Antioxidant defense of children and adolescents with atopic dermatitis: Association with disease severity

Background: Atopic dermatitis (AD) is a relapsing, chronic cutaneous inflammatory disease with onset, in general, in early childhood. Chronic skin inflammation is associated with overproduction of reactive oxygen species (ROS) such as superoxide and hydrogen peroxide. Oxidative stress, an imbalance between the production of free radicals and antioxidant defense, results in tissue inflammation due to the upregulation of genes that encode inflammatory cytokines. This condition plays an important role in the pathogenesis of AD. Objective: To compare the antioxidant defense in children and adolescents with AD with that of healthy individuals and to verify the association of antioxidant defense with disease severity and nutritional status. Methods: Cross-sectional study that evaluated 48 children and adolescents with AD and 25 controls for nutritional assessment (body mass index z score [BMIZ] and height for age z score [HAZ]) and levels of vitamins A, C, E, and D, zinc (Zn), copper (Cu), antioxidant enzymes (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GPx]), high-sensitivity C-reactive protein (CRP) and interleukin 33 (IL-33). Results: There was no significant difference in the comparison between AD and control groups for serum levels of vitamins (A, D, C, and E), copper, and antioxidant enzymes. Serum zinc levels were higher in the AD group (β = 24.20; 95% CI 13.95–34.91; P < 0.001) even after adjusting the BMIZ, HAZ, gender, IL-33, and CRP. Children and adolescents with moderate or severe AD compared to mild AD (SCORAD – 36.7±17.4 vs 11.8 ± 3.9; P < 0.001) had lower values of the vitamin E/total lipid ratio (3.68 [0.29;12.63] vs 5.92 [3.27;17.37]; P = 0.013) (AU)

Acrodermatitis enteropathica during parenteral nutrition: a pediatric case report.

Background and aim Acrodermatitis enteropathica is a rare disorder characterized by the triad composed by dermatitis, alopecia and diarrhoea. Its acquired form can be caused by inadequate zinc intake, malabsorptive processes, excessive renal or intestinal loss. A rare cause of acquired zinc deficiency is iatrogenic nutritional deficiency due to parenteral nutrition. The diagnosis can be really difficult because the early clinical signs are non-specific and patient's eventual comorbidities can often mask symptoms. Methods: A 5-years-old child affected by several comorbidities, consequent to C. Koseri meningo-encephalitis occurred in the neonatal period, was admitted to Pediatric ward for acute pancreatitis and  had been fed via total parenteral nutrition for one month. Symptoms started approximately 15 days after the start of a  standardized parenteral nutrition mixture. The child presented with diarrhoea, alopecia and erythematous bullous skin lesions, distributed predominantly in acral and periorificial sites and not responsive to topical treatments. Zinc serum dosage were very low (10 µg/dL, with normal values 68-107 µg/dL). Clinical improvement was very fast after oral zinc supplementation (5mg/daily), with a rapid regularisation in the intestinal habits and re-epithelialization of the skin lesions. Results and Conclusions: Trace elements are an essential component of parenteral nutrition. The supplementation of trace elements is an important part of the parenteral nutrition prescription. Even few days of zinc shortage, especially in frail patients, may cause a severe dermatitis that can be easily prevented. Despite its rarity, acrodermatitis enteropathica should be strongly considered in the differential diagnosis of skin lesions for these patients.

Metal Exposure and Risk of Parkinson Disease: A Systematic Review and Meta-Analysis.

Metal exposure has been suggested as a possible environmental risk factor for Parkinson disease (PD). We searched the PubMed, EMBASE, and Cochrane databases to systematically review the literature on the relationship between metal exposure and PD risk and to examine the overall quality of each study and the exposure assessment method. A total of 83 case-control studies and 5 cohort studies published during the period 1963-July 2021 were included, of which 73 were graded as being of low or moderate overall quality. Investigators in 69 studies adopted self-reported exposure and biomonitoring after disease diagnosis for exposure assessment approaches. The meta-analyses showed that concentrations of copper and iron in serum and concentrations of zinc in either serum or plasma were lower, while concentrations of magnesium in CSF and zinc in hair were higher, among PD cases as compared with controls. Cumulative lead levels in bone were found to be associated with increased risk of PD. We did not find associations between other metals and PD. The current level of evidence for associations between metals and PD risk is limited, as biases from methodological limitations cannot be ruled out. High-quality studies assessing metal levels before disease onset are needed to improve our understanding of the role of metals in the etiology of PD.

Study on the Zinc Nutritional Status and Risk Factors of Chinese 6-18-Year-Old Children.

Zinc is an essential micronutrient that is involved in several metabolic processes, especially children's growth and development. Although many previous studies have evaluated the zinc nutritional status of children, there are very few reports on children aged 6-18 years old. Furthermore, there are few reports on children's zinc nutrition status based on the Chinese population. According to WHO data, the prevalence of zinc deficiency in Asian countries is rather high and has resulted in high child mortality. In this study, we aimed to comprehensively assess zinc nutritional status and the prevalence of zinc deficiency among children aged 6-18 years in China based on nationally representative cross-sectional data. Subgroup comparisons were made under possible influencing factors. The potential risk factors of zinc deficiency were also discussed. A total of 64,850 children, equally male and female, were recruited from 150 monitoring sites in 31 provinces through stratified random sampling from China National Nutrition and Health Survey of Children and Lactating Mothers (CNNHS 2016-2017). Median and interquartile intervals were used to represent the overall zinc concentration levels and different subgroups. A Chi-square test was used to compare serum zinc levels and the prevalence of zinc deficiency in children under different group variables. In order to study the influencing factors of zinc deficiency, multiple logistic regression was utilized. It was found that the median concentration of serum Zn was 88.39 µg/dL and the prevalence of Zn deficiency was 9.62%. The possible influence factors for Zn deficiency were sex, anemia, nutritional status, city type and income. By conducting a subgroup analysis of the factors, it was found that males; those with anemia, stunting and low income; and children living in rural areas have a higher risk of Zn deficiency. This study offers a comprehensive analysis of Zn nutritional status among Chinese children, which provides reliable data for policy formulation to improve the zinc nutrition status of children.

Serum Cu, Zn and IL-1ß Levels May Predict Fetal Miscarriage Risk After IVF Cycles: A Nested Case-Control Study.

To explore the association between serum-related indicators (levels of inflammatory cytokines and essential trace elements) and miscarriage risk among infertile women undergoing assisted reproductive techniques (ART) on the 14th day after embryo transfer, and to develop and establish a multivariable algorithm model that might predict pregnancy outcome. According to a nested case-control study design, a total of 100 miscarriage cases and 100 live birth controls were included in this study, and women in both groups were infertile and have underwent in vitro fertilization (IVF). Pregnancy tests were performed and serum levels of five essential trace elements (vanadium (V), copper (Cu), zinc (Zn), selenium (Se) and molybdenum (Mo)) and five inflammatory cytokines (interleukin-1ß (IL-1ß), IL-6, IL-8, IL-10 and tumor necrosis factor-α (TNF-α)) of the participants were measured on the 14th day after embryo transfer. The serum levels of five inflammatory cytokines were determined by multiple magnetic bead enzyme immunity analyzer; and the serum concentrations of five elements were determined simultaneously by inductively coupled plasma‒mass spectrometry (ICP ‒ MS). The logistic regression was used to evaluate the relationship between these serum indices and miscarriage risk among women undergoing ART, and a predictive model of pregnancy outcome based on these indices was established. The levels of IL-10, IL-1ß and TNF-α of infertile women in the live birth group were significantly higher than those in the miscarriage group (p = 0.009, p < 0.001, p = 0.006), and the levels of V, Cu, Zn and Se of infertile women in the live birth group were also significantly higher than those in the miscarriage group (all p < 0.001). Through logistic regression analyses, we found that serum levels of IL-1ß, TNF-α, V, Cu, Zn and Se were significantly and negatively associated with miscarriage risk. Different combination prediction models were generated according to the results of logistic regression analyses, and the combination of IL-1ß, Cu and Zn had the best prediction performance. The area under the curve (AUC) was 0.776, the sensitivity of the model was 60% and the specificity was 84%. In conclusion, the serum-related indicators of women undergoing ART on the 14th day after embryo transfer, including the inflammatory cytokines such as IL-1ß and TNF-α and the essential trace metal elements such as V, Cu, Zn and Se, were negatively correlated with miscarriage risk. A multivariate algorithm model to predict pregnancy outcome among women undergoing ART was established, which showed that IL-1ß, Cu and Zn might synergistically predict pregnancy outcome.

Assessment of intracellular zinc levels in infants with food protein–induced allergic proctocolitis

Background: Food protein–induced allergic proctocolitis (FPIAP) is characterized by bloody stools in well-appearing infants. Zinc is a micronutrient that plays a crucial role in immune modulation and is essential for cellular function during immune response. Although there are studies on the assessment of intracellular zinc levels in allergic diseases, no data is available on erythrocyte zinc levels of patients with FPIAP. Objective: This study aimed to assess the erythrocyte zinc levels of children with allergic proctocolitis and compare zinc levels with clinical and demographic characteristics. Methods: This was a case–control study that prospectively compared 50 patients with FPIAP and 50 healthy children without malnutrition. The erythrocyte zinc levels of children were determined using atomic absorption spectrophotometry. Results: Fifty patients with FPIAP, including 28 (51%) girls, with median age of 7.1 ± 2.9 (3–14) months and 50 healthy children, including 26 (53.1%) girls, with median age of 7.7 ± 2.8 (3–13) months were included in the study. Seventy percent (n = 35) of the patients with FPIAP started to have symptoms while they were exclusively breastfeeding. Offending allergen foods were cow’s milk (78%), egg (40%), sesame (10%), hazelnut (8%), almond (6%), beef (6%), and peanuts (6%, n = 3). Intracellular (erythrocyte) zinc levels in patients with FPIAP were lower than in the healthy control group (495.5 ± 134 µg/dL, 567.3 ± 154.4 µg/dL, respectively, P = 0.01). Patients with FPIAP aged younger than 6 months had lower intracellular zinc levels compared with those aged above 6 months (457 ± 137 µg/dL; 548 ± 112 µg/dL, respectively, P = 0.01). There was no relationship between zinc levels and time of symptom onset, presence of concomitant disease, being allergic to multiple foods, and family history of atopy (P > 0.05). Conclusions: FPIAP is a food allergy with limited information on its pathogenesis (AU)

Evaluation of Serum Levels of Copper and Zinc in Patients with Celiac Disease Seropositivity: Findings from the National Health and Nutrition Examination Survey.

Celiac disease is a multisystem immune based disorder, caused by an immune-mediated reaction to ingested gluten with increasing prevalence in the USA. Celiac disease can cause a wide variety of symptoms, including gastrointestinal symptoms (diarrhea, abdominal distention, or abdominal pain), which may affect absorption of many nutritional components. All patients with celiac disease should remain on a strict and lifelong gluten-free diet, which are often low in certain trace elements such as zinc. On the other hand, zinc and copper as the essential trace elements have been hypothesized to help maintain optimum function of the immune system. Then, this study aims to examine the association between celiac disease seropositivity and serum zinc and copper levels. A nationally representative sample from National Health and Nutrition Examination Survey (2011-2014) was analyzed. Celiac disease seropositivity was determined using the tissue transglutaminase IgA antibody test (IgA-TTG). Multivariable linear regression models were performed with celiac disease seropositivity as a predictor and serum zinc and copper levels as outcome. The present study included 4732 participants (1398 children aged 6-19 years and 3334 adults aged ≥ 20 years). The weighted prevalence of celiac disease seropositivity was higher (11.6/1000) among children aged 6-19 years compared to that (6.3/1000) among adults aged ≥ 20 years. In the stratified analysis by age, the multivariable linear regression analysis revealed that among children aged 6-19 years, celiac disease seropositivity was associated with 5.32 (95% CI, - 9.71 to - 0.92) µg/dL lower serum zinc level, but not associated with serum copper level. However, the association between celiac disease seropositivity and serum zinc level was not statistically significant among adults aged 20 years or older. Future prospective studies are warranted to confirm these findings.

Association of CYP19A1 Gene, Plasma Zinc, and Urinary Zinc with the Risk of Type 2 Diabetes Mellitus in a Chinese Population.

To explore the effects of CYP19A1 gene polymorphisms, plasma zinc, and urinary zinc levels and their interactions on type 2 diabetes mellitus (T2DM) in residents of Gongcheng County, Guangxi, China. The case-control study was used for the investing. The MassARRAY System was applied to genotype the CYP19A1 genes rs752760, rs10046, rs10459592, and rs700518 in 540 study subjects. Plasma and urinary zinc concentrations were measured by inductively coupled plasma mass spectrometry (ICP-MS). Conditional logistic regression showed that rs752760 and plasma zinc were associated with T2DM risks with ORs of 0.593 (95% CI: 0.371-0.948) and 0.563 (95% CI: 0.356-0.889), respectively. Unconditional logistic regression analysis showed an association between urinary zinc levels and the risk of T2DM as well, with an OR of 0.352 (95% CI: 0.212-0.585). The results of the multiplicative interaction model showed that the rs752760 T allele was associated with a significantly reduced risk of T2DM with moderate/low plasma zinc levels, with ORs of 0.340 (95% CI: 0.161-0.715) and 0.583 (95% CI: 0.346-0.981), respectively, and the rs752760 T allele was also associated with a significantly decreased risk of T2DM with moderate/low urinary zinc levels, with ORs of 0.358 (95% CI: 0.201-0.635) and 0.321 (95% CI: 0.183-0.562), respectively. CYP19A1 rs752760 T allele and moderate/low plasma/urinary zinc levels reduce the risk of T2DM.

Association between Serum Zinc and Toll-like-Receptor- Related Innate Immunity and Infectious Diseases in Well-Nourished Children with a Low Prevalence of Zinc Deficiency: A Prospective Cohort Study.

Existing reports focus on zinc-associated immunity and infection in malnourished children; however, whether zinc also plays an important role in the immune homeostasis of the non-zinc-deficient population remained unknown. This study aimed to investigate the association between zinc status and toll-like receptor (TLR)-related innate immunity and infectious outcome in well-nourished children. A total of 961 blood samples were collected from 1 through 5 years of age. Serum zinc was analyzed, and mononuclear cells isolated to assess TNF-α, IL-6, and IL-10 production by ELISA after stimulation with TLR ligands. Childhood infections were analyzed as binary outcomes with logistic regression. The prevalence of zinc deficiency was 1.4-9.6% throughout the first 5 years. There was significant association between zinc and TLR-stimulated cytokine responses. Higher serum zinc was associated with decreased risk of ever having pneumonia (aOR: 0.94; 95% CI: 0.90, 0.99) at 3 years, and enterocolitis (aOR: 0.96; 95% CI: 0.93, 0.99) at 5 years. Serum zinc was lower in children who have had pneumonia before 3 years of age (72.6 ± 9 vs. 81.9 ± 13 µg/dL), and enterocolitis before 5 years (89.3 ± 12 vs. 95.5 ± 13 µg/dL). We emphasize the importance of maintaining optimal serum zinc in the young population.

Zinc deficiency and associated factors among pregnant women's attending antenatal clinics in public health facilities of Konso Zone, Southern Ethiopia.

BACKGROUND: Zinc is an essential mineral known to be important for the normal physiological functions of the immune system. It is one of the basic nutrients required during pregnancy for the normal development and growth of the fetus. However, Zinc deficiency during pregnancy causes irreversible effects on the newborn such as growth impairment, spontaneous abortion, congenital malformations and poor birth outcomes. Even though, the effect of Zinc deficiency is devastating during pregnancy, there is scarcity of evidence on Zinc deficiency and related factors among pregnant women in the current study area. OBJECTIVE: To assess Zinc deficiency and associated factors among pregnant women attending antenatal clinics in public health facilities of Konso Zone, Southern Ethiopia. METHODS: Institution based cross-sectional study was conducted among randomly selected 424 pregnant mothers. Data were collected using pre tested questionnaire (for interview part), and 5 blood sample was drawn for serum zinc level determination. Data were entered to Epi-Data version 3.1 software and exported to SPSS version 25 for analysis. Binary logistic regression analysis was computed and independent variables with a p-value ≤ 0.25 were included in multivariable analysis. Serum zinc level was determined using atomic absorption spectroscopy by applying clean and standard procedures in the laboratory. Finally adjusted odds ratio with 95% confidence level, P-value < 0.05 was used to identify significant factors for Zinc deficiency. RESULT: The prevalence of Zinc deficiency was found to be 128 (30.26%) with the mean serum zinc level of 0.56±0.12 g/dl. Age, 25-34 years [AOR 2.14 (1.19,3.82)], and 35-49 years [AOR 2.59 (1.15, 5.85)], type of occupation, farming [AOR 6.17 (1.36, 28.06)], lack of antenatal follow up during pregnancy [AOR 3.57 (1.05,12.14)], lack of freedom to purchase food items from market [AOR 3.61 (1.27, 10.27)], and inadequate knowledge on nutrition [AOR 3.10(1.58, 6.08)] were factors associated with Zinc deficiency. CONCLUSION: Zinc deficiency is a public health problem among pregnant mothers in the current study area. Improving maternal nutritional knowledge, motivating to have frequent antenatal follow up, and empowering to have financial freedom to purchase food items from market were the modifiable factors to reduce Zinc deficiency. Nutritional intervention that focused on improving nutritional knowledge and insuring access to Zinc sources food items should be delivered for pregnant mothers.

Serum copper-to-zinc ratio and risk of incident pneumonia in caucasian men: a prospective cohort study.

Serum copper (Cu) and zinc (Zn), essential micronutrients that have important immunomodulatory and antimicrobial properties, are biomarkers of ageing. Serum Cu/Zn-ratio may be a more reliable marker for age-related degenerative conditions compared with serum Cu or Zn alone. We aimed to assess the association between Cu/Zn-ratio and the risk of incident pneumonia in a prospective cohort study. Serum levels of Cu and Zn were measured at baseline using atomic absorption spectrometry in 2503 men aged 42-61 years in the Kuopio Ischemic Heart Disease prospective cohort study. Hazard ratios (HRs) with confidence intervals (CIs) were calculated for incident pneumonia using Cox regression models. A total of 599 cases of pneumonia occurred during a median follow-up of 26.1 years. Serum Cu/Zn-ratio and Cu were each linearly associated with incident pneumonia. A unit increase in Cu/Zn-ratio was associated with an increased risk of pneumonia in analysis adjusted for potential confounders including C-reactive protein (HR 1.65; 95% CI 1.17-2.33). The corresponding adjusted HR (95% CI) was 2.04 (1.22-3.40) for serum Cu. The association between serum Zn and pneumonia was curvilinear. Compared to the bottom tertile of Zn, the multivariable adjusted HRs (95% CIs) for incident pneumonia were 0.68 (0.55-0.83) and 0.96 (0.79-1.16) for the middle and top tertiles of Zn, respectively. Further analysis in the same participants showed that Cu/Zn-ratio might be a stronger risk indicator for pneumonia than serum C-reactive protein. In middle-aged and older Finnish men, increased serum Cu/Zn-ratio and Cu concentrations are each linearly associated with an increased risk of incident pneumonia.

The Effect of Circulating Zinc, Selenium, Copper and Vitamin K1 on COVID-19 Outcomes: A Mendelian Randomization Study.

Background & Aims: Previous results from observational, interventional studies and in vitro experiments suggest that certain micronutrients possess anti-viral and immunomodulatory activities. In particular, it has been hypothesized that zinc, selenium, copper and vitamin K1 have strong potential for prophylaxis and treatment of COVID-19. We aimed to test whether genetically predicted Zn, Se, Cu or vitamin K1 levels have a causal effect on COVID-19 related outcomes, including risk of infection, hospitalization and critical illness. Methods: We employed a two-sample Mendelian Randomization (MR) analysis. Our genetic variants derived from European-ancestry GWAS reflected circulating levels of Zn, Cu, Se in red blood cells as well as Se and vitamin K1 in serum/plasma. For the COVID-19 outcome GWAS, we used infection, hospitalization or critical illness. Our inverse-variance weighted (IVW) MR analysis was complemented by sensitivity analyses including a more liberal selection of variants at a genome-wide sub-significant threshold, MR-Egger and weighted median/mode tests. Results: Circulating micronutrient levels show limited evidence of association with COVID-19 infection, with the odds ratio [OR] ranging from 0.97 (95% CI: 0.87-1.08, p-value = 0.55) for zinc to 1.07 (95% CI: 1.00-1.14, p-value = 0.06)-i.e., no beneficial effect for copper was observed per 1 SD increase in exposure. Similarly minimal evidence was obtained for the hospitalization and critical illness outcomes with OR from 0.98 (95% CI: 0.87-1.09, p-value = 0.66) for vitamin K1 to 1.07 (95% CI: 0.88-1.29, p-value = 0.49) for copper, and from 0.93 (95% CI: 0.72-1.19, p-value = 0.55) for vitamin K1 to 1.21 (95% CI: 0.79-1.86, p-value = 0.39) for zinc, respectively. Conclusions: This study does not provide evidence that supplementation with zinc, selenium, copper or vitamin K1 can prevent SARS-CoV-2 infection, critical illness or hospitalization for COVID-19.

Essential metals, vitamins and antioxidant enzyme activities in COVID-19 patients and their potential associations with the disease severity.

The role of micronutrient deficiency in the pathogenesis of COVID-19 has been reviewed in the literature; however, the data are limited and conflicting. This study investigated the association between the status of essential metals, vitamins, and antioxidant enzyme activities in COVID-19 patients and disease severity. We recruited 155 patients, who were grouped into four classes based on the Adults guideline for the Management of Coronavirus Disease 2019 at King Faisal Specialist & Research Centre (KFSH&RC): asymptomatic (N = 16), mild (N = 49), moderate (N = 68), and severe (N = 22). We measured serum levels of copper (Cu), zinc (Zn), selenium (Se), vitamin D3, vitamin A, vitamin E, total antioxidant capacity, and superoxide dismutase (SOD). Among the patients, 30%, 25%, 37%, and 68% were deficient in Se (< 70.08 µg/L), Zn (< 0.693 µg/mL), vitamin A (< 0.343 µg/mL), and vitamin D3 (< 20.05 µg/L), respectively, and SOD activity was low. Among the patients, 28% had elevated Cu levels (> 1.401 µg/mL, KFSH&RC upper reference limit). Multiple regression analysis revealed an 18% decrease in Se levels in patients with severe symptoms, which increased to 30% after adjusting the model for inflammatory markers. Regardless of inflammation, Se was independently associated with COVID-19 severity. In contrast, a 50% increase in Cu levels was associated with disease severity only after adjusting for C-reactive protein, reflecting its possible inflammatory and pro-oxidant role in COVID-19 pathogenesis. We noted an imbalance in the ratio between Cu and Zn, with ~ 83% of patients having a Cu/Zn ratio > 1, which is an indicator of inflammation. Cu-to-Zn ratio increased to 45% in patients with mild symptoms and 34%-36% in patients with moderate symptoms compared to asymptomatic patients. These relationships were only obtained when one of the laboratory parameters (lymphocyte or monocyte) or inflammatory markers (neutrophil-to-lymphocyte ratio) was included in the regression model. These findings suggest that Cu/Zn might further exacerbate inflammation in COVID-19 patients and might be synergistically associated with disease severity. A 23% decrease in vitamin A was seen in patients with severe symptoms, which disappeared after adjusting for inflammatory markers. This finding may highlight the potential role of inflammation in mediating the relationship between COVID-19 severity and vitamin A levels. Despite our patients' low status of Zn, vitamin D3, and antioxidant enzyme (SOD), there is no evidence of their role in COVID-19 progression. Our findings reinforce that deficiency or excess of certain micronutrients plays a role in the pathogenesis of COVID-19. More studies are required to support our results.

Evaluation of the Diagnostic and Predictive Value of Glutamic Acid Decarboxylase, Zinc Transporter 8 Serum Levels in Alzheimer's Disease.

BACKGROUND: Identification of validated peripheral biomarkers for Alzheimer's Disease, leading to an early diagnosis of the disease, would be valuable for predicting progression and targeted therapeutics. In this regard, serum levels of GADA, ZnT8A, Zn, vitamin D, and leukocyte expression of brain-derived neurotrophic factor (BDNF) gene were investigated in Alzheimer's patients and control group. METHODS: Serum levels of GADA, ZnT8A, Zn, and vitamin D and leukocyte expression of the BDNF gene were evaluated in 40 AD patients and 40 control cases. The diagnostic value of investigated factors was examined with the receiver operating characteristic (ROC). RESULTS: The results showed significant differences of p < 0.0001, p < 0.0001, and p = 0.0006 between AD patients and control individuals in GADA, Zn, and ZnT8A serum levels, respectively. No significant difference was observed in the serum concentration of vitamin D between AD patients and control cases (p = 0.2993). The expression level of the BDNF gene in AD patients was different from control cases, but it was not statistically significant (p > 0.05). Moreover, ROC curve analysis disclosed a diagnostic potency for serum levels of GADA, Zn, and ZnT8A for AD with an area under the ROC curve of > 0.7 (p < 0.0001, p < 0.0001, and p = 0.0007, respectively). CONCLUSIONS: The results demonstrated the higher serum levels of GADA and ZnT8A and lower serum concentrations of Zn in the patient group. Therefore, these parameters can be discussed as possibly diagnostic in AD cases.

Serum concentration of zinc is elevated in clinically stable bipolar disorder patients.

BACKGROUND: Bipolar disorder (BD) is a chronic psychiatric disorder characterized by recurrent mood episodes interspersed with euthymic periods. A growing number of studies have indicated that zinc plays an important role in coordinating immune responses, as well as being involved in synaptic transmission. In the current study, we set out to measure serum levels of zinc in a meticulously phenotyped cohort of 121 euthymic BD subjects and 30 matched controls. METHODS: Serum levels of zinc were measured by photometry. To assess the interplay between zinc levels and immune activation in BD, we measured serum levels of high-sensitive C-reactive protein (hsCRP) levels by immunoturbidimetric assay, and serum levels of monocyte chemoattractant protein-1 (MCP-1), chitinase 3-like protein 1 (YKL-40), and soluble cluster of differentiation 14 (sCD14) by electrochemiluminescence enzyme-linked immunosorbent assays. The baseline clinical diagnostic instrument for BD was the Affective Disorder Evaluation, and executive functioning was assessed by using the Delis-Kaplan Executive Function System. RESULTS: Controlling for potential confounding factors, BD patients displayed increased serum levels of zinc unrelated to hsCRP, MCP-1, YKL-40, and sCD14 levels. Serum levels of zinc did not associate with executive functioning or measurements of disease severity. DISCUSSION: This study suggests that the zinc homeostasis is disturbed in BD and that this dyshomeostasis is not related to ongoing mood symptoms or immune activation. Of note, serum levels were increased and hence do not support continuous zinc supplementation in BD.

Platelet Total PLA2 Activity, Serum Oxidative Level, and Plasma Cu/Zn Ratio: A Vicious Cycle with a Potential Role to Monitor MCI and Alzheimer's Disease Progression.

Alzheimer's disease (AD) has no cure, mainly because of late diagnosis. Early diagnostic biomarkers are crucial. Phospholipases A2 (PLA2) are hydrolases with several functions in the brain, nevertheless their deregulation contributes to neurodegeneration. We evaluated platelet total PLA2 activity (ptotPLA2) in healthy elderly subjects (HE, n = 102), patients suffering from mild cognitive impairment (MCI, n = 90) and AD (n = 91). Platelets are considered "circulating neurons" and ptotPLA2 appears to mirror the cerebral activity. ptotPLA2 of the three cohorts was similar, but in MCI the higher ptotPLA2 the worse the global cognitive status (Mini Mental State Examination score [MMSE]) and in AD the lower ptotPLA2 the more severe the pathology stage (Clinical Dementia Rating [CDR]). Accordingly, MCI with MMSE ≥26 overlapped HE, in MCI with MMSE <26 and in AD with CDR 1 ptotPLA2 increased, in AD with CDR 2 ptotPLA2 decreased. In MCI ptotPLA2 positively correlated with blood oxidation and inflammation, in AD it was the opposite. Finally, Discrimination Index (DI)-calculated multiplying ptotPLA2, oxidative level and Cu/Zn ratio (an inflammation parameter)-differentiated MCI patients who progressed to dementia in the following 24 months and AD patients with the worse pathology development. Summarizing, ptotPLA2 changes during MCI and AD progression, is linked, in opposite way, to oxidative/inflammatory status in MCI and AD and might help, when included in DI, to identify MCI converters to dementia and AD patients with the more severe prognosis. ptotPLA2 may have a diagnostic/prognostic value and be a potential therapeutic target.

Relationship between serum zinc level and sepsis-induced coagulopathy.

BACKGROUND: We investigated whether a decrease in the serum zinc level (SZL) among patients with sepsis admitted to the intensive care unit (ICU) was related to sepsis-induced coagulopathy. METHODS: All patients (≥20 years) with a diagnosis of sepsis defined by Sepsis-3 criteria, presenting to the ICU between June 2016 and July 2017, were enrolled. Demographic characteristics and the Sequential Organ Failure Assessment (SOFA) and Japanese Association of Acute Medicine (JAAM) disseminated intravascular coagulation (DIC) scores were recorded. Blood samples were collected upon admission and analyzed for SZL. RESULTS: One hundred patients with sepsis (median age, 70 years) were enrolled. Patients with SOFA scores ≥8 had a significantly lower SZL compared to those with SOFA scores <8 (p < 0.001). The SZL in the DIC group (JAAM DIC score ≥4) was significantly lower than that in the non-DIC group (JAAM DIC score <4) (p < 0.001). Analysis of receiver operating characteristic (ROC) curves for prediction of sepsis-induced DIC based on SZL in patients with sepsis showed a cut-off value of 25 µg/dL for zinc level and a sensitivity of 63% and a specificity of 72% with AUC of 0.7 (p = 0.0065). CONCLUSION: We observed that SZL reflects organ failure, particularly coagulopathy, in patients with sepsis.

Prenatal metal mixture concentrations and reward motivation in children.

Reward motivation is a complex umbrella term encompassing the cognitions, emotions, and behaviors involved in the activation, execution, and persistence of goal-directed behavior. Altered reward motivation in children is characteristic of many neurodevelopmental and psychiatric disorders. Previously difficult to operationalize, the Progressive Ratio (PR) task has been widely used to assess reward motivation in animal and human studies, including children. Because the neural circuitry supporting reward motivation starts developing during pregnancy, and is sensitive to disruption by environmental toxicants, including metals, the goal of this study was to examine the association between prenatal concentrations of a mixture of neurotoxic metals and reward motivation in children. We measured reward motivation by administering a PR test to 373 children ages 6-8 years enrolled in the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) Study in Mexico City. Children were asked to press a response lever for a token reward; one press on the response lever was required to earn the first token and each subsequent token required an additional 10 lever presses. Maternal blood concentrations of lead, manganese, zinc, arsenic, cadmium, and selenium were measured using inductively-coupled plasma mass spectrometry during the 2nd and 3rd trimesters of pregnancy. We performed generalized Weighted Quantile Sum (gWQS) regression analyses to examine associations between the prenatal metal mixture and reward motivation; adjusting for child sex, birthweight and age; and maternal IQ, education, and socioeconomic status. The prenatal metal mixture was significantly associated with higher motivation as indicated by more lever presses (ß = 0.02, p < 0.001) and a shorter time between receiving the reinforcer and the first press (ß = 0.23, p = 0.01), and between subsequent presses (ß = 0.07, p = 0.005). Contributions of different metals to this association differed by trimester and child sex. These findings suggest that children with increased exposure to metal during the 2nd and 3rd trimesters of gestation demonstrate increased reward motivation, which may reflect a tendency to perseverate or hypersensitivity to positive reinforcement.

Slc39a4 in the small intestine predicts zinc absorption and utilization: a comprehensive analysis of zinc transporter expression in response to diets of varied zinc content in young mice.

Zinc homeostasis is primarily maintained by zinc transporters that regulate zinc uptake and efflux in the small intestine; however, the relative contribution of the many zinc transporters identified (Slc39a1-14, Slc30a1-10) to dietary zinc absorption and utilization remains unknown. The objective of this study was to determine the expression of Slc39a1-14 and Slc30a1-10 in the small intestine and their relative contribution to dietary zinc absorption in mice. Five-week-old male C57BL/6J mice were fed modified AIN-93G diets containing <1, 30, or 100ppm zinc (n=15 mice/diet). Following 1 week of feeding, mice were given an oral gavage containing 67Zn and liver and plasma isotope appearance was determined 6-h later by ICP-MS. Expression of Slc39a1-14 and Slc30a1-10 was determined in mucosa from duodenum, jejunum, and ileum. Plasma and liver total zinc concentrations were not different after one week of feeding (P>.05). Liver and plasma appearance of 67Zn was greater in mice fed <1ppm compared to the 30ppm (P<.0001) and 100ppm (P<.0001) zinc diets. With the exception of Slc39a2, Slc39a12, Slc30a3, and Slc30a8, the remaining zinc transporters were expressed across all diets and intestinal segments. Expression of Slc39a4, Slc39a11, and Slc30a6 changed with diet (Pdiet<.05 for all); expression of Slc39a5, Slc39a7, Slc39a11, Slc39a14, Slc30a1, Slc30a2, Slc30a4, Slc30a5, Slc30a7, and Slc30a10 changed by intestinal segment (Psegment<.05 for all). Slc39a4 was the only transporter positively associated with liver (r2=0.316, P<.001) and plasma (r2=0.189, P<.01) 67Zn appearance. Although most zinc transporters are expressed in the small intestine, intestinal Slc39a4 predicts fractional zinc absorption and utilization in young mice.