Plasma Zinc Deficiency Research Articles

Энтеропатический акродерматит у детей

Enteropathic acrodermatitis is a rare hereditary form of zinc deficiency, characterized by periorial and acral dermatitis, alopecia and diarrhea. Refers to congenital disorders of zinc metabolism, inherited as an autosomal recessive disease resulting from mutations in the gene for the zinc transporter SLC39A4. The prevalence ranges from 1 to 9:1,000,000, with an overall incidence of 1:500,000 newborns. The disease usually manifests itself in infancy, within a few weeks of stopping breastfeeding and switching the baby to a cow's milk-based formula, or in the first days of life if artificially fed from birth. The classical clinical manifestations of acrodermatitis enteropathic are characterized by the triad: acral and periofital dermatitis, alopecia and diarrhea, but all three signs together occur only in 20% of cases. Diarrhea may develop concurrently with skin symptoms, may precede or occur later. Characteristic signs of skin lesions include sharply demarcated, dry, scaly erythematous plaques or edematous foci with vesicles and pustules on the skin of the elbow and knee joints, distal extremities, genitals, in the inguinal folds, which are usually symmetrically distributed, have sharp boundaries and irregular outlines. The course of the skin syndrome is long, as it progresses, non-healing erosive and ulcerative areas appear. Plasma zinc deficiency is the gold standard for diagnosis. Most infants with AE have low plasma zinc concentrations (<500 mcg/L or <50 mcg/dl), but a level of less than 70 mcg/L on an empty stomach or less than 65 mcg/dl in older non-dieting children is considered diagnostically significant. Treatment for this disease usually includes enteral or parenteral zinc administration, at a dose of 1-3 mg/kg/day. for elemental zinc. A clinical response is observed within 5–10 days. Supportive zinc therapy is necessary throughout the patient's life, although periods of remission have been reported. Topical therapy is also used: Dexpanthenol in the form of a cream, applied 3 times a day in the area of dermatitis, can enhance re-epithelialization. There is no significant evidence of improvement with topical zinc application. No activity restrictions are required for patients with acrodermatitis enteropathic. Key words: zinc deficiency, enteropathic acrodermatitis, children

Zinc nutritional status influences ZnT1 and ZIP4 gene expression in children with a high risk of zinc deficiency

IntroductionSubclinical deficiency of zinc is associated with impairment of immune system function, growth, and cognitive development in children. Although plasma zinc is the best available biomarker of the risk of zinc deficiency in populations, its sensitivity for early detection of deficiency is limited. Therefore, we aimed to investigate zinc deficiency among preschool children and its relationship with whole blood gene expression of zinc transporters ZIP4 and ZnT1. Material and methodsThis cross-sectional study included 139 children aged 32–76 months enrolled in philanthropic day-care centers. We performed an anthropometric evaluation, weighed food record and dietary record for dietary assessment, blood sample collection for zinc, and whole blood gene expression analyses of ZnT1 (SLC30A1) and ZIP4 (SLC39A4). ResultsZinc deficiency was observed in 26.6 % of the children despite adequate zinc intake and a phytate:zinc molar ratio < 18. Usual zinc intake did not affect whole blood gene expression of zinc transporters, but zinc status influenced ZnT1 and ZIP4 whole blood mRNA. Children with zinc deficiency exhibited 37.1 % higher ZnT1 expression and 45.3 % lower ZIP4 expression than children with adequate zinc (p < 0.05). ConclusionChildren with plasma zinc deficiency exhibited higher expression of ZnT1 and lower expression of ZIP4 in whole blood mRNA, reinforcing the existence of strong regulation of mineral homeostasis according to the nutritional status, indicating that this analysis may be useful in the evaluation of dietary interventions.

Low Plasma Zinc Is Associated with Higher Mitochondrial Oxidative Stress and Faster Liver Fibrosis Development in the Miami Adult Studies in HIV Cohort

BackgroundOxidative stress and reduced antioxidants may be a trigger for liver fibrogenesis. Reducing oxidative stress through higher antioxidant concentration may be a potential antifibrotic target. ObjectiveWe aimed to investigate longitudinally whether plasma zinc, an antioxidant, is related to mitochondrial oxidative stress and the progression of liver fibrosis in the Miami Adult Studies in HIV (MASH) cohort. MethodsA prospective observational cohort study was conducted in 487 predominantly African American HIV-monoinfected and HIV/hepatitis C virus (HCV)–coinfected adults with a mean ± SD age of 47.08 ± 7.67 y from the MASH cohort and followed for a median of 34 mo. Blood was collected for plasma zinc and measures were used to calculate the fibrosis-4 (FIB-4) score (aspartate amino transferase, alanine aminotransferase, and platelets). Plasma zinc deficiency was defined as <0.75 mg/L. Total DNA was extracted from peripheral blood mononuclear cells and mitochondrial DNA (mtDNA) 8-hydroxyguanosine (8-oxo-dG) was determined. Adjusted mixed models were used to assess the relations between zinc, stage of liver disease, and oxidative stress over time and compared between HIV and HIV/HCV groups. ResultsZinc concentrations (β: −0.368, SE = 0.172; P = 0.033) and deficiency were associated with lower FIB-4 scores over time (β: 0.381, SE = 0.118; P = 0.001). Compared with those who were not zinc deficient, zinc-deficient participants had an increased risk of having more-progressed liver disease (OR: 1.91; 95% CI: 1.15, 3.16; P = 0.012). Higher mtDNA 8-oxo-dG was associated with zinc deficiency (β: 0.049, SE = 0.024; P = 0.044) and higher FIB-4 scores over time (β: 0.597, SE = 0.168, P < 0.001). ConclusionLower plasma zinc concentrations were associated with liver fibrosis progression and mitochondrial oxidative stress in the HIV and HIV/HCV groups. Zinc may play a role in the impact of liver disease outcomes.

Implications of Low Zinc and Copper Levels As Well As Altered Iron Trafficking Proteins on Oxidant Stress in Patients with Transfusion Dependant Thalassemia

Introduction:Patients with transfusion dependent thalassemia (TDT) have a genetic anemia that causes incomplete erythropoiesis and iron overload. Plasma zinc deficiency is also seen in roughly 25% of patients with TDT. Iron overload is thought to be related to a number of secondary complications in TDT including cardiomyopathy and diabetes. However, in TDT the effects of altered Zn status are not as well characterized and the effects of low copper (Cu) are even less well known. One possible cause of these complications is oxidative damage to tissues. This oxidative stress can be caused by labile plasma iron (LPI), a component of the non-transferrin bound iron pool, which is often seen in individuals suffering from iron overload. LPI is both redox-active and chelatable and is the likely culprit distributing iron to extra-hepatic tissues. Through reactive Fenton chemistry, LPI, can also cause lipid peroxidation releasing malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE), which are damage-associated molecular patterns and markers of oxidative tissue damage that activate the immune system to induce inflammation. Incomplete erythropoiesis as well as transfusional iron overload are responsible for an increase in the amount of poorly handled, redox active LPI in TDT. Thus, we hypothesized that changes in the levels of key iron trafficking proteins (such as soluble transferrin receptor (sTfR) or hemopexin) would affect oxidative stress levels in TDT. We also hypothesized that metal dyshomeostasis, such as a functional Zn or Cu deficiency would affect oxidative stress.Aims: The purpose of this pilot project is to 1) Determine the state of circulating levels of oxidative stress markers and iron trafficking proteins in TDT patients and 2) Explore the relationship between the markers and proteins measured in (1)and the Zn and Cu status of TDT patients.Methods:39 subjects with informed consent were enrolled (29 patients with TDT and 10 controls). Liver iron concentration (LIC) was measured by a superconducting quantum interference device (SQUID™). LPI was measured using dihydrorhodamine 123. Both MDA and MDA + 4-HNE were measured using N-methyl-2-phenylindole. The iron trafficking proteins sTfR, transferrin, haptoglobin and hemopexin were measured by immunoassay isolation followed by multiplex multiple reaction monitoring mass spectrometry. Zn and Cu were assessed by inductively coupled plasma atomic emission spectroscopy. Fructosamine was measured by quantitative spectrophotometry.Results: Patients with TDT had elevated LIC levels of 2681 ± 2424 ug iron/g wet weight. Plasma levels of the iron trafficking proteins, transferrin, hemopexin and haptoglobin were all decreased in TDT patients (P<0.001) with a corresponding increase in soluble transferrin receptor (StfR) and the LPI (P<0.001). Serum Zn was significantly reduced in TDT patients (p = 0.028) and urinary Zn was significantly elevated (p =0.024). Serum Cu was also significantly reduced in TDT patients (p =0.026). Reduced Zn levels in TDT patients correlated with elevated MDA levels (p = 0.0195, R = -0.382) as were serum Cu levels (p = 0.0158, R = -0.394). Reduced levels of plasma iron trafficking proteins (haptoglobin, hemopexin, and transferrin) were correlated with elevated levels of MDA and LPI (all p-values < 0.05). Plasma MDA was also correlated with fructosamine levels (p < 0.001, R= 0.57).Conclusion: Metal dyshomeostasis involving Zn and Cu may be important contributors to oxidative stress and iron injury in TDT. We confirm previous findings in TDT of elevated levels of LPI as well as the oxidative stress markers MDA and 4-HNE. We expand previous findings of reduced transferrin levels in TDT to show a similar reduction in both haptoglobin and hemopexin. StfR levels were elevated in TDT patients, possibly due to a strong erythropoietic drive. Both reduced haptoglobin and hemopexin as well as decreased Zn and Cu levels and increased Zn excretion appear to be present in TDT. These preliminary findings suggest that low levels of Zn, Cu, haptoglobin and hemopexin may be related to increased oxidative stress and LPI in TDT, which could be important contributors to secondary complications of TDT. DisclosuresWalter:Apopharma: Research Funding.

Zinc Deficiency Is associated With Depressive Symptoms-Results From the Berlin Aging Study II.

Zinc plays an important role for behavioral and mental function, maintaining the correct functions of intracellular signal transduction, cellular and trans-membrane transport, protein synthesis, and antioxidant system. We investigated both dietary zinc intake and plasma zinc levels and the correlation with depressive symptoms in a large sample of community-dwelling old. One thousand five hundred fourteen older people (aged 60-84 years, 772 women) from the Berlin Aging Study II were included. Zinc intake was assessed by the EPIC Food Frequency Questionnaire. Plasma zinc levels were assessed with atomic-absorption spectrophotometry. Depressive symptoms were assessed with the "Center for Epidemiological Studies Depression Scale" and the "Geriatric Depression Scale." Zinc deficiency in blood plasma was found in 18.7% of participants, and depressive symptoms in 15.7%. Participants with depressive symptoms had lower energy-adjusted zinc intake (median 11.1 vs 11.6 µmol/L; p = .048) and lower plasma zinc levels (median 12.2 vs12.3 mg/dL; p = .037). Even after adjustment for known predictors of depression, plasma zinc deficiency remained significantly associated with depressive symptoms (odds ratio: 1.490, 95% confidence interval: 1.027-2.164; p = .036). In the multiple logistic regression model stratified by sex, we found that plasma zinc deficiency was strongly associated with a higher risk for depressive symptoms in women (odds ratio: 1.739, 95% confidence interval: 1.068-2.833; p = .026). Plasma zinc deficiency was common in our old study population. An increase in dietary zinc and higher plasma zinc levels may reduce the risk of depressive symptoms. A screening for reduced dietary zinc intake or plasma zinc deficiency might be beneficial in older people at risk of depressive symptoms.

Lower Plasma Zinc Levels in Hyperglycemic People Living with HIV in the MASH cohort.

Zinc deficiency is prevalent in HIV and hyperglycemic patients. Antiretroviral therapy (ART) is a treatment to control HIV progression; however it increases the risk for hyperglycemia. The objective of this study was to assess the plasma zinc levels in hyperglycemic people living with HIV (PLWH). Secondary analysis was conducted on the data from the Miami Adult Studies in HIV (MASH) cohort in Florida. Patients were categorized into hyperglycemic group (fasting blood glucose ≥100 mg/dL) and normal group (<100 mg/dL). Plasma zinc status and CD4 levels were lower in the hyperglycemic group, however the difference was not significant. There was a greater percentage of plasma zinc deficiency in the hyperglycemic group (69%) compared to the normoglycemic group (64%). Although not statistically significant, related biomarkers such as plasma zinc levels and CD4 levels were lower in the hyperglycemic group. This may be due to the role zincplays in the immune system. Due to the fact that there was a higher percentage of plasma zinc deficiency in the hyperglycemic group (69%) compared to the normoglycemic group (64%), it is important to monitor and manage blood glucose levels to minimize complications. Our findings along with previous findings suggest that zinc supplementation may benefit hyperglycemic PLWH.

Preoperative Plasma Zinc Deficiency Common in Cardiac Surgery Patients but Does Not Affect Clinical Outcomes in the Intensive Care Unit

Preoperative Plasma Zinc Deficiency Common in Cardiac Surgery Patients but Does Not Affect Clinical Outcomes in the Intensive Care Unit

Zinc, metallothioneins and immunosenescence: effect of zinc supply as nutrigenomic approach

Ageing is an inevitable biological process associated with gradual and spontaneous biochemical and physiological changes and increased susceptibility to diseases. Nutritional factor, zinc, known to be involved in improving immunity, may remodel some of the age-associated changes, leading to a healthy ageing. "In Vitro" studies involving human lymphocytes exposed to endotoxins, and "in vivo" studies comparing old and young mice fed with low dietary zinc suggest that zinc is important for both innate and adaptive immune efficiency, and more optimal inflammatory/immune response. The intracellular zinc homeostasis is mainly regulated by Metallothioneins (MT), via ion release through the reduction of thiol groups in MT molecule. These processes are crucial because mediating the zinc signalling within the immune cells assigning to zinc a role of "second messenger". Zinc homeostasis is altered in ageing partly due to higher expression levels of MT, leading to an increased sequestration of zinc, resulting in less availability of free intracellular zinc. Improvement of immune functions and stress response systems occurs in elderly after physiological zinc supplementation. The main reason behind these effects seems to be related to a like "hormetic" response induced by zinc. However, the choice of old subjects for zinc supplementation has to be performed in relationship to the specific genetic background of MT and pro-inflammatory cytokine (IL-6) because the latter is involved both in MT gene expression and in intracellular zinc homeostasis. Old subjects carrying GG genotypes (termed C- carriers) in IL-6--174G/C locus display increased IL-6 production, low intracellular zinc ion availability, impaired innate immune response and enhanced MT. By contrast, old subjects carrying GC and CC genotypes (termed C+ carriers) in the same IL-6--174 locus displayed satisfactory intracellular zinc and innate immune response. Moreover, male carriers of C+ allele are more prone to reach centenarian age than C- ones. Therefore, old C- subjects are likely to benefit more from zinc supplementation restoring NK cell cytotoxicity and improving the zinc status. Plasma zinc deficiency and the altered immune response is more evident when the genetic variations of IL-6 polymorphism are associated with the genetic variations of MT1A in position +647, suggesting that the genetic variations of IL-6 and MT1A are very useful tools for the identification of old people who effectively need zinc supplementation.

Plasma Retinol, Thyroid Stimulating Hormone and Zinc as Predictors of Bone Mineral Density Status

Background: Conflicting results on the association between serum retinol level and bone mineral density (BMD) have been published. Thyroid hormones are essential for skeletal development and have direct effect on bone formation and resorption. Bone has one of the highest concentrations of zinc of all tissues, and has been shown to release zinc during deficiency for soft tissue metabolism. Objective: The objective of this study was to assess the relation between plasma levels of retinol, thyroid stimulating hormone (TSH) & zinc and BMD of Egyptian adolescents and adults. Method: The study was a part of a cross sectional national survey conducted by National Nutrition Institute. The sample was a multistage stratified random. Target individuals were classified into two age groups (10- ≤ 18 and 28-≤ 59 years). Bone mineral density and plasma levels of retinol, TSH and zinc were determined. Results: Low and high plasma retinol levels were more prevalent among osteoporotic adolescent and adult males respectively than in normal subjects.. The reverse was observed in adult females. Bone mineral density correlated negatively with plasma retinol level in adult males and females and positively in adolescent males, while among females the association was significant (P = 0.030) and stronger. The highest deficiency of TSH was found among adult and adolescent osteoporotic males, followed by osteopenic adult males and adolescent females. Highly statistically significant difference (P < 0.001) existed between osteoporotic and normal adult males concerning TSH deficiency. The prevalence of zinc deficiency ranged from 5.7% to 9.5% for all target individuals. Plasma Zn levels were correlated negatively with bone mineral density in adult males and females. Conclusion: The results of this study reflects the controversy on the association of plasma retinol and BMD. However, the predominant finding revealed that both low and high plasna retinol levels compromise bone health. Bone status and thyroid function support the adverse effect of hyperthyroidism upon either bone osteoporosis or osteopenia and subsequently upon fracture risk. Plasma zinc deficiency correlated negatively with BMD in adult osteoporotic men.

342 ZINC PEFICIENCY IN INFANTS WITH FETAL ALCOHOL SYNDROME

Renal clearance of zinc was examined in 6 infants with fetal alcohol syndrome (FAS) to determine if there is a link between prenatal exposure to ethanol and zinc deficiency in the development of fetal dysmorphogenesis. Eight healthy age-matched infants served as controls. There was no significant difference in creatinine clearance, urine flow rate, or fractional water excretion values between the two groups. Plasma concentrations of zinc were significantly lower in FAS patients (62.5±2.8 μg/dL) in comparison to controls (70.3±2.3 μg/dL), (P<.00005). Urinary excretion of zinc in FAS patients averaged 646±125 μg/24 hr; significantly higher than in control subjects (330±184 μg/24 hr), (P<.00005). Fractional excretion of zinc (FEZn was significantly higher in FAS patients (2.8±1.1%) compared to control group (1.4±.07%), (P=.02), but the mean filtered zinc (FZn) was significantly lower in patients than in controls (P=.02). The changes in FEZn for FAS patients varied inversely with urine flow rate (r=-.58, P=.002) and with FZn (r=-.39, P=.0001), but varied directly with fractional water excretion (r=.20, P=.008). Thus: (1) Plasma zinc deficiency is present in infants with FAS; (2) increased fractional clearance of zinc appears to be responsible for decreased plasma zinc concentrations; (3) relative zinc deficiency in FAS patients may be responsible for some of the features associated with the syndrome.