Obesity and thyroid cancer: epidemiologic associations and underlying mechanisms

The incidence of thyroid cancer has been rising over the past few decades along with a parallel increase in obesity. Observational studies have provided evidence for a potential association between the two. By contrast, clinical data for a link between type 2 diabetes mellitus, a condition strongly associated with obesity, and thyroid cancer are limited and largely not supportive of such an association. Obesity leads to hypoadiponectinemia, a pro‐inflammatory state, and insulin resistance, which, in turn, leads to high circulating insulin and insulin‐like growth factor‐1 levels, thereby possibly increasing the risk for thyroid cancer. Thus, insulin resistance possibly plays a pivotal role in underlying the observed association between obesity and thyroid cancer, potentially leading to the development and/or progression of thyroid cancer, through its interconnections with other factors including insulin‐like growth factor‐1, adipocytokines/cytokines and thyroid‐stimulating hormone. In this review, epidemiological and clinical evidence and potential mechanisms underlying the proposed association between obesity and thyroid cancer risk are reviewed. If the association between obesity and thyroid cancer demonstrated in observational studies proves to be causal, targeting obesity (and/or downstream mediators of risk) could be of importance in the prevention and management of thyroid cancer.     

Moderate drinking, psychological factors, and cardiovascular protection: reply

We thank Dr Viktor uli for his interest in our article ‘The     

Moderate drinking, psychological factors, and cardiovascular protection

Two recent EHJ articles^1,2 add to the evidence that moderatealcohol consumption, compared to heavy or non-drinking, hasbeneficial effect in reducing mortality from ischaemic heartdisease. Interesting information is that the effect is independentand cannot be compensated by physical activity.² The     

Prevention of cardiovascular risk by moderate alcohol consumption: epidemiologic evidence and plausible mechanisms

An inverse association between moderate alcohol intake and cardiovascular risk, in particular coronary disease and ischemic stroke, has been shown in many epidemiologic studies. In addition, several other diseases are also known to occur less frequently in moderate drinkers than in non-drinkers, whereas excess of drinking is invariably harmful. However, some concern has been recently raised about the possibility that at all dosages the harm of alcohol could overcome its beneficial effects. We present here the epidemiologic and mechanistic evidence to support the protective effect of moderate alcohol intake against cardiovascular disease and all-cause mortality.     

The low-carbohydrate diet and cardiovascular risk factors: Evidence from epidemiologic studies

AimsObesity is an important public health issue because of its high prevalence and concomitant increase in risk of cardiovascular diseases. Low carbohydrate diets are popular for weight loss and weight management but are not recommended in leading guidelines due to the perception that increases in dietary fat intake may lead to an adverse cardiovascular risk profile. To clarify the effects of a low-carbohydrate diet for weight loss on cardiovascular disease risk factors as compared to a low fat diet for weight loss, we systematically reviewed data from randomized controlled clinical trials and large observational studies.Data synthesisWe searched the MEDLINE database (Jan 1966–Nov 2013) to identify studies that examined a low-carbohydrate diet as compared to a low-fat diet for weight loss or the improvement of cardiovascular disease risk factors.ConclusionsRecent randomized controlled trials document that low-carbohydrate diets not only decrease body weight but also improve cardiovascular risk factors. In light of this evidence from randomized controlled trials, dietary guidelines should be re-visited advocating a healthy low carbohydrate dietary pattern as an alternative dietary strategy for the prevention of obesity and cardiovascular disease risk factors.     

Fetal or infantile exposure to ethanol promotes ethanol ingestion in adolescence and adulthood: a theoretical review

BACKGROUND: Despite good evidence that ethanol abuse in adulthood is more likely the earlier human adolescents begin drinking, it is unclear why the early onset of drinking occurs in the first place. A review of experimental studies with animals complemented by clinical, epidemiologic and experimental studies with humans supports the idea that precipitating conditions for ethanol abuse occur well before adolescence, in terms of very early exposure to ethanol as a fetus or infant. Experimental studies with animals indicate, accordingly, that ethanol intake during adolescence or adulthood is potentiated by much earlier exposure to ethanol as a fetus or infant. METHODS: Two broad theoretical frameworks are suggested to explain the increase in affinity for ethanol that follows very early exposure to ethanol, one based on effects of mere exposure and the other on associative conditioning. Studied for 50 years or more in several areas of psychology, "effects of mere exposure" refers to enhanced preference expressed for flavors, or just about any stimuli, that are relatively familiar. An alternative framework, in terms of associative conditioning, is guided by this working hypothesis: During ethanol exposure the fetus or infant acquires an association between ethanol's orosensory (odor/taste) and pharmacological consequences, causing the animal subsequently to seek out ethanol's odor and taste. RESULTS AND CONCLUSIONS: The implication that ethanol has rewarding consequences for the fetus or young infant is supported by recent evidence with perinatal rats. Paradoxically, several studies have shown that such early exposure to ethanol may in some circumstances make the infant treat ethanol-related events as aversive, and yet enhanced intake of ethanol in adolescence is nevertheless a consequence. Alternative interpretations of this paradox are considered among the varied circumstances of early ethanol exposure that lead subsequently to increased affinity for ethanol.     

运动对心血管保护作用及机制研究进展

生理状况下,运动训练可显著提高机体代谢水平,发挥抗炎、抗衰老、调节血压和抗抑郁的功能,长期规律的运动训练有助于增加心排出量,促进生理性心肌重构,增强机体对心血管疾病的耐受性,对心血管疾病一级预防作用显著,已被多个指南推荐用于心血管疾病及代谢相关疾病的预防和治疗。运动发挥心血管保护作用的机制较为复杂,包括改善心肌能量代谢,促进冠脉循环,延缓病理性心肌重构等,本文将综述近年来运动对于心肌梗死前后的心肌保护作用相关进展,为深入探讨运动发挥心血管保护作用提供理论依据。     

Central and peripheral vagal mechanisms involved in gastric protection against ethanol injury

Abstract Activation of medullary thyrotropin-releasing hormone (TRH), at a dose subthreshold to increase gastric acid secretion, protects the gastric mucosa against ethanol injury through vagal cholinergic pathways in urethane-anaesthetized rats. Peripheral mediators involve the efferent function of capsaicin-sensitive splanchnic afferents leading to calcitonin gene-related peptide (CGRP)- and nitric oxide (NO)-dependent gastric vasodilatory mechanisms. In addition, gastric prostaglandins participate in gastric protection through mechanisms independent of the stimulation of gastric mucosal blood flow and mucus secretion. Medullary TRH has physiological relevance in the vagal-dependent adaptive gastric protection induced by mild (acid or ethanol), followed by strong, irritants. Additional neuropeptides, namely peptide YY (PYY), somatostatin analogues, CGRP and adrenomedullin, also act in the brainstem to induce a vagal-dependent gastric protection against ethanol through interactions with their specific receptors in the medulla. Central PYY and adrenomedullin act through vagal cholinergic prostaglandins and NO pathways, while somatostatin analogue acts through vagal non-adrenergic, non-cholinergic vasoactive intestinal peptide and NO mechanisms. Although their biological relevance is still to be established, these peptides provide additional tools to investigate the multiple vagal-dependent mechanisms which increase the resistance of the gastric mucosa to injury.     

Intracisternal thyrotropin-releasing hormone-induced vagally mediated gastric protection against ethanol lesions: Central and peripheral mechanisms

Abstract The vagus is involved in mediating gastric cytoprotection and adaptive cytoprotection. However, the central and peripheral mechanisms through which the vagus expresses its action are still poorly known. Medullary thyrotropin-releasing hormone (TRH) plays an important role in the vagal regulation of gastric function. The stable TRH analogue, RX 77368, micro-injected into the cisterna magna or the dorsal motor nucleus (DMN) of the vagus at a dose that did not influence gastric acid secretion prevented gastric injury induced by intragastric administration of 60% ethanol in conscious or urethane-anaesthetized rats. The cytoprotective action of TRH is mediated through vagal cholinergic release of prostaglandin E₂ (PGE₂). Prostaglandin E₂ action is unrelated to changes in gastric mucosal blood flow (GMBF). In addition, other peripheral mechanisms involve calcitonin gene-related peptide (CGRP) contained in capsaicin sensitive afferent fibres and nitric oxide, both of which mediate the associated increase in GMBF induced by intracisternal injection of RX 77368. These data indicate that medullary TRH induces vagally mediated gastric protection against ethanol lesions. Its action is expressed through the muscarinic dependent release of PGE₂ and nitric oxide, and efferent function of capsaicin-sensitive afferent fibres releasing CGRP.     

Eplerenone: cardiovascular protection

Data from animal studies and clinical trials indicate that aldosterone causes cardiovascular and renal injury through mineralocorticoid receptor-dependent mechanisms. However, although aldosterone receptor antagonism reduces mortality in patients with congestive heart failure, the progestational and antiandrogenic side effects of the nonspecific aldosterone receptor antagonist, spironolactone, have limited its usefulness in the treatment of hypertension. This review provides an overview of the pharmacology, efficacy, and safety of a new, more selective aldosterone receptor antagonist, eplerenone, in the context of emerging concepts of the role of aldosterone in cardiovascular toxicity.     

适量饮酒与心血管健康

白20世纪初认识到饮酒具有抗动脉粥样硬化作用以来,饮酒与心血管健康的关系开始受到关注[1].20世纪70年代末注意到饮酒量与冠心病死亡率呈负相关,1989年世界卫生组织(WHO)MONICA计划流行病学调查发现"法国反常(the french paradox)"现象,即法国人在冠心病危险因素与其他西方国家相仿的背景下,冠心病死亡率却显著低于这些国家.     

Dietary fiber and cardiovascular disease: Experimental and epidemiologic advances

Recently reported experimental studies offer insight into the various mechanisms through which dietary fiber may reduce the risk of cardiovascular disease (CVD) in humans. Although most work has focused on traditional risk factors, studies have begun to explore less studied areas of risk such as fibrinolysis. Epidemiologic results have consistently demonstrated inverse associations between dietary fiber, particularly cereal fiber and whole grain foods, and the development of CVD morbidity and mortality. These associations have been observed in both men and women and are not accounted for by potential confounders such as other dietary and lifestyle factors; nor can they be fully explained by body habitus, antioxidants, and other nutrients found in fiber-rich foods. The evidence to date supports clear recommendations for a diet based on fiber-rich foods.     

Metabolic responses of forearm and adipose tissues to acute ethanol ingestion

Although excess ethanol consumption is often considered to lead to adiposity, the metabolic routes by which this might occur are not clear. We have investigated some metabolic consequences of acute ethanol ingestion by measuring arteriovenous differences across forearm muscle and subcutaneous adipose tissue for 6 hours after ingestion of 47.5 g ethanol, in seven normal subjects fasted overnight. The expected systemic effects of ethanol ingestion were observed: slight lowering of the plasma glucose concentration, depression of plasma nonesterified fatty acid (NEFA) concentrations, and elevation of the blood lactate/pyruvate and 3-hydroxybutyrate/acetoacetate ratios. There was a marked reduction in blood total ketone bodies in relation to plasma NEFA concentrations. However, the only major change observed in peripheral tissue metabolism was an increased uptake of acetate into forearm muscle, equivalent, in whole-body terms, to only 3% of the ethanol load. Adipose tissue appeared to show a reduced cytoplasmic state in that it exported an increased ratio of lactate to pyruvate after ethanol ingestion. However, this reduced state did not lead to increased fatty acid reesterification within adipose tissue. No mechanism was clearly identified whereby ethanol ingestion might lead to net deposition of triacylglycerol in adipose tissue.     

Distribution of the global cardiovascular risk in the Italian population: results from the cardiovascular epidemiologic observatory]

BACKGROUND: The aim of this study was to assess the 10-year cardiovascular risk categories using risk chart, recently set up by the National Institute of Health in the population examined by the Cardiovascular Epidemiologic Observatory. METHODS: 3745 men and 3664 women aged 40-69 years were classified into five risk categories (< 5 %; 5-10%; 10-15%; 15-20%; > or = 20%) taking into account age, smoking habit, history of diabetes, systolic blood pressure, serum cholesterol and excluding those already under treatment for hypertension and hypercholesterolaemia or experienced a previous major cardiovascular event (1937 persons: 955 men, 982 women). RESULTS: Proportion of people estimated at risk in 10 years > or = 20% is minimal in the youngest age range, increases in adulthood, duplicates in smokers and is higher in diabetics. In non-diabetic men that proportion varies between 3.4% in non-smokers and 5.6% in smokers. All women at risk are already under specific treatment. CONCLUSIONS: Cardiovascular Epidemiologic Observatory data allowed to assess the expected proportion of individuals at risk in 10 years > or = 20%. Besides attention to high-risk individuals, preventive measures supporting a healthier lifestyle in the general population must be adopted, considering that it will produce the greatest number of events.     

Effect of daily ethanol ingestion on intestinal permeability to macromolecules

The effects of regular ethyl alcohol ingestion on morphological and permeability characteristics of the small intestine were assessed in mature rats using the tracer protein, horseradish peroxidase. Thirty adult rats were divided into two groups and provided a standard commercial diet in pellet form. Each morning, after an overnight fast, every animal in the experimental group was administered by gavage an aliquot of 20% ethanol; animals in the control group were provided aliquots of 20% sucrose in water by the same method. After 4 and 8 weeks on the gavage routine (and 10 days and 4 weeks after gavage cessation), jejunal permeability to horseradish peroxidase was examined in animals from each group. Using a routine ligated-loop procedure and light and electron microscopy, ethanol-exposed rats demonstrated increased intestinal permeability to horseradish peroxidase by 4 weeks; sucrose-exposed animals revealed little alteration in mucosal integrity. It is proposed that regular ingestion of sizable amounts of alcohol alters morphological characteristics of the gut and increase the permeability of the mucosa to undigested macromolecules.