1,721,018 research outputs found
Thyroid Function: a Target for Endocrine Disruptors, Air Pollution, and Radiofrequencies
No full text: Thyroid diseases are progressively increasing, mainly in terms of congenital hypothyroidism, thyroiditis, and childhood thyrotoxicosis. A rapid increase in the incidence of thyroid cancer in children and adolescents has also been observed in the last decades, mirroring the incidence trend observed in adults. This epidemiologic tendency is paralleled by a progressive increment in costs for diagnosis and treatment of thyroid disease. Thyroid diseases depend on both genetic and environmental factors. Growing evidence link both altered thyroid function and thyroid cancer with a number of widely diffused toxic chemicals of anthropogenic origin. These synthetic substances persistently contaminate the environmental matrices (i.e., air, soil, water) and the food chain, and bio-accumulate in humans, starting from in utero life. Environmental toxics as air pollutants, endocrine disruptors, and high-frequency electromagnetic fields can act through common pathways, on common targets, and with trans-generational effects, with combined mechanisms contributing to thyroid damage. As shown by experimental and epidemiologic observation, these mechanisms include modulation of hormone synthesis, transportation and metabolism, direct interference with thyroid hormone receptors, modulation of gene expression, and autoimmunity. Available evidences linking environmental pollutants and thyroid disease, including cancer, should not be underestimated in consideration of the wide, worldwide, and increasing spread of these toxic substances, and of the key role of thyroid hormones in maintaining the systemic metabolic homeostasis and during the development. Thus, primary prevention measures are urgently needed in particular to protect children, the most exposed and vulnerable subjects
Confirmatory factor analysis of the Patient Assessment of Constipation-Symptoms (PAC-SYM) among patients with chronic constipation
No full textPAC-SYM is widely adopted to asses constipation severity. However, it has been validated in a small sample, few items have been included based on expert opinion and not on empirical grounds, and its factor structure has never been replicated. We aimed at evaluating the psychometric properties of PAC-SYM in patients with chronic constipation.We enrolled 2,203 outpatients with chronic constipation in two waves. We used wave I sample to test the psychometric properties of the PAC-SYM and wave II sample to cross-validate its factor structure, to assess criterion validity, responsiveness to clinical change, and its minimal clinically important difference.Only a minority of patients reported any rectal tearing (38 %). Deletion of such item leads to a 11-item version (M:PAC-SYM). The remaining items in the rectal domain were moderately correlated with the stool domain. Exploratory factor analysis and confirmatory factor analysis revealed a bifactor structure with two subscales (stool and abdominal symptoms) and a general severity factor. The M:PAC-SYM demonstrated excellent reliability, moderate correlation with SF-12 and treatment satisfaction (r = 0.28-0.45), discrimination across Rome III criteria for functional constipation and abdominal pain, and responsiveness to clinical change (beta = -0.49; omega (2) = 0.25). M:PAC-SYM minimal clinically important difference was 0.24.Our analysis shows that the rectal domain may not represent a relevant cluster of symptoms for patients with chronic constipation. We developed a modified version of the PAC-SYM which might better represent symptom severity of most patients seeking care in gastroenterology referral centers
Therapy of gallstone disease: What it was, what it is, what it will be
No full text: 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 non-surgical 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
Obesity and the risk and prognosis of gallstone disease and pancreatitis
No full textObesity is a risk factor for the formation of cholesterol gallstones and exposes patients to increased risk of gallstone-related complications and cholecystectomy. Rapid weight loss achieved by very low calorie diets or bariatric surgery is also a risk factor for cholelithiasis in obese patients, and therapy should take into account the higher prevalence of gallstones, the possibility of more frequent complications and the need for prophylactic treatment with oral ursodeoxycholic acid during weight loss. Obesity is also frequent in children and adolescents, and the burden of cholesterol cholelithiasis is increasing in this population. The chance to develop acute pancreatitis and the severity of the disease are higher in obese subjects because of specific pathogenic factors, including supersaturated bile and crystal formation, rapid weight loss, and visceral obesity. All health policies aimed at reducing the incidence of obesity worldwide will decrease the incidence of gallstones and gallstone-related complications. The pathophysiological scenarios and the therapeutic implications for obesity, gallstone disease, and pancreatitis are discussed. (C) 2014 Elsevier Ltd. All rights reserved
Microbiota in health and irritable bowel syndrome: current knowledge, perspectives and therapeutic options
No full textAbstract The gastrointestinal tract is a natural reservoir of microbiota. The gut is germ-free at birth, but rapidly becomes host to various bacteria establishing a progressively mutual relationship. The composition of gut microbiota is individual-specific and depends on the genotype of the host and environmental factors. Novel techniques have been used to characterize gastrointestinal microbiota, including genomic approaches. The bacterial profile shows that dominant and minor phyla are present in the gastrointestinal tract. From the proximal to the distal segments of the gut the bacterial density gradually increases, reaching an estimated 10(11) to 10(12) bacteria per gram of colonic content. Dynamic interactions between gut and microbiota play a physiological role in metabolic, protective and structural functions, while dysbiosis contributes to several diseases. Microbiota appear to play a role in IBS, where qualitative and quantitative changes of bacteriaoccur in IBS subtypes. Initial therapeutic approaches in IBS have focused on microbiota. The relationship between perturbations of the microbiota, mucosal inflammation and IBS remains to be further investigated.The gastrointestinal tract is a natural reservoir of microbiota. The gut is germ-free at birth, but rapidly becomes host to various bacteria establishing a progressively mutual relationship. The composition of gut microbiota is individual-specific and depends on the genotype of the host and environmental factors. Novel techniques have been used to characterize gastrointestinal microbiota, including genomic approaches. The bacterial profile shows that dominant and minor phyla are present in the gastrointestinal tract. From the proximal to the distal segments of the gut the bacterial density gradually increases, reaching an estimated 10(11) to 10(12) bacteria per gram of colonic content. Dynamic interactions between gut and microbiota play a physiological role in metabolic, protective and structural functions, while dysbiosis contributes to several diseases. Microbiota appear to play a role in IBS, where qualitative and quantitative changes of bacteriaoccur in IBS subtypes. Initial therapeutic approaches in IBS have focused on microbiota. The relationship between perturbations of the microbiota, mucosal inflammation and IBS remains to be further investigated
The role of microbiota in nonalcoholic fatty liver disease
No full textNonalcoholic fatty liver disease (NAFLD) is the most frequent liver disease worldwide. Gut microbiota can play a role in the pathogenesis of NAFLD since dysbiosis is associated with reduced bacterial diversity, altered Firmicutes/Bacteroidetes ratio, a relative abundance of alcohol-producing bacteria, or other specific genera. Changes can promote disrupted intestinal barrier and hyperpermeability, filtration of bacterial products, activation of the immune system, and pro-inflammatory changes in the intestine, in the liver, and at a systemic level. Microbiota-derived molecules can contribute to the steatogenic effects. The link between gut dysbiosis and NAFLD, however, is confused by several factors which include age, BMI, comorbidities, dietary components, and lifestyle. The role of toxic chemicals in food and water requires further studies in both gut dysbiosis and NAFLD. We can anticipate that gut microbiota manipulation will represent a potential therapeutic tool to delay or reverse the progression of NAFLD, paving the way to primary prevention measures
Effects of dietary education, followed by a tailored fructose-restricted diet in adults with fructose malabsorption
No full textOBJECTIVE: Fructose is absorbed by GLUT transporters in the small intestine. If this process is inadequate, abdominal symptoms because of fructose intolerance may arise. The effect of a tailored fructose-restricted diet on gastrointestinal complaints was assessed in patients with fructose intolerance. MATERIALS AND METHODS: Following an abnormal fructose breath test (50 g), 107 patients (64 also with lactose intolerance) entered three study periods: weeks 0-32 (free diet), weeks 32-36 (progressive increasing amount of fructose up to quantity inducing symptoms, 'trigger dose'), and weeks 36-48 (tailored fructose-restricted diet according to the 'trigger dose'). A subgroup of 15 patients underwent additional fructose breath tests (35, 25 g) to compare three different doses. RESULTS: At baseline, the most frequent symptoms were bloating and abdominal pain, and were more severe with combined fructose and lactose intolerance. During the free diet, patients reported eliminating (48%) or reducing (52%) fructose-containing foods, with a significant improvement in symptoms (abdominal pain from 79.7 +/- 1.3 to 19.3 +/- 1.8 mm; bloating from 83.1 +/- 1.3 to 19.4 +/- 1.8 mm; number of evacuations/day from 3.9 +/- 0.16 to 1.1 +/- 0.04; Bristol score from 5.1 +/- 0.14 to 3.8 +/- 0.1, P < 0.00001). During the tailored fructose-restricted diet, the consistent improvement in symptoms persisted and was similar to the improvement on free diet (abdominal pain 23.6 +/- 1.9 mm; bloating 19.4 +/- 1.8 mm; number of evacuations/day 1.7 +/- 0.07; Bristol score 3.5 +/- 0.06, P<0.00001 vs. baseline). A dose-dependent effect of fructose was observed on symptoms during the fructose breath test. CONCLUSION: In our setting, individuals with fructose intolerance show an inappropriate dietary self-management. By contrast, a tailored fructose-restricted diet improves gastrointestinal symptoms without senseless food deprivation
Current views on genetics and epigenetics of cholesterol gallstone disease
No full text: 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
The interaction of bile acids and gut inflammation influences the pathogenesis of inflammatory bowel disease
No full textBile acids (BA) are amphipathic molecules originating from cholesterol in the liver and from microbiota-driven biotransformation in the colon. In the gut, BA play a key role in fat digestion and absorption and act as potent signaling molecules on the nuclear farnesoid X receptor (FXR) and membrane-associated G protein-coupled BA receptor-1 (GPBAR-1). BA are, therefore, involved in the maintenance of gut barrier integrity, gene expression, metabolic homeostasis, and microbiota profile and function. Disturbed BA homeostasis can activate pro-inflammatory pathways in the gut, while inflammatory bowel diseases (IBD) can induce gut dysbiosis and qualitative and/or quantitative changes of the BA pool. These factors contribute to impaired repair capacity of the mucosal barrier, due to chronic inflammation. A better understanding of BA-dependent mechanisms paves the way to innovative therapeutic tools by administering hydrophilic BA and FXR agonists and manipulating gut microbiota with probiotics and prebiotics. We discuss the translational value of pathophysiological and therapeutic evidence linking BA homeostasis to gut inflammation in IBD
Clinical, cytological and histological profile of a large cohort of patients with thyroid nodule living in Apulia.
No full text- …
