Iron Deficiency Caused by Intestinal Iron Loss-Novel Candidate Genes for Severe Anemia.

The adult human body contains about 4 g of iron. About 1-2 mg of iron is absorbed every day, and in healthy individuals, the same amount is excreted. We describe a patient who presents with severe iron deficiency anemia with hemoglobin levels below 6 g/dL and ferritin levels below 30 ng/mL. Although red blood cell concentrates and intravenous iron have been substituted every month for years, body iron stores remain depleted. Diagnostics have included several esophago-gastro-duodenoscopies, colonoscopies, MRI of the liver, repetitive bone marrow biopsies, psychological analysis, application of radioactive iron to determine intact erythropoiesis, and measurement of iron excretion in urine and feces. Typically, gastrointestinal bleeding is a major cause of iron loss. Surprisingly, intestinal iron excretion in stool in the patient was repetitively increased, without gastrointestinal bleeding. Furthermore, whole exome sequencing was performed in the patient and additional family members to identify potential causative genetic variants that may cause intestinal iron loss. Under different inheritance models, several rare mutations were identified, two of which (in CISD1 and KRI1) are likely to be functionally relevant. Intestinal iron loss in the current form has not yet been described and is, with high probability, the cause of the severe iron deficiency anemia in this patient.

New microfluidic paper-based analytical device for iron determination in urine samples.

Iron is an important micronutrient involved in several mechanisms in the human body and can be an important biomarker. In this work, a simple and disposable microfluidic paper-based analytical device (µPAD) was developed for the quantification of iron in urine samples. The detection was based on the colorimetric reaction between iron(II) and bathophenanthroline and the reduction of iron(III) to iron(II) with hydroxylamine. The developed µPAD enabled iron determination in the range 0.07-1.2 mg/L, with a limit of detection of 20 µg/L and a limit of quantification of 65 µg/L, thus suitable for the expected values in human urine. Additionally, targeting urine samples, the potential interference of the samples color was overcome by incorporating a sample blank assessment for absorbance subtraction. Stability studies revealed that the device was stable for 15 days prior to usage and that the formed colored product was stable for scanning up to 3 h. The accuracy of the developed device was established by analyzing urine samples (#26) with the developed µPAD and with the atomic absorption spectrometry method; the relative deviation between the two sets of results was below 9.5%.

Copper Resistance Promotes Fitness of Methicillin-Resistant Staphylococcus aureus during Urinary Tract Infection.

Urinary tract infection (UTI) is one of the most common infectious conditions affecting people in the United States and around the world. Our knowledge of the host-pathogen interaction during UTI caused by Gram-positive bacterial uropathogens is limited compared to that for Gram-negative pathogens. Here, we investigated whether copper and the primary copper-containing protein, ceruloplasmin, are mobilized to urine during naturally occurring UTI caused by Gram-positive uropathogens in patients. Next, we probed the role of copper resistance in the fitness of methicillin-resistant Staphylococcus aureus (MRSA) during experimental UTI in a murine model. Our findings demonstrate that urinary copper and ceruloplasmin content are elevated during UTI caused by Enterococcus faecalis, S. aureus, S. epidermidis, and S. saprophyticus. MRSA strains successfully colonize the urinary tract of female CBA mice with selective induction of inflammation in the kidneys but not the bladder. MRSA mutants lacking CopL, a copper-binding cell surface lipoprotein, and the ACME genomic region containing copL, exhibit decreased fitness in the mouse urinary tract compared to parental strains. Copper sensitivity assays, cell-associated copper and iron content, and bioavailability of iron during copper stress demonstrate that homeostasis of copper and iron is interlinked in S. aureus. Importantly, relative fitness of the MRSA mutant lacking the ACME region is further decreased in mice that receive supplemental copper compared to the parental strain. In summary, copper is mobilized to the urinary tract during UTI caused by Gram-positive pathogens, and copper resistance is a fitness factor for MRSA during UTI. IMPORTANCE Urinary tract infection (UTI) is an extremely common infectious condition affecting people throughout the world. Increasing antibiotic resistance in pathogens causing UTI threatens our ability to continue to treat patients in the clinics. Better understanding of the host-pathogen interface is critical for development of novel interventional strategies. Here, we sought to elucidate the role of copper in host-Staphylococcus aureus interaction during UTI. Our results reveal that copper is mobilized to the urine as a host response in patients with UTI. Our findings from the murine model of UTI demonstrate that copper resistance is involved in the fitness of methicillin-resistant S. aureus (MRSA) during interaction with the host. We also establish a critical link between adaptation to copper stress and iron homeostasis in S. aureus.

A Friendly Complexing Agent for Spectrophotometric Determination of Total Iron.

Iron, one of the most common metals in the environment, plays a fundamental role in many biological as well as biogeochemical processes, which determine its availability in different oxidation states. Its relevance in environmental and industrial chemistry, human physiology, and many other fields has made it necessary to develop and optimize analysis techniques for accurate determination. Spectrophotometric methods are the most frequently applied in the analytical determination of iron in real samples. Taking advantage of the fact that desferrioxamine B, a trihydroxamic acid used since the 1970s in chelation therapy for iron overload treatment, forms a single stable 1:1 complex with iron in whichever oxidation state it can be found, a smart spectrophotometric method for the analytical determination of iron concentration was developed. In particular, the full compliance with the Lambert-Beer law, the range of iron concentration, the influence of pH, and the interference of other metal ions have been taken into account. The proposed method was validated in terms of LoD, LoQ, linearity, precision, and trueness, and has been applied for total iron determination in natural water certified material and in biological reference materials such as control human urine and control serum.

Kidney iron deposition by R2* is associated with haemolysis and urinary iron.

Kidney iron deposition measured by R2* (magnetic resonance imaging) MRI is posited to result from tubular reabsorption of filtered haemoglobin due to intravascular haemolysis. In chronically transfused sickle cell disease (SCD), R2* is elevated and positively correlated with lactate dehydrogenase (LDH). To account for contributions to renal iron from systemic iron overload, we evaluated kidney R2*, urinary iron and haemolysis markers in 62 non-transfused SCD patients. On multivariate analysis, kidney R2* was associated with urinary iron and LDH (R2  = 0·55, P < 0·0001). Our study confirms that kidney R2* is associated with intravascular haemolysis and raises important questions regarding the role of iron in SCD nephropathy.

Evaluation of the release of nickel and titanium under orthodontic treatment.

The metal alloys used in dentistry are made mainly of nickel (Ni), titanium (Ti), and other elements such as molybdenum (Mo), zirconium (Zr), iron (Fe), tin (Sn), chrome (Cr), carbon (C), copper (Cu) and niobium (Nb) which can release metal ions in unstable environments. The aim of this work was determine the salivary pH before and during orthodontic treatment; evaluate the release of metal ions, mainly Ni and Ti, in urine and saliva using Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES); and evaluate the corrosion using Scanning Electronic Microscopy (SEM). In this study, we selected 35 individuals under orthodontic treatment, from whom saliva and urine samples were collected in 3 stages: (a) basal, (b) at 3 and (c) 6 months after the placement of the fixed appliances. SEM analyzed the Ni-Ti (0.016″) and stainless steel (SS) (0.016 × 0.022″) archs after 1 month of being in contact with the oral cavity. Statistical analysis was performed with Stata using the ANOVA model of repeated measures with a p < 0.05. A statistically significant difference in the concentration of Ni in saliva were found between 3 and 6 months of intervention and Ti in urine was found 3 and 6 months.

Exacerbation of Neonatal Hemolysis and Impaired Renal Iron Handling in Heme Oxygenase 1-Deficient Mice.

In most mammals, neonatal intravascular hemolysis is a benign and moderate disorder that usually does not lead to anemia. During the neonatal period, kidneys play a key role in detoxification and recirculation of iron species released from red blood cells (RBC) and filtered out by glomeruli to the primary urine. Activity of heme oxygenase 1 (HO1), a heme-degrading enzyme localized in epithelial cells of proximal tubules, seems to be of critical importance for both processes. We show that, in HO1 knockout mouse newborns, hemolysis was prolonged despite a transient state and exacerbated, which led to temporal deterioration of RBC status. In neonates lacking HO1, functioning of renal molecular machinery responsible for iron reabsorption from the primary urine (megalin/cubilin complex) and its transfer to the blood (ferroportin) was either shifted in time or impaired, respectively. Those abnormalities resulted in iron loss from the body (excreted in urine) and in iron retention in the renal epithelium. We postulate that, as a consequence of these abnormalities, a tight systemic iron balance of HO1 knockout neonates may be temporarily affected.

Effects of exposure to high temperatures on serum, urine and sweat concentrations of iron and copper.

The objective of this research was to determine the acute effect of a maximum test until exhaustion in normothermia and hyperthermia, and after repeated exposure to heat at high temperatures on the homeostasis of Fe and Cu. The sample was composed of twenty-nine male university students. The participants were divided into a control group (CG) and an experimental group (EG). All of them underwent an incremental test until exhaustion in normothermia and hyperthermia before and after the repeated exposure of EG to heat at high temperatures, consisting of 9 heat acclimatisation sessions in the sauna. Samples of urine and blood were taken before and after each test. Additionally, sweat samples were collected in the hyperthermia test. The samples were frozen at -80 °C for further analysis by ICP-MS. None of the metal concentrations in serum were affected by hyperthermia or exposure to heat. Urinary Fe increased in CG in the hyperthermia test before Heat exposure at High Temperature (HEHT)(p < 0.05) and in both groups after HEHT (p < 0.05). In EG there was an increase in the urinary excretion of Cu after HEHT (p < 0.01) in both trials. Fe suffered a decrease in sweat in EG after exposure to heat (p < 0.05). The concentrations of Fe and Cu in serum were not affected by acute exercise and exposure to high temperatures. However, there was a decrease in excretion of Fe in sweat due to HEHT, and an increase in urinary excretion in both. Therefore, we think that in conditions of high temperatures for long periods of time, attention should be paid to the body levels of these metals.

Assessment of copper, iron, zinc and manganese status and speciation in patients with Parkinson's disease: A pilot study.

BACKGROUND: The objective of this pilot study was to assess iron (Fe), copper (Cu), zinc (Zn), and manganese (Mn) status (hair, serum, and urine) and speciation (serum) in Parkinson's disease (PD) patients. METHODS: A pilot study involving a total of 27 subjects (13 PD patients, 14 controls) was performed. Serum, urine, and hair metal content was assessed using ICP-MS. Speciation analysis of Cu, Zn, Fe, and Mn was performed using a hybrid HPLC-ICP-MS system. RESULTS: Group comparisons did not reveal any significant group difference in serum Cu, Zn, Fe, and Mn total metal level between PD patients and controls. Speciation analysis revealed a significant decrease in Cu/ceruloplasmin copper in association with elevation of low-molecular weight species (amino acids)-bound copper. It is proposed that in PD, binding of Cu(II) ions to ceruloplasmin is reduced and free copper ions coordinate with low molecular weight ligands. The level of Mn-albumin complexes in PD patients was more than 4-fold higher as compared to the respective value in the control group. The observed difference may be considered as a marker of redistribution between high and low molecular weight ligands. CONCLUSIONS: Metal speciation is significantly affected in serum of PD-patients. These findings are indicative of the potential role of metal metabolism and PD pathogenesis, although the exact mechanisms of such associations require further detailed studies.

A nanocellulose-based colorimetric assay kit for smartphone sensing of iron and iron-chelating deferoxamine drug in biofluids.

The current work describes the development of a "nanopaper-based analytical device (NAD)", through the embedding of curcumin in transparent bacterial cellulose (BC) nanopaper, as a colorimetric assay kit for monitoring of iron and deferoxamine (DFO) as iron-chelating drug in biological fluids such as serum blood, urine and saliva. The iron sensing strategy using the developed assay kit is based on the decrease of the absorbance/color intensity of curcumin-embedded in BC nanopaper (CEBC) in the presence of Fe(III), due to the formation of Fe(III)-curcumin complex. On the other hand, releasing of Fe(III) from Fe(III)-CEBC upon addition of DFO as an iron-chelating drug, due to the high affinity of this drug to Fe(III) in competition with curcumin, which leads to recovery of the decreased absorption/color intensity of Fe(III)-CEBC, is utilized for selective colorimetric monitoring of this drug. The absorption/color changes of the fabricated assay kit as output signal can be monitored by smartphone camera or by using a spectrophotometer. The results of our developed sensor agreed well with the results from a clinical reference method for determination of Fe(III) concentration in human serum blood samples, which revealed the clinical applicability of our developed assay kit. Taken together, regarding the advantageous features of the developed sensor as an easy-to-use, non-toxic, disposable, cost-effective and portable assay kit, along with those of smartphone-based sensing, it is anticipated that this sensing bioplatform, which we name lab-on-nanopaper, will find utility for sensitive, selective and easy diagnosis of iron-related diseases (iron deficiency and iron overload) and therapeutic drug monitoring (TDM) of iron-chelating drugs in clinical analysis as well.

Reproducibility of essential elements chromium, manganese, iron, zinc and selenium in spot samples, first-morning voids and 24-h collections from healthy adult men.

Evaluation of Cr, Mn, Fe, Zn and Se in humans is challenged by the potentially high within-individual variability of these elements in biological specimens, which are poorly characterised. This study aimed to evaluate their within-day, between-day and between-month variability in spot samples, first-morning voids and 24-h collections. A total of 529 spot urine samples (including eighty-eight first-morning voids and 24-h collections) were collected from eleven Chinese adult men on days 0, 1, 2, 3, 4, 30, 60 and 90 and analysed for these five elements using inductively coupled plasma-MS. Intraclass correlation coefficients (ICC) were utilised to characterise the reproducibility, and their sensitivity and specificity were analysed to assess how well a single measurement classified individuals' 3-month average exposures. Serial measurements of Zn in spot samples exhibited fair to good reproducibility (creatinine-adjusted ICC = 0·47) over five consecutive days, which became poor when the samples were gathered months apart (creatinine-adjusted ICC = 0·33). The reproducibility of Cr, Mn, Fe and Se in spot samples was poor over periods ranging from days to months (creatinine-adjusted ICC = 0·01-0·12). Two spot samples were sufficient for classifying 60 % of the men who truly had the highest (top 33 %) 3-month average Zn concentrations; for Cr, Mn, Fe and Se, however, at least three specimens were required to achieve similar sensitivities. In conclusion, urinary Cr, Mn, Fe, Zn and Se concentrations showed a strong within-individual variability, and a single measurement is not enough to efficiently characterise individuals' long-term exposures.

Urinary iron excretion for evaluating iron chelation efficacy in children with thalassemia major.

BACKGROUND: In patients with thalassemia major, examination routinely used for the evaluation of iron load in Indonesia is serum ferritin, but it is strongly influenced by other factors such as infections, inflammation and vitamin C levels. Evaluation of urinary iron excretion is an important and easy method to indicate iron chelation efficacy. OBJECTIVE: To determine the efficacy of iron chelation therapy by urinary iron examination and to evaluate its correlation with the time of transfusion, serum ferritin level, transferrin saturation and T2* MRI. METHODS: Prospective cohort study was conducted in children with thalassemia major aged 7-<18 years old who received DFP therapy. Twenty-four-hour urine collections were examined through inductively coupled plasma - mass spectrometry (ICP-MS). Patient's serum ferritin, transferrin saturation, peripheral blood, differential count and T2* MRI was documented during the study. Data analysis is based on urine iron level, body iron balance and the correlation between urine iron level, serum ferritin, transferrin saturation and T2* MRI and dosage of DFP. RESULTS: Thirty (55%) subjects showed a higher urine iron level on the day prior to transfusion (mean: 12,828 SD ±12,801 µg/24 h) in comparison to post transfusion (mean: 10,985 SD ±10,023 µg/24 h). All subjects had positive iron balance (mean 524 SD ±230 mg). There were positive correlation between urine iron level and transferrin saturation (r = 0.559, p = 0.01) and serum ferritin (r = 0.291, p = 0.03), no correlation found with T2* MRI results. CONCLUSIONS: There is a relationship to urinary iron excretion in response to chelation therapy and the degree of iron load.

Therapeutic mechanism of combined oral chelation therapy to maximize efficacy of iron removal in transfusion-dependent thalassemia major - a pilot study.

OBJECTIVES: Three iron chelators are used to treat transfusion-dependent beta-thalassemia: desferrioxamine (DFO), deferasirox (DFX), and deferiprone (DFP). Compliance is low for DFO as it cannot be administered orally. Combined administration of DFP and DFX is orally available, however, the therapeutic mechanism is unknown. This pilot study investigated the iron removal mechanisms of DFX and DFP treatment in patients with transfusion-dependent thalassemia major. METHODS: Each patient received three treatments sequentially: (1) DFX monotherapy, (2) DFP monotherapy, and (3) DFX/DFP combination therapy with a four-day washout period between each treatment. Urine and stool specimens were collected to determine the primary outcome of iron excretion volumes. RESULTS: The mean iron excretion was seven times higher after combination therapy with DFX and DFP. Monotherapies also increased excretions volumes, though to a significantly lesser degree. Combined administration of DFX and DFP achieves maximum iron removal in transfusion-dependent thalassemia major compared to monotherapy with either drug. CONCLUSIONS: We suggest combination therapy in chronic severe iron overload cases, especially for patients in poor compliance with DFO/DFP combination therapy or those exhibiting poor iron removal from DFX or DFP monotherapy.

Pharmacokinetics of ferric bepectate-a new intravenous iron drug for treating iron deficiency.

IV iron is indicated in clinical conditions, where rapid anaemia alleviation and repletion of iron stores are required. The acute toxicity of IV iron is ascribed to the presence of labile iron in plasma. Thus, shorter plasma residence time might improve the safety profile, even for compounds holding-on the iron tightly. In this single-centre, open-label, single-dose escalation study, we evaluated the elimination kinetics of ferric bepectate (FBP) compared to those of ferric carboxymaltose (FCM). Thirty-three iron-depleted anaemic patients who had undergone cardiac surgery were included and received 200, 500 or 1500 mg FBP or 500 mg FCM. Plasma drug curves were subjected to model-free analysis. Because saturation kinetics was found, a compartmental model with limited elimination capacity was applied. Urinary iron excretion was also analysed. The initial non-compartmental analysis revealed an increasing AUC/dose ratio for FBP. For both drugs, the central distribution compartment corresponded to plasma volume, and elimination followed Michaelis-Menten saturation kinetics. Maximal elimination rates (Vmax ) were 224 mg/h and 81 mg/h for FBP 500 mg and FCM 500 mg, respectively; drug concentrations at half Vmax (Km ), 99 mg/L and 212 mg/L, respectively; and terminal plasma half-life (T½), 3.05 h and 8.96 h, respectively. Both drugs were equally effective in eliciting an early ferritin rise. Urinary iron excretion was measurable in all patients receiving FCM but not in those receiving FBP, which was well tolerated. Intravenous iron drugs are subject to capacity-limited elimination with different saturation thresholds. Urinary iron excretion can be used as a surrogate for labile plasma iron.

Comparison of Chromium and Iron Distribution in Serum and Urine among Healthy People and Prediabetes and Diabetes Patients.

The effect of chromium (Cr) and iron (Fe) on prevalence of diabetes has received great attention. This study investigated serum and urinary Cr and Fe levels among patients with impaired fasting glucose (IFG), impaired glucose tolerance (IGT), type 1 diabetes (T1D), and type 2 diabetes (T2D) in the Northeast Chinese population. From January 2010 to October 2011, patients with IFG (n=12), IGT (n=15), T1D (n=25), T2D (n=137) and healthy controls (n=50) were enrolled in the First Hospital of Jilin University. Trace elements were detected using an inductively coupled plasma spectrometer. Serum Cr levels decreased in T2D without complications, diabetic retinopathy (DR), diabetic peripheral neuropathy (DPN), and diabetic nephropathy (DN) (P<0.05). The urinary Cr level in T1D was the highest of all, which significantly exceeded those of the T2D groups with and without complications. No significant differences of serum Fe levels were found among all groups. The urinary Fe level of T1D was significantly increased (P<0.05). The correlation between serum Cr and serum Fe in T2D was obviously positive (P<0.05). One month of simvastatin therapy exerted no effects on serum or urinary Cr and Fe levels. These results suggest the potential role of Cr and Fe in diabetes should receive attention.

Iron handling by the human kidney: glomerular filtration and tubular reabsorption both contribute to urinary iron excretion.

In physiological conditions, circulating iron can be filtered by the glomerulus and is almost completely reabsorbed by the tubular epithelium to prevent urinary iron wasting. Increased urinary iron concentrations have been associated with renal injury. However, it is not clear whether increased urinary iron concentrations in patients are the result of increased glomerular iron filtration and/or insufficient tubular iron reabsorption and if these processes contribute to renal injury. We measured plasma and urine iron parameters and urinary tubular injury markers in healthy human subjects ( n = 20), patients with systemic iron overload ( n = 20), and patients with renal tubular dysfunction ( n = 18). Urinary iron excretion parameters were increased in both patients with systemic iron overload and tubular dysfunction, whereas plasma iron parameters were only increased in patients with systemic iron overload. In patients with systemic iron overload, increased urinary iron levels were associated with elevated circulating iron, as indicated by transferrin saturation (TSAT), and increased body iron, as suggested by plasma ferritin concentrations. In patients with tubular dysfunction, enhanced urinary iron and transferrin excretion were associated with distal tubular injury as indicated by increased urinary glutathione S-transferase pi 1-1 (GSTP1-1) excretion. In systemic iron overload, elevated urinary iron and transferrin levels were associated with increased injury to proximal tubules, indicated by increased urinary kidney injury marker 1 (KIM-1) excretion. Our explorative study demonstrates that both glomerular filtration of elevated plasma iron levels and insufficient tubular iron reabsorption could increase urinary iron excretion and cause renal injury.

On-off-on fluorescent carbon dots from waste tea: Their properties, antioxidant and selective detection of CrO42-, Fe3+, ascorbic acid and L-cysteine in real samples.

In this work, we reported an economical plant-based hydrothermal method for one-pot green synthesis of water-soluble carbon dots (Tea-CDs) by using waste tea extract as a carbon source. The synthesized Tea-CDs were characterized by UV-visible, fluorescence, FT-IR, TEM, XPS and XRD. The Tea-CDs were found to remove hydroxyl and superoxide anion radical in vitro. In addition, the Tea-CDs exhibited bright blue fluorescence under UV-light (λex = 365 nm), and the fluorescence could be effectively quenched by CrO42- and Fe3+ ions. Meanwhile, the fluorescence of Tea-CDs-CrO42- and Tea-CDs-Fe3+ systems could be again easily recovered by ascorbic acid (AA) and L-cysteine (L-Cys). As an on-off-on fluorescent nano-sensor of the Tea-CDs, the sensitive detection of CrO42-, Fe3+, AA and L-Cys were all performed, showing that the good linear relationships between fluorescence intensity of Tea-CDs and concentration of all testing samples. Finally, the sensors successfully detected CrO42-, Fe3+, AA and L-Cys in commercially available real samples with satisfactory recovery ranges. The prepared sensors offer distinct advantages including low cost, simple handling, good sensitivity and high selectivity.

Graphite Furnace Atomic Absorption Spectrometric Evaluation of Iron Excretion in Mouse Urine Caused by Whole-Body Gamma Irradiation.

A procedure for the determination of iron in mice urine using graphite furnace atomic absorption spectrometry was developed. The mice urinary samples contain many organic compounds in the matrix, whose concentrations are approximately 20%, and the value is 30-fold higher compared to those found in human urine. Moreover, only 0.2 mL or less of urine was obtained as a sample volume per urination event. It was difficult to decompose the organic materials in the samples by wet digestion using mineral acids and oxidising agents, because of the tiny volumes. In this experiment, raw urinary samples were placed directly into the graphite tube furnace for analysis. The organic contents were simply ashed during the preheating stages. To facilitate ashing in the furnace, air was invaded from the surroundings by interrupting the stream of argon gas. Atomic absorption was measured at 248.3270 nm (wavelength for atomic absorption), with the background monitored at 247.0658 nm (wavelength for background correction). The optimised instrument operating conditions precluded the use of chemical modification technique. The analytical procedures used are quite simple, i.e. an aliquot of raw urine sample was injected directly into the graphite tube furnace and was followed by a suitable heating programme with no chemical modifier. Therefore, this method is useful for scientists who are not familiar with delicate chemical experiments. The proposed analytical method was applied as a kind of biomarker by determining iron concentrations in urinary samples of mice, which were irradiated with 4 Gy of gamma irradiation to their whole body. The time dependence of the iron concentration was determined, and the iron concentrations increased within 1 day of irradiation exposure, then decreased to ordinal values after several days.

Metal Biomonitoring and Comparative Assessment in Urine of Workers in Lead-Zinc and Steel-Iron Mining and Smelting.

The exposure of heavy metals (lead (Pb), cadmium (Cd), copper (Cu), nickel (Ni), and metalloid arsenicals) and their effects on workers' health from a lead-zinc mine (145 workers) and a steel smelting plant (162 workers) was investigated. Information on subject characteristics was obtained through a questionnaire. We determined the urinary levels of Pb, Cd, Cu, Ni, and arsenicals (including inorganic arsenic (iAs), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA), as were 8-hydroxydeoxyguanosine (8-OHdG) and cystatin C. Lead-zinc mine foundry workers had significantly higher concentrations of urinary Pb, Cd, Cu, Ni, iAs, and MMA than did steel smelting plant workers. Individuals who had consumed seafood in the previous 3 days had higher concentrations of urinary Ni than did individuals who had not consumed seafood. The urinary Cd concentrations in the two groups of factory workers may have been affected by daily smoking. There was no significant difference in urinary 8-OHdG between workers from the lead-zinc mine foundry and the steel smelting plant. Urinary Pb and Cd had significant positive linear dose-dependent effects on 8-OHdG. Urinary cystatin C, a sensitive biological indicator reflecting early renal damage, was found at higher levels in lead-zinc mine workers than in steel smelting plant workers. Binary logistic regression analysis showed that age and urinary Cd were significantly associated with urinary cystatin C. These results indicated that workers from lead-zinc mines may be exposed to higher levels of heavy metals which could lead to greater risk of kidney damage.

Multiplex recognition and logic devices for molecular robot prototype based on an europium(iii)-cyclen system.

Molecular robot provides a promising way to receive response signals and make decisions with intelligent information processing at the molecule level. In this work, a molecular robot prototype based on a europium(III)-cyclen complex (EuL) was designed and assembled, consisting of multiplex sensing and information processing in a single system. By utilizing the Eu3+ ion as a central processing unit (CPU) and terpyridine (Terpy) group as an arm of the molecular robot, multiplex detection function of this molecular robot can be accomplished in three test channels: the detection of Fe2+ with UV-vis, Zn2+ using photoluminescence, and Mn2+ using magnetic resonance imaging. The optimized structures revealed that the transition metal ions bound by the arms of two EuL molecules formed a hexacoordination octahedral rigidity structure in the adducts. For the structure of L and EuL, three pyridine rings of Terpy unit were not in a plane, and they were fixed to form a plane when captured the transition metal ions during the formation of the adducts. In addition, three different modes of molecular logic devices (OR, INHIBIT, and YES) were established based on relevant signals in the multiplex detection channels. The sensing of metal ions in human urine using EuL was also carried out, and the result demonstrated the presence of good recoveries and high analytical precision. Such a molecular robot prototype is expected to be used in intelligent medical diagnostics and, in particular, information processing at molecular level.