Foetal programming by maternal thyroid disease

Foetal programming is an emerging concept that links a wide range of exposures during foetal life to later development of disease. Thyroid disorders are common in women of reproductive age, and careful management of pregnant women suffering from thyroid disease is important considering the crucial role of thyroid hormones during early brain development. It is possible that maternal thyroid dysfunction in pregnancy may lead to structural and/or functional changes during foetal brain development. Such an effect could later predispose the offspring to an increased risk of neurologic or psychiatric disease. We recently observed that children born to mothers with thyroid dysfunction had an increased risk of developing seizure disorders, autism spectrum disorders, attention‐deficit hyperactivity disorders and psychiatric disease in adolescence and young adulthood. In the review, we discuss the concept of potential foetal programming by maternal thyroid disease.     

Cardiovascular Risk and Psoriasis: Beyond the Traditional Risk Factors

Psoriasis is an autoimmune disease resulting in plaques of the skin. Similar to atherosclerosis, inflammation is integral to the initiation and propagation of plaque development. Mounting evidence has emerged demonstrating that psoriasis not only is associated with increased prevalence of cardiovascular risk factors, but also is an independent risk factor for the development of cardiovascular disease. Systemic therapies for moderate to severe psoriasis can increase the cardiovascular risk. Despite the evidence that psoriasis is an independent risk factor for cardiovascular disease, current guidelines only address managing traditional risk factors. An interdisciplinary approach is needed to find the necessary steps beyond classic risk reduction and detection of early cardiovascular disease in patients with psoriasis, as well as to develop a cardiovascular disease preventive regimen.     

Serum uric acid is not an independent risk factor for coronary heart disease

Many large epidemiologic studies have confirmed a positive association between raised serum uric acid and risk of coronary heart disease or cardiovascular disease, both in the general population and among hypertensive patients. There is much controversy concerning the role of uric acid as an independent risk factor in the development of coronary heart disease because serum uric acid is related to many of the established etiologic risk factors for cardiovascular disease that could confound the observed association. This review finds little support for an independent causal role for serum uric acid in the development of coronary heart disease.     

慢性肾脏病胰岛素抵抗的研究进展

胰岛素抵抗是代谢综合征的核心.胰岛素抵抗和高胰岛素血症在慢性肾脏病的早期即可出现,某些脂肪细胞因子如瘦素、脂联素、抵抗素在慢性肾脏病胰岛素抵抗的发生、发展中起重要作用.胰岛素抵抗可增加慢性肾脏病患者心血管疾病的发病率和死亡率,促进肾脏病的进展,临床上需要于预.     

Shared genetics in coeliac disease and other immune-mediated diseases

Identifying disease-associated variants can improve the predictive models of disease risk and provide mechanistic insights into disease development. Coeliac disease (CD) is the only autoimmune trait with a known environmental trigger, which makes it an excellent model for studying the complexity of genetic and environmental factors in the development of autoimmunity. In this review, we will focus on the genetic loci that have recently been associated with CD and that contain genes involved in innate and adaptive immunity. Some of these loci are shared with other immune-mediated diseases, suggesting an overlap of the genetic mechanisms involved in the development of such diseases. Some therapies, e.g. tumour necrosis factor inhibitors or a gluten-free diet, are already proving effective for more than one autoimmune disease. Follow-up of individuals with a high genetic risk of CD and other autoimmune diseases could help to elucidate the role of environmental factors (such as infectious agents or alterations in the microbiome) and prevent disease development.     

The Central Opioid System in Liver Disease and Its Complications

The best known example of an interaction between the liver and the brain is hepatic encephalopathy. In the 90s a central nervous system origin of the pruritis of cholestatic liver disease and more recently of fatigue of liver disease has been suggested. Hence, three important manifestations of liver disease may be of central origin. Evidence is accumulating that the central opioid system is involved in the development of these manifestations. This short review summarizes current knowledge on the role of the opioid system in development of these liver disease manifestations.     

Molecular genetics and age-related disease.

Maintenance and repair processes are crucial to the pathogenesis of ageing and late-onset disease. Thus, there is increasing recognition of the importance of genetic factors in the development of late-onset conditions such as stroke, Parkinson's disease and osteoporosis, and accumulating evidence for a genetic component in the development of chronic obstructive pulmonary disease. We review the approaches and problems in the genetic investigation of complex disorders in old age, taking chronic obstructive pulmonary disease as an example.     

Prospective study of the evolution of Raynaud's phenomenon

Seventy-four patients with Raynaud's phenomenon and no associated illness were followed prospectively to determine whether a secondary disease would develop, and clinical and laboratory assessments were performed at study entry to determine their association with the subsequent development of disease. After an average of 2.7 years of follow-up (range 0.5 to 5.7 years), outcome information was available on 58 persons (78.4 percent). A connective tissue disease developed in 11 (19.0 percent): three systemic sclerosis and eight CREST syndrome. The two variables at entry most strongly associated with the subsequent development of a connective tissue disease were an abnormal nailfold capillary pattern (adjusted odds ratio = 26.82, 95 percent confidence interval = 4.69, 153.2) and an abnormal pulmonary function test result (odds ratio = 4.78, 95 percent confidence interval = 1.02, 22.41). The positive association of an abnormal barium esophagram, presence of antinuclear antibodies, and cutaneous abnormalities did not reach statistical significance. The development of connective tissue diseases in this group of patients is not rare. An abnormal nailfold capillary pattern is strongly associated with the subsequent development of systemic sclerosis or CREST syndrome in patients with Raynaud's phenomenon.     

Concept of Crohn's disease being conditioned by four main components, and irritable bowel syndrome being an incomplete Crohn's disease

Several mechanisms have been proposed for the development of Crohn's disease. Evidence in favour of a unifying 4-component concept to explain the development of Crohn's disease is presented. The four components are a genetic predisposition to an increased intestinal permeability, the key and initial triggering factor being an oral-pharyngeal bacterium that increases the mucosal permeability of the small intestine with only a minimal inflammatory reaction, an adherent-invasive strain of Escherichia coli that penetrates the mucosa and causes an acute inflammatory reaction in the intestinal wall, and finally a secondary invasion of bacteria causing the chronic inflammatory characteristics. Irritable bowel syndrome (IBS) is a functional bowel disorder with intermittent symptoms of varying intensity. Clinically, there is evidence to suggest a link between IBS patients with diarrhoea and patients with Crohn's disease. The common denominator and initial trigger for IBS with diarrhoea and Crohn's disease seems to be an increased small intestinal permeability, probably caused by an oral-pharyngeal bacterial strain. The important missing factor in IBS patients seems to be the adherent-invasive strain of E. coli in the proximal colon, causing the acute inflammatory process in patients with Crohn's disease. IBS with diarrhoea can then be looked upon as an incomplete Crohn's disease.     

Rheumatic syndromes associated with malignancy

The relation between rheumatic syndromes and an underlying malignancy is a complex one. As a result of autoimmunity, an aberrant immune response, or the use of immunomodulatory drugs, many of the rheumatic diseases appear to pose an increased risk for the development of malignancy. Unfortunately, for many of the same reasons, the presence of an underlying malignancy can result in the development of features of rheumatic disease. Awareness of the associations between rheumatic syndromes and malignancy will aid the clinician in the accurate diagnosis of underlying pathology, more effective treatment of both the symptoms and underlying disease, and appropriate surveillance for the development of later complications.     

Impact of diabetes on the severity of liver disease

The prevalence of type 2 diabetes is higher in patients who have liver diseases, such as nonalcoholic fatty liver disease, chronic viral hepatitis, hemochromatosis, alcoholic liver disease, and cirrhosis. The development of diabetes in patients with cirrhosis is well recognized, but evidence is emerging that the development of chronic liver disease and progression to cirrhosis may occur after the diagnosis of diabetes and that diabetes plays a role in the initiation and progression of liver injury. This article provides an overview of the evidence for an increased prevalence of diabetes in a range of liver diseases; the effect of diabetes on the severity of disease; the potential mechanisms whereby coexistent diabetes exacerbates progression of hepatic fibrosis; and the impact of obesity, insulin resistance, and type 2 diabetes on clinical outcomes.     

HLA-B27: an important genetic risk factor for lone aortic regurgitation and severe conduction system abnormalities

PURPOSE: HLA-B27, an immunogenetic marker that is present in 8 percent of the white population around the world, has been found to be an important risk factor for the development of a group of rheumatic disorders, the seronegative spondyloarthropathies. Our objective was to assess the possible role of HLA-B27 and the associated inflammatory disease process in the development of lone aortic regurgitation. PATIENTS AND METHODS: A group of 91 patients with lone aortic regurgitation were studied by HLA typing and clinical and roentgenologic examination. RESULTS: The HLA-B27-associated inflammatory disease process was found to be the probable underlying cause in 15 to 20 percent of patients with lone aortic regurgitation of different degrees of severity. Furthermore, HLA-B27 was found in 88 percent of the male patients with the combination of aortic regurgitation and severe conduction system abnormalities. CONCLUSION: We suggest that this cardiac syndrome should be regarded as an HLA-B27-associated syndrome, sometimes part of ankylosing spondylitis or Reiter's disease, but just as often presenting without obvious rheumatic disease. The marker is thus an important and widely distributed risk factor not only for the development of rheumatic disease but also for acquired aortic regurgitation and sever conduction system abnormalities.     

NK细胞与冠心病的关系

冠心病（CHD）是动脉粥样硬化导致器官病变的最常见类型,也是危害人类健康的常见病,近年来研究表明炎症免疫反应与CHD的发生、发展及心梗后的损伤修复密切相关。NK细胞作为先天性免疫系统的重要组成成分,参与了CHD的发生、发展及缺血后的心肌重塑。本文简要概括了NK细胞与CHD的研究进展,以期为CHD的治疗提供新的思路。     

Proteomic remodeling of mitochondria in heart failure

Heart failure (HF) is a common disease that has been attributed, in part, to deprivation of cardiac energy. As a result, the interplay between metabolism and adenosine triphosphate production is fundamental in determining the mechanisms driving the disease progression. Due to its central role in energy production, metabolism, calcium homeostasis, and oxidative stress, the mitochondrion has been suggested to play a pivotal role in the progression of the heart to failure. Nevertheless, the mitochondrion's specific role(s) and the proteins contributing to the development and progression of HF are not entirely clear. Thus, changes in mitochondrial proteomic make-up during HF have garnered great interest. With the continued development of advanced tools for assessing proteomic make-up, characterization of mitochondrial proteomic changes during disease states such as HF are being realized. These studies have begun to identify potential biomarkers of disease progression as well as protein targets that may provide an avenue for therapeutic intervention. The goal of this review is to highlight some of the changes in mitochondrial proteomic make-up that are associated with the development of HF in an effort to identify target axes and candidate proteins contributing to disease development. Results from a number of different HF models will be evaluated to gain insight into some of the similarities and differences in mitochondrial proteomic alterations associated with morphological and functional changes that result from the disease. Congest Heart Fail.     

Inflammation and immune response in atherosclerosis

Atherosclerosis is an inflammatory disease with a significant autoimmune component. Studies using transgenic murine models have clarified that recruitment of mononuclear leukocytes through vascular leukocyte-adhesion molecules and chemokines, differentiation of monocytes to macrophages, and endocytosis through scavenger receptors all are of decisive importance for atherosclerosis in hypercholesterolemic mice. T and B cells modulate disease progression and lesion development is reduced in mice lacking adaptive immunity. In particular, local immune responses eliciting Th1 effector mechanisms appear to be proatherogenic, whereas protective immune responses can be induced by immunization with oxidized low-density lipoprotein. Thus, innate immunity is necessary for atherosclerosis, whereas adaptive immunity is an important modulator of disease development.     

Helicobacter pylori: a new cardiovascular risk factor?

There is increasing evidence that certain microbial agents may have an etiopathogenic role in the development of atherothrombosis. Helicobacter pylori, a bacterium that causes peptic ulcer disease, has been suggested as one of the microbes involved in the development of atherothrombosis. This hypothesis is based on the following observations: a) a higher prevalence of Helicobacter pylori infection in patients with coronary artery disease, myocardial infarction, or cerebrovascular disease; b) the coincidence of Helicobacter pylori infection and cardiovascular risk factors, such as serum cholesterol and triglyceride concentrations and plasma fibrinogen; c) Helicobacter pylori seropositivity correlates with acute-phase proteins associated with higher risk of coronary disease, such as C-reactive protein, and d) controversial PCR studies indicating the presence of Helicobacter pylori in atheromas. Analysis of the scientific evidence suggests that Helicobacter pylori infection could indirectly contribute to the development and severity of atherothrombosis and cardiovascular disease.     

Is susceptibility to tuberculosis acquired or inherited?

Tuberculosis is an ongoing major public health problem on a global scale. One of the striking features of the disease is that only an estimated 10% of immunocompetent persons infected by the causative pathogen Mycobacterium tuberculosis will develop clinical signs of disease. This well-established epidemiological observation has prompted an intense search for the factors that trigger advancement of infection to disease in the small proportion of susceptible individuals. Central to this search is the questions if tuberculosis patients are inherently susceptible to the disease or if disease development is promoted by specific environmental factors. It is known that genetic and non-genetic factors of both the bacterium and the host have impact on the host response to M. tuberculosis. Yet, little is known about the interaction of these different factors and the resulting impact on disease development. Recent work suggests that in addition to common host susceptibility genes a second group of susceptibility loci exists the action of which strongly depends on the individual's clinical and exposure history. The latter genes may have a very strong effect on promoting advancement from infection to disease only in specific epidemiological settings. These findings suggest that a more detailed knowledge of gene-environment interactions in tuberculosis is necessary to understand why a small proportion of individuals are susceptible to the disease whilst the majority of humans are naturally resistant to tuberculosis.     

Crohn's disease presenting with erythema nodosum as an early sign: a case report

Erythema nodosum is the most common form of septal panniculitis and the most frequent skin manifestation associated with inflammatory bowel disease, affecting up to 15% of Crohn's disease patients. Since the development of erythema nodosum is closely related with a variety of disorders and condition, it can serve as an important early sign of systemic disease. Here, we present the occurrence of erythema nodosum as an early sign of Cronh's disease in a 16-year-old woman.     

Risks for glucose intolerance

Cardiovascular disease is the major cause of morbidity and mortality in diabetics. In this article, the prevalence of cardiovascular disease in diabetes is described, and the factors that influence the development of cardiovascular disease are explored. The interaction of other risk factors for cardiovascular disease and glucose intolerance and the question of whether glucose intolerance is truly an independent risk factor are also discussed.     

一氧化氮与先天性心脏病合并肺动脉高压

一氧化氮是一种脂溶性气体,它具有独特的理化性质和生物学活性,主要由血管内皮产生,在先天性心脏病合并肺动脉高压的发生、发展过程中起到了重要作用。吸入一氧化氮气体,可选择性扩张肺血管,降低肺动脉阻力和肺动脉压。现主要综述一氧化氮与先天性心脏病合并肺动脉高压的相互作用关系及一氧化氮在治疗上的研究进展。