Gerald F. Combs

Chemopreventive Agents: Selenium

The element selenium (Se) was recognized only 40 years ago as being essential in the nutrition of animals and humans. It is recognized as being an essential component of a number of enzymes, in which it is present as the amino acid selenocysteine. Se compounds have also been found to inhibit tumorigenesis in a variety of animal models, and recent studies indicate that supplemental Se in human diets may reduce cancer risk. The antitumorigenic activities have been associated with Se intakes that correct nutritionally deficient status in animals, as well as higher intakes that are substantially greater than those associated with maximal expression of the selenocysteine-containing enzymes. Therefore, it is proposed that while some cancer protection, particularly that involving antioxidant protection, involves selenoenzymes, specific Se metabolites, which are produced in significant amounts at relatively high Se intakes, also discharge antitumorigenic functions. According to this two-stage model of the roles of Se in cancer prevention, individuals with nutritionally adequate Se intakes may benefit from Se supplementation. Evidence for chemoprevention by Se and for the apparent mechanisms underlying these effects is reviewed to the end of facilitating the development of the potential of Se compounds as cancer chemopreventive agents.

Naturally Occurring Thiamine Deficiency Causing Reproductive Failure in Finger Lakes Atlantic Salmon and Great Lakes Lake Trout

Abstract A maternally transmitted, noninfectious disease known as the Cayuga syndrome caused 100% mortality in larval offspring of wild-caught landlocked Atlantic salmon Salmo salar from several of New Yorks Finger Lakes. Survival of lake trout Salvelinus namaycush from Lakes Erie and Ontario was also impaired, but not until yolk absorption was nearly complete; moreover, mortality was greatly reduced relative to that of the salmon (range: 5–87%). Tissue concentrations of thiamine hydrochloride were severely reduced in these salmonid fish relative to unaffected control stocks. Afflicted Atlantic salmon treated with thiamine by yolk-sac injection or by bath immersion recovered completely from the Cayuga syndrome, as evidenced by the quantified reversal of abnormal swimming behaviors only 2 d after treatment and by the excellent survival (>95%) of the treated Atlantic salmon through 1.5 months of feeding. These data represent the first evidence of a vitamin deficiency causing the complete reproductive failu...

The Nutritional Prevention of Cancer: 400 Mcg Per Day Selenium Treatment

Nonexperimental studies suggest that individuals with higher selenium (Se) status are at decreased risk of cancer. The Nutritional Prevention of Cancer (NPC) study randomized 1,312 high-risk dermatology patients to 200-mcg/day of Se in selenized yeast or a matched placebo; selenium supplementation decreased the risk of lung, colon, prostate, and total cancers but increased the risk of nonmelanoma skin cancer. In this article, we report on a small substudy in Macon, GA, which began in 1989 and randomized 424 patients to 400-mcg/day of Se or to matched placebo. The subjects from both arms had similar baseline Se levels to those treated by 200 mcg, and those treated with 400-mcg attained plasma Se levels much higher than subjects treated with 200 mcg. The 200-mcg/day Se treatment decreased total cancer incidence by a statistically significant 25%; however, 400-mcg/day of Se had no effect on total cancer incidence.

Selenium in Foods

Publisher Summary The chapter discusses the research on Selenium in foods, its chemical speciation, geographic variation and various other factors. Analytical methods for analysis of Se in foods include fluorometry, atomic absorption spectrophotometry, neutron activation analysis, proton-induced x-ray emission measurement, and double isotope dilution method. Selenium occurs in proteins as analogs of amino acids, in plants as selenomethoinine and in animals as selenocysteine. Geographic variation in selenium content of foods is discussed. The variations of the Se content are due to the geographical differences in the amount and availabilities of Se in soils. The Se content of foods of plant origin can vary within a particular geographic region according to specific climatic conditions such as plant growth, maturity at harvest and crop yield. The livestock diets reflect the Se status of locally produced feedstuffs and animal products. Se in liquid formula foods varies according to combination of ingredients used and Se content in those ingredients. Utilization of dietary Se is explained. It is the net result of physiological and metabolic processes that convert a portion of ingested food Se into metabolically active form, necessary for physiological function. Three approaches to evaluate the relative efficacy of known amounts of Se are discussed. The amount of Se in human diets is explained. Focus on further research should be to improve the characterization of Se in core foods, to understand the factors affecting the bioavailability of Se from meals and to understand the health hazards associated with low and high intake of Selenium.

The Engorgement of Swarming Worker Honeybees

SummaryThe weight and sugar concentration of the food load in the honey stomach of worker honeybees were measured. The food load of workers in swarms 4 hours after issuing weighed 4 times as much as that of workers in colonies not preparing to swarm. All workers in a swarm were not equally engorged, and different engorgement did not appear to be responsible for colony segregation at the time of swarm issuance. Worker engorgement occurred gradually during the 10 days prior to swarm issuance. Its measurement may therefore serve as method of swarm prediction.

Metabolic Activation of Oxygen by Nitrofurantoin in the Young Chick

Anaerobic incubations containing nitrofurantoin, and NADPH-generating system, and chick hepatic microsomes produced an electron spin resonance spectrum identified as the nitro anion free radical. Aerobically, nitrofurantoin markedly stimulated oxygen consumption, superoxide formation, and NADPH oxidation in hepatic microsomal preparations from control and selenium-deficient chicks. The nitrofurantoin-stimulated oxidation of NADPH was inhibited by superoxide dismutase (SOD). The superoxide-dependent oxidation of NADPH did not appear to be mediated by an NADP• radical, as has been shown for lactate dehydrogenase. Further, the aerobic metabolism of the nitro drug was also affected by SOD, suggesting the existence of a previously unreported metabolic pathway for nitrofurantoin. These studies support the growing body of evidence which suggests that nitrofurantoin toxicity is mediated, at least in part, by the metabolic activation of oxygen by the nitro aromatic anion radical. Further, these data suggest that superoxide may be involved in the oxidative metabolism of the aromatic nitro compounds.

Distribution of Food Reserves in “Model” Honeybee Swarm Clusters

Summary“Model” swarm clusters, which display behaviour typical of natural swarm clusters, were used in the study of swarm food reserves. The food reserves of a “model” cluster were unevenly distributed among workers of two behavioural modes: active workers, which rapidly consumed food in their scouting activities; and quiescent workers, which acted chiefly as reservoirs for food storage. The absence of the queen from an unfed cluster affected the distribution of food, and also resulted in a more rapid decline of food reserves in the quiescent workers; feeding the queenless cluster negated that effect of queenlessness. The depressed flight activity from a fed cluster suggests that the amount of food reserves may influence the proportions of bees in the cluster that display active and quiescent behaviours.

THE EFFECT OF SELENIUM AND VITAMIN E DEFICIENCY ON THE TOXICITY OF NITROFURANTOIN IN THE CHICK

Publisher Summary This chapter discusses the effect of selenium and vitamin E deficiency on the toxicity of nitrofurantoin in chick. Nitrofurantoin (N-[5–nitro–2–furfurylidine]–l–amino–hydantoin) is a commonly used urinary tract antimicrobial drug. It has been implicated in a number of drug-induced toxicities, the most common of which is associated with pulmonary injury. Recent studies suggest that the acute toxicity of this drug is mediated by an oxidative stress resulting from the futile reductive metabolism of the drug. In the study described in the chapter, the nitro compound is reduced to the nitro aromatic anion free radical, which is, then, re-oxidized by molecular oxygen regenerating the parent compound and forming superoxide. Superoxide, then, disproportionates to form hydrogen peroxide and ultimately the hydroxyl radical. One line of defense for the aerobic organism against these activated forms of oxygen is the selenium dependent glutathione peroxidase. The chapter explains that the toxicity of nitrofurantoin in the 10–12 day old chick is increased by decreasing the activity of this enzyme. In this animal model, it is found that vitamin E affords no protection against the toxicity of this nitro drug. Data supports the hypothesis that the toxicity of nitrofurantoin in vivo is because of activated forms of oxygen.

Chapter 9 – Vitamin K

Vitamin K is best known for its function in blood clotting. Vitamin K is the generic descriptor for 2-methyl-1,4-napthoquionone and its derivatives exhibiting quantitatively the antihemorrhagic activity of phylloquinone. Sources of vitamin K include synthesis by the gut microbiome and vitamin K–rich foods, such as green leafy vegetables and vegetable oils. Vitamin K is fat soluble and requires micellularization for absorption. It functions in blood clotting through the posttranslational modification of glutamate residues to produce γ-carboxyglumate (Gla) residues; Gla proteins include a series of clotting factors. It may also function in bone and cardiovascular health. The predominant clinical sign of vitamin K deficiency is coagulopathy, which results in prolonged clotting time and can lead to anemia.

Chapter 7 – Vitamin D

Vitamin D, the “sunshine vitamin,” is a hormone produced from sterols in the body by the action of ultraviolet light on the skin, although most people require the vitamin through the diet. Vitamin D is the generic descriptor for steroids exhibiting the biological activity of cholecalciferol. Sources of vitamin D include biosynthesis through the actions of ultraviolet light in the skin and through the diet as ergocalciferol (vitamin D2) or cholecalciferol (vitamin D3). Primary sources include fatty fishes and fortified foods, such as milk. Vitamin D is fat soluble and requires micellularization for absorption. Vitamin D supports bone health by promoting calcium absorption, and it also confers function as a regulator of gene expression. It may also function in immunity, cardiovascular health, and antioxidant regulation. Poor vitamin D status results in rickets in children and osteoporosis in adults.