Essential Nutritional Factors Research Articles

Role of nutritional zinc in the prevention of osteoporosis

Zinc is known as an essential nutritional factor in the growth of the human and animals. Bone growth retardation is a common finding in various conditions associated with dietary zinc deficiency. Bone zinc content has been shown to decrease in aging, skeletal unloading, and postmenopausal conditions, suggesting its role in bone disorder. Zinc has been demonstrated to have a stimulatory effect on osteoblastic bone formation and mineralization; the metal directly activates aminoacyl-tRNA synthetase, a rate-limiting enzyme at translational process of protein synthesis, in the cells, and it stimulates cellular protein synthesis. Zinc has been shown to stimulate gene expression of the transcription factors runt-related transcription factor 2 (Runx2) that is related to differentiation into osteoblastic cells. Moreover, zinc has been shown to inhibit osteoclastic bone resorption due to inhibiting osteoclast-like cell formation from bone marrow cells and stimulating apoptotic cell death of mature osteoclasts. Zinc has a suppressive effect on the receptor activator of nuclear factor (NF)-kappaB ligand (RANKL)-induced osteoclastogenesis. Zinc transporter has been shown to express in osteoblastic and osteoclastic cells. Zinc protein is involved in transcription. The intake of dietary zinc causes an increase in bone mass. beta-Alanyl-L: -histidinato zinc (AHZ) is a zinc compound, in which zinc is chelated to beta-alanyl-L: -histidine. The stimulatory effect of AHZ on bone formation is more intensive than that of zinc sulfate. Zinc acexamate has also been shown to have a potent-anabolic effect on bone. The oral administration of AHZ or zinc acexamate has the restorative effect on bone loss under various pathophysiologic conditions including aging, skeletal unloading, aluminum bone toxicity, calcium- and vitamin D-deficiency, adjuvant arthritis, estrogen deficiency, diabetes, and fracture healing. Zinc compounds may be designed as new supplementation factor in the prevention and therapy of osteoporosis.

Dietary zinc absorption is mediated by ZnT1 in Drosophila melanogaster

Zinc is an essential nutritional factor involved in many key biological processes. However, the physiological function of zinc transporters at the organismal level is not well characterized. Early embryonic lethality of Znt1 knockout mice precludes functional analysis of the role of ZnT1 in dietary zinc absorption. Here, we report the identification and characterization of the Drosophila ZnT1 orthologue, dZnT1, for its role in Drosophila dietary zinc absorption. In cell culture, dZnT1 promoted zinc transport to reduce cytoplasmic zinc levels. Ubiquitous RNA interference of dZnT1 in Drosophila resulted in developmental arrest under restriction of dietary zinc, while dZnT1-overexpressing flies exhibited hypersensitivity to zinc. dZnT1 was prominently expressed in restricted regions of the midgut and exhibited a distribution on the basolateral membrane of the enterocytes. Gut-specific silencing of dZnT1 was sufficient to evoke lethality under zinc scarcity. Human ZnT1, but not ZnT7 or ZnT4, could rescue the zinc-acquiring defects caused by dZnT1 silencing. Taken together, our results proved that dZnT1 is a key zinc transporter in dietary zinc absorption, functioning by pumping zinc out of the enterocytes across the basolateral membrane. This study will be helpful in understanding the fundamental process of acquiring dietary zinc in higher eukaryotes.

C. Eijkman (1858–1930) and Sir F.G. Hopkins (1861–1947): The dawn of vitamins and other essential nutritional growth factors

C. Eijkman (1858–1930) and Sir F.G. Hopkins (1861–1947): The dawn of vitamins and other essential nutritional growth factors

Inhalation Toxicity of Propineb. Part II: Results of Mechanistic Studies in Rats

Previous repeated inhalation exposure studies revealed two independent organotropic effects of inhaled propineb dust: One was restricted to the lung, the other to muscle weakness of hindlimbs. These effects were believed to be causally related to the principle decomposition products of this type of dithiocarbamate in the biological milieu and related to zinc and carbon disulfide. Two mechanistic 1-wk inhalation studies were performed, each focusing on one of these findings. The 7 × 6-h/day repeated-exposure inhalation study analyzed whether the nature of the response occurring at the alveolar level is "adaptive" or "early adverse" and whether soluble zinc is the causative agent. Groups of 18 female rats were exposed nose-only to mean concentrations of 0, 1.1, 5.5, and 25.8 mg propineb/m 3 and 6.9 mg ZnO/m 3. On postexposure days 1, 3, and 15 the time course of responses was analyzed by bronchoalveolar lavage (BAL), including quantification of Zn and metallothionein (MT) in BAL cells. Clinical evidence of muscular weakness was investigated separately in 20 female Wistar rats exposed to 70 mg propineb/m 3 on 5 consecutive days (6 h/day), followed by a 2-wk postexposure period. Clinical signs, body weights, and feed and water consumption were recorded as frequently as technically feasible. Fifty percent of rats received an oral cysteine supplementation to verify/refute the hypothesis that the incapacitation observed in previous studies is the cause of emaciation and associated impairment of CS 2 detoxification. The findings of the first study are consistent with this hypothesis, namely, that soluble Zn triggers a series of pulmonary events that is consistent with the homeostasis of this essential metal. It is concluded, accordingly, that the adjusted maximal workplace level for ZnO is also valid for propineb to preclude Zn-mediated responses to occur in the lung. With respect to muscular effects, this mechanistic study demonstrates further that the increased detoxification capacity afforded by oral supplementation of cysteine mitigates markedly the toxic potency of propineb. Procedural variables specific to the inhalation bioassay appear to be decisive for the elicitation of muscular effects. The major variable is considered to be the large drop in body weights associated with each exposure session and the concomitantly decreased uptake of essential nutritional factors (e.g., cysteine) involved in the detoxification of this compound. Accordingly, the muscular deficits elicited by high concentrations of propineb are viewed to be secondary effects in an animal species likely to be more susceptible to this type of change than humans (Pauluhn & Rosenbruch, 2003).

Synthesis of stable analogues of thiamine di- and triphosphate as tools for probing a new phosphorylation pathway.

Thiamine (vitamin B1) is an essential nutritional factor metabolized inside the body in its mono-, di-, and triphosphate forms. Although the action of thiamine and thiamine diphosphate have been intensely investigated, many questions remain unanswered and the role of thiamine triphosphate is still especially unknown. To probe recent hypotheses on the implication of thiamine triphosphate in a new phosphorylation pathway involving synaptic proteins, we synthesized a series of thiamine di- and triphosphate analogues that are resistant to both enzymatic and chemical hydrolyses. The key step in the preparation of the title compounds is the coupling of thiamine propyl disulfide with adequately protected methylenebis-phosphonic acid, the corresponding triphosphate analogue, and difluoromethylenebisphosphonic acid.

Selenium Supplementation Enhances the Expression of Interleukin 2 Receptor Subunits and Internalization of Interleukin 2

Selenium (Se) is an essential nutritional factor that was shown previously by us to alter the kinetics of expression of high affinity (p55/p75) interleukin 2 receptors (IL-2R). This study shows that dietary (2 ppm for 8 weeks) or in vitro (1 x 10(-7) M) supplementation with Se (as sodium selenite) results in a significant upregulation of the expression of both the p55 and p70/75 IL-2 binding sites on the surface of concanavalin A-stimulated lymphocytes from C57BL/6J mice. This resulted in the formation of significantly higher numbers of high affinity IL-2R/cell with preservation of the normal ratio of high affinity to total IL-2 binding sites/cell. The high affinity IL-2R on cells from Se-supplemented animals functioned normally in terms of ligand binding and kinetics of IL-2 internalization, but their greater numbers/cell resulted in the internalization of significantly larger amounts of IL-2/cell. As Se supplementation results in an earlier expression of greater numbers of high affinity IL-2R, the presence of Se in the cell environment can result in an accelerated clonal expansion of activated lymphocytes.

Effect of selenium on the expression of high affinity interleukin 2 receptors.

Selenium (Se) is an essential nutritional factor that has been shown to affect the development and expression of cell-mediated immune responses. This study shows that dietary (2 ppm for 8 weeks) or in vitro (1 x 10(-7) M) supplementation with Se results in a significant increase in the number of high affinity interleukin (IL) 2-binding sites (Kd of 10(-11) M) on the surface of concanavalin A-stimulated lymphocytes from C57BL/6J mice, whereas Se deficiency (0.02 ppm for 8 weeks) has the opposite effect. Se supplementation or deficiency apparently alters the kinetics of IL-2 receptor expression. Supplementation with Se in vivo or in vitro resulted in an earlier expression of high affinity IL-2 receptors, whereas Se deficiency resulted in a delayed expression of lower numbers of receptors. To exert its effect on IL-2 receptor expression, Se must be present or absent in the cell environment 8-24 hr after stimulation, and it most likely affects processes in the cytoplasmic and/or nuclear compartments of activated lymphocytes. Thus, in the presence of continuous immunologic stimulation, the presence or absence of Se in the cell environment can result in an accelerated or delayed clonal expansion of immunocompetent lymphocytes, respectively.

Regulation of cellular immune responses by selenium.

Selenium (Se) is an essential nutritional factor that affects the development and expression of cell-mediated immune responses directed toward malignant cells. These studies have shown that dietary (2 ppm for 8 wk) or in in vitro (1 x 10(-7)M) supplementation with Se (as sodium selenite) results in a significant enhancement of the proliferative responses of spleen lymphocytes from C57Bl/6J mice in response to stimulation with mitogen or antigen. Se deficiency (0.02 ppm for 8 wk) had the opposite effect. The alterations in the ability of the cells to proliferate, which occurred in the absence of changes in the endogenous levels of interleukin-2 (Il2) or interleukin 1, were apparently related to the ability of Se to alter the kinetics of expression of high-affinity Il2 receptors on the surface of activated lymphocytes. This resulted in an enhanced or delayed clonal expansion of the cells, and in an increased or decreased frequency of cytotoxic cells within a given cell population. The changes in tumor cytotoxicity were paralleled by changes in the amounts of lymphotoxin produced by the activated cells. Dietary Se modulations had a comparable effect on macrophage-mediated tumor cytodestruction. The results also suggested that Se exerts its effect 8-24 h after stimulation, and that it most likely affects processes in the cytoplasmic and/or nuclear compartments of activated lymphocytes.

Selenium and Immune Cell Functions. II. Effect on Lymphocyte-Mediated Cytotoxicity

Selenium (Se) is an essential nutritional factor with a chemopreventive potential. This study examined the ability of C57BL/6J mice, maintained for 8 weeks on Se-deficient (0.02 ppm Se), normal (0.20 ppm Se), or Se-supplemented (2.00 ppm Se) Torula yeast-based diets, to generate cytotoxic lymphocytes (CTL) and to destroy tumor cells. CTL were generated in vivo by intraperitoneal immunization with P815 cells and in vitro by allogeneic stimulation of cells from animals maintained on a normal diet in media supplemented with 1 x 10(-9) to 1 x 10(-6) M Se (as selenite). Lymphocytes from animals maintained on the Se-supplemented diet had a greater ability to destroy tumor cells than lymphocytes from animals maintained on the normal diet, whereas Se deficiency reduced the cytotoxicity. The effects on cytotoxicity were accompanied by parallel changes in the levels of lymphotoxin produced. The greatest enhancement of tumor cytodestruction occurred with supplementation of 1 x 10(-7) M Se, whereas with 1 x 10(-6) M there was inhibition of the cytotoxic responses. The stimulatory effect of Se occurred during the phase of CTL generation rather than during the lytic phase of cytotoxicity. These results indicated that Se supplementation enhances CTL generation and the ability of a host to destroy malignant cells, whereas Se deficiency has the opposite effect.

Chelating agents in medicine.

AbstractIn recent years there has been a growing awareness of the importance of trace metals in the environment, in their dichotomous role as essential nutritional factors on the one hand, and as toxic agents on the other. The apparent ambivalent nature of metal ions is shown as a continuum in a wide range dose-response curve. The response on the curve, being a function of dosage, covers survival of the organism through a deficiency state to normal health, toxicity, and death. This particular review deals with the toxic effects of this dose-response curve and the use of chelating agents to remove execessive quantities of metal ions which are producing toxic effects. The metals discussed include: (1) Heavy metal ions-lead, mercury, and cadmium; (2) essential trace metals in toxic excessive quantities-chromium, cobalt, copper, iron, manganese, molybdenum, selenium, and zinc; (3) less common toxic metal ions-aluminum, antimony, arsenic, beryllium, nickel, tellurium, thallium, and tin. Radioactive metals are ...

Some Nutritional Aspects of Experimental Infection with Salmonella pullorum

For many years the microbiologist has recognized that animals maintained on diets deficient in essential nutritional factors have demonstrated a marked increase or decrease in susceptibility to certain bacterial, rickettsial, and viral infections (5,7,9,10). It seemed probable that an inadequate vitamin supply during infection could produce a metabolic defect not necessarily associated with a clinical state of vitamin deficiency. A defect such as this could possibly be of decided advantage to the invading pathogen. Hill and Garren (6) recently reported that chicks receiving high levels of all of the essential vitamins and an antioxidant had a decreased susceptibility to infection by Salmonella gallinarum. This communication is devoted to reporting the effects of individual members of the B-complex and certain of their antimetabolites on experimental pullorum disease, and the nutritional factors that are necessary to maintain normal hemoglobin concentrations during infection. The basic approach of the investigation nevertheless yields information of clinical value. Attention is directed to the fact that vitamins are not necessarily beneficial in certain diseases, and may actually be harmful. The avian pathologist will have use for this information in evaluating chemotherapy.

The Nutritive Value of Cottonseed for Chicks as Affected by Methods of Processing and Content of Pigment Glands

SINCE cottonseed meal was one of the first protein concentrates to be fed to livestock on a large scale, numerous investigations were published relative to its nutritive value before the importance of balanced diets, and of vitamins, and other essential nutritional factors was recognized. Proper evaluation of cottonseed as a protein feed is rendered difficult by the mass of confusing and contradictory data which accumulated during the period of these early nutritional investigations.Numerous recent investigations have established the high nutritive value of hydraulic- and screw-pressed cottonseed meals produced by expression of the oil from cooked cottonseed. These cottonseed meals represent one of the most important sources of concentrated protein presently available to livestock feeders. The nutritive value of uncooked cottonseed has been established for beef cattle (Clark, 1936), but for other livestock it is generally believed (Olcott, 1941, 1942) that cooking is essential in order to obtain cottonseed meal .

THE PREVALENCE OF MALNUTRITION

Recent estimates of the prevalence of malnutrition in the United States have varied so greatly that the Food and Nutrition Board of the National Research Council has assigned to us, as a subcommittee, the task of evaluating existing evidence on this question. Among the reasons for the widely varying estimates is the lack of criteria for the diagnosis of malnutrition. It is therefore necessary before discussion of the evidence that terms be defined. DEFINITIONS Nutritional exists as soon as adequate amounts of an essential nutritional factor or factors fail to reach the milieu interne. Dietary inadequacy means the failure to ingest an essential nutritional factor or factors in amounts sufficient to meet the existing requirement of the body. Nutritional inadequacy means not only the failure to ingest, i. e. dietary inadequacy, but failure to absorb, to retain and to utilize an essential nutritional factor or factors in amounts sufficient

Further Studies on Dietary Factors Associated with Nutritional Muscle Dystrophy: Five Figures

Further Studies on Dietary Factors Associated with Nutritional Muscle Dystrophy: Five Figures