Effect of oral contraceptive agents on ascorbic acid metabolism in the rhesus monkey.

PubMed

Weininger, J; King, J C

1982-06-01

Ascorbic acid (AA) metabolism was studied in six sexually mature female rhesus monkeys with normal menstrual cycles before and during oral contraceptive administration. The animals were fed a commercial monkey stock diet (15% protein) containing no AA and given a 100 mg AA tablet daily throughout the study. After an initial adaptation period and a control period (total 8 months), combined-type oral contraceptive agents (OCAs) (50 micrograms mestranol and 1 mg norethindrone for 21 days each month) were administered to each monkey for 4 months. Serum copper and ceruloplasmin were significantly elevated during OCA treatment. There were no significant changes in plasma or leukocyte AA values during OCA use; however, urinary AA excretion decreased significantly. During the last month of the control period and the 3rd month of OCA treatment, 50 muCi of 1-14C-L-ascorbic acid were injected intravenously into each monkey. Urinary excretion of radioactivity, measured for 1 month, indicated a significantly faster AA turnover rate during the period of OCA use. These results suggest that women using OCAs may have an increased dietary requirement for AA.

The Urinary Bladder Transcriptome and Proteome Defined by Transcriptomics and Antibody-Based Profiling

PubMed Central

Habuka, Masato; Fagerberg, Linn; Hallström, Björn M.; Pontén, Fredrik; Yamamoto, Tadashi; Uhlen, Mathias

2015-01-01

To understand functions and diseases of urinary bladder, it is important to define its molecular constituents and their roles in urinary bladder biology. Here, we performed genome-wide deep RNA sequencing analysis of human urinary bladder samples and identified genes up-regulated in the urinary bladder by comparing the transcriptome data to those of all other major human tissue types. 90 protein-coding genes were elevated in the urinary bladder, either with enhanced expression uniquely in the urinary bladder or elevated expression together with at least one other tissue (group enriched). We further examined the localization of these proteins by immunohistochemistry and tissue microarrays and 20 of these 90 proteins were localized to the whole urothelium with a majority not yet described in the context of the urinary bladder. Four additional proteins were found specifically in the umbrella cells (Uroplakin 1a, 2, 3a, and 3b), and three in the intermediate/basal cells (KRT17, PCP4L1 and ATP1A4). 61 of the 90 elevated genes have not been previously described in the context of urinary bladder and the corresponding proteins are interesting targets for more in-depth studies. In summary, an integrated omics approach using transcriptomics and antibody-based profiling has been used to define a comprehensive list of proteins elevated in the urinary bladder. PMID:26694548

Impaired zinc and copper status in children with burn injuries: need to reassess nutritional requirements.

PubMed

Voruganti, V Saroja; Klein, Gordon L; Lu, Hong-Xing; Thomas, Suchmor; Freeland-Graves, Jeanne H; Herndon, David N

2005-09-01

Major burns are associated with impaired Zn and Cu status. These micronutrients are essential for bone matrix formation, linear growth, and wound healing. This study evaluated the status of Zn and Cu in burned children and assessed adequacy of supplementation. Six children, mean total body surface area (TBSA), 54+/-9% (S.D.), were recruited. Nutrient intakes, plasma, wound exudate, and 24h urine samples were collected and analyzed for Zn and Cu. Bone mineral content was assessed by dual energy X-ray absorptiometry. Dietary Zn and Cu were three times the dietary reference, and mean plasma concentrations of Zn and Cu were low at admission and discharge. Urinary Zn was elevated at admission, whereas Cu was elevated at both times. Wound Zn and Cu concentrations exceeded plasma concentrations, suggesting that inflammatory wound exudate was a primary route of loss. We demonstrate that burn injury in children results in low plasma levels of Zn and Cu that are inadequately compensated during hospitalization.

Increased urinary levels of tissue polypeptide specific antigen (TPS) in alcoholics.

PubMed

Barros, Paula; Gonzalez-Quintela, Arturo; Mella, Carmen; Perez, Luis-Fernando

2006-01-01

Urinary levels of tissue polypeptide specific antigen (TPS, cytokeratin-18) have been proposed as a marker of urothelial malignancies. Previous studies have shown that serum TPS levels are elevated in alcoholics. This study was designed to determine whether alcoholics had elevated urinary TPS levels as well. Serum and urinary TPS levels were determined in 24 alcoholics and 15 healthy controls by means of a commercial chemiluminiscent immunoassay. Serum TPS levels were higher in alcoholics than in controls (median 332 U/L, range 51-21241 U/L versus median 17 U/L, range 15-65 U/L, respectively, p<0.001). Urinary TPS levels were also higher in alcoholics than in controls (median 244 U/L, range 22-1267 U/L versus median 66.5 U/L, range 15-600 U/L, respectively, p=0.001). Urinary TPS levels were correlated with serum TPS levels in alcoholics. Urinary TPS levels are elevated in alcoholics. Consequently, the specificity of urinary TPS as a tumor marker may be limited in alcoholics.

Impact on sediments and water by release of copper from chalcopyrite bearing rock due to acidic mine drainage

NASA Astrophysics Data System (ADS)

Shukla, Anoop Kant; Pradhan, Manoj; Tiwari, Onkar Nath

2018-04-01

Mining activity causes transition of rock-mass from its original position in earth into open environment. The action of environmental elements such air, water, microorganisms leads to oxidation of minerals which constitute the rock. The oxidation of sulphide minerals in presence of moisture releases acidic mine discharge (AMD). The acidic nature of AMD causes leaching of metals from rock minerals. Dissolution of other minerals may occur upon reaction with AMD. Chalcopyrite (CuFeS2) undergoes oxidation in acidic condition releasing copper among other products. This study reveals contamination of copper in sediment samples and seepage water from the tailing dam of a large copper project in located in central India. Elevation was studied using GIS to ascertain to the topographic elevation of tailing dam area. It was located at relatively high altitude causing seepage to flow away from tailing dam. The seepage water from tailing dam was found to be acidic with mean pH value of 4.0 and elevated copper content. Similarly, sediments from seepage water flow displayed elevated copper concentration. The copper concentration in seepage water was found with a mean value of 10.73 mg/l. The sediments from seepage water flow also displayed elevated copper concentration with mean value of 26.92 g/kg. This indicates impact on sediments by release of copper due to acidic mine drainage.

Draft Genome Sequences of Four Alteromonas macleodii Strains Isolated from Copper Coupons and Grown Long-Term at Elevated Copper Levels.

PubMed

Cusick, Kathleen D; Dale, Jason R; Little, Brenda J; Biffinger, Justin C

2016-11-23

Alteromonas macleodii is a marine bacterium involved in the early stages of biofouling on ship hulls treated with copper as an antifouling agent. We report here the draft genome sequences of an A. macleodii strain isolated from copper coupons and three laboratory mutants grown long-term at elevated copper levels. Copyright © 2016 Cusick et al.

Behavior of heavy metals in human urine and blood following calcium disodium ethylenediamine tetraacetate injection: observations in metal workers.

PubMed

Sata, F; Araki, S; Murata, K; Aono, H

1998-06-12

To evaluate the effects of calcium disodium ethylenediamine tetraacetate (CaEDTA) on the behavior of 8 heavy metals in human urine and blood, CaEDTA was administered for 1 h by intravenous injection to 18 male metal foundry workers, whose blood lead concentrations (PbB) were between 16 and 59 (mean 34) microg/dl. Significant increases were found in urinary excretion of manganese, chromium, lead, zinc, and copper after the start of CaEDTA injection. Urinary chromium excretion reached a maximal level within 1 h after the start of injection, while urinary manganese, lead, and zinc excretion reached their highest concentrations between 1 and 2 h. Urinary copper excretion reached the highest level between 2 and 4 h. The rapid increases in urinary excretion of five metals were different from the "circadian rhythms," which are the normal, daily variations in renal glomerular filtration, reabsorption, and excretory mechanisms. Plasma lead concentrations were highest 1.5 h after the start of the 1-h injection, while plasma zinc concentration became lowest 5 h after the start of CaEDTA injection. Data suggest that manganese and chromium absorbed in human tissues might be mobilized by CaEDTA.

Accuracy of the radioactive copper incorporation test in the diagnosis of Wilson disease.

PubMed

Członkowska, Anna; Rodo, Maria; Wierzchowska-Ciok, Agata; Smolinski, Lukasz; Litwin, Tomasz

2018-02-08

In Wilson disease (WD), copper accumulates in the liver and other tissues because of mutations in the ATP7B copper transporter gene. Early and effective anticopper treatment is crucial. However, routine diagnostic methods based on clinical findings, copper metabolism tests, liver biopsies and DNA analyses do not always provide a conclusive diagnosis. The aim was to evaluate radioactive copper incorporation as a diagnostic test. We included cases with a diagnosis of WD supported by radiocopper testing and later, when available, confirmed by DNA analysis. Incorporation of 64 Cu was measured at 2, 24 and 48 hours following intravenous injection. Diagnostic accuracy (area under the receiver operating characteristic curve [AUC]), sensitivity, specificity and predictive value were assessed for 24 hours/2 hours and 48 hours/2 hours 64 Cu ratios and compared with serum measurements of ceruloplasmin, copper, non-ceruloplasmin-bound copper and urinary 24-hours copper excretion. Patients having two pathogenic ATP7B mutations (homozygotes/compound heterozygotes) (n = 74) had significantly lower 24 hours/2 hours and 48 hours/2 hours 64 Cu ratios than heterozygote controls (n = 21) (mean 0.14 and 0.12 vs 0.49 and 0.63, respectively; both P < .001). Of note, 24 hours/2 hours and 48 hours/2 hours 64 Cu ratios had excellent diagnostic accuracy, with AUCs approaching 1, and only 24-hours urinary copper excretion displayed similar positive features. Other copper metabolism tests studied had lower accuracy, specificity and sensitivity. The radioactive copper test had excellent diagnostic accuracy and may be useful in the evaluation of new therapies aimed at restoring ATP7B function. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Influence of injected caffeine on the metabolism of calcium and the retention and excretion of sodium, potassium, phosphorus, magnesium, zinc and copper in rats.

PubMed

Yeh, J K; Aloia, J F; Semla, H M; Chen, S Y

1986-02-01

Mineral metabolism was studied by the metabolic balance technique in rats with and without administration of caffeine. Caffeine was injected subcutaneously each day at either 2.5 mg or 10 mg/100 g body weight for 2 wk before the balance studies. Urinary volume excretion was higher in the group given caffeine than in the control group, but the creatinine clearance was not different. Urinary excretion of potassium, sodium, inorganic phosphate, magnesium and calcium, but not of zinc and copper, was also higher in the rats given caffeine. The rank order of the difference was the same as the percent of ingested mineral excreted in urine in the absence of caffeine. Caffeine caused a negative balance of potassium, sodium and inorganic phosphate. There was no significant difference from the control levels and in the apparent metabolic balance of calcium and magnesium. The urinary and fecal excretion of zinc and copper were found to be unaffected by caffeine. It is suggested that chronic administration of caffeine may lead to a tendency toward deficiency of those minerals that are excreted primarily in urine.

Development of Low Cost Contacts to Silicon Solar Cells

NASA Technical Reports Server (NTRS)

Iles, P. A.; Tanner, D. P.

1979-01-01

Different electroless plating systems were evaluated in conjunction with copper electroplating. All tests involved simultaneous deposition of front and back contacts using a standard cell materials. Cells with good adhesion and good curve fill factors were obtained using a palladium-chromium-copper metallization system. The final copper contact system was evaluated to determine if the copper would migrate at elevated temperatures. The copper migrated at elevated temperatures causing cell output degradation.

Risk of death in heart disease is associated with elevated urinary globotriaosylceramide.

PubMed

Schiffmann, Raphael; Forni, Sabrina; Swift, Caren; Brignol, Nastry; Wu, Xiaoyang; Lockhart, David J; Blankenship, Derek; Wang, Xuan; Grayburn, Paul A; Taylor, Matthew R G; Lowes, Brian D; Fuller, Maria; Benjamin, Elfrida R; Sweetman, Lawrence

2014-02-04

Elevated urinary globotriaosylceramide (Gb3) has been considered a hallmark of Fabry disease, an X-linked lysosomal disorder that is a risk factor for most types of heart disease. We screened 1421 consecutive patients with common forms of heart disease for Fabry disease by measuring urinary Gb3 in whole urine using tandem mass spectrometry, α-galactosidase A activity in dried blood spots, and we looked for GLA mutations by parallel sequencing of the whole gene (exons and introns) in pooled genomic DNA samples followed by Sanger sequencing verification. GLA variants were found in 13 patients. In the 1408 patients without GLA mutations, urinary Gb3 levels were significantly higher in heart disease patients compared to 116 apparently healthy controls (median difference=10.0 ng/mL and P<0.001). Urinary lipid profiling showed that levels of 5 other lipids significantly distinguished between urine of patients with Fabry disease (n=7) and heart disease patients with elevated urinary Gb3 (n=6). Sphingomyelin and Gb3 levels were abnormal in the left ventricular wall of patients with ischemic heart failure. Elevated levels of urinary Gb3 were independently associated with increased risk of death in the average follow-up of 17 months (hazard ratio=1.59 for increase in Gb3 of 200, 95% CI=1.36 and 1.87, and P<0.0001). In heart disease patients who do not have Fabry disease or GLA gene mutations, a higher level of urinary Gb3 is positively associated with near-term mortality. The elevation of urinary Gb3 and that of other lipids suggests that heart disease is associated with multiorgan lipid abnormalities. clinicaltrials.gov. Unique Identifier: NCT01019629.

Risk of Death in Heart Disease is Associated With Elevated Urinary Globotriaosylceramide

PubMed Central

Schiffmann, Raphael; Forni, Sabrina; Swift, Caren; Brignol, Nastry; Wu, Xiaoyang; Lockhart, David J.; Blankenship, Derek; Wang, Xuan; Grayburn, Paul A.; Taylor, Matthew R. G.; Lowes, Brian D.; Fuller, Maria; Benjamin, Elfrida R.; Sweetman, Lawrence

2014-01-01

Background Elevated urinary globotriaosylceramide (Gb3) has been considered a hallmark of Fabry disease, an X‐linked lysosomal disorder that is a risk factor for most types of heart disease. Methods and Results We screened 1421 consecutive patients with common forms of heart disease for Fabry disease by measuring urinary Gb3 in whole urine using tandem mass spectrometry, α‐galactosidase A activity in dried blood spots, and we looked for GLA mutations by parallel sequencing of the whole gene (exons and introns) in pooled genomic DNA samples followed by Sanger sequencing verification. GLA variants were found in 13 patients. In the 1408 patients without GLA mutations, urinary Gb3 levels were significantly higher in heart disease patients compared to 116 apparently healthy controls (median difference=10.0 ng/mL and P<0.001). Urinary lipid profiling showed that levels of 5 other lipids significantly distinguished between urine of patients with Fabry disease (n=7) and heart disease patients with elevated urinary Gb3 (n=6). Sphingomyelin and Gb3 levels were abnormal in the left ventricular wall of patients with ischemic heart failure. Elevated levels of urinary Gb3 were independently associated with increased risk of death in the average follow‐up of 17 months (hazard ratio=1.59 for increase in Gb3 of 200, 95% CI=1.36 and 1.87, and P<0.0001). Conclusions In heart disease patients who do not have Fabry disease or GLA gene mutations, a higher level of urinary Gb3 is positively associated with near‐term mortality. The elevation of urinary Gb3 and that of other lipids suggests that heart disease is associated with multiorgan lipid abnormalities. Clinical Trial Registration URL: clinicaltrials.gov. Unique Identifier: NCT01019629. PMID:24496231

Copper and zinc level in biological samples from healthy subjects of vegetarian food habit in reference to community environment.

PubMed

Bhattacharya, R D; Patel, T S; Pandya, C B

1985-01-01

Many epidemiologists have found a correlation between copper and zinc in the community environment and diseases, such as myocardial and vascular pathologies, and diabetes. The purpose of this study was to investigate the total daily intake of these two metals in cooked food, drinking water and air and their respective levels in blood and urine. A chronobiological methodology has been adopted to establish the reference values of these two metals in biological samples. It has been observed that the daily intake of copper is within the recommended value, whereas its urinary excretion is high. The daily intake of zinc is below the recommended value and its urinary excretion is also high. Both the metals showed a temporal oscillation pattern in blood and urine. A possible chronic zinc deficiency has been anticipated in this particular ethnic group of vegetarian food habit.

Host-specific induction of Escherichia coli fitness genes during human urinary tract infection

PubMed Central

Subashchandrabose, Sargurunathan; Hazen, Tracy H.; Brumbaugh, Ariel R.; Himpsl, Stephanie D.; Smith, Sara N.; Ernst, Robert D.; Rasko, David A.; Mobley, Harry L. T.

2014-01-01

Uropathogenic Escherichia coli (UPEC) is the predominant etiological agent of uncomplicated urinary tract infection (UTI), manifested by inflammation of the urinary bladder, in humans and is a major global public health concern. Molecular pathogenesis of UPEC has been primarily examined using murine models of UTI. Translational research to develop novel therapeutics against this major pathogen, which is becoming increasingly antibiotic resistant, requires a thorough understanding of mechanisms involved in pathogenesis during human UTIs. Total RNA-sequencing (RNA-seq) and comparative transcriptional analysis of UTI samples to the UPEC isolates cultured in human urine and laboratory medium were used to identify novel fitness genes that were specifically expressed during human infection. Evidence for UPEC genes involved in ion transport, including copper efflux, nickel and potassium import systems, as key fitness factors in uropathogenesis were generated using an experimental model of UTI. Translational application of this study was investigated by targeting Cus, a bacterial copper efflux system. Copper supplementation in drinking water reduces E. coli colonization in the urinary bladder of mice. Additionally, our results suggest that anaerobic processes in UPEC are involved in promoting fitness during UTI in humans. In summary, RNA-seq was used to establish the transcriptional signature in UPEC during naturally occurring, community acquired UTI in women and multiple novel fitness genes used by UPEC during human infection were identified. The repertoire of UPEC genes involved in UTI presented here will facilitate further translational studies to develop innovative strategies against UTI caused by UPEC. PMID:25489107

Urinary Angiotensinogen Excretion Level Is Associated With Elevated Blood Pressure in the Normotensive General Population.

PubMed

Sato, Emiko; Wang, An Yi; Satoh, Michihiro; Nishikiori, Yoko; Oba-Yabana, Ikuko; Yoshida, Mai; Sato, Hiroshi; Ito, Sadayoshi; Hida, Wataru; Mori, Takefumi

2018-05-07

Inflammation, intrarenal renin-angiotensin system (RAS) activation, oxidative stress, and carbonyl stress have been postulated to play a fundamental role in controlling blood pressure. However, little is known about the association among renal RAS activation, carbonyl stress, and blood pressure elevation. We evaluated the relationship between blood pressure elevation and either renal RAS activity or carbonyl stress in the general population (N = 355) in Japan. To minimize the effect of antihypertensive drug therapy, we divided participants into 3 groups (normotensive, hypertensive-with-non-medication, and hypertensive-with-medication). Intrarenal RAS activity and carbonyl stress were indicated by the urinary angiotensinogen (AGT) and carbonyl compound excretion levels, respectively. The urinary AGT and carbonyl compound excretion levels were significantly associated with blood pressure. Using a stepwise multiple regression analysis, we found that the urinary AGT excretion levels were strongly associated with blood pressure elevation, compared with inflammation, oxidative stress, and carbonyl stress markers, in all groups. Urinary carbonyl compound excretion was significantly associated with blood pressure in only the hypertensive-without-medication group. Furthermore, blood pressure was significantly increased in these participants, and both the urinary AGT and carbonyl compound levels were high. The urinary AGT excretion levels were strongly associated with elevated blood pressure in normotensive people, and inappropriate renal RAS activity and carbonyl stress independently contributed to the development of hypertension. These findings suggest that RAS activation, particularly renal RAS activation exert a fundamental role in the pathogenesis of hypertension in the general population.

Ordering pattern and performance of biochemical tests for diagnosing pheochromocytoma between 2000 and 2008.

PubMed

Yu, Run

2009-01-01

To examine what tests are ordered by physicians for pheochromocytoma diagnosis and how those tests perform in modern clinical practice. In this case series, electronic medical records of patients seen between January 2000 and July 2008 at a large academic hospital in Los Angeles, California, were queried, and patients older than 15 years who underwent any 1 of 5 tests for pheochromocytoma (measurement of plasma catecholamines, plasma fractionated metanephrines, urinary catecholamines, urinary metanephrines, or urinary vanillylmandelic acid) were identified. Because testing was performed in various reference laboratories, test results were classified into 1 of 3 categories: (a) markedly elevated, (b) moderately elevated, or (c) normal. Patient demographics, clinical history, test results, imaging study findings, and pathology records were reviewed. A total of 3980 tests were ordered for 1898 patients. Pretest probability was 2.2% (based on 681 patients in whom pheochromocytoma was confirmed or excluded), and hypertension was the most common indication for testing. The number of patients tested and the number of tests ordered increased over the years. The ordering pattern stabilized since 2006 when urinary metanephrines, urinary catecholamines, and plasma metanephrines were ordered more frequently. Sensitivity was highest for urinary metanephrines and vanillylmandelic acid, specificity was highest for vanillylmandelic acid and urinary catecholamines, and positive likelihood ratio was highest for vanillylmandelic acid. Positive predictive value for markedly elevated test results was 39% to 83%, while that for moderately elevated test results was only 2% to 14%. Ordering pattern and test performance differ significantly from those recommended and reported by large centers. The best testing strategy should incorporate local experience. Categorizing test results as markedly elevated, moderately elevated, and normal is important for result interpretation.

Urinary p-cresol is elevated in young French children with autism spectrum disorder: a replication study.

PubMed

Gabriele, Stefano; Sacco, Roberto; Cerullo, Sonia; Neri, Cristina; Urbani, Andrea; Tripi, Gabriele; Malvy, Joëlle; Barthelemy, Catherine; Bonnet-Brihault, Frédérique; Persico, Antonio M

2014-09-01

The aromatic compound p-cresol (4-methylphenol) has been found elevated in the urines of Italian autistic children up to 8 years of age. The present study aims at replicating these initial findings in an ethnically distinct sample and at extending them by measuring also the three components of urinary p-cresol, namely p-cresylsulfate, p-cresylglucuronate and free p-cresol. Total urinary p-cresol, p-cresylsulfate and p-cresylglucuronate were significantly elevated in 33 French autism spectrum disorder (ASD) cases compared with 33 sex- and age-matched controls (p < 0.05). This increase was limited to ASD children aged ≤8 years (p < 0.01), and not older (p = 0.17). Urinary levels of p-cresol and p-cresylsulfate were associated with stereotypic, compulsive/repetitive behaviors (p < 0.05), although not with overall autism severity. These results confirm the elevation of urinary p-cresol in a sizable set of small autistic children and spur interest into biomarker roles for p-cresol and p-cresylsulfate in autism.

Renal function in urinary schistosomiasis in the Natal Province of South Africa.

PubMed

Coopan, R M; Naidoo, K; Jialal, I

1987-11-01

Renal function was assessed in 101 schoolchildren with active urinary schistosomiasis by measuring serum creatinine, urate, urea, and B2-microglobulin, urinary B2 microglobulin, and the glomerular filtration rate. Glomerular function in all subjects was normal as were serum creatinine, urate, and urea levels. Serum B2-microglobulin was elevated in only 8% of subjects while urinary B2-microglobulin only was raised in 7% of subjects, indicating proximal tubular dysfunction, a previously unreported feature in urinary schistosomiasis. Urinary tract abnormalities were found in 43% of subjects consenting to an excretory urogram but no correlation with biochemical parameters of renal function was noted. Serum angiotensin converting enzyme level measured in 70 subjects was elevated in 11% of subjects and was regarded as a possible measure of increased granulomatous activity.

Effect of dietary copper on the copper content of urine, parotid saliva, and sweat in humans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Turnlund, J.R.

Eleven young men were confined to a metabolic research unit to study the effect of the level of dietary copper (Cu) on Cu metabolism. They were fed a constant diet containing the following three levels of dietary Cu: adequate Cu (1.68 mg/d) for 24 days (MP1), low Cu (0.785 mg/d) for 42 days (MP2), and high Cu (7.53 mg/d) for 24 days (MP3). Urine was collected throughout the study and Cu was determined in 6-day pools from the beginning of the study, the end of each MP, and the midpoint of MP2. Parotid saliva was collected near the end ofmore » each MP. Sweat was collected from the upper arm and ancillary area of three subjects for 2-day periods near the end of each MP. Urinary Cu averaged 0.34, 0.34 and 0.33 {mu}mol/d for MP 1, 2, and 3, respectively. Individual averages ranged from 0.16 to 0.39 {mu}mol/d. Parotid saliva Cu averaged 13.4, 13.0, and 12.0 nmol/L for MP 1, 2 and 3, respectively. Individual averages ranged from 6.9 to 17.8 nmol/L. Sweat Cu levels were very low and did not appear to be affected by dietary Cu. The limited data suggest that sweat losses would have little effect on Cu balance. Neither urinary nor salivary Cu was affected by dietary Cu or related to indices of Cu status (serum Cu, ceruloplasmin, or erythrocyte superoxide dismutase). Urinary and salivary Cu differed significantly among individuals. Results suggest that urinary, salivary, and sweat Cu do not play a role in regulating Cu retention or affect Cu status of humans.« less

Mobilisation of heavy metals into the urine by CaEDTA: relation to erythrocyte and plasma concentrations and exposure indicators.

PubMed

Araki, S; Aono, H; Murata, K

1986-09-01

To investigate the effects of calcium disodium ethylenediamine tetra-acetate (CaEDTA) on the urinary excretion, erythrocyte, and plasma concentrations and exposure indicators of seven heavy metals, CaEDTA was administered by intravenous infusion to 20 workers exposed to lead, zinc, and copper. The workers' blood lead concentrations ranged from 22 to 59 micrograms/dl (mean 38 micrograms/dl (1.8 mumol/l]. The 24 hour urinary excretion of metals after CaEDTA administration (mobilisation yield) was on average 13 times the background excretion for lead, 11 times for zinc, 3.8 times for manganese, 3.4 times for cadmium, 1.3 times for copper, and 1.1 times for chromium; no significant increase was found for mercury. The mobilisation yield of lead (MPb) was significantly correlated with whole blood and erythrocyte concentrations and the urinary excretion of lead but not with its plasma concentration; similarly, the mobilisation yield of cadmium was significantly correlated with its erythrocyte concentration. In addition, MPb was significantly correlated with intra-erythrocytic enzyme delta-aminolaevulinic acid dehydratase activity and urinary coproporphyrin excretion. The relation between the mobilisation yield of heavy metals and their body burden (and toxic signs) is discussed in the light of these findings.

Mobilisation of heavy metals into the urine by CaEDTA: relation to erythrocyte and plasma concentrations and exposure indicators.

PubMed Central

Araki, S; Aono, H; Murata, K

1986-01-01

To investigate the effects of calcium disodium ethylenediamine tetra-acetate (CaEDTA) on the urinary excretion, erythrocyte, and plasma concentrations and exposure indicators of seven heavy metals, CaEDTA was administered by intravenous infusion to 20 workers exposed to lead, zinc, and copper. The workers' blood lead concentrations ranged from 22 to 59 micrograms/dl (mean 38 micrograms/dl (1.8 mumol/l]. The 24 hour urinary excretion of metals after CaEDTA administration (mobilisation yield) was on average 13 times the background excretion for lead, 11 times for zinc, 3.8 times for manganese, 3.4 times for cadmium, 1.3 times for copper, and 1.1 times for chromium; no significant increase was found for mercury. The mobilisation yield of lead (MPb) was significantly correlated with whole blood and erythrocyte concentrations and the urinary excretion of lead but not with its plasma concentration; similarly, the mobilisation yield of cadmium was significantly correlated with its erythrocyte concentration. In addition, MPb was significantly correlated with intra-erythrocytic enzyme delta-aminolaevulinic acid dehydratase activity and urinary coproporphyrin excretion. The relation between the mobilisation yield of heavy metals and their body burden (and toxic signs) is discussed in the light of these findings. PMID:3092853

Dramatic elevation in urinary amino terminal titin fragment excretion quantified by immunoassay in Duchenne muscular dystrophy patients and in dystrophin deficient rodents.

PubMed

Robertson, Alan S; Majchrzak, Mark J; Smith, Courtney M; Gagnon, Robert C; Devidze, Nino; Banks, Glen B; Little, Sean C; Nabbie, Fizal; Bounous, Denise I; DiPiero, Janet; Jacobsen, Leslie K; Bristow, Linda J; Ahlijanian, Michael K; Stimpson, Stephen A

2017-07-01

Enzyme-linked and electrochemiluminescence immunoassays were developed for quantification of amino (N-) terminal fragments of the skeletal muscle protein titin (N-ter titin) and qualified for use in detection of urinary N-ter titin excretion. Urine from normal subjects contained a small but measurable level of N-ter titin (1.0 ± 0.4 ng/ml). A 365-fold increase (365.4 ± 65.0, P = 0.0001) in urinary N-ter titin excretion was seen in Duchene muscular dystrophy (DMD) patients. Urinary N-ter titin was also evaluated in dystrophin deficient rodent models. Mdx mice exhibited low urinary N-ter titin levels at 2 weeks of age followed by a robust and sustained elevation starting at 3 weeks of age, coincident with the development of systemic skeletal muscle damage in this model; fold elevation could not be determined because urinary N-ter titin was not detected in age-matched wild type mice. Levels of serum creatine kinase and serum skeletal muscle troponin I (TnI) were also low at 2 weeks, elevated at later time points and were significantly correlated with urinary N-ter titin excretion in mdx mice. Corticosteroid treatment of mdx mice resulted in improved exercise performance and lowering of both urinary N-ter titin and serum skeletal muscle TnI concentrations. Low urinary N-ter titin levels were detected in wild type rats (3.0 ± 0.6 ng/ml), while Dmd mdx rats exhibited a 556-fold increase (1652.5 ± 405.7 ng/ml, P = 0.002) (both at 5 months of age). These results suggest that urinary N-ter titin is present at low basal concentrations in normal urine and increases dramatically coincident with muscle damage produced by dystrophin deficiency. Urinary N-ter titin has potential as a facile, non-invasive and translational biomarker for DMD. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Copper accumulation in senescent cells: Interplay between copper transporters and impaired autophagy.

PubMed

Masaldan, Shashank; Clatworthy, Sharnel A S; Gamell, Cristina; Smith, Zoe M; Francis, Paul S; Denoyer, Delphine; Meggyesy, Peter M; Fontaine, Sharon La; Cater, Michael A

2018-06-01

Cellular senescence is characterized by irreversible growth arrest incurred through either replicative exhaustion or by pro-oncogenic cellular stressors (radioactivity, oxidative stress, oncogenic activation). The enrichment of senescent cells in tissues with age has been associated with tissue dyshomeostasis and age-related pathologies including cancers, neurodegenerative disorders (e.g. Alzheimer's, Parkinson's, etc.) and metabolic disorders (e.g. diabetes). We identified copper accumulation as being a universal feature of senescent cells [mouse embryonic fibroblasts (MEF), human prostate epithelial cells and human diploid fibroblasts] in vitro. Elevated copper in senescent MEFs was accompanied by elevated levels of high-affinity copper uptake protein 1 (Ctr1), diminished levels of copper-transporting ATPase 1 (Atp7a) (copper export) and enhanced antioxidant defence reflected by elevated levels of glutathione (GSH), superoxide dismutase 1 (SOD1) and glutaredoxin 1 (Grx1). The levels of intracellular copper were further increased in senescent MEFs cultured in copper supplemented medium and in senescent Mottled Brindled (Mo br ) MEFs lacking functional Atp7a. Finally, we demonstrated that the restoration/preservation of autophagic-lysosomal degradation in senescent MEFs following rapamycin treatment correlated with attenuation of copper accumulation in these cells despite a further decrease in Atp7a levels. This study for the first time establishes a link between Atp7a and the autophagic-lysosomal pathway, and a requirement for both to effect efficient copper export. Such a connection between cellular autophagy and copper homeostasis is significant, as both have emerged as important facets of age-associated degenerative disease. Copyright © 2018. Published by Elsevier B.V.

Selection of Fecal Enterococci Exhibiting tcrB-Mediated Copper Resistance in Pigs Fed Diets Supplemented with Copper † ▿

PubMed Central

Amachawadi, R. G.; Shelton, N. W.; Shi, X.; Vinasco, J.; Dritz, S. S.; Tokach, M. D.; Nelssen, J. L.; Scott, H. M.; Nagaraja, T. G.

2011-01-01

Copper, as copper sulfate, is increasingly used as an alternative to in-feed antibiotics for growth promotion in weaned piglets. Acquired copper resistance, conferred by a plasmid-borne, transferable copper resistance (tcrB) gene, has been reported in Enterococcus faecium and E. faecalis. A longitudinal field study was undertaken to determine the relationship between copper supplementation and the prevalence of tcrB-positive enterococci in piglets. The study was done with weaned piglets, housed in 10 pens with 6 piglets per pen, fed diets supplemented with a normal (16.5 ppm; control) or an elevated (125 ppm) level of copper. Fecal samples were randomly collected from three piglets per pen on days 0, 14, 28, and 42 and plated on M-Enterococcus agar, and three enterococcal isolates were obtained from each sample. The overall prevalence of tcrB-positive enterococci was 21.1% (38/180) in piglets fed elevated copper and 2.8% (5/180) in the control. Among the 43 tcrB-positive isolates, 35 were E. faecium and 8 were E. faecalis. The mean MICs of copper for tcrB-negative and tcrB-positive enterococci were 6.2 and 22.2 mM, respectively. The restriction digestion of the genomic DNA of E. faecium or E. faecalis with S1 nuclease yielded a band of ∼194-kbp size to which both tcrB and the erm(B) gene probes hybridized. A conjugation assay demonstrated cotransfer of tcrB and erm(B) genes between E. faecium and E. faecalis strains. The higher prevalence of tcrB-positive enterococci in piglets fed elevated copper compared to that in piglets fed normal copper suggests that supplementation of copper in swine diets selected for resistance. PMID:21705534

Urinary heavy metals in Hispanics 40–85 years old in Doña Ana County, New Mexico

PubMed Central

Adams, Scott V.; Barrick, Brian; Freney, Emily P.; Shafer, Martin M.; Song, Xiaoling; Vilchis, Hugo; Newcomb, Polly A.; Ulery, April

2017-01-01

As, Cd, Pb, and U exposure among older Hispanic adults residing in underserved communities in southern New Mexico was investigated. Personal information was obtained by standardized interview from 188 adults age 40–85y. Urinary metal concentrations were measured and compared to results from the National Health and Nutritional Examination Survey (NHANES). Urinary As and U in study participants significantly (P<0.05) exceeded NHANES reference values. Elevated urinary As concentration was significantly associated with older age, Latin American birthplace, clinic site, private well drinking water, higher self-rated health, and diabetes. Higher urinary Cd was significantly associated with older age, clinic site, female sex, agricultural work, and current cigarette smoking. No personal characteristics were significantly associated with urinary Pb or U. Our results suggest elevated levels of As and U in this population. PMID:26666397

Low-dose copper infusion into the coronary circulation induces acute heart failure in diabetic rats: New mechanism of heart disease.

PubMed

Cheung, Carlos Chun Ho; Soon, Choong Yee; Chuang, Chia-Lin; Phillips, Anthony R J; Zhang, Shaoping; Cooper, Garth J S

2015-09-01

Diabetes impairs copper (Cu) regulation, causing elevated serum Cu and urinary Cu excretion in patients with established cardiovascular disease; it also causes cardiomyopathy and chronic cardiac impairment linked to defective Cu homeostasis in rats. However, the mechanisms that link impaired Cu regulation to cardiac dysfunction in diabetes are incompletely understood. Chronic treatment with triethylenetetramine (TETA), a Cu²⁺-selective chelator, improves cardiac function in diabetic patients, and in rats with heart disease; the latter displayed ∼3-fold elevations in free Cu²⁺ in the coronary effluent when TETA was infused into their coronary arteries. To further study the nature of defective cardiac Cu regulation in diabetes, we employed an isolated-perfused, working-heart model in which we infused micromolar doses of Cu²⁺ into the coronary arteries and measured acute effects on cardiac function in diabetic and non-diabetic-control rats. Infusion of CuCl₂ solutions caused acute dose-dependent cardiac dysfunction in normal hearts. Several measures of baseline cardiac function were impaired in diabetic hearts, and these defects were exacerbated by low-micromolar Cu²⁺ infusion. The response to infused Cu²⁺ was augmented in diabetic hearts, which became defective at lower infusion levels and underwent complete pump failure (cardiac output = 0 ml/min) more often (P < 0.0001) at concentrations that only moderately impaired function of control hearts. To our knowledge, this is the first report describing the acute effects on cardiac function of pathophysiological elevations in coronary Cu²⁺. The effects of Cu²⁺ infusion occur within minutes in both control and diabetic hearts, which suggests that they are not due to remodelling. Heightened sensitivity to the acute effects of small elevations in Cu²⁺ could contribute substantively to impaired cardiac function in patients with diabetes and is thus identified as a new mechanism of heart disease. Copyright © 2015 Elsevier Inc. All rights reserved.

THE IMPACT OF ORTHOPHOSPHATE ON COPPER CORROSION AND CHLORINE DEMAND

EPA Science Inventory

In 1991, EPA promulgated the Lead and Copper Rule, which established a copper action level of 1.3 mg/L in a 1-liter, first-draw sample collected from the consumer’s tap. Excessive corrosion of copper can lead to elevated copper levels at the consumer's tap, and in some cases, can...

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gough, Mallory, E-mail: m.gough1@lancaster.ac.uk; Blanthorn-Hazell, Sophee, E-mail: s.blanthorn-hazell@lancaster.ac.uk; Delury, Craig, E-mail: c.delury@lancaster.ac.uk

Highlights: • Copper levels are elevated in the tumour microenvironment. • APP mitigates copper-induced growth inhibition of DU145 prostate cancer (PCa) cells. • The APP intracellular domain is a prerequisite; soluble forms have no effect. • The E1 CuBD of APP is also a prerequisite. • APP copper binding potentially mitigates copper-induced PCa cell growth inhibition. - Abstract: Copper plays an important role in the aetiology and growth of tumours and levels of the metal are increased in the serum and tumour tissue of patients affected by a range of cancers including prostate cancer (PCa). The molecular mechanisms that enablemore » cancer cells to proliferate in the presence of elevated copper levels are, therefore, of key importance in our understanding of tumour growth progression. In the current study, we have examined the role played by the amyloid precursor protein (APP) in mitigating copper-induced growth inhibition of the PCa cell line, DU145. A range of APP molecular constructs were stably over-expressed in DU145 cells and their effects on cell proliferation in the presence of copper were monitored. Our results show that endogenous APP expression was induced by sub-toxic copper concentrations in DU145 cells and over-expression of the wild-type protein was able to mitigate copper-induced growth inhibition via a mechanism involving the cytosolic and E1 copper binding domains of the full-length protein. APP likely represents one of a range of copper binding proteins that PCa cells employ in order to ensure efficient proliferation despite elevated concentrations of the metal within the tumour microenvironment. Targeting the expression of such proteins may contribute to therapeutic strategies for the treatment of cancers.« less

Clinically distinct presentations of copper deficiency myeloneuropathy and cytopenias in a patient using excessive zinc-containing denture adhesive.

PubMed

Cathcart, Sahara J; Sofronescu, Alina G

2017-08-01

While copper deficiency has long been known to cause cytopenias, copper deficiency myeloneuropathy is a more recently described entity. Here, we present the case of two clinically distinct presentations of acquired copper deficiency syndromes secondary to excessive use of zinc-containing denture adhesive over five years: myeloneuropathy and severe macrocytic anemia and neutropenia. Extensive laboratory testing and histologic evaluation of the liver and bone marrow, were necessary to rule out other disease processes and establish the diagnosis of copper deficiency. The initial presentation consisted of a myelopathy involving the posterior columns. Serum and urine copper were significantly decreased, and serum zinc was elevated. On second presentation (five years later), multiple hematological abnormalities were detected. Serum copper was again decreased, while serum zinc was elevated. Zinc overload is a preventable cause of copper deficiency syndromes. This rare entity presented herein highlights the importance of patient, as well as provider, education. Copyright © 2017 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Zinc in denture adhesive: a rare cause of copper deficiency in a patient on home parenteral nutrition

PubMed Central

Prasad, Rakesh; Hawthorne, Barney; Durai, Dharmaraj; McDowell, Ian

2015-01-01

A 65-year-old woman with Crohn's disease, who had been on home parenteral nutrition for many years, presented with perioral paraesthesia and a burning sensation in the mouth. Initial blood tests including serum ferritin, vitamin B12 and folate, were normal apart from mild pancytopaenia. Serum copper was low, in spite of receiving regular copper in her parenteral feeds. The copper in her parenteral feeds was increased initially, but when it did not improve, she was started on weekly intravenous copper infusions. She was using dental adhesive, which had zinc in it, and a possibility that this was causing her copper deficiency was raised. Serum zinc levels were normal, but urinary zinc was very high. The patient was advised to use zinc-free dental adhesive and her copper level returned to normal within a few months with normalisation of her pancytopaenia, and partial resolution of her oral paraesthesia. PMID:26452740

Laser fragmentation of foreign bodies in the urinary tract: an in vitro study and clinical application.

PubMed

Bedke, Jens; Kruck, Stephan; Schilling, David; Matter, Anton; Horstmann, Marcus; Sievert, Karl-Dietrich; Stenzl, Arnulf; Nagele, Udo

2010-04-01

Foreign bodies of the urinary tract represent a urologic emergency. First-line treatment is endoscopic removal, but this is often impeded by restricted space, especially in the urethra. We postulated that foreign objects could be fragmented by Holmium:YAG laser and investigated its effect on objects of varying composition. In a specially designed stage flushed with physiologic saline, medical and non-medical objects of differing composition and diameter were subjected to fragmentation by Holmium:YAG at powers of 18 and 30 W. In additional thermal experiments, 5,000 J was applied to differing volumes of 0.9% sodium chloride. Experiments were repeated ten times. With one exception (16 Ch silicon catheter) all medical objects were fragmented (latex urinary catheter, ureteral stents, and guidewires). Of non-medical objects (wood, steel, copper, graphite, and nylon) only copper wire was not amenable to laser dissection. These in vitro results were applied in two patients who presented with a pencil (wood and graphite) in the urethra or bladder. After Holmium:YAG laser fragmentation, the pencil could be removed by forceps each. Foreign objects in the urinary tract can be fragmented with a Holmium:YAG laser. When foreign bodies are too big for initial endoscopic extraction, the clinician should consider this technique as a reasonable and atraumatic option to avoid open surgery.

Characterization of Proteinuria in Dogue de Bordeaux Dogs, a Breed Predisposed to a Familial Glomerulonephropathy: A Retrospective Study.

PubMed

Lavoué, Rachel; Trumel, Catherine; Smets, Pascale M Y; Braun, Jean-Pierre; Aresu, Luca; Daminet, Sylvie; Concordet, Didier; Palanché, Florence; Peeters, Dominique

2015-01-01

Dogue de Bordeaux dog has been reported to be predisposed to a familial glomerulonephropathy that displays some morphological modifications reported in focal and segmental glomerulosclerosis. Prevalence of quantitatively abnormal renal proteinuria was recently reported to be 33% in this breed. The nature of the proteinuria was assessed by sodium dodecyl sulfate-agarose gel electrophoresis and determinations of urinary markers (urinary retinol-binding protein, urinary N-acetyl-β-glucosaminidase, urinary albumin and urinary immunoglobulin G) on stored specimens. Diagnostic performances of sodium dodecyl sulfate-agarose gel electrophoresis to identify dogs with elevated urinary biomarkers were assessed. Samples from 102 adult Dogue de Bordeaux dogs (47 non-proteinuric [urine protein-to-creatinine ratio ≤ 0.2], 20 borderline-proteinuric [0.2< urine protein-to-creatinine ratio ≤ 0.5] and 35 proteinuric dogs [urine protein-to-creatinine ratio >0.5]) were used, of which 2 were suffering from familial glomerulonephropathy. The electrophoretic protein patterns, for all but one proteinuric dog, were indicative of a glomerular origin and, in all dogs, the urinary albumin concentration related to creatinine concentration and the urinary immunoglobulin G concentration related to creatinine concentration were above the upper limit of the reference interval established for the breed. Sensitivity and specificity of sodium dodecyl sulfate-agarose gel electrophoresis identifying dogs with elevated urinary albumin concentration were 94% and 92%, respectively, while diagnostic performance of sodium dodecyl sulfate-agarose gel electrophoresis in detecting dogs with elevated urinary immunoglobulin G concentration yielded sensitivity and specificity of 90% and 74%, respectively. These results suggest that all proteinuric and some borderline-proteinuric Dogue de Bordeaux dogs likely have underlying glomerular lesions and that sodium dodecyl sulfate-agarose gel electrophoresis and urinary markers might be useful to screen dogs with borderline-proteinuria. Additional investigations are warranted to assess if these findings are related to the familial glomerulonephropathy.

An association between urinary cadmium and urinary stone disease in persons living in cadmium-contaminated villages in northwestern Thailand: A population study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Swaddiwudhipong, Witaya, E-mail: swaddi@hotmail.com; Mahasakpan, Pranee; Limpatanachote, Pisit

Excessive urinary calcium excretion is the major risk of urinary stone formation. Very few population studies have been performed to determine the relationship between environmental cadmium exposure and urinary stone disease. This population-based study examined an association between urinary cadmium excretion, a good biomarker of long-term cadmium exposure, and prevalence of urinary stones in persons aged 15 years and older, who lived in the 12 cadmium-contaminated villages in the Mae Sot District, Tak Province, northwestern Thailand. A total of 6748 persons were interviewed and screened for urinary cadmium and urinary stone disease in 2009. To test a correlation between urinarymore » excretion of cadmium and calcium, we measured urinary calcium content in 1492 persons, who lived in 3 villages randomly selected from the 12 contaminated villages. The rate of urinary stones significantly increased from 4.3% among persons in the lowest quartile of urinary cadmium to 11.3% in the highest quartile. An increase in stone prevalence with increasing urinary cadmium levels was similarly observed in both genders. Multiple logistic regression analysis revealed a positive association between urinary cadmium levels and stone prevalence, after adjusting for other co-variables. The urinary calcium excretion significantly increased with increasing urinary cadmium levels in both genders, after adjusting for other co-variables. Elevated calciuria induced by cadmium might increase the risk of urinary stone formation in this environmentally exposed population. - Research highlights: {yields} Excessive calciuria is the major risk of urinary stone formation. {yields} We examine cadmium-exposed persons for urinary cadmium, calcium, and stones. {yields} The rate of urinary stones increases with increasing urinary cadmium. {yields} Urinary calcium excretion increases with increasing urinary cadmium. {yields} Elevated calciuria induced by cadmium may increase the risk of urinary stones.« less

ELEMENTAL MERCURY IN COPPER, SILVER, AND GOLD ORES: AN UNEXPECTED CONTRIBUTION TO LAKE SUPERIOR SEDIMENTS WITH GLOBAL IMPLICATIONS

EPA Science Inventory

Mercury and copper inventories are low in central Lake Superior and increase markedly towards the Keweenaw Peninsula...where copper, mercury, and silver inventories are elevated and highly correlated. High copper, silver, and mercury inventories can be traced back to shoreline st...

The Impact of Hexametaphosphate, Orthophosphate, and Temperature on Copper Corrosion and Release

EPA Science Inventory

Excessive corrosion of copper plumbing can lead to elevated copper levels at consumer’s tap or pinhole leaks. Corrosion control solutions include pH adjustment or phosphate addition. Orthophosphate has been shown to reduce copper levels in some cases while the role of polyphosp...

Copper and Lead Corrosion in a Full Scale Home Plumbning system Simulation

EPA Science Inventory

The corrosion of household or premise plumbing materials (such as copper, brass, and solder) and the metal release that results from that corrosion can cause numerous problems, ranging from elevated lead and copper levels to blue water and copper pinhole leaks. If left untreate...

In long-term bedridden elderly patients with dietary copper deficiency, biochemical markers of bone resorption are increased with copper supplementation during 12 weeks.

PubMed

Kawada, Etsuo; Moridaira, Kazuaki; Itoh, Katsuhiko; Hoshino, Ayami; Tamura, Jun'ichi; Morita, Toyoho

2006-01-01

Although the effect of copper on bone has been tested in animals and healthy subjects, no studies concerning the effect of copper supplementation on bone metabolism in patients with copper deficiency have been reported because of the rarity of these patients. This study was conducted to investigate the effect of copper supplementation on bone metabolism in copper-deficient patients. This study included 10 patients (83.7 +/- 8.3 years) with dietary copper deficiency under long-term bed rest for more than 12 months. They had their diets supplemented with copper sulfate (3 mg/day) over 12 weeks in addition to their diet of only one kind of enteral food with a low concentration of copper. Serum copper and ceruloplasmin, urinary deoxypyridinoline (DPD) and collagen-type 1 N-telopeptide (NTX) (biomarkers of bone resorption), serum osteocalcin (OC) and bone-specific alkaline phosphatase (Bone ALP) (biomarkers of bone formation) were analyzed at baseline, 4 and 12 weeks after copper supplementation. DPD and NTX excretion were significantly increased 4 weeks after copper supplementation (p = 0.009 and p = 0.013, respectively). Serum bone ALP and OC were not significantly changed 12 weeks after copper supplementation (p = 0.051 and p = 0.594). In patients with nutritional copper deficiency, bone resorption markers are increased with copper supplementation. Copyright (c) 2006 S. Karger AG, Basel.

IL-6 does not predict current urolithiasis in stone formers.

PubMed

Rieder, Jocelyn M; Nisbet, Alan A; Lesser, Timothy; Franke, Ethan I; Brusky, John P; Parekh, Ashish R; Kaptein, John; Bellman, Gary C

2008-10-01

Interleukin-6 (IL-6), an inflammatory marker, has previously been found to be elevated in the urine of patients with urolithiasis. Oxalate and other stone precursors have been shown to increase IL-6 production in proximal tubular epithelial cells in vitro. We examined whether urinary IL-6 could be used as a screening test to determine current urolithiasis in individuals who are known to form urinary stones. Thirty-five adult patients with current urolithiasis demonstrated on imaging were enrolled in the study. Exclusion criteria included disease known to elevate IL-6. Each patient provided a pre-treatment urine specimen and one month after proven to be stone-free an additional urine specimen was obtained. The urinary IL-6/creatinine ratio was determined for both specimens and compared. Ten patients provided both specimens. The mean pre-operative urinary IL-6/creatinine ratio before the procedure was 1.63 pg/mL. The mean post procedure urinary IL-6/creatinine ratio after the patient was confirmed to be stone-free was 1.81 pg/mL. These were not significantly different (p=0.38). Preoperative urinary IL-6/creatinine ratio did not correlate to stone size (r=0.15) and no correlation was seen between time from treatment and stone free IL-6/creatinine ratio (r=0.48). Urinary IL-6 is not a good screening test for current urolithiasis in stone-forming individuals. It is elevated whether the stone is present or not.

The effects of CaEDTA injection on lead, zinc, copper and ALAD in erythrocyte, plasma and urine in lead-exposed workers: a 24-h observation.

PubMed

Aono, H; Araki, S

1984-01-01

To evaluate the effects of calcium disodium ethylenediamine tetraacetate (CaEDTA) on the concentrations of lead, zinc and copper in plasma, erythrocyte and urine, and the delta-aminolevulinic acid dehydratase (ALAD) activity in erythrocyte, we administered CaEDTA in 1-h intravenous infusion to ten male gun metal founders with blood-lead concentration of 39 to 64 micrograms/dl (mean 49 micrograms/dl). We found that the plasma concentration of lead, following a rapid rise within the first 3 h, fell temporarily to the level significantly lower than the initial level 19 h after start of the infusion. The plasma concentration of zinc fell to the minimal level 5 h after the infusion; and the erythrocyte concentration of zinc and the ALAD activity concurrently rose to the maximal level 5 h after the infusion. By contrast, no significant alteration was observed in the concentrations of copper in plasma and erythrocyte. The maximal level of urinary metal excretion was attained during the period between 1 and 2 h after start of CaEDTA infusion for lead; within 2 h for zinc; and between 2 and 4 h for copper. The urinary metal excretion returned to the initial level 14 to 24 h after infusion for zinc and copper; but lead excretion was still higher than the initial level during this period. The difference in the kinetics of the three metals following CaEDTA injection is discussed in the light of these findings.

Copper in the sediment and sea surface microlayer near a fallowed, open-net fish farm.

PubMed

Loucks, Ronald H; Smith, Ruth E; Fisher, Clyde V; Fisher, E Brian

2012-09-01

Sediment and sea surface microlayer samples near an open-net salmon farm in Nova Scotia, were analysed for copper. Copper is a constituent of the feed and is an active ingredient of anti-foulants. The salmon farm was placed in fallow after 15 years of production. Sampling was pursued over 27 months. Elevated copper concentrations in the sediments indicated the farm site as a source. Bubble flotation due to gas-emitting sediments from eutrophication is a likely process for accumulating copper in the sea surface microlayer at enriched concentrations. Elevated and enriched concentrations in the sea surface microlayer over distance from the farm site led, as a result of wind-drift, to an enlarged farm footprint. The levels of copper in both sediments and sea surface microlayer exceeded guidelines for protection of marine life. Over the 27 months period, copper levels persisted in the sediments and decreased gradually in the sea surface microlayer. Copyright © 2012 Elsevier Ltd. All rights reserved.

The effects of copper on blood and biochemical parameters of rainbow trout (Oncorhynchus mykiss)

USGS Publications Warehouse

Dethloff, G.M.; Schlenk, D.; Khan, S.; Bailey, H.C.

1999-01-01

Metals are released into aquatic systems from many sources, often at sublethal concentrations. The effects of sublethal concentrations of metals on fish are not entirely understood. The objective of this study was to determine the hematological and biochemical effects of a range of copper concentrations (6.4, 16.0, 26.9 ??g Cu/L) on rainbow trout (Oncorhynchus mykiss) over a prolonged period of time. Trout were exposed to copper, and, at intervals of 3, 7, 14, and 21 days, selected parameters were evaluated. Hemoglobin, hematocrit, plasma glucose, and plasma cortisol levels were elevated in trout exposed to 26.9 ??g Cu/L at day 3 and then returned to levels comparable to control fish. Plasma protein and lactate levels were not significantly altered in trout from any copper treatment. Hepatic copper concentration and hepatic metallothionein mRNA expression were consistently elevated in trout exposed to 26.9 ??g Cu/L. Both of these parameters stabilized by day 3, with only hepatic copper concentration showing a further increase at day 21. Hepatic copper concentration and hepatic metallothionein mRNA expression appear to be robust indicators of copper exposure. Most blood-based parameters evaluated appear to be associated with a transitory, nonspecific stress response. The return of elevated hematological and biochemical parameters to control levels after 3 days and thestabilization of hepatic metallothionein mRNA expression and copper concentration over a similar time period suggested acclimation to dissolved copper at 26.9 ??g/L. Further analysis of the data on blood-based parameters indicated that certain parameters (hemoglobin, hematocrit, plasma glucose, plasma cortisol) may be useful in field monitoring.

Late onset of Wilson's disease in a family with genetic haemochromatosis.

PubMed

Dib, Nina; Valsesia, Emmanuelle; Malinge, Marie Claire; Mauras, Yves; Misrahi, Micheline; Calès, Paul

2006-01-01

We report the coexistence of Wilson's disease and genetic haemochromatosis in one family. The diagnosis of genetic haemochromatosis was established in a 52-year-old man. Among his siblings, one 57-year-old sister and one 55-year-old brother had decreased copper and ceruloplasmin levels in serum and increased urinary copper excretion. The sister shared the same human leucocyte antigen haplotypes and was homozygous for the HFE mutation C282Y, like the propositus. However, she had normal liver iron content and increased liver copper content. Her dietary copper intake was probably excessive. The association of Wilson's disease and genetic haemochromatosis is rare and has only been described twice. The onset of Wilson's disease after 50 years of age is rare; Wilson's disease should be considered in any patient with unexplained chronic liver disease; an excess in liver copper content might be induced by excessive dietary input in a susceptible individual.

COPPER RESEARCH UPDATE

EPA Science Inventory

This presentation provides an update and overview of new research results and remaining research needs with respect to copper corrosion control issues. The topics to be covered include: occurrence of elevated copper release in systems that meet the Action Level; impact of water c...

Multiple metals exposure in a small-scale artisanal gold mining community.

PubMed

Basu, Niladri; Nam, Dong-Ha; Kwansaa-Ansah, Edward; Renne, Elisha P; Nriagu, Jerome O

2011-04-01

Urinary metals were characterized in 57 male residents of a small-scale gold mining community in Ghana. Chromium and arsenic exceeded health guideline values for 52% and 34%, respectively, of all participants. About 10-40% of the participants had urinary levels of aluminum, copper, manganese, nickel, selenium, and zinc that fell outside the U.S. reference range. Exposures appear ubiquitous across the community as none of the elements were associated with occupation, age, and diet. Copyright © 2011 Elsevier Inc. All rights reserved.

The influence of season and living environment on children's urinary 1-hydroxypyrene levels in Ulaanbaatar, Mongolia.

PubMed

Chen, Yi-Ting; Huang, Yu-Kai; Luvsan, Munkh-Erdene; Gombojav, Enkhjargal; Ochir, Chimedsuren; Bulgan, Jargal; Chan, Chang-Chuan

2015-02-01

Heating indoor living environments elevates air pollution in Ulaanbaatar, Mongolia. This study was conducted to investigate the influence of season and living environment on children's urinary 1-hydroxypyrene (1-OHP) levels in Ulaanbaatar, Mongolia. Our study subjects were 320 children aged 11-15 years living in gers, brick houses and apartments, in ger and non-ger areas of Ulaanbaatar. Spot urine samples and questionnaires were collected three times from each subject in three seasons, September (warm) and December (cold) in 2011 and March (moderate) in 2012. Urinary 1-OHP was analyzed by high-performance liquid chromatography with fluorescent detection (HPLC/FLD). Generalized estimating equation (GEE) models were applied to estimate the seasonal and residential effects on 1-OHP levels, adjusting for demographic and environmental factors. Children's urinary 1-OHP levels showed significant seasonal differences with 0.30 ± 0.57 μmol/mol creatinine in cold season, 0.14 ± 0.12 μmol/mol creatinine in moderate season, and 0.14 ± 0.21 μmol/mol creatinine in warm season. After controlling confounding factors, the GEE model showed that season, living area, and housing type had significant influence on children's urinary 1-OHP levels. Urinary 1-OHP levels in the cold and moderate seasons were, respectively 2.13 and 1.37 times higher than the warm season. Urinary 1-OHP levels for children living in ger areas were 1.27 times higher than those living in non-ger areas. Children who lived in gers or brick houses had 1.58 and 1.34 times higher 1-OHP levels, respectively, compared with those living in apartments. Children's urinary 1-OHP levels were associated with either estimated NO2 or SO2 concentrations at their home addresses in Ulaanbaatar. Mongolian children's urinary 1-OHP levels were significantly elevated during the cold season, and for those living in ger areas, gers, or brick houses in Ulaanbaatar. Children's urinary 1-OHP levels were associated PAH co-pollutants SO2 and NO2, suggesting elevated 1-OHP levels may be attributable to PAH emissions from coal burning and traffic respectively, with indoor emissions from stoves further contributing to elevated 1-OHP in some children. Copyright © 2014 Elsevier Inc. All rights reserved.

Environmental Exposure to Arsenic, Lead, and Cadmium in People Living near Janghang Copper Smelter in Korea.

PubMed

Kim, Yong-Dae; Eom, Sang-Yong; Yim, Dong-Hyuk; Kim, In-Soo; Won, Hee-Kwan; Park, Choong-Hee; Kim, Guen-Bae; Yu, Seung-Do; Choi, Byung-Sun; Park, Jung-Duck; Kim, Heon

2016-04-01

Concentrations of heavy metals exceed safety thresholds in the soil near Janghang Copper Refinery, a smelter in Korea that operated from 1936 to 1989. This study was conducted to evaluate the level of exposure to toxic metals and the potential effect on health in people living near the smelter. The study included 572 adults living within 4 km of the smelter and compared them with 413 controls group of people living similar lifestyles in a rural area approximately 15 km from the smelter. Urinary arsenic (As) level did not decrease according to the distance from the smelter, regardless of gender and working history in smelters and mines. However, in subjects who had no occupational exposure to toxic metals, blood lead (Pb) and cadmium (Cd) and urinary Cd decreased according to the distance from the smelter, both in men and women. Additionally, the distance from the smelter was a determinant factor for a decrease of As, Pb, and Cd in multiple regression models, respectively. On the other hands, urinary Cd was a risk factor for renal tubular dysfunction in populations living near the smelter. These results suggest that Janghang copper smelter was a main contamination source of As, Pb, and Cd, and populations living near the smelter suffered some adverse health effects as a consequence. The local population should be advised to make efforts to reduce exposure to environmental contaminants, in order to minimize potential health effects, and to pay close attention to any health problems possibly related to toxic metal exposure.

Urine lipoarabinomannan glycan in HIV-negative patients with pulmonary tuberculosis correlates with disease severity.

PubMed

Paris, Luisa; Magni, Ruben; Zaidi, Fatima; Araujo, Robyn; Saini, Neal; Harpole, Michael; Coronel, Jorge; Kirwan, Daniela E; Steinberg, Hannah; Gilman, Robert H; Petricoin, Emanuel F; Nisini, Roberto; Luchini, Alessandra; Liotta, Lance

2017-12-13

An accurate urine test for pulmonary tuberculosis (TB), affecting 9.6 million patients worldwide, is critically needed for surveillance and treatment management. Past attempts failed to reliably detect the mycobacterial glycan antigen lipoarabinomannan (LAM), a marker of active TB, in HIV-negative, pulmonary TB-infected patients' urine (85% of 9.6 million patients). We apply a copper complex dye within a hydrogel nanocage that captures LAM with very high affinity, displacing interfering urine proteins. The technology was applied to study pretreatment urine from 48 Peruvian patients, all negative for HIV, with microbiologically confirmed active pulmonary TB. LAM was quantitatively measured in the urine with a sensitivity of >95% and a specificity of >80% ( n = 101) in a concentration range of 14 to 2000 picograms per milliliter, as compared to non-TB, healthy and diseased, age-matched controls (evaluated by receiver operating characteristic analysis; area under the curve, 0.95; 95% confidence interval, 0.9005 to 0.9957). Urinary LAM was elevated in patients with a higher mycobacterial burden ( n = 42), a higher proportion of weight loss ( n = 37), or cough ( n = 50). The technology can be configured in a variety of formats to detect a panel of previously undetectable very-low-abundance TB urinary analytes. Eight of nine patients who were smear-negative and culture-positive for TB tested positive for urinary LAM. This technology has broad implications for pulmonary TB screening, transmission control, and treatment management for HIV-negative patients. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

The Application of Orthophosphate to Reduce Elevated Copper Levels in a New Building with High DIC Water

EPA Science Inventory

Public water utilities in the United States are required to meet the 1991 Lead and Copper Rule action level of 1.3 mg/L for copper I drinking water. The effect of water chemistry on Cu(II) solubility has been studied, and drawing upon conclusions from this research , new copper ...

Excretion of Zinc and Copper Increases in Men during 3 Weeks of Bed Rest, with or without Artificial Gravity12

PubMed Central

Heacox, Hayley N; Gillman, Patricia L; Zwart, Sara R; Smith, Scott M

2017-01-01

Background: Zinc and copper have many physiologic functions and little or no functional storage capability, so persistent losses of either element present health concerns, especially during extended-duration space missions. Objectives: We evaluated the effects of short-term bed rest (BR), a spaceflight analog, on copper and zinc metabolism to better understand the role of these nutrients in human adaptation to (simulated) spaceflight. We also investigated the effect of artificial gravity on copper and zinc homeostasis. Methods: Zinc and copper balances were studied in 15 men [mean ± SD age: 29 ± 3 y; body mass index (in kg/m2): 26.4 ± 2.2] before, during, and after 21 d of head-down tilt BR, during which 8 of the participants were subjected to artificial gravity (AG) by centrifugation for 1 h/d. Control subjects were transferred onto the centrifuge but were not exposed to centrifugation. The study was conducted in a metabolic ward; all urine and feces were collected. Data were analyzed by 2-factor repeated-measures ANOVA. Results: Urinary zinc excretion values for control and AG groups were 33% and 14%, respectively, higher during BR than before BR, and fecal zinc excretion values for control and AG groups were 36% and 19%, respectively, higher during BR, resulting in 67% and 82% lower net zinc balances for controls and AG, respectively (both P < 0.01), despite lower nutrient intake during BR. Fecal copper values for control and AG groups were 40% and 33%, respectively, higher during BR than before BR (P < 0.01 for both). Urinary copper did not change during BR, but a 19% increase was observed after BR compared with before BR in the AG group (P < 0.05). Conclusions: The increased fecal excretion of copper and zinc by men during BR suggests that their absorption of these minerals from the diet was reduced, secondary to the release of minerals from bone and muscle. These findings highlight the importance of determining dietary requirements for astronauts on space missions and ensuring provision and intake of all nutrients. PMID:28490676

Excretion of Zinc and Copper Increases in Men during 3 Weeks of Bed Rest, with or without Artificial Gravity.

PubMed

Heacox, Hayley N; Gillman, Patricia L; Zwart, Sara R; Smith, Scott M

2017-06-01

Background: Zinc and copper have many physiologic functions and little or no functional storage capability, so persistent losses of either element present health concerns, especially during extended-duration space missions. Objectives: We evaluated the effects of short-term bed rest (BR), a spaceflight analog, on copper and zinc metabolism to better understand the role of these nutrients in human adaptation to (simulated) spaceflight. We also investigated the effect of artificial gravity on copper and zinc homeostasis. Methods: Zinc and copper balances were studied in 15 men [mean ± SD age: 29 ± 3 y; body mass index (in kg/m 2 ): 26.4 ± 2.2] before, during, and after 21 d of head-down tilt BR, during which 8 of the participants were subjected to artificial gravity (AG) by centrifugation for 1 h/d. Control subjects were transferred onto the centrifuge but were not exposed to centrifugation. The study was conducted in a metabolic ward; all urine and feces were collected. Data were analyzed by 2-factor repeated-measures ANOVA. Results: Urinary zinc excretion values for control and AG groups were 33% and 14%, respectively, higher during BR than before BR, and fecal zinc excretion values for control and AG groups were 36% and 19%, respectively, higher during BR, resulting in 67% and 82% lower net zinc balances for controls and AG, respectively (both P < 0.01), despite lower nutrient intake during BR. Fecal copper values for control and AG groups were 40% and 33%, respectively, higher during BR than before BR ( P < 0.01 for both). Urinary copper did not change during BR, but a 19% increase was observed after BR compared with before BR in the AG group ( P < 0.05). Conclusions: The increased fecal excretion of copper and zinc by men during BR suggests that their absorption of these minerals from the diet was reduced, secondary to the release of minerals from bone and muscle. These findings highlight the importance of determining dietary requirements for astronauts on space missions and ensuring provision and intake of all nutrients. © 2017 American Society for Nutrition.

Evolution of a Heavy Metal Homeostasis/Resistance Island Reflects Increasing Copper Stress in Enterobacteria

PubMed Central

Staehlin, Benjamin M.; Gibbons, John G.; Rokas, Antonis; O’Halloran, Thomas V.; Slot, Jason C.

2016-01-01

Copper homeostasis in bacteria is challenged by periodic elevation of copper levels in the environment, arising from both natural sources and human inputs. Several mechanisms have evolved to efflux copper from bacterial cells, including the cus (copper sensing copper efflux system), and pco (plasmid-borne copper resistance system) systems. The genes belonging to these two systems can be physically clustered in a Copper Homeostasis and Silver Resistance Island (CHASRI) on both plasmids and chromosomes in Enterobacteria. Increasing use of copper in agricultural and industrial applications raises questions about the role of human activity in the evolution of novel copper resistance mechanisms. Here we present evidence that CHASRI emerged and diversified in response to copper deposition across aerobic and anaerobic environments. An analysis of diversification rates and a molecular clock model suggest that CHASRI experienced repeated episodes of elevated diversification that could correspond to peaks in human copper production. Phylogenetic analyses suggest that CHASRI originated in a relative of Enterobacter cloacae as the ultimate product of sequential assembly of several pre-existing two-gene modules. Once assembled, CHASRI dispersed via horizontal gene transfer within Enterobacteriaceae and also to certain members of Shewanellaceae, where the original pco module was replaced by a divergent pco homolog. Analyses of copper stress mitigation suggest that CHASRI confers increased resistance aerobically, anaerobically, and during shifts between aerobic and anaerobic environments, which could explain its persistence in facultative anaerobes and emergent enteric pathogens. PMID:26893455

Validating the use of embryonic fish otoliths as recorders of sublethal exposure to copper in estuarine sediments.

PubMed

Barbee, Nicole C; Greig, Alan; Swearer, Stephen E

2013-07-01

In this study we explore the use of fish otoliths ('earbones') as a tool for detecting exposure to heavy metals in sediments. Because otoliths are metabolically inert and incorporate chemical impurities during growth, they can potentially provide a more permanent record of pollutant exposure history in aquatic environments than soft tissues. To validate this technique we cultured embryos of a native Australian fish, the common Galaxias (Galaxias maculatus), in the laboratory on sediments spiked with copper in a concentration gradient. Our aims were to test whether exposure to copper contaminated sediments is recorded in the otoliths of embryos and determine over what range in concentrations we can detect differences in exposure. We found elevated copper levels in otoliths of embryos exposed to high copper concentrations in sediments, suggesting that otoliths can be used as a tool to track a history of exposure to elevated copper levels in the environment. Copyright © 2013 Elsevier Ltd. All rights reserved.

Copper as a target for prostate cancer therapeutics: copper-ionophore pharmacology and altering systemic copper distribution.

PubMed

Denoyer, Delphine; Pearson, Helen B; Clatworthy, Sharnel A S; Smith, Zoe M; Francis, Paul S; Llanos, Roxana M; Volitakis, Irene; Phillips, Wayne A; Meggyesy, Peter M; Masaldan, Shashank; Cater, Michael A

2016-06-14

Copper-ionophores that elevate intracellular bioavailable copper display significant therapeutic utility against prostate cancer cells in vitro and in TRAMP (Transgenic Adenocarcinoma of Mouse Prostate) mice. However, the pharmacological basis for their anticancer activity remains unclear, despite impending clinical trails. Herein we show that intracellular copper levels in prostate cancer, evaluated in vitro and across disease progression in TRAMP mice, were not correlative with copper-ionophore activity and mirrored the normal levels observed in patient prostatectomy tissues (Gleason Score 7 & 9). TRAMP adenocarcinoma cells harbored markedly elevated oxidative stress and diminished glutathione (GSH)-mediated antioxidant capacity, which together conferred selective sensitivity to prooxidant ionophoric copper. Copper-ionophore treatments [CuII(gtsm), disulfiram & clioquinol] generated toxic levels of reactive oxygen species (ROS) in TRAMP adenocarcinoma cells, but not in normal mouse prostate epithelial cells (PrECs). Our results provide a basis for the pharmacological activity of copper-ionophores and suggest they are amendable for treatment of patients with prostate cancer. Additionally, recent in vitro and mouse xenograft studies have suggested an increased copper requirement by prostate cancer cells. We demonstrated that prostate adenocarcinoma development in TRAMP mice requires a functional supply of copper and is significantly impeded by altered systemic copper distribution. The presence of a mutant copper-transporting Atp7b protein (tx mutation: A4066G/Met1356Val) in TRAMP mice changed copper-integration into serum and caused a remarkable reduction in prostate cancer burden (64% reduction) and disease severity (grade), abrogating adenocarcinoma development. Implications for current clinical trials are discussed.

Copper as a target for prostate cancer therapeutics: copper-ionophore pharmacology and altering systemic copper distribution

PubMed Central

Denoyer, Delphine; Pearson, Helen B.; Clatworthy, Sharnel A.S.; Smith, Zoe M.; Francis, Paul S.; Llanos, Roxana M.; Volitakis, Irene; Phillips, Wayne A.; Meggyesy, Peter M.; Masaldan, Shashank; Cater, Michael A.

2016-01-01

Copper-ionophores that elevate intracellular bioavailable copper display significant therapeutic utility against prostate cancer cells in vitro and in TRAMP (Transgenic Adenocarcinoma of Mouse Prostate) mice. However, the pharmacological basis for their anticancer activity remains unclear, despite impending clinical trails. Herein we show that intracellular copper levels in prostate cancer, evaluated in vitro and across disease progression in TRAMP mice, were not correlative with copper-ionophore activity and mirrored the normal levels observed in patient prostatectomy tissues (Gleason Score 7 & 9). TRAMP adenocarcinoma cells harbored markedly elevated oxidative stress and diminished glutathione (GSH)-mediated antioxidant capacity, which together conferred selective sensitivity to prooxidant ionophoric copper. Copper-ionophore treatments [CuII(gtsm), disulfiram & clioquinol] generated toxic levels of reactive oxygen species (ROS) in TRAMP adenocarcinoma cells, but not in normal mouse prostate epithelial cells (PrECs). Our results provide a basis for the pharmacological activity of copper-ionophores and suggest they are amendable for treatment of patients with prostate cancer. Additionally, recent in vitro and mouse xenograft studies have suggested an increased copper requirement by prostate cancer cells. We demonstrated that prostate adenocarcinoma development in TRAMP mice requires a functional supply of copper and is significantly impeded by altered systemic copper distribution. The presence of a mutant copper-transporting Atp7b protein (tx mutation: A4066G/Met1356Val) in TRAMP mice changed copper-integration into serum and caused a remarkable reduction in prostate cancer burden (64% reduction) and disease severity (grade), abrogating adenocarcinoma development. Implications for current clinical trials are discussed. PMID:27175597

Bladder rupture caused by postpartum urinary retention.

PubMed

Dueñas-García, Omar Felipe; Rico, Hugo; Gorbea-Sanchez, Viridiana; Herrerias-Canedo, Tomas

2008-08-01

Postpartum bladder rupture is an uncommon surgical emergency and a diagnostic challenge. A primigravida delivered a healthy newborn without complications at 39.4 weeks of gestation. The patient was admitted 80 hours postpartum with abdominal pain, oliguria, hematuria, and pain that worsened during the previous 4 hours. An inserted Foley catheter drained only a small amount of urine, and serum creatinine was elevated (3.5 mg/dL). A laparotomy was performed and revealed a 10-cm hole in the urinary bladder. The bladder was repaired and the patient was discharged 15 days after surgery. The follow-up cystoscopy revealed adequate healing of the bladder. Urinary retention can lead to serious complications, including bladder rupture. Postpartum bladder rupture due to urinary retention should be ruled out if there is a history of abdominal pain, oliguria, and elevated of serum creatinine.

Fibroblast Growth Factor 23 Levels Associate with AKI and Death in Critical Illness.

PubMed

Leaf, David E; Jacob, Kirolos A; Srivastava, Anand; Chen, Margaret E; Christov, Marta; Jüppner, Harald; Sabbisetti, Venkata S; Martin, Aline; Wolf, Myles; Waikar, Sushrut S

2017-06-01

Elevated plasma levels of the osteocyte-derived hormone fibroblast growth factor 23 (FGF23) have emerged as a powerful biomarker of cardiovascular disease and death in patients with CKD. Whether elevated urinary or plasma FGF23 levels are prospectively associated with AKI and death in critically ill patients is unknown. We therefore conducted a prospective cohort study of 350 critically ill patients admitted to intensive care units at an academic medical center to investigate whether higher urinary FGF23 levels associate with the composite end point of AKI or in-hospital mortality (AKI/death). We measured urinary FGF23 levels within 24 hours of admission to the intensive care unit. In a subcohort ( n =131) we also measured plasma levels of FGF23, calcium, phosphate, parathyroid hormone, and vitamin D metabolites. Urinary and plasma FGF23 levels, but not other mineral metabolites, significantly associated with AKI/death. In multivariate analyses, patients in the highest compared with the lowest quartile of urinary FGF23 had a 3.9 greater odds (95% confidence interval, 1.6 to 9.5) of AKI/death. Higher urinary FGF23 levels also independently associated with greater hospital, 90-day, and 1-year mortality; longer length of stay; and several other important adverse outcomes. In conclusion, elevated FGF23 levels measured in the urine or plasma may be a promising novel biomarker of AKI, death, and other adverse outcomes in critically ill patients. Copyright © 2017 by the American Society of Nephrology.

Chemical composition and binary mixture of human urinary stones using FT-Raman spectroscopy method.

PubMed

Selvaraju, R; Raja, A; Thiruppathi, G

2013-10-01

In the present study the human urinary stones were observed in their different chemical compositions of calcium oxalate monohydrate, calcium oxalate dihydrate, calcium phosphate, struvite (magnesium ammonium phosphate), uric acid, cystine, oxammite (ammonium oxalate monohydrate), natroxalate (sodium oxalate), glushinkite (magnesium oxalate dihydrate) and moolooite (copper oxalate) were analyzed using Fourier Transform-Raman (FT-Raman) spectroscopy. For the quantitative analysis, various human urinary stone samples are used for ratios calculation of binary mixtures compositions such as COM/COD, HAP/COD, HAP/COD, Uric acid/COM, uric acid/COD and uric acid/HAP. The calibration curve is used for further analysis of binary mixture of human urinary stones. For the binary mixture calculation the various intensities bands at 1462 cm(-1) (I(COM)), 1473 cm(-1) (I(COD)), 961 cm(-1) (I(HAP)) and 1282 cm(-1) (I(UA)) were used. Copyright © 2013 Elsevier B.V. All rights reserved.

Genomic and Transcriptomic Analyses to Identify Pathways Involved in Nanoparticle Generation in the Ubiquitous Marine Bacterium Alteromonas macleodii Under Elevated Copper Conditions

NASA Astrophysics Data System (ADS)

Cusick, K. D.; Dale, J.; Little, B.; Cockrell, A.; Biffinger, J.

2016-02-01

Alteromonas macleodii is a ubiquitous marine bacterium that clusters by molecular analyses into two ecotypes: surface and deep-water. Our group isolated a marine bacterium from copper coupons that generates nanoparticles (NPs) at elevated copper concentrations. Sequencing of the 16S rRNA gene identified it as an A. macleodii strain. In phylogenetic analyses based on the gyrB gene, it clustered with other surface isolates; however, it formed a unique cluster separate from that of other surface isolates based on rpoB gene sequences. Copper is commonly employed as an antifouling agent on the hulls of ships, and so copper tolerance and NP generation is under investigation in this strain. The overall goals of this study were: (1) to determine if copper tolerance is the result of changes at the genetic or transcriptional level and (2) to identify the genes involved in NP formation. Sub-cultures were established from the initial isolate in which copper concentrations were increased in .25 mM increments through multiple generations. These sub-cultures were assayed for NP formation in seawater medium supplemented with 3-4 mM copper. Scanning electron microscopy revealed large aggregates of NPs on the exterior surface of all sub-cultures. Additionally, a portion of the cells in all sub-cultures displayed an elongated morphology in comparison to the wild-type. No NPs were observed in wild-type controls grown without the addition of increased copper. Metagenomic sequencing of natural populations of A. macleodii revealed extreme divergence in several large genomic regions whose content includes genes coding for exopolysaccharide production and metal resistance. High-throughput sequencing is being used to determine whether copper tolerance and NP generation is the result of genetic or transcriptional changes. These results will be extended to natural communities to gain insights into the role of bacterial NPs during conditions of elevated metal concentrations in coastal systems.

Proteome characterization of copper stress responses in the roots of sorghum

USDA-ARS?s Scientific Manuscript database

Copper (Cu) is an essential micronutrient for all living organisms, but at elevated concentrations, it is extremely toxic to plants and can inactivate and disturb protein structures. To explore the molecular changes involved in the copper stress response, a study was conducted using the roots of sor...

Control of New Copper Corrosion in High-Alkalinity Drinking Water using Orthophosphate - article

EPA Science Inventory

Research and field experience have shown that high-alkalinity waters can be associated with elevated copper levels in drinking water. The objective of this study was to document the application of orthophosphate to the distribution system of a building with a copper problem asso...

Copper-redox cycling by coumarin-di(2-picolyl)amine hybrid molecule leads to ROS-mediated DNA damage and apoptosis: A mechanism for cancer chemoprevention.

PubMed

Khan, Saman; Zafar, Atif; Naseem, Imrana

2018-06-25

Coumarin is an important bioactive pharmacophore. It is found in plants as a secondary metabolite and exhibits diverse pharmacological properties including anticancer effects against different malignancies. Therapeutic efficacy of coumarin derivatives depends on the pattern of substitution and conjugation with different moieties. Cancer cells contain elevated copper as compared to normal cells that plays a role in angiogenesis. Thus, targeting copper in malignant cells via copper chelators can serve as an attractive targeted anticancer strategy. Our previous efforts led to the synthesis of di(2-picolyl)amine-3(bromoacetyl)coumarin hybrid molecule (ligand-L) endowed with DNA/Cu(II) binding properties, and ROS generation ability in the presence of copper ions. In the present study, we aimed to validate copper-dependent cytotoxic action of ligand-L against malignant cells. For this, we used a cellular model system of copper (Cu) overloaded lymphocytes (CuOLs) to simulate malignancy-like condition. In CuOLs, lipid peroxidation/protein carbonylation, ROS generation, DNA fragmentation and apoptosis were investigated in the presence of ligand-L. Results showed that ligand-L-Cu(II) interaction leads to ROS generation, lipid peroxidation/protein carbonylation (oxidative stress parameters), DNA damage, up-regulation of p53 and mitochondrial-mediated apoptosis in treated lymphocytes. Further, pre-incubation with neocuproine (membrane permeable copper chelator) and ROS scavengers attenuated the DNA damage and apoptosis. These results suggest that cellular copper acts as molecular target for ligand-L to propagate redox cycling and generation of ROS via Fenton-like reaction leading to DNA damage and apoptosis. Further, we showed that ligand-L targets elevated copper in breast cancer MCF-7 and colon cancer HCT116 cells leading to a pro-oxidant inhibition of proliferation of cancer cells. In conclusion, we propose copper-dependent ROS-mediated mechanism for the cytotoxic action of ligand-L in malignant cells. Thus, targeting elevated copper represents an effective therapeutic strategy for selective cytotoxicity against malignant cells. Copyright © 2018 Elsevier B.V. All rights reserved.

Porphyrinuria in childhood autistic disorder: Implications for environmental toxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nataf, Robert; Skorupka, Corinne; Amet, Lorene

To address a possible environmental contribution to autism, we carried out a retrospective study on urinary porphyrin levels, a biomarker of environmental toxicity, in 269 children with neurodevelopmental and related disorders referred to a Paris clinic (2002-2004), including 106 with autistic disorder. Urinary porphyrin levels determined by high-performance liquid chromatography were compared between diagnostic groups including internal and external control groups. Coproporphyrin levels were elevated in children with autistic disorder relative to control groups. Elevation was maintained on normalization for age or to a control heme pathway metabolite (uroporphyrin) in the same samples. The elevation was significant (P < 0.001).more » Porphyrin levels were unchanged in Asperger's disorder, distinguishing it from autistic disorder. The atypical molecule precoproporphyrin, a specific indicator of heavy metal toxicity, was also elevated in autistic disorder (P < 0.001) but not significantly in Asperger's. A subgroup with autistic disorder was treated with oral dimercaptosuccinic acid (DMSA) with a view to heavy metal removal. Following DMSA there was a significant (P = 0.002) drop in urinary porphyrin excretion. These data implicate environmental toxicity in childhood autistic disorder.« less

Porphyrinuria in childhood autistic disorder: implications for environmental toxicity.

PubMed

Nataf, Robert; Skorupka, Corinne; Amet, Lorene; Lam, Alain; Springbett, Anthea; Lathe, Richard

2006-07-15

To address a possible environmental contribution to autism, we carried out a retrospective study on urinary porphyrin levels, a biomarker of environmental toxicity, in 269 children with neurodevelopmental and related disorders referred to a Paris clinic (2002-2004), including 106 with autistic disorder. Urinary porphyrin levels determined by high-performance liquid chromatography were compared between diagnostic groups including internal and external control groups. Coproporphyrin levels were elevated in children with autistic disorder relative to control groups. Elevation was maintained on normalization for age or to a control heme pathway metabolite (uroporphyrin) in the same samples. The elevation was significant (P < 0.001). Porphyrin levels were unchanged in Asperger's disorder, distinguishing it from autistic disorder. The atypical molecule precoproporphyrin, a specific indicator of heavy metal toxicity, was also elevated in autistic disorder (P < 0.001) but not significantly in Asperger's. A subgroup with autistic disorder was treated with oral dimercaptosuccinic acid (DMSA) with a view to heavy metal removal. Following DMSA there was a significant (P = 0.002) drop in urinary porphyrin excretion. These data implicate environmental toxicity in childhood autistic disorder.

Elevated urinary podocyte-derived extracellular microvesicles in renovascular hypertensive patients

PubMed Central

Kwon, Soon Hyo; Woollard, John R.; Saad, Ahmed; Garovic, Vesna D.; Zand, Ladan; Jordan, Kyra L.; Textor, Stephen C.

2017-01-01

ABSTRACT Background: An increased number of podocyte-derived extracellular vesicles (pEVs) may reflect podocyte injury in renal disease. Elevated glomerular pressure and other insults may injure podocytes, yet it remains unclear whether the numbers of pEVs are altered in hypertensive patients. We tested the hypothesis that urinary pEV levels would be elevated in patients with renovascular hypertension (RVH) compared with essential hypertension (EH) or healthy volunteers (HVs). Methods: We prospectively enrolled patients with EH (n = 30) or RVH (n = 31) to study renal blood flow (RBF) and cortical perfusion using multidetector computed tomography under controlled condition (regulated sodium intake and renin—angiotensin blockade). After isolation from urine samples, pEVs (nephrin and podocalyxin positive) were characterized by flow cytometry. Fourteen RVH patients were studied again 3 months after stenting or continued medical therapy. HVs (n = 15) served as controls. Results: The fraction of pEV among urinary EVs was elevated in RVH compared with HVs and EH (11.4 ± 6.4, 6.8 ± 3.4 and 6.3 ± 3.7%, respectively; P < 0.001) and remained unchanged after 3 additional months of therapy and after controlling for clinical parameters. However, eGFR- and age-adjusted pEV levels did not correlate with any clinical or renal parameters. Conclusions: In hypertensive patients under controlled conditions, urinary pEV levels are elevated in patients with RVH and low eGFR compared with patients with EH and relatively preserved renal function. These pEVs may reflect podocyte injury secondary to kidney damage, and their levels might represent a novel therapeutic target. PMID:27190371

Elevated urinary level of vitamin D-binding protein as a novel biomarker for diabetic nephropathy

PubMed Central

TIAN, XIAO-QIN; ZHAO, LI-MIN; GE, JIA-PU; ZHANG, YAN; XU, YAN-CHENG

2014-01-01

Improving the early prediction and detection of diabetic nephropathy (DN) remains a great challenge in disease management. The aim of this study was to evaluate the early detection power of urinary vitamin D-binding protein (VDBP) for the diagnosis of DN. Urine samples were obtained from 45 healthy volunteers and 105 diabetic patients with normoalbuminuria (DM group), microalbuminuria (DN1 group) and macroalbuminuria (DN2 group) (n=35 per group). The VDBP expression patterns in urine from patients and controls were quantified by western blot analysis. The excretion levels of urinary VDBP were quantified with enzyme-linked immunosorbent assay. The quantification results were obtained by correcting for creatinine expression and showed that urinary VDBP levels were significantly elevated in the patients of the DN1 and DN2 groups compared with those of the DM group and normal controls (1,011.33±325.30 and 1,406.34±239.66 compared with 466.54±213.63 and 125.48±98.27 ng/mg, respectively) (P<0.001). Receiver operating characteristic analysis of urinary VDBP levels for the diagnosis of DN rendered an optimum cut-off value of 552.243 ng/mg corresponding to 92.86% sensitivity and 85.00% specificity, which also showed an area under the ROC curve of 0.966. In conclusion, the findings of the present study suggest that urinary VDBP may be a potential biomarker for the early detection and prevention of DN. Further studies are required to examine the pathogenic mechanisms of elevated VDBP levels and their role in the diagnosis of DN. PMID:24396416

Bulk Nanocrystalline Metals: Review of the Current State of the Art and Future Opportunities for Copper and Copper Alloys

DTIC Science & Technology

2014-05-13

nanocrystalline materials using mechanical alloying, the alloy development and synthesis process for stabilizing these materials at elevated temperatures, and...the physical and mechanical properties of nanocrystalline materials with a focus throughout on nanocrystalline copper and a nanocrystalline Cu-Ta...approaches as well as experimental results for grain growth, grain boundary processes, and deformation mechanisms in nanocrystalline copper are

Elevated copper impairs hepatic nuclear receptor function in Wilson's disease

USDA-ARS?s Scientific Manuscript database

Wilson's disease (WD) is an autosomal recessive disorder that results in accumulation of copper in the liver as a consequence of mutations in the gene encoding the copper-transporting P-type ATPase (ATP7B). WD is a chronic liver disorder, and individuals with the disease present with a variety of co...

Leaf proteome characterization in the context of physiological and morphological changes in response to copper stress in sorghum

USDA-ARS?s Scientific Manuscript database

Copper (Cu) is an essential micronutrient required for the growth and development of plants. However, at elevated concentrations in soil, copper is very toxic to plant cells due to its inhibitory effects against many physiological and biochemical processes. In spite of its potential physiological an...

Slow intestinal transit contributes to elevate urinary p-cresol level in Italian autistic children.

PubMed

Gabriele, Stefano; Sacco, Roberto; Altieri, Laura; Neri, Cristina; Urbani, Andrea; Bravaccio, Carmela; Riccio, Maria Pia; Iovene, Maria Rosaria; Bombace, Francesca; De Magistris, Laura; Persico, Antonio M

2016-07-01

The uremic toxin p-cresol (4-methylphenol) is either of environmental origin or can be synthetized from tyrosine by cresol-producing bacteria present in the gut lumen. Elevated p-cresol amounts have been previously found in the urines of Italian and French autism spectrum disorder (ASD) children up until 8 years of age, and may be associated with autism severity or with the intensity of abnormal behaviors. This study aims to investigate the mechanism producing elevated urinary p-cresol in ASD. Urinary p-cresol levels were thus measured by High Performance Liquid Chromatography in a sample of 53 Italian ASD children assessed for (a) presence of Clostridium spp. strains in the gut by means of an in vitro fecal stool test and of Clostridium difficile-derived toxin A/B in the feces, (b) intestinal permeability using the lactulose/mannitol (LA/MA) test, (c) frequent use of antibiotics due to recurrent infections during the first 2 years of postnatal life, and (d) stool habits with the Bristol Stool Form Scale. Chronic constipation was the only variable significantly associated with total urinary p-cresol concentration (P < 0.05). No association was found with presence of Clostridium spp. in the gut flora (P = 0.92), augmented intestinal permeability (P = 0.18), or frequent use of antibiotics in early infancy (P = 0.47). No ASD child was found to carry C. difficile in the gut or to release toxin A/B in the feces. In conclusion, urinary p-cresol levels are elevated in young ASD children with increased intestinal transit time and chronic constipation. Autism Res 2016, 9: 752-759. © 2015 International Society for Autism Research, Wiley Periodicals, Inc. © 2015 International Society for Autism Research, Wiley Periodicals, Inc.

A Combined Ecological and Epidemiologic Investigation of Metals Exposure amongst Indigenous Peoples Near the Marlin Mine in Western Guatemala

PubMed Central

Basu, Niladri; Abare, Marce; Buchanan, Susan; Cryderman, Diana; Nam, Dong-Ha; Sirkin, Susannah; Schmitt, Stefan; Hu, Howard

2016-01-01

In August 2009 a combined epidemiological and ecological pilot study was conducted to investigate allegations of human rights abuses in the form of exposures to toxic metals experienced by mine workers and Indigenous Mam Mayan near the Marlin Mine in Guatemala. In the human study there were no differences in blood and urine metals when comparing five mine workers with eighteen non-mine workers, and there were no discernible relationships between metals exposures and self-reported health measures in any study group. On the other hand, individuals residing closest to the mine had significantly higher levels of certain metals (urinary mercury, copper, arsenic, zinc) when compared to those living further away. Levels of blood aluminum, manganese, and cobalt were elevated in comparison to established normal ranges in many individuals; however, there was no apparent relationship to proximity to the mine or occupation, and thus are of unclear significance. In the ecological study, several metals (aluminum, manganese, cobalt) were found significantly elevated in the river water and sediment sites directly below the mine when compared to sites elsewhere. When the results of the human and ecological results are combined, they suggest that exposures to certain metals may be elevated in sites near the mine but it is not clear if the current magnitude of these elevations poses a significant threat to health. The authors conclude that more robust studies are needed while parallel efforts to minimize the ecological and human impacts of mining proceed. This is critical particularly as the impact of the exposures found could be greatly magnified by expected increases in mining activity over time, synergistic toxicity between metals, and susceptibility for the young and those with pre-existing disease. PMID:20952048

Exposure to Pb, Cd, and As mixtures potentiates the production of oxidative stress precursors: 30-day, 90-day, and 180-day drinking water studies in rats.

PubMed

Whittaker, Margaret H; Wang, Gensheng; Chen, Xue-Qing; Lipsky, Michael; Smith, Donald; Gwiazda, Roberto; Fowler, Bruce A

2011-07-15

Exposure to chemical mixtures is a common and important determinant of toxicity and is of particular concern due to their appearance in sources of drinking water. Despite this, few in vivo mixture studies have been conducted to date to understand the health impact of chemical mixtures compared to single chemicals. Interactive effects of lead (Pb), cadmium (Cd) and arsenic (As) were evaluated in 30-, 90-, and 180-day factorial design drinking water studies in rats designed to test the hypothesis that ingestion of such mixtures at individual component Lowest-Observed-Effect-Levels (LOELs) results in increased levels of the pro-oxidant delta aminolevulinic acid (ALA), iron, and copper. LOEL levels of Pb, Cd, and As mixtures resulted in the increased presence of mediators of oxidative stress such as ALA, copper, and iron. ALA increases were followed by statistically significant increases in kidney copper in the 90- and 180-day studies. Statistical evidence of interaction was identified for six biologically relevant variables: blood delta aminolevulinic acid dehydratase (ALAD), kidney ALAD, urinary ALA, urinary iron, kidney iron, and kidney copper. The current investigations underscore the importance of considering interactive effects that common toxic agents such as Pb, Cd, and As may have upon one another at low-dose levels. The interactions between known toxic trace elements at biologically relevant concentrations shown here demonstrate a clear need to rigorously review methods by which national/international agencies assess health risks of chemicals, since exposures may commonly occur as complex mixtures. Copyright © 2011. Published by Elsevier Inc.

Urinary Angiotensinogen and Renin Excretion are Associated with Chronic Kidney Disease.

PubMed

Juretzko, Annett; Steinbach, Antje; Hannemann, Anke; Endlich, Karlhans; Endlich, Nicole; Friedrich, Nele; Lendeckel, Uwe; Stracke, Sylvia; Rettig, Rainer

2017-01-01

Several studies sought to identify new biomarkers for chronic kidney disease (CKD). As the renal renin-angiotensin system is activated in CKD, urinary angiotensinogen or renin excretion may be suitable candidates. We tested whether urinary angiotensinogen or renin excretion is elevated in CKD and whether these parameters are associated with estimated glomerular filtration rate (eGFR). We further tested whether urinary angiotensinogen or renin excretion may convey additional information beyond that provided by albuminuria. We measured urinary and plasma angiotensinogen, renin, albumin and creatinine in 177 CKD patients from the Greifswald Approach to Individualized Medicine project and in 283 healthy controls from the Study of Health in Pomerania. The urinary excretion of specific proteins is given as protein-to-creatinine ratio. Receiver operating characteristic (ROC) curves, spearman correlation coefficients and linear regression models were calculated. Urinary angiotensinogen [2,511 (196-31,909) vs. 18.6 (8.3-44.0) pmol/g, *P<0.01] and renin excretion [0.311 (0.135-1.155) vs. 0.069 (0.045-0.148) pmol/g, *P<0.01] were significantly higher in CKD patients than in healthy controls. The area under the ROC curve was significantly larger when urinary angiotensinogen, renin and albumin excretion were combined than with urinary albumin excretion alone. Urinary angiotensinogen (ß-coefficient -2.405, standard error 0.117, P<0.01) and renin excretion (ß-coefficient -0.793, standard error 0.061, P<0.01) were inversely associated with eGFR. Adjustment for albuminuria, age, sex, systolic blood pressure and body mass index did not significantly affect the results. Urinary angiotensinogen and renin excretion are elevated in CKD patients. Both parameters are negatively associated with eGFR and these associations are independent of urinary albumin excretion. In CKD patients urinary angiotensinogen and renin excretion may convey additional information beyond that provided by albuminuria. © 2017 The Author(s)Published by S. Karger AG, Basel.

Elevated postvoid residual urine volume predicting recurrence of urinary tract infections in toilet-trained children.

PubMed

Chang, Shang-Jen; Tsai, Li-Ping; Hsu, Chun-Kai; Yang, Stephen S

2015-07-01

The aim of this study was to examine whether toilet-trained children with a history of febrile urinary tract infection (fUTI) and elevated postvoid residual (PVR) urine volume according to a recently published PVR nomogram were at greater risk of UTI recurrence. One month after recovery from febrile UTI, constipation was diagnosed according to the Rome III criteria, and lower urinary tract (LUT) function was evaluated with two sets of uroflowmetry and PVR by ultrasonography. For children aged ≦ 6 and ≧ 7 years, elevated PVR is defined as >20 and >10 ml, respectively. Cox proportion hazards regression was used to evaluate the risk factors for recurrence of UTI. Between 2005 and 2011, 60 children aged 6.5 ± 2.5 years (boy:girl ratio 27:33) were enrolled for analysis. Univariate analysis showed that recurrent febrile UTI was more commonly observed in children with elevated PVR [repetitive elevated PVR: hazard ratio (HR) 5.75, 95% confidence interval (CI) 1.41-23.4; one elevated PVR: HR 4.53, 95% CI 1.01-20.2] and high-grade vesicoureteral reflux (VUR; HR 4.53, 95% CI 1.46-14.07). Multivariate analysis showed that younger age (HR 1.37, 95% CI 1.03-1.82, p < 0.01) and elevated PVR (HR 2.88, 95% CI 1.44-5.73, p = 0.01) were significant, independent risk factors for recurrent febrile UTI--but not gender, presence of high-grade VUR and constipation. Elevated PVR defined by the new PVR nomogram predicted recurrent UTI in children with history of febrile UTI. Care should be taken to manage children with elevated PVR.

Oral administration of copper to rats leads to increased lymphocyte cellular DNA degradation by dietary polyphenols: implications for a cancer preventive mechanism.

PubMed

Khan, Husain Y; Zubair, Haseeb; Ullah, Mohd F; Ahmad, Aamir; Hadi, Sheikh M

2011-12-01

To account for the observed anticancer properties of plant polyphenols, we have earlier proposed a mechanism which involves the mobilization of endogenous copper ions by polyphenols leading to the generation of reactive oxygen species (ROS) that serve as proximal DNA cleaving agents and lead to cell death. Over the last decade we have proceeded to validate our hypothesis with considerable success. As a further confirmation of our hypothesis, in this paper we first show that oral administration of copper to rats leads to elevated copper levels in lymphocytes. When such lymphocytes with a copper overload were isolated and treated with polyphenols EGCG, genistein and resveratrol, an increased level of DNA breakage was observed. Further, preincubation of lymphocytes having elevated copper levels with the membrane permeable copper chelator neocuproine, resulted in inhibition of polyphenol induced DNA degradation. However, membrane impermeable chelator of copper bathocuproine, as well as iron and zinc chelators were ineffective in causing such inhibition in DNA breakage, confirming the involvement of endogenous copper in polyphenol induced cellular DNA degradation. It is well established that serum and tissue concentrations of copper are greatly increased in various malignancies. In view of this fact, the present results further confirm our earlier findings and strengthen our hypothesis that an important anticancer mechanism of plant polyphenols could be the mobilization of intracellular copper leading to ROS-mediated cellular DNA breakage. In this context, it may be noted that cancer cells are under considerable oxidative stress and increasing such stress to cytotoxic levels could be a successful anticancer approach.

The Critical Importance of Urinary Concentrating Ability in the Generation of Urinary Carbon Dioxide Tension

PubMed Central

Arruda, Jose A. L.; Nascimento, Luiz; Mehta, Pradeep K.; Rademacher, Donald R.; Sehy, John T.; Westenfelder, Christof; Kurtzman, Neil A.

1977-01-01

Measurement of urine to blood (U-B) carbon dioxide tension (PCO2) gradient during alkalinization of the urine has been suggested to assess distal H+ secretion. A fact that has not been considered in previous studies dealing with urinary PCO2 is that dissolution of HCO3 in water results in elevation of PCO2 which is directly proportional to the HCO3 concentration. To investigate the interrelationship of urinary HCO3 and urinary acidification, we measured U-B PCO2 in (a) the presence of enhanced H+ secretion and decreased concentrating ability i.e., chronic renal failure (CRF), (b) animals with normal H+ secretion and decreased concentrating ability, Brattleboro (BB) rats, and (c) the presence of both impaired H+ secretion and concentrating ability (LiCl treatment and after release of unilateral ureteral obstruction). At moderately elevated plasma HCO3 levels (30-40 meq/liter), normal rats achieved a highly alkaline urine (urine pH > 7.8) and raised urine HCO3 concentration and U-B PCO2. At similar plasma HCO3 levels, BB rats had a much higher fractional water excretion and failed to raise urine pH, urine HCO3 concentration, and U-B PCO2 normally. At a very high plasma HCO3 (>50 meq/liter), BB rats raised urine pH, urine HCO3 concentration, and U-B PCO2 to the same levels seen in normals. CRF rats failed to raise urine pH, urine HCO3, and U-B PCO2 normally at moderately elevated plasma HCO3 levels; at very high plasma HCO3 levels, CRF rats achieved a highly alkaline urine but failed to raise U-B PCO2. Dogs and patients with CRF were also unable to raise urine pH, urine HCO3 concentration, and U-B PCO2 normally at moderately elevated plasma HCO3 levels. In rats, dogs, and man, U-B PCO2 was directly related to urine HCO3 concentration and inversely related to fractional water excretion. At moderately elevated plasma HCO3 levels, animals with a distal acidification defect failed to raise U-B PCO2; increasing the plasma HCO3 to very high levels resulted in a significant increase in urine HCO3 concentration and U-B PCO2. The observed urinary PCO2 was very close to the PCO2 which would be expected by simple dissolution of a comparable amount of HCO3 in water. These data demonstrate that, in highly alkaline urine, urinary PCO2 is largely determined by concentration of urinary HCO3 and cannot be used as solely indicating distal H+ secretion. PMID:893680

Hypertension increases urinary excretion of immunoglobulin G, ceruloplasmin and transferrin in normoalbuminuric patients with type 2 diabetes mellitus.

PubMed

Ohara, Nobumasa; Hanyu, Osamu; Hirayama, Satoshi; Nakagawa, Osamu; Aizawa, Yoshifusa; Ito, Seiki; Sone, Hirohito

2014-02-01

Increased urinary excretion of certain plasma proteins, such as immunoglobulin G (IgG), ceruloplasmin and transferrin, with different molecular radii of 55 Å or less and different isoelectric points have been reported to precede development of microalbuminuria in patients who have diabetes mellitus with hypertension. We examined how hypertension affects these urinary proteins in a diabetic state. Excretion of IgG, ceruloplasmin, transferrin, albumin, α2-macroglobulin with a large molecular radius of 88 Å and N-acetylglucosaminidase in first-morning urine samples were measured in normoalbuminuric patients (urinary albumin-to-creatinine ratio < 15 mg/g) with hypertension and nondiabetes mellitus (group hypertension, n = 32), type 2 diabetes mellitus and normotension (group diabetes mellitus, n = 52) and type 2 diabetes mellitus and hypertension (group Both, n =45), and in age-matched controls (n = 72). Urinary IgG, ceruloplasmin, transferrin, albumin and N-acetylglucosaminidase and estimated glomerular filtration rate (eGFR) were significantly elevated in groups diabetes mellitus and Both compared with controls. Furthermore, urinary IgG, ceruloplasmin and transferrin in group Both were significantly higher than those in group diabetes mellitus. These exhibited a positive and relatively strong association with eGFR compared with controls. No significant difference in urinary albumin or N-acetylglucosaminidase was found between the two diabetic groups. In contrast, group hypertension had elevated urinary transferrin without any changes in the other compounds. Urinary α2-macroglobulin did not differ among the four groups. These findings suggest that normoalbuminuric diabetic patients without hypertension have both glomerular hemodynamic changes such as increased intraglomerular hydraulic pressure and altered proximal tubules, and that hypertension increases intraglomerular hydraulic pressure. Increased urinary IgG, ceruloplasmin and transferrin may reflect an increase in intraglomerular hydraulic pressure.

Thermal behavior of copper processed by ECAP at elevated temperatures

NASA Astrophysics Data System (ADS)

Gonda, Viktor

2018-05-01

Large amount of strengthening can be achieved by equal channel angular pressing (ECAP), by the applied severe plastic deformation during the processing. For pure metals, this high strength is accompanied with low thermal stability due to the large activation energy for recrystallization. In the present paper, the chosen technological route was elevated temperature single pass ECAP processing of copper, and its effect on the thermal behavior during the restoration processes of the deformed samples was studied.

Isolating metal-tolerant bacteria capable of removing copper, chromium, and arsenic from treated wood

Treesearch

Carol A. Clausen

2000-01-01

Bioremediation of chromated copper arsenate-treated waste wood with one or more metal-tolerant bacteria is a potential method of naturally releasing metals from treated wood fibre. Sampling eight environments with elevated levels of copper, chromium, and arsenic resulted in the isolation of 28 bacteria with the capability of releasing one or more of the components from...

Metal Dyshomeostasis and Inflammation in Alzheimer's and Parkinson's Diseases: Possible Impact of Environmental Exposures

PubMed Central

Myhre, Oddvar; Utkilen, Hans; Duale, Nur; Brunborg, Gunnar; Hofer, Tim

2013-01-01

A dysregulated metal homeostasis is associated with both Alzheimer's (AD) and Parkinson's (PD) diseases; AD patients have decreased cortex and elevated serum copper levels along with extracellular amyloid-beta plaques containing copper, iron, and zinc. For AD, a putative hepcidin-mediated lowering of cortex copper mechanism is suggested. An age-related mild chronic inflammation and/or elevated intracellular iron can trigger hepcidin production followed by its binding to ferroportin which is the only neuronal iron exporter, thereby subjecting it to lysosomal degradation. Subsequently raised neuronal iron levels can induce translation of the ferroportin assisting and copper binding amyloid precursor protein (APP); constitutive APP transmembrane passage lowers the copper pool which is important for many enzymes. Using in silico gene expression analyses, we here show significantly decreased expression of copper-dependent enzymes in AD brain and metallothioneins were upregulated in both diseases. Although few AD exposure risk factors are known, AD-related tauopathies can result from cyanobacterial microcystin and β-methylamino-L-alanine (BMAA) intake. Several environmental exposures may represent risk factors for PD; for this disease neurodegeneration is likely to involve mitochondrial dysfunction, microglial activation, and neuroinflammation. Administration of metal chelators and anti-inflammatory agents could affect disease outcomes. PMID:23710288

Wilson disease - currently used anticopper therapy.

PubMed

Członkowska, Anna; Litwin, Tomasz

2017-01-01

Wilson disease (WD) is a genetic disorder of copper metabolism that can be treated successfully with pharmacologic treatment. Two groups of drugs are currently used: chelators (e.g., d-penicillamine and trientine), which increase urinary copper excretion, and zinc salts, which inhibit copper absorption in the digestive tract. The mechanisms of action lead to a negative copper balance, stopping pathologic accumulation of copper in the tissues and clearing affected organs of copper overload. Due to a lack of prospective clinical trials, the use of drugs depends mainly on center experience and the accessibility in different countries or regions. This chapter presents the different reports and recommendations regarding WD treatment. In addition to the different expert opinions on pharmacologic agents, there are a few axioms regarding WD treatment: treatment should start immediately after diagnosis, even in clinically presymptomatic cases; the patient should be treated for life, making compliance a key factor in treatment success; and the treatment should be monitored regularly via liver and hematologic tests, neurologic examination, and copper metabolism, modifying the treatment accordingly. Other drugs proposed for WD treatment (e.g., tetrathiomolybdate) are in clinical trials and lack current recommendations. Thus, only the currently available options for WD pharmacologic treatment are discussed. © 2017 Elsevier B.V. All rights reserved.

Intake of Trace Metals and the Risk of Incident Kidney Stones.

PubMed

Ferraro, Pietro Manuel; Gambaro, Giovanni; Curhan, Gary C; Taylor, Eric N

2018-06-01

The association between the intake of trace metals and the risk of incident stones has not been longitudinally investigated. We performed a prospective analysis of 193,551 participants in the Health Professionals Follow-up Study, and the Nurses' Health Study I and II. During a followup of 3,316,580 person-years there was a total of 6,576 incident stones. We used multivariate regression models to identify associations of the intake of zinc, iron, copper and manganese with the risk of stones. In a subset of participants with 24-hour urine collections we examined the association between the intake of trace metals and urine composition. After multivariate adjustment total and dietary intakes of zinc and iron were not significantly associated with incident stones. A higher intake of manganese was associated with a lower risk of stones. The pooled HR of the highest quintile of total manganese intake compared with the lowest intake was 0.82 (95% CI 0.68-0.98, p = 0.02). Total but not dietary copper intake was marginally associated with a higher risk of stones (pooled HR 1.14, 95% CI 1.02-1.28, p = 0.01). There were no statistically significant associations of the total intake of manganese and copper with urinary supersaturation. Zinc and iron intake was not associated with a risk of stones. Copper intake may be associated with a higher risk in some individuals. Higher total manganese intake was associated with a lower risk of stones but not with traditional 24-hour urinary composite markers of stone risk. Further research is needed to elucidate the mechanisms by which manganese may reduce kidney stone formation. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Changes in plasma and urinary nitrite after birth in premature infants at risk for necrotizing enterocolitis

PubMed Central

Pun, Priti; Jones, Jesica; Wolfe, Craig; Deming, Douglas D.; Power, Gordon G.; Blood, Arlin B.

2016-01-01

Background Plasma nitrite serves as a reservoir of nitric oxide (NO) bioactivity. Because nitrite ingestion is markedly lower in newborns than adults, we hypothesized plasma nitrite levels would be lower in newborns than in adults, and that infants diagnosed with necrotizing enterocolitis (NEC), a disease characterized by ischemia and bacterial invasion of intestinal walls, would have lower levels of circulating nitrite in the days prior to diagnosis. Methods Single blood and urine samples were collected from 9 term infants and 12 adults, 72 preterm infants every 5 d for 3 wk, and from 13 lambs before and after cord occlusion. Results Nitrite fell 50% relative to cord levels in the first day after birth; and within 15 min after cord occlusion in lambs. Urinary nitrite was higher in infants than adults. Plasma and urinary nitrite levels in infants who developed NEC were similar to those of preterm control infants on days 1 and 5, but significantly elevated at 15 and 20 d after birth. Conclusion Plasma nitrite falls dramatically at birth while newborn urinary nitrite levels are significantly greater than adults. Acute NEC is associated with elevated plasma and urinary nitrite levels. PMID:26539663

Nickel exposure is associated with the prevalence of type 2 diabetes in Chinese adults.

PubMed

Liu, Gang; Sun, Liang; Pan, An; Zhu, Mingjiang; Li, Zi; ZhenzhenWang, Zhenzhen; Liu, Xin; Ye, Xingwang; Li, Huaixing; Zheng, He; Ong, Choon Nam; Yin, Huiyong; Lin, Xu; Chen, Yan

2015-02-01

Nickel exposure can induce hyperglycaemia in rodents, but little is known about its association with abnormal glucose metabolism in humans. We aimed to investigate the association of nickel exposure with the prevalence of type 2 diabetes in Chinese adults. A total of 2115 non-institutionalized men and women aged 55 to 76 years from Beijing and Shanghai were included, and urinary nickel concentration was assessed by inductively coupled plasma mass spectroscopy. The prevalence of type 2 diabetes was compared across urinary nickel quartiles. Fasting plasma glucose, insulin, lipids, C-reactive protein and glycated haemoglobin A1c, as well as urinary albumin and creatinine were measured. The median concentration of urinary nickel was 3.63 mg/l (interquartile range: 2.29–5.89 mg/l), and the prevalence of diabetes was 35.3% (747 cases/2115 persons). Elevated levels of urinary nickel were associated with higher fasting glucose, glycated haemoglobin A1c, insulin and homeostatic model assessment of insulin resistance (all P<0.01). The odds ratios (95% confidence interval) for diabetes across the increasing urinary nickel quartiles were 1.27 (0.97–1.67), 1.78 (1.36–2.32) and 1.68 (1.29–2.20), respectively (referencing to 1.00), after multivariate adjustment including lifestyle factors, body mass index and family history of diabetes (P for trend <0.001). The association remained unchanged after further controlling for urinary creatinine and C-reactive protein (P for trend <0.001). Increased urinary nickel concentration is associated with elevated prevalence of type 2 diabetes in humans.

Spontaneous abortions among nickel-exposed female refinery workers.

PubMed

Vaktskjold, Arild; Talykova, Ljudmila V; Chashchin, Valerij P; Odland, Jon Ø; Nieboer, Evert

2008-04-01

A case-control study to investigate whether women employed in nickel-exposed work areas in early pregnancy are at elevated risk of spontaneous abortion (SA). Data about pregnancy outcome and maternal factors were obtained about each delivery and SA from women in selected work places. Each pregnancy record was assigned a categorical nickel (Ni) exposure rating according to the women's occupations at pregnancy onset. The guidelines were the water-soluble Ni subfraction of the inhalable aerosol fraction obtained by personal monitoring for nickel- and copper-refinery workers or/and measured urinary-Ni concentrations. The unadjusted odds ratio for the association between the maternal exposure to Ni and an SA for Ni-exposed women was 1.38 (95% confidence interval: 1.04-1.84), and the adjusted was 1.14 (0.95-1.37). In conclusion, there was no statistical association between maternal occupational exposure to water-soluble Ni in early pregnancy and the risk of self-reported SA. The findings do not exclude the possibility of a weak excess risk, or a risk in the first weeks of pregnancy.

Human Urinary Composition Controls Antibacterial Activity of Siderocalin* ♦

PubMed Central

Shields-Cutler, Robin R.; Crowley, Jan R.; Hung, Chia S.; Stapleton, Ann E.; Aldrich, Courtney C.; Marschall, Jonas; Henderson, Jeffrey P.

2015-01-01

During Escherichia coli urinary tract infections, cells in the human urinary tract release the antimicrobial protein siderocalin (SCN; also known as lipocalin 2, neutrophil gelatinase-associated lipocalin/NGAL, or 24p3). SCN can interfere with E. coli iron acquisition by sequestering ferric iron complexes with enterobactin, the conserved E. coli siderophore. Here, we find that human urinary constituents can reverse this relationship, instead making enterobactin critical for overcoming SCN-mediated growth restriction. Urinary control of SCN activity exhibits wide ranging individual differences. We used these differences to identify elevated urinary pH and aryl metabolites as key biochemical host factors controlling urinary SCN activity. These aryl metabolites are well known products of intestinal microbial metabolism. Together, these results identify an innate antibacterial immune interaction that is critically dependent upon individualistic chemical features of human urine. PMID:25861985

Clinical Significance of Postvoid Residual Volume in Older Ambulatory Women

PubMed Central

Huang, Alison J.; Brown, Jeanette S.; Boyko, Edward J.; Moore, Elya E.; Scholes, Delia; Walter, Louise C.; Lin, Feng; Vittinghoff, Eric; Fihn, Stephan D.

2013-01-01

Objectives To examine the prevalence, natural history, and clinical significance of elevations in postvoid residual (PVR) volume in ambulatory older women Design Prospective cohort study Setting Group health plan in Washington state Participants 987 ambulatory women aged 55 to 75 years Measurements PVR was measured by bladder ultrasonography at baseline, 1 year, and 2 years. Participants completed questionnaires about urinary symptoms and provided urine samples for microbiologic evaluation. Results Of the 987 participants, 79% had a PVR <50 mL, 10% had a PVR of 50–99 mL, 6% had a PVR of 100–199 mL, and 5% had a PVR ≥200 mL at baseline. Of women with a PVR <50, 66% reported at least one urinary symptom at baseline. Of women with a PVR ≥200 mL, 27% reported no significant symptoms at baseline. In adjusted analyses using data from all study visits, women with a PVR ≥100 mL were more likely to report urinating >8 times during the day (OR=1.42, CI=1.07–1.87), and women with a PVR ≥200 mL were more likely to report weekly urgency incontinence (OR=1.50, CI=1.03–2.18), versus those with a PVR <50 mL. Elevated PVR was not associated with increased risk of stress incontinence, nocturnal frequency, or urinary tract infection in adjusted analyses. Forty-six percent of those with a PVR ≥200 mL and 63% of those with a PVR of 100–199 mL at baseline had a PVR <50 mL at 2 years. Conclusion Over 10% of ambulatory older women may have a PVR ≥100 mL associated with increased risk of some urinary symptoms, but many with elevated PVR are asymptomatic, and elevations in PVR frequently resolve within 2 years. Symptom-guided management of urinary symptoms may be more appropriate than PVR-guided management in this population. PMID:21806559

Talitrid amphipods (Crustacea) as biomonitors for copper and zinc

NASA Astrophysics Data System (ADS)

Rainbow, P. S.; Moore, P. G.; Watson, D.

1989-06-01

Data are presented on the copper and zinc concentrations of four talitrid amphipod species (standard dry weight 10 mg), i.e. Orchestia gammarellus (Pallas), O. mediterranea Costa, Talitrus saltator Montagu and Talorchestia deshayesii (Audouin), from 31 sites in S.W. Scotland, N. Wales and S.W. England. More limited data are also presented for cadmium in O. gammarellus (three sites) and T. deshayesii (one site). In S.W. Scotland, copper concentrations were raised significantly in O. gammarellus from Whithorn and Auchencairn (Solway) and Loch Long and Holy Loch (Clyde). In S.W. England, copper concentrations were highest at Restronguet Creek, Torpoint and Gannel (Cornwall). Samples of O. gammarellus from Islay (inner Hebrides) taken adjacent to the effluent outfalls of local whisky distilleries fell into two groups based on copper concentrations (presumably derived from copper stills), the higher copper levels deriving from the more productive distilleries. High copper levels were found in T. saltator and Tal. deshayesii from Dulas Bay (Wales). Zinc levels in O. gammarellus were high in Holy Loch and Auchencairn (Scotland), Gannel and Torpoint (England) but extremely elevated (as was Zn in O. mediterranea) at Restronguet Creek. Zinc was also high in T. saltator from Dulas Bay (Wales), but not in Tal. deshayesii. Cadmium levels in O. gammarellus from Kilve (Bristol Channel) were much raised. These differences (a) conform with expectations of elevated bioavailability of these metals from well researched areas (S.W. England & N. Wales), and (b) identify hitherto unappreciated areas of enrichment in S.W. Scotland. Orchestia gammarellus is put forward as a suitable biomonitor for copper and zinc in British coastal waters.

Turning tumor-promoting copper into an anti-cancer weapon via high-throughput chemistry.

PubMed

Wang, F; Jiao, P; Qi, M; Frezza, M; Dou, Q P; Yan, B

2010-01-01

Copper is an essential element for multiple biological processes. Its concentration is elevated to a very high level in cancer tissues for promoting cancer development through processes such as angiogenesis. Organic chelators of copper can passively reduce cellular copper and serve the role as inhibitors of angiogenesis. However, they can also actively attack cellular targets such as proteasome, which plays a critical role in cancer development and survival. The discovery of such molecules initially relied on a step by step synthesis followed by biological assays. Today high-throughput chemistry and high-throughput screening have significantly expedited the copper-binding molecules discovery to turn "cancer-promoting" copper into anti-cancer agents.

Copper modified carbon molecular sieves for selective oxygen removal

NASA Technical Reports Server (NTRS)

Sharma, Pramod K. (Inventor); Seshan, Panchalam K. (Inventor)

1992-01-01

Carbon molecular sieves modified by the incorporation of finely divided elemental copper useful for the selective sorption of oxygen at elevated temperatures. The carbon molecular sieves can be regenerated by reduction with hydrogen. The copper modified carbon molecular sieves are prepared by pyrolysis of a mixture of a copper-containing material and polyfunctional alcohol to form a sorbent precursor. The sorbent precursors are then heated and reduced to produce copper modified carbon molecular sieves. The copper modified carbon molecular sieves are useful for sorption of all concentrations of oxygen at temperatures up to about 200.degree. C. They are also useful for removal of trace amount of oxygen from gases at temperatures up to about 600.degree. C.

VAPOR PHASE MERCURY SORPTION BY ORGANIC SULFIDE MODIFIED BIMETALLIC IRON-COPPER NANOPARTICLE AGGREGATES

EPA Science Inventory

Novel organic sulfide modified bimetallic iron-copper nanoparticle aggregate sorbent materials have been synthesized for removing elemental mercury from vapor streams at elevated temperatures (120-140 °C). Silane based (disulfide silane and tetrasulfide silane) and alkyl sulfide ...

Investigating relationships between biomarkers of exposure and environmental copper and manganese levels in house dusts from a Portuguese industrial city.

PubMed

Reis, A P; Costa, S; Santos, I; Patinha, C; Noack, Y; Wragg, J; Cave, M; Sousa, A J

2015-08-01

This study reports on data obtained from a pilot survey focusing on house dust and toenail metal(loids) concentrations in residents living in the industrial city of Estarreja. The study design hereby described aims at investigating relationships between human toenails and both copper and manganese levels in settled house dusts. A total of 21 households and 30 individuals were recruited for the pilot study: 19 households corresponding to 27 residents living near the industrial complex, forming the exposed group, plus 2 households and 3 residents from residential areas with no anticipated environmental contaminants that were used for comparison. Factorial analysis was used for source identification purposes. Investigation on the potential influence of environmental factors over copper and manganese levels in the toenails was carried out via questionnaire data and multiple correspondence analysis. The results show that copper concentrations are more elevated in the indoor dusts, while manganese concentrations are more elevated in the outdoor dust samples. The geometrical relationships in the datasets suggest that the backyard soil is a probable source of manganese to the indoor dust. Copper and manganese contents in the toenail clippings are more elevated in children than in adults, but the difference between the two age groups is not statistically significant (p > 0.05). Investigation of environmental factors influencing the exposure-biomarker association indicates a probable relationship between manganese contents in indoor dust and manganese levels in toenail clippings, a result that is partially supported by the bioaccessibility estimates. However, for copper, no relationship was found between indoor dusts and the biomarkers of exposure.

Elevated Squamous Cell Carcinoma Antigen, Cytokeratin 19 Fragment, and Carcinoembryonic Antigen Levels in Diabetic Nephropathy

PubMed Central

Chen, Jianzhong; Zhang, Bin; Chen, Qingguang; Qiu, Yan; Luo, Qian; Gen, Yanna; Meng, Jiali

2017-01-01

Objective We aimed to explore whether squamous cell carcinoma antigen (SCC), cytokeratin 19 fragment (Cyfra21-1), neuron-specific enolase (NSE), and carcinoembryonic antigen (CEA) are elevated in diabetic nephropathy (DN) and the association between urinary albumin-to-creatinine ratio (UACR) and tumor markers in diabetic patients. Methods Nondialysis patients with diabetes (n = 261) and 90 healthy controls were enrolled. DN was defined as an UACR ≥ 30 mg/g in the absence of a urinary tract infection or other renal abnormalities. Results Patients with DN had significantly higher serum SCC, Cyfra21-1, and CEA levels than those with normoalbuminuria and healthy controls. The rates of positive SCC, Cyfra21-1, and CEA significantly increased with increasing urinary albumin excretion (all P for trend < 0.001). In contrast, NSE was not affected by DN. SCC, Cyfra21-1, and CEA were significantly and positively correlated with UACR. In logistic regression, after multivariable adjustment, increased UACR was associated with increased odds ratio of elevated tumor marker levels (all P for trend < 0.05). Conclusions Serum levels of SCC, Cyfra21-1, and CEA are markedly increased with increasing urinary albumin excretion, which affects the specificity for diagnosis for lung cancer. Appropriate interpretation of tumor markers in diabetic patients is mandatory to avoid unnecessary and even hazardous biopsies. PMID:28744310

Elevated CO2 levels affects the concentrations of copper and cadmium in crops grown in soil contaminated with heavy metals under fully open-air field conditions.

PubMed

Guo, Hongyan; Zhu, Jianguo; Zhou, Hui; Sun, Yuanyuan; Yin, Ying; Pei, Daping; Ji, Rong; Wu, Jichun; Wang, Xiaorong

2011-08-15

Elevated CO(2) levels and the increase in heavy metals in soils through pollution are serious problems worldwide. Whether elevated CO(2) levels will affect plants grown in heavy-metal-polluted soil and thereby influence food quality and safety is not clear. Using a free-air CO(2) enrichment (FACE) system, we investigated the impacts of elevated atmospheric CO(2) on the concentrations of copper (Cu) or cadmium (Cd) in rice and wheat grown in soil with different concentrations of the metals in the soil. In the two-year study, elevated CO(2) levels led to lower Cu concentrations and higher Cd concentrations in shoots and grain of both rice and wheat grown in the respective contaminated soil. Elevated CO(2) levels slightly but significantly lowered the pH of the soil and led to changes in Cu and Cd fractionation in the soil. Our study indicates that elevated CO(2) alters the distribution of contaminant elements in soil and plants, thereby probably affecting food quality and safety.

Molecular Mediators Governing Iron-Copper Interactions

PubMed Central

Gulec, Sukru; Collins, James F.

2015-01-01

Given their similar physiochemical properties, it is a logical postulate that iron and copper metabolism are intertwined. Indeed, iron-copper interactions were first documented over a century ago, but the homeostatic effects of one on the other has not been elucidated at a molecular level to date. Recent experimental work has, however, begun to provide mechanistic insight into how copper influences iron metabolism. During iron deficiency, elevated copper levels are observed in the intestinal mucosa, liver, and blood. Copper accumulation and/or redistribution within enterocytes may influence iron transport, and high hepatic copper may enhance biosynthesis of a circulating ferroxidase, which potentiates iron release from stores. Moreover, emerging evidence has documented direct effects of copper on the expression and activity of the iron-regulatory hormone hepcidin. This review summarizes current experimental work in this field, with a focus on molecular aspects of iron-copper interplay and how these interactions relate to various disease states. PMID:24995690

Effect of thiomolybdate and ammonium molybdate in pregnant guinea pigs and their offspring.

PubMed

Howell, J M; Shunxiang, Y; Gawthorne, J M

1993-09-01

Groups of eight guinea pigs and their offspring were given drinking water containing molybdenum as ammonium molybdate (AM) or thiomolybdate (TM) throughout and subsequent to pregnancy. All adult females had oestrous cycles and conception rates were unaffected. Fetal death was common in groups given the high dose of TM. The concentration of copper in liver was reduced in all groups at all ages except for pups killed at birth from animals given AM. The concentration of molybdenum was elevated in liver and kidney of all groups and was statistically significant in the majority. The concentration in plasma of copper, molybdenum and copper insoluble in trichloroacetic acid was elevated in all groups. Superoxide dismutase activity was significantly reduced in dams and six-week-old pups in which TM administration commenced before mating. Histological damage occurred in the pancreas of animals given AM or TM. The effects on the fetus and pancreas were considered to result from copper deficiency rather than molybdenum toxicity.

Neuronal differentiation is associated with a redox-regulated increase of copper flow to the secretory pathway

PubMed Central

Hatori, Yuta; Yan, Ye; Schmidt, Katharina; Furukawa, Eri; Hasan, Nesrin M.; Yang, Nan; Liu, Chin-Nung; Sockanathan, Shanthini; Lutsenko, Svetlana

2016-01-01

Brain development requires a fine-tuned copper homoeostasis. Copper deficiency or excess results in severe neuro-pathologies. We demonstrate that upon neuronal differentiation, cellular demand for copper increases, especially within the secretory pathway. Copper flow to this compartment is facilitated through transcriptional and metabolic regulation. Quantitative real-time imaging revealed a gradual change in the oxidation state of cytosolic glutathione upon neuronal differentiation. Transition from a broad range of redox states to a uniformly reducing cytosol facilitates reduction of the copper chaperone Atox1, liberating its metal-binding site. Concomitantly, expression of Atox1 and its partner, a copper transporter ATP7A, is upregulated. These events produce a higher flux of copper through the secretory pathway that balances copper in the cytosol and increases supply of the cofactor to copper-dependent enzymes, expression of which is elevated in differentiated neurons. Direct link between glutathione oxidation and copper compartmentalization allows for rapid metabolic adjustments essential for normal neuronal function. PMID:26879543

Neuronal differentiation is associated with a redox-regulated increase of copper flow to the secretory pathway.

PubMed

Hatori, Yuta; Yan, Ye; Schmidt, Katharina; Furukawa, Eri; Hasan, Nesrin M; Yang, Nan; Liu, Chin-Nung; Sockanathan, Shanthini; Lutsenko, Svetlana

2016-02-16

Brain development requires a fine-tuned copper homoeostasis. Copper deficiency or excess results in severe neuro-pathologies. We demonstrate that upon neuronal differentiation, cellular demand for copper increases, especially within the secretory pathway. Copper flow to this compartment is facilitated through transcriptional and metabolic regulation. Quantitative real-time imaging revealed a gradual change in the oxidation state of cytosolic glutathione upon neuronal differentiation. Transition from a broad range of redox states to a uniformly reducing cytosol facilitates reduction of the copper chaperone Atox1, liberating its metal-binding site. Concomitantly, expression of Atox1 and its partner, a copper transporter ATP7A, is upregulated. These events produce a higher flux of copper through the secretory pathway that balances copper in the cytosol and increases supply of the cofactor to copper-dependent enzymes, expression of which is elevated in differentiated neurons. Direct link between glutathione oxidation and copper compartmentalization allows for rapid metabolic adjustments essential for normal neuronal function.

Diagnostic value of potassium level in a spot urine sample as an index of 24-hour urinary potassium excretion in unselected patients hospitalized in a hypertension unit

PubMed Central

Symonides, Bartosz; Wojciechowska, Ewa; Gryglas, Adam; Gaciong, Zbigniew

2017-01-01

Background Primary hyperaldosteronism may be associated with elevated 24-hour urinary potassium excretion. We evaluated the diagnostic value of spot urine (SU) potassium as an index of 24-hour urinary potassium excretion. Methods We measured SU and 24-hour urinary collection potassium and creatinine in 382 patients. Correlations between SU and 24-hour collections were assessed for potassium levels and potassium/creatinine ratios. We used the PAHO formula to estimate 24-hour urinary potassium excretion based on SU potassium level. The agreement between estimated and measured 24-hour urinary potassium excretion was evaluated using the Bland-Altman method. To evaluate diagnostic performance of SU potassium, we calculated areas under the curve (AUC) for SU potassium/creatinine ratio and 24-hour urinary potassium excretion estimated using the PAHO formula. Results Strongest correlation between SU and 24-hour collection was found for potassium/creatinine ratio (r = 0.69, P<0.001). The PAHO formula underestimated 24-hour urinary potassium excretion by mean 8.3±18 mmol/d (95% limits of agreement -28 to +44 mmol/d). Diagnostic performance of SU potassium/creatinine ratio was borderline good only if 24-hour urinary potassium excretion was largely elevated (AUC 0.802 for 120 mmol K+/24 h) but poor with lower values (AUC 0.696 for 100 mmol K+/24 h, 0.636 for 80 mmol K+/24 h, 0.675 for 40 mmol K+/24 h). Diagnostic performance of 24-hour urinary potassium excretion estimated by the PAHO formula was excellent with values above 120 mmol/d and good with lower values (AUC 0.941 for 120 mmol K+/24 h, 0.819 for 100 mmol K+/24 h, 0.823 for 80 mmol K+/24 h, 0.836 for 40 mmol K+/24 h). Conclusions Spot urine potassium/creatinine ratio might be a marker of increased 24-hour urinary potassium excretion and a potentially useful screening test when reliable 24-hour urine collection is not available. The PAHO formula allowed estimation of the 24-hour urinary potassium excretion based on SU measurements with reasonable clinical accuracy. PMID:28662194

Microplastic Deformation of Submicrocrystalline Copper at Room and Elevated Temperatures

NASA Astrophysics Data System (ADS)

Dudarev, E. F.; Pochivalova, G. P.; Tabachenko, A. N.; Maletkina, T. Yu.; Skosyrskii, A. B.; Osipov, D. A.

2017-02-01

of investigations of submicrocrystalline copper subjected to cold rolling after abc pressing by methods of backscatter electron diffraction and x-ray diffraction analysis are presented. It is demonstrated that after such combined intensive plastic deformation, the submicrocrystalline structure with average grain-subgrain structure elements having sizes of 0.63 μm is formed with relative fraction of high-angle grain boundaries of 70% with texture typical for rolled copper. Results of investigation of microplastic deformation of copper with such structure at temperatures in the interval 295-473 K and with submicrocrystalline structure formed by cold rolling of coarse-grained copper are presented.

Diabetic cardiomyopathy is associated with defective myocellular copper regulation and both defects are rectified by divalent copper chelation

PubMed Central

2014-01-01

Background Heart disease is the leading cause of death in diabetic patients, and defective copper metabolism may play important roles in the pathogenesis of diabetic cardiomyopathy (DCM). The present study sought to determine how myocardial copper status and key copper-proteins might become impaired by diabetes, and how they respond to treatment with the Cu (II)-selective chelator triethylenetetramine (TETA) in DCM. Methods Experiments were performed in Wistar rats with streptozotocin (STZ)-induced diabetes with or without TETA treatment. Cardiac function was analyzed in isolated-perfused working hearts, and myocardial total copper content measured by particle-induced x-ray emission spectroscopy (PIXE) coupled with Rutherford backscattering spectrometry (RBS). Quantitative expression (mRNA and protein) and/or activity of key proteins that mediate LV-tissue-copper binding and transport, were analyzed by combined RT-qPCR, western blotting, immunofluorescence microscopy, and enzyme activity assays. Statistical analysis was performed using Student’s t-tests or ANOVA and p-values of < 0.05 have been considered significant. Results Left-ventricular (LV) copper levels and function were severely depressed in rats following 16-weeks’ diabetes, but both were unexpectedly normalized 8-weeks after treatment with TETA was instituted. Localized myocardial copper deficiency was accompanied by decreased expression and increased polymerization of the copper-responsive transition-metal-binding metallothionein proteins (MT1/MT2), consistent with impaired anti-oxidant defences and elevated susceptibility to pro-oxidant stress. Levels of the high-affinity copper transporter-1 (CTR1) were depressed in diabetes, consistent with impaired membrane copper uptake, and were not modified by TETA which, contrastingly, renormalized myocardial copper and increased levels and cell-membrane localization of the low-affinity copper transporter-2 (CTR2). Diabetes also lowered indexes of intracellular (IC) copper delivery via the copper chaperone for superoxide dismutase (CCS) to its target cuproenzyme, superoxide dismutase-1 (SOD1): this pathway was rectified by TETA treatment, which normalized SOD1 activity with consequent bolstering of anti-oxidant defenses. Furthermore, diabetes depressed levels of additional intracellular copper-transporting proteins, including antioxidant-protein-1 (ATOX1) and copper-transporting-ATPase-2 (ATP7B), whereas TETA elevated copper-transporting-ATPase-1 (ATP7A). Conclusions Myocardial copper deficiency and defective cellular copper transport/trafficking are revealed as key molecular defects underlying LV impairment in diabetes, and TETA-mediated restoration of copper regulation provides a potential new class of therapeutic molecules for DCM. PMID:24927960

Copper crystallite in carbon molecular sieves for selective oxygen removal

NASA Technical Reports Server (NTRS)

Sharma, Pramod K. (Inventor); Seshan, Panchalam K. (Inventor)

1993-01-01

Carbon molecular sieves modified by the incorporation of finely divided elemental copper useful for the selective sorption of oxygen at elevated temperatures. The carbon molecular sieves can be regenerated by reduction with hydrogen. The copper modified carbon molecular sieves are prepared by pyrolysis of a mixture of a copper-containing material and polyfurfuryl alcohol to form a sorbent precursor. The sorbent precursors are then heated and reduced to produce copper modified carbon molecular sieves. The copper modified carbon molecular sieves are useful for sorption of all concentrations of oxygen at temperatures up to about 200.degree. C. They are also useful for removal of trace amount of oxygen from gases at temperatures up to about 600.degree. C.

Genetic variation in metallothionein and metal-regulatory transcription factor 1 in relation to urinary cadmium, copper, and zinc

PubMed Central

Adams, Scott V.; Barrick, Brian; Freney, Emily P.; Shafer, Martin M.; Makar, Karen; Song, Xiaoling; Lampe, Johanna; Vilchis, Hugo; Ulery, April; Newcomb, Polly A.

2015-01-01

Background Metallothionein (MT) proteins play critical roles in the physiological handling of both essential (Cu and Zn) and toxic (Cd) metals. MT expression is regulated by metal-regulatory transcription factor 1 (MTF1). Hence, genetic variation in the MT gene family and MTF1 might therefore influence excretion of these metals. Methods 321 women were recruited in Seattle, WA and Las Cruces, NM and provided demographic information, urine samples for measurement of metal concentrations by mass spectrometry and creatinine, and blood or saliva for extraction of DNA. Forty-one single nucleotide polymorphisms (SNPs) within the MTF1 gene region and the region of chromosome 16 encoding the MT gene family were selected for genotyping in addition to an ancestry informative marker panel. Linear regression was used to estimate the association of SNPs with urinary Cd, Cu, and Zn, adjusted for age, urinary creatinine, smoking history, study site, and ancestry. Results Minor alleles of rs28366003 and rs10636 near the MT2A gene were associated with lower urinary Cd, Cu, and Zn. Minor alleles of rs8044719 and rs1599823, near MT1A and MT1B, were associated with lower urinary Cd and Zn, respectively. Minor alleles of rs4653329 in MTF1 was associated with lower urinary Cd. Conclusions These results suggest that genetic variation in the MT gene region and MTF1 influences urinary Cd, Cu, and Zn excretion. PMID:26529669

Porins Increase Copper Susceptibility of Mycobacterium tuberculosis

PubMed Central

Speer, Alexander; Rowland, Jennifer L.; Haeili, Mehri; Niederweis, Michael

2013-01-01

Copper resistance mechanisms are crucial for many pathogenic bacteria, including Mycobacterium tuberculosis, during infection because the innate immune system utilizes copper ions to kill bacterial intruders. Despite several studies detailing responses of mycobacteria to copper, the pathways by which copper ions cross the mycobacterial cell envelope are unknown. Deletion of porin genes in Mycobacterium smegmatis leads to a severe growth defect on trace copper medium but simultaneously increases tolerance for copper at elevated concentrations, indicating that porins mediate copper uptake across the outer membrane. Heterologous expression of the mycobacterial porin gene mspA reduced growth of M. tuberculosis in the presence of 2.5 μM copper by 40% and completely suppressed growth at 15 μM copper, while wild-type M. tuberculosis reached its normal cell density at that copper concentration. Moreover, the polyamine spermine, a known inhibitor of porin activity in Gram-negative bacteria, enhanced tolerance of M. tuberculosis for copper, suggesting that copper ions utilize endogenous outer membrane channel proteins of M. tuberculosis to gain access to interior cellular compartments. In summary, these findings highlight the outer membrane as the first barrier against copper ions and the role of porins in mediating copper uptake in M. smegmatis and M. tuberculosis. PMID:24013632

Essentiality of copper in humans.

PubMed

Uauy, R; Olivares, M; Gonzalez, M

1998-05-01

The biochemical basis for the essentiality of copper, the adequacy of the dietary copper supply, factors that condition deficiency, and the special conditions of copper nutriture in early infancy are reviewed. New biochemical and crystallographic evidence define copper as being necessary for structural and catalytic properties of cuproenzymes. Mechanisms responsible for the control of cuproprotein gene expression are not known in mammals; however, studies using yeast as a eukaryote model support the existence of a copper-dependent gene regulatory element. Diets in Western countries provide copper below or in the low range of the estimated safe and adequate daily dietary intake. Copper deficiency is usually the consequence of decreased copper stores at birth, inadequate dietary copper intake, poor absorption, elevated requirements induced by rapid growth, or increased copper losses. The most frequent clinical manifestations of copper deficiency are anemia, neutropenia, and bone abnormalities. Recommendations for dietary copper intake and total copper exposure, including that from potable water, should consider that copper is an essential nutrient with potential toxicity if the load exceeds tolerance. A range of safe intakes should be defined for the general population, including a lower safe intake and an upper safe intake, to prevent deficiency as well as toxicity for most of the population.

Ultra-deep oxidation and exotic copper formation at the late pliocene boyongan and bayugo porphyry copper-gold deposits, surigao, philippines: Geology, mineralogy, paleoaltimetry, and their implications for Geologic, physiographic, and tectonic controls

USGS Publications Warehouse

Braxton, D.P.; Cooke, D.R.; Ignacio, A.M.; Rye, R.O.; Waters, P.J.

2009-01-01

The Boyongan and Bayugo porphyry copper-gold deposits are part of an emerging belt of intrusion-centered gold-rich deposits in the Surigao district of northeast Mindanao, Philippines. Exhumation and weathering of these Late Pliocene-age deposits has led to the development of the world's deepest known porphyry oxidation profile at Boyongan (600 m), and yet only a modest (30-70 m) oxidation profile at adjacent Bayugo. Debris flows, volcanic rocks, and fluviolacustrine sediments accumulating in the actively extending Mainit graben subsequently covered the deposits and preserved the supergene profiles. At Boyongan and Bayugo, there is a vertical transition from shallower supergene copper oxide minerals (malachite + azurite + cuprite) to deeper sulfide-stable assemblages (chalcocite ?? hypogene sulfides). This transition provides a time-integrated proxy for the position of the water table at the base of the saturated zone during supergene oxidation. Contours of the elevation of the paleopotentiometric surface based on this min- eralogical transition show that the thickest portions of the unsaturated zone coincided with a silt-sand matrix diatreme breccia complex at Boyongan. Within the breccia complex, the thickness of the unsaturated zone approached 600 in, whereas outside the breccia complex (e.g., at Bayugo), the thickness averaged 50 m. Contours of the paleopotentiometric surface suggest that during weathering, groundwater flowed into the breccia complex from the north, south, and east, and exited along a high permeability zone to the west. The high relief (>550 m) on the elevation of the paleopotentiometric surface is consistent with an environment of high topographic relief, and the outflow zone to the west of the breccia complex probably reflects proximity to a steep scarp intersecting the western breccia complex margin. Stable isotope paleoaltimetry has enabled estimation of the elevation of the land surface, which further constrains the physiographic setting during supergene oxidation. Isotopic measurements of oxygen in supergene kaolinite from Boyongan suggest that local paleometeoric water involved in weathering had a ??180 composition of approximately -5.7 per mil. At the latitude of the southern Philippines, this value corresponds to Pleistocene rain water condensing at elevations between 750 and 1,050 m above contemporary sea level, providing a maximum estimate for the surface elevation during weathering of the porphyry systems. Physiographic reconstuctions suggest that the deep oxidation profile at Boyongan formed in an environment of high topographic relief immediately east of a prominent (>550 m) escarpment. The high permeability contrast between the breccia complex and the surrounding wall rocks, coupled with the proximity of the breccia complex to the escarpment, led to a depressed groundwater table and a vertically extensive unsaturated zone in the immediate vicinity of Boyongan. This thick vadose zone and the low hypogene pyrite/copper sulfide ratios (0.6) at Boyongan promoted in situ oxidation of copper sulfides with only modest (<200 m) supergene remobilization of copper. In contrast, higher hypogene pyrite/chalcopyrite ratios (2.3) at Bayugo led to greater acid production during weathering and more complete leaching of copper above the base of oxidation. This process promoted significant (600 m) lateral dispersion of copper down the paleohydraulic gradient into the diatreme breccia comple, ultimately leading to the formation of an exotic copper deposit. ?? 2009 Society of Economices Geologists, Inc.

Carbohydrate metabolism in erythrocytes of copper deficient rats.

PubMed

Brooks, S P J; Cockell, K A; Dawson, B A; Ratnayake, W M N; Lampi, B J; Belonje, B; Black, D B; Plouffe, L J

2003-11-01

Dietary copper deficiency is known to adversely affect the circulatory system of fructose-fed rats. Part of the problem may lie in the effect of copper deficiency on intermediary metabolism. To test this, weanling male Long-Evans rats were fed for 4 or 8 weeks on sucrose-based diets containing low or adequate copper content. Copper deficient rats had significantly lower plasma and tissue copper as well as lower plasma copper, zinc-superoxide dismutase activity. Copper deficient rats also had a significantly higher heart:body weight ratio when compared to pair-fed controls. Direct measurement of glycolysis and pentose phosphate pathway flux in erythrocytes using (13)C NMR showed no differences in carbon flux from glucose or fructose to pyruvate but a significantly higher flux through the lactate dehydrogenase locus in copper deficient rats (approximately 1.3 times, average of glucose and glucose + fructose measurements). Copper-deficient animals had significantly higher erythrocyte concentrations of glucose, fructose, glyceraldehyde 3-phosphate and NAD(+). Liver metabolite levels were also affected by copper deficiency being elevated in glycogen and fructose 1-phosphate content. The results show small changes in carbohydrate metabolism of copper deficient rats.

Hypertrophic osteoarthropathy, spider naevi and oestrogen hyperexcretion associated with adenocarcinoma.

PubMed Central

Brear, S. G.; Edwards, J. D.; Rademaker, M.; Doyle, L.

1985-01-01

We describe two patients with hypertrophic osteoarthropathy, spider naevi and elevated 24 h urinary oestrogen excretion associated with an adenocarcinoma. In one of the patients, the spider naevi and the clinical signs of hypertrophic osteoarthropathy disappeared and the 24 h urinary oestrogen returned to normal following removal of the tumour. Images Figure 1 PMID:4059145

Cellulose gum and copper nanoparticles based hydrogel as antimicrobial agents against urinary tract infection (UTI) pathogens.

PubMed

Al-Enizi, Abdullah M; Ahamad, Tansir; Al-Hajji, Abdullah Baker; Ahmed, Jahangeer; Chaudhary, Anis Ahmad; Alshehri, Saad M

2018-04-01

In the present study, stable copper nanoparticles (CuNPs) were successfully prepared in the hydrogel matrix. The prepared nanocomposite (HCuNPs) was characterized via x-ray diffraction (XRD), electron microscopy (TEM), and energy-dispersive (EDX) and x-ray photoelectron spectroscopic (XPS) studies. The wide scan XPS spectra support the presence of C, N and O in neat hydrogel; while, the XPS spectra of HCuNPs demonstrate the presence of Cu along with C, N, and O elements. TEM studies show the formation of spherical shaped CuNPs in the size range from 7 to 12nm. The rheology results reveal that the storage modulus (G') of the HCuNPs was found to be higher than the loss modulus (G"). Additionally, the antibacterial activities and cytotoxic were carried out against urinary tract infection (UTI) microbes and HeLa (cervical) cells respectively. The antibacterial results reveal that HCuNPs composites show higher zone of inhibition against these pathogens then that of corresponding hydrogel matrix. The cytotoxic effects suggest that the prepared nanocomposite could be used as promising candidates for biomedical applications. Copyright © 2017 Elsevier B.V. All rights reserved.

Inert electrode containing metal oxides, copper and noble metal

DOEpatents

Ray, Siba P.; Woods, Robert W.; Dawless, Robert K.; Hosler, Robert B.

2001-01-01

A cermet composite material is made by treating at an elevated temperature a mixture comprising a compound of iron and a compound of at least one other metal, together with an alloy or mixture of copper and a noble metal. The alloy or mixture preferably comprises particles having an interior portion containing more copper than noble metal and an exterior portion containing more noble metal than copper. The noble metal is preferably silver. The cermet composite material preferably includes alloy phase portions and a ceramic phase portion. At least part of the ceramic phase portion preferably has a spinel structure.

Inert electrode containing metal oxides, copper and noble metal

DOEpatents

Ray, Siba P.; Woods, Robert W.; Dawless, Robert K.; Hosler, Robert B.

2000-01-01

A cermet composite material is made by treating at an elevated temperature a mixture comprising a compound of iron and a compound of at least one other metal, together with an alloy or mixture of copper and a noble metal. The alloy or mixture preferably comprises particles having an interior portion containing more copper than noble metal and an exterior portion containing more noble metal than copper. The noble metal is preferably silver. The cermet composite material preferably includes alloy phase portions and a ceramic phase portion. At least part of the ceramic phase portion preferably has a spinel structure.

Elevated urinary neutrophil gelatinase-associated lipocalcin after acute heart failure treatment is associated with worsening renal function and adverse events

PubMed Central

Collins, Sean P.; Hart, Kimberly W.; Lindsell, Christopher J.; Fermann, Gregory J.; Weintraub, Neal L.; Miller, Karen F.; Roll, Susan N.; Sperling, Matthew I.; Sawyer, Douglas B.; Storrow, Alan B.

2012-01-01

Aims Reliable detectors of worsening renal function (WRF) in Emergency Department (ED) patients with acute heart failure (AHF) are limited. We hypothesized that initial urinary neutrophil gelatinase-associated lipocalcin (NGAL) levels, and changes in urinary NGAL levels after initial ED AHF therapy, would be associated with WRF and adverse events. Methods and results Urinary NGAL upon ED presentation and 12–24 h after ED treatment was measured in a cohort of ED patients with AHF. NGAL was corrected for urinary creatinine (uCr). WRF was defined as RIFLE stages 1, 2, or 3, or a creatinine increase of ≥0.3 mg/dL. Patients were prospectively followed for 5- and 30-day adverse cardiovascular events. The 399 patients had a median age of 63 years, 50% were Caucasian, and 62% were male. Those with WRF at 72–96 h were more likely to have a higher initial NGAL value (71 vs. 32 ng NGAL/mg uCr) (P = 0.005), and a higher NGAL level at 12–24 h after ED therapy (107 vs. 25ng NGAL/mg uCr, P < 0.001). In a multivariable model, NGAL at 12–24 h remained a significant predictor of WRF (P = 0.012). Of all variables available 12–24 h after initial therapy, the only significant predictor of 30-day events was an elevated urinary NGAL level (P = 0.02). Conclusions Urinary NGAL levels determined 12–24 h after ED therapy are significantly associated with both WRF at 72–96 h and 30-day adverse events. This suggests that early management strategies may have an impact on subsequent WRF and outcomes. If confirmed, NGAL may have a role for guiding therapeutic decisions. PMID:22733980

Separation methods applicable to urinary creatine and creatinine.

PubMed

Smith-Palmer, Truis

2002-12-05

Urinary creatinine has been analyzed for many years as an indicator of glomerular filtration rate. More recently, interest in studying the uptake of creatine as a result of creatine supplementation, a practice increasingly common among bodybuilders and athletes, has lead to a need to measure urinary creatine concentrations. Creatine levels are of the same order of magnitude as creatinine levels when subjects have recently ingested creatine, while somewhat elevated urinary creatine concentrations in non-supplementing subjects can be an indication of a degenerative disease of the muscle. Urinary creatine and creatinine can be analyzed by HPLC using a variety of columns. Detection methods include absorption, fluorescence after post-column derivatization, and mass spectrometry, and some methods have been automated. Capillary zone electrophoresis and micellar electrokinetic capillary chromatography have also been used to analyze urinary creatine and creatinine. Creatine and creatinine have also been analyzed in serum and tissue using HPLC and CE, and many of these separations could also be applicable to urinary analysis.

Bioavailable copper modulates oxidative phosphorylation and growth of tumors

PubMed Central

Ishida, Seiko; Andreux, Pénélope; Poitry-Yamate, Carole; Auwerx, Johan; Hanahan, Douglas

2013-01-01

Copper is an essential trace element, the imbalances of which are associated with various pathological conditions, including cancer, albeit via largely undefined molecular and cellular mechanisms. Here we provide evidence that levels of bioavailable copper modulate tumor growth. Chronic exposure to elevated levels of copper in drinking water, corresponding to the maximum allowed in public water supplies, stimulated proliferation of cancer cells and de novo pancreatic tumor growth in mice. Conversely, reducing systemic copper levels with a chelating drug, clinically used to treat copper disorders, impaired both. Under such copper limitation, tumors displayed decreased activity of the copper-binding mitochondrial enzyme cytochrome c oxidase and reduced ATP levels, despite enhanced glycolysis, which was not accompanied by increased invasiveness of tumors. The antiproliferative effect of copper chelation was enhanced when combined with inhibitors of glycolysis. Interestingly, larger tumors contained less copper than smaller tumors and exhibited comparatively lower activity of cytochrome c oxidase and increased glucose uptake. These results establish copper as a tumor promoter and reveal that varying levels of copper serves to regulate oxidative phosphorylation in rapidly proliferating cancer cells inside solid tumors. Thus, activation of glycolysis in tumors may in part reflect insufficient copper bioavailability in the tumor microenvironment. PMID:24218578

Stabilization of Oxidized Copper Nanoclusters in Confined Spaces

DOE PAGES

Akter, Nusnin; Wang, Mengen; Zhong, Jian-Qiang; ...

2018-01-04

Copper is an important industrial catalyst. The ability to manipulate the oxidation state of copper clusters in a controlled way is critical to understanding structure–reactivity relations of copper catalysts at the molecular level. Experimentally, cupric oxide surfaces or even small domains can only be stabilized at elevated temperatures and in the presence of oxygen, as copper can be easily reduced under reaction conditions. Herein bilayer silica films grown on a metallic substrate are used to trap diluted copper oxide clusters. By combining in situ experiments with first principles calculations, it is found that the confined space created by the silicamore » film leads to an increase in the energy barrier for Cu diffusion. Dispersed copper atoms trapped by the silica film can be easily oxidized by surface oxygen chemisorbed on the metallic substrate, which results in the formation and stabilization of Cu 2+ cations.« less

A case of sleep apnea syndrome manifesting severe hypertension with high plasma norepinephrine levels.

PubMed

Makino, Shinya; Iwata, Masanobu; Fujiwara, Masayoshi; Ike, Shinpei; Tateyama, Hitone

2006-06-01

A 55-year-old female was admitted to our hospital with severe hypertension (274/140 mmHg). Endocrinological examination revealed that her plasma levels of norepinephrine (NE) was elevated with high levels of urinary NE, normetanephrine and vanillylmandelic acid (VMA), suggesting the presence of pheochromocytoma. However, neither computed tomography nor MIBG scintigraphy detected any catecholamine-producing tumor in or outside the adrenal glands. She was screened with full polysomnography because of heavy snoring, and the diagnosis of severe obstructive sleep apnea syndrome (OSAS) was made. She was treated with calcium channel blocker for three weeks, but severe hypertension persisted. After treatment with nasal continuous positive airway pressure (CPAP) was added, her blood pressure gradually lowered week by week. Concomitantly, the levels of plasma and urinary NE, urinary normetanephrine and urinary VMA were normalized following nasal CPAP therapy for 2 weeks. Additional treatments with alpha-adrenergic blocker further decreased her home blood pressure. After a year, she continued nasal CPAP therapy and her blood pressure was nearly below 160/100 mmHg. Urinary NE level was slightly above normal range and other catecholamines stayed within the normal range. This case shows that patients with OSAS could develop severe hypertension through elevated sympathetic tone, mimicking pheochromocytoma. Nasal CPAP therapy is recommended not only to improve hypertension and catecholamine excess but also to distinguish the condition from pheochromocytoma.

Distribution and Fate of Energetics on DoD Test and Training Ranges: Interim Report 5

DTIC Science & Technology

2005-04-01

aluminum, arsenic, and iron were naturally elevated (Ampleman et al. 2003). A cadmium concentration at 0.3 ppb was observed in one sample. Copper...copper concentration was twice the CCME criterion. Iron was also observed in the Shaver River sample at three times the CCME criterion. Concentrations...mainly in C-295, the first site visited. Copper and iron were found at high concentrations in almost all samples; however, only one or two samples showed

Restrained management of copper level enhances the antineoplastic activity of imatinib in vitro and in vivo.

PubMed

Hassan, Iftekhar; Khan, Azmat Ali; Aman, Shazia; Qamar, Wajhul; Ebaid, Hossam; Al-Tamimi, Jameel; Alhazza, Ibrahim M; Rady, Ahmed M

2018-01-26

The present study was designed to investigate if elevated copper level can be targeted to enhance the efficacy of a significant anticancer drug, imatinib (ITB). The antineoplastic activity of this drug was assessed in the HepG2, HEK-293, MCF-7 and MDA-MD-231 cells targeting elevated copper level as their common drug target. The cell lines were treated with the different doses of copper chloride (Cu II) and disulfiram (DSF) alone as well as in their combinations with the drug for 24 h in standard culture medium and conditions. The treated cells were subjected to various assays including MTT, PARP, p-53, caspase-7, caspase-3, LDH and single cell electrophoresis. The study shows that DSF and Cu (II) synergizes the anticancer activity of ITB to a significant extent in a dose-specific way as evidenced by the combinations treated groups. Furthermore, the same treatment strategy was employed in cancer-induced rats in which the combinations of ITB-DSF and ITB-Cu II showed enhanced antineoplastic activity as compared to ITB alone. However, DSF was more effective than Cu (II) as an adjuvant to the drug. Hence, restrained manipulation of copper level in tumor cells can orchestrate the redox and molecular dispositions inside the cells favoring the induction of apoptosis.

The Activity of Menkes Disease Protein ATP7A Is Essential for Redox Balance in Mitochondria.

PubMed

Bhattacharjee, Ashima; Yang, Haojun; Duffy, Megan; Robinson, Emily; Conrad-Antoville, Arianrhod; Lu, Ya-Wen; Capps, Tony; Braiterman, Lelita; Wolfgang, Michael; Murphy, Michael P; Yi, Ling; Kaler, Stephen G; Lutsenko, Svetlana; Ralle, Martina

2016-08-05

Copper-transporting ATPase ATP7A is essential for mammalian copper homeostasis. Loss of ATP7A activity is associated with fatal Menkes disease and various other pathologies. In cells, ATP7A inactivation disrupts copper transport from the cytosol into the secretory pathway. Using fibroblasts from Menkes disease patients and mouse 3T3-L1 cells with a CRISPR/Cas9-inactivated ATP7A, we demonstrate that ATP7A dysfunction is also damaging to mitochondrial redox balance. In these cells, copper accumulates in nuclei, cytosol, and mitochondria, causing distinct changes in their redox environment. Quantitative imaging of live cells using GRX1-roGFP2 and HyPer sensors reveals highest glutathione oxidation and elevation of H2O2 in mitochondria, whereas the redox environment of nuclei and the cytosol is much less affected. Decreasing the H2O2 levels in mitochondria with MitoQ does not prevent glutathione oxidation; i.e. elevated copper and not H2O2 is a primary cause of glutathione oxidation. Redox misbalance does not significantly affect mitochondrion morphology or the activity of respiratory complex IV but markedly increases cell sensitivity to even mild glutathione depletion, resulting in loss of cell viability. Thus, ATP7A activity protects mitochondria from excessive copper entry, which is deleterious to redox buffers. Mitochondrial redox misbalance could significantly contribute to pathologies associated with ATP7A inactivation in tissues with paradoxical accumulation of copper (i.e. renal epithelia). © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

The Activity of Menkes Disease Protein ATP7A Is Essential for Redox Balance in Mitochondria

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bhattacharjee, Ashima; Yang, Haojun; Duffy, Megan

Copper-transporting ATPase ATP7A is essential for mammalian copper homeostasis. Loss of ATP7A activity is associated with fatal Menkes disease and various other pathologies. In cells, ATP7A inactivation disrupts copper transport from the cytosol into the secretory pathway. Using fibroblasts from Menkes disease patients and mouse 3T3-L1 cells with a CRISPR/Cas9-inactivated ATP7A, we demonstrate that ATP7A dysfunction is also damaging to mitochondrial redox balance. In these cells, copper accumulates in nuclei, cytosol, and mitochondria, causing distinct changes in their redox environment. Quantitative imaging of live cells using GRX1-roGFP2 and HyPer sensors reveals highest glutathione oxidation and elevation of H2O2 in mitochondria,more » whereas the redox environment of nuclei and the cytosol is much less affected. Decreasing the H2O2 levels in mitochondria with MitoQ does not prevent glutathione oxidation; i.e. elevated copper and not H2O2 is a primary cause of glutathione oxidation. Redox misbalance does not significantly affect mitochondrion morphology or the activity of respiratory complex IV but markedly increases cell sensitivity to even mild glutathione depletion, resulting in loss of cell viability. Thus, ATP7A activity protects mitochondria from excessive copper entry, which is deleterious to redox buffers. Mitochondrial redox misbalance could significantly contribute to pathologies associated with ATP7A inactivation in tissues with paradoxical accumulation of copper (i.e. renal epithelia).« less

The Activity of Menkes Disease Protein ATP7A Is Essential for Redox Balance in Mitochondria*

PubMed Central

Bhattacharjee, Ashima; Yang, Haojun; Duffy, Megan; Robinson, Emily; Conrad-Antoville, Arianrhod; Lu, Ya-Wen; Capps, Tony; Braiterman, Lelita; Wolfgang, Michael; Murphy, Michael P.; Yi, Ling; Kaler, Stephen G.; Lutsenko, Svetlana; Ralle, Martina

2016-01-01

Copper-transporting ATPase ATP7A is essential for mammalian copper homeostasis. Loss of ATP7A activity is associated with fatal Menkes disease and various other pathologies. In cells, ATP7A inactivation disrupts copper transport from the cytosol into the secretory pathway. Using fibroblasts from Menkes disease patients and mouse 3T3-L1 cells with a CRISPR/Cas9-inactivated ATP7A, we demonstrate that ATP7A dysfunction is also damaging to mitochondrial redox balance. In these cells, copper accumulates in nuclei, cytosol, and mitochondria, causing distinct changes in their redox environment. Quantitative imaging of live cells using GRX1-roGFP2 and HyPer sensors reveals highest glutathione oxidation and elevation of H2O2 in mitochondria, whereas the redox environment of nuclei and the cytosol is much less affected. Decreasing the H2O2 levels in mitochondria with MitoQ does not prevent glutathione oxidation; i.e. elevated copper and not H2O2 is a primary cause of glutathione oxidation. Redox misbalance does not significantly affect mitochondrion morphology or the activity of respiratory complex IV but markedly increases cell sensitivity to even mild glutathione depletion, resulting in loss of cell viability. Thus, ATP7A activity protects mitochondria from excessive copper entry, which is deleterious to redox buffers. Mitochondrial redox misbalance could significantly contribute to pathologies associated with ATP7A inactivation in tissues with paradoxical accumulation of copper (i.e. renal epithelia). PMID:27226607

Genetic variation in metallothionein and metal-regulatory transcription factor 1 in relation to urinary cadmium, copper, and zinc

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adams, Scott V., E-mail: sadams@fhcrc.org; Barrick, Brian; Christopher, Emily P.

Background: Metallothionein (MT) proteins play critical roles in the physiological handling of both essential (Cu and Zn) and toxic (Cd) metals. MT expression is regulated by metal-regulatory transcription factor 1 (MTF1). Hence, genetic variation in the MT gene family and MTF1 might influence excretion of these metals. Methods: 321 women were recruited in Seattle, WA and Las Cruces, NM and provided demographic information, urine samples for measurement of metal concentrations by mass spectrometry and creatinine, and blood or saliva for extraction of DNA. Forty-one single nucleotide polymorphisms (SNPs) within the MTF1 gene region and the region of chromosome 16 encodingmore » the MT gene family were selected for genotyping in addition to an ancestry informative marker panel. Linear regression was used to estimate the association of SNPs with urinary Cd, Cu, and Zn, adjusted for age, urinary creatinine, smoking history, study site, and ancestry. Results: Minor alleles of rs28366003 and rs10636 near the MT2A gene were associated with lower urinary Cd, Cu, and Zn. Minor alleles of rs8044719 and rs1599823, near MT1A and MT1B, were associated with lower urinary Cd and Zn, respectively. Minor alleles of rs4653329 in MTF1 were associated with lower urinary Cd. Conclusions: These results suggest that genetic variation in the MT gene region and MTF1 influences urinary Cd, Cu, and Zn excretion. - Highlights: • Genetic variation in metallothionein (MT) genes was assessed in two diverse populations. • Single nucleotide polymorphisms (SNPs) in MT genes were associated with mean urinary Cd, Cu and Zn. • Genetic variation may influence biomarkers of exposure, and associations of exposure with health.« less

Industrial Tests to Modify Molten Copper Slag for Improvement of Copper Recovery

NASA Astrophysics Data System (ADS)

Guo, Zhengqi; Zhu, Deqing; Pan, Jian; Zhang, Feng; Yang, Congcong

2018-04-01

In this article, to improve the recovery of copper from copper slag by flotation process, industrial tests of the modification process involving addition of a composite additive into molten copper slag were conducted, and the modified slag was subjected to the flotation process to confirm the modification effect. The phase evolution of the slag in the modification process was revealed by thermodynamic calculations, x-ray diffraction, optical microscopy and scanning electron microscopy. The results show that more copper was transformed and enriched in copper sulfide phases. The magnetite content in the modified slag decreased, and that of "FeO" increased correspondingly, leading to a better fluidity of the molten slag, which improved the aggregation and growth of fine particles of the copper sulfide minerals. Closed-circuit flotation tests of the original and modified slags were conducted, and the results show that the copper recovery increased obviously from 69.15% to 73.38%, and the copper grade of concentrates was elevated slightly from 20.24% to 21.69%, further confirming that the industrial tests of the modification process were successful. Hence, the modification process has a bright future in industrial applications for enhancing the recovery of copper from the copper slag.

Process for removing copper in a recoverable form from solid scrap metal

DOEpatents

Hartman, Alan D.; Oden, Laurance L.; White, Jack C.

1995-01-01

A process for removing copper in a recoverable form from a copper/solid ferrous scrap metal mix is disclosed. The process begins by placing a copper/solid ferrous scrap metal mix into a reactor vessel. The atmosphere within the reactor vessel is purged with an inert gas or oxidizing while the reactor vessel is heated in the area of the copper/solid ferrous scrap metal mix to raise the temperature within the reactor vessel to a selected elevated temperature. Air is introduced into the reactor vessel and thereafter hydrogen chloride is introduced into the reactor vessel to obtain a desired air-hydrogen chloride mix. The air-hydrogen chloride mix is operable to form an oxidizing and chloridizing atmosphere which provides a protective oxide coating on the surface of the solid ferrous scrap metal in the mix and simultaneously oxidizes/chloridizes the copper in the mix to convert the copper to a copper monochloride gas for transport away from the solid ferrous scrap metal. After the copper is completely removed from the copper/solid ferrous scrap metal mix, the flows of air and hydrogen chloride are stopped and the copper monochloride gas is collected for conversion to a recoverable copper species.

Urinary Angiostatin - A Novel Putative Marker of Renal Pathology Chronicity in Lupus Nephritis*

PubMed Central

Wu, Tianfu; Du, Yong; Han, Jie; Singh, Sandeep; Xie, Chun; Guo, Yuyuan; Zhou, Xin J.; Ahn, Chul; Saxena, Ramesh; Mohan, Chandra

2013-01-01

There is a critical need to identify biomarkers for Systemic Lupus Erythematosus (SLE) which has a high prevalence of renal failure. When urine from patients with lupus nephritis was recently screened for the levels of ∼280 molecules using an exploratory array-based proteomic platform, elevated angiostatin levels were noted. Angiostatin is a bioactive fragment of plasminogen, and has been known to have modulatory function in angiogenesis and inflammation. The significant elevation in urinary angiostatin was next validated in an independent cohort of SLE patients (n = 100) using ELISA. Among patients with SLE, urine angiostatin was significantly increased in active SLE compared with inactive SLE, correlating well with the SLEDAI disease activity index and SLICC renal activity score (r = 0.66, p < 0.0001). ROC curve analysis further confirmed that urinary angiostatin had the capacity to discriminate patients with active SLE from those with inactive disease. Patients with Class IV lupus nephritis exhibited the highest levels of urinary angiostatin. Immunohistochemistry staining localized angiostatin expression to the renal tubular cells in these patients. Finally, when paired urine-kidney samples procured concurrently from patients with LN were next examined, urine angiostatin levels correlated strongly with the renal pathology chronicity index, but not with the activity index. Given that Class IV lupus nephritis and renal pathology chronicity changes forebode poor renal and patient survival, urinary angiostatin emerges as a novel noninvasive marker of renal disease in SLE. Longitudinal studies are in progress to further assess the disease-predictive potential of urinary angiostatin. PMID:23345539

DOE Office of Scientific and Technical Information (OSTI.GOV)

Akter, Nusnin; Wang, Mengen; Zhong, Jian-Qiang

Copper is an important industrial catalyst. The ability to manipulate the oxidation state of copper clusters in a controlled way is critical to understanding structure–reactivity relations of copper catalysts at the molecular level. Experimentally, cupric oxide surfaces or even small domains can only be stabilized at elevated temperatures and in the presence of oxygen, as copper can be easily reduced under reaction conditions. Herein bilayer silica films grown on a metallic substrate are used to trap diluted copper oxide clusters. By combining in situ experiments with first principles calculations, it is found that the confined space created by the silicamore » film leads to an increase in the energy barrier for Cu diffusion. Dispersed copper atoms trapped by the silica film can be easily oxidized by surface oxygen chemisorbed on the metallic substrate, which results in the formation and stabilization of Cu 2+ cations.« less

Multiple Elemental Exposures Amongst Workers at the Agbogbloshie Electronic Waste (E-Waste) Site in Ghana

PubMed Central

Srigboh, Roland Kofi; Basu, Niladri; Stephens, Judith; Asampong, Emmanuel; Perkins, Marie; Neitzel, Richard L.; Fobil, Julius

2016-01-01

Electronic waste (e-waste) recycling is growing worldwide and raising a number of environmental health concerns. One of the largest e-waste sites is Agbogbloshie (Ghana). While several toxic elements have been reported in Agbogbloshie’s environment, there is limited knowledge of human exposures there. The objectives of this study were to characterize exposures to several essential (copper, iron, manganese, selenium, zinc) and toxic (arsenic, cadmium, cobalt, chromium, mercury, nickel, lead) elements in the urine and blood of male workers (n=58) at Agbogbloshie, as well as females (n=11) working in activities that serve the site, and to relate these exposures to sociodemographic and occupational characteristics. The median number of years worked at the site was 5, and the average worker indicated being active in 6.8 tasks (of 9 key e-waste job categories). Additionally, we categorized four main e-waste activities (in brackets % of population self-reported main activity): dealing (22.4%), sorting (24.1%), dismantling (50%), and burning (3.4%) e-waste materials. Many blood and urinary elements (including essential ones) were within biomonitoring reference ranges. However, blood cadmium (1.2 ug/L median) and lead (6.4 ug/dl; 67% above U.S. CDC/NIOSH reference level), and urinary arsenic (38.3 ug/L; 39% above U.S. ATSDR value) levels were elevated compared to background populations elsewhere. Workers who burned e-waste tended to have the highest biomarker levels. The findings of this study contribute to a growing body of work at Agbogbloshie (and elsewhere) to document that individuals working within e-waste sites are exposed to a number of toxic elements, some at potentially concerning levels. PMID:27580259

Multiple elemental exposures amongst workers at the Agbogbloshie electronic waste (e-waste) site in Ghana.

PubMed

Srigboh, Roland Kofi; Basu, Niladri; Stephens, Judith; Asampong, Emmanuel; Perkins, Marie; Neitzel, Richard L; Fobil, Julius

2016-12-01

Electronic waste (e-waste) recycling is growing worldwide and raising a number of environmental health concerns. One of the largest e-waste sites is Agbogbloshie (Ghana). While several toxic elements have been reported in Agbogbloshie's environment, there is limited knowledge of human exposures there. The objectives of this study were to characterize exposures to several essential (copper, iron, manganese, selenium, zinc) and toxic (arsenic, cadmium, cobalt, chromium, mercury, nickel, lead) elements in the urine and blood of male workers (n = 58) at Agbogbloshie, as well as females (n = 11) working in activities that serve the site, and to relate these exposures to sociodemographic and occupational characteristics. The median number of years worked at the site was 5, and the average worker indicated being active in 6.8 tasks (of 9 key e-waste job categories). Additionally, we categorized four main e-waste activities (in brackets % of population self-reported main activity): dealing (22.4%), sorting (24.1%), dismantling (50%), and burning (3.4%) e-waste materials. Many blood and urinary elements (including essential ones) were within biomonitoring reference ranges. However, blood cadmium (1.2 μg/L median) and lead (6.4 μg/dl; 67% above U.S. CDC/NIOSH reference level), and urinary arsenic (38.3 μg/L; 39% above U.S. ATSDR value) levels were elevated compared to background populations elsewhere. Workers who burned e-waste tended to have the highest biomarker levels. The findings of this study contribute to a growing body of work at Agbogbloshie (and elsewhere) to document that individuals working within e-waste sites are exposed to a number of toxic elements, some at potentially concerning levels. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effect of Hygrophila spinosa in ethylene glycol induced nephrolithiasis in rats.

PubMed

Ingale, Kundan G; Thakurdesai, Prasad A; Vyawahare, Neeraj S

2012-01-01

Hygrophila spinosa (Acanthaceae) is traditionally used to treat urinary calculi. The present study aimed to evaluate the antiurolithiatic activity of methanolic extract of Hygrophila spinosa (Acanthaceae) in ethylene glycol induced nephrolithiasic rats. Methanolic extract of Hygrophila spinosa (HSME) (250 and 500 mg/ kg body weight) was administered orally to male Wistar albino rats. Ethylene glycol (EG) was used to induce nephrolithiasis. The parameters studied included water intake, urinary volume, urinary pH, urinary and kidney oxalate and calcium, urinary magnesium and serum uric acid. Ethylene glycol feeding resulted in hyperoxaluria as well as increased renal excretion of calcium and serum uric acid along with decreased excretion of urinary magnesium. Treatment with HSME significantly reduced the elevated urinary oxalate, urinary calcium and serum uric acid with increase in reduced urinary magnesium. Ethylene glycol feeding also resulted in increased levels of calcium and oxalate in kidney which was decreased after the treatment with HSME. The increased deposition of stone forming constituents in the kidneys of ethylene glycol treated rats was significantly lowered by treatment with HSME. The results indicate that the aerial parts of Hygrophila spinosa are endowed with antiurolithiatic activity, thereby justifying its traditional claim.

l-Arginine normalizes NOS activity and zinc-MT homeostasis in the kidney of mice chronically exposed to inorganic mercury.

PubMed

Piacenza, Francesco; Malavolta, Marco; Cipriano, Catia; Costarelli, Laura; Giacconi, Robertina; Muti, Elisa; Tesei, Silvia; Pierpaoli, Sara; Basso, Andrea; Bracci, Massimo; Bonacucina, Viviana; Santarelli, Lory; Mocchegiani, Eugenio

2009-09-28

Inorganic mercury (HgCl2) exposure provokes damage in many organs, especially kidney. Inducible nitric oxide synthase (iNOS) expression, total NOS activity and the profiles of zinc (Zn), copper (Cu) and Hg as well as their distribution when bound to specific intracellular proteins, including metallothioneins (MT), were studied during HgCl2 exposure and after l-arginine treatment in C57BL/6 mouse kidney. HgCl2 exposure modulates differently iNOS expression and NOS activity, increasing iNOS expression but, conversely, decreasing total NOS activity in the mouse kidney. Moreover, during Hg exposure an increased MT production occurs. The kidney damage leads to a loss of urinary proteins, increased plasma creatinine and high Zn mobilization with consequent increased urinary Zn excretion. l-arginine treatment recovers NOS activity and induces a normalization of MT induction, plasma creatinine values and urinary proteins excretion, suggesting that l-arginine may limit kidney damages by Hg exposure.

Early life low-level cadmium exposure is positively associated with increased oxidative stress

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kippler, Maria; Bakhtiar Hossain, Mohammad; Department of Laboratory Medicine, Section of Occupational and Environmental Medicine, Lund University, Lund

Environmental exposure to cadmium (Cd) is known to induce oxidative stress, a state of imbalance between the production of reactive oxygen species (ROS) and the ability to detoxify them, in adults. However, data are lacking on potential effects in early-life. We evaluated urinary concentrations of 8-oxo-7,8-dihydro-2 Prime -deoxyguanosine (8-oxodG), a recognized marker of oxidative DNA damage, in relation to Cd exposure in 96 predominantly breast-fed infants (11-17 weeks of age) in rural Bangladesh. Urinary 8-oxodG was measured using liquid chromatography tandem mass spectrometry and Cd in urine and breast milk by inductively coupled plasma mass spectrometry. Median concentration of 8-oxodGmore » was 3.9 nmol/L, urinary Cd 0.30 {mu}g/L, and breast-milk Cd 0.13 {mu}g/L. In linear regression analyses, urinary 8-oxodG was positively associated with Cd in both urine (p=0.00067) and breast milk (p=0.0021), and negatively associated with body weight (kg; p=0.0041). Adjustment for age, body weight, socio-economic status, urinary arsenic, as well as magnesium, calcium, and copper in breast milk did not change the association between Cd exposure and urinary 8-oxodG. These findings suggest that early-life low-level exposure to Cd via breast milk induces oxidative stress. Further studies are warranted to elucidate whether this oxidative stress is associated with impaired child health and development.« less

Copper Ion from Cu2O Crystal Induces AMPK-Mediated Autophagy via Superoxide in Endothelial Cells

PubMed Central

Seo, Youngsik; Cho, Young-Sik; Huh, Young-Duk; Park, Heonyong

2016-01-01

Copper is an essential element required for a variety of functions exerted by cuproproteins. An alteration of the copper level is associated with multiple pathological conditions including chronic ischemia, atherosclerosis and cancers. Therefore, copper homeostasis, maintained by a combination of two copper ions (Cu+ and Cu2+), is critical for health. However, less is known about which of the two copper ions is more toxic or functional in endothelial cells. Cubic-shaped Cu2O and CuO crystals were prepared to test the role of the two different ions, Cu+ and Cu2+, respectively. The Cu2O crystal was found to have an effect on cell death in endothelial cells whereas CuO had no effect. The Cu2O crystals appeared to induce p62 degradation, LC3 processing and an elevation of LC3 puncta, important processes for autophagy, but had no effect on apoptosis and necrosis. Cu2O crystals promote endothelial cell death via autophagy, elevate the level of reactive oxygen species such as superoxide and nitric oxide, and subsequently activate AMP-activated protein kinase (AMPK) through superoxide rather than nitric oxide. Consistently, the AMPK inhibitor Compound C was found to inhibit Cu2O-induced AMPK activation, p62 degradation, and LC3 processing. This study provides insight on the pathophysiologic function of Cu+ ions in the vascular system, where Cu+ induces autophagy while Cu2+ has no detected effect. PMID:26743904

CopZ from Bacillus subtilis interacts in vivo with a copper exporting CPx-type ATPase CopA.

PubMed

Radford, David S; Kihlken, Margaret A; Borrelly, Gilles P M; Harwood, Colin R; Le Brun, Nick E; Cavet, Jennifer S

2003-03-14

The structure of the hypothetical copper-metallochaperone CopZ from Bacillus subtilis and its predicted partner CopA have been studied but their respective contributions to copper export, -import, -sequestration and -supply are unknown. DeltacopA was hypersensitive to copper and contained more copper atoms cell(-1) than wild-type. Expression from the copA operator-promoter increased in elevated copper (not other metals), consistent with a role in copper export. A bacterial two-hybrid assay revealed in vivo interaction between CopZ and the N-terminal domain of CopA but not that of a related transporter, YvgW, involved in cadmium-resistance. Activity of copper-requiring cytochrome caa(3) oxidase was retained in deltacopZ and deltacopA. DeltacopZ was only slightly copper-hypersensitive but deltacopZ/deltacopA was more sensitive than deltacopA, implying some action of CopZ that is independent of CopA. Significantly, deltacopZ contained fewer copper atoms cell(-1) than wild-type under these conditions. CopZ makes a net contribution to copper sequestration and/or recycling exceeding any donation to CopA for export.

Rate and Regulation of Copper Transport by Human Copper Transporter 1 (hCTR1)*

PubMed Central

Maryon, Edward B.; Molloy, Shannon A.; Ivy, Kristin; Yu, Huijun; Kaplan, Jack H.

2013-01-01

Human copper transporter 1 (hCTR1) is a homotrimer of a 190-amino acid monomer having three transmembrane domains believed to form a pore for copper permeation through the plasma membrane. The hCTR1-mediated copper transport mechanism is not well understood, nor has any measurement been made of the rate at which copper ions are transported by hCTR1. In this study, we estimated the rate of copper transport by the hCTR1 trimer in cultured cells using 64Cu uptake assays and quantification of plasma membrane hCTR1. For endogenous hCTR1, we estimated a turnover number of about 10 ions/trimer/s. When overexpressed in HEK293 cells, a second transmembrane domain mutant of hCTR1 (H139R) had a 3-fold higher Km value and a 4-fold higher turnover number than WT. Truncations of the intracellular C-terminal tail and an AAA substitution of the putative metal-binding HCH C-terminal tripeptide (thought to be required for transport) also exhibited elevated transport rates and Km values when compared with WT hCTR1. Unlike WT hCTR1, H139R and the C-terminal mutants did not undergo regulatory endocytosis in elevated copper. hCTR1 mutants combining methionine substitutions that block transport (M150L,M154L) on the extracellular side of the pore and the high transport H139R or AAA intracellular side mutations exhibited the blocked transport of M150L,M154L, confirming that Cu+ first interacts with the methionines during permeation. Our results show that hCTR1 elements on the intracellular side of the hCTR1 pore, including the carboxyl tail, are not essential for permeation, but serve to regulate the rate of copper entry. PMID:23658018

Separation of sulfated urinary glycosaminoglycans by high-resolution electrophoresis for isotyping of mucopolysaccharidoses in Malaysia.

PubMed

Nor, Azimah; Zabedah, Md Yunus; Norsiah, Md Desa; Ngu, Lock Hock; Suhaila, Abd Rahman

2010-06-01

Mucopolysaccharidoses (MPS) are a group of inherited disorders caused by the deficiency of specific lysosomal enzymes involved in glycosaminoglycans (GAGs) degradation. Currently, there are 11 enzyme deficiencies resulting in seven distinct MPS clinical syndromes and their subtypes. Different MPS syndromes cannot be clearly distinguished clinically due to overlapping signs and symptoms. Measurement of GAGs content in urine and separation of GAGs using high-resolution electrophoresis (HRE) are very useful initial screening tests for isotyping of MPS before specific enzyme diagnostics. In this study, we measured total urinary GAGs by a method using dimethylmethylene blue (DMB), and followed by isolation and separation of GAGs using high resolution electrophoresis (HRE) technique. Of 760 urine samples analyzed, 40 have abnormal GAGs HRE patterns. Thirty-five of these 40 cases have elevated urinary GAGs levels as well. These abnormal HRE patterns could be classified into 4 patterns: Pattern A (elevated DS and HS; suggestive of MPS I, II or VII; 16 cases), Pattern B (elevated HS and CS; suggestive of MPS III; 17 cases), and Pattern C (elevated KS and CS; suggestive of MPS IV, 5 cases), and Pattern D (elevated DS; suggestive of MPS VI; 2 cases). Based on the GAGs HRE pattern and a few discriminating clinical signs, we performed selective enzymatic investigation in 16 cases. In all except one case with MPS VII, the enzymatic diagnosis correlated well with the provisional MPS type as suggested by the abnormal HRE pattern. Our results showed that GAGs HRE is a useful, inexpensive and practical first-line screening test when MPS is suspected clinically, and it provides an important guide to further enzymatic studies on a selective basis.

Morning pulse pressure is associated more strongly with elevated albuminuria than systolic blood pressure in patients with type 2 diabetes mellitus: post hoc analysis of a cross-sectional multicenter study.

PubMed

Ushigome, Emi; Fukui, Michiaki; Hamaguchi, Masahide; Matsumoto, Shinobu; Mineoka, Yusuke; Nakanishi, Naoko; Senmaru, Takafumi; Yamazaki, Masahiro; Hasegawa, Goji; Nakamura, Naoto

2013-09-01

Recently, focus has been directed toward pulse pressure as a potentially independent risk factor for micro- and macrovascular disease. This study was designed to examine the relationship between pulse pressure taken at home and elevated albuminuria in patients with type 2 diabetes. This study is a post hoc analysis of a cross-sectional multicenter study. Home blood pressure measurements were performed for 14 consecutive days in 858 patients with type 2 diabetes. We investigated the relationship between systolic blood pressure or pulse pressure in the morning or in the evening and urinary albumin excretion using univariate and multivariate analyses. Furthermore, we measured area under the receiver-operating characteristic curve (AUC) to compare the ability to identify elevated albuminuria, defined as urinary albumin excretion equal to or more than 30 mg/g creatinine, of systolic blood pressure or pulse pressure. Morning systolic blood pressure (β=0.339, P<0.001) and morning pulse pressure (β=0.378, P<0.001) were significantly associated with logarithm of urinary albumin excretion independent of other potential co-factors. AUC for elevated albuminuria in morning systolic blood pressure and morning pulse pressure were 0.668 (0.632-0.705; P<0.001) and 0.694 (0.659-0.730; P<0.001), respectively. AUC of morning pulse pressure was significantly greater than that of morning systolic blood pressure (P=0.040). Our findings implicate that morning pulse pressure is associated with elevated albuminuria in patients with type 2 diabetes, which suggests that lowering morning pulse pressure could prevent the development and progression of diabetic nephropathy. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Tissue accumulation and urinary excretion of chromium in rats fed diets containing graded levels of chromium chloride or chromium picolinate.

PubMed

Yoshida, Munehiro; Hatakeyama, Erika; Hosomi, Ryota; Kanda, Seiji; Nishiyama, Toshimasa; Fukunaga, Kenji

2010-08-01

To attempt a risk assessment of the excess intake of trivalent chromium (Cr), tissue Cr accumulation and urinary Cr excretion were examined in weanling rats fed experimental diets containing graded levels of Cr chloride (CrCl3) or Cr picolinate (CrPic). Thirty-six male weanling 4-weeks-old Wistar rats were divided into six groups and fed a casein-based semi-purified diet (Cr content: <0.02 microg/g) supplemented with 1, 10, or 100 microg Cr/g as CrCl3 or CrPic for 28 days. Among the experimental groups, no significant difference was observed in body weight; however, supplementation of 100 microg Cr/g to the diets caused a significant low liver weight irrespective of the chemical species of Cr. Activities of serum aspartate aminotransferase and alanine aminotransferase were significantly elevated in rats given CrPic at 100 microg Cr/g. In the liver, kidney and femur, Cr accumulation increased with elevation of the dietary Cr level. No influence of the difference in the chemical species of supplemented Cr was observed in the liver and kidney, but CrCl3 caused significantly higher Cr accumulation than CrPic in the femur of rats given 100 microg Cr/g. Daily urinary Cr excretion elevated with the increase of the dietary Cr level. Rats given CrPic showed significantly higher daily urinary Cr excretion than those given CrCl3, particularly at a dietary Cr level of 100 microg/g. The rate of urinary Cr excretion in rats given CrPic was constant, irrespective of the dietary Cr level, but that of rats given CrCl3 fell with the increase of the dietary Cr level. These results indicate that the lowest adverse effect level of dietary Cr is less than 100 microg/g, irrespective of the chemical species of Cr.

Thermal conductivity and thermal expansion of graphite fiber/copper matrix composites

NASA Technical Reports Server (NTRS)

Ellis, David L.; Mcdanels, David L.

1991-01-01

The high specific conductivity of graphite fiber/copper matrix (Gr/Cu) composites offers great potential for high heat flux structures operating at elevated temperatures. To determine the feasibility of applying Gr/Cu composites to high heat flux structures, composite plates were fabricated using unidirectional and cross-plied pitch-based P100 graphite fibers in a pure copper matrix. Thermal conductivity of the composites was measured from room temperature to 1073 K, and thermal expansion was measured from room temperature to 1050 K. The longitudinal thermal conductivity, parallel to the fiber direction, was comparable to pure copper. The transverse thermal conductivity, normal to the fiber direction, was less than that of pure copper and decreased with increasing fiber content. The longitudinal thermal expansion decreased with increasing fiber content. The transverse thermal expansion was greater than pure copper and nearly independent of fiber content.

Thermal conductivity and thermal expansion of graphite fiber-reinforced copper matrix composites

NASA Technical Reports Server (NTRS)

Ellis, David L.; Mcdanels, David L.

1993-01-01

The high specific conductivity of graphite fiber/copper matrix (Gr/Cu) composites offers great potential for high heat flux structures operating at elevated temperatures. To determine the feasibility of applying Gr/Cu composites to high heat flux structures, composite plates were fabricated using unidirectional and cross-plied pitch-based P100 graphite fibers in a pure copper matrix. Thermal conductivity of the composites was measured from room temperature to 1073 K, and thermal expansion was measured from room temperature to 1050 K. The longitudinal thermal conductivity, parallel to the fiber direction, was comparable to pure copper. The transverse thermal conductivity, normal to the fiber direction, was less than that of pure copper and decreased with increasing fiber content. The longitudinal thermal expansion decreased with increasing fiber content. The transverse thermal expansion was greater than pure copper and nearly independent of fiber content.

Controlled atmosphere for fabrication of cermet electrodes

DOEpatents

Ray, Siba P.; Woods, Robert W.

1998-01-01

A process for making an inert electrode composite wherein a metal oxide and a metal are reacted in a gaseous atmosphere at an elevated temperature of at least about 750.degree. C. The metal oxide is at least one of the nickel, iron, tin, zinc and zirconium oxides and the metal is copper, silver, a mixture of copper and silver or a copper-silver alloy. The gaseous atmosphere has an oxygen content that is controlled at about 5-3000 ppm in order to obtain a desired composition in the resulting composite.

Controlled atmosphere for fabrication of cermet electrodes

DOEpatents

Ray, S.P.; Woods, R.W.

1998-08-11

A process is disclosed for making an inert electrode composite wherein a metal oxide and a metal are reacted in a gaseous atmosphere at an elevated temperature of at least about 750 C. The metal oxide is at least one of the nickel, iron, tin, zinc and zirconium oxides and the metal is copper, silver, a mixture of copper and silver or a copper-silver alloy. The gaseous atmosphere has an oxygen content that is controlled at about 5--3000 ppm in order to obtain a desired composition in the resulting composite. 2 figs.

Design and Fabrication of Smart Diapers with Antibacterial Yarn

PubMed Central

Lin, Jia-Horng; Shiu, Bing-Chiuan; Lou, Ching-Wen

2017-01-01

In this study, intelligent eco-diapers are made by combining antibacterial yarns coated with quaternary ammonium salts with conductive yarns to improve caretaking for urinary incontinence. The combination of conductive yarns and sensors can detect the moisture content in eco-diapers, and an alarm is sent when moisture is significant. A wireless module is used to send detected signals to a smartphone or tablet PC via the Internet. This concept is used for a scenario in which nurses do not randomly check on patients in a long-term care institution. When used offline, eco-diapers can send caregivers an alarm for the need to change diapers via cell phones. The diameters of the copper and silver-plated copper fibers are 0.08 and 0.10 mm, respectively. Cotton yarns are twisted with copper and silver-plated copper fibers to form the conductive yarns, which are 0.12 mm in diameter. Moreover, 30-count cotton and 150 D nylon yarns are coated with quaternary ammonium salt via dyeing and finishing processes to form antibacterial yarns. In the current study, intelligent eco-diapers are tested for their electrical and antibacterial properties as specified by AATC and JISL test standards. PMID:29065646

Urinary renin, but not angiotensinogen or aldosterone, reflects the renal renin-angiotensin-aldosterone system activity and the efficacy of renin-angiotensin-aldosterone system blockade in the kidney.

PubMed

van den Heuvel, Mieke; Batenburg, Wendy W; Jainandunsing, Sjaam; Garrelds, Ingrid M; van Gool, Jeanette M G; Feelders, Richard A; van den Meiracker, Anton H; Danser, A H Jan

2011-11-01

To study which renin-angiotensin-aldosterone system (RAAS) component best reflects renal RAAS activity. We measured urinary and plasma renin, prorenin, angiotensinogen, aldosterone, albumin and creatinine in 101 diabetic and nondiabetic patients with or without hypertension. Plasma prorenin was elevated in diabetic patients. Urinary prorenin was undetectable. Urinary albumin and renin were higher in diabetic patients. Men had higher plasma renin/prorenin levels, and lower plasma angiotensinogen levels than women. Plasma creatinine and albumin were also higher in men. Urinary RAAS components showed no sexual dimorphism, whereas urinary creatinine and albumin were higher in men. Angiotensin-converting enzyme inhibitors and angiotensin II type 1 receptor blockers increased plasma renin and decreased plasma angiotensinogen, without altering plasma aldosterone. In contrast, in urine, these drugs decreased renin and aldosterone without affecting angiotensinogen. When analyzing all patients together, urinary angiotensinogen excretion closely mimicked that of albumin, whereas urinary angiotensinogen and albumin levels both were 0.05% or less of their concomitant plasma levels. This may reflect the identical glomerular filtration and tubular handling of both proteins, which have a comparable molecular weight. In contrast, urinary renin excretion did not correlate with urinary albumin excretion, and the urinary/plasma concentration ratio of renin was more than 200 times the ratio of albumin, despite its comparable molecular weight. Urinary aldosterone excretion closely followed urinary creatinine excretion. The increased urinary renin levels in diabetes and the decreased urinary renin levels following RAAS blockade, occurring independently of changes in plasma renin, reflect the activated renal RAAS in diabetes and the success of RAAS blockade in the kidney, respectively. Urinary renin, therefore, more closely reflects renal RAAS activity than urinary angiotensinogen or aldosterone.

Comparison of ultrafiltration and solid phase extraction for the separation of free and protein-bound serum copper for the Wilson's disease diagnosis.

PubMed

Bohrer, Denise; Do Nascimento, Paulo Cícero; Ramirez, Adrian G; Mendonça, Jean Karlo A; De Carvalho, Leandro M; Pomblum, Solange Cristina G

2004-07-01

The determination of the ratio free/protein-bound serum copper along with urinary copper can be used as a preliminary test for the Wilson's Disease diagnosis. In this work, the determination of these copper fractions in serum samples was carried out in two different ways; after separation of the copper bound to proteins from the free fraction by a column for protein adsorption and by ultrafiltration. As proteins can be adsorbed onto plastic polymeric surfaces, polyethylene (PE) with different molecular weights in powder form was investigated for protein adsorption. A small column was adapted in a flow system to carry out a solid-phase extraction (SPE) on-line. Preliminary experiments defined conditions for protein retention and elution and column saturation. Good performance was achieved using Mg(NO3)2 solution as carrier and methanol as eluent. The presence of proteins in both fraction (column effluent and eluate) was checked by the Coomassie Brilliant Blue test. Copper was measured by graphite furnace atomic absorption spectrometry. The measurement in the column effluent furnished the free-fraction of copper while the copper measured in the eluate the bound-fraction. The method was compared with ultrafiltration (20 kDa), measuring the free-copper in the ultrafiltrate. For the determination of protein-bound copper, the copper found in the ultrafitrate was discounted from the total copper measured in the sample. Serum samples of 10 individuals were analyzed by both methods with good agreement of the results. The regression plots, obtained by analysing the samples by both methods, presented r2 and slope of 0.97 and 0.96 for free copper and 1.00 and 1.00 for bound copper, respectively. Protein-bound copper (PB) concentrations ranged from 74 to 2074 microg/l and free-copper (F) from 22 to 54 microg/l. The ratio F/PB, calculated from SPE data, was 29.7% for one individual, with Wilson Disease well-characterized, and ranged from 1.2% to 5.2% for the others. The SPE method performed well in terms of accuracy and precision, and showed good agreement with the UF. Advantages of SPE are small sample volume (50 microl), separation carried out in 10 min, and the use of the same column for several analyses. Copyright 2004 Elsevier B.V.

Regulation of extracellular copper-binding proteins in copper-resistant and copper-sensitive mutants of Vibrio alginolyticus.

PubMed Central

Harwood, V J; Gordon, A S

1994-01-01

Extracellular proteins of wild-type Vibrio alginolyticus were compared with those of copper-resistant and copper-sensitive mutants. One copper-resistant mutant (Cu40B3) constitutively produced an extracellular protein with the same apparent molecular mass (21 kDa) and chromatographic behavior as copper-binding protein (CuBP), a copper-induced supernatant protein which has been implicated in copper detoxification in wild-type V. alginolyticus. Copper-sensitive V. alginolyticus mutants displayed a range of alterations in supernatant protein profiles. CuBP was not detected in supernatants of one copper-sensitive mutant after cultures had been stressed with 50 microM copper. Increased resistance to copper was not induced by preincubation with subinhibitory levels of copper in the wild type or in the copper-resistant mutant Cu40B3. Copper-resistant mutants maintained the ability to grow on copper-amended agar after 10 or more subcultures on nonselective agar, demonstrating the stability of the phenotype. A derivative of Cu40B3 with wild-type sensitivity to copper which no longer constitutively expressed CuBP was isolated. The simultaneous loss of both constitutive CuBP production and copper resistance in Cu40B3 indicates that constitutive CuBP production is necessary for copper resistance in this mutant. These data support the hypothesis that the extracellular, ca. 20-kDa protein(s) of V. alginolyticus is an important factor in survival and growth of the organism at elevated copper concentrations. The range of phenotypes observed in copper-resistant and copper-sensitive V. alginolyticus indicate that altered sensitivity to copper was mediated by a variety of physiological changes. Images PMID:8031076

Development of graphite/copper composites utilizing engineered interfaces. M.S. Thesis Final Report

NASA Technical Reports Server (NTRS)

Devincent, Sandra M.

1991-01-01

In situ measurements of graphite/copper alloy contact angles were made using the sessile drop method. The interfacial energy values obtained from these measurements were then applied to a model for the fiber matrix interfacial debonding phenomenon found in graphite/copper composites. The formation obtained from the sessile drop tests led to the development of a copper alloy that suitably wets graphite. Characterization of graphite/copper alloy interfaces subjected to elevated temperatures was conducted using Scanning Electron Microscopy, Energy Dispersive Spectroscopy, Auger Electron Spectroscopy, and X Ray Diffraction analyses. These analyses indicated that during sessile drop tests conducted at 1130 C for 1 hour, copper alloys containing greater than 0.98 at pct chromium form continuous reaction layers of approx. 10 microns in thickness. The reaction layers are adherent to the graphite surface. The copper wets the reaction layer to form a contact angle of 60 deg or less. X ray diffraction results indicate that the reaction layer is Cr3C2.

Fracture toughness of copper-base alloys for ITER applications: A preliminary report

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alexander, D.J.; Zinkle, S.J.; Rowcliffe, A.F.

1997-04-01

Oxide-dispersion strengthened copper alloys and a precipitation-hardened copper-nickel-beryllium alloy showed a significant reduction in toughness at elevated temperature (250{degrees}C). This decrease in toughness was much larger than would be expected from the relatively modest changes in the tensile properties over the same temperature range. However, a copper-chromium-zirconium alloy strengthened by precipitation showed only a small decrease in toughness at the higher temperatures. The embrittled alloys showed a transition in fracture mode, from transgranular microvoid coalescence at room temperature to intergranular with localized ductility at high temperatures. The Cu-Cr-Zr alloy maintained the ductile microvoid coalescence failure mode at all test temperatures.

Evaluation of Temporal Changes in Urine-based Metabolomic and Kidney Injury Markers to Detect Compound Induced Acute Kidney Tubular Toxicity in Beagle Dogs.

PubMed

Wagoner, M P; Yang, Y; McDuffie, J E; Klapczynski, M; Buck, W; Cheatham, L; Eisinger, D; Sace, F; Lynch, K M; Sonee, M; Ma, J-Y; Chen, Y; Marshall, K; Damour, M; Stephen, L; Dragan, Y P; Fikes, J; Snook, S; Kinter, L B

2017-01-01

Urinary protein biomarkers and metabolomic markers have been leveraged to detect acute Drug Induced Kidney Injury (DIKI) in rats; however, the utility of these indicators to enable early detection of DIKI in canine models has not been well documented. Therefore, we evaluated temporal changes in biomarkers and metabolites in urine from male and female beagle dogs. Gentamicin- induced kidney lesions in male dogs were characterized by moderate to severe tubular epithelial cell degeneration/necrosis, epithelial cell regeneration and dilation; and a unique urinebased metabolomic fingerprint. These metabolite changes included time and treatment-dependent increases in lactate, taurine, glucose, lactate, alanine, and citrate as well as 9 other known metabolites. As early as 3 days post dose, gentamicin induced increases in urinary albumin, clusterin, neutrophil gelatinase associated protein (NGAL) and total protein concentrations. Urinary albumin, clusterin, and NGAL showed earlier and more robust elevations than traditional kidney safety biomarkers, blood urea nitrogen and serum creatinine. Elevations in urinary kidney injury molecule 1 (KIM-1) were less reliable for detection of gentamicin nephrotoxicity in dogs based on values generated utilizing multiple first-generation, canine-specific KIM-1 immunoassays. The metabolic fingerprint was further evaluated in male and female dogs that received Compound A which induced slightly reversible renal tubular alterations characterized as degeneration/necrosis and concurrent significant increases in urinary taurine amongst other markers. These data support further investigations to demonstrate the value of urinary metabolites, albumin, clusterin, NGAL and taurine as promising markers to enable early detection of DIKI in dogs. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

YKL-40 Associates with Renal Recovery in Deceased Donor Kidney Transplantation

PubMed Central

Puthumana, Jeremy; Hall, Isaac E.; Reese, Peter P.; Schröppel, Bernd; Weng, Francis L.; Thiessen-Philbrook, Heather; Doshi, Mona D.; Rao, Veena; Lee, Chun Geun; Elias, Jack A.; Cantley, Lloyd G.

2017-01-01

Deceased donor kidneys with AKI are often discarded for fear of poor transplant outcomes. Donor biomarkers that predict post-transplant renal recovery could improve organ selection and reduce discard. We tested whether higher levels of donor urinary YKL-40, a repair phase protein, associate with improved recipient outcomes in a prospective cohort study involving deceased kidney donors from five organ procurement organizations. We measured urinary YKL-40 concentration in 1301 donors (111 had AKI, defined as doubling of serum creatinine) and ascertained outcomes in the corresponding 2435 recipients, 756 of whom experienced delayed graft function (DGF). Donors with AKI had higher urinary YKL-40 concentration (P<0.001) and acute tubular necrosis on procurement biopsies (P=0.05). In fully adjusted analyses, elevated donor urinary YKL-40 concentration associated with reduced risk of DGF in both recipients of AKI donor kidneys (adjusted relative risk, 0.51 [95% confidence interval (95% CI), 0.32 to 0.80] for highest versus lowest YKL-40 tertile) and recipients of non-AKI donor kidneys (adjusted relative risk, 0.79 [95% CI, 0.65 to 0.97]). Furthermore, in the event of DGF, elevated donor urinary YKL-40 concentration associated with higher 6-month eGFR (6.75 [95% CI, 1.49 to 12.02] ml/min per 1.73 m2) and lower risk of graft failure (adjusted hazard ratio, 0.50 [95% CI, 0.27 to 0.94]). These findings suggest that YKL-40 is produced in response to tubular injury and is independently associated with recovery from AKI and DGF. If ultimately validated as a prognostic biomarker, urinary YKL-40 should be considered in determining the suitability of donor kidneys for transplant. PMID:27451287

Maintaining K+ balance on the low-Na+, high-K+ diet

PubMed Central

Cornelius, Ryan J.; Wang, Bangchen; Wang-France, Jun

2016-01-01

A low-Na+, high-K+ diet (LNaHK) is considered a healthier alternative to the “Western” high-Na+ diet. Because the mechanism for K+ secretion involves Na+ reabsorptive exchange for secreted K+ in the distal nephron, it is not understood how K+ is eliminated with such low Na+ intake. Animals on a LNaHK diet produce an alkaline load, high urinary flows, and markedly elevated plasma ANG II and aldosterone levels to maintain their K+ balance. Recent studies have revealed a potential mechanism involving the actions of alkalosis, urinary flow, elevated ANG II, and aldosterone on two types of K+ channels, renal outer medullary K+ and large-conductance K+ channels, located in principal and intercalated cells. Here, we review these recent advances. PMID:26739887

Copper uptake and retention in liver parenchymal cells isolated from nutritionally copper-deficient rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Van den Berg, G.J.; de Goeij, J.J.; Bock, I.

1991-08-01

Copper uptake and retention were studied in primary cultures of liver parenchymal cells isolated from copper-deficient rats. Male Sprague-Dawley rats were fed a copper-deficient diet (less than 1 mg Cu/kg) for 10 wk. Copper-deficient rats were characterized by low copper concentrations in plasma and liver, anemia, low plasma ceruloplasmin oxidase activity and increased 64Cu whole-body retention. Freshly isolated liver parenchymal cells from copper-deficient rats showed a higher 64Cu influx, which was associated with a higher apparent Vmax of 45 {plus minus} 4 pmol Cu.mg protein-1.min-1 as compared with 30 {plus minus} 3 pmol Cu.mg protein-1.min-1 for cells isolated from copper-sufficientmore » rats. No significant difference in the apparent Km (approximately 30 mumol/L) was observed. Relative 64Cu efflux from cells from copper-deficient rats was significantly smaller than the efflux from cells from copper-sufficient rats after prelabeling as determined by 2-h efflux experiments. Analysis of the medium after efflux from cells from copper-deficient rats showed elevated protein-associated 64Cu, suggesting a higher incorporation of radioactive copper during metalloprotein synthesis. Effects of copper deficiency persist in primary cultures of parenchymal cells derived from copper-deficient rats, and short-term cultures of these cells offer a prospect for the study of cell biological aspects of the metabolic adaptation of the liver to copper deficiency.« less

Factors affecting catalysis of copper corrosion products in NDMA formation from DMA in simulated premise plumbing.

PubMed

Zhang, Hong; Andrews, Susan A

2013-11-01

This study investigated the effects of corrosion products of copper, a metal commonly employed in household plumbing systems, on N-nitrosodimethylamine (NDMA) formation from a known NDMA precursor, dimethylamine (DMA). Copper-catalyzed NDMA formation increased with increasing copper concentrations, DMA concentrations, alkalinity and hardness, but decreased with increasing natural organic matter (NOM) concentration. pH influenced the speciation of chloramine and the interactions of copper with DMA. The transformation of monochloramine (NH2Cl) to dichloramine and complexation of copper with DMA were involved in elevating the formation of NDMA by copper at pH 7.0. The inhibiting effect of NOM on copper catalysis was attributed to the rapid consumption of NH2Cl by NOM and/or the competitive complexation of NOM with copper to limit the formation of DMA-copper complexes. Hardness ions, as represented by Ca(2+), also competed with copper for binding sites on NOM, thereby weakening the inhibitory effect of NOM on NDMA formation. Common copper corrosion products also participated in these reactions but in different ways. Aqueous copper released from malachite [Cu2CO3(OH)2] was shown to promote NDMA formation while NDMA formation decreased in the presence of CuO, most likely due to the adsorption of DMA. Copyright © 2013 Elsevier Ltd. All rights reserved.

Physiological responses of coastal phytoplankton (Visakhapatnam, SW Bay of Bengal, India) to experimental copper addition.

PubMed

Biswas, Haimanti; Bandyopadhyay, Debasmita

2017-10-01

Trace amount of copper (Cu) is essential for many physiological processes; however, it can be potentially toxic at elevated levels. The impact of variable Cu concentrations on a coastal phytoplankton community was investigated along a coastal transect in SW Bay of Bengal. A small increase in Cu supply enhanced the concentrations of particulate organic carbon, particulate organic nitrogen, biogenic silica, total pigment, phytoplankton cell and total bacterial count. At elevated Cu levels all these parameters were adversely affected. δ 13 C POM and δ 15 N POC reflected a visible signature of both beneficial and toxic impacts of Cu supply. Skeletonema costatum, the dominant diatom species, showed higher tolerance to increasing Cu levels relative to Chaetoceros sp. Cyanobacteria showed greater sensitivity to copper than diatoms. The magnitude of Cu toxicity on the phytoplankton communities was inversely related to the distance from the coast. Co-enrichment of iron alleviated Cu toxicity to phytoplankton. Copyright © 2017 Elsevier Ltd. All rights reserved.

Urinary heavy metal levels and relevant factors among people exposed to e-waste dismantling.

PubMed

Wang, Hongmei; Han, Mei; Yang, Suwen; Chen, Yanqing; Liu, Qian; Ke, Shen

2011-01-01

Primitive electronic waste (e-waste) recycling has become a growing environmental concern, and toxic heavy metals released from e-waste activities may continue to threaten the health of local people. To study the impact of heavy metals in people around e-waste sites, 349 people from e-waste recycling sites (exposure group) and 118 people from a green plantation (control group) were surveyed, and their urinary levels of lead (UPb), cadmium (UCd), manganese (UMn), copper (UCu), and Zinc (UZn) were assayed. Questionnaire surveys for risk factors were also performed and analyzed by using the Pearson correlation analysis. Results indicated that the levels of urinary Cd in both occupational dismantling people {GM(GSD) 0.72(0.71) ug/L} and non-occupational dismantling people {GM(GSD) 0.50(0.79) ug/L} were higher than the control group {GM(GSD) 0.27(0.85) ug/L}. Further analyses of correlations between urinary heavy metal levels and exposure factors in the exposed group revealed positive relationship between the duration of dismantling and the level of UPb (p < 0.05). Meanwhile, rice sources from local village have a positive correlation with the level of UPb and UCd (p < 0.01). Other factors, however, may also have influences on heavy metal burden, and not all urinary heavy metal levels can be contributed to e-waste dismantling exposure levels. Primitive e-waste recycling activities may contribute to the changes of urinary heavy metal levels and increase the health risk for those chronically working on e-waste dismantling. Copyright © 2010 Elsevier Ltd. All rights reserved.

Role of Copper and Homocysteine in Pressure Overload Heart Failure

PubMed Central

Hughes, William M.; Rodriguez, Walter E.; Rosenberger, Dorothea; Chen, Jing; Sen, Utpal; Tyagi, Neetu; Moshal, Karni S.; Vacek, Thomas; Kang, Y. James

2009-01-01

Elevated levels of homocysteine (Hcy) (known as hyperhomocysteinemia HHcy) are involved in dilated cardiomyopathy. Hcy chelates copper and impairs copper-dependent enzymes. Copper deficiency has been linked to cardiovascular disease. We tested the hypothesis that copper supplement regresses left ventricular hypertrophy (LVH), fibrosis and endothelial dysfunction in pressure overload DCM mice hearts. The mice were grouped as sham, sham + Cu, aortic constriction (AC), and AC + Cu. Aortic constriction was performed by transverse aortic constriction. The mice were treated with or without 20 mg/kg copper supplement in the diet for 12 weeks. The cardiac function was assessed by echocardiography and electrocardiography. The matrix remodeling was assessed by measuring matrix metalloproteinase (MMP), tissue inhibitor of metalloproteinases (TIMPs), and lysyl oxidase (LOX) by Western blot analyses. The results suggest that in AC mice, cardiac function was improved with copper supplement. TIMP-1 levels decreased in AC and were normalized in AC + Cu. Although MMP-9, TIMP-3, and LOX activity increased in AC and returned to baseline value in AC + Cu, copper supplement showed no significant effect on TIMP-4 activity after pressure overload. In conclusion, our data suggest that copper supplement helps improve cardiac function in a pressure overload dilated cardiomyopathic heart. PMID:18679830

Identification of Noninvasive Biomarkers for Alcohol-Induced Liver Disease Using Urinary Metabolomics and the Ppara-null Mouse

PubMed Central

Manna, Soumen K.; Patterson, Andrew D.; Yang, Qian; Krausz, Kristopher W.; Li, Henghong; Idle, Jeffrey R.; Fornace, Albert J.; Gonzalez, Frank J.

2010-01-01

Alcohol-induced liver disease (ALD) is a leading cause of non-accident-related deaths in the United States. Although liver damage caused by ALD is reversible when discovered at the earlier stages, current risk assessment tools are relatively non-specific. Identification of an early specific signature of ALD would aid in therapeutic intervention and recovery. In this study the metabolic changes associated with alcohol-induced liver disease were examined using alcohol-fed male Ppara-null mouse as a model of ALD. Principal components analysis of the mass spectrometry-based urinary metabolic profile showed that alcohol-treated wild-type and Ppara-null mice could be distinguished from control animals without information on history of alcohol consumption. The urinary excretion of ethyl-sulfate, ethyl-β-D-glucuronide, 4-hydroxyphenylacetic acid, and 4-hydroxyphenylacetic acid sulfate was elevated and that of the 2-hydroxyphenylacetic acid, adipic acid, and pimelic acid was depleted during alcohol treatment in both wild-type and the Ppara-null mice albeit to different extents. However, indole-3-lactic acid was exclusively elevated by alcohol exposure in Ppara-null mice. The elevation of indole-3-lactic acid is mechanistically related to the molecular events associated with development of ALD in alcohol-treated Ppara-null mice. This study demonstrated the ability of metabolomics approach to identify early, noninvasive biomarkers of ALD pathogenesis in Ppara-null mouse model. PMID:20540569

Urinary chromium concentrations in humans following ingestion of safe doses of hexavalent and trivalent chromium: Implications for biomonitoring

DOE Office of Scientific and Technical Information (OSTI.GOV)

Finley, B.L.; Scott, P.K.; Norton, R.L.

1996-08-09

This study evaluates the significance of increased urinary chromium concentrations as a marker of chromium exposure and potential health risk. Six human volunteers ingested trivalent chromium [Cr(III)] and hexavalent chromium [Cr(VI)] at doses that are known to be safe but higher than typical levels. The following dosing regimen was used: d 1-7, 200 {mu}g/d chromium picolinate; d 8-10, Cr(VI) ingestion at the U.S. Environmental Protection Agency (EPA) reference dose (RfD) of 0.005 mg/kg/d; d 11-13, no dose; d 14-16, Cr(III) ingestion at the U.S. EPA RfD of 1.0 mg/kg/d; and 17-18, postdose. Findings are as follows: (1) ingestion of 200more » {mu}g/d of chromium picolinate yielded significantly elevated urine concentrations such that each participant routinely exceeded background, (2) ingestion of the Cr(VI) RfD (0.005 mg/kg/d) yielded individual mean urinary chromium levels (1.2-2.3 {mu}g/L) and a pooled mean urinary chromium level (2.4 {mu}g/L) that significantly exceeded background, and (3) ingestion of the Cr(III) RfD yielded no significantly exceeded background, and (3) ingestion of the Cr(III) RfD yielded no significant increase in urinary chromium concentrations, indicating that little, if any, absorption occurred. Our work identified three critical issues that need to be accounted for in any future studies that will use urinary chromium as a marker of exposure. First, a minimum urinary chromium concentration of approximately 2 {mu}g/L should be used as a screening level to critically identify individuals who may have experienced elevated exposures to chromium. Second, if Cr(III) levels in soils are known to be less than 80,000 ppm and the Cr(III) is insoluble, urinary chromium concentrations are not an appropriate marker of exposure. Third, newer forms of chromium supplements that contain organic forms of Cr(III) must be considered potential confounders and their contribution to residential chromium uptake must be carefully evaluated. 19 refs., 7 figs., 3 tabs.« less

Diagnostic and prognostic stratification in the emergency department using urinary biomarkers of nephron damage: a multicenter prospective cohort study.

PubMed

Nickolas, Thomas L; Schmidt-Ott, Kai M; Canetta, Pietro; Forster, Catherine; Singer, Eugenia; Sise, Meghan; Elger, Antje; Maarouf, Omar; Sola-Del Valle, David Antonio; O'Rourke, Matthew; Sherman, Evan; Lee, Peter; Geara, Abdallah; Imus, Philip; Guddati, Achuta; Polland, Allison; Rahman, Wasiq; Elitok, Saban; Malik, Nasir; Giglio, James; El-Sayegh, Suzanne; Devarajan, Prasad; Hebbar, Sudarshan; Saggi, Subodh J; Hahn, Barry; Kettritz, Ralph; Luft, Friedrich C; Barasch, Jonathan

2012-01-17

This study aimed to determine the diagnostic and prognostic value of urinary biomarkers of intrinsic acute kidney injury (AKI) when patients were triaged in the emergency department. Intrinsic AKI is associated with nephron injury and results in poor clinical outcomes. Several urinary biomarkers have been proposed to detect and measure intrinsic AKI. In a multicenter prospective cohort study, 5 urinary biomarkers (urinary neutrophil gelatinase-associated lipocalin, kidney injury molecule-1, urinary liver-type fatty acid binding protein, urinary interleukin-18, and cystatin C) were measured in 1,635 unselected emergency department patients at the time of hospital admission. We determined whether the biomarkers diagnosed intrinsic AKI and predicted adverse outcomes during hospitalization. All biomarkers were elevated in intrinsic AKI, but urinary neutrophil gelatinase-associated lipocalin was most useful (81% specificity, 68% sensitivity at a 104-ng/ml cutoff) and predictive of the severity and duration of AKI. Intrinsic AKI was strongly associated with adverse in-hospital outcomes. Urinary neutrophil gelatinase-associated lipocalin and urinary kidney injury molecule 1 predicted a composite outcome of dialysis initiation or death during hospitalization, and both improved the net risk classification compared with conventional assessments. These biomarkers also identified a substantial subpopulation with low serum creatinine at hospital admission, but who were at risk of adverse events. Urinary biomarkers of nephron damage enable prospective diagnostic and prognostic stratification in the emergency department. Copyright © 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Diagnostic and Prognostic Stratification in the Emergency Department Using Urinary Biomarkers of Nephron Damage

PubMed Central

Nickolas, Thomas L.; Schmidt-Ott, Kai M.; Canetta, Pietro; Forster, Catherine; Singer, Eugenia; Sise, Meghan; Elger, Antje; Maarouf, Omar; Sola-Del Valle, David Antonio; O'Rourke, Matthew; Sherman, Evan; Lee, Peter; Geara, Abdallah; Imus, Philip; Guddati, Achuta; Polland, Allison; Rahman, Wasiq; Elitok, Saban; Malik, Nasir; Giglio, James; El-Sayegh, Suzanne; Devarajan, Prasad; Hebbar, Sudarshan; Saggi, Subodh J.; Hahn, Barry; Kettritz, Ralph; Luft, Friedrich C.; Barasch, Jonathan

2012-01-01

Objectives This study aimed to determine the diagnostic and prognostic value of urinary biomarkers of intrinsic acute kidney injury (AKI) when patients were triaged in the emergency department. Background Intrinsic AKI is associated with nephron injury and results in poor clinical outcomes. Several urinary biomarkers have been proposed to detect and measure intrinsic AKI. Methods In a multicenter prospective cohort study, 5 urinary biomarkers (urinary neutrophil gelatinase–associated lipocalin, kidney injury molecule-1, urinary liver-type fatty acid binding protein, urinary interleukin-18, and cystatin C) were measured in 1,635 unselected emergency department patients at the time of hospital admission. We determined whether the biomarkers diagnosed intrinsic AKI and predicted adverse outcomes during hospitalization. Results All biomarkers were elevated in intrinsic AKI, but urinary neutrophil gelatinase-associated lipocalin was most useful (81% specificity, 68% sensitivity at a 104-ng/ml cutoff) and predictive of the severity and duration of AKI. Intrinsic AKI was strongly associated with adverse in-hospital outcomes. Urinary neutrophil gelatinase-associated lipocalin and urinary kidney injury molecule 1 predicted a composite outcome of dialysis initiation or death during hospitalization, and both improved the net risk classification compared with conventional assessments. These biomarkers also identified a substantial subpopulation with low serum creatinine at hospital admission, but who were at risk of adverse events. Conclusion Urinary biomarkers of nephron damage enable prospective diagnostic and prognostic stratification in the emergency department. PMID:22240130

Severe polyuria after the resection of adrenal pheochromocytoma.

PubMed

Tobe, Musashi; Ito, Keiichi; Umeda, Shun; Sato, Akinori; Adaniya, Noriaki; Tanaka, Yuji; Hayakawa, Masamichi; Asano, Tomohiko

2010-12-01

A 73-year-old male patient with hypertension and hyperglycemia was referred to our hospital because of a diagnosis regarding his left adrenal tumor. Because the levels of urinary metanephrine and normetanephrine were elevated, and (131) I-MIBG scintigraphy showed intense uptake in the adrenal tumor, the tumor was diagnosed as a pheochromocytoma. An adrenalectomy was carried out. Severe polyuria, which was accompanied by a rapid decrease in central venous pressure, started 1 hour after the operation. Urine output of more than 8000 mL/day continued until the 16th postoperative day. Plasma antidiuretic hormone (ADH) levels were within the normal range. Plasma human atrial natriuretic peptide (hANP) and brain natriuretic peptide (BNP) were elevated postoperatively, and the elevation of these peptides was one possible cause for the severe polyuria. Because ADH levels in the tumor fluid were not elevated, the tumor was not an ADH-secreting tumor. Urinary β2-microglobulin was significantly elevated after the operation, thus suggesting that renal tubule dysfunction might also have been involved in the polyuria. However, the mechanism of polyuria after the resection of adrenal pheochromocytoma is not fully understood. Polyuria after the resection of adrenal pheochromocytoma is extremely rare, and the present subject is the second case to date. © 2010 The Japanese Urological Association.

Trace elements are associated with urinary 8-hydroxy-2'-deoxyguanosine level: a case study of college students in Guangzhou, China.

PubMed

Lu, Shaoyou; Ren, Lu; Fang, Jianzhang; Ji, Jiajia; Liu, Guihua; Zhang, Jianqing; Zhang, Huimin; Luo, Ruorong; Lin, Kai; Fan, Ruifang

2016-05-01

Many trace heavy elements are carcinogenic and increase the incidence of cancer. However, a comprehensive study of the correlation between multiple trace elements and DNA oxidative damage is still lacking. The aim of this study is to investigate the relationships between the body burden of multiple trace elements and DNA oxidative stress in college students in Guangzhou, China. Seventeen trace elements in urine samples were determined by inductively coupled plasma-mass spectrometry (ICP-MS). Urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of DNA oxidative stress, was also measured using liquid chromatography tandem mass spectrometer (LC-MS/MS). The concentrations of six essential elements including manganese (Mn), copper (Cu), nickel (Ni), selenium (Se), strontium (Sr), and molybdenum (Mo), and five non-essential elements including arsenic (As), cadmium (Cd), aluminum (Al), stibium (Sb), and thallium (Tl), were found to be significantly correlated with urinary 8-OHdG levels. Moreover, urinary levels of Ni, Se, Mo, As, Sr, and Tl were strongly significantly correlated with 8-OHdG (P < 0.01) concentration. Environmental exposure and dietary intake of these trace elements may play important roles in DNA oxidative damage in the population of Guangzhou, China.

Variations in plasma and urinary lipids in response to enzyme replacement therapy for Fabry disease patients by nanoflow UPLC-ESI-MS/MS.

PubMed

Byeon, Seul Kee; Kim, Jin Yong; Lee, Jin-Sung; Moon, Myeong Hee

2016-03-01

A deficiency of α-galactosidase A causes Fabry disease (FD) by disrupting lipid metabolism, especially trihexosylceramide (THC). Enzyme replacement therapy (ERT) is clinically offered to FD patients in an attempt to lower the accumulated lipids. Studies on specific types of lipids that are directly or indirectly altered by FD are very scarce, even though they are crucial in understanding the biological process linked to the pathogenesis of FD. We performed a comprehensive lipid profiling of plasma and urinary lipids from FD patients with nanoflow liquid chromatography electrospray-ionization tandem mass spectrometry (nLC-ESI-MS/MS) and identified 129 plasma and 111 urinary lipids. Among these, lipids that exhibited alternations (>twofold) in patients were selected as targets for selected reaction monitoring (SRM)-based high-speed quantitation using nanoflow ultra-performance LC-ESI-MS/MS (nUPLC-ESI-MS/MS) and 31 plasma and 26 urinary lipids showed significant elevation among FD patients. Higher percentages of sphingolipids (SLs; 48% for plasma and 42% for urine) were highly elevated in patients; whereas, a smaller percentage of phospholipids (PLs; 15% for plasma and 13% for urine) were significantly affected. Even though α-galactosidase A is reported to affect THC only, the results show that other classes of lipids (especially SLs) are changed as well, indicating that FD not only alters metabolism of THC but various classes of lipids too. Most lipids showing significant increases in relative amounts before ERT decreased after ERT, but overall, ERT influenced plasma lipids more than urinary lipids.

Changes in urinary Cu, Zn, and Se levels in cancer patients after treatment with Sha Shen Mai Men Dong Tang

PubMed Central

Lai, Tung-Yuan; Kuo, Hsien-Wen

2015-01-01

Sha Shen Mai Men Dong Tang (SMD-2; 沙參麥冬湯 shā shēn mài dōng tāng) is a Chinese medicinal herb (CMH; 中草藥 zhōng cǎo yào) used to treat symptoms associated with cancer therapy. The objective of this study was to assess the effect of SMD-2 on the levels of urinary copper (Cu), zinc (Zn), and selenium (Se) in lung cancer patients and head and neck cancer patients receiving chemoradiotherapy. Forty-two head and neck cancer patients and 10 lung cancer patients participated in our clinical trial. Each patient received chemoradiotherapy for 4 weeks. In addition, each patient was treated with SMD-2 for 8 weeks, including 2 weeks prior to and after the chemoradiotherapy treatment. Comparison of urinary Cu, Zn, and Se levels and the ratios of Zn to Cu and Se to Cu at three time points in the two types of cancer were assessed using the generalized estimating equations (GEEs). After the patients received chemoradiotherapy for 4 weeks, SMD-2 treatment was found to be associated with a significant decrease in urinary Cu levels, whereas urinary Zn and Se levels increased significantly. In addition, the ratios of Zn to Cu and Se to Cu in the urine samples of these patients also increased significantly. Both the urinary Zn levels and the ratio of Zn to Cu in head and neck cancer patients were significantly higher than in lung cancer patients. Urinary Zn and Se levels and the ratios of Zn to Cu and Se to Cu, but not urinary Cu levels, increased significantly during and after treatment when assessed using the GEE model. The SMD-2 treatments significantly increased Zn and Se levels in the urine of head and neck cancer patients. Increased Zn and Se levels in urine strengthened immune system. PMID:27114935

Urinary interleukin-6 as a predictor of radiographic progression in rheumatoid arthritis: A 3-year evaluation.

PubMed

Park, Yune-Jung; Yoo, Seung-Ah; Kim, Ga-Ram; Cho, Chul-Soo; Kim, Wan-Uk

2016-10-12

Previously, we demonstrated that the urine proteome signature of patients with rheumatoid arthritis (RA) reflects inflammation-related cellular processes. Here, we measured interleukin (IL)-6, IL-8, and chemokine ligand 2 (CCL2) concentrations in the urine of RA patients and prospectively investigated their role in predicting RA activity and prognosis. One hundred seventy-three RA patients and 62 non-RA controls were recruited. Urinary IL-6, CCL2, and IL-8 levels were elevated in RA patients and correlated well with disease activity. Urinary IL-6 level at presentation was an independent risk factor of radiographic progression at 1 and 3 years. High urinary IL-6 level increased the risk ratio of radiographic progression by 2.9-fold, which was comparable to high serum CRP. Moreover, combination of urinary IL-6 and serum CRP measures synergistically increased the predictability of radiographic progression. In a subgroup with normal ESR, patients with the highest tertile of urinary IL-6 were at 6.4-fold greater risk of radiographic progression. Conclusively, high urinary IL-6 level at presentation is an independent risk factor for radiographic progression of RA, reflecting disease activity. Urinary IL-6 in combination with serum CRP may be a useful parameter for estimating RA prognosis.

A study of oxidative stress, cytokines and glutamate in Wilson disease and their asymptomatic siblings.

PubMed

Kalita, Jayantee; Kumar, Vijay; Misra, Usha K; Ranjan, Abhay; Khan, Hamidullah; Konwar, Rituraj

2014-09-15

Free copper in Wilson disease (WD) is toxic and may reduce antioxidant, increase oxidative stress marker and thereby cytokine release and excitotoxic injury, but there is paucity of studies in humans. We report oxidative stress markers, cytokines and glutamate in neurologic WD and correlate these with their clinical severity, laboratory findings and extent of Magnetic resonance imaging (MRI) changes. 29 patients with neurologic WD and 9 asymptomatic WD siblings were included and their clinical, treatment history, disease severity, biochemical findings and MRI changes were noted. Glutathione (GSH), total antioxidant capacity (TAC) and malonodialdehyde (MDA) were measured by spectrophotometer, cytokines by cytokine bead array and glutamate by the fluorometer. In WD patients, the glutathione (mean±SEM, 2.20±0.06 vs. 2.73±0.04mg/dl, P<0.001) and TAC (1.70±0.03 vs. 2.29±0.02 Trolox_Eq_mmol/l, P<0.001) were reduced, and MDA and glutamate (23.93±0.54 vs. 19.96±0.27μmol/l; P<0.001) were increased (4.7±0.11 vs. 3.03±0.52nmol/ml, P<0.001) compared to controls. The serum IL6 {median (IQRs), 9.42(10.92) vs. 5.2(5.34) pg/ml; P=0.001}, IL8 {12.37(10.92) vs. 5.63(5.52) pg/ml; P<0.001}, IL10 {8.33(8.3) vs. 2.05(1.37) pg/ml; P=0.001} and TNFα {6.14(8.95) vs. 3.61(3.58) pg/ml; P<0.001} were also increased in WD patients compared to controls. These changes were more marked in the neurologic WD compared to asymptomatic WD and in the untreated compared to treated patients. TAC correlated with duration of illness, serum free copper, 24hour urinary copper and serum ceruloplasmin, and glutamate with MDA, TNFα, ceruloplasmin and 24-hour urinary copper. In WD patients, antioxidants are reduced and MDA, cytokines and glutamate are increased which are more marked in symptomatic neurologic WD than asymptomatic patients. Copyright © 2014 Elsevier B.V. All rights reserved.

ESD coating of copper with TiC and TiB2 based ceramic matrix composites

NASA Astrophysics Data System (ADS)

Talas, S.; Mertgenç, E.; Gökçe, B.

2016-08-01

In automotive industry, the spot welding is a general practice to join smaller sections of a car. This welding is specifically carried out in short time and in an elevated number with certain pressure applied on copper electrodes. In addition, copper electrodes are expected to endure against cyclic mechanical pressure and temperature that is released during the passage of the current. The deformation and oxidation behaviour of copper electrodes during service appear with increasing temperature of medium and they also need to be cleaned and cooled or replaced for the continuation of joining process. The coating of copper electrodes with ceramic matrix composites can provide alternative excellent high temperature strength and ensures both economic and efficient use of resources. This study shows that the ESD coating of copper electrodes with a continuous film of ceramic phase ensures an improved resistance to thermal effects during the service and the change in content of film may be critical for cyclic alloying.

Urinary pH as a Risk Factor for Stone Type

NASA Astrophysics Data System (ADS)

Sakhaee, Khashayar

2007-04-01

A high urinary pH is main risk factor for the calcium phosphate stone formation; however, its pathophysiologic mechanism has not been fully understood. The introduction of Topiramate in the treatment of various neurological disorders has been complicated by metabolic acidosis, significant hypocitraturia, elevated urinary pH, and calcium phosphate stone formation. This model provides a probe to investigate the pathophysiologic mechanism of calcium phosphate stone formation and perhaps to develop appropriate countermeasures in the future. On the other hand an unduly acidic urine predisposes one to uric acid nephrolithiasis. Our recent investigation linking low urinary pH, and defective renal ammoniagenesis to insulin resistance provides new knowledge to unfold the pathophysiology of uric acid nephrolithiasis. The metabolic profile leading to uric acid stone may emerge as one of the components of metabolic syndrome.

Urinary porphyrins as biomarkers for arsenic exposure among susceptible populations in Guizhou Province, China

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ng, J.C.; Wang, J.P.; Zheng, B.S.

2005-08-07

Coal from some areas in Guizhou Province contains elevated levels of arsenic. This has caused arsenicosis in individuals who use arsenic-contaminated coal for the purposes of heating, cooking and drying of food in poorly ventilated dwellings. The population at risk has been estimated to be approximately 200,000 people. We analyzed the porphyrin excretion profile using a HPLC method in urine samples collected from 113 villagers who lived in Xing Ren district, a coal-borne arsenicosis endemic area and from 30 villagers from Xing Yi where arsenicosis is not prevalent. Urinary porphyrins were higher in the arsenic exposed group than those inmore » the control group. The correlation between urinary arsenic and porphyrin concentrations demonstrated the effect of arsenic on heme biosynthesis resulting in increased porphyrin excretion. Both uroporphyrin and coproporphyrin III showed significant increases in the excretion profile of the younger age ({lt} 20 years) arsenic-exposed group, suggesting that porphyrins could be used as early warning biomarkers of chronic arsenic exposure in humans. Greater increases of urinary arsenic and porphyrins in women, children and older age groups who spend much of their time indoors suggest that they might be at a higher risk. Whether elevated porphyrins could predict adverse health effects associated with both cancer and non-cancer end-points in chronically arsenic-exposed populations need further investigation.« less

Low Serum Testosterone Levels Are Associated with Elevated Urinary Mandelic Acid, and Strontium Levels in Adult Men According to the US 2011–2012 National Health and Nutrition Examination Survey

PubMed Central

Liu, Hui; Héroux, Paul; Zhang, Qunwei; Jiang, Zhao-Yan; Gu, Aihua

2015-01-01

Background Little is known regarding the effects of environmental exposure of chemicals on androgenic system in the general population. We studied 5,107 subjects included in the National Health and Nutrition Examination Survey (2011–2012). Methods Urinary, serum, and blood levels of 15 subclasses comprising 110 individual chemicals were analyzed for their association with serum testosterone levels. The subjects were divided into high and low testosterone groups according to the median testosterone concentration (374.51 ng/dL). Odds ratios (ORs) of individual chemicals in association with testosterone were estimated using logistic regression after adjusting for age, ethnicity, cotinine, body mass index, creatinine, alcohol, and the poverty income ratio. Results Adjusted ORs for the highest versus lowest quartiles of exposure were 2.12 (95% CI: 1.07, 4.21; Ptrend = 0.044), 1.84 (95% CI: 1.02, 3.34; Ptrend = 0.018) for the association between urinary mandelic acid, and strontium quartiles with low testosterone concentrations in adult men, respectively. However, no association was observed for the remaining chemicals with testosterone. Conclusions The National Health and Nutrition Examination Survey data suggest that elevations in urinary mandelic acid, and strontium levels are negatively related to low serum testosterone levels in adult men. PMID:25996772

Adenocarcinoma arising in urinary bladder endocervicosis.

PubMed

Nakaguro, Masato; Tsuzuki, Toyonori; Shimada, Satoko; Taki, Tetsuro; Tsuchiyama, Mari; Kitamura, Atsuko; Suzuki, Yasuhiko; Nakano, Yojiro; Ono, Kenzo

2016-02-01

Endocervicosis is a rare benign condition characterized by the presence of endocervical-type mucinous glands. Urinary bladder endocervicosis forms an elevated lesion in the posterior wall of the urinary bladder and is sometimes misdiagnosed as a malignant tumor clinically and pathologically. Herein we describe the first case of adenocarcinoma arising in urinary bladder endocervicosis. The patient, a 58-year-old woman, presented with asymptomatic hematuria. Cystoscopy revealed a nodular mass measuring 4 cm in diameter in the posterior wall, and total cystectomy was performed. Histology revealed that the elevated lesion of the bladder wall was composed of haphazard proliferation of cystic glands lined by benign endocervical-type epithelium. An adenocarcinoma arose at the center of this endocervicosis. Mucin histochemistry revealed the presence of sulfomucin in both the endocervicosis and adenocarcinoma components. Immunohistochemically, the endocervicosis was positive for cytokeratin (CK) 7, AE1/AE3, CAM5.2, HBME1, CA19-9, and estrogen receptor (ER), and negative for CK20, CDX2, progesterone receptor (PR), MUC5AC, and β-catenin. The adenocarcinoma showed similar immunohistochemical results, except for loss of ER expression and a slight increase in the ratio of Ki-67-positive cells. This case indicates that endocervicosis, known as a benign lesion, harbors the possibility of malignant transformation. © 2016 The Authors. Pathology International published by Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

Role of (Pro)Renin Receptor in Albumin Overload-Induced Nephropathy in Rats.

PubMed

Fang, Hui; Deng, Mokan; Zhang, Linlin; Lu, Aihua; Su, Jiahui; Xu, Chuanming; Zhou, Li; Wang, Lei; Ou, Jing-Song; Wang, Weidong; Yang, Tianxin

2018-05-30

Proteinuria is not only a common feature of chronic kidney diseases (CKD) but also an independent risk factor promoting CKD progression to end-stage renal failure. However, the underlying molecular mechanisms for protein overload-induced renal injury remain elusive. The present study examined the role of (pro)renin receptor (PRR) in pathogenesis of albumin overload (AO)-induced nephropathy and activation of intrarenal renin-angiotensin system (RAS) in rats. Wistar rats underwent unilateral nephrectomy and were treated for 7 weeks with vehicle, bovine serum albumin (5 g/kg/d via a single i.p. injection) alone or in conjunction with a PRR decoy inhibitor PRO20 (500 μg/kg/d via 3 s.c. injections). The AO rat model exhibited severe proteinuria, tubular necrosis, and interstitial fibrosis, oxidative stress, inflammation, accompanied by elevated urinary N-acetyl-beta-D-glucosaminidase activity and urinary β2-microglobulin secretion, all of which were significantly attenuated by PRO20. Urinary and renal levels of renin, angiotensinogen (AGT), and Ang II were elevated by AO and suppressed by PRO20, contrasting to largely unaltered plasma levels of the RAS parameters. The AO model also showed increased renal expression of full-length PRR and soluble PRR (sPRR) and urinary excretion of sPRR. Taken together, we conclude that PRR antagonism with PRO20 alleviates AO-induced nephropathy via inhibition of intrarenal RAS.

Copper-complexing ligands produced by an intact estuarine microbial community in response to copper stress.

NASA Astrophysics Data System (ADS)

Bingham, J.; Dryden, C.; Gordon, A.

2002-12-01

Copper is both an important nutrient and a pollutant in the marine environment. By studying the interactions between microorganisms and copper in the Elizabeth River (VA), home to a major Naval Base, we field tested the hypothesis that picoplankton and/or bacterioplankton produce strong, copper-complexing ligands in response to elevated copper concentrations. A simple light/ dark test was used to distinguish between heterotrophic and phototrophic ligand production. Samples were bottled and moored, submerged one meter, for a week. Direct counts using DAPI stain and epiflourescence were conducted to find concentrations of picoplankton and bacterioplankton. Using cathodic stripping voltammetry, we found the total copper concentrations, and then from a titration of the ligands by copper, the ligand concentrations and conditional stability constants were obtained. The Elizabeth River naturally had between 10-20 nM total dissolved copper concentrations. However when copper complexation was considered we found that the levels of bio-available Cu(II) ions were much lower. In fact in the natural samples the levels were not high enough to affect the relative reproductive rates of several microorganisms. Naturally there was a 50 nM "buffer zone" of ligand to total dissolved copper concentration. Furthermore, when stressed with excess copper, healthy picoplankton produced enough ligand to alleviate toxicity, and rebuild the buffer zone. However bacterioplankton only produced enough ligand so that they were no longer affected. Therefore, intact estuarine communities regulate copper bioavailability and toxicity with ligand production.

Second-Generation Difluorinated Cyclooctynes for Copper-Free Click Chemistry

PubMed Central

2008-01-01

The 1,3-dipolar cycloaddition of azides and activated alkynes has been used for site-selective labeling of biomolecules in vitro and in vivo. While copper catalysis has been widely employed to activate terminal alkynes for [3 + 2] cycloaddition, this method, often termed “click chemistry”, is currently incompatible with living systems because of the toxicity of the metal. We recently reported a difluorinated cyclooctyne (DIFO) reagent that rapidly reacts with azides in living cells without the need for copper catalysis. Here we report a novel class of DIFO reagents for copper-free click chemistry that are considerably more synthetically tractable. The new analogues maintained the same elevated rates of [3 + 2] cycloaddition as the parent compound and were used for imaging glycans on live cells. These second-generation DIFO reagents should expand the use of copper-free click chemistry in the hands of biologists. PMID:18680289

Reaction layer formation at the graphite/copper-chromium alloy interface

NASA Technical Reports Server (NTRS)

Devincent, Sandra M.; Michal, Gary M.

1992-01-01

Sessile drop tests were used to obtain information about copper chromium alloys that suitably wet graphite. Characterization of graphite/copper-chromium alloy interfaces subjected to elevated temperatures were conducted using scanning electron micrography, energy dispersive spectroscopy, auger electron spectroscopy, and x ray diffraction analyses. These analyses indicate that during sessile drop tests conducted at 1130 C for one hour, copper alloys containing greater than 0.98 percent chromium form continuous reaction layers of approximately 10 micron thickness. The reaction layers adhere to the graphite surface. The copper wets the reaction layer to form a contact angle of 60 degrees or less. X ray diffraction results indicate that the reaction layer is chromium carbide. The kinetics of reaction layer formation were modelled in terms of bulk diffusion mechanisms. Reaction layer thickness is controlled initially by the diffusion of Cr out of Cu alloy and later by the diffusion of C through chromium carbide.

Second-generation difluorinated cyclooctynes for copper-free click chemistry.

PubMed

Codelli, Julian A; Baskin, Jeremy M; Agard, Nicholas J; Bertozzi, Carolyn R

2008-08-27

The 1,3-dipolar cycloaddition of azides and activated alkynes has been used for site-selective labeling of biomolecules in vitro and in vivo. While copper catalysis has been widely employed to activate terminal alkynes for [3 + 2] cycloaddition, this method, often termed "click chemistry", is currently incompatible with living systems because of the toxicity of the metal. We recently reported a difluorinated cyclooctyne (DIFO) reagent that rapidly reacts with azides in living cells without the need for copper catalysis. Here we report a novel class of DIFO reagents for copper-free click chemistry that are considerably more synthetically tractable. The new analogues maintained the same elevated rates of [3 + 2] cycloaddition as the parent compound and were used for imaging glycans on live cells. These second-generation DIFO reagents should expand the use of copper-free click chemistry in the hands of biologists.

Reaction layer formation at the graphite/copper-chromium alloy interface

NASA Technical Reports Server (NTRS)

Devincent, Sandra M.; Michal, Gary M.

1993-01-01

Sessile drop tests were used to obtain information about copper chromium alloys that suitably wet graphite. Characterization of graphite/copper-chromium alloy interfaces subjected to elevated temperatures were conducted using scanning electron micrography, energy dispersive spectroscopy, Auger electron spectroscopy, and X-ray diffraction analyses. These analyses indicate that during sessile drop tests conducted at 1130 C for one hour, copper alloys containing greater than 0.98 percent chromium form continuous reaction layers of approximately 10 micron thickness. The reaction layers adhere to the graphite surface. The copper wets the reaction layer to form a contact angle of 60 degrees or less. X-ray diffraction results indicate that the reaction layer is chromium carbide. The kinetics of reaction layer formation were modelled in terms of bulk diffusion mechanisms. Reaction layer thickness is controlled initially by the diffusion of Cr out of Cu alloy and later by the diffusion of C through chromium carbide.

Copper recovery and cyanide oxidation by electrowinning from a spent copper-cyanide electroplating electrolyte.

PubMed

Dutra, A J B; Rocha, G P; Pombo, F R

2008-04-01

Copper-cyanide bleed streams arise from contaminated baths from industrial electroplating processes due to the buildup of impurities during continuous operation. These streams present an elevated concentration of carbonate, cyanide and copper, constituting a heavy hazard, which has to be treated for cyanide destruction and heavy metals removal, according to the local environmental laws. In the Brazilian Mint, bleed streams are treated with sodium hypochlorite, to destroy cyanide and precipitate copper hydroxide, a solid hazardous waste that has to be disposed properly in a landfill or treated for metal recovery. In this paper, a laboratory-scale electrolytic cell was developed to remove the copper from the bleed stream of the electroplating unit of the Brazilian Mint, permitting its reutilization in the plant and decreasing the amount of sludge to waste. Under favorable conditions copper recoveries around 99.9% were achieved, with an energy consumption of about 11 kWh/kg, after a 5-h electrolysis of a bath containing copper and total cyanide concentrations of 26 and 27 g/L, respectively. Additionally, a substantial reduction of the cyanide concentration was also achieved, decreasing the pollution load and final treatment costs.

ATP7B mediates vesicular sequestration of copper: insight into biliary copper excretion.

PubMed

Cater, Michael A; La Fontaine, Sharon; Shield, Kristy; Deal, Yolanda; Mercer, Julian F B

2006-02-01

The Wilson protein (ATP7B) regulates levels of systemic copper by excreting excess copper into bile. It is not clear whether ATP7B translocates excess intrahepatic copper directly across the canalicular membrane or sequesters this copper into exocytic vesicles, which subsequently fuse with canalicular membrane to expel their contents into bile. The aim of this study was to clarify the mechanism underlying ATP7B-mediated copper detoxification by investigating endogenous ATP7B localization in the HepG2 hepatoma cell line and its ability to mediate vesicular sequestration of excess intracellular copper. Immunofluorescence microscopy was used to investigate the effect of copper concentration on the localization of endogenous ATP7B in HepG2 cells. Copper accumulation studies to determine whether ATP7B can mediate vesicular sequestration of excess intracellular copper were performed using Chinese hamster ovary cells that exogenously expressed wild-type and mutant ATP7B proteins. In HepG2 cells, elevated copper levels stimulated trafficking of ATP7B to pericanalicular vesicles and not to the canalicular membrane as previously reported. Mutation of an endocytic retrieval signal in ATP7B caused the protein to constitutively localize to vesicles and not to the plasma membrane, suggesting that a vesicular compartment(s) is the final trafficking destination for ATP7B. Expression of wild-type and mutant ATP7B caused Chinese hamster ovary cells to accumulate copper in vesicles, which subsequently undergo exocytosis, releasing copper across the plasma membrane. This report provides compelling evidence that the primary mechanism of biliary copper excretion involves ATP7B-mediated vesicular sequestration of copper rather than direct copper translocation across the canalicular membrane.

Effect of Long-Term Systolic Blood Pressure Trajectory on Kidney Damage in the Diabetic Population: A Prospective Study in a Community-Based Chinese Cohort.

PubMed

Li, Jian-Chao; Tian, Jun; Wu, Shou-Ling; Wang, Zhi-Jun; Zhang, Xiao-Fei; Jia, Dao; Ding, Rong-Jing; Xiao, Xiong-Fu; Fan, Yu-Bo; Hu, Da-Yi

2018-05-20

Previous studies have shown that hypertension is an important factor contributing to the occurrence and progression of diabetic kidney damage. However, the relationship between the patterns of blood pressure (BP) trajectory and kidney damage in the diabetic population remains unclear. This prospective study investigated the effect of long-term systolic BP (SBP) trajectory on kidney damage in the diabetic population based on an 8-year follow-up community-based cohort. This study included 4556 diabetic participants among 101,510 participants. BP, estimated glomerular filtration rate (eGFR), and urinary protein were measured every 2 years from 2006 to 2014. SBP trajectory was identified by the censored normal modeling. Five discrete SBP trajectories were identified according to SBP range and the changing pattern over time. Kidney damage was evaluated through eGFR and urinary protein value. A multivariate logistic regression model was used to analyze the influence of different SBP trajectory groups on kidney damage. We identified five discrete SBP trajectories: low-stable group (n = 864), moderate-stable group (n = 1980), moderate increasing group (n = 609), elevated decreasing group, (n = 679), and elevated stable group (n = 424). The detection rate of kidney damage in the low-stable group (SBP: 118-124 mmHg) was the lowest among the five groups. The detection rate of each kidney damage index was higher in the elevated stable group (SBP: 159-172 mmHg) compared with the low-stable group. For details, the gap was 4.14 (11.6% vs. 2.8%) in eGFR <60 ml·min -1 ·1.73 m -2 and 3.66 (17.2% vs. 4.7%), 3.38 (25.0% vs. 7.4%), and 1.8 (10.6% vs. 5.9%) times in positive urinary protein, eGFR <60 ml·min -1 ·1.73 m -2 and/or positive urinary protein, and eGFR decline ≥30%, respectively (P < 0.01). An elevated stable SBP trajectory is an independent risk factor for kidney damage in the diabetic population.

[Clinical trials of flomoxef in complicated urinary tract infections].

PubMed

Ohta, N; Sudoko, H; Fukuta, K; Nakano, M; Ushiyama, T; Tajima, A; Aso, Y; Masuda, H; Suzuki, A; Suzuki, K

1987-10-01

Flomoxef (6315-S, FMOX), a new oxacephem antibiotic was studied clinically in 27 patients with complicated urinary tract infections. FMOX was intravenously administered at a dose of 1.0 g twice daily for 5 days. Clinical effect of FMOX on patients with complicated urinary tract infections were excellent in 11.5%, moderate in 57.7% and overall clinical efficacy rate was 69.2%. During the treatment with FMOX, urticaria was observed in 1 case. In laboratory tests, a decrease of RBC, Hb and Ht in 1 case, a decrease of WBC in 1 case and an elevation of GPT in another case were observed. But these abnormal values were slight and transient.

Effect of potential renal acid load of foods on urinary citrate excretion in calcium renal stone formers.

PubMed

Trinchieri, Alberto; Lizzano, Renata; Marchesotti, Federica; Zanetti, Giampaolo

2006-02-01

The aim of this study was to investigate the influence of the potential renal acid load (PRAL) of the diet on the urinary risk factors for renal stone formation. The present series comprises 187 consecutive renal calcium stone patients (114 males, 73 females) who were studied in our stone clinic. Each patient was subjected to an investigation including a 24-h dietary record and 24-h urine sample taken over the same period. Nutrients and calories were calculated by means of food composition tables using a computerized procedure. Daily PRAL was calculated considering the mineral and protein composition of foods, the mean intestinal absorption rate for each nutrient and the metabolism of sulfur-containing amino acids. Sodium, potassium, calcium, magnesium, phosphate, oxalate, urate, citrate, and creatinine levels were measured in the urine. The mean daily PRAL was higher in male than in female patients (24.1+/-24.0 vs 16.1+/-20.1 mEq/day, P=0.000). A significantly (P=0.01) negative correlation (R=-0.18) was found between daily PRAL and daily urinary citrate, but no correlation between PRAL and urinary calcium, oxalate, and urate was shown. Daily urinary calcium (R=0.186, P=0.011) and uric acid (R=0.157, P=0.033) were significantly related to the dietary intake of protein. Daily urinary citrate was significantly related to the intakes of copper (R=0.178, P=0.015), riboflavin (R=0.20, P=0.006), piridoxine (R=0.169, P=0.021) and biotin (R=0.196, P=0.007). The regression analysis by stepwise selection confirmed the significant negative correlation between PRAL and urinary citrate (P=0.002) and the significant positive correlation between riboflavin and urinary citrate (P=0.000). Urinary citrate excretion of renal stone formers (RSFs) is highly dependent from dietary acid load. The computation of the renal acid load is advisable to investigate the role of diet in the pathogenesis of calcium stone disease and it is also a useful tool to evaluate the lithogenic potential of the diet of the individual patient.

Characterization of failure processes in tungsten copper composites under fatigue loading conditions

NASA Technical Reports Server (NTRS)

Kim, Yong-Suk; Verrilli, Michael J.; Gabb, Timothy P.

1989-01-01

A fractographic and metallographic investigation was performed on specimens of a tungsten fiber reinforced copper matrix composite (9 vol percent), which had experienced fatigue failures at elevated temperatures. Major failure modes and possible failure mechanisms, with an emphasis placed on characterizing fatigue damage accumulation, were determined. Metallography of specimens fatigued under isothermal cyclic loading suggested that fatigue damage initiates in the matrix. Cracks nucleated within the copper matrix at grain boundaries, and they propagated through cavity coalescence. The growing cracks subsequently interacted with the reinforcing tungsten fibers, producing a localized ductile fiber failure. Examinations of interrupted tests before final failure confirmed the suggested fatigue damage processes.

The insulation of copper wire by the electrostatic coating process

NASA Astrophysics Data System (ADS)

Wells, M. G. H.

1983-06-01

A review of the fluidized bed electrostatic coating process and materials available for application to flat copper conductor has been made. Lengths of wire were rolled and electrostatically coated with two epoxy insulations. Electrical tests were made in air on coated samples at room and elevated temperatures. Compatibility tests in the cooling/lubricating turbine oil at temperatures up to 220 deg. C were also made. Recommendations for additional work are provided.

Nocturnal Urinary Excretion of FSH and LH in Children and Adolescents With Normal and Early Puberty.

PubMed

Kolby, Nanna; Busch, Alexander S; Aksglaede, Lise; Sørensen, Kaspar; Petersen, Jorgen Holm; Andersson, Anna-Maria; Juul, Anders

2017-10-01

Clinical use of single serum gonadotropin measurements in children is limited by the pulsatile secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). However, first morning voided (FMV) urine may integrate the fluctuating gonadotropin serum levels. We aimed to evaluate urinary and serum gonadotropin levels according to age, sex, and pubertal stage in healthy children and to assess the clinical use of FMV urinary gonadotropins in children with disordered puberty. Cross-sectional part of the COPENHAGEN Puberty Study and longitudinal study of patients. Population-based and outpatient clinic. Eight hundred forty-three healthy children from the COPENHAGEN Puberty Study and 25 girls evaluated for central precocious puberty (CPP). Clinical pubertal staging, including serum and urinary gonadotropin levels. Urinary gonadotropins increased with advancing age and pubertal development and were detectable in FMV urine before physical signs of puberty. FMV urinary LH correlated strongly with basal (r = 0.871, P < 0.001) and gonadotropin-releasing hormone (GnRH)-stimulated serum LH (r = 0.82, P < 0.001). Urinary LH was superior to urinary FSH in differentiating the pubertal stage. Receiver operating curve analysis revealed that a cut-off standard deviation (SD) score of 2 for urinary LH (IU/L) gave a sensitivity of 75% and a specificity of 92% in predicting a positive GnRH stimulation test (LHmax > 5 IU/L). Urinary concentrations of LH decreased after 3 months of GnRH treatment to levels below +2 SDs. Urinary gonadotropin levels increased before the onset of puberty and were elevated in girls with CPP. We suggest urinary LH as an alternative noninvasive method to improve diagnosing and therapeutic management of children with disordered puberty. Copyright © 2017 Endocrine Society

Low serum zinc is associated with elevated risk of cadmium nephrotoxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, Yu-Sheng, E-mail: Lin.Yu-Sheng@epa.gov; Ho, Wen-Chao; Caffrey, James L.

Background: Despite animal evidence suggests that zinc modulates cadmium nephrotoxicity, limited human data are available. Objective: To test the hypothesis that low serum zinc concentrations may increase the risk of cadmium-mediated renal dysfunction in humans. Methods: Data from 1545 subjects aged 20 or older in the National Health and Nutrition Examination Survey (NHANES), 2011–2012 were analyzed. Renal function was defined as impaired when estimated glomerular filtration rate (eGFR) fell below 60 ml/min/1.73 m{sup 2} and/or the urinary albumin-to-creatinine ratio surpassed 2.5 in men and 3.5 mg/mmol in women. Results: Within the study cohort, 117 subjects had reduced eGFR and 214more » had elevated urinary albumin. After adjusting for potential confounders, subjects with elevated blood cadmium (>0.53 μg/L) were more likely to have a reduced eGFR (odds ratio [OR]=2.21, 95% confidence interval [CI]: 1.09–4.50) and a higher urinary albumin (OR=2.04, 95% CI: 1.13–3.69) than their low cadmium (<0.18 μg/L) peers. In addition, for any given cadmium exposure, low serum zinc is associated with elevated risk of reduced eGFR (OR=3.38, 95% CI: 1.39–8.28). A similar increase in the odds ratio was observed between declining serum zinc and albuminuria but failed to reach statistical significance. Those with lower serum zinc/blood cadmium ratios were likewise at a greater risk of renal dysfunction (p<0.01). Conclusions: This study results suggest that low serum zinc concentrations are associated with an increased risk of cadmium nephrotoxicity. Elevated cadmium exposure is global public health issue and the assessment of zinc nutritional status may be an important covariate in determining its effective renal toxicity. - Highlights: • Blood cadmium was associated with increased risk of nephrotoxicity. • Low serum zinc may exacerbate risk of cadmium-mediated renal dysfunction. • Both zinc deficiency and elevated cadmium exposure are global public health issues. • Nutritional status is important in the assessment of cadmium nephrotoxicity.« less

Bladder Cancer

MedlinePlus

... have an elevated risk of developing bladder cancer. Chronic bladder inflammation. Chronic or repeated urinary infections or inflammations (cystitis), ... the world, squamous cell carcinoma is linked to chronic bladder inflammation caused by the parasitic infection known as schistosomiasis. ...

Elevated Levels of Urinary Markers of Oxidative DNA and RNA Damage in Type 2 Diabetes with Complications.

PubMed

Liu, Xinle; Gan, Wei; Zou, Yuangao; Yang, Bin; Su, Zhenzhen; Deng, Jin; Wang, Lanlan; Cai, Jianping

2016-01-01

The mechanisms underlying progression of type 2 diabetes are complex and varied. Recent studies indicated that oxidative stress provided a new sight. To further assess the relationship between nucleic acid oxidation and complications in patients with type 2 diabetes and explore its possible molecular mechanisms, we studied 1316 subjects, including 633 type 2 diabetes patients and 683 age- and sex-matched healthy controls. Urinary levels of DNA oxidation marker 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo) and RNA oxidation marker 8-oxo-7,8-dihydroguanosine (8-oxoGuo) were measured by ultraperformance liquid chromatography and mass spectrometry (UPLC-MS/MS). Serum glucose, HbA1c, total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides (TG) were also determined. The results showed significantly elevated levels of both the urinary 8-oxodGuo and 8-oxoGuo in diabetes patients with/without complications compared with age-matched healthy control subjects (p = 0.02 and p < 0.001, resp.). Patients with complications, especially macrovascular complications, exhibited higher levels of 8-oxoGuo than those without complications, while there was no difference in the concentrations of serum glucose and lipids. The finding indicates the role for oxidative damage to DNA and RNA, as a molecular mechanism contributing to the progression of type 2 diabetes. Elevated levels of 8-oxoGuo may be a risk factor for type 2 diabetes complications, especially in diabetic macrovascular complications.

Urinary free light chains may help to identify infection in patients with elevated systemic inflammation due to rheumatic disease.

PubMed

Bramlage, Carsten P; Froelich, Britta; Wallbach, Manuel; Minguet, Joan; Grupp, Clemens; Deutsch, Cornelia; Bramlage, Peter; Müller, Gerhard A; Koziolek, Michael

2017-04-01

The risk of infection in patients with rheumatic diseases is elevated, but a clear marker to differentiate the cause of the systemic inflammation is missing. We assessed the ability urinary immunoglobulin free light chains (FLCs) to indicate the presence of infection in patients with rheumatic disease. We performed a retrospective analysis of patients with rheumatic disease attending the Georg-August University Hospital in Goettingen, Germany, from January 2011 to December 2013. Subjects were included if they had urine levels of κ and λ FLCs available. A reference group of patients without autoimmune disease, but with documented infection, was constructed. A total of 1500 patients had their urinary FLCs quantified during the study period. Of the 382 patients with rheumatic disease, 172 (45%) displayed no systemic inflammation, 162 (42%) had inflammation due to the underlying disease activity, and 48 (13%) had inflammation due to a confirmed infection. Urinary FLC concentrations were much higher in patients with rheumatic diseases and infection (κ 68.8 ± 81.8 mg/L, λ 31.4 ± 53.5 mg/L) compared to those with inflammation due to rheumatic disease activity (κ 22.7 ± 26.3 mg/L, λ 8.1 ± 9.1 mg/L, κ p < 0.001, λ p = 0.004). Urinary κ FLCs demonstrated good ability to predict infection, with a sensitivity of 63% and specificity of 84%. Urinary λ FLCs gave similar values, with a sensitivity of 65% and specificity of 81%. FLCs may be useful for distinguishing inflammation due to rheumatic disease activity from that due to the additional presence of infection. The ability to quantify these proteins in urine provides a simple alternative to the use of blood.

Impact of prenatal exposure to cadmium on cognitive development at preschool age and the importance of selenium and iodine.

PubMed

Kippler, Maria; Bottai, Matteo; Georgiou, Vaggelis; Koutra, Katerina; Chalkiadaki, Georgia; Kampouri, Mariza; Kyriklaki, Andriani; Vafeiadi, Marina; Fthenou, Eleni; Vassilaki, Maria; Kogevinas, Manolis; Vahter, Marie; Chatzi, Leda

2016-11-01

The evidence regarding a potential link of low-to-moderate iodine deficiency, selenium status, and cadmium exposure during pregnancy with neurodevelopment is either contradicting or limited. We aimed to assess the prenatal impact of cadmium, selenium, and iodine on children's neurodevelopment at 4 years of age. The study included 575 mother-child pairs from the prospective "Rhea" cohort on Crete, Greece. Exposure to cadmium, selenium and iodine was assessed by concentrations in the mother's urine during pregnancy (median 13 weeks), measured by ICPMS. The McCarthy Scales of Children's Abilities was used to assess children's general cognitive score and seven different sub-scales. In multivariable-adjusted regression analysis, elevated urinary cadmium concentrations (≥0.8 µg/L) were inversely associated with children's general cognitive score [mean change: -6.1 points (95 % CI -12; -0.33) per doubling of urinary cadmium; corresponding to ~0.4 SD]. Stratifying by smoking status (p for interaction 0.014), the association was restricted to smokers. Urinary selenium was positively associated with children's general cognitive score [mean change: 2.2 points (95 % CI -0.38; 4.8) per doubling of urinary selenium; ~0.1 SD], although the association was not statistically significant. Urinary iodine (median 172 µg/L) was not associated with children's general cognitive score. In conclusion, elevated cadmium exposure in pregnancy of smoking women was inversely associated with the children's cognitive function at pre-school age. The results indicate that cadmium may adversely affect neurodevelopment at doses commonly found in smokers, or that there is an interaction with other toxicants in tobacco smoke. Additionally, possible residual confounding cannot be ruled out.

Mechanisms of Contact-Mediated Killing of Yeast Cells on Dry Metallic Copper Surfaces▿

PubMed Central

Quaranta, Davide; Krans, Travis; Santo, Christophe Espírito; Elowsky, Christian G.; Domaille, Dylan W.; Chang, Christopher J.; Grass, Gregor

2011-01-01

Surfaces made of copper or its alloys have strong antimicrobial properties against a wide variety of microorganisms. However, the molecular mode of action responsible for the antimicrobial efficacy of metallic copper is not known. Here, we show that dry copper surfaces inactivate Candida albicans and Saccharomyces cerevisiae within minutes in a process called contact-mediated killing. Cellular copper ion homeostasis systems influenced the kinetics of contact-mediated killing in both organisms. Deregulated copper ion uptake through a hyperactive S. cerevisiae Ctr1p (ScCtr1p) copper uptake transporter in Saccharomyces resulted in faster inactivation of mutant cells than of wild-type cells. Similarly, lack of the C. albicans Crp1p (CaCrp1p) copper-efflux P-type ATPase or the metallothionein CaCup1p caused more-rapid killing of Candida mutant cells than of wild-type cells. Candida and Saccharomyces took up large quantities of copper ions as soon as they were in contact with copper surfaces, as indicated by inductively coupled plasma mass spectroscopy (ICP-MS) analysis and by the intracellular copper ion-reporting dye coppersensor-1. Exposure to metallic copper did not cause lethality through genotoxicity, deleterious action on a cell's genetic material, as indicated by a mutation assay with Saccharomyces. Instead, toxicity mediated by metallic copper surfaces targeted membranes in both yeast species. With the use of Live/Dead staining, onset of rapid and extensive cytoplasmic membrane damage was observed in cells from copper surfaces. Fluorescence microscopy using the indicator dye DiSBaC2(3) indicated that cell membranes were depolarized. Also, during contact-mediated killing, vacuoles first became enlarged and then disappeared from the cells. Lastly, in metallic copper-stressed yeasts, oxidative stress in the cytoplasm and in mitochondria was elevated. PMID:21097600

Dynamic magnetic resonance imaging of the behavior of the mid-urethra in healthy and stress incontinent women.

PubMed

Rinne, Kirsi Marja; Kainulainen, Sakari; Aukee, Sinikka; Heinonen, Seppo; Nilsson, Carl Gustaf

2010-03-01

Support of the mid-urethra is thought to be an essential element of urinary continence in the female. Our aim was to image the behavior of the mid-urethra in healthy volunteers and in stress urinary incontinence (SUI) patients by dynamic magnetic resonance imaging (MRI). Prospective study. Gynecology outpatient clinic association with Department of Radiology in University Hospital of Kuopio, Finland. Fifteen healthy volunteers and 40 SUI women underwent dynamic MRI at rest, during pelvic floor muscle contraction, coughing and voiding with a bladder volume of 200 ml. Our aim was to determine the precise location and movement of the mid-urethra during these activities. The co-ordinate location and movement of the mid-urethra. Continent volunteers can elevate their mid-urethra significantly higher than incontinent women. Moreover, the mid-urethra of incontinent women rotated significantly more dorsocaudally during straining and coughing than in continent women. Elevation of the mid-urethra was more marked in continent compared to urinary incontinent women on pelvic floor muscle contraction suggesting sufficient support of the urethra. Downward movement of the mid-urethra was more significant in stress incontinent women than in continent volunteers.

Decreased fucosylated PSA as a urinary marker for high Gleason score prostate cancer.

PubMed

Fujita, Kazutoshi; Hayashi, Takuji; Matsuzaki, Kyosuke; Nakata, Wataru; Masuda, Mika; Kawashima, Atsunari; Ujike, Takeshi; Nagahara, Akira; Tsuchiya, Mutsumi; Kobayashi, Yuka; Nojima, Satoshi; Uemura, Motohide; Morii, Eiichi; Miyoshi, Eiji; Nonomura, Norio

2016-08-30

Fucosylation is an important oligosaccharide modification associated with cancer and inflammation. We investigated whether urinary fucosylated PSA (Fuc-PSA) levels could be used for the detection of high Gleason score prostate cancer. Urine samples were collected from men with abnormal digital rectal examination findings or elevated serum PSA levels, before prostate biopsy. Lectin-antibody ELISA was used to quantify the Lewis-type or core-type fucosylated PSA (PSA-AAL) and core-type fucosylated PSA (PSA-PhoSL) in the urine samples. Both types of urinary Fuc-PSA were significantly decreased in the men with prostate cancer compared with the men whose biopsies were negative for cancer (P = 0.026 and P < 0.001, respectively). Both were also significantly associated with the Gleason scores of the biopsy specimens (P = 0.001 and P < 0.001, respectively). Multivariate analysis showed that PSA density, urinary PSA-AAL, and urinary PSA-PhoSL were independent predictors of high Gleason score prostate cancer. The area under the receiver-operator characteristic curve (AUC) value for the prediction of cancers of Gleason score ≥ 7 was 0.69 for urinary PSA-AAL and 0.72 for urinary PSA-PhoSL. In contrast, the AUC value was 0.59 for serum PSA, 0.63 for PSA density, and 0.58 for urinary PSA. In conclusion, a decreased urinary Fuc-PSA level is a potential marker for the detection of high Gleason score prostate cancer.

Decreased fucosylated PSA as a urinary marker for high Gleason score prostate cancer

PubMed Central

Fujita, Kazutoshi; Hayashi, Takuji; Matsuzaki, Kyosuke; Nakata, Wataru; Masuda, Mika; Kawashima, Atsunari; Ujike, Takeshi; Nagahara, Akira; Tsuchiya, Mutsumi; Kobayashi, Yuka; Nojima, Satoshi; Uemura, Motohide; Morii, Eiichi; Miyoshi, Eiji; Nonomura, Norio

2016-01-01

Fucosylation is an important oligosaccharide modification associated with cancer and inflammation. We investigated whether urinary fucosylated PSA (Fuc-PSA) levels could be used for the detection of high Gleason score prostate cancer. Urine samples were collected from men with abnormal digital rectal examination findings or elevated serum PSA levels, before prostate biopsy. Lectin-antibody ELISA was used to quantify the Lewis-type or core-type fucosylated PSA (PSA-AAL) and core-type fucosylated PSA (PSA-PhoSL) in the urine samples. Both types of urinary Fuc-PSA were significantly decreased in the men with prostate cancer compared with the men whose biopsies were negative for cancer (P = 0.026 and P < 0.001, respectively). Both were also significantly associated with the Gleason scores of the biopsy specimens (P = 0.001 and P < 0.001, respectively). Multivariate analysis showed that PSA density, urinary PSA-AAL, and urinary PSA-PhoSL were independent predictors of high Gleason score prostate cancer. The area under the receiver-operator characteristic curve (AUC) value for the prediction of cancers of Gleason score ≥ 7 was 0.69 for urinary PSA-AAL and 0.72 for urinary PSA-PhoSL. In contrast, the AUC value was 0.59 for serum PSA, 0.63 for PSA density, and 0.58 for urinary PSA. In conclusion, a decreased urinary Fuc-PSA level is a potential marker for the detection of high Gleason score prostate cancer. PMID:27494861

Association between Concentrations of Metals in Urine and Adult Asthma: A Case-Control Study in Wuhan, China

PubMed Central

Huang, Xiji; Xie, Jungang; Cui, Xiuqing; Zhou, Yun; Wu, Xiaojie; Lu, Wei; Shen, Yan; Yuan, Jing; Chen, Weihong

2016-01-01

Background Several metals have been reported to be associated with childhood asthma. However, the results on relationships between metals and risk of childhood asthma are inconclusive, and the research on adult asthma in the Chinese general population is rare. Objectives To investigate potential associations between levels of urinary metals and adult asthma. Methods A case-control study of 551 adult asthma cases and 551 gender- and age-matched controls was conducted in Wuhan, China. Demographic information was obtained, and lung function was assessed. The urinary concentrations of 22 metals were measured by inductively coupled plasma mass spectrometry. Results After adjusting for other metalsand other covariates, urinary cadmium, molybdenum, chromium, copper, uranium and selenium were positively associated with asthma, with odds ratios (95% CI) of 1.69 (1.00, 2.85), 3.76 (2.30, 6.16), 4.89 (3.04, 7.89), 6.06 (3.27, 11.21), 6.99 (4.37, 11.19) and 9.17 (4.16, 20.21), respectively. By contrast, urinary lead, barium, iron, zinc, nickel, manganese and rubidium were negatively associated with asthma, with odds ratios (95% CI) of 0.48 (0.29, 0.80), 0.44 (0.27, 0.71), 0.41 (0.26, 0.64), 0.40 (0.24, 0.66), 0.30 (0.22, 0.41), 0.23 (0.14, 0.39) and 0.07 (0.03, 0.15), respectively. When comparing urinary metals in different subgroups of cases with those in matched controls, the associations of above 13 metals with asthma prevalence were nearly the same. Conclusions Our results suggested that asthma prevalence in the Chinese adults was positively associated with urinary chromium, chromium, selenium, molybdenum, cadmium, and uranium, and negatively associated with urinary manganese, iron, nickel, zinc, rubidium, barium and lead. Additional research with larger populations in different regions is required to support our findings. PMID:27191859

Biomarkers of oxidative stress and its association with the urinary reducing capacity in bus maintenance workers.

PubMed

Sauvain, Jean-Jacques; Setyan, Ari; Wild, Pascal; Tacchini, Philippe; Lagger, Grégoire; Storti, Ferdinand; Deslarzes, Simon; Guillemin, Michel; Rossi, Michel J; Riediker, Michael

2011-05-30

Exposure to particles (PM) induces adverse health effects (cancer, cardiovascular and pulmonary diseases). A key-role in these adverse effects seems to be played by oxidative stress, which is an excess of reactive oxygen species relative to the amount of reducing species (including antioxidants), the first line of defense against reactive oxygen species. The aim of this study was to document the oxidative stress caused by exposure to respirable particles in vivo, and to test whether exposed workers presented changes in their urinary levels for reducing species. Bus depot workers (n = 32) exposed to particles and pollutants (respirable PM4, organic and elemental carbon, particulate metal content, polycyclic aromatic hydrocarbons, NOx, O3) were surveyed over two consecutive days. We collected urine samples before and after each shift, and quantified an oxidative stress biomarker (8-hydroxy-2'-deoxyguanosine), the reducing capacity and a biomarker of PAH exposure (1-hydroxypyrene). We used a linear mixed model to test for associations between the oxidative stress status of the workers and their particle exposure as well as with their urinary level of reducing species. Workers were exposed to low levels of respirable PM4 (range 25-71 μg/m3). However, urinary levels of 8-hydroxy-2'-deoxyguanosine increased significantly within each shift and between both days for non-smokers. The between-day increase was significantly correlated (p < 0.001) with the concentrations of organic carbon, NOx, and the particulate copper content. The within-shift increase in 8OHdG was highly correlated to an increase of the urinary reducing capacity (Spearman ρ = 0.59, p < 0.0001). These findings confirm that exposure to components associated to respirable particulate matter causes a systemic oxidative stress, as measured with the urinary 8OHdG. The strong association observed between urinary 8OHdG with the reducing capacity is suggestive of protective or other mechanisms, including circadian effects. Additional investigations should be performed to understand these observations.

Communication between the N and C Termini Is Required for Copper-stimulated Ser/Thr Phosphorylation of Cu(I)-ATPase (ATP7B)*

PubMed Central

Braiterman, Lelita T.; Gupta, Arnab; Chaerkady, Raghothama; Cole, Robert N.; Hubbard, Ann L.

2015-01-01

The Wilson disease protein ATP7B exhibits copper-dependent trafficking. In high copper, ATP7B exits the trans-Golgi network and moves to the apical domain of hepatocytes where it facilitates elimination of excess copper through the bile. Copper levels also affect ATP7B phosphorylation. ATP7B is basally phosphorylated in low copper and becomes more phosphorylated (“hyperphosphorylated”) in elevated copper. The functional significance of hyperphosphorylation remains unclear. We showed that hyperphosphorylation occurs even when ATP7B is restricted to the trans-Golgi network. We performed comprehensive phosphoproteomics of ATP7B in low versus high copper, which revealed that 24 Ser/Thr residues in ATP7B could be phosphorylated, and only four of these were copper-responsive. Most of the phosphorylated sites were found in the N- and C-terminal cytoplasmic domains. Using truncation and mutagenesis, we showed that inactivation or elimination of all six N-terminal metal binding domains did not block copper-dependent, reversible, apical trafficking but did block hyperphosphorylation in hepatic cells. We showed that nine of 15 Ser/Thr residues in the C-terminal domain were phosphorylated. Inactivation of 13 C-terminal phosphorylation sites reduced basal phosphorylation and eliminated hyperphosphorylation, suggesting that copper binding at the N terminus propagates to the ATP7B C-terminal region. C-terminal mutants with either inactivating or phosphomimetic substitutions showed little effect upon copper-stimulated trafficking, indicating that trafficking does not depend on phosphorylation at these sites. Thus, our studies revealed that copper-dependent conformational changes in the N-terminal region lead to hyperphosphorylation at C-terminal sites, which seem not to affect trafficking and may instead fine-tune copper sequestration. PMID:25666620

Metabolic alkalosis during immobilization in monkeys (M. nemestrina)

NASA Technical Reports Server (NTRS)

Young, D. R.; Yeh, I.; Swenson, R. S.

1983-01-01

The systemic and renal acid-base response of monkeys during ten weeks of immobilization was studied. By three weeks of immobilization, arterial pH and bicarbonate concentrations were elevated (chronic metabolic alkalosis). Net urinary acid excretion increased in immobilized animals. Urinary bicarbonate excretion decreased during the first three weeks of immobilization, and then returned to control levels. Sustained increases in urinary ammonium excretion were seen throughout the time duration of immobilization. Neither potassium depletion nor hypokalemia was observed. Most parameters returned promptly to the normal range during the first week of recovery. Factors tentatively associated with changes in acid-base status of monkeys include contraction of extracellular fluid volume, retention of bicarbonate, increased acid excretion, and possible participation of extrarenal buffers.

Elevated urine levels of heparin-binding protein in children with urinary tract infection.

PubMed

Kjölvmark, Charlott; Akesson, Per; Linder, Adam

2012-08-01

Urinary tract infection (UTI) is a common infection diagnosis in children, and efficient diagnosis and treatment are important to avoid serious complications. In this study we investigated whether urinary levels of neutrophil-derived heparin-binding protein (HBP) can be used as a marker of UTI in children. These results were compared to those of dipstick analysis, interleukin-6 (IL-6) analysis in urine, and bacterial culturing. Seventy-eight children aged 0-18 years with fever and/or symptoms indicating UTI were enrolled in a prospective consecutive study. Urine samples were cultured and analyzed with dipstick, and concentrations of HBP and IL-6 were measured. Fifteen patients were classified as having UTI, 30 patients had fever but were diagnosed with a non-urinary tract infection, and 33 patients had neither UTI nor fever. Using a urine HBP (U-HBP) cut-off level of 32 ng/mL, the sensitivity and specificity for detecting UTI were 93.3 and 90.3 %, respectively. Receiver operating characteristic curves demonstrated that U-HBP levels were a higher specificity indicator of UTI than urine white blood cell counts or urine IL-6 levels; they also showed a higher sensitivity than the results of the urine nitrite test. All patients with significant growth of clinically relevant bacteria had elevated U-HBP levels. The results indicate that rapid analysis of U-HBP can provide helpful guidance in the management of children with suspected UTI.

A historical case of beaten-copper cranium.

PubMed

Rühli, Frank J; Nicklisch, Nicole; Alt, Kurt W

2007-01-01

The authors present the oldest historical case of a so-called beaten-copper cranium. The typical pattern was identified on a skull from a child, probably a boy, who died at approximately 6 years of age and was buried in a provisional cemetery used during the siege of Hanau, Germany, in 1635 and 1636. Morphological and radiological analyses of the severe digitate impressions ubiquitous on the child's endocranium support the diagnosis of chronically elevated intracranial pressure due to hydrocephalus.

Elemental composition of human semen is associated with motility and genomic sperm defects among older men

PubMed Central

Schmid, Thomas E.; Grant, Patrick G.; Marchetti, Francesco; Weldon, Rosana H.; Eskenazi, Brenda; Wyrobek, Andrew J.

2013-01-01

BACKGROUND Older men tend to have poorer semen quality and are generally at higher risks for infertility and abnormal reproductive outcomes. METHODS We employed proton-induced X-ray emission (PIXE, 3 MeV proton beam) to investigate the concentrations of zinc, copper, calcium, sulfur, chlorine, potassium, titanium, iron and nickel in washed sperm and seminal plasma from non-smoking groups of 10 older men (65–80 years old) and 10 younger men (22–28 years old) who were concurrently assayed for sperm function and genomicly defective sperm. RESULTS The older group showed elevated zinc, copper and calcium in sperm and elevated sulfur in seminal plasma compared with the younger men. The older group also showed reduced motility as well as increased sperm DNA fragmentation, achondroplasia mutations, DNA strand breaks and chromosomal aberrations. Sperm calcium and copper were positively associated with sperm DNA fragmentation (P < 0.03). Seminal sulfur was positively associated with sperm DNA fragmentation and chromosomal aberrations (P < 0.04), and negatively associated with sperm motility (P < 0.05). Sperm calcium was negatively associated with sperm motility, independent of male age (P = 0.01). CONCLUSIONS We identified major differences in elemental concentrations between sperm and seminal plasma and that higher sperm copper, sulfur and calcium are quantitatively associated with poorer semen quality and increased frequencies of genomic sperm defects. PMID:23042799

Inflammation, coagulation, endothelial dysfunction and oxidative stress in prediabetes--Biomarkers as a possible tool for early disease detection for rural screening.

PubMed

Maschirow, L; Khalaf, K; Al-Aubaidy, H A; Jelinek, H F

2015-06-01

This study aims to increase understanding of the connection between oxidative stress and inflammation in diabetes disease progression to provide a basis for investigating improved diagnostic possibilities, treatment and prevention of prediabetes. Differences in the level of biochemical markers of oxidative stress (erythrocyte GSH/GSSG and urinary 8-isoprostane), inflammation (CRP, IL-6), endothelial dysfunction (plasma homocysteine, urinary 8-hydroxy-2-deoxy-guanosine) and coagulation/fibrinolysis (C5a, D-Dimer) were determined in prediabetes and control subjects. While no difference was found in the 8-isoprostane levels between the two groups, the erythrocyte GSH/GSSG ratio was significantly reduced in the prediabetes group compared to control, indicating increased oxidative stress in the prediabetic state. Both urinary 8-OHdG and surprisingly also plasma homocysteine were significantly elevated in the prediabetes group, indicating endothelial dysfunction. The inflammation markers were slightly elevated in the prediabetic subjects and the same trend was found for the coagulation/fibrinolysis markers C5a and D-Dimer. These results were however not significant. The small elevation of blood glucose levels in the prediabetic state may have a detectable influence on endothelial function as indicated by changes to 8-OHdG, indicating an increased DNA-damage and homocysteine release from endothelial cells. Increased oxidative stress as indicated by the reduced GSH/GSSG ratio is likely to be the link between the moderate hyperglycaemia in prediabetes and pathological changes in endothelial function, which in the long-term may promote atherogenesis and result in the development of cardiovascular disease. Early detection of prediabetes is essential to avoid diabetes development and the associated complications like cardiovascular disease. The GSH/GSSG ratio and biomarkers like urinary 8-OHdG and plasma homocysteine offer a possible tool for the assessment of prediabetes in prevention screenings. Copyright © 2015. Published by Elsevier Inc.

Epoetin beta pegol alleviates oxidative stress and exacerbation of renal damage from iron deposition, thereby delaying CKD progression in progressive glomerulonephritis rats.

PubMed

Hirata, Michinori; Tashiro, Yoshihito; Aizawa, Ken; Kawasaki, Ryohei; Shimonaka, Yasushi; Endo, Koichi

2015-12-01

The increased deposition of iron in the kidneys that occurs with glomerulopathy hinders the functional and structural recovery of the tubules and promotes progression of chronic kidney disease (CKD). Here, we evaluated whether epoetin beta pegol (continuous erythropoietin receptor activator: CERA), which has a long half-life in blood and strongly suppresses hepcidin-25, exerts renoprotection in a rat model of chronic progressive glomerulonephritis (cGN). cGN rats showed elevated urinary total protein excretion (uTP) and plasma urea nitrogen (UN) from day 14 after the induction of kidney disease (day 0) and finally declined into end-stage kidney disease (ESKD), showing reduced creatinine clearance with glomerulosclerosis, tubular dilation, and tubulointerstitial fibrosis. A single dose of CERA given on day 1, but not on day 16, alleviated increasing uTP and UN, thereby delaying ESKD. In the initial disease phase, CERA significantly suppressed urinary 8-OHdG and liver-type fatty acid-binding protein (L-FABP), a tubular damage marker. CERA also inhibited elevated plasma hepcidin-25 levels and alleviated subsequent iron accumulation in kidneys in association with elevated urinary iron excretion and resulted in alleviation of growth of Ki67-positive tubular and glomerular cells. In addition, at day 28 when the exacerbation of uTP occurs, a significant correlation was observed between iron deposition in the kidney and urinary L-FABP. In our study, CERA mitigated increasing kidney damage, thereby delaying CKD progression in this glomerulonephritis rat model. Alleviation by CERA of the exacerbation of kidney damage could be attributable to mitigation of tubular damage that might occur with lowered iron deposition in tubules. © 2015 Chugai Pharmaceutical Co., Ltd. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Supplementation with zinc in rats enhances memory and reverses an age-dependent increase in plasma copper.

PubMed

Sandusky-Beltran, Leslie A; Manchester, Bryce L; McNay, Ewan C

2017-08-30

Zinc and copper are essential trace elements. Dyshomeostasis in these two metals has been observed in Alzheimer's disease, which causes profound cognitive impairment. Insulin therapy has been shown to enhance cognitive performance; however, recent data suggest that this effect may be at least in part due to the inclusion of zinc in the insulin formulation used. Zinc plays a key role in regulation of neuronal glutamate signaling, suggesting a possible link between zinc and memory processes. Consistent with this, zinc deficiency causes cognitive impairments in children. The effect of zinc supplementation on short- and long-term recognition memory, and on spatial working memory, was explored in young and adult male Sprague Dawley rats. After behavioral testing, hippocampal and plasma zinc and copper were measured. Age increased hippocampal zinc and copper, as well as plasma copper, and decreased plasma zinc. An interaction between age and treatment affecting plasma copper was also found, with zinc supplementation reversing elevated plasma copper concentration in adult rats. Zinc supplementation enhanced cognitive performance across tasks. These data support zinc as a plausible therapeutic intervention to ameliorate cognitive impairment in disorders characterized by alterations in zinc and copper, such as Alzheimer's disease. Copyright © 2017 Elsevier B.V. All rights reserved.

Overexpression of copper transporter CTR1 in the brain barrier of North Ronaldsay sheep: implications for the study of neurodegenerative disease.

PubMed

Haywood, S; Vaillant, C

2014-01-01

Age-related regulatory failure of the brain barrier towards the influx of redox metals such as copper and iron may be associated with the pathological changes that characterize dementias such as Alzheimer's diseases (ADs) and amyotrophic lateral sclerosis (ALS). The integrity of the brain barrier to regulate copper in the brain is maintained by the complex interplay of membrane-located transporters, of which copper transporter 1 (CTR1) exerts a defining role. North Ronaldsay (NR) sheep are a primitive breed that have adapted to a copper-deficient environment by an enhanced uptake of the metal, resulting in copper overload in the liver and brain. This study reports that CTR1 is overexpressed in both the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCB) of adult NR sheep when compared with a domesticated breed. The excess copper is stored ultimately in astrocytes as non-injurious copper-metallothionein (MT). NR sheep have apparently retained an immature regulatory setting for CTR1 in the BBB, promoting facilitated copper uptake into the brain. This putative failure of maturation of CTR1 allows insight into the regulatory control of brain copper homeostasis, whereby the BBB and BCB act in concert to sequester excess copper and protect neurons from injury. The elevated copper content of the ageing human brain may derive from a dysregulation of CTR1 at the brain barrier, with a return to the default (immature) setting and implications for neurodegenerative disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

Mining legacy across a wetland landscape: high mercury in Upper Peninsula (Michigan) rivers, lakes, and fish.

PubMed

Kerfoot, W Charles; Urban, Noel R; McDonald, Cory P; Zhang, Huanxin; Rossmann, Ronald; Perlinger, Judith A; Khan, Tanvir; Hendricks, Ashley; Priyadarshini, Mugdha; Bolstad, Morgan

2018-04-25

A geographic enigma is that present-day atmospheric deposition of mercury in the Upper Peninsula of Michigan is low (48%) and that regional industrial emissions have declined substantially (ca. 81% reduction) relative to downstate. Mercury levels should be declining. However, state (MDEQ) surveys of rivers and lakes revealed elevated total mercury (THg) in Upper Peninsula waters and sediment relative to downstate. Moreover, Western Upper Peninsula (WUP) fish possess higher methyl mercury (MeHg) levels than Northern Lower Peninsula (NLP) fish. A contributing explanation for elevated THg loading is that a century ago the Upper Peninsula was a major industrial region, centered on mining. Many regional ores (silver, copper, zinc, massive sulfides) contain mercury in part per million concentrations. Copper smelters and iron furnace-taconite operations broadcast mercury almost continuously for 140 years, whereas mills discharged tailings and old mine shafts leaked contaminated water. We show that mercury emissions from copper and iron operations were substantial (60-650 kg per year) and dispersed over relatively large areas. Moreover, lake sediments in the vicinity of mining operations have higher THg concentrations. Sediment profiles from the Keweenaw Waterway show that THg accumulation increased 50- to 400-fold above modern-day atmospheric deposition levels during active mining and smelting operations, with lingering MeHg effects. High MeHg concentrations are geographically correlated with low pH and dissolved organic carbon (DOC), a consequence of biogeochemical cycling in wetlands, characteristic of the Upper Peninsula. DOC can mobilize metals and elevate MeHg concentrations. We argue that mercury loading from mining is historically superimposed upon strong regional wetland effects, producing a combined elevation of both THg and MeHg in the Western Upper Peninsula.

High mortality rates occur in copper deficient rats exposed to a normally nonlethal endotoxin treatment

DOE Office of Scientific and Technical Information (OSTI.GOV)

DiSilvestro, R.; Joseph, E.; Yang, F.L.

Endotoxin hepatotoxicity is proposed to occur by processes which could be retarded by 3 copper enzymes: ceruloplasmin, Cu-Zn superoxide dismutase (SOD), and extracellular (EC) SOD. Weanling rats fed low copper for 40 days showed low activity levels of these enzymes, and a very high mortality rate 20 h after endotoxin injection. No rats fed adequate copper died from this treatment. In addition, serum transaminase activities, indicators of liver damage, were elevated by 3 h to a greater extent in the deficient rats than in the adequates. The high susceptibility to endotoxemia in the deficient rats was not associated with lowmore » hepatic glutathione, high liver malondialedhyde, nor restricted metallothionein induction 3 h after endotoxin injection. Endotoxin reduced serum EC SOD activities in adequate and deficient rats, but final values were lower in the latter. Studies on roles of specific copper enzymes in resistance to endotoxemia are currently underway.« less

Evolution of copper arsenate resistance for enhanced enargite bioleaching using the extreme thermoacidophile Metallosphaera sedula.

PubMed

Ai, Chenbing; McCarthy, Samuel; Liang, Yuting; Rudrappa, Deepak; Qiu, Guanzhou; Blum, Paul

2017-12-01

Adaptive laboratory evolution (ALE) was employed to isolate arsenate and copper cross-resistant strains, from the copper-resistant M. sedula CuR1. The evolved strains, M. sedula ARS50-1 and M. sedula ARS50-2, contained 12 and 13 additional mutations, respectively, relative to M. sedula CuR1. Bioleaching capacity of a defined consortium (consisting of a naturally occurring strain and a genetically engineered copper sensitive strain) was increased by introduction of M. sedula ARS50-2, with 5.31 and 26.29% more copper recovered from enargite at a pulp density (PD) of 1 and 3% (w/v), respectively. M. sedula ARS50-2 arose as the predominant species and modulated the proportions of the other two strains after it had been introduced. Collectively, the higher Cu 2+ resistance trait of M. sedula ARS50-2 resulted in a modulated microbial community structure, and consolidating enargite bioleaching especially at elevated PD.

Body of Knowledge (BOK) for Copper Wire Bonds

NASA Technical Reports Server (NTRS)

Rutkowski, E.; Sampson, M. J.

2015-01-01

Copper wire bonds have replaced gold wire bonds in the majority of commercial semiconductor devices for the latest technology nodes. Although economics has been the driving mechanism to lower semiconductor packaging costs for a savings of about 20% by replacing gold wire bonds with copper, copper also has materials property advantages over gold. When compared to gold, copper has approximately: 25% lower electrical resistivity, 30% higher thermal conductivity, 75% higher tensile strength and 45% higher modulus of elasticity. Copper wire bonds on aluminum bond pads are also more mechanically robust over time and elevated temperature due to the slower intermetallic formation rate - approximately 1/100th that of the gold to aluminum intermetallic formation rate. However, there are significant tradeoffs with copper wire bonding - copper has twice the hardness of gold which results in a narrower bonding manufacturing process window and requires that the semiconductor companies design more mechanically rigid bonding pads to prevent cratering to both the bond pad and underlying chip structure. Furthermore, copper is significantly more prone to corrosion issues. The semiconductor packaging industry has responded to this corrosion concern by creating a palladium coated copper bonding wire, which is more corrosion resistant than pure copper bonding wire. Also, the selection of the device molding compound is critical because use of environmentally friendly green compounds can result in internal CTE (Coefficient of Thermal Expansion) mismatches with the copper wire bonds that can eventually lead to device failures during thermal cycling. Despite the difficult problems associated with the changeover to copper bonding wire, there are billions of copper wire bonded devices delivered annually to customers. It is noteworthy that Texas Instruments announced in October of 2014 that they are shipping microcircuits containing copper wire bonds for safety critical automotive applications. An evaluation of copper wire bond technology for applicability to spaceflight hardware may be warranted along with concurrently compiling a comprehensive understanding of the failure mechanisms involved with copper wire bonded semiconductor devices.

Ring World

NASA Image and Video Library

2007-03-01

Our robotic emissary, flying high above Saturn, captured this view of an alien copper-colored ring world. The overexposed planet has deliberately been removed to show the unlit rings alone, seen from an elevation of 60 degrees

Influence of essential trace minerals and micronutrient insufficiencies on harmful metal overload in a Mongolian patient with multiple sclerosis.

PubMed

Komatsu, Fumio; Kagawa, Yasuo; Kawabata, Terue; Kaneko, Yoshinori; Kudoh, Hideki; Purvee, Baatar; Otgon, Jugder; Chimedregzen, Ulziiburen

2012-07-01

Parkinson's disease and other neurological disorders are prevalent in Mongolia. Our previous studies revealed a significant correlation of these diseases with high oxidative stress due to a high body burden of harmful metals, such as manganese, iron, lead, cadmium, and aluminum. This report describes a 37-year-old male Mongolian patient with multiple sclerosis and essential micronutrient deficiency. This patient demonstrated high oxidative stress, as shown by high urinary 8-hydroxy-2'-deoxyguanosine levels of 14.7 and 14.3 ng/mg creatinine (crea), although his hair levels of these toxic metals were markedly lower than other Mongolians. In addition, this patient was deficient not only in various essential minerals, including selenium, magnesium, copper, cobalt, vanadium, and nickel, but also in micronutrients such as vitamin B6, C, E, folic acid, niacin, and β-carotene. Furthermore, after taking 2,3-dimercaptosuccinic acid, a chelating agent, urinary excretion of lead, cadmium, manganese, aluminum, iron, copper, and lithium were increased 156-, 8.4-, 7.6-, 4.3-, 3.3-, 2.1-, and 2.1-fold, respectively. These results suggest that this patient suffered from a deficiency in micronutrients such as essential minerals and vitamins, which resulted in a disturbance in the ability to excrete harmful metals into the urine and hair. It is possible that a deficiency of micronutrients and a high burden of heavy metals play a role in the pathogenesis of multiple sclerosis. Nutritional treatment may be an effective approach to this disease.

Clinical Utility of Urinary CD90 as a Biomarker for Prostate Cancer Detection — EDRN Public Portal

Cancer.gov

Tumor-associated stromal cells differ from normal gland-associated stromal cells in gene expression. Genes up-regulated in these stromal cells are potential cancer biomarkers, especially those encoding secreted or extracellular proteins. These proteins might be detected in urine. CD90/THY1 is one such candidate. A clinical test based on urinary CD90 would be useful in reducing the number of unnecessary biopsies done because of abnormal serum PSA and/or DRE finding. Elevated CD90 protein is found in tumor tissue and urine.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liao, Ya-Tang; Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taiwan; Genomics Research Center, Academia Sinica, Taiwan

Arsenic ingestion has been linked to increasing global prevalence of and mortality from cardiovascular disease (CVD); arsenic can be removed from drinking water to reduce related health effects. Lactate dehydrogenase (LDH) is used for the evaluation of acute arsenic toxicity in vivo and in vitro, but it is not validated for the evaluation of long-term, chronic arsenic exposure. The present study examined the long-term effect of chronic arsenic exposure on CVD and serum LDH levels, after consideration of arsenic metabolism capacity. A total of 380 subjects from an arseniasis-endemic area and 303 from a non-endemic area of southwestern Taiwan weremore » recruited in 2002. Various urinary arsenic species were analyzed using high-performance liquid chromatography (HPLC) and hydride generation systems. Fasting serum was used for quantitative determination of the total LDH activity. A significant dose–response relationship was observed between arsenic exposure and LDH elevation, independent of urinary arsenic profiles (P < 0.001). Furthermore, abnormal LDH elevation was associated with CVD mortality after adjustment for Framingham risk scores for 10-year CVD and arsenic exposure (hazard ratio, 3.98; 95% confidence interval, 1.07–14.81). LDH was elevated in subjects with arsenic exposure in a dose-dependent manner. LDH is a marker of arsenic toxicity associated with CVD mortality. Results of this study have important implications for use in ascertaining long-term arsenic exposure risk of CVD. -- Highlights: ► We showed that arsenic exposure was correlated with LDH elevation. ► LDH elevation was related to arsenic methylation capacity. ► Abnormal LDH elevation can be a marker of susceptibility to CVD mortality.« less

Hepatocellular Carcinoma: An Unusual Complication of Longstanding Wilson Disease.

PubMed

Gunjan, Deepak; Shalimar; Nadda, Neeti; Kedia, Saurabh; Nayak, Baibaswata; Paul, Shashi B; Gamanagatti, Shivanand Ramachandra; Acharya, Subrat K

2017-06-01

Wilson disease is caused by the accumulation of copper in the liver, brain or other organs, due to the mutation in ATP7B gene, which encodes protein that helps in excretion of copper in the bile canaliculus. Clinical presentation varies from asymptomatic elevation of transaminases to cirrhosis with decompensation. Hepatocellular carcinoma is a known complication of cirrhosis, but a rare occurrence in Wilson disease. We present a case of neurological Wilson disease, who later developed decompensated cirrhosis and hepatocellular carcinoma.

Ligand- and base-free copper(II)-catalyzed C-N bond formation: cross-coupling reactions of organoboron compounds with aliphatic amines and anilines.

PubMed

Quach, Tan D; Batey, Robert A

2003-11-13

[reaction: see text] A ligandless and base-free Cu-catalyzed protocol for the cross-coupling of arylboronic acids and potassium aryltrifluoroborate salts with primary and secondary aliphatic amines and anilines is described. The process utilizes catalytic copper(II) acetate monohydrate and 4 A molecular sieves in dichloromethane at slightly elevated temperatures under an atmosphere of oxygen. A broad range of functional groups are tolerated on both of the cross-coupling partners.

Urinary Biomarkers and Obstructive Sleep Apnea in Patients with Down Syndrome

PubMed Central

Elsharkawi, Ibrahim; Gozal, David; Macklin, Eric A.; Voelz, Lauren; Weintraub, Gil; Skotko, Brian G.

2017-01-01

Study Objectives The study aim was to compare urinary biomarkers in individuals with Down syndrome (DS) with and without obstructive sleep apnea (OSA) to those of age- and sex-matched neurotypically developing healthy controls (HC). We further investigated whether we could predict OSA in individuals with DS using these biomarkers. Methods Urine samples were collected from 58 individuals with DS the night before or the morning after their scheduled overnight polysomnogram or both, of whom 47 could be age- and sex-matched to a sample of 43 HC. Concentrations of 12 neurotransmitters were determined by enzyme-linked immunosorbent assay. Log-transformed creatinine-corrected assay levels were normalized. Normalized z-scores were compared between individuals with DS vs. HC, between individuals with DS with vs. without OSA, and to derive composite models to predict OSA. Results Most night-sampled urinary biomarkers were elevated among individuals with DS relative to matched HC. No urinary biomarker levels differed between individuals with DS with vs. without OSA. A combination of four urinary biomarkers predicted AHI > 1 with a positive predictive value of 90% and a negative predictive value of 68%. Conclusions Having DS, even in the absence of concurrent OSA, is associated with a different urinary biomarker profile when compared to HC. Therefore, while urinary biomarkers may be predictive of OSA in the general pediatric population, a different approach is needed in interpreting urinary biomarker assays in individuals with DS. Certain biomarkers also seem promising to be predictive of OSA in individuals with DS. PMID:28522103

The metabolic impact of methamphetamine on the systemic metabolism of rats and potential markers of methamphetamine abuse.

PubMed

Zheng, Tian; Liu, Linsheng; Shi, Jian; Yu, Xiaoyi; Xiao, Wenjing; Sun, Runbing; Zhou, Yahong; Aa, Jiye; Wang, Guangji

2014-07-01

Although the stimulating and psychotropic effects of methamphetamine (METH) on the nervous system are well documented, the impact of METH abuse on biological metabolism and the turnover of peripheral transmitters are poorly understood. Metabolomics has the potential to reveal the effect of METH abuse on systemic metabolism and potential markers suggesting the underlying mechanism of toxicity. In this study, male Sprague Dawley rats were intraperitoneally injected with METH at escalating doses of mg kg(-1) for 5 consecutive days and then were withdrawn for 2 days. The metabolites in the serum and urine were profiled and the systemic effects of METH on metabolic pathways were evaluated. Multivariate statistical analysis showed that METH caused distinct deviations, whereas the withdrawal of METH restored the metabolic patterns towards baseline. METH administration elevated energy metabolism, which was manifested by the distinct depletion of branched-chain amino acids, accelerated tricarboxylic-acid cycle and lipid metabolism, reduced serum glycerol-3-phosphate, and elevated serum and urinary 3-hydroxybutyrate and urinary glycerol. In addition to the increased serum levels of the excitatory amino acids glutamate and aspartate (the inhibitory neurotransmitters in the brain), a marked decline in serum alanine and glycine after METH treatment suggested the activation and decreased inhibition of the nervous system and hence elevated nervous activity. Withdrawal of METH for 2 days efficiently restored all but a few metabolites to baseline, including serum creatinine, citrate, 2-ketoglutarate, and urinary lactate. Therefore, these metabolites are potential markers of METH use, and they may be used to facilitate the diagnosis of METH abuse.

Activity of the sympathoadrenal system in cosmonauts during 25-day space flight on station Mir

NASA Astrophysics Data System (ADS)

Kvetňanský, R.; Noskov, V. B.; Blazicek, P.; Gharib, C.; Popova, I. A.; Gauquelin, G.; Macho, L.; Guell, A.; Grigoriev, A. I.

The activity of the sympathoadrenal system in cosmonauts was studied by measuring plasma and urinary catecholamines and their metabolites and conjugates. The appliance Plasma 02 was used for collecting, processing, and storing blood and urine samples from the cosmonauts during the course of a 25-day flight on board the station Mir. Plasma and urine concentrations of adrenaline (A), noradrenaline (NA), and dopamine (DA) as well as urinary levels of vanillylmandelic acid (VMA) and homovanillic acid (HVA), and plasma levels of catecholamine sulphates were determined before, during and after the space flight. Plasma NA levels were slightly elevated on day 9 and plasma A on day 20, whereas plasma DA levels were unchanged. However, most of the changes were within the normal range of control values. Sulphates of plasma catecholamines did not change during flight but they were significantly elevated after landing. Urinary levels of A, NA, DA, VMA, and HVA were comparable with preflight values but were elevated at the different intervals studied after landing. The results obtained suggest that in the short period of about 9 days of the cosmonaut's stay in space the sympathoadrenal system was slightly activated indicating a mild stressful influence of the initial period of flight. This short-term space flight compared to long-term flight did not as markedly activate the sympathoadrenal system during the process of re-adaptation to Earth's gravity after landing. Our data suggest that weightlessness is not a stressful factor activating the sympathoadrenal system but it sensitizes the responsiveness of this system during the re-adaptation period after space flight.

Urinary 1-hydroxypyrene and 8-hydroxydeoxyguanosine levels among coke-oven workers for 2 consecutive days.

PubMed

Nguyen, Thi-To-Uyen; Kawanami, Shoko; Kawai, Kazuaki; Kasai, Hiroshi; Li, Yun-Shan; Inoue, Jinro; Ngoan, Le Tran; Horie, Seichi

2014-01-01

This study evaluated the levels of exposure to polycyclic aromatic hydrocarbons (PAHs) and their relationship with oxidative DNA damage among Vietnamese coke-oven workers. We collected urine from 36 coke-oven workers (exposed group) at the beginning and end of the shift on 2 consecutive days. We also collected urine from 78 medical staff (control group). Information was collected by questionnaire about smoking status, drinking habit, and working position. Urinary 1-hydroxypyrene (1-OHP) and 8-hydroxydeoxyguanosine (8-OH-dG) were measured using HPLC. All statistical analyses were performed with SPSS version 19. Urinary 1-OHP was significantly higher in the coke-oven workers than in the control group (p<0.05). Top-oven workers had the highest levels of internal exposure to PAHs, followed by side-oven and then bottom-oven workers (5.41, 4.41 and 1.35 ng/mg creatinine, respectively, at the end of the shift on day 2). Urinary 8-OH-dG was significantly higher in top- and side-oven workers at the end of the shift on day 2 (4.63 and 5.88 ng/mg creatinine, respectively) than in the control group (3.85 ng/mg creatinine). Based on a multi-regression analysis, smoking status had a significant effect on urinary 8-OH-dG (p=0.049). Urinary 1-OHP tended to have a positive correlation with urinary 8-OH-dG (p=0.070). Vietnamese coke-oven workers were exposed to PAHs during their work shift. Urinary 1-OHP exceeded the recommended limit, and elevated oxidative DNA damage occurred in top- and side-oven workers on the second day of work. A tendency for positive correlation was found between urinary 1-OHP and urinary 8-OH-dG.

Determinants of Brushite Stone Formation: A Case-Control Study

PubMed Central

Siener, Roswitha; Netzer, Linda; Hesse, Albrecht

2013-01-01

Purpose The occurrence of brushite stones has increased during recent years. However, the pathogenic factors driving the development of brushite stones remain unclear. Methods Twenty-eight brushite stone formers and 28 age-, sex- and BMI-matched healthy individuals were enrolled in this case-control study. Anthropometric, clinical, 24 h urinary parameters and dietary intake from 7-day weighed food records were assessed. Results Pure brushite stones were present in 46% of patients, while calcium oxalate was the major secondary stone component. Urinary pH and oxalate excretion were significantly higher, whereas urinary citrate was lower in patients as compared to healthy controls. Despite lower dietary intake, urinary calcium excretion was significantly higher in brushite stone patients. Binary logistic regression analysis revealed pH>6.50 (OR 7.296; p = 0.035), calcium>6.40 mmol/24 h (OR 25.213; p = 0.001) and citrate excretion <2.600 mmol/24 h (OR 15.352; p = 0.005) as urinary risk factors for brushite stone formation. A total of 56% of patients exhibited distal renal tubular acidosis (dRTA). Urinary pH, calcium and citrate excretion did not significantly differ between patients with or without dRTA. Conclusions Hypercalciuria, a diminished citrate excretion and an elevated pH turned out to be the major urinary determinants of brushite stone formation. Interestingly, urinary phosphate was not associated with urolithiasis. The increased urinary oxalate excretion, possibly due to decreased calcium intake, promotes the risk of mixed stone formation with calcium oxalate. Neither dietary factors nor dRTA can account as cause for hypercalciuria, higher urinary pH and diminished citrate excretion. Further research is needed to define the role of dRTA in brushite stone formation and to evaluate the hypothesis of an acquired acidification defect. PMID:24265740

Binational arsenic exposure survey: methodology and estimated arsenic intake from drinking water and urinary arsenic concentrations.

PubMed

Roberge, Jason; O'Rourke, Mary Kay; Meza-Montenegro, Maria Mercedes; Gutiérrez-Millán, Luis Enrique; Burgess, Jefferey L; Harris, Robin B

2012-04-01

The Binational Arsenic Exposure Survey (BAsES) was designed to evaluate probable arsenic exposures in selected areas of southern Arizona and northern Mexico, two regions with known elevated levels of arsenic in groundwater reserves. This paper describes the methodology of BAsES and the relationship between estimated arsenic intake from beverages and arsenic output in urine. Households from eight communities were selected for their varying groundwater arsenic concentrations in Arizona, USA and Sonora, Mexico. Adults responded to questionnaires and provided dietary information. A first morning urine void and water from all household drinking sources were collected. Associations between urinary arsenic concentration (total, organic, inorganic) and estimated level of arsenic consumed from water and other beverages were evaluated through crude associations and by random effects models. Median estimated total arsenic intake from beverages among participants from Arizona communities ranged from 1.7 to 14.1 µg/day compared to 0.6 to 3.4 µg/day among those from Mexico communities. In contrast, median urinary inorganic arsenic concentrations were greatest among participants from Hermosillo, Mexico (6.2 µg/L) whereas a high of 2.0 µg/L was found among participants from Ajo, Arizona. Estimated arsenic intake from drinking water was associated with urinary total arsenic concentration (p < 0.001), urinary inorganic arsenic concentration (p < 0.001), and urinary sum of species (p < 0.001). Urinary arsenic concentrations increased between 7% and 12% for each one percent increase in arsenic consumed from drinking water. Variability in arsenic intake from beverages and urinary arsenic output yielded counter intuitive results. Estimated intake of arsenic from all beverages was greatest among Arizonans yet participants in Mexico had higher urinary total and inorganic arsenic concentrations. Other contributors to urinary arsenic concentrations should be evaluated.

Urinary C‑X‑C motif chemokine 13 is a noninvasive biomarker of antibody‑mediated renal allograft rejection.

PubMed

Chen, Dajin; Zhang, Jian; Peng, Wenhan; Weng, Chunhua; Chen, Jianghua

2018-06-22

Noninvasive monitoring methods of immune status are preferred by transplant recipients. The present study investigated whether urinary C‑X‑C motif chemokine 13 (CXCL13) had the potential to reflect ongoing immune processes within renal allografts. Using an ELISA assay, the level of urinary CXCL13 was quantified in a total of 146 renal allograft recipients and 40 healthy controls at scheduled intervals and at the time of the indicated or protocol biopsy. The results of the present study revealed that urinary CXCL13/creatinine (Cr) was lower in normal transplants compared with in those with acute tubular necrosis (ATN; P=0.001), chronic allograft nephropathy (CAN; P=0.01), and acute rejection (AR; P<0.0001), which was associated with a good diagnostic performance for AR [area under the curve (AUC)=0.818, P<0.0001). In addition, urinary CXCL13/Cr levels in patients with AR were also higher than that of patients with graft dysfunction but no rejection, including ATN and CAN (P=0.034). Notably, urinary CXCL13 distinguished between acute antibody‑mediated rejection (ABMR) and acute cellular rejection, with an AUC of 0.856. Furthermore, patients with steroid‑resistant AR exhibited significantly increased urinary CXCL13/Cr levels than patients with reversible AR (P=0.001). Additionally, elevated levels of urinary CXCL13/Cr within the first month of transplant were predictive of graft function at 3 and 6 months (P=0.044 and P=0.04, respectively). Collectively, the findings of the present study indicated that the noninvasive investigation of urinary CXCL13/Cr may be valuable for the detection of AR, particularly ABMR. In addition, high urinary CXCL13/Cr levels predicted a poor response to steroid treatment and compromised graft function.

Binational Arsenic Exposure Survey: Methodology and Estimated Arsenic Intake from Drinking Water and Urinary Arsenic Concentrations

PubMed Central

Roberge, Jason; O’Rourke, Mary Kay; Meza-Montenegro, Maria Mercedes; Gutiérrez-Millán, Luis Enrique; Burgess, Jefferey L.; Harris, Robin B.

2012-01-01

The Binational Arsenic Exposure Survey (BAsES) was designed to evaluate probable arsenic exposures in selected areas of southern Arizona and northern Mexico, two regions with known elevated levels of arsenic in groundwater reserves. This paper describes the methodology of BAsES and the relationship between estimated arsenic intake from beverages and arsenic output in urine. Households from eight communities were selected for their varying groundwater arsenic concentrations in Arizona, USA and Sonora, Mexico. Adults responded to questionnaires and provided dietary information. A first morning urine void and water from all household drinking sources were collected. Associations between urinary arsenic concentration (total, organic, inorganic) and estimated level of arsenic consumed from water and other beverages were evaluated through crude associations and by random effects models. Median estimated total arsenic intake from beverages among participants from Arizona communities ranged from 1.7 to 14.1 µg/day compared to 0.6 to 3.4 µg/day among those from Mexico communities. In contrast, median urinary inorganic arsenic concentrations were greatest among participants from Hermosillo, Mexico (6.2 µg/L) whereas a high of 2.0 µg/L was found among participants from Ajo, Arizona. Estimated arsenic intake from drinking water was associated with urinary total arsenic concentration (p < 0.001), urinary inorganic arsenic concentration (p < 0.001), and urinary sum of species (p < 0.001). Urinary arsenic concentrations increased between 7% and 12% for each one percent increase in arsenic consumed from drinking water. Variability in arsenic intake from beverages and urinary arsenic output yielded counter intuitive results. Estimated intake of arsenic from all beverages was greatest among Arizonans yet participants in Mexico had higher urinary total and inorganic arsenic concentrations. Other contributors to urinary arsenic concentrations should be evaluated. PMID:22690182

Urinary level of nickel and acute leukaemia in Chinese children.

PubMed

Yang, Y; Jin, X M; Yan, C H; Tian, Y; Tang, J Y; Shen, X M

2008-10-01

The 8-hydroxy-2'-deoxyguanosine (8-OHdG), an oxidized nucleoside of DNA, not only is a widely used biomarker for the measurement of endogenous oxidative DNA damage but might also be a risk factor for many diseases including cancer. Metal exposure may play an important role in oxidative DNA damage among children. However, few studies on urinary 8-OHdG and metals have been conducted in children with acute leukemia. In the present study, urinary Ni and 8-OHdG were examined in 116 children with acute leukaemia (94 acute lymphoid leukaemia [ALL] and 22 acute myeloid leukaemia [AML]) and 51 healthy child controls. Our result showed that urinary Ni in acute leukaemia patients (ALL: 68.40 +/- 133.98, AML: 41.48 +/- 76.31 ng/mg creatinine) was significantly higher than that in controls (62.47 +/- 124.90 vs 17.63 +/- 46.17 ng/mg creatinine, P < 0.05). Similarly, the pretherapy level of urinary 8-OHdG in patients (ALL: 11.83 +/- 16.23, AML: 12.36 +/- 11.36 ng/mg creatinine) was significantly elevated compared with controls (11.92 +/- 15.42 vs 4.03 +/- 4.70 ng/mg creatinine, P < 0.05). Moreover, urinary 8-OHdG and urinary Ni showed a weak but significant association with increased risk of childhood leukaemia. The present study suggests that Ni may be an etiologic factor for childhood acute leukaemia by oxidative DNA damage.

Ultraviolet Light-Assisted Copper Oxide Nanowires Hydrogen Gas Sensor

NASA Astrophysics Data System (ADS)

Sihar, Nabihah; Tiong, Teck Yaw; Dee, Chang Fu; Ooi, Poh Choon; Hamzah, Azrul Azlan; Mohamed, Mohd Ambri; Majlis, Burhanuddin Yeop

2018-05-01

We fabricated copper oxide nanowires (CuO NWs) ultraviolet (UV) light-assisted hydrogen gas sensor. The fabricated sensor shows promising sensor response behavior towards 100 ppm of H2 at room temperature and elevated temperature at 100 °C when exposed to UV light (3.0 mW/cm2). One hundred-cycle device stability test has been performed, and it is found that for sample elevated at 100 °C, the UV-activated sample achieved stability in the first cycle as compared to the sample without UV irradiation which needed about 10 cycles to achieve stability at the initial stage, whereas the sample tested at room temperature was able to stabilize with the aid of UV irradiation. This indicates that with the aid of UV light, after some "warming up" time, it is possible for the conventional CuO NW sensor which normally work at elevated temperature to function at room temperature because UV source is speculated to play a dominant role to increase the interaction of the surface of CuO NWs and hydrogen gas molecules absorbed after the light exposure.

Dysregulation of iron and copper homeostasis in nonalcoholic fatty liver

PubMed Central

Aigner, Elmar; Weiss, Günter; Datz, Christian

2015-01-01

Elevated iron stores as indicated by hyperferritinemia with normal or mildly elevated transferrin saturation and mostly mild hepatic iron deposition are a characteristic finding in subjects with non-alcoholic fatty liver disease (NAFLD). Excess iron is observed in approximately one third of NAFLD patients and is commonly referred to as the “dysmetabolic iron overload syndrome”. Clinical evidence suggests that elevated body iron stores aggravate the clinical course of NAFLD with regard to liver-related and extrahepatic disease complications which relates to the fact that excess iron catalyses the formation of toxic hydroxyl-radicals subsequently resulting in cellular damage. Iron removal improves insulin sensitivity, delays the onset of type 2 diabetes mellitus, improves pathologic liver function tests and likewise ameliorates NAFLD histology. Several mechanisms contribute to pathologic iron accumulation in NAFLD. These include impaired iron export from hepatocytes and mesenchymal Kupffer cells as a consequence of imbalances in the concentrations of iron regulatory factors, such as hepcidin, cytokines, copper or other dietary factors. This review summarizes the knowledge about iron homeostasis in NAFLD and the rationale for its therapeutic implications. PMID:25729473

Ultraviolet Light-Assisted Copper Oxide Nanowires Hydrogen Gas Sensor.

PubMed

Sihar, Nabihah; Tiong, Teck Yaw; Dee, Chang Fu; Ooi, Poh Choon; Hamzah, Azrul Azlan; Mohamed, Mohd Ambri; Majlis, Burhanuddin Yeop

2018-05-15

We fabricated copper oxide nanowires (CuO NWs) ultraviolet (UV) light-assisted hydrogen gas sensor. The fabricated sensor shows promising sensor response behavior towards 100 ppm of H 2 at room temperature and elevated temperature at 100 °C when exposed to UV light (3.0 mW/cm 2 ). One hundred-cycle device stability test has been performed, and it is found that for sample elevated at 100 °C, the UV-activated sample achieved stability in the first cycle as compared to the sample without UV irradiation which needed about 10 cycles to achieve stability at the initial stage, whereas the sample tested at room temperature was able to stabilize with the aid of UV irradiation. This indicates that with the aid of UV light, after some "warming up" time, it is possible for the conventional CuO NW sensor which normally work at elevated temperature to function at room temperature because UV source is speculated to play a dominant role to increase the interaction of the surface of CuO NWs and hydrogen gas molecules absorbed after the light exposure.

Influence of Alloying upon Grain-Boundary Creep

NASA Technical Reports Server (NTRS)

Rhines, F N; Bond, W E; Kissel, M A

1957-01-01

Grain-boundary displacement, occurring in bicrystals during creep at elevated temperature (350 degrees c), has been measured as a function of the copper content (0.1 to 3 percent) in a series of aluminum-rich aluminum-copper solid-solution alloys. The minimums in stress and temperature, below which grain-boundary motion does not occur, increase regularly with the copper content as would be expected if recovery is necessary for movement. Otherwise, the effects, if any, of the copper solute upon grain-boundary displacement and its rate are too small for identification by the experimental technique employed. It was shown, additionally, that grain-boundary displacement appears regular and proceeds at a constant rate if observed parallel to the stress axis, whereas the motion is seen to occur in a sequence of surges and the rate to diminish with time if the observations are made perpendicular to the stress axis.

Roofing Materials Assessment: Investigation of Five Metals in Runoff from Roofing Materials.

PubMed

Winters, Nancy; Granuke, Kyle; McCall, Melissa

2015-09-01

To assess the contribution of five toxic metals from new roofing materials to stormwater, runoff was collected from 14 types of roofing materials and controls during 20 rain events and analyzed for metals. Many of the new roofing materials evaluated did not show elevated metals concentrations in the runoff. Runoff from several other roofing materials was significantly higher than the controls for arsenic, copper, and zinc. Notably, treated wood shakes released arsenic and copper, copper roofing released copper, PVC roofing released arsenic, and Zincalume® and EPDM roofing released zinc. For the runoff from some of the roofing materials, metals concentrations decreased significantly over an approximately one-year period of aging. Metals concentrations in runoff were demonstrated to depend on a number of factors, such as roofing materials, age of the materials, and climatic conditions. Thus, application of runoff concentrations from roofing materials to estimate basin-wide releases should be undertaken cautiously.

Polymodal Responses in C. elegans Phasmid Neurons Rely on Multiple Intracellular and Intercellular Signaling Pathways

PubMed Central

Zou, Wenjuan; Cheng, Hankui; Li, Shitian; Yue, Xiaomin; Xue, Yadan; Chen, Sixi; Kang, Lijun

2017-01-01

Animals utilize specialized sensory neurons enabling the detection of a wide range of environmental stimuli from the presence of toxic chemicals to that of touch. However, how these neurons discriminate between different kinds of stimuli remains poorly understood. By combining in vivo calcium imaging and molecular genetic manipulation, here we investigate the response patterns and the underlying mechanisms of the C. elegans phasmid neurons PHA/PHB to a variety of sensory stimuli. Our observations demonstrate that PHA/PHB neurons are polymodal sensory neurons which sense harmful chemicals, hyperosmotic solutions and mechanical stimulation. A repulsive concentration of IAA induces calcium elevations in PHA/PHB and both OSM-9 and TAX-4 are essential for IAA-sensing in PHA/PHB. Nevertheless, the PHA/PHB neurons are inhibited by copper and post-synaptically activated by copper removal. Neuropeptide is likely involved in copper removal-induced calcium elevations in PHA/PHB. Furthermore, mechanical stimulation activates PHA/PHB in an OSM-9-dependent manner. Our work demonstrates how PHA/PHB neurons respond to multiple environmental stimuli and lays a foundation for the further understanding of the mechanisms of polymodal signaling, such as nociception, in more complex organisms. PMID:28195191

Impact of copper toxicity on stone-head cabbage (Brassica oleracea var. capitata) in hydroponics.

PubMed

Ali, Sajid; Shahbaz, Muhammad; Shahzad, Ahmad Naeem; Khan, Hafiz Azhar Ali; Anees, Moazzam; Haider, Muhammad Saleem; Fatima, Ammara

2015-01-01

Arable soils are frequently subjected to contamination with copper as the consequence of imbalanced fertilization with manure and organic fertilizers and/or extensive use of copper-containing fungicides. In the present study, the exposure of stone-head cabbage (Brassica oleracea var. capitata) to elevated Cu(2+) levels resulted in leaf chlorosis and lesser biomass yield at ≥2 µ M. Root nitrate content was not statistically affected by Cu(2+) levels, although it was substantially decreased at ≥5 µ M Cu(2+) in the shoot. The decrease in nitrate contents can be related to lower nitrate uptake rates because of growth inhibition by Cu-toxicity. Shoot sulfate content increased strongly at ≥2 µ M Cu(2+) indicating an increase in demand for sulfur under Cu stress. Furthermore, at ≥2 µM concentration, concentration of water-soluble non-protein thiol increased markedly in the roots and to a smaller level in the shoot. When exposed to elevated concentrations of Cu(2+) the improved sulfate and water-soluble non-protein thiols need further studies for the evaluation of their direct relation with the synthesis of metal-chelating compounds (i.e., phytochelatins).

Integrated metabolomic analysis of the nano-sized copper particle-induced hepatotoxicity and nephrotoxicity in rats: A rapid invivo screening method for nanotoxicity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lei Ronghui; Department of Public Health, Xi'an Jiaotong University, Xi'an 710061; Wu Chunqi

2008-10-15

Despite an increasing application of copper nanoparticles, there is a serious lack of information concerning their impact on human health and the environment. In this study, the biochemical compositions of urine, serum, and extracts of liver and kidney tissues of rats treated with nano-copper at the different doses (50, 100, and 200 mg/kg/d for 5 d) were investigated using {sup 1}H NMR techniques with the pattern recognition methods. Serum biochemical analysis and histopathological examinations of the liver and kidney of all the rats were simultaneously performed. All the results indicated that the effects produced by nano-copper at a dose ofmore » 100 or 50 mg/kg/d were less than those induced at a higher dose of 200 mg/kg/d. Nano-copper induced overt hepatotoxicity and nephrotoxicity at 200 mg/kg/d for 5 d, which mainly involved scattered dot hepatocytic necrosis and widespread renal proximal tubule necrosis. Increased citrate, succinate, trimethylamine-N-oxide, glucose, and amino acids, accompanied by decreased creatinine levels were observed in the urine; furthermore, elevated levels of lactate, 3-hydroxybutyrate, acetate, creatine, triglycerides, and phosphatide and reduced glucose levels were observed in the serum. The predominant changes identified in the liver tissue aqueous extracts included increased lactate and creatine levels together with reduced glutamine and taurine levels, and the metabolic profile of the kidney tissue aqueous extracts showed an increase in lactate and a drop in glucose. In the chloroform/methanol extracts of the liver and kidney tissues, elevated triglyceride species were identified. These changes suggested that mitochondrial failure, enhanced ketogenesis, fatty acid {beta}-oxidation, and glycolysis contributed to the hepatotoxicity and nephrotoxicity induced by nano-copper at 200 mg/kg/d for 5 d. An increase in triglycerides in the serum, liver and kidney tissues could serve as a potential sensitive biomarker reflecting the lipidosis induced by nano-copper. The data generated from the current study completely supports the fact that an integrated metabolomic approach is promising for the development of a rapid invivo screening method for nanotoxicity.« less

Urinary excretion of 5-hydroxyindoleacetic acid, serotonin and 6-sulphatoxymelatonin in normoserotonemic and hyperserotonemic autistic individuals.

PubMed

Mulder, Erik J; Anderson, George M; Kemperman, Ramses F J; Oosterloo-Duinkerken, Alida; Minderaa, Ruud B; Kema, Ido P

2010-01-01

A substantial proportion of individuals with autism have elevated levels of platelet serotonin (5-HT). We examined whether platelet hyperserotonemia is associated with increased gut 5-HT synthesis, altered 5-HT catabolism or altered melatonin production. Urinary excretion of 5-hydroxyindoleacetic acid (5-HIAA) and 5-HT was compared in 10 normoserotonemic and 10 hyperserotonemic age-matched autistic individuals. The relationship of urinary 6-sulfatoxymelatonin (6-SM) excretion to platelet 5-HT, and to urinary 5-HT and 5-HIAA excretion, was also examined. In the hyperserotonemic group, significant increases at trend level in urinary excretion of 5-HIAA (p = 0.061) and 5-HT (p = 0.071) and a significant decrease for 6-SM were found (p = 0.027). The urinary 5-HIAA:5-HT ratio was similar in the normo- versus the hyperserotonemic groups. The catabolism of 5-HT does not differ in the groups, but greater exposure of the platelet to 5-HT cannot be ruled out as a cause of the platelet hyperserotonemia of autism. Although only trend level significant, the data point to a need for larger studies to examine more thoroughly the relationships between platelet hyperserotonemia, gut 5-HT synthesis and melatonin production. (c) 2009 S. Karger AG, Basel.

Systemic serum amyloid A as a biomarker for exposure to zinc and/or copper-containing metal fumes.

PubMed

Baumann, R; Gube, M; Markert, A; Davatgarbenam, S; Kossack, V; Gerhards, B; Kraus, T; Brand, P

2018-01-01

Zinc- and copper-containing welding fumes increase systemic C-reactive protein (CRP). The aim of this study was to investigate the performance of the biomarkers serum amyloid A (SAA) and soluble vascular cell adhesion molecule-1 (VCAM-1) in this regard. Fifteen male subjects were exposed under controlled conditions to welding fumes containing either zinc, or copper, or copper and zinc for 6 h. Plasma samples were collected before, 6 and 24 h after start of exposure and biomarkers therein were measured by electrochemiluminescent assay. For each exposure, systemic concentrations of systemic SAA, but not VCAM-1, increased significantly at 24 h after exposure start compared with baseline ("copper only": P=0.0005, "zinc only": P=0.027, "copper and zinc": P=0.001). SAA showed a wider range of concentrations than did CRP and its levels increased up to 19-fold after welding fume exposure. The recognition of copper as a potential harmful component in welding fumes, also independent from zinc, deserves further consideration. SAA might represent a new sensitive biomarker for potential subclinical sterile inflammation after inhalation of copper- and/or zinc-containing welding fumes. As elevations of CRP and SAA protein have both been linked to a higher risk for cardiovascular disease, these findings might particularly be important for long-term welders.

Molecular control of copper homeostasis in filamentous fungi: increased expression of a metallothionein gene during aging of Podospora anserina.

PubMed

Averbeck, N B; Borghouts, C; Hamann, A; Specke, V; Osiewacz, H D

2001-01-01

The lifespan of the ascomycete Podospora anserina was previously demonstrated to be significantly increased in a copper-uptake mutant, suggesting that copper is a potential stressor involved in degenerative processes. In order to determine whether changes in copper stress occur in the cells during normal aging of cultures, we cloned and characterized a gene coding for a component of the molecular machinery involved in the control of copper homeostasis. This gene, PaMt1, is a single-copy gene that encodes a metallothionein of 26 amino acids. The coding sequence of PaMt1 is interrupted by a single intron. The deduced amino acid sequence shows a high degree of sequence identity to metallothioneins of the filamentous ascomycete Neurospora crassa and the basidiomycete Agaricus bisporus, and to the N-terminal portion of mammalian metallothioneins. Levels of PaMt1 transcript increase in response to elevated amounts of copper in the growth medium and during aging of wild-type cultures. In contrast, in the long-lived mutant grisea, transcript levels first increase but then decrease again. The ability of wild-type cultures to respond to exogenous copper stress via the induction of PaMt1 transcription is not affected as they grow older.

Yeast and Mammalian Metallothioneins Functionally Substitute for Yeast Copper-Zinc Superoxide Dismutase

NASA Astrophysics Data System (ADS)

Tamai, Katherine T.; Gralla, Edith B.; Ellerby, Lisa M.; Valentine, Joan S.; Thiele, Dennis J.

1993-09-01

Copper-zinc superoxide dismutase catalyzes the disproportionation of superoxide anion to hydrogen peroxide and dioxygen and is thought to play an important role in protecting cells from oxygen toxicity. Saccharomyces cerevisiae strains lacking copper-zinc superoxide dismutase, which is encoded by the SOD1 gene, are sensitive to oxidative stress and exhibit a variety of growth defects including hypersensitivity to dioxygen and to superoxide-generating drugs such as paraquat. We have found that in addition to these known phenotypes, SOD1-deletion strains fail to grow on agar containing the respiratory carbon source lactate. We demonstrate here that expression of the yeast or monkey metallothionein proteins in the presence of copper suppresses the lactate growth defect and some other phenotypes associated with SOD1-deletion strains, indicating that copper metallothioneins substitute for copper-zinc superoxide dismutase in vivo to protect cells from oxygen toxicity. Consistent with these results, we show that yeast metallothionein mRNA levels are dramatically elevated under conditions of oxidative stress. Furthermore, in vitro assays demonstrate that yeast metallothionein, purified or from whole-cell extracts, exhibits copper-dependent antioxidant activity. Taken together, these data suggest that both yeast and mammalian metallothioneins may play a direct role in the cellular defense against oxidative stress by functioning as antioxidants.

POSTSURGICAL RECURRENT CUSHING DISEASE: CLINICAL BENEFIT OF EARLY INTERVENTION IN PATIENTS WITH NORMAL URINARY FREE CORTISOL.

PubMed

Carroll, Ty B; Javorsky, Bradley R; Findling, James W

2016-10-01

To assess the performance of biochemical markers in the detection of recurrent Cushing disease (CD), as well as the potential benefit of early intervention in recurrent CD patients with elevated late-night salivary cortisol (LNSC) and normal urinary free cortisol (UFC). The design was a single-center, retrospective chart review. Patients treated by the authors from 2008-2013 were included. Recurrence was defined by postsurgical remission of CD with subsequent abnormal LNSC, UFC, or dexamethasone suppression test (DST). We identified 15 patients with postsurgical recurrent CD after initial remission; all but one underwent testing with LNSC, DST, and UFC. Although 12 of 15 patients had normal UFC at time of recurrence, DST was abnormal in 11 of 15, and all 14 patients with LNSC results had ≥1 elevated measurement. Nine patients (7 with normal UFC) showed radiologic evidence of a pituitary tumor at time of recurrence. Among the 14 patients with available follow-up data, 12 have demonstrated significant improvement since receiving treatment. Five patients underwent repeat pituitary surgery and 4 achieved clinical and biochemical remission. Eight patients received mifepristone or cabergoline, and 6 showed clinical and/or biochemical improvement. Three patients (2 with prior mifepristone) underwent bilateral adrenalectomy and 2 demonstrated significant clinical improvements. LNSC is more sensitive than UFC or DST for detection of CD recurrence. Prompt intervention when LNSC is elevated, despite normal UFC, may yield significant clinical benefit for many patients with CD. Early treatment for patients with recurrent CD should be prospectively evaluated, utilizing LNSC elevation as an early biochemical marker. ACTH = adrenocorticotropic hormone CD = Cushing disease CS = Cushing syndrome CV = coefficient of variation DST = dexamethasone suppression test IPSS = inferior petrosal sinus sampling LNSC = late-night salivary cortisol QoL = quality of life TSS = transsphenoidal adenoma resection UFC = urinary free cortisol.

Interactions between accumulated copper, bacterial community structure and histamine levels in crayfish meat during storage.

PubMed

Soedarini, Bernadeta; van Gestel, Cornelis A M; van Straalen, Nico M; Widianarko, Budi; Röling, Wilfred F M

2014-08-01

Pollution in aquaculture areas may negatively impact edible species and threaten seafood quality and safety. The aim of this study was to determine the interaction between copper and bacteria in the aquatic habitat and their impact upon crustaceans. Marbled crayfish was chosen as a model of aquatic crustaceans and the influence of metal contamination on bacterial community structure in water used to culture crayfish and in crayfish themselves was investigated. Histamine, an allergen commonly formed by certain groups of bacteria in crustacean edible tissue during storage, was also determined. Copper exposure increased its concentration in crayfish meat by 17.4%, but the copper concentration remained within acceptable food safety limits. Elevated copper levels affected the bacterial community both in the water used to cultivate crayfish and in the marbled crayfish themselves. Cluster analysis of 16S rRNA-gene based microbial community fingerprints revealed that copper impacted the bacterial community in the water and in the crayfish meat. However, copper exposure reduced the formation of histamine in crayfish meat during storage by 66.3%. Copper from the habitat appears to reduce histamine accumulation in crayfish meat during storage by affecting the bacterial community structure of the cultivation water and most likely also in the intestine of the crayfish. From a food safety point of view, copper treatment during the aqua culturing of crustaceans has a positive impact on the postharvest stage. © 2013 Society of Chemical Industry.

Extreme urinary betaine losses in type 2 diabetes combined with bezafibrate treatment are associated with losses of dimethylglycine and choline but not with increased losses of other osmolytes.

PubMed

Lever, Michael; McEntyre, Christopher J; George, Peter M; Slow, Sandy; Elmslie, Jane L; Lunt, Helen; Chambers, Stephen T; Parry-Strong, Amber; Krebs, Jeremy D

2014-10-01

Betaine deficiency is a probable cardiovascular risk factor and a cause of elevated homocysteine. Urinary betaine excretion is increased by fibrate treatment, and is also often elevated in diabetes. Does fibrate further increase betaine excretion in diabetes, and does it affect the plasma concentrations and excretions of related metabolites and of other osmolytes? Samples from a previous study of type 2 diabetes were selected if participants were taking bezafibrate (n = 32). These samples were compared with participants matched for age and gender and not on a fibrate (comparator group, n = 64). Betaine, related metabolites, and osmolytes were measured in plasma and urine samples from these 96 participants. Median urinary betaine excretion in those on bezafibrate was 5-fold higher than in the comparator group (p < 0.001), itself 3.5-fold higher than the median reported for healthy populations. In the bezafibrate group, median dimethylglycine excretion was higher (9-fold, p < 0.001). Excretions of choline, and of the osmolytes myo-inositol, taurine and glycerophosphorylcholine, were not significantly different between groups. Some participants excreted more betaine than usual dietary intakes. Several betaine fractional clearances were >100 %. Betaine excretion correlated with excretions of the osmolytes myo-inositol and glycerophosphorylcholine, and also with the excretion of choline and N,N-dimethylglycine, but it was inconclusive whether these relationships were affected by bezafibrate therapy. Increased urinary betaine excretions in type 2 diabetes are further increased by fibrate treatment, sometimes to more than their dietary intake. Concurrent betaine supplementation may be beneficial.

Factitious Cushing's syndrome masquerading as Cushing's disease.

PubMed

Thynne, Tilenka; White, Graham H; Burt, Morton G

2014-03-01

Factitious Cushing's syndrome is extremely rare. The diagnosis is challenging as cross-reactivity of synthetic corticosteroids or their metabolites in immunoassay measurements of plasma or urinary cortisol can make distinguishing between true and factitious Cushing's syndrome difficult. Adrenocorticotropin (ACTH) is usually suppressed in factitious Cushing's syndrome. A 54-year-old woman presented with clinical and biochemical features of Cushing's syndrome and an unsuppressed ACTH concentration. She denied recent exogenous corticosteroid use. Initial investigations revealed a markedly elevated urinary free cortisol, mildly elevated midnight salivary cortisol and normal morning cortisol concentration. Plasma ACTH was not suppressed at 13 ng/l (RR 10-60 ng/l). A pituitary MRI was normal, but inferior petrosal sinus sampling (IPSS) revealed a post corticotrophin releasing hormone ACTH ratio >20:1 in the left petrosal sinus. Ketoconazole therapy amplified discordance between the urinary free and morning plasma cortisol concentrations. Further investigation of this discordance using high-pressure liquid chromatography tandem mass spectrometry (HPLC-MS/MS) revealed a urinary free cortisol excretion of only 20 nmol/24 h, but prednisolone excretion of 16,200 nmol/24 h. Factitious Cushing's syndrome can mimic endogenous ACTH-dependent hypercortisolism during initial investigations and IPSS. This case highlights the importance of (i) recognizing the significance of discordant results; (ii) using an ACTH assay capable of reliably differentiating ACTH-dependent from ACTH-independent Cushing's syndrome; and (iii) appreciating that IPSS is only useful to localize the source of ACTH in confirmed ACTH-dependent Cushing's syndrome. In this case, measurement of corticosteroids by HPLC-MS/MS was essential in reaching the correct diagnosis. © 2013 John Wiley & Sons Ltd.

Effect of an acid mine drainage effluent on phytoplankton biomass and primary production at Britannia Beach, Howe Sound, British Columbia.

PubMed

Levings, C D; Varela, D E; Mehlenbacher, N M; Barry, K L; Piercey, G E; Guo, M; Harrison, P J

2005-12-01

We investigated the effect of acid mine drainage (AMD) from an abandoned copper mine at Britannia Beach (Howe Sound, BC, Canada) on primary productivity and chlorophyll a levels in the receiving waters of Howe Sound before, during, and after freshet from the Squamish River. Elevated concentrations of copper (integrated average through the water column >0.050 mgl(-1)) in nearshore waters indicated that under some conditions a small gyre near the mouth of Britannia Creek may have retained the AMD from Britannia Creek and from a 30-m deep water outfall close to shore. Regression and correlation analyses indicated that copper negatively affected primary productivity during April (pre-freshet) and November (post-freshet). Negative effects of copper on primary productivity were not supported statistically for July (freshet), possibly because of additional effects such as turbidity from the Squamish River. Depth-integrated average and surface chlorophyll a were correlated to copper concentrations in April. During this short study we demonstrated that copper concentrations from the AMD discharge can negatively affect both primary productivity and the standing stock of primary producers in Howe Sound.

Rupture testing for the quality control of electrodeposited copper interconnections in high-speed, high-density circuits

NASA Technical Reports Server (NTRS)

Zakraysek, Louis

1987-01-01

Printed Wiring Multilayer Board (PWMLB) structures for high speed, high density circuits are prone to failure due to the microcracking of electrolytic copper interconnections. The failure can occur in the foil that makes up the inner layer traces or in the plated through holes (PTH) deposit that forms the layer to layer interconnections. It is shown that there are some distinctive differences in the quality of Type E copper and that these differences can be detected before its use in a PWMLB. It is suggested that the strength of some Type E copper can be very low when the material is hot and that it is the use of this poor quality material in a PWMLB that results in PTH and inner layer microcracking. Since the PWMLB failure in question are induced by a thermal stress, and since the poorer grades of Type E materials used in these structures are susceptible to premature failure under thermal stress, the use of elevated temperature rupture and creep rupture testing is proposed as a means for screening copper foil, or its PTH equivalent, in order to eliminate the problem of Type E copper microcracking in advanced PWMLBs.

In vivo toxic effects of 4-methoxy-5-hydroxy-canthin-6-one in zebrafish embryos via copper dyshomeostasis and oxidative stress.

PubMed

Gong, Guiyi; Jiang, Lingling; Lin, Qinghua; Liu, Wenyuan; He, Ming-Fang; Zhang, Jie; Feng, Feng; Qu, Wei; Xie, Ning

2018-01-01

Dysfunction of copper homeostasis can lead to a host of disorders, which might be toxic sometimes. 4-Methoxy-5-hydroxy-canthin-6-one (CAN) is one of the major constituents from Picrasma quassioides and responsible for its therapeutic effects. In this work, we evaluated the toxic effect of CAN (7.5μM) on zebrafish embryos. CAN treatment decreased survival, delayed hatching time and induced malformations (loss of pigmentation, pericardial edema, as well as hematologic and neurologic abnormalities). Besides, exogenous copper supplementation rescued the pigmentation and cardiovascular defects in CAN-treated embryos. Further spectroscopic studies revealed a copper-chelating activity of CAN. Then its regulation on the expressions of copper homeostasis related genes also be analyzed. In addition, CAN lowered the total activity of SOD, elevated the ROS production and altered the oxidative related genes transcriptions, which led to oxidative stress. In conclusion, we demonstrated that CAN (7.5μM) might exert its toxic effects in zebrafish embryos by causing copper dyshomeostasis and oxidative stress. It will give insight into the risk assessment and prevention of CAN-mediated toxicity. Copyright © 2017 Elsevier Inc. All rights reserved.

Iron plaque formation and heavy metal uptake in Spartina alterniflora at different tidal levels and waterlogging conditions.

PubMed

Xu, Yan; Sun, Xiangli; Zhang, Qiqiong; Li, Xiuzhen; Yan, Zhongzheng

2018-05-30

Tidal flat elevation in the estuarine wetland determines the tidal flooding time and flooding frequency, which will inevitably affect the formation of iron plaque and accumulations of heavy metals (HMs) in wetland plants. The present study investigated the formation of iron plaque and HM's (copper, zinc, lead, and chromium) accumulation in S. alterniflora, a typical estuarine wetland species, at different tidal flat elevations (low, middle and high) in filed and at different time (3, 6, 9, 12 h per day) of waterlogging treatment in greenhouse conditions. Results showed that the accumulation of copper, zinc, lead, and chromium in S. alterniflora was proportional to the exchangeable fraction of these metals in the sediments, which generally increased with the increase of waterlogging time, whereas the formations of iron plaque in roots decreased with the increase of waterlogging time. Under field conditions, the uptake of copper and zinc in the different parts of the plants generally increased with the tidal levels despite the decrease in the metals' exchangeable fraction with increasing tidal levels. The formation of iron plaque was found to be highest in the middle tidal positions and significantly lower in low and high tidal positions. Longer waterlogging time increased the metals' accumulation but decreased the formation of iron plaque in S. alterniflora. The binding of metal ions on iron plaque helped impede the uptake and accumulation of copper and chromium in S. alterniflora. Copyright © 2018 Elsevier Inc. All rights reserved.

Pharmacological Evaluation of Naproxen Metal Complexes on Antinociceptive, Anxiolytic, CNS Depressant, and Hypoglycemic Properties

PubMed Central

Das, Narhari; Abdur Rahman, S. M.

2016-01-01

Purpose. The present study was designed to investigate the antinociceptive, anxiolytic, CNS depressant, and hypoglycemic effects of the naproxen metal complexes. Methods. The antinociceptive activity was evaluated by acetic acid-induced writhing method and radiant heat tail-flick method while anxiolytic activity was evaluated by elevated plus maze model. The CNS depressant activity of naproxen metal complexes was assessed using phenobarbitone-induced sleeping time test and the hypoglycemic test was performed using oral glucose tolerance test. Results. Metal complexes significantly (P < 0.001) reduced the number of abdominal muscle contractions induced by 0.7% acetic acid solution in a dose dependent manner. At the dose of 25 mg/kg body weight p.o. copper, cobalt, and zinc complexes exhibited higher antinociceptive activity having 59.15%, 60.56%, and 57.75% of writhing inhibition, respectively, than the parent ligand naproxen (54.93%). In tail-flick test, at both doses of 25 and 50 mg/kg, the copper, cobalt, silver, and zinc complexes showed higher antinociceptive activity after 90 minutes than the parent drug naproxen. In elevated plus maze (EPM) model the cobalt and zinc complexes of naproxen showed significant anxiolytic effects in dose dependent manner, while the copper, cobalt, and zinc complexes showed significant CNS depressant and hypoglycemic activity. Conclusion. The present study demonstrated that copper, cobalt, and zinc complexes possess higher antinociceptive, anxiolytic, CNS depressant, and hypoglycemic properties than the parent ligand. PMID:27478435

Airborne arsenic and urinary excretion of arsenic metabolites during boiler cleaning operations in a Slovak coal-fired power plant.

PubMed Central

Yager, J W; Hicks, J B; Fabianova, E

1997-01-01

Little information is available on the relationship between occupational exposure to inorganic arsenic in coal fly ash and urinary excretion of arsenic metabolites. This study ws undertaken in a coal-fired power plant in Slovakia during a routine maintenance outage. Arsenic was measured in the breathing zone of workers during 5 consecutive workdays, and urine samples were obtained for analysis of arsenic metabolites--inorganic arsenic (Asi), monomethylarsonic acid (MMA), and dimethylarsinic acid (DMA)--prior to the start of each shift. Results from a small number of cascade impactor air samples indicated that approximately 90% of total particle mass and arsenic was present in particle size fractions >/= 3.5 micron. The 8-hr time-weighted average (TWA) mean arsenic air concentration was 48.3 microg/m3 (range 0.17-375.2) and the mean sum of urinary arsenic (SigmaAs) metabolites was 16.9 microg As/g creatinine (range 2.6-50.8). For an 8-hr TWA of 10 microg/m3 arsenic from coal fly ash, the predicted mean concentration of the SigmaAs urinary metabolites was 13.2 microg As/G creatinine [95% confidence interval (CI), 10.1-16.3). Comparisons with previously published studies of exposure to arsenic trioxide vapors and dusts in copper smelters suggest that bioavailability of arsenic from airborne coal fly ash (as indicated by urinary excretion) is about one-third that seen in smelters and similar settings. Arsenic compound characteristics, matrix composition, and particle size distribution probably play major roles in determining actual uptake of airborne arsenic. Images Figure 1. A Figure 1. B Figure 2. PMID:9347899

An investigation of roof runoff during rain events at the Royal Military College of Canada and potential discharge to Lake Ontario.

PubMed

Kelly, David G; Weir, Ron D; White, Steven D

2011-01-01

The Royal Military College of Canada, located on the north eastern shore of Lake Ontario, possesses an abundance of copper roofs and lacks surface water treatment prior to discharge into Lake Ontario. Rainwater, roof runoff and soil samples were collected and analyzed for copper and other parameters. Copper was consistently detected in runoff samples with average concentrations of 3200 +/- 2100 microg/L. Multivariable linear regression analysis for a dependant copper runoff concentration yielded an adjusted R2 value of 0.611, based on an independent variable model using minimum temperature, maximum temperature, total precipitation, and wind speed. Lake water samples taken in the vicinity of storm water outfalls draining areas with copper roofs ranged from 2.0 to 40 microg/L copper. Such data exceed the 2.0 microg/L Canadian Water Quality Guidelines for the Protection of Aquatic Life as outlined by the Canadian Council of Ministers of the Environment (CCME). Analysis of raw, filtered and digested forms suggested that the majority of copper present in runoff and lake water samples was in a dissolved form. The majority of soils taken in this study displayed copper concentrations below the 63 microg/g CCME residential/parkland land use limits. These findings suggested that ion exchange processes between runoff water and soil do not occur to a sufficient extent to elevate copper levels in soil. It may therefore be concluded that the eventual fate of copper, which is not discharged via storm water outfalls, is lost to the water table and Lake Ontario through the sub-soil.

The Effects of an Acute Bout of Strenuous Aerobic Exercise on Plasma, Erythrocyte, Urinary and Dietary Values for Selected Trace Minerals

DTIC Science & Technology

1996-12-09

some serum copper parameters in trained professional soccer players and control subjects. J. Sports Med. Phys. Fitness. 31:4123-416, 1991. 110. Ruz, M...WOMAN’S UNIVERSITY DEPARTMENT OF NUTRITION AND FOOD SCIENCES COLLEGE OF HEALTH SCIENCES BY KIMBERLY K. EDGREN, RD, BS, CDE DENTON, TEXAS DECEMBER 1996...of the requirements for the degree of Master of Science, with a major in Nutrition . Bett,/B. Alfor ,Ph.D., Major Professor We have read this thesis and

Role of water balance in the enhanced potassium excretion and hypokalaemia of rats with diabetes insipidus.

PubMed Central

Fernández-Repollet, E; Martínez-Maldonado, M; Opava-Stitzer, S

1980-01-01

1. The role of water balance in the hypokalaemia of rats with diabetes insipidus (DI rats) was studied. 2. After a 3-day balance study DI rats had a lower muscle potassium content, and plasma [K+], and the urinary excretion of potassium in response to oral KCl loading was reduced when compared to normal rats. The hypokalaemia was found to be associated with elevated concentrations of potassium in renal medulla and papilla when compared to values in normal Long-Evans rats. 3. During a 9-day balance study urinary potassium excretion was higher than that of normal rats on days 1-3, but not different on days 4-9; this transient elevation was observed in DI rats on normal, high and low potassium diets. On a low potassium diet the urinary potassium excretion of DI rats fell to minimal levels, making unlikely the existence of a renal defect in potassium handling. 4. Muscle potassium content and plasma [K+] were normal after 9 days in metabolism cages. This spontaneous reversal of the hypokalaemia of DI rats was associated with increased water content of renal medulla and papilla, and decreased potassium concentration in these zones. 5. The effect of acute mild dehydration on potassium handling of DI rats was evaluated. Water deprivation for 1-8 hr was sufficient to raise the urinary potassium excretion of DI rats above that of DI rats drinking ad lib. Renal tissue [K+] was significantly increased after 8 hr of dehydration. Water deprivation also enhanced the response of DI rats to an oral KCl load. Two days of chronic dehydration in the form of water rationing also significantly enhanced the urinary potassium excretion of DI rats. 6. These data suggest that chronic mild dehydration may be responsible for the modest potassium deficiency observed in DI rats via alterations in renal tissue [K+] and consequently in urinary potassium excretion. Correction of dehydration during prolonged periods in metabolism cages may account for the spontaneous reversal of the hypokelaemic condition. PMID:7441565

Copper-resistant bacteria reduces oxidative stress and uptake of copper in lentil plants: potential for bacterial bioremediation.

PubMed

Islam, Faisal; Yasmeen, Tahira; Ali, Qasim; Mubin, Muhammad; Ali, Shafaqat; Arif, Muhammad Saleem; Hussain, Sabir; Riaz, Muhammad; Abbas, Farhat

2016-01-01

For effective microbe-assisted bioremediation, metal-resistant plant growth-promoting bacteria (PGPB) must facilitate plant growth by restricting excess metal uptake in plants, leading to prevent its bio-amplification in the ecosystem. The aims of our study were to isolate and characterize copper (Cu)-resistant PGPB from waste water receiving contaminated soil. In addition, we investigated the phytotoxic effect of copper on the lentil plants inoculated with copper-resistant bacteria Providencia vermicola, grown in copper-contaminated soil. Copper-resistant P. vermicola showed multiple plant growth promoting characteristics, when used as a seed inoculant. It protected the lentil plants from copper toxicity with a considerable increase in root and shoot length, plant dry weight and leaf area. A notable increase in different gas exchange characteristics such as A, E, C i , g s , and A/E, as well as increase in N and P accumulation were also recorded in inoculated plants as compared to un-inoculated copper stressed plants. In addition, leaf chlorophyll content, root nodulation, number of pods, 1,000 seed weight were also higher in inoculated plants as compared with non-inoculated ones. Anti-oxidative defense mechanism improved significantly via elevated expression of reactive oxygen species -scavenging enzymes including ascorbate peroxidase, superoxide dismutase, catalase, and guaiacol peroxidase with alternate decrease in malondialdehyde and H2O2 contents, reduced electrolyte leakage, proline, and total phenolic contents suggesting that inoculation of P. vermicola triggered heavy metals stress-related defense pathways under copper stress. Overall, the results demonstrated that the P. vermicola seed inoculation confer heavy metal stress tolerance in lentil plant which can be used as a potent biotechnological tool to cope with the problems of copper pollution in crop plants for better yield.

Occurrence of the Transferable Copper Resistance Gene tcrB among Fecal Enterococci of U.S. Feedlot Cattle Fed Copper-Supplemented Diets

PubMed Central

Amachawadi, R. G.; Alvarado, C. A.; Mainini, T. R.; Vinasco, J.; Drouillard, J. S.; Nagaraja, T. G.

2013-01-01

Copper, an essential micronutrient, is supplemented in the diet at elevated levels to reduce morbidity and mortality and to promote growth in feedlot cattle. Gut bacteria exposed to copper can acquire resistance, which among enterococci is conferred by a transferable copper resistance gene (tcrB) borne on a plasmid. The present study was undertaken to investigate whether the feeding of copper at levels sufficient to promote growth increases the prevalence of the tcrB gene among the fecal enterococci of feedlot cattle. The study was performed with 261 crossbred yearling heifers housed in 24 pens, with pens assigned randomly to a 2×2 factorial arrangement of treatments consisting of dietary copper and a commercial linseed meal-based energy protein supplement. A total of 22 isolates, each identified as Enterococcus faecium, were positive for tcrB with an overall prevalence of 3.8% (22/576). The prevalence was higher among the cattle fed diets supplemented with copper (6.9%) compared to normal copper levels (0.7%). The tcrB-positive isolates always contained both erm(B) and tet(M) genes. Median copper MICs for tcrB-positive and tcrB-negative enterococci were 22 and 4 mM, respectively. The transferability of the tcrB gene was demonstrated via a filter-mating assay. Multilocus variable number tandem repeat analysis revealed a genetically diverse population of enterococci. The finding of a strong association between the copper resistance gene and other antibiotic (tetracycline and tylosin) resistance determinants is significant because enterococci remain potential pathogens and have the propensity to transfer resistance genes to other bacteria in the gut. PMID:23666328

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sarwar, Tarique; Zafaryab, Md; Husain, Mohammed Amir

Ferulic acid (FA) is a plant polyphenol showing diverse therapeutic effects against cancer, diabetes, cardiovascular and neurodegenerative diseases. FA is a known antioxidant at lower concentrations, however at higher concentrations or in the presence of metal ions such as copper, it may act as a pro-oxidant. It has been reported that copper levels are significantly raised in different malignancies. Cancer cells are under increased oxidative stress as compared to normal cells. Certain therapeutic substances like polyphenols can further increase this oxidative stress and kill cancer cells without affecting the proliferation of normal cells. Through various in vitro experiments we havemore » shown that the pro-oxidant properties of FA are enhanced in the presence of copper. Comet assay demonstrated the ability of FA to cause oxidative DNA breakage in human peripheral lymphocytes which was ameliorated by specific copper-chelating agent such as neocuproine and scavengers of ROS. This suggested the mobilization of endogenous copper in ROS generation and consequent DNA damage. These results were further validated through cytotoxicity experiments involving different cell lines. Thus, we conclude that such a pro-oxidant mechanism involving endogenous copper better explains the anticancer activities of FA. This would be an alternate non-enzymatic, and copper-mediated pathway for the cytotoxic activities of FA where it can selectively target cancer cells with elevated levels of copper and ROS. - Highlights: • Pro-oxidant properties of ferulic acid are enhanced in presence of copper. • Ferulic acid causes oxidative DNA damage in lymphocytes as observed by comet assay. • DNA damage was ameliorated by copper chelating agent neocuproine and ROS scavengers. • Endogenous copper is involved in ROS generation causing DNA damage. • Ferulic acid exerts cancer cell specific cytotoxicity as observed by MTT assay.« less

Evaluation of Thermal Stability of Ausferrite in Austempered Ductile Iron Using Differential Scanning Calorimetry

NASA Astrophysics Data System (ADS)

Warsinski, Karl C.

Austempered Ductile Iron (ADI) is prone to changes in microstructure and mechanical properties when exposed to elevated service temperatures. Differential Scanning Calorimetry has been used to evaluate the stabilizing effects of copper, nickel, molybdenum, and cobalt on the ausferrite structure. Previous studies have conflated the effects of various alloy additions, and little effort has been made to systematically catalog the effects of individual elements. The focus of the current research has been to identify alloying elements that more strongly stabilize the ausferrite structure in order to improve service life of ADI at elevated temperatures. Nickel has been shown to have a moderate stabilizing effect, while copper and molybdenum cause a much sharper increase in activation energy. Cobalt has a high stabilizing effect at 0.5% addition by weight, but a further increase to 2.36% results in a slight decrease in activation energy.

Aluminum-Silicon Alloy Having Improved Properties at Elevated Temperatures and Articles Cast Therefrom

NASA Technical Reports Server (NTRS)

Lee, Jonathan A. (Inventor); Chen, Po-Shou (Inventor)

2002-01-01

An aluminum alloy suitable for high temperature applications, such as heavy duty pistons and other internal combustion applications. having the following composition, by weight percent (wt %): Silicon: 11.0-14.0; Copper: 5.6-8.0; Iron: 0-0.8; Magnesium: 0.5-1.5; Nickel: 0.05-0.9; Manganese: 0.5-1.5; Titanium: 0.05-1.2; Zirconium: 0.12-1.2; Vanadium: 0.05-1.2; Zinc: 0.005-0.9; Strontium: 0.001-0.1; Aluminum: balance. In this alloy the ratio of silicon:magnesium is 10-25, and the ratio of copper:magnesium is 4-15. After an article is cast from this alloy, the article is treated in a solutionizing step which dissolves unwanted precipitates and reduces any segregation present in the original alloy. After this solutionizing step, the article is quenched, and is then aged at an elevated temperature for maximum strength.

Exosomal Fetuin-A identified by proteomics: a novel urinary biomarker for detecting acute kidney injury

PubMed Central

Zhou, Hua; Pisitkun, Trairak; Aponte, Angel; Yuen, Peter S.T.; Hoffert, Jason D.; Yasuda, Hideo; Hu, Xuzhen; Chawla, Lakhmir; Shen, Rong-Fong; Knepper, Mark A.; Star., Robert A.

2008-01-01

Urinary exosomes containing apical membrane and intracellular fluid are normally secreted into the urine from all nephron segments, and may carry protein markers of renal dysfunction and structural injury. We aimed to discover biomarkers in urinary exosomes to detect acute kidney injury (AKI) which has a high mortality and morbidity. Animals were injected intravenously with cisplatin. Urinary exosomes were isolated by differential centrifugation. Protein changes were evaluated by two-dimensional difference in gel electrophoresis and changed proteins were identified by MALDI-TOF-TOF or LC-MS/MS. The identified candidate biomarkers were validated by western blotting in individual urine samples from rats subjected to cisplatin injection; bilateral ischemia and reperfusion (I/R); volume depletion (VD); and ICU patients with and without AKI. We identified 18 proteins that were increased and 9 proteins that were decreased 8 hr after cisplatin. Most of the candidates could not be validated by western blotting. However, exosomal Fetuin-A increased 52.5-fold at day 2 (1 day before serum creatinine increase and tubule damage) and remained elevated 51.5-fold at day 5 (peak renal injury) after cisplatin injection. By immuno-electron microscopy and elution studies, Fetuin-A was located inside urinary exosomes. Urinary Fetuin-A was increased 31.6-fold in the early phase (2~8hr) of ischemia/reperfusion, but not in prerenal azotemia. Urinary exosomal Fetuin-A also increased in three ICU patients with AKI compared to the patients without AKI. We conclude that 1) Proteomic analysis of urinary exosomes can provide biomarker candidates for the diagnosis of AKI; 2) Urinary Fetuin-A might be a predictive biomarker of structural renal injury. PMID:17021608

Exacerbation of underlying hypothyroidism caused by proteinuria and induction of urinary thyroxine loss: case report and subsequent investigation.

PubMed

Chandurkar, Vikram; Shik, John; Randell, Edward

2008-01-01

To describe a patient with excess urinary thyroxine (T4) excretion and worsening of preexisting hypothyroidism in the setting of nephrotic syndrome and to determine whether excess urinary T4 excretion is present in other patients with proteinuria. We present data regarding the patient's initial presentation, diagnostic studies, and course of her illness. We suspected urinary T4 loss to be the cause of her presentation and analyzed her urine sample for total T4. We also analyzed differences in urinary T4 excretion in 22 patients with proteinuria and 16 control patients without proteinuria. Relevant medical literature is reviewed. A 44-year-old woman presented with a 3-month history of increasing fluid retention, weight gain, and fatigue. She had long-standing hypothyroidism on a stable levothyroxine dosage, 125 mcg/d. She had gained 27 kg and had developed significant edema. She had a grossly elevated thyroid-stimulating hormone level of 91 mIU/L. Her condition worsened, and a urinary protein measurement was 14.06 g/24 h-diagnostic of nephrotic syndrome. The levothyroxine dosage was increased to 225 mcg/d. Urinary total T4 concentration in a 24-hour sample was 59.0 microg/L (83.1 microg/24 h), indicating that a substantial fraction of her orally ingested T4 was lost in urine. Urinary total T4 excretion was significantly higher in patients with proteinuria (mean +/- standard deviation, 18.0 +/- 18.2 microg/L) vs control patients without proteinuria (mean, 3.8 +/- 1.8 microg/L) (P = .0014). In the patient described, urinary T4 loss due to proteinuria and nephrotic syndrome resulted in a severe exacerbation of underlying hypothyroidism.

Electrochemical fabrication of nanoporous copper films in choline chloride-urea deep eutectic solvent.

PubMed

Zhang, Q B; Abbott, Andrew P; Yang, C

2015-06-14

Nanoporous copper films were fabricated by a facile electrochemical alloying/dealloying process without the need of a template. A deep eutectic solvent made from choline chloride (ChCl) and urea was used with zinc oxide as the metal salt. Cyclic voltammetry was used to characterise the electrochemical reduction of zinc and follow Cu-Zn alloy formation on the copper substrate at elevated temperatures from 353 to 393 K. The alloy formation was confirmed by X-ray diffraction spectra. 3D, open and bicontinuous nanoporous copper films were obtained by in situ electrochemically etching (dealloying) of the zinc component in the Cu-Zn surface alloys at an appropriate potential (-0.4 V vs. Ag). This dealloying process was found to be highly temperature dependent and surface diffusion controlled, which involved the self-assembly of copper atoms at the alloy/electrolyte interface. Additionally, the effects of the deposition parameters, including deposition temperature, current density as well as total charge density on resulting the microstructure were investigated by scanning electron microscopy, and atomic force microscope.

Effects of metal mining and milling on boundary waters of Yellowstone National Park, USA

USGS Publications Warehouse

Nimmo, D.R.; Willox, M.J.; Lafrancois, T.D.; Chapman, P.L.; Brinkman, S.F.; Greene, J.C.

1998-01-01

Aquatic resources in Soda Butte Creek within Yellowstone National Park, USA, continue to be threatened by heavy metals from historical mining and milling activities that occurred upstream of the park's boundary. This includes the residue of gold, silver, and copper ore mining and processing in the early 1900s near Cooke City, Montana, just downstream of the creek's headwaters. Toxicity tests, using surrogate test species, and analyses of metals in water, sediments, and macroinvertebrate tissue were conducted from 1993 to 1995. Chronic toxicity to test species was greater in the spring than the fall and metal concentrations were elevated in the spring with copper exceeding water quality criteria in 1995. Tests with amphipods using pore water and whole sediment from the creek and copper concentrations in the tissue of macroinvertebrates and fish also suggest that copper is the metal of concern in the watershed. In order to understand current conditions in Soda Butte Creek, heavy metals, especially copper, must be considered important factors in the aquatic and riparian ecosystems within and along the creek extending into Yellowstone National Park.

Long-term risk of renal and urinary tract diseases in childhood cancer survivors: A population-based cohort study.

PubMed

Bonnesen, Trine Gade; Winther, Jeanette F; Asdahl, Peter H; de Fine Licht, Sofie; Gudmundsdottir, Thorgerdur; Sällfors Holmqvist, Anna; Madanat-Harjuoja, Laura-Maria; Tryggvadottir, Laufey; Wesenberg, Finn; Birn, Henrik; Olsen, Jørgen H; Hasle, Henrik

2016-09-01

Childhood cancer has been associated with long-term risk of urinary tract diseases, but risk patterns remain to be comprehensively investigated. We analysed the lifetime risk of urinary tract diseases in survivors of childhood cancer in the Nordic countries. We identified 32,519 one-year survivors of childhood cancer diagnosed since the 1940s and 1950s in the five Nordic cancer registries and selected 211,156 population comparisons of a corresponding age, sex, and country of residence from the national population registries. To obtain information on all first-time hospitalizations for a urinary tract disease, we linked all study subjects to the national hospital registry of each country. Relative risks (RRs) and absolute excess risks (AERs) and associated 95% confidence intervals (CIs) for urinary tract diseases among cancer survivors were calculated with the appropriate morbidity rates among comparisons as reference. We observed 1645 childhood cancer survivors ever hospitalized for urinary tract disease yielding an RR of 2.5 (95% CI 2.4-2.7) and an AER of 229 (95% CI 210-248) per 100,000 person-years. The cumulative risk at age 60 was 22% in cancer survivors and 10% in comparisons. Infections of the urinary system and chronic kidney disease showed the highest excess risks, whereas survivors of neuroblastoma, hepatic and renal tumours experienced the highest RRs. Survivors of childhood cancer had an excess risk of urinary tract diseases and for most diseases the risk remained elevated throughout life. The highest risks occurred following therapy of childhood abdominal tumours. Copyright © 2016 Elsevier Ltd. All rights reserved.

Association of increased urine brain derived neurotrophic factor with lower urinary tract symptoms in men with benign prostatic hyperplasia.

PubMed

Wang, Long-Wang; Li, Jian-Long; Yu, Yi; Xiao, Rui-Hai; Huang, Hong-Wei; Kuang, Ren-Rui; Hai, Bo

2017-08-01

Urinary brain-derived neurotrophic factor (BDNF), an ubiquitous neurotrophin, was found to rise in patients with benign prostatic hyperplasia (BPH). We hypothesized that the urinary level of BDNF could be a potential biomarker for lower urinary tract symptoms (LUTS) in patients with BPH. Totally, 76 patients with BPH-caused LUTS and 32 male control subjects without BPH were enrolled. International Prostate Symptom Score (IPSS) was applied to assess the symptom severity of LUTS. Urodynamic tests were performed for the diagnosis of underlying detrusor overactivity (DO) in the patients with BPH. Urine samples were collected from all subjects. Urinary BDNF levels were measured using enzyme-linked immunosorbent assays and normalized by urinary creatinine (Cr) levels. Seventy-six BPH patients were divided into moderate LUTS group (n=51, 720) according to the IPSS. Of the 76 BPH patients, DO was present in 34 (44.7%) according to the urodynamic test. The urinary BDNF/Cr levels were significantly higher in BPH patients with moderate LUTS (8.29±3.635, P<0.0001) and severe LUTS (11.8±6.44, P<0.0001) than normal controls (1.71±0.555). Patients with severe LUTS tended to have higher urinary BDNF/Cr levels than patients with moderate LUTS (11.8±6.44 vs. 8.29±3.635, P=0.000). The conditions of BPH with LUTS correlated with elevated urinary BDNF levels, and urinary BDNF levels were even higher in BPH-DO patients. The results of this study have provided evidence to suggest that urinary BDNF level test could evaluate the severity of LUTS in BPH patients, and BDNF level can be used as a biomarker for the diagnosis of DO in BPH patients.

Copper Tolerance and Characterization of a Copper-Responsive Operon, copYAZ, in an M1T1 Clinical Strain of Streptococcus pyogenes

PubMed Central

Gordon, Lily D.; Fang, Zhong; Holder, Robert C.; Reid, Sean D.

2015-01-01

ABSTRACT Infection with Streptococcus pyogenes is associated with a breadth of clinical manifestations ranging from mild pharyngitis to severe necrotizing fasciitis. Elevated levels of intracellular copper are highly toxic to this bacterium, and thus, the microbe must tightly regulate the level of this metal ion by one or more mechanisms, which have, to date, not been clearly defined. In this study, we have identified two virulence mechanisms by which S. pyogenes protects itself against copper toxicity. We defined a set of putative genes, copY (for a regulator), copA (for a P1-type ATPase), and copZ (for a copper chaperone), whose expression is regulated by copper. Our results indicate that these genes are highly conserved among a range of clinical S. pyogenes isolates. The copY, copA, and copZ genes are induced by copper and are transcribed as a single unit. Heterologous expression assays revealed that S. pyogenes CopA can confer copper tolerance in a copper-sensitive Escherichia coli mutant by preventing the accumulation of toxic levels of copper, a finding that is consistent with a role for CopA in copper export. Evaluation of the effect of copper stress on S. pyogenes in a planktonic or biofilm state revealed that biofilms may aid in protection during initial exposure to copper. However, copper stress appears to prevent the shift from the planktonic to the biofilm state. Therefore, our results indicate that S. pyogenes may use several virulence mechanisms, including altered gene expression and a transition to and from planktonic and biofilm states, to promote survival during copper stress. IMPORTANCE Bacterial pathogens encounter multiple stressors at the host-pathogen interface. This study evaluates a virulence mechanism(s) utilized by S. pyogenes to combat copper at sites of infection. A better understanding of pathogen tolerance to stressors such as copper is necessary to determine how host-pathogen interactions impact bacterial survival during infections. These insights may lead to the identification of novel therapeutic targets that can be used to address antibiotic resistance. PMID:26013489

Copper Tolerance and Characterization of a Copper-Responsive Operon, copYAZ, in an M1T1 Clinical Strain of Streptococcus pyogenes.

PubMed

Young, Christie A; Gordon, Lily D; Fang, Zhong; Holder, Robert C; Reid, Sean D

2015-08-01

Infection with Streptococcus pyogenes is associated with a breadth of clinical manifestations ranging from mild pharyngitis to severe necrotizing fasciitis. Elevated levels of intracellular copper are highly toxic to this bacterium, and thus, the microbe must tightly regulate the level of this metal ion by one or more mechanisms, which have, to date, not been clearly defined. In this study, we have identified two virulence mechanisms by which S. pyogenes protects itself against copper toxicity. We defined a set of putative genes, copY (for a regulator), copA (for a P1-type ATPase), and copZ (for a copper chaperone), whose expression is regulated by copper. Our results indicate that these genes are highly conserved among a range of clinical S. pyogenes isolates. The copY, copA, and copZ genes are induced by copper and are transcribed as a single unit. Heterologous expression assays revealed that S. pyogenes CopA can confer copper tolerance in a copper-sensitive Escherichia coli mutant by preventing the accumulation of toxic levels of copper, a finding that is consistent with a role for CopA in copper export. Evaluation of the effect of copper stress on S. pyogenes in a planktonic or biofilm state revealed that biofilms may aid in protection during initial exposure to copper. However, copper stress appears to prevent the shift from the planktonic to the biofilm state. Therefore, our results indicate that S. pyogenes may use several virulence mechanisms, including altered gene expression and a transition to and from planktonic and biofilm states, to promote survival during copper stress. Bacterial pathogens encounter multiple stressors at the host-pathogen interface. This study evaluates a virulence mechanism(s) utilized by S. pyogenes to combat copper at sites of infection. A better understanding of pathogen tolerance to stressors such as copper is necessary to determine how host-pathogen interactions impact bacterial survival during infections. These insights may lead to the identification of novel therapeutic targets that can be used to address antibiotic resistance. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

The Influence of Marine Microfouling on the Corrosion Behaviour of Passive Materials and Copper Alloys

DTIC Science & Technology

2008-01-02

to organometallic catalysis, acidification of the electrode surface, the combined effects of elevated H20 2 and decreased pH and the production of...Ennoblement in marine waters has been ascribed to depolarization of the oxygen reduction reaction due to organometallic catalysis, acidification of the...organometallic catalysis, acidification of the electrode surface, the combined effects of elevated hydrogen peroxide (H202) and decreased pH and the production

Integrated exposure assessment of sewage workers to genotoxicants: an urinary biomarker approach and oxidative stress evaluation

PubMed Central

2011-01-01

Background Sewage workers are exposed to multiple chemicals among which many are suspected genotoxicants. Therefore, they might incur DNA damage and oxidative stress. We aimed to explore integrated urinary biomarkers, assessing the overall urine genotoxicity by in vitro comet and micronucleus assays and measuring urinary 8-oxo-2'-deoxyguanosine. Methods During three consecutive working days, polycyclic aromatic hydrocarbons and volatile organic compounds were sampled in workplace air of 34 sewage and 30 office workers, as indicators of airborne exposure. The last day, subjects collected their 24 hours urine. Genotoxicity of urinary extracts was assessed by comet and micronucleus assays on a HepG2 cell line. Using competitive enzymatic immunoassay we evaluated the 24 hours urinary 8-oxo-2'-deoxyguanosine excretion. Benzo(a)pyrene toxicity equivalent factors and inhalation unit risk for Benzo(a)pyrene and benzene were used to give an estimate of cancer risk levels. Results Workplace air concentrations of polycyclic aromatic hydrocarbons (e.g. 23.7 [range 2.4-104.6] ng.m-3 for fluoranthene) and volatile organic compounds (e.g. 19.1 ± 2.9 [standard error] μ.m-3 for benzene) were elevated in sewage compared to office workplaces (P < 0.01) and corresponded to an increased lifetime cancer risk. The urinary extracts of sewage workers showed higher genotoxicity (P < 0.001) than office workers. Conclusions The integrated and non-specific urinary biomarkers of exposure showed that sewage workers experience exposure to mixtures of genotoxicants in the workplace. PMID:21435260

Integrated exposure assessment of sewage workers to genotoxicants: an urinary biomarker approach and oxidative stress evaluation.

PubMed

Al Zabadi, Hamzeh; Ferrari, Luc; Sari-Minodier, Irène; Kerautret, Marie-Aude; Tiberguent, Aziz; Paris, Christophe; Zmirou-Navier, Denis

2011-03-24

Sewage workers are exposed to multiple chemicals among which many are suspected genotoxicants. Therefore, they might incur DNA damage and oxidative stress. We aimed to explore integrated urinary biomarkers, assessing the overall urine genotoxicity by in vitro comet and micronucleus assays and measuring urinary 8-oxo-2'-deoxyguanosine. During three consecutive working days, polycyclic aromatic hydrocarbons and volatile organic compounds were sampled in workplace air of 34 sewage and 30 office workers, as indicators of airborne exposure. The last day, subjects collected their 24 hours urine. Genotoxicity of urinary extracts was assessed by comet and micronucleus assays on a HepG2 cell line. Using competitive enzymatic immunoassay we evaluated the 24 hours urinary 8-oxo-2'-deoxyguanosine excretion. Benzo(a)pyrene toxicity equivalent factors and inhalation unit risk for Benzo(a)pyrene and benzene were used to give an estimate of cancer risk levels. Workplace air concentrations of polycyclic aromatic hydrocarbons (e.g. 23.7 [range 2.4-104.6] ng.m-3 for fluoranthene) and volatile organic compounds (e.g. 19.1 ± 2.9 [standard error] μ.m-3 for benzene) were elevated in sewage compared to office workplaces (P < 0.01) and corresponded to an increased lifetime cancer risk. The urinary extracts of sewage workers showed higher genotoxicity (P < 0.001) than office workers. The integrated and non-specific urinary biomarkers of exposure showed that sewage workers experience exposure to mixtures of genotoxicants in the workplace.

Cytokines profile and its correlation with endothelial damage and oxidative stress in patients with type 1 diabetes mellitus and nephropathy.

PubMed

Pestana, Rodrigo M C; Domingueti, Caroline P; Duarte, Rita C F; Fóscolo, Rodrigo B; Reis, Janice S; Rodrigues, Ana Maria S; Martins, Laís B; Sousa, Lirlândia P; Lage, Daniela P; Ferreira, Cláudia N; Ferreira, Adaliene V M; Fernandes, Ana P; Gomes, Karina B

2016-08-01

The aim of the present study was to investigate the association between the presence of albuminuria and cytokines profile with biomarkers of endothelial damage and oxidative stress in patients with type 1 diabetes mellitus (DM1). The sample was composed by 35 healthy individuals, 63 DM1 patients with normoalbuminuria (<30 mg of albumin/g of creatinine) and 62 DM1 patients with micro- and macroalbuminuria (≥30 mg of albumin/g of creatinine). Plasma and urinary cytokines (TNF-α, IL-6 and IL-10) and thrombomodulin levels were determined by ELISA. Oxidative status was evaluated using the TBARS and MTT assays. Diabetic patients were characterized by elevated levels of urinary cytokines TNF-α, IL-6 and IL-10. Those with macroalbuminuria presented significantly higher TNF-α and IL-10 urinary levels when compared to other groups. Urinary and plasmatic levels of TNF-α were positively correlated with plasma levels of cystatin C, creatinine, urea and albuminuria, while they were negatively correlated with estimated glomerular filtration rate. Urinary IL-10 levels proved positive correlation with fasting glucose, HbA1c, thrombomodulin and TBARS, while IL-6 plasma levels were positively correlated with HbA1c and albuminuria. Only urinary TNF-α levels were associated with the presence and severity of macroalbuminuria, after logistic regression analysis. This finding suggests that measurement of urinary TNF-α level may be helpful to evaluate progression to nephropathy in DM1 patients.

Urinary monocyte chemoattractant protein-1 (MCP-1) and connective tissue growth factor (CCN2) as prognostic markers for progression of diabetic nephropathy.

PubMed

Tam, Frederick W K; Riser, Bruce L; Meeran, Karim; Rambow, JoAnn; Pusey, Charles D; Frankel, Andrew H

2009-07-01

Profibrotic growth factors and inflammatory chemokines have been implicated in the pathogenesis of diabetic nephropathy (DN). However, measurement of urinary monocyte chemoattractant protein-1 (MCP-1) and connective tissue growth factor (CCN2) as prognostic markers has not previously been reported, and neither have two such molecules in urine been examined in a single study of DN. In this prospective observational study, 43 adult diabetic patients were studied, 40 were followed up for 6years. Urinary MCP-1/creatinine ratios were found to be significantly higher in patients with macroalbuminuria (3.3- and 2.1-fold higher (p<0.01) than normoalbuminuric and microalbuminuric patients, respectively). CCN2 exhibited a pattern different from that of urinary MCP-1. Urinary CCN2/creatinine ratios were greatly elevated in both microalbuminuric and macroalbuminuric patients (125- and 74-fold higher than normoalbuminuric patients, respectively, p<0.01 and p<0.05, respectively). Further, urinary CCN2, but not MCP-1, correlated with progression of microalbuminuria (R=0.49, p<0.05). In contrast, MCP-1, but not CCN2, correlated with the rate of eGFR decline for all patients (R=0.61, p<0.0001), reflective of its predictive value in patients with macroalbuminuria, but not for patients with microalbuminuria or normoalbuminuria. In conclusion, increased urinary CCN2 is associated with the early progression of DN, whereas MCP-1 is associated with later stage disease.

Bisphenol A exposure is associated with low-grade urinary albumin excretion in children of the United States

PubMed Central

Trasande, Leonardo; Attina, Teresa; Trachtman, Howard

2012-01-01

Urinary bisphenol A (BPA), a widely-used biomarker of exposure to BPA, has been associated with cardiometabolic derangements in laboratory studies and with low-grade albuminuria in Chinese adults. Despite the known unique vulnerability of children to environmental chemicals, no studies have examined associations of urinary BPA with albuminuria in children. Since exposure to BPA is widespread in the United States population, we examined data from 710 children in the 2009–10 National Health and Nutrition Examination Survey with urinary BPA measurements and first morning urine samples with creatinine values. Controlled for a broad array of sociodemographic and environmental risk factors as well as insulin resistance and elevated cholesterol, children with the highest compared to the lowest quartile of urinary BPA had a significant 0.91 mg/g higher albumin-to-creatinine ratio, adjusted for the urinary BPA concentration. When the multivariable model was reprised substituting continuous measures of BPA, a significant 0.28 mg/g albumin-to-creatinine ratio increase was identified for each log unit increase in urinary BPA. Thus, an association of BPA exposure with low-grade albuminuria is consistent with previous results found in Chinese adults and documents this in children in the United States. Our findings broaden the array of adverse effects of BPA to include endothelial dysfunction as evidenced by the low-grade albuminuria and support proactive efforts to prevent harmful exposures. PMID:23302717

Organochlorines and heavy metals in 17-year cicadas pose no apparent dietary threat to birds

USGS Publications Warehouse

Clark, D.R.

1992-01-01

Organochlorine and heavy metal concentrations in 17-year cicadas from Prince Georges and Anne Arundel Counties, Maryland, were well below levels known to be harmful to birds. Cicadas contained concentrations of metals similar to or less than other local invertebrates except they contained more copper than did earthworms. Copper and lead concentrations in cicadas from one site may have been elevated by sewage plant effluent deposited during river floodings. Cicadas from the median of a major highway did not contain more lead than cicadas from non-traffic sites.

Copper-Catalyzed, Directing Group-Assisted Fluorination of Arene and Heteroarene C-H Bonds

PubMed Central

Truong, Thanh; Klimovica, Kristine; Daugulis, Olafs

2013-01-01

We have developed a method for direct, copper-catalyzed, auxiliary-assisted fluorination of β-sp2 C-H bonds of benzoic acid derivatives and γ-sp2 C-H bonds of α,α-disubstituted benzylamine derivatives. The reaction employs CuI catalyst, AgF fluoride source, and DMF, pyridine, or DMPU solvent at moderately elevated temperatures. Selective mono- or difluorination can be achieved by simply changing reaction conditions. The method shows excellent functional group tolerance and provides a straightforward way for the preparation of ortho-fluorinated benzoic acids. PMID:23758609

Results of a preimpoundment water-quality study of Swatara Creek, Pennsylvania

USGS Publications Warehouse

Fishel, David K.; Richardson, J.E.

1986-01-01

The impoundment will act as a sediment trap and thus reduce the concentrations of total phosphorus, iron, aluminum, lead, copper, and zinc immediately downstream from the impoundment. Large storm discharges and releases from the hypolimnion of the reservoir to attain the winter-pool level may contain low oxygen concentrations and elevated concentrations of iron, aluminum, lead, copper, and zinc. Unless conservation releases from the multi-level release gates are carefully controlled, low dissolved-oxygen levels and high metal concentrations may degrade the downstream water quality and be detrimental to the aquatic community.

Biomarkers of oxidative stress and its association with the urinary reducing capacity in bus maintenance workers

PubMed Central

2011-01-01

Background Exposure to particles (PM) induces adverse health effects (cancer, cardiovascular and pulmonary diseases). A key-role in these adverse effects seems to be played by oxidative stress, which is an excess of reactive oxygen species relative to the amount of reducing species (including antioxidants), the first line of defense against reactive oxygen species. The aim of this study was to document the oxidative stress caused by exposure to respirable particles in vivo, and to test whether exposed workers presented changes in their urinary levels for reducing species. Methods Bus depot workers (n = 32) exposed to particles and pollutants (respirable PM4, organic and elemental carbon, particulate metal content, polycyclic aromatic hydrocarbons, NOx, O3) were surveyed over two consecutive days. We collected urine samples before and after each shift, and quantified an oxidative stress biomarker (8-hydroxy-2'-deoxyguanosine), the reducing capacity and a biomarker of PAH exposure (1-hydroxypyrene). We used a linear mixed model to test for associations between the oxidative stress status of the workers and their particle exposure as well as with their urinary level of reducing species. Results Workers were exposed to low levels of respirable PM4 (range 25-71 μg/m3). However, urinary levels of 8-hydroxy-2'-deoxyguanosine increased significantly within each shift and between both days for non-smokers. The between-day increase was significantly correlated (p < 0.001) with the concentrations of organic carbon, NOx, and the particulate copper content. The within-shift increase in 8OHdG was highly correlated to an increase of the urinary reducing capacity (Spearman ρ = 0.59, p < 0.0001). Conclusions These findings confirm that exposure to components associated to respirable particulate matter causes a systemic oxidative stress, as measured with the urinary 8OHdG. The strong association observed between urinary 8OHdG with the reducing capacity is suggestive of protective or other mechanisms, including circadian effects. Additional investigations should be performed to understand these observations. PMID:21619715

Elevated CXC chemokines in urine noninvasively discriminate OAB from UTI.

PubMed

Tyagi, Pradeep; Tyagi, Vikas; Qu, Xianggui; Chuang, Yao Chi; Kuo, Hann-Chorng; Chancellor, Michael

2016-09-01

Overlapping symptoms of overactive bladder (OAB) and urinary tract infection (UTI) often complicate the diagnosis and contribute to overprescription of antibiotics. Inflammatory response is a shared characteristic of both UTI and OAB and here we hypothesized that molecular differences in inflammatory response seen in urine can help discriminate OAB from UTI. Subjects in the age range of (20-88 yr) of either sex were recruited for this urine analysis study. Urine specimens were available from 62 UTI patients with positive dipstick test before antibiotic treatment. Six of these patients also provided urine after completion of antibiotic treatment. Subjects in cohorts of OAB (n = 59) and asymptomatic controls (n = 26) were negative for dipstick test. Urinary chemokines were measured by MILLIPLEX MAP Human Cytokine/Chemokine Immunoassay and their association with UTI and OAB was determined by univariate and multivariate statistics. Significant elevation of CXCL-1, CXCL-8 (IL-8), and CXCL-10 together with reduced levels for a receptor antagonist of IL-1A (sIL-1RA) were seen in UTI relative to OAB and asymptomatic controls. Elevated CXCL-1 urine levels predicted UTI with odds ratio of 1.018 and showed a specificity of 80.77% and sensitivity of 59.68%. Postantibiotic treatment, reduction was seen in all CXC chemokines with a significant reduction for CXCL-10. Strong association of CXCL-1 and CXCL-10 for UTI over OAB indicates mechanistic differences in signaling pathways driving inflammation secondary of infection in UTI compared with a lack of infection in OAB. Urinary chemokines highlight molecular differences in the paracrine signaling driving the overlapping symptoms of UTI and OAB. Copyright © 2016 the American Physiological Society.

Effects of Antiproteinuric Intervention on Elevated Connective Tissue Growth Factor (CTGF/CCN-2) Plasma and Urine Levels in Nondiabetic Nephropathy

PubMed Central

Slagman, Maartje C.J.; Nguyen, Tri Q.; Waanders, Femke; Vogt, Liffert; Hemmelder, Marc H.; Goldschmeding, Roel; Navis, Gerjan

2011-01-01

Summary Background and objectives Connective Tissue Growth Factor (CTGF/CCN-2) is a key player in fibrosis. Plasma CTGF levels predict end-stage renal disease and mortality in diabetic chronic kidney disease (CKD), supporting roles in intra- and extrarenal fibrosis. Few data are available on CTGF in nondiabetic CKD. We investigated CTGF levels and effects of antiproteinuric interventions in nondiabetic proteinuric CKD. Design, setting, participants, & measurements In a crossover randomized controlled trial, 33 nondiabetic CKD patients (3.2 [2.5 to 4.0] g/24 h proteinuria) were treated during 6-week periods with placebo, ARB (100 mg/d losartan), and ARB plus diuretics (100 mg/d losartan plus 25 mg/d hydrochlorothiazide) combined with consecutively regular and low sodium diets (193 ± 62 versus 93 ± 52 mmol Na+/d). Results CTGF was elevated in plasma (464 [387 to 556] pmol/L) and urine (205 [135 to 311] pmol/24 h) of patients compared with healthy controls (n = 21; 96 [86 to 108] pmol/L and 73 [55 to 98] pmol/24 h). Urinary CTGF was lowered by antiproteinuric intervention, in proportion to the reduction of proteinuria, with normalization during triple therapy (CTGF 99 [67 to 146] in CKD versus 73 [55 to 98] pmol/24 h in controls). In contrast, plasma CTGF was not affected. Conclusions Urinary and plasma CTGF are elevated in nondiabetic CKD. Only urinary CTGF is normalized by antiproteinuric intervention, consistent with amelioration of tubular dysfunction. The lack of effect on plasma CTGF suggests that its driving force might be independent of proteinuria and that short-term antiproteinuric interventions are not sufficient to correct the systemic profibrotic state in CKD. PMID:21784839

Association of polycyclic aromatic hydrocarbons metabolites and risk of diabetes in coke oven workers.

PubMed

Yang, Liangle; Yan, Kai; Zeng, Dan; Lai, Xuefeng; Chen, Xuguang; Fang, Qin; Guo, Huan; Wu, Tangchun; Zhang, Xiaomin

2017-04-01

Elevated polycyclic aromatic hydrocarbons (PAHs) metabolites have recently been linked to increased risk of diabetes in the general population, but little is known about the risk of diabetes due to high pollution levels of PAHs exposure. We aimed to examine whether occupational exposure to PAHs would be one of the important risk factors for diabetes in the coke oven workers. A total of 1472 coke oven workers with complete data were qualified for the present study. We measured 12 urinary monohydroxy polycyclic aromatic hydrocarbons (OH-PAHs) by gas chromatography-mass spectrometry (GC-MS). Multiple logistic regression was used to evaluate the associations between urinary OH-PAHs and risk of diabetes, with adjustment for the potential confounders. We found that elevated urinary 4-hydroxyphenanthrene (4-OHPh) was significantly associated, in a dose-dependent manner, with increased risk of diabetes (P trend  = 0.003). Compared with individuals with 4-OHPh in the lowest quartile, the adjusted odds ratio (OR) of diabetes among those in the highest quartile was 2.80 (95% CI = 1.37-5.71). In stratified analysis, the association was more prominent in those who were smokers, overweight (BMI ≥24 kg/m 2 ), with longer working years (≥20 years) and worked at coke oven settings. In addition, high levels of 4-OHPh combined with longer working years or overweight had a joint effect on the risk of diabetes. Our data suggested that elevated 4-OHPh was dose-responsive associated with increased risk of diabetes in the coke oven workers. The risk assessment of diabetes related to occupational PAHs exposure should take working years and BMI into consideration. Copyright © 2017 Elsevier Ltd. All rights reserved.

Determination of copper and iron in biological samples of viral hepatitis (A-E) female patients.

PubMed

Afridi, Hassan Imran; Kazi, Tasneem Gul; Kazi, Naveed Gul; Jamali, Mohammad Khan; Sarfaraz, Raja Adil; Arain, Mohammad Balal; Kandhro, Ghulam Abbas; Shah, Abdul Qadir; Baig, Jamil Ahmed; Jalbani, Nusrat; Ansari, Rehana

2009-01-01

There is accumulative evidence that the metabolism of iron and copper is altered in viral hepatic diseases, and these nutrients might have specific roles in their pathogenesis and progress. The aim of present study was to compare the level of copper (Cu) and iron (Fe) in biological samples (serum, urine, and scalp hair) of female patients suffering from different viral hepatitis (A, B, C, D, and E; n = 253) of age range 31-45 years. For comparative study, 95 healthy females of the same age group residing in the same city were selected. The elements in the biological samples were analyzed by flame atomic absorption spectrophotometry, prior to microwave-assisted acid digestion. The validity and accuracy of the methodology was checked by using certified reference materials (CRMs) and with those values obtained by conventional wet acid digestion method on same CRMs. The results of this study showed that the mean values of Cu and Fe were higher in sera and scalp hair samples of hepatitis patients than age-matched control subjects, while the difference was significant (p < 0.001), in the cases of viral hepatitis B and viral hepatitis C as compared to viral hepatitis A, D, and E. The urinary levels of these elements were found higher in the hepatitis patients than in the age-matched healthy controls (p < 0.05). These results are consistent with literature-reported data, confirming that hepatic iron and copper overload can directly cause lipid peroxidation and eventually hepatic damage.

Anaerobic Copper Toxicity and Iron-Sulfur Cluster Biogenesis in Escherichia coli.

PubMed

Tan, Guoqiang; Yang, Jing; Li, Tang; Zhao, Jin; Sun, Shujuan; Li, Xiaokang; Lin, Chuxian; Li, Jianghui; Zhou, Huaibin; Lyu, Jianxin; Ding, Huangen

2017-08-15

While copper is an essential trace element in biology, pollution of groundwater from copper has become a threat to all living organisms. Cellular mechanisms underlying copper toxicity, however, are still not fully understood. Previous studies have shown that iron-sulfur proteins are among the primary targets of copper toxicity in Escherichia coli under aerobic conditions. Here, we report that, under anaerobic conditions, iron-sulfur proteins in E. coli cells are even more susceptible to copper in medium. Whereas addition of 0.2 mM copper(II) chloride to LB (Luria-Bertani) medium has very little or no effect on iron-sulfur proteins in wild-type E. coli cells under aerobic conditions, the same copper treatment largely inactivates iron-sulfur proteins by blocking iron-sulfur cluster biogenesis in the cells under anaerobic conditions. Importantly, proteins that do not have iron-sulfur clusters (e.g., fumarase C and cysteine desulfurase) in E. coli cells are not significantly affected by copper treatment under aerobic or anaerobic conditions, indicating that copper may specifically target iron-sulfur proteins in cells. Additional studies revealed that E. coli cells accumulate more intracellular copper under anaerobic conditions than under aerobic conditions and that the elevated copper content binds to the iron-sulfur cluster assembly proteins IscU and IscA, which effectively inhibits iron-sulfur cluster biogenesis. The results suggest that the copper-mediated inhibition of iron-sulfur proteins does not require oxygen and that iron-sulfur cluster biogenesis is the primary target of anaerobic copper toxicity in cells. IMPORTANCE Copper contamination in groundwater has become a threat to all living organisms. However, cellular mechanisms underlying copper toxicity have not been fully understood up to now. The work described here reveals that iron-sulfur proteins in Escherichia coli cells are much more susceptible to copper in medium under anaerobic conditions than they are under aerobic conditions. Under anaerobic conditions, E. coli cells accumulate excess intracellular copper, which specifically targets iron-sulfur proteins by blocking iron-sulfur cluster biogenesis. Since iron-sulfur proteins are involved in diverse and vital physiological processes, inhibition of iron-sulfur cluster biogenesis by copper disrupts multiple cellular functions and ultimately inhibits cell growth. The results from this study illustrate a new interplay between intracellular copper toxicity and iron-sulfur cluster biogenesis in bacterial cells under anaerobic conditions. Copyright © 2017 American Society for Microbiology.

Anaerobic Copper Toxicity and Iron-Sulfur Cluster Biogenesis in Escherichia coli

PubMed Central

Tan, Guoqiang; Yang, Jing; Li, Tang; Zhao, Jin; Sun, Shujuan; Li, Xiaokang; Lin, Chuxian; Li, Jianghui; Zhou, Huaibin

2017-01-01

ABSTRACT While copper is an essential trace element in biology, pollution of groundwater from copper has become a threat to all living organisms. Cellular mechanisms underlying copper toxicity, however, are still not fully understood. Previous studies have shown that iron-sulfur proteins are among the primary targets of copper toxicity in Escherichia coli under aerobic conditions. Here, we report that, under anaerobic conditions, iron-sulfur proteins in E. coli cells are even more susceptible to copper in medium. Whereas addition of 0.2 mM copper(II) chloride to LB (Luria-Bertani) medium has very little or no effect on iron-sulfur proteins in wild-type E. coli cells under aerobic conditions, the same copper treatment largely inactivates iron-sulfur proteins by blocking iron-sulfur cluster biogenesis in the cells under anaerobic conditions. Importantly, proteins that do not have iron-sulfur clusters (e.g., fumarase C and cysteine desulfurase) in E. coli cells are not significantly affected by copper treatment under aerobic or anaerobic conditions, indicating that copper may specifically target iron-sulfur proteins in cells. Additional studies revealed that E. coli cells accumulate more intracellular copper under anaerobic conditions than under aerobic conditions and that the elevated copper content binds to the iron-sulfur cluster assembly proteins IscU and IscA, which effectively inhibits iron-sulfur cluster biogenesis. The results suggest that the copper-mediated inhibition of iron-sulfur proteins does not require oxygen and that iron-sulfur cluster biogenesis is the primary target of anaerobic copper toxicity in cells. IMPORTANCE Copper contamination in groundwater has become a threat to all living organisms. However, cellular mechanisms underlying copper toxicity have not been fully understood up to now. The work described here reveals that iron-sulfur proteins in Escherichia coli cells are much more susceptible to copper in medium under anaerobic conditions than they are under aerobic conditions. Under anaerobic conditions, E. coli cells accumulate excess intracellular copper, which specifically targets iron-sulfur proteins by blocking iron-sulfur cluster biogenesis. Since iron-sulfur proteins are involved in diverse and vital physiological processes, inhibition of iron-sulfur cluster biogenesis by copper disrupts multiple cellular functions and ultimately inhibits cell growth. The results from this study illustrate a new interplay between intracellular copper toxicity and iron-sulfur cluster biogenesis in bacterial cells under anaerobic conditions. PMID:28576762

Polyelectrolyte-mediated assembly of copper-phthalocyanine tetrasulfonate multilayers and the subsequent production of nanoparticulate copper oxide thin films.

PubMed

Chickneyan, Zarui Sara; Briseno, Alejandro L; Shi, Xiangyang; Han, Shubo; Huang, Jiaxing; Zhou, Feimeng

2004-07-01

An approach to producing films of nanometer-sized copper oxide particulates, based on polyelectrolyte-mediated assembly of the precursor, copper(II)phthalocyanine tetrasulfonate (CPTS), is described. Multilayered CPTS and polydiallyldimethylammonium chloride (PDADMAC) were alternately assembled on different planar substrates via the layer-by-layer (LbL) procedure. The growth of CPTS multilayers was monitored by UV-visible spectrometry and quartz crystal microbalance (QCM) measurements. Both the UV-visible spectra and the QCM data showed that a fixed amount of CPTS could be attached to the substrate surface for a given adsorption cycle. Cyclic voltammograms at the CPTS/PDADMAC-covered gold electrode exhibited a decrease in peak currents with the layer number, indicating that the permeability of CPTS multilayers on the electrodes had diminished. When these CPTS multilayered films were calcined at elevated temperatures, uniform thin films composed of nanoparticulate copper oxide could be produced. Ellipsometry showed that the thickness of copper oxide nanoparticulate films could be precisely tailored by varying the thickness of CPTS multilayer films. The morphology and roughness of CPTS multilayer and copper oxide thin films were characterized by atomic force microscopy. X-ray diffraction (XRD) measurements indicated that these thin films contained both CuO and Cu2O nanoparticles. The preparation of such copper oxide thin films with the use of metal complex precursors represents a new route for the synthesis of inorganic oxide films with a controlled thickness.

Copper speciation in the gill microenvironment of carp (Cyprinus carpio) at various levels of pH.

PubMed

Tao, Shu; Long, Aimin; Xu, Fuliu; Dawson, R W

2002-07-01

The fish gill microenvironment of Cyprinus carpio under stress of copper exposure was investigated. pH and other parameters including free copper activity, alkalinity, and inorganic and organic carbons in the surrounding water (inspired water) and in the gill microenvironment (expired water) were measured or calculated at various levels of pH and varying total copper concentrations. The chemical equilibrium calculation (from MINEQA2) and complexation modeling (mucus-copper) were coupled to calculate both species distribution. The results indicate that the pH in the fish gill microenvironment was different from that in the surrounding water with a balance point around 6.9. The secretion of both CO(2) and mucus was affected in both linear and nonlinear ways when the fish were exposed to elevated concentrations of copper. The complexation capacity of the gill mucus was characterized by a conditional stability constant (logk(Cu-mucus)) of 5.37 along with a complexation equivalent concentration (L(Cu-mucus)) of 0.96 mmol Cu/mg C. For both the fish microenvironment and the surrounding water, the dominant copper species shifted from Cu(2+) to CuCO(3)(0) and to Cu(OH)(2)(0) when the pH of the surrounding water changed from 6.12 to 8.11. The change in copper speciation in the gill microenvironment is smaller than that in the surrounding water due to the pH buffering capacity of the fish gills.

Flavonoids-induced redox cycling of copper ions leads to generation of reactive oxygen species: A potential role in cancer chemoprevention.

PubMed

Arif, Hussain; Sohail, Aamir; Farhan, Mohd; Rehman, Ahmed Abdur; Ahmad, Aamir; Hadi, S M

2018-01-01

Flavonoids, a class of polyphenols are known to be effective inducers of apoptosis and cytotoxicity in cancer cells. It is believed that antioxidant activity of polyphenols cannot fully account for induction of apoptosis and chemotherapeutic prevention in various cancers. In this article, by employing single cell alkaline gel electrophoresis (comet assay), we established that antioxidants, flavonoids such as (myricetin=MN, fisetin=FN, quercetin=QN, kaempferol=KL and galangin=GN) can cause cellular DNA breakage, also act as pro-oxidant in presence of transition metal ion such as copper. It was observed that the extent of cellular DNA breakage was found significantly higher in presence of copper. Hydroxyl radicals are generated as a sign of flavonoids' pro-oxidant nature through redox recycling of copper ions. Further, a dose-dependent inhibition of proliferation of breast cancer cells MDA-MB-231 by MN was found leading to pro-oxidant cell death, as assessed by MTT assay. Since levels of copper are considerably elevated in tissue, cell and serum during various malignancies, suggesting that cancer cells would be more subject to copper induced oxidative DNA breakage. Such a copper dependent pro-oxidant cytotoxic mechanism better explains the anticancer activity and preferential cytotoxicity of dietary phytochemicals against cancer cells. Copyright © 2017 Elsevier B.V. All rights reserved.

Urinary Podocyte Microparticles Identify Prealbuminuric Diabetic Glomerular Injury

PubMed Central

Burger, Dylan; Thibodeau, Jean-Francois; Holterman, Chet E.; Burns, Kevin D.; Touyz, Rhian M.

2014-01-01

Microparticles (MPs) are small (0.1–1.0 µm) vesicles shed from the surface of cells in response to stress. Whether podocytes produce MPs and whether this production reflects glomerular injury are unclear. We examined MP formation in cultured human podocytes (hPODs) and diabetic mice. hPODs were exposed to cyclical stretch, high glucose (HG; 25 mM), angiotensin II, or TGF-β. Urinary podocyte MPs were assessed in three mouse models of diabetic nephropathy: streptozotocin (STZ)-treated, OVE26, and Akita mice. Cyclic stretch and HG increased MP release as assessed by flow cytometry (P<0.01 and P<0.05, respectively, versus controls). Inhibition of Rho-kinase (ROCK) with fasudil blocked HG-induced podocyte MP formation. STZ-treated (8 weeks) mice exhibited increased urinary podocyte MPs compared with age-matched nondiabetic mice. Similarly, 16-week-old OVE26 mice had elevated levels of urinary podocyte MPs compared with wild-type littermates (P<0.01). In 1 week post-STZ–treated and 6- and 12-week-old Akita mice, urinary podocyte MPs increased significantly compared with those MPs in nondiabetic mice, despite normal urinary albumin levels. Our results indicate that podocytes produce MPs that are released into urine. Podocyte-derived MPs are generated by exposure to mechanical stretch and high glucose in vitro and could represent early markers of glomerular injury in diabetic nephropathy. PMID:24676640

Copper and zinc content in wild game shot with lead or non-lead ammunition – implications for consumer health protection

PubMed Central

Sommerfeld, Christine; Müller-Graf, Christine; Selhorst, Thomas; Greiner, Matthias; Gerofke, Antje; Ulbig, Ellen; Gremse, Carl; Spolders, Markus; Schafft, Helmut; Lahrssen-Wiederholt, Monika

2017-01-01

The aim of this study was to examine the contamination of game meat with copper and zinc and establish whether the use of alternative (non-lead) ammunition can lead to higher or unsafe levels of copper and zinc in the meat of roe deer, wild boar and red deer. The research project “Safety of game meat obtained through hunting” (LEMISI) was conducted in Germany with the purpose of examining the entry of lead as well as copper and zinc into the meat of hunted game when using either lead or non-lead ammunition. The outcome of this study shows that the usage of both lead-based ammunition and alternative non-lead ammunition results in the entry of copper and zinc into the edible parts of the game. Using non-lead ammunition does not entail dangerously elevated levels of copper and zinc, so replacing lead ammunition with alternative ammunition does not introduce a further health problem with regard to these metals. The levels of copper and zinc in game meat found in this study are in the range found in previous studies of game. The content of copper and zinc in game meat is also comparable to those regularly detected in meat and its products from livestock (pig, cattle, sheep) for which the mean human consumption rate is much higher. From the viewpoint of consumer health protection, the use of non-lead ammunition does not pose an additional hazard through copper and zinc contamination. A health risk due to the presence of copper and zinc in game meat at typical levels of consumer exposure is unlikely for both types of ammunition. PMID:28934259

Copper and zinc content in wild game shot with lead or non-lead ammunition - implications for consumer health protection.

PubMed

Schlichting, Daniela; Sommerfeld, Christine; Müller-Graf, Christine; Selhorst, Thomas; Greiner, Matthias; Gerofke, Antje; Ulbig, Ellen; Gremse, Carl; Spolders, Markus; Schafft, Helmut; Lahrssen-Wiederholt, Monika

2017-01-01

The aim of this study was to examine the contamination of game meat with copper and zinc and establish whether the use of alternative (non-lead) ammunition can lead to higher or unsafe levels of copper and zinc in the meat of roe deer, wild boar and red deer. The research project "Safety of game meat obtained through hunting" (LEMISI) was conducted in Germany with the purpose of examining the entry of lead as well as copper and zinc into the meat of hunted game when using either lead or non-lead ammunition. The outcome of this study shows that the usage of both lead-based ammunition and alternative non-lead ammunition results in the entry of copper and zinc into the edible parts of the game. Using non-lead ammunition does not entail dangerously elevated levels of copper and zinc, so replacing lead ammunition with alternative ammunition does not introduce a further health problem with regard to these metals. The levels of copper and zinc in game meat found in this study are in the range found in previous studies of game. The content of copper and zinc in game meat is also comparable to those regularly detected in meat and its products from livestock (pig, cattle, sheep) for which the mean human consumption rate is much higher. From the viewpoint of consumer health protection, the use of non-lead ammunition does not pose an additional hazard through copper and zinc contamination. A health risk due to the presence of copper and zinc in game meat at typical levels of consumer exposure is unlikely for both types of ammunition.

Hydrophobic Sand Is a Non-Toxic Method of Urine Collection, Appropriate for Urinary Metal Analysis in the Rat

PubMed Central

Hoffman, Jessica F.; Vergara, Vernieda B.; Mog, Steven R.; Kalinich, John F.

2017-01-01

Hydrophobic sand is a relatively new method of urine collection in the rodent, comparable to the established method using a metabolic cage. Urine samples are often used in rodent research, especially for biomarkers of health changes after internal contamination from embedded metals, such as in a model of a military shrapnel wound. However, little research has been done on the potential interference of hydrophobic sand with urine metal concentrations either by contamination from the sand particulate, or adsorption of metals from the urine. We compare urine collected from rats using the metabolic cage method and the hydrophobic sand method for differences in metal concentration of common urinary metals, and examine physical properties of the sand material for potential sources of contamination. We found minimal risk of internal contamination of the rat by hydrophobic sand, and no interference of the sand with several common metals of interest (cobalt, strontium, copper, and manganese), although we advise caution in studies of aluminum in urine. PMID:29051457

Speeding up solar disinfection (SODIS): effects of hydrogen peroxide, temperature, pH, and copper plus ascorbate on the photoinactivation of E. coli.

PubMed

Fisher, Michael B; Keenan, Christina R; Nelson, Kara L; Voelker, Bettina M

2008-03-01

Solar disinfection, or SODIS, shows tremendous promise for point-of-use drinking water treatment in developing countries, but can require 48 h or more for adequate disinfection in cloudy weather. In this research, we show that a number of low-cost additives are capable of accelerating SODIS. These additives included 100-1000 muM hydrogen peroxide, both at room temperature and at elevated temperatures, 0.5 - 1% lemon and lime juice, and copper metal or aqueous copper plus ascorbate, with or without hydrogen peroxide. Laboratory and field experiments indicated that additives might make SODIS more rapid and effective in both sunny and cloudy weather, developments that could help make the technology more effective and acceptable to users.

Progesterone, selected heavy metals and micronutrients in pregnant Nigerian women with a history of recurrent spontaneous abortion.

PubMed

Ajayi, O O; Charles-Davies, M A; Arinola, O G

2012-06-01

Environmental and endocrine factors have been implicated in the aetiology of recurrent abortion, with poorly understood roles. Luteal phase insufficiency marked with insufficient progesterone secretion has been reported. To define the involvement of progesterone, trace metals, and Vitamin E in pregnant women with history of recurrent spontaneous abortion. Convenience sampling method was used to recruit 69 pregnant women aged 21-41 years with gestational age of 0-20 weeks in this case-control study. Thirty five (cases) and thirty four (controls) had previous and no history of recurrent spontaneous abortion respectively. Demographic characteristics and 10 mls of blood samples were obtained from each subject. Serum obtained was used for the determination of progesterone, zinc, copper, selenium, iron, magnesium, manganese, chromium, lead, cadmium, and serum vitamin E by standard methods. Results showed statistically significant decreases (p<0.05) in the serum zinc, copper, and vitamin E and a significant elevation (p<0.05) in the serum selenium, lead, and cadmium in cases compared with controls. Insignificant decrease (p=0.07) was observed in the serum progesterone when cases were compared with controls. Results suggest that elevated serum heavy metals (cadmium and lead) and reduction of essential micronutrients (zinc, copper and vitamin E) may contribute to recurrent spontaneous abortion.

mPGES-1-derived PGE2 mediates dehydration natriuresis

PubMed Central

Jia, Zhanjun; Liu, Gang; Sun, Ying; Kakizoe, Yutaka; Guan, Guangju; Zhang, Aihua; Zhou, Shu-Feng

2013-01-01

PGE2 is a natriuretic factor whose production is elevated after water deprivation (WD) but its role in dehydration natriuresis is not well-defined. The goal of the present study was to investigate the role of microsomal prostaglandin E synthase-1 (mPGES-1) in dehydration natriuresis. After 24-h WD, wild-type (WT) mice exhibited a significant increase in 24-h urinary Na+ excretion accompanied with normal plasma Na+ concentration and osmolality. In contrast, WD-induced elevation of urinary Na+ excretion was completely abolished in mPGES-1 knockout (KO) mice in parallel with increased plasma Na+ concentration and a trend increase in plasma osmolality. WD induced a 1.8-fold increase in urinary PGE2 output and a 1.6-fold increase in PGE2 content in the renal medulla of WT mice, both of which were completely abolished by mPGES-1 deletion. Similar patterns of changes were observed for urinary nitrate/nitrite and cGMP. The natriuresis in dehydrated WT mice was associated with a significant downregulation of renal medullary epithelial Na channel-α mRNA and protein, contrasting to unaltered expressions in dehydrated KO mice. By quantitative RT-PCR, WD increased the endothelial nitric oxide synthase (eNOS), inducible NOS, and neuronal NOS expressions in the renal medulla of WT mice by 3.9-, 1.48-, and 2.6-fold, respectively, all of which were significantly blocked in mPGES-1 KO mice. The regulation of eNOS expression was further confirmed by immunoblotting. Taken together, our results suggest that mPGES-1-derived PGE2 contributes to dehydration natriuresis likely via NO/cGMP. PMID:23171554

Urinary neutrophil gelatinase associated lipocalin as a biomarker in ifosfamide induced chronic renal failure.

PubMed

Kesik, V; Demirkaya, E; Buyukpamukçu, M

2015-12-01

Neutrophil gelatinase associated lipocalin (NGAL) have been used with great success in acute renal failure and in some cases in chronic nephrotoxicity. In this work, we aimed to investigate urinary NGAL as an early marker of chronic renal failure (CRF). We investigated urinary NGAL of 29 children treated with ifosfamide chemotherapy and compared them with those of 12 healthy children. Urinary β2 microglobulin, serum cystatin C, and creatinine clearance analyses were also studied. The median age was 11 years (4-21) and median remission time was 4.3 years (1.8-14.4). The cumulative dose of ifosfamide was 36 g. Glomerular filtration rate was decreased in 41.4% and urine β2 microglobulin levels and serum cystatin C levels were elevated in 31% of the patients. As the remission time increased, serum creatinine and cystatin C levels were also increased. The sensitivity for β2 microglobulin and cystatin C in demonstrating CRF was 35.2% and 23% and specificity was 33.2% and 50% respectively. The 24-hour urine NGAL cut-off level for demonstrating CRF was found to be 1.065 ng/mL/24 hours. The sensitivity and specificity for this cut-off value were 83% and 77%, respectively. NGAL levels were significantly higher in the study group as compared with the control group. Although ifosfamide treatment was suggested to be safe with no complication of renal failure under a dose of 80 g/m2, chronic renal failure and deficits in glomerular and tubular function could be seen when the remission time increased. Elevated NGAL levels may be a good option in determining CRF.

Assessment of murine bladder permeability with fluorescein: validation with cyclophosphamide and protamine.

PubMed

Eichel, L; Scheidweiler, K; Kost, J; Shojaie, J; Schwarz, E; Messing, E; Wood, R

2001-07-01

Bladder hyperpermeability should result in elevated blood levels of intravesically administered agents. Reabsorption from a hyperpermeable bladder should result in prolonged urinary excretion of an agent after parenteral administration. To test these hypotheses, urinary clearance and plasma levels of sodium fluorescein (NaF) were measured in mice before and during cyclophosphamide (CYP) and protamine-induced hemorrhagic cystitis. To measure the plasma uptake of NaF from the bladder, 10 mg/mL NaF was instilled, either by catheter or retrograde urethral infusion, 15 minutes before retro-orbital or ventricular sampling. The plasma levels were measured 24 hours and 14 days after exposure to CYP 300 mg/kg or 15 minutes after instillation of protamine 10 mg/mL. Hourly urine concentrations were measured immediately after intraperitoneal administration of 10 mg/kg NaF. Pretreatment samples were compared with those obtained 24 hours after intraperitoneal administration of 300 mg/kg CYP. Urinary NaF excretion was delayed in CYP-exposed mice. A bi-exponential model provided an appropriate fit of the data, both before and after CYP administration. The plasma levels of NaF were significantly elevated at 24 hours and 14 days after CYP exposure when sampled by ventricular nick or retro-orbitally. The median concentration of fluorescein in the protamine-treated mice was significantly higher than in the control mice. Fluorescein can be used to measure alterations in bladder permeability after bladder mucosal injury in mice. Urinary excretion of NaF is a bi-exponential process that is delayed after bladder mucosal injury, presumably because of increased mucosal permeability and resorption from the urine into the bloodstream.

Novel urinary biomarkers and their association with urinary heavy metals in chronic kidney disease of unknown aetiology in Sri Lanka: a pilot study

PubMed

Wanigasuriya, K; Jayawardene, I; Amarasiriwardena, C; Wickremasinghe, R

2017-12-26

Chronic kidney disease of unknown etiology (CKDu) has emerged as a significant public health problem in Sri Lanka. The role of environmental exposure to cadmium and arsenic in the aetiology of CKDu is still unclear. Identification of a panel of novel urinary biomarkers would be invaluable in the study of toxin mediated damage postulated to be the aetiology of CKDu. The aims of this study were to evaluate the profile of novel urinary biomarkers in CKDu patients and identify any association with environmental exposure to heavy metals. Thirty seven randomly selected CKDu patients attending a renal clinic in the North Central Province and two control groups namely a farmer group (n=39) and a non-farmer group (n=40) from a non-endemic area were included in this comparative cross sectional study. Urine samples were analyzed for heavy metals and five urinary biomarkers. CKDu patients had significantly elevated urinary levels of fibrinogen (198.2 ng/mg creatinine p<0.001), clusterin (3479 ng/mg creatinine p<0.001), cystatin-C (5124.8 ng/mg creatinine p<0.001) and β2-microglobulin (9913.4 ng/mg creatinine p<0.001) compared to the control groups. Fibrinogen and β2-microglobulin were the best to discriminate CKDu patients from normal individuals with the receiver operator areas under the curve being 0.867 and 0.853, respectively. Urinary fibrinogen and KIM-1 levels correlated positively with urinary arsenic levels. KIM-1 levels correlated positively with urinary mercury and lead levels but no correlation was seen with urinary cadmium levels. Fibrinogen and β2-microglobulin have the potential of being a screening tool for detection of CKDu and may aid the early diagnosis of toxin mediated tubular injury in CKDu. Their usefulness need to be further validated in a larger epidemiological study of patients with early stages of CKDu.

Hydrogenation of CO 2 on ZnO/Cu(100) and ZnO/Cu(111) Catalysts: Role of Copper Structure and Metal–Oxide Interface in Methanol Synthesis

DOE PAGES

Palomino, Robert M.; Ramirez, Pedro J.; Liu, Zongyuan; ...

2017-08-21

The results of kinetic tests and ambient-pressure X-ray photoelectron spectroscopy (AP-XPS) show the important role played by a ZnO–copper interface in the generation of CO and the synthesis of methanol from CO 2 hydrogenation. The deposition of nanoparticles of ZnO on Cu(100) and Cu(111), θ oxi < 0.3 monolayer, produces highly active catalysts. The catalytic activity of these systems increases in the sequence: Cu(111) < Cu(100) < ZnO/Cu(111) < ZnO/Cu(100). The structure of the copper substrate influences the catalytic performance of a ZnO–copper interface. Furthermore, size and metal–oxide interactions affect the chemical and catalytic properties of the oxide making themore » supported nanoparticles different from bulk ZnO. The formation of a ZnO–copper interface favors the binding and conversion of CO 2 into a formate intermediate that is stable on the catalyst surface up to temperatures above 500 K. Alloys of Zn with Cu(111) and Cu(100) were not stable at the elevated temperatures (500–600 K) used for the CO 2 hydrogenation reaction. However, reaction with CO 2 oxidized the zinc, enhancing its stability over the copper substrates.« less

Hydrogenation of CO 2 on ZnO/Cu(100) and ZnO/Cu(111) Catalysts: Role of Copper Structure and Metal–Oxide Interface in Methanol Synthesis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Palomino, Robert M.; Ramirez, Pedro J.; Liu, Zongyuan

The results of kinetic tests and ambient-pressure X-ray photoelectron spectroscopy (AP-XPS) show the important role played by a ZnO–copper interface in the generation of CO and the synthesis of methanol from CO 2 hydrogenation. The deposition of nanoparticles of ZnO on Cu(100) and Cu(111), θ oxi < 0.3 monolayer, produces highly active catalysts. The catalytic activity of these systems increases in the sequence: Cu(111) < Cu(100) < ZnO/Cu(111) < ZnO/Cu(100). The structure of the copper substrate influences the catalytic performance of a ZnO–copper interface. Furthermore, size and metal–oxide interactions affect the chemical and catalytic properties of the oxide making themore » supported nanoparticles different from bulk ZnO. The formation of a ZnO–copper interface favors the binding and conversion of CO 2 into a formate intermediate that is stable on the catalyst surface up to temperatures above 500 K. Alloys of Zn with Cu(111) and Cu(100) were not stable at the elevated temperatures (500–600 K) used for the CO 2 hydrogenation reaction. However, reaction with CO 2 oxidized the zinc, enhancing its stability over the copper substrates.« less

Skeletal unloading and dietary copper depletion are detrimental to bone quality of mature rats

NASA Technical Reports Server (NTRS)

Smith, Brenda J.; King, Jarrod B.; Lucas, Edralin A.; Akhter, Mohammed P.; Arjmandi, Bahram H.; Stoecker, Barbara J.

2002-01-01

This study was designed to examine the skeletal response to copper depletion and mechanical unloading in mature animals. In a 2 x 2 experimental design, 5.5-mo-old male Sprague-Dawley rats (n = 36) consumed either the control (AIN-93M) or Cu-depletion ((-)Cu) diet beginning 21 d before suspension and throughout the remainder of the study. Half of the rats in each dietary treatment group were either tail-suspended (TS) or kept ambulatory (AMB) for 28 d. Lower bone mineral densities (BMD) of 5th lumbar vertebra (L5) (P < 0.05) and femur were observed with (-)Cu and TS, but no differences were noted in the BMD of the humerus. Mechanical strength in the femur and vertebra decreased in response to TS, but were unaffected by copper depletion. Urinary deoxypyridinoline, an index of bone resorption, was significantly greater in TS rats, but unaltered by (-)Cu. No changes in serum or bone alkaline phosphatase activity, an indicator of bone formation, were observed. Our findings suggest that TS and (-)Cu decreased BMD in unloaded femur and vertebra but had no effect on normally loaded humerus. Bone loss with TS appeared to be related to accelerated bone resorption. Alterations in bone metabolism and bone mechanical properties in the mature skeleton resulting from (-)Cu warrant further investigation.

Soluble fragments of e-cadherin cell-adhesion molecule increase in urinary-excretion of cancer-patients, potentially indicating its shedding from epithelial tumor-cells.

PubMed

Katayama, M; Hirai, S; Yasumoto, M; Nishikawa, K; Nagata, S; Otsuka, M; Kamihagi, K; Kato, I

1994-11-01

E-cadherin (Ecad) is well known to be a calcium-ion-dependent cell-cell adhesion molecule expressed mostly in epithelial tissues. Previous immunohistochemical studies suggested that this cell adhesion molecule acts as an invasion suppressor and is negligibly detected in cancer metastatic regions. Soluble Ecad fragments derived from the proteolysed membrane-associated form were detected in culture supernatants of two cell lines, COLO 205 and A-431, with normal distribution of cell surface Ecad. Soluble Ecad levels released into culture of COLO 205 exhibiting reduced cell-cell adhesion were apparently elevated above those of A-431 with tight cell-cell adhesion. Furthermore, human circulation and urine continuously contain soluble Ecad which consists mainly of homogeneous 75-85 kDa extracellular domains. Soluble Ecad urinary level per urinary creatinine level was found to be significantly elevated in 53% of patients suffering from various types of cancers including lung, liver, stomach, colon and rectal cancers, as compared with those in the age-matched healthy subjects. These results suggest that dysfunction of cell surface Ecad is responsible for its enhanced proteolytic shedding in tumorigenesis, which may lead to the decrease of cell surface Ecads. Furthermore, excretion of high levels of soluble Ecad fragments potentially indicates the progression of epithelial tumors excessively degrading cell surface Ecad in clinical subjects.

Increased levels of urinary PGE-M, a biomarker of inflammation, occur in association with obesity, aging and lung metastases in patients with breast cancer

PubMed Central

Morris, Patrick G.; Zhou, Xi Kathy; Milne, Ginger L.; Goldstein, Daniel; Hawks, Laura C.; Dang, Chau T.; Modi, Shanu; Fornier, Monica N.; Hudis, Clifford A.; Dannenberg, Andrew J.

2013-01-01

Elevated levels of cyclooxygenase (COX)-derived prostaglandin E2 (PGE2) occur in inflamed tissues. To evaluate the potential links between inflammation and breast cancer, levels of urinary prostaglandin E-metabolite (PGE-M), a stable end metabolite of PGE2, were quantified. We enrolled 400 patients with breast cancer: controls with early breast cancer (n=200), lung metastases (n=100) and metastases to other sites (n=100). Patients completed a questionnaire, provided urine and had measurements of height and weight. Urinary PGE-M was quantified by mass spectrometry. Ever smokers with lung metastasis who had not been exposed to NSAIDs had the highest PGE-M levels. PGE-M levels were increased in association with elevated BMI (p<0.001), aging (p<0.001), pack-year smoking history (p=0.02), lung metastases (p=0.02) and recent cytotoxic chemotherapy (p=0.03). Conversely, use of NSAIDs, prototypic inhibitors of COX activity, was associated with reduced PGE-M levels (p<0.001). Based on the current findings, PGE-M is likely to be a useful biomarker for the selection of high risk subgroups to determine the utility of interventions that aim to reduce inflammation and possibly the development and progression of breast cancer, especially in overweight and obese women. PMID:23531446

Nonclassic presentation of pheochromocytoma: difficulties in diagnosis and management of the normotensive patient.

PubMed

Gonzalez-Pantaleon, Adalberto D; Simon, Barbara

2008-01-01

To report an unusual presentation of pheochromocytoma along with challenges in diagnosis and management. We report a clinical case history and describe diagnostic methods and pitfalls. The preoperative medical preparation in a normotensive patient is described. A 33-year-old man fell off a ladder, resulting in C6 paraplegia. After C7-T1 laminectomy, he was transferred to a rehabilitation center where he reported lightheadedness, shortness of breath, and chest pain during therapy sessions. A left adrenal mass was incidentally discovered during the workup to rule out a pulmonary embolism. He reported no history of hypertension, and no elevated blood pressure readings had been documented. Magnetic resonance imaging of the adrenal glands showed a well-defined left adrenal mass measuring 3.9 x 3.2 x 3.3 cm, which was hyperintense on T2-weighted images. Twenty-four hour urinary catecholamine concentrations were unremarkable; urinary metanephrines were markedly elevated. During hospital admission, blood pressure was in the low to normotensive range, requiring a cautious approach to alpha-adrenergic blockade and surgical preparation. He under-went uneventful laparoscopic left adrenalectomy; surgical pathology was consistent with pheochromocytoma. This case illustrates a nonclassic presentation of pheochromocytoma and demonstrates that urinary catecholamines alone are not sufficient for a biochemical diagnosis of large pheochromocytomas. Preoperative preparation in normotensive patients can be achieved with alpha-adrenergic blockade, hydration, and liberal salt intake.

The urinary proteome and metabonome differ from normal in adults with mitochondrial disease.

PubMed

Hall, Andrew M; Vilasi, Annalisa; Garcia-Perez, Isabel; Lapsley, Marta; Alston, Charlotte L; Pitceathly, Robert D S; McFarland, Robert; Schaefer, Andrew M; Turnbull, Doug M; Beaumont, Nick J; Hsuan, Justin J; Cutillas, Pedro R; Lindon, John C; Holmes, Elaine; Unwin, Robert J; Taylor, Robert W; Gorman, Grainne S; Rahman, Shamima; Hanna, Michael G

2015-03-01

We studied the extent and nature of renal involvement in a cohort of 117 adult patients with mitochondrial disease, by measuring urinary retinol-binding protein (RBP) and albumin; established markers of tubular and glomerular dysfunction, respectively. Seventy-five patients had the m.3243A>G mutation and the most frequent phenotypes within the entire cohort were 14 with MELAS, 33 with MIDD, and 17 with MERRF. Urinary RBP was increased in 29 of 75 of m.3243A>G patients, whereas albumin was increased in 23 of the 75. The corresponding numbers were 16 and 14, respectively, in the 42 non-m.3243A>G patients. RBP and albumin were higher in diabetic m.3243A>G patients than in nondiabetics, but there were no significant differences across the three major clinical phenotypes. The urine proteome (mass spectrometry) and metabonome (nuclear magnetic resonance) in a subset of the m.3243A>G patients were markedly different from controls, with the most significant alterations occurring in lysosomal proteins, calcium-binding proteins, and antioxidant defenses. Differences were also found between asymptomatic m.3243A>G carriers and controls. No patients had an elevated serum creatinine level, but 14% had hyponatremia, 10% had hypophosphatemia, and 14% had hypomagnesemia. Thus, abnormalities in kidney function are common in adults with mitochondrial disease, exist in the absence of elevated serum creatinine, and are not solely explained by diabetes.

Urinary volatile organic compounds as potential biomarkers for renal cell carcinoma

PubMed Central

WANG, DONGCHUN; WANG, CHANGSONG; PI, XIN; GUO, LEI; WANG, YUE; LI, MINGJUAN; FENG, YUE; LIN, ZIWEI; HOU, WEI; LI, ENYOU

2016-01-01

Currently, there is no adequate, sensitive, reproducible, specific and noninvasive biomarker that can reliably be used to detect renal cell carcinoma (RCC). Previous studies have elucidated the urinary non-volatile metabolic profile of RCC. However, whether urinary volatile organic compound (VOC) profiles are able to identify RCC remains to be elucidated. In the present study, urine was collected from 22 patients with RCC and 25 healthy subjects. Principal component analysis and orthogonal partial least square discriminant analysis were used to compare the data of patients and healthy subjects, and preoperative and postoperative patients undergoing radical nephrectomy. In total, 11 VOC biomarkers were elevated in the RCC patients compared to the healthy subjects, which were phenol; decanal; 1,6-dioxacyclododecane-7,12-dione; 1-bromo-1-(3-methyl-1-pentenylidene)-2,2,3,3-tetramethyl-cyclopropane; nonanal; 3-ethyl-3-methylheptane; isolongifolene-5-ol; 2,5-cyclohexadiene-1,4-dione, 2,6-bis(1,1-dimethylethyl); tetradecane; aniline; and 2,6,10,14-tetramethyl-pentadecane. Three biomarkers were decreased in RCC patients: styrene, 4-heptanone and dimethylsilanediol. In preoperative patients, 2-ethyl-1-hexanol and cyclohexanone were elevated, while 6-t-butyl-2,2,9,9-tetramethyl-3,5-decadien-7-yne were decreased when compared to postoperative patients. Compared with the healthy subjects, RCC has a unique VOC profile, suggesting that VOC profiles may be a useful diagnostic assay for RCC. PMID:27347408

Serial urinary IL-2, IL-6, IL-8, TNFalpha, UBC, CYFRA 21-1 and NMP22 during follow-up of patients with bladder cancer receiving intravesical BCG.

PubMed

Sanchez-Carbayo, M; Urrutia, M; Romani, R; Herrero, M; Gonzalez de Buitrago, J M; Navajo, J A

2001-01-01

We evaluated the potential role of serial preinstillation levels of several interleukins, TNFalpha and urinary tumor markers to monitor patients with bladder cancer receiving intravesical BCG. 121 urine samples were collected from: patients with bladder cancer treated with BCG (group 1); patients with bladder cancer receiving other intravesical treatment (group 2) and patients with urinary tract infections (group 3). Cytokines [IL-2, IL6 and [L8] and TNFalpha and urinary tumor markers [UBC, CYFRA 21-1 and NMP22] were measured by immunoassays. In 3 out of 15 BCG non-responders that recurred over the period of the study, no cytokine peak for IL-2, IL-6 or TNFa were detected. Urinary tumor markers increased in 2 out of 3 of these patients earlier than scheduled cystoscopies. Cytokine measurement was heterogeneous among 12 out of 15 BCG-responding patients: there were low levels of IL-6 and TNFalpha and peaks of IL-2 and IL-8 in 10 out of 12 and 4 out of 12 patients, respectively. During responding patients' follow-up we observed false-positive results in 7 out of 65 urine samples for UBC, 8 out of 65 for CYFRA 21-1 and 20 out of 65 for NMP22. Urinary tract infections were the main factor associated with non-specific elevations of IL-6 and IL-8 and urinary tumor markers in all groups of patients. Although larger series are required to confirn our preliminary observations, our data argue for a potential predictive role for IL-2 of favourable response to BCG therapy. Monitoring BCG with urinary tumor markers could early detect recurrence in non-responding patients.

Urinary corticosterone metabolite responses to capture and captivity in the cane toad (Rhinella marina).

PubMed

Narayan, Edward J; Cockrem, John F; Hero, Jean-Marc

2011-09-01

Urinary corticosterone metabolite responses to capture have recently been shown for the first time in amphibians, and in the present study urinary corticosterone metabolite responses to capture and to confinement in captivity were measured in adult cane toads (Rhinella marina) in Queensland, Australia. An adrenocorticotropic hormone (ACTH) challenge was used to provide a biological validation for urinary corticosterone metabolite concentrations measured by radioimmunoassay (RIA). Urinary corticosterone metabolite increased 1-2 days after ACTH but not saline injection and then returned to initial values, indicating that the RIA could detect changes in corticosterone secretion in toads. Urinary corticosterone metabolite responses to short-term capture and restraint in plastic bags were first apparent 2h after capture of wild toads. Toads held communally in captivity for 5 days had elevated urinary corticosterone metabolite concentrations. Mean corticosterone concentrations declined significantly after a further 7 days in individual housing chambers. There was no sex difference in urinary corticosterone metabolite responses of toads to ACTH challenge, short-term capture or captivity. The relative amount of variation in the mean corticosterone responses was quantified by calculating coefficients of variation (CV) for each mean corticosterone response. Mean corticosterone at 0 min was more variable for captive toads than wild toads. Furthermore, initial corticosterone concentrations (0 min) were more variable than concentrations during the ACTH challenge, short-term capture and captivity. There was little change in the amount of variation of mean corticosterone levels between male and female toads with increasing time in captivity (12-29 days). This study has shown individual corticosterone responses of amphibians for the first-time, and has provided a novel method for quantifying the relative amount of variation in amphibian corticosterone responses. Copyright © 2011 Elsevier Inc. All rights reserved.

Profiling of Kidney Injury Biomarkers in Patients Receiving Cisplatin: Time-Dependent Changes in the Absence of Clinical Nephrotoxicity

PubMed Central

George, Blessy; Wen, Xia; Mercke, Nickie; Gomez, Madeleine; O’Bryant, Cindy; Bowles, Daniel W.; Hu, Yichun; Hogan, Susan L.

2016-01-01

The success of cisplatin-containing regimens to treat solid tumors is limited, in part, by nephrotoxicity. In rodents, several urinary proteins have emerged as more sensitive indicators of cisplatin-induced kidney injury. We sought to characterize time-dependent changes in the urinary concentrations of 12 proteins including KIM-1, calbindin, β2M, and TFF3 after cisplatin therapy. Urine was collected at baseline, 3 (range: 2-5), and 10 (range: 9-11) days from 57 patients with solid tumors receiving outpatient cisplatin therapy (≥ 25 mg/m2). Serum creatinine was largely unchanged after cisplatin infusion. However, compared to baseline values, several novel biomarkers were significantly increased in the urine including β2M, which was 3-fold higher by day 3 (p<0.0001). Urinary KIM-1 and TFF3 were elevated 2-fold by day 10 (p=0.002 and p=0.002, respectively) whereas calbindin levels were increased 8-fold (p<0.0001). We report novel time-dependent changes in the urinary excretion of noninvasive markers of subclinical kidney injury after cisplatin treatment. PMID:28002630

Increased urinary excretion of acidic mucopolysaccharides in exophthalmos

PubMed Central

Winand, Roger J.

1968-01-01

The excretion of mucopolysaccharides normally found in urine (chondroitin, chondroitin sulfates A and C, keratosulfate, and heparitin sulfate) is increased approximately twofold in patients with progresive exophthalmos. A threefold elevation of total serum mucopolysaccharides is also found. These increases are unrelated to thyroid function. PMID:4235688

Pathological changes in growing dogs fed on a balanced cassava (Manihot esculenta Crantz) diet.

PubMed

Kamalu, B P

1993-05-01

Studies were carried out to determine the effects of the toxic principle linamarin, a cyanogenic glucoside, in a diet containing cassava (Manihot esculenta Crantz) in the form of gari fed to growing dogs for 14 weeks. There were three groups of dogs, each comprising six animals. One group was fed on a control diet with rice as the carbohydrate source, the second group was fed on cassava (gari) as the carbohydrate source and which was expected to release 10.8 mg HCN/kg cooked food, the third group was fed on the control diet to which enough NaCN was added at feeding time to release 10.8 mg HCN/kg cooked food in order to monitor the effects of the HCN released from gari. All diets contained 130 g crude protein (N x 6.25)/kg and were supplemented with vitamins and minerals. Each animal was given approximately 100 g diet/kg body weight for the duration of the experiment. The biochemical variables investigated were plasma electrolytes, serum proteins, plasma-free amino acids, plasma enzymes and urine protein, and the histology of some metabolically active tissues, namely liver, kidney, myocardium, testis and adrenal gland, was studied. The gari diet caused an elevated plasma thiocyanate concentration (P < 0.01), elevated 24 h urinary thiocyanate excretion and elevated urinary protein excretion (P < 0.01), lowered serum albumin (P < 0.05), a plasma-free amino acid profile which resembled that found in kwashiorkor, lowered plasma K and Ca (P < 0.05). The rice + cyanide diet caused an elevated plasma thiocyanate (P < 0.01) and a 24 h urinary thiocyanate excretion that was significantly higher (P < 0.01) than that of the dogs fed on gari, but caused a urinary protein excretion that was significantly lower than that of the dogs fed on gari (P < 0.01), lowered serum albumin (P < 0.05), a plasma-free amino acid profile that indicated that the amino acids were not being utilized to the same extent as in the control (rice) group but were accumulating. Neither diet had an effect on plasma gamma-glutamyltransferase (EC 2.3.2.2), alanine aminotransferase (EC 2.6.1.2) or isocitrate dehydrogenase (EC 1.1.1.42) activities, plasma Na, Mg, and P concentrations. The gari diet caused generalized congestion and haemorrhage, periportal vacuolation of the liver, swelling, vacuolation and rupture of the epithelial cells of the proximal convoluted tubules of the kidney, myocardial degeneration and adrenal gland degeneration.(ABSTRACT TRUNCATED AT 400 WORDS)

Leucine and Protein Metabolism in Obese Zucker Rats

PubMed Central

She, Pengxiang; Olson, Kristine C.; Kadota, Yoshihiro; Inukai, Ayami; Shimomura, Yoshiharu; Hoppel, Charles L.; Adams, Sean H.; Kawamata, Yasuko; Matsumoto, Hideki; Sakai, Ryosei; Lang, Charles H.; Lynch, Christopher J.

2013-01-01

Branched-chain amino acids (BCAAs) are circulating nutrient signals for protein accretion, however, they increase in obesity and elevations appear to be prognostic of diabetes. To understand the mechanisms whereby obesity affects BCAAs and protein metabolism, we employed metabolomics and measured rates of [1-14C]-leucine metabolism, tissue-specific protein synthesis and branched-chain keto-acid (BCKA) dehydrogenase complex (BCKDC) activities. Male obese Zucker rats (11-weeks old) had increased body weight (BW, 53%), liver (107%) and fat (∼300%), but lower plantaris and gastrocnemius masses (−21–24%). Plasma BCAAs and BCKAs were elevated 45–69% and ∼100%, respectively, in obese rats. Processes facilitating these rises appeared to include increased dietary intake (23%), leucine (Leu) turnover and proteolysis [35% per g fat free mass (FFM), urinary markers of proteolysis: 3-methylhistidine (183%) and 4-hydroxyproline (766%)] and decreased BCKDC per g kidney, heart, gastrocnemius and liver (−47–66%). A process disposing of circulating BCAAs, protein synthesis, was increased 23–29% by obesity in whole-body (FFM corrected), gastrocnemius and liver. Despite the observed decreases in BCKDC activities per gm tissue, rates of whole-body Leu oxidation in obese rats were 22% and 59% higher normalized to BW and FFM, respectively. Consistently, urinary concentrations of eight BCAA catabolism-derived acylcarnitines were also elevated. The unexpected increase in BCAA oxidation may be due to a substrate effect in liver. Supporting this idea, BCKAs were elevated more in liver (193–418%) than plasma or muscle, and per g losses of hepatic BCKDC activities were completely offset by increased liver mass, in contrast to other tissues. In summary, our results indicate that plasma BCKAs may represent a more sensitive metabolic signature for obesity than BCAAs. Processes supporting elevated BCAA]BCKAs in the obese Zucker rat include increased dietary intake, Leu and protein turnover along with impaired BCKDC activity. Elevated BCAAs/BCKAs may contribute to observed elevations in protein synthesis and BCAA oxidation. PMID:23527196

Multiple metal exposures and their correlation with monoamine neurotransmitter metabolism in Chinese electroplating workers.

PubMed

Wu, Lin-Lin; Gong, Wei; Shen, Si-Peng; Wang, Zhong-He; Yao, Jia-Xi; Wang, Jun; Yu, Jing; Gao, Rong; Wu, Gang

2017-09-01

Excessive metal exposure has been recognized as one of the detrimental factors for brain damage. However, the potential adverse effects induced by heavy metals on monoamine neurotransmitter pathways remains poorly understood. Our study aimed to investigate the possible association between metal exposure and neurotransmitter metabolism. By a cross-sectional investigation, 224 electroplating workers and 213 non-electroplating exposure workers were recruited in the exposure and control groups. Metal exposure levels were analyzed using inductively-coupled plasma mass spectrometry and monoamine neurotransmitter pathway metabolites were measured by ultra-performance liquid chromatography tandem mass spectrometry in human urine samples. Multivariate linear regression model was used to assess the dose-response relationships of urinary metals and neurotransmitter pathway metabolites. Significant dose-dependent trends of urinary vanadium quartiles with all metabolites were observed, and the trends demonstrated significance after multiple testing correction. It also showed that urinary chromium levels were significantly associated with decreased serotonin level and cadmium was positively associated with norepinephrine and epinephrine. In addition, arsenic was positively associated with tryptophan, serotonin, dopamine and norepinephrine. Iron was positively associated with increased homovanillic acid (HVA) and epinephrine while nickel was negatively associated with increased epinephrine levels. Zinc was positively related to tryptophan, kynurenin (KYN), 5-hydroxyindole acetic acid (5-HIAA), dopamine, HVA and norepinephrine. There was no significant association between urinary copper with any other metabolites after adjusting of multiple metal models. Metal exposure may be associated with neurotransmitter metabolism disturbances. The present work is expected to provide some support in the prevention and management of metal-associated neurological diseases. Copyright © 2017. Published by Elsevier Ltd.

Dietary flavonols contribute to false-positive elevation of homovanillic acid, a marker of catecholamine-secreting tumors.

PubMed

Combet, Emilie; Lean, Michael E J; Boyle, James G; Crozier, Alan; Davidson, D Fraser

2011-01-14

Urinary homovanillic acid (HVA) measurement is used routinely as a marker of the first test for the screening of catecholamine-secreting tumors and dopamine metabolism, but generates a large number of false-positive results. With no guidelines for dietary restrictions prior to the test, we hypothesize that consumption of flavonol-rich foods (such as onions, tomatoes, tea) prior to urinary catecholamine screening could be responsible for false-positive urinary HVA in healthy subjects. A randomized, crossover dietary intervention was carried out in healthy subjects (n=17). Volunteers followed either a low or high-flavonol diet, for a duration of 3 days, prior to providing a 24-h urine sample for HVA measurement using a routine, validated liquid chromatography method as well as a gas chromatography-mass spectrometry method. Dietary flavonol intake significantly increased urinary HVA excretion (p < 0.001), with 3 out of 17 volunteers (20%) exceeding the 40 μmol/24 h upper limit of normal for HVA excretion (false-positive result). Dietary flavonols commonly found in foodstuff such as tomatoes, onions, and tea, interfered with the routine urinary HVA screening test and should be avoided in the three-day run-up to the test. Copyright © 2010 Elsevier B.V. All rights reserved.

Copper toxicity and bioaccumulation in Chinese cabbage (Brassica pekinensis Rupr.).

PubMed

Xiong, Zhi-Ting; Wang, Hai

2005-04-01

Copper is among the major heavy metal contaminants in the environment with various anthropogenic and natural sources. Human health risk from heavy metal bioaccumulation in vegetables has been a subject of growing concern in recent years. To investigate Cu phytotoxic effects and bioaccumulation in the popular vegetable Chinese cabbage (Brassica pekinensis Rupr) as well as the implications for human health due to Cu in the vegetable supply, seed germination and pot culture experiments with this vegetable were carried out. Six levels (0, 0.008, 0.031, 0.125, 0.5, and 2.0 mM/L) and 3 levels (0, 0.2, and 1.0 mM/kg) of Cu treatments were performed for the seed germination and pot culture experiments, respectively. The LC(50) of Cu for seed germination of Chinese cabbage was 0.348 mM/L. In the pot culture experiments, Cu treatments significantly increased electrolyte leakage and peroxidase activity of shoot tissues, demonstrating Cu phytotoxicity to the plants. On the other hand, Cu treatments significantly stimulated, instead of reduced, chlorophyll content. Cu treatments did not show a significant effect on shoot biomass. Compared to the control, Cu treatments significantly elevated the Cu content of the shoots-9.9, 42.5, and 119.0 mg/kg (DW) of Cu were detected in the 0, 0.2, and 1.0 mM/kg treatments, respectively. These results showed that although the plants accumulated an elevated copper content and suffered damage to some extent under Cu treatment, they looked healthy. It was suggested that Chinese cabbage with an elevated Cu content and without showing visible symptoms of damage possibly could cause a risk to human health from the transfer of the metal in food.

Urinary Peptides in Rett Syndrome.

ERIC Educational Resources Information Center

Solaas, K. M.; Skjeldal, O.; Gardner, M. L. G.; Kase, B. F.; Reichelt, K. L.

2002-01-01

A study found a significantly higher level of peptides in the urine of 53 girls with Rett syndrome compared with controls. The elevation was similar to that in 35 girls with infantile autism. Levels of peptides were lower in girls with classic Rett syndrome than those with congenital Rett syndrome. (Contains references.) (Author/CR)

Copper tolerance in Frankia sp. strain EuI1c involves surface binding and copper transport.

PubMed

Rehan, Medhat; Furnholm, Teal; Finethy, Ryan H; Chu, Feixia; El-Fadly, Gomaah; Tisa, Louis S

2014-09-01

Several Frankia strains have been shown to be copper-tolerant. The mechanism of their copper tolerance was investigated for Frankia sp. strain EuI1c. Copper binding was shown by binding studies. Unusual globular structures were observed on the surface of the bacterium. These globular structures were composed of aggregates containing many relatively smaller "leaf-like" structures. Scanning electron microscopy with energy-dispersive X-ray (SEM-EDAX) analysis of these structures indicated elevated copper and phosphate levels compared to the control cells. Fourier transform infrared spectroscopy (FTIR) analysis indicated an increase in extracellular phosphate on the cell surface of copper-stressed cells. Bioinformatics' analysis of the Frankia sp. strain EuI1c genome revealed five potential cop genes: copA, copZ, copC, copCD, and copD. Experiments with Frankia sp. strain EuI1c using qRT-PCR indicated an increase in messenger RNA (mRNA) levels of the five cop genes upon Cu(2+) stress. After 5 days of Cu(2+) stress, the copA, copZ, copC, copCD, and copD mRNA levels increased 25-, 8-, 18-, 18-, and 25-fold, respectively. The protein profile of Cu(2+)-stressed Frankia sp. strain EuI1c cells revealed the upregulation of a 36.7 kDa protein that was identified as FraEuI1c_1092 (sulfate-binding periplasmic transport protein). Homologues of this gene were only present in the genomes of the Cu(2+)-resistant Frankia strains (EuI1c, DC12, and CN3). These data indicate that copper tolerance by Frankia sp. strain EuI1c involved the binding of copper to the cell surface and transport proteins.

Copper Capture in a Thioether-Functionalized Porous Polymer Applied to the Detection of Wilson’s Disease

PubMed Central

2016-01-01

Copper is an essential nutrient for life, but at the same time, hyperaccumulation of this redox-active metal in biological fluids and tissues is a hallmark of pathologies such as Wilson’s and Menkes diseases, various neurodegenerative diseases, and toxic environmental exposure. Diseases characterized by copper hyperaccumulation are currently challenging to identify due to costly diagnostic tools that involve extensive technical workup. Motivated to create simple yet highly selective and sensitive diagnostic tools, we have initiated a program to develop new materials that can enable monitoring of copper levels in biological fluid samples without complex and expensive instrumentation. Herein, we report the design, synthesis, and properties of PAF-1-SMe, a robust three-dimensional porous aromatic framework (PAF) densely functionalized with thioether groups for selective capture and concentration of copper from biofluids as well as aqueous samples. PAF-1-SMe exhibits a high selectivity for copper over other biologically relevant metals, with a saturation capacity reaching over 600 mg/g. Moreover, the combination of PAF-1-SMe as a material for capture and concentration of copper from biological samples with 8-hydroxyquinoline as a colorimetric indicator affords a method for identifying aberrant elevations of copper in urine samples from mice with Wilson’s disease and also tracing exogenously added copper in serum. This divide-and-conquer sensing strategy, where functional and robust porous materials serve as molecular recognition elements that can be used to capture and concentrate analytes in conjunction with molecular indicators for signal readouts, establishes a valuable starting point for the use of porous polymeric materials in noninvasive diagnostic applications. PMID:27285482

Chronic copper exposure causes spatial memory impairment, selective loss of hippocampal synaptic proteins, and activation of PKR/eIF2α pathway in mice.

PubMed

Ma, Quan; Ying, Ming; Sui, Xiaojing; Zhang, Huimin; Huang, Haiyan; Yang, Linqing; Huang, Xinfeng; Zhuang, Zhixiong; Liu, Jianjun; Yang, Xifei

2015-01-01

Copper is an essential element for human growth and development; however, excessive intake of copper could contribute to neurotoxicity. Here we show that chronic exposure to copper in drinking water impaired spatial memory with simultaneous selective loss of hippocampal pre-synaptic protein synapsin 1, and post-synaptic density protein (PSD)-93/95 in mice. Copper exposure was shown to elevate the levels of nitrotyrosine and 8-hydroxydeoxyguanosine (8-OHdG) in hippocampus, two markers of oxidative stress. Concurrently, we also found that copper exposure activated double stranded RNA-dependent protein kinase (PKR) as evidenced by increased ratio of phosphorylated PKR at Thr451 and total PKR and increased the phosphorylation of its downstream signaling molecule eukaryotic initiation factor 2α (eIF2α) at Ser51 in hippocampus. Consistent with activation of PKR/eIF2α signaling pathway which was shown to mediate synaptic deficit and cognitive impairment, the levels of activating transcription factor 4 (ATF-4), a downstream signaling molecule of eIF2α and a repressor of CREB-mediated gene expression, were significantly increased, while the activity of cAMP response elements binding protein (CREB) was inactivated as suggested by decreased phosphorylation of CREB at Ser133 by copper exposure. In addition, the expression of the pro-apoptotic target molecule C/EBP homology protein (CHOP) of ATF-4 was upregulated and hippocampal neuronal apoptosis was induced by copper exposure. Taken together, we propose that chronic copper exposure might cause spatial memory impairment, selective loss of synaptic proteins, and neuronal apoptosis through the mechanisms involving activation of PKR/eIF2α signaling pathway.

Influence of Dietary Copper on Serum Growth-Related Hormone Levels and Growth Performance of Weanling Pigs.

PubMed

Wang, Jianguo; Zhu, Xiaoyan; Guo, Yazhou; Wang, Zhe; Zhao, Baoyu; Yin, Yunhou; Liu, Guowen

2016-07-01

To investigate the effect of dietary copper on serum growth-related hormones levels and growth performance, a total of 60 weanling pigs were randomly assigned to six groups each containing 10 pigs, fed on basal diets supplemented with 0 (control), 100, 150, 200, 250, and 300 mg/kg copper sulfate for 80 days, respectively. The average daily gain (ADG), feed to gain ratio (F/G), feed intake and serum growth hormone (GH), insulin (INS), insulin-like growth factor 1 (IGF-1), and insulin-like growth factor-binding protein 3 (IGFBP-3) levels were detected at interval of 20 days. The results revealed that ADG, and serum GH, INS, IGF-1, and IGFBP-3 concentrations were increased significantly in the pigs fed on diets added with 100, 150, 200, 250, and 300 mg/kg copper sulfate. Meanwhile, in the pigs supplemented with 250 mg/kg copper sulfate, ADG was increased significantly from the 40th to the 60th day of the experiment (P < 0.01), and the levels of GH, INS, IGF-1, and IGFBP-3 in serum were elevated significantly from the 20th to the 40th day of the experiment (P < 0.01). It is concluded that effects of copper supplemented in the diet on the growth of pigs were related to the increasing levels of GH, INS, IGF-1, and IGFBP-3 in serum which were induced by copper. High dietary copper increase the concentrations of growth-related hormones in serum, resulting in improving the growth performance of weanling pigs.

Catalytic therapy of cancer by ascorbic acid involves redox cycling of exogenous/endogenous copper ions and generation of reactive oxygen species.

PubMed

Hadi, S M; Ullah, M F; Shamim, U; Bhatt, S H; Azmi, A S

2010-01-01

Catalytic therapy is a cancer treatment modality based on the generation of reactive oxygen species (ROS) through administration of ascorbate/medicinal herbal extracts and copper. It is known that antioxidants such as ascorbate also exhibit prooxidant activity in the presence of transition metals such as copper. Based on our work and that in the literature, in this review we propose a mechanism for the cytotoxic action of ascorbate against cancer cells. It involves redox cycling of exogenous/endogenous copper ions and the consequent generation of ROS leading to oxidative DNA breakage. Using human peripheral lymphocytes and the Comet assay, we have shown that ascorbic acid is able to cause oxidative breakage in cellular DNA. Such DNA degradation is inhibited by neocuproine (a Cu(I) sequestering agent) and scavengers of ROS indicating that the cellular DNA breakage involves the generation of Cu(I) and formation of ROS. Similar results are also obtained with plant polyphenol antioxidants that are important constituents of medicinal herbal extracts. Copper is an essential component of chromatin and can take part in redox reactions. It is well established that tissue, cellular and serum copper levels are considerably elevated in various malignancies. Therefore, cancer cells may be more subject to electron transfer between copper ions and ascorbate/plant polyphenols to generate ROS. In this review we cite evidence to indicate that in catalytic therapy cytotoxic action against cancer cells involves redox cycling of exogenous/endogenous copper ions. Copyright © 2010 S. Karger AG, Basel.

Different roles of glutathione in copper and zinc chelation in Brassica napus roots.

PubMed

Zlobin, Ilya E; Kartashov, Alexander V; Shpakovski, George V

2017-09-01

We investigated the specific features of copper and zinc excess action on the roots of canola (Brassica napus L.) plants. Copper rapidly accumulated in canola root cells and reached saturation during several hours of treatment, whereas the root zinc content increased relatively slowly. Excessive copper and zinc entry inside the cell resulted in significant cell damage, as evidenced by alterations in plasmalemma permeability and decreases in cellular enzymatic activity. Zinc excess specifically damaged root hair cells, which correlated with a pronounced elevation of their labile zinc level. In vitro, we showed that reduced glutathione (GSH) readily reacted with copper ions to form complexes with blocked sulfhydryl groups. In contrast, zinc ions were ineffective as glutathione blockers, and glutathione molecules did not lose their specific chemical activity in the presence of Zn 2+ ions. The effect of copper and zinc excess on the glutathione pool in canola root cells was analysed by a combination of biochemical determination of total and oxidized glutathione contents and fluorescent staining of free reduced glutathione with monochlorobimane dye. Excess copper led to dose-dependent diminution of free reduced glutathione contents in the root cells, which could not be explained by the loss of total cellular glutathione or its oxidation. In contrast, we observed little effect of much higher intracellular zinc concentrations on the free reduced glutathione content. We concluded that GSH plays an important role in copper excess, but not zinc excess chelation, in canola root cells. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Subneurotoxic copper(II)-induced NF-κB-dependent microglial activation is associated with mitochondrial ROS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hu, Zhuqin; Yu, Fengxiang; Gong, Ping

2014-04-15

Microglia-mediated neuroinflammation and the associated neuronal damage play critical roles in the pathogenesis of neurodegenerative disorders. Evidence shows an elevated concentration of extracellular copper(II) in the brains of these disorders, which may contribute to neuronal death through direct neurotoxicity. Here we explored whether extracellular copper(II) triggers microglial activation. Primary rat microglia and murine microglial cell line BV-2 cells were cultured and treated with copper(II). The content of tumor necrosis factor-α (TNF-α) and nitric oxide in the medium was determined. Extracellular hydrogen peroxide was quantified by a fluorometric assay with Amplex Red. Mitochondrial superoxide was measured by MitoSOX oxidation. At subneurotoxicmore » concentrations, copper(II) treatment induced a dose- and time-dependent release of TNF-α and nitric oxide from microglial cells, and caused an indirect, microglia-mediated neurotoxicity that was blocked by inhibition of TNF-α and nitric oxide production. Copper(II)-initiated microglial activation was accompanied with reduced IkB-α expression as well as phosphorylation and translocation of nuclear factor-κB (NF-κB) p65 and was blocked by NF-κB inhibitors (BAY11-7082 and SC-514). Moreover, copper(II) treatment evoked a rapid release of hydrogen peroxide from microglial cells, an effect that was not affected by NADPH oxidase inhibitors. N-acetyl-cysteine, a scavenger of reactive oxygen species (ROS), abrogated copper(II)-elicited microglial release of TNF-α and nitric oxide and subsequent neurotoxicity. Importantly, mitochondrial production of superoxide, paralleled to extracellular release of hydrogen peroxide, was induced after copper(II) stimulation. Our findings suggest that extracellular copper(II) at subneurotoxic concentrations could trigger NF-κB-dependent microglial activation and subsequent neurotoxicity. NADPH oxidase-independent, mitochondria-derived ROS may be involved in this activation. - Highlights: • Subneurotoxic copper(II) triggers NF-κB-dependent microglial activation. • This activation leads to hippocampal neuronal death. • This activation may involve mitochondria-derived reactive oxygen species.« less

Does Dietary Copper Supplementation enhance or diminish PCB126 Toxicity in Rodent Liver?

PubMed Central

Lai, Ian K.; Klaren, William D.; Li, Miao; Wels, Brian; Simmons, Donald L.; Olivier, Alicia K.; Haschek, Wanda M.; Wang, Kai; Ludewig, Gabriele; Robertson, Larry W.

2013-01-01

Copper is essential for the function of the mitochondrial electron transport chain and several antioxidant proteins. However, in its free form copper can participate in Fenton-like reactions that produce reactive hydroxyl radicals. Aryl-hydrocarbon receptor (AhR) agonists, including the most potent polychlorinated biphenyl (PCB) congener, 3,3',4,4',5-pentachlorobiphenyl (PCB126), increase copper levels in rodent livers. This is accompanied by biochemical and toxic changes. To assess the involvement of copper in PCB toxicity, male Sprague Dawley rats were fed an AIN-93G diet with differing dietary copper levels: low (2 ppm), adequate (6 ppm), and high (10 ppm). After three weeks, rats from each group were given a single ip injection of corn oil (control), 1, or 5 μmol/kg body weight PCB126. Two weeks following injections, biochemical and morphological markers of hepatic toxicity, trace metal status, and hepatic gene expression of metalloproteins were evaluated. Increasing dietary copper was associated with elevated tissue levels of copper and ceruloplasmin. In the livers of PCB126-treated rats the hallmark signs of AhR activation were present, including increased cytochrome P-450 and lipid levels, and decreased glutathione. In addition a doubling of hepatic copper levels was seen and overall metals homeostasis was disturbed, resulting in decreased hepatic selenium, manganese, zinc and iron. Expression of key metalloproteins was either decreased (cytochrome c oxidase), unchanged (ceruloplasmin and CuZnSOD) or increased (tyrosinase, metallothionein 1 and 2) with exposure to PCB126. Increases in metallothionein may contribute/reflect the increased copper seen. Alterations in dietary copper did not amplify or abrogate the hepatic toxicity of PCB126. PCB126 toxicity, i.e. oxidative stress and steatosis, is clearly associated with disturbed metals homeostasis. Understanding the mechanisms of this disturbance may provide tools to prevent liver toxicity by other AhR agonists. PMID:23527585

Does Peak Urine Flow Rate Predict the Development of Incident Lower Urinary Tract Symptoms in Men with Mild to No Current Symptoms? Results from REDUCE.

PubMed

Simon, Ross M; Howard, Lauren E; Moreira, Daniel M; Roehrborn, Claus; Vidal, Adriana; Castro-Santamaria, Ramiro; Freedland, Stephen J

2017-09-01

We determined whether decreased peak urine flow is associated with future incident lower urinary tract symptoms in men with mild to no lower urinary tract symptoms. Our population consisted of 3,140 men from the REDUCE (Reduction by Dutasteride of Prostate Cancer Events) trial with mild to no lower urinary tract symptoms, defined as I-PSS (International Prostate Symptom Score) less than 8. REDUCE was a randomized trial of dutasteride vs placebo for prostate cancer prevention in men with elevated prostate specific antigen and negative biopsy. I-PSS measures were obtained every 6 months throughout the 4-year study. The association between peak urine flow rate and progression to incident lower urinary tract symptoms, defined as the first of medical treatment, surgery or sustained and clinically significant lower urinary tract symptoms, was tested by multivariable Cox models, adjusting for various baseline characteristics and treatment arm. On multivariable analysis as a continuous variable, decreased peak urine flow rate was significantly associated with an increased risk of incident lower urinary tract symptoms (p = 0.002). Results were similar in the dutasteride and placebo arms. On univariable analysis when peak flow was categorized as 15 or greater, 10 to 14.9 and less than 10 ml per second, flow rates of 10 to 14.9 and less than 10 ml per second were associated with a significantly increased risk of incident lower urinary tract symptoms (HR 1.39, p = 0.011 and 1.67, p <0.001, respectively). Results were similar on multivariable analysis, although in the 10 to 14.9 ml per second group findings were no longer statistically significant (HR 1.26, p = 0.071). In men with mild to no lower urinary tract symptoms a decreased peak urine flow rate is independently associated with incident lower urinary tract symptoms. If confirmed, these men should be followed closer for incident lower urinary tract symptoms. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Comparison of Urinary Biomarkers of Exposure in Humans Using Electronic Cigarettes, Combustible Cigarettes, and Smokeless Tobacco.

PubMed

Lorkiewicz, Pawel; Riggs, Daniel W; Keith, Rachel J; Conklin, Daniel J; Xie, Zhengzhi; Sutaria, Saurin; Lynch, Blake; Srivastava, Sanjay; Bhatnagar, Aruni

2018-06-02

Cigarette smoking is associated with an increase in cardiovascular disease risk, attributable in part to reactive volatile organic chemicals (VOCs). However, little is known about the extent of VOC exposure due to the use of other tobacco products. We recruited 48 healthy, tobacco users in four groups: cigarette, smokeless tobacco, occasional users of first generation e-cigarette and e-cigarette menthol and 12 healthy nontobacco users. After abstaining for 48 h, tobacco users used an assigned product. Urine was collected at baseline followed by five collections over a 3-h period to measure urinary metabolites of VOCs, nicotine, and tobacco alkaloids. Urinary levels of nicotine were ≃2-fold lower in occasional e-cigarette and smokeless tobacco users than in the cigarette smokers; cotinine and 3-hydroxycotinine levels were similar in all groups. Compared with nontobacco users, e-cigarette users had higher levels of urinary metabolites of xylene, cyanide, styrene, ethylbenzene, and benzene at baseline and elevated urinary levels of metabolites of xylene, N,N-dimethylformamide, and acrylonitrile after e-cigarette use. Metabolites of acrolein, crotonaldehyde, and 1,3-butadiene were significantly higher in smokers than in users of other products or nontobacco users. VOC metabolite levels in smokeless tobacco group were comparable to those found in nonusers with the exception of xylene metabolite-2-methylhippuric acid (2MHA), which was almost three fold higher than in nontobacco users. Smoking results in exposure to a range of VOCs at concentrations higher than those observed with other products, and first generation e-cigarette use is associated with elevated levels of N,N-dimethylformamide and xylene metabolites. This study shows that occasional users of first generation e-cigarettes have lower levels of nicotine exposure than the users of combustible cigarettes. Compared with combustible cigarettes, e-cigarettes, and smokeless tobacco products deliver lower levels of most VOCs, with the exception of xylene, N,N-dimethylformamide, and acrylonitrile, whose metabolite levels were higher in the urine of e-cigarette users than nontobacco users. Absence of anatabine in the urine of e-cigarette users suggests that measuring urinary levels of this alkaloid may be useful in distinguishing between users of e-cigarettes and combustible cigarettes. However, these results have to be validated in a larger cohortcomprised of users of e-cigarettes of multiple brands.

Antiurolithiatic Effect of Sirupeelai Samoola Kudineer: A Polyherbal Siddha Decoction on Ethylene Glycol-induced Renal Calculus in Experimental Rats

PubMed Central

Vasanthi, A. Hannah Rachel; Muthulakshmi, V.; Gayathri, V.; Manikandan, R.; Ananthi, S.; Kuruvilla, Sarah

2017-01-01

Background: Sirupeelai Samoola Kudineer (SK), a polyherbal decoction containing four medicinal plants has been used in Siddha system of medicine, practiced in Southern parts of India for the management of urolithiasis. Objective: The present study is carried out to scientifically validate the traditional claim and to study the mechanism of action of the drug. Materials and Methods: In the present study, anti-urolithiatic effect of SK was evaluated in Sprague-Dawley rats using ethylene glycol through drinking water and intraperitoneal injection of sodium oxalate. Renal damage was confirmed by the increased production of thiobarbituric acid reactive substance (TBARS). Results: Co-treatment with SK to urolithiatic rats for 21 days significantly prevented the elevation of renal and urinary stone biomarkers in plasma and renal tissue thereby preventing renal damage and the formation of renal calculi. Administration of SK at all doses and cystone restored the antioxidant (glutathione) levels by preventing the elevation of TBARS in the kidney tissue, which was further confirmed by histological sections. Conclusions: SK treatment promotes diuresis which leads to flushing of the renal stones and maintains the alkaline environment in the urinary system which probably mediates the antilithiatic activity. SK provides structural and functional protection to the kidneys by enhancing its physiological function against stone formation and validates its clinical use. SUMMARY SK exhibited antilithiatic and diuretic potential in ethylene glycol and sodium oxalate induced urolithiasis in ratsElevated urinary stone markers (Calcium, oxalate, uric acid, magnesium and phosphates) in plasma and renal tubular enzymes (LDH, GGT, ALP, AST ALT) in urolithiatic rats were reversed by SK treatmentSK administration significantly reduced the level of renal stress markers like Urea, Creatinine, LPO and elevated SOD, GPx, GSH levels aiding in nephroprotectionSK also provides structural and functional protection against ethylene glycol- induced renal calculus in rats as evidenced by histopathological studies. Abbreviations used: SK: Sirupeelai Samoola Kudineer; TBARS: ThioBarbituric Acid Reactive Substances; SOD: SuperOxide Dismutase; GPx: Gluthathione peroxidase; GSH- Glutathione; LPO: Lipid peroxidation as measured as TBARS; AST: Aspartate AminoTransferase; ALT: Alanine Amino transferase; GGT: Gamma Glutamyl Transferase; LDH: Lactate Dehydrogenase. PMID:28808392

Evidence for widespread, severe brain copper deficiency in Alzheimer's dementia.

PubMed

Xu, Jingshu; Church, Stephanie J; Patassini, Stefano; Begley, Paul; Waldvogel, Henry J; Curtis, Maurice A; Faull, Richard L M; Unwin, Richard D; Cooper, Garth J S

2017-08-16

Datasets comprising simultaneous measurements of many essential metals in Alzheimer's disease (AD) brain are sparse, and available studies are not entirely in agreement. To further elucidate this matter, we employed inductively-coupled-plasma mass spectrometry to measure post-mortem levels of 8 essential metals and selenium, in 7 brain regions from 9 cases with AD (neuropathological severity Braak IV-VI), and 13 controls who had normal ante-mortem mental function and no evidence of brain disease. Of the regions studied, three undergo severe neuronal damage in AD (hippocampus, entorhinal cortex and middle-temporal gyrus); three are less-severely affected (sensory cortex, motor cortex and cingulate gyrus); and one (cerebellum) is relatively spared. Metal concentrations in the controls differed among brain regions, and AD-associated perturbations in most metals occurred in only a few: regions more severely affected by neurodegeneration generally showed alterations in more metals, and cerebellum displayed a distinctive pattern. By contrast, copper levels were substantively decreased in all AD-brain regions, to 52.8-70.2% of corresponding control values, consistent with pan-cerebral copper deficiency. This copper deficiency could be pathogenic in AD, since levels are lowered to values approximating those in Menkes' disease, an X-linked recessive disorder where brain-copper deficiency is the accepted cause of severe brain damage. Our study reinforces others reporting deficient brain copper in AD, and indicates that interventions aimed at safely and effectively elevating brain copper could provide a new experimental-therapeutic approach.

Catalysts for coal liquefaction processes

DOEpatents

Garg, Diwakar

1986-01-01

Improved catalysts for catalytic solvent refining or hydroliquefaction of non-anthracitic coal at elevated temperatures under hydrogen pressure in a hydrogen donor solvent comprise a combination of zinc or copper, or a compound thereof, and a Group VI or non-ferrous Group VIII metal, or a compound thereof.

Catalysts for coal liquefaction processes

DOEpatents

Garg, D.

1986-10-14

Improved catalysts for catalytic solvent refining or hydroliquefaction of non-anthracitic coal at elevated temperatures under hydrogen pressure in a hydrogen donor solvent comprise a combination of zinc or copper, or a compound thereof, and a Group VI or non-ferrous Group VIII metal, or a compound thereof.

Detection and Evaluation of Elevated Lead Release from Service Lines: A Field Study

EPA Science Inventory

Comparative stagnation sampling conducted in 32 homes in Chicago, Illinois with lead service (LSLs) demonstrated that the existing regulatory sampling protocol under the U. S. Lead and Copper Rule (LCR) systematically underestimated lead corrosion. Lead levels were highest within...

Copper and zinc runoff from land application of composted poultry litter

USDA-ARS?s Scientific Manuscript database

Regions with long-term animal manure applications based upon nitrogen (N) requirements have concerns for elevated nutrient levels. Most attention has focused on phosphorus (P), but concern of heavy metal accumulation has received attention due to perceived environmental concerns. Some nutrient-dense...

Thrust chamber material technology program

NASA Technical Reports Server (NTRS)

Andrus, J. S.; Bordeau, R. G.

1989-01-01

This report covers work performed at Pratt & Whitney on development of copper-based materials for long-life, reusable, regeneratively cooled rocket engine thrust chambers. The program approached the goal of enhanced cyclic life through the application of rapid solidification to alloy development, to introduce fine dispersions to strengthen and stabilize the alloys at elevated temperatures. After screening of alloy systems, copper-based alloys containing Cr, Co, Hf, Ag, Ti, and Zr were processed by rapid-solidification atomization in bulk quantities. Those bulk alloys showing the most promise were characterized by tensile testing, thermal conductivity testing, and elevated-temperature, low-cycle fatigue (LFC) testing. Characterization indicated that Cu- 1.1 percent Hf exhibited the greatest potential as an improved-life thrust chamber material, exhibiting LCF life about four times that of NASA-Z. Other alloys (Cu- 0.6 percent Zr, and Cu- 0.6 percent Zr- 1.0 percent Cr) exhibited promise for use in this application, but needed more development work to balance properties.

[Renal handling of beta2 microglobulin. Its significance in carriers of adolescent nephronophthisis (NPH3)].

PubMed

Fernández, Carmen; Araque, Carolina; Méndez, Jorge; Angulo, Luisa; Fargier, Bernardo

2007-06-01

The adolescent nephronophthisis (NPH3) is a variant of the nephronophthisis. In Venezuela, one to three patients have been registered each year, all of them belonging to the same family tree. The objective of this study was to evaluate the function of the proximal convoluted tubule in NPHP3 carriers; using the beta2M as biological marker. Eight carriers, 7 heterozygotes and 1 homozygote, with normal renal function were compared with a 10 healthy subjects (control group). Serum beta2 microglobulin (beta2M), urinary beta2M, the quotient urinary beta2M/urinary creatinine and the beta2M fractional excretion were determinated. The filtered beta2M and the percentage of reabsortion were calculated. We observed an increase in the plasmatic concentration of beta2M but not related with a decrease of the glomerular filtration. The urinary beta2M, the beta2M/urinary creatinine relation and the fractional excretion of beta2M were normal. The filtered load of beta2M was elevated without increase in the excretion or percentage of reabsortion. We conclude that in our group of NPH3 carriers, functional changes in the proximal convoluted tubule, when measured by urinary excretion of beta2M, were absent. This finding suggests the existence of other mechanism of uptake or degradation of the substance in the proximal convoluted tubule, which have yet to be elucidated.

Preoperative urinary tract obstruction in scoliosis patients.

PubMed

Suzuki, Shigeru; Kotani, Toshiaki; Mori, Kazuetsu; Kawamura, Ken; Ohtake, Akira

2017-01-01

While the association between scoliosis and cardiac and respiratory function impairments has been well characterized in clinical practice and research, the potential effect of scoliosis on urinary tract structure and renal function has received little attention. Therefore, the purpose of this study was to evaluate the preoperative clinical characteristics of urinary tract structure and renal function in pediatric patients with idiopathic scoliosis, using a combination of blood tests, urinalysis, and imaging. Preoperative measures of urinary tract structure and renal function were obtained for 16 patients, 13-17 years old, scheduled for corrective surgery for idiopathic scoliosis. Preoperative assessment included blood test and urinalysis, combined with structural imaging on ultrasound (US), magnetic resonance imaging (MRI), magnetic resonance urography (MRU), and radioisotope tracing (RI), using technetium-99 m mercaptoacetyltriglycine ( 99m Tc-MAG3). Differences in blood and urine tests between patients with and without urinary tract obstruction (UTO) were evaluated for significance using Mann-Whitney U test. For all 16 patients, blood tests and MRU were within normal limits. Dilatation of the renal pelvis was identified on US in eight patients (50.0%). UTO was identified on RI in six patients (37.5%). UTO was associated with elevated β2-microglobulin concentration. Urinary β2-microglobulin concentration >0.7 μg/mg Cr differentiated patients with UTO from those without UTO, with a sensitivity of 100% and specificity of 70%. β2-Microglobulin concentration may be a useful marker to screen for asymptomatic UTO in patients with idiopathic scoliosis. © 2016 Japan Pediatric Society.

Photogrammetry for environmental monitoring: the use of drones and hydrological models for detection of soil contaminated by copper.

PubMed

Capolupo, Alessandra; Pindozzi, Stefania; Okello, Collins; Fiorentino, Nunzio; Boccia, Lorenzo

2015-05-01

Campania Region of Southern Italy has a complex environmental situation, due to geogenic and anthropogenic soil pollution. Some of the pollutants such as copper are mobilized in the organic matter. It has been shown that wetlands provide physical as well as biogeochemical barriers against pollutants. Therefore, the objective of this study was to introduce and test an innovative approach able to predict copper accumulation points at plot scales, using a combination of aerial photos, taken by drones, micro-rill network modelling and wetland prediction indices usually used at catchment scales. Data were collected from an area measuring 4500 m(2) in Trentola Ducenta locality of Caserta Province of southern Italy. The photos processing with a fifth generation software for photogrammetry resulted in a high resolution Digital Elevation Model (DEM), used to study micro-rill processes. The DEM was also used to test the ability of Topographic Index (TI) and the Clima-Topographic Index (CTI) to predict copper sedimentation points at plot scale (0.1-10 ha) by comparing the map of the predicted and the actual copper distribution in the field. The DEM obtained with a resolution of 30 mm showed a high potential for the study of micro-rill processes and TI and CTI indices were able to predict zones of copper accumulation at a plot scale. Copyright © 2015 Elsevier B.V. All rights reserved.

The effectiveness of surface liming in ameliorating the phytotoxic effects of soil contaminated by copper acid leach pad solution in an arid ecosystem

NASA Astrophysics Data System (ADS)

Golos, Peter

2016-04-01

Revegetation of sites following soil contamination can be challenging especially in identifying the most effective method for ameliorating phytotoxic effects in arid ecosystems. This study at a copper mine in the Great Sandy Desert of Western Australia investigated vegetation restoration of a site contaminated by acid (H2SO4) leach pad solution. Elevated soil copper at low soil pH is phytotoxic to plant roots inhibiting root elongation. In arid ecosystems where rapid root growth is crucial for seedling survival post germination physical or chemical barriers to root growth need to be identified and ameliorated. Initial attempt at rehabilitation of contaminated site with hydrated lime (CaOH2) at 2 tonnes/ha followed by ripping to 30 cm depth then seeding was ineffective as successful seedling emergence was followed by over 90% seedling mortality which was 10-fold greater than seedling mortality in an uncontaminated reference site. High mortality was attributed to seedling roots being impededed as soil water was more than 3-fold greater at 5 to 40 cm depth in contaminated site than reference site. In response to high seedling mortality after emergence test pits were dug to 1 m deep to collect soil samples at 10 cm intervals for phytotoxicity testing and to measure soil pH-CaCl2, copper (DPTA ion extraction), electrical conductivity and gravimetric water content in three replicate pits at three replicate sites. Also, soil impedance was measured down the soil profile at 5 cm intervals at six replicate points/pit. For phytotoxicity testing soil samples were placed into three replicate plastic pots/sample and seeded with 10 seeds of Avena sativa and watered daily. Seedlings were harvested after at least two weeks after seedling emergence and rooting depth in pots measured. There was no difference in seedling emergence and survival of seedlings between contaminated and uncontaminated soil samples however mean seedling root growth was significantly lower in soil samples collected at >10 cm depth than the control. Mean soil pH at 0-10 cm was higher (>7.2) at all sites treated with lime compared to uncontaminated soil (5.5). At depths greater than 10 cm soil pH was <4.6. Soil copper was >16 mg/kg in all contaminated soil samples compared to 0.5 mg/kg in control. High seedling mortality in contaminated site is attributed to low soil pH and elevated soil copper levels which inhibited plant root growth and hence access to soil water. While surface liming of soil increased soil pH ameliorating the effect of elevated soil copper, this was only effective in the top 10 cm due to low solubility of hydrated lime. To improve seedling survival lime will need to be incorporated into the contaminated soil profile to allow plants to access soil water at depth. This study highlights the importance of the need to assess the phytotoxic effects of soil contamination and the effectiveness of amelioration treatments and with proper reference to its ecological context. To improve the success of vegetation restoration of sites contaminated with acidic copper solution, lime needs to be incorporated into the contaminated soil profile to allow plant roots to access soil water at depth. This study highlights the importance of the need to assess the phytotoxic effects of soil contamination and the effectiveness of amelioration treatments and with proper reference to its ecological context.

Metabolic profiling in Maturity-onset diabetes of the young (MODY) and young onset type 2 diabetes fails to detect robust urinary biomarkers.

PubMed

Gloyn, Anna L; Faber, Johan H; Malmodin, Daniel; Thanabalasingham, Gaya; Lam, Francis; Ueland, Per Magne; McCarthy, Mark I; Owen, Katharine R; Baunsgaard, Dorrit

2012-01-01

It is important to identify patients with Maturity-onset diabetes of the young (MODY) as a molecular diagnosis determines both treatment and prognosis. Genetic testing is currently expensive and many patients are therefore not assessed and are misclassified as having either type 1 or type 2 diabetes. Biomarkers could facilitate the prioritisation of patients for genetic testing. We hypothesised that patients with different underlying genetic aetiologies for their diabetes could have distinct metabolic profiles which may uncover novel biomarkers. The aim of this study was to perform metabolic profiling in urine from patients with MODY due to mutations in the genes encoding glucokinase (GCK) or hepatocyte nuclear factor 1 alpha (HNF1A), type 2 diabetes (T2D) and normoglycaemic control subjects. Urinary metabolic profiling by Nuclear Magnetic Resonance (NMR) and ultra performance liquid chromatography hyphenated to Q-TOF mass spectrometry (UPLC-MS) was performed in a Discovery set of subjects with HNF1A-MODY (n = 14), GCK-MODY (n = 17), T2D (n = 14) and normoglycaemic controls (n = 34). Data were used to build a valid partial least squares discriminate analysis (PLS-DA) model where HNF1A-MODY subjects could be separated from the other diabetes subtypes. No single metabolite contributed significantly to the separation of the patient groups. However, betaine, valine, glycine and glucose were elevated in the urine of HNF1A-MODY subjects compared to the other subgroups. Direct measurements of urinary amino acids and betaine in an extended dataset did not support differences between patients groups. Elevated urinary glucose in HNF1A-MODY is consistent with the previously reported low renal threshold for glucose in this genetic subtype. In conclusion, we report the first metabolic profiling study in monogenic diabetes and show that, despite the distinct biochemical pathways affected, there are unlikely to be robust urinary biomarkers which distinguish monogenic subtypes from T2D. Our results have implications for studies investigating metabolic profiles in complex traits including T2D.

Associations between polycyclic aromatic hydrocarbon (PAH) exposure and oxidative stress in people living near e-waste recycling facilities in China.

PubMed

Lu, Shao-You; Li, Yan-Xi; Zhang, Jian-Qing; Zhang, Tao; Liu, Gui-Hua; Huang, Ming-Zhi; Li, Xiao; Ruan, Ju-Jun; Kannan, Kurunthachalam; Qiu, Rong-Liang

2016-09-01

Emission of polycyclic aromatic hydrocarbons (PAHs) from e-waste recycling activities in China is known. However, little is known on the association between PAH exposure and oxidative damage to DNA and lipid content in people living near e-waste dismantling sites. In this study, ten hydroxylated polycyclic aromatic hydrocarbons (OH-PAHs) and two biomarkers [8-hydroxy-2'-deoxyguanosine (8-OHdG) and malondialdehyde (MDA)] of oxidative stress were investigated in urine samples collected from people living in and around e-waste dismantling facilities, and in reference population from rural and urban areas in China. The urinary levels of ∑10OH-PAHs determined in e-waste recycling area (GM: 25.4μg/g Cre) were significantly higher (p<0.05) than those found in both rural (11.7μg/g Cre) and urban (10.9μg/g Cre) reference areas. The occupationally exposed e-waste workers (36.6μg/g Cre) showed significantly higher (p<0.01) urinary Σ10OH-PAHs concentrations than non-occupationally exposed people (23.2μg/g Cre) living in the e-waste recycling site. The differences in urinary Σ10OH-PAHs levels between smokers (23.4μg/g Cre) and non-smokers (24.7μg/g Cre) were not significant (p>0.05) in e-waste dismantling sites, while these differences were significant (p<0.05) in rural and urban reference areas; this indicated that smoking is not associated with elevated levels of PAH exposure in e-waste dismantling site. Furthermore, we found that urinary concentrations of Σ10OH-PAHs and individual OH-PAHs were significantly associated with elevated 8-OHdG, in samples collected from e-waste dismantling site; the levels of urinary 1-hydroxypyrene (1-PYR) (r=0.284, p<0.01) was significantly positively associated with MDA. Our results indicate that the exposure to PAHs at the e-waste dismantling site may have an effect on oxidative damage to DNA among selected participants, but this needs to be validated in large studies. Copyright © 2016 Elsevier Ltd. All rights reserved.

The Bone Building Blues: Self-hardening copper-doped calcium phosphate cement and its in vitro assessment against mammalian cells and bacteria.

PubMed

Rau, Julietta V; Wu, Victoria M; Graziani, Valerio; Fadeeva, Inna V; Fomin, Alexander S; Fosca, Marco; Uskoković, Vuk

2017-10-01

A blue calcium phosphate cement with optimal self-hardening properties was synthesized by doping whitlockite (β-TCP) with copper ions. The mechanism and the kinetics of the cement solidification process were studied using energy dispersive X-ray diffraction and it was found out that hardening was accompanied by the phase transition from TCP to brushite. Reduced lattice parameters in all crystallographic directions resulting from the rather low (1:180) substitution rate of copper for calcium was consistent with the higher ionic radius of the latter. The lower cationic hydration resulting from the partial Ca→Cu substitution facilitated the release of constitutive hydroxyls and lowered the energy of formation of TCP from the apatite precursor at elevated temperatures. Addition of copper thus effectively inhibited the formation of apatite as the secondary phase. The copper-doped cement exhibited an antibacterial effect, though exclusively against Gram-negative bacteria, including E. coli, P. aeruginosa and S. enteritidis. This antibacterial effect was due to copper ions, as demonstrated by an almost negligible antibacterial effect of the pure, copper-free cement. Also, the antibacterial activity of the copper-containing cement was significantly higher than that of its precursor powder. Since there was no significant difference between the kinetics of the release of copper from the precursor TCP powder and from the final, brushite phase of the hardened cement, this has suggested that the antibacterial effect was not solely due to copper ions, but due to the synergy between cationic copper and a particular phase and aggregation state of calcium phosphate. Though inhibitory to bacteria, the copper-doped cement increased the viability of human glial E297 cells, murine osteoblastic K7M2 cells and especially human primary lung fibroblasts. That this effect was also due to copper ions was evidenced by the null effect on viability increase exhibited by the copper-free cements. The difference in the mechanism of protection of dehydratases in prokaryotes and eukaryotes was used as a rationale for explaining the hereby evidenced selectivity in biological response. It presents the basis for the consideration of copper as a dually effective ion when synergized with calcium phosphates: toxic for bacteria and beneficial for the healthy cells. Copyright © 2017 Elsevier B.V. All rights reserved.

Inexpensive Method of Testing Ambient and Thermally Elevated Resistive and Piezoresistive Thin-Film Pressure Gauges

NASA Astrophysics Data System (ADS)

Armstrong, Christopher; Rae, Philip; Heatwole, Eric; Tasker, Douglas; Los Alamos National Labortatory Team

2017-06-01

Manganin is an alloy that changes resistance when subjected to high-pressure, but is insensitive to temperature changes. Resistance curves as a function of pressure for these gauges have been established. Another commonly used piezoresistive pressure sensor are thin-film carbon gauges, which are more pressure sensitive than manganin gauges. Carbon gauge response in high temperature is not well quantified. The current research is focused on verifying these established resistance curves as well as verifying this specific experimental configuration. In this research the carbon gauges' resistance change is measured for thermally elevated gauges. In this setup a 20 mm caliber gun drove planar copper projectiles at the gauge, which was embedded in a copper anvil. The Hugoniot relationship allows for a comparison between observed and theoretical pressure over a pressure range 5 to 20 GPa for manganin gauges and 1 to 5 GPa for carbon gauges. The comparison between the data obtained in this research and that of others shows that the pressure-resistance curve of manganin does to not vary between lots of manganin. Additionally, the data shows that this setup is a relatively inexpensive quick means of testing gauge response to high-pressure shocks and is suitable for elevated temperature.

Elevated corrosion rates and hydrogen sulfide in homes with 'Chinese Drywall'.

PubMed

Allen, Joseph G; MacIntosh, David L; Saltzman, Lori E; Baker, Brian J; Matheson, Joanna M; Recht, Joel R; Minegishi, Taeko; Fragala, Matt A; Myatt, Theodore A; Spengler, John D; Stewart, James H; McCarthy, John F

2012-06-01

In December 2008, the U.S. Consumer Product Safety Commission (CPSC) began receiving reports about odors, corrosion, and health concerns related to drywall originating from China. In response, a detailed environmental health and engineering evaluation was conducted of 41 complaint and 10 non-complaint homes in the Southeast U.S. Each home investigation included characterization of: 1) drywall composition; 2) indoor and outdoor air quality; 3) temperature, moisture, and building ventilation; and 4) copper and silver corrosion rates. Complaint homes had significantly higher hydrogen sulfide concentrations (mean 0.82 vs.

Urinary ß2-microglobulin in very preterm neonates with chorioamnionitis.

PubMed

Nishimaki, Shigeru; Shima, Yoshio; Sato, Miho; An, Hiromi; Fujita, Shujiro; Iwasaki, Shiho; Horiguchi, Haruko; Seki, Kazuo; Yokota, Shumpei

2011-12-01

It is important to identify premature infants with prenatal inflammation as it contributes to short- and long-term complications. Our object was to study how prenatal inflammation affects the urinary β(2)-microglobulin (β(2)-MG) level. Preterm neonates were divided based on the presence of chorioamnionitis (CAM) into the CAM (n = 100) and non-CAM groups (n = 117). These were further subdivided into five groups each: 30 preterm neonates of 23-26; 42 neonates of 27-28; 54 neonates of 29-30; 51 neonates of 31-32; and 40 neonates of 33-34 weeks' gestation. The urinary β(2)-MG level within 48 h of birth was significantly higher in the CAM group than in the non-CAM group among the neonates of 23-26 weeks' gestation (18.3 ± 6.9 vs 10.0 ± 5.6 × 10(4) μg/gCr, p = 0.0018) and the neonates of 27-28 weeks' gestation (16.2 ± 10.8 vs 8.8 ± 3.3 × 10(4) μg/gCr, p = 0.0101). However, there was no difference in urinary β(2)-MG level between the CAM and the non-CAM group among the neonates ≥ 29 weeks 'gestation. Moreover, the elevated urinary β(2)-MG level in the neonates ≤ 28 weeks ' gestation with CAM had disappeared by 1 week after birth. The reasons for the increase in urinary β(2)-MG level within 48 h of birth in very preterm neonates (≤ 28 weeks' gestation) with CAM are believed to be not only prematurity, but also prenatal inflammation. It is suggested that the urinary β(2)-MG level during the early postnatal period can identify prenatal inflammation.

Excretion of Avenanthramides, Phenolic Acids and their Major Metabolites Following Intake of Oat Bran

PubMed Central

Schär, Manuel Y.; Corona, Giulia; Soycan, Gulten; Dine, Clemence; Kristek, Angelika; Alsharif, Sarah N. S.; Behrends, Volker; Lovegrove, Alison; Shewry, Peter R.

2017-01-01

Scope Wholegrain has been associated with reduced chronic disease mortality, with oat intake particularly notable for lowering blood cholesterol and glycemia. To better understand the complex nutrient profile of oats, we studied urinary excretion of phenolic acids and avenanthramides after ingestion of oat bran in humans. Methods and results After a 2‐d (poly)phenol‐low diet, seven healthy men provided urine 12 h before and 48 h after consuming 60 g oat bran (7.8 μmol avenanthramides, 139.2 μmol phenolic acids) or a phenolic‐low (traces of phenolics) control in a crossover design. Analysis by ultra‐high performance liquid chromatography (UPLC)–MS/MS showed that oat bran intake resulted in an elevation in urinary excretion of 30 phenolics relative to the control, suggesting that they are oat bran‐derived. Mean excretion levels were elevated between 0–2 and 4–8 h, following oat bran intake, and amounted to a total of 33.7 ± 7.3 μmol total excretion (mean recovery: 22.9 ± 5.0%), relative to control. The predominant metabolites included: vanillic acid, 4‐ and 3‐hydroxyhippuric acids, and sulfate‐conjugates of benzoic and ferulic acids, which accounted collectively for two thirds of total excretion. Conclusion Oat bran phenolics follow a relatively rapid urinary excretion, with 30 metabolites excreted within 8 h of intake. These levels of excretion suggest that bound phenolics are, in part, rapidly released by the microbiota. PMID:29024323

[Leiomyoma of the small bowel with hypercalcaemia: presence of a substance with parathormone activity (author's transl)].

PubMed

Rathaus, M; Bernheim, J L; Griffel, B; Bernheim, J; Taragan, R; Gutman, A

1979-10-22

A leiomyoma of the small bowel produced laboratory features of hyperparathyroidism which disappeared promptly after tumour resection. Hypercalcaemia, hypophosphatemia, hyperchloremia, elevated chloride/phosphorus ratio, increased urinary cyclic AMP, and blood levels of immunoreactive parathormone were present. Electron microscopy showed dense round granules in the tumour cells.

Association of urinary citrate with acid-base status, bone resorption, and calcium excretion in older men and women

USDA-ARS?s Scientific Manuscript database

Context: Elevated urine net acid excretion (NAE), indicative of subclinical metabolic acidosis, has been associated with higher bone turnover. While NAE is the gold-standard clinical measure of acid-base status, it is impractical to measure in most clinical/research settings. Urine citrate, which is...

Urinary isoflavone concentrations are inversely associated with lower cardiometabolic risk markers in pregnant U.S. women

USDA-ARS?s Scientific Manuscript database

Some evidence suggests that phytoestrogens such as soy-derived isoflavones may have beneficial effects on cardiovascular health and glycemic control. These data are mainly limited to postmenopausal women or individuals at elevated cardiometabolic risk. There is a lack of data for pregnant women who ...

Investigation of Health Effects According to the Exposure of Low Concentration Arsenic Contaminated Ground Water

PubMed Central

Hong, Young-seoub; Ye, Byeong-jin; Kim, Yu-mi; Kim, Byoung-gwon; Kang, Gyeong-hui; Kim, Jeong-jin; Song, Ki-hoon; Kim, Young-hun

2017-01-01

Recent epidemiological studies have reported adverse health effects, including skin cancer, due to low concentrations of arsenic via drinking water. We conducted a study to assess whether low arsenic contaminated ground water affected health of the residents who consumed it. For precise biomonitoring results, the inorganic (trivalent arsenite (As III) and pentavalent arsenate (As V)) and organic forms (monomethylarsonate (MMA) and dimethylarsinate (DMA)) of arsenic were separately quantified by combining high-performance liquid chromatography and inductively coupled plasma mass spectroscopy from urine samples. In conclusion, urinary As III, As V, MMA, and hair arsenic concentrations were significantly higher in residents who consumed arsenic contaminated ground water than control participants who consumed tap water. But, most health screening results did not show a statistically significant difference between exposed and control subjects. We presume that the elevated arsenic concentrations may not be sufficient to cause detectable health effects. Consumption of arsenic contaminated ground water could result in elevated urinary organic and inorganic arsenic concentrations. We recommend immediate discontinuation of ground water supply in this area for the safety of the residents. PMID:29186890

GRCop-84: A High Temperature Copper-based Alloy For High Heat Flux Applications

NASA Technical Reports Server (NTRS)

Ellis, David L.

2005-01-01

While designed for rocket engine main combustion chamber liners, GRCop-84 (Cu-8 at.% Cr-4 at.% Nb) offers potential for high heat flux applications in industrial applications requiring a temperature capability up to approximately 700 C (1292 F). GRCop-84 is a copper-based alloy with excellent elevated temperature strength, good creep resistance, long LCF lives and enhanced oxidation resistance. It also has a lower thermal expansion than copper and many other low alloy copper-based alloys. GRCop-84 can be manufactured into a variety of shapes such as tubing, bar, plate and sheet using standard production techniques and requires no special production techniques. GRCop-84 forms well, so conventional fabrication methods including stamping and bending can be used. GRCop-84 has demonstrated an ability to be friction stir welded, brazed, inertia welded, diffusion bonded and electron beam welded for joining to itself and other materials. Potential applications include plastic injection molds, resistance welding electrodes and holders, permanent metal casting molds, vacuum plasma spray nozzles and high temperature heat exchanger applications.

Is ciprofloxacin safe in patients with solitary kidney and upper urinary tract infection?

PubMed

Gluhovschi, Gheorghe; Gadalean, Florica; Gluhovschi, Cristina; Velciov, Silvia; Petrica, Ligia; Bob, Flaviu; Bozdog, Gheorghe; Kaycsa, Adriana

2016-12-01

The solitary kidney (SK) undergoes adaptive phenomena of hyperfunction and hyperfiltration. These secondary adaptive phenomena can make it more vulnerable to potentially nephrotoxic therapies. Adverse reactions of the kidneys to ciprofloxacin are rare, but sometimes severe. Therefore, our study sought to assess the reactions to ciprofloxacin of patients with solitary kidney (SK) and urinary tract infection (UTI) by means of urinary biomarkers. We studied 19 patients with SK and urinary tract infection (UTI) who had been administered a 7-day treatment with intravenous ciprofloxacin. Urinary N-acetyl-beta-d-glucosaminidase, alpha 1-microglobulin, and estimated glomerular filtration rate (eGFR) of these patients were measured at the initiation and at the end of treatment. In 47.37% patients NAG diminished under ciprofloxacin treatment. This observation has the significance of favourable evolution of the tubulointerstitial lesions caused by UTI and lack of nephrotoxic effects; 52.63% cases presented an increase of urinary NAG, a fact that suggests a nephrotoxic effect of ciprofloxacin. The evolution of urinary alpha 1-microglobulin was similar to that one of urinary NAG. Only one of three cases with chronic kidney disease (CKD) stage 5 presented acute kidney injury, associated with increase in the tubular markers. In spite of the high variability of the urinary biomarkers, UTI evolved favourably in these cases; eGFR increased in 16 out of 19 patients, a fact which is indicative of a good outcome of renal function, even in patients with elevated levels of the tubular damage biomarkers. This observation supports the hypothesis that eGFR may be dissociated from the biomarkers which assess tubular injury. In SK patients the occurrence of AKI is not frequent, although the urinary biomarkers rise in some patients treated with ciprofloxacin. This is related not only to the nephrotoxic effect of the drug, but probably to the association of other factors (allergy, individual susceptibility). In SK patients, renal tubular biomarkers, especially NAG, allow monitoring of tubular injury and impose caution in prescribing ciprofloxacin treatment, mainly to patients at risk. Ciprofloxacin is relatively safe regarding its nephrotoxicity, while caution is required in vulnerable patients. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

E057: Renal Stone Risk Assessment During Space Flight: Assessment and Countermeasure Validation

NASA Technical Reports Server (NTRS)

Whitson, Peggy A.; Pietrzyk, Robert A.; Jones, Jeffrey A.; Sams, Clarence F.

2001-01-01

Exposure to the microgravity environment results in many metabolic and physiological changes to humans. Body fluid volumes, electrolyte levels, and bone and muscle undergo changes as the human body adapts to the weightless environment. Changes in the urinary biochemistry occur as early as flight day 3-4 in the short duration Shuttle crewmembers. Significant decreases were observed both in fluid intake and urinary output. Other significant changes were observed in the urinary pH, calcium, potassium and uric acid levels. During Shuttle missions, the risk of calcium oxalate stone formation increased early in the flight, continued at elevated levels throughout the flight and remained in the increased risk range on landing day. The calcium phosphate risk was significantly increased early in-flight and remained significantly elevated throughout the remainder of the mission. Results from the long duration Shuttle-Mir missions followed a similar trend. Most long duration crewmembers demonstrated increased urinary calcium levels despite lower dietary calcium intake. Fluid intake and urine volumes were significantly lower during the flight than during the preflight. The calcium oxalate risk was increased relative to the preflight levels during the early in-flight period and continued in the elevated risk range for the remainder of the space flight and through two weeks postflight. Calcium phosphate risk for these long duration crewmembers increased during flight and remained in the increased risk range throughout the flight and following landing. The complexity, expense and visibility of the human space program require that every effort be made to protect the health of the crewmembers and ensure the success of the mission. Results from our early investigations clearly indicate that exposure to the microgravity environment of space significantly increases the risk of renal stone formation. The early studies have indicated specific avenues for development of countermeasures for the increased renal stone risk observed during and following space flight. Increased hydration and implementation of pharmacological countermeasures are being tested for their efficacy in mitigating the in-flight risk of renal stones. Maintaining the health and well-being of crewmembers during space flight requires a means of minimizing potential detrimental health effects of microgravity. The formation of a renal stone during flight obviously has severe consequences for the affected crewmember as well as the success of the mission.

EFFECTS OF BACTERIAL ENDOTOXINS ON METABOLISM

PubMed Central

Berry, L. Joe; Smythe, Dorothy S.

1961-01-01

In vitro secretion of glycocorticoids by adrenal glands pooled from several control mice was compared with that of glands removed from animals following injections of either ACTH or endotoxin. Both substances prevent glycocorticoid synthesis stimulated in vitro with ACTH. Cholesterol content of adrenal glands under these conditions was nearly depleted, indicating maximal response to ACTH or endotoxin prior to their removal for the in vitro tests. In an effort to account physiologically for the manner in which endotoxin suppresses or prevents the rise in urinary nitrogen excreted in response to ACTH, blood non-protein nitrogen levels (NPN) were determined. The following experimental conditions resulted in increased urinary nitrogen excretion but did not alter blood NPN: cortisone given alone or at the same time as endotoxin; ACTH alone; dichloroisoproterenol (DCI) given concurrently with endotoxin; and lactalbumin digest injected intraperitoneally. Increases (2- to 3-fold) in blood NPN were observed when endotoxin was given alone, concurrently with ACTH, or 3 hours prior to cortisone, DCI, or lactalbumin digest. Urinary nitrogen excretion showed no change under these conditions. The elevation in blood NPN in endotoxin-poisoned mice was found to be due almost entirely to urea nitrogen and not to amino acid nitrogen or to other nitrogenous wastes. Blood clearance of mulin, phenol red excretion, and urea elimination were each determined in control and in endotoxin-poisoned mice. The latter mice showed impaired renal function. Treatment with diuretics (diuril and aminophylline) failed to alter oliguria or elevated blood NPN. Hydergine treatment was also without effect. Total carcass NPN and urinary nitrogen excretion data were combined to give a picture of total protein catabolized by mice under different experimental conditions. Cortisone injected at the same time as endotoxin or 3 hours later resulted in the same increase in total NPN. However, in the former case all the extra nitrogen appeared in the urine while in the latter it remained in the carcass. ACTH given alone or concurrently with endotoxin produced large increases in total NPN but less in poisoned mice. This suggests that endotoxin suppresses adrenal response to ACTH. Urea injected into normal mice was recovered quantitatively in urine while in endotoxin-poisoned mice it was partitioned between carcass and urine. Elevation of carcass NPN by means of urea injections failed to alter the lethality of an LD70 dose of endotoxin. PMID:19867206

Copper aluminate spinel in the stabilization and detoxification of simulated copper-laden sludge.

PubMed

Tang, Yuanyuan; Shih, Kaimin; Chan, King

2010-06-01

This study aims to evaluate the feasibility of stabilizing copper-laden sludge by the application of alumina-based ceramic products. The processing temperature, material leaching behaviour, and the effect of detoxification were investigated in detail. CuO was used to simulate the copper-laden sludge and X-ray Diffraction was performed to monitor the incorporation of copper into the copper aluminate spinel (CuAl(2)O(4)) phase in ceramic products. It was found that the development of CuAl(2)O(4) increased with elevating temperatures up to and including 1000 degrees C in the 3h short-sintering scheme. When the sintering temperature went above 1000 degrees C, the CuAl(2)O(4) phase began to decompose due to the high temperature transformation to CuAlO(2). The leachability and leaching behaviour of CuO and CuAl(2)O(4) were compared by usage of a prolonged leaching test modified from US EPA's toxicity characteristic leaching procedure. The leaching results show that CuAl(2)O(4) is superior to CuO for the purpose of copper immobilization over longer leaching periods. Furthermore, the detoxification effect of CuAl(2)O(4) was tested through bacterial adhesion with Escherichia coli K12, and the comparison of bacterial adhesion on CuO and CuAl(2)O(4) surfaces shows the beneficial detoxification effect in connection with the formation of the CuAl(2)O(4) spinel. This study demonstrates the feasibility of transforming copper-laden sludge into the spinel phase by using readily available and inexpensive ceramic materials, and achieving a successful reduction of metal mobility and toxicity.

Cancer cell-selective killing polymer/copper combination.

PubMed

He, Huacheng; Altomare, Diego; Ozer, Ufuk; Xu, Hanwen; Creek, Kim; Chen, Hexin; Xu, Peisheng

2016-01-01

Chemotherapy has been adopted for cancer treatment for decades. However, its efficacy and safety are frequently compromised by the multidrug-resistance of cancer cells and the poor cancer cell selectivity of anticancer drugs. Hereby, we report a combination of a pyridine-2-thiol containing polymer and copper which can effectively kill a wide spectrum of cancer cells, including drug resistant cancer cells, while sparing normal cells. The polymer nanoparticle enters cells via an exofacial thiol facilitated route, and releases active pyridine-2-thiol with the help of intracellularly elevated glutathione (GSH). Due to their high GSH level, cancer cells are more vulnerable to the polymer/copper combination. In addition, RNA microarray analysis revealed that the treatment can reverse cancer cells' upregulated oncogenes (CIRBP and STMN1) and downregulated tumor suppressor genes (CDKN1C and GADD45B) to further enhance the selectivity for cancer cells.

Copper mediated polymerization without external deoxygenation or oxygen scavengers.

PubMed

Liarou, Evelina; Whitfield, Richard; Anastasaki, Athina; Engelis, Nikolaos G; Jones, Glen R; Velonia, Kelly; Haddleton, David

2018-05-14

Overcoming the challenge of rigorous deoxygenation in copper mediated controlled radical polymerization processes (e.g. ATRP), we report a simple Cu(0)-RDRP system in the absence of external additives (e.g. reducing agents, enzymes etc.). By simply adjusting the headspace of the reaction vessel, a wide range of monomers, namely acrylates, methacrylates, acrylamides and styrene, can be polymerized in a controlled manner yielding polymers with low dispersities, near-quantitative conversions and high end group fidelity. Significantly, this approach is scalable (~ 125 g), tolerant to elevated temperatures, compatible with both organic and aqueous media and does not rely on external stimuli which may limit the monomer pool. The robustness and versatility of this methodology is further demonstrated by the applicability to a number of other copper mediated techniques including conventional ATRP and light-mediated approaches. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Wilson’s disease: A review of what we have learned

PubMed Central

Rodriguez-Castro, Kryssia Isabel; Hevia-Urrutia, Francisco Javier; Sturniolo, Giacomo Carlo

2015-01-01

Wilson’s disease (WD), which results from the defective ATP7B protein product, is characterized by impaired copper metabolism and its clinical consequences vary from an asymptomatic state to fulminant hepatic failure, chronic liver disease with or without cirrhosis, neurological, and psychiatric manifestations. A high grade of suspicion is warranted to not miss cases of WD, especially less florid cases with only mild elevation of transaminases, or isolated neuropsychiatric involvement. Screening in first and second relatives of index cases is mandatory, and treatment must commence upon establishment of diagnosis. Treatment strategies include chelators such as D-penicillamine and trientine, while zinc salts act as inductors of methallothioneins, which favor a negative copper balance and a reduction of free plasmatic copper. As an orphan disease, research is lacking in this field, especially regarding therapeutic strategies which are associated with better patient compliance and which could eventually also reverse established injury. PMID:26692151

Metabolism during hypodynamia

NASA Technical Reports Server (NTRS)

Federov, I. V.

1980-01-01

Physical immobilization, inaction due to space travel, a sedentary occupation, or bed confinement due to a chronic illness elicit similar alternations in the metabolism of man and animals (rat, rabbit, dog, mouse). After a preliminary period of weight loss, there is eventually weight gain due to increased lipid storage. Protein catabolism is enhanced and anabolism depressed, with elevated urinary excretion of amino acids, creatine, and ammonia. Glycogen stores are depleted and glyconeogenesis is accelerated. Polyuria develops with subsequent redistribution of body fluids in which the blood volume of the systemic circulation is decreased and that of pulmonary circulation increased. This results in depressed production of vasopressin by the posterior pituitary which further enhances urinary water and salt loss.

Disappearance of multiple hyperechoic liver nodules in sporadic porphyria cutanea tarda after treatment with ledipasvir/sofosbuvir for hepatitis C.

PubMed

Takata, Kazuhide; Shakado, Satoshi; Sakamoto, Keiko; Fukuda, Hiromi; Yamauchi, Ryo; Fukuda, Sho; Kunimoto, Hideo; Umeda, Kaoru; Tanaka, Takashi; Yokoyama, Keiji; Morihara, Daisuke; Takeyama, Yasuaki; Irie, Makoto; Sakisaka, Shotaro

2017-10-01

Ultrasonography in a 60-year-old man with chronic hepatitis C (CHC) demonstrated multiple hyperechoic nodules. Radiological investigations did not reveal any signs of malignancy. However, magnetic resonance chemical shift imaging showed multiple focal fatty changes in the liver. Urinary levels of uroporphyrin and coproporphyrin were elevated, and we made a diagnosis of porphyria cutanea tarda. Direct-acting antivirals, ledipasvir/sofosbuvir, were initiated for CHC, which led to sustained viral response, resolution of the liver nodules, and normalization of urinary porphyrin. Hepatitis C virus infection can cause porphyria cutanea tarda with multiple hyperechoic liver nodules, which might be cured by direct-acting antivirals.

Elevation of urinary adipsin in preeclampsia: correlation with urine protein concentration and the potential use for a rapid diagnostic test.

PubMed

Wang, Tao; Zhou, Rong; Gao, Linbo; Wang, Yanyun; Song, Changping; Gong, Yunhui; Jia, Jin; Xiong, Wei; Dai, Li; Zhang, Lin; Hu, Huaizhong

2014-10-01

Early diagnosis and treatment of preeclampsia are essential for prevention of seizure development and fetus maturation. Although various methods have been developed for predicting or monitoring the onset of preeclampsia, a simple assay that can be used as a home or point of care test remains unavailable. We attempted to find a urinary protein that could be used as a biomarker for developing such a test. Urinary samples were collected from 124 preeclampsia and 135 healthy pregnant women for screening using a protein array technology and quantification by ELISA. A urinary protein, adipsin, was found significantly increased, and the adipsin creatinine ratio was closely correlated with the urinary 24-hour protein in patients with preeclampsia. When combined with the increased diastolic blood pressure (≥90 mm Hg), the sensitivity was 90.3% and the specificity reached 100.0% for preeclampsia diagnosis. We then developed a laminar flow immunoassay for rapid diagnosis, and the sensitivity and specificity were 89.04% and 100%, respectively, when combined with increased diastolic blood pressure. Because of the easiness of sample collection, assay conduction, and result interpretation, this urine test can be potentially used as a home test for monitoring preeclampsia onset for high-risk pregnant women and as a rapid test for a preliminary diagnosis for emergency patients at hospitals. © 2014 American Heart Association, Inc.

Copper Indium Gallium Diselenide Solar Cells | Photovoltaic Research | NREL

Science.gov Websites

primary research areas that are currently our focus are the following: Understanding effects of material . Such metastable effects frustrate the repeatable and accurate measurement of a module's performance in by perturbing the voltage bias or temperature. Another associated challenge is that elevated

Distribution of copper, iron, and zinc in biological samples (scalp hair, serum, blood, and urine) of Pakistani viral hepatitis (A-E) patients and controls.

PubMed

Kolachi, Nida Fatima; Kazi, Tasneem Gul; Afridi, Hassan Imran; Kazi, Naveed; Kandhro, Ghulam Abbas; Shah, Abdul Qadir; Baig, Jameel Ahmed; Wadhwa, Sham Kumar; Khan, Sumaira; Shah, Faheem; Jamali, Mohammad Khan; Arain, Mohammad Balal

2011-10-01

The aim of the present study was to compare the level of copper (Cu), iron (Fe) and zinc (Zn) in biological samples (serum, blood, urine, and scalp hair) of patients suffering from different viral hepatitis (A, B, C, D, and E; n = 521) of both gender age ranged 31-45 years. For comparative study, 255 age-matched control subjects, of both genders residing in the same city were selected as referents. The elements in the biological samples were analyzed by flame atomic absorption spectrophotometry, prior to microwave-assisted acid digestion. The validity and accuracy of the methodology was checked by using certified reference materials (CRMs) and with those values obtained by conventional wet acid digestion method on same CRMs. The results of this study showed that the mean values of Cu and Fe were higher in blood, sera, and scalp hair samples of hepatitis patients, while Zn level was found to be lower than age-matched control subjects. The urinary levels of these elements were found to be higher in the hepatitis patients than in the age-matched healthy controls (p < 0.05). These results are consistent with literature-reported data, confirming that the deficiency of zinc and hepatic iron and copper overload can directly cause lipid peroxidation and eventually hepatic damage.

The modulation of corticosteroid metabolism by hydrocortisone therapy in patients with hypopituitarism increases tissue glucocorticoid exposure.

PubMed

Sherlock, Mark; Behan, Lucy Ann; Hannon, Mark J; Alonso, Aurora Aragon; Thompson, Christopher J; Murray, Robert D; Crabtree, Nicola; Hughes, Beverly A; Arlt, Wiebke; Agha, Amar; Toogood, Andrew A; Stewart, Paul M

2015-11-01

Patients with hypopituitarism have increased morbidity and mortality. There is ongoing debate about the optimum glucocorticoid (GC) replacement therapy. To assess the effect of GC replacement in hypopituitarism on corticosteroid metabolism and its impact on body composition. We assessed the urinary corticosteroid metabolite profile (using gas chromatography/mass spectrometry) and body composition (clinical parameters and full body DXA) of 53 patients (19 female, median age 46 years) with hypopituitarism (33 ACTH-deficient/20 ACTH-replete) (study A). The corticosteroid metabolite profile of ten patients with ACTH deficiency was then assessed prospectively in a cross over study using three hydrocortisone (HC) dosing regimens (20/10 mg, 10/10 mg and 10/5 mg) (study B) each for 6 weeks. 11 beta-hydroxysteroid dehydrogenase 1 (11β-HSD1) activity was assessed by urinary THF+5α-THF/THE. Endocrine Centres within University Teaching Hospitals in the UK and Ireland. Urinary corticosteroid metabolite profile and body composition assessment. In study A, when patients were divided into three groups - patients not receiving HC and patients receiving HC≤20 mg/day or HC>20 mg/day - patients in the group receiving the highest daily dose of HC had significantly higher waist-to-hip ratio (WHR) than the ACTH replete group. They also had significantly elevated THF+5α-THF/THE (P=0.0002) and total cortisol metabolites (P=0.015). In study B, patients on the highest HC dose had significantly elevated total cortisol metabolites and all patients on HC had elevated THF+5α-THF/THE ratios when compared to controls. In ACTH-deficient patients daily HC doses of >20 mg/day have increased WHR, THF+5α-THF/THE ratios and total cortisol metabolites. GC metabolism and induction of 11β-HSD1 may play a pivitol role in the development of the metabolically adverse hypopituitary phenotype. © 2015 European Society of Endocrinology.

Trace elements and organic compounds in streambed sediment and aquatic biota from the Sacramento River Basin, California, October and November 1995

USGS Publications Warehouse

MacCoy, Dorene E.; Domagalski, Joseph L.

1999-01-01

Elevated levels of trace elements and hydrophobic organic compounds were detected in streambed sediments and aquatic biota [Asiatic clam (Corbicula fluminea) or bottom-feeding fish] of the Sacramento River Basin, California, during October and November 1995. Trace elements detected included cadmium, copper, mercury, lead, and zinc. Elevated levels of cadmium, copper, and zinc in the upper Sacramento River are attributed to a mining land use, and elevated levels of zinc and lead in an urban stream, and possibly in the lower Sacramento River, are attributed to urban runoff processes. Elevated levels of mercury in streambed sediment are attributed to either past mercury mining or to the use of mercury in past gold mining operations. Mercury mining was an important land use within the Coast Ranges in the past and gold mining was an important land use of the Sierra Nevada in the past. Mercury was the only trace element found in elevated levels in the tissue of aquatic biota, and those levels also could be attributed to either mining or urban runoff. Hydrophobic organic compounds also were detected in streambed sediments and aquatic biota. The most frequently detected compounds were DDT and its breakdown products, dieldrin, oxychlordane, and toxaphene. Differences were found in the types of compounds detected at agricultural sites and the urban site. Although both types of sites had measurable concentrations of DDT or its breakdown products, the urban site also had measurable concentrations of pesticides used for household pest control. Few semivolatile compounds were detected in the streambed sediments of any site. The semivolatile compound p-cresol, a coal-tar derivative associated with road maintenance, was found in the highest concentration.

Blood Pressure Associated with Arsenic Methylation and Arsenic Metabolism Caused by Chronic Exposure to Arsenic in Tube Well Water.

PubMed

Wei, Bing Gan; Ye, Bi Xiong; Yu, Jiang Ping; Yang, Lin Sheng; Li, Hai Rong; Xia, Ya Juan; Wu, Ke Gong

2017-05-01

The effects of arsenic exposure from drinking water, arsenic metabolism, and arsenic methylation on blood pressure (BP) were observed in this study. The BP and arsenic species of 560 participants were determined. Logistic regression analysis was applied to estimate the odds ratios of BP associated with arsenic metabolites and arsenic methylation capability. BP was positively associated with cumulative arsenic exposure (CAE). Subjects with abnormal diastolic blood pressure (DBP), systolic blood pressure (SBP), and pulse pressure (PP) usually had higher urinary iAs (inorganic arsenic), MMA (monomethylated arsenic), DMA (dimethylated arsenic), and TAs (total arsenic) than subjects with normal DBP, SBP, and PP. The iAs%, MMA%, and DMA% differed slightly between subjects with abnormal BP and those with normal BP. The PMI and SMI were slightly higher in subjects with abnormal PP than in those with normal PP. Our findings suggest that higher CAE may elevate BP. Males may have a higher risk of abnormal DBP, whereas females have a higher risk of abnormal SBP and PP. Higher urinary iAs may increase the risk of abnormal BP. Lower PMI may elevate the BP. However, higher SMI may increase the DBP and SBP, and lower SMI may elevate the PP. Copyright © 2017 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

Elevated urinary leukotriene E4 levels are associated with hospitalization for pain in children with sickle cell disease.

PubMed

Jennings, Jeanine E; Ramkumar, Thiruvamoor; Mao, Jingnan; Boyd, Jessica; Castro, Mario; Field, Joshua J; Strunk, Robert C; DeBaun, Michael R

2008-08-01

Cysteinyl leukotrienes (CsyLTs) are inflammatory mediators produced by white blood cells. Leukotriene LTE(4) is the stable metabolite of CsyLTs, which can be measured in urine. We tested two hypotheses among children with sickle cell disease (SCD): (1) baseline urinary LTE(4) levels are elevated in children with SCD when compared with controls; and (2) baseline LTE(4) levels are associated with an increased incidence rate of hospitalization for SCD-related pain. Baseline LTE(4) levels were measured in children with SCD (cases) and children without SCD matched for age and ethnicity (controls). Medical records of cases were reviewed to assess the frequency of hospitalization for pain within 3 years of study entry. LTE(4) levels were obtained in 71 cases and 22 controls. LTE(4) levels were higher in cases compared with controls (median LTE(4): 100 vs. 57 pg/mg creatinine, P < 0.001). After adjustment for age and asthma diagnosis, a greater incidence rate of hospitalization for pain was observed among children with SCD in the highest LTE(4) tertile when compared with the lowest (114 vs. 52 episodes per 100 patient-years, P = 0.038). LTE(4) levels are elevated in children with SCD when compared with controls. LTE(4) levels are associated with an increased rate of hospitalizations for pain. Copyright 2008 Wiley-Liss, Inc.

Thermal regime, predation danger and the early marine exit of sockeye salmon Oncorhynchus nerka.

PubMed

Katinic, P J; Patterson, D A; Ydenberg, R C

2015-01-01

Marine exit timing of sockeye salmon Oncorhynchus nerka populations on the Haida Gwaii Archipelago, British Columbia, Canada, is described, with specific focus on Copper Creek. Marine exit in Copper Creek occurs > 130 days prior to spawning, one of the longest adult freshwater residence periods recorded for any O. nerka population. Copper Creek presents an easy upstream migration, with mild water temperatures (7 to 14°  C), short distance (13·1 km) and low elevation gain (41 m) to the lake where fish hold prior to spawning. An energetic model estimates that <1% of the initial energy reserve is required for upstream migration, compared with 62% for lake holding and 38% for reproductive development. Historical records suggest that it is unlikely that water temperature in any of the O.nerka streams in Haida Gwaii has ever exceeded the presumed temperature threshold (19° C) for early marine exit. Although it is not impossible that the thermal tolerance of Copper Creek O.nerka is very low, the data presented here appear inconsistent with thermal avoidance as an explanation for the early marine exit timing in Copper Creek and in three other populations on the archipelago with early marine exit. © 2014 The Fisheries Society of the British Isles.

Bioaccumulation of metals in plants, arthropods, and mice at a seasonal wetland.

PubMed

Torres, K C; Johnson, M L

2001-11-01

Concentrations of arsenic, cadmium, copper, lead, and nickel were measured in soils, house mice (Mus musculus), and the main food items of this omnivorous mouse to examine the occurrence of these metals in selected components of a seasonal wetland. Soil concentrations of copper, lead, and (in some areas) nickel were elevated, but extractable soil concentrations indicated low bioavailability of metals. Levels of most metals in mice and composited arthropods were consistent with reference site concentrations from other studies. However, copper was found to be particularly mobile within the local ecosystem and accumulated in house mouse carcasses and composited arthropods at substantial levels. Metal residues in Scirpus robustus (alkali bulrush) roots exceeded those in seeds, consistent with patterns of bioaccumulation commonly observed in plants. Uptake and bioaccumulation factors for S. robustus seeds and roots, arthropods, and mouse carcasses and livers are reported. Concentrations of lead and nickel in S. robustus roots exhibited significant linear relationships with levels in soils. Copper levels in S. robustus seeds varied significantly with those in house mouse livers, suggesting that trophic transfer of copper from this food source to mice occurred. However, other spatial patterns of bioaccumulation in S. robustus and house mice relative to soil/seed concentrations were absent. Metal levels in house mice bore no relation to body weight or estimated age.

A norovirus outbreak triggered by copper intoxication on a coach trip from the Netherlands to Germany, April 2010.

PubMed

Hoefnagel, J; van de Weerdt, Dh; Schaefer, O; Koene, R

2012-03-01

We report an unusual outbreak of norovirus infection on a coach trip. Overall, 30 of 40 people (including drivers and crew) developed nausea, vomiting and/or diarrhoea, 11 of them on the first day of the trip. The incidence epidemic curve showed a first peak on Day 1 and a second on Day 4. Nine passengers were hospitalised with gastrointestinal symptoms. Norovirus was found in stool samples from two patients, but the infection could not explain the first peak in the epidemic curve only a few hours after departure. Interviews with the passengers and an inspection of the coach and its water supply implicated the water used for coffee and tea as the potential source. Microbiological investigations of the water were negative, but chemical analysis showed a toxic concentration of copper. Blood copper levels as well as renal and liver function were determined in 28 of the 32 passengers who had been exposed to the water. One passenger who did not have gastrointestinal symptoms had an elevated copper level of 25.9 μmol/L, without loss of liver or renal function. It is likely that the spread of norovirus was enhanced because of vomiting of one of the passengers due to copper intoxication.

Urinary metal and polycyclic aromatic hydrocarbon biomarkers in boilermakers exposed to metal fume and residual oil fly ash.

PubMed

Mukherjee, Sutapa; Rodrigues, Ema; Aeschliman, David B; Houk, R S; Palmer, Lyle J; Woodin, Mark A; Weker, Robert; Christiani, David C

2005-06-01

Boilermakers are occupationally exposed to known carcinogens. The association of urinary 1-hydroxy-pyrene (1-OHP), a biomarker of polycyclic aromatic hydrocarbon (PAH) exposure, with biomarkers of metal exposure (vanadium, chromium, manganese, nickel, copper, and lead) in boilermakers exposed to metal fume from welding and dust particulates from residual oil fly ash (ROFA) was examined. A repeated measures cohort study was conducted during the overhaul of an oil-fired boiler. Twice-daily urine samples were obtained for 5 days and analyzed for cotinine, 1-OHP, and metals. Generalized estimating equations (GEE) were used to model the multivariate relationship of 1-OHP to the explanatory variables. Metal and 1-OHP levels were determined for 165 urine samples from 20 boilermakers and these levels increased during the workweek. However, the 1-OHP level was not significantly associated with any individual metal level at any time point. This suggests that boilermakers were occupationally exposed to PAH and metals, but 1-OHP as a PAH biomarker was unable to serve as a surrogate marker of metal exposure for the metals measured in this study.

Glutamic acid leaching of synthetic covellite - A model system combining experimental data and geochemical modeling.

PubMed

Barthen, R; Karimzadeh, L; Gründig, M; Grenzer, J; Lippold, H; Franke, K; Lippmann-Pipke, J

2018-04-01

For Kupferschiefer mining established pyrometallurgical and acidic bioleaching methods face numerous problems. This is due to the finely grained and dispersed distribution of the copper minerals, the complex mineralogy, comparably low copper content, and the possibly high carbonate and organic content in this ore. Leaching at neutral pH seemed worth a try: At neutral pH the abundant carbonates do not need to be dissolved and therewith would not consume excessive amounts of provided acids. Certainly, copper solubility at neutral pH is reduced compared to an acidic environment; however, if copper complexing ligands would be supplied abundantly, copper contents in the mobile phase could easily reach the required economic level. We set up a model system to study the effect of parameters such as pH, microorganisms, microbial metabolites, and organic ligands on covellite leaching to get a better understanding of the processes in copper leaching at pH ≥ 6. With this model system we could show that glutamic acid and the microbial siderophore desferrioxamine B promote covellite dissolution. Both experimental and modeling data showed that pH is an important parameter in covellite dissolution. An increase of pH from 6 to 9 could elevate copper extraction in the presence of glutamic acid by a factor of five. These results have implications for both development of a biotechnological process regarding metal extraction from Kupferschiefer, and for the interaction of bacterial metabolites with the lithosphere and potential mobilization of heavy metals in alkaline environments. Copyright © 2018 Elsevier Ltd. All rights reserved.

[Metabolism of serotonin in autism in children].

PubMed

Bursztejn, C; Ferrari, P; Dreux, C; Braconnier, A; Lancrenon, S

1988-01-01

In this controlled study of 22 autistic children and 22 normal controls matched for age and sex, the frequency of hyperserotonemia in infantile autism was confirmed. Platelet serotonin was elevated in patients. Comparative to controls, serotonin was also high in urine of autistic patients, while, on the contrary there was no difference for the urinary excretion of 5-HIAA. No difference was observed either for serotonin uptake and efflux or for MAO activity, in isolated platelets. The elevation of plasma free tryptophan - significant only with the Kolmogorov Smirnov test - suggests that 5-HT biosynthesis might be enhanced. In the group of patient reported in this study, disorders of serotonin metabolism are associated with disturbances of platelet catecholamines, and also with elevated immunoglobulins and enhanced cellular immunity reactions.

Urinary Levels of N-Nitroso Compounds in Relation to Risk of Gastric Cancer: Findings from the Shanghai Cohort Study

PubMed Central

Xu, Ling; Qu, Yong-Hua; Chu, Xin-Di; Wang, Renwei; Nelson, Heather H.; Gao, Yu-Tang; Yuan, Jian-Min

2015-01-01

Background N-Nitroso compounds are thought to play a significant role in the development of gastric cancer. Epidemiological data, however, are sparse in examining the associations between biomarkers of exposure to N-nitroso compounds and the risk of gastric cancer. Methods A nested case-control study within a prospective cohort of 18,244 middle-aged and older men in Shanghai, China, was conducted to examine the association between urinary level of N-nitroso compounds and risk of gastric cancer. Information on demographics, usual dietary intake, and use of alcohol and tobacco was collected through in-person interviews at enrollment. Urinary levels of nitrate, nitrite, N-nitroso-2-methylthiazolidine-4-carboxylic acid (NMTCA), N-nitrosoproline (NPRO), N-nitrososarcosine (NSAR), N-nitrosothiazolidine-4-carboxylic acid (NTCA), as well as serum H. pylori antibodies were quantified in 191 gastric cancer cases and 569 individually matched controls. Logistic regression method was used to assess the association between urinary levels of N-nitroso compounds and risk of gastric cancer. Results Compared with controls, gastric cancer patients had overall comparable levels of urinary nitrate, nitrite, and N-nitroso compounds. Among individuals seronegative for antibodies to H. pylori, elevated levels of urinary nitrate were associated with increased risk of gastric cancer. The multivariate-adjusted odds ratios for the second and third tertiles of nitrate were 3.27 (95% confidence interval = 0.76–14.04) and 4.82 (95% confidence interval = 1.05–22.17), respectively, compared with the lowest tertile (P for trend = 0.042). There was no statistically significant association between urinary levels of nitrite or N-nitroso compounds and risk of gastric cancer. Urinary NMTCA level was significantly associated with consumption of alcohol and preserved meat and fish food items. Conclusion The present study demonstrates that exposure to nitrate, a precursor of N-nitroso compounds, may increase the risk of gastric cancer among individuals without a history of H. pylori infection. PMID:25658333

Urinary levels of N-nitroso compounds in relation to risk of gastric cancer: findings from the shanghai cohort study.

PubMed

Xu, Ling; Qu, Yong-Hua; Chu, Xin-Di; Wang, Renwei; Nelson, Heather H; Gao, Yu-Tang; Yuan, Jian-Min

2015-01-01

N-Nitroso compounds are thought to play a significant role in the development of gastric cancer. Epidemiological data, however, are sparse in examining the associations between biomarkers of exposure to N-nitroso compounds and the risk of gastric cancer. A nested case-control study within a prospective cohort of 18,244 middle-aged and older men in Shanghai, China, was conducted to examine the association between urinary level of N-nitroso compounds and risk of gastric cancer. Information on demographics, usual dietary intake, and use of alcohol and tobacco was collected through in-person interviews at enrollment. Urinary levels of nitrate, nitrite, N-nitroso-2-methylthiazolidine-4-carboxylic acid (NMTCA), N-nitrosoproline (NPRO), N-nitrososarcosine (NSAR), N-nitrosothiazolidine-4-carboxylic acid (NTCA), as well as serum H. pylori antibodies were quantified in 191 gastric cancer cases and 569 individually matched controls. Logistic regression method was used to assess the association between urinary levels of N-nitroso compounds and risk of gastric cancer. Compared with controls, gastric cancer patients had overall comparable levels of urinary nitrate, nitrite, and N-nitroso compounds. Among individuals seronegative for antibodies to H. pylori, elevated levels of urinary nitrate were associated with increased risk of gastric cancer. The multivariate-adjusted odds ratios for the second and third tertiles of nitrate were 3.27 (95% confidence interval = 0.76-14.04) and 4.82 (95% confidence interval = 1.05-22.17), respectively, compared with the lowest tertile (P for trend = 0.042). There was no statistically significant association between urinary levels of nitrite or N-nitroso compounds and risk of gastric cancer. Urinary NMTCA level was significantly associated with consumption of alcohol and preserved meat and fish food items. The present study demonstrates that exposure to nitrate, a precursor of N-nitroso compounds, may increase the risk of gastric cancer among individuals without a history of H. pylori infection.

Elevated plasma and urinary concentrations of green tea catechins associated with improved plasma lipid profile in healthy Japanese women.

PubMed

Takechi, Ryusuke; Alfonso, Helman; Hiramatsu, Naoko; Ishisaka, Akari; Tanaka, Akira; Tan, La'Belle; Lee, Andy H

2016-03-01

This study investigated green tea catechins in plasma and urine and chronic disease biomarkers. We hypothesized that plasma and urinary concentration of green tea catechins are associated with cardiovascular disease and diabetes biomarkers. First void urine and fasting plasma samples were collected from 57 generally healthy females aged 38 to 73 years (mean, 52 ± 8 years) recruited in Himeji, Japan. The concentrations of plasma and urinary green tea catechins were determined by liquid chromatography coupled with mass tandem spectrometer. Low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglyceride, glucose, insulin, glycated hemoglobin, and C-reactive protein in plasma/serum samples were analyzed by a commercial diagnostic laboratory. Statistical associations were assessed using Spearman correlation coefficients. The results showed weak associations between plasma total catechin and triglyceride (r = -0.30) and LDL cholesterol (r = -0.28), whereas plasma (-)-epigallocatechin-3-gallate, (-)-epigallocatechin, (-)-epicatechin-3-gallate, and (-)-epicatechin exhibited weak to moderate associations with triglyceride or LDL cholesterol, but little associations with HDL cholesterol, body fat, and body mass index were evident. Urinary total catechin was weakly associated with triglyceride (r = -0.19) and LDL cholesterol (r = -0.15), whereas urinary (-)-epigallocatechin-3-gallate (r = -0.33), (-)-epigallocatechin (r = -0.23), and (-)-epicatechin-3-gallate (r = -0.33) had weak to moderate correlations with triglyceride and similarly with body fat and body mass index. Both plasma (r = -0.24) and urinary (r = -0.24) total catechin, as well as individual catechins, were weakly associated with glycated hemoglobin. Plasma total and individual catechins were weakly to moderately associated with C-reactive protein, but not the case for urinary catechins. In conclusion, we found weak to moderate associations between plasma and urinary green tea catechin concentrations and plasma biomarkers of cardiovascular disease and diabetes. Copyright © 2016 Elsevier Inc. All rights reserved.

Influence of BMI in nephrolithiasis in an Appalachian pediatric population: A single-center experience.

PubMed

Murphy, Margaret O; Erpelding, Scott G; Chishti, Aftab S; Dugan, Adam; Ziada, Ali; Kiessling, Stefan G

2018-06-07

The prevalence of pediatric nephrolithiasis has increased significantly in the past 20 years. Metabolic abnormalities predisposing adults to nephrolithiasis in obese patients include increased urinary sodium and uric acid excretion as well as low urine pH; however, limited data are available in the pediatric population. The aim was to investigate whether obese pediatric patients presenting with nephrolithiasis have a unique metabolic profile similar to reported findings in obese adults with nephrolithiasis. A retrospective chart review was performed in children aged 1-18 years seen at Kentucky Children's Hospital between 2010 and 2016. Inclusion criteria included all patients with documented stones confirmed by ultrasonography or computed tomography. A total of 111 patient charts were reviewed in the study with a mean age of 11.8 ± 4.2 years. Seventy patients (63%) had a normal BMI and 41 patients (37%) were considered overweight/obese. There was no statistically significant relationship between BMI and stone recurrence. Obese patients had significantly decreased levels of urinary citrate, oxalate, magnesium, and potassium with significant elevations of urinary urea nitrogen, ammonia, and low urine pH compared with normal weight patients (Summary Figure). Several groups have reported on metabolic findings within obese and non-obese pediatric patients. A Turkish study reported increased oxalate excretion and hypocitraturia in obese patients while a Korean study also reported increased rates of hypocitraturia in recurrent stone formers. Similar to these studies, we did find significant differences in citrate within our study population; however, we found significantly lower levels of urinary oxalate in obese patients. The majority of these studies do not report an association with BMI and urine pH although this has been reported in the adult population and our findings support an inverse relationship between body mass index (BMI) and pH. Our group found a higher level of calcium phosphate stones, supporting of Eisner's findings that high BMI is associated with increased supersaturation of calcium phosphate. Limitations of our study include being a single center and retrospective in nature. Our study demonstrates differences in types of stones and urinary metabolites in an obese pediatric population suggestive of different metabolic profiles contributing to stone disease. We report similar association between BMI and urine pH, urinary potassium, and citrate. This study confirmed our primary hypothesis that obese pediatric patients would have a different urinary mineral profile as evidenced by lower levels of citrate and potassium and low urine pH; however, obese patients did not exhibit significantly elevated urinary sodium and uric acid when normalized to weight, as described in the adult population. Our study did not confirm our secondary hypothesis that stone composition would be associated with BMI status or stone recurrence. Copyright © 2018 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Relative efficacy of carbenicillin indanyl sodium and of trimethoprim/sulfamethoxazole in urinary-tract infections.

PubMed

Seneca, H

1979-05-01

In a 10-day study, carbenicillin indanyl sodium cured urinary-tract infections in 22 of 30 patients (ages, 24-91). In 3 of the remaining patients the treatment was a failure; in 3 others the drug had to be discontinued because of diarrhea and vomiting; and in 2 instances it induced overgrowth of Candida albicans in the urine. Carbenicillin was lethal to Pseudomonas aeruginosa in all 9 cases, to Proteus mirabilis in all 6 cases, and to enterococcus in all 3 cases. A trimethoprim/sulfamethoxazole combination cured urinary-tract infections in 18 of 30 other patients (ages, 28-91), but failed in 3. In 3 patients it gave rise to a skin rash; in 2 to elevation of blood urea nitrogen and creatinine levels; in 1 to neutropenia; and in 1 to overgrowth of Candida albicans in the urine. Reinfection occurred in 2 patients. Carbenicillin indanyl sodium was more effective than the sulfonamide/trimethoprim combination.

Imported occupational lead poisoning: report of four cases.

PubMed

Petracca, M; Scafa, F; Boeri, R; Flachi, Daniela; Candura, S M

2013-01-01

In most industrialized countries, occupational lead poisoning has become increasingly rare, however this metal remains a serious health hazard in the rest of the world. We observedfour male patients (aged 35 / 54 years) who had suffered recurrent abdominal pain due to recent lead exposure (for 7 to 13 months) in two Chinese battery recycling plants. On their return to Italy, three of them presented normocytic, normochromic anaemia. The diagnosis was confirmed by high lead levels in the blood and urine, decreased erythrocyte delta-aminolevulinic acid dehydratase (ALA-D), raised erythrocyte zinc protoporphyrin (ZP), and elevated urinary excretion of b-aminolevulinic acid (ALA-U) and porphyrins. Chelation with EDTA resulted in increased urinary lead excretion, improvement of the clinical picture, decreased ZP, and progressive normalization of the other lead biomarkers (Pb-B, ALA-D, ALA-U, urinary porphyrins). Temporary work in developing countries may result in imported lead poisoning. Differential diagnosis of this unusual condition requires careful medical history collection and specific toxicological analysis. Preventive measures for workers going abroad are needed.

Elemental properties of copper slag and measured airborne exposures at a copper slag processing facility.

PubMed

Mugford, Christopher; Gibbs, Jenna L; Boylstein, Randy

2017-08-01

In 1974, the National Institute for Occupational Safety and Health recommended a ban on the use of abrasives containing >1% silica, giving rise to abrasive substitutes like copper slag. We present results from a National Institute for Occupational Safety and Health industrial hygiene survey at a copper slag processing facility that consisted of the collection of bulk samples for metals and silica; and full-shift area and personal air samples for dust, metals, and respirable silica. Carcinogens, suspect carcinogens, and other toxic elements were detected in all bulk samples, and area and personal air samples. Area air samples identified several areas with elevated levels of inhalable and respirable dust, and respirable silica: quality control check area (236 mg/m 3 inhalable; 10.3 mg/m 3 respirable; 0.430 mg/m 3 silica), inside the screen house (109 mg/m 3 inhalable; 13.8 mg/m 3 respirable; 0.686 mg/m 3 silica), under the conveyor belt leading to the screen house (19.8 mg/m 3 inhalable), and inside a conveyor access shack (11.4 mg/m 3 inhalable; 1.74 mg/m 3 respirable; 0.067 mg/m 3 silica). Overall, personal dust samples were lower than area dust samples and did not exceed published occupational exposure limits. Silica samples collected from a plant hand and a laborer exceeded the American Conference of Governmental Industrial Hygienist Threshold Limit Value of 0.025 µg/m 3 . All workers involved in copper slag processing (n = 5) approached or exceeded the Occupational Safety and Health Administration permissible exposure limit of 10 µg/m 3 for arsenic (range: 9.12-18.0 µg/m 3 ). Personal total dust levels were moderately correlated with personal arsenic levels (R s = 0.70) and personal respirable dust levels were strongly correlated with respirable silica levels (R s = 0.89). We identified multiple areas with elevated levels of dust, respirable silica, and metals that may have implications for personal exposure at other facilities if preventive measures are not taken. To our knowledge, this is the first attempt to characterize exposures associated with copper slag processing. More in-depth air monitoring and health surveillance is needed to understand occupational exposures and health outcomes in this industry.

Open-label study evaluating outpatient urethral sphincter injections of onabotulinumtoxinA to treat women with urinary retention due to a primary disorder of sphincter relaxation (Fowler's syndrome).

PubMed

Panicker, Jalesh N; Seth, Jai H; Khan, Shahid; Gonzales, Gwen; Haslam, Collette; Kessler, Thomas M; Fowler, Clare J

2016-05-01

To assess the efficacy (defined as improvements in maximum urinary flow rate [Qmax ] of ≥50%, post-void residual urine volume [PVR] and scores on the International Prostate Symptom Score [IPSS] questionnaire) and safety of urethral sphincter injections of onabotulinumtoxinA in women with a primary disorder of urethral sphincter relaxation, characterised by an elevated urethral pressure profile (UPP) and specific findings at urethral sphincter electromyography (EMG), i.e. Fowler's syndrome. In this open-label pilot Institutional Review Board-approved study, 10 women with a primary disorder of urethral sphincter relaxation (elevated UPP, sphincter volume, and abnormal EMG) presenting with obstructed voiding (five) or in complete urinary retention (five) were recruited from a single tertiary referral centre. Baseline symptoms were assessed using the IPSS, and Qmax and PVR were measured. After 2% lidocaine injection, 100 U of onabotulinumtoxinA was injected into the striated urethral sphincter, divided on either side, under EMG guidance. Patients were reviewed at 1, 4 and 10 weeks after injection, and assessed using the IPSS, Qmax and PVR measurements. The UPP was repeated at week 4. The mean (range) patient age was 40 (25-65) years, and the mean symptom scores on the IPSS improved from 25.6 to 14.1, and the mean 'bother' score reduced from 6.1 to 3.5 at week 10. As compared with a baseline mean Qmax of 8.12 mL/s in the women who could void, the Qmax improved to 15.8 mL/s at week 10. Four of the five women in complete retention could void spontaneously, with a mean Qmax of 14.3 mL/s at week 10. The mean PVR decreased from 260 to 89 mL and the mean static UPP improved from 113 cmH2 O at baseline to 90 cmH2 O. No serious side-effects were reported. Three women with a history of recurrent urinary tract infections developed a urinary tract infection. There were no reports of stress urinary incontinence. Seven of the 10 women opted to return for repeat injections. This pilot study shows an improvement in patient-reported lower urinary tract symptoms, and the objective parameters of Qmax , PVR and UPP, at 10 weeks after urethral sphincter injections of onabotulinumtoxinA. No serious side-effects were reported. This treatment could represent a safe outpatient treatment for young women in retention due to a primary disorder of urethral sphincter relaxation. However, a larger study is required to confirm the findings of this pilot study. © 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.

Spectroscopy of Cu(II)-PcoC and the multicopper oxidase function of PcoA, two essential components of Escherichia coli pco copper resistance operon.

PubMed

Huffman, David L; Huyett, Jennifer; Outten, F Wayne; Doan, Peter E; Finney, Lydia A; Hoffman, Brian M; O'Halloran, Thomas V

2002-08-06

The plasmid-encoded pco copper resistance operon in Escherichia coli consists of seven genes that are expressed from two pco promoters in response to elevated copper; however, little is known about how they mediate resistance to excess environmental copper. Two of the genes encode the soluble periplasmic proteins PcoA and PcoC. We show here that inactivation of PcoC, and PcoA to a lesser extent, causes cells to become more sensitive to copper than wild-type nonresistant strains, consistent with a tightly coupled detoxification pathway. Periplasmic extracts show copper-inducible oxidase activity, attributed to the multicopper oxidase function of PcoA. PcoC, a much smaller protein than PcoA, binds one Cu(II) and exhibits a weak electronic transition characteristic of a type II copper center. ENDOR and ESEEM spectroscopy of Cu(II)-PcoC and the (15)N- and Met-CD(3)-labeled samples are consistent with a tetragonal ligand environment of three nitrogens and one aqua ligand "in the plane". A weakly associated S-Met and aqua are likely axial ligands. At least one N is a histidine and is likely trans to the in-plane aqua ligand. The copper chemistry of PcoC and the oxidase function of PcoA are consistent with the emerging picture of the chromosomally encoded copper homeostasis apparatus in the E. coli cell envelope [Outten, F. W., Huffman, D. L., Hale, J. A., and O'Halloran, T. V. (2001) J. Biol. Chem. 276, 30670-30677]. We propose a model for the plasmid system in which Cu(I)-PcoC functions in this copper efflux pathway as a periplasmic copper binding protein that docks with the multiple repeats of Met-rich domains in PcoA to effect oxidation of Cu(I) to the less toxic Cu(II) form. The solvent accessibility of the Cu(II) in PcoC may allow for metal transfer to other plasmid and chromosomal factors and thus facilitate removal of Cu(II) from the cell envelope.

Earth Observations taken by the Expedition 22 Crew

NASA Image and Video Library

2009-12-09

ISS022-E-008282 (9 Dec. 2009) --- One of the world?s leading copper mines, Escondida, in the Atacama Desert of Chile, is featured in this image photographed by an Expedition 22 crew member on the International Space Station. The copper mining industry is a major part of the Chilean economy. The mine is located 170 kilometers southeast of Chile?s port city of Antofagasta, in the hyper arid northern Atacama Desert at an elevation of 3,050 meters (approximately 10,000 feet) above sea level. Escondida produces mainly copper concentrates; assisted by gravity, the concentrates are piped as slurry down to the smaller port of Coloso just south of Antofagasta where they are dewatered for shipping. The photograph features a large light tan and gray waste or ?spoil? materials impoundment area (center) of the mine complex. The copper-bearing waste, which is a large proportion of the material excavated from open pits to the north (not in frame), is poured into the impoundment area as a liquid (green region at photo?s center), and dries to the lighter-toned spoil seen in the image. The spoil is held behind a retaining dam, just a little more than one kilometer in length, visible as a straight line at lower left. ?Escondida? means ?hidden? in Spanish, and refers to the fact that the copper ore body was buried beneath hundreds of meters of barren rock and had to be located by a laborious drilling program following a geologic trend established from other copper occurrences.

Chromatographic Separation and Visual Detection on Wicking Microfluidic Devices: Quantitation of Cu2+ in Surface, Ground, and Drinking Water.

PubMed

Bandara, Gayan C; Heist, Christopher A; Remcho, Vincent T

2018-02-20

Copper is widely applied in industrial and technological applications and is an essential micronutrient for humans and animals. However, exposure to high environmental levels of copper, especially through drinking water, can lead to copper toxicity, resulting in severe acute and chronic health effects. Therefore, regular monitoring of aqueous copper ions has become necessary as recent anthropogenic activities have led to elevated environmental concentrations of copper. On-site monitoring processes require an inexpensive, simple, and portable analytical approach capable of generating reliable qualitative and quantitative data efficiently. Membrane-based lateral flow microfluidic devices are ideal candidates as they facilitate rapid, inexpensive, and portable measurements. Here we present a simple, chromatographic separation approach in combination with a visual detection method for Cu 2+ quantitation, performed in a lateral flow microfluidic channel. This method appreciably minimizes interferences by incorporating a nonspecific polymer inclusion membrane (PIM) based assay with a "dot-counting" approach to quantification. In this study, hydrophobic polycaprolactone (PCL)-filled glass microfiber (GMF) membranes were used as the base substrate onto which the PIM was evenly dispensed as an array of dots. The devices thus prepared were then selectively exposed to oxygen radicals through a mask to generate a hydrophilic surface path along which the sample was wicked. Using this approach, copper concentrations from 1 to 20 ppm were quantified from 5 μL samples using only visual observation of the assay device.

Urinary CCN2 (CTGF) as a possible predictor of diabetic nephropathy: preliminary report.

PubMed

Riser, Bruce L; Cortes, Pedro; DeNichilo, Mark; Deshmukh, Poornima V; Chahal, Parminder S; Mohammed, Ali K; Yee, Jerry; Kahkonen, Dorothy

2003-08-01

It is currently impossible to reliably predict which diabetic patients will develop nephropathy and progress to kidney failure. Microalbuminuria, often regarded as a predictor of overt diabetic renal disease is, in fact, an indicator of established glomerular damage. We have shown that glomerular expression of the prosclerotic cytokine CCN2 (CTGF) is greatly up-regulated early in experimental and in human diabetes and mesangial cell exposure to CCN2 increases its production of extracellular matrix (ECM) molecules responsible for glomerulosclerosis. As an early marker, we therefore investigated the presence of CCN2 in urine and the relationship to diabetes and/or renal disease in an experimental model of diabetes and in a limited patient population. Urine samples from (1) healthy rats, (2) rats made diabetic by streptozotocin (STZ), (3) healthy human volunteers, (4) diabetic patients with renal disease, and (5) diabetic patients without renal disease were examined by Western blotting and/or enzyme-linked immunosorbent assay (ELISA) for qualitative and quantitative analysis of the of CCN2. Low levels of urinary CCN2 were present in healthy, control rats, but were increased approximately sevenfold overall in STZ-diabetic animals. CCN2 levels were the highest at week 3 of diabetes, then decreased with time, but remained significantly elevated over controls even after 32 weeks. Consistently low levels of urinary CCN2 were also detected in healthy volunteers (mean value, 7.1 CCN2/mg creatinine). However, levels were elevated approximately sixfold in the majority of diabetic patients with nephropathy. A small number of the diabetic patients not yet exhibiting evidence of renal involvement demonstrated CCN2 urinary levels that were ninefold greater than controls. The remaining normoalbuminuric diabetic patients demonstrated CCN2 levels indistinguishable from those of healthy volunteers. Analysis by Western blotting confirmed the identity of the urinary CCN2. A molecular species equivalent to full-length CCN2 (37/39 kD doublet) was present in healthy controls. In contrast, the nephropathic group demonstrated multiple CCN2 bands. These findings support our hypothesis that CCN2 is up-regulated early in the evolution of glomerulosclerosis, including that of diabetes. We contend that urinary CCN2 may both stage nephropathy and predict those patients who are destined for progressive glomerulosclerosis and end-stage renal disease (ESRD). Cross-sectional and prospective studies of larger, well-defined diabetic patients groups will be required to prove this hypothesis, and are ongoing.

Effect of intradermal human recombinant copper-zinc superoxide dismutase on random pattern flaps in rats.

PubMed

Schein, Ophir; Westreich, Melvyn; Shalom, Avshalom

2013-09-01

Studies have focused on enhancing flap viability using superoxide dismutase (SOD), but only a few used SOD from human origin, and most gave the compound systemically. We evaluated the ability of SOD to improve random skin flap survival using human recombinant copper-zinc superoxide dismutase (Hr-CuZnSOD) in variable doses, injected intradermally into the flap. Seventy male Sprague Dawley rats were randomly assigned into 4 groups. Cephalic random pattern flaps were elevated on their backs and intradermal injections of different dosages of Hr-CuZnSOD were given 15 minutes before surgery. Flap survival was evaluated by fluorescein fluorescence. Analysis of variance (ANOVA) and t test statistical analyses were performed. Flap survival in all treated groups was significantly better than in the controls. The beneficial effect of HR-CuZnSOD on flap survival is attained when it is given intradermally into the flap tissue. Theoretically, Hr-CuZnSOD delivered with local anesthetics used in flap elevation may be a valuable clinical tool. Copyright © 2012 Wiley Periodicals, Inc.

Catecholamines profiles at diagnosis: Increased diagnostic sensitivity and correlation with biological and clinical features in neuroblastoma patients.

PubMed

Verly, Iedan R N; van Kuilenburg, André B P; Abeling, Nico G G M; Goorden, Susan M I; Fiocco, Marta; Vaz, Frédéric M; van Noesel, Max M; Zwaan, C Michel; Kaspers, GertJan L; Merks, Johannes H M; Caron, Huib N; Tytgat, Godelieve A M

2017-02-01

Neuroblastoma (NBL) accounts for 10% of the paediatric malignancies and is responsible for 15% of the paediatric cancer-related deaths. Vanillylmandelic acid (VMA) and homovanillic acid (HVA) are most commonly analysed in urine of NBL patients. However, their diagnostic sensitivity is suboptimal (82%). Therefore, we performed in-depth analysis of the diagnostic sensitivity of a panel of urinary catecholamine metabolites. Retrospective study of a panel of 8 urinary catecholamine metabolites (VMA, HVA, 3-methoxytyramine [3MT], dopamine, epinephrine, metanephrine, norepinephrine and normetanephrine [NMN]) from 301 NBL patients at diagnosis. Special attention was given to subgroups, metaiodobenzylguanidine (MIBG) non-avid tumours and VMA/HVA negative patients. Elevated catecholamine metabolites, especially 3MT, correlated with nine out of 12 NBL characteristics such as stage, age, MYCN amplification, loss of heterozygosity for 1p and bone-marrow invasion. The combination of the classical markers VMA and HVA had a diagnostic sensitivity of 84%. NMN was the most sensitive single diagnostic metabolite with overall sensitivity of 89%. When all 8 metabolites were combined, a diagnostic sensitivity of 95% was achieved. Among the VMA and HVA negative patients, were also 29% with stage 4 disease, which usually had elevation of other catecholamine metabolites (93%). Diagnostic sensitivity for patients with MIBG non-avid tumour was improved from 33% (VMA and/or HVA) to 89% by measuring the panel. Our study demonstrates that analysis of a urinary catecholamine metabolite panel, comprising 8 metabolites, ensures the highest sensitivity to diagnose NBL patients. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effects of profession on urinary PAH metabolite levels in the US population.

PubMed

Liu, Bian; Jia, Chunrong

2016-01-01

Although exposure to polycyclic aromatic hydrocarbons (PAHs) is common in both environmental and occupational settings, few studies have compared PAH exposure among people with different professions. The purpose of this study was to investigate the variations in recent PAH exposure among different occupational groups over time using national representative samples. The study population consisted of 4162 participants from the 2001 to 2008 National Health and Nutrition Examination Survey, who had both urinary PAH metabolites and occupational information. Four corresponding monohydroxy-PAH urine metabolites: naphthalene (NAP), fluorene (FLUO), phenanthrene (PHEN), and pyrene (PYR) among seven broad occupational groups were analyzed using weighted linear regression models, adjusting for creatinine levels, sociodemographic factors, smoking status, and sampling season. The overall geometric mean concentrations of NAP, FLUO, PHEN, and PYR were 6927, 477, 335, and 87 ng/L, respectively. All four PAH metabolites were elevated in the "extractive, construction, and repair (ECR)" group, with 21-42 % higher concentrations than those in the reference group of "management." Similar trends were seen in the "operators, fabricators, and laborers (OFL)" group for FLUO, PHEN, and PYR. In addition, both "service" and "support" groups had elevated FLUO. Significant (p < 0.001) upward temporal trends were seen in NAP and PYR, with an approximately 6-17 % annual increase, and FLUO and PHEN remained relatively stable. Race and socioeconomic status show independent effects on PAH exposure. Heterogeneous distributions of urinary PAH metabolites among people with different job categories exist at the population level. The upward temporal trends in NAP and PYR warrant reduction in PAH exposure, especially among those with OFL and ECR occupations.

Prediction of Thermal Fatigue in Tooling for Die-casting Copper via Finite Element Analysis

NASA Astrophysics Data System (ADS)

Sakhuja, Amit; Brevick, Jerald R.

2004-06-01

Recent research by the Copper Development Association (CDA) has demonstrated the feasibility of die-casting electric motor rotors using copper. Electric motors using copper rotors are significantly more energy efficient relative to motors using aluminum rotors. However, one of the challenges in copper rotor die-casting is low tool life. Experiments have shown that the higher molten metal temperature of copper (1085 °C), as compared to aluminum (660 °C) accelerates the onset of thermal fatigue or heat checking in traditional H-13 tool steel. This happens primarily because the mechanical properties of H-13 tool steel decrease significantly above 650 °C. Potential approaches to mitigate the heat checking problem include: 1) identification of potential tool materials having better high temperature mechanical properties than H-13, and 2) reduction of the magnitude of cyclic thermal excursions experienced by the tooling by increasing the bulk die temperature. A preliminary assessment of alternative tool materials has led to the selection of nickel-based alloys Haynes 230 and Inconel 617 as potential candidates. These alloys were selected based on their elevated temperature physical and mechanical properties. Therefore, the overall objective of this research work was to predict the number of copper rotor die-casting cycles to the onset of heat checking (tool life) as a function of bulk die temperature (up to 650 °C) for Haynes 230 and Inconel 617 alloys. To achieve these goals, a 2D thermo-mechanical FEA was performed to evaluate strain ranges on selected die surfaces. The method of Universal Slopes (Strain Life Method) was then employed for thermal fatigue life predictions.

Association between arsenic exposure from a coal-burning power plant and urinary arsenic concentrations in Prievidza District, Slovakia.

PubMed

Ranft, Ulrich; Miskovic, Peter; Pesch, Beate; Jakubis, Pavel; Fabianova, Elenora; Keegan, Tom; Hergemöller, Andre; Jakubis, Marian; Nieuwenhuijsen, Mark J

2003-06-01

To assess the arsenic exposure of a population living in the vicinity of a coal-burning power plant with high arsenic emission in the Prievidza District, Slovakia, 548 spot urine samples were speciated for inorganic As (Asinorg), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), and their sum (Assum). The urine samples were collected from the population of a case-control study on nonmelanoma skin cancer (NMSC). A total of 411 samples with complete As speciations and sufficient urine quality and without fish consumption were used for statistical analysis. Although current environmental As exposure and urinary As concentrations were low (median As in soil within 5 km distance to the power plant, 41 micro g/g; median urinary Assum, 5.8 microg/L), there was a significant but weak association between As in soil and urinary Assum(r = 0.21, p < 0.01). We performed a multivariate regression analysis to calculate adjusted regression coefficients for environmental As exposure and other determinants of urinary As. Persons living in the vicinity of the plant had 27% higher Assum values (p < 0.01), based on elevated concentrations of the methylated species. A 32% increase of MMA occurred among subjects who consumed homegrown food (p < 0.001). NMSC cases had significantly higher levels of Assum, DMA, and Asinorg. The methylation index Asinorg/(MMA + DMA) was about 20% lower among cases (p < 0.05) and in men (p < 0.05) compared with controls and females, respectively.

Association between arsenic exposure from a coal-burning power plant and urinary arsenic concentrations in Prievidza District, Slovakia.

PubMed Central

Ranft, Ulrich; Miskovic, Peter; Pesch, Beate; Jakubis, Pavel; Fabianova, Elenora; Keegan, Tom; Hergemöller, Andre; Jakubis, Marian; Nieuwenhuijsen, Mark J

2003-01-01

To assess the arsenic exposure of a population living in the vicinity of a coal-burning power plant with high arsenic emission in the Prievidza District, Slovakia, 548 spot urine samples were speciated for inorganic As (Asinorg), monomethylarsonic acid (MMA), dimethylarsinic acid (DMA), and their sum (Assum). The urine samples were collected from the population of a case-control study on nonmelanoma skin cancer (NMSC). A total of 411 samples with complete As speciations and sufficient urine quality and without fish consumption were used for statistical analysis. Although current environmental As exposure and urinary As concentrations were low (median As in soil within 5 km distance to the power plant, 41 micro g/g; median urinary Assum, 5.8 microg/L), there was a significant but weak association between As in soil and urinary Assum(r = 0.21, p < 0.01). We performed a multivariate regression analysis to calculate adjusted regression coefficients for environmental As exposure and other determinants of urinary As. Persons living in the vicinity of the plant had 27% higher Assum values (p < 0.01), based on elevated concentrations of the methylated species. A 32% increase of MMA occurred among subjects who consumed homegrown food (p < 0.001). NMSC cases had significantly higher levels of Assum, DMA, and Asinorg. The methylation index Asinorg/(MMA + DMA) was about 20% lower among cases (p < 0.05) and in men (p < 0.05) compared with controls and females, respectively. PMID:12782488

Matrix Metalloproteinase-7 Is a Urinary Biomarker and Pathogenic Mediator of Kidney Fibrosis

PubMed Central

Zhou, Dong; Tian, Yuan; Sun, Ling; Zhou, Lili; Xiao, Liangxiang; Tan, Roderick J.; Tian, Jianwei; Fu, Haiyan

2017-01-01

Matrix metalloproteinase-7 (MMP-7), a secreted zinc– and calcium–dependent endopeptidase, is a transcriptional target of canonical Wnt/β-catenin signaling. Because Wnt/β-catenin is activated in diseased kidney, we hypothesized that urinary MMP-7 level may be used as a noninvasive surrogate biomarker for fibrotic lesions. To test this hypothesis, we conducted a cross-sectional study, measuring urinary MMP-7 levels in a cohort of 102 patients with CKD. Compared with normal subjects, patients with various kidney disorders had markedly elevated urinary levels of MMP-7. Furthermore, urinary MMP-7 levels closely correlated with renal fibrosis scores in patients. In mice, knockout of MMP-7 ameliorated the fibrotic lesions and expression of matrix genes induced by obstructive injury. Genetic ablation of MMP-7 also preserved E-cadherin protein expression and substantially reduced the expression of total and dephosphorylated β-catenin and the de novo expression of vimentin and fibroblast-specific protein 1 in renal tubules of obstructed kidneys. In vitro, MMP-7 proteolytically degraded E-cadherin in proximal tubular cells, leading to β-catenin liberation and nuclear translocation and induction of β-catenin target genes by a mechanism independent of Wnt ligands. Finally, pharmacologic inhibition of MMP-7 immediately after obstructive injury reduced renal fibrosis in vivo. These results suggest that MMP-7 not only can serve as a noninvasive biomarker but also is an important pathogenic mediator of kidney fibrosis. PMID:27624489

Experimental lead intoxication in dogs: a comparison of blood lead and urinary delta-aminolevulinic acid following intoxication and chelation therapy.

PubMed Central

Green, R A; Selby, L A; Zumwalt, R W

1978-01-01

Intravenous lead administration to dogs produced an acute syndrome of lead intoxication charcterized by depression, vomiting, anorexia and weight loss. The effect of chelation therapy with calcium disodium ethylene diamine tetraacetate, penicillamine or both was determined by serially monitoring changes in blood lead and urine delta-aminolevulinic acid. Following therapy, blood lead values were significantly lower in chelated dogs than non-treated lead exposed dogs on days 7 and 10. Urine delta-aminolevulinic acid at day 7 was significantly higher in untreated lead exposed dogs than in other groups. There was no significant difference in blood lead or urine delta-aminolevulinic acid between lead intoxicated dogs which underwent the indicated chelation therapy protocols. There was, however, a trend for higher urinary delta-aminolevulinic acid excretion in those intoxicated dogs undergoing calcium disodium ethylene diamine tetraacetate therapy as opposed to those undergoing penicilamine therapy. There was no significant correlation between blood lead and urinary delta-aminolevulinic acid previous to lead exposure. However, after lead exposure significant correlation was present at days 4, 7, 10 and 14. Certain lead exposed dogs following chelation therapy were noted to have normal blood lead levels but elevated urinary delta-aminolevulinic acid suggesting that blood lead does not always correlate with metabolic effects of lead in the body. Urinary delta-aminolevulinic acid was therefore recommended as an additional laboratory parameter which improved assessment of lead exposure in dogs, particularly in determining adequacy of chelation therapy. PMID:667707

Urinary leukotriene E4, obesity, and adenotonsillar hypertrophy in Chinese children with sleep disordered breathing.

PubMed

Shen, Yuelin; Xu, Zhifei; Shen, Kunling

2011-08-01

Sleep disordered breathing (SDB) has been associated with increased inflammatory responses. Changes in the level of pro-inflammatory leukotrienes (LTs) may initiate or exacerbate pediatric SDB and may play a major role in end-organ morbidity. The objective of the study was to investigate the relationship of LT productions with severity of SDB, obesity, and adenotonsillar hypertrophy in children. Prospective, observational study that included standard questionnaires, physical examinations, overnight polysomnography (PSG), and urinary leukotriene E(4) (LTE(4)) assay. Sleep Center and Laboratory of Nutriology. 282 children with SDB and 94 healthy control subjects were recruited. Urinary LTE(4) levels were elevated in children with SDB compared to the controls, and LTE(4) productions emerged disease severity- and obesity-dependent increases. In stepwise multiple regression analysis, the independent predictors of the apnea-hypopnea index (AHI) included LTE(4) level and adenotonsillar-size sum score (P < 0.001 respectively; adjusted R(2)=0.318). A positive relationship between LTE(4) urinary level and adenotonsillar-size sum scores was present in the underweight/normal weight SDB subjects (r=0.276; P < 0.001), but not in the overweight/obese children (P > 0.05). Systemic inflammation mediated by LTs participates in the pathophysiological mechanisms of SDB in children. The magnitude of inflammation as reflected by urinary LTE(4) is significantly related to the severity of SDB and obesity. However, a correlation between LTE(4) concentration and adenotonsillar size is present only among nonobese children.

Urinary concentrations of PAH and VOC metabolites in marijuana users.

PubMed

Wei, Binnian; Alwis, K Udeni; Li, Zheng; Wang, Lanqing; Valentin-Blasini, Liza; Sosnoff, Connie S; Xia, Yang; Conway, Kevin P; Blount, Benjamin C

2016-03-01

Marijuana is seeing increased therapeutic use, and is the world's third most-popular recreational drug following alcohol and tobacco. This widening use poses increased exposure to potentially toxic combustion by-products from marijuana smoke and the potential for public health concerns. To compare urinary metabolites of polycyclic aromatic hydrocarbons (PAHs) and volatile organic compounds (VOCs) among self-reported recent marijuana users and nonusers, while accounting for tobacco smoke exposure. Measurements of PAH and VOC metabolites in urine samples were combined with questionnaire data collected from participants in the National Health and Nutrition Examination Surveys (NHANES) from 2005 to 2012 in order to categorize participants (≥18years) into exclusive recent marijuana users and nonusers. Adjusted geometric means (GMs) of urinary concentrations were computed for these groups using multiple regression analyses to adjust for potential confounders. Adjusted GMs of many individual monohydroxy PAHs (OH-PAHs) were significantly higher in recent marijuana users than in nonusers (p<0.05). Urinary thiocyanate (p<0.001) and urinary concentrations of many VOC metabolites, including metabolites of acrylonitrile (p<0.001) and acrylamide (p<0.001), were significantly higher in recent marijuana users than in nonusers. We found elevated levels of biomarkers for potentially harmful chemicals among self-identified, recent marijuana users compared with nonusers. These findings suggest that further studies are needed to evaluate the potential health risks to humans from the exposure to these agents when smoking marijuana. Published by Elsevier Ltd.

[Effects of n-hexane exposure on human serum myelin basic proteins].

PubMed

Zhou, Wei; Yi, Juan; Huang, Hui-Ping; Xiang, Ying-Ping; He, Jia-Xi; Liu, Qing-Jun; Huang, Xian-Qing

2011-06-01

To explore the effects of n-hexane on expression of serum myelin proteins (MBP) in workers occupationally exposed to n-hexane. In this study, 269 workers exposed to n-hexane for more than one year and 104 subjects not exposed to n-hexane served as the exposure group and the control group, respectively. The urinary 2,5-hexanedione levels in all subjects were detected. On the basis of urinary 2,5-hexanedione levels, the exposure group was divided into the high exposure sub-group and low exposure sub-group. The serum myelin basic protein (MBP) levels were measured by ELISA kit. The mean concentration of urinary 2,5-hexanedione in the exposed group was (3.10 +/- 1.35) mg/L. The concentration of urinary 2,5-hexanedione in the control group was undetectable. The levels of serum MBP in the high exposure sub-group and low exposure sub-group were (2.43 +/- 0.24) and (1.62 +/- 0.23) microg/L, respectively, which were significantly higher than that (0.78 +/- 0.12) microg/L in the controls (P < 0.01). Pearson correlation analysis showed the positive correlation between serum MBP levels and urinary 2,5-hexanedione levels (r = 0.781, P < 0.01). The results of present study showed that the serum MBP levels of workers occupationally exposed to n-hexane significantly elevated, and the serum MBP can serve as the effective biomarker of n-hexane exposure.

Urinary concentrations of PAH and VOC metabolites in marijuana users

PubMed Central

Wei, Binnian; Alwis, K. Udeni; Li, Zheng; Wang, Lanqing; Valentin-Blasini, Liza; Sosnoff, Connie S.; Xia, Yang; Conway, Kevin P.; Blount, Benjamin C.

2016-01-01

Background Marijuana is seeing increased therapeutic use, and is the world’s third most-popular recreational drug following alcohol and tobacco. This widening use poses increased exposure to potentially toxic combustion by-products from marijuana smoke and the potential for public health concerns. Objectives To compare urinary metabolites of polycyclic aromatic hydrocarbons (PAHs) and volatile organic compounds (VOCs) among self-reported recent marijuana users and nonusers, while accounting for tobacco smoke exposure. Methods Measurements of PAH and VOC metabolites in urine samples were combined with questionnaire data collected from participants in the National Health and Nutrition Examination Surveys (NHANES) from 2005 to 2012 in order to categorize participants (≥18 years) into exclusive recent marijuana users and nonusers. Adjusted geometric means (GMs) of urinary concentrations were computed for these groups using multiple regression analyses to adjust for potential confounders. Results Adjusted GMs of many individual monohydroxy PAHs (OH-PAHs) were significantly higher in recent marijuana users than in nonusers (p < 0.05). Urinary thiocyanate (p < 0.001) and urinary concentrations of many VOC metabolites, including metabolites of acrylonitrile (p < 0.001) and acrylamide (p < 0.001), were significantly higher in recent marijuana users than in nonusers. Conclusions We found elevated levels of biomarkers for potentially harmful chemicals among self-identified, recent marijuana users compared with nonusers. These findings suggest that further studies are needed to evaluate the potential health risks to humans from the exposure to these agents when smoking marijuana. PMID:26690539

"Bulk" Nanocrystalline Metals: Review of the Current State of the Art and Future Opportunities for Copper and Copper Alloys

NASA Astrophysics Data System (ADS)

Tschopp, M. A.; Murdoch, H. A.; Kecskes, L. J.; Darling, K. A.

2014-06-01

It is a new beginning for innovative fundamental and applied science in nanocrystalline materials. Many of the processing and consolidation challenges that have haunted nanocrystalline materials are now more fully understood, opening the doors for bulk nanocrystalline materials and parts to be produced. While challenges remain, recent advances in experimental, computational, and theoretical capability have allowed for bulk specimens that have heretofore been pursued only on a limited basis. This article discusses the methodology for synthesis and consolidation of bulk nanocrystalline materials using mechanical alloying, the alloy development and synthesis process for stabilizing these materials at elevated temperatures, and the physical and mechanical properties of nanocrystalline materials with a focus throughout on nanocrystalline copper and a nanocrystalline Cu-Ta system, consolidated via equal channel angular extrusion, with properties rivaling that of nanocrystalline pure Ta. Moreover, modeling and simulation approaches as well as experimental results for grain growth, grain boundary processes, and deformation mechanisms in nanocrystalline copper are briefly reviewed and discussed. Integrating experiments and computational materials science for synthesizing bulk nanocrystalline materials can bring about the next generation of ultrahigh strength materials for defense and energy applications.

The prooxidant action of dietary antioxidants leading to cellular DNA breakage and anticancer effects: implications for chemotherapeutic action against cancer.

PubMed

Ullah, M F; Ahmad, Aamir; Khan, Husain Y; Zubair, H; Sarkar, Fazlul H; Hadi, S M

2013-11-01

Plant-derived dietary antioxidants have attracted considerable interest in recent past for their ability to induce apoptosis and regression of tumors in animal models. While it is believed that the antioxidant properties of these agents may contribute to lowering the risk of cancer induction by impeding oxidative injury to DNA, it could not account for apoptosis induction and chemotherapeutic observations. In this article, we show that dietary antioxidants can alternatively switch to a prooxidant action in the presence of transition metals such as copper. Such a prooxidant action leads to strand breaks in cellular DNA and growth inhibition in cancer cells. Further, the cellular DNA breakage and anticancer effects were found to be significantly enhanced in the presence of copper ions. Moreover, inhibition of antioxidant-induced DNA strand breaks and oxidative stress by Cu(I)-specific chelators bathocuproine and neocuproine demonstrated the role of endogenous copper in the induction of the prooxidant mechanism. Since it is well established that tissue, cellular, and serum copper levels are considerably elevated in various malignancies, such a prooxidant cytotoxic mechanism better explains the anticancer activity of dietary antioxidants against cancer cells.

A retrospective comparison of two vaginal mesh kits in the management of anterior and apical vaginal prolapse: long-term results for apical fixation and quality of life.

PubMed

Lamblin, Gery; Gouttenoire, Chloé; Panel, Laure; Moret, Stéphanie; Chene, Gautier; Courtieu, Christophe

2016-12-01

To compare apical correction in stage ≥3 cystocele between two mesh kits. This was a retrospective, nonrandomized study that compared two groups matched on anterior/apical POP-Q stage: 84 received Elevate Ant™ single-incision mesh (Elevate Ant group) and 42 Perigee™ transvaginal mesh (Perigee group). Follow-up at 1 and 2 years comprised objective (POP-Q) and subjective (PFDI-20, PFIQ-7, PISQ-12) assessments. The primary endpoint was objective success: 2-year apical POP-Q stage ≤1. Secondary endpoints were anterior POP-Q stage, subjective results and complications. Groups were comparable in terms of age (66.6 and 64.7 years, respectively; p = 0.19), BMI (both 25.4 kg/m 2 ; p = 0.93), and history of hysterectomy (7.2 % and 14.3 %; p = 0.21) or prolapse surgery (12 % and 14.3 %; p = 0.72). Operative time was shorter in the Elevate Ant group (54.1 vs. 62.5 min; p = 0.048), and the 2-year objective apical success rate was higher (92.9 % vs. 66.7 %; p < 0.0001), with better point C correction (-5 vs. -3.8; p = 0.006). Function improved in both groups, with significantly better PFIQ-7 (p = 0.03) and PFDI-20 (p = 0.02) scores in the Elevate Ant group at 2 years. Vaginal exposure was not seen in the Elevate Ant group but occurred in two patients in the Perigee group (p = 0.33). Factors associated with success were age >65 years (OR 7.16, 95 % CI 1.83 - 27.97) and treatment with Elevate Ant mesh (OR 10.16, 95 % CI 2.78 - 37.14). Postoperative stress urinary incontinence rate was greater with the Elevate Ant group (29.8 % and 16.7 %; p = 0.11). The use of the Elevate Ant mesh was associated with significantly better apical correction at 2 years. Function improved in both groups, but with a significantly better PFDI-20 score in the Elevate Ant group at 1 and 2 years. The postoperative stress urinary incontinence rate, however, tended to be greater in the Elevate Ant group. The results need confirming with longer follow-up of these cohorts and in randomized studies.

Major urinary metabolites of 6-keto-prostaglandin F2α in mice[S

PubMed Central

Kuklev, Dmitry V.; Hankin, Joseph A.; Uhlson, Charis L.; Hong, Yu H.; Murphy, Robert C.; Smith, William L.

2013-01-01

Western diets are enriched in omega-6 vs. omega-3 fatty acids, and a shift in this balance toward omega-3 fatty acids may have health benefits. There is limited information about the catabolism of 3-series prostaglandins (PG) formed from eicosapentaenoic acid (EPA), a fish oil omega-3 fatty acid that becomes elevated in tissues following fish oil consumption. Quantification of appropriate urinary 3-series PG metabolites could be used for noninvasive measurement of omega-3 fatty acid tone. Here we describe the preparation of tritium- and deuterium-labeled 6-keto-PGF2α and their use in identifying urinary metabolites in mice using LC-MS/MS. The major 6-keto-PGF2α urinary metabolites included dinor-6-keto-PGF2α (∼10%) and dinor-13,14-dihydro-6,15-diketo-PGF1α (∼10%). These metabolites can arise only from the enzymatic conversion of EPA to the 3-series PGH endoperoxide by cyclooxygenases, then PGI3 by prostacyclin synthase and, finally, nonenzymatic hydrolysis to 6-keto-PGF2α. The 6-keto-PGF derivatives are not formed by free radical mechanisms that generate isoprostanes, and thus, these metabolites provide an unbiased marker for utilization of EPA by cyclooxygenases. PMID:23644380

First case of Propionibacterium acnes urinary tract infection in a dog.

PubMed

Harada, Kazuki; Shimizu, Takae; Tsuka, Takeshi; Imagawa, Tomohiro; Takeuchi, Takashi

2015-12-21

Propionibacterium acnes has been rarely isolated as a commensal from dogs, but there is little evidence of pathogenicity. Urinary tract infections are common in dogs and are typically caused by various commensal bacteria. Here we present the first case report of a urinary tract infection caused by P. acnes. A 6-year-old female Japanese Shiba Inu was hospitalized for polyuria, polydipsia, and severe hematuria. At admission, blood tests revealed leukocytosis, slight anemia, decreased albumin, and slightly elevated blood urea nitrogen. Computerized tomography showed gas accumulation on the inner side of the bladder wall. Urinalysis revealed proteinuria and bilirubinuria without glycosuria. The urine sediment contained large numbers of erythrocytes and leukocytes. Additionally, rod-shaped bacteria were detected by Diff-Quik staining. Enrofloxacin and metronidazole were administered empirically; however, the renal function declined sharply and the patient died 2 days later. Bacteriological examination revealed that the causative agent was Propionibacterium acnes, which was identified as sequence type 53 via multilocus sequence typing. This isolate showed high susceptibility to ampicillin, amoxicillin/clavulanic acid, cefoxitin, imipenem, clindamycin, tetracycline, chloramphenicol, and enrofloxacin, but was resistant to metronidazole. To the best of our knowledge, this is the first case report of a dog with urinary tract infection caused by P. acnes.

Protein shedding in urothelial bladder cancer: prognostic implications of soluble urinary EGFR and EpCAM.

PubMed

Bryan, R T; Regan, H L; Pirrie, S J; Devall, A J; Cheng, K K; Zeegers, M P; James, N D; Knowles, M A; Ward, D G

2015-03-17

Better biomarkers must be found to develop clinically useful urine tests for bladder cancer. Proteomics can be used to identify the proteins released by cancer cell lines and generate candidate markers for developing such tests. We used shotgun proteomics to identify proteins released into culture media by eight bladder cancer cell lines. These data were compared with protein expression data from the Human Protein Atlas. Epidermal growth factor receptor (EGFR) was identified as a candidate biomarker and measured by ELISA in urine from 60 noncancer control subjects and from 436 patients with bladder cancer and long-term clinical follow-up. Bladder cancer cell lines shed soluble EGFR ectodomain. Soluble EGFR is also detectable in urine and is highly elevated in some patients with high-grade bladder cancer. Urinary EGFR is an independent indicator of poor bladder cancer-specific survival with a hazard ratio of 2.89 (95% CI 1.81-4.62, P<0.001). In multivariable models including both urinary EGFR and EpCAM, both biomarkers are predictive of bladder cancer-specific survival and have prognostic value over and above that provided by standard clinical observations. Measuring urinary EGFR and EpCAM may represent a simple and useful approach for fast-tracking the investigation and treatment of patients with the most aggressive bladder cancers.

Urinary fibronectin levels in patients treated with intravesical bacillus Calmette-Guérin for superficial bladder cancer.

PubMed

Danişman, A; Bulut, K; Kukul, E; Ozen, I; Sevük, M

2000-01-01

Intravesical bacillus Calmette-Guérin (BCG) has been shown to be an effective treatment for superficial transitional cell carcinoma (TCC) of the bladder, but the precise mechanism of action of BCG remains poorly understood. Fibronectin (FN), an important component of the extracellular matrix, has been found to play a role in BCG therapy. Some studies have shown that the soluble form of FN can compete efficiently with the matrix form of binding to the specific receptors on the bacteria and could consequently diminish the effect of BCG treatment. To evaluate a possible correlation between the urinary levels of FN and the efficacy of BCG therapy, we determined prospectively the urinary FN levels in 38 patients with TCC of the bladder and in 25 control subjects without malignancy matched for age and sex. All TCC patients were treated with transurethral tumor resection plus 6 weekly intravesical BCG instillations. After an average follow-up of 30 months, 8 patients (21.1%) had recurrent tumors, while 30 (78.9%) were free of tumor after intravesical BCG therapy. Urinary levels of FN in cancer patients have been shown to be significantly higher than controls (p < 0.001). These elevated levels were not decreased significantly after the operation (p > 0. 05). It was also found that the mean urinary FN levels were not statistically significant between patients with recurrence and complete remission. The data suggest that BCG-bladder tumor cell binding is not influenced by soluble fibronectin and urinary FN may not be a ideal marker for selecting patients to BCG therapy. Copyright 2000 S. Karger AG, Basel

Smoking modify the effects of polycyclic aromatic hydrocarbons exposure on oxidative damage to DNA in coke oven workers.

PubMed

Yang, Jin; Zhang, Hongjie; Zhang, Huitao; Wang, Wubin; Liu, Yanli; Fan, Yanfeng

2017-07-01

Coke oven emissions containing polycyclic aromatic hydrocarbons (PAHs) are predominant toxic constituents of particulate air pollution that have been linked to increased risk of lung cancer. Numerous epidemiological studies have suggested that oxidative DNA damage may play a pivotal role in the carcinogenic mechanism of lung cancer. Little is known about the effect of interaction between PAHs exposure and lifestyle on DNA oxidative damage. The study population is composed by coke oven workers (365) and water treatment workers (144), and their urinary levels of four PAH metabolites and 8-hydroxydeoxyguanosine (8-OHdG) were determined. Airborne samples of exposed sites (4) and control sites (3) were collected, and eight carcinogenic PAHs were detected by high-performance liquid chromatography. The median values of the sum of eight carcinogenic PAHs and BaP in exposed sites were significantly higher than control sites (P < 0.01). The study found that the urinary PAH metabolites were significantly elevated in coke oven workers (P < 0.01). Multivariate logistic regression analysis revealed that the risk of high levels of urinary 8-OHdG will increase with increasing age, cigarette consumption, and levels of urinary 1-hydroxypyrene, and P for trend were all <0.05. Smoking can significantly modify the effects of urinary 1-hydroxypyrene on high concentrations urinary 8-OHdG, during co-exposure to both light or heavy smoking and high 1-hydroxypyrene levels (OR 4.28, 95% CI 1.32-13.86 and OR 5.05, 95% CI 1.63-15.67, respectively). Our findings quantitatively demonstrate that workers exposed to coke oven fumes and smoking will cause more serious DNA oxidative damage.

The challenge of cystine and struvite stone formers: clinical, metabolic and surgical assessment

PubMed Central

Yamaçake, Kleiton G. R.; Marchini, Giovanni S.; Reis, Sabrina; Danilovic, Alexandre; Vicentini, Fábio C.; Torricelli, Fábio C. M.; Srougi, Miguel; Mazzucchi, Eduardo

2016-01-01

ABSTRACT Purpose: To compare the clinical, metabolic, and calculi characteristics of cystine and struvite stone patients after percutaneous nephrolithotripsy (PCNL). Material and Methods: Between January/2006-July/2013, 11 cystine stone patients were treated in our clinic. Of those, 3 were excluded due to incomplete follow-up. Eight cystine stone patients (2 with bilateral disease; 10 renal units-RU) were considered for further analysis. A cohort of 8 struvite stone formers (10RU) was matched having the same age, gender, body mass index (BMI) and Guys stone score. Analyzed parameters comprised demographic data, serum/urinary metabolic evaluation and surgical outcomes. Results: Both groups had 6 female patients. Groups were similar in regards to age, gender, BMI, stone burden, and serum creatinine (p=NS). All patients had PCNL as the first surgical treatment modality. Stone free rate (SFR) after the first PCNL tended to be lower (0%) in the cystine compared to the struvite group (40%)(p=0.08). Final SFR after secondary procedures increased to 70% in cystine and 80% in struvite patients (p=1.0); mean number of procedures to achieve stone free status was higher in the first group (3.57 vs. 2.0;p=0.028). Hypocitraturia was found in all patients, but struvite cases presented with lower mean urinary citrate levels (p=0.016). Other common abnormalities were elevated urinary pH (cystine 75% and struvite 62.5%;p=1.0) and low urinary volume (62.5%,37.5%;p=0.63). Conclusion: Multiple interventions and suboptimal stone free rates are trait of the significant stone burden of struvite and cystine patients. Underlying metabolic abnormalities characterized by increased urinary pH, hypocitraturia and low urinary volume are often encountered in both populations. PMID:27622279

Estimating 24-Hour Urinary Sodium Excretion From Casual Urinary Sodium Concentrations in Western Populations

PubMed Central

Brown, Ian J.; Dyer, Alan R.; Chan, Queenie; Cogswell, Mary E.; Ueshima, Hirotsugu; Stamler, Jeremiah; Elliott, Paul

2013-01-01

High intakes of dietary sodium are associated with elevated blood pressure levels and an increased risk of cardiovascular disease. National and international guidelines recommend reduced sodium intake in the general population, which necessitates population-wide surveillance. We assessed the utility of casual (spot) urine specimens in estimating 24-hour urinary sodium excretion as a marker of sodium intake in the International Cooperative Study on Salt, Other Factors, and Blood Pressure. There were 5,693 participants recruited in 1984–1987 at the ages of 20–59 years from 29 North American and European samples. Participants were randomly assigned to test or validation data sets. Equations derived from casual urinary sodium concentration and other variables in the test data were applied to the validation data set. Correlations between observed and estimated 24-hour sodium excretion were 0.50 for individual men and 0.51 for individual women; the values were 0.79 and 0.71, respectively, for population samples. Bias in mean values (observed minus estimated) was small; for men and women, the values were −1.6 mmol per 24 hours and 2.3 mmol per 24 hours, respectively, at the individual level and −1.8 mmol per 24 hours and 2.2 mmol per 24 hours, respectively, at the population level. Proportions of individuals with urinary 24-hour sodium excretion above the recommended levels were slightly overestimated by the models. Casual urine specimens may be a useful, low-burden, low-cost alternative to 24-hour urine collections for estimation of population sodium intakes; ongoing calibration with study-specific 24-hour urinary collections is recommended to increase validity. PMID:23673246

High specificity of spot urinary free metanephrines in diagnosis and prognosis of pheochromocytomas and paragangliomas by HPLC with electrochemical detection.

PubMed

Zuo, Ming; Zhen, Qianna; Zhang, Xiaoqing; Zou, Wenbi; Yang, Xiangchun; Tian, Gang; Shi, Zhenghu; Li, Qifu; Ding, Min

2018-03-01

The metanephrines (MNs) in plasma and urine were proposed as biomarkers for the diagnosis of pheochromocytomas and paragangliomas (PPGLs). However, plasma free MNs and 24h urinary fractionated MNs were not satisfactory enough in specificity for the diagnosis of PPGLs. Moreover, the collection of 24h urine was inconvenient. This work examined the diagnostic and prognostic efficiency of free MNs in spot urine for PPGLs. We measured free MNs concentration in spot urine and plasma of 28 PPGLs patients and 155 control subjects by HPLC with electrochemical detection. Postoperative free MNs levels in spot urine and plasma of 14 PPGLs patients were also determined. Creatinine (Cr) concentration was used for the correction of urine volume. The specificity of spot urinary free MNs/Cr in the diagnosis of PPGLs was significantly higher than that of plasma free MNs [normetanephrine (NMN), 98.7% (95.4%-99.8%) vs 93.0% (87.4%-96.6%); metanephrine (MN), 93.6% (88.5%-96.9%) vs 84.5% (77.5%-90.0%)]. Meanwhile, the positive likelihood ratios for spot urinary free NMN/Cr and MN/Cr were 69.21 and 13.29, compared with 12.68 and 5.30 for plasma free NMN and MN, respectively. For the PPGLs patients underwent surgery, the plasma free MNs level appeared an abnormal elevation and yielded false-positive results for some patients. Our findings were validated in an independent cohort, resulting in the specificity of 100% for both urinary free NMN/Cr and MN/Cr, and 97.3% and 83.8% for plasma free NMN and MN, respectively. Spot urinary free MNs/Cr, superior to plasma free MNs, presented a promising biomarker for the diagnosis and prognosis of PPGLs. Copyright © 2017 Elsevier B.V. All rights reserved.

The interplay between siderophore secretion and coupled iron and copper transport in the heterocyst-forming cyanobacterium Anabaena sp. PCC 7120.

PubMed

Nicolaisen, Kerstin; Hahn, Alexander; Valdebenito, Marianne; Moslavac, Suncana; Samborski, Anastazia; Maldener, Iris; Wilken, Corinna; Valladares, Ana; Flores, Enrique; Hantke, Klaus; Schleiff, Enrico

2010-11-01

Iron uptake is essential for Gram-negative bacteria including cyanobacteria. In cyanobacteria, however, the iron demand is higher than in proteobacteria due to the function of iron as a cofactor in photosynthesis and nitrogen fixation, but our understanding of iron uptake by cyanobacteria stands behind the knowledge in proteobacteria. Here, two genes involved in this process in the heterocyst-forming cyanobacterium Anabaena sp. PCC 7120 were identified. ORF all4025 encodes SchE, a putative cytoplasmic membrane-localized transporter involved in TolC-dependent siderophore secretion. Inactivation of schE resulted in an enhanced sensitivity to high metal concentrations and decreased secretion of hydroxamate-type siderophores. ORF all4026 encodes a predicted outer membrane-localized TonB-dependent iron transporter, IacT. Inactivation of iacT resulted in decreased sensitivity to elevated iron and copper levels. Expression of iacT from the artificial trc promoter (P(trc)) resulted in sensitization against tested metals. Further analysis showed that iron and copper effects are synergistic because a decreased supply of iron induced a significant decrease of copper levels in the iacT insertion mutant but an increase of those levels in the strain carrying P(trc)-iacT. Our results unravel a link between iron and copper homeostasis in Anabaena sp. PCC 7120. Copyright © 2010 Elsevier B.V. All rights reserved.

Pheochromocytoma of urinary bladder - a case report.

PubMed

Sharma, Shaleen; Gokhro, Sunil; Sharma, K K; Sadasukhi, T C

2007-08-01

Pheochromocytomas are catecholamine producing neuroendocrine tumours. Bladder involvement with pheochromocytoma is rare that usually presents with hypertension, hematuria and syncope often related to voiding. Clinical manifestation may be inconsistent and high index of suspicion is required for accurate diagnosis. We report a case, who presented with gross intermittent hematuria and mild elevation of pulserate and bloodpressure. Patient was adequately treated with partial cystectomy.

The Presence Of Strange Males' Odor Induces Behavioral Responses And Elevated Levels Of Low Molecular Weight Proteins Excreted In The Urine Of Mature Water Vole Males (Arvicola amphibius L).

PubMed

Nazarova, Galina G; Proskurniak, Lyudmila P; Yuzhik, Ekaterina I

2016-03-01

We hypothesized that low molecular weight urinary proteins play a role in male-male chemical communication in the water vole, Arvicola ampibius L. We studied the effect of placing soiled litter from strange males into the cage of another sexually mature male on the intensity of its digging and scattering, urination on the litter, and alteration in the levels of low molecular weight proteins (15-25 kDa) excreted in the urine before and after 4 days of exposure as determined by chip electrophoresis. The intensity of digging and scattering was positively correlated with levels of testosterone in serum of males exposed to strange male odors (r = 0.56; P < 0.01), as well as with the concentration of low molecular weight proteins in the donor's urine (r = 0.52, P < 0.05). At the end of the experiment, the level of low molecular weight protein in excreted urine was elevated in the males exposed to the strange male's litter. These results highlight the importance of quantitative inter-individual variation of low molecular weight urinary proteins in the modulation of the physiology and behavior of conspecifics.

Mercury contribution to an Adirondack lake

DOE Office of Scientific and Technical Information (OSTI.GOV)

Scrudato, R.J.; Long, D.; Weinbloom, R.

1987-01-01

Elevated copper, lead, and zinc concentrations in the upper 10 to 20 cm of sediment sampled from Cranberry Lake, a large Adirondack lake, are attributed to atmospheric contributions. Pb-210 and pollen core data, however, suggest Cranberry Lake also received mercury discharges during the turn of the century when the area was the center of extensive lumbering and related activities. Elevated mercury concentrations in Cranberry Lake smallmouth bass derived from remobilization from mercury-contaminated bottom sediments which increased the bioavailability to Cranberry Lake organisms. Mercury remobilization and accumulation by fish are promoted by fluctuating pH values resulting from acid precipitation.

Mercury contribution to an adirondack lake

NASA Astrophysics Data System (ADS)

Scrudato, R. J.; Long, D.; Weinbloom, Robert

1987-10-01

Elevated copper, lead, and zinc concentrations in the upper 10 to 20 cm of sediment sampled from Cranberry Lake, a large Adirondack lake, are attributed to atmospheric contributions. Pb-210 and pollen core data, however, suggest Cranberry Lake also received mercury discharges during the turn of the century when the area was the center of extensive lumbering and related activities. Elevated mercury concentrations in Cranberry Lake smallmouth bass derived from remobilization from mercury-contaminated bottom sediments which increased the bioavailability to Cranberry Lake organisms. Mercury remobilization and accumulation by fish are promoted by fluctuating pH values resulting from acid precipilation.

Public health assessment for petitioned Phelps Dodge Corp Douglas Reduction Works, Douglas, Cochise County, Arizona, Region 9. Cerclis No. AZD008397143. Final report

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

The Phelps-Dodge site, a former copper-smelting operation just outside Douglas and possibly Agua Prieta, Sonora, Mexico. This site contributed to lead-contaminated surface soils in residential areas in Douglas. Exposure to the lead-contaminated soils may have contributed and/or caused elevated blood levels in children living in both Douglas, AZ and Agua Prieta, Sonora, Mexico. Past emissions from the smelter included arsenic, lead, sulfur dioxide, inhalable particulate matter, and other heavy metals. The levels detected by air monitoring were elevated above health guidelines.

Exposure of flight attendants to pyrethroid insecticides on commercial flights: urinary metabolite levels and implications

PubMed Central

Wei, Binnian; Mohan, Krishnan R.; Weisel, Clifford P.

2011-01-01

Pyrethroid insecticides have been used for disinsection of commercial aircrafts. However, little is known about the pyrethroids exposure of flight attendants. The objective of the study was to assess pyrethroids exposure of flight attendants working on commercial aircrafts through monitoring the urinary pyrethroids metabolite levels. Eighty four urine samples were collected from 28 flight attendants, 18 – 65 years of age, with seventeen working on planes that were non-disinsected, and eleven working on planes that had been disinsected. Five urinary metabolites of pyrethroids were measured using gas chromatographic–mass spectrometric method: 3-phenoxybenzoic acid (3-PBA), cis-/trans-3-(2,2-Dichlorovinyl)-2,2-dimethylcyclo-propane carboxylic acid (cis-/trans-Cl2CA), cis-3-(2,2-dibromovinyl)-2,2-dimethylcyclo-propane-1-carboxylic acid (cis-Br2CA) and 4-fluoro-3-phenoxybenzoic acid (4F-3-PBA). Flight attendants working on disinsected planes had significantly higher urinary levels of 3-PBA, cis- and trans-Cl2CA in pre, post- and 24hr-post flight samples than those on planes which did not report having been disinsected. Urinary levels of cis-Br2CA and 4F-3-PBA did not show significant differences between the two groups. Flight attendants working on international flights connected to Australia had higher urinary levels of 3-PBA, cis- and trans-Cl2CA than those on either domestic and other international flights flying among Asia, Europe and North America. Post-disinsection duration (number of days from disinsection date to flight date) was the most significant factor affecting the urinary pyrethroid metabolites levels of 3-PBA, cis- and trans-Cl2CA of the group flying on disinsected aircraft. It was concluded that working on commercial aircrafts disinsected by pyrethroids resulted in elevated body burden of 3-PBA, cis- and trans-Cl2CA. PMID:21937269

Utility of urinary biomarkers as a diagnostic tool for early diabetic nephropathy in patients with type 2 diabetes mellitus.

PubMed

Vijay, Soorampally; Hamide, Abdoul; Senthilkumar, Gandhipuram Periyasamy; Mehalingam, Vadivelan

2018-04-12

Renal tubulo-interstitial damage has an important role in the pathogenesis of early diabetic nephropathy. Urinary biomarkers can help in the detection of early nephropathy in type 2 diabetic patients. The aim of this study was to estimate the levels of urinary neutrophil gelatinase associated lipocalin (NGAL) and cystatin-C in type 2 diabetic patients with early diabetic nephropathy & to compare them with diabetic patients without nephropathy and to correlate urinary NGAL and cystatin-C levels with microalbuminuria in them. Cross-sectional comparative study. The study was conducted on 126 patients with type 2 diabetes along with 30 control subjects attending the outpatient care department of a tertiary care teaching hospital. There were 3 study groups-diabetic patients with microalbuminuria, diabetic patients without albuminuria and control subjects who were non-diabetic without any renal disease. Details on duration of diabetes and glycemic status were obtained from the patients. Urine examination was done for subjects in all the groups to look for microalbuminuria along with estimation of NGAL and cystatin-C levels. Samples were stored at -20 °C in the deep freezer. Urinary NGAL and cystatin-C levels were significantly elevated in patients with microalbuminuria (228.18 & 3.23 ng/ml) as compared to those without albuminuria (146.12 & 2.61 ng/ml) and in control subjects (26.56 & 0.30 ng/ml). Urinary NGAL and cystatin-C levels showed a linear correlation with microalbuminuria in diabetic patients. Urinary NGAL and cystatin-C levels were increased in type 2 diabetic patients with early diabetic nephropathy as compared to patients without nephropathy. Urine NGAL and cystatin-C levels also showed a positive correlation with microalbuminuria (urine albumin-creatinine ratio) in patients with type 2 diabetes mellitus. Copyright © 2018 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Direct radioimmunoassay of urinary estrogen and pregnanediol glucuronides during the menstrual cycle

DOE Office of Scientific and Technical Information (OSTI.GOV)

Stanczyk, F.Z.; Miyakawa, I.; Goebelsmann, U.

Assays measuring immunoreactive estrone glucuronide (E/sub 1/G), estradiol-3-glucuronide (E/sub 2/-3G), estradiol-17..beta..-glucuronide (E/sub 2/-17G), estriol-3-glucuronide (E/sub 3/-3G), estriol-16..cap alpha..-glucuronide (E/sub 3/-16G), and pregnanediol-3..cap alpha..-glucuronide (Pd-3G) directly in diluted urine were developed and validated. These estrogen and pregnanediol glucuronide fractions were measured in aliquots of 24-hour and overnight samples of urine collected daily from seven women for one menstrual cycle. Urinary hormone excretion was correlated with daily serum estradiol (E/sub 2/), progesterone (P), and lutenizing hormonee (LH) levels. A sharp midcycle LH peak preceded by a preovulatory rise in serum E/sub 2/ and followed by luteal phase serum P levels were notedmore » in each of the seven apparently ovulatory cycles. Twenty-four-hour and overnight urinary excretion patterns of estrogen glucuronides were similar to those of serum E/sub 2/. Of the five estrogen glucuronide fractions tested, excretion of E/sub 2/-17G exhibited the earliest and steepest ascending slope of the preovulatory estrogen surge and correlated best with serum E/sub 2/ levels. Urinary excretion of E/sub 1/-G, E/sub 2/-3G, and E/sub 3/-16G also showed an early and steep preovulatory rise and preceded that of E/sub 3/-3G, whereas urinary excretion of E/sub 3/-3G exhibited the poorest correlation with serum E/sub 2/ concentrations. The urinary excretion of Pd-3G rose parallel to serum P levels and was markedly elevated 2 to 3 days after the midcycle LH peak in both 24-hour and overnight collections of urine. These results indicate that among the urinary estrogen conjugate fractions tested, E/sub 2/-17G is the one that most suitably predicts ovulation.« less

[RESULTS OF DUST FACTOR IN COPPER PYROMETALLURGY].

PubMed

Adrianovskiy, V I; Lipatov, G Ya; Zebzeeva, N V; Kuzmina, E A

2016-01-01

The dust entering the air of the working zone of metallurgical shops was shown to be presented by a disintegration aerosols originating in crushing and transporting ore materials and condensation occurring in the course of smelting, converting and fire-refining copper. The overwhelming majority of the grains have a size of 2.1-5.0 mm, which determines a fixed condition of the presence of given dust in the working area, its long presence in the deeper parts of the respiratory system. At the preparatory stages in the composition of the dust there are presented significant amounts of crystalline silicon dioxide possessing of the fibrogenic impact on the body. In the dust the presence of the crystalline silicon dioxide, arsenic, nickel, cadmium determines its carcinogenic hazard. The elevated dustiness of the air is noted with the reflective and especially mine melting, due to the imperfection of the technological equipment and sanitary technical devices. Autogenous smelting processes have demonstrated their hygienic advantage over outdated methods of producing blister copper mining and smelting reflectivity.

Cu self-sputtering MD simulations for 0.1-5 keV ions at elevated temperatures

NASA Astrophysics Data System (ADS)

Metspalu, Tarvo; Jansson, Ville; Zadin, Vahur; Avchaciov, Konstantin; Nordlund, Kai; Aabloo, Alvo; Djurabekova, Flyura

2018-01-01

Self-sputtering of copper under high electric fields is considered to contribute to plasma buildup during a vacuum breakdown event frequently observed near metal surfaces, even in ultra high vacuum condition in different electric devices. In this study, by means of molecular dynamics simulations, we analyze the effect of surface temperature and morphology on the yield of self-sputtering of copper with ion energies of 0.1-5 keV. We analyze all three low-index surfaces of Cu, {1 0 0}, {1 1 0} and {1 1 1}, held at different temperatures, 300 K, 500 K and 1200 K. The surface roughness relief is studied by either varying the angle of incidence on flat surfaces, or by using arbitrary roughened surfaces, which result in a more natural distribution of surface relief variations. Our simulations provide detailed characterization of copper self-sputtering with respect to different material temperatures, crystallographic orientations, surface roughness, energies, and angles of ion incidence.

Effects of acid-mine wastes on aquatic ecosystems

Treesearch

John David Parsons

1976-01-01

The Cedar Creek Basin (39th N parallel 92nd W meridian) was studied for the period June 1952 through August 1954 to observe the effects of both continuous and periodic acid effluent flows on aquatic communities. The acid strip-mine effluent contained ferric and ferrous iron, copper, lead, zinc, aluminum, magnesium, titratable acid, and elevated hydrogen ion...

Effects of nonylphenol and ethinylestradiol on copper redhorse (Moxostoma hubbsi), an endangered species.

PubMed

Maltais, Domynick; Roy, Robert L

2014-10-01

The copper redhorse, Moxostoma hubbsi, is an endangered species endemic to Quebec. The presence of contaminants, in particular endocrine disrupting chemicals (EDCs), in its habitat has been advanced as partly responsible for the reproductive difficulties encountered by the species. In the present study, immature copper redhorse were exposed to the estrogenic surfactant nonylphenol (NP; 1, 10 and 50µg/l) and the synthetic estrogen 17α-ethinylestradiol (EE2; 10ng/l) for 21 days in a flow-through system. The endpoints investigated included general health indicators (hepatosomatic index and hematocrit), thyroid hormones, sex steroids, brain aromatase activity, plasma and mucus vitellogenin (VTG), cytochrome P4501A protein expression and ethoxyresorufin-O-deethylase activity, heat shock protein 70 (HSP70) and muscle acetylcholinesterase. Exposure to 10ng EE2/l significantly increased brain aromatase activity. Exposure to 50µg NP/l resulted in a significant reduction of plasma testosterone concentrations and a significant induction of hepatic HSP70 protein expression. NP at 50µg/l also induced plasma and mucus VTG. The presence of elevated VTG levels in the surface mucus of immature copper redhorse exposed to NP, and its correlation to plasma VTG, supports the use of mucus VTG as a non-invasive biomarker to evaluate copper redhorse exposure to EDCs in the environment and contribute to restoration efforts of the species. The results of the present study indicate that exposure to high environmentally relevant concentrations of NP and EE2 can affect molecular endpoints related to reproduction in the copper redhorse. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

Fetal and neonatal iron deficiency but not copper deficiency increases vascular complexity in the developing rat brain

PubMed Central

Bastian, Thomas W.; Santarriaga, Stephanie; Nguyen, Thu An; Prohaska, Joseph R.; Georgieff, Michael K.; Anderson, Grant W.

2015-01-01

Objectives Anemia caused by nutritional deficiencies, such as iron and copper deficiencies, is a global health problem. Iron and copper deficiencies have their most profound effect on the developing fetus/infant, leading to brain development deficits and poor cognitive outcomes. Tissue iron depletion or chronic anemia can induce cellular hypoxic signaling. In mice, chronic hypoxia induces a compensatory increase in brain blood vessel outgrowth. We hypothesized that developmental anemia, due to iron or copper deficiencies, induces angiogenesis/vasculogenesis in the neonatal brain. Methods To test our hypothesis, three independent experiments were performed where pregnant rats were fed iron- or copper-deficient diets from gestational day 2 through mid-lactation. Effects on the neonatal brain vasculature were determined using qPCR to assess mRNA levels of angiogenesis/vasculogenesis-associated genes and GLUT1 immunohistochemistry (IHC) to assess brain blood vessel density and complexity. Results Iron deficiency, but not copper deficiency, increased mRNA expression of brain endothelial cell- and angiogenesis/vasculogenesis-associated genes (i.e. Glut1, Vwf, Vegfa, Ang2, Cxcl12, and Flk1) in the neonatal brain, suggesting increased cerebrovascular density. Iron deficiency also increased hippocampal and cerebral cortical blood vessel branching by 62% and 78%, respectively. Discussion This study demonstrates increased blood vessel complexity in the neonatal iron-deficient brain, which is likely due to elevated angiogenic/vasculogenic signaling. At least initially, this is probably an adaptive response to maintain metabolic substrate homeostasis in the developing iron-deficient brain. However, this may also contribute to long-term neurodevelopmental deficits. PMID:26177275

Age of Supergene oxidation and enrichment in the chilean porphyry copper province

USGS Publications Warehouse

Sillitoe, R.H.; McKee, E.H.

1996-01-01

Twenty-five samples of supergene alunite collected from deeply developed supergene profiles in porphyry copper deposits and prospects between latitudes 20?? and 27?? S in northern Chile yield K/Ar ages ranging from about 34 to 14 Ma. Therefore supergene oxidation and enrichment processes were active from the early Oligocene to the middle Miocene, a minimum of 20 m.y. Supergene activity at individual deposits lasted for at least 0.4 to 6.2 m.y. The early Oligocene supergene activity affected deposits in the Paleocene porphyry copper belt, whereas early and middle Miocene supergene processes are documented in the Early Cretaceous, Paleocene, and late Eocene to early Oligocene porphyry copper belts. Middle Miocene oxidation also affected the oldest epithermal gold-silver deposits in the Maricunga belt farther east. Supergene activity commenced no less than 11 m.y. after generation of each porphyry copper deposit because of the time required to unroof the copper-bearing parts of the system. Supergene activity throughout northern Chile ceased at -14 Ma. The geologic features of deposits and prospects and their morphotectonic positions, present latitudes, and present elevations display no obvious correlations with the supergene chronology. Exploration for major cumulative enrichment blankets should not be carried out either beneath thick sequences of piedmont gravels (?? ignimbrites) of Oligocene through middle Miocene age unless their accumulation is demonstrably late in the documented history of supergene activity, or in porphyry copper provinces, such as those of central Chile and northwestern Argentina, which formed after ??? 14 Ma. The uplift responsible for efficient cumulative copper enrichment is difficult to correlate convincingly with the brief pulses of compressive tectonism postulated for northern Chile and contiguous areas unless their effects were much more prolonged. Intensifying aridity is confirmed as the likely reason for the cessation of supergene activity in northern Chile, and tectonic uplift was its most probable cause. However, more fundamental global controls producing a period of chemical weathering followed by worldwide dessication also may have played a role.

Dietary salt loading increases nitric oxide synthesis in transgenic mice overexpressing sodium-proton exchanger.

PubMed

Kiraku, J; Nakamura, T; Sugiyama, T; Takahashi, N; Kuro-o, M; Fujii, J; Nagai, R

1999-06-01

We studied the role of nitric oxide (NO) synthesis in amelioration of blood pressure elevation during dietary salt loading in transgenic mice overexpressing sodium proton exchanger. Systolic blood pressure rose after starting salt loading only in the high-salt group of transgenic mice. However, this elevation of blood pressure was not continued. Urinary excretion of inorganic nitrite and nitrate in the high-salt group of transgenic mice was significantly higher than in the high-salt group of control mice. These results suggest that increased NO synthesis in response to salt loading is one of the anti-hypertensive mechanisms in transgenic mice overexpressing sodium proton exchanger.

Reversibility of increased intestinal permeability to 51Cr-EDTA in patients with gastrointestinal inflammatory diseases

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jenkins, R.T.; Jones, D.B.; Goodacre, R.L.

1987-11-01

Intestinal permeability in adults with inflammatory gastrointestinal diseases was investigated by measuring the 24-h urinary excretion of orally administered /sup 51/Cr-EDTA. Eighty controls along with 100 patients with Crohn's disease, 46 patients with ulcerative colitis, 20 patients with gluten-sensitive enteropathy, and 18 patients with other diseases were studied. In controls, the median 24-h excretion was 1.34%/24 h of the oral dose. Patients with Crohn's disease (median 2.96%/24 h), ulcerative colitis (median 2.12%/24 h), and untreated gluten-sensitive enteropathy (median 3.56%/24 h) had significantly elevated urinary excretion of the probe compared to controls (p less than 0.0001). Increased 24-h urinary excretion ofmore » /sup 51/Cr-EDTA had a high association with intestinal inflammation (p less than 0.0001). Test specificity and sensitivity were 96% and 57%, respectively. A positive test has a 96% probability of correctly diagnosing the presence of intestinal inflammation, whereas a negative test has a 50% probability of predicting the absence of disease.« less

The Effect of Shift Work on Urogenital Disease: a Systematic Review.

PubMed

Deng, Nanfu; Haney, Nora M; Kohn, Taylor P; Pastuszak, Alexander W; Lipshultz, Larry I

2018-05-28

Non-standard shift work schedules negatively impact the overall health of shift workers, and several studies have shown that shift work, specifically, is detrimental to urogenital health. The aims of this study are to systematically review the literature and determine the effect of shift work on the outcomes of hypogonadism, male infertility, lower urinary tract symptoms, and urogenital cancers. Recent evidence supports associations between non-standard shift work and an increase in the frequency of prostate cancer and the severity of erectile dysfunction, lower urinary tract symptoms, and hypogonadal symptoms, as well as worsening of semen parameters and fertility. These associations are strengthened by the presence of shift work sleep disorder (SWSD) which affects up to 20% of shift workers. No studies have assessed the impact of shift work on the frequency or severity of nephrolithiasis, interstitial cystitis, pelvic pain, prostatitis, or urinary tract infections. Non-standard shift work has been associated with a variety of negative health outcomes and urologic complications, especially with concurrent shift work sleep disorder. Recognition of these elevated risks among shift workers can aid in more effective screening for urologic conditions.

Lipoxygenase products in the urine correlate with renal function and body temperature but not with acute transplant rejection.

PubMed

Reinhold, Stephan W; Scherl, Thomas; Stölcker, Benjamin; Bergler, Tobias; Hoffmann, Ute; Weingart, Christian; Banas, Miriam C; Kollins, Dmitrij; Kammerl, Martin C; Krüger, Bernd; Kaess, Bernhard; Krämer, Bernhard K; Banas, Bernhard

2013-02-01

Acute transplant rejection is the leading cause of graft loss in the first months after kidney transplantation. Lipoxygenase products mediate pro- and anti-inflammatory actions and thus we aimed to correlate the histological reports of renal transplant biopsies with urinary lipoxygenase products concentrations to evaluate their role as a diagnostic marker. This study included a total of 34 kidney transplant recipients: 17 with an acute transplant rejection and 17 controls. LTE4, LTB4, 12-HETE and 15-HETE concentrations were measured by enzyme immunoassay. Urinary lipoxygenase product concentrations were not significantly changed during an acute allograft rejection. Nevertheless, LTB4 concentrations correlated significantly with the body temperature (P ≤ 0.05) 3 months after transplantation, and 12- and 15-HETE concentrations correlated significantly with renal function (P ≤ 0.05) 2 weeks after transplantation. In conclusion, our data show a correlation for LTB4 with the body temperature 3 months after transplantation and urinary 12- and 15-HETE concentrations correlate positively with elevated serum creatinine concentrations but do not predict acute allograft rejection.

Uplift and submarine formation of some Melanesian porphyry copper deposits: Stable isotope evidence

USGS Publications Warehouse

Chivas, A.R.; O'Neil, J.R.; Katchan, G.

1984-01-01

Hydrogen and oxygen isotope analyses of sericites and kaolinites from four young porphyry copper deposits (Ok Tedi (1.2 Ma) and Yandera (6.5 Ma), Papua New Guinea; Koloula (1.5 Ma), Solomon Islands; and Waisoi (<5 Ma), Fiji) indicate that the fluids from which these minerals precipitated were of mixed magmatic and non-magmatic sources. The non-magmatic component of the fluid from the island arc deposits (Koloula, Waisoi) was ocean water. For Ok Tedi, the non-magmatic component was a meteoric water with an isotopic composition different from that of the present meteoric water in the region. The isotopic signature of the former meteoric water is consistent with a surface elevation of 200 m a.s.l. or less at the time of mineralization. The deposit was later exposed and supergene kaolinitization commenced at approximately 1200 m a.s.l. Uplift and erosion has continued to the present at which time the elevation of the exposed deposit is 1800 m a.s.l. This rate of uplift is consistent with that known from other geological evidence. If the rate of uplift were approximately constant during the last 1.2 Ma, the age of supergene enrichment can be dated at approximately 0.4 Ma B.P. Similarly, influx of meteoric water at Yandera occurred when the ground surface above the deposit was at an elevation of approximately 600 m a.s.l. The deposit's present elevation is 1600 m a.s.l. In this case a total uplift of approximately 2.2 km is indicated, with removal of 1.2 km of overburden by erosion. ?? 1984.

Biochemical abnormalities in workers exposed to molybdenum dust.

PubMed

Walravens, P A; Moure-Eraso, R; Solomons, C C; Chappell, W R; Bentley, G

1979-01-01

Exposure to molybdenum in dust was measured in a molybdenite roasting plant. This exposure was accompanied by large elevations of serum ceruloplasmin and smaller increases in mean serum uric acid levels in the workers. Absorption of molybdenum from the dust was demonstrated by increases in plasma and urinary molybdenum levels. It remains necessary to demonstrate whether such exposure results in long-term health effects.

Retrospective Study of Serum Sclerostin Measurements in Bed Rest Subjects

NASA Technical Reports Server (NTRS)

Spatz, J. M.; Fields, E. E.; Yu, E. W.; Divieti, Pajevic P.; Bouxsein, M. L.; Sibonga, M. L.; Zwart, S. R.; Smith, S. M.

2011-01-01

Animal models and human studies suggest that osteocytes regulate the skeleton s response to mechanical unloading at the cellular level in part by an increase in sclerostin, an inhibitor of the anabolic Wnt pathway. However, few studies have reported changes in serum sclerostin in humans exposed to reduced mechanical loading. Thus, we determined changes in serum sclerostin and bone turnover markers in healthy adult men who participated in a controlled bed rest study. Seven healthy adult men (31 +/- 3 yrs old) underwent 90-day six-degree head down tilt bed rest at the University of Texas Medical Branch in Galveston's Institute for Translational Sciences - Clinical Research Center (ITS-CRC). Serum sclerostin, PTH, serum markers of bone turnover (bone specific alkaline phosphatase, RANKL/OPG, and osteocalcin), urinary calcium and phosphorus excretion, and 24 hour pooled urinary markers of bone resorption (NTX, DPD, PYD) were evaluated pre-bed rest (BL), bed rest day 28 (BR-28), bed rest day 60 (BR-60), and bed rest day 90 (BR-90). In addition, bone mineral density (BMD) was assessed by dual-energy X-ray absorptiometry (DXA) at BL, BR-60, and post bed rest day 5 (BR+5). Data are reported as mean +/- standard deviation. We used repeated measures ANOVA to compare baseline values to BR-28, BR-60, and BR-90. RESULTS Consistent with prior reports, BMD declined significantly (1-2% per month) at weight-bearing skeletal sites (spine, hip, femur neck, and calcaneus). Serum sclerostin levels were elevated above BL at BR-28 (+29% +/- 20%, p = 0.003), BR-60 (+42% +/- 31%, p < 0.001), and BR-90 (22% +/- 21%, p = 0.07). Serum PTH levels were reduced at BR-28 (-17% +/- 16%, p = 0.02), BR-60 (-24% +/- 14%, p = 0.03), and returned to baseline at BR-90 (-21% +/- 21%, p = 0.14). Serum bone turnover markers did not change, however urinary bone resorption markers and calcium were significantly elevated following bed rest (p < 0.01). CONCLUSION We observed an increase of serum sclerostin associated with decreased serum PTH and elevated bone resorption markers in otherwise healthy men subjected to long-term immobilization.

Evaluation of the usefulness of novel biomarkers for drug-induced acute kidney injury in beagle dogs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhou, Xiaobing; Graduate School of Peking Union Medical College, Dongcheng District, Beijing, 100730; Ma, Ben

As kidney is a major target organ affected by drug toxicity, early detection of renal injury is critical in preclinical drug development. In past decades, a series of novel biomarkers of drug-induced nephrotoxicity were discovered and verified in rats. However, limited data regarding the performance of novel biomarkers in non-rodent species are publicly available. To increase the applicability of these biomarkers, we evaluated the performance of 4 urinary biomarkers including neutrophil gelatinase-associated lipocalin (NGAL), clusterin, total protein, and N-acetyl-β-D-glucosaminidase (NAG), relative to histopathology and traditional clinical chemistry in beagle dogs with acute kidney injury (AKI) induced by gentamicin. The resultsmore » showed that urinary NGAL and clusterin levels were significantly elevated in dogs on days 1 and 3 after administration of gentamicin, respectively. Gene expression analysis further provided mechanistic evidence to support that NGAL and clusterin are potential biomarkers for the early assessment of drug-induced renal damage. Furthermore, the high area (both AUCs = 1.000) under receiver operator characteristics (ROC) curve also indicated that NGAL and clusterin were the most sensitive biomarkers for detection of gentamicin-induced renal proximal tubular toxicity. Our results also suggested that NAG may be used in routine toxicity testing due to its sensitivity and robustness for detection of tissue injury. The present data will provide insights into the preclinical use of these biomarkers for detection of drug-induced AKI in non-rodent species. - Highlights: • Urinary NGAL, clusterin and NAG levels were significantly elevated in canine AKI. • NGAL and clusterin gene expression were increased following treatment with gentamicin. • NGAL and clusterin have high specificity and sensitivity for detection of AKI.« less

Long-term, adverse genitourinary outcomes among endometrial cancer survivors in a large, population-based cohort study.

PubMed

Soisson, Sean; Ganz, Patricia A; Gaffney, David; Rowe, Kerry; Snyder, John; Wan, Yuan; Deshmukh, Vikrant; Newman, Mike; Fraser, Alison; Smith, Ken; Herget, Kimberly; Hanson, Heidi A; Wu, Yelena P; Stanford, Joseph; Werner, Theresa L; Setiawan, Veronica Wendy; Hashibe, Mia

2018-03-01

With the increasing incidence of endometrial cancer, the high survival rate, and the large number of endometrial cancer survivors, investigations of long-term genitourinary outcomes are important for the management of these outcomes among endometrial cancer survivors. Cohorts of 2648 endometrial cancer survivors diagnosed in the state of Utah between 1997 and 2012 and 10,503 general population women were identified. All ICD-9 diagnosis codes were collected from the state's two largest healthcare systems and statewide databases. Multivariate Cox regression models were used to estimate hazard ratios at 1-5years and >5-10years after endometrial cancer diagnosis for genitourinary outcomes. Endometrial cancer survivors were at elevated risk for urinary system disorders between 1 and 5years (HR: 1.64, 95% CI: 1.50-1.78) and >5-10years (HR: 1.40, 95% CI: 1.26-1.56) and genital organ disorders between 1 and 5years (HR: 1.71, 95% CI: 1.58-2.03) and >5-10years (HR: 1.33, 95% CI: 1.19-1.49). Significantly elevated risk was observed among endometrial cancer survivors for renal failure, chronic kidney disease, urinary tract infections, and nonmalignant breast conditions, persisting between >5-10years. Between 1 and 5years after cancer diagnosis, those with higher stage, higher grade, older age and treated with radiation or chemotherapy were at higher risk for urinary disorders. Endometrial cancer survivors were at higher risk for many genitourinary outcomes compared to women from the general population. This study presents evidence suggesting the necessity of increased monitoring and counseling for genitourinary disorders for endometrial cancer patients both immediately after treatment cessation and for years afterwards. Copyright © 2018 Elsevier Inc. All rights reserved.

Calcium, magnesium, and phosphorus metabolism, and parathyroid-calcitonin function during prolonged exposure to elevated CO2 concentrations on submarines.

PubMed

Messier, A A; Heyder, E; Braithwaite, W R; McCluggage, C; Peck, A; Schaefer, K E

1979-01-01

Studies of calcium and phosphorus metabolism and acid-base balance were carried out on three Fleet Ballistic Missile (FBM) submarines during prolonged exposure to elevated concentrations of CO2. The average CO2 concentration in the submarine atmosphere during patrols ranged from 0.85% to 1% CO2. In the three studies, in which 9--15 subjects participated, the urinary excretion of calcium and phosphate fell during the first three weeks to a level commensurate with a decrease in plasma calcium and increase in phosphorus. In the fourth week of one patrol, a marked increase was found in urinary calcium excretion, associated with a rise in blood PCO2 and bicarbonate. Urinary calcium excretion decreased again during the 5th to 8th week, with a secondary decrease in blood pH and plasma calcium. During the third patrol, the time course of acid-base changes corresponded well with that found during the second patrol. There was a trend toward an increase in plasma calcium between the fourth and fifth week commensurate with the transient rise in pH and bicarbonate. Plasma parathyroid and calcitonin hormone activities were measured in two patrols and no significant changes were found. Hydroxyproline excretion decreased in the three-week study and remained unchanged in the second patrol, which lasted 57 days. It is suggested that during prolonged exposure to low levels of CO2 (up to 1% CO2), calcium metabolism is controlled by the uptake and release of CO2 in the bones. The resulting phases in bone buffering, rather than renal regulation, determine acid-base balance.

Weight loss induced by chronic dapagliflozin treatment is attenuated by compensatory hyperphagia in diet-induced obese (DIO) rats.

PubMed

Devenny, James J; Godonis, Helen E; Harvey, Susan J; Rooney, Suzanne; Cullen, Mary J; Pelleymounter, Mary Ann

2012-08-01

Dapagliflozin is a potent and selective sodium glucose cotransporter-2 (SGLT2) inhibitor which promotes urinary glucose excretion and induces weight loss. Since metabolic compensation can offset a negative energy balance, we explored the potential for a compensatory physiological response to the weight loss induced by dapagliflozin. Dapagliflozin was administered (0.5-5 mpk; p.o.) to diet-induced obese (DIO) rats with or without ad libitum access to food for 38 days. Along with inducing urinary glucose excretion, chronic administration of dapagliflozin dose-dependently increased food and water intake relative to vehicle-treated controls. Despite this, it reduced body weight by 4% (relative to controls) at the highest dose. The degree of weight loss was increased by an additional 9% if hyperphagia was prevented by restricting food intake to that of vehicle controls. Neither oxygen consumption (vO2) or the respiratory exchange ratio (RER) were altered by dapagliflozin treatment alone. Animals treated with dapagliflozin and pair-fed to vehicle controls (5 mpk PF-V) showed a reduction in RER and an elevation in nonfasting β-hydroxybutyrate (BHBA) relative to ad libitum-fed 5 mpk counterparts. Fasting BHBA was elevated in the 1 mpk, 5 mpk, and 5 mpk PF-V groups. Serum glucose was reduced in the fasted, but not the unfasted state. Insulin was reduced in the non-fasted state. These data suggest that in rodents, the persistent urinary glucose excretion induced by dapagliflozin was accompanied by compensatory hyperphagia, which attenuated the weight loss induced by SGLT2 inhibition. Therefore, it is possible that dapagliflozin-induced weight loss could be enhanced with dietary intervention.

Influence of Long-Distance Bicycle Riding on Serum/Urinary Biomarkers of Prostate Cancer

PubMed Central

Heger, Zbynek; Gumulec, Jaromir; Ondrak, Ales; Skoda, Jan; Zitka, Zdenek; Cernei, Natalia; Masarik, Michal; Zitka, Ondrej; Adam, Vojtech

2016-01-01

Herein, we present a study focused on the determination of the influence of long-distance (53 km) bicycle riding on levels of chosen biochemical urinary and serum prostate cancer (PCa) biomarkers total prostate-specific antigen (tPSA), free PSA (fPSA) and sarcosine. Fourteen healthy participants with no evidence of prostate diseases, in the age range from 49–57 years with a median of 52 years, underwent physical exercise (mean race time of 150 ± 20 min, elevation increase of 472 m) and pre- and post-ride blood/urine sampling. It was found that bicycle riding resulted in elevated serum uric acid (p = 0.001, median 271.76 vs. 308.44 µmol/L pre- and post-ride, respectively), lactate (p = 0.01, median 2.98 vs. 4.8 mmol/L) and C-reactive protein (p = 0.01, 0.0–0.01 mg/L). It is noteworthy that our work supports the studies demonstrating an increased PSA after mechanical manipulation of the prostate. The subjects exhibited either significantly higher post-ride tPSA (p = 0.002, median 0.69 vs. 1.1 ng/mL pre- and post-ride, respectively) and fPSA (p = 0.028, median 0.25 vs. 0.35 ng/mL). Contrary to that, sarcosine levels were not significantly affected by physical exercise (p = 0.20, median 1.64 vs. 1.92 µmol/mL for serum sarcosine, and p = 0.15, median 0.02 µmol/mmol of creatinine vs. 0.01 µmol/mmol of creatinine for urinary sarcosine). Taken together, our pilot study provides the first evidence that the potential biomarker of PCa—sarcosine does not have a drawback by means of a bicycle riding-induced false positivity, as was shown in the case of PSA. PMID:26999116

Klotho and S100A8/A9 as Discriminative Markers between Pre-Renal and Intrinsic Acute Kidney Injury

PubMed Central

Kim, Ae Jin; Ro, Han; Kim, Hyunsook; Chang, Jae Hyun; Lee, Hyun Hee; Chung, Wookyung; Jung, Ji Yong

2016-01-01

Early detection and accurate differentiation of the cause of AKI may improve the prognosis of the patient. However, to date, there are few reliable biomarkers that can discriminate between pre-renal and intrinsic AKI. In this study, we determined whether AKI is associated with altered serum and urinary levels of Klotho, S100A8/A9 (an endogenous ligand of toll-like receptor 4), and neutrophil gelatinase-associated lipocalin (NGAL), which may allow differentiation between pre-renal and intrinsic AKI. A volume-depleted pre-renal AKI model was induced in male Sprague Dawley rats fed a low-salt diet (0.03%) without water 96 h before two intraperitoneal (IP) injections of furosemide (20 mg/kg) at a 24 h interval. In contrast, in the cisplatin-induced intrinsic AKI model, animals were given a single IP injection of cisplatin (5 mg/kg). All of the animals were euthanized 72 h after the first IP injection. Serum and urinary levels of Klotho, S100A8/A9, and NGAL were measured using an enzyme-linked immunosorbent assay. We also performed a proof-of-concept cross-sectional study to measure serum and urinary biomarkers in 61 hospitalized patients with established AKI. Compared to the intrinsic AKI group, the pre-renal AKI group showed a marked depression in urinary Klotho levels (13.21±17.32 vs. 72.97±17.96 pg/mL; P = 0.002). In addition, the intrinsic AKI group showed marked elevation of S100A8/A9 levels compared to the pre-renal AKI group (2629.97±598.05 ng/mL vs. 685.09±111.65 ng/mL; P = 0.002 in serum; 3361.11±250.86 ng/mL vs. 741.72±101.96 ng/mL; P = 0.003 in urine). There was no difference in serum and urinary NGAL levels between the pre-renal and intrinsic AKI groups. The proof-of-concept study with the hospitalized AKI patients also demonstrated decreased urinary Klotho in pre-renal AKI patients and increased urinary S100A8/A9 concentrations in intrinsic AKI patients. The attenuation of urinary Klotho and increase in urinary S100A8/A9 may allow differentiation between pre-renal and intrinsic AKI. PMID:26799323

Prostaglandins E and F in endocrine diarrheagenic syndromes.

PubMed Central

Jaffe, B M; Condon, S

1976-01-01

The role of prostaglandins in endocrine diarrheagenic syndromes was evaluated by measuring peripheral concentration of immunoreactive PGE and PGF in patients with non-endocrine diarrhea as well as those with the Zollinger-Ellison (Z-E) syndrome, MCT, carcinoid tumors and the WDHA syndrome. In 21 normals, PGE and PGF levels averaged 272 +/- 18 and 119 +/- 14 pg/ml, respectively. Twenty eight patients with diarrhea of non-endocrine origin (mainly inflammatory bowel disease) had levels indistinguishable from normal, i.e. 353 +/- 25 and 77 +/- 37 pg/ml, respectively. Among 29 patients with the Zollinger-Ellison syndrome (mean gastrin 6127 +/- 3267 pg/ml) only 2 had significantly elevated PGE levels; mean PGE levels, 382 +/- 32 pg/ml, were not significantly different from normal and did not correlate with either diarrhea or the serum gastrin concentration. In contrast, 18 of 22 patients with carcinoid tumors (mean blood serotonin concentration 1655 +/- 604 ng/ml; mean urinary excretion of 5 HIAA 66.8 +/- 16.7 mg/day) had elevated peripheral concentrations of PGE. The mean PGE level (1367 +/- 245 pg/ml) was significantly elevated (P less than 0.001). Nonetheless PGE levels did not correlate with diarrhea, blood concentrations of serotonin, or urinary indole excretion. MCT (mean serum calcitonin 24.5 +/- 6.3 ng/ml) was similarly associated with consistent (18/19) elevation in peripheral concentrations of PGE (mean 1922 +/- 541 pg/ml; P less than 0.001). Inthis syndrome, PGE levels were higher in patients with diarrhea and in those with markedly elevated serum thyrocalcitonin levels. Finally, 8 of 21 patients with the WDHA syndrome had increased levels of PGE. Although 13 of 17 patients had high levels of VIP (mean 8133 pg/ml), 2 patients had hyperprostaglandinemia in the face of normal peripheral concentrations of VIP. In one patient the serum PGE level was elevated prior to resection of the primary pancreatic neoplasm (9939 pg/ml) as well as the subsequent extirpation of a solitary hepatic metastasis (1063 pg/ml); following each procedure the diarrhea abated and the PGE level returned to normal. In none of these syndromes were mean PGF levels elevated. The study has documented hyperprostaglandinemia in some endocrine diarrheagenic syndromes and validated the usefullness of measurements of PGE in patients with unexplained diarrhea. PMID:189708

Urinary porphyrin excretion in neurotypical and autistic children.

PubMed

Woods, James S; Armel, Sarah E; Fulton, Denise I; Allen, Jason; Wessels, Kristine; Simmonds, P Lynne; Granpeesheh, Doreen; Mumper, Elizabeth; Bradstreet, J Jeffrey; Echeverria, Diana; Heyer, Nicholas J; Rooney, James P K

2010-10-01

Increased urinary concentrations of pentacarboxyl-, precopro- and copro-porphyrins have been associated with prolonged mercury (Hg) exposure in adults, and comparable increases have been attributed to Hg exposure in children with autism (AU). This study was designed to measure and compare urinary porphyrin concentrations in neurotypical (NT) children and same-age children with autism, and to examine the association between porphyrin levels and past or current Hg exposure in children with autism. This exploratory study enrolled 278 children 2-12 years of age. We evaluated three groups: AU, pervasive developmental disorder-not otherwise specified (PDD-NOS), and NT. Mothers/caregivers provided information at enrollment regarding medical, dental, and dietary exposures. Urine samples from all children were acquired for analyses of porphyrin, creatinine, and Hg. Differences between groups for mean porphyrin and Hg levels were evaluated. Logistic regression analysis was conducted to determine whether porphyrin levels were associated with increased risk of autism. Mean urinary porphyrin concentrations are naturally high in young children and decline by as much as 2.5-fold between 2 and 12 years of age. Elevated copro- (p < 0.009), hexacarboxyl- (p < 0.01) and pentacarboxyl- (p < 0.001) porphyrin concentrations were significantly associated with AU but not with PDD-NOS. No differences were found between NT and AU in urinary Hg levels or in past Hg exposure as determined by fish consumption, number of dental amalgam fillings, or vaccines received. These findings identify disordered porphyrin metabolism as a salient characteristic of autism. Hg exposures were comparable between diagnostic groups, and a porphyrin pattern consistent with that seen in Hg-exposed adults was not apparent.

Urinary vitamin D-binding protein, a novel biomarker for lupus nephritis, predicts the development of proteinuric flare.

PubMed

Go, D J; Lee, J Y; Kang, M J; Lee, E Y; Lee, E B; Yi, E C; Song, Y W

2018-01-01

Lupus nephritis (LN) is a major complication of systemic lupus erythematosus (SLE). Conventional biomarkers for assessing renal disease activity are imperfect in predicting clinical outcomes associated with LN. The aim of this study is to identify urinary protein biomarkers that reliably reflect the disease activity or predict clinical outcomes. A quantitative proteomic analysis was performed to identify protein biomarker candidates that can differentiate between SLE patients with and without LN. Selected biomarker candidates were further verified by enzyme-linked immunosorbent assay using urine samples from a larger cohort of SLE patients ( n = 121) to investigate their predictive values for LN activity measure. Furthermore, the association between urinary levels of a selected panel of potential biomarkers and prognosis of LN was assessed with a four-year follow-up study of renal outcomes. Urinary vitamin D-binding protein (VDBP), transthyretin (TTR), retinol binding protein 4 (RBP4), and prostaglandin D synthase (PTGDS) were significantly elevated in SLE patients with LN, especially in patients with active LN ( n = 21). Among them, VDBP well correlated with severity of proteinuria (rho = 0.661, p < 0.001) and renal SLE Disease Activity Index (renal SLEDAI) (rho = 0.520, p < 0.001). In the four-year follow-up, VDBP was a significant risk factor (hazard ratio 9.627, 95% confidence interval 1.698 to 54.571, p = 0.011) for the development of proteinuric flare in SLE patients without proteinuria ( n = 100) after adjustments for multiple confounders. Urinary VDBP correlated with proteinuria and renal SLEDAI, and predicted the development of proteinuria.

Hypertension and Hyperglycemia Synergize to Cause Incipient Renal Tubular Alterations Resulting in Increased NGAL Urinary Excretion in Rats

PubMed Central

Blázquez-Medela, Ana M.; García-Sánchez, Omar; Blanco-Gozalo, Víctor; Quiros, Yaremi; Montero, María J.; Martínez-Salgado, Carlos; López-Novoa, José M.; López-Hernández, Francisco J.

2014-01-01

Background Hypertension and diabetes are the two leading causes of chronic kidney disease (CKD) eventually leading to end stage renal disease (ESRD) and the need of renal replacement therapy. Mortality among CKD and ESRD patients is high, mostly due to cardiovascular events. New early markers of risk are necessary to better anticipate the course of the disease, to detect the renal affection of additive risk factors, and to appropriately handle patients in a pre-emptive and personalized manner. Methods Renal function and NGAL urinary excretion was monitored in rats with spontaneous (SHR) or L-NAME induced hypertension rendered hyperglycemic (or not as controls). Results Combination of hypertension and hyperglycemia (but not each of these factors independently) causes an increased urinary excretion of neutrophil gelatinase-associated lipocalin (NGAL) in the rat, in the absence of signs of renal damage. Increased NGAL excretion is observed in diabetic animals with two independent models of hypertension. Elevated urinary NGAL results from a specific alteration in its tubular handling, rather than from an increase in its renal expression. In fact, when kidneys of hyperglycaemic-hypertensive rats are perfused in situ with Krebs-dextran solution containing exogenous NGAL, they excrete more NGAL in the urine than hypertensive rats. We also show that albuminuria is not capable of detecting the additive effect posed by the coexistence of these two risk factors. Conclusions Our results suggest that accumulation of hypertension and hyperglycemia induces an incipient and quite specific alteration in the tubular handling of NGAL resulting in its increased urinary excretion. PMID:25148248

Hypertension and hyperglycemia synergize to cause incipient renal tubular alterations resulting in increased NGAL urinary excretion in rats.

PubMed

Blázquez-Medela, Ana M; García-Sánchez, Omar; Blanco-Gozalo, Víctor; Quiros, Yaremi; Montero, María J; Martínez-Salgado, Carlos; López-Novoa, José M; López-Hernández, Francisco J

2014-01-01

Hypertension and diabetes are the two leading causes of chronic kidney disease (CKD) eventually leading to end stage renal disease (ESRD) and the need of renal replacement therapy. Mortality among CKD and ESRD patients is high, mostly due to cardiovascular events. New early markers of risk are necessary to better anticipate the course of the disease, to detect the renal affection of additive risk factors, and to appropriately handle patients in a pre-emptive and personalized manner. Renal function and NGAL urinary excretion was monitored in rats with spontaneous (SHR) or L-NAME induced hypertension rendered hyperglycemic (or not as controls). Combination of hypertension and hyperglycemia (but not each of these factors independently) causes an increased urinary excretion of neutrophil gelatinase-associated lipocalin (NGAL) in the rat, in the absence of signs of renal damage. Increased NGAL excretion is observed in diabetic animals with two independent models of hypertension. Elevated urinary NGAL results from a specific alteration in its tubular handling, rather than from an increase in its renal expression. In fact, when kidneys of hyperglycaemic-hypertensive rats are perfused in situ with Krebs-dextran solution containing exogenous NGAL, they excrete more NGAL in the urine than hypertensive rats. We also show that albuminuria is not capable of detecting the additive effect posed by the coexistence of these two risk factors. Our results suggest that accumulation of hypertension and hyperglycemia induces an incipient and quite specific alteration in the tubular handling of NGAL resulting in its increased urinary excretion.

The Effect of Feeding Purified versus Chow Diet on Bone Changes Produced by Hindlimb Suspension of Female Rats

NASA Technical Reports Server (NTRS)

Tou, Janet; Arnaud, Sara B.; Grindeland, Richard; Wade, Charles

2004-01-01

Spaceflight simulation studies use chow diets while spaceflight studies use a semi-purified &et. To determine whether the differences in these diets would affect the changes in unweighted bone, we compared the effects of purified vs chow diet on bone parameters, urinary calcium, plasma estradiol, and urinary corticosterone (CORT) in sexually mature female Sprague-Dawley rats. Rats fed purified AIN-93G or chow diet were kept ambulatory (AMB) or subjected to a spaceflight simulation model of unweighted hindlimbs (HLS) for 38 days. Body mass of treatment groups was similar although food intake and caloric density of the diets differed. Both HLS diet groups showed similar decreases in bone mineral content and mechanical strength in unweighted femurs compared to AMB (p<0.05). However, femur length was lower (p<0.05) in the chow-fed than AIN-93G fed groups. Urinary calcium excretion was greater in chow than AIN-93G fed rats, consistent with the higher level of calcium in the diet. Plasma estradiol was lower in HLS than in AMB fed AIN-93G, but similar in HLS and AMB chow fed groups. Femur mineral content was related to plasma estradiol (r(sup 2) =0.91, p<0.00l). Urinary CORT excretion was increased during initial HLS and elevated in HLS/chow-fed rats. Diets did not appear to affect the osteopenia induced by unweighting, but effects on bone growth, calcium excretion, plasma estradiol and urinary CORT do not support the view that these diets can by used interchangeably in bone studies.

Urinary neutrophil gelatinase-associated lipocalin, a biomarker for systemic inflammatory response syndrome in patients with nephrolithiasis.

PubMed

Zhu, Wei; Liu, Min; Wang, Guang-Chun; Che, Jian-Ping; Xu, Yun-Fei; Peng, Bo; Zheng, Jun-Hua

2014-03-01

The objective of this study was to determine the diagnostic value of neutrophil gelatinase-associated lipocalin (NGAL), C-reactive protein (CRP), and procalcitonin (PCT) in the prognosis of patients presenting with the systemic inflammatory response syndrome (SIRS) with nephrolithiasis. Urine NGAL protein levels were measured by enzyme-linked immunosorbent assay in 87 patients presenting with nephrolithiasis who were diagnosed as SIRS. Additionally, 52 patients presenting with nephrolithiasis but without urinary tract infection and 30 healthy controls were also included in the study. Levels of serum CRP and PCT were also taken into consideration. Median urinary NGAL levels were significantly increased in the SIRS cohorts compared with nephrolithiasis without urinary tract infection patients (4.28 ng/mL versus 2.69 ng/mL, P < 0.001), and NGAL was markedly elevated even in the early stage of SIRS (3.23 ng/mL versus 2.69 ng/mL, P < 0.001). According to the receiver-operating characteristic analysis, NGAL demonstrated a high diagnostic value compared with either PCT or CRP. In the later stage of SIRS, NGAL remained a highly sensitive (76.8%) and specific (86.5%) diagnostic marker compared with either PCT or CRP. Moreover, the area under the curves of NGAL (0.822) were also superior to those seen in either PCT (0.657) or CRP (0.761). Urinary NGAL is a highly sensitive and specific predictor of SIRS for patients presenting with nephrolithiasis. Further study of NGAL as a reliable biomarker of SIRS is required. Copyright © 2014 Elsevier Inc. All rights reserved.

Zinc, copper, and nitrogen balances during bed rest and fluoride supplementation in healthy adult males

NASA Technical Reports Server (NTRS)

Krebs, J. M.; Schneider, V. S.; LeBlanc, A. D.

1988-01-01

The effects of bed rest and fluoride supplementation on zinc, copper, and nitrogen balances and Zn and Cu serum levels were measured in 15 healthy males. Subjects aged 19-54 y remained on a metabolic research ward for 10 wk. During weeks 1-5, subjects were ambulatory. During wks 6-10 they remained in continuous bed rest. During weeks 3-10 nine subjects received 10 or 20 mg F/d as sodium fluoride. Daily urine and weekly fecal composites were made and biweekly fasting blood samples were taken. Dietary intakes were 1.40 +/- 0.17 mg Cu/d (22.0 +/- 2.7 mumol Cu/d), 10.82 +/- 0.49 mg Zn/d (165.6 +/- 7.6 mumol Zn/d), and 14.27 +/- 0.23 g N/d (1019 +/- 16 mmol N/d). Bed rest increased urinary Zn and N excretions and fecal Zn excretions and decreased Zn balance (p less than 0.05) whereas Cu balance was unchanged. During bed rest, F supplementation increased Zn and N balances compared with untreated control subjects (p less than 0.05). These results are compatible with bone and muscle atrophy during bed rest and increased bone formation with F supplementation.

Ignition and Combustion Characteristics of Pure Bulk Metals: Normal-Gravity Test Results

NASA Technical Reports Server (NTRS)

Abbud-Madrid, A.; Fiechtner, G. J.; Branch, M. C.; Daily, J. W.

1994-01-01

An experimental apparatus has been designed for the study of bulk metal ignition under elevated, normal and reduced gravity environments. The present work describes the technical characteristics of the system, the analytical techniques employed, the results obtained from the ignition of a variety of metals subjected to normal gravity conditions and the first results obtained from experiments under elevated gravity. A 1000 W xenon short-arc lamp is used to irradiate the top surface of a cylindrical metal specimen 4 mm in diameter and 4 mm high in a quiescent pure-oxygen environment at 0.1 MPa. Iron, titanium, zirconium, magnesium, zinc, tin, and copper specimens are investigated. All these metals exhibit ignition and combustion behavior varying in strength and speed. Values of ignition temperatures below, above or in the range of the metal melting point are obtained from the temperature records. The emission spectra from the magnesium-oxygen gas-phase reaction reveals the dynamic evolution of the ignition event. Scanning electron microscope and x-ray spectroscopic analysis provide the sequence of oxide formation on the burning of copper samples. Preliminary results on the effect of higher-than-normal gravity levels on the ignition of titanium specimens is presented.

Growth and physiological responses of some Capsicum frutescens varieties to copper stress

NASA Astrophysics Data System (ADS)

Jadid, Nurul; Maziyah, Rizka; Nurcahyani, Desy Dwi; Mubarokah, Nilna Rizqiyah

2017-06-01

Copper (Cu) is an essential micronutrient participating in various physiological processes. However, excessive uptake of this micronutrient could potentially affect plant growth and development as well as plant productivity. In this present work, growth and physiological responses of some Capsicum frustescens varieties to Cu stress were determined. Three C. frutescens varieties used in this work were var. Bara, CF 291, and Genie. In addition, these varieties were treated with different concentration of Cu (0, 30, 70, and 120 ppm). The growth and physiological responses measured in this work included plant height, root length, malondialdehyde (MDA), and chlorophyll. The result showed that all varieties tested relatively displayed plant growth reduction including plant height and root length. Likewise, an increase of MDA level, a major bioindicator for oxidative damage was also found in all varieties following exposure to elevated Cu concentration. Finally, the chlorophyll content was also affected indicated by a decreased amount of chlorophyll, especially in var. CF291. The overall results demonstrated that elevated Cu concentration might decrease C. frutescens productivity where among the three varieties tested, var CF 291 seemed to be the most sensitive varieties to Cu stress.

Surface-water/ground-water interaction of the Spokane River and the Spokane Valley/Rathdrum Prairie aquifer, Idaho and Washington

USGS Publications Warehouse

Caldwell, Rodney R.; Bowers, Craig L.

2003-01-01

Although trace-element concentrations sometimes exceeded aquatic-life criteria in the water of the Spokane River and were elevated above national median values in the bed sediment, trace-element concentrations of all river and ground-water samples were at levels less than U.S. Environmental Protection Agency drinking-water standards. The Spokane River appears to be a source of cadmium, copper, zinc, and possibly lead in the near-river ground water. Dissolved cadmium, copper, and lead concentrations generally were less than 1 microgram per liter (µg/L) in the river water and ground water. During water year 2001, dissolved zinc concentrations were similar in water from near-river wells (17-71 µg/L) and the river water (22-66 µg/L), but were less than detection levels in wells farther from the river. Arsenic, found to be elevated in ground water in parts of the aquifer, does not appear to have a river source. Although the river does influence the ground-water chemistry in proximity to the river, it does not appear to adversely affect the ground-water quality to a level of human-health concern.

Geomorphology and river dynamics of the lower Copper River, Alaska

USGS Publications Warehouse

Brabets, Timothy P.; Conaway, Jeffrey S.

2009-01-01

Located in south-central Alaska, the Copper River drains an area of more than 24,000 square miles. The average annual flow of the river near its mouth is 63,600 cubic feet per second, but is highly variable between winter and summer. In the winter, flow averages approximately 11,700 cubic feet per second, and in the summer, due to snowmelt, rainfall, and glacial melt, flow averages approximately 113,000 cubic feet per second, an order of magnitude higher. About 15 miles upstream of its mouth, the Copper River flows past the face of Childs Glacier and enters a large, broad, delta. The Copper River Highway traverses this flood plain, and in 2008, 11 bridges were located along this section of the highway. The bridges cross several parts of the Copper River and in recent years, the changing course of the river has seriously damaged some of the bridges.Analysis of aerial photography from 1991, 1996, 2002, 2006, and 2007 indicates the eastward migration of a channel of the Copper River that has resulted in damage to the Copper River Highway near Mile 43.5. Migration of another channel in the flood plain has resulted in damage to the approach of Bridge 339. As a verification of channel change, flow measurements were made at bridges along the Copper River Highway in 2005–07. Analysis of the flow measurements indicate that the total flow of the Copper River has shifted from approximately 50 percent passing through the bridges at Mile 27, near the western edge of the flood plain, and 50 percent passing through the bridges at Mile 36–37 to approximately 5 percent passing through the bridges at Mile 27 and 95 percent through the bridges at Mile 36–37 during average flow periods.The U.S. Geological Survey’s Multi-Dimensional Surface-Water Modeling System was used to simulate water-surface elevation and velocity, and to compute bed shear stress at two areas where the Copper River is affecting the Copper River Highway. After calibration, the model was used to examine the effects that betterments, such as guide banks or bridge extensions, would have on flow conditions and to provide sound conceptual information that could help decide if a proposed betterment will work or determine potential problems that need to be addressed for a particular betterment. The ability of the model to simulate these hydraulic conditions was constrained by the accuracy and level of channel geometry detail, which is constantly changing in the lower Copper River.

Tyrosinase inhibition due to interaction of homocyst(e)ine with copper: the mechanism for reversible hypopigmentation in homocystinuria due to cystathionine beta-synthase deficiency.

PubMed

Reish, O; Townsend, D; Berry, S A; Tsai, M Y; King, R A

1995-07-01

Deficiency of cystathionine beta-synthase (CBS) is a genetic disorder of transsulfuration resulting in elevated plasma homocyst(e)ine and methionine and decreased cysteine. Affected patients have multisystem involvement, which may include light skin and hair. Reversible hypopigmentation in treated homocystinuric patients has been infrequently reported, and the mechanism is undefined. Two CBS-deficient homocystinuric patients manifested darkening of their hypopigmented hair following treatment that decreased plasma homocyst(e)ine. We hypothesized that homocyst(e)ine inhibits tyrosinase, the major pigment enzyme. The activity of tyrosinase extracted from pigmented human melanoma cells (MNT-1) that were grown in the presence of homocysteine was reduced in comparison to that extracted from cells grown without homocysteine. Copper sulfate restored homocyst(e)ine-inhibited tyrosinase activity when added to the culture cell media at a proportion of 1.25 mol of copper sulfate per 1 mol of DL-homocysteine. Holo-tyrosinase activity was inhibited by adding DL-homocysteine to the assay reaction mixture, and the addition of copper sulfate to the reaction mixture prevented this inhibition. Other tested compounds, L-cystine and betaine did not affect tyrosinase activity. Our data suggest that reversible hypopigmentation in homocystinuria is the result of tyrosinase inhibition by homocyst(e)ine and that the probable mechanism of this inhibition is the interaction of homocyst(e)ine with copper at the active site of tyrosinase.

Tyrosinase inhibition due to interaction of homocyst(e)ine with copper: the mechanism for reversible hypopigmentation in homocystinuria due to cystathionine beta-synthase deficiency.

PubMed Central

Reish, O; Townsend, D; Berry, S A; Tsai, M Y; King, R A

1995-01-01

Deficiency of cystathionine beta-synthase (CBS) is a genetic disorder of transsulfuration resulting in elevated plasma homocyst(e)ine and methionine and decreased cysteine. Affected patients have multisystem involvement, which may include light skin and hair. Reversible hypopigmentation in treated homocystinuric patients has been infrequently reported, and the mechanism is undefined. Two CBS-deficient homocystinuric patients manifested darkening of their hypopigmented hair following treatment that decreased plasma homocyst(e)ine. We hypothesized that homocyst(e)ine inhibits tyrosinase, the major pigment enzyme. The activity of tyrosinase extracted from pigmented human melanoma cells (MNT-1) that were grown in the presence of homocysteine was reduced in comparison to that extracted from cells grown without homocysteine. Copper sulfate restored homocyst(e)ine-inhibited tyrosinase activity when added to the culture cell media at a proportion of 1.25 mol of copper sulfate per 1 mol of DL-homocysteine. Holo-tyrosinase activity was inhibited by adding DL-homocysteine to the assay reaction mixture, and the addition of copper sulfate to the reaction mixture prevented this inhibition. Other tested compounds, L-cystine and betaine did not affect tyrosinase activity. Our data suggest that reversible hypopigmentation in homocystinuria is the result of tyrosinase inhibition by homocyst(e)ine and that the probable mechanism of this inhibition is the interaction of homocyst(e)ine with copper at the active site of tyrosinase. Images Figure 1 PMID:7611281

EXAMINATION OF THE OXIDATION PROTECTION OF ZINC COATINGS FORMED ON COPPER ALLOYS AND STEEL SUBSTRATES

DOE Office of Scientific and Technical Information (OSTI.GOV)

Papazoglou, M.; Chaliampalias, D.; Vourlias, G.

2010-01-21

The exposure of metallic components at aggressive high temperature environments, usually limit their usage at similar application because they suffer from severe oxidation attack. Copper alloys are used in a wide range of high-quality indoor and outdoor applications, statue parts, art hardware, high strength and high thermal conductivity applications. On the other hand, steel is commonly used as mechanical part of industrial set outs or in the construction sector due to its high mechanical properties. The aim of the present work is the examination of the oxidation resistance of pack cementation zinc coatings deposited on copper, leaded brass and steelmore » substrates at elevated temperature conditions. Furthermore, an effort made to make a long-term evaluation of the coated samples durability. The oxidation results showed that bare substrates appear to have undergone severe damage comparing with the coated ones. Furthermore, the mass gain of the uncoated samples was higher than this of the zinc covered ones. Particularly zinc coated brass was found to be more resistant to oxidation conditions in which it was exposed as it has the lower mass gain as compared to the bare substrates and zinc coated copper. Zinc coated steel was also proved to be more resistive than the uncoated steel.« less

Trace-metal leaching from plumbing materials exposed to acidic ground water in three areas of the coastal plain of New Jersey

USGS Publications Warehouse

Kish, G.R.; Macy, J.A.; Mueller, R.T.

1987-01-01

The U.S. Geological Survey analyzed trace metal concentrations in tap water from domestic wells in newly constructed homes in Berkeley Township, Ocean County and Galloway Township, Atlantic County, N. J. The potable water distribution systems in all of the homes sampled are constructed primarily of copper with lead-based solder points. Home water treatment is used in Berkeley Township but not in Galloway Township. Tap water was collected after the water had been standing in the pipes overnight. In Berkeley, 6 to 11 samples exceeded both the U.S. Environmental Protection Agency 's primary drinking water regulation (DWR) for lead (50 microgram/L) and the secondary drinking water regulation (SDWR) for copper (1,000 microgram/L). In Galloway, 12 of 14 samples exceeded the DWR for lead and 13 of 14 exceeded the SDWR for copper. After collecting the standing-water samples, the water was left running for 15 minutes and a second sample was collected. None of the running-water samples exceeded the regulations for lead or copper. Available data suggest a correlation between the residence time of soft, acidic groundwater in new home plumbing systems and elevated trace-metal concentrations in drinking water derived from domestic wells within the New Jersey Coastal Plain. (USGS)

Evaluating the role of ion composition on the toxicity of copper to Ceriodaphnia dubia in very hard waters.

PubMed

Gensemer, Robert W; Naddy, Rami B; Stubblefield, William A; Hockett, J Russell; Santore, Robert; Paquin, Paul

2002-09-01

The mitigating effect of increasing hardness on metal toxicity is reflected in water quality criteria in the United States over the range of 25-400 mgl(-1) (as CaCO(3)). However, waters in the arid west of the US frequently exceed 400 mgl(-1) hardness, and the applicability of hardness-toxicity relationships in these waters is unknown. Acute toxicity tests with Ceriodaphnia dubia were conducted at hardness levels ranging from approximately 300 to 1,200 mgl(-1) using reconstituted waters that mimic two natural waters with elevated hardness: (1) alkaline desert southwest streams (Las Vegas Wash, NV), and (2) low alkalinity waters from a CaSO(4)-treated mining effluent in Colorado. The moderately-alkaline EPA synthetic hard water was also included for comparison. Copper toxicity did not consistently vary as a function of hardness, but likely as a function of other water quality characteristics (e.g., alkalinity or other correlated factors). The hardness equations used in regulatory criteria, therefore, may not provide an accurate level of protection against copper toxicity in all types of very hard waters. However, the mechanistic Biotic ligand model generally predicted copper toxicity within +/-2X of observed EC(50) values, and thus may be more useful than hardness for modifying water quality criteria.

Urinary Concentrations of Bisphenols and Their Association with Biomarkers of Oxidative Stress in People Living Near E-Waste Recycling Facilities in China.

PubMed

Zhang, Tao; Xue, Jingchuan; Gao, Chuan-zi; Qiu, Rong-liang; Li, Yan-xi; Li, Xiao; Huang, Ming-zhi; Kannan, Kurunthachalam

2016-04-05

In this study, concentrations of bisphenol A (BPA) and seven other bisphenols (BPs) were measured in urine samples collected from people living in and around e-waste dismantling facilities, and in matched reference population from rural and urban areas in China. BPA, bisphenol S (BPS), and bisphenol F (BPF) were frequently detected (detection frequencies: > 90%) in urine samples collected from individuals who live near e-waste facilities, with geometric mean (GM) concentrations of 2.99 (or 3.75), 0.361 (or 0.469), and 0.349 (or 0.435) ng/mL (or μg/g Cre), respectively; the other five BPs were rarely found in urine samples, regardless of the sampling location. The urinary concentrations of BPA and BPF, but not BPS, were significantly higher in individuals from e-waste recycling locations than did individuals from a rural reference location. Our findings indicated that e-waste dismantling activities contribute to human exposure to BPA and BPF. 8-Hydroxy-2'-deoxyguanosine (8-OHdG) was measured in urine as a marker of oxidative stress. In the e-waste dismantling location, urinary 8-OHdG was significantly and positively correlated (p < 0.001) with urinary BPA and BPS, but not BPF; a similar correlation was also observed in reference sites. These findings suggest that BPA and BPS exposures are associated with elevated oxidative stress.

The Yanomami Indians in the INTERSALT Study.

PubMed

Mancilha-Carvalho, Jairo de Jesus; Souza e Silva, Nelson Albuquerque

2003-03-01

To study the distribution and interrelationship among constitutional and biochemical variables with blood pressure (BP) in an population of Yanomami indians. To compare these findings with those of other populations. The Yanomami indians were part of the INTERSALT, a study comprising 10,079 males and females, aged from 20 to 59 years, belonging to 52 populations in 32 countries in Africa, the Americas, Asia, and Europe. Each of the 52 centers was required to accrue 200 individuals, 25 participants in each age group. The variables analyzed were as follows: age, sex, arterial BP, urinary sodium and potassium excretion (24-hour urine), body mass index, and alcohol ingestion. The findings in the Yanomami population were as follows: a very low urinary sodium excretion (0.9 mmol/24 h); mean systolic and diastolic BP levels of 95.4 mmHg and 61.4 mmHg, respectively; no cases of hypertension or obesity; and they have no knowledge of alcoholic beverages. Their BP levels do not elevate with age. The urinary sodium excretion relates positively and the urinary potassium excretion relates negatively to systolic BP. This correlation was maintained even when controlled for age and body mass index. A positive relation between salt intake and blood pressure was detected in the analysis of a set of diverse populations participating in the INTERSALT Study, including populations such as the Yanomami Indians. The qualitative observation of their lifestyle provided additional information.

[Assessment of dietary intake and urinary excretion of sodium and potassium in adults].

PubMed

Cornejo, Karen; Pizarro, Fernando; Atalah, Eduardo; Galgani, José E

2014-06-01

Hypertension is associated with elevated sodium and low potassium intakes. The determination of sodium and potassium intake by dietary records is inaccurate, being its measurement from 24-h urine collection the reference method. To determine urinary sodium and potassium excretion in adults. To compare dietary sodium and potassium intake and their excretion from an isolated urine sample against the reference method. Seventy healthy adults aged 35 ± 8 years with a body mass index 25 ± 2 kg/m² (36 women) were studied. Urine was collected over 24 h, including an isolated urine sample taken in fasting conditions. Additionally, three 24-h dietary records were performed. Reported sodium and potassium intake was 2,720 ± 567 and 1,068 ± 433 mg/day, respectively. In turn, urinary excretion of sodium and potassium was 4,770 ± 1,532 and 1,852 ± 559 mg/day, respectively. These latter values were significantly higher than those obtained by dietary records. Furthermore, the urinary sodium and potassium excretion estimated from an isolated urine sample was 4,839 ± 1,355 and 1,845 ± 494 mg/day, respectively. These values were similar to those obtained with a 24 h urine collection. Dietary records underestimated electrolyte intake when compared with the reference method. Using an isolated urine sample to estimate electrolyte intake may be a reliable alternative.

Urinary leukotriene E(4) levels are not increased prior to high-altitude pulmonary edema.

PubMed

Bärtsch, P; Eichenberger, U; Ballmer, P E; Gibbs, J S; Schirlo, C; Oelz, O; Mayatepek, E

2000-05-01

To examine whether increased urinary cysteinyl-leukotriene E(4) (LTE(4)) excretion, which has been found to be elevated in patients presenting with high-altitude pulmonary edema (HAPE), precedes edema formation. Prospective studies in a total of 12 subjects with susceptibility to HAPE. In a chamber study, seven subjects susceptible to HAPE and five nonsusceptible control subjects were exposed for 24 h to an altitude of 450 m (control day), and exposed for 20 h to 4,000 m after slow decompression over 4 h. In a field study, prospective measurements at low and high altitude were performed in five subjects developing HAPE at 4,559 m. Mountaineers with a radiographically documented history of HAPE and control subjects who did not develop HAPE with identical high-altitude exposure. 24-h urine collections. In the hypobaric chamber, none of the subjects developed HAPE. The 24-h urinary LTE(4) did not differ between HAPE susceptible and control subjects, nor between hypoxia and normoxic control day. In the field study, urinary LTE(4) was not increased in subjects with HAPE compared to values obtained prior to HAPE at high altitude and during 2 control days at low altitude. These data do not provide evidence that cysteinyl-leukotriene-mediated inflammatory response is associated with HAPE susceptibility or the development of HAPE within the context of our studies.

Metal endowment reflected in chemical composition of silicates and sulfides of mineralized porphyry copper systems, Urumieh-Dokhtar magmatic arc, Iran

NASA Astrophysics Data System (ADS)

Zarasvandi, Alireza; Rezaei, Mohsen; Raith, Johann G.; Pourkaseb, Houshang; Asadi, Sina; Saed, Madineh; Lentz, David R.

2018-02-01

The present work attempts to discriminate between the geochemical features of magmatic-hydrothermal systems involved in the early stages of mineralization in high grade versus low grade porphyry copper systems, using chemical compositions of silicate and sulfide minerals (i.e., plagioclase, biotite, pyrite and chalcopyrite). The data indicate that magmatic plagioclase in all of the porphyry copper systems studied here has high An% and Al content with a significant trend of evolution toward AlAl3SiO8 and □Si4O8 endmembers, providing insight into the high melt water contents of the parental magmas. Comparably, excess Al and An% in the high grade deposits appears to be higher than that of selected low grade deposits, representing a direct link between the amounts of exsolving hydrothermal fluids and the potential of metal endowment in porphyry copper deposits (PCDs). Also, higher Al contents accompanied by elevated An% are linked to the increasing intensity of disruptive alteration (phyllic) in feldspars from the high grade deposits. As calculated from biotite compositions, chloride contents are higher in the exsolving hydrothermal fluids that contributed to the early mineralization stages of highly mineralized porphyry systems. However, as evidenced by scattered and elevated log (fH2O)/(fHF) and log (fH2O)/(fHCl) values, chloride contents recorded in biotite could be influenced by post potassic fluids. Geothermometry of biotite associated with the onset of sulfide mineralization indicates that there is a trend of increasing temperature from high grade to low grade porphyry systems. Significantly, this is coupled with a sharp change in copper content of pyrite assemblages precipitated at the early stages of mineralization such that Cu decreased with increasing temperature. Based on EMPA and detailed WDS elemental mapping, trace elements do not exhibit complex compositional zoning or solid solution in the sulfide structure. Nevertheless, significant amounts of Cu and Au are contained in pyrite assemblages as micro- to nano-sized inclusions, especially in the high grade fertile porphyry deposits. However, unexpectedly high concentrations of Te, Se, and Re may be associated with early stage of sulfide mineralization, especially when there is no epithermal lithocap. This may highlight the significance of trace metals partitioning in the sulfides formed at the early stages of mineralization in PCDs.

Controlled copper ion release from phosphate-based glasses improves human umbilical vein endothelial cell survival in a reduced nutrient environment.

PubMed

Stähli, Christoph; Muja, Naser; Nazhat, Showan N

2013-02-01

The success of tissue engineering is dependent on rapid scaffold vascularization after engraftment. Copper ions are well known to be angiogenic but exhibit cytotoxicity at elevated doses. The high sensitivity to copper concentration underlines the need of a controlled release mechanism. This study investigated the effect of copper ions released from phosphate-based glasses (PGs) on human umbilical vein endothelial cells (HUVECs) under standard growth conditions (SGC), as well as in a reduced nutrient environment (RNE) with decreased bovine serum and growth factor concentrations to approximate conditions in the core of large volume scaffolds where nutrient diffusion is limited. Initially, HUVECs were exposed to a range of CuCl(2) concentrations in order to identify an optimal response in terms of their metabolism, viability, and apoptotic activity. Under SGC, HUVEC metabolic activity and viability were reduced in a dose-dependent manner in the presence of 0.44-12 ppm Cu(2+). In contrast, HUVEC death induced by the RNE was delayed by an optimal dose of 4 ppm Cu(2+), which was associated with a down-regulation of apoptosis as evidenced by caspase-3/7 activity. Copper ion release from soluble PGs of the formulation 50P(2)O(5)-30CaO-(20-x)Na(2)O-xCuO [mol%] (x=0, 1, 5 and 10) demonstrated a controllable increase with CuO content. The presence of 4 ppm copper ions released from the 10% CuO PG composition reproduced the delay in HUVEC death in the RNE, suggesting the potential of these materials to extend survival of transplanted endothelial cells in large volume scaffolds.

Effects of acidic recharge on groundwater at the St. Kevin Gulch site, Leadville, Colorado

USGS Publications Warehouse

Paschke, S.S.; Harrison, W.J.; Walton-Day, K.

2001-01-01

The acid rock drainage-affected stream of St. Kevin Gulch recharges the Quaternary sand and gravel aquifer of Tennessee Park, near Leadville, Colorado, lowering pH and contributing iron, cadmium, copper, zinc and sulphate to the ground-water system. Dissolved metal mobility is controlled by the seasonal spring runoff as well as oxidation/reduction (redox) reactions in the aquifer. Oxidizing conditions occur in the unconfined portions of the aquifer whilst sulphate-reducing conditions are found down gradient where semi-confined groundwater flow occurs beneath a natural wetland. Iron-reducing conditions occur in the transition from unconfined to semi-confined groundwater flow. Dissolved iron concentrations are low to not detectable in the alluvial fan recharge zone and increase in a down gradient direction. The effects of low-pH, metal-rich recharge are pronounced during low-flow in the fall when there is a defined area of low pH groundwater with elevated concentrations of dissolved zinc, cadmium, copper and sulphate adjacent to St. Kevin Gulch. Dissolved metal and sulphate concentrations in the recharge zone are diluted during spring runoff, although the maximum concentrations of dissolved zinc, cadmium, copper and sulphate occur at selected down gradient locations during high flow. Dissolved zinc, cadmium and copper concentrations are low to not detectable, whereas dissolved iron concentrations are greatest, in groundwater samples from the sulphate-reducing zone. Attenuation of zinc, cadmium and copper beneath the wetland suggests sulphide mineral precipitation is occurring in the semi-confined aquifer, in agreement with previous site investigations and saturation index calculations. Adsorption of dissolved zinc, cadmium and copper onto iron hydroxides is a minor attenuation process due to the low pH of the groundwater system.

Thiamine and its phosphate esters in relation to cardiometabolic risk factors in Saudi Arabs.

PubMed

Al-Daghri, Nasser M; Al-Attas, Omar S; Alkharfy, Khalid M; Alokail, Majed S; Abd-Alrahman, Sherif H; Sabico, Shaun

2013-09-23

Thiamine deficiency has suggested to be linked to several insulin-resistance complications. In this study, we aim to associate circulating thiamine levels among cardiometabolic parameters in an Arab cohort using a simple, sensitive, rapid and selective high-performance liquid chromatography (HPLC) method that has recently been developed. A total of 236 randomly selected, consenting Saudi adult participants (166 males and 70 females) were recruited and screened for the presence of the metabolic syndrome (MetS) using the modified National Cholesterol Education Program-Adult Treatment Panel III definition. Blood thiamine and its derivatives were quantified using HPLC. A total of 140 participants (53.9%) had MetS. The levels of thiamine and its derivatives of those with MetS were not significantly different from those without. However, hypertensive subjects had significantly higher urinary thiamine (P = 0.03) as well as significantly lower levels of thiamine diphosphate (TDP) (P = 0.01) and total thiamine (P = 0.02) than the normotensive subjects, even after adjusting for age and body mass index (BMI). Furthermore, age- and BMI-matched participants with elevated blood glucose levels had significantly lower levels of thiamine monophosphate (P = 0.020), TDP (P < 0.001) and total thiamine (P < 0.001) and significantly elevated levels of urinary thiamine (P = 0.005) compared to normoglycemic participants. Low thiamine levels are associated with elevated blood glucose and hypertension in Saudi adults. Determination of thiamine status may be considered and corrected among patients with, or at high risk for, MetS, but the question whether thiamine deficiency correction translates to improved cardiometabolic status needs further longitudinal investigation.

Relations of benthic macroinvertebrates to concentrations of trace elements in water, streambed sediments, and transplanted bryophytes and stream habitat conditions in nonmining and mining areas of the upper Colorado River basin, Colorado, 1995-98

USGS Publications Warehouse

Mize, Scott V.; Deacon, Jeffrey R.

2002-01-01

Intensive mining activity and highly mineralized rock formations have had significant impacts on surface-water and streambed-sediment quality and aquatic life within the upper reaches of the Uncompahgre River in western Colorado. A synoptic study by the U.S. Geological Survey National Water-Quality Assessment Program was completed in the upper Uncompahgre River Basin in 1998 to better understand the relations of trace elements (with emphasis on aluminum, arsenic, copper, iron, lead, and zinc concentrations) in water, streambed sediment, and aquatic life. Water-chemistry, streambed-sediment, and benthic macroinvertebrate samples were collected during low-flow conditions between October 1995 and July 1998 at five sites on the upper Uncompahgre River, all downstream from historical mining, and at three sites in drainage basins of the Upper Colorado River where mining has not occurred. Aquatic bryophytes were transplanted to all sites for 15 days of exposure to the water column during which time field parameters were measured and chemical water-quality and benthic macroinvertebrate samples were collected. Stream habitat characteristics also were documented at each site. Certain attributes of surface-water chemistry among streams were significantly different. Concentrations of total aluminum, copper, iron, lead, and zinc in the water column and concentrations of dissolved aluminum, copper, and zinc were significantly different between nonmining and mining sites. Some sites associated with mining exceeded Colorado acute aquatic-life standards for aluminum, copper, and zinc and exceeded Colorado chronic aquatic-life standards for aluminum, copper, iron, lead, and zinc. Concentrations of copper, lead, and zinc in streambed sediments were significantly different between nonmining and mining sites. Generally, concentrations of arsenic, copper, lead, and zinc in streambed sediments at mining sites exceeded the Canadian Sediment Quality Guidelines probable effect level (PEL), except at two mining sites where concentrations of copper and zinc were below the PEL. Concentrations of arsenic, copper, iron, and lead in transplanted bryophytes were significantly different between nonmining and mining sites. Bioconcentration factors calculated for 15-day exposure using one-half of the minimum reporting level were significantly different between nonmining and mining sites. In general, concentrations of trace elements in streambed sediment and transplanted bryophytes were more closely correlated than were the concentrations of trace elements in the water column with streambed sediments or concentrations in the water column with transplanted bryophytes. Stream habitat was rated as optimal to suboptimal using the U.S. Environmental Protection Agency Rapid Bioassessment Protocols for all sites in the study area. Generally, stream habitat conditions were similar at nonmining compared to mining sites and were suitable for diverse macroinvertebrate communities. All study sites had optimal instream habitat except two mining sites with suboptimal instream habitat because of disturbances in stream habitat. The benthic macroinvertebrate community composition at nonmining sites and mining sites differed. Mining sites had significantly lower total abundance of macroinvertebrates, fewer numbers of taxa, and lower dominance of Ephemeroptera (mayflies), Plecoptera (stoneflies), and Trichoptera (caddisflies), and a larger percentage of tolerant species than did nonmining sites. The predominance of Baetis sp. (mayflies), Hydropsychidae (caddisflies), and large percentage of Orthocladiinae chironomids (midges) at mining sites indicated that these species may be tolerant to elevated trace-element concentrations. The absence of Heptageniidae (mayflies), Chloroperlidae (stoneflies), and Rhyacophila sp. (caddisflies) at mining sites indicated that these species may be sensitive to elevated trace-element concentrations. Comparison of field parameters and

Challenges in the Management of Mucopolysaccharidosis Type II (Hunter's Syndrome) in a Developing Country: a Case Report.

PubMed

Rasheeedah, Ibraheem; Patrick, Oladele; Abdullateef, AbdulAzeez; Mohammed, Abdulkadri; Sherifat, Katibi; Gbadebo, Ibraheem

2015-07-01

Mucopolysaccharidosis type II (Hunter's syndrome) is an X-linked chromosomal storage disorder due to deficiency of the lysosomal enzyme iduronate-2-sulfatase with patients rarely living till adulthood. Failure to identify patients early could contribute to an increased morbidity as identified in this case report. An eight year old patient with Hunter's syndrome identified five years after disease onset with severe cardiovascular complications exemplifies the challenges faced in resource-limited countries towards making diagnosis and treatment of rare conditions. Elevated urinary glycosaminoglycans levels or a strong clinical suspicion of Hunter's syndrome, as identified in the index case, is a prerequisite for enzyme activity testing. Urinary mucopolysaccharide(MPS) level was 69.6 mg/mmol(normal range is 0.0 - 11.6 mg/mmol), and the confirming MPS electrophoresis analysis showed elevated heparan sulphate in the urine sample. Enzyme activity testing, with absent or very low iduronate-2-sulfatase activity, is diagnostic. However, the scarce availability and high cost of these tests is another constraint in making a diagnosis. Identification and management of mucopolysaccharidosis type II pose a problem in resource-constrained countries due to late presentation, lack of facility for diagnosis and treatment, cost and expertise required for the management.

Metabolism of /sup 90/Sr and other elements in man, April 1, 1976--March 31, 1977 (extended without additional funding to March 31, 1978) and renewal proposal, April 1, 1978--March 31, 1979

DOE Office of Scientific and Technical Information (OSTI.GOV)

Spencer, H.

1977-01-01

Trace element studies of cadmium, copper, zinc, lead, manganese, and nickel were carried out under strictly controlled dietary conditions in adult males during different calcium intakes. Complete metabolic balances of the trace elements listed above were determined in each 6-day metabolic period for several weeks by analyzing the constant diet and the urinary and fecal excretions of these naturally occurring elements, using atomic absorption spectroscopy. Strontium-90 metabolism studies in man were carried out in order to complete previously initiated investigations. Publications and presentations of papers derived from studies carried out during the current contract period are listed.

Intravesical foreign body–induced bladder calculi resulting in obstructive renal failure

PubMed Central

Kamal, Fadi; Clark, Aaron T.D.; Lavallée, Luke Thomas; Roberts, Matthew; Watterson, James

2008-01-01

We report the case of a 30-year-old man who presented with obstructive renal failure and urosepsis due to bladder outlet–obstructing bladder calculi that formed around 3 copper wires that were self-inserted into his urinary bladder 15 years previously. We present the evaluation, imaging and management of the unique complications resulting from the self-insertion of an intra-vesical foreign body. Our patient’s case was unique for 2 reasons. First, the length of time (15 yr) from foreign body insertion to presentation is the longest interval reported in the literature. Second, this is the first report of bladder calculi induced by the insertion of a foreign body that resulted in obstructive renal failure. PMID:18953457

Experimental and ab Initio Study of Catena(bis(μ2-iodo)-6-methylquinoline-copper(I)) under Pressure: Synthesis, Crystal Structure, Electronic, and Luminescence Properties.

PubMed

Aguirrechu-Comerón, Amagoia; Hernández-Molina, Rita; Rodríguez-Hernández, Plácida; Muñoz, Alfonso; Rodríguez-Mendoza, Ulises R; Lavín, Vı́ctor; Angel, Ross J; Gonzalez-Platas, Javier

2016-08-01

Copper(I) iodine compounds can exhibit interesting mechanochromic and thermochromic luminescent properties with important technological applications. We report the synthesis and structure determination by X-ray diffraction of a new polymeric staircase copper(I) iodine compound catena(bis(μ2-iodo)-6-methylquinoline-copper(I), [C10H9CuIN]. The structure is composed of isolated polymeric staircase chains of copper-iodine coordinated to organic ligands through Cu-N bonds. High pressure X-ray diffraction to 6.45 GPa shows that the material is soft, with a bulk modulus K0 = 10.2(2)GPa and a first derivative K'0 = 8.1(3), typical for organometallic compounds. The unit-cell compression is very anisotropic with the stiffest direction [302] arising from a combination of the stiff CuI ladders and the shear of the planar quinolone ligands over one another. Full structure refinements at elevated pressures show that pressures reduce the Cu···Cu distances in the compound. This effect is detected in luminescence spectra with the appearance of four sub-bands at 515, 600, 647, and 712 nm above 3.5 GPa. Red-shifts are observed, and they are tentatively associated with interactions between copper(I) ions due to the shortening of the Cu···Cu distances induced by pressure, below twice the van der Waals limit (2.8 Å). Additionally, ab initio simulations were performed, and they confirmed the structure and the results obtained experimentally for the equation of state. The simulation allowed the band structure and the electronic density of states of this copper(I) iodine complex to be determined. In particular, the band gap decreases slowly with pressure in a quadratic way with dEg/dP = -0.011 eV/GPa and d(2)Eg/dP(2) = 0.001 eV/GPa(2).

Wilson's Disease: a challenge of diagnosis. The 5-year experience of a tertiary centre.

PubMed

Gheorghe, Liana; Popescu, Irinel; Iacob, Speranta; Gheorghe, Cristian; Vaidan, Roxana; Constantinescu, Alexandra; Iacob, Razvan; Becheanu, Gabriel; Angelescu, Corina; Diculescu, Mircea

2004-09-01

Because molecular diagnosis is considered impractical and no patognomonic features have been described, diagnosis of Wilson's disease (WD) using clinical and biochemical findings is still challenging. We analysed predictive factors for the diagnosis in 55 patients with WD diagnosed in our centre between 1st January 1999 and 1st April 2004. All patients presented predominant liver disease classified as: 1) asymptomatic, found incidentally, 2) chronic hepatitis or cirrhosis, or 3) fulminant hepatic failure. Diagnosis was considered as classic (two out of the three following criteria: 1) serum ceruloplasmin < 20 mg/dl, 2) the presence of Kayser-Fleischer rings and/or 3) hepatic copper > 250 mg/g dry weight liver tissue), and non-classic (clinical manifestations plus laboratory parameters suggesting impaired copper metabolism). The association between the predictive factors and non-classic diagnosis was assessed based on the level of statistical significance (p value<0.05) associated with the chi-squared test in contingency tables. Multivariate analysis was performed by logistic regression using SPSS 10. There were 31 males (56.3%) and 24 females (43.7%) with the mean age at diagnosis of 20.92 +/- 9.97 years (4-52 years); 51 patients (92.7%) were younger than 40 years. Asymptomatic WD was diagnosed in 14 patients (25.4%), chronic liver disease due to WD in 29 patients (52.8%) and fulminant hepatic failure in 12 patients (21.8%). The classic diagnosis was made in 32 patients (58.18%). In the univariate analysis the non-classic diagnosis was associated with: age>18 years (p=0.03), increased copper excretion (p<0.0001), Coombs-negative hemolysis (p=0.03), absence of neurological manifestations (p<0.0001). Multivariate analysis identified age over 18 years, increased urinary copper, and isolated hepatic involvement as independent predictors. In clinical practice, WD should be considered also in patients who do not fulfil classic criteria. Independent factors associated with non-classic diagnosis were age over 18 years, increased cupruresis and isolated liver disease.

Idiopathic orthostatic hypotension: Recent data (eleven cases) and review of the literature

NASA Technical Reports Server (NTRS)

Ninet, J.; Annat, G.; Boisson, D.; Holzhapfel, L.; Vincent, M.; Peyrin, L.; Michel, D.; Schott, B.; Devic, M.; Levrat, R.

1981-01-01

Eight cases of Shy-Drager syndrome and three of Bradbury-Eggleston idiopathic orthostatic hypotension were examined. In all cases, examination of circulatory reflexes showed major dysfunction of the sympathetic vasoconstrictor system. Anomalies in the vagal cardiomoderator system were less constant. Normal urinary elimination of catecholamines was recorded daily. Characteristically, no elevation of blood or urine norepinephrine levels were found in orthostatism. Insulin hypoglycemia normally raised urinary adrenalin elimination in three of ten patients. Plasma dopa-beta-hydroxylase activity was normal. Renin-angiotensin-aldosterone system showed variable activity at basal state but usually rose during orthostatism. On the average, very low homovanillic acid levels were found in cerebrospinal fluid before and after probenecid; hydroxyindolacetic acid was normal. Cerebral autoregulation had deteriorated in two of four cases. Physiopathologically the two clinical types are indistinguishable with or without central neurological signs.

Role of body mass index in school-aged children with lower urinary tract dysfunction: Does weight classification predict treatment outcome?

PubMed

Arlen, Angela M; Cooper, Christopher S; Leong, Traci

2017-10-01

Lower urinary tract (LUT) dysfunction comprises a large percentage of pediatric urology referrals. Childhood obesity is a major health concern, and has been associated with voiding symptoms. We assessed the impact of body mass index (BMI) on treatment outcomes of children presenting with LUT or bladder-bowel dysfunction (BBD). Children aged 5-17 years diagnosed with non-neurogenic LUT dysfunction and no prior urologic diagnoses were identified. Patient demographics including BMI, lower urinary tract symptoms, constipation, medical and psychologic comorbidities, imaging, and treatment outcomes were evaluated. BMI was normalized by age and gender according to percentiles: underweight < 5th, healthy 5th to <85th, overweight 85th to <95th, and obese > 95th percentile. Uni- and multivariate analyses were performed to identify predictors of treatment response. During an 18-month period, 100 children (54 girls, 46 boys) met the inclusion criteria. The mean age at diagnosis was 7.7 ± 2.4 years, and mean length of follow-up 15.3 ± 13.1 months. Sixty-nine patients were a normal weight, 22 were overweight, and nine were obese. Fifteen percent of the children had complete treatment response, 63% partial response, and 22% non-response. On univariate analysis, children with elevated BMI (p = 0.04) or history of urinary tract infection (p = 0.01) were statistically more likely to not respond to treatment. Controlling for all other variables, children with BMI > 85th percentile had 3.1 times (95% CI 1.11-8.64; p = 0.03) increased odds of treatment failure (Table). BBD management includes implementation of a bowel program and timed voiding regimen, with additional treatment modalities tailored on the basis of the prevailing symptoms. We observed that school-aged children with a BMI ≥ 85th percentile were over three times more likely to experience treatment failure when controlling for all other patient characteristics including constipation and a history of urinary tract infection. Limitations of the study include the relatively small sample size, lack of uroflow with electromyography to confirm the presence or the absence of detrusor sphincter dyssynergia, and inconsistent anticholinergic dosing. Nearly one-third of school-aged children presenting to our institution with LUT or BBD were overweight or obese when normalized for age and gender. Children with LUT dysfunction and elevated BMI are significantly less likely to experience treatment response. Copyright © 2017 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Human biomonitoring of chromium and nickel from an experimental exposure to manual metal arc welding fumes of low and high alloyed steel.

PubMed

Bertram, Jens; Brand, Peter; Schettgen, Thomas; Lenz, Klaus; Purrio, Ellwyn; Reisgen, Uwe; Kraus, Thomas

2015-05-01

The uptake and elimination of metals from welding fumes is currently not fully understood. In the Aachen Workplace Simulation Laboratory (AWSL) it is possible to investigate the impact of welding fumes on human subjects under controlled exposure conditions. In this study, the uptake and elimination of chromium or chromium (VI) respectively as well as nickel was studied in subjects after exposure to the emissions of a manual metal arc welding process using low or high alloyed steel. In this present study 12 healthy male non-smokers, who never worked as welders before, were exposed for 6h to welding fumes of a manual metal arc welding process. In a three-fold crossover study design, subjects were exposed in randomized order to either clean air, emissions from welding low alloyed steel, and emissions from welding high alloyed steel. Particle mass concentration of the exposure aerosol was 2.5mg m(-3). The content of chromium and nickel in the air was determined by analysing air filter samples on a high emission scenario. Urine analysis for chromium and nickel was performed before and after exposure using methods of human biomonitoring. There were significantly elevated chromium levels after exposure to welding fumes from high alloyed steel compared to urinary chromium levels before exposure to high alloyed welding fumes, as well as compared to the other exposure scenarios. The mean values increased from 0.27 µg l(-1) to 18.62 µg l(-1). The results were in good agreement with already existing correlations between external and internal exposure (German exposure equivalent for carcinogenic working materials EKA). The variability of urinary chromium levels was high. For urinary nickel no significant changes could be detected at all. Six-hour exposure to 2.5mg m(-3) high alloyed manual metal arc welding fumes lead to elevated urinary chromium levels far higher (7.11-34.16 µg l(-1)) than the German biological exposure reference value (BAR) of 0.6 µg l(-1) directly after exposure. On the other hand mean urinary nickel concentrations slightly increased, but did not exceed background levels due to lower bioavailability. We could underline with our single exposure experiment that a welding work related chromium exposure can be measured immediately after the work shift, while the same is not possible for nickel exposure due to lower nickel bioavailability. The data provide useful information for real occupational welding work places. © The Author 2014. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.

Constitutive response of passivated copper films to thermal cycling

NASA Astrophysics Data System (ADS)

Shen, Y.-L.; Ramamurty, U.

2003-02-01

The thermomechanical behavior of passivated thin copper films is studied. Stresses in copper films of thickness ranging from 125 to 1000 nm, deposited on quartz or silicon substrates and passivated with silicon oxide, were measured using the curvature method. The thermal cycling spans a temperature range from -196 to 600 °C. The measured mechanical behavior was found to be rate insensitive within the heating/cooling rate range of 5-25 °C/min. It was observed that the passivated films do not exhibit a significant stress relaxation at elevated temperatures that is normally found in unpassivated films. Furthermore, a significant strain hardening during the course of thermal loading was noted. Simple continuum plasticity analyses show that the experimentally measured stress-temperature response can only be rationalized with a kinematic hardening model. Analytical procedures for extracting the constitutive properties of the films that were developed on the basis of such a model are presented. The initial yield strength is higher and tends to be less temperature dependent in thinner films. The strain hardening rate is found to increase with decreasing film thickness.

Irradiation effects in tungsten-copper laminate composite

DOE PAGES

Garrison, L. M.; Katoh, Yutai; Snead, Lance L.; ...

2016-09-19

Tungsten-copper laminate composite has shown promise as a structural plasma-facing component as compared to tungsten rod or plate. The present study evaluated the tungsten-copper composite after irradiation in the High Flux Isotope Reactor (HFIR) at temperatures of 410–780 °C and fast neutron fluences of 0.02–9.0 × 10 25 n/m 2, E > 0.1 MeV, 0.0039–1.76 displacements per atom (dpa) in tungsten. Tensile tests were performed on the composites, and the fracture surfaces were analyzed with scanning electron microscopy. Before irradiation, the tungsten layers had brittle cleavage failure, but the overall composite had 15.5% elongation at 22 °C. After only 0.0039more » dpa this was reduced to 7.7% elongation, and no ductility was observed after 0.2 dpa at all irradiation temperatures when tensile tested at 22 °C. In conclusion, tor elevated temperature tensile tests after irradiation, the composite only had ductile failure at temperatures where the tungsten was delaminating or ductile.« less

Cytotoxicity and genotoxicity of nano - and microparticulate copper oxide: role of solubility and intracellular bioavailability.

PubMed

Semisch, Annetta; Ohle, Julia; Witt, Barbara; Hartwig, Andrea

2014-02-13

Nano- or microscale copper oxide particles (CuO NP, CuO MP) are increasingly applied as catalysts or antimicrobial additives. This increases the risk of adverse health effects, since copper ions are cytotoxic under overload conditions. The extra- and intracellular bioavailability of CuO NP and CuO MP were explored. In addition, different endpoints related to cytotoxicity as well as direct and indirect genotoxicity of the copper oxides and copper chloride (CuCl2) were compared. Comprehensively characterized CuO NP and CuO MP were analysed regarding their copper ion release in model fluids. In all media investigated, CuO NP released far more copper ions than CuO MP, with most pronounced dissolution in artificial lysosomal fluid. CuO NP and CuCl2 caused a pronounced and dose dependent decrease of colony forming ability (CFA) in A549 and HeLa S3 cells, whereas CuO MP exerted no cytotoxicity at concentrations up to 50 μg/mL. Cell death induced by CuO NP was at least in part due to apoptosis, as determined by subdiploid DNA as well as via translocation of the apoptosis inducing factor (AIF) into the cell nucleus. Similarly, only CuO NP induced significant amounts of DNA strand breaks in HeLa S3 cells, whereas all three compounds elevated the level of H2O2-induced DNA strand breaks. Finally, all copper compounds diminished the H2O2-induced poly(ADP-ribosyl)ation, catalysed predominantly by poly(ADP-ribose)polymerase-1 (PARP-1); here, again, CuO NP exerted the strongest effect. Copper derived from CuO NP, CuO MP and CuCl2 accumulated in the soluble cytoplasmic and nuclear fractions of A549 cells, yielding similar concentrations in the cytoplasm but highest concentrations in the nucleus in case of CuO NP. The results support the high cytotoxicity of CuO NP and CuCl2 and the missing cytotoxicity of CuO MP under the conditions applied. For these differences in cytotoxicity, extracellular copper ion levels due to dissolution of particles as well as differences in physicochemical properties of the particles like surface area may be of major relevance. Regarding direct and indirect genotoxicity, especially the high copper content in the cell nucleus derived after cell treatment with CuO NP appears to be decisive.

Cytotoxicity and genotoxicity of nano - and microparticulate copper oxide: role of solubility and intracellular bioavailability

PubMed Central

2014-01-01

Background Nano- or microscale copper oxide particles (CuO NP, CuO MP) are increasingly applied as catalysts or antimicrobial additives. This increases the risk of adverse health effects, since copper ions are cytotoxic under overload conditions. Methods The extra- and intracellular bioavailability of CuO NP and CuO MP were explored. In addition, different endpoints related to cytotoxicity as well as direct and indirect genotoxicity of the copper oxides and copper chloride (CuCl2) were compared. Results Comprehensively characterized CuO NP and CuO MP were analysed regarding their copper ion release in model fluids. In all media investigated, CuO NP released far more copper ions than CuO MP, with most pronounced dissolution in artificial lysosomal fluid. CuO NP and CuCl2 caused a pronounced and dose dependent decrease of colony forming ability (CFA) in A549 and HeLa S3 cells, whereas CuO MP exerted no cytotoxicity at concentrations up to 50 μg/mL. Cell death induced by CuO NP was at least in part due to apoptosis, as determined by subdiploid DNA as well as via translocation of the apoptosis inducing factor (AIF) into the cell nucleus. Similarly, only CuO NP induced significant amounts of DNA strand breaks in HeLa S3 cells, whereas all three compounds elevated the level of H2O2-induced DNA strand breaks. Finally, all copper compounds diminished the H2O2-induced poly(ADP-ribosyl)ation, catalysed predominantly by poly(ADP-ribose)polymerase-1 (PARP-1); here, again, CuO NP exerted the strongest effect. Copper derived from CuO NP, CuO MP and CuCl2 accumulated in the soluble cytoplasmic and nuclear fractions of A549 cells, yielding similar concentrations in the cytoplasm but highest concentrations in the nucleus in case of CuO NP. Conclusions The results support the high cytotoxicity of CuO NP and CuCl2 and the missing cytotoxicity of CuO MP under the conditions applied. For these differences in cytotoxicity, extracellular copper ion levels due to dissolution of particles as well as differences in physicochemical properties of the particles like surface area may be of major relevance. Regarding direct and indirect genotoxicity, especially the high copper content in the cell nucleus derived after cell treatment with CuO NP appears to be decisive. PMID:24520990

Process for recovering uranium

DOEpatents

MacWood, G. E.; Wilder, C. D.; Altman, D.

1959-03-24

A process useful in recovering uranium from deposits on stainless steel liner surfaces of calutrons is presented. The deposit is removed from the stainless steel surface by washing with aqueous nitric acid. The solution obtained containing uranium, chromium, nickel, copper, and iron is treated with an excess of ammonium hydroxide to precipitnte the uranium, iron, and chromium and convert the nickel and copper to soluble ammonio complexions. The precipitated material is removed, dried and treated with carbon tetrachloride at an elevated temperature of about 500 to 600 deg C to form a vapor mixture of UCl/ sub 4/, UCl/sub 5/, FeCl/sub 3/, and CrCl/sub 4/. The UCl/sub 4/ is separated from this vapor mixture by selective fractional condensation at a temperature of about 500 to 400 deg C.

PROCESS FOR RECOVERING URANIUM

DOEpatents

MacWood, G.E.; Wilder, C.D.; Altman, D.

1959-03-24

A process is described for recovering uranium from deposits on stainless steel liner surfaces of calutrons. The deposit is removed from the stainless steel surface by washing with aqueous nitric acid. The solution obtained containing uranium, chromium, nickels copper, and iron is treated with excess of ammonium hydroxide to precipitatc the uranium, irons and chromium and convert thc nickel and copper to soluble ammonia complexions. The precipitated material is removed, dried, and treated with carbon tetrachloride at an elevated temperature of about 500 to 600 deg C to form a vapor mixture of UCl/sub 4/, UCl/sub 5/, FeCl/ sub 3/, and CrCl/sub 4/. The UCl/sub 4/ is separated from this vapor mixture by selective fractional condensation at a temprrature of about 300 to400 deg C.

Benzoin Radicals as Reducing Agent for Synthesizing Ultrathin Copper Nanowires.

PubMed

Cui, Fan; Dou, Letian; Yang, Qin; Yu, Yi; Niu, Zhiqiang; Sun, Yuchun; Liu, Hao; Dehestani, Ahmad; Schierle-Arndt, Kerstin; Yang, Peidong

2017-03-01

In this work, we report a new, general synthetic approach that uses heat driven benzoin radicals to grow ultrathin copper nanowires with tunable diameters. This is the first time carbon organic radicals have been used as a reducing agent in metal nanowire synthesis. In-situ temperature dependent electron paramagnetic resonance (EPR) spectroscopic studies show that the active reducing agent is the free radicals produced by benzoins under elevated temperature. Furthermore, the reducing power of benzoin can be readily tuned by symmetrically decorating functional groups on the two benzene rings. When the aromatic rings are modified with electron donating (withdrawing) groups, the reducing power is promoted (suppressed). The controllable reactivity gives the carbon organic radical great potential as a versatile reducing agent that can be generalized in other metallic nanowire syntheses.

Clinical results from first use of prostate stent as fiducial for radiotherapy of prostate cancer.

PubMed

Carl, Jesper; Nielsen, Jane; Holmberg, Mats; Larsen, Erik Hoejkjaer; Fabrin, Knud; Fisker, Rune V

2011-05-01

A clinical feasibility study using a removable prostate stent as fiducial for image-guided radiotherapy (IGRT) of localized prostate cancer (PC). The study included patients with local or locally advanced PC. The clinical target volume (CTV) was outlined on magnetic resonance (MR) images co-registered to planning computer tomography (CT) images. Daily online IGRT was delivered using the stent as fiducial. Risk of migration was estimated using multiple MR. Acute urinary toxicity was scored using the international prostate symptom score (IPSS). Late gastro-intestinal (GI) and genito-urinary (GU) toxicity was scored using the Radio Therapy Oncology Group (RTOG) score, biochemical failure (BF) was defined as an elevation of prostate specific antigen (PSA) above nadir plus 2 ng/ml after radiotherapy. One hundred men were enrolled in the study. Ninety completed radiotherapy with the stent as fiducial. No migration of the stent was seen, but three cases of dislocation of the stent to the bladder were observed. Acute urinary toxicity based on IPSS was comparable to toxicity in patients who had gold markers (GM) as fiducials. Removal of the stent was associated with a high frequency of urinary retention. Late GI and GU toxicity and BF were comparable to those of other studies, but longer observation time is needed. This study reports the first clinical results of using a prostate stent as fiducial. No migration of the stent observed. Dislocation of the stent to the urinary bladder was observed in three cases, requiring removal of the stent and insertion of a new fiducial. Acute toxicity during radiotherapy evaluated from IPSS was comparable to toxicity in patients with GM. Removal of the stent was associated with a high frequency of post procedural urinary retention. Late toxicity and BF were comparable to those of other studies, though longer observation time is needed.

Cadmium body burden and increased blood pressure in middle-aged American Indians: the Strong Heart Study.

PubMed

Franceschini, N; Fry, R C; Balakrishnan, P; Navas-Acien, A; Oliver-Williams, C; Howard, A G; Cole, S A; Haack, K; Lange, E M; Howard, B V; Best, L G; Francesconi, K A; Goessler, W; Umans, J G; Tellez-Plaza, M

2017-03-01

Cadmium (Cd) is an environmental pollutant that has been associated with cardiovascular disease in populations, but the relationship of Cd with hypertension has been inconsistent. We studied the association between urinary Cd concentrations, a measure of total body burden, and blood pressure in American Indians, a US population with above national average Cd burden. Urinary Cd was measured using inductively coupled plasma mass spectrometry, and adjusted for urinary creatinine concentration. Among 3714 middle-aged American Indian participants of the Strong Heart Study (mean age 56 years, 41% male, 67% ever-smokers, 23% taking antihypertensive medications), urinary Cd ranged from 0.01 to 78.48 μg g -1 creatinine (geometric mean=0.94 μg g -1 ) and it was correlated with smoking pack-year among ever-smokers (r 2 =0.16, P<0.0001). Participants who were smokers were on average light-smokers (mean 10.8 pack-years), and urinary Cd was similarly elevated in light- and never-smokers (geometric means of 0.88 μg g -1 creatinine for both categories). Log-transformed urinary Cd was significantly associated with higher systolic blood pressure in models adjusted for age, sex, geographic area, body mass index, smoking (ever vs never, and cumulative pack-years) and kidney function (mean blood pressure difference by lnCd concentration (β)=1.64, P=0.002). These associations were present among light- and never-smokers (β=2.03, P=0.002, n=2627), although not significant among never-smokers (β=1.22, P=0.18, n=1260). Cd was also associated with diastolic blood pressure among light- and never-smokers (β=0.94, P=0.004). These findings suggest that there is a relationship between Cd body burden and increased blood pressure in American Indians, a population with increased cardiovascular disease risk.

Cadmium body burden and increased blood pressure in middle-aged American Indians: the Strong Heart Study

PubMed Central

Franceschini, Nora; Fry, Rebecca; Balakrishnan, Poojitha; Navas-Acien, Ana; Oliver-Williams, Clare; Howard, Annie G; Cole, Shelley A; Haack, Karin; Lange, Ethan M.; Howard, Barbara V.; Best, Lyle G; Francesconi, Kevin A.; Goessler, Walter; Umans, Jason G; Tellez-Plaza, Maria

2016-01-01

Cadmium is an environmental pollutant that has been associated with cardiovascular disease in populations, but the relationship of cadmium with hypertension has been inconsistent. We studied the association between urinary cadmium concentrations, a measure of total body burden, and blood pressure in American Indians, a U.S. population with above national average cadmium burden. Urinary cadmium (Cd) was measured using inductively coupled plasma mass spectrometry, and adjusted for urinary creatinine concentration. Among 3,714 middle-aged American Indian participants of the Strong Heart Study (mean age 56 years, 41% male, 67% ever-smokers, 23% taking anti-hypertensive medications), urinary Cd ranged from 0.01 to 78.48 μg/g creatinine (geometric mean=0.94 μg/g) and it was correlated with smoking pack-year among ever-smokers (r2=0.16, P<0.0001). Participants who were smokers were on average light smokers (mean 10.8 pack-years), and urinary Cd was similarly elevated in light- and never-smokers (geometric means of 0.88 μg/g creatinine for both categories). Log-transformed urinary Cd was significantly associated with higher systolic blood pressure in models adjusted for age, sex, geographic area, body mass index, smoking (ever vs. never, and cumulative pack-years) and kidney function (mean blood pressure difference by lnCd concentration [β]=1.64, P=0.002). These associations were present among light- and never-smokers (β=2.03, P=0.002, n=2,627), although not significant among never-smokers (β=1.22, P=0.18, n=1,260). Cd was also associated with diastolic blood pressure among light- and never-smokers (β=0.94, P=0.004). These findings suggest there is a relationship between cadmium body burden and increased blood pressure in American Indians, a population with increased cardiovascular disease risk. PMID:27629244

Prolonged winter undernutrition and the interpretation of urinary allantoin:creatinine ratios in white-tailed deer

USGS Publications Warehouse

DelGiudice, Glenn D.; Kerr, Ken D.; Mech, L. David; Seal, Ulysses S.

2000-01-01

The urinary allantoin:creatinine (A:C) ratio (expressed in micromoles of allantoin to micromoles of creatinine) has shown potential as an index of recent winter energy intake in preliminary controlled studies of elk (Cervus elaphus) involving mild condition deterioration (up to 11% loss of body mass). To ensure reliable nutritional assessments of free-ranging cervids by measuring A:C ratios of urine in snow, it is essential to extend this work. We assessed the effect of moderate and severe winter nutritional restriction on urinary A:C ratios of captive white-tailed deer (Odocoileus virginianus) that lost up to 32% body mass and related these ratios to metabolizable energy intake (MEI), body-mass loss, and other reported nutritional indicators. Deer in the control group were fed a low-protein, low-energy diet ad libitum, whereas deer in the treatment group were fed restricted amounts of the same diet. MEI was below the winter maintenance requirement for all deer, but was lower (P = 0.029) in treatment deer than in control deer. Percent body-mass loss differed between the two groups as the study progressed, and represented the full range of physiological tolerance (0-32% loss). Mean A:C ratios of control deer, which lost up to 17.4% body mass, showed a slight increasing (P = 0.086) trend, whereas initially similar A:C ratios of severely restricted deer increased (P = 0.0002) markedly by the eighth week (0.52 vs. 0.09 µmol:µmol). The urinary A:C ratio was not related (P = 0.839) to recent (2 days prior to urine sampling) MEI, but there was a marginally significant relation (r2 = 0.42, P = 0.110) between the A:C ratio and cumulative percent mass loss. The urinary A:C ratio was directly related to urinary urea nitrogen:creatinine (r2 = 0.59, P < 0.0001) and 3-methylhistidine:creatinine (r2 = 0.43, P < 0.0001) ratios. This study confirms that elevated and increasing A:C ratios may be due either to increasing energy intake or to accelerated tissue catabolism and increased endogenous contributions to urinary allantoin excretion.

Sensitivity and specificity of a single emergency department measurement of urinary neutrophil gelatinase-associated lipocalin for diagnosing acute kidney injury.

PubMed

Nickolas, Thomas L; O'Rourke, Matthew J; Yang, Jun; Sise, Meghan E; Canetta, Pietro A; Barasch, Nicholas; Buchen, Charles; Khan, Faris; Mori, Kiyoshi; Giglio, James; Devarajan, Prasad; Barasch, Jonathan

2008-06-03

A single serum creatinine measurement cannot distinguish acute kidney injury from chronic kidney disease or prerenal azotemia. To test the sensitivity and specificity of a single measurement of urinary neutrophil gelatinase-associated lipocalin (NGAL) and other urinary proteins to detect acute kidney injury in a spectrum of patients. Prospective cohort study. Emergency department of Columbia University Medical Center, New York, New York. 635 patients admitted to the hospital with acute kidney injury, prerenal azotemia, chronic kidney disease, or normal kidney function. Diagnosis of acute kidney injury was based on the RIFLE (risk, injury, failure, loss, and end-stage) criteria and assigned by researchers who were blinded to experimental measurements. Urinary NGAL was measured by immunoblot, N-acetyl-beta-d-glucosaminidase (NAG) by enzyme measurement, alpha1-microglobulin and alpha(1)-acid glycoprotein by immunonephelometry, and serum creatinine by Jaffe kinetic reaction. Experimental measurements were not available to treating physicians. Patients with acute kidney injury had a significantly elevated mean urinary NGAL level compared with the other kidney function groups (416 microg/g creatinine [SD, 387]; P = 0.001). At a cutoff value of 130 microg/g creatinine, sensitivity and specificity of NGAL for detecting acute injury were 0.900 (95% CI, 0.73 to 0.98) and 0.995 (CI, 0.990 to 1.00), respectively, and positive and negative likelihood ratios were 181.5 (CI, 58.33 to 564.71) and 0.10 (CI, 0.03 to 0.29); these values were superior to those for NAG, alpha1-microglobulin, alpha1-acid glycoprotein, fractional excretion of sodium, and serum creatinine. In multiple logistic regression, urinary NGAL level was highly predictive of clinical outcomes, including nephrology consultation, dialysis, and admission to the intensive care unit (odds ratio, 24.71 [CI, 7.69 to 79.42]). All patients came from a single center. Few kidney biopsies were performed. A single measurement of urinary NGAL helps to distinguish acute injury from normal function, prerenal azotemia, and chronic kidney disease and predicts poor inpatient outcomes.

Sensitivity and Specificity of a Single Emergency Department Measurement of Urinary Neutrophil Gelatinase–Associated Lipocalin for Diagnosing Acute Kidney Injury

PubMed Central

Nickolas, Thomas L.; O’Rourke, Matthew J.; Yang, Jun; Sise, Meghan E.; Canetta, Pietro A.; Barasch, Nicholas; Buchen, Charles; Khan, Faris; Mori, Kiyoshi; Giglio, James; Devarajan, Prasad; Barasch, Jonathan

2010-01-01

Background A single serum creatinine measurement cannot distinguish acute kidney injury from chronic kidney disease or prerenal azotemia. Objective To test the sensitivity and specificity of a single measurement of urinary neutrophil gelatinase–associated lipocalin (NGAL) and other urinary proteins to detect acute kidney injury in a spectrum of patients. Design Prospective cohort study. Setting Emergency department of Columbia University Medical Center, New York, New York. Participants 635 patients admitted to the hospital with acute kidney injury, prerenal azotemia, chronic kidney disease, or normal kidney function. Measurements Diagnosis of acute kidney injury was based on the RIFLE (risk, injury, failure, loss, and end-stage) criteria and assigned by researchers who were blinded to experimental measurements. Urinary NGAL was measured by immunoblot, N-acetyl-β-D-glucosaminidase (NAG) by enzyme measurement, α1-microglobulin and α1-acid glycoprotein by immunonephelometry, and serum creatinine by Jaffe kinetic reaction. Experimental measurements were not available to treating physicians. Results Patients with acute kidney injury had a significantly elevated mean urinary NGAL level compared with the other kidney function groups (416 μg/g creatinine [SD, 387]; P = 0.001). At a cutoff value of 130 μg/g creatinine, sensitivity and specificity of NGAL for detecting acute injury were 0.900 (95% CI, 0.73 to 0.98) and 0.995 (CI, 0.990 to 1.00), respectively, and positive and negative likelihood ratios were 181.5 (CI, 58.33 to 564.71) and 0.10 (CI, 0.03 to 0.29); these values were superior to those for NAG, α1-microglobulin, α1-acid glycoprotein, fractional excretion of sodium, and serum creatinine. In multiple logistic regression, urinary NGAL level was highly predictive of clinical outcomes, including nephrology consultation, dialysis, and admission to the intensive care unit (odds ratio, 24.71 [CI, 7.69 to 79.42]). Limitations All patients came from a single center. Few kidney biopsies were performed. Conclusion A single measurement of urinary NGAL helps to distinguish acute injury from normal function, prerenal azotemia, and chronic kidney disease and predicts poor inpatient outcomes. PMID:18519927

Identification of a sensitive urinary biomarker, selenium-binding protein 1, for early detection of acute kidney injury.

PubMed

Kim, Kyeong Seok; Yang, Hun Yong; Song, Hosup; Kang, Ye Rim; Kwon, JiHoon; An, JiHye; Son, Ji Yeon; Kwack, Seung Jun; Kim, Young-Mi; Bae, Ok-Nam; Ahn, Mee-Young; Lee, Jaewon; Yoon, Sungpil; Lee, Byung Mu; Kim, Hyung Sik

2017-01-01

Acute kidney injury (AKI) is associated with increased mortality rate in patients but clinically available biomarkers for disease detection are currently not available. Recently, a new biomarker, selenium-binding protein 1 (SBP1), was identified for detection of nephrotoxicity using proteomic analysis. The aim of this study was to assess the sensitivity of urinary SBP1 levels as an early detection of AKI using animal models such as cisplatin or ischemia/reperfusion (I/R). Sprague-Dawley rats were injected with cisplatin (6 mg/kg, once i.p.) and sacrificed at 1, 3, or 5 days after treatment. Ischemia was achieved by bilaterally occluding both kidneys with a microvascular clamp for 45 min and verified visually by a change in tissue color. After post-reperfusion, urine samples were collected at 9, 24, and 48 hr intervals. Urinary excretion of protein-based biomarkers was measured by Western blot analysis. In cisplatin-treated rats, mild histopathologic alterations were noted at day 1 which became severe at day 3. Blood urea nitrogen (BUN) and serum creatinine (SCr) levels were significantly increased at day 3. Levels of urinary excretion of SBP1, neutrophil gelatinase-associated lipocalin (NGAL), and a tissue inhibitor of metalloproteinase-1 (TIMP-1) were markedly elevated at day 3 and 5 following drug treatment. In the vehicle-treated I/R group, serum levels of BUN and SCr and AST activity were significantly increased compared to sham. Urinary excretion of SBP1 and NGAL rose markedly following I/R. The urinary levels of SBP1, NGAL, TIMP-1, and KIM-1 proteins excreted by AKI patients and normal subjects were compared. Among these proteins, a marked rise in SBP1 was observed in urine of patients with AKI compared to normal subjects. Based upon receiver-operator curves (ROC), SBP1 displayed a higher area under the curve (AUC) scores than levels of SCr, BUN, total protein, and glucose. In particular, SBP1 protein was readily detected in small amounts of urine without purification. Data thus indicate that urinary excretion of SBP1 may be useful as a reliable biomarker for early diagnosis of AKI in patients.

Diagnostic Value of Urinary Mevalonic Acid Excretion in Patients with a Clinical Suspicion of Mevalonate Kinase Deficiency (MKD).

PubMed

Jeyaratnam, Jerold; Ter Haar, Nienke M; de Sain-van der Velden, Monique G M; Waterham, Hans R; van Gijn, Mariëlle E; Frenkel, Joost

2016-01-01

In patients suffering from mevalonate kinase deficiency (MKD), the reduced enzyme activity leads to an accumulation of mevalonic acid which is excreted in the urine. This study aims to evaluate the diagnostic value of urinary mevalonic acid measurement in patients with a clinical suspicion of mevalonate kinase deficiency. In this single-center, retrospective analysis, all patients in whom both measurement of mevalonic acid and genetic testing had been performed in the preceding 17 years have been included. The presence of two pathogenic MVK mutations or demonstration of decreased enzyme activity was considered to be the gold standard for the diagnosis of MKD. Sixty-one patients were included in this study. Thirteen of them harbored two MVK mutations; twelve of them showed elevated levels of mevalonic acid. Forty-eight patients did not harbor any MVK mutations, yet five of them excreted increased amounts of mevalonic acid. This corresponds to a sensitivity of 92%, a specificity of 90%, a positive predictive value of 71%, and a negative predictive value of 98%. The positive likelihood ratio is 10 and the negative likelihood ratio is 0.09. MKD seems very unlikely in patients with a normal mevalonic acid excretion, but it cannot be excluded completely. Further, a positive urinary mevalonic acid excretion still requires MVK analysis to confirm the diagnosis of MKD. Therefore, detection of urinary mevalonic acid should not be mandatory before genetic testing. However, as long as genetic testing is not widely available and affordable, measurement of urinary mevalonic acid is a fair way to select patients for MVK gene analysis or enzyme assay.

Strong positive associations between seafood, vegetables, and alcohol with blood mercury and urinary arsenic levels in the Korean adult population.

PubMed

Park, Sunmin; Lee, Byung-Kook

2013-01-01

Blood mercury and urinary arsenic levels are more than fivefold greater in the Korean population compared with those of the United States. This may be related to the foods people consumed. Therefore, we examined the associations between food categories and mercury and arsenic exposure in the Korean adult population. Data regarding nutritional, biochemical, and health-related parameters were obtained from a cross-sectional study, the 2008-2009 Korean National Health and Nutrition Examination Survey (3,404 men and women age ≥ 20 years). The log-transformed blood mercury and urinary arsenic levels were regressed against the frequency tertiles of each food group after covariate adjustment for sex, age, residence area, education level, smoking status, and drinking status using food-frequency data. Blood mercury levels in the high consumption groups compared to the low consumption groups were elevated by about 20 percents with salted fish, shellfish, whitefish, bluefish, and alcohol, and by about 9-14 percents with seaweeds, green vegetables, fruits and tea, whereas rice did not affect blood mercury levels. Urinary arsenic levels were markedly increased with consumption of rice, bluefish, salted fish, shellfish, whitefish, and seaweed, whereas they were moderately increased with consumption of grains, green and white vegetables, fruits, coffee, and alcohol. The remaining food categories tended to lower these levels only minimally. In conclusion, the typical Asian diet, which is high in rice, salted fish, shellfish, vegetables, alcoholic beverages, and tea, may be associated with greater blood mercury and urinary arsenic levels. This study suggests that mercury and arsenic contents should be monitored and controlled in soil and water used for agriculture to decrease health risks from heavy-metal contamination.

Urinary Porphyrin Excretion in Neurotypical and Autistic Children

PubMed Central

Woods, James S.; Armel, Sarah E.; Fulton, Denise I.; Allen, Jason; Wessels, Kristine; Simmonds, P. Lynne; Granpeesheh, Doreen; Mumper, Elizabeth; Bradstreet, J. Jeffrey; Echeverria, Diana; Heyer, Nicholas J.; Rooney, James P.K.

2010-01-01

Background Increased urinary concentrations of pentacarboxyl-, precopro- and copro-porphyrins have been associated with prolonged mercury (Hg) exposure in adults, and comparable increases have been attributed to Hg exposure in children with autism (AU). Objectives This study was designed to measure and compare urinary porphyrin concentrations in neurotypical (NT) children and same-age children with autism, and to examine the association between porphyrin levels and past or current Hg exposure in children with autism. Methods This exploratory study enrolled 278 children 2–12 years of age. We evaluated three groups: AU, pervasive developmental disorder-not otherwise specified (PDD-NOS), and NT. Mothers/caregivers provided information at enrollment regarding medical, dental, and dietary exposures. Urine samples from all children were acquired for analyses of porphyrin, creatinine, and Hg. Differences between groups for mean porphyrin and Hg levels were evaluated. Logistic regression analysis was conducted to determine whether porphyrin levels were associated with increased risk of autism. Results Mean urinary porphyrin concentrations are naturally high in young children and decline by as much as 2.5-fold between 2 and 12 years of age. Elevated copro- (p < 0.009), hexacarboxyl- (p < 0.01) and pentacarboxyl- (p < 0.001) porphyrin concentrations were significantly associated with AU but not with PDD-NOS. No differences were found between NT and AU in urinary Hg levels or in past Hg exposure as determined by fish consumption, number of dental amalgam fillings, or vaccines received. Conclusions These findings identify disordered porphyrin metabolism as a salient characteristic of autism. Hg exposures were comparable between diagnostic groups, and a porphyrin pattern consistent with that seen in Hg-exposed adults was not apparent. PMID:20576582

Effect of urban traffic, individual habits, and genetic polymorphisms on background urinary 1-hydroxypyrene excretion.

PubMed

Cocco, Pierluigi; Moore, Patrick S; Ennas, Maria G; Tocco, Maria G; Ibba, Antonio; Mattuzzi, Silvia; Meloni, Michele; Monne, Maria; Piras, Giovanna; Collu, Stefania; Satta, Giannina; Zucca, Mariagrazia; Scarpa, Aldo; Flore, Costantino

2007-01-01

Potential sources of exposure to polycyclic aromatic hydrocarbons (PAHs) and genetic polymorphisms were investigated in relation to their contribution to interindividual variation in baseline levels of urinary 1-hydroxypyrene (1-OHP) excretion in subjects without occupational exposure to PAHs. Urinary excretion of 1-OHP was measured in 114 subjects, including 48 women and 66 men. Questionnaire information was collected on possible environmental and individual sources of PAH exposure. A subset of 70 individuals also was evaluated for a single-nucleotide polymorphism (Ex7+295C-->T) in the cytochrome P-450 1A2 (CYP1A2) gene, and 61 of these also were evaluated for the glutathione transferase T1 (GSTT1) gene polymorphism. 1-OHP values did not show a significant seasonal variability and were unaffected by age; education; body mass index; smoking status, including passive smoking; or the C-->T base substitution in position 295 of exon 7 of the CYP1A2 gene. After reciprocal adjustment with logistic regression, living in a heavily trafficked urban area (odds ratio, 4.9; 95% confidence interval, 1.0-24.9), and frequent intake of grilled meat (odds ratio, 6.9; 95% confidence interval, 1.1-43.5) were significant predictors of background urinary 1-OHP levels of 0.50 microg/g creatinine or greater. Elevated risks also were associated with daily alcohol intake greater than 65 g and the nonnull GSTT1 genotype. Our study shows that exposure to urban traffic, dietary habits, and the nonnull GSTT1 genotype may contribute to interindividual variation in background levels of 1-OHP urinary excretion in subjects without occupational exposure to PAHs.

Renal Evaluation in Women with Preeclampsia

PubMed Central

Facca, T.A.; Kirsztajn, G. Mastroianni; Pereira, A.R.; Moreira, S.R.; Teixeira, V.P.C.; Nishida, S.K.; Sass, N.

2012-01-01

Background/Aims Preeclampsia (PE) is a cause of glomerulopathy worldwide. Urinary retinol-binding protein (RBP) is a marker of proximal tubular dysfunction, albuminuria is an endothelial injury marker, urine protein:creatinine ratio (PCR) may have a predictive value for renal disease later in life, and, recently, podocyturia has been proposed as a sensitive tool in pregnancy, but it needs to be tested. The aim of this study was to evaluate renal involvement in PE and healthy pregnancy. Methods Case-control study with 39 pregnant women assessed after 20 weeks of gestation (25 in the control group, CG, and 14 in the PE group) by performing urinary tests. Results Mean (±SD) age and gestational age of the CG were 26.9 ± 6.4 years and 37.1 ± 5.0 weeks, and of the PE group 26.4 ± 6.9 years and 30.6 ± 5.6 weeks, respectively (p = 0.001). Mean (±SD) urinary RBP (p = 0.017), albuminuria (p = 0.002), and urinary albumin concentration (UAC) ratio (p = 0.006) of the CG were 0.4 ± 0.7 mg/l, 7.3 ± 6.9 mg/l, and 8.2 ± 6.7 mg/g and of the PE group 2.0 ± 4.4 mg/l, 2,267.4 ± 2,130.8 mg/l (p = 0.002), and 3,778.9 ± 4,296.6 mg/g (p = 0.006), respectively. Mean (±SD) urine PCR in the PE group was 6.7 ± 6.1 g/g (p < 0.001). No statistical differences were found between podocyturia in the CG and PE group (p = 0.258). Conclusions Urinary RBP, PCR, albuminuria, and UAC ratio were elevated in the PE group in comparison to the CG. Podocyturia did not predict PE. PMID:22740065

An increase in renal dopamine does not stimulate natriuresis after fava bean ingestion123

PubMed Central

Garland, Emily M; Cesar, Tericka S; Lonce, Suzanna; Ferguson, Marcus C; Robertson, David

2013-01-01

Background: Fava beans (Vicia faba) contain dihydroxyphenylalanine (dopa), and their ingestion may increase dopamine stores. Renal dopamine regulates blood pressure and blood volume via a natriuretic effect. Objective: The objective was to determine the relation between dietary fava beans, plasma and urinary catechols, and urinary sodium excretion in 13 healthy volunteers. Design: Catechol and sodium data were compared by using a longitudinal design in which all participants consumed a fixed-sodium study diet on day 1 and the fixed-sodium diet plus fava beans on day 2. Blood was sampled at 1, 2, 4, and 6 h after a meal, and 3 consecutive 4-h urine samples were collected. Results: Mean (±SD) plasma dopa was significantly greater 1 h after fava bean consumption (11,670 ± 5440 compared with 1705 ± 530 pg/mL; P = 0.001) and remained elevated at 6 h. Plasma dopamine increased nearly 15-fold during this period. Fava bean consumption also increased urinary dopamine excretion to 306 ± 116, 360 ± 235, and 159 ± 111 μg/4-h urine sample compared with 45 ± 21, 54 ± 29, and 44 ± 17 μg in the 3 consecutive 4-h samples after the control diet (P ≤ 0.005). These substantial increases in plasma and urinary dopa and dopamine were unexpectedly associated with decreased urinary sodium. Conclusion: The failure of fava bean consumption to provoke natriuresis may indicate that dopa concentrations in commercially available beans do not raise renal dopamine sufficiently to stimulate sodium excretion, at least when beans are added to a moderate-sodium diet in healthy volunteers. This trial was registered at clinicaltrials.gov as NCT01064739. PMID:23553159

Controlling the misuse of cobalt in horses.

PubMed

Ho, Emmie N M; Chan, George H M; Wan, Terence S M; Curl, Peter; Riggs, Christopher M; Hurley, Michael J; Sykes, David

2015-01-01

Cobalt is a well-established inducer of hypoxia-like responses, which can cause gene modulation at the hypoxia inducible factor pathway to induce erythropoietin transcription. Cobalt salts are orally active, inexpensive, and easily accessible. It is an attractive blood doping agent for enhancing aerobic performance. Indeed, recent intelligence and investigations have confirmed cobalt was being abused in equine sports. In this paper, population surveys of total cobalt in raceday samples were conducted using inductively coupled plasma mass spectrometry (ICP-MS). Urinary threshold of 75 ng/mL and plasma threshold of 2 ng/mL could be proposed for the control of cobalt misuse in raceday or in-competition samples. Results from administration trials with cobalt-containing supplements showed that common supplements could elevate urinary and plasma cobalt levels above the proposed thresholds within 24 h of administration. It would therefore be necessary to ban the use of cobalt-containing supplements on raceday as well as on the day before racing in order to implement and enforce the proposed thresholds. Since the abuse with huge quantities of cobalt salts can be done during training while the use of legitimate cobalt-containing supplements are also allowed, different urinary and plasma cobalt thresholds would be required to control cobalt abuse in non-raceday or out-of-competition samples. This could be achieved by setting the thresholds above the maximum urinary and plasma cobalt concentrations observed or anticipated from the normal use of legitimate cobalt-containing supplements. Urinary threshold of 2000 ng/mL and plasma threshold of 10 ng/mL were thus proposed for the control of cobalt abuse in non-raceday or out-of-competition samples. Copyright © 2014 John Wiley & Sons, Ltd.