1,721,026 research outputs found
Diet and contaminants: driving the rise to obesity epidemics?
No full textThe obesity epidemic is spreading worldwide without reversal trend and despite specific policies oriented to dietary habits and lifestyle, which seem to have modest effects. Genetic factors only partly explain the rise, whereas environmental factors seem to play a key role, mainly by gene-environment interactions through epigenetic mechanisms. A number of animal and human studies point to maternal diet, intestinal microbiota and chemicals introduced as contaminants with food, all factors able to increase the risk of obesity. Widely diffused toxics (mainly BPA, phthalates, pesticides) are able to promote obesity in children and adults, mainly by acting on the differentiation pathway linking multipotent stromal stem cell to mature adipocyte, modulating epigenetic factors and influencing a series of mechanisms finally leading to altered dietary habits, increased adipocyte formation and fat storage. Furthermore, the adipose tissue is an important target for several chemicals (mainly POPs) which represent a threat to metabolic health. In conclusion, besides excessive individual energy intake and inadequate lifestyle, other broadly diffused and modifiable factors (mainly ingestion of toxic chemicals with food) seem to have a critical role in the rapid epidemiological growing of obesity, also considering trans-generational transmission of risk and later development of obesity due to exposure during early life. Further studies are needed, to better assess interactions between cumulative effects of toxic food contaminants and modification of diet and lifestyle, and to verify the efficacy of primary prevention strategies acting on all these factors and potentially able to reverse the continuous rising of the obesity epidemic
Preventing a mass disease: The case of gallstones disease: Role and competence for family physicians
Full text linkGallstone 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
Cholesterol cholelithiasis: part of a systemic metabolic disease, prone to primary prevention
No full textIntroduction: Cholesterol gallstone disease have relationships with various conditions linked with insulin resistance, but also with heart disease, atherosclerosis, and cancer. These associations derive from mechanisms active at a local (i.e. gallbladder, bile) and a systemic level and are involved in inflammation, hormones, nuclear receptors, signaling molecules, epigenetic modulation of gene expression, and gut microbiota. Despite advanced knowledge of these pathways, the available therapeutic options for symptomatic gallstone patients remain limited. Therapy includes oral litholysis by the bile acid ursodeoxycholic acid (UDCA) in a small subgroup of patients at high risk of postdissolution recurrence, or laparoscopic cholecystectomy, which is the therapeutic radical gold standard treatment. Cholecystectomy, however, may not be a neutral event, and potentially generates health problems, including the metabolic syndrome. Areas covered: Several studies on risk factors and pathogenesis of cholesterol gallstone disease, acting at a systemic level have been reviewed through a PubMed search. Authors have focused on primary prevention and novel potential therapeutic strategies. Expert commentary: The ultimate goal appears to target the manageable systemic mechanisms responsible for gallstone occurrence, pointing to primary prevention measures. Changes must target lifestyles, as well as experimenting innovative pharmacological tools in subgroups of patients at high risk of developing gallstones
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
Advances in the pathophysiology, diagnosis and management of chronic diarrhoea from bile acid malabsorption: a systematic review
No full text: Bile acid malabsorption (BAM) is an important disorder of digestive pathophysiology as it generates chronic diarrhoea. This condition originates from intricate pathways involving bile acid synthesis and metabolism in the liver and gut, the composition of gut microbiota, enterohepatic circulation and key receptors as farnesoid X receptor (FXR), fibroblast growth factor receptor 4 (FGFR4), and the G-protein bile acid receptor-1 (GPBAR-1). Although symptoms can resemble those related to disorders of gut brain interaction, accurate diagnosis of BAM may greatly benefit the patient. The empiric diagnosis of BAM is primarily based on the clinical response to bile acid sequestrants. Specific tests including the 48-hour fecal bile acid test, serum levels of 7α-hydroxy-4-cholesten-3-one (C4) and fibroblast growth factor 19 (FGF19), and the 75Selenium HomotauroCholic Acid Test (SeHCAT) are not widely available. Nevertheless, lack of diagnostic standardization of BAM may account for poor recognition and delayed management. Beyond bile acid sequestrants, therapeutic approaches include the use of FXR agonists, FGF19 analogues, glucagon-like peptide-1 (GLP-1) receptor agonists, and microbiota modulation. These novel agents can best make their foray into the therapeutic armamentarium if BAM does not remain a diagnosis of exclusion. Ignoring BAM as a specific condition may continue to contribute to increased healthcare costs and reduced quality of life. Here, we aim to provide a comprehensive review of the pathophysiology, diagnosis, and management of BAM
Environmental health, COVID-19, and the syndemic: internal medicine facing the challenge
Full text linkInternists are experts in complexity, and the COVID-19 pandemic is disclosing complex and unexpected interactions between communicable and non-communicable diseases, environmental factors, and socio-economic disparities. The medicine of complexity cannot be limited to facing comorbidities and to the clinical management of multifaceted diseases. Evidence indicates how climate change, pollution, demographic unbalance, and inequalities can affect the spreading and outcomes of COVID-19 in vulnerable communities. These elements cannot be neglected, and a wide view of public health aspects by a “one-health” approach is strongly and urgently recommended. According to World Health Organization, 35% of infectious diseases involving the lower respiratory tract depend on environmental factors, and infections from SARS-Cov-2 is not an exception. Furthermore, environmental pollution generates a large burden of non-communicable diseases and disabilities, increasing the individual vulnerability to COVID-19 and the chance for the resilience of large communities worldwide. In this field, the awareness of internists must increase, as privileged healthcare providers. They need to gain a comprehensive knowledge of elements characterizing COVID-19 as part of a syndemic. This is the case when pandemic events hit vulnerable populations suffering from the increasing burden of chronic diseases, disabilities, and social and economic inequalities. Mastering the interplay of such events requires a change in overall strategy, to adequately manage not only the SARS-CoV-2 infection but also the growing burden of non-communicable diseases by a “one health” approach. In this context, experts in internal medicine have the knowledge and skills to drive this change
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
Chronic alcoholics retain dyspeptic symptoms, pan-enteric dysmotility and autonomic neuropathy before and after abstinence
No full textObjective: To carry out a comprehensive study on gastrointestinal symptoms, motility and autonomic neuropathy in chronic alcoholics before and one year after abstinence. Methods: Dyspeptic symptoms (questionnaires), fasting and postprandial gallbladder and gastric motility (ultrasonography), oro-cecal transit time (lactulose H2-breath test), stool form score (indirect marker of colonic transit), and autonomic neuropathy (sweat spot test, R-R ratio) were assessed at baseline in 268 subjects (136 chronic alcoholics and 132 healthy controls). A subgroup of 39 patients was re-evaluated after 12 months of abstinence. Results: Chronic alcoholics had increased dyspepsia, delayed gastric emptying and oro-cecal transit time but faster gallbladder emptying, with slightly accelerated colonic transit. Sympathetic, but not parasympathetic, autonomic dysfunction was found. Dyspeptic symptoms and functional alterations of gastric emptying and oro-cecal transit tests were still present after 12-month abstinence, whereas gallbladder motility, stool form score and sympathetic function improved. Conclusions: Chronic alcoholics exhibit combined and interdependent presence of dyspeptic symptoms, impaired motility at different levels of the gastrointestinal tract, with sympathetic dysfunction. Only a few of these abnormalities improve after one year of abstinence from alcohol
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 physical presence of gallstone modulates ex vivo cholesterol crystallization pathways of human bile
Full text linkCholesterol crystallization is an essential step toward gallstone formation. Although model bile studies showed that competition occurs between the gallstone surface and the surrounding aqueous phase for cholesterol molecules available for crystallization, this has not been investigated in human bile
- …
