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1.
Wilson's Disease: A Review for the General Pediatrician.
Capone, K, Azzam, RK
Pediatric annals. 2018;(11):e440-e444
Abstract
Wilson's disease, also known as hepatolenticular degeneration, is an autosomal recessive genetic disorder due to a mutation of the ATP7B gene resulting in impaired hepatic copper excretion and copper accumulation in various tissues. It is associated with the classic triad of cirrhosis, neurological manifestations, and the ocular finding of Kayser-Fleischer rings; however, the clinical presentation can vary greatly from incidental findings of abnormal liver enzymes to acute liver failure necessitating liver transplant. Pediatric patients may present with subtle findings including asymptomatic hepatomegaly, transaminitis, changes in behavior, movement disorders, or school failure. The general pediatrician may be the first to recognize these symptoms and should consider Wilson's disease in their differential diagnosis. Wilson's disease can be managed with lifelong chelation or zinc therapy in patients who present early in the disease; therefore, pediatricians should have a low threshold for referral to a pediatric hepatologist for further evaluation when it is suspected. [Pediatr Ann. 2018;47(11):e440-e444.].
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2.
Pregnancy after bariatric surgery: Maternal and fetal outcomes of 39 pregnancies and a literature review.
Costa, MM, Belo, S, Souteiro, P, Neves, JS, Magalhães, D, Silva, RB, Oliveira, SC, Freitas, P, Varela, A, Queirós, J, et al
The journal of obstetrics and gynaecology research. 2018;(4):681-690
Abstract
AIM: We aimed to evaluate the impact of bariatric surgery (BS) on maternal and fetal outcomes. METHODS A retrospective, descriptive, observational study of 39 pregnant women who underwent BS in our institution between 2010 and 2014 was carried out. A sample of women who became pregnant after BS was evaluated, based on data concerning pregnancy, childbirth, and newborns. RESULTS Of the 1182 patients who underwent BS at our institution during the study period, 1016 (85.9%) were women. Thirty-nine of these women (with an average age of 31 ± 4.8 years) became pregnant (one twin pregnancy) and 29 of the 39 had undergone a gastric bypass. The mean time interval between BS and pregnancy was 16.6 ± 4.8 months; however, 16 (41%) women became pregnant less than a year after BS. The pre-BS body mass index (BMI) of the 39 women was 44.5 ± 6.2 kg/m2 . The women had a mean BMI of 30.2 ± 3.8 kg/m2 when they got pregnant and they gained 13.2 ± 7.3 kg during pregnancy. Iron deficiency was observed in 18 (46.1%) women, 16 (45.7%) had vitamin B12 deficiency, 12 (66.8%) had zinc deficiency, and 20 (60.6%) had vitamin D deficiency. Three women developed gestational diabetes mellitus. Premature rupture of membranes occurred in two pregnancies, preterm delivery in five, and there was one spontaneous abortion. Cesarean section was performed in seven cases. The average newborn weight was 3002 ± 587 g, five were small for gestational age, and one had macrosomia. Three infants had to be admitted to an intensive care unit. CONCLUSION Although pregnancy after BS is safe and well tolerated, close monitoring by a multidisciplinary team is required to evaluate complications resulting from BS, especially a deficit of micronutrients.
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3.
Absorption Mechanisms of Iron, Copper, and Zinc: An Overview.
Nishito, Y, Kambe, T
Journal of nutritional science and vitaminology. 2018;(1):1-7
Abstract
Essential trace elements play pivotal roles in numerous structural and catalytic functions of proteins. Adequate intake of essential trace elements from the daily diet is indispensable to the maintenance of health, and their deficiency leads to a variety of conditions. However, excessive amounts of these trace elements may be highly toxic, and in some cases, may cause damage by the production of harmful reactive oxygen species. Homeostatic dysregulation of their metabolism increases the risk of developing diseases. Specific transport proteins that facilitate influx or efflux of trace elements play key roles in maintaining the homeostasis. Recent elucidation of their crucial functions significantly facilitated our understanding of the molecular mechanisms of iron (Fe), copper (Cu), and zinc (Zn) absorption in the small intestine. This paper summarizes their absorption mechanisms, with a focus on indispensable functions of the molecules involved in it, and briefly discusses the mechanisms of homeostatic control of each element at the cellular and systemic levels.
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4.
Effect of Oral Zinc Supplementation on the Thiol Oxido-Reductive Index and Thiol-Related Enzymes in Seminal Plasma and Spermatozoa of Iraqi Asthenospermic Patients.
Alsalman, ARS, Almashhedy, LA, Hadwan, MH
Biological trace element research. 2018;(2):340-349
Abstract
A thiol group plays an essential role in sperm metabolism and the antioxidative defense state. Zinc is the second most abundant element in the human body, following iron. The present study was conducted to study the effect of zinc supplementation on the characteristics of semen along with thiol and thiol-related enzymes in semen of asthenospermic patients. Semen samples were obtained from 60 fertile and 60 asthenospermic men, from couples who had consulted the infertility clinic of Babil Hospital (Hillah city, Iraq). The subfertile group was treated with zinc; every participant took two 220 mg capsules of zinc sulfate per day for 3 months. Semen samples were obtained (before and after zinc supplementation). The levels of reduced thiol, oxidized thiol, thiol oxido-reductive index, and thiol-related enzymes activities were determined in spermatozoa and seminal plasma of patients and healthy groups. Oxidized thiol levels were significantly higher in the infertile patients compared to that in the fertile group. Conversely, reduced thiol level, sulfhydryl oxidase activity, and glutathione peroxidase activity significantly decreased in the infertile patients compared to that in the fertile group. Oxidized thiol levels, reduced thiol levels, and thiol-related enzymes activities of the infertile patients were restored to normal values after treatment with zinc. However, reduced and oxidized thiol levels in spermatozoa did not change significantly in the group treated with zinc. The quantitative values for RSH/RSSR and thiol-related enzymes may provide useful means to qualitatively express the oxidant/antioxidant balance in clinical and epidemiologic studies. ClinicalTrials.gov Identifier: NCT02985905.
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5.
A framework for model analysis across multiple experiment regimes: Investigating effects of zinc on Xylella fastidiosa as a case study.
Aggarwal, M, Hussaini, MY, De La Fuente, L, Navarrete, F, Cogan, NG
Journal of theoretical biology. 2018;:88-100
Abstract
Mathematical models are ubiquitous in analyzing dynamical biological systems. However, it might not be possible to explicitly account for the various sources of uncertainties in the model and the data if there is limited experimental data and information about the biological processes. The presence of uncertainty introduces problems with identifiability of the parameters of the model and determining appropriate regions to explore with respect to sensitivity and estimates of parameter values. Since the model analysis is likely dependent on the numerical estimates of the parameters, parameter identifiability should be addressed beforehand to capture biologically relevant parameter space. Here, we propose a framework which uses data from different experiment regimes to identify a region in the parameter space over which subsequent mathematical analysis can be conducted. Along with building confidence in the parameter estimates, it provides us with variations in the parameters due to changes in the experimental conditions. To determine significance of these variations, we conduct global sensitivity analysis, allowing us to make testable hypothesis for effects of changes in the experimental conditions on the biological system. As a case study, we develop a model for growth dynamics and biofilm formation of a bacterial plant pathogen, and use our framework to identify possible effects of zinc on the bacterial populations in different metabolic states. The framework reveals underlying issues with parameter identifiability and identifies a suitable region in the parameter space, sensitivity analysis over which informs us about the parameters that might be affected by addition of zinc. Moreover, these parameters prove to be identifiable in this region.
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6.
Two zinc-binding domains in the transporter AdcA from Streptococcus pyogenes facilitate high-affinity binding and fast transport of zinc.
Cao, K, Li, N, Wang, H, Cao, X, He, J, Zhang, B, He, QY, Zhang, G, Sun, X
The Journal of biological chemistry. 2018;(16):6075-6089
Abstract
Zinc is an essential metal in bacteria. One important bacterial zinc transporter is AdcA, and most bacteria possess AdcA homologs that are single-domain small proteins due to better efficiency of protein biogenesis. However, a double-domain AdcA with two zinc-binding sites is significantly overrepresented in Streptococcus species, many of which are major human pathogens. Using molecular simulation and experimental validations of AdcA from Streptococcus pyogenes, we found here that the two AdcA domains sequentially stabilize the structure upon zinc binding, indicating an organization required for both increased zinc affinity and transfer speed. This structural organization appears to endow Streptococcus species with distinct advantages in zinc-depleted environments, which would not be achieved by each single AdcA domain alone. This enhanced zinc transport mechanism sheds light on the significance of the evolution of the AdcA domain fusion, provides new insights into double-domain transporter proteins with two binding sites for the same ion, and indicates a potential target of antimicrobial drugs against pathogenic Streptococcus species.
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7.
Network Analysis of Se-and Zn-related Proteins in the Serum Proteomics Expression Profile of the Endemic Dilated Cardiomyopathy Keshan Disease.
Wang, S, Lv, Y, Wang, Y, Du, P, Tan, W, Lammi, MJ, Guo, X
Biological trace element research. 2018;(1):40-48
Abstract
Keshan disease (KD) is an endemic cardiomyopathy with high mortality. Selenium (Se) and zinc (Zn) deficiencies are closely related to KD. The molecular mechanism of KD pathogenesis is still unclear. There are only few studies on the interaction of trace elements and proteins associated with the pathogenesis of KD. In this study, isobaric tags for relative and absolute quantitation (iTRAQ)-coupled two-dimensional liquid chromatography tandem mass spectrometry (2DLC-MS/MS) technique analysis was used to analyze the differential expression of proteins from serum samples. Comparative Toxicogenomics Database (CTD) was used to screen Se- and Zn-associated proteins. Then, pathway and network analyses of Se- and Zn-associated proteins were constituted by Cytoscape ClueGO and GeneMANIA plugins. One hundred and five differentially expressed proteins were obtained by 2DLC-MS/MS, among them 19 Se- and 3 Zn-associated proteins. Fifty-two pathways were identified from ClueGO and 1 network from GeneMANIA analyses. The results showed that Se-associated proteins STAT3 and MAPK1 and Zn-associated proteins HIF1A and PARP1, the proteins involved in HIF-1 signaling pathway and apoptosis pathway, may play significant roles in the pathogenesis of KD. The approach of this study would be also beneficial for further dissecting molecular mechanism of other trace element-associated disease.
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8.
Higher serum zinc levels may reduce the risk of cervical cancer in Asian women: A meta-analysis.
Xie, Y, Wang, J, Zhao, X, Zhou, X, Nie, X, Li, C, Huang, F, Yuan, H
The Journal of international medical research. 2018;(12):4898-4906
Abstract
OBJECTIVE This meta-analysis was conducted to examine the possible association between serum zinc concentration and cervical cancer risk. METHODS PubMed, WanFang, China National Knowledge Infrastructure, and SinoMed databases were searched for relevant articles published between January 1980 and September 2017. Results were combined using a random-effects model, and pooled standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated to compare serum zinc levels in patients with cervical cancer versus controls. Publication bias was evaluated using Begg's funnel plot and Egger's regression asymmetry test. RESULTS Twelve articles regarding serum zinc levels and cervical cancer were included in this meta-analysis. Combined results showed that serum zinc levels in cervical cancer cases were significantly lower than in controls without cervical cancer (summary SMD -1.379, 95% CI -1.527, -1.231), with high heterogeneity ( I2 = 98.8%). Analysis of data stratified by geographic location showed a significant association between serum zinc levels and cervical cancer risk in Asian populations (summary SMD -1.391, 95% CI -1.543, -1.239). CONCLUSIONS Higher serum zinc levels may be a protective factor for cervical cancer in Asian women.
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9.
Tuning site-specific dynamics to drive allosteric activation in a pneumococcal zinc uptake regulator.
Capdevila, DA, Huerta, F, Edmonds, KA, Le, MT, Wu, H, Giedroc, DP
eLife. 2018
Abstract
MarR (multiple antibiotic resistance repressor) family proteins are bacterial repressors that regulate transcription in response to a wide range of chemical signals. Although specific features of MarR family function have been described, the role of atomic motions in MarRs remains unexplored thus limiting insights into the evolution of allostery in this ubiquitous family of repressors. Here, we provide the first experimental evidence that internal dynamics play a crucial functional role in MarR proteins. Streptococcus pneumoniae AdcR (adhesin-competence repressor) regulates ZnII homeostasis and ZnII functions as an allosteric activator of DNA binding. ZnII coordination triggers a transition from somewhat independent domains to a more compact structure. We identify residues that impact allosteric activation on the basis of ZnII-induced perturbations of atomic motions over a wide range of timescales. These findings appear to reconcile the distinct allosteric mechanisms proposed for other MarRs and highlight the importance of conformational dynamics in biological regulation.
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10.
Surfactant and heavy metal interaction in poplar: a focus on SDS and Zn uptake.
Pierattini, EC, Francini, A, Raffaelli, A, Sebastiani, L
Tree physiology. 2018;(1):109-118
Abstract
Surfactants are widely used detergent ingredients and, thanks to their chemical properties, they are applied for remediation of sites polluted by heavy metals and organic contaminants, both in soil flushing and in phytoremediation. However, their direct effects on tree physiology especially in consociation with heavy metal pollution, as well as their possible absorption by plants, have not been appropriately investigated. In order to evaluate plant uptake/translocation of the surfactant sodium dodecyl sulfate (SDS) and the heavy metal zinc (Zn) in Populus alba L. Villafranca clone, SDS was applied alone (0.5 mM) or in combination with Zn (1 mM). Physiological effects on plant growth and photosynthetic performance were investigated. An increasing trend of Zn translocation towards basal leaves as a consequence of SDS co-treatment (1 mM Zn + 0.5 mM SDS; P = 0.03) was observed, proving the ability of SDS to improve heavy metals translocation. However, SDS exposure (both in 0.5 mM SDS and 1 mM Zn + 0.5 mM SDS treated plants) resulted in the appearance of foliar necrosis that expanded with an acropetal trend and finally led to leaf abscission. This phenotype may be caused by the emergence of an additional stress during the experimental trial, which could be related to the dissociation of sodium (Na) ions from the dodecyl sulfate molecules in the hydroponic system. In fact, while liquid chromatography-tandem mass spectrometry measurements revealed that dodecyl sulfate is mainly retained at root levels, Na is translocated to the aerial parts of the plant.