mixed monolayers of cholesterol and one of two different molecular weight polystyrenes were formed at an air-water interface to investigate their interactions and to determine whether the size of the polystyrene affected the interaction. The pressure-area (pi-A) isocycles of mixed monolayers of cholesterol and polystyrene MW 2700 or polystyrene MW32700 showed that strongest attractive interactions occur at high surface pressures and in polystyrene rich films. The excess area and excess free energy of mixing were most negative at high surface pressures and at high mole fraction of polystyrene. The most stable mixed monolayers were formed with X(PS2700) = 0.9 and X(PS32700) = 0.09. Microscopic observation of the mixed monolayers of cholesterol and polystyrene showed the formation of stable islands in the cholesterol/polystyrene mixtures. These observations, the nature of the inflection points in the isocycles, and the anomalous changes in free energy lead us to conclude that there is a stable rearrangement of polystyrene into compact islands when it is mixed with cholesterol. Any excess cholesterol is excluded from these islands and remains as a separate film surrounding the islands.

  6. A conserved degron containing an amphipathic helix regulates the cholesterol-mediated turnover of human squalene monooxygenase, a rate-limiting enzyme in cholesterol synthesis.

    Science.gov (United States)

    Chua, Ngee Kiat; Howe, Vicky; Jatana, Nidhi; Thukral, Lipi; Brown, Andrew J

    2017-12-08

    Cholesterol biosynthesis in the endoplasmic reticulum (ER) is tightly controlled by multiple mechanisms to regulate cellular cholesterol levels. Squalene monooxygenase (SM) is the second rate-limiting enzyme in cholesterol biosynthesis and is regulated both transcriptionally and post-translationally. SM undergoes cholesterol-dependent proteasomal degradation when cholesterol is in excess. The first 100 amino acids of SM (designated SM N100) are necessary for this degradative process and represent the shortest cholesterol-regulated degron identified to date. However, the fundamental intrinsic characteristics of this degron remain unknown. In this study, we performed a series of deletions, point mutations, and domain swaps to identify a 12-residue region (residues Gln-62-Leu-73), required for SM cholesterol-mediated turnover. Molecular dynamics and circular dichroism revealed an amphipathic helix within this 12-residue region. Moreover, 70% of the variation in cholesterol regulation was dependent on the hydrophobicity of this region. Of note, the earliest known Doa10 yeast degron, Deg1, also contains an amphipathic helix and exhibits 42% amino acid similarity with SM N100. Mutating SM residues Phe-35/Ser-37/Leu-65/Ile-69 into alanine, based on the key residues in Deg1, blunted SM cholesterol-mediated turnover. Taken together, our results support a model whereby the amphipathic helix in SM N100 attaches reversibly to the ER membrane depending on cholesterol levels; with excess, the helix is ejected and unravels, exposing a hydrophobic patch, which then serves as a degradation signal. Our findings shed new light on the regulation of a key cholesterol synthesis enzyme, highlighting the conservation of critical degron features from yeast to humans. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. Cholesterol Level: Can It Be Too Low?

    Science.gov (United States)

    ... total cholesterol level has been associated with some health problems. Doctors are still trying to find out more about the connection between low cholesterol and health risks. There is no consensus on how to ...

  8. Cholesterol granuloma of the petrous apex: CT diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Lo, W.W.M.; Solti-Bohman, L.G.; Brackmann, D.E.; Gruskin, P.

    1984-12-01

    Cholesterol granuloma of the petrous apex is a readily recognizable and treatable entity that is more common than previously realized. Cholesterol granuloma grows slowly in the petrous apex as a mass lesion until it produces hearing loss, tinnitus, vertigo, and facial twitching. Twelve cases of cholesterol granuloma of the petrous apex are illustrated; ten of these analyzed in detail, especially with respect to CT findings. A sharply and smoothly marginated expansile lesion in the petrous apex, isodense with plain and nonenhancing on CT, is in all probability a cholesterol granuloma. Preoperative recognition by CT is important for planning proper treatment.

  9. Cholesterol granuloma of the petrous apex: CT diagnosis

    International Nuclear Information System (INIS)

    Lo, W.W.M.; Solti-Bohman, L.G.; Brackmann, D.E.; Gruskin, P.

    1984-01-01

    Cholesterol granuloma of the petrous apex is a readily recognizable and treatable entity that is more common than previously realized. Cholesterol granuloma grows slowly in the petrous apex as a mass lesion until it produces hearing loss, tinnitus, vertigo, and facial twitching. Twelve cases of cholesterol granuloma of the petrous apex are illustrated; ten of these analyzed in detail, especially with respect to CT findings. A sharply and smoothly marginated expansile lesion in the petrous apex, isodense with plain and nonenhancing on CT, is in all probability a cholesterol granuloma. Preoperative recognition by CT is important for planning proper treatment

  10. Simultaneous measurement of cholesterol 7 alpha-hydroxylase activity by reverse-phase high-performance liquid chromatography using both endogenous and exogenous [4-14C]cholesterol as substrate

    International Nuclear Information System (INIS)

    Hylemon, P.B.; Studer, E.J.; Pandak, W.M.; Heuman, D.M.; Vlahcevic, Z.R.; Chiang, J.Y.

    1989-01-01

    The HPLC-spectrophotometric method for measuring cholesterol 7 alpha-hydroxylase activity was modified by using a C-18 reverse-phase column to separate 7 alpha-hydroxy-4-cholesten-3-one and 4-cholesten-3-one and by adding 7 beta-hydroxycholesterol to each reaction mixture as an internal recovery standard. With this method, we were able to simultaneously measure cholesterol 7 alpha-hydroxylase activity using endogenous cholesterol and exogenous [4- 14 C]cholesterol as substrate. Rat liver cytosol differentially stimulated (286%) the 7 alpha-hydroxylation of exogenous [4- 14 C]-cholesterol. In contrast, total cholesterol 7 alpha-hydroxylase activity was stimulated only 35% by cytosol. This method should prove useful for studying mechanisms of cholesterol delivery to cholesterol 7 alpha-hydroxylase

  11. Amperometric cholesterol biosensor based on the direct electrochemistry of cholesterol oxidase and catalase on a graphene/ionic liquid-modified glassy carbon electrode.

    Science.gov (United States)

    Gholivand, Mohammad Bagher; Khodadadian, Mehdi

    2014-03-15

    Cholesterol oxidase (ChOx) and catalase (CAT) were co-immobilized on a graphene/ionic liquid-modified glassy carbon electrode (GR-IL/GCE) to develop a highly sensitive amperometric cholesterol biosensor. The H2O2 generated during the enzymatic reaction of ChOx with cholesterol could be reduced electrocatalytically by immobilized CAT to obtain a sensitive amperometric response to cholesterol. The direct electron transfer between enzymes and electrode surface was investigated by cyclic voltammetry. Both enzymes showed well-defined redox peaks with quasi-reversible behaviors. An excellent sensitivity of 4.163 mA mM(-1)cm(-2), a response time less than 6s, and a linear range of 0.25-215 μM (R(2)>0.99) have been observed for cholesterol determination using the proposed biosensor. The apparent Michaelis-Menten constant (KM(app)) was calculated to be 2.32 mM. The bienzymatic cholesterol biosensor showed good reproducibility (RSDsascorbic acid and uric acid. The CAT/ChOx/GR-IL/GCE showed excellent analytical performance for the determination of free cholesterol in human serum samples. © 2013 Elsevier B.V. All rights reserved.

  12. Cholesterol, bile acid and triglyceride metabolism intertwined

    NARCIS (Netherlands)

    Schonewille, Marleen

    2016-01-01

    Hyperlipidemie wordt gekarakteriseerd door verhoogd plasma cholesterol en/of triglyceriden en sterk geassocieerd met het risico op cardiovasculaire aandoeningen. Dit proefschrift beschrijft onderzoek naar de regulatie van plasma cholesterol en triglyceriden concentraties en de achterliggende

  13. Preparation, extraction and dosage of labelled cholesterol (D and C{sup 14}); Preparation, extraction et dosage de cholesterol marque (D et C{sup 14})

    Energy Technology Data Exchange (ETDEWEB)

    Bugnard, L; Chevallier, F; Coursaget, J [Commissariat a l' Energie Atomique, Saclay(France). Centre d' Etudes Nucleaires

    1953-07-01

    We returned in this note the techniques that we used for the preparation of labelled cholesterol. The chemical exchange of hydrogen enabling to contain deutero-cholesterol until 4 percent deuterium. The biologic synthesis, done on living rats or on their liver maintained in survival, permits, on the other hand, to get active cholesterol from acetate of containing sodium of the carbon 14. We indicated the techniques of extraction and dosage of the marked cholesterol. The radioactivity is measured with a Geiger-Muller counter. (M.B.) [French] Nous avons rapporte dans cette note les techniques que nous avons utilisees pour la preparation de cholesterol marque. L'echange chimique d'hydrogene conduit a du deuterio-cholesterol pouvant contenir jusqu'a 4 pour cent de deuterium. La synthese biologique, effectuee sur des rats vivants ou sur leur foie maintenu en survie, permet, d'autre part, d'obtenir du cholesterol radio-actif a partir d'acetate de sodium contenant du carbone 14. Nous avons indique les techniques d'extraction et de dosage du cholesterol marque. Sa radioactivite est mesuree au compteur de Geiger-Muller. (M.B.)

  14. Cholesterol: Its Regulation and Role in Central Nervous System Disorders

    OpenAIRE

    Matthias Orth; Stefano Bellosta

    2012-01-01

    Cholesterol is a major constituent of the human brain, and the brain is the most cholesterol-rich organ. Numerous lipoprotein receptors and apolipoproteins are expressed in the brain. Cholesterol is tightly regulated between the major brain cells and is essential for normal brain development. The metabolism of brain cholesterol differs markedly from that of other tissues. Brain cholesterol is primarily derived by de novo synthesis and the blood brain barrier prevents the uptake of lipoprotein...

  15. Cholesterol turnover and metabolism in two patients with abetalipoproteinemia

    International Nuclear Information System (INIS)

    Goodman, D.S.; Deckelbaum, R.J.; Palmer, R.H.; Dell, R.B.; Ramakrishnan, R.; Delpre, G.; Beigel, Y.; Cooper, M.

    1983-01-01

    Total body turnover of cholesterol was studied in two patients with abetalipoproteinemia, a 32-year-old man and a 31-year-old woman. The patients received [14C]cholesterol intravenously, and the resulting specific activity-time curves (for 40 and 30 weeks, respectively) were fitted with a three-pool model. Parameters were compared with those from studies of cholesterol turnover in 82 normal and hyperlipidemic subjects. A three-pool model gave the best fit for the abetalipoproteinemic patients, as well as for the 82 previously studied subjects, suggesting general applicability of this model. Cholesterol production rates in the two abetalipoproteinemic subjects (0.82 and 0.89 g/day) were close to values predicted for persons of their body weight. Thus, total body turnover rate of cholesterol was quite normal in abetalipoproteinemia, confirming previous reports. Very low values (9.2 and 8.4 g) were found for M1, the size of the rapidly exchanging compartment pool 1, in the two abetalipoproteinemic subjects. These values were well below the values predicted (from the comparison study population) for normal persons of this size with low plasma cholesterol levels. For one patient, total body exchangeable cholesterol was very low, although not significantly below the predicted values for a person of his size. In the second patient, the observed estimate for total body exchangeable cholesterol was well within the range of values predicted for persons of her size with low to extremely low cholesterol levels

  16. Membrane cholesterol mediates the cellular effects of monolayer graphene substrates.

    Science.gov (United States)

    Kitko, Kristina E; Hong, Tu; Lazarenko, Roman M; Ying, Da; Xu, Ya-Qiong; Zhang, Qi

    2018-02-23

    Graphene possesses extraordinary properties that promise great potential in biomedicine. However, fully leveraging these properties requires close contact with the cell surface, raising the concern of unexpected biological consequences. Computational models have demonstrated that graphene preferentially interacts with cholesterol, a multifunctional lipid unique to eukaryotic membranes. Here we demonstrate an interaction between graphene and cholesterol. We find that graphene increases cell membrane cholesterol and potentiates neurotransmission, which is mediated by increases in the number, release probability, and recycling rate of synaptic vesicles. In fibroblasts grown on graphene, we also find an increase in cholesterol, which promotes the activation of P2Y receptors, a family of receptor regulated by cholesterol. In both cases, direct manipulation of cholesterol levels elucidates that a graphene-induced cholesterol increase underlies the observed potentiation of each cell signaling pathway. These findings identify cholesterol as a mediator of graphene's cellular effects, providing insight into the biological impact of graphene.

  17. FLIM studies of 22- and 25-NBD-cholesterol in living HEK293 cells: Plasma membrane change induced by cholesterol depletion

    Czech Academy of Sciences Publication Activity Database

    Ostašov, Pavel; Sýkora, Jan; Brejchová, Jana; Olžyńska, Agnieszka; Hof, Martin; Svoboda, Petr

    167-168, FEB-MAR (2013), s. 62-69 ISSN 0009-3084 R&D Projects: GA ČR(CZ) GAP207/12/0919 Institutional research plan: CEZ:AV0Z50110509 Institutional support: RVO:67985823 ; RVO:61388955 Keywords : cholesterol depletion * beta-Cyclodextrin * 22-NBD-cholesterol * 25-NBD-cholesterol * FLIM studies * intact HEK293 cells Subject RIV: CE - Biochemistry; CF - Physical ; Theoretical Chemistry (UFCH-W) Impact factor: 2.593, year: 2013

  18. Normal Non-HDL Cholesterol, Low Total Cholesterol, and HDL Cholesterol Levels in Sickle Cell Disease Patients in the Steady State: A Case-Control Study of Tema Metropolis.

    Science.gov (United States)

    Ephraim, Richard K D; Adu, Patrick; Ake, Edem; Agbodzakey, Hope; Adoba, Prince; Cudjoe, Obed; Agoni, Clement

    2016-01-01

    Background. Abnormal lipid homeostasis in sickle cell disease (SCD) is characterized by defects in plasma and erythrocyte lipids and may increase the risk of cardiovascular disease. This study assessed the lipid profile and non-HDL cholesterol level of SCD patients. Methods. A hospital-based cross-sectional study was conducted in 50 SCD patients, in the steady state, aged 8-28 years, attending the SCD clinic, and 50 healthy volunteers between the ages of 8-38 years. Serum lipids were determined by enzymatic methods and non-HDL cholesterol calculated by this formula: non-HDL-C = TC-HDL-C. Results. Total cholesterol (TC) ( p = 0.001) and high-density lipoprotein cholesterol (HDL-C) ( p < 0.0001) were significantly decreased in cases compared to controls. The levels of non-HDL-C, low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) were similar among the participants. The levels of decrease in TC and HDL were associated with whether a patient was SCD-SS or SCD-SC. Systolic blood pressure and diastolic blood pressure were each significantly associated with increased VLDL [SBP, p = 0.01, OR: 0.74 (CI: 0.6-0.93); DBP, p = 0.023, OR: 1.45 (CI: 1.05-2.0)]. Conclusion. Dyslipidemia is common among participants in this study. It was more pronounced in the SCD-SS than in SCD-SC. This dyslipidemia was associated with high VLDL as well as increased SBP and DBP.

  19. Influence of sex and age on fasting and post-prandial gallbladder volumes

    International Nuclear Information System (INIS)

    Pazzi, P.; Putinati, S.; Barbieri, D.; Trevisani, L.; Limoni, G.; Lupi, L.; Bighi, S.

    1989-01-01

    Aging and female sex are major risk factors for cholesterol gallstones: in addition to hepatic secretion of lithogenic bile, decreased gallbladder contractility may play a role in such physiological conditions. This study was aimed at evaluating the effect of age and sex on gallbladder kinetics in healthy subjects. Gallbladder volume was measured on the US images of 157 fasting subjects using the sum-of-cylinders method. No significant difference was observed between males and females. On the contrary, age was shown to have a significant positive correlation with fasting gallbladder volume, particulary in males. In a second group of 63 healthy volunteers gallbladder volumes were evaluated both before and after a standard meal. The subjects were grouped according to age, and fasting gallbladder volume appeared to be significantly greater in the groups formed by older people. Gallbladder volumes were compared in younger groups (under 35), and gallbladder emptying resulted to be much more complete in males than in females. On the contrary, no significant differences was observed between males and famales over50 - which suggests a possible role of sex - and age-related hormonal factors. The above changes in gallbladder function may facilitate bile stasis which might in turn contribute to the increased risk for cholesterol gallstones notoriously associated with advanced age and female sex

  20. Biochemical characterization of cholesterol-reducing Eubacterium.

    Science.gov (United States)

    Mott, G E; Brinkley, A W; Mersinger, C L

    1980-12-01

    We characterized two isolates of cholesterol-reducing Eubacterium by conducting conventional biochemical tests and by testing various sterols and glycerolipids as potential growth factors. In media containing cholesterol and plasmenylethanolamine, the tests for nitrate reduction, indole production, and gelatin and starch hydrolyses were negative, and no acid was produced from any of 22 carbohydrates. Both isolates hydrolyzed esculin to esculetin, indicating beta-glycosidase activity. In addition to plasmenylethanolamine, five other lipids which contain an alkenyl ether residue supported growth of Eubacterium strain 403 in a lecithin-cholesterol base medium. Of six steroids tested, cholesterol, cholest-4-en-3-one, cholest-4-en-3 beta-ol (allocholesterol), and androst-5-en-3 beta-ol-17-one supported growth of Eubacterium strain 403. All four steroids were reduced to the 3 beta-ol, 5 beta-H products. The delta 5 steroids cholest-5-en-3 alpha-ol (epicholesterol) and 22,23-bisnor-5-cholenic acid-3-beta-ol were not reduced and did not support growth of the Eubacterium strain.