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, Sep 29, 2015
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    • "Many previous studies have shown that the gallstone disease risk factors are multifactorial (Panpimanmas & Manmee, 2009). These risk factors include increasing age, sex, dietary, high calorie intake, low fiber intake, high refined carbohydrates, hyper triglyceridaemia, physical inactivity, pregnancy, parity, overweight and obesity (Portincasa et al., 2006; Cariati, 2013; Storti et al, 2005; Panpimanmas & Manmee, 2009; Henao-Morán et al., 2014; Chandran et al., 2014). "
    Global journal of health science 07/2015; 8(4). DOI:10.5539/gjhs.v8n4p60
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    • "Consumption of simple sugars and saturated fat has been mostly associated to a higher risk, while fibre intake consistently reduces the risk (Portincasa, 2006). "
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    ABSTRACT: Dietary hypocholesterolemic spices - curcumin (active compound of turmeric (Curcuma longa) and capsaicin (active compound of red pepper (Capsicum annuum), the active principles of spices - turmeric (Curcuma longa) and red pepper (Capsicum annuum), fenugreek (Trigonella foenum-graecum) seeds, garlic (Allium sativum), and onion (Allium cepa) are documented to have anti-cholelithogenic property in animal model. These spices prevent the induction of cholesterol gallstones by lithogenic high cholesterol diet and also regress the pre-established cholesterol gallstones, by virtue of their hypolipidemic potential. The antilithogenic influence of these spices is primarily attributable to their hypocholesterolemic effect. Increased cholesterol saturation index, cholesterol: phospholipid ratio and cholesterol: bile acid ratio in the bile caused by the lithogenic diet was countered by these spices. The anti-lithogenicity of these hypocholesterolemic spices was considered to be due also to their influence on biliary proteins which have pro-nucleating activity and anti-nucleating activity. Investigations on the involvement of biliary proteins in cholesterol crystal nucleation revealed that in an in vitro bile model, low molecular weight biliary proteins of the lithogenic diet fed animals have a pro-nucleating activity. On the contrary, low molecular weight biliary proteins of the animals fed hypocholesterolemic spices along with lithogenic diet showed a potent anti-nucleating activity.
    Critical reviews in food science and nutrition 07/2015; DOI:10.1080/10408398.2014.1003783 · 5.18 Impact Factor
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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 · 2.89 Impact Factor
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