Keshan Disease Research Articles

The effect of organic selenium on the metabolism of free-radicals in rats fed on grains from Keshan disease areas

The effect of organic selenium on the metabolism of free-radicals in rats fed on grains from Keshan disease areas

Free radical metabolism in autopsy myocardium of Keshan disease

Free radical metabolism in autopsy myocardium of Keshan disease

Study on the superprecipitation of cardiac actomyosin of the rat fed on grains from Keshan disease areas

Study on the superprecipitation of cardiac actomyosin of the rat fed on grains from Keshan disease areas

Cellular enzymatic spectrum in myocardium of Keshan disease patients

Cellular enzymatic spectrum in myocardium of Keshan disease patients

Superoxide dismutase activities in erythrocytes from population in Keshan disease area

Superoxide dismutase activities in erythrocytes from population in Keshan disease area

Correlation of myocardium and serum enzymes in Keshan disease model animals

Correlation of myocardium and serum enzymes in Keshan disease model animals

Serum biochemical assay in population in Keshan disease area

Serum biochemical assay in population in Keshan disease area

Concentration of trace elements in hair from children living in a Keshan disease district in China

The hair from 9 children living in a Keshan disease prevalent district and from 10 children living in a Keshan disease non-prevalent district in China was analyzed. At the same time, the hair from 35 children of the same age residing in Tsukuba district in Japan was analyzed for comparison of the concentration of essential trace elements with that of children living in the Keshan disease prevalent district. Se concentration was determined by a fluorophotometric method and 16 other elements were analyzed by ICP emission spectrometry. Hg was analyzed by the heating evaporation method and by neutron activation analysis. The Se concentration in the hair of children living in the prevalent district was very low, being one-tenth that of the Japanese. The Ni concentration was particularly low in the prevalent district, and it determined to study more about the effects of Ni deficiency on health. In the prevalent district, Mg and Ca levels were low and those of Pb, Fe, Al, Ti were relatively high. Mn concentrations of both districts in China were very high when compared to the Japanese. The results of this study showed that the low Se concentration in Keshan disease is in agreement with previously reported data. Ecological factors, including nutrition were considered to be important in the etiology of this disease.

STUDY ON RUBIDIUM CONCENTRATION OF DIFFERENT SAMPLES FROM KESHAN DISEASE AREA OF SICHUAN PROVINCE

Rubidium (Rb) concentration in different samples collected from Keshan disease (KD) area of Sichuan Province has been determined with PIXE and NAA (Neutron Activity Analysis), and compared with that in three non-KD areas. About 200 erythrocyte samples of healthy children aged from 6 to 11 were collected from four different areas with various selenium status. 20 rice samples and 6 soil samples were taken from two of above four areas. The results showed that Rb content of erythrocyte of children in KD area (Dechang county) was three times that in the other three non-KD areas. The Rb contents of rice and soil in KD area were higher than that in non-KD areas, too. The abnormal high Rb concentration in erythrocyte of children depended on the Rb intake and the Rb level of the living environment.

Fatty acid composition of blood lipids in Chinese children consuming high erucic acid rapeseed oil.

The fatty acid patterns of oils, blood plasma and erythrocyte lipids from 28 children in the Shaanxi province of the People's Republic of China were determined by capillary gas liquid chromatography. The main source of fat in this region is rapeseed oil. The analysis of locally available rapeseed oil shows a high erucic acid content (mean 43.83%, range 33.91-50.48%). According to protocol data, about 3% of the daily nutrient energy is provided by erucic acid. Despite a low fat intake in Chinese children, the composition of the fatty acids of the fractions analyzed showed normal patterns. However, erucic acid was found in all fractions analyzed. Data on erucic acid in human tissue are scarce. Although there are no indications of erucic acid toxicity in man, it is known to cause cardiac lipidosis and necrosis in rats. The question remains open if erucic acid aggravates selenium deficiency symptoms which are known to be associated with Keshan disease, an endemic cardiomyopathy.

Scientific rationale for the 1989 Recommended Dietary Allowance for selenium

During the past 15 years, our knowledge of human selenium requirements has improved greatly, primarily because of research conducted in the People's Republic of China. Dietary surveys demonstrated that Keshan disease, a juvenile cardiomyopathy, was absent in parts of China where the food supply provided at least 19 and 13 micrograms selenium per day for men and women, respectively. Such intakes can be regarded as minimum daily requirements for selenium. Chinese scientists also carried out a study in an area where Keshan disease was prevalent to determine the amount of dietary selenium needed to maximize the activity of the selenium-containing enzyme, glutathione peroxidase, in plasma. For a man weighing 60 kg, enzymatic activity reached a plateau at selenium intakes of about 40 micrograms per day. These data were used by the US National Research Council as the basis for its 1989 Recommended Dietary Allowance (RDA) for selenium. The RDA was calculated as 70 and 55 micrograms per day for adult men and women, respectively, after correcting for differences in body size and taking into consideration possible individual variations in requirements. This RDA is readily satisfied by typical diets in countries with relatively selenium-rich soils, such as the United States. In selenium-poor areas of the world (eg, China, New Zealand, Scandinavia), diets would not readily furnish such intakes.

Geo-ecological zones and endemic diseases in China — a sample study by remote sensing

This paper distinguishes three geo-ecological zones in China: the southeast wet zone, the northwest dry zone and the intermediate transitive zone. The relationships between geo-ecological zone and endemic diseases are highlighted, with examples on schistosomiasis, Keshan and Kaschin Beck diseases, and fluorosis. Remote sensing technology has proved to be useful in identifying, analyzing and monitoring the distribution of these diseases.

Role of Uric Acid as an Endogenous Radical Scavenger and Antioxidant

Attention is being increasingly focused on the involvement of radicals and oxidants in the genesis, maintenance, or exacerbation of various physiologic and pathologic alterations of cell and organ function. Table 1 lists some of the better established examples in which radical species, such as the superoxide (O2−) and hydroxyl (OH) radicals, and oxidants, such as singlet oxygen, hydrogen peroxide (H2O2), hypochlorous acid (HOCl), and aldehydes, are believed to play a causal role. 1 Halliwell B Gutteridge JMC Free radicals in biology and medicine. Clarendon Press, Oxford1989 Google Scholar In view of the general chemical reactivity of all these metabolic intermediates, a pronounced effect on biologic systems is to be expected. Table 1—Cell and Organ Dysfunctions with a Presumed Etiologic Link to Radicals and Oxidants Aging Irradiation injury Ischemia and reperfusion injury ARDS, sepsis Atherosclerosis Autoimmune diseases Glomerulonephritis Rheumatoid arthritis Cancer Hyperoxia Iron overload Keshan disease Vitamin E deficiency Xenobiotic toxicity Pharmaceuticals Insecticides Smoking Smog Open table in a new tab

A preliminary study on the antimutagenic effect of seleno-malt

Seleno- malt is an organic Selenium product recently developed in China. Seleno- malt itself is not genotixic. It antagonized the mutagenic effect of aflatoxin B1. The antagonistic activity was 10–15 times higher than Selenoyeast may be used as a food additive in areas with low selenium level for the prevention of Ke-Shan disease and Cancer.

Selenium in geo-ecosystem and its relation to endemic diseases in China

In China, Se deficiency is associated with Keshan disease and Kaschin-Beck disease. This paper further demonstrates this relationship by studying the Se levels in the geo-ecosystem substances, including soil, plant, herbage, food grain, wool and human hair in disease affected areas and in control non-disease areas. Buteha Qi and Tailai counties in Northeast China were selected as the typical areas for these studies. The results show that in affected areas the average Se contents were: for soil, 0.125mg kg1, plants, 0.057 mg kg−1; herbage, 0.026 mg kg1; wheat, 0.012 mg kg−1; maize, 0.008 mg kg1; wool, 0.046 mg kg−; and human hair, 0.144 mg kg1. In the control area, the substances mentioned above all had higher Se contents compared with those in the affected area. Thus, it was shown that the geo-ecosystem of the affected area was low in Se, an important reason for the occurrence of Keshan disease and Kaschin-Beck disease. In recent years, some increase in the Se level of human hair was also found in the studied areas. This increase coincides with the decline, since the mid 1980's, of the incidence of the two diseases. An elevation in hair Se may, therefore, be a good indication of an improved Se intake of the subject population.

Selenium in Pediatric Nutrition

Se is an essential nutrient that provides antioxidant protection in concert with vitamin E. Several selenoproteins have been identified, but only one, SeGSHpx, has a known function, that of neutralizing toxic hydroperoxides. Plasma Se concentration, being responsive to changes in Se intake, is the most practical and widely used measure of nutritional Se status. The plasma Se concentrations of the majority of healthy infants and children fall within the range of 50 to 150 micrograms/L. Although SeGSHpx activity measures the metabolically functional form of Se, the lack of a standardized analytical method has limited its usefulness as an index of nutritional Se status. Se deficiency was first observed in animals, but it is now recognized to occur in humans. Two human diseases associated with severe nutritional Se deficiency have been reported from China: a juvenile cardiomyopathy named Keshan disease and a chondrodystrophy named Kaschin-Beck disease. Long-term TPN, which provides negligible amounts of intrinsic Se, has been demonstrated in some cases to result in biochemical and clinical impairment. Although there are no consistent signs and symptoms characteristic of TPN-associated Se deficiency in addition to the low blood selenium levels, some patients will experience leg muscle pain and altered serum transaminase and creatine kinase activities. These manifestation of Se deficiency usually take years to develop. Recent information about the amount of dietary Se needed to maximize plasma SeGSHpx activity in adult men has allowed for better estimates of the Se requirement for humans. Recommended daily dietary allowances published recently by the National Academy of Sciences have been revised for infants and children in this paper by making appropriate adjustments for the protein requirements of these age-groups. These recommended intakes for Se can generally be met by consuming adequate amounts of cereals, meat, eggs, dairy products, human milk, and infant formula, which are good sources of highly available Se and are of low risk of providing excess amounts of Se. Suboptimal Se intakes by pregnant women may predispose their infants to low Se status at birth, which in turn may affect the infants ability to maintain adequate Se status during the first few months of life. In those situations where protein intake is restricted, such as in phenylketonuria and maple syrup urine disease, Se-supplemented formulas should be used. The most critical situation for Se supplementation is in pediatric patients receiving long-term TPN therapy.(ABSTRACT TRUNCATED AT 400 WORDS)

Oxidative Damage in Myocardial Mitochondria of Keshan Disease. An Endemic Cardiomyopathy in China.

It has been shown in this study that the selenium (Se) content and glutathione peroxidase (GSH-Px) activity in blood and tissues of Keshan disease (KD) patients were lower than those of control subjects. Also these patients showed abnormal lipid composition of plasma and of membranes of erythrocytes and myocardium, such as a decrease in phospholipid (PL) and in cardiolipin (CL) and an increase in the molar ratio of cholesterol/PL and of sphingomyelin/phosphatidylcholine. In addition the cytochrome c oxidase (CCO) activity in their myocardial mitochondria was decreased.A guinea pig model fed cereals from Yunnan, a KD-endemic area, for 15 weeks, showed a series of changes similar to those observed in KD patients, as above, such as decreases in Se level and activity of GSH-Px and of glutathione-S-transferase, and significant increases in lipid peroxides, hydroperoxides (conjugated dienes), and fluorescent chromolipids. The lipid composition of myocardial mitochondria in the animal model was abnormal; especially, the CL was decreased. Even though the CCO content was almost unchanged, activity of the enzyme was decreased remarkably. This result coincides exactly with the changes seen in the circular dichroism spectra of myocardial mitochondria, the peak values (208 and 224nm) of which were lower significantly than those of the control.

A study on the inhibition of rat myocardium glutathione peroxidase and glutathione reductase by moniliformin

In preparations of Wistar rat myocardium, Km values of GSH-Px to the substrates, H2O2 and GSH, as determined by the DTNB method, were 1.9 x 10(-4) mol/L and 2.0 x 10(-3) mol/L respectively. The Km value of GSSG-R to GSSG was 6.0 x 10(-5) mol/L by UV spectrophotometric assay. In vitro, the activity of GSH-Px was inhibited by 1.0, 6.0 and 16.0 mmol/L synthetic moniliformin (MF) with the corresponding activities of 89.4%, 65.2% and 47.9% of control values (n = 6). The activities of GSSG-R in the presence of 16.0 and 32.0 mmol/L MF were 74.4% and 61.9% of controls (n = 5) respectively. These results revealed that the inhibition of GSH-Px by MF was stronger than that of GSSG-R. As determined by Lineweaver-Burk and of Dixon plots, the inhibition of GSH-Px and GSSG-R by MF was competitive and noncompetitive, respectively. The affinity of GSH-Px to MF was higher than that of GSSG-R because the inhibition constant Ki of the former (6.0 mmol/L) was less than that of the latter (39 mmol/L). We suggest that the mechanism of toxic-damaging effects of MF on myocardium, may be closely related to the failure of remove of free radicals by some enzymes, as GSH-Px and GSSG-R, and that MF may be involved in keshan disease.

Common denominators in the etiology and pathology of visceral lesions of cystic fibrosis and Keshan disease

The common denominator of a unique disseminated multi-focal miliary myocardial hyaline necrosis and fibrosis in Keshan disease (KSD) and cystic fibrosis (CF) and a commonality of the affected age groups of fetuses and preschool children led to the review of existing KSD autopsy material to search for pancreatic and hepatic lesions considered pathognomonic for CF. Pancreatic lesions considered pathognomonic for CF were found in 595, or 35% of 1700 documented cases of KSD. The pancreatic lesions were limited to tissues of fetuses and preschool children. Adults dying of KSD had diagnostic lesions limited to the cardiovascular system, liver, and skeletal muscle. Varying degrees of focal biliary cirrhosis were identified in 850, or 50% of the KSD autopsies, and 85, or 5% developed severe lobular cirrhosis. The common denominator in CF and KSD appears to be a primary or induced secondary selenium deficiency in age-susceptible humans, prenatally at or around 22 wk of fetal life, during early postnatal life, or during the rapid-growth preschool years. The basic difference between the natural history of CF and KSD is that the selenium deficiency is totally environmental in KSD and appears to be the result of a maternal malabsorptive syndrome or an abnormality of selenium transfer in CF.

Selenium and cardiovascular disease

For humans, ecological and epidemiological results are reported that show a relationship between the serum selenium concentration and cardiovascular disease in populations where low serum selenium concentrations are found, e.g., in Eastern Finland. From clinical studies done in Germany (FRG and GDR), Finland, and Sweden, subnormal serum selenium and partially whole blood selenium concentrations are reported in patients with acute myocardial infarction. For patients with coronary arteriosclerosis, subnormal serum selenium concentrations are reported from the USA and Germany and subnormal whole blood selenium concentrations from Germany. Subnormal serum and subnormal whole blood selenium concentrations of patients with cardiomyopathy are reported from non Keshan disease affected areas in Germany, France, and China. In selenium deficiency, an accumulation of lipid peroxides in the heart may occur, especially under ischemic conditions and if ischemic tissue is reperfused. Lipid peroxides in the heart may damage the cell membrane and may lead to an impaired calcium transport with an uncontrolled calcium accumulation in the cell. This may result in an activation of phospholipids, and, in consequence, to an enhanced formation of arachidonic acid. An increased concentration of lipid peroxides owing to selenium deficiency may shift the prostaglandin synthesis from prostacyclin to thromboxane, causing enhanced blood pressure and platelet aggregability. From animal experiments, it is known that selenium protects against cardiotoxic elements, cardiotoxic xenobiotics, and viral infections that affect the heart. Selenium deficiency may also be a secondary factor in the causation of hypertension and myocardial ischemia.