Sample records for cholesterol gallstone formation

  1. Aspirin prevention of cholesterol gallstone formation in prairie dogs. (United States)

    Lee, S P; Carey, M C; LaMont, J T


    When prairie dogs (Cynomys ludovicianus) are fed a diet containing cholesterol, a marked increase in gallbladder mucin secretion parallels the evolution of cholesterol supersaturated bile. Gelation of mucin precedes the precipitation of cholesterol liquid and solid crystals and the development of gallstones. Aspirin given to prairie dogs inhibited mucin hypersecretion and gel accumulation and prevented gallstone formation without influencing the cholesterol content of supersaturated bile. This suggests that gallbladder mucin is a nucleation matrix for cholesterol gallstones.

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

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    Mary Carmen Vázquez


    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. High level of deoxycholic acid in human bile does not promote cholesterol gallstone formation

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    Ulf Gustafsson; Staffan Sahlin; Curt Einarsson


    AIM: To study whether patients with excess deoxycholic acid (DCA) differ from those with normal percentage of DCA with respect to biliary lipid composition and cholesterol saturation of gallbladder bile.METHODS: Bile was collected during operation through puncturing into the gallbladder from 122 cholesterol gallstone patients and 46 gallstone-free subjects undergoing cholecystectomy. Clinical data, biliary lipids, bile acid composition,presence of crystals and nucleation time were analyzed.RESULTS: A subgroup of gallstone patients displayeda higher proportion of DCA in bile than gallstone free subjects.By choosing a cut-off level of the 90th percentile, a group of 13 gallstone patients with high DCA levels (mean 50percent of total bile acids) and a large group of 109 patients with normal DCA levels (mean 21 percent of total bile acids)were obtained. The mean age of the patients with high DCA levels was higher than that of the group with normal levels (mean age: 62 years vs45 years) and so was the mean BMI (28.3 vs. 24.7). Plasma levels of cholesterol and triglycerides were slightly higher in the DCA excess groups compared with those in the normal DCA group. There was no difference in biliary lipid composition, cholesterol saturation, nucleation time or occurrence of cholesterol crystals in bile between patients with high and normal levels of DCA.CONCLUSION: Gallstone patients with excess DCA were of older age and had higher BMI than patients with normal DCA. The two groups of patients did not differ with respect to biliary lipid composition, cholesterol saturation, nucleation time or occurrence of cholesterol crystals. It is concluded that DCA in bile does not seem to contribute to gallstone formation in cholesterol gallstone patients.

  4. Spontaneous gallstone formation in deer mice: interaction of cholesterol, bile acids, and dietary fiber. (United States)

    Ginnett, Dorothy A; Theis, Jerold H; Kaneko, J Jerry


    A study of the physiologic and ecologic factors involved in a spontaneous seasonal gallstone cycle of deer mice (Peromyscus maniculatus gambelii) was conducted at the Tulelake National Wildlife Refuge (California, USA) from March 1991 to June 1992. The specific hypothesis examined was whether or not seasonal increases in dietary fiber intake provides the necessary conditions for a solubility defect, or supersaturation mechanism, resulting in precipitation of cholesterol gallstones. Results indicated that in addition to the seasonal gallstone prevalence cycle, these deer mice exhibit significant seasonal cycling in serum cholesterol, serum bile acids, fecal bile acids, and diet composition. These physiologic and dietary cycles were phase-advanced 3 mo over the gallstone prevalence cycle, indicating an approximate 3 mo time period for gallstone formation under field conditions. Further, seasonal dietary fiber (plant material and seeds) was positively correlated with both serum cholesterol and the fecal bile acids. This suggests that in wild deer mice, variations in dietary fiber may significantly affect the resorption of bile acids, thereby providing a potential physiologic and nutritional mechanism for spontaneous cholesterol gallstone formation.

  5. Effect of intestinal transit on the formation of cholesterol gallstones in hamsters

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    Ying Fan; Shuo-Dong Wu; Bei-Bei Fu


    BACKGROUND: The effect of "intestinal transit" has become a new ifeld of interest in the study of the pathogenesis of cholesterol gallstones. This study was undertaken to further test this notion and ascertain the relationship between impaired intestinal transit function and cholesterol gallstones. METHODS: A total of 64 hamsters were divided into 2 groups, experimental and control. Each was subdivided into 4 subgroups for sacriifce at different time. A high-cholesterol diet and a standard diet were fed to each group. The geometric center, which represents the intestinal transit function was calculated. RESULTS: The growth of all hamsters was normal. Cholesterol gallstones were found in 2 hamsters at the end of the 4th week. The geometric center values for the experimental and control groups were 2.3891±0.3923 vs. 2.7730±0.5283, at the end of week 3;1.8148±0.4312 vs. 3.2294±1.1613 at week 4;1.8451±0.3700 vs. 2.9075±0.3756 at week 5;and 1.8025±0.3413 vs. 3.0920±0.5622 at week 6. CONCLUSION: A high cholesterol diet can signiifcantly reduce the intestinal transit function and facilitate the formation of cholesterol gallstones.

  6. Gastrointestinal migrating motor complex during early stage of cholesterol gallstone formation in guinea pigs

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    Wang Ling; Bai Wenyuan; Ma Yongzhi; Gu Yong


    Objective: To determine the changes of gastrointestinal migrating motor complex (MMC) during the early stage of cholesterol gallstone formation. Methods: Totally 45 healthy adult guinea pigs were randomly and equally divided into 3 groups, that is, normal control, group B (1% cholesterol diet for 2 weeks) and group C (1% cholesterol diet for 4 weeks). Three pairs of silver electrodes were inserted into the gastric antrum, duodenum and jejunum of every animal respectively. Record of gastrointestinal MMC of these guinea pigs were recorded and analyzed.Gallbladder bile was taken to detect the formation of cholesterol gallstone. Results: There were only 29 guineapigs living. The MMC cycle time and the duration of phase Ⅱ were prolonged significantly and gradually compared with the control group (P<0.01), but the duration of phase Ⅲ became significantly and gradually shorter. Conclusion:During the early stage of cholesterol gallstone formation, the MMC cycle time and the duration of phase Ⅱ are prolonged and the duration of phase Ⅲ is shortened

  7. Characteristics of mRNA levels of hepatic key enzymes in cholesterol metabolism of genetically gallstone-susceptible mice

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    许国强; 赵力


    @@ Our previous study1 indicated that biliary cholesterol hypersecretion was the key pathophysiological defect of gallstone formation. Lith genes determine biliary cholesterol hypersecretion and susceptibility to cholesterol gallstone formation in C57L mice.

  8. Crystallogeny fundamentals of the cholesterol gallstone

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    Wu Jie; Zhou Jianli; He Lijun; Qu Xingang; Gu Lin; Yang Haimin


    The nucleation mechanism and crystal growth process of the cholesterol gallstone are studied and a systematic theory expounded by crystallogeny is proposed. Normal feed and stone-forming feed were used to raise guinea pigs in the control and stone-causing groups respectively. The state and transformation of liquid crystal vesicles, the appearance of crystal nuclei, and the formation of microcrystal grains were observed under a polarizing microscope during the experimental period. It was found that the liquid crystal vesicles in the bile of the control group were small, scattered, and always existed as single forms, and no shaped gallstone crystals were formed.While in the stone-causing group, liquid crystal vesicles grew to larger ones, and then aggregated to form large liquid crystal cells. Solid crystal growth along the edge of these liquid crystal cells formed microcrystal grains. These demonstrated that bile liquid crystal vesicles form the basic nuclei of cholesterol gallstone. Heterogeneous nucleation is the common process in the formation of crystal nuclei and crystal growth.

  9. Osteopontin Deficiency Alters Biliary Homeostasis and Protects against Gallstone Formation. (United States)

    Lin, Jing; Shao, Wei-Qing; Chen, Zong-You; Zhu, Wen-Wei; Lu, Lu; Cai, Duan; Qin, Lun-Xiu; Jia, Hu-Liang; Lu, Ming; Chen, Jin-Hong


    The precipitation of excess biliary cholesterol as solid crystals is a prerequisite for cholesterol gallstone formation, which occurs due to disturbed biliary homeostasis. Biliary homeostasis is regulated by an elaborate network of genes in hepatocytes. If unmanaged, the cholesterol crystals will aggregate, fuse and form gallstones. We have previously observed that the levels of osteopontin (OPN) in bile and gallbladder were reduced in gallstone patients. However, the role and mechanism for hepatic OPN in cholesterol gallstone formation is undetermined. In this study, we found that the expression of hepatic OPN was increased in gallstone patients compared with gallstone-free counterparts. Then, we observed that OPN-deficient mice were less vulnerable to cholesterol gallstone formation than wild type mice. Further mechanistic studies revealed that this protective effect was associated with alterations of bile composition and was caused by the increased hepatic CYP7A1 expression and the reduced expression of hepatic SHP, ATP8B1, SR-B1 and SREBP-2. Finally, the correlations between the expression of hepatic OPN and the expression of these hepatic genes were validated in gallstone patients. Taken together, our findings reveal that hepatic OPN contributes to cholesterol gallstone formation by regulating biliary metabolism and might be developed as a therapeutic target for gallstone treatments.


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    Rohini Bipin Bhadre


    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.

  11. Microstructural analysis of bile: relevance to cholesterol gallstone pathogenesis. (United States)

    Rubin, M; Pakula, R; Konikoff, F M


    The study of physical-chemical factors and pathways leading to cholesterol crystallization in bile has important clinical relevance. The major processes in cholesterol gallstone formation can be subdivided into nucleation, formation and precipitation of solid crystals (crystallization), crystal growth, crystal agglomeration and stone growth. A clear understanding of the microstructural events occurring during the earliest stages of these processes in bile is crucial for the identification of factors possibly delaying or preventing precipitation of cholesterol crystals and, therefore, gallstone formation in bile. Detection and characterization of microstructures in native and model biles can be achieved by both direct and indirect techniques. Direct imaging techniques provide more readily interpretable information, but sample preparation problems, particularly for electron microscopy, are a source of artifacts. Moreover, microscopic techniques provide only qualitative data without the possibility to quantitate or to analyse the composition of microstructures. Several indirect techniques have been used to obtain additional microstructural information about nucleating bile. These techniques have the disadvantage of often being model dependent in addition to constraints specific for each method. The systematic, judicious use of a combination of complementary direct and indirect techniques have led to a comprehensive understanding of the various microstructural processes and interactions occurring during bile secretion, flow in the biliary tract and storage in the gallbladder. This forms the basis for our current understanding of cholesterol nucleation, crystallization and gallstone formation.

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

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


    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...

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

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    Bilal O Al-Jiffry


    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.

  14. Raphanus sativus L. var niger as a source of phytochemicals for the prevention of cholesterol gallstones. (United States)

    Castro-Torres, Ibrahim Guillermo; De la O-Arciniega, Minarda; Gallegos-Estudillo, Janeth; Naranjo-Rodríguez, Elia Brosla; Domínguez-Ortíz, Miguel Ángel


    Raphanus sativus L. var niger (black radish) is a plant of the cruciferous family with important ethnobotanical uses for the treatment of gallstones in Mexican traditional medicine. It has been established that the juice of black radish decreases cholesterol levels in plasma and dissolves gallstones in mice. Glucosinolates, the main secondary metabolites of black radish, can hydrolyze into its respective isothiocyanates and have already demonstrated antioxidant properties as well as their ability to diminish hepatic cholesterol levels; such therapeutic effects can prevent the formation of cholesterol gallstones. This disease is considered a current problem of public health. In the present review, we analyze and discuss the therapeutic effects of the main glucosinolates of black radish, as well as the effects that this plant has on cholesterol gallstones disease.

  15. Effect of Larrea tridentata (creosote bush) on cholesterol gallstones and bile secretion in hamsters. (United States)

    Arteaga, Silvia; Carmona, Agustín; Luis, Juana; Andrade-Cetto, Adolfo; Cárdenas, René


    Larrea tridentata (Sesse and Moc. ex DC.) Coville is used for the treatment of gallstones in traditional Mexican medicine. The possible prevention or elimination of gallstones by ethanolic and aqueous extracts of the leaves and twigs of L. tridentata was tested in hamsters fed a rich carbohydrate, fat-free diet. In addition, the effects of the ethanolic extract and its main metabolite, nordihydroguaiaretic acid, on bile secretion in the perfused liver were tested. In the experiment on prevention of gallstones, the dry ethanolic extract at a level of 0.5% of diet completely inhibited gallstone formation, lowered biliary moles percent cholesterol and increased the proportion of chenodeoxycholic acid of hepatic bile. The dry aqueous extract at a level of 1% of diet did not affect gallstone frequency or biliary parameters. In the experiment on elimination of gallstones, the ethanolic extract significantly reduced gallstone frequency, gallbladder bile cholesterol concentration and moles percent cholesterol. Both the ethanolic extract and nordihydroguaiaretic acid had cholestatic effects in the perfused liver, with an EC50 of 34 and 28 mg dL-1, respectively, when perfused for 10 min. This effect was reversible with concentrations up to 40 mg dL-1. The results indicate that L. tridentata could be useful in the treatment of gallstone disease, however care must be taken due to its hepatotoxicity.

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

    DEFF Research Database (Denmark)

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


    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...

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

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    Agostino Di Ciaula


    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.

  18. Gallstones

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    Gabriel E Njeze


    Full Text Available 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. Data extracted from these sources included authors, country, year of publication, age and sex of patients, pathogenesis, risk factors for development of gallstones, racial distribution, presenting symptoms, complications and treatment. Gallstones occur worldwide, however it is commonest among North American Indians and Hispanics but low in Asian and African populations. High biliary protein and lipid concentrations are risk factors for the formation of gallstones, while gallbladder sludge is thought to be the usual precursor of gallstones. Biliary calcium concentration plays a part in bilirubin precipitation and gallstone calcification. Treatment of gallstones should be reserved for those with symptomatic disease, while prophylactic cholecystectomy is recommended for specific groups like children, those with sickle cell disease and those undergoing weight-loss surgical treatments. Treatment should be undertaken for a little percentage of patients with gallstones, as majority of those who harbor them never develop symptoms. The group that should undergo cholecystectomy include those with symptomatic gallstones, sickle cell disease patients with gall stones, and patients with morbid obesity who are undergoing laparotomy for other reasons.


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    Rajani Sharma


    Full Text Available Gallstone is one of the major gastrointestinal problems. There are many factors which leads to gallstone formation, like age, sex, obesity etc. Many factors are still under study. In our study we have tried to analyse our data of gallstone patients with the factors which have already been studied in past elsewhere but not in Jharkhand. In a data survey in Jharkhand region of India, we have tried to study different risk factors of gallstone formation. It was analysed that cholesterol rich diet especially nonvegetarian consumption (68% of patients were nonvegetarian and age are the major influencing factors. Gallstones are found more frequently in women than men. The ratio of male to female gallstone patients is about 1: 3. It was seen that 72.6% of the cases were in the age of 21-50. This means that with growing age incidence of gallstone increases. In our study we found out that genetics, diabetes and smoking are not much related to gallstone formation.

  20. Ezetimbe as potential treatment for cholesterol gallstones: The need for clinical trials

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    Mohamed; H; Ahmed


    Obesity is associated with insulin resistance, nonalcoholic fatty liver disease (NAFLD) and gallstones. High fat diets (unsaturated fats) rich in cholesterol have been demonstrated to produce not only gallstones but also NAFLD and insulin resistance. Interestingly, a high incidence of gallstones is being reported in association with insulin resistance and NAFLD. Laparoscopic cholecystectomy is the best definitive therapy for symptomatic gallbladder disease. Ezetimibe is a drug that inhibits the absorption o...

  1. Cholesterol 7alpha-hydrolase (CYP7A1) c.-278A>C promoter polymorphism in gallstone disease patients. (United States)

    Juzyszyn, Zygmunt; Kurzawski, Mateusz; Lener, Agnieszka; Modrzejewski, Andrzej; Pawlik, Andrzej; Droździk, Marek


    There is growing evidence that gallstone formation may be genetically determined. Cholesterol 7alpha-hydrolase (CYP7A1) is an enzyme that catalyzes the first, rate-limiting reaction of cholesterol catabolic pathway. Recently, a common c.-278A>C polymorphism (rs3808607:G>T) has been described in CYP7A1 gene, associated with altered plasma lipid levels. The aim of this study was to verify the finding that CYP7A1 polymorphism may be associated with gallstone disease. Frequency and distribution of the studied alleles did not differ significantly between the patients (-278C; minor allele frequency: 0.45) and the controls (0.48). No significant gender-related differences of allele frequencies or distribution were noted. We conclude that CYP7A1 promoter polymorphism is not a valuable marker of gallstone disease susceptibility in a Polish population.

  2. Progress in the study on the composition and formation mechanism of gallstone

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    Our serial studies from 1970s on chemical composition, structure determination and formation mechanism of gallstones were reviewed. The chemical component investigation of brown-pigment gallstone demonstrated that it consists of macromolecules such as proteins, glycoproteins, polysaccharides, bilirubin polymers and pigment polymers, and biomolecules such as cholesterol, bile salts, calcium salts of carbonate, phosphate, fatty acids and bilirubinate as well as various metal ions. The binding of metal ions with bile salts and bilirubin plays important roles in gallstone formation, i.e., calcium bilirubinate complex is the major constitute of brown-pigment gallstones, and copper bilirubinate complex is critical in the black color appearance of black-pigment gallstone. The cross section of many gallstones exhibits a concentric ring structure composed of various small particles with a fractal character. This is nonlinear phenomenon in gallstone formation. A typical model system of metal ions-deoxycholate (or cholate)-gel was chosen to mimic an in vitro pattern formation system. The experimental results suggested that a nonlinear scientific concept should be considered in understanding gallstone formation. Minor changes in the chemical composition and/or the microenvironment may lead to very different precipitate patterns with a variety of shapes, colors, appearances, and structures. A new model was suggested that periodical templets of periodical and fractal patterns were formed in the initial stage, then the spatio-temporal patterns grew gradually on it. Furthermore, the interaction between divalent metal ions and bile salts in vitro was investigated, and the results indicated that non-stoichiometric M(DC)2-NaDC mixed complexes with mixed micelles structure can be formed in physiological condition.

  3. Ezetimibe: Its Novel Effects on the Prevention and the Treatment of Cholesterol Gallstones and Nonalcoholic Fatty Liver Disease

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    Ornella de Bari


    Full Text Available The cholesterol absorption inhibitor ezetimibe can significantly reduce plasma cholesterol concentrations by inhibiting the Niemann-Pick C1-like 1 protein (NPC1L1, an intestinal sterol influx transporter that can actively facilitate the uptake of cholesterol for intestinal absorption. Unexpectedly, ezetimibe treatment also induces a complete resistance to cholesterol gallstone formation and nonalcoholic fatty liver disease (NAFLD in addition to preventing hypercholesterolemia in mice on a Western diet. Because chylomicrons are the vehicles with which the enterocytes transport cholesterol and fatty acids into the body, ezetimibe could prevent these two most prevalent hepatobiliary diseases possibly through the regulation of chylomicron-derived cholesterol and fatty acid metabolism in the liver. It is highly likely that there is an intestinal and hepatic cross-talk through the chylomicron pathway. Therefore, understanding the molecular mechanisms whereby cholesterol and fatty acids are absorbed from the intestine could offer an efficacious novel approach to the prevention and the treatment of cholesterol gallstones and NAFLD.

  4. Antilithogenic influence of dietary capsaicin and curcumin during experimental induction of cholesterol gallstone in mice. (United States)

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


    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.

  5. Determinants for gallstone formation - a new data cohort study and a systematic review with meta-analysis

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


    OBJECTIVE: Only few determinants of gallstone formation have been identified in cohort studies. The aim was to identify further determinants for gallstones in a Danish cohort and to perform a meta-analysis of results from existing cohorts. MATERIAL AND METHODS: Data from a cohort study was used...... on a prospective protocol, a systematic review of the literature was performed identifying all articles dealing with determinants of incident gallstones. Meta-analyses of comparable determinants were performed through fixed effect models. RESULTS: Participants with no gallstones at baseline and with at least one....... In addition, BMI was positively associated in men. The systematic review additionally identified associations for comorbidities, parity, and dietary factors. Meta-analysis confirmed the significant associations for incident gallstones and age, female sex, BMI, and non-HDL cholesterol. No significant...

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

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


    AIMS: Ezetimibe reduces plasma levels of low-density lipoprotein (LDL) cholesterol by inhibiting Niemann-Pick C1-Like protein 1 (NPC1L1), the transporter responsible for cholesterol uptake from the intestine into enterocytes and from the bile into hepatocytes. We tested the hypothesis that genetic...... 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...... score, LDL cholesterol decreased stepwise up to 3.5% (0.12 mmol/L) and total cholesterol up to 1.9% (0.11 mmol/L) (P-trend: 2 × 10(-12) and 2 × 10(-9)). The cumulative incidence by age of IVD decreased, while that of symptomatic gallstone disease increased as a function of increasing genotype score (P...

  7. Effect of beta-muricholic acid on the prevention and dissolution of cholesterol gallstones in C57L/J mice. (United States)

    Wang, David Q-H; Tazuma, Susumu


    This study investigated whether beta-muricholic acid, a natural trihydroxy hydrophilic bile acid of rodents, acts as a biliary cholesterol-desaturating agent to prevent cholesterol gallstones and if it facilitates the dissolution of gallstones compared with ursodeoxycholic acid (UDCA). For gallstone prevention study, gallstone-susceptible male C57L mice were fed 8 weeks with a lithogenic diet (2% cholesterol and 0.5% cholic acid) with or without 0.5% UDCA or beta-muricholic acid. For gallstone dissolution study, additional groups of mice that have formed gallstones were fed chow with or without 0.5% beta-muricholic acid or UDCA for 8 weeks. One hundred percent of mice fed the lithogenic diet formed cholesterol gallstones. Addition of beta-muricholic acid and UDCA decreased gallstone prevalence to 20% and 50% through significantly reducing biliary secretion rate, saturation index, and intestinal absorption of cholesterol, as well as inducing phase boundary shift and an enlarged Region E that prevented the transition of cholesterol from its liquid crystalline phase to solid crystals and stones. Eight weeks of beta-muricholic acid and UDCA administration produced complete gallstone dissolution rates of 100% and 60% compared with the chow (10%). We conclude that beta-muricholic acid is more effective than UDCA in treating or preventing diet-induced or experimental cholesterol gallstones in mice.

  8. DNA synthesis index: higher for human gallbladders with cholesterol gallstones than with pigment gallstones

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    Lamote, J.; Putz, P.; Francois, M.; Willems, G.


    (/sup 3/H)dThd uptake by the gallbladder epithelium was estimated in 33 patients with cholesterol stones, in 13 patients with pigment stones, and in 12 gallbladders without stones. Proliferative parameters were estimated by autoradiography after in vitro incubation with (/sup 3/H)-dThd. Stones were identified by quantitative infrared spectroscopy. The degree of inflammation of the gallbladder wall was estimated by a histologic scoring method. In the gallbladders containing cholesterol stones the DNA synthesis index (1.39 +/- 0.28%) was higher (P less than .01) than in the gallbladders without stones (0.19 +/- 0.04%). No significant increase in proliferative parameters was found in the gallbladders with pigment stones (0.24 +/- 0.06%). No correlation was found between total stone number, weight or volume, and the DNA synthesis index. No evidence was observed that inflammation could influence the epithelial cell proliferation. Something in the bile of patients with cholesterol stones rather than the physical presence of stones may be the cause of the variations observed.

  9. 豚鼠胆囊胆固醇结石形成过程中肠道传输功能下降的细胞及分子机制探讨%Cellular and molecular mechanism of slow intestinal transit during formation of cholesterol gallstones in guinea pig model

    Institute of Scientific and Technical Information of China (English)

    范莹; 吴硕东; 殷振华; 付倍蓓


    目的 探讨豚鼠胆囊胆固醇结石形成过程中肠道传输功能下降的细胞和分子机制及其与胆石形成的关系.方法 健康雄性豚鼠40只,4周龄,体质量120~ 125 g.将其随机分为实验组与对照组,每组20只.实验组给予致石饲料(胆固醇含量2%),对照组给予正常颗粒饲料.8周造模结束后,用逆转录聚合酶链反应(RT-PCR)检测小肠组织中c-kit及scf的mRNA的表达情况,利用末端回肠全层铺片免疫荧光化学染色及激光共聚焦显微镜观察各组Cajal样间质细胞(ICCs)数量的变化.结果 RT-PCR结果显示,与对照组相比,实验组豚鼠小肠c-kit(0.316±0.056 vs 0.912±0.103;t=6.582,P<0.01)和scf(0.499±0.012 vs 0.899±0.124;t=6.163,P<0.01)的mRNA水平的表达量下降;对照组豚鼠回肠ICCs平均阳性面积为(56.24±2.68)%,实验组为(22.26±1.14)%,较对照组明显降低(t=15.256,P<0.01).结论 饮食诱导的豚鼠胆囊胆固醇结石形成过程中,小肠c-kit和scf基因mRNA表达水平下降,ICCs数量明显减少.c-kit/scf通路抑制可能参与胆囊胆固醇结石的形成过程中肠道传输功能下降的发生.%Objective To investigate the cellular and molecular mechanism of slow intestinal transit during the formation of cholesterol gallstones in guinea pig model, and study its relationship with gallstone formation. Methods Forty healthy male guinea pigs of 4-week old and 120 - 150 g body weight were randomly divided into 2 groups, namely experimental group and control group(n= 20). The experimental group was fed high cholesterol diet (cholesterol 2 %), and control group fed normal diet. The guinea pigs were sacrificed after 8 weeks. Reverse transcription polymerase chain reaction(RT-PCR) was used to determine the expression of c-kit and scf mRNA. Change in the numbers of interstitial Cajal cells(ICCs) in terminal ileum was observed by immunohistochemical method. Results Compared with the control group, the mRNA expression of c-kit(0

  10. Investigation of Surface-Enhanced Raman Spectra of Human Gallstones on Colloidal Silver

    Institute of Scientific and Technical Information of China (English)


    The surface-enhanced Raman scatterihg (SERS) spectra of human gallstones is investigated. Complicated Raman bands were due to multiple components that include bilirubin, bilirubinate salts, cholesterol, fatty salts and proteins. The results suggest that besides bilirubin and cholesterol, fatty salts and proteins may play an important role in the formation of gallstone. The experimental data supply an useful information for the research of the formation mechanism of gallstones.

  11. Progress in the study on the composition and formation mechanism of gallstone

    Institute of Scientific and Technical Information of China (English)

    SUN; Ying


    photoacoustic spectroscopy of dental calculus, Microchim. Acta, 1988, 2: 133-136.[24]Taylor, D. R., Crowther, R. S., Wu, J. G. et al., Calcium carbonate in cholesterol gallstones: polymorphism, distribution,and hypotheses about pathogenesis, Hepatology, 1995, 22(2): 488-496.[25]Liu, J. H., Soloway, R. D., Wu, J. G. et al., How does Ca bilirubinate bind to protein in gallstones? Gastroenterology, 1994,106(4): A346.[26]Wagner, A. J., Wu, J. G., Soloway, R. D. et al., Does the structure of calcium bilirubinate provide special properties contributing to its precipitation in bile? A comparison with other metal bilirubinates by Fourier transform infrared spectroscopy (FT-IR), Hepatology, 1987, 7(5): 1138-1139.[27]Wu, J. G., Soloway, R. D., Xu, D. F. et al., FT-IR study on calcium ions binding to bilirubin, 7th International Conference on FTS, Abstract Program p2.6, SPIE, 1989, 1145: 264.[28]Yang, Z. L., Soloway, R. D., Wu, J. G. et al., Calcium binds with both the carboxyl and pyrrole groups of bilirubinate in vitro formation of non-stoichoimetric salt, Gastroenterology, 1991, 100(5): A813.[29]Yang, B. J., Wu, J. G., Soloway, R. D. et al., Normal coordinate analysis of bilirubin vibrational spectra: effects of intramolecular hydrogen bonding, Spectrochimica Acta, 1993, 49A(12): 1735-1746.[30]Soloway, R. D., Wu, J. G., Yang, Z. L. et al., Why does Ca++ vary from 3 to 12% in non-stoichiometric calcium bilirubinates? Gastroenterology, 1994, 106(4): A359.[31]Wu, E., Wu, J. G., Xu, G. X. et al., Gallstone analysis by ESR spectroscopy, Chinese Science Bulletin, 1989, 34(23):1996-2000.[32]Guo. H.. Soloway, R. D., Wu, J. G. et al., Dependence of equilibrium swelling on an interaction between calcium bilirubinate and protein, Gastroenterology, 1990, 98(5): A249.[33]Shen G. R., Li, W. H., Wu, J. G. et al., Measurement and characterization of black gallstone composition using extraction with serial solvents, Gastroenterology, 1997, 112(4): A523.[34

  12. Relationship between bilirubin free radical and formation of pigment gallstone

    Institute of Scientific and Technical Information of China (English)

    Xiang-Tao Liu; Jian Hu


    In this paper, we summarize the main progresses made inour group in the field of the mechanism of pigment gallstoneformation. It was found that after treetment with freeradicals, bilirubin (BR) was changed into free radical itself,and a semiquinone free radical and a superoxide free radicalbound with metal were recognized, which was detected byESR (electron spin resonance). By the meana of NMR(nuclear magnetic resonance) and IR (Infra-red spectra), itwas postulated that bilirubin polymerized through thereaction between the vinyl group and the hydroxyl groupunder the attack of free radicals. It was also found thatbilirubin free radical were liable to calcify in a kinetic study.Because of its chemical properties, bilirubin free radical wasshown to be cytotoxic to hepetocyte, which wasdemonstrated based on the following facts: induction ofphospholipid peroxidation (LPO), leakage of lactatedehydrogenase (LDH) and decrease of glutathione. As tothe mechanism of bilirubin-induced cytotoxicity, it waspostulated that the main target of bilirubin free radical wasthe cell membrane, including phospholipid and membranebound proteins, especially spectrin, a content ofcytoskeleton. Based on the results mentioned above, it wasdeduced that bilirubin free radical is the key factor thatinitiates and promotes the formation of pigment gallstone,which is consistent with other researches in recent years.

  13. Retroperitoneal Abscess Formation as a Result of Spilled Gallstones during Laparoscopic Cholecystectomy: An Unusual Case Report

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    Grigoris Chatzimavroudis


    Full Text Available One of the complications of laparoscopic cholecystectomy for gallstone disease that seems to exceed that of the traditional open method is the gallbladder perforation and gallstone spillage. Its incidence can occur in up to 40% of patients, and in most cases its course is uneventful. However in few cases an abdominal abscess can develop, which may lead to significant morbidity. Rarely an abscess formation due to spilled and lost gallstones may occur in the retroperitoneal space. We herein report the case of a female patient who presented with clinical symptoms of sepsis six months following laparoscopic cholecystectomy. Imaging investigations revealed the presence of a retroperitoneal abscess due to retained gallstones. Due to patient’s decision to refuse abscess’s surgical drainage, she underwent CT-guided drainage. The 24-month followup of the patient has been uneventful, and the patient remains in good general condition.

  14. Possible relationship between intestinal barrier function and formation of pigment gallstones in hamsters

    Institute of Scientific and Technical Information of China (English)

    Ying Fan; Shuo-Dong Wu; Lei Sun; Bei-Bei Fu; Yang Su


    BACKGROUND: The presence of bacteria in bile is an important factor in the formation of pigment gallstones. The bile of healthy people is sterile and bacteria in the biliary system come from endogenous infection from the gut. Yet, the route of bacterial translocation into the bile duct is still unclear. Theoretically, two routes exist:one is through the intestinal barrier and the other is by direct relfux from the sphincter of Oddi. This study was undertaken to explore the relationship between the effectiveness of intestinal barrier and the formation of pigment gallstones in hamsters. METHODS: Thirty-two hamsters were divided into an experimental and a control group, with 16 hamsters in each group. A low protein and high cellulose diet was given for 6 weeks to induce the formation of pigment gallstones in the experimental group (PS) and a normal diet was given to the control group (CON). Morphological changes, changes in the levels of serum endotoxin and diamine oxidase, and changes in the numbers of B lymphocytes, plasma cells and secretory immunoglobin A (sIgA) in the intestinal mucosa were assessed after 6 weeks. RESULTS:Four hamsters died during lithogenesis and body weight decreased in the PS group. Pigment gallstones were found in 11 hamsters at the end of the experiment, giving a lithogenesis rate of 91.67%. The serum endotoxin level before and after gallstone formation in the PS group was 0.2960±0.1734 U/ml and 8.2964±4.6268 U/ml, respectively (P CONCLUSIONS:A low protein and high cellulose diet can markedly reduce intestinal barrier function and facilitate the formation of pigment gallstones. The decrease of intestinal barrier function may take part in the formation of pigment gallstones.

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

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    Cong Lin


    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.

  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;


    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....... 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...... linkage disequilibrium (r(2) = 0.95). [(3) H]-cholesterol export assays of allelic constructs harboring these genetic candidate variants demonstrated increased transport activity (3.2-fold, P = 0.003) only for the ABCG8-19H variant, which was also superior in nested logistic regression models in German (P...

  17. Inhibition of cholesterol crystallization under bilirubin deconjugation: partial characterization of mechanisms whereby infected bile accelerates pigment stone formation. (United States)

    Nakai, Kuniharu; Tazuma, Susumu; Nishioka, Tomoji; Chayama, Kazuaki


    Pigment gallstones have been reported to be closely associated with biliary tract infection. We previously reported that addition of unconjugated bilirubin (UCB), which is deconjugated by beta-glucuronidase in infected bile, could enhance cholesterol crystal formation in supersaturated model bile (MB). The present study evaluated the effect of beta-glucuronidase on the processes of pigment gallstone formation and cholesterol crystallization. Supersaturated MB (taurocholate/lecithin/cholesterol at 71:18:11, a total lipid concentration of 10.0 g/dl and a cholesterol saturation index (CSI) of 2.0) and native rat bile were mixed at a ratio of 3:1. Then, mixed bile was incubated with or without beta-glucuronidase and changes of the following parameters were investigated over time: (1) the UCB/total bilirubin ratio; (2) cholesterol crystal formation; (3) the precipitate weight and the cholesterol concentration in the precipitate and supernatant; and (4) the lipid distribution of vesicles in the supernatant. Compared with beta-glucuronidase-free bile, (1) beta-glucuronidase-containing bile showed a significant increase of the UCB/total bilirubin ratio, (2) as well as a significantly longer nucleation time (96+/-17.0 vs. 114+/-20.0) and fewer cholesterol crystals. (3) The precipitate weight and the cholesterol concentration in the precipitate were significantly increased, while the cholesterol concentration in supernatant was decreased. (4) When mixed bile was incubated with beta-glucuronidase, the cholesterol concentration in the vesicles was lower than in bile without beta-glucuronidase. The precipitate weight and the cholesterol concentration in the precipitate was increased by incubation with beta-glucuronidase, while cholesterol concentration was decreased in the supernatant (especially in the vesicles). This means that bile vesicles were more stable and it was more difficult for cholesterol crystals to form. Thus, the presence of beta-glucuronidase may inhibit the

  18. Genetic variants involved in gallstone formation and capsaicin metabolism,and the risk of gallbladder cancer in Chilean women

    Institute of Scientific and Technical Information of China (English)

    Sergio; Báez; Yasuo; Tsuchiya; Alfonso; Calvo; Martha; Pruyas; Kazutoshi; Nakamura; Chikako; Kiyohara; Mari; Oyama; Masaharu; Yamamoto


    AIM:To determine the effects of genetic variants associated with gallstone formation and capsaicin (a pungent component of chili pepper) metabolism on the risk of gallbladder cancer (GBC).METHODS: A total of 57 patients with GBC, 119 patients with gallstones, and 70 controls were enrolled in this study. DNA was extracted from their blood or paraffi n block sample using standard commercial kits. The statuses of the genetic variants were assayed using Taqman SNP Genotyping Assays or Custom Taqman SNP Genotypi...

  19. Formation of cholesterol bilayer domains precedes formation of cholesterol crystals in cholesterol/dimyristoylphosphatidylcholine membranes: EPR and DSC studies. (United States)

    Mainali, Laxman; Raguz, Marija; Subczynski, Witold K


    Saturation-recovery EPR along with DSC were used to determine the cholesterol content at which pure cholesterol bilayer domains (CBDs) and cholesterol crystals begin to form in dimyristoylphosphatidylcholine (DMPC) membranes. To preserve compositional homogeneity throughout the membrane suspension, lipid multilamellar dispersions were prepared using a rapid solvent exchange method. The cholesterol content increased from 0 to 75 mol %. With spin-labeled cholesterol analogues, it was shown that the CBDs begin to form at ~50 mol % cholesterol. It was confirmed by DSC that the cholesterol solubility threshold for DMPC membranes is detected at ~66 mol % cholesterol. At levels above this cholesterol content, monohydrate cholesterol crystals start to form. The major finding is that the formation of CBDs precedes formation of cholesterol crystals. The region of the phase diagram for cholesterol contents between 50 and 66 mol % is described as a structured one-phase region in which CBDs have to be supported by the surrounding DMPC bilayer saturated with cholesterol. Thus, the phase boundary located at 66 mol % cholesterol separates the structured one-phase region (liquid-ordered phase of DMPC with CBDs) from the two-phase region where the structured liquid-ordered phase of DMPC coexists with cholesterol crystals. It is likely that CBDs are precursors of monohydrate cholesterol crystals.

  20. Metastable and equilibrium phase diagrams of unconjugated bilirubin IXα as functions of pH in model bile systems: Implications for pigment gallstone formation. (United States)

    Berman, Marvin D; Carey, Martin C


    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.

  1. Role of nucleation of bile liquid crystal in gallstone formation

    Institute of Scientific and Technical Information of China (English)

    Hai-Ming Yang; Jie Wu; Jin-Yi Li; Lin Gu; Min-Fei Zhou


    AIM: To explore the role of bile liquid crystal in the process of gallbladder stone formation and to provide bases for preventing and treating cholelithiasis.METHODS: 46 guinea pigs, half males and half females,were randomly divided into control group and stone-causing group. Normal feed and stoneleading feed were used respectively to raise guinea pigs in the control group and stone-causing group. The guinea pigs were killed in three batches during the raising period. Under polarizing microscope, the pattern changes of bile liquid crystal in the gallbladder biles of the guinea pigs in the control group and stone-causing group were dynamicly observed respectively in single-blind trial.RESULTS: It was found that there were few crystals in the guinea pigs′biles of the control group, and their Malta cross was small and scattered, and existed in single form. With the increase of the feeding days, bile liquid crystals grew and Malta cross became bigger with their distribution densified, denser somewhere, but always existed in single form. While those of the stone-causing group had more bile liquid crystals, Malta cross was big and merged in strings.With the increase of the feeding days, bile liquid crystals grew in amount and strings of Malta cross increased and became bigger. The crosses in strings were arranged more and more regularly and they gradually changed into stone crystals.CONCLUSION: Formation of gallbladder stone is a process of nucleation from different substances, and the causing-stone gallbladder bile is a constantly supersaturated solution, and bile liquid crystal is a nucleation factor in the formation of gallbladder stones. The process of nucleation includes gathering, merging and phase-changing of bile liquid crystals.The process of gathering, merging of bile liquid crystal is the key to nucleation.

  2. ApoB-100, ApoE and CYP7A1 gene polymorphisms in Mexican patients with cholesterol gallstone disease

    Institute of Scientific and Technical Information of China (English)

    Sánchez-Cuén; Jaime; Aguilar-Medina; Maribel; Arámbula-Meraz; Eliakym; Romero-Navarro; José; Granados; Julio; Sicairos-Medina; Laura; Ramos-Payán; Rosalío


    AIM: To determine the possible association of the ApoB100 (Xba Ⅰ ), ApoE (Hha Ⅰ ) and CYP7A1 (Bsa Ⅰ ) gene polymorphisms, with the development of cholesterol gallstone disease (GD) in a Mexican population. METHODS: The polymorphisms were analyzed by polymerase chain reaction followed by restriction fragment length polymorphism, in two groups matched by ethnicity, age and sex: patients with GD (n = 101) and stone-free control subjects (n = 101). RESULTS: Allelic frequencies in patients and controls were: 34....

  3. Hepatic Mttp deletion reverses gallstone susceptibility in L-Fabp knockout mice. (United States)

    Xie, Yan; Fung, Ho Yee Joyce; Newberry, Elizabeth P; Kennedy, Susan; Luo, Jianyang; Crooke, Rosanne M; Graham, Mark J; Davidson, Nicholas O


    Previous studies demonstrated that L-Fabp KO mice are more susceptible to lithogenic diet (LD)-induced gallstones because of altered hepatic cholesterol metabolism and increased canalicular cholesterol secretion. Other studies demonstrated that liver-specific deletion of microsomal triglyceride transfer protein (Mttp-LKO) reduced LD-induced gallstone formation by increasing biliary phospholipid secretion. Here we show that mice with combined deletion (i.e., DKO mice) are protected from LD-induced gallstone formation. Following 2 weeks of LD feeding, 73% of WT and 100% of L-Fabp KO mice developed gallstones versus 18% of Mttp-LKO and 23% of DKO mice. This phenotype was recapitulated in both WT and L-Fabp KO mice treated with an Mttp antisense oligonucleotide (M-ASO). Biliary cholesterol secretion was increased in LD-fed L-Fabp KO mice and decreased in DKO mice. However, phospholipid secretion was unchanged in LD-fed Mttp-LKO and DKO mice as well as in M-ASO-treated mice. Expression of the canalicular export pump ABCG5/G8 was reduced in LD-fed DKO mice and in M-ASO-treated L-Fabp KO mice. We conclude that liver-specific Mttp deletion not only eliminates apical lipoprotein secretion from hepatocytes but also attenuates canalicular cholesterol secretion, which in turn decreases LD-induced gallstone susceptibility.

  4. Preventing a Mass Disease: The Case of Gallstones Disease: Role and Competence for Family Physicians (United States)

    Di Ciaula, Agostino; Grattagliano, Ignazio


    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. PMID:27468338

  5. Chemical characterization of gallstones: an approach to explore the aetiopathogenesis of gallstone disease in Sri Lanka.

    Directory of Open Access Journals (Sweden)

    Harshi Weerakoon

    Full Text Available Records on gallstones and associated ailments in Sri Lankan community are scarce, despite frequent detection of gallstone disease. Identification of the chemical composition of gallstones in the local setting is important in defining aetiopathogenic factors which in turn are useful in implementing therapeutic and preventive strategies. This study aimed to describe the chemical composition of gallstones and the socio-demographic factors of a cohort of Sri Lankan patients with gallstone disease.Data on clinical and socio-demographic factors, and gallstones removed at surgery were collected from patients with cholelithiasis admitted to Teaching Hospital, Peradeniya, Sri Lanka from May 2011 to December 2012. External and cross sectional morphological features of gallstones were recorded by naked eye observation. Compositional analysis was carried out by Fourier Transform Infrared Spectroscopy, X - ray Powder Diffraction, and Atomic Absorption Spectrophotometry. Scanning Electron Microscopy was used to identify the microstructure of gallstones.Data of 102 patients were analyzed. Of them majority (n = 77, 76% were females with a female: male ratio of 3:1. Mean age of the study group was 46.1±11.6 years. All the patients had primary gallbladder stones. According to the physical and chemical analysis, majority (n = 54, 53% were pigment gallstones followed by mixed cholesterol gallstones (n = 38, 37%. Only 10 (9% had pure cholesterol gallstones. Calcium bilirubinate, calcium carbonate and calcium phosphate were the commonest calcium salts identified in pigment gallstones and core of mixed cholesterol gallstones.Presence of a pigment nidus in gallstones is a common feature in majority of Sri Lankan patients denoting the possible role of elevated unconjugated bilirubin in bile on the pathogenesis of GS. Hence it is imperative to explore this further to understand the aetiopathogenesis of GS among Sri Lankans.

  6. 肝脏胰岛素抵抗诱发胆结石形成的研究%Induction of gallstone formation by hepatic insulin resistance

    Institute of Scientific and Technical Information of China (English)

    徐健; 徐良; 李林涛; 查斯洛


    Objective To observe the induction effect of hepatic insulin resistance on gallstone formation.Methods Liver insulin receptor knockout mice were employed as research subjects (mouse model),and the incidence of gallstones caused by hthogenic diet was measured.Secretion of bile acids and the expression of related enzymes such as cholesterol 7-hydroxylase (Cyp7a1),cholesterol 12 alpha hydroxylase (Cyp8b1),cholesterol 7 alpha hydroxylase (Cyp7b1) and cholesterol 27 alpha hydroxylase (Cyp27a1),the expression of the farnesoid derivative X receptor (farnesoid-X-receptor,FXR),liver cholesterol content and the cholesterol transporter ATP binding cassette transporter G5 (Abcg5) and Abcg8 expression were assayed.Results The incidence of gallstones in model group was 100%,about 8 times higher than normal mice after lithogenic diet administration.Bile acid level in model mice was 9.2 μmol/g and less than the value of 14.9 μmol/g in normal group significantly.The FXR and Cyp7a1,Cyp8b1,Cyp7bl and Cyp27a1 expression levels were all decreased,and cholesterol content was 2.2 mg/g liver tissue in model mice,and that was 1.2 mg/g liver tissue in normal mice (P < 0.05).The expression of Abcg5 and Abcg8 was also increased in model mice.Conclusion The hepatic insulin resistance in mice inhibits FXR,Cyp7a1,Cyp8b1,Cyp7b1 and Cyp27a1 expression,and increases Abcg5 and Abcg8 expression,resulting in the decreased bile acid levels and increased cholesterol ratio,finally inducing formation of gallstones.%目的 观察肝脏胰岛素抵抗对胆结石形成的诱导作用.方法 使用肝脏胰岛素受体敲除小鼠作为研究对象(模型鼠),分别研究致结石饮食条件下胆结石的发生;胆酸的分泌量和胆固醇7-羟化酶(Cyp7a1)、胆固醇12α羟化酶(Cyp8b1)、胆固醇7α羟化酶(Cyp7b1)和胆固醇27α羟化酶(Cyp27a1)的表达以及法尼酯衍生物X受体(FXR)的表达;肝胆固醇的含量以及胆固醇转运体三 磷酸腺苷结合盒转运体G5(Abcg5

  7. Hyodeoxycholic acid: a new approach to gallstone prevention. (United States)

    McSherry, C K; Mosbach, E H; Cohen, B I; Une, M; Stenger, R J; Singhal, A K


    Hyodeoxycholic acid and its isomer, 6 beta-hyodeoxycholic acid, when added to a lithogenic diet prevented the formation of cholesterol gallstones and crystals in prairie dogs. This beneficial effect occurred in the presence of bile supersaturated with cholesterol. Hyodeoxycholic acid abolished the feedback inhibition of hepatic hydroxymethylglutaryl coenzyme A reductase activity, the rate-limiting enzyme of cholesterol synthesis, and prevented elevations in serum and liver cholesterol observed in animals fed a 0.4 percent cholesterol diet. The gallbladder bile of the animals fed hyodeoxycholic acid and 6 beta-hyodeoxycholic acid contained abundant liquid crystals. This suggests that these bile acids prevented the transition of cholesterol from its liquid crystalline phase to solid crystals and stones.

  8. XbaⅠpolymorphisms of apolipoprotein B gene:Another risk factor of gallstone formation after radical gastrectomy

    Institute of Scientific and Technical Information of China (English)


    AIM:To prospectively investigate the association between the XbaⅠpolymorphisms of apolipoprotein B (APOB)gene and gallstone formation following gastrectomy.METHODS:The study was conducted between January 2005 and December 2006.A total of 186 gastric cancer patients who had undergone radical gastrectomy were grouped according to XbaⅠpolymorphisms of APOB gene(X+X-group,n=24 and X-X-group,n =162)and compared.The XbaⅠpolymorphisms of APOB gene were detected by polymerase chain reaction-restriction fragment len...

  9. Aspirin inhibits formation of cholesterol rafts in fluid lipid membranes. (United States)

    Alsop, Richard J; Toppozini, Laura; Marquardt, Drew; Kučerka, Norbert; Harroun, Thad A; Rheinstädter, Maikel C


    Aspirin and other non-steroidal anti-inflammatory drugs have a high affinity for phospholipid membranes, altering their structure and biophysical properties. Aspirin has been shown to partition into the lipid head groups, thereby increasing membrane fluidity. Cholesterol is another well known mediator of membrane fluidity, in turn increasing membrane stiffness. As well, cholesterol is believed to distribute unevenly within lipid membranes leading to the formation of lipid rafts or plaques. In many studies, aspirin has increased positive outcomes for patients with high cholesterol. We are interested if these effects may be, at least partially, the result of a non-specific interaction between aspirin and cholesterol in lipid membranes. We have studied the effect of aspirin on the organization of 1,2-dipalmitoyl-sn-glycero-3-phosphatidylcholine (DPPC) membranes containing cholesterol. Through Langmuir-Blodgett experiments we show that aspirin increases the area per lipid and decreases compressibility at 32.5 mol% cholesterol, leading to a significant increase of fluidity of the membranes. Differential scanning calorimetry provides evidence for the formation of meta-stable structures in the presence of aspirin. The molecular organization of lipids, cholesterol and aspirin was studied using neutron diffraction. While the formation of rafts has been reported in binary DPPC/cholesterol membranes, aspirin was found to locally disrupt membrane organization and lead to the frustration of raft formation. Our results suggest that aspirin is able to directly oppose the formation of cholesterol structures through non-specific interactions with lipid membranes.

  10. Analysis Algerian's Gallstones with Infrared Spectrum and Methods of Prevention and Treatment for Cholelithiasis in Algeria

    Institute of Scientific and Technical Information of China (English)


    To analyze the type of Algerian's gallstones and put forward relative measures of prevention and treatment, The NICOLET 170SX FT-IR spectrometer was used to measure the infra-red spectrum and analyze the feature of spectrum of Algerian's gallstones. The results shown that Algerian have cholesterol gallstones. Reasons to form Algerian's multiple cholesterol gallstones were investigated. We have put forward five suggestions to prevent and treat cholelithiasis.

  11. Visualization of extracellular matrix components within sectioned Salmonella biofilms on the surface of human gallstones.

    Directory of Open Access Journals (Sweden)

    Joanna M Marshall

    Full Text Available Chronic carriage of Salmonella Typhi is mediated primarily through the formation of bacterial biofilms on the surface of cholesterol gallstones. Biofilms, by definition, involve the formation of a bacterial community encased within a protective macromolecular matrix. Previous work has demonstrated the composition of the biofilm matrix to be complex and highly variable in response to altered environmental conditions. Although known to play an important role in bacterial persistence in a variety of contexts, the Salmonella biofilm matrix remains largely uncharacterized under physiological conditions. Initial attempts to study matrix components and architecture of the biofilm matrix on gallstone surfaces were hindered by the auto-fluorescence of cholesterol. In this work we describe a method for sectioning and direct visualization of extracellular matrix components of the Salmonella biofilm on the surface of human cholesterol gallstones and provide a description of the major matrix components observed therein. Confocal micrographs revealed robust biofilm formation, characterized by abundant but highly heterogeneous expression of polysaccharides such as LPS, Vi and O-antigen capsule. CsgA was not observed in the biofilm matrix and flagellar expression was tightly restricted to the biofilm-cholesterol interface. Images also revealed the presence of preexisting Enterobacteriaceae encased within the structure of the gallstone. These results demonstrate the use and feasibility of this method while highlighting the importance of studying the native architecture of the gallstone biofilm. A better understanding of the contribution of individual matrix components to the overall biofilm structure will facilitate the development of more effective and specific methods to disrupt these bacterial communities.

  12. Prevalence and characteristics of gallstone disease in an Iranian population:a study on cadavers

    Institute of Scientific and Technical Information of China (English)

    Esmaail Farzaneh; Hassan Toifghi Zavvareh; Jaber Gharadaghi; Mehrdad Sheikhvatan


    BACKGROUND:The prevalence of gallstones is low in Asians. In Iran, many factors inlfuence the prevalence of this disease. The aim of this study was to determine the prevalence of gallbladder stones and their chemical characteristics in a population by the study of cadavers. METHODS: In this cross-sectional study, autopsies were performed on 253 cadavers of more than 13 years old. The cadavers were studied to determine the number, location of stone formation, chemical composition, dry weight, and mean diameter of stones in the gallbladder and common bile duct. RESULTS:The prevalence of gallstone disease in these cadavers was 6.3% (men 4.7%, women 8.6%, not signiifcantly different, P=0.216). There was a positive relationship between the age and prevalence of gallstone disease (P=0.033). The most common stone compositions were cholesterol and oxalate. The mean diameter (P=0.0058) and dry weight (P CONCLUSIONS:The prevalence of gallstones differed among age groups. Diameter and dry weight of gallstones were dependent on location of stone formation and chemical composition.

  13. Impaired cholecystokinin-induced gallbladder emptying incriminated in spontaneous "black" pigment gallstone formation in germfree Swiss Webster mice. (United States)

    Woods, Stephanie E; Leonard, Monika R; Hayden, Joshua A; Brophy, Megan Brunjes; Bernert, Kara R; Lavoie, Brigitte; Muthupalani, Sureshkumar; Whary, Mark T; Mawe, Gary M; Nolan, Elizabeth M; Carey, Martin C; Fox, James G


    "Black" pigment gallstones form in sterile gallbladder bile in the presence of excess bilirubin conjugates ("hyperbilirubinbilia") from ineffective erythropoiesis, hemolysis, or induced enterohepatic cycling (EHC) of unconjugated bilirubin. Impaired gallbladder motility is a less well-studied risk factor. We evaluated the spontaneous occurrence of gallstones in adult germfree (GF) and conventionally housed specific pathogen-free (SPF) Swiss Webster (SW) mice. GF SW mice were more likely to have gallstones than SPF SW mice, with 75% and 23% prevalence, respectively. In GF SW mice, gallstones were observed predominately in heavier, older females. Gallbladders of GF SW mice were markedly enlarged, contained sterile black gallstones composed of calcium bilirubinate and cholecystokinin (CCK), gallbladders of fasted GF SW mice showed impaired emptying (females: 29%; males: 1% emptying), whereas SPF SW females and males emptied 89% and 53% of volume, respectively. Bilirubin secretion rates of GF SW mice were not greater than SPF SW mice, repudiating an induced EHC. Gallstones likely developed in GF SW mice because of gallbladder hypomotility, enabled by features of GF physiology, including decreased intestinal CCK concentration and delayed intestinal transit, as well as an apparent genetic predisposition of the SW stock. GF SW mice may provide a valuable model to study gallbladder stasis as a cause of black pigment gallstones.

  14. Gallstones: an intestinal disease? (United States)

    Van Erpecum, K J; Van Berge-Henegouwen, G P


    Current evidence suggests that impaired intestinal motility may facilitate gallstone formation by influencing biliary deoxycholate levels or by modulating interdigestive gall bladder motility (fig 2), although a primary intestinal defect in gallstone pathogenesis has not yet been demonstrated. In the cold war period, most interesting events, from a political point of view, occurred at the border between capitalist and communist systems, near the iron curtain. Similarly, the gall bladder and biliary tract can be viewed as the border between liver and intestinal tract, where many interesting things occur with profound impact on both systems. Combined efforts by researchers in the field of hepatology and gastrointestinal motility should brake down the Berlin wall of ignorance of one of the most common diseases in the Western world.

  15. Recurrent Gallstone Ileus


    Hayes, Nicolas; Saha, Sanjoy


    Mechanical small bowel obstructions caused by gallstones account for 1% to 3% of cases. In these patients, 80% to 90% of residual gallstones in these patients will pass through a remaining fistula without consequence. Recurrent gallstone ileus has been reported in 5% of patients. We report the case of a woman, aged 72 years, who presented with mechanical small bowel obstruction caused by gallstone ileus. After successful surgical therapy for gallstone ileus, the patient's symptoms recurred, a...

  16. Gallstone ileus: CT findings

    Energy Technology Data Exchange (ETDEWEB)

    Delabrousse, E.; Bartholomot, B.; Sohm, O.; Kastler, B. [Dept. of Radiology A, CHU Jean Minjoz, University of Besancon (France); Wallerand, H. [Dept. of Surgery, CHU Jean Minjoz, University of Besancon (France)


    Gallstone ileus is a rare complication of recurrent gallstone cholecystitis. The classic radiographic triad of small bowel obstruction, pneumobilia and ectopic gallstone on abdominal plain radiograph is described with CT imaging. Because of the better resolution of CT compared with abdominal radiography and its recent accession to emergency use, radiologists should be aware of CT findings of gallstone ileus. We report a case in which gallstone ileus was initially diagnosed by CT. (orig.)

  17. Effects of YangGanLiDan Granule on PPAR - γ and CYP7A1 of Liver in Mice with Cholesterol Gallstone%养肝利胆颗粒对胆固醇结石小鼠肝脏中PPAR-γ及CYP7A1表达的影响

    Institute of Scientific and Technical Information of China (English)

    梁晓强; 顾宏刚; 章学林; 张静喆; 刘胜


    Objective :To observe the effects of YangGanLiDan granule (YGLD) on liver perosisome proliferator activated reeeptor gamma ( PPAR - γ) and Cholesterol 7 alpha - hydroxylase ( CYP7A1 ) in C57BL/6J mice model with cholesterol gallstone.Methods:Thirty - eight C57BL/6J mice were randomly divided into normal control group ( n = 10) ,untreated group ( n = 15 ) and YGLD group (n = 13).Cholesterol gallstone was induced in mice of the latter two groups by feeding high cholesterol diet.Mice in the YGLD group were intragastricly administered YGLD 2.lg/( kg · d).After 8 - weeks treatment,animals were sacrificed and sampled to calculate the incidences of stone formation.The expression of PPAR - γand GYP7A1 in liver tissues were detected.Results:The incidences of stone formation were 73.33 % in untreated group,0% in normal control group, and 30.77 % in the YGLD group.And the incidence in untreated group was significantly higher than those in the normal control group and the YGLD group( P <0.01 ).The expression of PPAR - γ and CYP7A1 were up - regulated after the treatment of YGLD.Conclusion:YGLD can deerease the incidence of stone formation,regulate PPAR -γand CYP7A1 up,which may be one of the mechanisms in the treatment and prevention of cholesterol gallstone disease.%目的:观察养肝利胆颖粒对胆固醉结石小鼠肝脏PPAR-γ及CYP7A1表达的影响.方法:38只C57BLJ6雌性小鼠随机分为正常对照组(n=10)、模型组(n=15)和养肝利胆颖粒组(n=13).其中后两组小鼠采用高脂饮食诱发法建立胆固醇结石模型.造模过程中,养肝利胆颗粒组小鼠予养肝利胆颖粒2.1g/(kg·d)灌胃治疗.8周后观察各组小鼠的成石率,并用Westem Blotting法检测肝脏中PPAR-γ及CYP7A1的表达.结果:养肝利胆颗粒组成石率显著降低(P<0.01),小鼠肝脏PPARγ及CYP7A1表达增强.结论:养肝利胆颗粒可通过增强肝脏PPAγ及CYP7A1的表达,从而发挥防治胆石病的作用.

  18. Biliary cholesterol secretion : More than a simple ABC

    NARCIS (Netherlands)

    Dikkers, Arne; Tietge, Uwe J. F.


    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 originat

  19. Metabolic syndrome and gallstone disease

    Institute of Scientific and Technical Information of China (English)

    Li-Ying Chen; Qiao-Hua Qiao; Shan-Chun Zhang; Yu-Hao Chen; Guan-Qun Chao; Li-Zheng Fang


    AIM:To investigate the association between metabolic syndrome (MetS) and the development of gallstone disease (GSD).METHODS:A cross-sectional study was conducted in 7570 subjects (4978 men aged 45.0 ± 8.8 years,and 2592 women aged 45.3 ± 9.5 years) enrolled from the physical check-up center of the hospital.The subjects included 918 patients with gallstones (653 men and 265 women) and 6652 healthy controls (4325 men and 2327 women) without gallstones.Body mass index (BMI),waist circumference,blood pressure,fasting plasma glucose (FPG) and serum lipids and lipoproteins levels were measured.Colorimetric method was used to measure cholesterol,high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C).Dextrose oxidizing enzyme method was used to measure FPG.Subjects were asked to complete a questionnaire that enquired about the information on demographic data,age,gender,histories of diabetes mellitus,hypertension,and chronic liver disease and so on.Metabolic syndrome was diagnosed according to the Adult Treatment Panel Ⅲ (ATP Ⅲ) criteria.Gallstones were defined by the presence of strong intraluminal echoes that were gravity-dependent or attenuated ultrasound transmission.RESULTS:Among the 7570 subjects,the prevalence of the gallstone disease was 12.1% (13.1% in men and 10.2% in women).BMI,waist circumference,systolic blood pressure,diastolic blood pressure,fasting blood glucose and serum triglyceride (TG) in cases group were higher than in controls,while serum high-density lipid was lower than in controls.There were significant differences in the waist circumference,blood pressure,FPG and TG between cases and controls.In an ageadjusted logistic regression model,metabolic syndrome was associated with gallstone disease.The age-adjusted odds ratio of MetS for GSD in men was 1.29 [95%confidence interval (CI),1.09-1.52; P =0.0030],and 1.68 (95% CI,1.26-2.25; P =0.0004) in women; the overall age-adjusted odds ratio of MetS for

  20. Effect of gallbladder hypomotility on cholesterol crystallization and growth in CCK-deficient mice. (United States)

    Wang, Helen H; Portincasa, Piero; Liu, Min; Tso, Patrick; Samuelson, Linda C; Wang, David Q-H


    We investigated the effect of gallbladder hypomotility on cholesterol crystallization and growth during the early stage of gallstone formation in CCK knockout mice. Contrary to wild-type mice, fasting gallbladder volumes were enlarged and the response of gallbladder emptying to a high-fat meal was impaired in knockout mice on chow or the lithogenic diet. In the lithogenic state, large amounts of mucin gel and liquid crystals as well as arc-like and tubular crystals formed first, followed by rapid formation of classic parallelogram-shaped cholesterol monohydrate crystals in knockout mice. Furthermore, three patterns of crystal growth habits were observed: proportional enlargement, spiral dislocation growth, and twin crystal growth, all enlarging solid cholesterol crystals. At day 15 on the lithogenic diet, 75% of knockout mice formed gallstones. However, wild-type mice formed very little mucin gel, liquid, and solid crystals, and gallstones were not observed. We conclude that lack of CCK induces gallbladder hypomotility that prolongs the residence time of excess cholesterol in the gallbladder, leading to rapid crystallization and precipitation of solid cholesterol crystals. Moreover, during the early stage of gallstone formation, there are two pathways of liquid and polymorph anhydrous crystals evolving to monohydrate crystals and three modes for cholesterol crystal growth.

  1. Impaired gallbladder motility and delayed orocecal transit contribute to pigment gallstone and biliary sludge formation in β-thalassemia major adults

    Institute of Scientific and Technical Information of China (English)

    Piero Portincasa; Giuseppe Palasciano; Antonio Moschetta; Massimo Berardino; Agostino Di Ciaula; Michele Vacca; Giuseppe Baldassarre; Anna Pietrapertosa; Rosario Cammarota; Nunzia Tannoia


    AIM: Gallbladder and gastrointestinal motility defects exist in gallstones patients and to a lesser extent in pigment gallstone patients. To investigated the role of gallbladder and gastrointestinal motility disorders in pigment gallstone formation in β-thalassemia major.METHODS: Twenty-three patients with β-thalassemia major (16 females; age range 18-37 years) and 70 controls (47 females, age range 18-40 years) were studied for gallbladder and gastric emptying (functional ultrasonography),orocecal transit (OCTT, H2-breath test), autonomic dysfunction (sweat-spot, cardiorespiratory reflex tests),bowel habits, gastrointestinal symptoms and quality of life (all with questionnaires). Gallbladder content (ultrasonography)was examined before and during 8-12 mo follow-up.RESULTS: Gallstones and/or biliary sludge were found in 13 (56%) patients. β-thalassemia major patients had increased fasting (38.0±4.8 mL vs20,3±0.7 mL, P= 0.0001)and residual (7.9±1.3 mL vs5.1±0.3 mL, P= 0.002) volume and slightly slower emptying (24.9±1.7 min vs20.1±0.7 min,P = 0.04) of the gallbladder, together with longer OCTT (132.2±7.8 min vs99.7±2.3 min, P= 0.00003) than controls.No differences in gastric emptying and bowel habits were found. Also, patients had higher dyspepsia (score: 6.7±1.2vs 4.9±0.2, P = 0.027), greater appetite (P = 0.000004)and lower health perception (P = 0.00002) than controls.Autonomic dysfunction was diagnosed in 52% of patients (positive tests: 76.2% and 66.7% for parasympathetic and sympathetic involvement, respectively). Patients developing sludge during follow-up (38%, 2 with prior stones) had increased fasting and residual gallbladder volume.CONCLUSION: Adult β-thalassemia major patients have gallbladder dysmotility associated with delayed small intestinal transit and autonomic dysfunction. These abnormalities apparently contribute together with haemolytic hyperbilirubinemia to the pathogenesis of pigment gallstones/sludge in β-thalassemia major.

  2. Complications of gallstones: the Mirizzi syndrome, gallstone ileus, gallstone pancreatitis, complications of "lost" gallstones. (United States)

    Zaliekas, Jill; Munson, J Lawrence


    Gallstones cause various problems besides simple biliary colic and choplecystitis. With chronicity of inflammation caused by gallstone obstruction of the cystic duct, the gallbladder may fuse to the extrahepatic biliary tree, causing Mirizzi syndrome, or fistulize into the intestinal tract, causing so-called gallstone ileus. Stones may pass out of the gallbladder and travel downstream through the common bile duct to obstruct the ampulla of Vater resulting in gallstone pancreatitis, or pass out of the gallbladder inadvertently during surgery, resulting in the syndromes associated with lost gallstones. This article examines these varied and complex complications, with recommendations for management based on the literature, the data, and perhaps some common sense.

  3. Recurrent gallstone ileus. (United States)

    Hayes, Nicolas; Saha, Sanjoy


    Mechanical small bowel obstructions caused by gallstones account for 1% to 3% of cases. In these patients, 80% to 90% of residual gallstones in these patients will pass through a remaining fistula without consequence. Recurrent gallstone ileus has been reported in 5% of patients. We report the case of a woman, aged 72 years, who presented with mechanical small bowel obstruction caused by gallstone ileus. After successful surgical therapy for gallstone ileus, the patient's symptoms recurred, and she was diagnosed with recurrent gallstone ileus requiring a repeat operation. While management of gallstone ileus can be achieved through a single-stage operation including enterolithotomy and cholecystectomy with repair of biliary-enteric fistula or by enterolithotomy alone, the literature supports enterolithotomy alone as the treatment of choice for gallstone ileus due to decreased mortality and morbidity. However, the latter approach does not obviate potential recurrence. We present this case of recurrent gallstone ileus to elucidate and review the pathogenesis, presentation, diagnosis, and consensus recommendations regarding management of this disorder.

  4. 对肝脏胰岛素抵抗诱发胆结石机制的研究%Experimental study of hepatic insulin resistance induction of gallstone formation

    Institute of Scientific and Technical Information of China (English)

    陶文雅; 朱峰; 王晨; 徐韦


    目的:分析肝脏胰岛素抵抗诱发胆结石的机制。方法:将肝脏胰岛素受体被敲除的C57BL/6小鼠作为模型小鼠,将健康的C57小鼠作为正常小鼠进行对照研究。对比观察两种小鼠在摄入高脂饮食后发生胆结石的情况、在摄入正常饮食时其体内胆汁酸的分泌量、其胆汁酸合成相关酶Cyp7a1、 Cyp8b1、Cyp7b1、Cyp27a1、法尼酯衍生物X受体(FXR)、腺苷三磷酸结合盒转运体Abcg5和Abcg8的表达、其肝脏和胆汁中胆固醇的浓度及胆汁的胆固醇饱和指数(CSI)等指标。结果:将模型小鼠用高脂饲料饲养3周后,共有83%的小鼠发生胆结石,可见胰岛素受体被敲除的小鼠易发生胆结石。在注射胰岛素后,正常小鼠及模型小鼠胆结石的发生率均有所增高,模型小鼠胆结石的发生率达100%。与正常小鼠相比,模型小鼠体内胆汁酸的分泌量明显较少(P<0.05),其体内Cyp7a1、 Cyp8b1、 Cyp7b1和Cyp27a1的mRNA表达明显降低(P<0.05),其体内FXR的mRNA表达与蛋白表达也明显降低(P <0.05)。与正常小鼠相比,模型小鼠体内肝胆固醇的浓度和CSI均较高(P <0.05),其体内Abcg5和Abcg8的mRNA表达及蛋白表达也较高(P<0.05)。结论:发生肝脏胰岛素抵抗的小鼠可因FXR、Cyp7a1、 Cyp8b1、 Cyp7b1和Cyp27a1的表达降低,胆汁酸的分泌减少及Abcg5和Abcg8的表达升高,导致胆汁中胆固醇的浓度增加而加速胆结石的发病。%Objective: To observe the induction effect of hepatic insulin resistance on gallstone formation. Methods: Liver insulin receptor knockout mice were employed as research subjects (mouse model), determined the occurrence of gallstones caused by lithogenic diet; secretion of bile acids and related enzymes such as Cyp7a1, Cyp8b1, Cyp7b1 and Cyp27a1, also the farnesoid derivative X receptor (farnesoid-X-receptor, FXR) expression; liver cholesterol content and the

  5. Cholesterol cholelithiasis in pregnant women: pathogenesis, prevention and treatment. (United States)

    de Bari, Ornella; Wang, Tony Y; Liu, Min; Paik, Chang-Nyol; Portincasa, Piero; Wang, David Q-H


    Epidemiological and clinical studies have found that gallstone prevalence is twice as high in women as in men at all ages in every population studied. Hormonal changes occurring during pregnancy put women at higher risk. The incidence rates of biliary sludge (a precursor to gallstones) and gallstones are up to 30 and 12%, respectively, during pregnancy and postpartum, and 1-3% of pregnant women undergo cholecystectomy due to clinical symptoms or complications within the first year postpartum. Increased estrogen levels during pregnancy induce significant metabolic changes in the hepatobiliary system, including the formation of cholesterol-supersaturated bile and sluggish gallbladder motility, two factors enhancing cholelithogenesis. The therapeutic approaches are conservative during pregnancy because of the controversial frequency of biliary disorders. In the majority of pregnant women, biliary sludge and gallstones tend to dissolve spontaneously after parturition. In some situations, however, the conditions persist and require costly therapeutic interventions. When necessary, invasive procedures such as laparoscopic cholecystectomy are relatively well tolerated, preferably during the second trimester of pregnancy or postpartum. Although laparoscopic operation is recommended for its safety, the use of drugs such as ursodeoxycholic acid (UDCA) and the novel lipid-lowering compound, ezetimibe would also be considered. In this paper, we systematically review the incidence and natural history of pregnancy-related biliary sludge and gallstone formation and carefully discuss the molecular mechanisms underlying the lithogenic effect of estrogen on gallstone formation during pregnancy. We also summarize recent progress in the necessary strategies recommended for the prevention and the treatment of gallstones in pregnant women.

  6. Impact of heme oxygenase-1 on cholesterol synthesis, cholesterol efflux and oxysterol formation in cultured astroglia. (United States)

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


    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.

  7. Gallstone ileus: a review. (United States)

    Masannat, Yazan; Masannat, Yanal; Shatnawei, Abdullah


    This article aims to review gallstone ileus in the literature addressing the pathophysiology, clinical presentation, radiological findings and treatment options of the condition. A literature search was done on gallstone ileus, for the period 1966-2005. Gallstone ileus is a disease of the elderly, causing up to one fourth of non-strangulation intestinal obstructions in patients older than 65 years of age. It is often missed or diagnosed late. The presentation is that of intestinal obstruction preceded by biliary complaints. Radiological features on plain X-rays include features of intestinal obstruction and pneumobilia, and an aberrant gallstone. Treatment depends on the site of the impacted stone, but surgery is needed in many cases. Gallstone ileus is a rare complication of a common condition. Because it primarily affects the elderly, mortality and morbidity are high, although they have improved over the years. Early diagnosis and treatment improve the outcome.

  8. Gallstones and colorectal cancer

    DEFF Research Database (Denmark)

    Jørgensen, Torben; Rafaelsen, Søren Rafael


    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.......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...... 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....

  9. Cholesterol: a novel regulatory role in myelin formation. (United States)

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


    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.

  10. Postmenopausal Estrogen Therapy and Risk of Gallstone Disease

    DEFF Research Database (Denmark)

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


    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...... was to examine the association between postmenopausal estrogen therapy and risk of gallstone disease and the impact of duration of treatment and use of opposing progestin. STUDY DESIGN: We conducted a population-based case-control study. Cases were postmenopausal women (defined as aged ≥45 years) with gallstone...... disease identified in the period 1996-2010. For each case, we selected ten population controls matched to cases by age and sex. We defined exposure as any use of estrogen (opposed and unopposed by progestin). Cases/controls were categorized as current estrogen users if their last prescription was redeemed...


    Directory of Open Access Journals (Sweden)

    N. A. Hohlacheva


    Full Text Available Goal. Study of the role of risk factors in mechanized gall stone formation depending on sex and age of patients. Material and methods We examined 210 patients with stage I gallstone disease (GSD. In verification of diagnosis used an ultrasound study of the hepatobiliary system, multi-grade duodenal sounding with subsequent macroscopic, microscopic, chemical and physical examination of bile. In the portions “b” and “C” bile was determined the total concentration of bile acids, cholesterol, with the subsequent calculation it consists of cholesterol ratio. Estimation of surface tension of bile viscosity and bile. In the studied blood levels of total cholesterol, lipoproteins of very low density, lowdensity lipoproteins, high density lipoproteins, triglycerides, were determined the coefficient of atherogenicity. To assess the degree of accumulation of body fat was used the Quetelet index. Studied the relative risk of anamnestic risk factors of GSD. Results. The features of biliary lithogenesis based on gender and age of patients. High value PR for the gall stone formation are female gender — 3,16, Mature and elderly age (older than 50 of 3.67. In young women, gall-stone formation is mainly due to the increase of cholesterol level of bile, at the age of 50 years with a decline in zhelchnokamennaja pool, increased viscosity and surface tension of bile. The most important risk factors of cholecystolithiasis are also gender differences: if women is multiple pregnancies and (or childbirth (more than 3 — OR 4,62, overweight (BMI over 26 — OR is 4.57 and the violation of the principles of good nutrition (eating disorders, overeating or starvation, the use of large quantities of animal fats — OR 3,94, for men it’s physical inactivity — OR a 4.25, the increase in KA — PR 3.87 and burdened by GSD genetics — OR of 2.05. Conclusion. The data obtained can be used in the organization of dispensary work with patients with hepatobiliary

  12. Cholesterol is essential for mitosis progression and its deficiency induces polyploid cell formation. (United States)

    Fernández, Carlos; Lobo Md, María del Val T; Gómez-Coronado, Diego; Lasunción, Miguel A


    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 14alpha-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.

  13. 胆囊胆固醇结石易患鼠和免患鼠肝胆脂质代谢和分泌的差别%Differences between hepatic and biliary lipid metabolism and secretion in genetically gallstone-susceptible and gallstone-resistant mice

    Institute of Scientific and Technical Information of China (English)

    许国强; 赵力; 等


    Objective To investigate differences between hepatic and biliary lipid metabolism and secretion of genetically gallstone-susceptible (C57L) and resistant (AKR) mice and the mechanism of cholesterol gallstone formation.Methods The inbred C57L and AKR mice were fed a lithogenic diet containing 15% fat, 1.25% cholesterol and 0.5% cholic acid for four weeks. Hepatic cholesterol content and secretion rates of biliary lipids, as well as phenotypes of the liver and gallbladder were determined and examined before and after the feeding of the lithogenic diet. Results Both before and after ingestion of the lithogenic diet, hepatic secretion rates of all biliary lipids in C57L mice were markedly higher than that of AKR mice (P<0.05, P<0.01, respectively), whereas hepatic cholesterol contents of C57L mice were significantly lower than that of AKR mice (P<0.05). Furthermore, after consumption of the lithogenic diet, the increase in hepatic secretion rate of biliary cholesterol in C57L mice was significantly higher than that in AKR mice (P<0.01). Cholesterol gallstones formed in C57L mice and fatty livers developed in AKR mice. Conclusions Biliary cholesterol hypersecretion is the key pathophysiological defect of gallstone formation, lith genes have effects on biliary cholesterol hypersecretion and susceptibility to cholesterol gallstone formation in C57L mice. Lithogenic bile is formed at the canalicular membrane and precedes the development of cholesterol gallstones. It is most likely that cholesterol and bile acid hyposecretion make the AKR strain susceptible to the development of fatty livers and resistant to gallstone formation.%目的研究胆囊胆固醇结石易患鼠(C57L)和免患鼠(AKR)肝胆脂质代谢和分泌的特征以及胆囊胆固醇结石形成的机制.方法用含15%脂肪、1.25%胆固醇和0.5%胆酸的结石餐饲喂C57L和AKR鼠四周,检测并比较两种鼠在结石餐干预前、后肝脏胆固醇含量、肝内胆汁中脂质的分泌率以及胆

  14. Reação peritoneal tardia ao calculo biliar humano, de colesterol, deixado na cavidade abdominal de ratos Late peritoneal reaction to human cholesterol gallstone left into abdominal cavity of rats

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    Luiz Carlos Bertges


    Full Text Available Foram avaliados os resultados tardios da colocação de cálculos biliares humanos, de colesterol, na cavidade peritoneal de ratos. Constituíram-se cinco grupos: cinco ratos foram apenas laparotomizados com manuseio da cavidade; cinco foram laparotomizados e receberam um ponto com fio monofilamentar cinco zeros no sulco paracólico direito e mesentério; dez receberam cálculos que foram deixados livres na cavidade peritoneal; em dez, os clculos foram fixados no sulco paracólico direito e, finalmente, dez tiveram clculos fixados no mesentério. Os animais foram mortos após cinco meses de pós-operatório quando se observou a cavidade abdominal e foi coletado material para estudo histopatológico. Concluiu-se que os cálculos não foram absorvidos, desenvolveram uma reação peritoneal do tipo corpo estranho com formação de plastrão e foram envolvidos por tecido fibroso e células inflamatórias.It was evaluated the late results of human gallstones placed into peritoneal cavity of rats. Five groups were created. In the first (group A five rats were submitted only to laparotomy and handling of abdominal cavity, in the second (group B five rats were submitted to laparotomy and a stitch was placed into right abdominal wall and in mesenterium between the ileus and cecum, in the third (group C ten rats received a gallstone left free into abdomen, in the fourth (group D ten rats received a gallstone fixed into right abdominal wall and in the fifth (group E ten rats received a gallstone fixed in mesenterium between the ileus and cecum. One rat in each group was selected to be use as a pilot and were re-laparotomized after 1 month and 3 months, in order to look for any possible alteration. All rats were dead after five months when the abdominal cavity was observed and specimens were collected around the gallstones to histopathology. ln groups A and B there were not important macroscopic alterations. The gallstones were not absorved in groups C, D

  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

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    Winnekendonk Guido


    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. Hepatobiliary imaging in gallstone ileus

    Energy Technology Data Exchange (ETDEWEB)

    Bocobo, G.R.; Slavin, J.D. Jr.; Rao, H.; Aseltine, D. Jr.; Spencer, R.P.


    Hepatobiliary imaging was performed in a woman who, at subsequent surgery, was found to have gallstone ileus due to a large gallstone obstructing the proximal jejunum. The triad of findings (failure of the radiopharmaceutical to pass beyond the point of obstruction, marked reflux into the stomach, and nonvisualization of the gallbladder) is nonspecific but, in the appropriate clinical setting, should suggest the possibility of gallstone ileus.

  17. Laparoscopic Treatment of Gallstone Ileus


    Huseyin Y. Bircan; Bora Koc; Umit Ozcelik; Ozgur Kemik; Alp Demirag


    Gallstone ileus is a rare complication of cholelithiasis that has high morbidity and mortality. An intestinal obstruction can be caused by migration of a large gallstone through a biliary enteric fistula or by impaction within the intestinal tract. In this study, we present the case of an 81-year-old woman with a mechanical bowel obstruction by a gallstone that was treated by laparoscopy.

  18. Laparoscopic treatment of gallstone ileus. (United States)

    Bircan, Huseyin Y; Koc, Bora; Ozcelik, Umit; Kemik, Ozgur; Demirag, Alp


    Gallstone ileus is a rare complication of cholelithiasis that has high morbidity and mortality. An intestinal obstruction can be caused by migration of a large gallstone through a biliary enteric fistula or by impaction within the intestinal tract. In this study, we present the case of an 81-year-old woman with a mechanical bowel obstruction by a gallstone that was treated by laparoscopy.

  19. Spontaneous formation of two-dimensional and three-dimensional cholesterol crystals in single hydrated lipid bilayers. (United States)

    Ziblat, Roy; Fargion, Iael; Leiserowitz, Leslie; Addadi, Lia


    Grazing incidence x-ray diffraction measurements were performed on single hydrated bilayers and monolayers of Ceramide/Cholesterol/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocyholine at varying concentrations. There are substantial differences in the phase and structure behavior of the crystalline domains formed within the bilayers relative to the corresponding monolayers, due to interactions between the opposing lipid leaflets. Depending on the lipid composition, these interactions lead to phase separation and formation of cholesterol crystals. The cholesterol and ceramide/cholesterol mixed phases were further characterized at 37°C by immunolabeling with specific antibodies recognizing ordered molecular arrays of cholesterol. Previous studies have shown that cholesterol may nucleate in artificial membranes to form thick two-dimensional bilayer crystals. The study herein demonstrates further growth of cholesterol into three-dimensional crystals. We believe that these results may provide further insight into the formation of cholesterol crystals in early stages of atherosclerosis inflammation.

  20. Monocytes from HIV+ individuals show impaired cholesterol efflux and increased foam cell formation after transendothelial migration (United States)

    MAISA, Anna; HEARPS, Anna C.; ANGELOVICH, Thomas A.; PEREIRA, Candida F.; ZHOU, Jingling; SHI, Margaret D.Y.; PALMER, Clovis S.; MULLER, William A.; CROWE, Suzanne M.; JAWOROWSKI, Anthony


    Design HIV+ individuals have an increased risk of atherosclerosis and cardiovascular disease which is independent of antiretroviral therapy and traditional risk factors. Monocytes play a central role in the development of atherosclerosis, and HIV-related chronic inflammation and monocyte activation may contribute to increased atherosclerosis, but the mechanisms are unknown. Methods Using an in vitro model of atherosclerotic plaque formation, we measured the transendothelial migration of purified monocytes from age-matched HIV+ and uninfected donors and examined their differentiation into foam cells. Cholesterol efflux and the expression of cholesterol metabolism genes were also assessed. Results Monocytes from HIV+ individuals showed increased foam cell formation compared to controls (18.9% vs 0% respectively, p=0.004) and serum from virologically suppressed HIV+ individuals potentiated foam cell formation by monocytes from both uninfected and HIV+ donors. Plasma TNF levels were increased in HIV+ vs control donors (5.9 vs 3.5 pg/ml, p=0.02) and foam cell formation was inhibited by blocking antibodies to TNF receptors, suggesting a direct effect on monocyte differentiation to foam cells. Monocytes from virologically suppressed HIV+ donors showed impaired cholesterol efflux and decreased expression of key genes regulating cholesterol metabolism, including the cholesterol transporter ABCA1 (p=0.02). Conclusions Monocytes from HIV+ individuals show impaired cholesterol efflux and are primed for foam cell formation following trans-endothelial migration. Factors present in HIV+ serum, including elevated TNF levels, further enhance foam cell formation. The pro-atherogenic phenotype of monocytes persists in virologically suppressed HIV+ individuals and may contribute mechanistically to increased atherosclerosis in this population. PMID:26244384

  1. Biliary cholesterol secretion: More than a simple ABC

    Institute of Scientific and Technical Information of China (English)

    Arne; Dikkers; Uwe; JF; Tietge


    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 f inal step for the elimination of cholesterol originating from cholesterol-laden macrophage foam cells in the vessel wall in a pathway named reverse cholesterol transport. On the other hand, cholesterol hypersecretion into the bile is considered the main pathophys...

  2. Biliary cholesterol secretion: More than a simple ABC


    Dikkers, Arne; Tietge, Uwe JF


    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 originating from cholesterol-laden macrophage foam cells in the vessel wall in a pathway named reverse cholesterol transport. On the other hand, cholesterol hypersecretion into the bile is considered the ...

  3. Perfringolysin O structure and mechanism of pore formation as a paradigm for cholesterol-dependent cytolysins. (United States)

    Johnson, Benjamin B; Heuck, Alejandro P


    Cholesterol-dependent cytolysins (CDCs) constitute a family of pore forming toxins secreted by Gram-positive bacteria. These toxins form transmembrane pores by inserting a large β-barrel into cholesterol-containing membrane bilayers. Binding of water-soluble CDCs to the membrane triggers the formation of oligomers containing 35-50 monomers. The coordinated insertion of more than seventy β-hairpins into the membrane requires multiple structural conformational changes. Perfringolysin O (PFO), secreted by Clostridium perfringens, has become the prototype for the CDCs. In this chapter, we will describe current knowledge on the mechanism of PFO cytolysis, with special focus on cholesterol recognition, oligomerization, and the conformational changes involved in pore formation.

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

    Energy Technology Data Exchange (ETDEWEB)

    Fujimoto, Y.; Hiramoto, M.; Kakinuma, K.; Ikekawa, N. (Tokyo Institute of Technology (Japan))


    Being administered to Locusta migratoria adult females, (6-{sup 3}H, 4-{sup 14}C)cholesterol was incorporated into ecdysone and 2-deoxyecdysone. The ratio of {sup 3}H/{sup 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.

  5. The role and mechanism of fatty acids in gallstones

    Institute of Scientific and Technical Information of China (English)

    Shuo-Dong Wu; Kazuhisa Uchiyama; Ying Fan


    BACKGROUND: Cholelithiasis is a common entity in China, but its etiology and pathogenesis have not been fully elucidated. Pigment stones of the intrahepatic and extrahepatic bile duct still form a high proportion in China, while they are rare in Europeans. To date, reports on fatty acids in stones remain few. We analyzed the quantity of fatty acids in different stones from Chinese and Japanese cases and discussed the role and mechanism of fatty acids in the formation of pigment stones. METHODS: Clinical data from 18 Chinese and 37 Japanese patients with different types of stones were analyzed using the procedure for extracting fatty acids from gallstones and high performance liquid chromatography. RESULTS: The total fatty acid and free fatty acid contents of pigment stones were markedly higher than those in black or cholesterol stones. The ratio of free saturated to free unsaturated fatty acids was highest in intrahepatic and less in extrahepatic pigment stones, which were signiifcantly different from the other two kinds of stones. CONCLUSIONS: This indicates that phospholipase participates in the course of pigment stone formation. The action of phospholipase A1 is more important than phospholipase A2.

  6. The Progression of Cholelithiasis to Gallstone Ileus: Do Large Gallstones Warrant Surgery? (United States)

    Freeman, Michael H; Mullen, Matthew G; Friel, Charles M


    Gallstone ileus is a rare cause of small bowel obstruction, classically occurring in patients with recurrent cholecystitis. The incidence of biliary enteric fistula and gallstone ileus in patients with large, asymptomatic gallstones is not known. We report a case of gallstone ileus, which occurred in the setting of a large, asymptomatic gallstone. This case suggests that large gallstones may warrant cholecystectomy, even in asymptomatic patients.

  7. Eicosapentaenoic acid reduces membrane fluidity, inhibits cholesterol domain formation, and normalizes bilayer width in atherosclerotic-like model membranes. (United States)

    Mason, R Preston; Jacob, Robert F; Shrivastava, Sandeep; Sherratt, Samuel C R; Chattopadhyay, Amitabha


    Cholesterol crystalline domains characterize atherosclerotic membranes, altering vascular signaling and function. Omega-3 fatty acids reduce membrane lipid peroxidation and subsequent cholesterol domain formation. We evaluated non-peroxidation-mediated effects of eicosapentaenoic acid (EPA), other TG-lowering agents, docosahexaenoic acid (DHA), and other long-chain fatty acids on membrane fluidity, bilayer width, and cholesterol domain formation in model membranes. In membranes prepared at 1.5:1 cholesterol-to-phospholipid (C/P) mole ratio (creating pre-existing domains), EPA, glycyrrhizin, arachidonic acid, and alpha linolenic acid promoted the greatest reductions in cholesterol domains (by 65.5%, 54.9%, 46.8%, and 45.2%, respectively) compared to controls; other treatments had modest effects. EPA effects on cholesterol domain formation were dose-dependent. In membranes with 1:1 C/P (predisposing domain formation), DHA, but not EPA, dose-dependently increased membrane fluidity. DHA also induced cholesterol domain formation without affecting temperature-induced changes in-bilayer unit cell periodicity relative to controls (d-space; 57Å-55Å over 15-30°C). Together, these data suggest simultaneous formation of distinct cholesterol-rich ordered domains and cholesterol-poor disordered domains in the presence of DHA. By contrast, EPA had no effect on cholesterol domain formation and produced larger d-space values relative to controls (60Å-57Å; pmembrane bilayer width, membrane fluidity, and cholesterol crystalline domain formation; suggesting omega-3 fatty acids with differing chain length or unsaturation may differentially influence membrane lipid dynamics and structural organization as a result of distinct phospholipid/sterol interactions.

  8. 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))


    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).

  9. Effects of tegaserod on bile composition and hepatic secretion in Richardson ground squirrels on an enriched cholesterol diet

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    Pfannkuche Hans-Juergen


    Full Text Available Abstract Background Tegaserod is effective in treating IBS patients with constipation, and does not alter gallbladder motility in healthy individuals or in patients with IBS. However, it is not known if tegaserod affects the biliary tract in gallstone disease, so to this end the effects of tegaserod on bile composition and hepatic secretion of Richardson ground squirrels maintained on an enriched cholesterol diet were examined. Results Animals were fed either a control (0.03% or enriched (1% cholesterol diet for 28 days, and treated s.c. with tegaserod (0.1 mg/kg BID or vehicle. Bile flow, bile acid, phospholipids and cholesterol secretion were measured with standard methods. Tegaserod treatment or enriched cholesterol diet, alone or combination, did not alter body or liver weights. The enriched cholesterol diet increased cholesterol saturation index (CSI, cholesterol concentrations in gallbladder and hepatic duct bile by ~50% and decreased bile acids in gallbladder bile by 17%. Tegaserod treatment reversed these cholesterol-induced changes. None of the treatments, drug or diet, altered fasting gallbladder volume, bile flow and bile salts or phospholipid secretion in normal diet and cholesterol-fed animals. However, tegaserod treatment prevented the decreases in bile acid pool size and cycling frequency caused by the enriched cholesterol diet, consequent to re-establishing normal bile acid to concentrations in the gall bladder. Tegaserod had no effect on these parameters with normal diet animals. Conclusion Tegaserod treatment results in increased enterohepatic cycling and lowers cholesterol saturation in the bile of cholesterol-fed animals. These effects would decrease conditions favorable to cholesterol gallstone formation.

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

    NARCIS (Netherlands)

    Moschetta, Antonio


    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

  11. Identification of Helicobacter pylori DNA in gallstones using Multiplex PCR

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    Shohreh Farshad


    Full Text Available Background: Recent studies showed a possible relationship between infections caused by some of Helicobacter members and gallstones formation. The aim of this study was identification of Helicobacter members in gallstones from patients with biliary diseases. Methods: Gallstones and bile samples from 33 patients were subjected to rapid urease test, culture and Multiplex-PCR using primers based on 16s rRNA and isocitrate dehydrogenase genes to identify Helicobacter genus and H. pylori species genes, respectively. This PCR was also done on bile samples from 40 autopsied gallbladders with normal pathology (as a control group. Results: In 18.1% of stones and 12.1% of bile samples, H. pylori DNA was detected using PCR. Rapid urease and cultures tests were negative for all samples. The genome of H. pylori was not detected in control group using PCR. Conclusion: H. pylori DNA was detected in gallstone, however, we are not sure of H. pylori viability in these samples. To clarify the clinical role of Helicobacter in gallbladder diseases, more investigations are needed to ascertain whether this microorganism is innocent bystander or active participant in gallstone formation.

  12. A Survey on Prevalence and Pathological Findings of Gallstones in Lori-Bakhtiari Sheep in Iran

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    Afshin Raoofi


    Full Text Available In a survey of 430 Lori-Bakhtiari sheep at a slaughterhouse in Iran, gallstones were found in the gallbladder of 7 sheep (1.6%. Biliary calculi were more frequent in adult and female sheep (<0.05. Chemical analysis of the gallstones revealed 6 sheep with pigment (bilirubin stones and 1 sheep with cholesterol stones. Chemical composition of bile in these sheep was evaluated. Bacteriologic analysis of the bile in the affected sheep revealed bacteria (Streptococcus spp., Klebsiella spp., Escherichia coli, and Salmonella spp. in 5 sheep. Microscopic examination of gallbladders revealed focal calcification, cystic glands, necrosis and atrophy of mucosal layer, edema, diffuse and focal infiltration of lymphocytes in submucosal layer, and hypertrophy of smooth muscles in sheep with gallstones. It was concluded that the prevalence of both types of gallstones in Lori-Bakhtiari sheep is low. Cholelithiasis can cause chronic inflammation of the gallbladder, but it is not likely to become clinically significant.

  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


    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......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......) 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. 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)


    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

  15. Spontaneous resolution of a gallstone ileus. (United States)

    Roberts, Ja; Lambrianides, Al


    Gallstone ileus is an uncommon complication of cholelithiasis, usually associated with an internal biliary fistula. Management of gallstone ileus is surgical with enterolithotomy the procedure of choice, followed by fistula closure either as a one or two stage procedure. In this case a 66 year old female presented with colicky abdominal pain, computed tomography (CT) clearly showing a gallstone ileus and cholecystoduodenal fistula. Despite this the patient refused surgery and went on to have spontaneous resolution of the obstruction and passage of gallstones.

  16. Therapy of gallstone disease:What it was,what it is,what it will be

    Institute of Scientific and Technical Information of China (English)

    Piero; Portincasa; Agostino; Di; Ciaula; Leonilde; Bonfrate; David; QH; Wang


    Cholesterol gallstone disease is a common clinical condition influenced by genetic factors,increasing age,female gender,and metabolic factors.Although laparoscopic cholecystectomy is currently considered the gold standard in treating patients with symptomatic gallstones,new perspectives regarding medical therapy of cholelithiasis are currently under discussion,also taking into account the pathogenesis of gallstones,the natural history of the disease and the analysis of the overall costs of therapy.A careful selection of patients may lead to successful nonsurgical therapy in symptomatic subjects with a functioning gallbladder harboring small radiolucent stones.The classical oral litholysis by ursodeoxycholic acid has been recently paralleled by new experimental observations,suggesting that cholesterol-lowering agents which inhibit cholesterol synthesis (statins) or intestinal cholesterol absorption (ezetimibe),or drugs acting on specific nuclear receptors involved in cholesterol and bile acid homeostasis,might be proposed as additional approaches for treating cholesterol gallstones.In this review we discuss old,recent and future perspectives on medical treatment of cholesterol cholelithiasis.

  17. A study on the choice of treatment for gallstones by ultrasonography and CT

    Energy Technology Data Exchange (ETDEWEB)

    Yamasaki, Yoji; Takeguchi, Toichiro; Sagawa, Hirohumi; Shimamura, Teruomi (Amakusa Central Hospital, Hondo, Kumamoto (Japan))


    In 183 patients with gallstones we compared the chemical composition with the ultrasonographic patterns and CT values of gallstones; the gallbladder (GB) contraction by yolk stimulation and the degree of inflammation with the thickness of GB wall measured by ultrasonography (US), and investigated the treatment for gallstones. According to the Tsuchiya's ultrasonographic classification, in stones larger than 10 mm in diameter, type I and II indicated cholesterol stones and type III did calcium bilirubinate stones or black stones; in smaller than 10 mm in diameter, the accumulated type without an acoustic shadow showed black stones. Although the diagnosis of chemical composition was insufficient by US. On the other hand, CT values closely reflected chemical composition. Gallstones with CT values less than 80 consisted of cholesterol, ones more than 80 and less than 200 consisted of bilirubine calcium, ones more than 200 showed that they contained more than 5 percent calcium carbonate and were positive in abdominal X-ray examination. Cases of less than 3 mm thickness of GB wall by US had a good GB contraction and a slight inflammation in GB wall; more than 5 mm had a poor contraction and a severe inflammation. In conclusion, chemical composition of gallstones, GB contraction and pathology of GB wall were able to be estimated by US and CT, and it should be helpful for the clinical choice of surgical or nonsurgical treatment such as bile acid resolution, extracorporeal shock wave lithotripsy, laparoscopic cholecystectomy and cholecystectomy under laparotomy. (author).

  18. Incidence of gallstone disease in Italy: Results from a multicenter, population-based Italian study (the MICOL project)

    Institute of Scientific and Technical Information of China (English)

    Davide Festi; Enrico Roda; Antonio Colecchia; Ada Dormi; Simona Capodicasa; Tommaso Staniscia; Adolfo F Attili; Paola Loria; Paolo Pazzi; Giuseppe Mazzella; Claudia Sama


    AIM:To evaluate gallstone incidence and risk factors in a large population-based study.METHODS:Gallstone incidence and risk factors,were evaluated by structured questionnaire and physical examination,respectively,in 9611 of 11 109(86.5%)subjects who were gallstone-free at the cross-sectional study.RESULTS:Six centers throughout Italy enrolled 9611 subjects (5477 males,4134 females,aged 3079 years),9517 of whom were included into analysis:424 subjects (4.4%) had gallstones and 61 (0.6%)had been cholecystectomized yielding a cumulative incidence of 0.67% per year (0.66% in males,0.81% in females).Increasing age,a high body mass index (BMI),a history of diabetes,peptic ulcer and angina,and low cholesterol and high triglyceride levels were identified as risk factors in men while,in females,the only risk factors were increasing age and a high BMI.Increasing age and pain in the right hypocondrium in men and increasing age in females were identified as predictors of gallstones.Pain in the epigastrium/right hypocondrium was the only symptom related to gallstones;furthermore,some characteristics of pain(forcing to rest,not relieved by bowel movements)were significantly associated with gallstones.No correlation was found between gallstone characteristics and clinical manifestations,while increasing age in men and increasing age and BMI in females were predictors of pain.CONCLUSION:Increasing age and BMI represent true risk factors for gallstone disease (GD);pain in the right hypocondrium and/or epigastrium is confirmed as the only symptom related to gallstones.

  19. [Gallstone ileus. Abdominal CT usefulness]. (United States)

    Sukkarieh, F; Brasseur, P; Bissen, L


    The authors report the case of a 93-year old woman referred to the emergency department and presenting with an intestinal obstruction. Abdominal CT reveals a biliary ileus caused by the migration and the impaction of a 3 cm gallstone in the small bowel. Surgical treatment by enterolithotomy was successful. In over 90% of cases, gallstone ileus is a complication of cholelithiasis and accounts for 25% of intestinal obstruction in patients over 65 years. To reduce morbidity and mortality, early diagnosis and prompt treatment are essential. Abdominal CT-scan is the gold standard technique.

  20. Gender and metabolic differences of gallstone diseases

    Institute of Scientific and Technical Information of China (English)

    Hui Sun; Hong Tang; Shan Jiang; Li Zeng; En-Qiang Chen; Tao-You Zhou; You-Juan Wang


    AIM: To investigate the risk factors for gallstone disease in the general population of Chengdu, China. METHODS: This study was conducted at the West China Hospital. Subjects who received a physical examination at this hospital between January and December 2007 were included. Body mass index, blood pressure, fasting plasma glucose, serum lipid and lipoproteins concentrations were analyzed. Gallstone disease was diagnosed by ultrasound or on the basis of a history of cholecystectomy because of gallstone disease. Unconditional logistic regression analysis was used to investigate the risk factors for gallstone disease, and the Chi-square test was used to analyze differences in the incidence of metabolic disorders between subjects with and without gallstone disease. RESULTS: A total of 3573 people were included, 10.7% (384/3573) of whom had gallstone diseases. Multiple logistic regression analysis indicated that the incidence of gallstone disease in subjects aged 40-64 or ≥ 65 years was significantly different from that in those aged 18-39 years ( P < 0.05); the incidence was higher in women than in men ( P < 0.05). In men, in women than in men ( P < 0.05). In men, a high level of fasting plasma glucose was obvious in gallstone disease ( P < 0.05), and in women, hypertriglyceridemia or obesity were significant in gallstone disease ( P < 0.05). CONCLUSION: We assume that age and sex are profoundly associated with the incidence of gallstone disease; the metabolic risk factors for gallstone disease were different between men and women.

  1. Ursodeoxycholic acid improves gastrointestinal motility defects in gallstone patients

    Institute of Scientific and Technical Information of China (English)

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


    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, gallbladder and gastric emptying (by ultrasound), oroileal transit time (OI∏) (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: OI∏ was longer in GS than in CTR (P <0.0001); UDCA significantly reduced OI∏ in GS (P <0.0001), but not in CTR. GS had longer gastric halfemptying 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.

  2. [The treatment of gallstone disease in the elderly

    NARCIS (Netherlands)

    Assen, S. van; Nagengast, F.M.; Goor, H. van; Cools, B.M.


    Gallstone diseases (asymptomatic, symptomatic and complicated) are frequently seen in the elderly; the prevalence increases proportionally with age. At higher ages (> 60 years) the presentation of symptomatic or complicated gallstone disease is frequently atypical. Complicated gallstone disease (


    Institute of Scientific and Technical Information of China (English)

    石景森; 任斌; 马庆久; 孟清翠; 汪涛; 田和平; 韩梅荣; 卢云; 刘绍浩; 吴谨光



  4. Laparoscopic-Assisted Enterolithotomy for Gallstone Ileus


    Gupta, Rahul A.; Shah, Chetan R.; Balsara, K P


    Gallstone ileus is a rare complication of cholelithiasis seen usually in elderly population with comorbidities. Most of the cases present as acute intestinal obstruction with the diagnosis being made intraoperatively. There exists controversy regarding appropriate emergency surgical treatment of gallstone ileus as to whether biliary tract surgery should be done during the first operation. Laparoscopy in recent years is also being used for management of such cases. We report a case of gallston...

  5. Spontaneous resolution of a gallstone ileus


    Roberts, JA; Lambrianides, AL


    Gallstone ileus is an uncommon complication of cholelithiasis, usually associated with an internal biliary fistula. Management of gallstone ileus is surgical with enterolithotomy the procedure of choice, followed by fistula closure either as a one or two stage procedure. In this case a 66 year old female presented with colicky abdominal pain, computed tomography (CT) clearly showing a gallstone ileus and cholecystoduodenal fistula. Despite this the patient refused surgery and went on to have ...

  6. Immediate Postoperative Pain: An Atypical Presentation of Dropped Gallstones after Laparoscopic Cholecystectomy

    Directory of Open Access Journals (Sweden)

    Samba Binagi


    Full Text Available Cholecystectomy is one of the most commonly performed surgical procedures in the United States. A common complication is dropped gallstones, and the diversity of their presentation poses a substantial diagnostic challenge. We report the case of a 58-year-old man presenting with chronic right upper quadrant hours status post cholecystectomy. Imaging demonstrated retained gallstones in the perihepatic space and symptoms remitted following their removal via laparoscopic operation. Gallstones are lost in roughly 1 in 40 cholecystectomies and are usually asymptomatic. The most common presentations are months or years status post cholecystectomy due to fistula, abscess, or sinus tract formation. We report this case hoping to bring light to a rare presentation for dropped gallstones and provide advice on the management of this common complication of cholecystectomy.

  7. Prevalence of gallstones and gallbladder disease in Canadian Micmac Indian women. (United States)

    Williams, C N; Johnston, J L; Weldon, K L


    The prevalence of gallstones and gallbladder disease was studied between October 1973 and June 1976 in Canadian Micmac Indian women aged 15 to 50 years in an inland rural community near Shubenacadie, NS. Of 132 women at risk 98 underwent cholecystography, 6 had a history of cholecystectomy (verified from hospital records) and 3 had cholecystectomy because of cholecystitis during the 3 years of the study. Of the 17 abnormal cholecystograms 10 showed radiolucent gallstones, and repeated studies documented gallstones in 6 of the 7 radiographs on which the gallbladder was not visualized. The prevalence of gallstones was found to be 211/1000, and that of gallbladder disease, 240/1000. The peak prevalence was at 30 to 39 years of age. The women with gallbladder disease were significantly more obese and of greater parity than those without gallbladder disease even when age was controlled. The Micmac Indian women of Nova Scotia appear to be at a much higher risk for the development of cholesterol gallstones and gallbladder disease than Caucasian women in Framingham, Massachusetts.

  8. A low-saturated-fat, low-cholesterol diet decreases plasma CETP activity and pre beta-HDL formation but does not affect cellular cholesterol efflux to plasma from type 1 diabetic patients

    NARCIS (Netherlands)

    De Vries, R; Beusekamp, BJ; Kerstens, MN; Groen, AK; Van Tol, A; Dullaart, RPF


    The aim of this study was to evaluate the effect of a low-saturated-fat, low-cholesterol diet on plasma lipopoproteins, pre beta-high density lipoprotein (HDL) formation, lecithin: cholesterol acyltransferase (LCAT), cholesteryl ester transfer protein (CETP) and phospholipid transfer protein (PLTP)

  9. Successful topical dissolution of cholesterol gallbladder stones using ethyl propionate. (United States)

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


    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.

  10. Abdominal Symptoms and Incident Gallstones in a Population Unaware of Gallstone Status

    DEFF Research Database (Denmark)

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


    criteria were no gallstones or cholecystectomy at baseline and attending a reexamination. Results. Of 3,785 participants, 2,845 fulfilled inclusion criteria. Changes in overall abdominal pain were not significantly different between incident gallstones or gallstone-free participants. Multiple adjusted...... logistic regression analyses showed that incident gallstones were significantly associated with debut of abdominal pain with projection, localized in the whole upper abdomen, and of longer duration. No significant associations for functional symptoms were identified. Conclusions. A new onset of abdominal......Introduction. Symptoms associated with newly formed gallstones have never been studied in a population unaware of their gallstones. The objective of this population-based cohort study was to determine which debut of abdominal symptoms was associated with newly formed gallstones. Materials...

  11. Ternary complexes of albumin-Mn(II)-bilirubin and Electron Spin Resonance studies of gallstones

    CERN Document Server

    Chikvaidze, E N; Kirikashvili, I N; Mamniashvili, G I


    The stability of albumin-bilirubin complex was investigated depending on pH of solution. It was shown that the stability of complex increases in presence of Mn(II) ions. It was also investigated the paramagnetic composition of gallstones by the electron spin resonance (ESR) method. It turned out that all investigated gallstones contain a free bilirubin radical-the stable product of its radical oxidation. Accordingly the paramagnetic composition gallstones could be divided on three main types: cholesterol, brown pigment and black pigment stones. ESR spectra of cholesterol stones is singlet with g=2.003 and splitting between components 1.0 mT. At the same time the brown gallstones, besides aforementioned signal contain the ESR spectrum which is characteristics for Mn(II) ion complexes with inorganic compounds and, finally, in the black pigment stones it was found out Fe(III) and Cu(II) complexes with organic compounds and a singlet of bilirubin free radical. It is supposed that crystallization centers of gallst...

  12. 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


    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.

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

    Directory of Open Access Journals (Sweden)

    Cyril F Reboul


    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.

  14. A new model for pore formation by cholesterol-dependent cytolysins. (United States)

    Reboul, Cyril F; Whisstock, James C; Dunstone, Michelle A


    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.

  15. 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.

  16. Formation of cholesterol ozonolysis products in vitro and in vivo through a myeloperoxidase-dependent pathway (United States)

    Tomono, Susumu; Miyoshi, Noriyuki; Shiokawa, Hidemi; Iwabuchi, Tomoe; Aratani, Yasuaki; Higashi, Tatsuya; Nukaya, Haruo; Ohshima, Hiroshi


    3β-Hydroxy-5-oxo-5,6-secocholestan-6-al (secosterol-A) and its aldolization product 3β-hydroxy-5β-hydroxy-B-norcholestane-6β-carboxaldehyde (secosterol-B) were recently detected in human atherosclerotic tissues and brain specimens, and they may play pivotal roles in the pathogenesis of atherosclerosis and neurodegenerative diseases. However, as their origin remains unidentified, we examined the formation mechanism, the stability, and the fate of secosterols in vitro and in vivo. About 40% of secosterol-A remained unchanged after 3 h incubation in the FBS-free medium, whereas 20% and 40% were converted to its aldehyde-oxidation product, 3β-hydroxy-5-oxo-secocholestan-6-oic acid, and secosterol-B, respectively. In the presence of FBS, almost all secosterol-A was converted immediately to these compounds. Secosterol-B in the medium, with and without FBS, was relatively stable, but ∼30% was converted to its aldehyde-oxidation product, 3β-hydroxy-5β-hydroxy-B-norcholestane-6-oic acid (secoB-COOH). When neutrophil-like differentiated human leukemia HL-60 (nHL-60) cells activated with PMA were cultured in the FBS-free medium containing cholesterol, significantly increased levels of secosterol-A and its aldehyde-oxidation product, but not secosterol-B, were formed. This secosterol-A formation was decreased in the culture of PMA-activated nHL-60 cells containing several reactive oxygen species (ROS) inhibitors and scavengers or in the culture of PMA-activated neutrophils isolated from myeloperoxidase (MPO)-deficient mice. Our results demonstrate that secoterol-A is formed by an ozone-like oxidant generated with PMA-activated neutrophils through the MPO-dependent mechanism. PMID:20921334

  17. Laparoscopic-assisted enterolithotomy for gallstone ileus. (United States)

    Gupta, Rahul A; Shah, Chetan R; Balsara, K P


    Gallstone ileus is a rare complication of cholelithiasis seen usually in elderly population with comorbidities. Most of the cases present as acute intestinal obstruction with the diagnosis being made intraoperatively. There exists controversy regarding appropriate emergency surgical treatment of gallstone ileus as to whether biliary tract surgery should be done during the first operation. Laparoscopy in recent years is also being used for management of such cases. We report a case of gallstone ileus diagnosed preoperatively and successfully treated by laparoscopic-assisted enterolithotomy.

  18. Twice recurrent gallstone ileus: a case report

    Directory of Open Access Journals (Sweden)

    Jones Rhys


    Full Text Available Abstract Introduction Gallstone ileus is a rare cause of bowel obstruction and results from the passage of gallstones into the bowel. Case presentation We present the case of an 83-year-old Caucasian woman who had three episodes of gallstone ileus, each of which was managed with simple enterotomy. This sequence is one of the first reported in the medical literature and may be seen to challenge the traditional surgical approach of enterotomy alone. Conclusions The available evidence comparing enterotomy alone with combined enterotomy, cholecystectomy, and fistula closure in the management of gallstone ileus is reviewed. Neither approach is clearly identified as superior, but available series suggest that simple enterotomy may be safer than a combined approach and does not result in a higher rate of recurrent biliary disease.

  19. Gallstones Linked to Higher Heart Disease Risk (United States)

    ... news/fullstory_160497.html Gallstones Linked to Higher Heart Disease Risk Researcher says study highlights a connection between ... may have a slightly increased risk of developing heart disease down the road, a large new study suggests. ...

  20. 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


    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.

  1. Emergency ultrasound and gallstone ileus. (United States)

    Zironi, Gianni; Modolon, Cecilia; Cavazza, Mario


    Gallstone ileus is an uncommon cause of mechanical obstruction due to a biliary stone that wedges the intestinal lumen. It is a surgical emergency representing a clinical and diagnostic challenge: the clinical manifestations are rarely specific, often causing diagnostic delay that can adversely affect the prognosis. Emergency ultrasound could be useful in assessing the level and identifying the cause of bowel obstruction. We report a case of a 74-year-old patient with a 6-day history of constipation and crampy abdominal pain without previous history of abdominal diseases. Emergency ultrasound led to an early diagnosis showing dilated small bowel loops with a shadowing mass inside consistent with an ileal stone, in the absence of aberrant located stone on plain abdominal film.

  2. Perforated Closed-Loop Obstruction Secondary to Gallstone Ileus of the Transverse Colon: A Rare Entity

    Directory of Open Access Journals (Sweden)

    S. P. Carr


    Full Text Available Introduction. Gallstone ileus (GSI of the colon is an extremely rare entity with potentially serious complications including perforation. Case Presentation. An 88-year-old man presented to the emergency department with abdominal pain and distension. Clinical exam revealed signs of peritonism. Computed tomography (CT revealed GSI of the transverse colon with a closed-loop large bowel obstruction (LBO and caecal perforation. The patient underwent emergency laparotomy. A right hemicolectomy was performed, the gallstone was removed, and a primary bowel anastomosis was undertaken. A Foley catheter was sutured into the residual gallbladder bed to create a controlled biliary fistula. The patient recovered well postoperatively with no complications. He was discharged home with the Foley catheter in situ. Discussion. Gallstone ileus is a difficult diagnosis both clinically and radiologically with only 50% of cases being diagnosed preoperatively. Most commonly it is associated with impaction at the ileocaecal valve and small bowel obstruction. Gallstone ileus should also be considered as a rare but potential cause of LBO. This is the first reported case of caecal perforation secondary to gallstone ileus of the transverse colon. Successful operative management consisted of a one-stage procedure with right hemicolectomy and formation of a controlled biliary fistula.

  3. Perforated closed-loop obstruction secondary to gallstone ileus of the transverse colon: a rare entity. (United States)

    Carr, S P; MacNamara, F T; Muhammed, K M; Boyle, E; McHugh, S M; Naughton, P; Leahy, A


    Introduction. Gallstone ileus (GSI) of the colon is an extremely rare entity with potentially serious complications including perforation. Case Presentation. An 88-year-old man presented to the emergency department with abdominal pain and distension. Clinical exam revealed signs of peritonism. Computed tomography (CT) revealed GSI of the transverse colon with a closed-loop large bowel obstruction (LBO) and caecal perforation. The patient underwent emergency laparotomy. A right hemicolectomy was performed, the gallstone was removed, and a primary bowel anastomosis was undertaken. A Foley catheter was sutured into the residual gallbladder bed to create a controlled biliary fistula. The patient recovered well postoperatively with no complications. He was discharged home with the Foley catheter in situ. Discussion. Gallstone ileus is a difficult diagnosis both clinically and radiologically with only 50% of cases being diagnosed preoperatively. Most commonly it is associated with impaction at the ileocaecal valve and small bowel obstruction. Gallstone ileus should also be considered as a rare but potential cause of LBO. This is the first reported case of caecal perforation secondary to gallstone ileus of the transverse colon. Successful operative management consisted of a one-stage procedure with right hemicolectomy and formation of a controlled biliary fistula.

  4. Human aortic fibrolipid lesions. Progenitor lesions for fibrous plaques, exhibiting early formation of the cholesterol-rich core. (United States)

    Bocan, T. M.; Guyton, J. R.


    The early development of the lipid-rich core and other features of atherosclerotic fibrous plaques has been elucidated by examining discrete, small regions of raised intima in human aorta, which often bear a resemblance to both fatty streaks and fibrous plaques. Approximately one-fourth of small raised lesions (less than 16 sq mm of surface area) contained little or no stainable lipid, while three-fourths had a characteristic appearance, which included a superficial layer of foam cells, a core of noncrystalline and/or crystalline lipid, and a developed or developing collagenous cap. Total intimal volumes of the lipid-containing lesions, termed "fibrolipid lesions," ranged from 3 to 43 microliters, with the majority less than 16 microliters. Core lipid in the smallest lesions was located in the musculoelastic layer of the intima. In larger lesions the core extended luminally into the elastic hyperplastic layer, and cholesterol crystals were found more frequently. Total cholesterol concentration in fibrolipid lesions was similar to that in fatty streaks; however, the ratio of unesterified to total cholesterol was relatively high, similar to that found in fibrous plaques. It is concluded that 1) the formation of a lipid-rich core and cholesterol crystallization are early events in the development of many raised lesions; 2) the consistent association between the superficial layer of foam cells and the deep-lying lipid-rich core raises the possibility of an influence, possibly indirect, of foam-cell lipid metabolism on core formation; and 3) the fibrolipid lesion may represent one stage in a potential transitional morphologic sequence between fatty streak and fibrous plaque. Images Figure 2 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 Figure 9 Figure 10 Figure 11 Figure 12 Figure 13 Figure 14 PMID:4025509

  5. Gallstones (United States)

    ... may cause swelling or infection in the: Gallbladder (cholecystitis) Tube that carries bile from the liver to ... Elsevier Saunders; 2012:chap 55. Read More Acute cholecystitis Bile Cholangitis Choledocholithiasis Chronic cholecystitis Gallbladder removal - laparoscopic ...

  6. High cholesterol diet increases osteoporosis risk via inhibiting bone formation in rats

    Institute of Scientific and Technical Information of China (English)

    Li YOU; Zheng-yan SHENG; Chuan-ling TANG; Lin CHEN; Ling PAN; Jin-yu CHEN


    To investigate the effects of high cholesterol diet on the development of osteoporosis and the underlying mechanisms in rats.Methods:Female Sprague-Dawley rats were randomly separated into 3 groups:(1) the high cholesterol fed rats were fed a high cholesterol diet containing 77% normal diet food,3% cholesterol and 20% lard for 3 months; (2) ovariectomised (OVX) rats were bilaterally ovariectomised and fed a standard diet; and (3) the control rats were fed the standard diet.Bone mineral density (BMD) of the rats was measured using dual-energy X-ray absorptiometry.Serum levels of oestradiol (E2),osteocalcin (BGP) and carboxy-terminal collagen crosslinks (CTX) were measured using ELISA.Gene expression profile was determined with microarray.Mouse osteoblast cells (MC3T3-E1) were used for in vitro study.Proliferation,differentiation and oxidative stress of the osteoblasts were investigated using MTT,qRT-PCR and biochemical methods.Results:In high cholesterol fed rats,the femur BMD and serum BGP level were significantly reduced,while the CTX level was significantly increased.DNA microarray analysis showed that 2290 genes were down-regulated and 992 genes were up-regulated in this group of rats.Of these genes,1626 were also down-regulated and 1466 were up-regulated in OVX rats.In total,370 genes were up-regulated in both groups,and 976 genes were down-regulated.Some of the down-regulated genes were found to code for proteins involved in the transforming growth factor beta (TGF-β)/bone morphogenic protein (BMP) and Wnt signaling pathways.The up-regulated genes were found to code for IL-6 and Ager with bone-resorption functions.Treatment of MC3T3-E1 cells with cholesterol (12.5-50μg/mL) inhibited the cell proliferation and differentiation in vitro in a concentration-dependent manner.The treatment also concentration-dependently reduced the expression of BMP2 and Cbfa1,and increased the oxidative injury in MC3T3-E1 cells.Conclusion:The results suggest a close

  7. Gallstone ileus of the sigmoid colon: an unusual cause of large-bowel obstruction. (United States)

    Osman, Nadir; Subar, Daren; Loh, Mong-Yang; Goscimski, Andrzej


    Gallstone ileus of the colon is an exceedingly rare cause of large-bowel obstruction. It is usually the result of fistula formation between the gallbladder and large bowel facilitating entry of the stone into gastrointestinal tract. Contrast enhanced abdominal computed tomography is an important diagnostic aid. Surgical management is the treatment of choice to prevent the disastrous complications of large-bowel obstruction. We describe the case of a 92-year-old man who presented with symptoms and signs of large-bowel obstruction. Radiological investigation showed a large gallstone impacted in the sigmoid colon. Open enterolithotomy was undertaken relieving the obstruction and the patient made a full recovery.

  8. Cholesterol Test (United States)

    ... AACC products and services. Advertising & Sponsorship: Policy | Opportunities Cholesterol Share this page: Was this page helpful? Also known as: Blood Cholesterol Formal name: Total Cholesterol Related tests: HDL Cholesterol , ...

  9. What's Cholesterol? (United States)

    ... los dientes Video: Getting an X-ray What's Cholesterol? KidsHealth > For Kids > What's Cholesterol? Print A A ... thing for food to be low in it? Cholesterol and Your Body Cholesterol (say: kuh-LES-tuh- ...

  10. What's Cholesterol? (United States)

    ... Room? What Happens in the Operating Room? What's Cholesterol? KidsHealth > For Kids > What's Cholesterol? A A A ... thing for food to be low in it? Cholesterol and Your Body Cholesterol (say: kuh-LES-tuh- ...

  11. SIRT6 reduces macrophage foam cell formation by inducing autophagy and cholesterol efflux under ox-LDL condition. (United States)

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


    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. This article is protected by copyright. All rights reserved.

  12. Cholesterol and stigmasterol within a sunflower oil matrix: Thermal degradation and oxysterols formation. (United States)

    Barriuso, Blanca; Ansorena, Diana; Poyato, Candelaria; Astiasarán, Iciar


    The characteristics of the lipid matrix surrounding sterols exert a great influence in their thermal oxidation process. The objective of this work was to assess the oxidation susceptibility of equal amounts of cholesterol and stigmasterol within a sunflower oil lipid matrix (ratio 1:1:200) during heating (180°C, 0-180min). Remaining percentage of sterols was determined and seven sterol oxidation products (SOPs) were analysed for each type of sterol along the heating treatment. Evolution of the fatty acid profile and vitamin E content of the oil was also studied. Overall oxidation status of the model system was assessed by means of Peroxides Value (PV) and TBARS. PV remained constant from 30min onwards and TBARS continued increasing along the whole heating treatment. Degradation of both cholesterol and stigmasterol fitted a first order curve (R(2)=0.937 and 0.883, respectively), with very similar degradation constants (0.004min(-1) and 0.005min(-1), respectively). However, higher concentrations of oxidation products were found from cholesterol (79μg/mg) than from stigmasterol (53μg/mg) at the end of the heating treatment. Profile of individual oxidation products was similar for both sterols, except for the fact that no 25-hydroxystigmasterol was detected. 7α-Hydroxy and 7-keto-derivatives were the most abundant SOPs at the end of the treatment. PUFA and vitamin E suffered a significant degradation along the process, which was correlated to sterols oxidation.

  13. Gallstone ileus resulting in strong intestinal obstruction

    Directory of Open Access Journals (Sweden)

    Israel Szajnbok

    Full Text Available Mechanic intestinal obstruction, caused by the passage of biliary calculus from vesicle to intestine, through fistulization, although not frequent, deserve study due to the morbi-mortality rates. Incidence in elder people explains the association with chronic degenerative diseases, increasing complexity in terms of therapy decision. Literature discusses the need and opportunity for the one or two-phase surgical attack of the cholecystenteric fistule, in front of the resolution on the obstructive urgency and makes reference to Gallstone Ileus as an exception for strong intestinal obstruction. The more frequent intestinal obstruction observed is when it occurs a Gallstone Ileus impacting in terms of ileocecal valve. The authors submit a Gallstone Ileus manifestation as causing strong intestinal obstruction, discussing aspects regarding diagnostic and treatment.

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

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


    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.

  15. Enteric motility alterations in experimental gallbladder cholesterol stones formation in guinea pigs%豚鼠胆囊胆固醇结石形成过程中小肠动力的变化

    Institute of Scientific and Technical Information of China (English)

    殷振华; 吴硕东; 范莹


    目的 观察豚鼠胆囊胆固醇结石形成过程中小肠动力的变化,探讨其在胆囊结石形成中的作用.方法 将40只豚鼠随机分为实验组与对照组,每组20只,实验组给予致石饲料(胆固醇含量2%),对照组给予正常颗粒饲料,8周造模结束后,利用多通道生理记录仪分别记录实验组与对照组豚鼠离体小肠肌条慢波和张力变化,分析其与胆囊胆固醇结石形成的关系,组间比较采用t检验.结果 豚鼠小肠离体肌条慢波频率实验组为5.70±1.05次/min,对照组为17.45±1.50次/min,振幅实验组为0.23±0.31 mv,对照组为0.78 ±0.17 my,实验组数据较对照组明显降低,P值分别为:4.56×10-25,4.00×10-13,均<0.05;组间比较t值分别为:-27.083,-13.236;豚鼠小肠离体肌条肌肉收缩频率实验组为5.94±1.25次/min,对照组为15.85±1.76次/min,张力效应值实验组为0.78±0.02g,对照组为1.20±0.11g,实验组数据较对照组明显降低,P值分别为2.41×10-20,1.55×10-13,均<0.05;组间比较t值分别为:- 19.448,- 17.307.结论 致石组豚鼠小肠动力较对照组明显下降,提示小肠动力异常可能在胆囊胆固醇结石形成过程中发挥作用.%Objective To study the changes in small intestinal motility during the process of gallbladder cholesterol stone formation.Methods Forty guinea pigs were divided into two groups of 20 each,the experiment group fed on high cholesterol diet ( cholesterol 2% ),while the control group on normal diet.Animals were sacrificed at 8 weeks.Slow wave and tension of the isolated small intestinal muscle specimen were measured using a multi-channel physiological recorder,and its relation to gallstone formation was assessed.Results Compared with the control group,the frequency and amplitude of the slow wave significantly reduced in the experimental group (5.70 ± 1.05/min vs.17.45 ± 1.50/min and 0.23 ± 0.31 my vs.0.78 ±0.17 mv respectively,P <0.05).The t-value between the two

  16. Study on the Controlled Gel Formation and Photochromic Properties of a New Cholesterol-bridge-naphthopyran Dyad

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Lin; Wang, Guang; Liu, Longbo; Wang, Ai Xia [Northeast Normal Univ., Jilin (China)


    A cholesterol-bridge-naphthopyran dyad (NP-MCB) was designed and synthesized. NP-MCB can readily self-assemble into gels under ultrasound-radiation in several organic solvents and the formed gels easily transfer to solution by heat. This reversible process can be repeated many times. Scanning Electron Microscopy results showed that the morphologies of all formed xerogels in different solvents have fibrillar microstructure. The gels formation was due to energy and pressure afforded by the ultrasonic process, resulting in formation of molecular hydrogen bonding and molecular aggregation. NP-MCB displayed the normal photochromism both in solution and gel states. The kinetic results confirm that the colored merocyanine in gels show a slower fading speed than that in solution due to the compact aggregation of NP-MCB molecules in gels. The xerogel film formed in polar gelling solvent had large surface wettability than that in nonpolar gelling solvent.

  17. Sonographic demonstration of a gallstone ileus

    Energy Technology Data Exchange (ETDEWEB)

    Uebel, H.E.; Wilhelm, F.


    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.

  18. 胆结石小鼠肝脏核受体基因LRH-1及其调控基因CYP7A1的表达%Gene expression of liver nuclear receptor LRH-1 and cholesterol 7-α hydroxylase genes in cholesterol gallstone mice

    Institute of Scientific and Technical Information of China (English)

    任明; 郭嵩; 杨士勇; 曹红勇


    目的:探讨胆固醇结石(GS)小鼠肝脏的核受体基因—旰核受体类似物1 (liver receptor homolog 1,LRH-1)及其调控基因胆固醇7α-羟化酶(cholesterol 7-α hydroxylase,CYP7A1)的表达.方法:雌性C57BL/6小鼠40只,分为2组,每组20只,分别予以正常饮食、高脂饮食喂养10周后处死.病理切片检查小鼠胆囊壁细胞组织学改变,实时定量PCR法测定肝脏LRH-1及CYP7A1表达量.Western Blot方法测定肝脏上述基因蛋白的表达量.结果:胆结石小鼠胆囊壁细胞呈现炎性改变.胆石组小鼠LRH-1 mRNA及蛋白表达均高于对照组(P<0.01),CYP7A1 mRNA及蛋白表达量较对照组升高(P<0.01).结论:啮齿动物肝脏LRH-1和CYP7A1的表达异常与胆囊胆固醇结石形成有关,可能共同在小鼠胆结石形成中发挥作用.

  19. Stepwise visualization of membrane pore formation by suilysin, a bacterial cholesterol-dependent cytolysin. (United States)

    Leung, Carl; Dudkina, Natalya V; Lukoyanova, Natalya; Hodel, Adrian W; Farabella, Irene; Pandurangan, Arun P; Jahan, Nasrin; Pires Damaso, Mafalda; Osmanović, Dino; Reboul, Cyril F; Dunstone, Michelle A; Andrew, Peter W; Lonnen, Rana; Topf, Maya; Saibil, Helen R; Hoogenboom, Bart W


    Membrane attack complex/perforin/cholesterol-dependent cytolysin (MACPF/CDC) proteins constitute a major superfamily of pore-forming proteins that act as bacterial virulence factors and effectors in immune defence. Upon binding to the membrane, they convert from the soluble monomeric form to oligomeric, membrane-inserted pores. Using real-time atomic force microscopy (AFM), electron microscopy (EM), and atomic structure fitting, we have mapped the structure and assembly pathways of a bacterial CDC in unprecedented detail and accuracy, focussing on suilysin from Streptococcus suis. We show that suilysin assembly is a noncooperative process that is terminated before the protein inserts into the membrane. The resulting ring-shaped pores and kinetically trapped arc-shaped assemblies are all seen to perforate the membrane, as also visible by the ejection of its lipids. Membrane insertion requires a concerted conformational change of the monomeric subunits, with a marked expansion in pore diameter due to large changes in subunit structure and packing.

  20. 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


    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.

  1. About Cholesterol (United States)

    ... Artery Disease Venous Thromboembolism Aortic Aneurysm More About Cholesterol Updated:Apr 3,2017 It may surprise you ... our bodies to keep us healthy. What is cholesterol and where does it come from? Cholesterol is ...

  2. Levels of serum leptin, cholecystokinin, plasma lipid and lipoprotein differ between patients with gallstone or/and those with hepatolithiasis

    Institute of Scientific and Technical Information of China (English)

    Zheng-Ming Lei; Ming-Xin Ye; Wen-Guang Fu; Yue Chen; Cheng Fang; Jing Li


    BACKGROUND:A signiifcant relationship exists among food intake and nutritional status and cholelithiasis, including gallstone and hepatolithiasis. Leptin is associated with obesity. This study was to investigate the differences in serum leptin levels in patients with gallstone and hepatolithiasis and to evaluate the relationships among leptin, cholecystokinin (CCK), lipid and lipoprotein concentrations. METHODS:Body mass index (BMI), serum leptin, CCK, insulin, lipid and lipoprotein concentrations, and liver function were measured in 382 patients with gallstone (GS group), 83 patients with hepatolithiasis (HS group) and 30 healthy controls (control group). The values of these indices were compared among the groups. In each group, Pearson's product-moment correlation coefifcient among these indices were evaluated. RESULTS:There were notable differences in serum leptin, CCK, total cholesterol, total triglycerides, apolipoprotein-a (APO-a), globulin, direct reacting bilirubin, and BMI between the GS and HS groups (P CONCLUSIONS:Leptin participates in modulating lipid metabolism. There are notable differences in leptin, serum lipid, and CCK between patients with gallstone and those with hepatolithiasis. The role of leptin in the pathophysiological course of cholelithiasis needs further investigation.

  3. Mucin and phospholipids determine viscosity of gallbladder bile in-patients with gallstones

    Institute of Scientific and Technical Information of China (English)

    Dieter Jungst; Anna Niemeyer; Iris Muller; Benedikta Zundt; Gunther Meyer; Martin Wilhelmi; Reginald del Pozo


    AIM An increased viscosity of gallbladder bile has been considered an important factor in the pathogenesis of gallstone disease. Besides lipids and proteins, mucin has been suggested to affect the viscosity of bile. To further clarify these issues we compared mucin, protein and the lipid components of hepatic and gallbladder bile and its viscosity in patients with gallstones.METHODS Viscosity of bile ( mpa. s ) wasmeasured using rotation viscosimetry in regard to the non-Newtonian property of bile at law shear rates.RESULTS Biliary viscosity was markedly higher in gallbladder bile of patients with cholesterol (5.00 ± 0.60 mpa. s, mean ± SEM, n --28) and mixed stones (3.50±0.68 mPa. s; n =8) compared to hepatic bile (0.92 ± 0.06 mpa. s,n -6). A positive correlation between mucin and viscosity was found in gallbladder biles (r=0.65; P<0.001) but not in hepatic biles. The addition of physiologic and supraphysiologic amounts of mucin to gallbladder bile resulted in a dose dependent non linear increase of its viscosity. A positive correlation was determined between phospholipid concentration and viscosity (r = 0.34, P<0.005) in gallbladder biles. However, no correlation was found between total protein or the other lipid concentrations and viscosity in both gallbladder and hepatic biles.CONCLUSION The viscosity of gallbladder bile is markedly higher than that of hepatic bile in patients with gallstones. The concentration of mucin is the major determinant of biliary viscosity and may contribute by this mechanism to the role of mucin in the pathogenesis of gallstones.

  4. Delayed phlegmon with gallstone fragments masquerading as soft tissue sarcoma (United States)

    Goodman, Laura F.; Bateni, Cyrus P.; Bishop, John W.; Canter, Robert J.


    Complications from lost gallstones after cholecystectomy are rare but varied from simple perihepatic abscess to empyema and expectoration of gallstones. Gallstone complications have been reported in nearly every organ system, although reports of malignant masquerade of retained gallstones are few. We present the case of an 87-year-old woman with a flank soft tissue tumor 4 years after laparoscopic cholecystectomy. The initial clinical, radiographic and biopsy findings were consistent with soft tissue sarcoma (STS), but careful review of her case in multidisciplinary conference raised the suspicion for retained gallstones rather than STS. The patient was treated with incisional biopsy/drainage of the mass, and gallstones were retrieved. The patient recovered completely without an extensive resectional procedure, emphasizing the importance of multidisciplinary sarcoma care to optimize outcomes for potential sarcoma patients. PMID:27333918

  5. Gallstone ileus of duodenum with huge duodenal stone


    Mohammad Ehsan; Mohammad Reza Ahangaran


    Gastrointestinal obstruction by a gallstone is an uncommon but important complication of biliary stone disease which mostly affects the elderly. The classic triad of radiological features includes pneumobilia, ectopic gallstone and evidence of intestinal obstruction. Terminal ileum is the most common site of obstruction, followed by jejunum and gastric outlet. We present a case of duodenal gallstone ileus of a large, fluid-density mixed biliary stone with a peripheral rim of hyperdensity (ver...

  6. Gallstone ileus of duodenum with huge duodenal stone

    Directory of Open Access Journals (Sweden)

    Mohammad Ehsan


    Full Text Available Gastrointestinal obstruction by a gallstone is an uncommon but important complication of biliary stone disease which mostly affects the elderly. The classic triad of radiological features includes pneumobilia, ectopic gallstone and evidence of intestinal obstruction. Terminal ileum is the most common site of obstruction, followed by jejunum and gastric outlet. We present a case of duodenal gallstone ileus of a large, fluid-density mixed biliary stone with a peripheral rim of hyperdensity (very fine calcification in CT scan. KEY WORDS: Gallstone ileus, duodenum, intestinal obstruction.

  7. Open Cholecystectomy for Surgical Treatment of Gallstones

    Directory of Open Access Journals (Sweden)

    Jorge Luis Estepa Pérez


    Full Text Available Background: cholecystectomy is one of the surgical procedures that are still practiced despite the passing of time. It remains the appropriate method to perform in the absence of advanced technology. Objective: to describe the results of the open cholecystectomy in the treatment of gallstones. Methods: a descriptive study was conducted in patients operated on for gallstones in 2012 in the María G. Guerrero Ramos Comprehensive Diagnostic Center in the Capital District, Bolivarian Republic of Venezuela. The information was obtained from medical records and a data collection model. The variables analyzed were: age, sex, associated diseases, signs and symptoms, results of the surgical treatment, outcome and complications. Results: a total of 147 patients underwent surgery; the 41-60 year age group and female patients predominated; right hypochondrial pain and intolerance to fatty foods and grains were the major signs and symptoms. Cefazolin was the most widely used antibiotic. Patients recovered satisfactorily, complications were minimal. Conclusions: open cholecystectomy remains useful for the treatment of gallstones in the absence of advanced technology.

  8. A Case of an Abdominal Wall Abscess Associated with Spilled Gallstones: Imaging Findings and Clinical Significance

    Energy Technology Data Exchange (ETDEWEB)

    Son, Youn Mi; Kim, Hyuk Jung; Bak, Cheol Hee [Seoul Medical Center, Seoul (Korea, Republic of)


    Laparoscopic cholecystectomy (LC) has been the gold standard for symptomatic gall stones for the last 20 years. The spillage of stones is reported in up to one-third of all LCs but clinical squeals caused by dropped gallstones are uncommon. We recently observed a patient with late abdominal wall abscess formation as a result of dropped gall stones after LC, who in the end, underwent open surgery because the medical therapy including antibiotics and percutaneous catheter drainage was not fully effective

  9. Effect of different cooking methods on lipid oxidation and formation of free cholesterol oxidation products (COPs) in Latissimus dorsi muscle of Iberian pigs. (United States)

    Broncano, J M; Petrón, M J; Parra, V; Timón, M L


    The aim of this work was to study the influence of different cooking methods (grilled (GR), fried (FP), microwave (MW) and roasted (RO)) on lipid oxidation and formation of free cholesterol oxidation products (COPs) of meat from Iberian pigs that have been fed on an intensive system. Moisture and total lipid content, TBARs, hexanal and COPs were measured in Latissimus dorsi muscle samples. Cooking did not produce changes in total lipid content in meat but induced significantly higher lipid oxidation (TBARs and hexanal values) (p<0.001) and cholesterol oxidation (COPs) (p<0.01). When the different cooking methods were studied, the grilled method was the least affected by lipid oxidation (TBARs and hexanal) compared to the others. There were no significant differences among different cooking methods on COPs values. The most abundant cholesterol oxides were both 7α-hydroxycholesterol and 7β-hydroxycholesterol in all groups studied.

  10. Value of ultrasonography in the diagnosis of gallstone ileus

    Energy Technology Data Exchange (ETDEWEB)

    Pedersen, P.R.; Kastberg Petersen, K.; Topp, S.W.


    Two patients are presented, both of whom were admitted to hospital because of abdominal pains. In both patients, ultrasonography showed gallstones in the lower abdomen and in the small bowel loops were found to be dilated. In both cases it was possible to diagnose the gallstone ileus by ultrasonography and to mark the abdomen as a guide to the surgeon.

  11. Cholesterol (image) (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 ...

  12. Imaging findings of intragastric gallstone and bouveret's syndrome : case report

    Energy Technology Data Exchange (ETDEWEB)

    Lim, Seong Youb; Seong, Hun; Park, Jong Yeon; Seo, Chang Hye; Jang, Kyung Jae; Cho, Seong Rak [Department of Radiology, Dae Dong Hospital, Pusan (Korea, Republic of)


    Gallstone ileus is a well-known complication of cholelithiasis, but is relatively rare. Most ectopic gallstones are located in the small bowel; they are rarely found in the stomach and duodenum. We describe the imaging findings of a case of intragastric gallstone, as well as a case in which duodenal obstruction was caused by a large gallstone (Bouveret's syndrome). (author)

  13. Gallstone ileus as a cause of upper intestinal obstruction

    Directory of Open Access Journals (Sweden)

    Israel Szajnbock

    Full Text Available Gallstone ileus, a mechanical intestinal obstruction caused by the passage of a gallstone into the intestinal lumen through a fistula, although not common, deserves to more carefully studied due to its morbidity and mortality. Its incidence among older-age groups explains its association with chronic and degenerative diseases, which increase the complexity of the treatment choice.The need and appropriateness of a surgical approach to a cholecystenteric fistula to solve the obstructive emergency, in a one or two stage procedure, has been discussed in the literature. It has also been reported that gallstone ileus is an uncommon cause of upper intestinal obstruction. Intestinal obstruction is seen more frequently after a gallstone impacts at the ileocecal valve. The authors report a case of gallstone ileus as a cause of upper intestinal obstruction and discuss its diagnosis and treatment.

  14. Primary hyperparathyroidism presenting as acute gallstone pancreatitis

    Institute of Scientific and Technical Information of China (English)

    HE Jian-hong; ZHANG Quan-bao; LI Yu-min; ZHU You-quan; LI Xun; SHI Bin


    @@ Primary hyperparathyroidism (PHPT) is a generalized disorder of calcium metabolism resulting from an abnormally high level of serum calcium and an increased level of parathormone (PTH).1,2 Traditionally, symptomatic PHPT patients present with a variety of disorders including fatigue, amyotrophy, memory impairment, emotional instability, hallucination, irritation, loss of consciousness, abdominal distention, nausea, vomiting, constipation, acute pancreatitis, refractory peptic ulcer, osteopenia, hypertension, etc.3-5 Acute pancreatitis (AP) is an uncommon presentation of PHPT.6-8 We report a typical case of primary hyperparathyroidism with hypercalcemic crisis presenting as acute gallstone pancreatitis.

  15. 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 INTRODUCTION: 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. OBJECTIVE: 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. MATERIAL AND METHODS: 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. RESULTS AND DISCUSSION: 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.

  16. 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


    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.

  17. Gallstone ileus one quarter of a century post cholecystectomy. (United States)

    Saedon, Mahmud; Gourgiotis, Stavros; Salemis, Nikolaos S; Majeed, Ali W; Zavos, Apostolos


    Gallstone ileus is a rare but potentially serious complication of cholelithiasis. It is usually preceded by history of biliary symptoms. It usually occurs as a result of a large gallstone creating and passing through a cholecysto-enteric fistula. Most of the time, the stone will pass the GI tract without any problems, but large enough stones can cause obstruction. The two most common locations of impaction are the terminal ileum and the ileocaecal valve because of the anatomical small diameter and less active peristalsis. We present an unusual case of small bowel obstruction secondary to gallstone ileus 24 years after an open cholecystectomy.

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

    Institute of Scientific and Technical Information of China (English)



    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.

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

    DEFF Research Database (Denmark)

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


    , 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...... was median 17.5 years and 99.8% complete. Cox regression analyses were performed. RESULTS: Gallstone events occurred in 16.6% participants of whom 7.2% were complicated and 9.4% were uncomplicated. Total events were associated to body mass index. Complicated events were associated to coffee consumption...

  20. Good vs. Bad Cholesterol (United States)

    ... Venous Thromboembolism Aortic Aneurysm More Good vs. Bad Cholesterol Updated:Apr 3,2017 Cholesterol can't dissolve ... test . View an animation of cholesterol . LDL (Bad) Cholesterol LDL cholesterol is considered the “bad” cholesterol because ...

  1. High Blood Cholesterol (United States)

    ... version of this page please turn Javascript on. High Blood Cholesterol What is High Blood Cholesterol? What is Cholesterol? Cholesterol is a ... heart disease. If Your Blood Cholesterol Is Too High Too much cholesterol in your blood is called ...

  2. Role of genetic variant A-204C of cholesterol 7alpha-hydroxylase (CYP7A1) in susceptibility to gallbladder cancer. (United States)

    Srivastava, Anvesha; Pandey, Sachchida Nand; Choudhuri, Gourdas; Mittal, Balraj


    Gallbladder carcinoma (GBC) usually arises in the background of gallstone disease. Cholesterol 7alpha-hydroxylase (CYP7A1) is a rate-limiting enzyme for cholesterol catabolism and bile acid synthesis. A-204C genetic polymorphism in CYP7A1 may influence gene expression and thus affect the risk of gallstone disease and GBC. We aimed to study the association of A-204C variation of CYP7A1 gene promoter polymorphism in GBC patients, gallstone patients and healthy subjects. The study included 141 histopathologically proven GBC patients, ultrasonographically proven 185 symptomatic gallstone patients and 200 gallstone-free healthy subjects. Genotyping was done by PCR-RFLP method. CYP7A1 A-204C genotypes in control population were in Hardy-Weinberg equilibrium. The CC genotype conferred marginally significant risk for gallstone disease (p=0.051; OR=1.54; 95% CI=0.9-3.4). In GBC patients, the CYP7A1 A-204C polymorphism conferred high risk for GBC at genotype (p=0.005; OR=2.78; 95% CI: 1.3-5.6) as well as allele levels (p=0.008; OR=1.58 and 95% CI: 1.1-2.2). After stratification of GBC patients on the basis of presence or absence of gallstones, CC genotype imparted higher risk for GBC without stones (p=0.002; OR=4.44: 95% CI=1.7-11.3). The association of the polymorphism with GBC was more pronounced in female GBC patients, and also in cancer patients who developed GBC at advanced age. The CC genotype of CYP7A1 is an independent genetic risk factor for GBC but plays a modest role in susceptibility to gallstone disease. The GBC pathogenesis by CYP7A1 polymorphism appears to be independent of gallstone pathway and probably involves genotoxicity due to lipid peroxidation mechanisms.

  3. Light-controlled formation of vesicles and supramolecular organogels by a cholesterol-bearing amphiphilic molecular switch

    NARCIS (Netherlands)

    van Herpt, Jochem T.; Areephong, Jetsuda; Stuart, Marc C. A.; Browne, Wesley R.; Feringa, Ben L.


    A new responsive material composed of an amphiphilic light-switchable dithienylethene unit functionalized with a hydrophobic cholesterol unit and a hydrophilic poly(ethylene glycol)-modified pyridinium group has been designed. This unique single-molecule system shows responsive light-switchable self

  4. Sphingolipid and cholesterol dependence of alphavirus membrane fusion - Lack of correlation with lipid raft formation in target liposomes

    NARCIS (Netherlands)

    Waarts, BL; Bittman, R; Wilschut, J


    Semliki Forest virus (SFV) and Sindbis virus (SIN) are enveloped viruses that infect their host cells by receptor-mediated endocytosis and subsequent fusion from within acidic endosomes. Fusion of the viral envelope requires the presence of both cholesterol and sphingolipids in the target membrane.

  5. Gallstone ileus of the colon: leave no stone unturned. (United States)

    Salemans, P B; Vles, G F; Fransen, S; Vliegen, R; Sosef, M N


    A case of gallstone ileus of the colon with illustrative pictures is presented, making the physicians more aware of this rare entity. Furthermore, the use of imaging modalities for diagnosis and decision making in management strategy is discussed.

  6. Gallstone Ileus of the Colon: Leave No Stone Unturned


    P. B. Salemans; Vles, G. F.; S. Fransen; Vliegen, R.; Sosef, M.N.


    A case of gallstone ileus of the colon with illustrative pictures is presented, making the physicians more aware of this rare entity. Furthermore, the use of imaging modalities for diagnosis and decision making in management strategy is discussed.

  7. Transient hepatic overexpression of Insulin-like growth factor 2 induces free cholesterol and lipid droplet formation

    Directory of Open Access Journals (Sweden)

    Sonja M Kessler


    Full Text Available Although insulin-like growth factor 2 (IGF2 has been reported to be overexpressed in steatosis and steatohepatitis, a causal role of IGF2 in steatosis development remains elusive. Aim of our study was to decipher the role of IGF2 in steatosis development.Hydrodynamic gene delivery of the Igf2 plasmid used for transient IGF2 overexpression employing codon-optimized plasmid DNA resulted in a strong induction of hepatic Igf2 expression. The exogenously delivered Igf2 had no influence on endogenous Igf2 expression. The downstream kinase AKT was activated in IGF2 animals. Decreased ALT levels mirrored the cytoprotective effect of IGF2. Serum cholesterol was increased and sulfo-phospho-vanillin colorimetric assay confirmed lipid accumulation in IGF2-livers without signs of inflammation. Interestingly, hepatic cholesterol and phospholipids, determined by thin layer chromatography and free cholesterol by filipin staining, were specifically increased. Lipid droplet (LD size was not changed, but their number was significantly elevated. Furthermore, free cholesterol, which can be stored in LDs and has been reported to be critical for steatosis progression, was elevated in IGF2 overexpressing mice. Accordingly, HmgCoAR was upregulated. To have a closer look at de novo lipid synthesis we investigated expression of the lipogenic transcription factor SREBP1 and its target genes. SREBP1 was induced and also SREBP1 target genes were slightly upregulated. Interestingly, the expression of Cpt1a, which is responsible for mitochondrial fatty acid oxidation, was induced. Hepatic Igf2 expression induces a fatty liver, characterized by increased cholesterol and phospholipids leading to accumulation of LDs. We therefore suggest a causal role for IGF2 in hepatic lipid accumulation.

  8. Nationwide epidemiological study of severe gallstone disease in Taiwan

    Directory of Open Access Journals (Sweden)

    Lin Jou-Wei


    Full Text Available Abstract Background Our study aimed to assess the nationwide trends in the incidence of severe gallstone disease in Taiwan among adults aged ≥20. Methods A retrospective longitudinal study was conducted using Taiwan National Health Insurance Research Database collected during 1997–2005. Patients with incident severe gallstone disease (acute cholecystitis, biliary pancreatitis, acute cholangitis and gallstone-related procedures (elective and non-elective cholecystectomy, endoscopic retrograde cholangiopancreatography [ERCP] that led to hospital admission were identified using ICD-9-CM diagnostic and procedure codes. Annual incidence rates of gallstone-related complications and procedures were calculated and their 95% confidence intervals (CI were estimated assuming a Poisson distribution. Results The hospital admission rate for severe gallstone disease increased with advancing age and the age-standardized rate (95% CI per 1000 population was 0.60 (0.59–0.60 for men and 0.59 (0.59–0.60 for women. Men had a higher rate of acute cholecystitis, probably due to the substantially lower rate of elective cholecystectomy among men than women. For those aged 20–39, hospital admissions for all gallstone-related complications and procedures increased significantly. For those aged ≥60, incidences of biliary pancreatitis, acute cholangitis, and hospital admission for gallstone receiving ERCP increased significantly without substantial change in the incidence of acute cholecystitis and despite a decreased rate of elective cholecystectomy. Conclusion This population-based study found a substantial increase in the rate of admission for severe gallstone disease among those aged 20–39. Concurrently, the incidences of biliary pancreatitis and acute cholangitis have risen among those aged ≥60.

  9. Successful endoscopic treatment of colonic gallstone ileus using electrohydraulic lithotripsy

    Institute of Scientific and Technical Information of China (English)

    Martin; D; Zielinski; Lincoln; E; Ferreira; Todd; H; Baron


    The surgical management of gallstone ileus is complex and potentially highly morbid.Initial management requires enterolithotomy and is generally followed by fistula resection at a later date.There have been reports of gallstone extraction using various endoscopic modalities to relieve the obstruction,however,to date,there has never been a published case of endoscopic stone extraction from the colon using electrohydraulic lithotripsy.In this report,we present the technique employed to successfully perform an...

  10. Ultrasound in the diagnosis of gallstone ileus: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jong Hwa; Lee, Hyeon Kyeong; Lee, Chae Kyeong; Lee, Sung Woo; Lee, Jun Hee [Dongguk University College of Medicine, Seoul (Korea, Republic of)


    Gallstone ileus is a relatively uncommon complication of gallbladder stone. It accompanies the fistula from gallbladder to small intestine, usually to duodenum with the mechanical obstruction of small bowel. The stone is most commonly located in the distal ileum. Its diagnosis can be made when the stone is detected in the obstructed bowel lumen by ultrasound. Here we report one case of gallstone ileus diagnosed by ultrasound and confirmed surgically.

  11. Pancreatic Pseudocyst Pleural Fistula in Gallstone Pancreatitis

    Directory of Open Access Journals (Sweden)

    Sala Abdalla


    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.

  12. Measurement of calcium content of gallstones by computed tomography and the relationship between gallbladder function and calcification of gallstones

    Energy Technology Data Exchange (ETDEWEB)

    Yoneda, Masashi; Tamasawa, Naoki; Takebe, Kazuo (Hirosaki Univ. (Japan). School of Medicine); Makino, Isao; Sakuraba, Kiyoshi; Tamura, Toyokazu


    To evaluate the relationship between gallbladder function and calcification of gallstones, we studied gallbladder contractility by oral cholecystography, the computed tomography (CT) number of stones for 30 gallstone patients, calcium content of 13 stones operatively extirpated, and the degree of inflammatory change in 13 surgical gallbladder specimens. There was significant correlation between the calcium content and CT numbers of stones, and 1% of the calcium content of gallstone was approximately equal to 40 Hounsfield Units (HU) of the CT number. The calcium content of stones in patients with normal gallbladder contractility was extrapolated to be below 1.5%, while that with poor contractility ranged from 0% to 21%. Additionally there is a possibility that calcium content increases, related to the inflammatory change of gallbladder. Hence our results suggested that measurement of the CT number of stones is useful to evaluate the calcium content of gallstones, and that the gallbladder contractility could be one of the factors to influence calcification of stones. (author).

  13. Rhinovirus uses a phosphatidylinositol 4-phosphate/cholesterol counter-current for the formation of replication compartments at the ER-Golgi interface. (United States)

    Roulin, Pascal S; Lötzerich, Mark; Torta, Federico; Tanner, Lukas B; van Kuppeveld, Frank J M; Wenk, Markus R; Greber, Urs F


    Similar to other positive-strand RNA viruses, rhinovirus, the causative agent of the common cold, replicates on a web of cytoplasmic membranes, orchestrated by host proteins and lipids. The host pathways that facilitate the formation and function of the replication membranes and complexes are poorly understood. We show that rhinovirus replication depends on host factors driving phosphatidylinositol 4-phosphate (PI4P)-cholesterol counter-currents at viral replication membranes. Depending on the virus type, replication required phosphatidylinositol 4-kinase class 3beta (PI4K3b), cholesteryl-esterase hormone-sensitive lipase (HSL) or oxysterol-binding protein (OSBP)-like 1, 2, 5, 9, or 11 associated with lipid droplets, endosomes, or Golgi. Replication invariably required OSBP1, which shuttles cholesterol and PI4P between ER and Golgi at membrane contact sites. Infection also required ER-associated PI4P phosphatase Sac1 and phosphatidylinositol (PI) transfer protein beta (PITPb) shunting PI between ER-Golgi. These data support a PI4P-cholesterol counter-flux model for rhinovirus replication.

  14. A pH-responsive drug nanovehicle constructed by reversible attachment of cholesterol to PEGylated poly(l-lysine) via catechol-boronic acid ester formation. (United States)

    Yang, Bin; Lv, Yin; Zhu, Jing-Yi; Han, Yun-Tao; Jia, Hui-Zhen; Chen, Wei-Hai; Feng, Jun; Zhang, Xian-Zheng; Zhuo, Ren-Xi


    The present work reports the construction of a drug delivery nanovehicle via a pH-sensitive assembly strategy for improved cellular internalization and intracellular drug liberation. Through spontaneous formation of boronate linkage in physiological conditions, phenylboronic acid-modified cholesterol was able to attach onto catechol-pending methoxypoly(ethylene glycol)-block-poly(l-lysine). This comb-type polymer can self-organize into a micellar nanoconstruction that is able to effectively encapsulate poorly water-soluble agents. The blank micelles exhibited negligible in vitro cytotoxicity, yet doxorubicin (DOX)-loaded micelles could effectively induce cell death at a level comparable to free DOX. Owing to the acid-labile feature of the boronate linkage, a reduction in environmental pH from pH 7.4 to 5.0 could trigger the dissociation of the nanoconstruction, which in turn could accelerate the liberation of entrapped drugs. Importantly, the blockage of endosomal acidification in HeLa cells by NH4Cl treatment significantly decreased the nuclear uptake efficiency and cell-killing effect mediated by the DOX-loaded nanoassembly, suggesting that acid-triggered destruction of the nanoconstruction is of significant importance in enhanced drug efficacy. Moreover, confocal fluorescence microscopy and flow cytometry assay revealed the effective internalization of the nanoassemblies, and their cellular uptake exhibited a cholesterol dose-dependent profile, indicating the contribution of introduced cholesterol functionality to the transmembrane process of the nanoassembly.

  15. The Unique Molecular Choreography of Giant Pore Formation by the Cholesterol-Dependent Cytolysins of Gram-Positive Bacteria. (United States)

    Tweten, Rodney K; Hotze, Eileen M; Wade, Kristin R


    The mechanism by which the cholesterol-dependent cytolysins (CDCs) assemble their giant β-barrel pore in cholesterol-rich membranes has been the subject of intense study in the past two decades. A combination of structural, biophysical, and biochemical analyses has revealed deep insights into the series of complex and highly choreographed secondary and tertiary structural transitions that the CDCs undergo to assemble their β-barrel pore in eukaryotic membranes. Our knowledge of the molecular details of these dramatic structural changes in CDCs has transformed our understanding of how giant pore complexes are assembled and has been critical to our understanding of the mechanisms of other important classes of pore-forming toxins and proteins across the kingdoms of life. Finally, there are tantalizing hints that the CDC pore-forming mechanism is more sophisticated than previously imagined and that some CDCs are employed in pore-independent processes.

  16. Spontaneous Formation of Two-Dimensional and Three-Dimensional Cholesterol Crystals in Single Hydrated Lipid Bilayers



    Grazing incidence x-ray diffraction measurements were performed on single hydrated bilayers and monolayers of Ceramide/Cholesterol/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocyholine at varying concentrations. There are substantial differences in the phase and structure behavior of the crystalline domains formed within the bilayers relative to the corresponding monolayers, due to interactions between the opposing lipid leaflets. Depending on the lipid composition, these interactions lead to pha...

  17. 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:, E-mail:


    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).

  18. Metabolic syndrome as a risk factor for gallstone disease

    Institute of Scientific and Technical Information of China (English)

    Nahum Méndez-Sánchez; Norberto C. Chavez-Tapia; Daniel Motola-Kuba; Karla Sanchez-Lara; Guadalupe Ponciano-Rodríguez; Héctor Baptista; Martha H. Ramos; Misael Uribe


    AIM: To establish an association between the presence of metabolic syndrome and the development of gallstone disease.METHOIDS: We carried out a cross-sectional study in a check-up unit in a university hospital in Mexico City. We enrolled 245 subjects, comprising 65 subjects with gallstones (36 women, 29 men) and 180 controls (79women and 101 men without gallstones). Body mass index, waist circumference, blood pressure, plasma insulin, and serum lipids and lipoproteins levels were measured. Insulin resistance was calculated by homeostasis model assessment. Unconditional logistic regressionanalysis (univariate and multivariate) was used to calculate the risk of gallstone disease associated with the presence of at least three of the criteria (Adult Treatment Panel Ⅲ). Analyses were adjusted for age and sex.RESULTS: Among 245 subjects, metabolic syndrome was present in 40% of gallstone disease subjects, compared with 17.2% of the controls, adjusted by age and gender (odds ratio (OR) = 2.79; 95%CI, 1.46-5.33; P = 0.002),a dose-dependent effect was observed with each component of metabolic syndrome (OR = 2.36, 95%CI, 0.72-7.71;P = 0.16 with one component and OR = 5.54, 95%CI,1.35-22.74; P = 0.02 with four components of metabolic syndrome). Homeostasis model assessment was significantly associated with gallstone disease (adjusted OR = 2.25;95%CI, 1.08-4.69; P = 0.03).CONCLUSION: We conclude that as for cardiovascular disease and diabetes mellitus, gallstone disease appears to be strongly associated with metabolic syndrome.

  19. Management of gallstones and gallbladder disease in patients undergoing gastric bypass

    Institute of Scientific and Technical Information of China (English)

    Bernabé; M; Quesada; Gustavo; Kohan; Hernán; E; Roff; Carlos; M; Canullán; Luis; T; Chiappetta; Porras


    The appropriate management of gallstones and gallbladder disease in patients undergoing gastric bypass remains unknown.Several therapeutic modalities are used and include performing cholecystectomy on all patients at the time of gastric bypass,performing concomitant cholecystectomy only when patients have gallstones and performing cholecystectomy only in the presence of both symptoms and gallstones.Some groups administer ursodeoxycholic acid for gallstone prevention in the postoperative period.All treatment...

  20. Lifestyle and gallstone disease: Scope for primary prevention

    Directory of Open Access Journals (Sweden)

    Sandeep Sachdeva


    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.

  1. Mirizzi syndrome and gallstone ileus: an unusual presentation of gallstone disease. (United States)

    Beltran, Marcelo A; Csendes, Attila


    We discuss the case of a man with an unusual complication of gallstone disease. An 85-year-old patient presented to the emergency department with a 3-week history of abdominal pain in the right upper abdominal quadrant. Thoracoabdominal radiography demonstrated that the whole extrahepatic biliary tree, including the common bile duct, common hepatic duct, gallbladder, and left and right hepatic ducts, were visibly delineated by air. The operative findings revealed a small shrunken gallbladder, a fistula between the gallbladder fundus and the gastric antrum, and a cholecystohepatic fistula, corresponding to Mirizzi syndrome, type II. A large gallstone was found impacted in the jejunum. This patient seems to have developed initially a cholecystohepatic fistula. Due to the acute inflammatory process, the stone eroded through the gallbladder wall and into the gastric antrum, passing from the antrum into the small bowel, where it became impacted. We suggest that the natural history of Mirizzi syndrome does not end with a cholecystobiliary fistula but that the continuous inflammation in the triangle of Calot may result in a complex fistula involving not only the biliary tract but also the adjacent viscera.

  2. [A case of jejunal perforation in gallstone ileus]. (United States)

    Taira, Akiko; Yamada, Masami; Takehira, Yasunori; Kageyama, Fujito; Yoshii, Shigeto; Murohisa, Gou; Yoshida, Kenichi; Iwaoka, Yasushi; Terai, Tomohiro; Uotani, Takahiro; Watanabe, Shinya; Noritake, Hidenao; Ikematu, Yoshito; Kanai, Toshikazu


    Gallstone ileus is a rare but important cause of small bowel obstruction in the geriatric population. A 65-year-old man with a twenty year history of cholecystolithiasis was admitted to our hospital with abdominal pain and vomiting. Physical exams showed abdominal defence and rebound tenderness. A plain abdominal X-ray suggested a small bowel obstruction and pneumobilia. CT scan revealed a 2.5-cm gallstone at the jejunum and air in the biliary tree. The patient underwent a emergency laparotomy based on a diagnosis of panperitonitis with a perforation associated with gallstone ileus. Operative findings revealed a jejunal perforation and a impacted stone on the anal side of perforation. Enterolithotomy and jejunal resection were performed with cholecystectomy and repairment of the cholecystoduodenal fistula.

  3. Metastatic breast cancer presenting as a gallstone ileus. (United States)

    Sahebally, Shaheel M; Sehgal, Rishabh; Kelly, Justin; Faul, Peter N; Waldron, David


    Metastatic breast cancer to the small bowel (SB) presenting as gallstone ileus and resulting in SB obstruction has not been described previously. A 76-year-old woman with previous metastatic breast cancer to the axial spine and hips presented with abdominal pain and bilious vomiting. CT scanning revealed SB obstruction consistent with gallstone ileus. The patient underwent two segmental SB resections for distal ileal strictures mimicking what appeared to be macroscopic Crohn's disease. The entero-biliary fistula was undisturbed. Pathological analysis revealed the dual pathologies of gallstone ileus and metastatic carcinoma from a breast primary causing luminal SB obstruction. Improvements in staging and treatment modalities have contributed to the increased overall long-term survival for breast cancer, compelling clinicians to consider metastatic breast cancer as a differential diagnosis in women presenting with new onset of gastrointestinal symptoms in order that appropriate treatment be administered in a timely fashion.

  4. Dietary fiber's benefit for gallstone disease prevention during rapid weight loss in obese patients. (United States)

    Sulaberidze, G; Okujava, M; Liluashvili, K; Tughushi, M; Bezarashvili, S


    The aim of present study was to compare the effects of very low calorie diets - protein rich and dietary fiber rich food based - on gallstones formation during rapid weight loss. 68 patients were involved into the study. The body weight index in all cases exceeding normal value and equaled to 35±4,7 kg/m2. For weight correction purposes during 5 weeks the patients in first group were kept on a 520-800 kcal diet of "Margi" food products, prepared according our technology, and in the second group on a protein rich diet of the same calorie content. The body weight and changes in the gall-bladder wall and content were assessed by sonography before starting the diet, after three weeks from the commencement of the diet and upon its completion. The measurement of the body weight after completion of the 5 week diet revealed decrease by 10.9±1,5kg in the first group and by 11,2±1,1kg in the second group. Sonography disclosed growth in the amount of biliary sludge in 3 cases in the first group and in 9 cases in the second group. The statistical analyses of results indicate successful and nearly equal reduction of body weight by means of dietary fiber rich and protein rich diet, but high fiber consumption showed statistically significant benefits for prevention of biliary slug accumulation. The study showed that, in the respect to weight loss, diets based on fiber rich and protein rich food are equal, but fiber rich diet has considerable privilege in prevention of gallstone disease. Our findings support the presence of known association between increased dietary fiber consumption and reduction of gallstone formation. Obesity and rapid weight loss are risk factors for development of gallstones. Taking in an account the beneficial effect of dietary fiber, the food rich with this nutrient, particularly low-calorie fiber rich food "Margi", can be recommended for rapid weight loss in obese patients.

  5. Women and Cholesterol (United States)

    ... Disease Venous Thromboembolism Aortic Aneurysm More Women and Cholesterol Updated:Apr 1,2016 The female sex hormone ... 2014. Related Sites Nutrition Center My Life Check Cholesterol • Home • About Cholesterol • Why Cholesterol Matters • Understand Your ...

  6. HDL Cholesterol Test (United States)

    ... products and services. Advertising & Sponsorship: Policy | Opportunities HDL Cholesterol Share this page: Was this page helpful? Also ... HDL; HDL-C Formal name: High-density Lipoprotein Cholesterol Related tests: Cholesterol ; LDL Cholesterol ; Triglycerides ; Lipid Profile ; ...

  7. Cholesterol IQ Quiz (United States)

    ... Peripheral Artery Disease Venous Thromboembolism Aortic Aneurysm More Cholesterol IQ Quiz Updated:Feb 2,2015 Begin the quiz Cholesterol • Home • About Cholesterol Introduction Good vs. Bad Cholesterol ...

  8. Cholesterol and Your Child (United States)

    ... Old Feeding Your 1- to 2-Year-Old Cholesterol and Your Child KidsHealth > For Parents > Cholesterol and ... child's risk of developing heart disease later. About Cholesterol Cholesterol is a waxy substance produced by the ...

  9. Lifestyle Changes and Cholesterol (United States)

    ... Venous Thromboembolism Aortic Aneurysm More Lifestyle Changes and Cholesterol Updated:Sep 26,2016 As part of a ... to the Terms and Conditions and Privacy Policy Cholesterol • Home • About Cholesterol • Why Cholesterol Matters • Understand Your ...

  10. Common Misconceptions about Cholesterol (United States)

    ... Venous Thromboembolism Aortic Aneurysm More Common Misconceptions about Cholesterol Updated:Apr 3,2017 Cholesterol can be both ... misconceptions about cholesterol. Click on each misconception about cholesterol to see the truth: My choices about diet ...

  11. LDL Cholesterol Test (United States)

    ... products and services. Advertising & Sponsorship: Policy | Opportunities LDL Cholesterol Share this page: Was this page helpful? Also ... LDL; LDL-C Formal name: Low-Density Lipoprotein Cholesterol Related tests: Cholesterol ; HDL Cholesterol ; Triglycerides ; Lipid Profile ; ...

  12. Radiological findings in biliary fistula and gallstone ileus

    Energy Technology Data Exchange (ETDEWEB)

    Oikarinen, H. [Univ. Hospital, Oulu (Finland). Dept. of Diagnostic Radiology; Paeivaensalo, M. [Univ. Hospital, Oulu (Finland). Dept. of Diagnostic Radiology; Tikkakoski, T. [Univ. Hospital, Oulu (Finland). Dept. of Diagnostic Radiology; Saarela, A. [Univ. Hospital, Oulu (Finland). Dept. of Surgery


    Purpose: Biliary fistual and gallstone ileus are rarely found. The diagnosis is difficult and may be delayed until operation. We reviewed the radiological findings in a retrospective material. Material and Methods: The cases of 16 patients treated for biliary fistula were analyzed with respect to findings at imaging. Ten patients had a spontaneous fistula. Nine of them had an internal bilioduodenal fistula and one had an external fistula with stones passing through a subcutaneous abscess. Five patients also had gallstone ileus and one patient a rare gastric outlet obstruction caused by a gallstone (Bouveret`s syndrome). Six patients had an iatrogenic fistula. One of them had internal bile ascites and 5 an external fistula, one of which was a biliocystic fistula resulting from attempted hepatic cyst sclerotherapy. Results: Various imaging modalities were used and there was often a delay in the diagnosis. Imaging did not show the fistula itself in any of the spontaneous cases. However, a nonvisualized or shrunken gallbladder seen at US often coexisted in these cases. CT yielded the diagnosis in one case of gallstone ileus, and a Gastrografin metal yielded it in the case of Bouveret`s syndrome. Fistulography and cholangiography provided a correct diagnosis of fistula in all cases of iatrogenic biliocutaneous fistulas. Conclusion: Patients with biliary fistula usually undergo examinations with nonspecific results. The imaging findings could be more specific if the possibility of this diagnosis were remembered. (orig.).

  13. Laparoscopic enterolithotomy is a valid option to treat gallstone ileus. (United States)

    Shiwani, Muhammad Hanif; Ullah, Quat


    Gallstone ileus is a well-recognized clinical entity. It usually affects elderly female patients, and very often diagnosis can be delayed resulting in high morbidity and mortality. An abdominal x-ray and computed tomographic (CT) scan of the abdomen may show classical radiological features of small bowel obstruction, pneumobilia, and an ectopic gallstone. Laparotomy and enterlithotomy with or without definite biliary surgery is an established treatment. Since 1992, many cases of laparoscopic-assisted enterolithotomy have been reported. Only a few cases of a totally laparoscopic approach have been documented. We present the case of a 75-year-old lady who presented with features of intestinal obstruction. A plain x-ray of the abdomen and a CT scan confirmed the classical features of gallstone ileus. A totally laparoscopic enterolithotomy was performed using 6 ports. A 6-cm gallstone was retrieved through a longitudinal enterotomy. The transverse closure of the enterotomy was performed with intracorporeal suturing, resulting in an uneventful postoperative recovery. We suggest that a CT scan helps in the early diagnosis of the cause of intestinal obstruction, and totally laparoscopic enterolithomy with intracorporeal enterotomy repair is a valid, safe option.

  14. Gallstone Ileus of the Colon: Leave No Stone Unturned

    Directory of Open Access Journals (Sweden)

    P. B. Salemans


    Full Text Available A case of gallstone ileus of the colon with illustrative pictures is presented, making the physicians more aware of this rare entity. Furthermore, the use of imaging modalities for diagnosis and decision making in management strategy is discussed.

  15. Transvaginal Hybrid NOTES Procedure for Treatment of Gallstone Ileus

    Directory of Open Access Journals (Sweden)

    Takuya Shiraishi


    Full Text Available Gallstone ileus is a rare mechanical bowel obstruction, and previously reported cases have been treated laparoscopically with good results. Although transvaginal hybrid NOTES without a minilaparotomy has been reported to decrease the incidence of surgical wound complications, to our knowledge, this procedure has not been used previously to treat gallstone ileus. We present a case of a 63-year-old woman who underwent transvaginal hybrid NOTES procedure for treatment of gallstone ileus. This case was admitted to our hospital following acute-onset abdominal pain and vomiting. We diagnosed gallstone ileus with cholecystoduodenal fistula by computed tomography and performed totally laparoscopic surgery using only three 5 mm abdominal ports with transvaginal specimen extraction and enterectomy. The patient’s postoperative course was uneventful, and laparoscopic cholecystectomy and fistula repair were performed 8 months after the initial surgery. The patient experienced additional pain relief and good cosmetic outcomes. In conclusion, using transvaginal hybrid NOTES may become a future option to minimize the invasiveness of other laparoscopic procedures.

  16. Cholesterol crystal binding of biliary immuno globulin A: visualization by fluorescence light microscopy

    Institute of Scientific and Technical Information of China (English)

    Frank Lammert; Stefan Sudfetd; Norbert Busch; Siegfried Matern


    AIM To assess potential contributions of biliary IgA for crystal agglomeration into gallstones, we visualized cholesterol crystal binding of biliary IgA.METHODS Crystal-binding biliary proteins were extracted from human gallbladder bile using lectin affinity chromatography. Biliary IgA was isolated from the bound protein fraction by immunoaffinity chromatography. Pure cholesterol monohydrate crystals were incubated with biliary IgA and fluoresceine isothiocyanate (FITC)-conjugated anti-lgA at 37C. Samples were examined under polarizing and fluorescence light microscopy with digital image processing.RESULTS Binding of biliary IgA to cholesterol monohydrate crystals could be visualized with FITC-conjugated anti-lgA antibodies. Peak fluorescence occurred at crystal edges and dislocations. Controls without biliary IgA or with biliary IgG showed no significant fluorescence.CONCLUSION Fluorescence light microscopy provided evidence for cholesterol crystal binding of biliary IgA. Cholesterol crystalbinding proteins like IgA might be important mediators of crystal agglomeration and growth of cholesterol gallstones by modifying the evolving crystal structures in vivo.

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

    DEFF Research Database (Denmark)

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


    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....

  18. Gallstone impacted in the rectosigmoid junction causing a biliary ileus and a sigmoid perforation. (United States)

    Van Kerschaver, O; Van Maele, V; Vereecken, L; Kint, M


    A gallstone ileus is an unusual form of bowel obstruction. Colonic gallstone ileus is rare, difficult to diagnose, and still has a high mortality rate. We present a case of biliary ileus caused by an impacted gallstone, causing necrosis and perforation of the rectosigmoid junction. A Hartmann's procedure was performed to treat the perforation and the obstruction. Cholecystectomy and closure of the cholecysto-colonic fistula were delayed until restoration of the intestinal continuity.

  19. In vivo exposure of young adult male rats to methoxychlor reduces serum testosterone levels and ex vivo Leydig cell testosterone formation and cholesterol side-chain cleavage activity. (United States)

    Murono, Eisuke P; Derk, Raymond C; Akgul, Yucel


    Methoxychlor (MC) was developed as a replacement for the banned pesticide DDT. After in vivo administration, it is metabolized in the liver to 2,2-bis(p-hydroxyphenyl)-1,1,1-trichloroethane (HPTE), which is proposed to be the active agent. Both MC and HPTE have been shown to exhibit weak estrogenic and antiandrogenic activities, and they are thought to exert their effects through estrogen and androgen receptors, respectively. Although in vitro studies using cultured rat Leydig cells have reported that HPTE inhibits both basal and hCG-stimulated testosterone formation, the response of circulating testosterone levels to in vivo MC has been more variable. Therefore, the current studies evaluated whether the daily in vivo administration of MC (0, 5, 40 and 200 mg/kg body weight) for a short duration (days 54-60 of age) by gavage altered serum testosterone levels and ex vivo Leydig cell testosterone formation in young adult male rats. These results demonstrate that both fluid-retained and fluid-expressed seminal vesicle weights declined to 44 and 60% of control, respectively, in the 200 mg/kg MC-exposed animals. Similarly, serum testosterone and dehydroepiandrosterone levels declined to 41 and 45% of control, respectively, in the 200 mg/kg MC-exposed animals; however, serum LH and FSH levels were unaffected. Ex vivo Leydig cell basal testosterone formation over 4h declined to 49% of control in animals exposed to 200 mg/kg MC, and ex vivo Leydig cell P450 cholesterol side-chain cleavage activity declined to 79 and 50% of control in animals exposed to 40 and 200 mg/kg of MC, respectively, supporting previous in vitro studies which demonstrated the sensitivity of this step to MC.

  20. What Is Cholesterol? (United States)

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness Cholesterol KidsHealth > For Teens > Cholesterol Print A A A ... High Cholesterol? en español ¿Qué es el colesterol? Cholesterol Is a Fat in the Blood Cholesterol (kuh- ...

  1. What Is Cholesterol? (United States)

    ... Loss Surgery? A Week of Healthy Breakfasts Shyness Cholesterol KidsHealth > For Teens > Cholesterol A A A What's ... High Cholesterol? en español ¿Qué es el colesterol? Cholesterol Is a Fat in the Blood Cholesterol (kuh- ...

  2. Mitochondrion-Targeted Peptide SS-31 Inhibited Oxidized Low-Density Lipoproteins-Induced Foam Cell Formation through both ROS Scavenging and Inhibition of Cholesterol Influx in RAW264.7 Cells. (United States)

    Hao, Shuangying; Ji, Jiajie; Zhao, Hongting; Shang, Longcheng; Wu, Jing; Li, Huihui; Qiao, Tong; Li, Kuanyu


    Foam cell formation as a result of imbalance of modified cholesterol influx and efflux by macrophages is a key to the occurrence and development of atherosclerosis. Oxidative stress is thought to be involved in the pathogenesis of atherosclerosis. SS-31 is a member of the Szeto-Schiller (SS) peptides shown to specifically target the inner mitochondrial membrane to scavenge reactive oxygen species. In this study, we investigated whether SS-31 may provide protective effect on macrophage from foam cell formation in RAW264.7 cells. The results showed that SS-31 inhibited oxidized low-density lipoproteins (ox-LDL)-induced foam cell formation and cholesterol accumulation, demonstrated by intracellular oil red O staining and measurement of cholesterol content. The mechanism was revealed that SS-31 did not only significantly attenuated ox-LDL-induced generation of reactive oxygen species (ROS) and increased the activities of superoxide dismutases, but also dose-dependently inhibited the expression of CD36 and LOX-1, two scavenger receptors of ox-LDL, while the expression of ATP-binding cassette A1 and G1, playing a pivotal role in cholesterol efflux, was not affected. As a result, SS-31 decreased pro-inflammatory cytokines such as interleukin 6 and tumor necrosis factor alpha, suggesting the prevention of inflammatory responses. In conclusion, our results demonstrate that SS-31 provides a beneficial effect on macrophages from foam cell formation, likely, through both ROS scavenging and inhibition of cholesterol influx. Therefore, SS-31 may potentially be of therapeutic relevance in prevention of human atherogenesis.

  3. An enzyme thermistor-based assay for total and free cholesterol. (United States)

    Raghavan, V; Ramanathan, K; Sundaram, P V; Danielsson, B


    A method to evaluate the free (FC) and total cholesterol (TC) in human serum, bile and gallstone extract using an enzyme thermistor (ET)-based flow injection analysis (FIA) is presented. The cholesterol in high-density (HDL-C) and low density lipoprotein (LDL-C) have also been evaluated. A heparin functionalized Sepharose column was employed for the isolation of HDL and LDL fractions from serum. The estimation of cholesterol and its esters was based on their reaction with cholesterol oxidase (CO), cholesterol esterase (CE) and catalase (CAT). Three different enzyme columns, i.e. co-immobilized CO/CAT (column A), only CE (column B) and co-immobilized CO/CE/CAT (column C) were prepared by cross-linking the enzymes on glass beads using glutaraldehyde. Column A was used for estimating FC and column C was used for estimating total cholesterol (cholesterol plus esterified cholesterol). Column B was used as a pre-column which could be switched 'in' or 'out' in conjunction with column A for the estimation of TC or FC, respectively. A calibration between 1.0 and 8.0 mmol/l for FC and 0. 25 and 4.0 mmol/l for TC was obtained. For more than 2000 assays with the ET device a C.V. of less than 4% was obtained. The assay time was approximately 4 min per assay. The cholesterol estimations on the ET correlated well with similar estimations using a commercially available cholesterol diagnostic kit.

  4. Radiological contribution to the diagnosis of gallstone ileus

    Energy Technology Data Exchange (ETDEWEB)

    Souchon, R.; Baer, U.; Bauknecht, K.J.; Kania, U.


    Between 1969 and 1982, 8 patients of ours were operated on for gallstone ileus. Signs found in the preoperative X-ray examination indicating this condition are analyzed retrospectively. The frequency and specificity of the X-ray signs found in the abdominal survey radiograph are compared with those reported in the literature. The value of oral contrast media administration in the detection of a cholecystointestinal fistula and localization of the obstruction is discussed.

  5. Gallstone spillage caused by spontaneously perforated hemorrhagic cholecystitis

    Institute of Scientific and Technical Information of China (English)


    There are occasional incidences of gallstone spillage during laparoscopic cholecystectomy, and there have been frequent reports on such a topic in the literature. To the best of our knowledge, however, there have been no reports about spilled stones caused by spontaneously perforated hemorrhagic cholecystitis. Here, we report the radiologic findings of spilled stones caused by spontaneously perforated hemorrhagic cholecystitis in a 55-year-old man.

  6. Is there an association between type 1 diabetes in children and gallbladder stones formation?

    Directory of Open Access Journals (Sweden)

    Abdulrahman A Al-Hussaini


    Full Text Available Background and Aims: A number of studies in adults have evaluated the prevalence of gallstones in the diabetic population and showed a significant association with type 1 diabetes (T1D and type 2 diabetes. The pediatric literature is limited to a single small case series. We conducted a cross-sectional study to evaluate for the presence of association between T1D in children and gallstones formation. Patients and Methods: Children diagnosed with T1D in a diabetic clinic have been examined for existence of gall bladder stone formation from November 2008 through November 2009. All have been subjected to the following: History, physical examination, blood tests (liver function tests, lipid profile, glycosylated hemoglobin [HbA1C], and an ultrasound (US of the gall bladder. Results: One hundred and five children with T1D have been enrolled consecutively over a 1-year period: age ranged between 8 months and 15.5 years, 62 patients were females. The mean age at diagnosis was 6.3 ± 2.9 years (range 0.85-11 years, mean duration of T1D was 2.2 ± 2.1 years (range 0.2-8 years, mean body mass index was 16.5 ± 3.4, mean HbA1c was 10.7 ± 2.4%, and 61.3% of patients had a HbA1c level >10%. The mean serum cholesterol was 4.16 ± 0.75 mmol/L (normal 3.65-5.15 mmol/L and mean serum triglyceride 1.02 ± 1.3 mmol/L (normal 0-1.7 mmol/L. Two patients had hyperlipidemia. US of the gallbladder did not show any case of gallstones or sludge formation. Conclusion: Data from our study do not show any association between T1D in children and gallstones formation, with diabetes duration of less than 8 years. The relatively short duration of diabetes and possibility that our study was underpowered might have been reasons for the absence of any association.

  7. Cholesterol Facts and Statistics (United States)

    ... Blood Pressure Salt Million Hearts® WISEWOMAN Program High Cholesterol Facts Recommend on Facebook Tweet Share Compartir As ... the facts about high cholesterol [PDF-281K] . High Cholesterol in the United States 73.5 million adults ( ...

  8. Get Your Cholesterol Checked (United States)

    ... Checked Print This Topic En español Get Your Cholesterol Checked Browse Sections The Basics Overview Cholesterol Test ... How often do I need to get my cholesterol checked? The general recommendation is to get your ...

  9. Dietary Fat and Cholesterol (United States)

    ... Conditions Nutrition & Fitness Emotional Health Dietary Fat and Cholesterol Posted under Health Guides . Updated 7 March 2017. + ... saturated fat found in red meat. What is cholesterol? Cholesterol is a fatlike substance that’s found in ...

  10. High Blood Cholesterol Prevention (United States)

    ... Million Hearts® WISEWOMAN Program Prevention and Management of High LDL Cholesterol: What You Can Do Recommend on ... like eating a healthy diet, can help prevent high cholesterol. High low-density lipoprotein (LDL) cholesterol increases ...

  11. Low serum levels of ghrelin are associated with gallstone disease

    Institute of Scientific and Technical Information of China (English)

    Nahum Méndez-Sánchez; Martha H Ramos; Héctor A Baptista-González; Misael Uribe; Guadalupe Ponciano-Rodríguez; Luisa Bermejo-Martínez; Antonio R Villa; Norberto C Chávez-Tapia; Daniel Zamora-Valdés; Raúl Pichardo-Bahena; Blanca Barredo-Prieto; Martha H Uribe-Ramos


    AIM: To explore the role of ghrelin in gallstone disease.METHODS: We carried out a cross-sectional study in 150 subjects, 38 with gallstones (cases) and 112 controls. We also did a real-time PCR-RT study in twenty gallbladder samples each. Body mass index (BMI),serum insulin, ghrelin, and serum lipids were measured.Logistic regression analyses (univariate and multivariate) were conducted to estimate the probability of gallstone disease associated with serum ghrelin concentrations.RESULTS: Cases were statistically different from controls in gender distribution (P = 0.01), age (53 vs 44 yr, P = 0.002), BMI (28 vs 25; P = 0.004), and glucose (5.26 vs 4.98 mmol/L; P = 0.05). The prevalence of ghrelin serum levels above the third tercile was lower in subjects without metabolic syndrome (P < 0.05). In a multivariate model, we found a protective effect, when ghrelin values were higher than the median value (OR = 0.27, 95%CI 0.09-0.82, P = 0.02). Twenty (20%) gallbladder specimens expressed ghrelin mRNA.CONCLUSION: Serum ghrelin concentrations are associated with a protective effect of GD.

  12. Cholesterol lowering, low cholesterol, and mortality. (United States)

    LaRosa, J C


    Cholesterol lowering in both primary and secondary prevention has been clearly demonstrated to lower coronary morbidity and, in secondary prevention, to lower coronary mortality as well. Putative dangers of cholesterol lowering remain unproven. Population studies linking low cholesterol to noncoronary mortalities do not demonstrate cause-and-effect relations. In fact, based on current studies, the opposite is more likely to be the case. Neither gender nor age should automatically exclude persons from cholesterol screening. Drug intervention, however, should be used conservatively, particularly in young adults and the elderly. Drugs should be used only after diet and lifestyle interventions have failed. The evidence linking high blood cholesterol to coronary atherosclerosis and cholesterol lowering to its prevention is broad-based and definitive. Concerns about cholesterol lowering and spontaneously low cholesterols should be pursued but should not interfere with the implementation of current public policies to reduce the still heavy burden of atherosclerosis in Western society.

  13. TOF-SIMS study of cystine and cholesterol stones. (United States)

    Ghumman, C A A; Moutinho, A M C; Santos, A; Tolstogouzov, A; Teodoro, O M N D


    Two different human stones, cystine and cholesterol from the kidney and gall bladder, were examined by time-of-flight secondary ion mass spectrometry using Ga(+) primary ions as bombarding particles. The mass spectra of kidney stone were compared with those measured for the standard compounds, cystine and cysteine. Similar spectra were obtained for the stone and cystine. The most important identification was based on the existence of the protonated molecules [M + H](+) and deprotonated molecules [M-H](-). The presence of cystine salt was also revealed in the stone through the sodiated cystine [M + Na](+) and the associated fragments, which might be due to the patient treatment history. In the gallstone, the deprotonated molecules [M-H](+) of cholesterol along with relatively intense characteristic fragments [M-OH](+) were detected.


    NARCIS (Netherlands)



    A 72-year-old woman presented with periods of colicky abdominal pain following endoscopic sphincterotomy and lithotripsy for choledocholithiasis. A diagnosis of intermittent gallstone ileus was made, while it appeared that a large gallstone, that was not removed from the common bile duct, obsructed

  15. Elevated body mass index as a causal risk factor for symptomatic gallstone disease:

    DEFF Research Database (Denmark)

    Stender, Stefan; Nordestgaard, Børge G; Tybjaerg-Hansen, Anne


    Elevated body mass index (BMI) is associated with an increased risk of gallstone disease. Whether this reflects a causal association is unknown. Using a Mendelian randomization approach, we studied 77,679 individuals from the general population. Of these, 4,106 developed symptomatic gallstone...

  16. Influence of dietary sugar on cholesterol and bile acid metabolism in the rat: Marked reduction of hepatic Abcg5/8 expression following sucrose ingestion. (United States)

    Apro, Johanna; Beckman, Lena; Angelin, Bo; Rudling, Mats


    Previous studies have indicated that dietary intake of sugar may lower bile acid production, and may promote cholesterol gallstone formation in humans. We studied the influence of dietary sucrose on cholesterol and bile acid metabolism in the rat. In two different experiments, rats received high-sucrose diets. In the first, 60% of the weight of standard rat chow was replaced with sucrose (high-sucrose diet). In the second, rats received a diet either containing 65% sucrose (controlled high-sucrose diet) or 65% complex carbohydrates, in order to keep other dietary components constant. Bile acid synthesis, evaluated by measurements of the serum marker 7-alpha-hydroxy-4-cholesten-3-one (C4) and of the hepatic mRNA expression of Cyp7a1, was markedly reduced by the high-sucrose diet, but not by the controlled high-sucrose diet. Both diets strongly reduced the hepatic - but not the intestinal - mRNA levels of Abcg5 and Abcg8. The differential patterns of regulation of bile acid synthesis induced by the two sucrose-enriched diets indicate that it is not sugar per se in the high-sucrose diet that reduces bile acid synthesis, but rather the reduced content of fiber or fat. In contrast, the marked reduction of hepatic Abcg5/8 observed is an effect of the high sugar content of the diets.

  17. Gallbladder motor function, plasma cholecystokinin and cholecystokinin receptor of gallbladder in cholesterol stone patients

    Institute of Scientific and Technical Information of China (English)

    Jian Zhu; Tian-Quan Han; Sheng Chen; Yu Jiang; Sheng-Dao Zhang


    AIM: To study the interactive relationship of gallbladder motor function, plasma cholecystokinin (CCK) and cholecystokinin A receptor (CCK-R) of gallbladder in patients with cholesterol stone disease.METHODS: Gallbladder motility was studied by ultrasonography in 33 patients with gallbladder stone and 10 health subjects as controls. Plasma CCK concentration was measured by radioimmunoassay in fasting status (CCK-f) and in 30 min after lipid test meal (CCK-30).Radioligand method was employed to analyze the amount and activity of CCK-R from 33 gallstone patients having cholecystectomy and 8 persons without gallstone died of severe trauma as controls.RESULTS: The percentage of cholesterol in the gallstone composition was more than 70%. The cholesterol stone type was indicated for the patients with gallbladder stone in this study. Based on the criterion of gallbladder residual fraction of the control group, 33 gallstone patients were divided into two subgroups, contractor group (14 cases)and non-contractor group (19 cases), The concentration of CCK-30 was significantly higher in non-contractor group than that in both contractor group and control group (55.86±3.86 pmol/l vs 37.85±0.88 pmol/l and 37.95±0.74 pmol/L, P<0.01), but there was no difference between contractor group and control group. Meanwhile no significant difference of the concentration of CCK-f could be observed among three groups. The amount of CCK-R was lower in non-contractor group than those in both control group and contractor group (10.27±0.94 fmol/mg vs24.59±2.39 fmol/mg and 22.66±0.55 fmol/mg, P<0.01).The activity of CCK-R shown as KD in non-contractor group decreased compared to that in control group and contractor group. Only was the activity of CCK-R lower in contractor group than that in control group. The ejection fraction correlated closely with the amount of CCK-R (r = 0.9683,P<0.01), and the concentration of CCK-30 correlated negatively with the amount of CCK-R closely (r = -0

  18. Which Abdominal Symptoms are Associated with Clinical Events in a Population Unaware of Their Gallstones?

    DEFF Research Database (Denmark)

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


    BACKGROUND: High rates of persistent symptoms are found following cholecystectomy in patients with gallstones. The aim of this population based cohort study was to determine which symptoms were associated with the development of clinical gallstone events in a population unaware of their gallstones....... MATERIAL AND METHODS: Three random population samples from Copenhagen (N = 6037) were examined with ultrasound during 1982-1994. Participants were not informed about gallstone status. Abdominal symptoms were assessed at baseline through a questionnaire. Follow-up for clinical events was performed through...... central registers until 2011. Multivariable Cox regression analyses were performed. RESULTS: Participants unaware of their gallstones (N = 595) were followed for median 17.5 years. A total of 16.6% participants developed clinical events. Both uncomplicated and complicated events were associated with high...

  19. Cooking for Lower Cholesterol (United States)

    ... Venous Thromboembolism Aortic Aneurysm More Cooking for Lower Cholesterol Updated:Oct 28,2016 A heart-healthy eating ... content was last reviewed on 04/21/2014. Cholesterol • Home • About Cholesterol • Why Cholesterol Matters • Understand Your ...

  20. Reverse cholesterol transport revisited

    Institute of Scientific and Technical Information of China (English)

    Astrid; E; van; der; Velde


    Reverse cholesterol transport was originally described as the high-density lipoprotein-mediated cholesterol flux from the periphery via the hepatobiliary tract to the intestinal lumen, leading to fecal excretion. Since the introduction of reverse cholesterol transport in the 1970s, this pathway has been intensively investigated. In this topic highlight, the classical reverse cholesterol transport concepts are discussed and the subject reverse cholesterol transport is revisited.

  1. Cholesterol and late-life cognitive decline. (United States)

    van Vliet, Peter


    High cholesterol levels are a major risk factor for cardiovascular disease, but their role in dementia and cognitive decline is less clear. This review highlights current knowledge on the role of cholesterol in late-life cognitive function, cognitive decline, and dementia. When measured in midlife, high cholesterol levels associate with an increased risk of late-life dementia and cognitive decline. However, when measured in late-life, high cholesterol levels show no association with cognitive function, or even show an inverse relation. Although statin treatment has been shown to associate with a lower risk of dementia and cognitive decline in observational studies, randomized controlled trials show no beneficial effect of statin treatment on late-life cognitive function. Lowering cholesterol levels may impair brain function, since cholesterol is essential for synapse formation and maturation and plays an important role in the regulation of signal transduction through its function as a component of the cell membrane. However, membrane cholesterol also plays a role in the formation and aggregation of amyloid-β. Factors that influence cholesterol metabolism, such as dietary intake, are shown to play a role in late-life cognitive function and the risk of dementia. In conclusion, cholesterol associates with late-life cognitive function, but the association is strongly age-dependent. There is no evidence that treatment with statins in late-life has a beneficial effect on cognitive function.

  2. Biophysical studies of cholesterol effects on chromatin. (United States)

    Silva, Isabel T G; Fernandes, Vinicius; Souza, Caio; Treptow, Werner; Santos, Guilherme Martins


    Changes in chromatin structure regulate gene expression and genome maintenance. Molecules that bind to the nucleosome, the complex of DNA and histone proteins, are key modulators of chromatin structure. Previous work indicated that cholesterol, a ubiquitous cellular lipid, may bind to chromatin in vivo, suggesting a potential function for lipids in modulating chromatin architecture. However, the molecular mechanisms of cholesterol action on chromatin structure have remained unclear. Here, we explored the biophysical impact of cholesterol on nucleosome and chromatin fibers reconstituted in vitro and characterized in silico the cholesterol binding to nucleosome. Our findings support that cholesterol assists 10nm and 30nm chromatin formation and induces folding of long chromatin fibers as a result of direct interaction of the cholesterol to six nucleosomal binding sites.

  3. Bouveret's syndrome complicated by a distal gallstone ileus

    Institute of Scientific and Technical Information of China (English)

    Rasim Gencosmanoglu; Resit Inceoglu; Caglar Baysal; Sertac Akansel; Nurdan Tozun


    AIM: Gastric outlet obstruction caused by duodenal impaction of a large gallstone migrated through a cholecystoduodenal fistula has been referred as Bouveret's syndrome. Endoscopic lithotomy is the first-step treatment,however, surgery is indicated in case of failure or complication during this procedure.METHODS: We report herein an 84-year-old woman presenting with features of gastric outlet obstruction due to impacted gallstone. She underwent an endoscopic retrieval which was unsuccessful and was further complicated by distal gallstone ileus. Physical examination was irrelevant.RESULTS: Endoscopy revealed multiple erosions around the cardia, a large stone in the second part of the duodenum causing complete obstruction, and wide ulceration in the duodenal wall where the stone was impacted. Several attempts of endoscopic extraction by using foreign body forceps failed and surgical intervention was mandatory. Preoperative ultrasound evidenced pneumobilia whilst computerized tomography showed a large stone, 5 cm×4 cm×3 cm, loggingat the proximal jejunum and another one, 2.5 cm×2 cm×2 cm,in the duodenal bulb causing a closed-loop syndrome. She underwent laparotomy and the jejunal stone was removed by enterotomy. Another stone reported as located in the duodenum preoperatively was found to be present in the gallbladder by intraoperative ultrasound. Therefore,cholecystoduodenal fistula was broken down, the stone was retrieved and cholecystectomy with duodenal repair was carried out. She was discharged after an uneventful postoperative course.CONCLUSION: As the simplest and the least morbid procedure, endoscopic stone retrieval should be attempted in the treatment of patients with Bouveret's syndrome.When it fails, surgical lithotomy consisting of simple enterotomy may solve the problem. Although cholecystectomy and cholecystoduodenal fistula breakdown is unnecessary in every case, conditions may urge the surgeon to perform such operations even though they carry high

  4. Value of CT in the diagnosis and management of gallstone ileus

    Institute of Scientific and Technical Information of China (English)

    Chih-Yung Yu; Cheng-Yu Chen; Chang-Chyi Lin; Rong-Yaun Shyu; Chung-Bao Hsieh; Hurng-Sheng Wu; Yeu-Sheng Tyan; Jen-I Hwang; Chang-Hsien Liou; Wei-Chou Chang


    IM: To retrospectively establish the diagnostic criteria of gallstone ileus on CT, and to prospectively apply these criteria to determine the diagnostic accuracy of CT to confirm or exclude gallstone ileus in patients who presented with acute small bowel obstruction (SBO). Another purposewas to ascertain whether the size of ecctopic gallstones would affect treatment strategy.METHODS: Fourteen CT scans in cases of proved gallstone ileus were evaluated retrospectively by two radiologists for the presence or absence of previously reported CT findings to establish the diagnostic criteria. These criteria were applied in a prospective contrast enhanced CT study of 165 patients with acute SBO, which included those 14 cases of gallstone ileus. The hard copy images of 165 CT studies were reviewed by a different group of two radiologists but without previous knowledge of the patient's final diagnosis. All CT data were further analyzed to determine the diagnostic accuracy of gallstone ileus when using CT in prospective evaluation of acute SBO. The size of ectopic gallstone on CT was correlated with the clinical course.RESULTS: The diagnostic criteria of gallstone ileus on CT were established retrospectively, which included: (1) SBO; (2) ectopic gallstone; either rim-calcified or total-calcified; (3) abnormal gall bladder with complete air collection, presence of air-fluid level, or fluid accumulation with irregular wall. Prospectively, CT confirmed the diagnosis in 13 cases of gallstone ileus with these three criteria. Only one false negative case could be identified. The remaining 151 patients are true negative cases and no false positive case could be disclosed. The overall sensitivity, specificity and accuracy of CT in diagnosing gallstone ileus were 93%, 100%; and 99%, respectively. Surgical exploration was performed in 13 patients of gallstone ileus with ectopic stones sized larger than 3 cm. One patient recovered uneventfully following conservative treatment with an

  5. The surgical treatment of a rare complication: gallstone ileus. (United States)

    Donati, Marcello; Cardì, Francesco; Brancato, Giovanna; Calò, Piergiorgio; Donati, Angelo


    The authors describe 3 cases of gallstone ileus observed in two different hospitals and evaluate the current rarity of this complication of the biliary lithiasis and/or of cholangiocarcinomas. There were two cases of stones at the ileal level and one case in the left colon. In one case a single surgical intervention was carried out while in the other a two-step strategy was adopted. Notwithstanding the fact that the correct strategy to adopt is still controversial in literature, the authors discuss the single and double step strategies and propose that the second intervention of the 2-step strategy should not be performed in high risk surgical patients.

  6. Emerging roles of the intestine in control of cholesterol metabolism

    Institute of Scientific and Technical Information of China (English)

    Janine K Kruit; Albert K Groen; Theo J van Berkel; Folkert Kuipers


    The liver is considered the major "control center" for maintenance of whole body cholesterol homeostasis. This organ is the main site for de novo cholesterol synthesis,clears cholesterol-containing chylomicron remnants and low density lipoprotein particles from plasma and is the major contributor to high density lipoprotein (HDL; good cholesterol) formation. The liver has a central position in the classical definition of the reverse cholesterol transport pathway by taking up peripheryderived cholesterol from lipoprotein particles followed by conversion into bile acids or its direct secretion into bile for eventual removal via the feces. During the past couple of years, however, an additional important role of the intestine in maintenance of cholesterol homeostasis and regulation of plasma cholesterol levels has become apparent. Firstly, molecular mechanisms of cholesterol absorption have been elucidated and novel pharmacological compounds have been identified that interfere with the process and positively impact plasma cholesterol levels. Secondly, it is now evident that the intestine itself contributes to fecal neutral sterol loss as a cholesterol-secreting organ. Finally, very recent work has unequivocally demonstrated that the intestine contributes significantly to plasma HDL cholesterol levels.Thus, the intestine is a potential target for novel antiatherosclerotic treatment strategies that, in addition to interference with cholesterol absorption, modulate direct cholesterol excretion and plasma HDL cholesterol levels.

  7. The role of oral contraceptive (OCP use in symptomatic gallstone disease

    Directory of Open Access Journals (Sweden)

    Karimian SF


    Full Text Available To examine the relation between oral contraceptive (OCPs use, body mass index, parity, familial history of gallstone disease, history of diabetes, history of hyperlipidemia and gallstone disease in women, we have undertaken a case-control study. The study population comparison 80 hospital patients with diagnosed acute gallstone disease as case group and 200 controls who were patients in hospital with no history of gallstone disease. The data were analyzed by Chi-square and T-student test. The results revealed that: The use of OCPs in case group is higher than that of control group. But there is no significant difference between them. No relation was found between gallstone disease and body mass index, parity, history of diabetes, familial history of gallstone disease, use of OCPs of different types and duration of use. While there was a significant difference between the 2 groups regarding history of hyperlipidemia (P<0.05. Finally we found no correlation between the history of use, types and duration of use of OCPs and symptomatic gallstone disease. There was no indication of any interaction between oral contraceptive use and other risk factors and duration of OCP use and other risk factors in the production of disease.

  8. Íleo biliar: enterolitotomia videoassistida Gallstone ileus: videoassisted enterolithotomy

    Directory of Open Access Journals (Sweden)

    Álvaro Queiroz de Godoy


    Full Text Available Treatment, morbidity and mortality of patients with gallstone ileus depend on an accurate diagnosis made in time, and also on a more adequate therapeutic option.A detailed clinical evaluation is fundamental for such diagnosis. Complementary exams like a simple radiological study of the abdomen, high and low endoscopies, an ultrasonography, and a tomography can also be performed. The therapeutic options include the removal of the obstructive factor separately, the performance of a treatment in two separate stages, or the performance of a complete treatment (removal of the calculus, cholecystectomy, and the closing of the fistula.This study aims to present a case report of an elderly man of high surgical risk, presenting gallstone ileus. He was submitted to an isolated videoassisted enterolithotomy through a minilaparotomy. Taking into consideration the patient’s advanced age and the lack of evidence as to other biliary associated pathologies, the chosen treatment seemed to be a good alternative. The evolution was good, and after an 8 month follow-up the patient was found well and with no biliary symptoms whatsoever.

  9. Analysis of correlation between depression and gallstones in the aged%老年人抑郁与胆结石相关性分析

    Institute of Scientific and Technical Information of China (English)



    Objective:To understand the relationship between depression and gallstones in the elderly in urban and rural areas. Methods:Using the GDS questionnaire and self made questionnaire.1 878 residents aged over 60 in a community in Shanghai were investigated and the physical examination was conducted.Results:The prevalence of gallstones in the elderly depression was higher.Conclusion:Depression in the elderly is one of the causes of gallstones.Strengthening the psychological intervention can prevent the formation of gallbladder stones.%目的:了解城乡结合地区老年人抑郁与胆结石的相关性。方法:应用GDS问卷及自制调查表,对上海某社区60岁以上1878例居民进行调查及体检。结果:老年人抑郁中胆结石的患病率更高。结论:老年人抑郁是胆结石成因之一,应加强社区抑郁心理干,预预防胆囊结石形成。

  10. Cholesterol testing and results (United States)

    Cholesterol test results; LDL test results; VLDL test results; HDL test results; Coronary risk profile results; Hyperlipidemia- ... Some cholesterol is considered good and some is considered bad. Different blood tests can be done to measure each ...

  11. Controlling Cholesterol with Statins (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 ...

  12. Cholesterol - drug treatment (United States)

    ... this page: // 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, ...

  13. Cholesterol and public policy. (United States)

    LaRosa, J C


    Cholesterol lowering in both primary and secondary prevention has been clearly demonstrated to lower coronary morbidity and, in secondary prevention, to lower coronary mortality as well. Putative dangers of cholesterol lowering remain unproven. Population studies linking low cholesterol to noncoronary mortalities do not demonstrate cause-and-effect relations. In fact, based on current studies, the opposite is more likely to be the case. Neither gender nor age should automatically exclude persons from cholesterol screening. Drug intervention, however, should be used conservatively, particularly in young adults and the elderly. Drugs should be used only after diet and lifestyle interventions have failed. The evidence linking high blood cholesterol to coronary atherosclerosis and cholesterol lowering to its prevention is broad-based and definitive. Concerns about cholesterol lowering and spontaneously low cholesterols should be pursued but should not interfere with the implementation of current public policies to reduce the still heavy burden of atherosclerosis in Western society.

  14. High blood cholesterol levels (United States)

    ... this page: // High blood cholesterol levels To use the sharing features ... stroke, and other problems. The medical term for high blood cholesterol is lipid disorder, hyperlipidemia, or hypercholesterolemia. ...

  15. Cholesterol oxides inhibit cholesterol esterification by lecithin: cholesterol acyl transferase

    Directory of Open Access Journals (Sweden)

    Eder de Carvalho Pincinato


    Full Text Available Cholesterol oxides are atherogenic and can affect the activity of diverse important enzymes for the lipidic metabolism. The effect of 7β-hydroxycholesterol, 7-ketocholesterol, 25-hydroxycholesterol, cholestan-3β,5α,6β-triol,5,6β-epoxycholesterol, 5,6α-epoxycholesterol and 7α-hydroxycholesterol on esterification of cholesterol by lecithin:cholesterol acyl transferase (LCAT, EC and the transfer of esters of cholesterol oxides from high density lipoprotein (HDL to low density lipoproteins (LDL and very low density lipoproteins (VLDL by cholesteryl ester transfer protein (CETP was investigated. HDL enriched with increasing concentrations of cholesterol oxides was incubated with fresh plasma as source of LCAT. Cholesterol and cholesterol oxides esterification was followed by measuring the consumption of respective free sterol and oxysterols. Measurements of cholesterol and cholesterol oxides were done by gas-chromatography. 14C-cholesterol oxides were incorporated into HDL2 and HDL3 subfractions and then incubated with fresh plasma containing LCAT and CETP. The transfer of cholesterol oxide esters was followed by measuring the 14C-cholesterol oxide-derived esters transferred to LDL and VLDL. All the cholesterol oxides studied were esterified by LCAT after incorporation into HDL particles, competing with cholesterol by LCAT. Cholesterol esterification by LCAT was inversely related to the cholesterol oxide concentration. The esterification of 14C-cholesterol oxides was higher in HDL3 and the transfer of the derived esters was greater from HDL2 to LDL and VLDL. The results suggest that cholesterol esterification by LCAT is inhibited in cholesterol oxide-enriched HDL particles. Moreover, the cholesterol oxides-derived esters are efficiently transferred to LDL and VLDL. Therefore, we suggest that cholesterol oxides may exert part of their atherogenic effect by inhibiting cholesterol esterification on the HDL surface and thereby disturbing

  16. Transintestinal and Biliary Cholesterol Secretion Both Contribute to Macrophage Reverse Cholesterol Transport in Rats

    NARCIS (Netherlands)

    de Boer, Jan Freark; Schonewille, Marleen; Dikkers, Arne; Koehorst, Martijn; Havinga, Rick; Kuipers, Folkert; Tietge, Uwe J F; Groen, Albert K


    OBJECTIVE: Reverse cholesterol transport comprises efflux of cholesterol from macrophages and its subsequent removal from the body with the feces and thereby protects against formation of atherosclerotic plaques. Because of lack of suitable animal models that allow for evaluation of the respective c

  17. What Your Cholesterol Levels Mean (United States)

    ... Disease Venous Thromboembolism Aortic Aneurysm More What Your Cholesterol Levels Mean Updated:Apr 3,2017 Keeping your ... content was last reviewed on 04/21/2014. Cholesterol • Home • About Cholesterol Introduction Good vs. Bad Cholesterol ...

  18. Home-Use Tests - Cholesterol (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) ...


    Directory of Open Access Journals (Sweden)

    Jerzy Kwapulińki


    Full Text Available The studies were carried out on the changes in arsenic content in concretions of gallstones which were taken from 93 women (33 smoking and 60 no smoking and 40 men (14 smoking and 26 no smoking, respectively. The elemental composition of gallstones was determined with ICP-AES method (Inductively Coupled Plasma – Atomic Emission Spectroscopy. Studies on arsenic occurrence in concretions of gallstones showed the presence of its higher concentrations in case of women (0,55 µg/g in comparison with men (0,50 µg/g. It was shown a differences in pattern of changes of arsenic concentration in gallstones in case of influence of behaviour factors (age, place of living, education, diet, coffee and alcohol consumption, smoking, obesity.

  20. Gallstone ileus obstructing within an incarcerated lumbar hernia: an unusual presentation of a rare diagnosis. (United States)

    Ziesmann, Markus Tyler; Alotaiby, Nouf; Al Abbasi, Thamer; Rezende-Neto, Joao B


    We describe an unusual case of a 74-year-old woman who presented with signs and symptoms of small-bowel obstruction and a clinically appreciable, irreducible, left-sided lumbar hernia associated with previous iliac crest bone graft harvesting. Palpation of the hernia demonstrated a small, firm mass within the loops of herniated bowel. CT scanning recognised an intraluminal gallstone at the transition point, establishing the diagnosis of gallstone ileus within an incarcerated lumbar hernia. The proposed explanatory mechanism is that of a gallstone migrating into an easily reducible hernia containing small bowel causing obstruction at the hernia neck by a ball-valve mechanism, resulting in proximal bowel dilation and thus hernia incarceration; it remains unclear when the stone entered the hernia, and whether it enlarged in situ or prior to entering the enteral tract. This is only the second reported instance in the literature of an intraluminal gallstone causing hernia incarceration.

  1. 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


    .52-2.36)) had approximatively twice the odds of gallstones than Danes. Inclusion of lifestyle factors (smoking, alcohol intake, coffee use) did not affect this result, whereas adjustment for body mass index (BMI), lipids, diabetes, and use of oral contraceptives, menopausal hormone therapy (MHT) and parity......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...... 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...

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

    DEFF Research Database (Denmark)

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


    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....

  3. Colovesical fistula due to a lost gallstone following laparoscopic cholecystectomy: report of a case. (United States)

    Daoud, F; Awwad, Z M; Masad, J


    We report the case of a 74-year-old man with a colovesical fistula caused by a gallstone that was lost during a laparoscopic cholecystectomy 7 months earlier. The patient was cured after undergoing colonoscopic removal of the stone. To our knowledge this is the first case report of such a complication in the English literature. The report reviews the outcome and complications of retained intraperitoneal gallstones.

  4. Prevalence of gallstone disease in first-degree relatives of patients with cholelithiasis

    Institute of Scientific and Technical Information of China (English)

    Adolfo Francesco Attili; Adriano De Santis; Fabia Attili; Enrico Roda; Davide Festi; Nicola Carulli


    AIM: To evaluate the influence of familiality on the prevalence of gallstone disease (GD) in Italy.METHODS: Families of 79 subjects with gallstones (cases) and of 79 subjects without gallstones (controls)were investigated for the presence of gallstones by ultrasonography. Index cases and index controls were matched for age, sex, and operative unit. Sixty-three and sixty-two husbands and wives of index cases and index controls, respectively, were also studied.RESULTS: Overall,the prevalence of GD was significantly higher (X2=14.52, P<0.001) in the 202 first-degree relatives of subjects with gallstones than that in the 201 first-degree relatives of subjects without gallstones (28.6% vs 12.4%, relative risk (RR) 1.80, 95% confidence interval (CI) 1.29-2.63). In particular,prevalence of GD was significantly higher in mothers,fathers, and sisters of index cases than that in the respective family members of index controls. The highest RR was observed in mothers (RR=2.35, 95%CI 1.38-4.3).Prevalence of GD was not obviously different in brothers and also in husbands and wives of index cases and index controls. Family members of index cases did not differ from family members of control cases with respect to the most important risk factors for gallstones (age, diabetes,BMI, and number of pregnancies) with an exception of a higher prevalence of diabetes in fathers of index controls than in fathers of index cases.CONCLUSION: This study confirms that familiality plays a very important role in the pathogenesis of gallstones.

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


    AIM: To investigate the effect of drinking sulphate-bicarbonate-calcium thermal water (TW) on risk factors for atherosclerosis and cholesterol gallstone disease. METHODS: 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. RESULTS: Blood lipids, oxysterols and vitamin E were not affected by either thermal or tap water consumption. Fasting gallbladder volume was significantly (P < 0.005) smaller at the end of the study than at baseline in the TW (15.7 ± 1.1 mL vs 20.1 ± 1.7 mL) but not in the tap water group (19.0 ± 1.4 mL vs 19.4 ± 1.5 mL). Total serum BA concentration was significantly (P < 0.05) higher at the end of the study than at baseline in the TW (5.83 ± 1.24 μmol vs 4.25 ± 1.00 μmol) but not in the tap 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 < 0.001), meat (P < 0.001) and vegetable (P < 0.005) portions consumed during the study and of bowel movements per day (P < 0.05) were significantly higher in the TW than in the tap water group. Body weight did not change at the end of the study as compared to baseline in both groups. CONCLUSION: 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. PMID:22408352

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

    Institute of Scientific and Technical Information of China (English)

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


    AIM:To investigate the effect of drinking sulphate-bicarbonate-calcium thermal water (TW) on risk factors for atherosclerosis and cholesterol gallstone disease.METHODS: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.RESULTS:Blood lipids,oxysterols and vitamin E were not affected by either thermal or tap water consumption.Fasting gallbladder volume was significantly (P <0.005) smaller at the end of the study than at baseline in the TW (15.7 ± 1.1 mL vs 20.1 ± 1.7 mL) but not in the tap water group (19.0 ± 1.4 mL vs 19.4 ± 1.5 mL).Total serum BA concentration was significantly (P <0.05) higher at the end of the study than at baseline in the TW (5.83-1.24 μmol vs 4.25 ± 1.00 μmol) but not in the tap 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 < 0.001),meat (P < 0.001) and vegetable (P < 0.005) portions consumed during the study and of bowel movements per day (P < 0.05) were significantly higher in the TW than in the tap water group.Body weight did not change at the end of the study as compared to baseline in both groups.CONCLUSION: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.

  7. Gallstone ileus following endoscopic retrograde cholangiopancreatography and sphincterotomy: a case report

    Directory of Open Access Journals (Sweden)

    Goyal Amit


    Full Text Available Abstract Introduction Gallstone ileus is a mechanical obstruction caused by the impaction of one or more gallstones within the lumen of any part of the gastrointestinal tract. Although the disorder is a rare cause of small bowel obstruction (1% to 2%, it has been reported to cause up to 25% of cases of non-strangulated small bowel obstruction in patients over 65 years of age. Case presentation We report a case of a 67-year-old woman who presented with gallstone ileus following endoscopic retrograde cholangiopancreatography and sphincterotomy for choledocholithiasis. She had a history of terminal ileum resection with ileocolic anastomosis for Crohn's disease. A 3 cm gallstone was found to be impacted just proximal to the previous ileocolic anastomosis. A second gallstone was found on digital examination of the proximal small bowel. Conclusion A gallstone may enter the gastrointestinal tract following endoscopic retrograde cholangiopancreatography and sphincterotomy and impact proximal to an anastomotic stricture as demonstrated here. The radiographic image of small bowel obstruction plus air in the biliary tree is a classic diagnostic finding. After stone extraction, the entire small bowel and colon should be digitally examined for further stones.

  8. Gallstone-relatedcomplicationsafterRoux-en-Y gastricbypass:aprospectivestudy

    Institute of Scientific and Technical Information of China (English)

    Rachid G Nagem; Alcino Lázaro-da-Silva


    BACKGROUND: Gastric  bypass  is  a  widespread  bariatric procedure that carries a high incidence of gallstone formation postoperatively. Controversy exists regarding the importance and consequences of gallstones in these patients. There are surgeons  who  consider  gallstone-related  complications after  gastric  bypass  important  enough  to  require  routine removal of the gallbladder during gastric bypass (prophylactic cholecystectomy). However, this can lead to increased costs and risks. This study aimed to identify complications related to cholelithiasis after Roux-en-Y gastric bypass (RYGBP). METHODS: This is a prospective observational study of 40 morbidly obese patients free of gallbladder disease. The patients underwent open RYGBP at a public hospital in Brazil from February to October 2007. They were followed up clinically and ultrasonographically at 6 months and 1, 2, and 3 years after surgery. Of the patients, 38 patients were followed up for 3 years. RESULTS: Eleven  patients  (28.9%)  developed  cholelithiasis, four (10.5%) experienced biliary pain, and 2 suffered from acute  biliary  pancreatitis  (5.3%).  These  patients  had  their gallbladders removed laparoscopically. No patient presented with  acute  cholecystitis,  choledocholithiasis,  or  bile  duct dilation during the follow-up period. There were no deaths. CONCLUSIONS: Gallstone-related complications after RYGBP were relatively common. Some of these complications, like acute pancreatitis, are known to have potentially severe outcomes. It seems reasonable to perform cholecystectomy

  9. Sesamin Enhances Cholesterol Efflux in RAW264.7 Macrophages


    Nan Liu; Chongming Wu; Lizhong Sun; Jun Zheng; Peng Guo


    Foam cells formation as a result of the uncontrolled cytophagy of modified cholesterol by macrophages plays a key role in the occurrence and development of atherosclerosis. Sesamin is an active constituent of Sesamum indicum which has been shown to possess multiple pharmacological activities. In this work, we investigated the effects of sesamin on foam cell formation and cholesterol efflux in RAW264.7 macrophages. Sesamin dose-dependently inhibited the enhanced cholesterol accumulation elicit...

  10. High rate of complicated idiopathic gallstone disease in pediatric patients of a North American tertiary care center

    Institute of Scientific and Technical Information of China (English)

    Denise Herzog; Guylaine Bouchard


    AIM:To assess spectrum and etiology of gallstones and biliary sludge in the pediatric population of a North American tertiary care centre.METHODS:Retrospective review of abdominal ultrasounds recorded at Saint Justine Hospital over a period of 24 mo(8/2003 to 8/2005)in patients<19 years of age.Patients<2 years of age were analyzed separately.RESULTS:The presence of gallstones was noted in 127 patients.In 107 it was a new diagnosis,in 48/105 (45.7%)patients>2 years of age idiopathic gallstone disease was found.These 48 patients represent 2.1% of the population who required ultrasound for abdominal pain.Complicated gallstone disease occurred in 28/48 with idiopathic disease,mainly adolescent girls.Patients with hemolytic disorders,cystic fibrosis,oncologic diseases or kidney transplantation and gallstones were asymptomatic and stones were detected during routine abdominal ultrasound.Twenty two patients<2 years of age not consulting for abdominal pain had gallstone disease of diverse etiology.Biliary sludge was seen in 84 patients,78.5% on total parenteral nutrition.In 4 patients,sludge progressed to gallstones.CONCLUSION:Idiopathic gallstone disease and its rate of complication are more frequent in our cohort than expected from previous studies.Adolescent girls with abdominal pain and idiopathic gallstones require special attention for complicated disease course.

  11. Regulation of cholesterol homeostasis. (United States)

    van der Wulp, Mariëtte Y M; Verkade, Henkjan J; Groen, Albert K


    Hypercholesterolemia is an important risk factor for cardiovascular disease. It is caused by a disturbed balance between cholesterol secretion into the blood versus uptake. The pathways involved are regulated via a complex interplay of enzymes, transport proteins, transcription factors and non-coding RNA's. The last two decades insight into underlying mechanisms has increased vastly but there are still a lot of unknowns, particularly regarding intracellular cholesterol transport. After decades of concentration on the liver, in recent years the intestine has come into focus as an important control point in cholesterol homeostasis. This review will discuss current knowledge of cholesterol physiology, with emphasis on cholesterol absorption, cholesterol synthesis and fecal excretion, and new (possible) therapeutic options for hypercholesterolemia.

  12. Cholesterol - what to ask your doctor (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 ...

  13. Elevated Cholesterol in the Coxiella burnetii Intracellular Niche Is Bacteriolytic (United States)

    Mulye, Minal; Samanta, Dhritiman; Winfree, Seth; Heinzen, Robert A.


    ABSTRACT Coxiella burnetii is an intracellular bacterial pathogen and a significant cause of culture-negative endocarditis in the United States. Upon infection, the nascent Coxiella phagosome fuses with the host endocytic pathway to form a large lysosome-like vacuole called the parasitophorous vacuole (PV). The PV membrane is rich in sterols, and drugs perturbing host cell cholesterol homeostasis inhibit PV formation and bacterial growth. Using cholesterol supplementation of a cholesterol-free cell model system, we found smaller PVs and reduced Coxiella growth as cellular cholesterol concentration increased. Further, we observed in cells with cholesterol a significant number of nonfusogenic PVs that contained degraded bacteria, a phenotype not observed in cholesterol-free cells. Cholesterol had no effect on axenic Coxiella cultures, indicating that only intracellular bacteria are sensitive to cholesterol. Live-cell microscopy revealed that both plasma membrane-derived cholesterol and the exogenous cholesterol carrier protein low-density lipoprotein (LDL) traffic to the PV. To test the possibility that increasing PV cholesterol levels affects bacterial survival, infected cells were treated with U18666A, a drug that traps cholesterol in lysosomes and PVs. U18666A treatment led to PVs containing degraded bacteria and a significant loss in bacterial viability. The PV pH was significantly more acidic in cells with cholesterol or cells treated with U18666A, and the vacuolar ATPase inhibitor bafilomycin blocked cholesterol-induced PV acidification and bacterial death. Additionally, treatment of infected HeLa cells with several FDA-approved cholesterol-altering drugs led to a loss of bacterial viability, a phenotype also rescued by bafilomycin. Collectively, these data suggest that increasing PV cholesterol further acidifies the PV, leading to Coxiella death. PMID:28246364

  14. Fecal bile acid excretion and messenger RNA expression levels of ileal transporters in high risk gallstone patients

    Directory of Open Access Journals (Sweden)

    Miquel Juan


    Full Text Available Abstract Background Cholesterol gallstone disease (GS is highly prevalent among Hispanics and American Indians. In GS, the pool of bile acids (BA is decreased, suggesting that BA absorption is impaired. In Caucasian GS patients, mRNA levels for ileal BA transporters are decreased. We aimed to determine fecal BA excretion rates, mRNA levels for ileal BA transporter genes and of regulatory genes of BA synthesis in Hispanic GS patients. Results Excretion of fecal BA was measured in seven GS females and in ten GS-free individuals, all with a body mass index 2O3 (300 mg/day for 10 days, and fecal specimens were collected on the last 3 days. Chromium was measured by a colorimetric method, and BA was quantitated by gas chromatography/mass spectroscopy. Intake of calories, nutrients, fiber and cholesterol were similar in the GS and GS-free subjects. Mean BA excretion levels were 520 ± 80 mg/day for the GS-free group, and 461 ± 105 mg/day for the GS group. Messenger RNA expression levels were determined by RT-PCR on biopsy samples obtained from ileum during diagnostic colonoscopy (14 GS-free controls and 16 GS patients and from liver during surgery performed at 8 and 10 AM (12 GS and 10 GS-free patients operated on for gastrointestinal malignancies, all with a body mass index Conclusion Hispanics with GS have fecal BA excretion rates and mRNA levels of genes for ileal BA transporters that are similar to GS-free subjects. However, mRNA expression levels of Cyp7A1 are increased in GS, indicating that regulation of BA synthesis is abnormal in Hispanics with GS.

  15. Gallstone ileus analysis of radiological findings in 27 patients

    Energy Technology Data Exchange (ETDEWEB)

    Lassandro, Francesco E-mail:; Gagliardi, Nicola; Scuderi, Maria; Pinto, Antonio; Gatta, Gianluca; Mazzeo, Raffaele


    Purpose: We retrospectively compared the clinical value of plain abdominal film, abdominal sonography and abdominal CT in diagnosing gallstone ileus in 27 patients. Material and methods: 27 patients (23 women and 4 men, age range 58-96 years; mean age 71.5 years) with surgically proven gallstone ileus were submitted to plain film, sonography and CT of the abdomen. Abdominal plain films were performed in 19 cases in upright position (postero-anterior projection), in eight cases in supine position. Abdominal US were performed with 3.5 and/or 7.5 MHz probes. CT was performed with a helical unit (slice thickness 4 mm, reconstruction interval 4 mm, pitch 1.5), after intravenous contrast agent (120 ml) infusion (3 ml/s, 55 s acquisition delay from bolus starting) and using a power injector. The following findings were searched on: pneumobilia, air in gallbladder, cholecysto-digestive fistula, extraluminal fluid, bowel loops dilatation, intestinal air-fluid levels, ectopic stones. Results: Plain abdominal films showed the following findings: air-fluid levels (77.78% of cases), bowel loops dilatation (88.89%), site of obstruction (44.4%), pneumobilia (37.04%), air in gallbladder (3.70%), ectopic stone (33.33%). Abdominal sonography demonstrated bowel loops dilatation (44.44%), extraluminal fluid (14.81%), ectopic stones (14.81%), gallbladder abnormalities, (37.04%), pneumobilia (55.56%). CT findings retrospectively observed were: bowel loops dilatation (92.59%), air-fluid levels (37.04%), bilio-digestive fistula (14.81%), pneumobilia (88.89%), ectopic stone (81.48%), extraluminal fluid (22.22%). The Rigler's triad, that is pneumobilia, bowel mechanical obstruction and ectopic stone detection was observed 4 times with RX (14.81%), 3 times with US (11.11%) and 21 times with CT (77.78%). Conclusions: Air-fluid levels and bowel loop dilatation were the radiological findings more frequently observed in our series. Plain abdominal film allowed us mainly to identify signs of

  16. National Cholesterol Education Month

    Centers for Disease Control (CDC) Podcasts


    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.

  17. Gallstone ileus in a patient with Crohn's disease: a case report. (United States)

    Toelen, C; Huyghe, M


    Gallstone ileus is a rare complication of cholelithiasis. Only 0,3-0,5% of all patients with gallstones will eventually suffer from this condition. It is well known that there is an increased prevalence of gallstones among patients with Crohn's disease, but gallstone ileus remains even in these patients an unfrequent condition. Because of the rarity of this disease and its presentation as an intestinal (sub)obstruction, mostly without biliary symptoms, diagnosis and surgical treatment are often delayed. We report the case of a 75-year-old woman with a long history of Crohn's disease presenting with intermittent symptoms of intestinal obstruction since several weeks. Symptoms were thought to be due to recurrence of Crohn's disease, but the patient did not respond to steroid therapy. Resection of the diseased ileocolic segment was performed and a large impacted stone was detected proximal of the stenotic segment. With this case report we want to emphasize how easily diagnosis of gallstone ileus can be missed, especially in Crohn's patients and we would like to discuss the different treatment options.

  18. What Causes High Blood Cholesterol? (United States)

    ... the NHLBI on Twitter. What Causes High Blood Cholesterol? Many factors can affect the cholesterol levels in your blood. You can control some ... but not others. Factors You Can Control Diet Cholesterol is found in foods that come from animal ...

  19. Bile acid sequestrants for cholesterol (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 ...

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

    DEFF Research Database (Denmark)

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


    % 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.......52; 95% CI, 1.05-6.04), and common bile duct stones (HR, 11.83; 95% CI, 1.54-91). There was an association between gallstones more than 5 years old and acute cholecystitis. Female sex was associated with all and uncomplicated events. We found a negative association between participant age and all events......, uncomplicated events, and acute cholecystitis. Comorbidities and female-associated factors (intake of birth control pills or estrogens and number of births) were not associated with events. Compared with men with a single stone of 10 mm or smaller (reference), women with multiple stones greater than 10 mm had...

  1. A survey on concomitant common bile duct stone and symptomatic gallstone and clinical values in Shiraz, Southern Iran (United States)

    Hosseini, Seyed Vahid; Ayoub, Abbass; Rezaianzadeh, Abbas; Bananzadeh, Ali Mohammad; Ghahramani, Leila; Rahimikazerooni, Salar; Khazraei, Hajar


    Background: Common bile duct stone (CBDS) as a result of gallstone is one of the gastrointestinal disorders. In this study, the incidence of CBDS and symptomatic gallstone in Shiraz were investigated, and their management suggested. Materials and Methods: This is a retrospective study that enrolled among 560 patients. The incidence of gallstone together with CBDS was evaluated using an ultrasonography studyand clinical data in the period between March 2014 and 2014 in Shiraz. Comparison between data was done using Student’s t-test or Chi-square test. Results: Of these patients, 18.6% were male, and 81.4% were female with a mean age of 47.67 ± 0.74 years. The concomitant rate of gallstone and CBDS was 8.6%. 6.8% of patients with concomitant of gallstone and CBDS showed symptoms while 1.8% had not been diagnosed before the operation. The mean of serum alkaline phosphatase level in patients with the only gallstone was 255.80 IU/L and patients with concomitant gallstone, and CBDS was 580.88 IU/L with a significant difference between two groups (P < 0.001). Furthermore, liver function tests (aspartate aminotransferase, alanine transaminase) showed a significant difference between two groups of patients (P < 0.01, P < 0.001). Conclusions: Clinical variables such as tenderness, fever, and Morphy sign were more severein patients with concomitant gallstone and CBDS. The concomitant rate of gallstone and CBDS in our society is less that Western countries and asymptomatic patients showed fewer ratios than other countries. We think the approach for asymptomatic CBDS patients with gallstone can be affected by our results. PMID:27656616

  2. Spontaneous gallbladder perforation, pericholecystic abscess and cholecystoduodenal ifstula as the ifrst manifestations of gallstone disease

    Institute of Scientific and Technical Information of China (English)

    Vui Heng Chong; Kian Soon Lim; Varkey Vallickad Mathew


    BACKGROUND: Gallstone disease is common, and complications that are frequently encountered include acute cholecystitis and acute pancreatitis, but rarely gallbladder perforation. METHOD: Data were retrospectively collected from clinical case notes and a literature review is presented. RESULTS: A 72-year-old lady presented with spontaneous gallbladder perforation, pericholecystic abscess and cholecystoduodenal ifstula as the ifrst manifestations of gallstone disease. She was previously well and had no abdominal complaints. Her condition was successfully managed with initial antibiotic therapy followed by interval cholecystectomy and ifstula repair. CONCLUSIONS: Our case highlighted some uncommon but severe complications which occurred simultaneously as the ifrst manifestations of previously asymptomatic gallstone disease. Such complications need to be considered in patients suspected of intra-abdominal sepsis, even when there are no characteristic symptoms.

  3. 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


    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 sys

  4. 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


    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)

  5. Gallstone fistula with a gastric duplication cyst: an unusual complication of cholecystitis (United States)

    Bhamrah, Jasprit; Diep, Phuoc-Tan; Bennet, John; Warren, Hugh


    Cholecystitis can result in complications if not completely treated. These include gallbladder empyema, perforation and cholecystoenteric fistula. We report the first incidence of cholecystitis resulting in a gallstone fistula with a gastric duplication cyst. A 71 year old patient presented with generalised peritonism that was worst in the epigastric area. Computer tomography (CT) revealed a perforated necrotic gallbladder. Emergency laparotomy, cholecystectomy, partial gastrectomy and Roux-en-Y reconstruction was required. The patient made a slow but full recovery. Pathology results revealed that chronic cholecystitis had resulted in a fistula with a duplication cyst overlying the greater curve of the stomach. Several one centimeter gallstones were found within the cyst cavity. PMID:24946358

  6. Cholesterol and Women's Health (United States)

    ... can I make to reduce my risk of cardiovascular disease? • Is there medication that can help reduce my cholesterol ... It also helps your body make vitamin D and produces the bile that helps you ...

  7. MD-2 binds cholesterol. (United States)

    Choi, Soo-Ho; Kim, Jungsu; Gonen, Ayelet; Viriyakosol, Suganya; Miller, Yury I


    Cholesterol is a structural component of cellular membranes, which is transported from liver to peripheral cells in the form of cholesterol esters (CE), residing in the hydrophobic core of low-density lipoprotein. Oxidized CE (OxCE) is often found in plasma and in atherosclerotic lesions of subjects with cardiovascular disease. Our earlier studies have demonstrated that OxCE activates inflammatory responses in macrophages via toll-like receptor-4 (TLR4). Here we demonstrate that cholesterol binds to myeloid differentiation-2 (MD-2), a TLR4 ancillary molecule, which is a binding receptor for bacterial lipopolysaccharide (LPS) and is indispensable for LPS-induced TLR4 dimerization and signaling. Cholesterol binding to MD-2 was competed by LPS and by OxCE-modified BSA. Furthermore, soluble MD-2 in human plasma and MD-2 in mouse atherosclerotic lesions carried cholesterol, the finding supporting the biological significance of MD-2 cholesterol binding. These results help understand the molecular basis of TLR4 activation by OxCE and mechanisms of chronic inflammation in atherosclerosis.

  8. MCPIP is induced by cholesterol and participated in cholesterol-caused DNA damage in HUVEC. (United States)

    Da, Jingjing; Zhuo, Ming; Qian, Minzhang


    Hypercholesterolemia is an important risk factor for atherosclerosis and cholesterol treatment would cause multiple damages, including DNA damage, on endothelial cells. In this work, we have used human umbilical vein endothelial cell line (HUVEC) to explore the mechanism of cholesterol induced damage. We have found that cholesterol treatment on HUVEC could induce the expression of MCPIP1. When given 12.5 mg/L cholesterol on HUVEC, the expression of MCPIP1 starts to increase since 4 hr after treatment and at 24 hr after treatment it could reach to 10 fold of base line level. We hypothesis this induction of MCPIP1 may contribute to the damaging process and we have used siRNA of MCPIP1 in further research. This MCPIP1 siRNA (siMCPIP) could down regulate MCPIP1 by 73.4% and when using this siRNA on HUVECs, we could see the cholesterol induced DNA damage have been reduced. We have detected DNA damage by γH2AX foci formation in nuclear, γH2AX protein level and COMET assay. Compare to cholesterol alone group, siMCPIP group shows much less γH2AX foci formation in nuclear after cholesterol treatment, less γH2AX protein level in cell and also less tail moment detected in COMET assay. We have also seen that using siMCPIP1 could result in less reactive oxygen species (ROS) in cell after cholesterol treatment. We have also seen that using siMCPIP could reduce the protein level of Nox4 and p47(phox), two major regulators in ROS production. These results suggest that MCPIP1 may play an important role in cholesterol induced damage.

  9. Metagenomic analysis reveals gallstone types associated with gut microbiome community composition%常见三种类型胆结石胆汁中细菌群落的检测

    Institute of Scientific and Technical Information of China (English)

    刘晶华; 王敏; 邹玉


    目的 探讨常见三种类型胆结石胆汁中所含微生物群落的差异性.方法 采用末端限制性片断长度多态性(T-RFLP)技术对50例三种类型胆结石患者的胆汁细菌群落进行基因序列分析.结果(1)细菌16S rDNA基因片段的阳性检出率为76%(38/50),三组之间阳性检出率差异无统计学意义;(2)三组细菌16S rDNA基因片段分析,纯胆固醇组的细菌群落主要以肺炎克雷伯氏菌和金黄色葡萄球菌为主;胆色素结石组主要包括普通变形杆菌、厌氧消化球菌等;混合性结石胆汁组主要为厌氧消化球菌、丙酸杆菌,其中还包括了胆色素结石胆汁组中未检测到的黄微杆菌和希氏短杆菌.结论 胆结石患者胆汁标本中细菌检出率较高,但各组细菌群落构成各有不同,且成分较为复杂.%Objective To determine if the types of gallstones are associated with different bacterial profiles in bile. Methods Gallstones and bile samples were obtained from 50 patients undergoing elective cholecystectomy. Gallstone chemical composition was determined by infrared spectrometry analysis using KBr tablets. The bacteria composition of corresponding bile samples were analyzed by terminal restriction fragment length polymorphism (T - RFLP) genetic sequencing of 16s ribosomal DNA (rDNA). Results Three types of gallstones were detected and the patients were grouped accordingly: pure cholesterol stones (n = 25 patients), pigment gallstones (n = 11), and mixed stones (n = 14). The overall positive detection rate of bacterial 16S rDNA gene fragments was 86% (43/50), and the positive rate was not significantly different among the three groups. The microbiome of the pure cholesterol group was mainly composed of Klebsiella pneumoniae and Staphylococcus aureus. The bile pigment stones group was mainly composed of Proteus vulgaris. The mixed group was mainly composed of anaerobic digestion bacteria propionic acid bacteria, and Microbacterium flavum

  10. Rhinovirus uses a phosphatidylinositol 4-phosphate/cholesterol counter-current for the formation of replication compartments at the ER-Golgi interface

    NARCIS (Netherlands)

    Roulin, Pascal S; Lötzerich, Mark; Torta, Federico; Tanner, Lukas B; van Kuppeveld, Frank J M; Wenk, Markus R; Greber, Urs F


    Similar to other positive-strand RNA viruses, rhinovirus, the causative agent of the common cold, replicates on a web of cytoplasmic membranes, orchestrated by host proteins and lipids. The host pathways that facilitate the formation and function of the replication membranes and complexes are poorly

  11. Gallstone ileus diagnosed by technetium-99m dimethyliminodiacetic acid cholescintigraphy. A case report

    Energy Technology Data Exchange (ETDEWEB)

    Elkin, C.M.; Weissmann, H.S.; Freeman, L.M.


    Tc-99m IDA cholescintigraphy frequently provides information regarding nonbiliary pathology, such as small bowel obstruction. The cholescintigraphic finding of functional cystic duct obstruction concomitant with persistent small bowel dilatation and lack of progression of labeled bile suggests the diagnosis of gallstone ileus.

  12. 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: [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)


    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.

  13. Abdominal wall abscess containing gallstones as a late complication to laparoscopic cholecystectomy performed 17 years earlier

    DEFF Research Database (Denmark)

    Christensen, Anders Mark; Christensen, Mads Mark


    of a 53-year-old woman who developed two abscesses--one intra-abdominally and one in the abdominal wall-17 years after an LC. Three gallstones were found during surgical excision of the abdominal wall abscess. Surgeons should strive to avoid perforation of the gall bladder during LC. If spillage...

  14. Correlation between thyroid function and nodular goiter accompanied with gallstone

    Institute of Scientific and Technical Information of China (English)

    Shihong Ma; Qinjiang Liu; Xiaofeng Hou



  15. Cholesterol and prostate cancer. (United States)

    Pelton, Kristine; Freeman, Michael R; Solomon, Keith R


    Prostate cancer risk can be modified by environmental factors, however the molecular mechanisms affecting susceptibility to this disease are not well understood. As a result of a series of recently published studies, the steroidal lipid, cholesterol, has emerged as a clinically relevant therapeutic target in prostate cancer. This review summarizes the findings from human studies as well as animal and cell biology models, which suggest that high circulating cholesterol increases risk of aggressive prostate cancer, while cholesterol lowering strategies may confer protective benefit. Relevant molecular processes that have been experimentally tested and might explain these associations are described. We suggest that these promising results now could be applied prospectively to attempt to lower risk of prostate cancer in select populations.

  16. Paraganglioma presenting as cholesterol granuloma of the petrous apex. (United States)

    Heman-Ackah, Selena E; Huang, Tina C


    We report the unique finding of a petrous apex cholesterol granuloma associated with a paraganglioma, also known as a glomus jugulare tumor, in a 52-year-old woman who presented to our department with pulsatile tinnitus, hearing loss, aural fullness, and disequilibrium. She had been treated for a petrous apex cholesterol granuloma 20 years earlier, at which time she had undergone drainage of the granuloma via subtotal petrous apicectomy. When she came to our facility approximately 20 years later, she had signs and symptoms consistent with a jugular paraganglioma, which was likely to have been present at the time of her initial presentation for the cholesterol granuloma. In fact, microscopic bleeding from the paraganglioma might have led to the formation of the cholesterol granuloma. The metachronous presentation of these two entities, which to our knowledge has not been reported previously in the literature, indicates the potential association of paragangliomas with the formation of cholesterol granulomas of the petrous apex.

  17. Orbitofrontal cholesterol granuloma. (United States)

    Chow, L P; McNab, A A


    Cholesterol granuloma of the orbital bones is a rare but readily recognisable condition. It is an osteolytic lesion with a granulomatous reaction surrounding cholesterol crystals, old haemorrhage and a fibrous capsule. There is a male preponderance and it usually occurs in young or middle-aged men. It is treatable with drainage and curettage via an orbitotomy, and craniotomy or wide bone removal is almost never required. Six cases of this condition were reviewed to highlight the typical clinical presentation, computed tomography and magnetic resonance results, and surgical management.

  18. Cholesterol and myelin biogenesis. (United States)

    Saher, Gesine; Simons, Mikael


    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.

  19. Metabolism of adrenal cholesterol in man (United States)

    Borkowski, Abraham; Delcroix, Claude; Levin, Sam


    The synthesis of adrenal cholesterol, its esterification and the synthesis of the glucocorticosteroid hormones were studied in vitro on human adrenal tissue. It was found that the synthesis of adrenal cholesterol may normally be small in the zona “fasciculata,” particularly when compared with the synthesis of the glucocorticosteroid hormones, that it is several times higher in the zona “reticularis” where esterified cholesterol is less abundant, and that under ACTH stimulation it increases strikingly and proportionally to the degree of esterified adrenal cholesterol depletion. On the other hand, the relative rate of esterification as well as the concentration of free adrenal cholesterol are remarkably stable: they do not differ according to the adrenal zonation and are unaffected by ACTH. Furthermore, from a qualitative point of view, the relative proportions of Δ1 and Δ2 cholesteryl esters formed in situ are similar to those anticipated from their relative concentrations, suggesting that the characteristic fatty acid distribution of the adrenal cholesteryl esters results from an in situ esterification rather than from a selective uptake of the plasma cholesteryl esters. Besides, the in vitro esterification reveals a propensity to the formation of the most unsaturated cholesteryl esters. Regarding hydrocortisone and corticosterone, their synthesis tends to be more elevated in the zona “fasciculata.” Despite its higher cholesterol concentration the zona “fasciculata” should not therefore be viewed as a quiescent functional complement to the zona “reticularis” and the cortical distribution of glucocorticosteroid hormone synthesis is quite distinct from that of adrenal cholesterol synthesis. PMID:4338120

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

    NARCIS (Netherlands)

    Jakulj, L.


    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 anti-atherosc

  1. Design and application of a new series of gallbladder endoscopes that facilitate gallstone removal without gallbladder excision (United States)

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


    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.

  2. Apolipoprotein M promotes mobilization of cellular cholesterol in vivo

    DEFF Research Database (Denmark)

    Elsøe, Sara; Christoffersen, Christina; Luchoomun, Jayraz


    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....

  3. Insoluble fraction of buckwheat (Fagopyrum esculentum Moench) protein possessing cholesterol-binding properties that reduce micelle cholesterol solubility and uptake by Caco-2 cells. (United States)

    Metzger, Brandon T; Barnes, David M; Reed, Jess D


    Buckwheat (Fagopyrum esculentum Moench) protein (BWP) exhibits hypocholesterolemic activity in several animal models by increasing fecal excretion of neutral and acidic sterols. In the current study, the ability of BWP to disrupt micelle cholesterol solubility by sequestration of cholesterol was investigated. When BWP (0.2%) was incubated with cholesterol and micelle lipid components prior to micelle formation, cholesterol solubility was reduced 40%. In contrast, cholesterol solubility was not decreased when BWP (0.2%) was incubated after micelle formation and incorporation of soluble cholesterol. Buckwheat flour, from which BWP was derived, had no significant effect on cholesterol solubility. Cholesterol uptake in Caco-2 cells from micelles made in the presence of BWP (0.2%) was reduced by 47, 36, 35, and 33% when compared with buckwheat flour, bovine serum albumin, casein, and gelatin, respectively. Reduction in cholesterol uptake in Caco-2 cells was dose-dependent, with maximum reductions at 0.1-0.4% BWP. In cholesterol-binding experiments, 83% of the cholesterol was associated with an insoluble BWP fraction, indicating strong cholesterol-binding capacity that disrupts solubility and uptake by Caco-2 cells.

  4. Regulation of cholesterol homeostasis

    NARCIS (Netherlands)

    van der Wulp, Mariette Y. M.; Verkade, Henkjan J.; Groen, Albert K.


    Hypercholesterolemia is an important risk factor for cardiovascular disease. It is caused by a disturbed balance between cholesterol secretion into the blood versus uptake. The pathways involved are regulated via a complex interplay of enzymes, transport proteins, transcription factors and non-codin

  5. Transintestinal cholesterol efflux

    NARCIS (Netherlands)

    van der Velde, Astrid E.; Brufau, Gemma; Groen, Albert K.


    Purpose of review Regulation of cholesterol homeostasis is a complex interplay of a multitude of metabolic pathways situated in different organs. The liver plays a central role and has received most attention of the research community. In this review, we discuss recent progress in the understanding

  6. Cholesterol: Up in Smoke. (United States)

    Raloff, Janet


    Discussed is the contribution cooked meat makes to air pollution. The dozens of compounds, including cholesterol, that are released when a hamburger is grilled are described. The potential effects of these emissions on humans and the urban environment are discussed. (KR)

  7. Cholesterol transport in model membranes (United States)

    Garg, Sumit; Porcar, Lionel; Butler, Paul; Perez-Salas, Ursula


    Physiological processes distribute cholesterol unevenly within the cell. The levels of cholesterol are maintained by intracellular transport and a disruption in the cell's ability to keep these normal levels will lead to disease. Exchange rates of cholesterol are generally studied in model systems using labeled lipid vesicles. Initially donor vesicles have all the cholesterol and acceptor vesicles are devoid of it. They are mixed and after some time the vesicles are separated and cholesterol is traced in each vesicle. The studies performed up to date have significant scatter indicating that the methodologies are not consistent. The present work shows in-situ Time-Resolved SANS studies of cholesterol exchange rates in unsaturated PC lipid vesicles. Molecular dynamics simulations were done to investigate the energetic and kinetic behavior of cholesterol in this system. This synergistic approach will provide insight into our efforts to understand cholesterol traffic.

  8. 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.

  9. Cholesterol excretion and colon cancer. (United States)

    Broitman, S A


    Populations consuming diets high in fat and cholesterol exhibit a greater incidence of colon cancer than those consuming less fat and cholesterol. Lowering elevated serum cholesterol levels experimentally or clinically is associated with increased large-bowel tumorigenesis. Thus, cholesterol lost to the gut, either dietary or endogenously synthesized, appears to have a role in large-bowel cancer. Whether the effect(s) is mediated by increases in fecal bile acid excretion or some other mechanism is not clear.

  10. Sesamin Enhances Cholesterol Efflux in RAW264.7 Macrophages

    Directory of Open Access Journals (Sweden)

    Nan Liu


    Full Text Available Foam cells formation as a result of the uncontrolled cytophagy of modified cholesterol by macrophages plays a key role in the occurrence and development of atherosclerosis. Sesamin is an active constituent of Sesamum indicum which has been shown to possess multiple pharmacological activities. In this work, we investigated the effects of sesamin on foam cell formation and cholesterol efflux in RAW264.7 macrophages. Sesamin dose-dependently inhibited the enhanced cholesterol accumulation elicited by oxidized low-density lipoprotein cholesterol (oxLDL in RAW264.7 cells. Treatment with sesamin (10 μM significantly enhanced cholesterol efflux mediated by high-density lipoprotein (HDL. Realtime quantitative PCR and luciferase assays showed that sesamin significantly increased the mRNA levels of PPARγ, LXRα, and ABCG1, and increased the transcriptional activity of PPARγ. The stimulating effect of sesamin on cholesterol efflux was substantially inhibited by the co-treatment with GW9662, a potent inhibitor of PPARγ. These results suggest that sesamin is a new inhibitor of foam cell formation that may stimulate cholesterol efflux through upregulation of the PPARγ-LXRα-ABCG1 pathway.

  11. Sesamin enhances cholesterol efflux in RAW264.7 macrophages. (United States)

    Liu, Nan; Wu, Chongming; Sun, Lizhong; Zheng, Jun; Guo, Peng


    Foam cells formation as a result of the uncontrolled cytophagy of modified cholesterol by macrophages plays a key role in the occurrence and development of atherosclerosis. Sesamin is an active constituent of Sesamum indicum which has been shown to possess multiple pharmacological activities. In this work, we investigated the effects of sesamin on foam cell formation and cholesterol efflux in RAW264.7 macrophages. Sesamin dose-dependently inhibited the enhanced cholesterol accumulation elicited by oxidized low-density lipoprotein cholesterol (oxLDL) in RAW264.7 cells. Treatment with sesamin (10 μM) significantly enhanced cholesterol efflux mediated by high-density lipoprotein (HDL). Realtime quantitative PCR and luciferase assays showed that sesamin significantly increased the mRNA levels of PPARγ, LXRα, and ABCG1, and increased the transcriptional activity of PPARγ. The stimulating effect of sesamin on cholesterol efflux was substantially inhibited by the co-treatment with GW9662, a potent inhibitor of PPARγ. These results suggest that sesamin is a new inhibitor of foam cell formation that may stimulate cholesterol efflux through upregulation of the PPARγ-LXRα-ABCG1 pathway.

  12. How to Get Your Cholesterol Tested (United States)

    ... Thromboembolism Aortic Aneurysm More How To Get Your Cholesterol Tested Updated:Apr 3,2017 Cholesterol plays a ... factors for heart disease and stroke . How is cholesterol tested? A cholesterol screening measures your level of ...

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

    Directory of Open Access Journals (Sweden)

    Rodgers John B


    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.

  14. Gallstone fistula with a gastric duplication cyst: an unusual complication of cholecystitis

    Directory of Open Access Journals (Sweden)

    Jasprit Bhamrah


    Full Text Available Cholecystitis can result in complications if not completely treated. These include gallbladder empyema, perforation and cholecystoenteric fistula.We report the first incidence of cholecystitis resulting in a gallstone fistula with a gastric duplication cyst. A 71 year old patient presented with generalised peritonism that was worst in the epigastric area. Computer tomography (CT revealed a perforated necrotic gallbladder. Emergency laparotomy, cholecystectomy, partial gastrectomy and Roux-en-Y reconstruction was required. The patient made a slow but full recovery.Pathology results revealed that chronic cholecystitis had resulted in a fistula with a duplication cyst overlying the greater curve of the stomach. Several one centimeter gallstones were found within the cyst cavity.

  15. Cholesterol crystal embolism (atheroembolism) (United States)



    Cholesterol crystal embolism, known as atheroembolic disease, is caused by showers of cholesterol crystals from an atherosclerotic plaque that occludes small arteries. Embolization can occur spontaneously or as an iatrogenic complication from an invasive vascular procedure (angiography or vascular surgery) and after anticoagulant therapy. The atheroembolism can give rise to different degrees of renal impairment. Some patients show a moderate loss of renal function, others severe renal failure requiring dialysis. Renal outcome can be variable: some patients deteriorate or remain on dialysis, some improve and some remain with chronic renal impairment. Clinically, three types of atheroembolic renal disease have been described: acute, subacute or chronic. More frequently a progressive loss of renal function occurs over weeks. Atheroembolization can involve the skin, gastrointestinal system and central nervous system. The diagnosis is difficult and controversial for the protean extrarenal manifestations. In the past, the diagnosis was often made post-mortem. In the last 10 yrs, awareness of atheroembolic renal disease has improved. The correct diagnosis requires the clinician to be alert. The typical patient is a white male aged >60 yrs with a history of hypertension, smoking and arterial disease. The presence of a classic triad (precipitating event, renal failure and peripheral cholesterol crystal embolization) suggests the diagnosis. This can be confirmed by a biopsy of the target organs. A specific treatment is lacking; however, it is an important diagnosis to make because an aggressive therapeutic approach can be associated with a more favorable clinical outcome. PMID:21977265

  16. Cholesterol binding to ion channels

    Directory of Open Access Journals (Sweden)

    Irena eLevitan


    Full Text Available Numerous studies demonstrated that membrane cholesterol is a major regulator of ion channel function. The goal of this review is to discuss significant advances that have been recently achieved in elucidating the mechanisms responsible for cholesterol regulation of ion channels. The first major insight that comes from growing number of studies that based on the sterol specificity of cholesterol effects, show that several types of ion channels (nAChR, Kir, BK, TRPV are regulated by specific sterol-protein interactions. This conclusion is supported by demonstrating direct saturable binding of cholesterol to a bacterial Kir channel. The second major advance in the field is the identification of putative cholesterol binding sites in several types of ion channels. These include sites at locations associated with the well-known cholesterol binding motif CRAC and its reversed form CARC in nAChR, BK, and TRPV, as well as novel cholesterol binding regions in Kir channels. Notably, in the majority of these channels, cholesterol is suggested to interact mainly with hydrophobic residues in non-annular regions of the channels being embedded in between transmembrane protein helices. We also discuss how identification of putative cholesterol binding sites is an essential step to understand the mechanistic basis of cholesterol-induced channel regulation. Clearly, however, these are only the first few steps in obtaining a general understanding of cholesterol-ion channels interactions and their roles in cellular and organ functions.

  17. Perforated Closed-Loop Obstruction Secondary to Gallstone Ileus of the Transverse Colon: A Rare Entity


    Carr, S. P.; MacNamara, F. T.; Muhammed, K. M.; Boyle, E; S. M. McHugh; Naughton, P.; Leahy, A


    Introduction. Gallstone ileus (GSI) of the colon is an extremely rare entity with potentially serious complications including perforation. Case Presentation. An 88-year-old man presented to the emergency department with abdominal pain and distension. Clinical exam revealed signs of peritonism. Computed tomography (CT) revealed GSI of the transverse colon with a closed-loop large bowel obstruction (LBO) and caecal perforation. The patient underwent emergency laparotomy. A right hemicolectomy w...

  18. Gallstone fistula with a gastric duplication cyst: an unusual complication of cholecystitis


    Jasprit Bhamrah; Phuoc-Tan Diep; John Bennet; Hugh Warren


    Cholecystitis can result in complications if not completely treated. These include gallbladder empyema, perforation and cholecystoenteric fistula. We report the first incidence of cholecystitis resulting in a gallstone fistula with a gastric duplication cyst. A 71 year old patient presented with generalised peritonism that was worst in the epigastric area. Computer tomography (CT) revealed a perforated necrotic gallbladder. Emergency laparotomy, cholecystectomy, partial gastrectomy and Roux-e...

  19. Human gallbladder morphology after gallstone dissolution with methyl tert-butyl ether. (United States)

    vanSonnenberg, E; Zakko, S; Hofmann, A F; D'Agostino, H B; Jinich, H; Hoyt, D B; Miyai, K; Ramsby, G; Moossa, A R


    The effects of methyl tert-butyl ether exposure on the human gallbladder in five patients who were treated for gallstones by contact dissolution is described. Two patients underwent cholecystectomy within 1 week of methyl tert-butyl ether treatment, one patient 2 weeks after, another 10 weeks after, and one 12 weeks after. Indications for cholecystectomy were bilirubinate stones (resistant to methyl tert-butyl ether), catheter dislodgement, bile leakage, and gallstone recurrence (2 patients). Gallstones were dissolved completely in three patients, there was approximately 50% stone reduction in one patient, and no dissolution occurred in the fifth patient. Each gallbladder was examined grossly and histologically. Electron microscopic evaluation was performed in one cases. Typical inflammatory findings of chronic cholecystitis were observed in each gallbladder and were most conspicuous in the submucosa; the mucosal and serosal surfaces were intact. Mild acute inflammatory changes were noted in the submucosa in the two patients with the shortest interval between methyl tert-butyl ether administration and cholecystectomy. There were no ulcerations in the mucosa and no unusual wall thickening or fibrosis in any patient. These observations support the safety of methyl tert-butyl ether perfusion in the human gallbladder; the mild acute changes may be a transient and reversible phenomenon.

  20. Reverse cholesterol transport: From classical view to new insights

    Institute of Scientific and Technical Information of China (English)

    Astrid; E; van; der; Velde


    Cholesterol is of vital importance for the human body. It is a constituent for most biological membranes, it is needed for the formation of bile salts, and it is the pre- cursor for steroid hormones and vitamin D. However, the presence of excess cholesterol in cells, and in particular in macrophages in the arterial vessel wall, might be harmful. The accumulation of cholesterol in arteries can lead to atherosclerosis, and in turn, to other cardiovascular diseases. The route that is primarily thought to be re...

  1. Characterization of placental cholesterol transport

    DEFF Research Database (Denmark)

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


    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...

  2. Cholesterol metabolism in Huntington disease. (United States)

    Karasinska, Joanna M; Hayden, Michael R


    The CNS is rich in cholesterol, which is essential for neuronal development and survival, synapse maturation, and optimal synaptic activity. Alterations in brain cholesterol homeostasis are linked to neurodegeneration. Studies have demonstrated that Huntington disease (HD), a progressive and fatal neurodegenerative disorder resulting from polyglutamine expansion in the huntingtin protein, is associated with changes in cellular cholesterol metabolism. Emerging evidence from human and animal studies indicates that attenuated brain sterol synthesis and accumulation of cholesterol in neuronal membranes represent two distinct mechanisms occurring in the presence of mutant huntingtin that influence neuronal survival. Increased knowledge of how changes in intraneuronal cholesterol metabolism influence the pathogenesis of HD will provide insights into the potential application of brain cholesterol regulation as a therapeutic strategy for this devastating disease.

  3. 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


    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

  4. Gallstone ileus inducing obstructive jaundice at the afferent loop of Roux-en-Y hepaticojejunostomy after bile duct cancer surgery: a case report. (United States)

    Lee, Hyun Gu; Hwang, Shin; Joo, Yo-Han; Cho, Yu-Jeong; Choi, Kyunghak


    The diagnosis of gallstone ileus is occasionally challenging due to the variability of its presentation. We herein present a very rare case of gallstone ileus inducing obstructive jaundice at the afferent loop of Roux-en-Y hepaticojejunostomy after 10 years of bile duct cancer surgery. We describe the case of a 74-year-old Korean woman with obstructive jaundice, treated conservatively. She showed severely impaired liver function test and obstructive jaundice. The computed tomography (CT) scan led to a diagnosis of very rare type of gallstones ileus at the afferent jejunal loop. Since the clinical manifestation was improved, we decided to observe her closely. On the next follow-up CT scan, the gallstone disappeared with mild distension of the afferent bowel loop, implicating spontaneous passage of the gallstone. She recovered and returned to normal life after 10 days of initiation of clinical manifestations. We presume that the gallstone may enter the afferent jejunal loop through the hepaticojejunostomy and later increase in size. The presence of narrow tract of intestine may facilitate the incidence of gallstone ileus. It appears to be the first report on this rare type of gallstone ileus inducing obstructive jaundice.

  5. Sterol transporter adenosine triphosphate-binding cassette transporter G8, gallstones, and biliary cancer in 62,000 individuals from the general population

    DEFF Research Database (Denmark)

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


    Gallstone disease, a risk factor for biliary cancer, has a strong heritable component, but the underlying genes are largely unknown. To test the hypothesis that ABCG8 (adenosine triphosphate-binding cassette transporter G8) Asp19His (D19H) genotype predicted risk of gallstones and biliary cancer ...

  6. Cholesterol Embolism: An Overlooked Diagnosis

    Directory of Open Access Journals (Sweden)

    Sinem Nihal ESATOĞLU


    Full Text Available Acute renal failure following angiography is usually due to radiocontrast nephropathy; however, cholesterol embolism should be kept in mind when making the differential diagnosis. Cholesterol embolism is a multisystem disease, usually seen in elderly men who have severe atherosclerosis. In this case report, we describe a patient with cholesterol embolism who had a typical clinical history of progressive renal failure. We hope that this case report will emphasize the importance of this overlooked syndrome.

  7. Resveratrol Protects Rabbits Against Cholesterol Diet-Induced Hyperlipidaemia. (United States)

    Tanko, Y; Jimoh, A; Ahmed, A; Mohammed, A; Ayo, J O


    The excessive consumption of high cholesterol diet has been associated with an increased incidence oflipidaemia. Lipidaemia is enhanced by formation of oxidative stress, lipid peroxidation and hyperglycaemia. The aim ofthese experiments was to investigate the protective effect of resveratrol co-administered with cholesterol diet inducedhyperlipidaemia in rabbits. Thirty rabbits divided into six groups of five animal (group= 5) each: group 1 = normal control,group 2 = cholesterol diet/high fat diet group only (HFD), group 3 = resveratrol 200 mg/kg (R200), group 4 = resveratrol400 mg/kg (R400), group 5 = HFD + R200 and group 6 = HFD + R400. The normal group was fed with standard animalfeeds only; while the HFD groups were fed with standard animal feeds + cholesterol diet (10% Groundnut oil, 20%Groundnut mill and 2% cholesterol). Resveratrol-treated rabbits received resveratrol suspended in 10 g/Lcarboxymethylcellulose (CMC) and the control group received the vehicle only, CMC. The preparations were administeredfor 8 weeks of experimental protocol. At the end of the study period, the animals were sacrificed. Blood and plasma sampleswere collected. Serum evaluation of lipid profile such as total cholesterol (TC), triacylglycerol (Tg), low density lipoproteincholesterol (LDP-c) and high density lipoprotein cholesterol (HDL-c) were also assessed. The results obtained showsignificant (P < 0.05) decrease in total cholesterol (TC), Low density lipoprotein cholesterol (LDP-c), total triacylglyceroland an increase in high density lipoprotein cholesterol (HDL-c) in resveratrol treated groups compared to HFD group only.In conclusion, the findings indicated that Resveratrol may contain polar products able to lower plasma lipid concentrationsand might be beneficial in treatment of hyperlipidemia and atherosclerosis.

  8. 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


    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.)

  9. 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.

  10. Food combinations for cholesterol lowering. (United States)

    Harland, Janice I


    Reducing elevated LDL-cholesterol is a key public health challenge. There is substantial evidence from randomised controlled trials (RCT) that a number of foods and food components can significantly reduce LDL-cholesterol. Data from RCT have been reviewed to determine whether effects are additive when two or more of these components are consumed together. Typically components, such as plant stanols and sterols, soya protein, β-glucans and tree nuts, when consumed individually at their target rate, reduce LDL-cholesterol by 3-9 %. Improved dietary fat quality, achieved by replacing SFA with unsaturated fat, reduces LDL-cholesterol and can increase HDL-cholesterol, further improving blood lipid profile. It appears that the effect of combining these interventions is largely additive; however, compliance with multiple changes may reduce over time. Food combinations used in ten 'portfolio diet' studies have been reviewed. In clinical efficacy studies of about 1 month where all foods were provided, LDL-cholesterol is reduced by 22-30 %, whereas in community-based studies of >6 months' duration, where dietary advice is the basis of the intervention, reduction in LDL-cholesterol is about 15 %. Inclusion of MUFA into 'portfolio diets' increases HDL-cholesterol, in addition to LDL-cholesterol effects. Compliance with some of these dietary changes can be achieved more easily compared with others. By careful food component selection, appropriate to the individual, the effect of including only two components in the diet with good compliance could be a sustainable 10 % reduction in LDL-cholesterol; this is sufficient to make a substantial impact on cholesterol management and reduce the need for pharmaceutical intervention.

  11. Cholesterol transport and regulation in the mammary gland. (United States)

    Ontsouka, Edgar C; Albrecht, Christiane


    The milk-producing alveolar epithelial cells secrete milk that remains after birth the principal source of nutrients for neonates. Milk secretion and composition are highly regulated processes via integrated actions of hormones and local factors which involve specific receptors and downstream signal transduction pathways. Overall milk composition is similar among mammalian species, although the content of individual constituents such as lipids may significantly differ from one species to another. The milk lipid fraction is essentially composed of triglycerides, which represent more than 95 % of the total lipids in human and commercialized bovine milk. Though sterols, including cholesterol, which is the major milk sterol, represent less than 0.5 % of the total milk lipid fraction, they are of key importance for several biological processes. Cholesterol is required for the formation of biological membranes especially in rapidly growing organisms, and for the synthesis of sterol-based compounds. Cholesterol found in milk originates predominantly from blood uptake and, to a certain extent, from local synthesis in the mammary tissue. The present review summarizes current knowledge on cellular mechanisms and regulatory processes determining intra- and transcellular cholesterol transport in the mammary gland. Cholesterol exchanges between the blood, the mammary alveolar cells and the milk, and the likely role of active cholesterol transporters in these processes are discussed. In this context, the hormonal regulation and signal transduction pathways promoting active cholesterol transport as well as potential regulatory crosstalks are highlighted.

  12. Lipid domains in bicelles containing unsaturated lipids and cholesterol. (United States)

    Cho, Hyo Soon; Dominick, Johnna L; Spence, Megan M


    We have created a stable bicelle system capable of forming micrometer-scale lipid domains that orient in a magnetic field, suitable for structural biology determination in solid-state NMR. The bicelles consisted of a mixture of cholesterol, saturated lipid (DMPC), and unsaturated lipid (POPC), a mixture commonly used to create domains in model membranes, along with a short chain lipid (DHPC) that allows formation of the bicelle phase. While maintaining a constant molar ratio of long to short chain lipids, q = ([POPC]+[DMPC])/[DHPC] = 3, we varied the concentrations of the unsaturated lipid, POPC, and cholesterol to observe the effects of the components on bicelle stability. Using (31)P solid-state NMR, we observed that unsaturated lipids (POPC) greatly destabilized the alignment of the membranes in the magnetic field, while cholesterol stabilized their alignment. By combining cholesterol and unsaturated lipids in the bicelles, we created membranes aligning uniformly in the magnetic field, despite very high concentrations of unsaturated lipids. These bicelles, with high concentrations of both cholesterol and unsaturated lipid, showed similar phase behavior to bicelles commonly used in structural biology, but aligned over a wider temperature range (291-314 K). Domains were observed by measuring time-dependent diffusion constants reflecting restricted diffusion of the lipids within micrometer-scale regions of the bicelles. Micron-scale domains have never been observed in POPC/DMPC/cholesterol vesicles, implying that bilayers in bicelles show different phase behavior than their counterparts in vesicles, and that bilayers in bicelles favor domain formation.

  13. Proinflammatory cytokines in alcohol or gallstone induced acute pancreatitis. A prospective study

    DEFF Research Database (Denmark)

    Novovic, Srdan; Andersen, Anders Møller; Ersbøll, Annette Kjaer


    , TNF-alpha, or CRP. Furthermore, no significant differences, either regarding the need for treatment at the intensive care unit or of 30-day mortality, were found. CONCLUSION: The present study confirms previous findings and supports the hypothesis that, except for IL-8, the biochemical profile...... to a standardized algorithm. Blood samples were obtained immediately on admission and, again, at days 1, 2, and 14. RESULTS: A significant effect of the etiology on the levels of IL-8 in the alcohol group as compared to the gallstone group (P=0.003) was found. No etiologic differences were observed for IL-6, IL-18...

  14. Gallstone-Induced Perforation of the Common Bile Duct in Pregnancy

    Directory of Open Access Journals (Sweden)

    N. Dabbas


    Full Text Available Spontaneous perforation of the extrahepatic biliary system is a rare presentation of ductal stones. We report the case of a twenty-year-old woman presenting at term with biliary peritonitis caused by common bile duct (CBD perforation due to an impacted stone in the distal common bile duct. The patient had suffered a single herald episode of acute gallstone pancreatitis during the third trimester. The patient underwent an emergency laparotomy, bile duct exploration, and removal of the ductal stone. The postoperative course was uneventful.

  15. Top Five Lifestyle Changes to Reduce Cholesterol (United States)

    Top 5 lifestyle changes to improve your cholesterol Lifestyle changes can help reduce cholesterol, keep you off cholesterol-lowering medications or enhance the effect of your medications. Here are five lifestyle ...

  16. Understand Your Risk for High Cholesterol (United States)

    ... Aortic Aneurysm More Understand Your Risk for High Cholesterol Updated:Apr 1,2016 LDL (bad) cholesterol is ... content was last reviewed on 04/21/2014. Cholesterol Guidelines: Putting the pieces together Myth vs. Truth – ...

  17. How Is High Blood Cholesterol Treated? (United States)

    ... the NHLBI on Twitter. How Is High Blood Cholesterol Treated? High blood cholesterol is treated with lifestyle ... need to follow a heart healthy diet . Lowering Cholesterol Using Therapeutic Lifestyle Changes TLC is a set ...

  18. Cholesterol metabolism and colon cancer. (United States)

    Broitman, S A; Cerda, S; Wilkinson, J


    While epidemiologic and concordant experimental data indicate a direct relationship between dietary fat (and presumably caloric) intake and the development of colon cancer, the effect of dietary cholesterol on this disease is still not clear. However, there appears to be a developing literature concerning an inverse relationship between serum and plasma cholesterol levels, and the risk for colon cancer. Findings that low serum cholesterol levels are apparent as early as ten years prior to the detection of colon cancer implies that sub clinical disease is probably not involved initially in this process. The possibility of low serum cholesterol as a bio-marker was considered in epidemiologic studies which focused upon obese men with lower than normal serum cholesterol levels who were found to be at increased risk to colon cancer. While the relationship between low serum cholesterol and colonic or intestinal cholesterol metabolism is presently not understood, current genetic studies provide a promising though as yet unexplored potential association. Alterations which occur during the developmental progression of colonic cancer include changes in chromosome 5, which also carries two genes vital to the biosynthesis and regulation of systemic and cellular cholesterol metabolism, 3-hydroxy-3-methylglutaryl coenzyme A synthase, and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCoA R). Regulation of cholesterol metabolism in intestinal cells in vivo and in vitro varies from that seen in normal fibroblasts or hepatocytes in terms of exogenous sources of cholesterol and how these sources regulate internal synthesis. Colonic cancer cells have been used to assess small bowel enterocyte cholesterol metabolism, which has been possible because of their ability to differentiate in culture, however information regarding true colonic enterocyte cholesterol metabolism is relatively scarce. Colonic cancer cells have been shown to possess a diminished or nonexistent ability to use

  19. Free cholesterol induces higher β-sheet content in Aβ peptide oligomers by aromatic interaction with Phe19.

    Directory of Open Access Journals (Sweden)

    Xiaolin Zhou

    Full Text Available Accumulating experimental evidence support an enhancing effect of free cholesterol on amyloid-beta (Aβ aggregation. To probe the mechanisms of cholesterol-mediated Aβ aggregation, we applied all-atom molecular dynamic simulations on Aβ42 peptides in presence of free cholesterol. Several control systems were also designed to examine the specificity of cholesterol-residue interactions, including mutation on aromatic residue, substitution of cholesterol with sphingomyelin (SM and DPPC bilayer, and a mixing SM and cholesterol. Each system was performed 4 independent simulations, with a total time of 560 ns. It was found that cholesterol increased β-sheet formation by 4 folds, but the Phe19→Ser mutation on Aβ42 peptide totally eliminated cholesterol's effect. A stable contact was recognized between the steroid group of cholesterol and the Benzyl group of Phe19. Interestingly, our simulation revealed a regular 1 ns time interval between the establishment of cholesterol-phenylalanine contact and consequent β-sheet formation, suggesting an important role of steroid-benzyl interaction in cholesterol-mediated aggregation. The presence of SM slightly increased β-sheet formation, but the mixture of cholesterol and SM had a strong induction effect. Also, the measurement of Phe19-lipid distance indicates that aromatic side chains of peptides prone to bind to cholesterol on the surface of the mixed micelle. In the DPPC system, polar chains were attracted to the surface of membrane, yielding moderate increase of β-sheet formation. These results shed light on the mechanism of cholesterol-mediated fibrillogenesis, and help to differentiate the effects of cholesterol and other lipids on β-sheet formation process.

  20. Formats

    Directory of Open Access Journals (Sweden)

    Gehmann, Ulrich


    Full Text Available In the following, a new conceptual framework for investigating nowadays’ “technical” phenomena shall be introduced, that of formats. The thesis is that processes of formatting account for our recent conditions of life, and will do so in the very next future. It are processes whose foundations have been laid in modernity and which will further unfold for the time being. These processes are embedded in the format of the value chain, a circumstance making them resilient to change. In addition, they are resilient in themselves since forming interconnected systems of reciprocal causal circuits.Which leads to an overall situation that our entire “Lebenswelt” became formatted to an extent we don’t fully realize, even influencing our very percep-tion of it.

  1. Effect of surgical methods of cholecystectomy on immunity and stress reaction in patients with gallstones

    Institute of Scientific and Technical Information of China (English)

    Cheng-Gang Li


    Objective:To observe the effect of the selection of surgical methods of cholecystectomy on the immunity and stress reaction in patients with gallstones.Methods:A total of 150 patients with gallstones merged with cholecystitis who were admitted in our hospital from February, 2013 to May, 2015 for cholecystectomy were included in the study and divided into LC group and MC group with 75 cases in each group. The patients in LC group were performed with laparoscopic cholecystectomy, while the patients in MC group were performed with mini-incision cholecystectomy. The related indicators of immunological function and stress reaction in the two groups were compared.Results:The immunological functions 1d after operation in the two groups were reduced, and the reduced degree of CD3+ and CD4+ in MC group was more significant (P0.05).Conclusions:LC and MC have their own advantages and disadvantages. The two surgical methods have small effects on the immunological function, but MC has a great effect on the postoperative stress reaction; therefore, during the treatment process, the surgical method should be selected according to the patients practical physical conditions.

  2. Serum leptin levels and insulin resistance are associated with gallstone disease in overweight subjects

    Institute of Scientific and Technical Information of China (English)

    Nahum Méndez-Sánchez; Luisa B Bermejo-Martínez; Yolanda Vi(n)als; Norberto C Chavez-Tapia; Irina Vander Graff; Guadalupe Ponciano-Rodríguez; Martha H Ramos; Misael Uribe


    AIM: To establish an association between the serum leptin levels and the development of gallstone disease (GD).METHODS: We carried out a non-matched case-controlled study in a university hospital in Mexico City. Two hundred and eighty-seven subjects were included: 97 cases with gallstones and 190 controls. Body mass index (BMI), fasting plasma leptin, insulin, serum lipid, and lipoprotein levels were measured. Insulin resistance was calculated by homeostasis model assessment (HOMA-IR). Unconditional logistic regression analysis (univariate and multivariate)stratified by BMI was used to calculate the risk of GD.RESULTS: The multivariate conditional regression analysis revealed a model for those patients with BMI <30. The selected variables in the model were HOMA-IR index with OR = 1.31, P= 0.02 and leptin higher than median with OR = 2.11, P= 0.05. In the stratum of BMI ≥30, we did not find a useful model.CONCLUSION: We concluded that insulin resistance and the development of GD appears to be associated with serum leptin levels in subjects with overweight, but not in obese subjects with similar metabolic profiles.

  3. Hand-assisted laparoscopic surgery for complex gallstone disease: A report of five cases

    Institute of Scientific and Technical Information of China (English)

    Qi Wei; Lai-Gen Shen; He-Ming Zheng


    AIM: To describe the use of hand-assisted laparoscopic surg-ery (HALS) as an alternative to open conversion for complex gall-stone diseases, including Mirizzi syndrome (MS) and mimic MS.METHODS: Five patients with MS and mimic MS of 232 consecutive patients undergoing laparoscopic cholecystectomies were analyzed. HALS without a hand-port device was performed as an alternative to open conversion if the anatomy was still unclear after the neck of the gallbladder was reached.RESULTS: HALS was performed on three patients with MS type Ⅰ and 2 with mimic MS owing to an undear or abnormal anatomy, or an unusual circumstance in which an impacted stone was squeezed out from the infundibulum or the aberrant cystic duct impossible with laparoscopic approach. The median operative time was 165 min (range, 115-190 min). The median hand-assisted time was 75 min (range, 65-100 min). The median postoperative stay was 4 d (range, 3-5 d). The postoperative course was uneventful, except for 1 patient complicated with a minor incision infection. CONCLUSION: HALS for MS type Ⅰ and mimic MS is safe and feasible. It simplifies laparoscopic procedure, and can be used as an alternative to open conversion for complex gallstone diseases.

  4. Is There an Association between Type 1 Diabetes in Children and Gallbladder Stones Formation?


    Abdulrahman A. Al-Hussaini; Alenizi, Ahmed S; Alzahrani, Musa D; Sulaiman, Nimer M.; Mannan Khan


    Background and Aims: A number of studies in adults have evaluated the prevalence of gallstones in the diabetic population and showed a significant association with type 1 diabetes (T1D) and type 2 diabetes. The pediatric literature is limited to a single small case series. We conducted a cross-sectional study to evaluate for the presence of association between T1D in children and gallstones formation. Patients and Methods: Children diagnosed with T1D in a diabetic clinic have been examined fo...

  5. 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


    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...

  6. Cholesterol testing on a smartphone. (United States)

    Oncescu, Vlad; Mancuso, Matthew; Erickson, David


    Home self-diagnostic tools for blood cholesterol monitoring have been around for over a decade but their widespread adoption has been limited by the relatively high cost of acquiring a quantitative test-strip reader, complicated procedure for operating the device, and inability to easily store and process results. To address this we have developed a smartphone accessory and software application that allows for the quantification of cholesterol levels in blood. Through a series of human trials we demonstrate that the system can accurately quantify total cholesterol levels in blood within 60 s by imaging standard test strips. In addition, we demonstrate how our accessory is optimized to improve measurement sensitivity and reproducibility across different individual smartphones. With the widespread adoption of smartphones and increasingly sophisticated image processing technology, accessories such as the one presented here will allow cholesterol monitoring to become more accurate and widespread, greatly improving preventive care for cardiovascular disease.

  7. Americans' Cholesterol Levels Keep Falling (United States)

    ... and 2013-2014, the CDC reported. Dr. David Friedman is chief of heart failure services at Long ... for cholesterol treatment, all seem to be working," Friedman said. The study was published online Nov. 30 ...

  8. Cholesterol Worships a New Idol

    Institute of Scientific and Technical Information of China (English)

    Ira G. Schulman


    The growing worldwide epidemic of cardiovascular disease suggests that new therapeutic strategies are needed to complement statins in the lowering of cholesterol levels. In a recent paper in Science, Tontonoz and colleagues have identified Idol as a protein that can control cholesterol levels by regulating the stability of the low-density lipoprotein receptor; inhibiting the activity of Idol could provide novel approaches for the treatment of cardiovascular disease.

  9. Cholesterol-dependent hemolytic activity of Passiflora quadrangularis leaves

    Directory of Open Access Journals (Sweden)

    L.N. Yuldasheva


    Full Text Available Plants used in traditional medicine are rich sources of hemolysins and cytolysins, which are potential bactericidal and anticancer drugs. The present study demonstrates for the first time the presence of a hemolysin in the leaves of Passiflora quadrangularis L. This hemolysin is heat stable, resistant to trypsin treatment, has the capacity to froth, and acts very rapidly. The hemolysin activity is dose-dependent, with a slope greater than 1 in a double-logarithmic plot. Polyethylene glycols of high molecular weight were able to reduce the rate of hemolysis, while liposomes containing cholesterol completely inhibited it. In contrast, liposomes containing phosphatidylcholine were ineffective. The Passiflora hemolysin markedly increased the conductance of planar lipid bilayers containing cholesterol but was ineffective in cholesterol-free bilayers. Successive extraction of the crude hemolysin with n-hexane, chloroform, ethyl acetate, and n-butanol resulted in a 10-fold purification, with the hemolytic activity being recovered in the n-butanol fraction. The data suggest that membrane cholesterol is the primary target for this hemolysin and that several hemolysin molecules form a large transmembrane water pore. The properties of the Passiflora hemolysin, such as its frothing ability, positive color reaction with vanillin, selective extraction with n-butanol, HPLC profile, cholesterol-dependent membrane susceptibility, formation of a stable complex with cholesterol, and rapid erythrocyte lysis kinetics indicate that it is probably a saponin.

  10. Cholesterol and benign prostate disease. (United States)

    Freeman, Michael R; Solomon, Keith R


    The origins of benign prostatic diseases, such as benign prostatic hyperplasia (BPH) and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), are poorly understood. Patients suffering from benign prostatic symptoms report a substantially reduced quality of life, and the relationship between benign prostate conditions and prostate cancer is uncertain. Epidemiologic data for BPH and CP/CPPS are limited, however an apparent association between BPH symptoms and cardiovascular disease (CVD) has been consistently reported. The prostate synthesizes and stores large amounts of cholesterol and prostate tissues may be particularly sensitive to perturbations in cholesterol metabolism. Hypercholesterolemia, a major risk factor for CVD, is also a risk factor for BPH. Animal model and clinical trial findings suggest that agents that inhibit cholesterol absorption from the intestine, such as the class of compounds known as polyene macrolides, can reduce prostate gland size and improve lower urinary tract symptoms (LUTS). Observational studies indicate that cholesterol-lowering drugs reduce the risk of aggressive prostate cancer, while prostate cancer cell growth and survival pathways depend in part on cholesterol-sensitive biochemical mechanisms. Here we review the evidence that cholesterol metabolism plays a role in the incidence of benign prostate disease and we highlight possible therapeutic approaches based on this concept.

  11. Steroidal Triterpenes of Cholesterol Synthesis

    Directory of Open Access Journals (Sweden)

    Damjana Rozman


    Full Text Available Cholesterol synthesis is a ubiquitous and housekeeping metabolic pathway that leads to cholesterol, an essential structural component of mammalian cell membranes, required for proper membrane permeability and fluidity. The last part of the pathway involves steroidal triterpenes with cholestane ring structures. It starts by conversion of acyclic squalene into lanosterol, the first sterol intermediate of the pathway, followed by production of 20 structurally very similar steroidal triterpene molecules in over 11 complex enzyme reactions. Due to the structural similarities of sterol intermediates and the broad substrate specificity of the enzymes involved (especially sterol-Δ24-reductase; DHCR24 the exact sequence of the reactions between lanosterol and cholesterol remains undefined. This article reviews all hitherto known structures of post-squalene steroidal triterpenes of cholesterol synthesis, their biological roles and the enzymes responsible for their synthesis. Furthermore, it summarises kinetic parameters of enzymes (Vmax and Km and sterol intermediate concentrations from various tissues. Due to the complexity of the post-squalene cholesterol synthesis pathway, future studies will require a comprehensive meta-analysis of the pathway to elucidate the exact reaction sequence in different tissues, physiological or disease conditions. A major reason for the standstill of detailed late cholesterol synthesis research was the lack of several steroidal triterpene standards. We aid to this efforts by summarizing commercial and laboratory standards, referring also to chemical syntheses of meiosis-activating sterols.

  12. Niacin to Boost Your HDL "Good" Cholesterol (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 ...

  13. Amperometric determination of serum total cholesterol with nanoparticles of cholesterol esterase and cholesterol oxidase. (United States)

    Aggarwal, V; Malik, J; Prashant, A; Jaiwal, P K; Pundir, C S


    We describe the preparation of glutaraldehyde cross-linked and functionalized cholesterol esterase nanoparticles (ChENPs) and cholesterol oxidase nanoparticles (ChOxNPs) aggregates and their co-immobilization onto Au electrode for improved amperometric determination of serum total cholesterol. Transmission electron microscope (TEM) images of ChENPs and ChOxNPs showed their spherical shape and average size of 35.40 and 56.97 nm, respectively. Scanning electron microscope (SEM) studies of Au electrode confirmed the co-immobilization of enzyme nanoparticles (ENPs). The biosensor exhibited optimal response at pH 5.5 and 40°C within 5 s when polarized at +0.25 V versus Ag/AgCl. The working/linear range of the biosensor was 10-700 mg/dl for cholesterol. The sensor showed high sensitivity and measured total cholesterol as low as 0.1 mg/dl. The biosensor was evaluated and employed for total cholesterol determination in sera of apparently healthy and diseased persons. The analytical recovery of added cholesterol was 90%, whereas the within-batch and between-batch coefficients of variation (CVs) were less than 2% and less than 3%. There was a good correlation (r = 0.99) between serum cholesterol values as measured by the standard enzymic colorimetric method and the current method. The initial activity of ENPs/working electrode was reduced by 50% during its regular use (200 times) over a period of 60 days when stored dry at 4°C.

  14. Development of lycopene-loaded nanostructured lipid carriers: effect of rice oil and cholesterol. (United States)

    Riangjanapatee, P; Müller, R H; Keck, C M; Okonogi, S


    Nanostructured lipid carriers (NLC) were developed using a skin-compatible surfactant and natural lipid materials (rice oil, cholesterol) to incorporate lycopene. Characteristics of the NLC were explored in comparison with nanoemulsions and solid-lipid nanoparticles (SLN). Photon correlation spectroscopy, laser diffractometry (LD) and differential scanning calorimetry were used to determine particle size and thermal stability. Particle size expressed as LD (0.99) was 405 nm for the SLN, 350 nm for the NLC without cholesterol and 287 nm for the NLC with cholesterol. Rice oil and cholesterol enabled the formation of smaller particles, but cholesterol also reduced drug stability in the NLC. To preserve chemical stability of lycopene in the NLC, cholesterol should be avoided and storage should be at 4 degrees C or at room temperature.

  15. Cholesterol metabolism in cholestatic liver disease and liver transplantation:From molecular mechanisms to clinical implications

    Institute of Scientific and Technical Information of China (English)

    Katriina; Nemes; Fredrik; ?berg; Helena; Gylling; Helena; Isoniemi


    The aim of this review is to enlighten the critical roles that the liver plays in cholesterol metabolism. Liver transplantation can serve as gene therapy or a source of gene transmission in certain conditions that affect cholesterol metabolism, such as low-density-lipoprotein(LDL) receptor gene mutations that are associated with familial hypercholesterolemia. On the other hand, cholestatic liver disease often alters cholesterol metabolism. Cholestasis can lead to formation of lipoprotein X(Lp-X), which is frequently mistaken for LDL on routine clinical tests. In contrast to LDL, Lp-X is non-atherogenic, and failure to differentiate between the two can interfere with cardiovascular risk assessment, potentially leading to prescription of futile lipid-lowering therapy. Statins do not effectively lower Lp-X levels, and cholestasis may lead to accumulation of toxic levels of statins. Moreover, severe cholestasis results in poor micellar formation, which reduces cholesterol absorption, potentially impairing the cholesterol-lowering effect of ezetimibe. Apolipoprotein B-100 measurement can help distinguish between atherogenic and non-atherogenic hypercholesterolemia. Furthermore, routine serum cholesterol measurements alone cannot reflect cholesterol absorption and synthesis. Measurements of serum non-cholesterol sterol biomarkers- such as cholesterol precursor sterols, plant sterols, and cholestanol- may help with the comprehensive assessment of cholesterol metabolism. An adequate cholesterol supply is essential for liver-regenerative capacity. Low preoperative and perioperative serum cholesterol levels seem to predict mortality in liver cirrhosis and after liver transplantation. Thus, accurate lipid profile evaluation is highly important in liver disease and after liver transplantation.

  16. Fatty liver, carotid disease and gallstones: A study of age-related associations

    Institute of Scientific and Technical Information of China (English)

    Amedeo Lonardo; Paola Loria; Silvia Lombardini; Federica Scaglioni; Stefano Ballestri; Anna Maria Verrone; Marco Bertolotti; Lucia Carulli; Dorval Ganazzi; Nicola Carulli


    AIM: To evaluate carotid intima-media thickening (IMT)and plaques, gallstone disease (GD) and fatty liver (FL)as a function of age.METHODS: In 449 subjects, FL and carotid disease were assessed ultrasonographically. In a subgroup of 65/449 patients with non-alcoholic fatty liver disease (NAFLD), carotid disease, GD and associated factors were determined.RESULTS: FL of unspecified etiology was more common in younger and GD in older individuals. FL subjects had an increased prevalence of IMT and a decreased prevalence of plaques and manifested carotid disease earlier. Plaques were more common in subjects with GD.Age was an independent predictor of carotid disease outcome and FL was a protective factor for plaques. In NAFLD, there was an inverse correlation between body weight and age and the latter independently predicted carotid findings.CONCLUSION: Cardiovascular risk in patients with FL and NAFLD needs to be assessed as a function of age and body weight.

  17. An unforgettable concurrence: Successfully managed gallstone ileus accompanied by diabetic nephropathy

    Directory of Open Access Journals (Sweden)

    Rikki Singal


    Full Text Available Background : Gallstone ileus is an uncommon complication of gall stones associated with potentially serious morbidity and mortality. Case Report: We reported a 60-year-old male case who presented with renal failure and pain in right hypochondriac region. He also had a history of brain infarcts along with diabetes which is an additional factor for mortality. On Computed Tomography of the abdomen, he was diagnosed to have cholecystocholedochal fistula including air in the gall bladder and obstruction in the distal part of the ileum. Computed tomography plays an important role to make the proper diagnosis and in treatment. Conclusion s: As in our case, diagnosis was challengeable because of renal failure,diabetes, septicaemia and intestinal obstruction (peritonitis. We did surgery on the basis of peritonitis which remains the only choice in such cases. . In follow- up of 1 month patient was doing well and asymptomatic.

  18. Management and outcome of recurrent gallstone ileus:A systematic review

    Institute of Scientific and Technical Information of China (English)

    Shovkat; Ahmad; Mir; Zeiad; Hussain; Christine; Ann; Davey; Glenn; Vincent; Miller; Srinivas; Chintapatla


    AIM: To help the surgeon in decision making whentreating a patient with recurrent gallstone ileus(RGSI). METHODS: A systematic review related to RGSI was performed using the databases CINAHL, EMBASE, MEDLINE via Pub Med from May 1912 to April 2015. All languages were included and the grey literature was also searched. The abstracts were explored for relevance to the topic and full texts obtained as appropriate. A manual search was carried out by scrutinising the reference lists of all the full text articles and further articles were identified and obtained. Total of 903 articles were identified, 656 were excluded after abstract review, 247 full text articles were reviewed and 91 articles selected for final analysis. There were 113 cases of RGSI. RESULTS: There were 113 cases of RGSI reported in 91 articles. The majority of the recurrences, 62.6%, occurred within 6 wk of the index event. The male to female ratio was 1:7. The mean age was 69.6 years(SD 11.2) with a range of 38-95 years. The small bowel was the commonest site of impaction(92.2%). Treatment data was available for 104 patients. The two main operations performed were:(1) Enterolithotomy without repair of biliary fistula in 70.1% of all patients with a procedural mortality rate of 16.4%(12/73) and(2) a single stage surgery approach involving enterolithotomy with cholecystectomy and repair of the biliary enteric fistula in 16.3% with a procedural mortality of 11.7%(2/17). A subset analysis over last 25 years showed mortality from eneterolithotomy was 4.8% while single stage mortality was 22.2%. Enterolithotomy alone was the commonest operation performed for RGSI with four patients(5.4%) having a further recurrence of gallstone ileus. CONCLUSION: Enterolithotomy alone or followed by a delayed two-stage treatment approach is the preferred choice offering low mortality and reduced risk of recurrence.

  19. Cholesterol confusion and statin controversy

    Institute of Scientific and Technical Information of China (English)

    Robert; Du; Broff; Michel; de; Lorgeril


    The role of blood cholesterol levels in coronary heart disease(CHD) and the true effect of cholesterollowering statin drugs are debatable. In particular,whether statins actually decrease cardiac mortality and increase life expectancy is controversial. Concurrently,the Mediterranean diet model has been shown to prolong life and reduce the risk of diabetes,cancer,and CHD. We herein review current data related to both statins and the Mediterranean diet. We conclude that the expectation that CHD could be prevented or eliminated by simply reducing cholesterol appears unfounded. On the contrary,we should acknowledge the inconsistencies of the cholesterol theory and recognize the proven benefits of a healthy lifestyle incorporating a Mediterranean diet to prevent CHD.

  20. Remnant cholesterol and ischemic heart disease

    DEFF Research Database (Denmark)

    Varbo, Anette; Nordestgaard, Børge G


    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...

  1. The effects of cholesterol concentration in lipid packing and domain registration in ternary mixture lipid multilayer (United States)

    Ma, Yicong; Ghosh, Sajal; Connelly, Laura; Lal, Ratneshwar; Sinha, Sunil


    The effects of cholesterol in membrane rafts formation remain a mystery even until today. In our study of model membrane multilayer systems consisting of DPPC/DOPC/Cholesterol, we have characterized the morphology changes using AFM and optical microscopy, and the bilayer electron density profile using X-ray reflectivity, as a function of cholesterol concentration. In this presentation, we shall discuss how the cholesterol concentration affects the lipid packing within the bilayer, as well as the interlayer coupling of phase separated domains. X-ray scattering, AFM and optical microscopy which look at different length scales would constitute a complete picture. Our results may shed new light on the understanding of the role of cholesterol in raft formation in biological membranes. This work is supported by a grant from the Biomolecular Materials Program, Division of Materials Science and Engineering, Basic Energy Sciences, US Department of Energy under Award no. DE-FG02-04ER46173.

  2. Polarizable multipolar electrostatics for cholesterol (United States)

    Fletcher, Timothy L.; Popelier, Paul L. A.


    FFLUX is a novel force field under development for biomolecular modelling, and is based on topological atoms and the machine learning method kriging. Successful kriging models have been obtained for realistic electrostatics of amino acids, small peptides, and some carbohydrates but here, for the first time, we construct kriging models for a sizeable ligand of great importance, which is cholesterol. Cholesterol's mean total (internal) electrostatic energy prediction error amounts to 3.9 kJ mol-1, which pleasingly falls below the threshold of 1 kcal mol-1 often cited for accurate biomolecular modelling. We present a detailed analysis of the error distributions.

  3. Regulation of biliary cholesterol secretion and reverse cholesterol transport

    NARCIS (Netherlands)

    Dikkers, Arne


    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 tra

  4. Cholesterol absorption and excretion in ileostomy subjects on high- and low-dietary-cholesterol intakes. (United States)

    Ellegård, L; Bosaeus, I


    Six healthy ileostomy subjects were given [3H]cholesterol and [14C]beta-sitosterol in a single meal together with two controlled diets containing 150 or 450 mg cholesterol/d. Each diet was eaten for 3 d. Cholesterol absorption and excretion of cholesterol, bile acids, fat, energy, and nitrogen were analyzed. Fractional cholesterol absorption increased from 44 +/- 2.6% (mean +/- SE) to 61 +/- 3.4% (P effluent, or excretion of energy, nitrogen, fat, and bile acids did not differ between periods. Endogenous cholesterol excretion remained unchanged whereas net cholesterol excretion (output minus intake) was 37% higher (P < 0.05) on low compared with high cholesterol intake.

  5. [Determination of trace elements in Mongolian medicine Susi-12 curing cholecystitis and gallstone disease by ICP-AES]. (United States)

    E, Er-Deng-sang; Hang, Gai-ba-te-re; Ba, Tu; Duan, Yi-wen


    Trace elements in Mongolian medicine Susi-12 for cholecystitis and gallstones were analyzed in order to discuss the relation between Susi-12's drug action and the trace elements. The analysis was carried out using the pressure seal microwave digestion and inductive coupled plasma atomic emission spectrometry (ICP-AES). It was found that the medicine contained great amount of trace elements, especially human-body-needed trace elements, such as Ca, Al, Mg, Fe, Sr, Mn, Zn, Cu etc., whereas heavy metals are very little, e.g. the contents of Pb, Cb, As etc are below the country's limit. The recoveries of standard addition are in the range of 94.63%-106.40%. The relative standard deviation RSDSusi-12 can effectively control and cure cholecystitis and gallstones, and the effective rate reaches 91.2% to 100%. So the trace elements in Susi-12 must have a close connection with the drug action.

  6. The ABC of cholesterol transport

    NARCIS (Netherlands)

    Plösch, Torsten


    Cholesterol fulfills an indispensable role in mammalian physiology. It is an important constituent of all cell membranes. Furthermore, it is the precursor of steroid hormones, which regulate a variety of physiological functions, and of bile salts, which are necessary for the generation of bile flow

  7. 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.


    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.

  8. [A case of gallstone ileus which the cholecystoduodenal fistula closed spontaneously after laparoscopic-assisted simple enterolithotomy]. (United States)

    Okubo, Hitoshi; Nogawa, Tatsuhiko; Jibiki, Masaaki


    A 47-year-old woman complaining of diarrhea and vomiting was admitted on the suspicion of gallstone ileus 4 days after onset. Upper gastrointestinal radiography by Gastrografin showed a cholecystoduodenal fistula. Laparoscopic-assisted simple enterolithotomy was performed. The omentum was severely adherent to the gall bladder and fistula, though biliary surgery was not performed. Without second look operation, for cholecystoduodenal fistula closed spontaneously.

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


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


    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...

  10. A prospective cohort study on the association between coffee drinking and risk of non-gallstone-related acute pancreatitis. (United States)

    Oskarsson, Viktor; Sadr-Azodi, Omid; Orsini, Nicola; Wolk, Alicja


    Only one previous study has examined the association between coffee consumption and risk of acute pancreatitis, and it found a reduced risk for alcohol-related episodes among high consumers of coffee. Therefore, we examined (1) the association between coffee consumption and risk of non-gallstone-related acute pancreatitis and (2) whether this association was modified by alcohol intake. Data were obtained from two prospective cohorts, the Cohort of Swedish Men and the Swedish Mammography Cohort, including 76 731 men and women (born 1914-1952). Coffee consumption was assessed at baseline with a FFQ, and the cohorts were followed up between 1998 and 2012 via linkage to national health registries. Hazard ratios were estimated using Cox models, with adjustment for potential confounding factors. During 1 035 881 person-years of total follow-up, 383 cases (246 in men and 137 in women) of incident non-gallstone-related acute pancreatitis were identified. Overall, and irrespective of whether a categorical or a continuous exposure model was used, we observed no association between coffee consumption and risk of non-gallstone-related acute pancreatitis (e.g. the multivariable-adjusted hazard ratio for each 1 cup/d increase in coffee consumption was 0·97; 95 % CI 0·92, 1·03). There was no evidence of effect modification by alcohol intake (P interaction=0·77). In conclusion, coffee consumption was not associated with risk of non-gallstone-related acute pancreatitis in this large prospective cohort study. Because of the limited number of epidemiological studies and their conflicting results, further research is needed to elucidate this potential association.

  11. Characterization of Lassa virus glycoprotein oligomerization and influence of cholesterol on virus replication. (United States)

    Schlie, Katrin; Maisa, Anna; Lennartz, Frank; Ströher, Ute; Garten, Wolfgang; Strecker, Thomas


    Mature glycoprotein spikes are inserted in the Lassa virus envelope and consist of the distal subunit GP-1, the transmembrane-spanning subunit GP-2, and the signal peptide, which originate from the precursor glycoprotein pre-GP-C by proteolytic processing. In this study, we analyzed the oligomeric structure of the viral surface glycoprotein. Chemical cross-linking studies of mature glycoprotein spikes from purified virus revealed the formation of trimers. Interestingly, sucrose density gradient analysis of cellularly expressed glycoprotein showed that in contrast to trimeric mature glycoprotein complexes, the noncleaved glycoprotein forms monomers and oligomers spanning a wide size range, indicating that maturation cleavage of GP by the cellular subtilase SKI-1/S1P is critical for formation of the correct oligomeric state. To shed light on a potential relation between cholesterol and GP trimer stability, we performed cholesterol depletion experiments. Although depletion of cholesterol had no effect on trimerization of the glycoprotein spike complex, our studies revealed that the cholesterol content of the viral envelope is important for the infectivity of Lassa virus. Analyses of the distribution of viral proteins in cholesterol-rich detergent-resistant membrane areas showed that Lassa virus buds from membrane areas other than those responsible for impaired infectivity due to cholesterol depletion of lipid rafts. Thus, derivation of the viral envelope from cholesterol-rich membrane areas is not a prerequisite for the impact of cholesterol on virus infectivity.

  12. What You Need to Know about Cholesterol (United States)

    ... 164304.html What You Need to Know About Cholesterol Heart expert explains the difference between good and ... 28, 2017 MONDAY, March 27, 2017 (HealthDay News) -- Cholesterol plays a vital role in your health, so ...

  13. Do You Know Your Cholesterol Levels? (United States)

    ... The Health Information Center Do You Know Your Cholesterol Levels? Print-friendly Version (PDF, 6.1 MB) ... Eat Smart Did you know that high blood cholesterol is a serious problem among Latinos? About one ...

  14. High Cholesterol: Medicines to Help You (United States)

    ... Consumers Consumer Information by Audience For Women High Cholesterol--Medicines To Help You Share Tweet Linkedin Pin ... side effects for each drug, check Drugs@FDA . Cholesterol Absorption Inhibitors Brand Name Generic Name Zetia Ezetimibe ...

  15. Active membrane cholesterol as a physiological effector. (United States)

    Lange, Yvonne; Steck, Theodore L


    Sterols associate preferentially with plasma membrane sphingolipids and saturated phospholipids to form stoichiometric complexes. Cholesterol in molar excess of the capacity of these polar bilayer lipids has a high accessibility and fugacity; we call this fraction active cholesterol. This review first considers how active cholesterol serves as an upstream regulator of cellular sterol homeostasis. The mechanism appears to utilize the redistribution of active cholesterol down its diffusional gradient to the endoplasmic reticulum and mitochondria, where it binds multiple effectors and directs their feedback activity. We have also reviewed a broad literature in search of a role for active cholesterol (as opposed to bulk cholesterol or lipid domains such as rafts) in the activity of diverse membrane proteins. Several systems provide such evidence, implicating, in particular, caveolin-1, various kinds of ABC-type cholesterol transporters, solute transporters, receptors and ion channels. We suggest that this larger role for active cholesterol warrants close attention and can be tested easily.

  16. Cholesterol, bile acid and triglyceride metabolism intertwined

    NARCIS (Netherlands)

    Schonewille, Marleen


    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 mechani

  17. 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)


    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

  18. Conversion of Exogenous Cholesterol into Glycoalkaloids in Potato Shoots, Using Two Methods for Sterol Solubilisation (United States)

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


    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

  19. Conversion of exogenous cholesterol into glycoalkaloids in potato shoots, using two methods for sterol solubilisation.

    Directory of Open Access Journals (Sweden)

    Erik V Petersson

    Full Text Available 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.

  20. Cholesterol metabolism and homeostasis in the brain


    Zhang, Juan; Qiang LIU


    Cholesterol is an essential component for neuronal physiology not only during development stage but also in the adult life. Cholesterol metabolism in brain is independent from that in peripheral tissues due to blood-brain barrier. The content of cholesterol in brain must be accurately maintained in order to keep brain function well. Defects in brain cholesterol metabolism has been shown to be implicated in neurodegenerative diseases, such as Alzheimer’s disease (AD), Huntington’s disease (HD)...

  1. Quercetin regulates hepatic cholesterol metabolism by promoting cholesterol-to-bile acid conversion and cholesterol efflux in rats. (United States)

    Zhang, Min; Xie, Zongkai; Gao, Weina; Pu, Lingling; Wei, Jingyu; Guo, Changjiang


    Quercetin, a common member of the flavonoid family, is widely present in plant kingdom. Despite that quercetin is implicated in regulating cholesterol metabolism, the molecular mechanism is poorly understood. We hypothesized that quercetin regulates cholesterol homeostasis through regulating the key enzymes involved in hepatic cholesterol metabolism. To test this hypothesis, we compared the profile of key enzymes and transcription factors involved in the hepatic cholesterol metabolism in rats with or without quercetin supplementation. Twenty male Wistar rats were randomly divided into control and quercetin-supplemented groups. Serum total cholesterol, triglyceride, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and total bile acids in feces and bile were measured. Hepatic enzymatic activities were determined by activity assay kit and high-performance liquid chromatography-based analyses. The messenger RNA (mRNA) and protein expressions were determined by reverse transcriptase polymerase chain reaction and Western blot analyses, respectively. The results showed that the activity of hepatic cholesterol 7α-hydroxylase, a critical enzyme in the conversion of cholesterol to bile acids, was significantly elevated by quercetin. The expression of cholesterol 7α-hydroxylase, as well as liver X receptor α, an important transcription factor, was also increased at both mRNA and protein levels by quercetin. However, quercetin exposure had no impact on the activity of hepatic HMG-CoA reductase, a rate-limiting enzyme in the biosynthesis of cholesterol. We also found that quercetin treatment significantly increased ATP binding cassette transporter G1 mRNA and protein expression in the liver, suggesting that quercetin may increase hepatic cholesterol efflux. Collectively, the results presented here indicate that quercetin regulates hepatic cholesterol metabolism mainly through the pathways that promote cholesterol-to-bile acid conversion and

  2. Mechanism of Resistance to Dietary Cholesterol

    Directory of Open Access Journals (Sweden)

    Lindsey R. Boone


    Full Text Available Background. Alterations in expression of hepatic genes that could contribute to resistance to dietary cholesterol were investigated in Sprague-Dawley rats, which are known to be resistant to the serum cholesterol raising action of dietary cholesterol. Methods. Microarray analysis was used to provide a comprehensive analysis of changes in hepatic gene expression in rats in response to dietary cholesterol. Changes were confirmed by RT-PCR analysis. Western blotting was employed to measure changes in hepatic cholesterol 7α hydroxylase protein. Results. Of the 28,000 genes examined using the Affymetrix rat microarray, relatively few were significantly altered. As expected, decreases were observed for several genes that encode enzymes of the cholesterol biosynthetic pathway. The largest decreases were seen for squalene epoxidase and lanosterol 14α demethylase (CYP 51A1. These changes were confirmed by quantitative RT-PCR. LDL receptor expression was not altered by dietary cholesterol. Critically, the expression of cholesterol 7α hydroxylase, which catalyzes the rate-limiting step in bile acid synthesis, was increased over 4-fold in livers of rats fed diets containing 1% cholesterol. In contrast, mice, which are not resistant to dietary cholesterol, exhibited lower hepatic cholesterol 7α hydroxylase (CYP7A1 protein levels, which were not increased in response to diets containing 2% cholesterol.

  3. Isolation of Cholesterol from an Egg Yolk (United States)

    Taber, Douglass F.; Li, Rui; Anson, Cory M.


    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…

  4. Intestinal cholesterol secretion : future clinical implications

    NARCIS (Netherlands)

    Jakulj, L.; Besseling, J.; Stroes, E. S. G.; Groen, A. K.


    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

  5. Public health aspects of serum cholesterol

    NARCIS (Netherlands)

    S. Houterman (Saskia)


    textabstractIn the beginning of this century Anitschkow and De Langen started pioneering work concerning the relation between cholesterol and coronary heart disease. Both showed that there was a possible relation between cholesterol in the diet, blood cholesterol levels and atherosclerosis. It took

  6. Cholesterol Screening: A Practical Guide to Implementation. (United States)

    Kingery, Paul M.


    Dry-chemistry cholesterol analysis has made screening feasible in a variety of settings. The article provides practical tips for the implementation of mass cholesterol screening using a portable dry-chemistry analyzer and discusses issues involved in conducting effective cholesterol screening programs from start to finish. (SM)

  7. A matrix of cholesterol crystals, but not cholesterol alone, primes human monocytes/macrophages for excessive endotoxin-induced production of tumor necrosis factor-alpha. Role in atherosclerotic inflammation?

    DEFF Research Database (Denmark)

    Bendtzen, Klaus; Christensen, Ole; Nielsen, Claus Henrik


    When exposed to small amounts of bacterial endotoxin, matrices of cholesterol crystals, but not cholesterol itself, primed human monocytes/macrophages to a highly augmented (>10-fold) production of inflammatory tumor necrosis factor-α. Priming also sensitized the cells, as 10- to 100-fold lower...... suggest that cholesterol matrix formation may play a pathogenic role in atherosclerotic inflammation, and they indicate a mechanism by which bacteria and/or bacterial products may play a role in processes leading to arteriosclerosis....

  8. Non-cholesterol sterols and cholesterol metabolism in sitosterolemia. (United States)

    Othman, Rgia A; Myrie, Semone B; Jones, Peter J H


    Sitosterolemia (STSL) is a rare autosomal recessive disease, manifested by extremely elevated plant sterols (PS) in plasma and tissue, leading to xanthoma and premature atherosclerotic disease. Therapeutic approaches include limiting PS intake, interrupting enterohepatic circulation of bile acid using bile acid binding resins such as cholestyramine, and/or ileal bypass, and inhibiting intestinal sterol absorption by ezetimibe (EZE). The objective of this review is to evaluate sterol metabolism in STSL and the impact of the currently available treatments on sterol trafficking in this disease. The role of PS in initiation of xanthomas and premature atherosclerosis is also discussed. Blocking sterols absorption with EZE has revolutionized STSL patient treatment as it reduces circulating levels of non-cholesterol sterols in STSL. However, none of the available treatments including EZE have normalized plasma PS concentrations. Future studies are needed to: (i) explore where cholesterol and non-cholesterol sterols accumulate, (ii) assess to what extent these sterols in tissues can be mobilized after blocking their absorption, and (iii) define the factors governing sterol flux.

  9. Distinct metabolic and vascular effects of dietary triglycerides and cholesterol in atherosclerotic and diabetic mouse models. (United States)

    Laplante, Marc-André; Charbonneau, Alexandre; Avramoglu, Rita Kohen; Pelletier, Patricia; Fang, Xiangping; Bachelard, Hélène; Ylä-Herttuala, Seppo; Laakso, Markku; Després, Jean-Pierre; Deshaies, Yves; Sweeney, Gary; Mathieu, Patrick; Marette, André


    Cholesterol and triglyceride-rich Western diets are typically associated with an increased occurrence of type 2 diabetes and vascular diseases. This study aimed to assess the relative impact of dietary cholesterol and triglycerides on glucose tolerance, insulin sensitivity, atherosclerotic plaque formation, and endothelial function. C57BL6 wild-type (C57) mice were compared with atherosclerotic LDLr(-/-) ApoB(100/100) (LRKOB100) and atherosclerotic/diabetic IGF-II × LDLr(-/-) ApoB(100/100) (LRKOB100/IGF) mice. Each group was fed either a standard chow diet, a 0.2% cholesterol diet, a high-fat diet (HFD), or a high-fat 0.2% cholesterol diet for 6 mo. The triglyceride-rich HFD increased body weight, glucose intolerance, and insulin resistance but did not alter endothelial function or atherosclerotic plaque formation. Dietary cholesterol, however, increased plaque formation in LRKOB100 and LRKOB100/IGF animals and decreased endothelial function regardless of genotype. However, cholesterol was not associated with an increase of insulin resistance in LRKOB100 and LRKOB100/IGF mice and, unexpectedly, was even found to reduce the insulin-resistant effect of dietary triglycerides in these animals. Our data indicate that dietary triglycerides and cholesterol have distinct metabolic and vascular effects in obese atherogenic mouse models resulting in dissociation between the impairment of glucose homeostasis and the development of atherosclerosis.

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

    KAUST Repository

    Mandal, Pritam


    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.

  11. D38-cholesterol as a Raman active probe for imaging intracellular cholesterol storage (United States)

    Alfonso-García, Alba; Pfisterer, Simon G.; Riezman, Howard; Ikonen, Elina; Potma, Eric O.


    We generated a highly deuterated cholesterol analog (D38-cholesterol) and demonstrated its use for selective vibrational imaging of cholesterol storage in mammalian cells. D38-cholesterol produces detectable signals in stimulated Raman scattering (SRS) imaging, is rapidly taken up by cells, and is efficiently metabolized by acyl-CoA cholesterol acyltransferase to form cholesteryl esters. Using hyperspectral SRS imaging of D38-cholesterol, we visualized cholesterol storage in lipid droplets. We found that some lipid droplets accumulated preferentially unesterified D38-cholesterol, whereas others stored D38-cholesteryl esters. In steroidogenic cells, D38-cholesteryl esters and triacylglycerols were partitioned into distinct sets of lipid droplets. Thus, hyperspectral SRS imaging of D38-cholesterol demonstrates a heterogeneous incorporation of neutral lipid species, i.e., free cholesterol, cholesteryl esters, and triacylglycerols, between individual lipid droplets in a cell.

  12. Dietary cholesterol and plasma lipoprotein profiles: Randomized controlled trials (United States)

    Early work suggested that dietary cholesterol increased plasma total cholesterol concentrations in humans. Given the relationship between elevated plasma cholesterol concentrations and cardiovascular disease risk, dietary guidelines have consistently recommended limiting food sources of cholesterol....

  13. Intestinal Farnesoid X Receptor Controls Transintestinal Cholesterol Excretion in Mice

    NARCIS (Netherlands)

    de Boer, Jan Freark; Schonewille, Marleen; Boesjes, Marije; Wolters, Henk; Bloks, Vincent W; Bos, Trijnie; van Dijk, Theo H; Jurdzinski, Angelika; Boverhof, Renze; Wolters, Justina C; Kuivenhoven, Jan A; van Deursen, Jan M; Oude Elferink, Ronald P J; Moschetta, Antonio; Kremoser, Claus; Verkade, Henkjan J; Kuipers, Folkert; Groen, Albert K


    BACKGROUND & AIMS: The role of the intestine in the maintenance of cholesterol homeostasis is increasingly recognized. Fecal excretion of cholesterol is the last step in the atheroprotective reverse cholesterol transport pathway, to which biliary and transintestinal cholesterol excretion (TICE) cont

  14. Hepatic expression of detoxification enzymes is decreased in human obstructive cholestasis due to gallstone biliary obstruction.

    Directory of Open Access Journals (Sweden)

    Jin Chai

    Full Text Available Levels of bile acid metabolic enzymes and membrane transporters have been reported to change in cholestasis. These alterations (e.g. CYP7A1 repression and MRP4 induction are thought to be adaptive responses that attenuate cholestatic liver injury. However, the molecular mechanisms of these adaptive responses in human obstructive cholestasis due to gallstone biliary obstruction remain unclear.We collected liver samples from cholestatic patients with biliary obstruction due to gallstones and from control patients without liver disease (n = 22 per group. The expression levels of bile acid synthetic and detoxification enzymes, membrane transporters, and the related nuclear receptors and transcriptional factors were measured.The levels of bile acid synthetic enzymes, CYP7B1 and CYP8B1, and the detoxification enzyme CYP2B6 were increased in cholestatic livers by 2.4-fold, 2.8-fold, and 1.9-fold, respectively (p<0.05. Conversely, the expression levels of liver detoxification enzymes, UGT2B4/7, SULT2A1, GSTA1-4, and GSTM1-4, were reduced by approximately 50% (p<0.05 in human obstructive cholestasis. The levels of membrane transporters, OSTβ and OCT1, were increased 10.4-fold and 1.8-fold, respectively, (p<0.05, whereas those of OSTα, ABCG2 and ABCG8 were all decreased by approximately 40%, (p<0.05 in human cholestatic livers. Hepatic nuclear receptors, VDR, HNF4α, RXRα and RARα, were induced (approximately 2.0-fold, (p<0.05 whereas FXR levels were markedly reduced to 44% of control, (p<0.05 in human obstructive cholestasis. There was a significantly positive correlation between the reduction in FXR mRNA and UGT2B4/7, SULT2A1, GSTA1, ABCG2/8 mRNA levels in livers of obstructive cholestatic patients (p<0.05.The levels of hepatic detoxification enzymes were significantly decreased in human obstructive cholestasis, and these decreases were positively associated with a marked reduction of FXR levels. These findings are consistent with impaired

  15. Epididymis cholesterol homeostasis and sperm fertilizing ability

    Institute of Scientific and Technical Information of China (English)

    Fabrice Saez; Aurélia Ouvrier; Jo(e)l R Drevet


    Cholesterol, being the starting point of steroid hormone synthesis, is a long known modulator of both female and male reproductive physiology especially at the level of the gonads and the impact cholesterol has on gametogenesis. Less is known about the effects cholesterol homeostasis may have on postgonadic reproductive functions. Lately, several data have been reported showing how imbalanced cholesterol levels may particularly affect the post-testicular events of sperm maturation that lead to fully fertile male gametes. This review will focus on that aspect and essentially centers on how cholesterol is important for the physiology of the mammalian epididymis and spermatozoa.

  16. Analysis of Cholesterol Trafficking with Fluorescent Probes

    DEFF Research Database (Denmark)

    Maxfield, Frederick R.; Wustner, Daniel


    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....

  17. Peptide mediators of cholesterol efflux (United States)

    Bielicki, John K.; Johansson, Jan


    The present invention provides a family of non-naturally occurring polypeptides having cholesterol efflux activity that parallels that of full-length apolipoproteins (e.g., Apo AI and Apo E), and having high selectivity for ABAC1 that parallels that of full-length apolipoproteins. The invention also provides compositions comprising such polypeptides, methods of identifying, screening and synthesizing such polypeptides, and methods of treating, preventing or diagnosing diseases and disorders associated with dyslipidemia, hypercholesterolemia and inflammation.

  18. Evaluating computational models of cholesterol metabolism. (United States)

    Paalvast, Yared; Kuivenhoven, Jan Albert; Groen, Albert K


    Regulation of cholesterol homeostasis has been studied extensively during the last decades. Many of the metabolic pathways involved have been discovered. Yet important gaps in our knowledge remain. For example, knowledge on intracellular cholesterol traffic and its relation to the regulation of cholesterol synthesis and plasma cholesterol levels is incomplete. One way of addressing the remaining questions is by making use of computational models. Here, we critically evaluate existing computational models of cholesterol metabolism making use of ordinary differential equations and addressed whether they used assumptions and make predictions in line with current knowledge on cholesterol homeostasis. Having studied the results described by the authors, we have also tested their models. This was done primarily by testing the effect of statin treatment in each model. Ten out of eleven models tested have made assumptions in line with current knowledge of cholesterol metabolism. Three out of the ten remaining models made correct predictions, i.e. predicting a decrease in plasma total and LDL cholesterol or increased uptake of LDL upon treatment upon the use of statins. In conclusion, few models on cholesterol metabolism are able to pass a functional test. Apparently most models have not undergone the critical iterative systems biology cycle of validation. We expect modeling of cholesterol metabolism to go through many more model topologies and iterative cycles and welcome the increased understanding of cholesterol metabolism these are likely to bring.

  19. Intracellular transport of cholesterol in mammalian cells

    Energy Technology Data Exchange (ETDEWEB)

    Brasaemle, D.L.


    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 ({sup 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.

  20. Cholesterol metabolism and homeostasis in the brain. (United States)

    Zhang, Juan; Liu, Qiang


    Cholesterol is an essential component for neuronal physiology not only during development stage but also in the adult life. Cholesterol metabolism in brain is independent from that in peripheral tissues due to blood-brain barrier. The content of cholesterol in brain must be accurately maintained in order to keep brain function well. Defects in brain cholesterol metabolism has been shown to be implicated in neurodegenerative diseases, such as Alzheimer's disease (AD), Huntington's disease (HD), Parkinson's disease (PD), and some cognitive deficits typical of the old age. The brain contains large amount of cholesterol, but the cholesterol metabolism and its complex homeostasis regulation are currently poorly understood. This review will seek to integrate current knowledge about the brain cholesterol metabolism with molecular mechanisms.

  1. Concentration-Dependent Diversifcation Effects of Free Cholesterol Loading on Macrophage Viability and Polarization

    Directory of Open Access Journals (Sweden)

    Xiaoyang Xu


    Full Text Available Background/Aims: The accumulation of free cholesterol in atherosclerotic lesions has been well documented in both animals and humans. In studying the relevance of free cholesterol buildup in atherosclerosis, contradictory results have been generated, indicating that free cholesterol produces both pro- and anti-atherosclerosis effects in macrophages. This inconsistency might stem from the examination of only select concentrations of free cholesterol. In the present study, we sought to investigate the implication of excess free cholesterol loading in the pathophysiology of atherosclerosis across a broad concentration range from (in µg/ml 0 to 60. Methods: Macrophage viability was determined by measuring formazan formation and flow cytometry viable cell counting. The polarization of M1 and M2 macrophages was differentiated by FACS (Fluorescence-Activated Cell Sorting assay. The secretion of IL-1β in macrophage culture medium was measured by ELISA kit. Macrophage apoptosis was detected by flow cytometry using a TUNEL kit. Results: Macrophage viability was increased at the treatment of lower concentrations of free cholesterol from (in µg/ml 0 to 20, but gradually decreased at higher concentrations from 20 to 60. Lower free cholesterol loading induced anti-inflammatory M2 macrophage polarization. The activation of the PPARγ (Peroxisome Proliferator-Activated Receptor gamma nuclear factor underscored the stimulation of this M2 phenotype. Nevertheless, higher levels of free cholesterol resulted in pro-inflammatory M1 activation. Moreover, with the application of higher free cholesterol concentrations, macrophage apoptosis and secretion of the inflammatory cytokine IL-1β increased significantly. Conclusion: These results for the first time demonstrate that free cholesterol could render concentration-dependent diversification effects on macrophage viability, polarization, apoptosis and inflammatory cytokine secretions, thereby reconciling the pros

  2. Expression profile of cholecystokinin type-A receptor in gallbladder cancer and gallstone disease

    Institute of Scientific and Technical Information of China (English)

    Rajani Rai; Mallika Tewari; Mohan Kumar; Tej Bali Singh; Hari S Shukla


    BACKGROUND: Regulatorypeptidereceptorshaveattractedthe interest of oncologists as a new promising approach for cancer pathology, imaging and therapy. Although cholecystokinin (CCK) is a potent modulator of gallbladder contractility and plays a potential role in pancreatic carcinogenesis through CCK type-A receptor (CCKAR), its role in gallbladder cancer (GBC) is still unknown and immunohistochemical detection of CCKAR in the gallbladder has not yet been reported. This novel case-control study aimed to investigate the expression profile of CCKAR in GBC and gallstone disease (GSD). METHODS: This study included 162 samples of gallbladder: 94 fromGBCand68fromGSD.ExpressionofCCKARwasanalyzed by immunohistochemistry and immunoblotting. The results were statistically correlated with disease history including age, sex, presenceofgallstone,stageanddifferentiation. RESULTS: CCKAR was positive in 30/68 (44.1%) of GSD and 72/94 (76.6%) of GBC samples. Fifty-one of the 72 (70.8%) CCKAR-positive GBC samples showed over-expression. Interestingly, consistent results also appeared in the immuno-blotting study. CONCLUSIONS: CCKARexpressionwassignificantlyincreased in GBC compared to GSD. Moreover, CCKAR expression was associated with the degree of tumor differentiation, i.e., less expression in poorly-differentiated tumors. Thus, it has future prognostic and therapeutic implications in the management of GBC.

  3. Computed tomographic differentiation between alcoholic and gallstone pancreatitis: Significance of distribution of infiltration or fluid collection

    Institute of Scientific and Technical Information of China (English)

    Young-Sun Kim; Yongsoo Kim; Sung-Kyu Kim; Hyunchul Rhim


    AIM: To evaluate the usefulness of various computed tomography (CT) findings including distribution of infiltration or fluid collection in differentiating the major etiologies of acute pancreatitis.METHODS: We reviewed 75 relatively severe cases of acute pancreatitis of alcoholic (n=43) or biliary stone(n=32) etiology having infiltration or fluid collection on CT. We compared the pancreatic size, CT grading,presence or absence of biliary calculi, and dilatation of pancreatic or bile duct. We also evaluated degree and the distribution of infiltration and fluid collection in each group.RESULTS: The sizes of pancreas were not different between alcohol group and stone group. Alcohol group showed higher CT grading than stone group (P<0.05). Presence of biliary stone and duct dilatation was statistically significant in differentiating etiology (P <0.05). Alcohol group showed significantly prominent peripancreatic pathology than stone group only in left peritoneal compartment (P = 0.020).CONCLUSION: Alcoholic pancreatitis tends to form more prominent peripancreatic changes than gallstone pancreatitis in relatively severe cases. This is evident on the anterior aspect of left abdomen. Although clinical history and some CT findings usually are a major determinant of the etiology, this pattern of peripancreatic pathology may have an ancillary role in determining the etiologies of acute pancreatitis in the equivocal cases.

  4. MicroRNA: a connecting road between apoptosis and cholesterol metabolism. (United States)

    Adlakha, Yogita K; Saini, Neeru


    Resistance to apoptosis leads to tumorigenesis and failure of anti-cancer therapy. Recent studies also highlight abrogated lipid/cholesterol metabolism as one of the root causes of cancer that can lead to metastatic transformations. Cancer cells are dependent on tremendous supply of cellular cholesterol for the formation of new membranes and continuation of cell signaling. Cholesterol homeostasis network tightly regulates this metabolic need of cancer cells on cholesterol and other lipids. Genetic landscape is also shared between apoptosis and cholesterol metabolism. MicroRNAs (miRNAs) are the new fine tuners of signaling pathways and cellular processes and are known for their ability to post-transcriptionally repress gene expression in a targeted manner. This review summarizes the current knowledge about the cross talk between apoptosis and cholesterol metabolism via miRNAs. In addition, we also emphasize herein recent therapeutic modulations of specific miRNAs and their promising potential for the treatment of deadly diseases including cancer and cholesterol related pathologies. Understanding of the impact of miRNA-based regulation of apoptosis and metabolic processes is still at its dawn and needs further research for the development of future miRNA-based therapies. As both these physiological processes affect cellular homeostasis, we believe that this comprehensive summary of miRNAs modulating both apoptosis and cholesterol metabolism will open uncharted territory for scientific exploration and will provide the foundation for discovering novel drug targets for cancer and metabolic diseases.

  5. Inhibition of Cholesterol Esterification Influences Cytokine Exspression in Lypopolisaccharide-activated P388D1 Macrophages

    Directory of Open Access Journals (Sweden)

    Rosa Rita Bonatesta


    Full Text Available Several in vivo and in vitro studies have demonstrated the involvement of infectious agents in the development of atherosclerosis. However, the mechanisms by which micro-organisms induce and/or aggravate atherosclerosis, are so far unclear. Accumulation of cholesterol esters and lipid laden cell formation are hallmark of the atherogenesis, however, the possible relationship between cholesterol esterification and the signal-transducing component of LPS recognition complex inducing cytokine secretion has not been yet investigated. In the present study, we investigated the effect of mevinolin, the ACAT inhibitor, Sandoz 58035, and plasma from statin-treated hypercholesterolemic patients on cholesterol metabolism and cytokine expression in LPS activated P388D1 macrophages. In P388D1 macrophages cholesterol synthesis and uptake, as well as cholesterol ester synthesis, were unchanged following LPS-activation. When cells were grown in presence of serum from patients under statin therapy, cholesterol esterification was lower compared to cells grown with plasma from healthy subjects, independently from the type of statin used. This effect was accompanied by inhibition of IL-1β expression in LPS activated cells. The ACAT inhibitor, Sandoz 58035, which completely blocked cholesterol esterification in normal and LPS-activated macrophages, prevented IL-1β and IL-6 over-expression in LPS activated cells. Although preliminary, these data point to a possible relationship between cholesterol esterification and cytokine production in macrophages, prospecting new possible mechanisms by which microbial or inflammatory agents may induce and/or accelerate the atherosclerotic process.

  6. Intermittent gastric outlet obstruction due to a gallstone migrated through a cholecysto-gastric fistula: A new variant of "Bouveret's syndrome"

    Institute of Scientific and Technical Information of China (English)

    Dimitry Arioli; Mario De Santis; Fabrizio Di Benedetto; Giorgio Enrico Gerunda; Maria Luisa Zeneroli; Ivo Venturini; Michele Masetti; Elisa Romagnoli; Antonella Scarcelli; Pietro Ballesini; Athos Borghi; Alessandro Barberini; Vincenzo Spina


    Bouveret's syndrome, defined as gastric outlet obstruction due to a large gallstone, is still one of the most dramatic biliary gallstone complications. Although new radiological and endoscopic techniques have made pre-surgical diagnosis possible in most cases and the death rate has dropped dramatically, "one-stage surgery" (biliary surgery carried out at the same time as the removal of the gut obstruction) should be still considered as the gold standard for the treatment of gallstone ileus. In this case, partial gastric outlet obstruction resulted in an atypical and insidious clinical presentation that allowed us to perform the conventional one-stage laparatomic procedure that completely solved the problem, thus avoiding any further complications.

  7. 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 BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: Our study showed strong association of D19H polymorphism with gallstone

  8. Imbalanced cholesterol metabolism in Alzheimer's disease. (United States)

    Xue-shan, Zhao; Juan, Peng; Qi, Wu; Zhong, Ren; Li-hong, Pan; Zhi-han, Tang; Zhi-sheng, Jiang; Gui-xue, Wang; Lu-shan, Liu


    Alzheimer's disease (AD) is a complex and multifactorial neurodegenerative disease that is mainly caused by β-amyloid accumulation. A large number of studies have shown that elevated cholesterol levels may perform a function in AD pathology, and several cholesterol-related gene polymorphisms are associated with this disease. Although numerous studies have shown the important function of cholesterol in AD pathogenesis and development, the underlying mechanism remains unclear. To further elucidate cholesterol metabolism disorder and AD, we first, review metabolism and regulation of the cholesterol in the brain. Second, we summarize the literature stating that hypercholesterolemia is one of the risk factors of AD. Third, we discuss the main mechanisms of abnormal cholesterol metabolism that increase the risk of AD. Finally, the relationships between AD and apolipoprotein E, PCSK9, and LRP1 are discussed in this article.

  9. Mucin gene expression in bile of patients with and without gallstone disease, collected by endoscopic retrograde cholangiography

    Institute of Scientific and Technical Information of China (English)

    Alexander Vilkin; Alex Geller; Zohar Levi; Yaron Niv


    AIM: To investigate the pattern of mucin expression and concentration in bile obtained during endoscopic retrograde cholangiography (ERC) in relation to gallstone disease.METHODS: Bile samples obtained at ERC from 29 consecutive patients, 17 with and 12 without gallstone disease were evaluated for mucin content by gel filtration on a Sepharose CL-4B column. Dot blot analysis for bile mucin apoproteins was performed with antibodies to Mucin 1 (MUC1), MUC2, MUC3, MUC5AC, MUC5B and MUC6. Staining intensity score (0-3) was used as a measure of antigen expression. RESULTS: MUC1, MUC2, MUC3, MUC5AC, MUC5B and MUC6 were demonstrated in 34.4%, 34.4%, 51.7%, 51.7%, 55.1% and 27.5% of bile samples, respectively. The staining intensity scores were 0.62 ± 0.94, 0.58 ± 0.90, 0.79 ± 0.97, 1.06 ± 1.22, 1.20 ± 1.26 and 0.41 ± 0.73, respectively. Mean mucin concentration measured in bile by the Sepharose CL-4B method was 22.8 ± 24.0 mg/mL (range 3.4-89.0 mg/mL). Mean protein concentration was 8.1 ± 4.8 mg/mL (range 1.7-23.2 mg/mL).CONCLUSION: High levels of MUC3, MUC5AC and MUC5B are expressed in bile aspirated during ERC examination. A specific pattern of mucin gene expression or change in mucin concentration was not found in gallstone disease.

  10. Two cases of cystic artery pseudoaneurysm rupture due to acute cholecystitis with gallstone impaction in the neck. (United States)

    Kaida, Shogo; Arahata, Kyouko; Itou, Asako; Takarabe, Sakiko; Kimura, Kayoko; Kishikawa, Hiroshi; Nishida, Jiro; Fujiyama, Yoshiki; Takigawa, Yutaka; Matsui, Junichi


    A cystic artery aneurysm is a rare cause of hemobilia. Herein, we report two cases of acute cholecystitis with a ruptured cystic artery pseudoaneurysm. Two patients (a 69-year-old man and an 83-year-old man) were admitted to our hospital because of acute cholecystitis with gallstone impaction in the neck. Percutaneous transhepatic gallbladder drainage (PTGBD) was performed for both patients. After a few days of PTGBD, gallbladder hemorrhage was observed. Abdominal angiography showed cystic artery aneurysm. A transcatheter arterial embolization was therefore performed, followed by an open cholecystectomy.

  11. 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.

  12. Raising HDL cholesterol in women

    Directory of Open Access Journals (Sweden)

    Danny J Eapen


    Full Text Available Danny J Eapen1, Girish L Kalra1, Luay Rifai1, Christina A Eapen2, Nadya Merchant1, Bobby V Khan11Emory University School of Medicine, Atlanta, GA, USA; 2University of South Florida School of Medicine, Tampa, FL, USAAbstract: High-density lipoprotein cholesterol (HDL-C concentration is essential in the determination of coronary heart disease (CHD risk in women. This is especially true in the postmenopausal state, where lipid profiles and CHD risk mimic that of age-matched men. Thus, interventions designed to reduce CHD risk by raising HDL-C levels may have particular significance during the transition to menopause. This review discusses HDL-C-raising therapies and the role of HDL in the primary prevention of CHD in women. Lifestyle-based interventions such as dietary change, aerobic exercise regimens, and smoking cessation are initial steps that are effective in raising HDL-C, and available data suggest women respond similarly to men with these interventions. When combined with pharmacotherapy, the effects of these lifestyle alterations are further amplified. Though studies demonstrating gender-specific differences in therapy are limited, niacin continues to be the most effective agent in raising HDL-C levels, especially when used in combination with fibrate or statin therapy. Emerging treatments such as HDL mimetic therapy show much promise in further raising HDL-C levels and improving cardiovascular outcomes.Keywords: high-density lipoprotein, HDL, women, cholesterol, heart disease

  13. Cholesterol oxidation products and their biological importance

    DEFF Research Database (Denmark)

    Kulig, Waldemar; Cwiklik, Lukasz; Jurkiewicz, Piotr


    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...

  14. Structure of Cholesterol in Lipid Rafts (United States)

    Toppozini, Laura; Meinhardt, Sebastian; Armstrong, Clare L.; Yamani, Zahra; Kučerka, Norbert; Schmid, Friederike; Rheinstädter, Maikel C.


    Rafts, or functional domains, are transient nano-or mesoscopic structures in the plasma membrane and are thought to be essential for many cellular processes such as signal transduction, adhesion, trafficking, and lipid or protein sorting. Observations of these membrane heterogeneities have proven challenging, as they are thought to be both small and short lived. With a combination of coarse-grained molecular dynamics simulations and neutron diffraction using deuterium labeled cholesterol molecules, we observe raftlike structures and determine the ordering of the cholesterol molecules in binary cholesterol-containing lipid membranes. From coarse-grained computer simulations, heterogenous membranes structures were observed and characterized as small, ordered domains. Neutron diffraction was used to study the lateral structure of the cholesterol molecules. We find pairs of strongly bound cholesterol molecules in the liquid-disordered phase, in accordance with the umbrella model. Bragg peaks corresponding to ordering of the cholesterol molecules in the raftlike structures were observed and indexed by two different structures: a monoclinic structure of ordered cholesterol pairs of alternating direction in equilibrium with cholesterol plaques, i.e., triclinic cholesterol bilayers.

  15. Curcumin retunes cholesterol transport homeostasis and inflammation response in M1 macrophage to prevent atherosclerosis. (United States)

    Chen, Fang-Yuan; Zhou, Juan; Guo, Ning; Ma, Wang-Ge; Huang, Xin; Wang, Huan; Yuan, Zu-Yi


    Lipoprotein cholesterol metabolism dysfunction in the arterial wall is a major contributor to atherosclerosis, and excessive lipid intake and failed cholesterol homeostasis may accelerate the atherogenic process. Curcumin exerts multiple effects by alleviating inflammation, hyperlipidemia, and atherosclerosis; however, its role in cholesterol transport homeostasis and its underlying impact on inflammatory M1 macrophages are poorly understood. This work aimed to investigate the effect of curcumin on cholesterol transport, the inflammatory response and cell apoptosis in M1 macrophages. RAW264.7 macrophages (M0) were induced with LPS plus IFN-γ for 12 h to develop a M1 subtype and were then incubated with curcumin at different concentrations (6.25 and 12.5 μmol/L) in the presence or absence of oxLDL. Then, cholesterol influx/efflux and foam cell formation as well as inflammation and apoptosis were evaluated. It was found that curcumin increased cholesterol uptake measured by the Dil-oxLDL binding assay, and simultaneously increased cholesterol efflux carried out by Apo-A1 and HDL in M1 cells. Curcumin further reinforced ox-LDL-induced cholesterol esterification and foam cell formation as determined by Oil Red O and BODIPY staining. Moreover, curcumin dramatically reduced ox-LDL-induced cytokine production such as IL-1β, IL-6 as well as TNF-α and M1 cell apoptosis. We also found that curcumin upregulated CD36 and ABCA1 in M1 macrophages. Curcumin increased PPARγ expression, which in turn promoted CD36 and ABCA1 expression. In conclusion, curcumin may increase the ability of M1 macrophages to handle harmful lipids, thus promoting lipid processing, disposal and removal, which may support cholesterol homeostasis and exert an anti-atherosclerotic effect.

  16. Solubilization of oils or addition of monoglycerides drives the formation of wormlike micelles with an elliptical cross-section in cholesterol-based surfactants: a study by rheology, SANS, and cryo-TEM. (United States)

    Afifi, Hala; Karlsson, Göran; Heenan, Richard K; Dreiss, Cécile A


    We report the formation of wormlike micelles (WLM) in poly(oxyethylene) cholesteryl ether (ChEO(10)) aqueous solutions by the addition of lipophilic monoglycerides at room temperature (monolaurin (ML), monocaprin (MC), and monocaprylin (MCL)) bearing 12-, 10-, and 8-carbon alkyl chains, respectively. A combination of rheology, small-angle neutron scattering (SANS), and cryo-TEM was used to study their viscoelastic properties and structure. With the successive addition of cosurfactant, a significant increase in viscosity and a clear solidlike behavior is obtained, suggesting the formation of a viscoelastic network of wormlike micelles. Only for MCL is typical Maxwellian behavior obtained. The onset of micellar growth, as detected by the occurrence of solidlike behavior and a significant increase in viscosity, is obtained for 0.30 (1 wt%), 0.34 (1 wt%), and 0.60 (1.5 wt%) cosurfactant/ChEO(10) molar ratios with ML, MC, and MCL, respectively. With ML and MC, extremely long relaxation times (exceeding 20 s) compared to those of MCL are obtained, and zero-shear viscosity values are more than 1 order of magnitude higher than with MCL. These results show that cosurfactants with longer alkyl chain lengths (ML and MC) induce the formation of longer wormlike micelles and do so at lower concentrations. SANS measurements on dilute solutions confirm that the viscoelastic behavior correlates with an increase in contour length and reveals an elliptical cross-section with an axial ratio of around 2. Cryo-TEM images provide visual evidence of the wormlike micelles and confirm the elliptical shape of the cross-section. The addition of small amounts of aliphatic oils (ethyl butyrate, EB, and ethyl caprylate, EC) and cyclic oils (peppermint, PP, and tea tree, TT, oils) to ChEO(10) solutions induces wormlike micelle formation at a lower cosurfactant concentration or even in its absence (for PP, TT, and EC) because of their probable localization in the palisade layer. The viscosity peak

  17. Cholesterol selectively regulates IL-5 induced mitogen activated protein kinase signaling in human eosinophils.

    Directory of Open Access Journals (Sweden)

    Mandy E Burnham

    Full Text Available Eosinophils function contributes to human allergic and autoimmune diseases, many of which currently lack curative treatment. Development of more effective treatments for eosinophil-related diseases requires expanded understanding of eosinophil signaling and biology. Cell signaling requires integration of extracellular signals with intracellular responses, and is organized in part by cholesterol rich membrane microdomains (CRMMs, commonly referred to as lipid rafts. Formation of these organizational membrane domains is in turn dependent upon the amount of available cholesterol, which can fluctuate widely with a variety of disease states. We tested the hypothesis that manipulating membrane cholesterol content in primary human peripheral blood eosinophils (PBEos would selectively alter signaling pathways that depend upon membrane-anchored signaling proteins localized within CRMMs (e.g., mitogen activated protein kinase [MAPK] pathway, while not affecting pathways that signal through soluble proteins, like the Janus Kinase/Signal Transducer and Activator of Transcription [JAK/STAT] pathway. Cholesterol levels were increased or decreased utilizing cholesterol-chelating methyl-β-cyclodextrin (MβCD, which can either extract membrane cholesterol or add exogenous membrane cholesterol depending on whether MβCD is preloaded with cholesterol. Human PBEos were pretreated with MβCD (cholesterol removal or MβCD+Cholesterol (MβCD+Chol; cholesterol delivery; subsequent IL-5-stimulated signaling and physiological endpoints were assessed. MβCD reduced membrane cholesterol in PBEos, and attenuated an IL-5-stimulated p38 and extracellular-regulated kinase 1/2 phosphorylation (p-p38, p-ERK1/2, and an IL-5-dependent increase in interleukin-1β (IL-1β mRNA levels. In contrast, MβCD+Chol treatment elevated PBEos membrane cholesterol levels and basal p-p38, but did not alter IL-5-stimulated phosphorylation of ERK1/2, STAT5, or STAT3. Furthermore, M

  18. Potential of BODIPY-cholesterol for analysis of cholesterol transport and diffusion in living cells

    DEFF Research Database (Denmark)

    Wüstner, Daniel; Lund, Frederik Wendelboe; Röhrl, Clemens


    Cholesterol is an abundant and important lipid component of cellular membranes. Analysis of cholesterol transport and diffusion in living cells is hampered by the technical challenge of designing suitable cholesterol probes which can be detected for example by optical microscopy. One strategy...... is to use intrinsically fluorescent sterols, as dehydroergosterol (DHE), having minimal chemical alteration compared to cholesterol but giving low fluorescence signals in the UV region of the spectrum. Alternatively, one can use dye-tagged cholesterol analogs and in particular BODIPY-cholesterol (BChol......), whose synthesis and initial characterization was pioneered by Robert Bittman. Here, we give a general overview of the properties and applications but also limitations of BODIPY-tagged cholesterol probes for analyzing intracellular cholesterol trafficking. We describe our own experiences...

  19. Black pepper and piperine reduce cholesterol uptake and enhance translocation of cholesterol transporter proteins. (United States)

    Duangjai, Acharaporn; Ingkaninan, Kornkanok; Praputbut, Sakonwun; Limpeanchob, Nanteetip


    Black pepper (Piper nigrum L.) lowers blood lipids in vivo and inhibits cholesterol uptake in vitro, and piperine may mediate these effects. To test this, the present study aimed to compare actions of black pepper extract and piperine on (1) cholesterol uptake and efflux in Caco-2 cells, (2) the membrane/cytosol distribution of cholesterol transport proteins in these cells, and (3) the physicochemical properties of cholesterol micelles. Piperine or black pepper extract (containing the same amount of piperine) dose-dependently reduced cholesterol uptake into Caco-2 cells in a similar manner. Both preparations reduced the membrane levels of NPC1L1 and SR-BI proteins but not their overall cellular expression. Micellar cholesterol solubility of lipid micelles was unaffected except by 1 mg/mL concentration of black pepper extract. These data suggest that piperine is the active compound in black pepper and reduces cholesterol uptake by internalizing the cholesterol transporter proteins.

  20. [Is there a relationship between cholesterol reduction, low levels of cholesterol and mortality?]. (United States)

    LaRosa, J C


    Cholesterol lowering in both primary and secondary prevention has been clearly demonstrated to lower coronary morbidity and, in secondary prevention, to lower coronary mortality as well. Putative dangers of cholesterol lowering remain unproven. Population studies linking low cholesterol to noncoronary mortalities do not demonstrate cause-and-effect relations. In fact, based on current studies, the opposite is more likely to be the case. Neither gender nor age should automatically exclude persons from cholesterol screening. Drug intervention, however, should be used conservatively, particularly in young adults and the elderly. Drugs should be used only after diet and lifestyle interventions have failed. The evidence linking high blood cholesterol to coronary atherosclerosis and cholesterol lowering to its prevention is broad-based and definitive. Concerns about cholesterol lowering and spontaneously low cholesterols should be pursued but should not interfere with the implementation of current public policies to reduce the still heavy burden of atherosclerosis in Western society.

  1. The prevalence and risk factors for gallstone disease in taiwanese vegetarians.

    Directory of Open Access Journals (Sweden)

    Yen-Chun Chen

    Full Text Available Gallstone disease (GSD and its complications are major public health issues globally. Although many community-based studies had addressed the risk factors for GSD, little is known about GSD prevalence and risk factors among Taiwanese vegetarians.This study included 1721 vegetarians who completed a questionnaire detailing their demographics, medical history, and life-styles. GSD was ascertained by ultrasonography or surgical history of cholecystectomy for GSD. The predictive probability of GSD for male and female vegetarians was estimated from the fitted model.The prevalence of GSD was 8.2% for both male and female vegetarians. The risk of GSD is similar in men and women across all age groups, and increases steadily with increasing age. For male vegetarians, age (OR: 1.04; 95% CI: 1.00-1.08 and serum total bilirubin level (OR: 2.35; 95% CI: 1.31-4.22 predict risk for GSD. For female vegetarians, age (OR: 1.03; 95% CI: 1.01-1.05, BMI (OR: 1.07; 95% CI: 1.01-1.13, and alcohol consumption (OR: 7.85; 95% CI: 1.83-33.73 are associated with GSD. GSD is not associated with type of vegetarian diet, duration of vegetarianism, low education level, physical inactivity, diabetes, coronary artery disease, cerebral vascular accident, chronic renal failure, hepatitis C virus infection, and lipid abnormalities. GSD is also not associated with age at menarche, postmenopausal status, and multiparity in female vegetarians.Risk factors useful for predicting GSD in vegetarians are (1 age and total bilirubin level in men, and (2 age, BMI, and alcohol consumption in women. Many previously identified risk factors for general population does not seem to apply to Taiwanese vegetarians.

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

    NARCIS (Netherlands)

    Vrins, Carlos L. J.


    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

  3. 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

  4. 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


    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

  5. 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 Albert; Tietge, Uwe J.F.; Brufau Dones, 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

  6. Ileus caused by cholesterol crystal embolization: A case report. (United States)

    Azuma, Shunjiro; Ikenouchi, Maiko; Akamatsu, Takuji; Seta, Takeshi; Urai, Shunji; Uenoyama, Yoshito; Yamashita, Yukitaka


    Cholesterol crystal embolization (CCE) is a rare systemic embolism caused by formation of cholesterol crystals from atherosclerotic plaques. CCE usually occurs during vascular manipulation, such as vascular surgery or endovascular catheter manipulation, or due to anticoagulation or thrombolytic therapy. We report a rare case of intestinal obstruction caused by spontaneous CCE. An 81-year-old man with a history of hypertension was admitted for complaints of abdominal pain, bloating, and anorexia persisting for 4 mo. An abdominal computed tomography revealed intestinal ileus. His symptoms were immediately relieved by an ileus tube insertion, and he was discharged 6 d later. However, these symptoms immediately reappeared and persisted, and partial resection of the small intestine was performed. A histopathological examination indicated that small intestine obstruction was caused by CCE. At the 12-mo follow-up, the patient showed no evidence of CCE recurrence. Thus, in cases of intestinal obstruction, CCE should also be considered.

  7. Cholesterol orientation and tilt modulus in DMPC bilayers


    Khelashvili, George; Pabst, Georg; Harries, Daniel


    We performed molecular dynamics (MD) simulations of hydrated bilayers containing mixtures of dimyristoylphosphatidylcholine (DMPC) and Cholesterol at various ratios, to study the effect of cholesterol concentration on its orientation, and to characterize the link between cholesterol tilt and overall phospholipid membrane organization. The simulations show a substantial probability for cholesterol molecules to transiently orient perpendicular to the bilayer normal, and suggest that cholesterol...

  8. The macrophage and its related cholesterol efflux as a HDL function index in atherosclerosis. (United States)

    Yamamoto, Suguru; Narita, Ichiei; Kotani, Kazuhiko


    The macrophage and its related cholesterol efflux are considered to be a key player in atherosclerotic formation in relation to the function of high-density lipoprotein (HDL). The HDL function can be evaluated by the reaction between lipid-loaded macrophages and lipid-acceptors in the HDL fraction from the plasma, apolipoprotein B-depleted serum, and/or whole serum/plasma. Recent studies have reported that an impaired cholesterol efflux of HDL is observed in patients with cardiometabolic diseases, such as dyslipidemia, diabetes mellitus, and chronic kidney disease. A population-based cohort study has reported an inverse association between the cholesterol efflux capacity of HDL and the incidence of atherosclerotic disease, regardless of the serum HDL-cholesterol level. Moreover, in this paper, when we summarized several clinical interventional studies of statin treatment that examined cholesterol efflux, a potential increase in the efflux in patients treated with statins was implied. However, the effect was not fully defined in the current situation because of the small sample sizes, lack of a unified protocol for measuring the efflux, and short-term intervention periods without cardiovascular outcomes in available studies. Further investigation is necessary to determine the effect of drugs on cholesterol efflux. With additional advanced studies, cholesterol efflux is a promising laboratory index to understand the HDL function.

  9. Cholesterol, the central lipid of mammalian cells

    NARCIS (Netherlands)

    Maxfield, F. R.; van Meer, G.


    Despite its importance for mammalian cell biology and human health, there are many basic aspects of cholesterol homeostasis that are not well understood. Even for the well-characterized delivery of cholesterol to cells via lipoproteins, a novel regulatory mechanism has been discovered recently, invo

  10. Evaluating computational models of cholesterol metabolism

    NARCIS (Netherlands)

    Paalvast, Yared; Kuivenhoven, Jan Albert; Groen, Albert K.


    Regulation of cholesterol homeostasis has been studied extensively during the last decades. Many of the metabolic pathways involved have been discovered. Yet important gaps in our knowledge remain. For example, knowledge on intracellular cholesterol traffic and its relation to the regulation of chol

  11. Prosopis farcta beans increase HDL cholesterol and decrease LDL cholesterol in ostriches (Struthio camelus). (United States)

    Omidi, Arash; Ansari nik, Hossein; Ghazaghi, Mahmood


    Ten blue-neck male ostriches (Struthio camelus) were fed Prosopis farcta beans throughout a 30-day experiment. Blood samples were collected from ostriches on days 0 and 30 to measure levels of high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, triglyceride, total serum protein, albumin, globulin, cholesterol, calcium, inorganic phosphorus, the activity of aspartate aminotransferase, alanine aminotransferase, and γ-glutamyl transferase (γ-GT). From days 0 to 30, HDL cholesterol, total protein, and globulins levels increased significantly whereas LDL cholesterol, inorganic phosphorus, and γ-GT activity decreased significantly.

  12. Trapping crystal nucleation of cholesterol monohydrate

    DEFF Research Database (Denmark)

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


    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...... in a monoclinic cholesterol . H2O phase, has been monitored and their structures characterized to near atomic resolution. Crystallographic evidence is presented that this multilayer phase is similar to that of a reported metastable cholesterol phase of undetermined structure obtained from bile before...... transformation to the triclinic phase of cholesterol . H2O, the thermodynamically stable macroscopic form. According to grazing incidence x-ray diffraction measurements and crystallographic data, a transformation from the monoclinic film structure to a multilayer of the stable monohydrate phase involves...

  13. The Structure of Cholesterol in Lipid Rafts

    CERN Document Server

    Toppozini, Laura; Armstrong, Clare L; Yamani, Zahra; Kucerka, Norbert; Schmid, Friederike; Rheinstaedter, Maikel C


    Rafts, or functional domains, are transient nano- or mesoscopic structures in the plasma membrane and are thought to be essential for many cellular processes such as signal transduction, adhesion, trafficking and lipid/protein sorting. Observations of these membrane heterogeneities have proven challenging, as they are thought to be both small and short-lived. With a combination of coarse-grained molecular dynamics simulations and neutron diffraction using deuterium labeled cholesterol molecules we observe raft-like structures and determine the ordering of the cholesterol molecules in binary cholesterol-containing lipid membranes. From coarse-grained computer simulations, heterogenous membranes structures were observed and characterized as small, ordered domains. Neutron diffraction was used to study the lateral structure of the cholesterol molecules. We find pairs of strongly bound cholesterol molecules in the liquid-disordered phase, in accordance with the umbrella model. Bragg peaks corresponding to orderin...

  14. Cholesterol in myelin biogenesis and hypomyelinating disorders. (United States)

    Saher, Gesine; Stumpf, Sina Kristin


    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.

  15. Biliary lipid, bile acid composition, and dietary correlations in Micmac Indian women. A population study. (United States)

    Williams, C N; Johnston, J L; McCarthy, S; Field, C A


    The precursor state for cholesterol gallstone formation is cholesterol-saturated bile. We studied a high-risk group for cholesterol gallstones to determine whether dietary variables affect bile cholesterol. Bile samples were analyzed from 46 Micmac Indian women without gallstones and 13 with gallstones for molar percentage cholesterol (MPC) and bile acid composition. The data were analyzed by multiple regression analysis with MPC as the dependent variable and the dietary variables, obtained from four consecutive-day food records, and biliary bile acid composition as the independent variables. In the 46 women without gallstones, obesity, calorie range/calorie intake, and iron and calcium intake were, in their order of importance, significant factors. In normal weight subjects (ponderal index > 12.5) relative obesity was still a significant correlate. Obesity and iron intake were positive correlates while calorie range/calorie intake and calcium intake varied inversely. When the effect of obesity was controlled, these factors were still significant in this group, as they were in the gallstone group. In addition, the duration of overnight fast obtained by history, together with the proportions of deoxycholic and chenodeoxycholic acids in bile were correlates of the biliary molar percentage cholesterol.

  16. Cholesterol modulates the interaction of the islet amyloid polypeptide with membranes. (United States)

    Caillon, Lucie; Duma, Luminita; Lequin, Olivier; Khemtemourian, Lucie


    The deposition of insoluble amyloid fibrils resulting from the aggregation of the human islet amyloid polypeptide (hIAPP) within the islet of Langerhans is a pathological feature of type 2 diabetes mellitus (T2DM). Increasing evidence indicates that biological membranes play a key role in amyloid aggregation, modulating among others the kinetics of amyloid formation, and being the target of toxic species generated during amyloid formation. In T2DM patients, elevated levels of cholesterol, an important determinant of the physical state of biological membranes, are observed in β-cells and are thought to directly impair β-cell function and insulin secretion. However, it is not known whether cholesterol enhances membrane-interaction or membrane-insertion of hIAPP. In this study, we investigated the effect of cholesterol incorporated in zwitterionic and anionic membranes. Our circular dichroism and liquid state NMR data reveal that 10-30% of cholesterol slightly affects the aggregational and conformational behaviour of hIAPP. Additional fluorescence results indicate that 10 and 20% of cholesterol slightly slow down the kinetics of oligomer and fibril formation while anionic lipids accelerate this kinetics. This behavior might be caused by differences in membrane insertion and therefore in membrane binding of hIAPP. The membrane binding affinity was evaluated using (1)H NMR experiments and our results show that the affinity of hIAPP for membranes containing cholesterol is significantly smaller than that for membranes containing anionic lipids. Furthermore, we found that hIAPP-induced membrane damage is synchronized to fibril formation in the absence and in the presence of cholesterol.

  17. Lysosomal acid lipase: At the crossroads of normal and atherogenic cholesterol metabolism

    Directory of Open Access Journals (Sweden)

    Joshua A Dubland


    Full Text Available Unregulated cellular uptake of apolipoprotein B-containing lipoproteins in the arterial intima leads to the formation of foam cells in atherosclerosis. Lysosomal acid lipase (LAL plays a crucial role in both lipoprotein lipid catabolism and excess lipid accumulation as it is the primary enzyme that hydrolyzes cholesteryl esters derived from both low density lipoprotein (LDL and modified forms of LDL. Evidence suggests that as atherosclerosis progresses, accumulation of excess free cholesterol in lysosomes leads to impairment of LAL activity, resulting in accumulation of cholesteryl esters in the lysosome as well as the cytosol in foam cells. Impaired metabolism and release of cholesterol from lysosomes can lead to downstream defects in ATP-binding cassette transporter A1 regulation, needed to offload excess cholesterol from plaque foam cells. This review focuses on the role LAL plays in normal cholesterol metabolism and how the associated changes in its enzymatic activity may ultimately contribute to atherosclerosis progression.

  18. Major Risk Factors for Heart Disease: High Blood Cholesterol (United States)

    ... Major Risk Factors for Heart Disease High Blood Cholesterol High blood cholesterol is another major risk factor for heart disease ... can do something about. The higher your blood cholesterol level, the greater your risk for developing heart ...

  19. High Blood Cholesterol: What You Need to Know (United States)

    ... Audiences Contact The Health Information Center High Blood Cholesterol: What You Need To Know Table of Contents ... Lifestyle Changes (TLC) Drug Treatment Resources Why Is Cholesterol Important? Your blood cholesterol level has a lot ...

  20. Cholesterol: Top Five Foods to Lower Your Numbers (United States)

    Cholesterol: Top foods to improve your numbers Diet can play an important role in lowering your cholesterol. Here are the top foods to lower your cholesterol and protect your heart. By Mayo Clinic Staff ...

  1. 9-cis β-Carotene Increased Cholesterol Efflux to HDL in Macrophages

    Directory of Open Access Journals (Sweden)

    Sapir Bechor


    Full Text Available Cholesterol efflux from macrophages is a key process in reverse cholesterol transport and, therefore, might inhibit atherogenesis. 9-cis-β-carotene (9-cis-βc is a precursor for 9-cis-retinoic-acid (9-cis-RA, which regulates macrophage cholesterol efflux. Our objective was to assess whether 9-cis-βc increases macrophage cholesterol efflux and induces the expression of cholesterol transporters. Enrichment of a mouse diet with βc from the alga Dunaliella led to βc accumulation in peritoneal macrophages. 9-cis-βc increased the mRNA levels of CYP26B1, an enzyme that regulates RA cellular levels, indicating the formation of RA from βc in RAW264.7 macrophages. Furthermore, 9-cis-βc, as well as all-trans-βc, significantly increased cholesterol efflux to high-density lipoprotein (HDL by 50% in RAW264.7 macrophages. Likewise, food fortification with 9-cis-βc augmented cholesterol efflux from macrophages ex vivo. 9-cis-βc increased both the mRNA and protein levels of ABCA1 and apolipoprotein E (APOE and the mRNA level of ABCG1. Our study shows, for the first time, that 9-cis-βc from the diet accumulates in peritoneal macrophages and increases cholesterol efflux to HDL. These effects might be ascribed to transcriptional induction of ABCA1, ABCG1, and APOE. These results highlight the beneficial effect of βc in inhibition of atherosclerosis by improving cholesterol efflux from macrophages.

  2. 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.


    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 b

  3. Two-stage vs single-stage management for concomitant gallstones and common bile duct stones

    Institute of Scientific and Technical Information of China (English)

    Jiong Lu; Yao Cheng; Xian-Ze Xiong; Yi-Xin Lin; Si-Jia Wu; Nan-Sheng Cheng


    AIM:To evaluate the safety and effectiveness of two-stage vs single-stage management for concomitant gallstones and common bile duct stones.METHODS:Four databases,including PubMed,Embase,the Cochrane Central Register of Controlled Trials and the Science Citation Index up to September 2011,were searched to identify all randomized controlled trials (RCTs).Data were extracted from the studies by two independent reviewers.The primary outcomes were stone clearance from the common bile duct,postoperative morbidity and mortality.The secondary outcomes were conversion to other procedures,number of procedures per patient,length of hospital stay,total operative time,hospitalization charges,patient acceptance and quality of life scores.RESULTS:Seven eligible RCTs [five trials (n =621)comparing preoperative endoscopic retrograde cholangiopancreatography (ERCP)/endoscopic sphincterotomy (EST) + laparoscopic cholecystectomy (LC) with LC +laparoscopic common bile duct exploration (LCBDE);two trials (n =166) comparing postoperative ERCP/EST + LC with LC + LCBDE],composed of 787 patients in total,were included in the final analysis.The metaanalysis detected no statistically significant difference between the two groups in stone clearance from the common bile duct [risk ratios (RR) =-0.10,95% confidence intervals (CI):-0.24 to 0.04,P =0.17],postoperative morbidity (RR =0.79,95% CI:0.58 to 1.10,P =0.16),mortality (RR =2.19,95% CI:0.33 to 14.67,P =0.42),conversion to other procedures (RR =1.21,95% CI:0.54 to 2.70,P =0.39),length of hospital stay (MD =0.99,95% CI:-1.59 to 3.57,P =0.45),total operative time (MD =12.14,95% CI:-1.83 to 26.10,P =0.09).Two-stage (LC + ERCP/EST) management clearly required more procedures per patient than single-stage (LC + LCBDE) management.CONCLUSION:Single-stage management is equivalent to two-stage management but requires fewer procedures.However,patient's condition,operator's expertise and local resources should be taken into account in

  4. A population-based cohort study of symptomatic gallstone disease in diabetic patients

    Institute of Scientific and Technical Information of China (English)

    Chi-Ming Liu; Chung-Te Hsu; Chung-Yi Li; Chu-Chieh Chen; Meng-Lun Liu; Jorn-Hon Liu


    AIM:To investigate the prevalence of gallstone disease (GSD) and to evaluate the risk of symptomatic GSD among diabetic patients.METHODS:The study was conducted by analyzing the National Health Research Institutes (NHRI) dataset of ambulatory care patients,inpatient claims,and the updated registry of beneficiaries from 2000 to 2008.A total of 615 532 diabetic patients without a prior history of hospital treatment or ambulatory care visits for symptomatic GSD were identified in the year 2000.Age-and gender-matched control individuals free from both GSD and diabetes from 1997 to 1999 were randomly selected from the NHIR database (n =614 871).The incidence densities of symptomatic GSD were estimated according to the subjects' diabetic status.The distributions of age,gender,occupation,income,and residential area urbanization were compared between diabetic patients and control subjects using Cox proportion hazards models.Differences between the rates of selected comorbidities were also assessed in the two groups.RESULTS:Overall,60 734 diabetic patients and 48 116control patients developed symptomatic GSD and underwent operations,resulting in cumulative operation rates of 9.87% and 7.83%,respectively.The age and gender distributions of both groups were similar,with a mean age of 60 years and a predominance of females.The diabetic group had a significantly higher prevalence of all comorbidities of interest.A higher incidence of symptomatic GSD was observed in females than in males in both groups.In the control group,females under the age of 64 had a significantly higher incidence of GSD than the corresponding males,but this difference was reduced with increasing age.The cumulative incidences of operations for symptomatic GSD in the diabetic and control groups were 13.06 and 9.52 cases per 1000 person-years,respectively.Diabetic men exhibited a higher incidence of operations for symptomatic GSD than did their counterparts in the control group (12.35vs 8.75 cases per

  5. Oxidative Stress before and after Operation in Patients with Chronic Cholecystits Containing Gallstone

    Institute of Scientific and Technical Information of China (English)


    To study the relationship of oxidative,antioxidative constitutents and antioxidases in blood with chronic cholceysitits containing gallstone,levels of lipoperoxides(LPO),nitric oxide(NO),vitamin C(VC),vitamin E(VE) and β-carotene(β-CAR)in plasma as well as level of LPO,activities of superoxide dismutase(SOD),catalase(CAT) and glutathione peroxidase(GSH-Px)in erythrocytes were investigated by spectrophotometric assay in 107 patients with this condition(PCg) and 100 healthy volunteers(HVs),Compared with HVs group,the average value of LPO and NO in plasma and that of LPO in erythrocytes of PCg group were significantly increased(P<0.0001),while that of VC,VE and β-CAR in plasma and the average activities of SOD,CAT and GSH-Px in erythrocytes were significantly decreased(P<0.0001),Linear regression and correlation analysis for 107 preoperative PCg showed that the vlue of LPO and NO in plasma and that of LPO in erythrocytes of PCg gradually increased (P<0.0001),representing a significant linear positive correlation.The value of VC,VE and β-CAR in plasma and that of SOD,CAT and GSH-Px in erythrocytes of PCg gradually decreased(P<0.0001),representing a significant linear negative correlation.Stepwise regression and correlation analysis for 107 preoperative PCg suggested that the closest correlation was observed between the course of disease and the value of NO and VC in plasma and that of SOD,GSH-Px and LPO in erythrocytes,r=0.7306,F=32.1408,P<0.0001,Compared with the preoperative PCg group,the average value of LPO and NO in plasma and that of LPO in erythrocytes of the postoperative PCg group were significantly decreased(P<0.0001),Furthermore,the average value of VC in plasma and that of SOD,CAT and GSH-Px in erythrocytes of the postoperative PCg group were significantly increased(P<0.0001),whereas no significant difference was found between their average value of VE and β-CAR in plasma,These finding suggested that oxidative stress was an aggravating pathologica

  6. Physiological and pathological implications of cholesterol. (United States)

    Cortes, Victor A; Busso, Dolores; Maiz, Alberto; Arteaga, Antonio; Nervi, Flavio; Rigotti, Attilio


    Cholesterol has evolved to fulfill sophisticated biophysical, cell signaling and endocrine requirements of animal systems. At a cellular level, cholesterol is found in membranes, where it increases both bilayer stiffness and impermeability to water and ions. Furthermore, cholesterol is integrated into specialized lipid-protein membrane microdomains with critical topographical and signaling functions. At an organismal level, cholesterol is the precursor for all steroid hormones, including gluco- and mineralo-corticoids, sex hormones and vitamin D, all of which regulate carbohydrate, sodium, reproductive and bone homeostasis, respectively. This sterol is also the precursor for bile acids, which are important for intestinal absorption of dietary lipids as well as energy and glucose metabolic regulation. Importantly, complex mechanisms maintain cholesterol within physiological ranges and the disregulation of these mechanisms results in embryonic or adult diseases, caused by either excessive or reduced tissue cholesterol levels. The causative role of cholesterol in these diseases has been demonstrated by diverse genetic and pharmacologic animal models that are commented in this review.

  7. Cholesterol oxidation products. Their occurrence and detection in our foodstuffs. (United States)

    Yan, P S


    The structural similarity of cholesterol oxidation products (COP) to native cholesterol and their xenobiotic effects prompt researchers to study the long-term effects of the assimilation of these compounds into our tissues. COP are present in our food system. The level of exposure changes as our food products and our food choices alter. Therefore, the presence of COP in our food system has to be carefully monitored and their presence in processed foods minimized by optimizing processing and storage conditions. This review will briefly discuss the chemistry of some commonly-occurring COP and their biological significance. A more in-depth survey of the literature on the pitfalls of COP determination is included. It is the intention of the author to impress the readers that 'exogenous' COP can easily form during sample preparation. These artifacts will hinder our understanding of factors that promote COP formation in foods. The effects of heating, dehydrating, packaging and the presence of highly unsaturated lipids on the levels of COP in cholesterol-containing foods are evaluated to gauge the levels of exposure to different consumer groups.

  8. Stabilization of distearoylphosphatidylcholine lamellar phases in propylene glycol using cholesterol. (United States)

    Harvey, Richard D; Ara, Nargis; Heenan, Richard K; Barlow, David J; Quinn, Peter J; Lawrence, M Jayne


    Phospholipid vesicles (liposomes) formed in pharmaceutically acceptable nonaqueous polar solvents such as propylene glycol are of interest in drug delivery because of their ability to improve the bioavailability of drugs with poor aqueous solubility. We have demonstrated a stabilizing effect of cholesterol on lamellar phases formed by dispersion of distearoylphosphatidylcholine (DSPC) in water/propylene glycol (PG) solutions with glycol concentrations ranging from 0 to 100%. The stability of the dispersions was assessed by determining the effect of propylene glycol concentration on structural parameters of the lamellar phases using a complementary combination of X-ray and neutron scattering techniques at 25 °C and in the case of X-ray scattering at 65 °C. Significantly, although stable lamellar phases (and liposomes) were formed in all PG solutions at 25 °C, the association of the glycol with the liposomes' lamellar structures led to the formation of interdigitated phases, which were not thermostable at 65 °C. With the addition of equimolar quantities of cholesterol to the dispersions of DSPC, stable lamellar dispersions (and indeed liposomes) were formed in all propylene glycol solutions at 25 °C, with the significant lateral phase separation of the bilayer components only detectable in propylene glycol concentrations above 60% (w/w). We propose that the stability of lamellar phases of the cholesterol-containing liposomes formed in propylene glycol concentrations of up to 60% (w/w) represent potentially very valuable drug delivery vehicles for a variety of routes of administration.

  9. A church-based cholesterol education program. (United States)

    Wiist, W H; Flack, J M


    The leading cause of death among black people in the United States is coronary heart disease, accounting for about 25 percent of the deaths. The Task Force on Black and Minority Health formed by the Secretary of Health and Human Services in 1985 subsequently recommended increased efforts to reduce risk factors for coronary heart disease in the black population. A stated focus of the National Heart, Lung, and Blood Institute's National Cholesterol Education Program has been that of reaching minority groups. This report describes a pilot cholesterol education program conducted in black churches by trained members of those churches. Cholesterol screening, using a Reflotron, and other coronary heart disease risk factor screening was conducted in six churches with predominantly black members and at a neighborhood library. A total of 348 persons with cholesterol levels of 200 milligrams per deciliter (mg per dl) or higher were identified. At the time of screening, all were provided brief counseling on lowering their cholesterol and were given a copy of the screening results. Half of those identified, all members of one church, were invited to attend a 6-week nutrition education class of 1 hour each week about techniques to lower blood cholesterol. Information about cholesterol was also mailed to them. They were designated as the education group. Persons in the church were trained to teach the classes. A report of the screening results was sent to the personal physicians of the remaining 174 people in other churches who had cholesterol levels of 200 mg per dl or higher. This group served as a usual care comparison group.Six months after the initial screening, members of both groups were invited for followup screening.Among the 75 percent of the education group who returned for followup screening there was a 23.4 mg per dl (10 percent) decrease in the mean cholesterol level. Thirty-six percent of the usual care group returned for followup screening; their mean cholesterol

  10. Acyl-coenzyme A:cholesterol acyltransferases


    Chang, Ta-Yuan; Li, Bo-Liang; Chang, Catherine C.Y.; Urano, Yasuomi


    The enzymes acyl-coenzyme A (CoA):cholesterol acyltransferases (ACATs) are membrane-bound proteins that utilize long-chain fatty acyl-CoA and cholesterol as substrates to form cholesteryl esters. In mammals, two isoenzymes, ACAT1 and ACAT2, encoded by two different genes, exist. ACATs play important roles in cellular cholesterol homeostasis in various tissues. This chapter summarizes the current knowledge on ACAT-related research in two areas: 1) ACAT genes and proteins and 2) ACAT enzymes as...

  11. Genetic therapies to lower cholesterol. (United States)

    Khoo, Bernard


    This review surveys the state-of-the-art in genetic therapies for familial hypercholesterolaemia (FH), caused most commonly by mutations in the LDL receptor (LDLR) gene. FH manifests as highly elevated low density lipoprotein (LDL) cholesterol levels and consequently accelerated atherosclerosis. Modern pharmacological therapies for FH are insufficiently efficacious to prevent premature cardiovascular disease, can cause significant adverse effects and can be expensive. Genetic therapies for FH have been mooted since the mid 1990s but gene replacement strategies using viral vectors have so far been unsuccessful. Other strategies involve knocking down the expression of Apolipoprotein B100 (APOB100) and the protease PCSK9 which designates LDLR for degradation. The antisense oligonucleotide mipomersen, which knocks down APOB100, is currently marketed (with restrictions) in the USA, but is not approved in Europe due to its adverse effects. To address this problem, we have devised a novel therapeutic concept, APO-skip, which is based on modulation of APOB splicing, and which has the potential to deliver a cost-effective, efficacious and safe therapy for FH.

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

    Directory of Open Access Journals (Sweden)

    Josefin Skogsberg


    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.

  13. [Cholesterol and atherosclerosis. Historical considerations and treatment]. (United States)

    Zárate, Arturo; Manuel-Apolinar, Leticia; Basurto, Lourdes; De la Chesnaye, Elsa; Saldívar, Iván


    Cholesterol is a precursor of steroid hormones and an essential component of the cell membrane, however, altered regulation of the synthesis, absorption and excretion of cholesterol predispose to cardiovascular diseases of atherosclerotic origin. Despite, the recognition of historical events for 200 years, starting with Michel Chevreul naming «cholesterol»; later on, Lobstein coining the term atherosclerosis and Marchand introducing it, Anichkov identifying cholesterol in atheromatous plaque, and Brown and Goldstein discovering LDL receptor; as well as the emerging of different drugs, such as fibrates, statins and cetrapibs this decade, promising to increase HDL and the most recent ezetimibe and anti-PCSK9 to inhibit the degradation of LDL receptor, however morbidity has not been reduced in cardiovascular disease.

  14. A new framework for reverse cholesterol transport: Non-biliary contributions to reverse cholesterol transport

    Institute of Scientific and Technical Information of China (English)

    Ryan; E; Temel; J; Mark; Brown


    Reduction of low-density lipoprotein-cholesterol through statin therapy has only modestly decreased coronary heart disease (CHD)-associated mortality in developed countries, which has prompted the search for alternative therapeutic strategies for CHD. Major efforts are now focused on therapies that augment high-density lipoprotein (HDL)-mediated reverse cholesterol transport (RCT), and ultimately increase the fecal disposal of cholesterol. The process of RCT has long been thought to simply involve HDL-media...

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

    Institute of Scientific and Technical Information of China (English)

    Carlos; LJ; Vrins


    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 the hepatobiliary secretion was considered to be the sole route involved in the RCT. However, observations from early studies in animals and humans already pointed towards the possibility of another route. In t...

  16. Assessing possible hazards of reducing serum cholesterol.


    Law, M. R.; Thompson, S. G.; Wald, N J


    OBJECTIVE--To assess whether low serum cholesterol concentration increases mortality from any cause. DESIGN--Systematic review of published data on mortality from causes other than ischaemic heart disease derived from the 10 largest cohort studies, two international studies, and 28 randomised trials, supplemented by unpublished data on causes of death obtained when necessary. MAIN OUTCOME MEASURES--Excess cause specific mortality associated with low or lowered serum cholesterol concentration....

  17. Cholesterol treatment practices of primary care physicians.


    Hyman, D J; Maibach, E W; Flora, J A; Fortmann, S.P.


    The active involvement of primary care physicians is necessary in the diagnosis and treatment of elevated blood cholesterol. Empirical evidence suggests that primary care physicians generally initiate dietary and pharmacological treatment at threshold values higher than is currently recommended. To determine current treatment thresholds and establish factors that distinguish physicians who are more likely to initiate therapy at lower cholesterol values, 119 primary care physicians in four nor...

  18. PAQR3 modulates cholesterol homeostasis by anchoring Scap/SREBP complex to the Golgi apparatus. (United States)

    Xu, Daqian; Wang, Zheng; Zhang, Yuxue; Jiang, Wei; Pan, Yi; Song, Bao-Liang; Chen, Yan


    Cholesterol biosynthesis is regulated by transcription factors SREBPs and their escort protein Scap. On sterol depletion, Scap/SREBP complex is transported from endoplasmic reticulum (ER) to the Golgi apparatus where SREBP is activated. Under cholesterol sufficient condition, Insigs act as anchor proteins to retain Scap/SREBP in the ER. However, the anchor protein of Scap/SREBP in the Golgi is unknown. Here we report that a Golgi-localized membrane protein progestin and adipoQ receptors 3 (PAQR3) interacts with Scap and SREBP and tethers them to the Golgi. PAQR3 promotes Scap/SREBP complex formation, potentiates SREBP processing and enhances lipid synthesis. The mutually exclusive interaction between Scap and PAQR3 or Insig-1 is regulated by cholesterol level. PAQR3 knockdown in liver blunts SREBP pathway and decreases hepatic cholesterol content. Disrupting the interaction of PAQR3 with Scap/SREBP by a synthetic peptide inhibits SREBP processing and activation. Thus, PAQR3 regulates cholesterol homeostasis by anchoring Scap/SREBP to the Golgi and disruption of such function reduces cholesterol biosynthesis.

  19. Squalene mono-oxygenase, a key enzyme in cholesterol synthesis, is stabilized by unsaturated fatty acids. (United States)

    Stevenson, Julian; Luu, Winnie; Kristiana, Ika; Brown, Andrew J


    SM (squalene mono-oxygenase) catalyses the first oxygenation step in cholesterol synthesis, immediately before the formation of the steroid backbone at lanosterol. SM is an important control point in the pathway, and is regulated at the post-translational level by accelerated cholesterol-dependent ubiquitination and proteasomal degradation, which is associated with the accumulation of squalene. Using model cell systems, we report that SM is stabilized by unsaturated fatty acids. Treatment with unsaturated fatty acids such as oleate, but not saturated fatty acids, increased protein levels of SM or SM-N100-GFP (the first 100 amino acids of SM fused to GFP) at the post-translational level and partially overcame cholesterol-dependent degradation, as well as reversing cholesterol-dependent squalene accumulation. Maximum stabilization required activation of fatty acids, but not triacylglycerol or phosphatidylcholine synthesis. The mechanism of oleate-mediated stabilization appeared to occur through reduced ubiquitination by the E3 ubiquitin ligase MARCH6. Stabilization of a cholesterol biosynthetic enzyme by unsaturated fatty acids may help maintain a constant cholesterol/phospholipid ratio.

  20. Cholesterol modulates the dimer interface of the β₂-adrenergic receptor via cholesterol occupancy sites. (United States)

    Prasanna, Xavier; Chattopadhyay, Amitabha; Sengupta, Durba


    The β2-adrenergic receptor is an important member of the G-protein-coupled receptor (GPCR) superfamily, whose stability and function are modulated by membrane cholesterol. The recent high-resolution crystal structure of the β2-adrenergic receptor revealed the presence of possible cholesterol-binding sites in the receptor. However, the functional relevance of cholesterol binding to the receptor remains unexplored. We used MARTINI coarse-grained molecular-dynamics simulations to explore dimerization of the β2-adrenergic receptor in lipid bilayers containing cholesterol. A novel (to our knowledge) aspect of our results is that receptor dimerization is modulated by membrane cholesterol. We show that cholesterol binds to transmembrane helix IV, and cholesterol occupancy at this site restricts its involvement at the dimer interface. With increasing cholesterol concentration, an increased presence of transmembrane helices I and II, but a reduced presence of transmembrane helix IV, is observed at the dimer interface. To our knowledge, this study is one of the first to explore the correlation between cholesterol occupancy and GPCR organization. Our results indicate that dimer plasticity is relevant not just as an organizational principle but also as a subtle regulatory principle for GPCR function. We believe these results constitute an important step toward designing better drugs for GPCR dimer targets.

  1. Dietary cholesterol modulates pathogen blocking by Wolbachia.

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    Eric P Caragata

    Full Text Available The bacterial endosymbiont Wolbachia pipientis protects its hosts from a range of pathogens by limiting their ability to form infections inside the insect. This "pathogen blocking" could be explained by innate immune priming by the symbiont, competition for host-derived resources between pathogens and Wolbachia, or the direct modification of the cell or cellular environment by Wolbachia. Recent comparative work in Drosophila and the mosquito Aedes aegypti has shown that an immune response is not required for pathogen blocking, implying that there must be an additional component to the mechanism. Here we have examined the involvement of cholesterol in pathogen blocking using a system of dietary manipulation in Drosophila melanogaster in combination with challenge by Drosophila C virus (DCV, a common fly pathogen. We observed that flies reared on cholesterol-enriched diets infected with the Wolbachia strains wMelPop and wMelCS exhibited reduced pathogen blocking, with viral-induced mortality occurring 2-5 days earlier than flies reared on Standard diet. This shift toward greater virulence in the presence of cholesterol also corresponded to higher viral copy numbers in the host. Interestingly, an increase in dietary cholesterol did not have an effect on Wolbachia density except in one case, but this did not directly affect the strength of pathogen blocking. Our results indicate that host cholesterol levels are involved with the ability of Wolbachia-infected flies to resist DCV infections, suggesting that cholesterol contributes to the underlying mechanism of pathogen blocking.

  2. Obesity, Cholesterol Metabolism and Breast Cancer Pathogenesis (United States)

    McDonnell, Donald P.; Park, Sunghee; Goulet, Matthew T.; Jasper, Jeff; Wardell, Suzanne E.; Chang, Ching-yi; Norris, John D.; Guyton, John R.; Nelson, Erik R.


    Obesity and altered lipid metabolism are risk factors for breast cancer in pre- and post-menopausal women. These pathologic relationships have been attributed in part to the impact of cholesterol on the biophysical properties of cell membranes and to the influence of these changes on signaling events initiated at the membrane. However, more recent studies have indicated that the oxysterol 27-hydroxycholesterol (27HC), and not cholesterol per se, may be the primary biochemical link between lipid metabolism and cancer. The enzyme responsible for production of 27HC from cholesterol, CYP27A1, is expressed primarily in the liver and in macrophages. In addition significantly elevated expression of this enzyme within breast tumors has also been observed. It is believed that 27HC, acting through the liver X receptor (LXR) in macrophages and possibly other cells is involved in maintaining organismal cholesterol homeostasis. It has also been shown recently that 27HC is an estrogen receptor (ER) agonist in breast cancer cells and that it stimulates the growth and metastasis of tumors in several models of breast cancer. These findings provide the rationale for the clinical evaluation of pharmaceutical approaches that interfere with cholesterol/27HC synthesis as a means to mitigate the impact of cholesterol on breast cancer pathogenesis. PMID:25060521

  3. Cholesterol content in meat of some Cyprinidae

    Directory of Open Access Journals (Sweden)

    Živković Dragić L.


    Full Text Available The aim of this paper was to examine cholesterol content in meat of five Cyprinidae species: white bream (Bllica bjoerkna L, carp bream (Abramis brama L, baltic vimba (Vimba vimba carinata Pallas, zope (Abramis balerus L and crucian carp (Carassius carassius gibelio Bloch from the river Danube. Cholesterol content was examined in the function of season factor and individual weight. Cholesterol concentration in meat of white bream carp bream, baltic vimba, zope and crucian carp is on average level below 20 mg/100 g of meat, which makes meat of these fish species nutritively very valuable. Cholesterol content is variable during the season. Its concentration in meat and in lipids is lowest during spring, during summer it increases and during autumn decreases, except in meat of white bream. Body weight has influence on cholesterol content when its concentration is expressed as % of cholesterol in lipids. Its content in lipids decreases with increasing of individual weight, except in meat of carp bream.

  4. Cholesterol suppresses antimicrobial effect of statins

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    Mohammad Reza Haeri


    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.


    Directory of Open Access Journals (Sweden)

    Małgorzata Ziarno


    Full Text Available The ability to in vitro cholesterol level reduction in laboratory media has been shown for numerous strains of lactic acid bacteria, but not for all strains of lactic bacteria used in the dairy industry. The aim of this work was the determination of the ability of selected thermophilic lactic acid bacteria to cholesterol assimilation during 24 h culture in MRS broth. Commercial starter cultures showed various ability to cholesterol assimilation from laboratory medium. In case of starter cultures used for production of traditional yoghurt, consisting of Streptococcus salivarius subsp. thermophilus and Lactobacillus delbrueckii subsp. bulgaricus, the quantity of assimilated cholesterol did not exceed 27% of its initial contents (0.7 g in 1 dm3. Starter cultures used for bioyoghurt production, containing also probiotic strains (came from Lactobacillus acidophilus species or Bifidobacterium genus assimilated from almost 18% to over 38% of cholesterol. For one monoculture of Lb. acidophilus, cholesterol assimilation ability of 49-55% was observed, despite that the number of bacterial cells in this culture was not different from number of bacteria in other cultures.

  6. 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


    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.

  7. Monitoring of cholesterol oxidation in a lipid bilayer membrane using streptolysin O as a sensing and signal transduction element. (United States)

    Shoji, Atsushi; Ikeya, Kana; Aoyagi, Miki; Takatsuji, Ryutaro; Yanagida, Akio; Shibusawa, Yoichi; Sugawara, Masao


    Streptolysin O (SLO), which recognizes sterols and forms nanopores in lipid membranes, is proposed as a sensing element for monitoring cholesterol oxidation in a lipid bilayer. The structural requirements of eight sterols for forming nanopores by SLO confirmed that a free 3-OH group in the β-configuration of sterols is required for recognition by SLO in a lipid bilayer. The extent of nanopore formation by SLO in lipid bilayers increased in the order of cholestanol<cholesterol<25-OH cholesterol and in a sterol concentration-dependent manner. The immobilization of liposomes consisting of PC, cholesterol and 4-cholesten-3-one exhibited a linear relationship between calcein permeability and the molar ratio of cholesterol and 4-cholesten-3-one. The SLO-based method was successfully applied for monitoring of cholesterol oxidase-mediated oxidation of cholesterol in a lipid bilayer. The potential of the SLO nanopore-based method for monitoring cholesterol oxidation in a lipid bilayer by other oxidative enzymes is also discussed.

  8. Cholesterol Promotes Interaction of the Protein CLIC1 with Phospholipid Monolayers at the Air–Water Interface

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    Khondker R. Hossain


    Full Text Available CLIC1 is a Chloride Intracellular Ion Channel protein that exists either in a soluble state in the cytoplasm or as a membrane bound protein. Members of the CLIC family are largely soluble proteins that possess the intriguing property of spontaneous insertion into phospholipid bilayers to form integral membrane ion channels. The regulatory role of cholesterol in the ion-channel activity of CLIC1 in tethered lipid bilayers was previously assessed using impedance spectroscopy. Here we extend this investigation by evaluating the influence of cholesterol on the spontaneous membrane insertion of CLIC1 into Langmuir film monolayers prepared using 1-palmitoyl-2-oleoylphosphatidylcholine, 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-ethanolamine and 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-L-serine alone or in combination with cholesterol. The spontaneous membrane insertion of CLIC1 was shown to be dependent on the presence of cholesterol in the membrane. Furthermore, pre-incubation of CLIC1 with cholesterol prior to its addition to the Langmuir film, showed no membrane insertion even in monolayers containing cholesterol, suggesting the formation of a CLIC1-cholesterol pre-complex. Our results therefore suggest that CLIC1 membrane interaction involves CLIC1 binding to cholesterol located in the membrane for its initial docking followed by insertion. Subsequent structural rearrangements of the protein would likely also be required along with oligomerisation to form functional ion channels.

  9. Cholesterol Promotes Interaction of the Protein CLIC1 with Phospholipid Monolayers at the Air–Water Interface (United States)

    Hossain, Khondker R.; Al Khamici, Heba; Holt, Stephen A.; Valenzuela, Stella M.


    CLIC1 is a Chloride Intracellular Ion Channel protein that exists either in a soluble state in the cytoplasm or as a membrane bound protein. Members of the CLIC family are largely soluble proteins that possess the intriguing property of spontaneous insertion into phospholipid bilayers to form integral membrane ion channels. The regulatory role of cholesterol in the ion-channel activity of CLIC1 in tethered lipid bilayers was previously assessed using impedance spectroscopy. Here we extend this investigation by evaluating the influence of cholesterol on the spontaneous membrane insertion of CLIC1 into Langmuir film monolayers prepared using 1-palmitoyl-2-oleoylphosphatidylcholine, 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-ethanolamine and 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-L-serine alone or in combination with cholesterol. The spontaneous membrane insertion of CLIC1 was shown to be dependent on the presence of cholesterol in the membrane. Furthermore, pre-incubation of CLIC1 with cholesterol prior to its addition to the Langmuir film, showed no membrane insertion even in monolayers containing cholesterol, suggesting the formation of a CLIC1-cholesterol pre-complex. Our results therefore suggest that CLIC1 membrane interaction involves CLIC1 binding to cholesterol located in the membrane for its initial docking followed by insertion. Subsequent structural rearrangements of the protein would likely also be required along with oligomerisation to form functional ion channels. PMID:26875987

  10. The Structural Basis of Cholesterol Activity in Membranes

    Energy Technology Data Exchange (ETDEWEB)

    Olsen, Brett N.; Bielska, Agata; Lee, Tiffany; Daily, Michael D.; Covey, Douglas F.; Schlesinger, Paul H.; Baker, Nathan A.; Ory, Daniel S.


    Although the majority of free cellular cholesterol is present in the plasma membrane, cholesterol homeostasis is principally regulated through sterol-sensing proteins that reside in the cholesterol-poor endoplasmic reticulum (ER). In response to acute cholesterol loading or depletion, there is rapid equilibration between the ER and plasma membrane cholesterol pools, suggesting a biophysical model in which the availability of plasma membrane cholesterol for trafficking to internal membranes modulates ER membrane behavior. Previous studies have predominantly examined cholesterol availability in terms of binding to extramembrane acceptors, but have provided limited insight into the structural changes underlying cholesterol activation. In this study, we use both molecular dynamics simulations and experimental membrane systems to examine the behavior of cholesterol in membrane bilayers. We find that cholesterol depth within the bilayer provides a reasonable structural metric for cholesterol availability and that this is correlated with cholesterol-acceptor binding. Further, the distribution of cholesterol availability in our simulations is continuous rather than divided into distinct available and unavailable pools. This data provide support for a revised cholesterol activation model in which activation is driven not by saturation of membrane-cholesterol interactions but rather by bulk membrane remodeling that reduces membrane-cholesterol affinity.

  11. Dairy products and plasma cholesterol levels

    Directory of Open Access Journals (Sweden)

    Lena Ohlsson


    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

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


    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 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 mice and hepatocytes. Taken together

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

    Directory of Open Access Journals (Sweden)

    Fourgeux Cynthia


    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.

  14. Perspective on plasma membrane cholesterol efflux and spermatozoal function

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    Dhastagir Sultan Sheriff


    Full Text Available The process of sperm maturation, capacitation, and fertilization occur in different molecular milieu provided by epididymis and female reproductive tract including oviduct. The different tissue environment with different oxygen tension and temperature may still influence the process of sperm maturation and capacitation. Reactive oxygen species (ROS is reported to be an initial switch that may activate the molecular process of capacitation. Therefore, the generation of reactive oxygen species and its possible physiological role depends upon a balance between its formation and degradation in an open environment provided by female reproductive tract. The sensitivity of the spermatozoa to the action of ROS may be due to its exposure for the first time to an oxygen rich external milieu compared to its internal milieu in the male reproductive tract. Reduced temperature in testicular environment coupled with reduced oxygen tension may be the right molecular environment for the process of spermatogenesis and spermiogenesis. The morphologically mature spermatozoa then may attain its motility in an environment provided by the caput epididymis wherein, the dyenin motor can become active. This ability to move forward will make the spermatozoa physiologically fit to undertake its sojourn in the competitive race of fertilization in a new oxygen rich female reproductive tract. The first encounter may be oxygen trigger or preconditioning of the spermatozoa with reactive oxygen species that may alter the spermatozoal function. Infertility is still one of the major global health problems that need medical attention. Apart from the development of artificial methods of reproduction and development of newer techniques in the field of andrology focuses attention on spermatozoal structure and metabolism. Therefore, understanding the molecular mechanisms involved in fertilization in general and that of sperm capacitation in particular may help lead to new and better

  15. A convenient synthesis of ezetimibe analogs as cholesterol ab sorption inhibitors

    Institute of Scientific and Technical Information of China (English)


    A convenient method for the synthesis of ezetimibe analogs as cholesterol absorption inhibitors was described.The key step in the synthesis was the intramolecular ring formation through Mitsunobu reaction.Furthermore,a new series of analogs was designed and synthesized.


    NARCIS (Netherlands)



    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 d

  17. Cholesterol content and methods for cholesterol determination in meat and poultry (United States)

    Available data for cholesterol content of beef, pork, poultry, and processed meat products were reported. Although the cholesterol concentration in meat and poultry can be influenced by various factors, effects of animal species, muscle fiber type, and muscle fat content are focused on in this revi...

  18. 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

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

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


    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.

  20. Lipoproteins, cholesterol homeostasis and cardiac health

    Directory of Open Access Journals (Sweden)

    Tyler F. Daniels, Karen M. Killinger, Jennifer J. Michal, Raymond W. Wright Jr., Zhihua Jiang


    Full Text Available Cholesterol is an essential substance involved in many functions, such as maintaining cell membranes, manufacturing vitamin D on surface of the skin, producing hormones, and possibly helping cell connections in the brain. When cholesterol levels rise in the blood, they can, however, have dangerous consequences. In particular, cholesterol has generated considerable notoriety for its causative role in atherosclerosis, the leading cause of death in developed countries around the world. Homeostasis of cholesterol is centered on the metabolism of lipoproteins, which mediate transport of the lipid to and from tissues. As a synopsis of the major events and proteins that manage lipoprotein homeostasis, this review contributes to the substantial attention that has recently been directed to this area. Despite intense scrutiny, the majority of phenotypic variation in total cholesterol and related traits eludes explanation by current genetic knowledge. This is somewhat disappointing considering heritability estimates have established these traits as highly genetic. Thus, the continued search for candidate genes, mutations, and mechanisms is vital to our understanding of heart disease at the molecular level. Furthermore, as marker development continues to predict risk of vascular illness, this knowledge has the potential to revolutionize treatment of this leading human disease.

  1. LDL cholesterol: controversies and future therapeutic directions. (United States)

    Ridker, Paul M


    Lifelong exposure to raised concentrations of LDL cholesterol increases cardiovascular event rates, and the use of statin therapy as an adjunct to diet, exercise, and smoking cessation has proven highly effective in reducing the population burden associated with hyperlipidaemia. Yet, despite consistent biological, genetic, and epidemiological data, and evidence from randomised trials, there is controversy among national guidelines and clinical practice with regard to LDL cholesterol, its measurement, the usefulness of population-based screening, the net benefit-to-risk ratio for different LDL-lowering drugs, the benefit of treatment targets, and whether aggressive lowering of LDL is safe. Several novel therapies have been introduced for the treatment of people with genetic defects that result in loss of function within the LDL receptor, a major determinant of inherited hyperlipidaemias. Moreover, the usefulness of monoclonal antibodies that extend the LDL-receptor lifecycle (and thus result in substantial lowering of LDL cholesterol below the levels achieved with statins alone) is being assessed in phase 3 trials that will enrol more than 60,000 at-risk patients worldwide. These trials represent an exceptionally rapid translation of genetic observations into clinical practice and will address core questions of how low LDL cholesterol can be safely reduced, whether the mechanism of LDL-cholesterol lowering matters, and whether ever more aggressive lipid-lowering provides a safe, long-term mechanism to prevent atherothrombotic complications.

  2. Laparoscopic Management of a Proximal Jejunal Gallstone Ileus with Patulous Ampulla and Choledochal Cyst-a Report of Unusual Presentation and a Review. (United States)

    Narkhede, Rajvilas Anil; Bada, Vijaykumar C; Kona, Lakshmi Kumari


    Gallstone ileus is a diagnosis of rarity, and a proximal site of obstruction in a young patient is even rare. Of the three cases in our experience, we found two cases of gallstone ileus (GSI) with typical epidemiology and presentation, one had combination of multiple rare associations. We report such a case, suspected to have gallstone ileus on ultrasound and confirmed diagnosis on computed tomography. Presence of biliary-enteric fistula, old age, and obstructive features, as in typical cases, was a bigger asset for diagnosis, but it was difficult to entertain diagnosis of GSI in young girl in absence of a demonstrable biliary-enteric fistula, with uncommon association of choledochal cyst and sickle cell disease. A very surprising finding, dilated major papilla, could however explain the pathogenesis which has also been reported in the past. Although differential opinions regarding management exist, we decided to follow two-stage surgery as our institute protocol. A minimal access approach has been immensely helpful in accurate diagnosis, and expedative management with early recovery has been proven in the past studies which we agreed with our experience.

  3. Macrophage specific caspase-1/11 deficiency protects against cholesterol crystallization and hepatic inflammation in hyperlipidemic mice.

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    Tim Hendrikx

    Full Text Available While non-alcoholic steatohepatitis (NASH is characterized by hepatic steatosis combined with inflammation, the mechanisms triggering hepatic inflammation are unknown. In Ldlr(-/- mice, we have previously shown that lysosomal cholesterol accumulation in Kupffer cells (KCs correlates with hepatic inflammation and cholesterol crystallization. Previously, cholesterol crystals have been shown to induce the activation of inflammasomes. Inflammasomes are protein complexes that induce the processing and release of pro-inflammatory cytokines IL-1b and IL-18 via caspase-1 activation. Whereas caspase-1 activation is independent of caspase-11 in the canonical pathway of inflammasome activation, caspase-11 was found to trigger caspase-1-dependent IL-1b and IL-18 in response to non-canonical inflammasome activators. So far, it has not been investigated whether inflammasome activation stimulates the formation of cholesterol crystals. We hypothesized that inflammasome activation in KCs stimulates cholesterol crystallization, thereby leading to hepatic inflammation.Ldlr (-/- mice were transplanted (tp with wild-type (Wt or caspase-1/11(-/- (dKO bone marrow and fed either regular chow or a high-fat, high-cholesterol (HFC diet for 12 weeks. In vitro, bone marrow derived macrophages (BMDM from wt or caspase-1/11(-/- mice were incubated with oxLDL for 24h and autophagy was assessed.In line with our hypothesis, caspase-1/11(-/--tp mice had less severe hepatic inflammation than Wt-tp animals, as evident from liver histology and gene expression analysis in isolated KCs. Mechanistically, KCs from caspase-1/11(-/--tp mice showed less cholesterol crystals, enhanced cholesterol efflux and increased autophagy. In wt BMDM, oxLDL incubation led to disturbed autophagy activity whereas BMDM from caspase-1/11(-/- mice had normal autophagy activity.Altogether, these data suggest a vicious cycle whereby disturbed autophagy and decreased cholesterol efflux leads to newly formed

  4. 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; Tybjærg-Hansen, Anne; Nordestgaard, Børge G


    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....

  5. 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.


    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 o

  6. Biliary microlithiasis, sludge, crystals, microcrystallization,andusefulnessof assessmentofnucleationtime

    Institute of Scientific and Technical Information of China (English)

    Vasitha Abeysuriya; Kemal I Deen; Navarathne MM Navarathne


    BACKGROUND:The process of microcrystallization, its sequel and the assessment of nucleation time is ignored. This systematic review aimed to highlight the importance of biliary microlithiasis, sludge, and crystals, and their association with gallstones, unexplained biliary pain, idiopathic pancreatitis, and sphincter of Oddi dysfunction. DATA SOURCES:Three reviewers performed a literature search of the PubMed database. Key words used were"biliary microlithiasis","biliary sludge","bile crystals","cholesterol crystallisation","bile microscopy","microcrystal formation of bile", "cholesterol monohydrate crystals", "nucleation time of cholesterol", "gallstone formation", "sphincter of Oddi dysfunction"and"idiopathic pancreatitis". Additional articles were sourced from references within the studies from the PubMed search. RESULTS:We found that biliary microcrystals account for almost all patients with gallstone disease, 7% to 79% with idiopathic pancreatitis, 83% with unexplained biliary pain, and 25%to 60%with altered biliary and pancreatic sphincter function. Overall, the detection of biliary microcrystals in gallstone disease has a sensitivity ranging from 55%to 87%and a speciifcity of 100%. In idiopathic pancreatitis, the presence of microcrystals ranges from 47%to 90%. A nucleation time less than 10 days in hepatic bile or ultra-ifltered gallbladder bile has a speciifcity of 100%for cholesterol gallstone disease. CONCLUSIONS:Biliary crystals are associated with gallstone disease, idiopathic pancreatitis, sphincter of Oddi dysfunction, unexplained biliary pain, and post-cholecystectomy biliary pain. Pathways of cholesterol super-saturation, crystallisation, and gallstone formation have been described with scientiifc support. Bile microscopy is a useful method to detect microcrystals and the assessment of nucleation time is a good method of predicting the risk of cholesterol crystallisation.

  7. CHOBIMALT: a cholesterol-based detergent. (United States)

    Howell, Stanley C; Mittal, Ritesh; Huang, Lijun; Travis, Benjamin; Breyer, Richard M; Sanders, Charles R


    Cholesterol and its hemisuccinate and sulfate derivatives are widely used in studies of purified membrane proteins but are difficult to solubilize in aqueous solution, even in the presence of detergent micelles. Other cholesterol derivatives do not form conventional micelles and lead to viscous solutions. To address these problems, a cholesterol-based detergent, CHOBIMALT, has been synthesized and characterized. At concentrations above 3−4 μM, CHOBIMALT forms micelles without the need for elevated temperatures or sonic disruption. Diffusion and fluorescence measurements indicated that CHOBIMALT micelles are large (210±30 kDa). The ability to solubilize a functional membrane protein was explored using a G-protein coupled receptor, the human kappa opioid receptor type 1 (hKOR1). While CHOBIMALT alone was not found to be effective as a surfactant for membrane extraction, when added to classical detergent micelles CHOBIMALT was observed to dramatically enhance the thermal stability of solubilized hKOR1.

  8. Ordering effects of cholesterol and its analogues

    DEFF Research Database (Denmark)

    Róg, Tomasz; Pasenkiewicz-Gierula, Marta; Vattulainen, Ilpo


    Without any exaggeration, cholesterol is one of the most important lipid species in eukaryotic cells. Its effects on cellular membranes and functions range from purely mechanistic to complex metabolic ones, besides which it is also a precursor of the sex hormones (steroids) and several vitamins....... In this review, we discuss the biophysical effects of cholesterol on the lipid bilayer, in particular the ordering and condensing effects, concentrating on the molecular level or inter-atomic interactions perspective, starting from two-component systems and proceeding to many-component ones e.g., modeling lipid...... rafts. Particular attention is paid to the roles of the methyl groups in the cholesterol ring system, and their possible biological function. Although our main research methodology is computer modeling, in this review we make extensive comparisons between experiments and different modeling approaches....

  9. Aspirin Increases the Solubility of Cholesterol in Lipid Membranes (United States)

    Alsop, Richard; Barrett, Matthew; Zheng, Sonbo; Dies, Hannah; Rheinstadter, Maikel


    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.

  10. [Basic mechanisms: absorption and excretion of cholesterol and other sterols]. (United States)

    Cofan Pujol, Montserrat


    Cholesterol is of vital importance for vertebrate cell membrane structure and function. It is obvious that adequate regulation of cholesterol homeostasis is essential. Hypercholesterolemia promotes atherosclerosis and thereby represents a major risk factor for cardiovascular disease. The liver has been considered the major site of control in maintenance of cholesterol homeostasis. The liver facilitates clearance of (very) low density lipoprotein particles and cholesterol-containing chylomicron remnants, synthesizes cholesterol, synthesizes and secretes (nascent) high density lipoprotein particles, secretes cholesterol and bile salts to bile, and is involved in reverse cholesterol transport. In recent years, however, the importance of the intestine in many aspects of cholesterol physiology is increasingly recognized. It has become apparent that direct secretion of cholesterol from the blood compartment into the intestine, or transintestinal cholesterol excretion, plays a major role in disposal of cholesterol via the feces. This review will discuss current knowledge on the physiology of cholesterol homeostasis, with emphasis on cholesterol absorption, cholesterol synthesis and fecal excretion, and therapeutic options for hypercholesterolemia.

  11. Alterations in the homeostasis of phospholipids and cholesterol by antitumor alkylphospholipids

    Directory of Open Access Journals (Sweden)

    Segovia Josefa L


    Full Text Available Abstract The alkylphospholipid analog miltefosine (hexadecylphosphocholine is a membrane-directed antitumoral and antileishmanial drug belonging to the alkylphosphocholines, a group of synthetic antiproliferative agents that are promising candidates in anticancer therapy. A variety of mechanisms have been suggested to explain the actions of these compounds, which can induce apoptosis and/or cell growth arrest. In this review, we focus on recent advances in our understanding of the actions of miltefosine and other alkylphospholipids on the human hepatoma HepG2 cell line, with a special emphasis on lipid metabolism. Results obtained in our laboratory indicate that miltefosine displays cytostatic activity and causes apoptosis in HepG2 cells. Likewise, treatment with miltefosine produces an interference with the biosynthesis of phosphatidylcholine via both CDP-choline and phosphatidylethanolamine methylation. With regard to sphingolipid metabolism, miltefosine hinders the formation of sphingomyelin, which promotes intracellular accumulation of ceramide. We have demonstrated for the first time that treatment with miltefosine strongly impedes the esterification of cholesterol and that this effect is accompanied by a considerable increase in the synthesis of cholesterol, which leads to higher levels of cholesterol in the cells. Indeed, miltefosine early impairs cholesterol transport from the plasma membrane to the endoplasmic reticulum, causing a deregulation of cholesterol homeostasis. Similar to miltefosine, other clinically-relevant synthetic alkylphospholipids such as edelfosine, erucylphosphocholine and perifosine show growth inhibitory effects on HepG2 cells. All the tested alkylphospholipids also inhibit the arrival of plasma-membrane cholesterol to the endoplasmic reticulum, which induces a significant cholesterogenic response in these cells, involving an increased gene expression and higher levels of several proteins related to the pathway of

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

    Directory of Open Access Journals (Sweden)

    Takahiro Furune


    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Kosicek, Marko, E-mail: [Division of Molecular Medicine, Ruder Boskovic Institute, Bijenicka 54, 10000 Zagreb (Croatia); Malnar, Martina, E-mail: [Division of Molecular Medicine, Ruder Boskovic Institute, Bijenicka 54, 10000 Zagreb (Croatia); Goate, Alison, E-mail: [Department of Psychiatry, Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, MO 63110 (United States); Hecimovic, Silva, E-mail: [Division of Molecular Medicine, Ruder Boskovic Institute, Bijenicka 54, 10000 Zagreb (Croatia)


    It has been suggested that cholesterol may modulate amyloid-{beta} (A{beta}) formation, a causative factor of Alzheimer's disease (AD), by regulating distribution of the three key proteins in the pathogenesis of AD ({beta}-amyloid precursor protein (APP), {beta}-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/A{beta} formation in these cholesterol-rich membrane microdomains. To test this we used CHO NPC1{sup -/-} 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, {gamma}-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 A{beta} 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. The role of cholesterol-sphingomyelin membrane nanodomains in the stability of intercellular membrane nanotubes

    Directory of Open Access Journals (Sweden)

    Veranič P


    Full Text Available Maruša Lokar1,*, Doron Kabaso1,2,*, Nataša Resnik3, Kristina Sepcic5, Veronika Kralj-Iglic4,6, Peter Veranic3, Robert Zorec2, Aleš Iglic1,6 1Laboratory of Biophysics, Faculty of Electrical Engineering, 2Laboratory of Neuroendocrinology-Molecular Cell Physiology, Faculty of Medicine, 3Institute of Cell Biology, Faculty of Medicine, 4Faculty of Health Sciences, 5Department of Biology, Biotechnical Faculty, 6Laboratory of Clinical Biophysics, Department of Orthopedic Surgery, Faculty of Medicine, University of Ljubljana, Ljubljana, Slovenia*These authors equally share first authorshipAbstract: Intercellular membrane nanotubes (ICNs are highly curved tubular structures that connect neighboring cells. The stability of these structures depends on the inner cytoskeleton and the cell membrane composition. Yet, due to the difficulty in the extraction of ICNs, the cell membrane composition remains elusive. In the present study, a raft marker, ostreolysin, revealed the enrichment of cholesterol-sphingomyelin membrane nanodomains along ICNs in a T24 (malignant urothelial cancer cell line. Cholesterol depletion, due to the addition of methyl-β-cyclodextrin, caused the dispersion of cholesterol-sphingomyelin membrane nanodomains and the retraction of ICNs. The depletion of cholesterol also led to cytoskeleton reorganization and to formation of actin stress fibers. Live cell imaging data revealed the possible functional coupling between the change from polygonal to spherical shape, cell separation, and the disconnection of ICNs. The ICN was modeled as an axisymmetric tubular structure, enabling us to investigate the effects of cholesterol content on the ICN curvature. The removal of cholesterol was predicted to reduce the positive spontaneous curvature of the remaining membrane components, increasing their curvature mismatch with the tube curvature. The mechanisms by which the increased curvature mismatch could contribute to the disconnection of ICNs are

  15. Dietary cholesterol promotes AOM-induced colorectal cancer through activating the NLRP3 inflammasome. (United States)

    Du, Qianming; Wang, Qing; Fan, Huimin; Wang, Jianing; Liu, Xiuting; Wang, Hong; Wang, Yajing; Hu, Rong


    Prolonged ingestion of a cholesterol-enriched diet induces chronic, auto-inflammatory responses resulting in significant health problems including colorectal cancer. Inflammasomes are thought to mediate intestinal homeostasis, and their dysregulation contributes to inflammatory bowel diseases and colitis-associated cancer (CAC). However, in vitro and in vivo information regarding the inflammation-inducing and tumor-promoting effect of cholesterol is lacking. Here we show that the cholesterol promoted colon carcinogenesis in azoxymethane (AOM)-treated mice through activating the NLRP3 inflammasome. High cholesterol diet (HCD) significantly increased inflammatory responses and tumor burden. Cholesterol crystals, detected in the colon of mice fed with HCD, also promoted NLRP3 inflammasome activation in macrophages, as indicated by elevated expression of cleaved caspase-1, formation of NLRP3-ASC-caspase-1 complex assembly, and higher IL-1β secretion. Importantly, cholesterol was found to inhibit the activity of AMPKα in macrophages, leading to a significant production of mitochondrial ROS, which in turn activated the NLRP3 inflammasome. Moreover, crystal uptake and cathepsin B accounted for cholesterol crystal-induced inactivation of AMPKα. Finally, HCD-induced increase in IL-1β secretion, macrophage infiltration and tumor burden was diminished by the deletion of NLRP3 in AOM-treated mice. Taken together, our findings demonstrate that the pro-inflammatory and cancer-promoting effects of HCD are mediated by the activation of NLRP3 inflammasome. Our study extended our knowledge on how dietary choices can influence processes involved in chronic inflammatory disorders and colorectal cancer.

  16. Comparison on Response and Dissolution Rates Between Ursodeoxycholic Acid Alone or in Combination With Chenodeoxycholic Acid for Gallstone Dissolution According to Stone Density on CT Scan (United States)

    Lee, Jae Min; Hyun, Jong Jin; Choi, In Young; Yeom, Suk Keu; Kim, Seung Young; Jung, Sung Woo; Jung, Young Kul; Koo, Ja Seol; Yim, Hyung Joon; Lee, Hong Sik; Lee, Sang Woo; Kim, Chang Duck


    Abstract Medical dissolution of gallstone is usually performed on radiolucent gallstones in a functioning gallbladder. However, absence of visible gallstone on plain abdominal x-ray does not always preclude calcification. This study aims to compare the response and dissolution rates between ursodeoxycholic acid (UDCA) alone or in combination with chenodeoxycholic acid (CDCA) according to stone density on computed tomography (CT) scan. A total of 126 patients underwent dissolution therapy with either UDCA alone or combination of CDCA and UDCA (CNU) from December 2010 to March 2014 at Korea University Ansan Hospital. In the end, 81 patients (CNU group = 44, UDCA group = 37) completed dissolution therapy for 6 months. Dissolution rate (percentage reduction in the gallstone volume) and response to therapy (complete dissolution or partial dissolution defined as reduction in stone volume of >50%) were compared between the 2 groups. Dissolution and response rates of sludge was also compared between the 2 groups. The overall response rate was 50.6% (CNU group 43.2% vs UDCA group 59.5%, P = 0.14), and the overall dissolution rate was 48.34% (CNU group 41.5% vs UDCA group 56.5%, P = 0.13). When analyzed according to stone density, response rate was 33.3%, 87.1%, 30.0%, and 6.2% for hypodense, isodense, hyperdense, and calcified stones, respectively. Response rate (85.7% vs 88.2%, P = 0.83) and dissolution rate (81.01% vs 85.38%, P = 0.17) of isodense stones were similar between CNU and UDCA group. When only sludge was considered, the overall response rate was 87.5% (CNU group 71.4% vs UDCA group 94.1%, P = 0.19), and the overall dissolution rate was 85.42% (CNU group 67.9% vs UDCA group 92.7%, P = 0.23). Patients with isodense gallstones and sludge showed much better response to dissolution therapy with CNU and UDCA showing comparable efficacy. Therefore, CT scan should be performed before medication therapy if stone dissolution is intended

  17. Systematic coarse graining from structure using internal states: application to phospholipid/cholesterol bilayer

    DEFF Research Database (Denmark)

    Murtola, Teemu; Karttunen, Mikko; Vattulainen, Ilpo


    We present a two-dimensional coarse-grained (CG) model for a lipid membrane composed of phospholipids and cholesterol. The effective CG interactions are determined using radial distribution functions (RDFs) from atom-scale molecular dynamics simulations using the inverse Monte Carlo (IMC) technique...... in the presence of internal states, in general, and present a modified IMC method for their inclusion. The new model agrees with the original models on large-scale structural features such as density fluctuations in pure dipalmitoylphosphocholine and cholesterol domain formation at intermediate concentrations...... and also indicates that ordered and disordered domains form at all cholesterol concentrations, even if the global density remains uniform. The inclusion of ordering also improves transferability of the interactions between different concentrations, but does not eliminate transferability problems completely...

  18. Cholesterol homeostasis: How do cells sense sterol excess? (United States)

    Howe, Vicky; Sharpe, Laura J; Alexopoulos, Stephanie J; Kunze, Sarah V; Chua, Ngee Kiat; Li, Dianfan; Brown, Andrew J


    Cholesterol is vital in mammals, but toxic in excess. Consequently, elaborate molecular mechanisms have evolved to maintain this sterol within narrow limits. How cells sense excess cholesterol is an intriguing area of research. Cells sense cholesterol, and other related sterols such as oxysterols or cholesterol synthesis intermediates, and respond to changing levels through several elegant mechanisms of feedback regulation. Cholesterol sensing involves both direct binding of sterols to the homeostatic machinery located in the endoplasmic reticulum (ER), and indirect effects elicited by sterol-dependent alteration of the physical properties of membranes. Here, we examine the mechanisms employed by cells to maintain cholesterol homeostasis.

  19. Intestinal SR-BI does not impact cholesterol absorption or transintestinal cholesterol efflux in mice. (United States)

    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 nonbiliary 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 in TICE has not been studied. To examine the role of intestinal SR-BI in TICE, sterol balance was measured in control mice and mice transgenically overexpressing SR-BI in the proximal small intestine (SR-BI(hApoCIII-ApoAIV-Tg)). SR-BI(hApoCIII-ApoAIV-Tg) mice had significantly lower plasma cholesterol levels compared with wild-type controls, yet SR-BI(hApoCIII-ApoAIV-Tg) mice had normal fractional cholesterol absorption and fecal neutral sterol excretion. Both in the absence or presence of ezetimibe, intestinal SR-BI overexpression had no impact on the amount of cholesterol excreted in the feces. To specifically study effects of intestinal SR-BI on TICE we crossed SR-BI(hApoCIII-ApoAIV-Tg) mice into a mouse model that preferentially utilized the TICE pathway for RCT (Niemann-Pick C1-like 1 liver transgenic), and likewise found no alterations in cholesterol absorption or fecal sterol excretion. Finally, mice lacking SR-BI in all tissues also exhibited normal cholesterol absorption and fecal cholesterol disposal. Collectively, these results suggest that SR-BI is not rate limiting for intestinal cholesterol absorption or for fecal neutral sterol loss through the TICE pathway.

  20. 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.

  1. Transport of maternal cholesterol to the fetus is affected by maternal plasma cholesterol concentrations in the golden Syrian hamster. (United States)

    Burke, Katie T; Colvin, Perry L; Myatt, Leslie; Graf, Gregory A; Schroeder, Friedhelm; Woollett, Laura A


    The fetus has a high requirement for cholesterol and synthesizes cholesterol at elevated rates. Recent studies suggest that fetal cholesterol also can be obtained from exogenous sources. The purpose of the current study was to examine the transport of maternal cholesterol to the fetus and determine the mechanism responsible for any cholesterol-driven changes in transport. Studies were completed in pregnant hamsters with normal and elevated plasma cholesterol concentrations. Cholesterol feeding resulted in a 3.1-fold increase in the amount of LDL-cholesterol taken up by the fetus and a 2.4-fold increase in the amount of HDL-cholesterol taken up. LDL-cholesterol was transported to the fetus primarily by the placenta, and HDL-cholesterol was transported by the yolk sac and placenta. Several proteins associated with sterol transport and efflux, including those induced by activated liver X receptor, were expressed in hamster and human placentas: NPC1, NPC1L1, ABCA2, SCP-x, and ABCG1, but not ABCG8. NPC1L1 was the only protein increased in hypercholesterolemic placentas. Thus, increasing maternal lipoprotein-cholesterol concentrations can enhance transport of maternal cholesterol to the fetus, leading to 1) increased movement of cholesterol down a concentration gradient in the placenta, 2) increased lipoprotein secretion from the yolk sac (shown previously), and possibly 3) increased placental NPC1L1 expression.

  2. Cholesterol levels in fragile X syndrome. (United States)

    Berry-Kravis, Elizabeth; Levin, Rebecca; Shah, Haroon; Mathur, Shaguna; Darnell, Jennifer C; Ouyang, Bichun


    Fragile X syndrome (FXS) is associated with intellectual disability and behavioral dysfunction, including anxiety, ADHD symptoms, and autistic features. Although individuals with FXS are largely considered healthy and lifespan is not thought to be reduced, very little is known about the long-term medical health of adults with FXS and no systematically collected information is available on standard laboratory measures from metabolic screens. During the course of follow up of a large cohort of patients with FXS we noted that many patients had low cholesterol and high density lipoprotein (HDL) values and thus initiated a systematic chart review of all cholesterol values present in charts from a clinic cohort of over 500 patients with FXS. Total cholesterol (TC), low density lipoprotein (LDL) and HDL were all significantly reduced in males from the FXS cohort relative to age-adjusted population normative data. This finding has relevance for health monitoring in individuals with FXS, for treatments with cholesterol-lowering agents that have been proposed to target the underlying CNS disorder in FXS based on work in animal models, and for potential biomarker development in FXS.

  3. Structure of cholesterol/ceramide monolayer mixtures

    DEFF Research Database (Denmark)

    Scheffer, L.; Solomonov, I.; Weygand, M.J.


    The structure of monolayers of cholesterol/ ceramide mixtures was investigated using grazing incidence x-ray diffraction, immunofluorescence, and atomic force microscopy techniques. Grazing incidence x-ray diffraction measurements showed the existence of a crystalline mixed phase of the two...

  4. Blood cholesterol, a public health perspective.

    NARCIS (Netherlands)

    Verschuren, W.M.M.


    Changes in total cholesterol levels (TC) were studied using data from three epidemiological studies: about 30,000 men and women aged 37-43 were examined between 1974 and 1980 (CB Project), about 80,000 men aged 33-37 between 1981 and 1986 (RIFOH Project) and 42,000 men and women aged 20-59 from 1987

  5. Garbanzo diet lowers cholesterol in hamsters (United States)

    Cholesterol-lowering potential of diets with 22% protein from Chickpea (Cicer arietinum, European variety of Garbanzo, Kabuli Chana), Bengal gram (Cicer arietinum, Asian variety of Garbanzo, Desi Chana, smaller in size, yellow to black color), lentils, soy protein isolate, hydrolyzed salmon protein...

  6. Cholesterol and sphingolipids in alcohol-induced liver injury. (United States)

    Fernández, Anna; Colell, Anna; Garcia-Ruiz, Carmen; Fernandez-Checa, José C


    The pathogenesis of alcohol-induced liver disease (ALD) is still poorly understood. One of the clues to its progression relates to the alcohol-mediated susceptibility of hepatocytes to cell death by reactive oxygen species (ROS) and inflammatory cytokines. Tumor necrosis factor alpha (TNF) has been considered a key ALD mediator with acidic sphingomyelinase (ASMase)-mediated ceramide generation playing a critical role. TNF receptor 1 and 2 knock-out mice or ASMase(-/-) mice exhibit resistance to alcohol-mediated fatty liver and cell death. Furthermore, alcohol feeding has been shown to sensitize hepatocytes to TNF due to the limitation of mitochondrial glutathione (mGSH) through impaired import of GSH from the cytosol due to altered membrane order parameter caused by mitochondrial cholesterol increase. Selective pharmacological depletion of mGSH sensitizes hepatocytes to TNF-mediated cell death, which reproduces the observations found with alcohol feeding. TNF signaling analyses in hepatocytes with or without mGSH depletion indicate that mGSH prevents cardiolipin peroxidation (CLOOH) formation by TNF-induced ROS via ASMase and that CLOOH cooperates with oligomerized Bax to cause mitochondrial outer membrane permeabilization through destabilization of the lipid bilayer via increased bilayer-to-inverted hexagonal phase transitions. Thus, activation of ASMase and cholesterol-mediated mGSH depletion both collaborate to promote alcohol-induced TNF-mediated hepatocellular damage, suggesting novel therapeutic opportunities in ALD.

  7. Effects of oxidation on the hydrolysis by cholesterol esterase of sitosteryl esters as compared to a cholesteryl ester. (United States)

    Julien-David, Diane; Ennahar, Saïd; Miesch, Michel; Geoffroy, Philippe; Raul, Francis; Aoude-Werner, Dalal; Lessinger, Jean-Marc; Marchioni, Eric


    Phytosteryl esters (PE) are used as ingredients in functional food to decrease plasma concentration of low density lipoprotein-cholesterol (LDL-C). Effective impairment of cholesterol absorption by PE suggests that these esters are hydrolyzed by the pancreatic cholesterol esterase (CEase, EC and the liberated sterol may interfere with cholesterol reducing its intestinal absorption. PE-enriched foods are marketed for cooking purposes, and temperature is one of the most important factors leading to the formation of oxidation products. Very little is known about the outcome of PE oxides during the digestive process. A new analytical method based on mass spectrometric detection directly after enzymatic reaction was developed to determine in vitro the activity of CEase on PE and their oxides present in functional food. Using this method, we identified a new inhibitor of CEase: sitosteryl 9,10-dihydroxystearate, which behaves as a non-competitive inhibitor of the hydrolysis of cholesteryl oleate and sitosteryl oleate.

  8. Trans Fat Now Listed With Saturated Fat and Cholesterol (United States)

    ... Trans Fat Now Listed With Saturated Fat and Cholesterol Share Tweet Linkedin Pin it More sharing options ... I Do About Saturated Fat, Trans Fat, and Cholesterol? When comparing foods, look at the Nutrition Facts ...

  9. Remnant cholesterol as a cause of ischemic heart disease

    DEFF Research Database (Denmark)

    Varbo, Anette; Benn, Marianne; Nordestgaard, Børge G


    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...

  10. Are You Taking the Right Treatment for Your High Cholesterol? (United States)

    ... you taking the right treatment for your high cholesterol? Our analysis and new guidelines could change your ... people consider a moderate-intensity statin (reduces LDL cholesterol by 30 percent to 50 percent) • People 40 ...

  11. Plasma Ubiquinone, Alpha-Tocopherol and Cholesterol in Man

    DEFF Research Database (Denmark)

    Karlsson, Jan; Diamant, Bertil; Edlund, Per Olof


    Farmakologi, Coenzyme Q10, free cholesterol, vitamin E, antioxidants, Alpha-Tocopherol, vitamin Q, plasma, LDL-particle......Farmakologi, Coenzyme Q10, free cholesterol, vitamin E, antioxidants, Alpha-Tocopherol, vitamin Q, plasma, LDL-particle...

  12. CDC Vital Signs: High Blood Pressure and Cholesterol (United States)

    ... the MMWR Science Clips High Blood Pressure and Cholesterol Out of Control Recommend on Facebook Tweet Share ... High Blood Pressure and High Cholesterol Among US Adults SOURCES: National Health and Nutrition ...

  13. 1 in 7 Obese People Has Normal Blood Pressure, Cholesterol (United States)

    ... in 7 Obese People Has Normal Blood Pressure, Cholesterol But that doesn't mean the excess weight ... people studied, 14 percent had normal blood sugar, cholesterol and blood pressure readings, the study found. Doctors ...

  14. Nonfasting triglycerides, cholesterol, and ischemic stroke in the general population

    DEFF Research Database (Denmark)

    Varbo, Anette; Nordestgaard, Børge G; Tybjaerg-Hansen, Anne


    Current guidelines on stroke prevention have recommendations on desirable cholesterol levels, but not on nonfasting triglycerides. We compared stepwise increasing levels of nonfasting triglycerides and cholesterol for their association with risk of ischemic stroke in the general population....

  15. Cholesterol paradox: a correlate does not a surrogate make. (United States)

    DuBroff, Robert


    The global campaign to lower cholesterol by diet and drugs has failed to thwart the developing pandemic of coronary heart disease around the world. Some experts believe this failure is due to the explosive rise in obesity and diabetes, but it is equally plausible that the cholesterol hypothesis, which posits that lowering cholesterol prevents cardiovascular disease, is incorrect. The recently presented ACCELERATE trial dumbfounded many experts by failing to demonstrate any cardiovascular benefit of evacetrapib despite dramatically lowering low-density lipoprotein cholesterol and raising high-density lipoprotein cholesterol in high-risk patients with coronary disease. This clinical trial adds to a growing volume of knowledge that challenges the validity of the cholesterol hypothesis and the utility of cholesterol as a surrogate end point. Inadvertently, the cholesterol hypothesis may have even contributed to this pandemic. This perspective critically reviews this evidence and our reluctance to acknowledge contradictory information.

  16. Elucidating the effects of cholesterol on the molecular packing of double-chained cationic lipid langmuir monolayers by infrared reflection-absorption spectroscopy. (United States)

    Kuo, An-Tsung; Chang, Chien-Hsiang


    Cholesterol has been suggested to play a role in stable vesicle formation by adjusting the molecular packing of the vesicular bilayer. To explore the mechanisms involved in adjusting the bilayer structure by cholesterol, the molecular packing behavior in a mimic outer layer of cationic dialkyldimethylammonium bromide (DXDAB)/cholesterol vesicular bilayer was investigated by the Langmuir monolayer approach with infrared reflection-absorption spectroscopy (IRRAS). The results indicated that the addition of cholesterol in the DXDAB Langmuir monolayers not only restrained the desorption of the DXDAB with short hydrocarbon chains, such as ditetradecyldimethylammonium bromide or dihexadecyldimethylammonium bromide, into the aqueous phase but also induced a condensing effect on the DXDAB monolayers. At a liquid-expanded (LE) state, the ordering effect of cholesterol accompanying the condensing effect occurred in the mixed DXDAB/cholesterol monolayers due to the tendency of maximizing hydrocarbon chain contact between cholesterol and the neighboring hydrocarbon chains. However, for the mixed monolayers containing the DXDAB with long hydrocarbon chains, such as dioctadecyldimethylammonium bromide (DODAB), the disordering effect of cholesterol took place at a liquid-condensed (LC) state. This was related to the molecular structure of cholesterol and hydrocarbon chain length of DODAB. The rigid sterol ring of cholesterol hindered the portion of neighboring hydrocarbon chains from motion. However, the flexible alkyl side-chain of cholesterol along with the corresponding portion of neighboring hydrocarbon chains formed a fluidic region, counteracting the enhanced conformational order induced by the sterol ring of cholesterol. Furthermore, the long hydrocarbon chains of DODAB possessed a more pronounced motion freedom, resulting in a more disordered packing of the monolayers.

  17. A population-based follow-up study on gallstone disease among type 2 diabetics in Kinmen, Taiwan

    Institute of Scientific and Technical Information of China (English)

    Tao-Hsin Tung; Hsiao-Man Ho; Hui-Chuan Shih; Pesus Chou; Jorn-Hon Liu; Victor TK Chen; De-Chuan Chan; Chi-Ming Liu


    AIM: To assess the incidence of and risk factors for gallstone disease (GSD) among type 2 diabetics in Kinmen,Taiwan.METHODS: A screening program for GSD was performed by two specialists who employed real-time abdominal ultrasound to examine the abdominal region after patients had fasted for at least eight hours. Screening, which was conducted in 2001, involved 848 patients diagnosed with type 2 diabetes. After exclusion of 63subjects with prevalent GSD, 377 participants without GSD were invited in 2002 for a second round of screening. A total of 281 (74.5%) subjects were re-examined.RESULTS: Among the 281 type 2 diabetics who had no GSD at the first screening, 10 had developed GSD by 2002. The incidence was 3.56% per year (95%CI:1.78% per year-6.24% per year). Using a Cox regression model, age (RR = 1.07, 95% CI: 1.00-1.14), waist circumference (RR = 1.12, 95% CI: 1.01-1.29), and ALT (RR = 1.13, 95%CI: 1.01-1.26) appeared to be significantly correlated with development of GSD.CONCLUSION: Older age is a known risk factor for the development of GSD. Our study shows that greater waist circumference and elevated ALT levels are also associated with the development of GSD among type 2 diabetics in Kinmen.

  18. Gallstone Ileus: a Surgical Emergency Presentation Íleo biliar: presentación en la urgencia quirúrgica

    Directory of Open Access Journals (Sweden)

    Reinaldo Jiménez Prendes


    Full Text Available The case of a 60 years old female patient with a history of gallstones that was admitted as an emergency because of abdominal pain, vomiting and abdominal distension of 2 days is presented. The patient presented also secondary moderate dehydration. In a simple abdominal radiography, radiological signs of intestinal occlusion were found. Electrolyte imbalance was corrected and an exploratory laparotomy was performed. Through this procedure, a large stone was found in the terminal ileum. Enterolithotomy was performed along with enterorraphy, thus solving the occlusion.Se presenta el caso de una paciente de 60 años de edad, con antecedentes de litiasis vesicular, que ingresó de urgencia por presentar un cuadro de dolor abdominal, vómitos y distensión en el abdomen con 2 días de evolución. De forma secundaria presentó una deshidratación moderada. En la radiografía simple de abdomen se constataron signos radiológicos de oclusión intestinal. Se corrigió el desequilibrio hidroelectrolítico y se realizó una laparotomía exploradora, en la que se encontró un cálculo grande enclavado en el íleon terminal. Se realizó una enterolitotomía con enterorrafia y resolvió el cuadro oclusivo.

  19. Polymer sorbent with the properties of an artificial cholesterol receptor (United States)

    Polyakova, I. V.; Ezhova, N. M.; Osipenko, A. A.; Pisarev, O. A.


    A cholesterol-imprinted polymer sorbent and the corresponding reticular control copolymer were synthesized from hydroxyethyl methacrylate and ethyleneglycol dimethacrylate. The sorption isotherms of cholesterol were analyzed using the generalized Langmuir and Freundlich equations. In the case of the imprinted reticular polymer, cholesterol sorption occurred on the energetically homogeneous binding centers, forming one monolayer, while the nonspecific sorption of cholesterol on the control copolymer occurred with energetically nonhomogeneous binding of the sorbate and depended on the physicochemical conditions of sorption.

  20. Effects of cholesterol and lipoproteins on endocytosis by a monocyte-like cell line. (United States)

    Esfahani, M; Scerbo, L; Lund-Katz, S; DePace, D M; Maniglia, R; Alexander, J K; Phillips, M C


    peroxidase binding and uptake by adsorptive endocytosis. The rate of fluid endocytosis and endosome formation seems to depend on cellular cholesterol content presumably because cholesterol is involved in maintaining the appropriate plasma membrane structure and fluidity.