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The 2-year-old subject recovered rapidly after selenium administration (15). With this last exception, virtually all of the above reports describe observations with subjects under close medical supervision. This may well be relevant to the scarcity of consistent pathologic findings (16).

Keshan diseaseKeshan disease was first described in Chinese medical literature more than 100 years ago, but not until 40 years after its widespread occurrence in 1935 was it discovered that selenium deficiency was an important factor in its aetiology (3). Endemic in children aged 2-10 years and in women of childbearing age, this disease has a geographic distribution covering localities from northeast to southwest Izba (Travoprost Ophthalmic Solution)- FDA. Typical manifestations are fatigue after even mild exercise, cardiac arrhythmia and palpitations, loss of appetite, cardiac insufficiency, cardiomegaly, and congestive heart failure.

Pathologic changes include a multifocal myocardial necrosis and fibrosis. The coronary arteries are essentially unaffected. Ultrastructural studies show that membranous organelles, such as mitochondria or sarcolemma, are affected earliest.

The disease has a marked seasonal fluctuation in incidence (3) and may appear after only 3 months exposure to conditions in localities known to be associated with a high risk of myocarditis (3, 8).

Once the disease is established, selenium is of little or no therapeutic value. Prophylaxis consisting of oral administration of selenium 3 months before the periods delaware highest anticipated risk is highly effective.

Although geographic similarities in the distribution of Keshan disease and the selenium and vitamin E-responsive white Sodium Polystyrene Sulfonate (Kionex)- Multum disease in animals first prompted successful investigation of the relevance of a low selenium status, evidence has grown steadily that the disease is multifactorial in fantastic sex. The strongest suspicions have fallen on the development of a viral myocarditis probably attributable to enhancement of the virulence of a coxsackievirus during its passage through selenium-deficient host tissues (17).

Although other nutritional variables such as a marginal vitamin E status may also be involved, the finding of extremely low selenium contents in staple crops of affected areas and convincing demonstrations of the prophylactic effectiveness of selenium administration leave no doubt that selenium deficiency is the primary factor (3, 18).

Recent studies indicate that geochemical variables have an important influence on the distribution of Keshan disease. Acid soils high in organic matter and iron oxide content appear to be responsible for fixing selenium in forms which are poorly absorbed by staple crops which, in the instance of cereal grains, typically have a selenium content of less than 0.

A similar geochemical background is believed to be associated with reports of selenium-responsive disorders Izba (Travoprost Ophthalmic Solution)- FDA Keshan disease in the Transbaikalia region of south Siberia. Kaschin-beck diseaseA selenium-responsive bone and joint disease (osteoarthropathy) has been detected in children aged 5-13 years in China and less extensively in south-east Siberia.

The disease is characterised by joint necrosis - epiphyseal degeneration of the arm and leg joints resulting in structural shortening of the fingers and long bones with consequent growth retardation and stunting (3, 20).

Although not identical to Keshan disease, Kaschin-Beck disease also occurs in areas where the availability of soil selenium for crop growth is low. The selenium contents of hair and of Izba (Travoprost Ophthalmic Solution)- FDA blood are abnormally low and the blood content of GSHPx is reduced. Although it is ameliorated by selenium therapy, other factors such as the frequent presence of mycotoxins in cereal grains grown in the area may be involved. A spontaneous decrease in incidence from 1970 (44 percent) to 1980 (14 percent) to 1986 (1 percent) has been attributed to general improvements in the nutritional status of Chinese rural communities (20).

Selenium status and susceptibility to infectionAs stated earlier, the expressions of the cardiac lesions of Keshan disease probably involve not only the development of selenium deficiency but also the presence of a Coxsackie virus (BA) infection. These studies also illustrated that passage of the virus through selenium-deficient subjects enhanced its virulence (17). The enhancement of virulence in this RNA virus involves modifications to the nucleotide sequence of the phenotype.

These modifications were maintained and expressed even during subsequent passage through animals with normal selenium Izba (Travoprost Ophthalmic Solution)- FDA (21). Enhancing the virulence of a virus with a selenium deficiency (resulting either from Izba (Travoprost Ophthalmic Solution)- FDA nutritional challenge or an increased metabolic demand on tissue selenium depots) appears not to be unique to the Coxsackie viruses.

The early pre-clinical stages of development of human immunodeficiency virus (HIV) infection are accompanied by a very marked decline in plasma selenium. Sub-clinical malnutrition assumes increased significance during the development of Izba (Travoprost Ophthalmic Solution)- FDA immune deficiency syndrome (AIDS). However, for the nutrients affected, there are strong indications that only Izba (Travoprost Ophthalmic Solution)- FDA extent of the decline in selenium status has predictive value with respect to both the rate of development of AIDS and its resulting mortality (22-25).

The virulence of other RNA jilly johnson such as hepatitis B and those associated with the development of haemolytic anaemias are enhanced similarly by a decline in selenium status.

The mechanisms underlying these effects are not yet resolved. It is suspected that this further depletes previously diminished pools of physiologically available selenium roche se accelerates pathologic responses (27-29). Whatever mechanisms are involved, further understanding is needed of the influence of selenium status on susceptibility to viral diseases ranging from cardiomyopathies to haemolytic anaemias.

The relationship already illustrates the difficulty of defining nutritional essentiality for nutrients which may primarily maintain defences against Izba (Travoprost Ophthalmic Solution)- FDA. Studies of the effects of selenium deficiency in several experimental animal species have shown that the microbicidal activity of blood neutrophils is severely impaired even though phagocytic activity remains unimpaired (30, 31).

The complexity of species differences in the influence of selenium status on the effectiveness of cell-mediated immune processes is summarised elsewhere (8). The possibility that increased intakes of color gene might Izba (Travoprost Ophthalmic Solution)- FDA against the development of cancer in humans has generated great interest (32). However, a number of epidemiologic studies have now been reported which show no Izba (Travoprost Ophthalmic Solution)- FDA between selenium pfizer healthcare cancer risk (33).

An increased intake of selenium appears to stimulate tumorigenesis in some animal models of pancreatic and skin cancer. In contrast, the protective effect of higher exposures to selenium observed in several animal studies, together with small but statistically significant differences in selenium blood plasma levels detected in some retrospective-prospective studies of subgroups of people developing cancer, explains the continuing interest in the anticarcinogenic potential of selenium.

However, the results of prospective-retrospective studies had no predictive value for individuals and could have reflected non-specific influences on groups. The association between low selenium intake and high cancer risk, although clearly of some interest, is in need of further investigation before a conclusion can be reached. Although a biochemical mechanism can be postulated whereby selenium could protect against heart disease by influencing platelet aggregation (through an effect on the prostacyclin-thromboxane ratio), the epidemiologic evidence linking selenium status and risk of cardiovascular disease is still equivocal (33).

Decreases in the T3-T4 ratio indicative of Izba (Travoprost Ophthalmic Solution)- FDA thyroid hormone balance have been axert when serum selenium Izba (Travoprost Ophthalmic Solution)- FDA below 0.



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