Effect of Maternal Marginal Zinc Deficiency on Development, Redox Status, and Gene Expression Related to Oxidation and Apoptosis in an Avian Embryo Model.

Maternal severe zinc (Zn) deficiency resulted in growth retardation and high mortality during embryonic development in human. Therefore, this study is aimed at evaluating the effect of maternal marginal Zn deficiency on the development and redox status to avoid severe Zn deficiency using an avian model. A total of 324 laying duck breeders at 214 days old were randomly allotted into 3 dietary Zn levels with 6 replicates of 18 ducks per replicate. The birds were fed experimental diets including 3 dietary supplemental Zn levels of 0 mg/kg (maternal Zn-deficient group, 29.2 mg Zn/kg diet), 60 mg/kg (maternal Zn-adequate group), and 120 mg/kg (maternal Zn-high group) for 6 weeks. Dietary Zn levels had on effect on egg production and fertility (P > 0.05), whereas dietary Zn deficiency decreased breeder plasma Zn concentration and erythrocytic alkaline phosphatase activity at week 6 and inhibited erythrocytic 5'-nucleotidase (5'-NT) activity at weeks 2, 4, and 6 (P < 0.05), indicating that marginal Zn-deficient status occurred after Zn depletion. Maternal marginal Zn deficiency increased embryonic mortality and contents of superoxide anion radical, MDA, and PPC and reduced MT content and CuZnSOD activity in duck embryonic livers on E29. The MDA content was positively correlated with embryonic mortality. Maternal marginal Zn deficiency increased BCL2-associated X protein and Caspase-9 mRNA expressions as well as decreased B-cell lymphoma-2 and MT1 mRNA and signal AKT1 and ERK1 protein expressions (P < 0.05). Breeder plasma Zn concentration and erythrocytic 5'-NT activities at week 6 were positively correlated with GSH-Px activity and GPx, MT1, and BCL2 mRNA expressions in embryonic livers on E29. In conclusion, erythrocytic 5'-NT activity could be more rapid and reliable to monitor marginal Zn-deficient status. Marginal Zn deficiency impaired hatchability and antioxidant defense system and then induced oxidative damage and apoptosis in the embryonic liver, contributing to the greater loss of duck embryonic death.

Onset Mechanism and Pharmaceutical Management of Dry Skin.

Dry skin is a common symptom of various conditions, and elderly individuals commonly exhibit this physiological symptom. Dry skin develops owing to sebum deficiency; however, the use of moisturizers can typically overcome this issue, particularly in patients in whom there are no other skin problems. If dry skin is left untreated, itching and eczema can occur, resulting in skin damage. Additionally, hemodialysis patients exhibit reduced barrier function and can experience pain associated with repeated needle insertion; the repeated use of lidocaine tape to manage the pain can cause further skin damage. To reduce the occurrence of dry skin, the skin is hydrated using moisturizers. Dry skin is also prominent in patients with varicose veins in the lower extremities, and many biochemical studies have shown that skin immunity is altered in patients with dry skin. Moreover, the incidences of dry skin and pruritus differ in male and female patients. Furthermore, in elderly patients, zinc deficiency is likely to cause dry skin, and zinc supplementation may maintain skin hydration. To date, few reports have described dry skin from a clinical point of view. In this review, research on dry skin is presented, and the findings of basic research studies are integrated.

Omega-3 Polyunsaturated Fatty Acid Deficiency and Progressive Neuropathology in Psychiatric Disorders: A Review of Translational Evidence and Candidate Mechanisms.

Meta-analytic evidence indicates that mood and psychotic disorders are associated with both omega-3 polyunsaturated fatty acid (omega-3 PUFA) deficits and progressive regional gray and white matter pathology. Although the association between omega-3 PUFA insufficiency and progressive neuropathological processes remains speculative, evidence from translational research suggests that omega-3 PUFA insufficiency may represent a plausible and modifiable risk factor not only for enduring neurodevelopmental abnormalities in brain structure and function, but also for increased vulnerability to neurodegenerative processes. Recent evidence from human neuroimaging studies suggests that lower omega-3 PUFA intake/status is associated with accelerated gray matter atrophy in healthy middle-aged and elderly adults, particularly in brain regions consistently implicated in mood and psychotic disorders, including the amygdala, anterior cingulate, hippocampus, prefrontal cortex, and temporal cortex. Human neuroimaging evidence also suggests that both low omega-3 PUFA intake/status and psychiatric disorders are associated with reductions in white matter microstructural integrity and increased rates of white matter hyperintensities. Preliminary evidence suggests that increasing omega-3 PUFA status is protective against gray matter atrophy and deficits in white matter microstructural integrity in patients with mood and psychotic disorders. Plausible mechanisms mediating this relationship include elevated pro-inflammatory signaling, increased synaptic regression, and reductions in cerebral perfusion. Together these associations encourage additional neuroimaging research to directly investigate whether increasing omega-3 PUFA status can mitigate neuropathological processes in patients with, or at high risk for, psychiatric disorders.

Involvement of caspases and their upstream regulators in myocardial apoptosis in a rat model of selenium deficiency-induced dilated cardiomyopathy.

Keshan disease is an endemic dilated cardiomyopathy (DCM) which is closely related with selenium-deficient diet in China. In the previous study, we reported that the low selenium status plays a pivotal role in the myocardial apoptosis in the DCM rats, however, the underlying mechanism remains unclear. The present study aimed to determine whether the intrinsic, extrinsic pathways and the upstream regulators were involved in the myocardial apoptosis of selenium deficiency-induced DCM rats. Therefore, the rat model of endemic DCM was induced by a selenium-deficient diet for 12 weeks. Accompanied with significant dilation and impaired systolic function of left ventricle, an enhanced myocardial apoptosis was detected by TUNEL assay. Western blot analysis showed remarkably increased protein levels of cleaved caspase-3, caspase-8, caspase-9, and cytosolic cytochrome c released from the mitochondria. In addition, the immunoreactivities of p53 and Bax were significantly up-regulated, while the anti-apoptotic Bcl-2 family members Bcl-2 and Bcl-X(L) were down-regulated. Furthermore, appropriate selenium supplement for another 4 weeks could partially reverse all the above changes. In conclusion, the intrinsic, extrinsic pathways and the upstream regulators such as p53, Bax, Bcl-2, and Bcl-X(L )were all involved in selenium deficiency-induced myocardial apoptosis.

Zinc deficiency mediates alcohol-induced apoptotic cell death in the liver of rats through activating ER and mitochondrial cell death pathways.

Hepatic zinc deficiency has been well documented in alcoholic patients, but the mechanisms by which zinc deficiency mediates cell death have not been well defined. The objectives of this study were to determine whether alcohol perturbs subcellular zinc homeostasis and how organelle zinc depletion may link with cell death pathways. Wistar rats were pair-fed with the Lieber-DeCarli control or ethanol diet for 5 mo. Chronic alcohol exposure significantly reduced zinc level in isolated hepatic endoplasmic reticulum (ER) and mitochondria. Among the detected zinc transporters, ER Zrt/Irt-like protein (ZIP)13 and mitochondrial ZIP8, which transport zinc from ER and mitochondria to cytosol, were significantly increased. Mitochondrial zinc transporter (ZnT) 4, which transports zinc from cytosol to mitochondria, was also increased. ER phosphorylated eukaryotic initiation factor 2α, activating transcription factor 4, and C/EBP homologous protein were significantly upregulated, and mitochondrial cytochrome c release and Bax insertion were detected in association with caspase-3 activation and apoptotic cell death. To define the role of zinc deficiency in ER and mitochondrial stress, H4IIEC3 cells were treated with 3 µM N,N,N',N'-tetrakis (2-pyridylmethyl) ethylenediamine for 6 h with or without supplementation with zinc or N-acetylcysteine (NAC). The results demonstrated that zinc deprivation induced caspase-3 activation and apoptosis in association with ER and mitochondria dysfunction, which were inhibited by zinc as low as 10 µM but not by 2 mM NAC. These results suggest that chronic ethanol exposure induced in ER and mitochondrial zinc deficiency might activate intrinsic cell death signaling pathway, which could not be effectively rescued by antioxidant treatment.

Effects of complementary and excess diet supplementation with selected minerals on their metabolism and distribution in the body: a model study.

BACKGROUND: n. The study was aimed at determining, on an animal model, effects of supplementing a diet, modified by substituting whole wheat and corn grains with white flour and sucrose, with calcium, magnesium, zinc, and chromium on metabolism of the minerals and their distribution in the body. METHODS: The study involved 4 groups of Wistar rat females (n = 11) fed: a standard feed (group I) containing, i.a., whole wheat and corn grains; modified feed (84% and 50% of whole wheat and corn grains, respectively, in the standard feed substituted with Type 500 wheat flour and sucrose, respectively) (group II); modified feed with complementary supplementation (elimination of Ca, Mg, Zn, and Cr deficiencies resulting from diet modification) (group III); and modified feed with excess supplementation (the same minerals applied in excess, i.e., amounts from 0.5 to 3 times higher than the deficiencies produced by diet modification) (group IV). The replacement of whole grains with white flour and sucrose, as well as the mineral  supplementation could, to some extent, imitate the contemporary eating habits and supplementation applied in food technology. The excess supplementation is, on the other hand, typical of current behaviours of various social groups. RESULTS: Both types of supplementation resulted in a significant increase in the perivisceral adipose tissue content, but did not affect the fat tissue content in muscles. The supplementation applied did not change the content of calcium, magnesium, and zinc in muscles, nor did it significantly change calcium and magnesium excretion with urine. However, changes in the ALP activity and calcitonin concentration did not suggest the deposition of the minerals in bones. CONCLUSIONS: Analysis of the results allowed to conclude that: 1) except for chromium, contents of the selected minerals in the tissues examined and urea, as well as concentrations of calcitonin and alkaline phosphatase (ALP) activities did not point to any significant effect of the supplementation applied on the body contents of those minerals; 2) effects observed as the accumulation of perivisceral, epicardial and intramuscular adipose tissue, as well as increased body weight increments could have been related to disturbed proportions of the minerals supplemented, their synergy and antagonism and, consequently, a potential generation of secondary deficiencies and excesses which could significantly affect individual metabolic pathways; 3) the intensity of changes observed was generally higher in the females receiving complementary supplementation, although their uptake of minerals studied was similar to that shown by the females kept on the standard diet.

The influence of the percentage of the common limb in weight loss and nutritional alterations after laparoscopic gastric bypass.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) is considered the gold standard for the treatment of morbid obesity. There is no consensus over ideal limb length when the bypass is created and published studies do not take into account the influence of the common limb (CL) on weight loss. The objective was to study the influence of the common limb after RYGB. The setting was the Virgen de la Arrixaca University Clinical Hospital in Murcia, Spain. MATERIAL AND METHODS: This prospective study includes 151 patients undergoing laparoscopic RYGB surgery for morbid obesity. The patients were divided into 2 groups according to their body mass index. The small intestine (SI) was measured using micro forceps so that the percentage of common limb (%CL) could then be compared against the total SI in each patient. The percentage of excess weight loss (%EWL) in relation to the %CL was calculated at 3, 12, and 24 months. A series of tests was conducted simultaneously to analyze nutritional deficiencies and their relation to the %CL. RESULTS: The total jejunoileal segment and the %CL in the groups of both obese and super-obese patients had no influence on the %EWL in either group for any of the periods studied. The patients with a %CL<50% had greater nutritional deficiencies in the follow-up period and required supplements and more frequent laboratory tests. CONCLUSIONS: The %CL has no effect on weight loss in RYGB patients. A lower %CL is related to greater nutritional deficiencies.

Thyroid volume, iodine intake, autoimmune thyroid disorders, inborn factors, and endocrine disruptors: twenty-year studies of multiple effects puzzle in Slovakia.

OBJECTIVE: The aim of this study was to evaluate multiple interrelations between several endogenous and exogenous effects and the thyroid volume and function in large groups of children, adolescents, and adults with a sufficient whole life intake of the iodine. SUBJECTS AND METHODS: The data were obtained either by cross sectioned or longitudinal studies in a total of 4998 children and adolescents (aged 7 to 17 years) and 2501 adults (1071 males and 1430 females aged 20-75 years). Thyroid volume (ThV) was measured by ultrasound, antibodies, and hormones by electrochemiluminiscent immunoassay, and endocrine disruptors (EDs, polychlorinated biphenyls-PCB, dichlorodiethyl-ichloroethylene-DDE, and hexachlorobenzene-HCB) by high resolution gas chromatography/mass spectrometry. RESULTS: 1. In large groups of boys and girls of age 7, 10, 13 or 17 years, the ThV was significantly higher in the 10th decile than in pooled nine lower deciles. Moreover, in 17-year old subjects significantly higher prevalence of hypoechogenicity by ultrasound, positive thyroperoxidase antibodies (TPOab), and increased thyrotropin (TSH) levels were found in the 10th decile. 2. In a small group of children, some individuals revealed consistently higher ThV during the whole 7-year follow-up period irrespective of supplementation with iodine. 3. In 325 sibling pairs of age 10-19 years, born within three years, three groups with different ThV/m2 of body surface were distinguished: Group A (183 pairs having both ThVs small), Group B (103 pairs having both ThVs large); Group C (33 pairs having one ThV small and the other one large). Similar aggregation of ThVs in three groups was observed in 13 pairs of discordant twins and 19 sibling triads in which all the siblings were born within four years. 4. In 42 concordant twins, several pairs had ThV nearly twice as high (in terms of both plain ThV or ThV/m2 of the body surface) as several other pairs of the same age which is assumed to be a result of a genetic background. 5. In large cohorts of males and females, a highly significant positive correlation was found between the ThV and high level of TPOab on one side and EDs on the other side. However, in nearly the same numbers of subjects with low TPOab, negative correlation was seen between ThV and disruptors. These observations may apparently support the synergic effect of the autoimmunity and EDs on the thyroid function. CONCLUSIONS: Several cases of an excessive thyroid growth in the iodine replenished children, adolescents, and adults may apparently result from the autoimmune thyroiditis, probably induced by immunogenic action of iodine in presumably disposed individuals. However, in some cases even simultaneous participation of EDs can not be excluded. Some observations have also suggested that excessive thyroid growth in the iodine replenished adolescent and adult population which was equally exposed to disruptors may also result from other reasons as the unfavorable hereditary background.

Increased Mauthner cell activity and escaping behaviour in seabream fed long-chain PUFA.

There is limited information on the specific effects of long-chain PUFA (LCPUFA) on neuron development and functioning. Deficiency of those essential fatty acids impairs escape and avoidance behaviour in fish, where Mauthner cells (M-cells) play a particularly important role in initiating this response. Gilthead seabream larvae fed two different LCPUFA profiles were challenged with a sonorous stimulus. Feeding n-3 LCPUFA increased the content of these fatty acids in fish tissues and caused a higher number of larvae to react to the stimulus with a faster burst swimming speed response. This faster startle response in fish fed n-3 LCPUFA was also associated with an increased immune-positive neural response, particularly in M-cells, denoting a higher production of acetylcholine. The present study shows the first evidence of the effect of n-3 LCPUFA on the functioning of particular neurons in fish, the M-cells and the behaviour response that they modulate to escape from a sound stimulus.

Brain histological changes in young mice submitted to diets with different ratios of n-6/n-3 polyunsaturated fatty acids during maternal pregnancy and lactation.

N-3 polyunsaturated fatty acids (n-3 PUFAs) are essential for brain development and function, but the appropriate quantity of dietary n-3 PUFAs and ratio of n-6/n-3 PUFAs have not been clearly determined. In this study, we investigated the effects of different dietary ratios of n-6/n-3 PUFAs on the brain structural development in mice and the expression of associated transcription factors. C57 BL/6J mice were fed with one of two categories of n-3 PUFA-containing diets (a flaxseed oil diet and a flaxseed/fish oil mixed diet) or an n-3 PUFA-deficient diet. For each of the n-3 PUFA diets, flaxseed oil or flaxseed/fish oil was combined with other oils to yield three different n-6/n-3 ratios, which ranged from 15.7:1 to 1.6:1. The feeding regimens began two months before mouse conception and continued throughout lactation for new pups. As compared with the n-3 PUFA-deficient diet, both the flaxseed oil n-3 PUFA diets and the flaxseed/fish oil n-3 PUFA diets significantly increased the expression levels of brain neuron-specific enolase, glial fibrillary acidic protein and myelin basic protein, somewhat dose-dependently, in new pup mice at 21 d and 42 d of age. The expression of PPAR-γ in the brains of pup mice was increased only at 7 d of age with the n-3 PUFA diet, and no changes in the expression of PPAR-α and PPAR-ß were found among all the diet groups. These results suggest that the higher intake amount of n-3 PUFAs with a low ratio of n-6/n-3 PUFAs at about 1-2:1, supplied during both maternal pregnancy and lactation, may be more beneficial for early brain development, and PPAR-γ may act in one of the pathways by which n-3 PUFAs promote early brain development.

Iodine: it's important in patients that require parenteral nutrition.

Iodine deficiency has multiple adverse effects on growth and development because of inadequate thyroid hormone production. Four methods are generally recommended for assessment of iodine nutrition: urinary iodine concentration, thyroid size, and blood concentrations of thyroid-stimulating hormone and thyroglobulin. Iodine intakes < or = 1 mg/d are well tolerated by most adults, because the thyroid is able to adjust to a wide range of intakes. A daily dose of 1 microg iodine/kg body weight is recommended for infants and children receiving parenteral nutrition (PN), but this is far below their requirement. Daily iodine requirements in adults receiving enteral nutrition or PN are estimated to be 70-150 microg, but most PN formulations do not contain iodine. Despite this, deficiency is unlikely because absorption from iodine-containing skin disinfectants and other adventitious sources can provide sufficient iodine. However, if chlorhexidine replaces iodine-containing disinfectants for catheter care, iodine deficiency may occur during long-term PN, and periodic testing of thyroid functions may be prudent. Infants may be particularly vulnerable because of their small thyroidal iodine store, but available data do not yet support routine supplementation of preterm infants with iodine. Adults may be less vulnerable because thyroidal iodine stores may be able to support thyroid hormone production for several months. More studies to clarify this issue would be valuable.

Artificial rearing of infant mice leads to n-3 fatty acid deficiency in cardiac, neural and peripheral tissues.

The ability to control the fatty acid content of the diet during early development is a crucial requirement for a one-generation model of docosahexaenoic acid (DHA; 22:6n3) deficiency. A hand feeding method using artificial rearing (AR) together with sterile, artificial milk was employed for feeding mice from postnatal day 2-15. The pups were fed an n-3 fatty acid adequate (3% alpha-linolenic acid (LNA; 18:3n3) + 1% 22:6n3) or a deficient diet (0.06% 18:3n3) with linoleic acid (LA; 18:2n6) as the only dietary source of essential fatty acids by AR along with a dam-reared control group (3.1% 18:3n3). The results indicate that restriction of n-3 fatty acid intake during postnatal development leads to markedly lower levels of brain, retinal, liver, plasma and heart 22:6n3 at 20 weeks of age with replacement by docosapentaenoic acid (DPAn6; 22:5n6), arachidonic acid (ARA; 20:4n6) and docosatetraenoic acid (DTA; 22:4n6). A detailed analysis of phospholipid classes of heart tissue indicated that phosphatidylethanolamine, phosphatidylcholine and cardiolipin were the major repositories of 22:6n3, reaching 40, 29 and 15%, respectively. A novel heart cardiolipin species containing four 22:6n3 moieties is described. This is the first report of the application of artificially rearing to mouse pup nutrition; this technique will facilitate dietary studies of knockout animals as well as the study of essential fatty acid (EFA) functions in the cardiovascular, neural and other organ systems.

Dietary selenium deficiency as well as excess supplementation induces multiple defects in mouse epididymal spermatozoa: understanding the role of selenium in male fertility.

Selenium (Se) is essential for male fertility. The present study was carried out to observe the defects associated with Se deficiency as well as excess Se supplementation by analyzing the sperm ultrastructure and chromatin organization. Different Se status mice were generated viz. Se deficient (group I), Se adequate (group II) and Se excess (group III) by feeding the respective diets for a period of 4 (group Ia, IIa and IIIa) and 8 weeks (group Ib, IIb and IIIb). Reduction in sperm concentration, motility and percentage fertility was observed in Se deficient and Se excess groups. Electron microscopy revealed mitochondrial swelling and gaps between adjacent mitochondria in mice fed Se-deficient diet for 4 weeks. At 8 weeks, several abnormalities such as loose contact of the mitochondrial helix with the plasma membrane, loss of mitochondria, retention of cytoplasmic droplet, fracturing of outer dense fibres and presence of both the midpiece and the principal piece cross-sections in a common plasma membrane were observed. In Se excess group, the predominant defect was the frequent presence of equidistant, cross-sectioned midpieces of the tail embedded in a common cytoplasm. These defects are indicative of loss of sperm motility. Spermatozoa from Se-deficient mice had incompletely condensed chromatin and indicated an increase in occurrence of DNA strand breaks. The animals fed Se excess diet also indicated increase in DNA breaks but this was significantly less than the deficient diet fed groups. Our study reveals the defects associated with Se deficiency that result in loss of reproductive ability and also reflects its possible harmful effects on spermatozoa after prolonged consumption at supranutritional level.

Concurrent repletion of iron and zinc reduces intestinal oxidative damage in iron- and zinc-deficient rats.

AIM: To understand the interactions between iron and zinc during absorption in iron- and zinc-deficient rats, and their consequences on intestinal oxidant-antioxidant balance. METHODS: Twenty-four weanling Wistar-Kyoto rats fed an iron- and zinc-deficient diet (< 6.5 mg Fe and 4.0 mg Zn/kg diet) for 4 wk were randomly divided into three groups (n = 8, each) and orally gavaged with 4 mg iron, 3.3 mg zinc, or 4 mg iron + 3.3 mg zinc for 2 wk. At the last day of repletion, 3 h before the animals were sacrificed, they received either 37 mBq of (55)Fe or (65)Zn, to study their localization in the intestine, using microautoradiography. Hemoglobin, iron and zinc content in plasma and liver were measured as indicators of iron and zinc status. Duodenal sections were used for immunochemical staining of ferritin and metallothionein. Duodenal homogenates (mitochondrial and cytosolic fractions), were used to assess aconitase activity, oxidative stress, functional integrity and the response of antioxidant enzymes. RESULTS: Concurrent repletion of iron- and zinc-deficient rats showed reduced localization of these minerals compared to rats that were treated with iron or zinc alone; these data provide evidence for antagonistic interactions. This resulted in reduced formation of lipid and protein oxidation products and better functional integrity of the intestinal mucosa. Further, combined repletion lowered iron-associated aconitase activity and ferritin expression, but significantly elevated metallothionein and glutathione levels in the intestinal mucosa. The mechanism of interactions during combined supplementation and its subsequent effects appeared to be due to through modulation of cytosolic aconitase, which in turn influenced the labile iron pool and metallothionein levels, and hence reduced intestinal oxidative damage. CONCLUSION: Concurrent administration of iron and zinc corrects iron and zinc deficiency, and also reduces the intestinal oxidative damage associated with iron supplementation.

Clinicopathological analysis of hematological disorders in tube-fed patients with copper deficiency.

OBJECT: Anemia and leukopenia caused by copper deficiency are well-documented consequences of long-term total parenteral nutrition. We measured the serum copper levels of bed-ridden patients receiving enteral feeding, and evaluated optical and ultrastructural features of bone marrow before and after copper supplementation. PATIENTS AND METHODS: Serum samples were obtained from 15 bed-ridden elderly patients receiving tube feeding (TF) and 10 age-matched bed-ridden patients who took food orally (CO), and the copper ceruloplasmin concentration of each sample was measured. Bone marrow samples were obtained from patients who exhibited copper deficiency and leukopenia and/or anemia before and after the copper supplementation, for use in light and electron microscopic analysis. RESULTS: The tube-fed patients had significantly lower mean serum copper and ceruloplasmin concentrations than the control patients. Seven of the 15 tube-fed patients had reduced serum copper concentrations and leukopenia. Six of those 7 patients also had anemia. Copper sulfate was administered to those 7 patients by enteral tube; their copper concentration, anemia and leukopenia improved within 1 month after they were administered copper sulfate. In the bone marrow examination before copper supplementation, light microscopy showed cytoplasmic vacuolization in both myeloid and erythroid precursors, and electron microscopy showed electron-dense deposits in mitochondria and cytoplasm of erythroid and myeloid cells. After copper supplementation, these pathological changes disappeared. CONCLUSIONS: Bicytopenia is likely to occur in tube-fed patients with copper deficiency. Copper deficiency appears to be associated with cytoplasmic vacuolization and electron-dense deposits in mitochondria in erythroid and myeloid cells.

Differential effects of dietary selenium (se) and folate on methyl metabolism in liver and colon of rats.

A previous study compared the effects of folate on methyl metabolism in colon and liver of rats fed a selenium-deficient diet (< 3 microg Se/kg) to those of rats fed a diet containing supranutritional Se (2 mg selenite/kg). The purpose of this study was to investigate the effects of folate and adequate Se (0.2 mg/kg) on methyl metabolism in colon and liver. Weanling, Fischer-344 rats (n = 8/diet) were fed diets containing 0 or 0.2 mg selenium (as selenite)/kg and 0 or 2 mg folic acid/kg in a 2 x 2 design. After 70 d, plasma homocysteine was increased (p < 0.0001) by folate deficiency; this increase was markedly attenuated (p < 0.0001) in rats fed the selenium-deficient diet compared to those fed 0.2 mg Se/kg. The activity of hepatic glycine N-methyltransferase (GNMT), an enzyme involved in the regulation of tissue S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH), was increased by folate deficiency (p < 0.006) and decreased by selenium deprivation (p < 0.0003). Colon and liver SAH were highest (p < 0.006) in rats fed deficient folate and adequate selenium. Although folate deficiency decreased liver SAM (p < 0.001), it had no effect on colon SAM. Global DNA methylation was decreased (p<0.04) by selenium deficiency in colon but not liver; folate had no effect. Selenium deficiency did not affect DNA methyltransferase (Dnmt) activity in liver but tended to decrease (p < 0.06) the activity of the enzyme in the colon. Dietary folate did not affect liver or colon Dnmt. These results in rats fed adequate selenium are similar to previous results found in rats fed supranutritional selenium. This suggests that selenium deficiency appears to be a more important modifier of methyl metabolism than either adequate or supplemental selenium.

Biotin deficiency in an infant fed with amino acid formula.

Biotin deficiency is rarely encountered in an infant on weaning from breast and formula feeding. It is characterized by alopecia and scaly, erythematous dermatitis distributed around the body orifices. We report a 5-month-old Japanese infant with typical skin lesions who had been diagnosed as a neonate with dyspepsia and fed only an amino acid formula. Serum and urine levels of biotin were below the normal range, but zinc and biotinidase were within normal range. Urinary excretion of 3-methylcrotonylglycine, 3-hydroxyisovaleric acid, and methylcitric acid was significantly elevated. Daily oral supplementation with 1 mg of biotin resulted in dramatic improvement of the periorificial dermatitis and hair growth together with a complete disappearance of the organic aciduria. Our case shows that the characteristic skin manifestations are the most important clue to the diagnosis of biotin deficiency and demonstrated that urinary excretion of biotin and organic aciduria, rather than the serum concentration of biotin, are the sensitive indicators for evaluating the patient's status of biotin deficiency.

DNA methylation, cancer susceptibility, and nutrient interactions.

DNA methylation is an important epigenetic mechanism of transcriptional control. DNA methylation plays an essential role in maintaining cellular function, and changes in methylation patterns may contribute to the development of cancer. Aberrant methylation of DNA (global hypomethylation accompanied by region-specific hypermethylation) is frequently found in tumor cells. Global hypomethylation can result in chromosome instability, and hypermethylation has been associated with the inaction of tumor suppressor genes. Preclinical and clinical studies suggest that part of the cancer-protective effects associated with several bioactive food components may relate to DNA methylation patterns. Dietary factors that are involved in one-carbon metabolism provide the most compelling data for the interaction of nutrients and DNA methylation because they influence the supply of methyl groups, and therefore the biochemical pathways of methylation processes. These nutrients include folate, vitamin B(12), vitamin B(6), methionine, and choline. However, looking at individual nutrients may be too simplistic. Dietary methyl (folate, choline, and methionine) deficiency in combination causes decreased tissue S-adeno-sylmethionine, global DNA hypomethylation, hepatic steatosis, cirrhosis, and ultimately hepatic tumorigenesis in rodents in the absence of carcinogen treatment. Other dietary components such as vitamin B(12), alcohol, and selenium may modify the response to inadequate dietary folate.

Ocular surface in Zn-deficient rats.

PURPOSE: We studied the cornea and conjunctiva of Zn-deficient rats with an electron microscope and time-of-flight secondary ion mass spectrometry (TOF-SIMS) to elucidate the role of trace elements in the cornea and conjunctiva. MATERIALS AND METHODS: Twenty-one-day-old Wistar Kyoto rats were fed a Zn-deficient diet and deionized water for 7 weeks and then killed. The control rats were fed a Zn-deficient diet and deionized water supplemented with 3 mg Zn/100 ml. After 7 weeks on the deficient diet, another group of rats was given drinking water containing 3 mg Zn/100 ml and the usual diet containing 4.7 mg Zn/100 g for 8 weeks for recovery. The cornea and conjunctiva were examined by electron microscopy and TOF-SIMS. RESULTS: Microvilli and microplicae in the most superficial layer of the epithelium of the Zn-deficient rat conjunctiva and cornea were prominently reduced, and dark cells were significantly increased. The numbers of goblet cells were decreased in the conjunctiva of the Zn-deficient group. Zn, Ca and Al ions were significantly fewer, but K, Fe, Cl and S ions were significantly more numerous in the Zn-deficient group than in the control group. In the cornea of the Zn-deficient group, there was significantly more Cl but less Ca and vitamin C than in the controls. DISCUSSION: Zn deficiency may interfere with protein, nucleic acid and collagen synthesis through the reduction of Zn-containing enzymes. Myosin-like substance, actin filaments and tonofibrils are important structural components for microvilli and microplicae in the epithelium. Maldevelopment of these structural components may be related to disturbed activities of Zn-containing enzymes in protein and collagen synthesis because of Zn deficiency. In addition, Zn deficiency caused changes in the levels of Zn and other trace elements such as Ca, Al, S, Fe, and Cl and vitamin C. CONCLUSION: Zn deficiency resulted in poorly developed microvilli and microplicae on the ocular surface tissues, reduced the number of goblet cells and changed the quantity of trace elements and vitamin C.

Dietary folate and selenium affect dimethylhydrazine-induced aberrant crypt formation, global DNA methylation and one-carbon metabolism in rats.

Several observations suggest a role for DNA methylation in cancer pathogenesis. Although both selenium and folate deficiency have been shown to cause global DNA hypomethylation and increased cancer susceptibility, the nutrients have different effects on one-carbon metabolism. Thus, the purpose of this study was to investigate the interactive effects of dietary selenium and folate. Weanling, Fischer-344 rats (n = 23/diet) were fed diets containing 0 or 2.0 mg selenium (as selenite)/kg and 0 or 2.0 mg folate/kg in a 2 x 2 factorial design. After 3 and 4 wk of a 12-wk experiment, 19 rats/diet were injected intraperitoneally with dimethylhydrazine (DMH, 25 mg/kg) and 4 rats/diet were administered saline. Selenium deficiency decreased (P < 0.05) colonic DNA methylation and the activities of liver DNA methyltransferase and betaine homocysteine methyltransferase and increased plasma glutathione concentrations. Folate deficiency increased (P < 0.05) the number of aberrant crypts per aberrant crypt foci, the concentration of colonic S-adenosylhomocysteine and the activity of liver cystathionine synthase. Selenium and folate interacted (P < 0.0001) to influence one-carbon metabolism and cancer susceptibility such that the number of aberrant crypts and the concentrations of plasma homocysteine and liver S-adenosylhomocysteine were the highest and the concentrations of plasma folate and liver S-adenosylmethionine and the activity of liver methionine synthase were the lowest in rats fed folate-deficient diets and supplemental selenium. These results suggest that selenium deprivation ameliorates some of the effects of folate deficiency, probably by shunting the buildup of homocysteine (as a result of folate deficiency) to glutathione.