Cholesterol gallstone disease

Department of Internal and Public Medicine, University Medical School, Bari, Italy.
The Lancet (Impact Factor: 45.22). 08/2006; 368(9531):230-9. DOI: 10.1016/S0140-6736(06)69044-2
Source: PubMed

ABSTRACT With a prevalence of 10-15% in adults in Europe and the USA, gallstones are the most common digestive disease needing admission to hospital in the West. The interplay between interprandial and postprandial physiological responses to endogenous and dietary lipids underscores the importance of coordinated hepatobiliary and gastrointestinal functions to prevent crystallisation and precipitation of excess biliary cholesterol. Indeed, identifying the metabolic and transcriptional pathways that drive the regulation of biliary lipid secretion has been a major achievement in the field. We highlight scientific advances in protein and gene regulation of cholesterol absorption, synthesis, and catabolism, and biliary lipid secretion with respect to the pathogenesis of cholesterol gallstone disease. We discuss the physical-chemical mechanisms of gallstone formation in bile and the active role of the gallbladder and the intestine. We also discuss gaps in our knowledge of the pathogenesis of gallstone formation and the potential for gene targeting in therapy.

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Available from: Piero Portincasa, Aug 01, 2015
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    • ". Many patients with metabolic syndrome experience acute pancreatitis, but its presence does not seem to affect the course of disease severity [98]. Obesity, however, is a well-recognized risk factor for AP because of its increased risk of (cholesterol) gallstones and biliary sludge, also as part of postoperative complication following gastric bypass surgery for morbid obesity [99] [7] [100]. It has been shown that the presence of increased pancreatic fat, as assessed by MRI, is not an independent predictor of post-ERCP pancreatitis [101], but increased BMI can act as an independent risk factor for a more severe course of acute pancreatitis, mainly in terms of prolonged hospitalization [102] and mortality [17], probably acting through the " toxic " effect of the increased amount of abdominal fat and an overactive systemic inflammatory response [103]. "
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    ABSTRACT: The worldwide obesity epidemic is paralleled by a rise in the incidence of pancreatic disorders ranging from "fatty" pancreas to pancreatitis and cancer. Body fat accumulation and pancreatic dysfunctions have common pathways, mainly acting through insulin resistance and low-grade inflammation, frequently mediated by the epigenome. These mechanisms are affected by lifestyle and by the toxic effects of fat and pollutants. An early origin is common, starting in pediatric age or during the fetal life in response to nutritional factors, endocrine disruptor chemicals (EDCs) or parental exposure to toxics. A "fatty pancreas" is frequent in obese and is able to induce pancreatic damage. The fat is a target of EDCs and of the cytotoxic/mutagenic effects of heavy metals, and is the site of bioaccumulation of lipophilic and persistent pollutants related with insulin resistance and able to promote pancreatic cancer. Increased Body Mass Index (BMI) can act as independent risk factor for a more severe course of acute pancreatitis and obesity is also a well-known risk factor for pancreatic cancer, that is related with BMI, insulin resistance, and duration of exposure to the toxic effects of fat and/or of environmental pollutants. All these mechanisms involve gene-environment interactions through epigenetic factors, and might be manipulated by primary prevention measures. Further studies are needed, pointing to better assess the interplays of modifiable factors on both obesity and pancreatic diseases, and to verify the efficacy of primary prevention strategies involving lifestyle and environmental exposure to toxics
    European Journal of Internal Medicine 12/2014; 25(10):865-873. DOI:10.1016/j.ejim.2014.10.012 · 2.30 Impact Factor
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    • "The risk factors associated with GSD are age, female gender, obesity, diabetes, dyslipidemia, high-calorie and low-fiber diets, low physical activity, long-term total parenteral nutrition use, and family history [1] [2] [3]. Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of the severity of fat accumulation in hepatocytes [5] [6], and it has a direct impact on hepatic cholesterol synthesis and the Correspondence: Yi-Ching Yang, MD, MPH, Department of Family Medicine, National Cheng Kung University Hospital, No.138, Sheng-Li Rd, Tainan City 70403, Taiwan. "
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    ABSTRACT: Abstract Objective. Nonalcoholic fatty liver disease (NAFLD) and gallstone disease (GSD) share some of the same risk factors. The association between NAFLD and GSD was inconsistent. Moreover, there are no studies on the association between GSD and the severity of NAFLD in the literature. The aim of this study was to determine the relationship between the severity of NAFLD and GSD in a Taiwanese population. Materials and methods. A total of 12,033 subjects were enrolled. The diagnoses of GSD and NAFLD were based on the finding of abdominal ultrasonography. The severity of NAFLD was divided into mild, moderate, and severe. Results. Compared with the non-GSD group, the GSD one was older and had a higher BMI, blood pressure, fasting plasma glucose, cholesterol, triglyceride, and higher prevalence of diabetes and hypertension, but they had a lower eGFR and HDL-C level and less prevalence of current smoking and alcohol drinking. There was a significant difference in the severity of NAFLD between subjects with and without GSD. Based on logistic regression, age ≥65 versus <40 years, 40-64.9 versus <40 years, female, current alcohol drinking, diabetes, hypertension, HDL-C level and moderate to severe NAFLD, but not mild NAFLD, were the independently associated risk factors of GSD. Conclusion. Moderate to severe, but not mild, NAFLD was associated with an increased risk of GSD, independent of the traditional cardio-metabolic risk factor. Age, female, diabetes, and hypertension were also related to a higher risk of GSD, but HDL-C level and moderate alcohol drinking showed a lower risk.
    Scandinavian Journal of Gastroenterology 07/2014; DOI:10.3109/00365521.2014.920912 · 2.33 Impact Factor
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    • "Cholesterol gallstones are one of the most frequent gastroenterological affections, representing a gallbladder disease (Portincasa et al., 2006); its prevalence in Western countries is 14–16%, caused by obesity and a high-fat diet. "
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    ABSTRACT: 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. Copyright © 2013 John Wiley & Sons, Ltd.
    Phytotherapy Research 02/2014; 28(2). DOI:10.1002/ptr.4964 · 2.40 Impact Factor
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