The Journal of Trace Elements in Experimental Medicine最新文献

{"title":"Oral copper loading test in humans","authors":"Mojgan Rahmaniyan, Kelley E. Johnston, Tsunenobu Tamura","doi":"10.1002/jtra.10025","DOIUrl":"https://doi.org/10.1002/jtra.10025","url":null,"abstract":"There has been no report of normal responses of plasma copper and/or ceruloplasmin concentrations after an oral loading dose of unlabeled copper in humans. To establish a normal plasma response curve following an oral dose, we performed a copper-loading test (10 mg elemental copper as copper sulfate) in six healthy adult subjects and monitored plasma copper and ceruloplasmin concentrations for 3.5 h. We found that there were no significant changes in plasma copper and ceruloplasmin concentrations following the oral dose in the subjects. The test was originally intended to evaluate whether there was copper malabsorption in a female patient who developed signs of copper deficiency with her plasma copper levels below 3.0 μmol/l after multiple gastrointestinal surgeries. She did not respond to oral copper sulfate administration but responded to a sublingual application of copper glycinate. These findings suggest that she does not have adequate intestinal copper absorption. In conclusion, the use of unlabeled copper, such as copper sulfate, for an oral loading test, seemingly simple and economical, does not appear to be a suitable means to evaluate copper absorption in humans and is discouraged. In case of copper malabsorption, sublingual administration of copper may be worth trying. J. Trace Elem. Exp. Med. 16: 61–66, 2003. © 2003 Wiley-Liss, Inc.","PeriodicalId":101243,"journal":{"name":"The Journal of Trace Elements in Experimental Medicine","volume":"16 2-3","pages":"61-66"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/jtra.10025","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72316362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Structure–activity relationship of insulinomimetic vanadyl–picolinate complexes in view of their clinical use","authors":"Hiromu Sakurai, Hiroyuki Yasui","doi":"10.1002/jtra.10036","DOIUrl":"https://doi.org/10.1002/jtra.10036","url":null,"abstract":"In view of the clinical use of vanadium compounds, we prepared seven analogs of a vanadylpicolinate complex (VO(pic)2) with VO(N2O2) coordination mode, which was found in 1995 to exhibit highly effective and long-term insulinomimetic activity in treating both streptozotocin (STZ)-induced type 1 diabetic rats (STZ rats) and hereditarily type 2 diabetic KK-A y mice by daily intraperitoneal (i.p.) injections and on oral administration, to find the structureactivity relationship of the complexes. Using an in vitro insulinomimetic evaluation of the complexes in terms of their inhibiting effect on free fatty acids release from isolated rat adipocytes treated with epinephrine (adrenaline), we found the activity (IC50 :5 0% inhibitor’s concentration of the complex on the free fatty acid release) to be as follows: VO(5ipa)2 > VO(3mpa)2 > VO(6mpa)2 > VO(3hpa)2 > VO(pic)2 > VO(6hpa)2 » VOSO4, indicating that the introduction of an electron-withdrawing halogen atom or an electron-donating methyl group at the 5th or 3rd position on the picolinate ligand causes stronger insulinomimetic activity than that of the lead complex VO(pic)2. Next we examined the pharmacokinetic features in the blood of the complexes by using the blood circulation-monitoring electron spin resonance method, in which good linear relationships between the pharmacokinetic parameters and the IC50 values were found. Based on the results, we tested the complexes and found that both VO(5ipa)2 and VO(3mpa)2 complexes treat type 1 diabetes in STZ rats. Because the daily oral administration of vanadyl complexes is the only method to treat type 1 diabetes in place of daily insulin injections, the present results will be useful for the development of vanadyl complexes with high safety and long-term activity. J. Trace Elem. Exp. Med. 16:269280, 2003. � 2003 Wiley-Liss, Inc.","PeriodicalId":101243,"journal":{"name":"The Journal of Trace Elements in Experimental Medicine","volume":"16 4","pages":"269-280"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/jtra.10036","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72362798","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insulin-like actions of vanadium: Potential as a therapeutic agent","authors":"Lucy Marzban, John H. McNeill","doi":"10.1002/jtra.10034","DOIUrl":"https://doi.org/10.1002/jtra.10034","url":null,"abstract":"Vanadium compounds are glucose-lowering agents that are shown to mimic/enhance most of the metabolic actions of insulin both in vitro and in vivo. Several studies have demonstrated that vanadium treatment lowers plasma glucose levels in experimental models of type 1 diabetes and enhances insulin sensitivity in models of type 2 diabetes. Therefore, these compounds have gained attention as candidates for oral therapy in both types of diabetes. Despite numerous studies, the mechanism(s) by which vanadium mediates its metabolic effects in vivo are still not completely understood. The finding that most of the insulin-like effects of vanadium in vitro are observed in the presence of high concentrations of vanadium that are not usually achieved in vivo suggests that these effects of vanadium may not have therapeutic relevance. Also, a growing body of evidence from in vivo studies indicates that enhancing glucose disposal in the peripheral tissues is not an adequate explanation for the glucose lowering effects of vanadium in vivo. Accordingly, recent studies suggest that suppression of hepatic glucose production through inhibition of key gluconeogenic enzymes might have an important role in mediating the glucoregulatory effects of vanadium. Several potential sites in the insulin-signaling pathways, including both receptor and postreceptor mechanisms, have been proposed for the insulin-like effects of vanadium compounds. In this review, we have attempted to discuss the possible molecular mechanism(s) underlying the metabolic effects of vanadium in vivo. J. Trace Elem. Exp. Med. 16:253–267, 2003. © 2003 Wiley-Liss, Inc.","PeriodicalId":101243,"journal":{"name":"The Journal of Trace Elements in Experimental Medicine","volume":"16 4","pages":"253-267"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/jtra.10034","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72362803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of three divalent cations: manganese, zinc, and magnesium on arterial blood pressures in guinea pigs","authors":"Nursen Onat,&nbsp;Öner Süzer","doi":"10.1002/jtra.10027","DOIUrl":"https://doi.org/10.1002/jtra.10027","url":null,"abstract":"Our aim was to compare the effects of the divalent cations, namely magnesium, zinc, and manganese on the arterial blood pressures and heart rate of guinea pigs. Eighteen guinea pigs weighing 500–700 g were divided into three groups (six in each group), and three divalent cations as sulfate salt (MgSO4, ZnSO4, MnSO4) were administered to all animals after 20-min period of stabilization and at three escalating concentrations (10−6, 10−5, 10−4 mol/kg intravenously, respectively) in 25-min intervals. Each animal received only one kind of cation. Arterial pressures and heart rate were measured and their derivatives were calculated (dp/dt). Our study showed that divalent cations lowered the arterial blood pressures. No significant differences were between groups for systolic, diastolic, and mean pressures, except that 10−4 mol/kg ZnSO4 was lethal. The heart rates values of ZnSO4 (202 ± 9) was significantly (P < 0.05) lower after 10−6 mol/kg than MgSO4 (230 ± 7). Three divalent cations caused to decrease on arterial pressures. Zn2+ caused cardiac arrest in the highest dose. Intravenous administration of Mn2+ and Mg2+ seems to have similar effects on arterial blood pressures and heart rate. Further work is needed to relate effects on Mn2+ for their possible use in the emergency department. J. Trace Elem. Exp. Med. 16:75–85, 2003. © 2003 Wiley-Liss, Inc.","PeriodicalId":101243,"journal":{"name":"The Journal of Trace Elements in Experimental Medicine","volume":"16 2-3","pages":"75-85"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/jtra.10027","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72316359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Zinc is essential for brain development and function","authors":"Harold H. Sandstead","doi":"10.1002/jtra.10042","DOIUrl":"https://doi.org/10.1002/jtra.10042","url":null,"abstract":"Zinc's roles in brain function are poorly understood. Zinc is essential pre- and postnatally for growth, maturation, and function. In early pregnancy, zinc is essential for cell multiplication and implantation of the embryo and for cell differentiation and organ formation. Deficiency causes teratology in all tissues. Zn deficiency in later pregnancy impairs neuronal replication and migration (as observed in cerebellar external granular cells). Synaptogenesis is impaired (as observed in Purkinje cells). It has been proposed that zinc deficiency impairs calcium channels causing a decrease in intracellular calcium that suppresses gene expression of growth factors and synthesis of nucleic acids and proteins. Whatever the mechanism, effects in experimental animals include poorly reversible impairments in learning and memory later in life, which appears associated with decreased neuronal survival. It is unknown if similar phenomena occur in humans. It is known however that low fetal growth, a process caused by maternal zinc deficiency, is risk factor for coronary heart disease, type 2 diabetes mellitus, chronic lung disease, and obesity. One wonders if fetal growth is related to later neuronal health and function. J. Trace Elem. Exp. Med. 16:165–173, 2003. © 2003 Wiley-Liss, Inc.","PeriodicalId":101243,"journal":{"name":"The Journal of Trace Elements in Experimental Medicine","volume":"16 4","pages":"165-173"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/jtra.10042","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72362797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulation of tyrosine phosphorylation cascades by phosphatases: What the actions of vanadium teach us","authors":"Philippa Hulley,&nbsp;Allan Davison","doi":"10.1002/jtra.10040","DOIUrl":"https://doi.org/10.1002/jtra.10040","url":null,"abstract":"Protein phosphorylation and dephosphorylation regulate much of the machinery of the cell. Emphasis in recent years has swung toward regulation by dephosphorylation. Much current research focuses on protein tyrosine phosphatases. Researchers of cellular regulation use vanadium as a probe because of its unparalleled ability to selectively inhibit protein tyrosine phosphatases at submicromolar concentrations. This review focuses on the biological actions of vanadium relevant to cellular regulatory cascades. Recent research has led to identification of control points and possible drug targets in 1) the glucose control mechanisms downstream from insulin receptors; 2) pathways regulating mitogenesis, tumor promotion, and other events downstream from growth factor receptors; 3) regulation of osteogenesis and possibilities for counteracting the bone damaging actions of glucocorticoids. An up-to-date understanding of the mechanisms by which vanadium acts and of its currently identified targets is prerequisite to the intelligent design of experiments of this kind. In this review, we will consider mechanisms at the enzymological level, in cellular regulatory cascades, and events affecting the cell or organism as a whole. J. Trace Elem. Exp. Med. 16:281–290, 2003. © 2003 Wiley-Liss, Inc.","PeriodicalId":101243,"journal":{"name":"The Journal of Trace Elements in Experimental Medicine","volume":"16 4","pages":"281-290"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/jtra.10040","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72362796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cadmium and human health: A perspective based on recent studies in China†","authors":"Gunnar Nordberg","doi":"10.1002/jtra.10039","DOIUrl":"https://doi.org/10.1002/jtra.10039","url":null,"abstract":"Cadmium (Cd) occurs in low concentrations in all human diets and in cigarettes. In contaminated areas and in certain occupations, high human exposures occur. In assessing risk to human health, it is important to identify the adverse effect that occurs at the lowest exposure level, i.e., the critical effect, which is crucial for preventive action. Excessive Cd exposure may give rise to renal, pulmonary, hepatic, skeletal, reproductive effects, and cancer. Previous evaluations (e.g., by WHO) have identified renal dysfunction, occurring in long-term Cd exposure, as the critical effect. However, skeletal and reproductive effects are also discussed as possible critical effects. For preventive action, information is important about exposure levels that give rise to the earliest (critical) effects. To gain new information on this issue, population groups in China exposed to high concentrations of Cd via rice and Cd-exposed workers were studied for possible renal, skeletal, and male reproductive toxicity. Skeletal effects in terms of decreased bone mineral density and an increased occurrence of fractures were found in groups of the general population living in the most Cd-exposed area. Our studies further show that renal effects measured by sensitive biomarkers, such as urinary content of beta-2-microglobulin, calcium, and N-acetyl-beta-D-glucosaminidase, occurs at lower cumulative exposures to Cd than those giving rise to skeletal effects and also at lower exposures than previously estimated, e.g., by WHO. The findings confirm the renal dysfunction as the critical effect of long-term Cd exposure. Metallothionein (MT) gene expression in peripheral blood lymphocytes was measured in Cd exposed workers. A higher prevalence of renal dysfunction was found among Cd exposed workers with low MT gene expression than among those with high MT gene expression, at similar blood and urinary Cd levels. MT gene expression in PBLC thus may be a biomarker for identifying sensitive population groups. J. Trace Elem. Exp. Med. 16:307–319, 2003. © 2003 Wiley-Liss, Inc.","PeriodicalId":101243,"journal":{"name":"The Journal of Trace Elements in Experimental Medicine","volume":"16 4","pages":"307-319"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/jtra.10039","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72362805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trace elements in human health and disease: An update","authors":"Ananda S. Prasad","doi":"10.1002/jtra.10057","DOIUrl":"https://doi.org/10.1002/jtra.10057","url":null,"abstract":"","PeriodicalId":101243,"journal":{"name":"The Journal of Trace Elements in Experimental Medicine","volume":"16 4","pages":""},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/jtra.10057","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72362806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dietary boron: An overview of the evidence for its role in immune function†","authors":"Curtiss D. Hunt","doi":"10.1002/jtra.10041","DOIUrl":"https://doi.org/10.1002/jtra.10041","url":null,"abstract":"This review summarizes the evidence for boron essentiality across the biological spectrum with special focus on biochemical pathways and biomolecules relevant to immune function. Boron is an essential trace element for at least some organisms in each of the phylogenetic kingdoms Eubacteria, Stramenopila (brown algae and diatoms), Viridiplantae (green algae and familiar green plants), Fungi, and Animalia. Discovery of several of the currently recognized boron-containing biomolecules was achieved because the bound boron formed four coordinate covalent bonds with the ligand, creating a thermodynamically stable complex that is almost undissociable in water. Boron is a constitutive element in three antibiotics and a quorum-sensing signal in bacteria. It enhances Fc receptor expression and interleukin-6 production in cultured mammalian macrophages. Boron binds tightly to the diadenosine polyphosphates and inhibits the in vitro activities of various serine protease and oxidoreductase enzymes. Physiological amounts of dietary boron decrease skinfold thickness after antigen injection in gilts and elevated circulating natural killer cells after adjuvant injection in rats. It is predicted that several boron biomolecules waiting discovery are signaling molecules that interact with the cell surface and are probably composed of two mirror or near-mirror halves stabilized by a single boron atom to form a large circular bio","PeriodicalId":101243,"journal":{"name":"The Journal of Trace Elements in Experimental Medicine","volume":"16 4","pages":"291-306"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/jtra.10041","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72362807","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Experimental stress-induced changes in trace element levels of various tissues in rats","authors":"Yunus Karakoc,&nbsp;Ertan Yurdakos,&nbsp;Tevfik Gulyasar,&nbsp;Murat Mengi,&nbsp;U. Bora Barutcu","doi":"10.1002/jtra.10023","DOIUrl":"https://doi.org/10.1002/jtra.10023","url":null,"abstract":"In this study, we investigated the effects of acute and chronic immobilization stress on the Zn, Cu, and Fe levels of the temporal lobe, brain stem, spleen, and liver tissues in rats. The animals in the acute stress group were put in the cages, one time only for 120 min. For the chronic stress groups (2h and 4h), the rats were kept in the cages daily for 2 and 4 h, respectively, for 5 consecutive days. Controls and immobilized rats were decapitated, and then tissue samples were taken. Zn, Cu, and Fe levels in the temporal lobe, brain stem, spleen, and liver were measured by flame atomic absorption spectrophotometer. Our results showed that acute immobilization stress causes endogenous Zn and Cu release from the brain tissues. In the 2h chronic stress group, Fe levels markedly increase in the temporal lobe and brain stem whereas they decrease in the spleen and liver. In the 4h chronic stress group, Fe levels increase in the temporal lobe and brain stem while Zn and Cu levels increase in the spleen and liver. In the acute and chronic immobilization stress groups, mobilization of Zn and Cu can be related to the induction of metallothionein (MT) in the liver and spleen but not in the brain. On the other hand, excess Fe in the temporal lobe and brain stem causes us to believe think that the brain iron transport proteins may be involved, and enhanced, by immobilization stress. J. Trace Elem. Exp. Med. 16:55–60, 2003. © 2003 Wiley-Liss, Inc.","PeriodicalId":101243,"journal":{"name":"The Journal of Trace Elements in Experimental Medicine","volume":"16 1","pages":"55-60"},"PeriodicalIF":0.0,"publicationDate":"2003-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1002/jtra.10023","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72324472","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}