Mutagenesis and cardiovascular diseases Molecular mechanisms, risk factors, and protective factors

Although no generalization can be made, it is of interest that cancer, cardiovascular diseases, and other chronic conditions often share common risk factors and common protective factors as well as common pathogenetic determinants, such as DNA damage, oxidative stress, and chronic inflammation. Atherosclerosis is the most important cause of vascular forms representing the major cause of death in the population of many geographical areas. A great deal of studies support the "response-to-injury" theory. A variety of experimental and epidemiological findings are also in favor of the somatic mutation theory, which maintains that the earliest event in the atherogenic process is represented by mutations in arterial smooth muscle cells, akin to formation of a benign tumor. These two theories can be harmonized, also taking into account the highly diversified nature of atherosclerotic lesions. Molecular epidemiology studies performed in our laboratory and other laboratories have shown that DNA adducts are systematically present in arterial smooth muscle cells, and their levels are correlated with atherogenic risk factors known from traditional epidemiology. Oxidative DNA damage was also consistently detected in these cells. The role of glutathione S-transferase polymorphisms on the frequency of the above molecular alterations and of arterial diseases is rather controversial. Prevention of both cancer and atherosclerosis is based on avoidance of exposure to risk factors and on fortification of the host defense mechanisms by means of dietary principles and chemopreventive drugs.     

Cardiovascular risk in pediatric-onset rheumatological diseases

Cardiovascular morbidity and mortality are becoming major health concerns for adults with inflammatory rheumatic diseases. The enhanced atherogenesis in this patient population is promoted by the exposure to traditional risk factors as well as nontraditional cardiovascular insults, such as corticosteroid therapy, chronic inflammation and autoantibodies. Despite definite differences between many adult-onset and pediatric-onset rheumatologic diseases, it is extremely likely that atherosclerosis will become the leading cause of morbidity and mortality in this pediatric patient population. Because cardiovascular events are rare at this young age, surrogate measures of atherosclerosis must be used. The three major noninvasive vascular measures of early atherosclerosis - namely, flow-mediated dilatation, carotid intima-media thickness and pulse wave velocity - can be performed easily on children. Few studies have explored the prevalence of cardiovascular risk factors and even fewer have used the surrogate vascular measures to document signs of early atherosclerosis in children with pediatric-onset rheumatic diseases. The objective of this review is to provide an overview on cardiovascular risk and early atherosclerosis in pediatric-onset systemic lupus erythematosus, juvenile idiopathic arthritis and juvenile dermatomyositis patients, and to review cardiovascular preventive strategies that should be considered in this population.     

The complexities of obesity and diabetes with the development and progression of pancreatic cancer

Pancreatic cancer (PC) is one of the most lethal malignant diseases with the worst prognosis. It is ranked as the fourth leading cause of cancer-related deaths in the United States. Many risk factors have been associated with PC. Interestingly, large numbers of epidemiological studies suggest that obesity and diabetes, especially type-2 diabetes, are positively associated with increased risk of PC. Similarly, these chronic diseases (obesity, diabetes, and cancer) are also a major public health concern. In the U.S. population, 50 percent are overweight, 30 percent are medically obese, and 10 percent have diabetes mellitus (DM). Therefore, obesity and DM have been considered as potential risk factors for cancers; however, the focus of this article is restricted to PC. Although the mechanisms responsible for the development of these chronic diseases leading to the development of PC are not fully understood, the biological importance of the activation of insulin, insulin like growth factor-1 (IGF-1) and its receptor (IGF-1R) signaling pathways in insulin resistance mechanism and subsequent induction of compensatory hyperinsulinemia has been proposed. Therefore, targeting insulin/IGF-1 signaling with anti-diabetic drugs for lowering blood insulin levels and reversal of insulin resistance could be useful strategy for the prevention and/or treatment of PC. A large number of studies have demonstrated that the administration of anti-diabetic drugs such as metformin and thiazolidinediones (TZD) class of PPAR-γ agonists decreases the risk of cancers, suggesting that these agents might be useful anti-tumor agents for the treatment of PC. In this review article, we will discuss the potential roles of metformin and TZD anti-diabetic drugs as anti-tumor agents in the context of PC and will further discuss the complexities and the possible roles of microRNAs (miRNAs) in the pathogenesis of obesity, diabetes, and PC.     

Recognition of genetic factors influencing the progression of hepatitis C : potential for personalized therapy

Infection with hepatitis C virus (HCV) is a major cause of chronic liver disease. Hepatic fibrosis may develop in subjects with chronic HCV infection, culminating in cirrhosis and an increased risk of hepatocellular carcinoma. The rate of development of fibrosis varies substantially between individuals; while it is influenced by a number of demographic and environmental factors, these account for only a small proportion of the variability.There are no clinical markers or tests that predict the rate of fibrosis progression in an individual subject. Thus, there has been increasing interest in the influence of host genetic factors on the rate of disease progression, and whether a genetic signature can be developed to reliably identify individuals at risk of severe disease. Numerous case-control, candidate gene, allele-association studies have examined the relationship between host single nucleotide polymorphisms or other genetic mutations and fibrosis in patients with chronic HCV infection. However, these studies have generally been irreproducible and disappointing. As seen with genetic studies for other diseases, small study cohorts and poor study design have contributed to limited meaningful findings. The successful determination of genetic signatures for fibrosis progression in chronic HCV will require multicenter collaborations using genome-wide association studies, with large, phenotypically well-defined sample sets. While these studies will require a significant financial commitment, a successful outcome offers the potential for personalized therapy and better patient management.     

Ionizing radiation and genetic risks: VI. Chronic multifactorial diseases: a review of epidemiological and genetical aspects of coronary heart disease,essential hypertension and diabetes mellitus

This paper provides a broad overview of the epidemiological and genetical aspects of common multifactorial diseases in man with focus on three well-studied ones, namely, coronary heart disease (CHD), essential hypertension (EHYT) and diabetes mellitus (DM). In contrast to mendelian diseases, for which a mutant gene either in the heterozygous or homozygous condition is generally sufficient to cause disease, for most multifactorial diseases, the concepts of `genetic susceptibility' and `risk factors' are more appropriate. For these diseases, genetic susceptibility is heterogeneous. The well-studied diseases such as CHD permit one to conceptualize the complex relationships between genotype and phenotype for chronic multifactorial diseases in general, namely that allelic variations in genes, through their products interacting with environmental factors, contribute to the quantitative variability of biological risk factor traits and thus ultimately to disease outcome. Two types of such allelic variations can be distinguished, namely those in genes whose mutant alleles have (i) small to moderate effects on the risk factor trait, are common in the population (polymorphic alleles) and therefore contribute substantially to the variability of biological risk factor traits and (ii) profound effects, are rare in the population and therefore contribute far less to the variability of biological risk factor traits. For all the three diseases considered in this review, a positive family history is a strong risk factor. CHD is one of the major contributors to mortality in most industrialized countries. Evidence from epidemiological studies, clinical correlations, genetic hyperlipidaemias etc., indicate that lipids play a key role in the pathogenesis of CHD. The known lipid-related risk factors include: high levels of low density lipoprotein cholesterol, low levels of high density lipoprotein cholesterol, high apoB levels (the major protein fraction of the low density lipoprotein particles) and elevated levels of Lp(a) lipoprotein. Among the risk factors which are not related to lipids are: high levels of homocysteine, low activity of paraoxonase and possibly also elevated plasma fibrinogen levels. In addition to the above, hypertension, diabetes and obesity (which themselves have genetic determinants) are important risk factors for CHD. Among the environmental risk factors are: high dietary fat intake, smoking, stress, lack of exercise etc. About 60% of the variability of the plasma cholesterol is genetic in origin. While a few genes have been identified whose mutant alleles have large effects on this trait (e.g., LDLR, familial defective apoB-100), variability in cholesterol levels among individuals in most families is influenced by allelic variation in many genes (polymorphisms) as well as environmental exposures. A proportion of this variation can be accounted for by two alleles of the apoE locus that increase (ϵ4) and decrease (ϵ2) cholesterol levels, respectively. A polymorphism at the apoB gene (XbaI) also has similar effects, but is probably not mediated through lipids. High density lipoprotein cholesterol levels are genetically influenced and are related to apoA1 and hepatic lipase (LIPC) gene functions. Mutations in the apoA1 gene are rare and there are data which suggest a role of allelic variation at or linked LIPC gene in high density lipoprotein cholesterol levels. Polymorphism at the apoA1–C3 loci is often associated with hypertriglyceridemia. The apo(a) gene which codes for Lp(a) is highly polymorphic, each allele determining a specific number of multiple tandem repeats of a unique coding sequence known as Kringle 4. The size of the gene correlates with the size of the Lp(a) protein. The smaller the size of the Lp(a) protein, the higher are the Lp(a) levels. Hyperhomocyst(e)inemia is a risk factor for myocardial infarction, stroke and peripheral vascular disease, but the precise nature and intensity of this association, the biochemical mechanisms involved and the role of environmental factors remain to be fully elucidated. Recently, it has been suggested that polymorphisms in genes that code for paraoxonase may need to be added to the list of genetic risk factors for CHD. There are suggestions that high plasma fibrinogen levels (which is exacerbated by smoking which also lowers high density lipoprotein cholesterol levels) may constitute yet another risk factor for CHD. Essential hypertension (EHYT) affects some 10–25% of the people of the industrial world. Its clinical relevance stems from the fact that it is one of the major risk factors for cardiovascular and renal diseases, especially, stroke, coronary heart disease and end-stage renal disease. The role of genetic factors in EHYT is clearly indicated by family studies in which correlations in blood pressure levels have been studied. The variations in the range and magnitude of these correlations however suggest that other, environmental factors must play an important role and which vary from individual to individual and population to population. No major genes controlling blood pressure have been identified. However during the past five years or so, linkage and association studies have shown that there are at least three gene loci, polymorphism at which may contribute to EHYT: these include the AGT, AT1 and ACE genes. Additionally, the molecular basis of three rare mendelian disorders associated with hypertension, namely those involved in glucocorticosteroid-remediable aldosteronism (GRA), Liddle syndrome and apparent mineralocorticosteroid excess (AME) have been delineated. On the basis of clinical phenotypes, four types of diabetes mellitus are distinguished, of which insulin-dependent diabetes melltius (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM) have been the subject of extensive studies. IDDM is a group of heterogeneous diseases probably resulting from exposure to some environmental agent(s) in those individuals with a genetically-determined susceptibility. IDDM is the result of the destruction of insulin-producing β-cells of the pancreas, principally by immunologically-mediated (autoimmune) mechanisms. The major defined risk factor is genetic susceptibility: apart from IDDM1 (linked to the HLA complex) and IDDM2 (in the insulin gene region) at least 10 other genes are involved, mutations at which cause susceptibility to IDDM. There is recent evidence for the possible involvement of an endogenous retrovirus in the aetiology of acute onset IDDM. NIDDM is a very common disease and its prevalence varies in different populations. As in the case of IDDM, its major determinant is genetic susceptibility. Compared to IDDM, the concordance rates in monozygotic twins and risks to first-degree relatives are higher. With the exception of MODY subtype with earlier onset, most cases have onset in middle or late life. The known geographical variations in the prevalence and studies of migrant populations suggest that environmental factors might also be important. The number of genes mutations at which cause susceptibility to NIDDM is not yet known and so far, one putative major gene locus has recently been identified in a Mexican–American population. Several candidate genes are currently being investigated. The available data indicate that some of the genes act through inherited susceptibility to insulin resistance and to decreased capacity for insulin secretion. Rare forms are due to dominant mutations i.e., the MODY diabetes and rarer still are forms due to the production of abnormal insulin due to mutations in the insulin gene itself. Finally, a small proportion of diabetes may be due to mutations in the mitochondrial genome. The attributes, risk factors and interrelationships between the three diseases considered in this review clearly show that the task of using this information for reliably predicting the risk of any of these diseases is formidable, even for a scenario of no radiation exposures, not to mention radiation scenarios. Nonetheless, these data provide a useful framework for developing models aimed at quantifying the response of these diseases to an increase in mutation rate due to radiation. One such model is discussed in a later paper of this series.     

Immunity Genes and Susceptibility to Otitis Media: A Comprehensive Review

Otitis media (OM) is a middle ear infection associated with inflammation and pain. This disease frequently afflicts humans and is the major cause of hearing loss worldwide. OM continues to be one of the most challenging diseases in the medical field due to its diverse host targets and wide range of clinical manifestations. Substantial morbidity associated with OM is further exacerbated by high frequency of recurrent infections leading to chronic suppurative otitis media (CSOM). Children have greater susceptibility to, and thus, suffer most frequently from OM, which can cause significant deterioration in quality of life. Genetic factors have been demonstrated, in large part by twin and family studies, to be key determinants of OM susceptibility. In this review, we summarize the current knowledge on immunity genes and selected variants that have been associated with predisposition to OM. In particular, polymorphisms in innate immunity and cytokine genes have been strongly linked with the risk of developing OM. Future studies employing state-of-the-art technologies, including next-generation sequencing (NGS), will aid in the identification of novel genes associated with susceptibility to OM. This, in turn, will open up avenues for identifying high-risk individuals and designing novel therapeutic strategies based on precise targeting of these genes.     

Polytomous disease mapping to detect uncommon risk factors for related diseases

A statistical model for jointly analysing the spatial variation of incidences of three (or more) diseases, with common and uncommon risk factors, is introduced. Deaths for different diseases are described by a logit model for multinomial responses (multinomial logit or polytomous logit model). For each area and confounding strata population (i.e. age-class, sex, race) the probabilities of death for each cause (the response probabilities) are estimated. A specic disease, the one having a common risk factor only, acts as the baseline category. The log odds are decomposed additively into shared (common to diseases different by the reference disease) and specic structured spatial variability terms, unstructured unshared spatial terms and confounders terms (such as age, race and sex) to adjust the crude observed data for their effects. Disease specic spatially structured effects are estimated; these are considered as latent variables denoting disease-specic risk factors. The model is presented with reference to a specic application. We considered the mortality data (from 1990 to 1994) relative to oral cavity, larynx and lung cancers in 13 age groups of males, in the 287 municipalities of Region of Tuscany (Italy). All these pathologies share smoking as a common risk factor; furthermore, two of them (oral cavity and larynx cancer) share alcohol consumption as a risk factor. All studies suggest that smoking and alcohol consumption are the major known risk factors for oral cavity and larynx cancers; nevertheless, in this paper, we investigate the possibility of other different risk factors for these diseases, or even the presence of an interaction effect (between smoking and alcohol risk factors) but with different spatial patterns for oral and larynx cancer. For each municipality and age-class the probabilities of death for each cause (the response probabilities) are estimated. Lung cancer acts as the baseline category. The log odds are decomposed additively into shared (common to oral cavity and larynx diseases) and specic structured spatial variability terms, unstructured unshared spatial terms and an age-group term. It turns out that oral cavity and larynx cancer have different spatial patterns for residual risk factors which are not the typical ones such as smoking habits and alcohol consumption. But, possibly, these patterns are due to different spatial interactions between smoking habits and alcohol consumption for the first and the second disease.     

What epidemiology has told us about risk factors and aetiopathogenesis in rheumatic diseases

This article will review how epidemiological studies have advanced our knowledge of both genetic and environmental risk factors for rheumatic diseases over the past decade. The major rheumatic diseases, including rheumatoid arthritis, juvenile idiopathic arthritis, psoriatic arthritis, ankylosing spondylitis, systemic lupus erythematosus, scleroderma, osteoarthritis, gout, and fibromyalgia, and chronic widespread pain, will be covered. Advances discussed will include how a number of large prospective studies have improved our knowledge of risk factors, including diet, obesity, hormones, and smoking. The change from small-scale association studies to genome-wide association studies using gene chips to reveal new genetic risk factors will also be reviewed.     

CARDIOVASCULAR DISEASE: PREVENTION AND REHABILITATION

Cardiovascular related diseases are the major cause of death in the United States. The primary goal of the physician should be prevention of these diseases; however, once problems occur, a definitive rehabilitation program must be instituted in addition to the medical and surgical treatment. Although risk factors for the development of cardiovascular disease are numerous, statistical reports suggest that control of these factors might delay or prevent such development. This presentation describes the recommended Physical Medicine and Rehabilitation Program for high-risk patients or those with existing cardiovascular disease. The basis of the physical fitness and rehabilitation program is controlled progression-of-energy-expenditure physical activity and exercise in metabolic equivalents (METS). Education plays a key role in decreasing the incidence of cardiovascular disease, and should start at an early age. Adults at high risk of developing cardiovascular disease should be offered medically supervised physical fitness exercise programs, with monitoring where necessary.     

What Is the Best Strategy for Reducing Deaths from Heart Disease?

BACKGROUND TO THE DEBATE: Coronary artery disease is a major cause of death worldwide. Two very different approaches have been proposed as a way of reducing these deaths. The "high risk" approach uses tools such as risk factor scoring and carotid ultrasound to try and identify those at highest risk, and then treats them aggressively. The "population" approach aims to shift the distribution of risk factors across a population in a beneficial direction with the goal of reducing heart disease in the whole population.     

The Association between the History of Cardiovascular Diseases and Chronic Low Back Pain in South Koreans: A Cross-Sectional Study

Background

Cardiovascular disease and related risk factors have been suggested as a mechanism leading to atherosclerosis of the lumbar vessels and consequent lumbar pain or sciatica. But there is continued controversy concerning its generalization. This study examined whether cardiovascular disease or its risk factors were associated with chronic low back pain (cLBP) in Koreans.

Methods

Health surveys and examinations were conducted on a nationally representative sample (n = 23,632) of Koreans. A total of 13,841 eligible participants (aged 20 to 89 years) were examined to determine the association between cardiovascular disease, the Framingham risk score, major cardiovascular risk factors (blood pressure, diabetes, cholesterol, and smoking habits) and chronic LBP.

Results

The total prevalence of cLBP was 16.6% (men: 10.8%, women: 21.1%) and that in patients with a history of cardiovascular diseases was 36.6% (men: 26.5%, women: 47.1%). The results showed that patients’ medical history of cardiovascular disease was significantly associated with cLBP in both men and women when adjusted for covariates (men: OR 2.16; 95%CI 1.34∼3.49; women: OR 2.26; 95%CI 1.51∼3.38). No association was observed between cLBP and the Framingham risk score, medication for hyperlipemia, hypertension, diabetes, and major cardiovascular risk factors (systolic blood pressure, total cholesterol, high density lipoprotein cholesterol, triglycerides, glucose and smoking habits) in either men or women.

Conclusions

The prevalence of cLBP is correlated to a history of cardiovascular disease, but not to the major cardiovascular risk factors from the Framingham study. Further studies on whether these results were affected by psychological factors in patients with a history of cardiovascular diseases or whether new potential risk factors from the artery atherosclerosis hypothesis applying to Koreans exist are needed.     

Infectious Agents and Neurodegeneration

A growing body of epidemiologic and experimental data point to chronic bacterial and viral infections as possible risk factors for neurodegenerative diseases, including Alzheimer??s disease, Parkinson??s disease and amyotrophic lateral sclerosis. Infections of the central nervous system, especially those characterized by a chronic progressive course, may produce multiple damage in infected and neighbouring cells. The activation of inflammatory processes and host immune responses cause chronic damage resulting in alterations of neuronal function and viability, but different pathogens can also directly trigger neurotoxic pathways. Indeed, viral and microbial agents have been reported to produce molecular hallmarks of neurodegeneration, such as the production and deposit of misfolded protein aggregates, oxidative stress, deficient autophagic processes, synaptopathies and neuronal death. These effects may act in synergy with other recognized risk factors, such as aging, concomitant metabolic diseases and the host??s specific genetic signature. This review will focus on the contribution given to neurodegeneration by herpes simplex type-1, human immunodeficiency and influenza viruses, and by Chlamydia pneumoniae.     

Cardiovascular co-morbidity in patients with rheumatic diseases

During recent years atherosclerosis, the major cause of cardiovascular disease (CVD), has been recognised as a chronic inflammatory condition in which rupture of atherosclerotic lesions appears to play a major role. The risk of CVD is raised in many rheumatic diseases. This risk is high in systemic lupus erythematosus - as much as a 50-times increase among middle-aged women has been reported. Studies on CVD and atherosclerosis in rheumatic disease could thus provide interesting information about CVD and atherosclerosis in addition to being an important clinical problem. A combination of traditional and nontraditional risk factors accounts for the increased risk of CVD and atherosclerosis in rheumatic disease. One interesting possibility is that atherosclerotic lesions in rheumatic disease are more prone to rupture than normal atherosclerotic lesions. It is also likely that increased risk of thrombosis may play an important role, not least in systemic lupus erythematosus. Further, it is not clear whether an increased risk of CVD is a general feature of rheumatic disease, or whether this only occurs among subgroups of patients. It should be emphasised that there is an apparent lack of treatment studies where CVD in rheumatic disease is the end point. Control of disease activity and of traditional risk factors, however, appears to be well founded in relation to CVD in rheumatic disease. Further studies are needed to determine the exact role of lipid-lowering drugs as statins. Hopefully novel therapies can be developed that target the causes of the inflammation in atherosclerotic lesions both in rheumatic patients and in the general population.     

慢性阻塞性肺疾病合并糖尿病患者肺部真菌感染病原学及易感因素分析

目的探讨慢性阻塞性肺疾病(COPD)合并糖尿病患者肺部真菌感染的病原学及易感因素。方法对58例COPD合并糖尿病肺部真菌感染患者进行病原学及预后分析,并与无糖尿病的COPD真菌感染患者76例进行比较。结果 2组患者病原菌均以白色念珠菌占首位,研究组真菌发病率高于对照组,预后较对照组更差。抗生素、年龄、糖皮质激素和营养状态等因素对2组患者真菌感染的影响差异无统计学意义。结论白色念珠菌仍是COPD患者肺部真菌感染的主要致病菌。糖尿病增加COPD患者感染真菌的风险,并且加重病情,影响预后。     

The probability of a sequential Plasmodium vivax infection following asymptomatic Plasmodium falciparum and P. vivax infections in Myanmar,Vietnam, Cambodia,and Laos

Increasing numbers of aging individuals with chronic co-morbidities travel to regions where falciparum malaria is endemic. Non-communicable diseases are now leading risk factors for death in such countries. Thus, the influence of chronic diseases on the outcome of falciparum malaria is an issue of major importance. Aim of the present study was to assess whether non-communicable diseases increase the risk for severe imported falciparum malaria. A retrospective observational study of all adult cases with imported falciparum malaria hospitalized between 2001 and 2015 in the tertiary care Charité University Hospital, Berlin, was performed. A total of 536 adult patients (median age 37 years; 31.3% female) were enrolled. Of these, 329 (61.4%) originated from endemic countries, 207 patients (38.6%) from non-endemic regions. Criteria for severe malaria were fulfilled in 68 (12.7%) cases. With older age, lack of previous malaria episodes, being a tourist, and delayed presentation, well-characterized risk factors were associated with severe malaria in univariate analysis. After adjustment for these potential confounders hypertension (adjusted odds ratio aOR, 3.06 95% confidence interval, CI 1.34–7.02), cardiovascular diseases (aOR, 8.20 95% CI 2.30–29.22), and dyslipidaemia (aOR, 6.08 95% CI 1.13–32.88) were individual diseases associated with severe disease in multivariable logistic regression. Hypertension proved an independent risk factor among individuals of endemic (aOR, 4.83, 95% CI 1.44–16.22) as well as of non-endemic origin (aOR, 3.60 95% CI 1.05–12.35). In imported falciparum malaria hypertension and its related diseases are risk factors for severe disease.     

Obesity is a common soil for premature cardiac aging and heart diseases - Role of autophagy

The advance in medical technology and healthcare has dramatically improved the average human lifespan. One of the consequences for longevity is the high prevalence of aging-related chronic disorders such as cardiovascular diseases, cancer and metabolic abnormalities. As the composition of aging population is raising in western countries, heart failure remains the number one cause of death with a more severe impact in the elderly. Obesity and aging are the most critical risk factors for increased susceptibility to heart failure in developing and developed countries. Numerous population-based and experimental data have depicted a close relationship between the age-related diseases and obesity. There is an overall agreement that obesity is causally linked to the development of cardiovascular disorders and severe premature cardiac aging. Accumulating evidence indicates that autophagy plays an important role in obesity, cardiac aging and diseases. In this review, we will focus on the role of autophagy in obesity-related cardiac aging and diseases, and how it regulates age-dependent changes in the heart.     

A review on coronary artery disease,its risk factors,and therapeutics

Coronary artery disease (CAD) is one of the major cardiovascular diseases affecting the global human population. This disease has been proved to be the major cause of death in both the developed and developing countries. Lifestyle, environmental factors, and genetic factors pose as risk factors for the development of cardiovascular disease. The prevalence of risk factors among healthy individuals elucidates the probable occurrence of CAD in near future. Genome-wide association studies have suggested the association of chromosome 9p21.3 in the premature onset of CAD. The risk factors of CAD include diabetes mellitus, hypertension, smoking, hyperlipidemia, obesity, homocystinuria, and psychosocial stress. The eradication and management of CAD has been established through extensive studies and trials. Antiplatelet agents, nitrates, β-blockers, calcium antagonists, and ranolazine are some of the few therapeutic agents used for the relief of symptomatic angina associated with CAD.     

Rheumatoid arthritis and periodontitis; a possible link via citrullination

Rheumatoid Arthritis (RA) and chronic and aggressive periodontitis are chronic inflammatory disorders characterized by deregulation of the host inflammatory response. Increased secretion of pro-inflammatory mediators results in soft and hard tissue destruction of the synovium and periodontium respectively. Both diseases share risk factors and have pathological pathways in common, resulting in loss of function and disability as a final clinical outcome. This article discusses possible interactions, particularly related to the periodontal pathogen Porphyromonas gingivalis, which could explain the observed association between these two prevalent diseases.     

炎症相关因子在血管性痴呆发病机制中的作用

血管性痴呆（vascular dementia,VD）是指由各种脑血管病,包括缺血性脑血管病、出血性脑血管病及急性与慢性缺氧性脑血管病引起的脑功能障碍,进而产生认知功能障碍的临床综合征。血管性痴呆是一种慢性进行性疾病,被认为是仅次于阿尔兹海默症,导致痴呆的第2位原因。目前,血管性痴呆的发病机制尚不明确,有可能与炎症、神经元损伤、胆碱能系统功能障碍、脑白质病变及氧化应激等有关。其中,炎症反应在急性与慢性脑缺血继发性脑损伤中起主要作用。抑制炎症能改善血管性痴呆动物模型的症状,显示炎症可能在血管性痴呆发病机制中发挥重要作用。参与炎症反应的相关因子,如细胞因子等可对中枢神经系统造成损伤。同时,炎症相关因子会触发炎症级联反应,加重脑损伤。本文总结了有关炎症相关因子参与导致血管性痴呆的各种病理损害和促进其发生发展的分子机制的最新研究进展,这些都有助于了解炎症相关因子在血管性痴呆发病机制中的作用。     

Helicobacter pylori infection: further evidence for the role of feco-oral transmission

BACKGROUND: Helicobacter pylori infection is recognized as a major cause of chronic digestive diseases with a major public health impact, yet the knowledge of transmission pathways is limited. We studied the transmission in employees taking care of institutionalized persons with mental disabilities with a documented high prevalence of H. pylori. MATERIALS AND METHODS: Six hundred and seventy-one health-care workers were screened for H. pylori serology. For each employee, information was collected on age, sex, father's and mother's education level, number of household members and number of children sleeping in the same bedroom during childhood, as well as lifestyle factors such as smoking and tropical journeys and occupational exposure data such as type of contact with inhabitants (changing napkins with stools, washing inhabitants, feeding inhabitants, personal contact) and seniority in the institution. RESULTS: Seroprevalence for H. pylori increased significantly with age. In univariate analysis, risk factors for H. pylori positivity were (age-adjusted): father's education, mean length of employment, smoking, contact with fecal materials of inhabitants, washing and feeding of inhabitants. Controlling for confounders, in multiple logistic regression analysis, only fecal contact remained as a significant risk factor for H. pylori infection. CONCLUSIONS: In health-care workers caring for a population with a high prevalence of H. pylori infection, there is an association with fecal transmission. This, however, does not rule out the possibility of other ways of transmission.