Biological Trace Element Research Research Articles

Comment on: Magnesium Depletion Score Predicts Diabetic Retinopathy Risk Among Diabetes: Findings from NHANES 2005-2018.

I read the work by Yuan Chen et al.Biol Trace Elem Res 201(6):2750-2756 2023 entitled "Magnesium depletion score predicts diabetic retinopathy risk among diabetes: findings from NHANES 2005-2018" which was published in the Biological Trace Element Research (volume 201, issue 6, June 2023), with great interest. The authors specified that magnesium depletion score was associated with diabetic retinopathy. However, there are some limitations that should be addressed properly: first, the correct diagnosis of diabetic retinopathy; second, the consideration for statistical method; and third, the conclusion drawn from this study. I believe there are a few points regarding study design and conclusion that, if addressed, would improve the quality of this article.

A 10-year Scientometric Analysis of the Characteristics of the Worldwide Publication on the Toxic Effects of Fluoride

To perform a 10-year scientometric analysis of the characteristics of the worldwide publication on the toxic effects of fluoride. A bibliometric study of the worldwide scientific production on the toxic effects of fluoride during the years 2011-2020 was performed. All metadata from the Scopus database were evaluated. These were then exported to SciVal (Elsevier) for analysis of quantity, collaboration, and impact indicators. We found that the "Biological Trace Element Research" was the most productive journal with 22 published manuscripts and that the most productive universities on the systemic toxic effects of fluoride on the body were Shanxi Agricultural University, Guizhou Medical University, and Huazhong University of Science and Technology with 31, 11, and 10 manuscripts, respectively. In addition, it was found that most of the world scientific production on the toxic effects of fluoride was published in Q1 level journals (top 25%). Finally, it was concluded that most of the total production on this topic was published in high-impact Q1 journals, with China being the leading country in terms of number and impact of publications. Finally, there was evidence of collaboration between the United States, China, and India, being the countries that led in co-authorship by country. This research is of clinical importance as it allows the identification of the most productive institutions, authors, and countries in this field. In this way, strategic alliances can be established to enhance the development of research.

Grape pomace in equine nutrition: effect on antioxidant status

Grape pomace in equine nutrition: effect on antioxidant status

Outcome of a public consultation on the Draft Scientific Opinion of the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) on Dietary Reference Values for iron

EFSA Supporting PublicationsVolume 12, Issue 10 876E Technical reportOpen Access Outcome of a public consultation on the Draft Scientific Opinion of the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) on Dietary Reference Values for iron European Food Safety Authority (EFSA), European Food Safety Authority (EFSA)Search for more papers by this author European Food Safety Authority (EFSA), European Food Safety Authority (EFSA)Search for more papers by this author First published: 21 October 2015 https://doi.org/10.2903/sp.efsa.2015.EN-876 Published date: 21 October 2015 Question number: EFSA-Q-2015-00260 AboutPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL References Bannon DI, Abounader R, Lees PS and Bressler JP, 2003. Effect of DMT1 knockdown on iron, cadmium, and lead uptake in Caco-2 cells. American Journal of Physiology. Cell Physiology, 284, C44– 50. D-A-CH (Deutsche Gesellschaft für Ernährung – Österreichische Gesellschaft für Ernährung – Schweizerische Gesellschaft für Ernährungsforschung – Schweizerische Vereinigung für Ernährung), 2013. Referenzwerte für die Nährstoffzufuhr. Umschau Braus Verlag, Frankfurt/Main, Germany, 292 pp. Dainty JR, Berry R, Lynch SR, Harvey LJ and Fairweather-Tait SJ, 2014. Estimation of dietary iron bioavailability from food iron intake and iron status. PLoS ONE, 9, e111824. EFSA (European Food Safety Authority), 2004. Scientific opinion of the Panel on Dietetic Products, Nutrition and Allergies (NDA Panel) on a request from the Commission related to the Tolerable Upper Intake Level of iron. The EFSA Journal 2004, 125, 1– 34. EFSA NDA Panel (EFSA Panel on Dietetic Products, Nutrition and Allergies), 2010. Scientific Opinion on principles for deriving and applying Dietary Reference Values. EFSA Journal 2010; 8(3):1458, 30 pp. doi:10.2903/j.efsa.2010.1458 EFSA NDA Panel (EFSA Panel on Dietetic Products, Nutrition and Allergies), 2013. Scientific Opinion on nutrient requirements and dietary intakes of infants and young children in the European Union. EFSA Journal 2013; 11(10):3408, 103 pp. doi:10.2903/j.efsa.2013.3408 EFSA NDA Panel (EFSA Panel on Dietetic Products, Nutrition and Allergies), 2015. Scientific Opinion on Dietary Reference Values for iron. EFSA Journal 2015; 13(10):4254, 115 pp. doi:10.2903/j.efsa.2015.4254 Fomon SJ, Nelson SE, Serfass RE and Ziegler EE, 2005. Absorption and loss of iron in toddlers are highly correlated. Journal of Nutrition, 135, 771– 777. Gallagher CM, Chen JJ and Kovach JS, 2011. The relationship between body iron stores and blood and urine cadmium concentrations in US never-smoking, non-pregnant women aged 20-49 years. Environmental Research, 111, 702– 707. Hopkins MR, Ettinger AS, Hernandez-Avila M, Schwartz J, Tellez-Rojo MM, Lamadrid-Figueroa H, Bellinger D, Hu H and Wright RO, 2008. Variants in iron metabolism genes predict higher blood lead levels in young children. Environmental Health Perspectives, 116, 1261– 1266. IOM (Institute of Medicine), 2001. Dietary Reference Intakes for vitamin A, vitamin K, arsenic, boron, chromium, copper, iodine, iron, manganese, molybdenum, nickel, silicon, vanadium, and zinc. Food and Nutrition Board. National Academy Press, Washington, DC, USA, 797 pp. Nordic Council of Ministers, 2014. Nordic Nutrition Recommendations 2012. Integrating nutrition and physical activity. Copenhagen, Denmark, 627 pp. Olsson IM, Bensryd I, Lundh T, Ottosson H, Skerfving S and Oskarsson A, 2002. Cadmium in blood and urine – impact of sex, age, dietary intake, iron status, and former smoking – association of renal effects. Environmental Health Perspectives, 110, 1185– 1190. SACN (Scientific Advisory Committee on Nutrition), 2010. Iron and health. The Stationery Office, London, UK, 373 pp. Shah F, Kazi TG, Afridi HI, Kazi N, Baig JA, Shah AQ, Khan S, Kolachi NF and Wadhwa SK, 2011. Evaluation of status of trace and toxic metals in biological samples (scalp hair, blood, and urine) of normal and anemic children of two age groups. Biological Trace Element Research, 141, 131– 149. Vahter M, Akesson A, Liden C, Ceccatelli S and Berglund M, 2007. Gender differences in the disposition and toxicity of metals. Environmental Research, 104, 85– 95. Wennberg M, Lundh T, Bergdahl IA, Hallmans G, Jansson JH, Stegmayr B, Custodio HM and Skerfving S, 2006. Time trends in burdens of cadmium, lead, and mercury in the population of northern Sweden. Environmental Research, 100, 330– 338. Zimmermann MB, 2008. Methods to assess iron and iodine status. British Journal of Nutrition, 99 Suppl 3, S2– 9. Volume12, Issue10October 2015876E ReferencesRelatedInformation

Conference Summary and Recent Advances: the 8th Conference on Metal Toxicity and Carcinogenesis.

Diseases caused by occupational and environmental exposure to metals are a public health concern. The underlying molecular mechanisms of metal toxicity and carcinogenicity remain largely unknown. Over 130 scientists attended the 8th Conference on Metal Toxicity and Carcinogenesis, presenting their various research concerns and recent findings to stimulate interactions and collaborations among scientists in the field. Several major areas were emphasized, including human & population studies, molecular & cellular mechanisms, biological targets, epigenetic effects, metabolism, and metal mixtures. Here we summarize presentations at the conference sessions and highlight the attendees’ latest work published in this special issue of Biological Trace Element Research.

Seeds of toxicity? Erythrocytes and lead-associated kidney damage.

Environmental lead contamination lingers despite decades of sharply declining use and release of the metal. As a consequence, low-level lead exposure remains common, with an average adult blood lead level in the general U.S. population of 1–2 μg/dL.1,2 Lead affects numerous organ systems, but specific mechanisms of damage are not always known. The authors of a new study in EHP present a hypothesis to explain lead-related toxicity in the kidney and support it with detailed in vivo and in vitro data.1 Current evidence suggests that kidney damage can occur at blood lead levels as low as 5 μg/dL.2 Specific populations, including people with preexisting kidney disease, diabetes, or hypertension, may be at even greater risk of effects of low-level lead exposure.2,3 Both in vivo and in vitro data highlight oxidative stress as a factor in lead-associated kidney damage, but it has been unclear how the stress is generated.1,2 A new study explores the role that aging red blood cells may play in lead-related kidney toxicity. In the current study, the researchers wove observations from previous investigations into a testable hypothesis. They took into account deposition of iron—presumably from iron-rich red blood cells (erythrocytes)—in kidneys of individuals with renal disorders. They also considered the kidney’s role in clearing erythrocytes from circulation as the cells become old or damaged. During a process called erythrophagocytosis, aging erythrocytes are enveloped and broken down by other cells. Erythrophagocytosis occurs primarily in cells of the spleen and liver, but proximal tubular epithelial cells in the kidney also have this capability. The signal that an erythrocyte needs to be removed from circulation comes from a compound called phosphatidylserine (PS). In a normal, healthy erythrocyte, PS is an internal cellular component, with no direct contact with the cell’s outer environment. Aged and damaged red blood cells begin to shift PS to the outer surface. Members of this research team previously found that lead exposure was associated with a surge in PS externalization, followed by enhanced erythrophagocytosis in the spleen.4 In this study the researchers hypothesized that lead exposure increases the number of PS-tagged erythrocytes, which are then consumed by the proximal tubular epithelial cells in the kidney. They further hypothesized that iron from the erythrocytes accumulates in the kidney cells, where it triggers the formation of reactive oxygen species, the first step in oxidative damage. The ultimate biological outcome of toxic exposures is frequently a combination of two factors—individual responses of multiple tissues and, subsequently, complex interactions of altered tissues—says study coauthor Jin-Ho Chung, a professor in the College of Pharmacy at Seoul National University. “We considered that lead-associated nephrotoxicity must be interpreted in the context of systems biology, rather than as sole and isolated damage to the kidney,” Chung says. Chung and his colleagues conducted a series of in vitro experiments with HK-2 cells5 and erythrocytes derived from volunteers’ blood samples. They showed that, in the absence of erythrocytes, the viability of lead-exposed HK-2 cells was not significantly different from the viability of unexposed HK-2 cells. A separate experiment demonstrated increased PS externalization in lead-exposed erythrocytes. And when lead-exposed erythrocytes were co-cultured with unexposed HK-2 cells, the HK-2 cells not only phagocytized the erythrocytes, but also showed increased production of reactive oxygen species, diminished viability, and greater expression of genes associated with kidney damage.1 Next, the in vitro findings were tested in rats. Samples of blood, spleen, and kidney tissue were collected from rats exposed to 0 or 1,000 ppm lead in drinking water for 12 weeks, then used for biochemical and histological analyses. These analyses revealed statistically significant changes consistent with kidney damage. A second 12-week experiment included tissue samples from rats that received 0, 250, or 1,000 ppm of lead acetate in drinking water; these results also supported the in vitro findings. The in vivo results also reflected two types of nephrotoxicity seen in epidemiological studies: proximal tubular nephropathy and interstitial fibrosis.1 William McClellan, a professor of medicine at Emory University in Atlanta who was not involved in the study, cautions against immediately extrapolating the findings to human health. He also notes that the findings will need replication. McClellan says, “I have a feeling that if they come up with comparable findings [for confirmation], there will be some strong interest in doing some human studies.”

PCBs and Impaired Cochlear Function in Children: Comparing Pre- and Postnatal Exposures

High stability, the quality that made polychlorinated biphenyls (PCBs) so useful in hundreds of industrial and commercial applications during the mid-1900s, has ensured the compounds’ continuing presence in the environment despite decades of banned and restricted use.1 This class of more than 200 structurally related chemicals has been linked to both cancer and noncancer outcomes,1 and some studies suggest prenatal or early-life exposure to PCBs may adversely affect the auditory system.2,3 A new study reported in EHP specifically links postnatal—but not prenatal—PCB exposure with impaired cochlear function.2 Clusters of hair cells populate the cochlea and detect sounds transmitted to the inner ear. The cochlea, an extremely sensitive organ in the inner ear, converts soundwave vibrations to nerve impulses transmitted to the brain. Cochlear damage can impair hearing and is a well-known side effect of certain antibiotics and chemotherapeutic drugs.4 Rodent studies have shown that PCBs, too, can affect the cochlea, leading to hearing loss.5 Some human studies have reported associations between PCB exposure and hearing impairment, particularly in children,6,7 although others have found no such association.8 The current study focused on mother–infant pairs from an ongoing birth cohort study in eastern Slovakia. Study participants enrolled during hospital stays for childbirth in 2002–2004. Maternal and cord blood samples were collected for PCB and lipid measurements, and children underwent blood tests at 6, 16, and 45 months of age. At 45 months, the children also underwent otological and auditory testing, including an assessment of distortion product otoacoustic emissions (DPOAEs), a measure of cochlear function. Health records provided information on the children’s births and subsequent medical visits. Mothers completed questionnaires at study enrollment and at the 16- and 45-month followup visits, providing sociodemographic information and data on lifestyle, diet, medical history, and other factors that could affect their children’s health and hearing. A total of 351 children were included in the study. Blood tests measured 15 PCB congeners, but analyses focused on PCB-153, which was detected in nearly all samples and closely correlated with total PCB concentrations. An inverse relationship existed between decreased DPOAE amplitude (a marker of diminished cochlear function) and postnatal serum PCB concentrations, with the strongest association observed for cumulative levels of PCBs. The authors suggest this could indicate that duration of exposure, rather than timing, is most important for cochlear development. No association was observed between prenatal PCB exposure and decreased DPOAE amplitude.2 The PCB-associated decrease in DPOAE amplitude was not large.2 “Certainly, the hearing impairment would be subclinical,” says study coauthor Tomas Trnovec, a professor of environmental medicine at Slovak Medical University in Bratislava. However, the cochlea is vulnerable to any number of environmental insults, including noise, organochlorine pesticides, and drugs, among others, Trnovec says. “The combined effect of these factors is completely unknown,” he says, adding that “under different settings and other data treatment … a prenatal exposure effect cannot be excluded.” It’s also unknown whether effects persist and whether continued exposure (combined with other stressors) builds on early damage. “In my opinion, PCB ototoxicity may be involved in the pathogenesis of hearing impairment in the adult population,” says Kyoung-Bok Min, an assistant professor in occupational and environmental medicine at South Korea’s Ajou University School of Medicine, who was not involved in the study. Min and colleagues recently reported an association between PCB serum levels and increased prevalence of hearing impairment in adults who participated in the National Health and Nutrition Examination Survey.9 “Further epidemiologic studies are needed in terms of whether the impact of exposure to PCBs on cochlear function changes throughout the life span of the human,” he says. In addition, Susan Schantz, a professor of veterinary biosciences and psychology at the University of Illinois at Urbana–Champaign, raises the possibility of potential impacts beyond hearing. “One of the things that really interests me—and that I don’t know the answer to—is what does that kind of a decrease [in DPOAE amplitude] mean? Would it be enough to have subtle impacts on language acquisition in children?” asks Schantz, who was not involved in the study. Previous PCB cohort studies have shown an adverse impact on cognitive function, including verbal abilities.10 “I’ve always wondered whether subtle changes in hearing could be affecting language development, and then that could be affecting verbal abilities,” Schantz says. The new study features a particularly strong design based on multiple PCB measurements in a well-characterized population. However, it did not account for potential effects of co-contaminants, which may produce damage when combined with other exposures.11 “I think it’s very interesting that they’re seeing reductions to amplitudes related to postnatal exposure,” says Schantz. “That’s not what I would have predicted based on the animal research, but I think it’s very interesting and potentially important.”

Outcome of a public consultation on the Draft Scientific Opinion of the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) on Dietary Reference Values for selenium

EFSA Supporting PublicationsVolume 11, Issue 10 670E Technical reportOpen Access Outcome of a public consultation on the Draft Scientific Opinion of the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) on Dietary Reference Values for selenium European Food Safety Authority (EFSA), European Food Safety Authority (EFSA)Search for more papers by this author European Food Safety Authority (EFSA), European Food Safety Authority (EFSA)Search for more papers by this author First published: 10 October 2014 https://doi.org/10.2903/sp.efsa.2014.EN-670 Published date: 10 October 2014 Question number: EFSA-Q-2014-00469 AboutPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat References Combs GF, Jr., Jackson MI, Watts JC, Johnson LK, Zeng H, Idso J, Schomburg L, Hoeg A, Hoefig CS, Chiang EC, Waters DJ, Davis CD and Milner JA, 2012. Differential responses to selenomethionine supplementation by sex and genotype in healthy adults. British Journal of Nutrition, 107, 1514– 1525. Dernovics M, Giusti P and Lobinski R, 2007. ICP-MS-assisted nanoHPLC-electrospray Q/time-of-flight MS/MS selenopeptide mapping in Brazil nuts. Journal of Analytical Atomic Spectrometry, 22, 41– 50. Duffield AJ, Thomson CD, Hill KE and Williams S, 1999. An estimation of selenium requirements for New Zealanders. American Journal of Clinical Nutrition, 70, 896– 903. EFSA NDA Panel (EFSA Panel on Dietetic Products, Nutrition and Allergies), 2010. Scientific Opinion on principles for deriving and applying Dietary Reference Values. EFSA Journal 2010; 8(3):1458, 30 pp. doi:10.2903/j.efsa.2010.1458 EFSA NDA Panel (EFSA Panel on Dietetic Products, Nutrition and Allergies), 2014. Scientific Opinion on Dietary Reference Values for selenium. EFSA Journal 2014; 12(10):3846, 67 pp. doi:10.2903/j.efsa.2014.3846 Hill KE, Motley AK, Winfrey VP and Burk RF, 2014. Selenoprotein p is the major selenium transport protein in mouse milk. PLoS ONE, 9, e103486. Hurst R, Armah CN, Dainty JR, Hart DJ, Teucher B, Goldson AJ, Broadley MR, Motley AK and Fairweather-Tait SJ, 2010. Establishing optimal selenium status: results of a randomized, double-blind, placebo-controlled trial. American Journal of Clinical Nutrition, 91, 923– 931. Hurst R, Collings R, Harvey LJ, King M, Hooper L, Bouwman J, Gurinovic M and Fairweather-Tait SJ, 2013. EURRECA-Estimating selenium requirements for deriving dietary reference values. Critical Reviews in Food Science and Nutrition, 53, 1077– 1096. Johnson CC, Fordyce FM and Rayman MP, 2010. Symposium on ‘Geographical and geological influences on nutrition’: Factors controlling the distribution of selenium in the environment and their impact on health and nutrition. Proceedings of the Nutrition Society, 69, 119– 132. Kokarnig S, Tsirigotaki A, Wiesenhofer T, Lackner V, Francesconi KA, Pergantis SA and Kuehnelt D, 2014. Concurrent quantitative HPLC-mass spectrometry profiling of small selenium species in human serum and urine after ingestion of selenium supplements. Journal of Trace Elements in Medicine and Biology. Kryukov GV, Castellano S, Novoselov SV, Lobanov AV, Zehtab O, Guigo R and Gladyshev VN, 2003. Characterization of mammalian selenoproteomes. Science, 300, 1439– 1443. Li Q, Li XZ, Wang T, Zhou LW, Feng HQ, Gao L, Pei JR, Lin C and Jiang CX, 2013. Selenoprotein P and Yunnan endemic sudden cardiac death–an ecological study. Biological Trace Element Research, 151, 14– 17. Loui A, Raab A, Braetter P, Obladen M and de Braetter VN, 2008. Selenium status in term and preterm infants during the first months of life. European Journal of Clinical Nutrition, 62, 349– 355. Michaelis M, Gralla O, Behrends T, Scharpf M, Endermann T, Rijntjes E, Pietschmann N, Hollenbach B and Schomburg L, 2014. Selenoprotein P in seminal fluid is a novel biomarker of sperm quality. Biochemical and Biophysical Research Communications, 443, 905– 910. Persson-Moschos M, Alfthan G and Akesson B, 1998. Plasma selenoprotein P levels of healthy males in different selenium status after oral supplementation with different forms of selenium. European Journal of Clinical Nutrition, 52, 363– 367. Rayman MP, Infante HG and Sargent M, 2008. Food-chain selenium and human health: spotlight on speciation. British Journal of Nutrition, 100, 238– 253. Rayman MP, Searle E, Kelly L, Johnsen S, Bodman-Smith K, Bath SC, Mao J and Redman CW, 2014. Effect of selenium on markers of risk of pre-eclampsia in UK pregnant women: a randomised, controlled pilot trial. British Journal of Nutrition, 1– 13. Xia Y, Hill KE, Li P, Xu J, Zhou D, Motley AK, Wang L, Byrne DW and Burk RF, 2010. Optimization of selenoprotein P and other plasma selenium biomarkers for the assessment of the selenium nutritional requirement: a placebo-controlled, double-blind study of selenomethionine supplementation in selenium-deficient Chinese subjects. American Journal of Clinical Nutrition, 92, 525– 531. Volume11, Issue10October 2014670E ReferencesRelatedInformation

Gender Differences Influence Renal Injury in Cisplatin-Treated Rats: Biochemical Evaluation

In a recent issue of Biological Trace Element Research,weread with great interest the article by Erman et al. “Effect ofLycopene Against Cisplatin-Induced Acute Renal Injury inRats:OrganicAnionandCationTransportersEvaluation”[1].Authorsaimed toinvestigate the possibleprotectiveeffects oflycopene on the cisplatin-induced acute renal injury and geneexpression levels of some receptors in kidney. They havereport that lycopene may protect the kidneys against injuryfrom cisplatin nephrotoxicity. This article is instructive interms of showing the effect of lycopene on cisplatin-inducednephrotoxicity. However, we would like to make some com-ments with respect to the study design.Cisplatin is an antineoplastic agent which is commonly usedtotreatsometumors,but itsusagehasbeenrestrictedbecauseofnephrotoxicity.Forthisreason,studiesareongoingtofindaprotective agent against this adverse effect of cisplatin. Animportant issue that should be considered in these studies isanimal’s gender which has significant effects on cisplatinnephrotoxicity. Previous studies report that one of the agentswhichthoughttoincreasethenephrotoxiceffectofcisplatinisestrogen [2]. Nevertheless, experimental animals’ gender hasnot been stated in their paper [1]. On the other hand, it isreported that lycopene has antiestrogenic activity in vitro [3].In this instance, the effectiveness of lycopene application willbedifferentinbothfemaleandmalerats.Ifthereisanygenderdifferences in study groups, the results should be reinterpret.In order to eliminate confusion on this issue, the gender ofexperimental animals should be stated in the article.In conclusion, the explanation of these concerns will cer-tainly provide the clearer information for the readers.Allotherauthorshavereadthemanuscriptandhaveagreedtosubmititinitscurrentformforconsiderationforpublicationin the Journal.References

Expression of Concern

The Editor in Chief would like to alert readers to the following three articles published in Biological Trace Element Research.

Redefining Low Lead Levels

Vol. 119, No. 5 PerspectivesOpen AccessRedefining Low Lead Levels Ivo Iavicoli Edward J. Calabrese Ivo Iavicoli Search for more papers by this author and Edward J. Calabrese Search for more papers by this author Published:1 May 2011https://doi.org/10.1289/ehp.1103489Cited by:1AboutSectionsPDF ToolsDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InReddit In the January 2011 issue of EHP, Giddabasappa et al. (2011) reported that gestational lead exposure (GLE) of C57BL/6 mice produced selective nonmonotonic increases in the numbers of rods and cone bipolar cells (BCs) in the adult retina. Interestingly, this increase was characterized by an inverted U-shaped dose–response curve. Moreover, findings of this study showed that GLE increases and prolongs proliferation of retinal progenitor cells (RPCs) without decreasing apoptosis. Consequently, this phenomenon produced an adult retina with normal lamination and a selectively increased number of rods and BCs. These results should be considered to define a more adequate risk assessment at low levels of lead exposure. In fact, other published articles have indicated that lead induced a biphasic dose–response relationship (Calabrese and Baldwin 2003).In experiments in Swiss mice using low-level lead exposures similar to and lower than those used by Giddabasappa et al. (2011), we observed an increase in the number of red blood cells, in female gestational parameters, and in Th1 cytokine levels (Iavicoli et al. 2003, 2004, 2006a, 2006b). For this reason, it would be interesting if Giddabasappa et al. could verify this increase in the number of neurons in the rod-signaling pathway at even lower blood lead levels (< 10 μg/dL). The findings of our studies were also implicated over several generations.In any case, we agree with Giddabasappa et al. (2011) that their findings, as ours, raise complex issue for toxicologists, pediatricians, public health regulators, and risk assessors who need to incorporate the occurrence of such U-shaped dose responses in the hazard and risk assessment process. In this context, these findings could be explained by the hormesis phenomenon, which is a dose–response relationship characterized by low-dose stimulation and high-dose inhibition (Calabrese 2008, 2009).ReferencesCalabrese EJ. 2008. Hormesis: why it is important to toxicology and toxicologists. Environ Toxicol Chem 27:1451-147418275256. Crossref, Medline, Google ScholarCalabrese EJ. 2009. Getting the dose-response wrong: why hormesis became marginalized and the threshold model accepted. Arch Toxicol 83:227-24719234688. Crossref, Medline, Google ScholarCalabrese EJ, Baldwin LA. 2003. Inorganics and hormesis. Crit Rev Toxicol 33:215-30412809427. Crossref, Medline, Google ScholarGiddabasappa A, Hamilton WR, Chaney S, Xiao W, Johnson JE, Mukherjee Set al.. 2011. Low-level gestational lead exposure increases retinal progenitor cell proliferation and rod photoreceptor and bipolar cell neurogenesis in mice. Environ Health Perspect 119:71-7720840909. Link, Google ScholarIavicoli I, Carelli G, Stanek EJ, Castellino N, Calabrese EJ. 2003. Effects of low doses of dietary lead on red blood cell production in male and female mice. Toxicol Lett 137:193-19912523962. Crossref, Medline, Google ScholarIavicoli I, Carelli G, Stanek EJ, Castellino N, Calabrese EJ. 2006a. Below background levels of blood lead impact cytokine levels in male and female mice. Toxicol Appl Pharmacol 210:94-9916289177. Crossref, Medline, Google ScholarIavicoli I, Carelli G, Stanek EJ, Castellino N, Calabrese EJ. 2004. Effects of low doses of dietary lead on puberty onset in female mice. Reprod Toxicol 19:35-4115336710. Crossref, Medline, Google ScholarIavicoli I, Carelli G, Stanek EJ, Castellino N, Li Z, Calabrese EJ. 2006b. Low doses of dietary lead are associated with a profound reduction in the time to the onset of puberty in female mice. Reprod Toxicol 22:586-59016713174. Crossref, Medline, Google ScholarFiguresReferencesRelatedDetailsCited By Corsetti G, Romano C, Stacchiotti A, Pasini E and Dioguardi F (2016) Endoplasmic Reticulum Stress and Apoptosis Triggered by Sub-Chronic Lead Exposure in Mice Spleen: a Histopathological Study, Biological Trace Element Research, 10.1007/s12011-016-0912-z, 178:1, (86-97), Online publication date: 1-Jul-2017. Vol. 119, No. 5 May 2011Metrics About Article Metrics Publication History Originally published1 May 2011Published in print1 May 2011 Financial disclosuresPDF download License information EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. 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Inability to assess the safety of chromium‐enriched yeast added for nutritional purposes as a source of chromium in food supplements and the bioavailability of chromium from this source, based on the supporting dossiers

EFSA JournalVolume 7, Issue 6 1083 StatementOpen Access Inability to assess the safety of chromium-enriched yeast added for nutritional purposes as a source of chromium in food supplements and the bioavailability of chromium from this source, based on the supporting dossiers European Food Safety Authority (EFSA), European Food Safety Authority (EFSA)Search for more papers by this author European Food Safety Authority (EFSA), European Food Safety Authority (EFSA)Search for more papers by this author First published: 17 June 2009 https://doi.org/10.2903/j.efsa.2009.1083Citations: 1 Panel members: F. Aguilar, U.R. Charrondiere, B. Dusemund, P. Galtier, J. Gilbert, D.M. Gott, S. Grilli, R. Guertler, G.E.N. Kass, J. Koenig, C. Lambré, J-C. Larsen, J-C. Leblanc, A. Mortensen, D. Parent-Massin, I. Pratt, I.M.C.M. Rietjens, I. Stankovic, P. Tobback, T. Verguieva, R.A. Woutersen. Acknowledgement: The European Food Safety Authority wishes to thank the members of the Working Group A on Food Additives and Nutrient Sources added to Food for the preparation of this opinion: F. Aguilar, N Bemrah, P. Galtier, J. Gilbert, S. Grilli, R. Guertler, G.E.N. Kass, C. Lambré, J.C. Larsen, J-C. Leblanc, A. Mortensen, I. Pratt, I. Stankovic. Adoption date: 13 May 2009 Published date: 17 June 2009 Question number: EFSA-Q-2005-097, EFSA-Q-2005-120, EFSA-Q-2005-205, EFSA-Q-2006-211, EFSA-Q-2006-212, EFSA-Q-2006-213 AboutPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat References Davis CM, Vincent JB, 1997. Chromium in carbohydrate and lipid metabolism. Journal of Biological Inorganic Chemistry 2, 675– 679. Ding WJ, Qian QF, Hou XL, Feng WY, Chen CY, Chai ZF, Zhang BR, Wang K, 2002. A preliminary study of chromium distribution in chromium-rich brewer's yeast cell by NAA. Biological Trace Element Research 88 (2), 193– 199. EC (European Commission), 2002. Directive 2002/46/EC of the European Parliament and of the Council of 10 June 2002 on the approximation of the laws of the Member States relating to food supplements. OJ L 183, 12.07.2002, p. 51. EFSA (European Food Safety Authority), 2008a. Opinion of the Scientific Panel on Biological Hazards on the maintenance of the list of QPS microorganisms intentionally added to food or feed. The EFSA Journal 923, 1– 48. EFSA (European Food Safety Authority), 2008b. Scientific Opinion of the Panel on Food Additives, Flavourings, Processing Aids and Materials in Contact with Food on a request from the Commission on certain bisglycinates and glycinate nicotinate as sources for copper, zinc, calcium, magnesium and chromium. The EFSA Journal 718, 1– 266. Hegóczki J, Suhajda Á, Janzsó B, Vereczkey G, 1997. Preparation of chromium enriched yeasts. Acta Alimentaria 26 (4), 345– 358. Lamson DW and Plaza SM, 2002. The Safety and efficacy of high-dose chromium. Alternative Medicine Review 7 (3), 218– 35. Mertz W, 1969. Chromium occurrence and function in biological systems. Physiological Reviews 49 (2), 163– 239. Vinson JA and Bose P, 1984. The effect of a high chromium yeast on the blood glucose control and blood lipids of normal and diabetic human subjects. Nutritional Reports International 30 (4), 911– 918. Zetic VG, Stehlik-Tomas V, Grba S, Lutilsky L, Kozlek D, 2001. Chromium uptake by Saccharomyces cerevisiae and isolation of glucose tolerance factor from yeast biomass. Journal of Biosciences 26 (2), 217– 223. Citing Literature Volume7, Issue6June 20091083 ReferencesRelatedInformation

Prenatal Lead Exposure and Schizophrenia: Further Evidence and More Neurobiological Connections

In 2004, Opler et al. published a study in Environmental Health Perspectives (EHP) suggesting an association between prenatal lead (Pb2+) exposure and schizophrenia (Opler et al. 2004). In the November 2008 issue of EHP, Opler et al. (2008) further supported this association using a different cohort of subjects. In a letter published in EHP in 2004 (Guilarte 2004), I indicated that a plausible neurobiological connection between prenatal Pb2+ exposure and schizophrenia may be that Pb2+ is a potent antagonist of the N-methyl d-aspartate (NMDA) receptor (NMDAR), and NMDAR hypofunction is thought to be involved in the pathophysiology of the disease. Since then, another plausible neurobiological connection has surfaced, and this relates to hippo campal neurogenesis. Neurogenesis occurs not only during development but is also prominent in the adult brain (Laplagne et al. 2006). A well-characterized neurogenic zone in the adult brain is the subgranular zone of the dentate gyrus (DG) in the hippocampus (Zhao et al. 2008). Although the significance of newly born neurons in the adult hippocampus is currently under investigation, the overwhelming evidence supports a role in hippocampus-dependent learning (Dupret et al. 2008; Imayoshi et al. 2008). Schizophrenia patients express cognitive deficits that may be related to hippocampal dysfunction (Gothelf et al. 2000; Sweatt 2004). So, what is the new neurobiological connection between Pb2+ exposure and schizophrenia? Recent evidence indicates that neurogenesis is decreased in schizophrenia patients, and this decrease may contribute to their cognitive dysfunction (Kempermann et al. 2008; Reif et al. 2006). In an animal model using the NMDAR antagonist phencyclidine (PCP) to induce schizophrenia-like symptoms in mice, Maeda et al. (2007) observed reduced DG neurogenesis that was reversed by the atypical anti-psychotic drug clozapine. Co-administration of d-serine and glycine also inhibited the PCP-induced decrease in neurogenesis. PCP, like Pb2+, is an NMDAR antagonist, and D-serine and glycine activate NMDAR; this suggests that chronic NMDAR hypofunction decreases neurogenesis in the hippo campus, an observation consistent with my comments in 2004 (Guilarte 2004). Models of developmental Pb2+ exposure have also shown decreased DG neurogenesis and are associated with deficits in learning (Jaako-Movits et al. 2005; Verina et al. 2007). Therefore, reduced DG neuro genesis appears to be a common factor in schizophrenia and in animal models of schizophrenia and developmental Pb2+ exposure. Schizophrenia is a neurodevelopmental disorder that is expressed later in life. Pb2+ is a neurotoxicant that is known to cause developmental abnormalities. Animal models of developmental Pb2+ exposure express a behavioral phenotype with features that overlap with those in animal models of schizophrenia, including increased spontaneous activity, decreased social interaction, and learning deficits (Moreira et al. 2001; Nihei et al. 2000). Also, some of the behavioral effects described in adolescents with early-life Pb2+ exposure are similar to those expressed in schizophrenia patients (Opler and Susser 2005). Thus, although the environmental causes of schizophrenia have not evaluated environmental toxicants, the emerging evidence from the human studies by Opler and colleagues and animal studies suggest that prenatal Pb2+ exposure may be an environmental risk factor for schizophrenia.

Response to Endothelial Dysfunction, Isoprostanes, and Copper Deficiency

HomeHypertensionVol. 52, No. 3Response to Endothelial Dysfunction, Isoprostanes, and Copper Deficiency Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBResponse to Endothelial Dysfunction, Isoprostanes, and Copper Deficiency Shahar Lavi and Amir Lerman Shahar LaviShahar Lavi Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minn Search for more papers by this author and Amir LermanAmir Lerman Division of Cardiovascular Diseases, Mayo Clinic, Rochester, Minn Search for more papers by this author Originally published28 Jul 2008https://doi.org/10.1161/HYPERTENSIONAHA.108.116475Hypertension. 2008;52:e28Other version(s) of this articleYou are viewing the most recent version of this article. Previous versions: July 28, 2008: Previous Version 1 We appreciate Klevay’s comments1 regarding the potential role of copper supplement for the treatment of endothelial dysfunction. Our study focused on the association among coronary endothelial dysfunction, local bioavailability of NO, and local reactive oxygen species generation.2 We demonstrated that, in patients with endothelial dysfunction, there is increased local ROS generation, reduced activity of antioxidants (superoxide dismutase) and preserved production of NO. However, there was no significant difference in the arterial levels of either isoprostanes or superoxide dismutase between patients with coronary endothelial dysfunction and patients with normal response to acetylcholine. The relationship among copper deficiency, isoprostanes, superoxide dismutase, and arterial response to acetylcholine3 is indeed very intriguing. Thus, it may be speculated that the relative deficiency of copper as a central molecule in the antioxidant axis may play a role in the mechanism of endothelial dysfunction.It should be noted that, although copper deficiency may have adverse effects on the cardiovascular system, high copper levels are associated with increased risk of death from cardiovascular disease. In fact, even the second quartile of copper was associated with a trend toward increased risk compared with the lowest quartile (hazard ratio: 1.84).4 Increased copper levels were also an independent predictor for acute myocardial infarction.5The use of copper in medicine dates to Hippocrates, but there are not much data to support its use in cardiovascular disease. The effect of antioxidants on endothelial function should be studied. Copper, an antioxidant nutrient, would be a potential agent.Sources of FundingThis study was supported by NIH grants K24, HL-69840, and R01 HL-63911 and the Mayo Foundation.DisclosuresNone.1 Klevay LM. Endothelial dysfunction, isoprostanes, and copper deficiency. Hypertension. 2008; 52: e27.LinkGoogle Scholar2 Lavi S, Yang EH, Prasad A, Mathew V, Barsness GW, Rihal CS, Lerman LO, Lerman A. The interaction between coronary endothelial dysfunction, local oxidative stress, and endogenous nitric oxide in humans. Hypertension. 2008; 51: 127–133.LinkGoogle Scholar3 Lynch SM, Frei B, Morrow JD, Roberts LJ II, Xu A, Jackson T, Reyna R, Klevay LM, Vita JA, Keaney JF Jr. Vascular superoxide dismutase deficiency impairs endothelial vasodilator function through direct inactivation of nitric oxide and increased lipid peroxidation. Arterioscler Thromb Vasc Biol. 1997; 17: 2975–2981.CrossrefMedlineGoogle Scholar4 Ford ES. Serum copper concentration and coronary heart disease among US adults. Am J Epidemiol. 2000; 151: 1182–1188.CrossrefMedlineGoogle Scholar5 Salonen JT, Salonen R, Korpela H, Suntioinen S, Tuomilehto J. Serum copper and the risk of acute myocardial infarction: a prospective population study in men in eastern Finland. Am J Epidemiol. 1991; 134: 268–276.CrossrefMedlineGoogle Scholar Previous Back to top Next FiguresReferencesRelatedDetailsCited By Suliburska J, Bogdański P, Pupek-Musialik D and Krejpcio Z (2010) Dietary Intake and Serum and Hair Concentrations of Minerals and their Relationship with Serum Lipids and Glucose Levels in Hypertensive and Obese Patients with Insulin Resistance, Biological Trace Element Research, 10.1007/s12011-010-8650-0, 139:2, (137-150), Online publication date: 1-Feb-2011. September 2008Vol 52, Issue 3 Advertisement Article InformationMetrics https://doi.org/10.1161/HYPERTENSIONAHA.108.116475 Originally publishedJuly 28, 2008 PDF download Advertisement SubjectsHypertension

Beyond the Bench: Bringing EXCITEment to the Classroom

Who are the scientists, public health officials, and policy makers who will monitor our relationship with the environment 20 years from now? Right now a lot of them are students in middle and high schools throughout the country. And it’s a certainty that these future stakeholders will need to develop the diversity of skills required to tackle the complex issues that arise where environmental and human health intersect––skills that go beyond the practice of simple classroom science experiments. Answering this call to train is Project EXCITE (Environmental Health Science Explorations through Cross-Disciplinary and Investigative Team Experiences), an NIEHS-supported program at Bowling Green State University (BGSU) in Ohio.

Carbon monoxide: from silent killer to potential remedy

All substances are poisonous, there is none which is not a poison. The right dose differentiates a poison from a remedy. —Paracelsus thoughts that come to mind when the words carbon monoxide (CO) are heard include accidental deaths from malfunctioning home appliances, suicides in closed garages

Natural Treatments for Metabolic Syndrome: Using Nutraceuticals to Thwart a Deadly Trend

Alternative and Complementary TherapiesVol. 9, No. 6 ArticlesNatural Treatments for Metabolic Syndrome: Using Nutraceuticals to Thwart a Deadly TrendChris D. Meletis and Jason BarkerChris D. MeletisSearch for more papers by this author and Jason BarkerSearch for more papers by this authorPublished Online:5 Jul 2004https://doi.org/10.1089/107628003322658548AboutSectionsPDF/EPUB ToolsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail FiguresReferencesRelatedDetailsCited byEffect of Dietary Garcinia cambogia Extract on Serum Essential Minerals (Calcium, Phosphorus, Magnesium) and Trace Elements (Iron, Copper, Zinc) in Rats Fed with High-Lipid Diet15 March 2012 | Biological Trace Element Research, Vol. 148, No. 3Herbals Used for Diabetes, Obesity, and Metabolic SyndromePrimary Care: Clinics in Office Practice, Vol. 37, No. 2 Volume 9Issue 6Dec 2003 To cite this article:Chris D. Meletis and Jason Barker.Natural Treatments for Metabolic Syndrome: Using Nutraceuticals to Thwart a Deadly Trend.Alternative and Complementary Therapies.Dec 2003.289-293.http://doi.org/10.1089/107628003322658548Published in Volume: 9 Issue 6: July 5, 2004PDF download

Peptides that regulate food intake.

in this issue of the journalare published the first group of papers submitted to the Special Call for Papers on the subject “Peptides that Regulate Food Intake.” These nine papers ([7a][1], [32a][2], [37a][3], [37b][4], [41a][5], [42a][6], [43a][7], [46a][8],[49a][9]) illustrate both the breadth

E-Junk explosion.

e-Junk explosion.

Cholesterol in Vascular and Valvular Calcification

In the early 1990s, the late Jeff Hoeg had the foresight to ask whether vascular calcification relates to the duration and severity of exposure to cholesterol. In a group of homozygous hyperlipidemic patients for whom detailed records of cholesterol levels were available over a long period of time, he and his colleagues found that coronary calcification scores by ultrafast computed tomographic scanning correlated significantly with the cholesterol year product.1 Studies that lack long-term cholesterol history may miss a correlation between lipids and calcification, because current treatments so dramatically change cholesterol levels as to make them unrepresentative of long-term exposure. See p 1927 In the present issue of Circulation , Pohle et al2 successfully overcame these difficulties by studying the rate of change in calcification as a function of change in lipid levels, excluding patients in whom treatment was altered during the study period. These investigators found that both coronary calcification and aortic valve calcification progress more rapidly in subjects with levels of LDL >130 mg/dL. This finding dovetails with those of Callister et al,3 who discovered that patients who successfully lowered their cholesterol levels with lipid-lowering agents significantly reduced the progression of coronary calcification. In a large population of young subjects, the risk factor that correlated most significantly with coronary calcification was LDL cholesterol.4 This relation was stronger than the correlation with age, smoking, fasting insulin, blood pressure, or male sex.4 In another study of asymptomatic outpatients, LDL cholesterol was the only risk factor correlating with progression of coronary calcification by electron-beam computed tomography over an 18-month period.5 The correlation of LDL cholesterol exposure to valvular and vascular calcification raises the possibility of a mechanistic role, which is also supported by in vitro studies. Two groups …