Keshan Disease Research Articles

Biomonitoring Equivalents for selenium

Selenium is an essential nutrient for human health with a narrow range between essentiality and toxicity. Selenium is incorporated into several proteins that perform important functions in the body. With insufficient selenium intake, the most notable effect is Keshan disease, an endemic cardiomyopathy in children. Conversely, excessive selenium intake can result in selenosis, manifested as brittle nails and hair and gastro-intestinal disorders. As such, guidance values have been established to protect against both insufficient and excessive selenium exposures. Dietary Reference Intakes (DRIs) have been established as standard reference values for nutritional adequacy in North America. To protect against selenosis resulting from exposure to excessive amounts of selenium, several government and non-governmental agencies have established a range of guidance values. Exposure to selenium is primarily through the diet, but monitoring selenium intake is difficult. Biomonitoring is a useful means of assessing and monitoring selenium status for both insufficient and excessive exposures. However, to be able to interpret selenium biomonitoring data, levels associated with both DRIs and toxicity guidance values are required. Biomonitoring Equivalents (BEs) were developed for selenium in whole blood, plasma and urine. The BEs associated with assuring adequate selenium intake (Estimated Average Requirements – EAR) are 100, 80 and 10μg/L in whole blood, plasma and urine, respectively. The BEs associated with protection against selenosis range from 400 to 480μg/L in whole blood, 180–230μg/L in plasma, and 90–110μg/L in urine. These BE values can be used by both regulatory agencies and public health officials to interpret selenium biomonitoring data in a health risk context.

Serum biomarkers of Keshan disease assessed using a protein profiling approach based on ClinProt technique.

The etiology of Keshan disease (KD), an endemic myocardiopathy in regions of China, is largely unknown. To show the protein changes in serum from KD patients versus controls and idiopathic dilated cardiomyopathy (IDCM) and to search specific biological markers for differential diagnosis for KD. Serum of 65 patients with KD was compared with 29 patients with IDCM, 62 controls from KD areas and 28 controls from non-KD areas by ClinProt/MALDI-ToF technique. The genetic algorithm, quick classifier algorithm and supervised neural network algorithm methods were used to screen marker proteins and establish diagnostic model. Thirty-four differential peaks were identified in KD patients compared with the healthy controls from non-KD areas. Thirty-eight differentially peaks were identified in KD patients and controls from KD areas; and sixty-seven differentially peaks were identified in patients with KD and patients with IDCM. We believe that marker protein peaks screened in KD patients, healthy controls and IDCM patients may provide clues for the differential diagnosis and treatment of KD.

TLR2-ICAM1-Gadd45α axis mediates the epigenetic effect of selenium on DNA methylation and gene expression in Keshan disease.

Keshan disease (KD) is a fatal dilated cardiomyopathy with unknown etiology, and selenium deficiency is considered the main cause of KD. Several observations implicate a role for altered DNA methylation in selenium deficiency-related diseases. The aim of the present study was to investigate the epigenetic effects of selenium (Se) on DNA methylation and gene expression in Keshan disease. Using methylated DNA immunoprecipitation chip (MeDIP-Chip) and quantitative RT-PCR, we identified two inflammatory-related genes (TLR2 and ICAM1) that were differentially methylated and expressed between normal individuals and KD patients. Results from DNA methylation profile between KD patients and normal individuals showed that selenium deficiency decreased methylation of CpG islands in promoter regions of TLR2 and ICAM1 and upregulated messenger RNA (mRNA) and protein levels of TLR2 and ICAM1. In rat animal model of Keshan disease, selenite treatment could increase TLR2 and ICAM1 promoter methylation, suppress these genes expression, and reduce infiltration of myocardial inflammatory cells. In cell culture model of Keshan disease, we found 5-Aza-dC (DNMT1 inhibitor) treatment in the presence of selenium-reduced mRNA and protein levels of DNMT1 regardless of TLR2 and ICAM1 promoter methylation status and expression levels of these genes. Selenite treatment suppressed the expression of the Gadd45α, TLR2, and ICAM1 in a concentration-dependent manner, while selenium deficiency increased the expression of the Gadd45α, TLR2, and ICAM1 and decreased TLR2 and ICAM1 promoter methylation level in a time-dependent manner. Our results revealed that TLR2-ICAM1-Gadd45α axis might play an important role in gene-specific active DNA demethylation during inflammatory response in myocardium.

Genome-wide study reveals an important role of spontaneous autoimmunity, cardiomyocyte differentiation defect and antiangiogenic activities in gender-specific gene expression in Keshan disease

Background Keshan disease (KD) is an endemic cardiomyopathy in China. The etiology of KD is still under debate and there is no effective approach to preventing and curing this disease. Young women of child-bearing age are the most frequent victims in rural areas. The aim of this study was to determine the differences between molecular pathogenic mechanisms in male and female KD sufferers. Methods We extracted RNA from the peripheral blood mononuclear cells of KD patients (12 women and 4 men) and controls (12 women and 4 men). Then the isolated RNA was amplified, labeled and hybridized to Agilent human 4×44k whole genome microarrays. Gene expression was examined using oligonucleotide microarray analysis. A quantitative polymerase chain reaction assay was also performed to validate our microarray results. Results Among the genes differentially expressed in female KD patients we identified: HLA-DOA, HLA-DRA, and HLA-DQA1 associated with spontaneous autoimmunity; BMP5 and BMP7, involved in cardiomyocyte differentiation defect; and ADAMTS 8, CCL23, and TNFSF15, implicated in anti-angiogenic activities. These genes are involved in the canonical pathways and networks recognized for the female KD sufferers and might be related to the pathogenic mechanism of KD. Conclusion Our results might help to explain the higher susceptibility of women to this disease.

H558R polymorphism in SCN5A is associated with Keshan disease and QRS prolongation in Keshan disease patients.

Keshan disease (KSD), a potentially fatal cardiomyopathy, has very high incidence in some selenium-poor regions of China. KSD may be accompanied with a variety of arrhythmia, which is associated with mutations in the gene coding for cardiac voltage-gated sodium channel (SCN5A). The molecular mechanism of KSD is still largely obscure. We aimed to determine the association between the H558R polymorphism of SCN5A and KSD. We recruited 71 patients with KSD and 80 geographical region-matched control subjects in our study. Vital sign and electrocardiographic (ECG) measurements were performed for heart rate, systolic pressure, diastolic pressure, PR interval, QT interval, QRS duration, ST-T changes and complete right bundle branch block (CRBBB), and H558R polymorphism was genotyped using the polymerase chain reaction single-strand conformation polymorphism (PCR-SSCP) method and sequencing. A significant association was found between the H558R polymorphism of exon 12 and KSD. Allele C carriers had a decreased risk for KSD with an odds ratio of 0.332 [95% confidence interval (CI), 0.160-0.692] as well as for QRS prolongation in KSD patients with an odds ratio of 0.089 (95%CI, 0.022-0.361). Our results provide support to the association between H558R polymorphism and the decreased risk for KSD. H558R polymorphism might increase susceptibility to KSD, and SCN5A containing the polymorphism might be a predisposing gene for QRS prolongation.

Long-term prognostic value of major and minor ECG abnormalities in latent Keshan disease with suspect chronic Keshan disease.

ObjectiveThis study aims to determine whether baseline electrocardiography (ECG) abnormalities, the appearance of new ECG abnormalities, or other clinical characteristics are associated with increased rates of progression to chronic Keshan disease (KD) among patients with latent KD.MethodsFour hundred and fourteen new latent KD patients from a monitored population in China were diagnosed and then followed for 10 years. Baseline and 10-year ECG abnormalities were classified according to the Minnesota Code as major and minor. Using Cox proportional hazards regression models, the addition of ECG abnormalities to traditional risk factors were examined to predict chronic KD events.ResultsIn 414 latent KD patients with ECG abnormalities, 220 (53.1%) had minor and 194 (46.9%) had major ECG abnormalities. During the follow-up, 92 (22.2%) patients experienced chronic KD events; 32 (14.5%) and 60 (30.9%) of these chronic KD events occurred in the minor and major ECG abnormalities groups, respectively. After adjustment for baseline potential confounders, the hazard ratios and 95% confidence intervals (CIs) for progression to chronic KD in latent KD patients with major ECG abnormalities versus those with minor ECG abnormalities was 2.43 (95% CI 1.58–3.93).ConclusionsMajor ECG abnormalities and new ventricular premature complex abnormalities that occurred during the follow-up were both associated with an increased risk of progression to chronic KD. Atrial fibrillation and right bundle branch block with left anterior hemiblock are the most strongly predictive components of major ECG abnormalities. Depending on the model, adding ECG abnormalities to traditional risk factors was associated with improved risk prediction in latent KD.

Comparative study on condition and related factors of Keshan disease and dilated cardiomyopathy in Shandong province

克山病是我国一种特有独立的地方性心肌病,经多年的综合防治,近年发病明显减少.本研究综合分析山东省克山病和非克山病病区扩张型心肌病(DCM)的病情及发病相关因素.1.对象与方法:(1)调查对象:根据《全国克山病监测方案(试行)》要求,选择沂水、莒县、邹城、沂源、莒南、滕州、青州7个县(市、区)作为克山病调查项目单位;按照《全国非克山病病区扩张型心肌病调查实施方案》要求,选取自然环境、生产生活方式与病区相似的高密市、博山区、淄川区、沂南县、苍山县、兖州市、临邑县7个非克山病病区作为DCM调查项目单位.每个项目单位随机选择2个乡(镇),每个乡(镇)选择1个自然村作为调查点;调查点内全部常住人口列为调查对象,以村常住人口600人以上为宜,要求检诊率不低于80％. 关键词：克山病;扩张型心肌病;硒含量

Mercury (Hg) and oxidative stress status in healthy mothers and its effect on birth anthropometric measures

This study was conducted to: (a) investigate the antagonistic interaction between selenium (Se) and mercury (Hg) in mothers and their newborns, (b) delineate the role of oxidative mechanisms induced by Hg exposure and (c) examine the protective effect of Se on Hg-induced oxidative stress and birth outcomes. Levels of Hg and Se were measured in umbilical cord blood and the placentas of 250 healthy mothers who participated in a study between 2006 and 2006 assessing prenatal exposure various pollutants. Levels of malondialdehyde (MDA) in cord and maternal blood and of 8-hydroxy-2-deoxyguanosine in urine were measured for assessing oxidative stress. Tail moment (TM) in the comet assay, as a biomarker of DNA damage was measured in samples of cord and maternal blood. The mean Se levels in umbilical cord blood (67.618±12.897μg/l) were lower than those reported in many countries, but none of the newborns had Se levels <20μg/l (the threshold limit of Keshan disease). More than 80% of the newborns, though, had Se levels below the 80μg/l needed for maximum glutathione peroxidase activity. Even though 18.6% of the newborns had levels of Hg ≥5.8μg/l (the reference dose of the Environmental Protection Agency), no relationship was observed with the biomarkers of oxidative stress. The mean placental Hg levels (0.056±0.075μg/g dry wt.) were higher than those reported for newborns with abnormal fetal development. Our study also documented significant placental transfer of Hg and Se to the fetus. The Hg/Se molar ratio in both cord blood and placental tissue was well below 1. The average amount of Se in both matrices was approximately 50-fold in molar excess over Hg. The molar excess of Se in the umbilical cord (0.843μmol/l), however, was lower than in placental tissues (13.098μmol/kg dry wt.). In further support of the relationships of Hg and Se on oxidative stress, we observed significantly lower levels of maternal MDA associated with Se levels in both cord blood and placental tissues and significantly higher TM levels associated with placental Hg in both newborns and their mothers. In contrast, Se/Hg molar ratios in placental tissues were positively associated with MDA and negatively with TM. The disproportion between Hg and Se might be influenced by the length of Hg exposure that in turn might affect Se bioavailability. Each birth anthropometric outcome was modeled as a function of Hg, Se and their interactions. After an adjustment for confounding variables, Hg in cord blood had a significantly positive rather than the expected negative association with crown-heel length. Placental Hg was associated with reduced birth height. Both associations were independent of prematurity. The status of Se in newborns was positively associated with crown-heel length and placental weight, with and without preterm births, and with birth weight, but only without preterm births. In contrast, a lower cephalization index was correlated with Se levels in cord blood, which may be an indicator of a detrimental effect on health. Our study, however, revealed associations between significantly lower levels of placental Se and several birth anthropometric measures (head circumference, birth weight and birth height) but the significance disappeared after excluding preterm births. Regression analyses generally indicated either significant or marginally significant Hg-Se antagonistic interactions that may have moderated the toxic effect of Hg on head circumference and birth weight. This finding may be due to chance or residual confounding and so may not be clinically relevant, but it may also suggest that Hg, Se and Hg-Se interactions are important factors for understanding Hg-induced adverse birth outcomes. Additional research will be necessary to evaluate the biological impact of combined metals in the assessment of fetal growth and development.

Mitochondrial-related gene expression profiles suggest an important role of PGC-1alpha in the compensatory mechanism of endemic dilated cardiomyopathy

Keshan disease (KD) is an endemic dilated cardiomyopathy with unclear etiology. In this study, we compared mitochondrial-related gene expression profiles of peripheral blood mononuclear cells (PBMCs) derived from 16 KD patients and 16 normal controls in KD areas. Total RNA was isolated, amplified, labeled and hybridized to Agilent human 4×44k whole genome microarrays. Mitochondrial-related genes were screened out by the Third-Generation Human Mitochondria-Focused cDNA Microarray (hMitChip3). Quantitative real-time PCR, immunohistochemical and biochemical parameters related mitochondrial metabolism were conducted to validate our microarray results. In KD samples, 34 up-regulated genes (ratios≥2.0) were detected by significance analysis of microarrays and ingenuity systems pathway analysis (IPA). The highest ranked molecular and cellular functions of the differentially regulated genes were closely related to amino acid metabolism, free radical scavenging, carbohydrate metabolism, and energy production. Using IPA, 40 significant pathways and four significant networks, involved mainly in apoptosis, mitochondrion dysfunction, and nuclear receptor signaling were identified. Based on our results, we suggest that PGC-1alpha regulated energy metabolism and anti-apoptosis might play an important role in the compensatory mechanism of KD. Our results may lead to the identification of potential diagnostic biomarkers for KD in PBMCs, and may help to understand the pathogenesis of KD.

Comparing gene expression profiles of Kashin-Beck and Keshan diseases occurring within the same endemic areas of China

In this study, differentially expressed genes in peripheral blood from patients with Kashin-Beck disease and Keshan disease were compared to further investigate the etiology and pathogenesis of both diseases, which occur in a common endemic area of China. Twenty Kashin-Beck disease patients and 12 healthy controls, and 16 Keshan disease patients and 16 healthy controls, were grouped into four pairs. Patients and controls were selected from common endemic areas for the two diseases. Total RNA was isolated from peripheral blood mononuclear cells from all patients and controls, and gene expression profiles analyzed by oligonucleotide microarrays. Sixteen genes differentially expressed in both Kashin-Beck disease and Keshan disease (versus controls) were identified, and comprised nine genes showing synchronous and seven asynchronous expression. The Comparative Toxicogenomics Database shows that expression and biological function of these genes can be affected by multiple environmental factors, including mycotoxin and selenium content, potential environmental risk factors for the two diseases. Thus, these shared differentially expressed genes may contribute to the distinct organ lesions, caused by common environmental risk factors of Kashin-Beck disease and Keshan disease.

Serum level of galectin-3 and its clinical significance in patients with chronic Keshan disease

ObjectiveKeshan disease (KD) is a fatal endemic dilated cardiomyopathy with unclear etiology and pathogenesis, and a high mortality in China. Pathologic studies confirmed that different degree of myocardial fibrosis existed in various types of KD. Myocardial fibrosis is an important contributor to the pathophysiology of left ventricular remodeling. Recently, galectin-3 (Gal-3) as a marker of cardiac fibrosis and heart failure was approved by the US FDA. The aim of this study was to evaluate the changes of serum level of Gal-3 in chronic KD (CKD) and their clinical implications. MethodsThe levels of serum Gal-3 were measured by using enzyme-linked immunosorbent assay (ELISA) in 37 CKD patients and 32 healthy controls. Echocardiography was used to determine parameter of left ventricular ejection fraction (LVEF) and left ventricular end-diastolic dimension (LVEDD). ResultsThe serum concentration of Gal-3 ([95.81±18.99] ng/ml versus [48.16±11.09] ng/ml, t=6.906, P<0.001) and LVEDD ([60.46±7.63] mm versus (42.69±10.66) mm, t=3.61, P<0.01) were significantly higher, while LVEF ([42.69±10.66]% versus [62.16±6.38]%, t=4.679, P<0.01) were significantly lower in CKD patients compared with healthy controls. A negative correlation was found between elevated Gal-3 and lower LVEF (r=−0.882, P<0.001) and a positive correlation was found between elevated Gal-3 levels and enlarged LVEDD (r=0.834, P<0.001) or higher NYHA class (r=0.854, P<0.01) in CKD patients. ConclusionSerum concentration of Gal-3 is strongly correlated with poorer left ventricular systolic function, enlarged LVEDD and higher New York Heart Association (NYHA) class, which may provide indirectly diagnostic information on myocardial fibrosis and heart function in CKD patients.

Oxidative Stress Is Involved in the Pathogenesis of Keshan Disease (an Endemic Dilated Cardiomyopathy) in China

Oxidative stress and selenoprotein deficiency are thought to be associated with the pathogenesis of Keshan disease (KD). However, to our knowledge, the level of oxidative stress and expression of selenoproteins have not been investigated in the myocardium of patients with KD. In this study, 8-hydroxy-2-deoxy guanosine (8-OH-dG), a marker of oxidative stress, was used to assess the level of oxidative stress, and thioredoxin reductase 1 (TrxR1) and glutathione peroxidase 1 (GPx1) were assessed to reflect the level of selenoproteins. Myocardial samples from 8 patients with KD and 9 non-KD patients (controls) were immunohistochemically stained for 8-OH-dG, TrxR1, and GPx1. The staining intensities were subsequently quantified using Olympus Image-Pro Plus 6.0 software. The data showed that the positive rate of 8-OH-dG expression in myocardial nuclei was higher in the KD group (68.6%) than that in the control group (2.4%). In addition, a positive correlation between the positive rate of 8-OH-dG and the degree of myocardial damage was observed in the KD group. The distribution of TrxR1 and GPx-1 was not associated with the distribution of myocardial damage. The expression of these two selenoproteins was higher in the control group than that in the KD group. Our study represents the first report on the expression profiles of oxidative stress and selenoproteins in the myocardium of patients with KD. The level of oxidative stress significantly increased and was positively correlated with the degree of myocardial damage in patients with KD. The selenoproteins, TrxR1 and GPx1, may have a role in the pathogenesis of KD.

Nucleic Acid Oxidation in Human Health and Disease

Growing scientific evidence suggests that oxidative stress plays an important role in human health and disease. Under oxidative stress, the excess levels of reactive oxygen species (ROS) may lead to modification of cellular nucleic acids. Oxidatively damaged DNA has been recognized in association with the development of aging, cancer, and some degenerative diseases. The topics covered in this special edition give some insight into how oxidatively damaged DNA is involved in human disease and its health impacts. This special issue contains five papers. Two papers are related to human disease, including Keshan disease and chronic kidney disease, while two papers cover the underlying mechanisms of inflammation-related carcinogenesis and the association between DNA damage and antioxidant capacity in humans. Finally, a paper summarizes the literature regarding the effect of phytoagents on nucleic acid oxidation in cancer cells. Keshan disease (KD) is an endemic cardiomyopathy of unknown etiology affecting inhabitants of a narrow belt between Northeast China and Southwest China. This region is known for low levels of selenium in the environment as well as in food. In an original research article entitled “Oxidative stress is involved in the pathogenesis of Keshan disease (an endemic dilated cardiomyopathy) in China,” J. Pei et al. demonstrate that oxidative stress in the myocardium may play a crucial role in KD. The authors found elevated 8-oxodG levels in myocardial nuclei of the KD patients. Moreover, the expression of glutathione peroxidase 1 and thioredoxin reductases 1 (selenoproteins) was important in the antioxidant system of the organism and higher in the control group than in patients suffering from KD. In a review article entitled “Oxidative stress and nucleic acid oxidation in patients with chronic kidney disease,” C.-C. Sung et al. provide a systematic review of the role of oxidative stress in chronic kidney disease (CKD). It begins with the mechanisms of radical production, antioxidant defense, pathogenesis, and recent biomarkers of oxidative stress in CKD patients. The authors also summarized and evaluated the potential benefit of antioxidant therapies in CKD patients, although their value as useful therapeutic tools is being tested and future studies are necessary to validate their prospective beneficial effects on CKD. Infectious agents (e.g., parasites and viruses) have been identified as carcinogenic to humans (IARC, group 1). The underlying mechanism of their carcinogenicity includes inflammation accompanied by generation of reactive oxygen (ROS) and nitrogen species (RNS). In a review article entitled “DNA damage in inflammation-related carcinogenesis and cancer stem cells,” S. Ohnishi et al. propose a model by which chronic inflammation by infectious agents induces generation of cancer stem cells. The authors suggest that tissue injury caused by ROS/RNS may activate progenitor/stem cells for regeneration. Oxidative stress may then cause multiple mutations which may result in the formation of mutant stem cells and cancer stem cells thus leading to carcinogenesis. In an original research article entitled “Is the oxidative DNA damage level of human lymphocyte correlated with the antioxidant capacity of serum or the base excision repair activity of lymphocyte?,” Y.-C. Tsai et al. investigate the individual levels of oxidative DNA base damage in the human lymphocyte from different donors (healthy and infected patients) and its correlation with total antioxidant levels in the serum and the DNA base excision repair capacity. The most important finding is that antioxidant serum levels may not change the steady state levels of the oxidative base damage in the DNA. One should also consider that antioxidants in our body protect us in acute and highly stressful situations when we have high levels of ROS in a short time period rather than decrease the steady state levels. In a review article entitled “Phytoagents for cancer management: regulation of nucleic acid oxidation, ROS, and related mechanisms,” W.-L. Lee et al. present a detailed review of the role of phytoagents as redox regulators of nucleic acid oxidation in carcinogenesis. On the concept of genetic heterogeneity caused by nucleic acid oxidation as a major driving force of cancer progression, the authors highlight how and why phytoagents induce or prevent oxidative stress and their potential use in cancer prevention or therapy.

Mycelial Growth of &amp;lt;i&amp;gt;Pleurotus&amp;lt;/i&amp;gt; Spp in Se-Enriched Culture Media

Selenium (Se) is an essential element to human. However, this element can be in low content in soil of some regions. Se deficiency may cause Keshan disease, thyroid dysfunction and osteoarthritis. The Se-enriched cereals are an interesting way to prevent these diseases. But, recent studies have shown that Se-enriched mushrooms are a better Se source. This occurs due to the high capacity of the fungi to absorb and transform the inorganic Se to organic forms, which are more bioavailable. Pleurotus ostreatus and Pleurotus eryngii are mushrooms species worldwide consumed and able to Se bioaccumulate. However, depending on the level of this element, it can be toxic for the fungus. Here we showed that the presence of the Se in culture medium decreases fungal growth rate, hyphae diameter and septum distance and causes alteration in color of colony. A garlic strong smell was directly proportional to Se level. P. eryngii was more tolerant to Se than P. ostreatus. So, it is important to screen this element level for Se-enriched mushroom production.

Advances in the study of genetic enrichment of selenium in plants

Selenium (Se) is a micronutrient essential for human and animal health. Due to the unbalanced distribution of Se resources in the world, Se deficiency is regarded as a major human health problem. Insufficient ingestion of Se in human caused a series of disease including Keshan disease and Kashin-Beck's disease. While some parts of the world was Se poisoning due to the Se ores on geological stratification or Se pollution. The using Se-enriched and/or hyperaccumulated green plants to treat these problems has acquired more and more attention worldwide from last decade. This paper describes current advances in the efforts of searching Se enriched plant genetic resources, clarifying the Se metabolism and accumulation mechanism in plants, and cloning key genes responsible for Se accumulation or hyper-accumulation and their transformation in plants.

The prevalence of Keshan disease in China

Sentinel surveillance of Keshan disease (KD) is limited by unable to give the prevalence rates and their estimates. This study was to find the national KD prevalence and the estimated patient numbers to provide evidence toward modifying the policy of KD prevention and control. Using a probability proportional to population size, randomized, multistage, and cluster sampling, we surveyed 101,127, measured grain selenium levels; and surveyed household income with pre-designed questionnaires. The national prevalence rates of KD, chronic KD and latent KD were 2.21%, 0.50%, and 1.71% respectively. Chronic KD patients are mainly in the provinces where KD had been seriously epidemic. The KD prevalence rate was higher in females (2.20%) than in males (1.98%). These were also higher in older age groups. The cases younger than 30 years accounted for 13.6%, indicating the possibility that KD is still occurring. Nationally, the estimated numbers of KD and chronic KD patients are 1,675,500 (95% CI, 1,608,500-1,747,300) and 379,800 (95% CI, 346,700-412,800) respectively. Multiple logistic regression analysis indicated that family income was a significant dependent variable (OR: -0.258, 95% CI: -0.332 to -0.185, p<0.001). More than 2000 chronic KD patients found in the study were treated in 2009-2011. The limitation of this study was that sampling size was determined at national level. KD is still a public health issue among the people of the historically severe endemic areas. Selenium supplementation, self-management program for chronic KD patients and translation epidemiology of KD surveillance should be strengthened.

An original discovery: selenium deficiency and Keshan disease (an endemic heart disease).

This is a review article telling a 50-years old story about the studies on selenium deficiency and Keshan disease in China, an endemic heart disease with high case-fatality, as an example of translational research. Extensive cross-sectional epidemiological studies showed that low selenium concentrations in cereal grains and low selenium status of local residents were associated with the occurrence of Keshan disease. Several large population based intervention trials using oral administration of sodium selenite tablets showed significant reduction of Keshan disease incidence. Based on the above evidence, it was concluded that selenium deficiency is the major cause of Keshan disease, although other etiological factors could not be ruled out. The implications of the findings include: provided critical scientific evidence for selenium being an essential trace element for humans; as scientific basis for identifying minimum requirement and RDA/RNI for selenium; and as solid reference for the formulation of effective preventive measures for Keshan disease in China.

Analysis of surveillance data of Keshan disease from 1995 - 2009 in Henan province

Objective To observe the change of conditions and study the epidemiology of Keshan disease from 1995 to 2009 in Henan province.Methods From 1995 to 2009,seriously ill township (village) of Keshan disease were selected as monitoring sites,and one cross-sectional survey was conducted annually.Resident population were asked of their disease history,and were taken clinical examination.Suspicious or suspected cases of Keshan disease and people with abnormal ECG were taken 2 m X-ray.Hair and wheat flour samples were collected for selenium testing.Results From 1995 to 2009,about 6632 people were checked,130 chronic and 52 latent cases of Keshan disease were identified,the total detection rates were between 1.12％ and 5.06％.The detectable rate for abnormal electrocardiogram and heart enlargement found through chest X-ray examination were 10.24％ -30.65％ and 32.4％ - 77.8％,respectively.The content of hair selenium tended to increase,the highest was in 2009 (357.12 μg/kg),and the lowest was in 1997( 142.68 μg/kg).Conclusion Keshan disease is stable in Henan province,and prevention and control measures should be strengthen gradually. Key words: Keshan disease; Surveillance; Electrocardiogram; Selenium

Keshan to Kansas

Keshan disease was so named after the discovery of endemic cardiomyopathy in Keshan's county in Heilongjiang Province of China, due to selenium deficient soil in those areas. Selenium deficiency is a widely accepted cause of Keshan disease. Early diagnosis and treatment affect the outcome greatly, and many studies and clinical trials confirmed the reversibility of heart failure after selenium replacement. Considering the potentially fatal outcome of KD, there are no specific guidelines about selenium replacement in overt heart failure secondary to Keshan disease. A 49 year old Caucasian female with past medical history of HTN, stroke with residual left sided weakness, multiple abdominal surgeries with colostomy, a PEG tube placed for dysphagia, and recurrent aspiration pneumonia presented with 2 weeks history of progressive SOA and dry cough. There was a JVD, bilateral diminished breath sounds and bilateral 2+ pitting pedal edema. Few hours after admission the patient was coded and had a run of ventricular tachycardia and torsades de pointes. She was recussistated and placed on vasopressors for some time. Pertinent lab work showed WBC: 29,000, magnesium: 0.7 meq/L, albumin: 1.4 g/dL, prealbumin: 6.9 mg/dL, TSH: 9 mLU/L, BNP: 8000 pg/mL, and chest X-ray showed: bilateral pleural effusion with pleural fluid analysis suggestive of transudative fluid. Diagnosis of heart failure was made. 2D echo showed global hypokinesia with EF 20%, and aortic, mitral, and tricuspid insufficiency. Considering patient's malnourished status we checked selenium levels which were 38 μg/mL. Selenium was replaced at a dose of 100 μg/day for 2 weeks; post therapy levels were 179 μg/mL and

The effect of DHEA treatment on the oxidative stress and myocardial fibrosis induced by Keshan disease pathogenic factors

Oxidative stress induced by the combined deficiencies of selenium (Se) and vitamin E (VE) is considered the basic factor of Keshan disease (KD). Dehydroepiandrosterone (DHEA) is a naturally occurring adrenal androgen that has antioxidant properties. We found that a Se- and VE-deficient diet induced KD lesions in rats, while 0.05, 0.125, and 0.25 g/kg DHEA caused a concentration-dependent inhibition in the development of oxidative stress and extracellular matrix (ECM) deposition in the left ventricles of the Se- and VE-deficient rats. In addition, DHEA counteracted activation of NFκB as well as the subsequent increase in TGFβ-1 and CTGF induced by the Se- and VE-deficient diet. These studies suggested that DHEA prevents oxidative stress and might be useful in treating Se and VE deficiency-related KD. These effects were based on its antioxidant effects and ECM deposition inhibition in left ventricles.