WorldWideScience

Sample records for comparing urinary biomarkers

  1. Monitoring low benzene exposure: comparative evaluation of urinary biomarkers, influence of cigarette smoking, and genetic polymorphisms.

    Science.gov (United States)

    Fustinoni, Silvia; Consonni, Dario; Campo, Laura; Buratti, Marina; Colombi, Antonio; Pesatori, Angela C; Bonzini, Matteo; Bertazzi, Pier A; Foà, Vito; Garte, Seymour; Farmer, Peter B; Levy, Leonard S; Pala, Mauro; Valerio, Federico; Fontana, Vincenzo; Desideri, Arianna; Merlo, Domenico F

    2005-09-01

    Benzene is a human carcinogen and an ubiquitous environmental pollutant. Identification of specific and sensitive biological markers is critical for the definition of exposure to low benzene level and the evaluation of the health risk posed by this exposure. This investigation compared urinary trans,trans-muconic acid (t,t-MA), S-phenylmercapturic acid, and benzene (U-benzene) as biomarkers to assess benzene exposure and evaluated the influence of smoking and the genetic polymorphisms CYP2E1 (RsaI and DraI) and NADPH quinone oxidoreductase-1 on these indices. Gas station attendants, urban policemen, bus drivers, and two groups of controls were studied (415 subjects). Median benzene exposure was 61, 22, 21, 9 and 6 microg/m(3), respectively, with higher levels in workers than in controls. U-benzene, but not t,t-MA and S-phenylmercapturic acid, showed an exposure-related increase. All the biomarkers were strongly influenced by cigarette smoking, with values up to 8-fold higher in smokers compared with nonsmokers. Significant correlations of the biomarkers with each other and with urinary cotinine were found. A possible influence of genetic polymorphism of CYP2E1 (RsaI and/or DraI) on t,t-MA and U-benzene in subjects with a variant allele was found. Multiple linear regression analysis correlated the urinary markers with exposure, smoking status, and CYP2E1 (RsaI; R(2) up to 0.55 for U-benzene). In conclusion, in the range of investigated benzene levels (<478 micro/m(3) or <0.15 ppm), smoking may be regarded as the major source of benzene intake; among the study indices, U-benzene is the marker of choice for biomonitoring low-level occupational and environmental benzene exposure.

  2. Urinary biomarkers in pediatric appendicitis.

    Science.gov (United States)

    Salö, Martin; Roth, Bodil; Stenström, Pernilla; Arnbjörnsson, Einar; Ohlsson, Bodil

    2016-08-01

    The diagnosis of pediatric appendicitis is still a challenge, resulting in perforation and negative appendectomies. The aim of this study was to evaluate novel biomarkers in urine and to use the most promising biomarkers in conjunction with the Pediatric Appendicitis Score (PAS), to see whether this could improve the accuracy of diagnosing appendicitis. A prospective study of children with suspected appendicitis was conducted with assessment of PAS, routine blood tests, and measurements of four novel urinary biomarkers: leucine-rich α-2-glycoprotein (LRG), calprotectin, interleukin 6 (IL-6), and substance P. The biomarkers were blindly determined with commercial ELISAs. Urine creatinine was used to adjust for dehydration. The diagnosis of appendicitis was based on histopathological analysis. Forty-four children with suspected appendicitis were included, of which twenty-two (50 %) had confirmed appendicitis. LRG in urine was elevated in children with appendicitis compared to children without (p appendicitis compared to those with phlegmonous appendicitis (p = 0.003). No statistical significances between groups were found for calprotectin, IL-6 or substance P. LRG had a receiver operating characteristic area under the curve of 0.86 (95 % CI 0.79-0.99), and a better diagnostic performance than all routine blood tests. LRG in conjunction with PAS showed 95 % sensitivity, 90 % specificity, 91 % positive predictive value, and 95 % negative predictive value. LRG, adjusted for dehydration, is a promising novel urinary biomarker for appendicitis in children. LRG in combination with PAS has a high diagnostic performance.

  3. Urinary Biomarkers of Brain Diseases

    Directory of Open Access Journals (Sweden)

    Manxia An

    2015-12-01

    Full Text Available Biomarkers are the measurable changes associated with a physiological or pathophysiological process. Unlike blood, urine is not subject to homeostatic mechanisms. Therefore, greater fluctuations could occur in urine than in blood, better reflecting the changes in human body. The roadmap of urine biomarker era was proposed. Although urine analysis has been attempted for clinical diagnosis, and urine has been monitored during the progression of many diseases, particularly urinary system diseases, whether urine can reflect brain disease status remains uncertain. As some biomarkers of brain diseases can be detected in the body fluids such as cerebrospinal fluid and blood, there is a possibility that urine also contain biomarkers of brain diseases. This review summarizes the clues of brain diseases reflected in the urine proteome and metabolome.

  4. Urinary Sugars--A Biomarker of Total Sugars Intake.

    Science.gov (United States)

    Tasevska, Natasha

    2015-07-01

    Measurement error in self-reported sugars intake may explain the lack of consistency in the epidemiologic evidence on the association between sugars and disease risk. This review describes the development and applications of a biomarker of sugars intake, informs its future use and recommends directions for future research. Recently, 24 h urinary sucrose and fructose were suggested as a predictive biomarker for total sugars intake, based on findings from three highly controlled feeding studies conducted in the United Kingdom. From this work, a calibration equation for the biomarker that provides an unbiased measure of sugars intake was generated that has since been used in two US-based studies with free-living individuals to assess measurement error in dietary self-reports and to develop regression calibration equations that could be used in future diet-disease analyses. Further applications of the biomarker include its use as a surrogate measure of intake in diet-disease association studies. Although this biomarker has great potential and exhibits favorable characteristics, available data come from a few controlled studies with limited sample sizes conducted in the UK. Larger feeding studies conducted in different populations are needed to further explore biomarker characteristics and stability of its biases, compare its performance, and generate a unique, or population-specific biomarker calibration equations to be applied in future studies. A validated sugars biomarker is critical for informed interpretation of sugars-disease association studies.

  5. Urinary tubular protein-based biomarkers in the rodent model of cisplatin nephrotoxicity: a comparative analysis of serum creatinine, renal histology, and urinary KIM-1, NGAL, and NAG in the initiation, maintenance, and recovery phases of acute kidney injury.

    Science.gov (United States)

    Sinha, Vikash; Vence, Luis M; Salahudeen, Abdulla K

    2013-03-01

    Several biomarkers are becoming available for the early detection of acute kidney injury (AKI), but few have been directly compared. To compare urinary kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), and N-acetyl glucosaminidase (NAG) against serum creatinine and renal histological score in the initiation, maintenance, and recovery phases of cisplatin (CP)-induced AKI. Sprague-Dawley rats (300-350 g) were injected once through their tail veins with CP (CP group) at 5.5 mg/kg or with same volume of normal saline vehicle (Control group). Rats were euthanized at 2, 4, 6, 12, and 24 hours, and on days 2, 3, 6, and 10 (n = 12 in the CP group and n = 6 in the Control group at each time point), and urine, blood, and kidney samples were analyzed. A significant increase in serum creatinine was noted by day 3 in the CP group versus Control group [1.46 (0.12) vs 0.28 (0.03) mg/dL; mean (SE); P CP group. Urinary kidney injury molecule-1 levels were significantly higher at 24 hours in the CP group than in the Control group [48.26 (13.13) vs 8.21 (3.31) pg/mg creatinine; P CP than in the Control group [NAG, 8.19 (0.82) vs 3.48 (0.40) pg/mg creatinine, P G 0.05; NGAL, 2911.80 (368.10) vs 1412.60 (250.20) pg/mg creatinine, P CP to discern the time course and pattern of expression.

  6. Are urinary PAHs biomarkers of controlled exposure to diesel exhaust?

    Science.gov (United States)

    Lu, Sixin S; Sobus, Jon R; Sallsten, Gerd; Albin, Maria; Pleil, Joachim D; Gudmundsson, Anders; Madden, Michael C; Strandberg, Bo; Wierzbicka, Aneta; Rappaport, Stephen M

    2014-06-01

    Urinary polycyclic aromatic hydrocarbons (PAHs) were evaluated as possible biomarkers of exposure to diesel exhaust (DE) in two controlled-chamber studies. We report levels of 14 PAHs from 28 subjects in urine that were collected before, immediately after and the morning after exposure. Using linear mixed-effects models, we tested for effects of DE exposure and several covariates (time, age, gender and urinary creatinine) on urinary PAH levels. DE exposures did not significantly alter urinary PAH levels. We conclude that urinary PAHs are not promising biomarkers of short-term exposures to DE in the range of 106-276 µg/m(3).

  7. Identification of urinary peptide biomarkers associated with rheumatoid arthritis.

    Directory of Open Access Journals (Sweden)

    Angelique Stalmach

    Full Text Available Early diagnosis and treatment of rheumatoid arthritis are associated with improved outcomes but current diagnostic tools such as rheumatoid factor or anti-citrullinated protein antibodies have shown limited sensitivity. In this pilot study we set out to establish a panel of urinary biomarkers associated with rheumatoid arthritis using capillary electrophoresis coupled to mass spectrometry. We compared the urinary proteome of 33 participants of the Scottish Early Rheumatoid Arthritis inception cohort study with 30 healthy controls and identified 292 potential rheumatoid arthritis-specific peptides. Amongst them, 39 were used to create a classifier model using support vector machine algorithms. Specific peptidic fragments were differentially excreted between groups; fragments of protein S100-A9 and gelsolin were less abundant in rheumatoid arthritis while fragments of uromodulin, complement C3 and fibrinogen were all increasingly excreted. The model generated was subsequently tested in an independent test-set of 31 samples. The classifier demonstrated a sensitivity of 88% and a specificity of 93% in diagnosing the condition, with an area under the receiver operating characteristic curve of 0.93 (p<0.0001. These preliminary results suggest that urinary biomarkers could be useful in the early diagnosis of rheumatoid arthritis. Further studies are currently being undertaken in larger cohorts of patients with rheumatoid arthritis and other athridities to assess the potential of the urinary peptide based classifier in the early detection of rheumatoid arthritis.

  8. Urinary biomarkers at early ADPKD disease stage.

    Directory of Open Access Journals (Sweden)

    Katja Petzold

    Full Text Available Autosomal dominant polycystic kidney disease (ADPKD is characterized by a decline in renal function at late disease stage when the majority of functional renal parenchyma is replaced by cystic tissue. Thus, kidney function, assessed by estimated glomerular filtration rate (eGFR does not well represent disease burden in early disease. Here, we investigated various urinary markers for tubular injury and their association with disease burden in ADPKD patients at early disease course.ADPKD patients between 18 and 40 years with an eGFR greater or equal to 70 ml per min per 1.73m2 were eligible for this cross-sectional study. Urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL, Kidney Injury Molecule-1 (KIM-1, and Uromodulin (UMOD were investigated by Enzyme-Linked Immunosorbent Assay. Clara Cell Protein 16 (CC16 was investigated by Latex Immuno Assay. Cryoscopy was performed to assess urine osmolality and Urinary Albumin-to-Creatinine Ratio (UACR was calculated. The association and the predictive properties of the markers on eGFR and height adjusted total kidney volume (htTKV was evaluated using multiple regression analysis, incorporating different control variables for adjustment. Internal bootstrapping validated the obtained results.In 139 ADPKD patients (age 31 ±7 years, mean eGFR of 93 ± 19 ml per min per 1.73 m2 the total kidney volume was negatively correlated with eGFR and UMOD and positive associated with age, UACR, KIM-1 and urine osmolality after adjustment for possible confounders. Urine osmolality and htTKV were also associated with eGFR, whereas no association of CC16, NGAL and UMOD with eGFR or htTKV was found.UACR and urinary KIM-1 are independently associated with kidney size but not with renal function in our study population. Urine osmolality was associated with eGFR and kidney volume following adjustment for multiple confounders. Despite statistical significance, the clinical value of our results is not yet conceivable

  9. Nucleic acids within urinary exosomes/microvesicles are potential biomarkers for renal disease

    OpenAIRE

    Miranda, Kevin C; Daniel T Bond; Mckee, Mary; Skog, Johan; Păunescu, Teodor G.; Da Silva, Nicolas; Brown, Dennis; Russo, Leileata M.

    2010-01-01

    Urinary exosomes or microvesicles are being studied intensively to identify potential new biomarkers for renal disease. We sought to identify whether these microvesicles contain nucleic acids. We isolated microvesicles from human urine in the same density range as that previously described for urinary exosomes and found them to have an RNA integrity profile similar to that of kidney tissue, including 18S and 28S rRNA. This profile was better preserved in urinary microvesicles compared with wh...

  10. Urinary APE1/Ref-1: A Potential Bladder Cancer Biomarker.

    Science.gov (United States)

    Choi, Sunga; Shin, Ju Hyun; Lee, Yu Ran; Joo, Hee Kyoung; Song, Ki Hak; Na, Yong Gil; Chang, Seok Jong; Lim, Jae Sung; Jeon, Byeong Hwa

    2016-01-01

    Bladder cancer (BCa) is one of the most common urothelial cancers with still noticeable incidence rate. Early detection of BCa is highly correlated with successful therapeutic outcomes. We previously showed that apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) was expressed at an increased level in the serum of BCa patients when compared to the level in healthy controls. In this study, we investigated whether urinary APE1/Ref-1 was also elevated in patients with BCa. In this case-control study, voided urine was collected from 277 subjects including 169 BCa patients and 108 non-BCa controls. Urinary APE1/Ref-1 level was assessed by enzyme-linked immunosorbent assay (ELISA). APE1/Ref-1 levels were significantly elevated in BCa patients relative to levels in non-BCa controls and were correlated with tumor grade and stage. Urinary APE1/Ref-1 levels were also higher in patients with recurrence history of BCa. The receiver operating characteristics (ROC) curve of APE1/Ref-1 showed an area under the curve of 0.83, indicating the reliability and validity of this biomarker. The optimal combination of sensitivity and specificity was determined to be 82% and 80% at a cut-off value of 0.376 ng/100 μL for detection of APE1/Ref-1 in urine. In conclusion, urinary APE1/Ref-1 levels measured from noninvasively obtained body fluids would be clinically applicable for diagnosis of BCa.

  11. Evaluation of kidney injury in dogs with pyometra based on proteinuria, renal histomorphology, and urinary biomarkers.

    Science.gov (United States)

    Maddens, B; Heiene, R; Smets, P; Svensson, M; Aresu, L; van der Lugt, J; Daminet, S; Meyer, E

    2011-01-01

    Proteinuria is a feature of pyometra-associated renal dysfunction, but its prevalence and clinical relevance are not well characterized. To define which subset of dogs with pyometra has clinically relevant kidney injury by quantification of proteinuria; light, immunofluorescence, and electron microscopic examination of kidney biopsy specimens; and measurement of urinary biomarkers. Forty-seven dogs with pyometra. Ten clinically healthy intact bitches of comparable age. Prospective study. Routine clinicopathological variables including urinary protein to creatinine ratio (UPC) were analyzed. Validated assays were used to quantify urinary biomarkers for glomerular (urinary albumin, urinary immunoglobulin G, urinary C-reactive protein, urinary thromboxane B(2)) and tubular function (urinary retinol-binding protein, urinary N-acetyl-β-d-glucosaminidase). Kidney biopsy specimens from 10 dogs with pyometra and dipstick urine protein concentrations of 2+ or 3+ were collected during ovariohysterectomy. Urinalysis was repeated within 3 weeks after surgery in 9 of the 10 dogs. UPC (median, range) was significantly higher in dogs with pyometra (0.48, 0.05-8.69) compared with healthy bitches (0.08, 0.02-0.16) (P dogs with pyometra had UPC>0.5, 12 had UPC>1.0, and 7 had UPC>2.0. Glomerulosclerosis and tubulointerstitial nephritis were common kidney biopsy findings in proteinuric dogs with pyometra. Dogs with glomerulosclerosis (5/10), either global or focal and segmental, had UPC>1.0 at ovariohysterectomy and afterward. Dogs with structural glomerular and tubular changes mostly had urinary biomarker to creatinine ratios above the 75th percentile. Dogs with pyometra and UPC>1.0 or high ratios of urinary biomarkers appear likely to have clinically relevant renal histologic lesions and require monitoring after ovariohysterectomy. Future studies should evaluate the role of pyometra-associated pathogenic mechanisms in causing or exacerbating focal and segmental glomerulosclerosis

  12. Urinary Biomarkers in Relapsing Antineutrophil Cytoplasmic Antibody-associated Vasculitis

    Science.gov (United States)

    Lieberthal, Jason G.; Cuthbertson, David; Carette, Simon; Hoffman, Gary S.; Khalidi, Nader A.; Koening, Curry L.; Langford, Carol A.; Maksimowicz-McKinnon, Kathleen; Seo, Philip; Specks, Ulrich; Ytterberg, Steven R.; Merkel, Peter A.; Monach, Paul A.

    2015-01-01

    Objective Glomerulonephritis (GN) is common in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), but tools for early detection of renal involvement are imperfect. We investigated 4 urinary proteins as markers of active renal AAV: alpha-1 acid glycoprotein (AGP), kidney injury molecule-1 (KIM-1), monocyte chemoattractant protein-1 (MCP-1), and neutrophil gelatinase-associated lipocalin (NGAL). Methods Patients with active renal AAV (n = 20), active nonrenal AAV (n = 16), and AAV in longterm remission (n = 14) were identified within a longitudinal cohort. Urinary biomarker concentrations (by ELISA) were normalized for urine creatinine. Marker levels during active AAV were compared to baseline remission levels (from 1–4 visits) for each patient. Areas under receiver-operating characteristic curves (AUC), sensitivities, specificities, and likelihood ratios (LR) comparing disease states were calculated. Results Baseline biomarker levels varied among patients. All 4 markers increased during renal flares (p < 0.05). MCP-1 discriminated best between active renal disease and remission: a 1.3-fold increase in MCP-1 had 94% sensitivity and 89% specificity for active renal disease (AUC = 0.93, positive LR 8.5, negative LR 0.07). Increased MCP-1 also characterized 50% of apparently nonrenal flares. Change in AGP, KIM-1, or NGAL showed more modest ability to distinguish active renal disease from remission (AUC 0.71–0.75). Hematuria was noted in 83% of active renal episodes, but also 43% of nonrenal flares and 25% of remission samples. Conclusion Either urinary MCP-1 is not specific for GN in AAV, or it identifies early GN not detected by standard assessment and thus has potential to improve care. A followup study with kidney biopsy as the gold standard is needed. PMID:23547217

  13. Identification of prostate cancer biomarkers in urinary exosomes.

    Science.gov (United States)

    Øverbye, Anders; Skotland, Tore; Koehler, Christian J; Thiede, Bernd; Seierstad, Therese; Berge, Viktor; Sandvig, Kirsten; Llorente, Alicia

    2015-10-01

    Exosomes have recently appeared as a novel source of non-invasive cancer biomarkers since tumour-specific molecules can be found in exosomes isolated from biological fluids. We have here investigated the proteome of urinary exosomes by using mass spectrometry to identify proteins differentially expressed in prostate cancer patients compared to healthy male controls. In total, 15 control and 16 prostate cancer samples of urinary exosomes were analyzed. Importantly, 246 proteins were differentially expressed in the two groups. The majority of these proteins (221) were up-regulated in exosomes from prostate cancer patients. These proteins were analyzed according to specific criteria to create a focus list that contained 37 proteins. At 100% specificity, 17 of these proteins displayed individual sensitivities above 60%. Even though several of these proteins showed high sensitivity and specificity for prostate cancer as individual biomarkers, combining them in a multi-panel test has the potential for full differentiation of prostate cancer from non-disease controls. The highest sensitivity, 94%, was observed for transmembrane protein 256 (TM256; chromosome 17 open reading frame 61). LAMTOR proteins were also distinctly enriched with very high specificity for patient samples. TM256 and LAMTOR1 could be used to augment the sensitivity to 100%. Other prominent proteins were V-type proton ATPase 16 kDa proteolipid subunit (VATL), adipogenesis regulatory factor (ADIRF), and several Rab-class members and proteasomal proteins. In conclusion, this study clearly shows the potential of using urinary exosomes in the diagnosis and clinical management of prostate cancer.

  14. Urinary biomarkers for prostate cancer: a review

    Institute of Scientific and Technical Information of China (English)

    Daphne Hessels; Jack A Schalken

    2013-01-01

    Although the routine use of serum prostate-specific antigen (PSA) testing has undoubtedly increased prostate cancer (PCa) detection,one of its main drawbacks is its lack of specificity.As a consequence,many men undergo unnecessary biopsies or treatments for indolent tumours.PCa-specific markers are needed for the early detection of the disease and the prediction of aggressiveness of a prostate tumour.Since PCa is a heterogeneous disease,a panel of tumour markers is fundamental for a more precise diagnosis.Several biomarkers are promising due to their specificity for the disease in tissue.However,tissue is unsuitable as a possible screening tool.Since urine can be easily obtained in a non-invasive manner,it is a promising substrate for biomarker testing.This article reviews the biomarkers for the non-invasive testing of PCa in urine.

  15. Urinary 1-hydroxypyrene as a biomarker of PAH exposure in 3-year-old Ukrainian children.

    Science.gov (United States)

    Mucha, Amy Pelka; Hryhorczuk, Daniel; Serdyuk, Andrij; Nakonechny, Joseph; Zvinchuk, Alexander; Erdal, Serap; Caudill, Motria; Scheff, Peter; Lukyanova, Elena; Shkiryak-Nyzhnyk, Zoreslava; Chislovska, Natalia

    2006-04-01

    Urinary 1-hydroxypyrene (1-OHP) is a biomarker of polycyclic aromatic hydrocarbon (PAH) exposure. We measured urinary 1-OHP in 48 children 3 years of age in Mariupol, Ukraine, who lived near a steel mill and coking facility and compared these with 1-OHP concentrations measured in 42 children of the same age living in the capital city of Kiev, Ukraine. Children living in Mariupol had significantly higher urinary 1-OHP and creatinine-adjusted urinary 1-OHP than did children living in Kiev (adjusted: 0.69 vs. 0.34 micromol/mol creatinine, p Mariupol has the highest reported mean urinary 1-OHP concentrations in children studied to date, most likely due to their proximity to a large industrial point source of PAHs.

  16. Parabens as Urinary Biomarkers of Exposure in Humans

    Science.gov (United States)

    Ye, Xiaoyun; Bishop, Amber M.; Reidy, John A.; Needham, Larry L.; Calafat, Antonia M.

    2006-01-01

    Background Parabens appear frequently as antimicrobial preservatives in cosmetic products, in pharmaceuticals, and in food and beverage processing. In vivo and in vitro studies have revealed weak estrogenic activity of some parabens. Widespread use has raised concerns about the potential human health risks associated with paraben exposure. Objectives Assessing human exposure to parabens usually involves measuring in urine the conjugated or free species of parabens or their metabolites. In animals, parabens are mostly hydrolyzed to p-hydroxybenzoic acid and excreted in the urine as conjugates. Still, monitoring urinary concentrations of p-hydroxybenzoic acid is not necessarily the best way to assess exposure to parabens. p-Hydroxybenzoic acid is a nonspecific biomarker, and the varying estrogenic bioactivities of parabens require specific biomarkers. Therefore, we evaluated the use of free and conjugated parent parabens as new biomarkers for human exposure to these compounds. Results We measured the urinary concentrations of methyl, ethyl, n-propyl, butyl (n- and iso-), and benzyl parabens in a demographically diverse group of 100 anonymous adults. We detected methyl and n-propyl parabens at the highest median concentrations (43.9 ng/mL and 9.05 ng/mL, respectively) in nearly all (> 96%) of the samples. We also detected other parabens in more than half of the samples (ethyl, 58%; butyl, 69%). Most important, however, we found that parabens in urine appear predominantly in their conjugated forms. Conclusions The results, demonstrating the presence of urinary conjugates of parabens in humans, suggest that such conjugated parabens could be used as exposure biomarkers. Additionally, the fact that conjugates appear to be the main urinary products of parabens may be important for risk assessment. PMID:17185273

  17. Reproducibility of urinary biomarkers in multiple 24-h urine samples.

    Science.gov (United States)

    Sun, Qi; Bertrand, Kimberly A; Franke, Adrian A; Rosner, Bernard; Curhan, Gary C; Willett, Walter C

    2017-01-01

    Limited knowledge regarding the reproducibility of biomarkers in 24-h urine samples has hindered the collection and use of the samples in epidemiologic studies. We aimed to evaluate the reproducibility of various markers in repeat 24-h urine samples. We calculated intraclass correlation coefficients (ICCs) of biomarkers measured in 24-h urine samples that were collected in 3168 participants in the NHS (Nurses' Health Study), NHSII (Nurses' Health Study II), and Health Professionals Follow-Up Study. In 742 women with 4 samples each collected over the course of 1 y, ICCs for sodium were 0.32 in the NHS and 0.34 in the NHSII. In 2439 men and women with 2 samples each collected over 1 wk to ≥1 mo, the ICCs ranged from 0.33 to 0.68 for sodium at various intervals between collections. The urinary excretion of potassium, calcium, magnesium, phosphate, sulfate, and other urinary markers showed generally higher reproducibility (ICCs >0.4). In 47 women with two 24-h urine samples, ICCs ranged from 0.15 (catechin) to 0.75 (enterolactone) for polyphenol metabolites. For phthalates, ICCs were generally ≤0.26 except for monobenzyl phthalate (ICC: 0.55), whereas the ICC was 0.39 for bisphenol A (BPA). We further estimated that, for the large majority of the biomarkers, the mean of three 24-h urine samples could provide a correlation of ≥0.8 with true long-term urinary excretion. These data suggest that the urinary excretion of various biomarkers, such as minerals, electrolytes, most polyphenols, and BPA, is reasonably reproducible in 24-h urine samples that are collected within a few days or ≤1 y. Our findings show that three 24-h samples are sufficient for the measurement of long-term exposure status in epidemiologic studies. © 2017 American Society for Nutrition.

  18. Urinary BTEX, MTBE and naphthalene as biomarkers to gain environmental exposure profiles of the general population.

    Science.gov (United States)

    Fustinoni, Silvia; Rossella, Federica; Campo, Laura; Mercadante, Rosa; Bertazzi, Pier Alberto

    2010-06-15

    The aim of this work was to evaluate urinary benzene, toluene, ethylbenzene, m+p-xylene, o-xylene (BTEX), methyl tert-butyl ether (MTBE), ethyl tert-butyl ether (ETBE), and naphthalene (NAP) as biomarkers of exposure to environmental pollutants. Personal air and urine samples from 108 subjects belonging to the Italian general population were compared. Urinary profiles were obtained by headspace gas chromatography-mass spectrometry. BTEX, MTBE, ETBE and NAP median airborne exposures during a 5-h sampling were 4.0, 25.3, 3.8, 9.3, 3.4, 3.4, <0.8, and 3.4 microg/m(3), respectively. Meanwhile, median urinary levels, as geometric means of three determinations were: 122, 397, 74, 127, 43, 49, <15, and 46 ng/L, respectively. Urinary benzene and toluene concentrations were 4.6- and 1.2-fold higher in smokers than in non-smokers. For most chemicals, significant positive correlations between airborne exposure (log-transformed) and the corresponding biological marker (log-transformed) were found, with Pearson's r values for correlation, ranging from 0.228 to 0.396. Multiple linear regression analysis showed that the urinary level of these chemicals was influenced by personal airborne exposure, urinary creatinine, and urinary cotinine, with R(2) 0.733 for benzene. Urinary chemicals are useful biomarkers of environmental exposure. Given the ease of rapidly obtaining urine samples, they represent a non-invasive alternative to blood chemical analysis. The possibility of obtaining urinary exposure profiles makes this method an appealing tool for environmental epidemiology.

  19. Ambient Melamine Exposure and Urinary Biomarkers of Early Renal Injury.

    Science.gov (United States)

    Wu, Chia-Fang; Peng, Chiung-Yu; Liu, Chia-Chu; Lin, Wen-Yi; Pan, Chih-Hong; Cheng, Ching-Mei; Hsieh, Hui-Min; Hsieh, Tusty-Jiuan; Chen, Bai-Hsiun; Wu, Ming-Tsang

    2015-11-01

    Information about environmental exposure to melamine and renal injury in adults is lacking. We investigated this relationship in 44 workers at two melamine tableware manufacturing factories in Taiwan (16 manufacturers, eight grinders, ten packers, and ten administrators) and 105 nonexposed workers (controls) at one shipbuilding company who were enrolled in August-December of 2012. For melamine workers, personal and area air samples were obtained at the worksite over 1 workweek (Monday-Friday). In the same week, pre- and post-shift one-spot urine samples were collected each workday and one first-spot urine sample was collected on each weekend morning and the following Monday morning. For each control, a one-spot urine sample was collected on Friday morning. A blood sample was also obtained from each participant at this time. Melamine levels were measured in air, urine, and serum, and early renal injury biomarkers were measured in urine. Urinary melamine concentrations in manufacturers increased sharply between pre- and post-shift measurements on Monday, remained significantly elevated throughout the workweek, and decreased over the weekend; changes in urinary melamine concentrations were substantially lower for other melamine workers. Manufacturers were exposed to the highest concentrations of ambient melamine and had significantly higher urinary and serum melamine concentrations than did the controls (Pmelamine levels were positively associated with urinary N-acetyl β-d-glucosaminidase (NAG) levels but not microalbumin levels, and the detectable β2-microglobulin rate increased in the manufacturers group. In conclusion, ambient melamine exposure may increase the levels of urinary biomarkers of renal tubular injury in this occupational setting.

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

    Directory of Open Access Journals (Sweden)

    Sari-Minodier Irène

    2011-03-01

    Full Text Available Abstract 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(apyrene toxicity equivalent factors and inhalation unit risk for Benzo(apyrene 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 P Conclusions The integrated and non-specific urinary biomarkers of exposure showed that sewage workers experience exposure to mixtures of genotoxicants in the workplace.

  1. Nucleic acids within urinary exosomes/microvesicles are potential biomarkers for renal disease.

    Science.gov (United States)

    Miranda, Kevin C; Bond, Daniel T; McKee, Mary; Skog, Johan; Păunescu, Teodor G; Da Silva, Nicolas; Brown, Dennis; Russo, Leileata M

    2010-07-01

    Urinary exosomes or microvesicles are being studied intensively to identify potential new biomarkers for renal disease. We sought to identify whether these microvesicles contain nucleic acids. We isolated microvesicles from human urine in the same density range as that previously described for urinary exosomes and found them to have an RNA integrity profile similar to that of kidney tissue, including 18S and 28S rRNA. This profile was better preserved in urinary microvesicles compared with whole cells isolated from urine, suggesting that microvesicles may protect RNA during urine passage. We were able to detect mRNA in the human urinary microvesicles encoding proteins from all regions of the nephron and the collecting duct. Further, to provide a proof of principle, we found that microvesicles isolated from the urine of the V-ATPase B1 subunit knockout mice lacked mRNA of this subunit while containing a normal amount of the B2 subunit and aquaporin 2. The microvesicles were found to be contaminated with extraneous DNA potentially on their surface; therefore, we developed a rapid and reliable means to isolate nucleic acids from within urine microvesicles devoid of this extraneous contamination. Our study provides an experimental strategy for the routine isolation and use of urinary microvesicles as a novel and non-invasive source of nucleic acids to further renal disease biomarker discovery.

  2. 8-Hydroxydeoxyguanosine as a urinary biomarker of oxidative DNA damage

    DEFF Research Database (Denmark)

    Loft, S; Fischer-Nielsen, A; Jeding, I B

    1993-01-01

    , rats, and mice. The excretion of 8OHdG decreased with age in rats in parallel with the decline in metabolic rate with advancing age. The excretion of 8OHdG reflects the formation and repair of only one out of approximately 20 described oxidative DNA modifications. So far, methods are not available......Living organisms are continuously exposed to reactive oxygen species as a consequence of biochemical reactions as well as external factors. Oxidative DNA damage has been implicated in aging, carcinogenesis and other degenerative diseases. The urinary excretion of the DNA repair product 8......-hydroxydeoxyguanosine (8OHdG) has been proposed as a noninvasive biomarker of oxidative DNA damage in humans in vivo. We have developed a three-dimensional HPLC analysis with electrochemical detection for the analysis of 8OHdG in urine and studied factors affecting the excretion of this biomarker in 83 healthy humans...

  3. Urinary micro-RNA biomarker detection using capped gold nanoslit SPR in a microfluidic chip.

    Science.gov (United States)

    Mousavi, Mansoureh Z; Chen, Huai-Yi; Lee, Kuang-Li; Lin, Heng; Chen, Hsi-Hsien; Lin, Yuh-Feng; Wong, Chung-Shun; Li, Hsiao Fen; Wei, Pei-Kuen; Cheng, Ji-Yen

    2015-06-21

    Successful diagnosis and treatment of many diseases depends on the availability of sensitive, reliable and low cost tools for the detection of the biomarkers associated with the diseases. Simple methods that use non-invasive biological samples are especially suitable for the deployment in the clinical environment. In this paper we demonstrate the application of a method that employs a capped gold nanoslit surface plasmon resonance (SPR) sensor and a microfluidic chip for the detection of a urinary nucleic acid biomarker in clinical samples. This method detects low concentrations of the biomarker in a relatively large volume (∼1 mL) of the sample. The method utilizes magnetic nanoparticles (MNPs) for the isolation of target molecules and signal enhancement in conjunction with surface plasmon resonance (SPR) on capped gold nanoslits. The ability of the method to detect urinary miRNA-16-5p in AKI patients was tested and the result was compared with the data obtained with the polymerase chain reaction (PCR). miRNA-16-5p has been found to be a specific and noninvasive biomarker for acute kidney injury (AKI). Our method allows the detection of the biomarker in the urine of AKI patients without amplification and labeling of the target molecules.

  4. Urinary ATP may be a dynamic biomarker of detrusor overactivity in women with overactive bladder syndrome.

    Directory of Open Access Journals (Sweden)

    Miguel Silva-Ramos

    Full Text Available BACKGROUND: Nowadays, there is a considerable bulk of evidence showing that ATP has a prominent role in the regulation of human urinary bladder function and in the pathophysiology of detrusor overactivity. ATP mediates nonadrenergic-noncholinergic detrusor contractions in overactive bladders. In vitro studies have demonstrated that uroepithelial cells and cholinergic nerves from overactive human bladder samples (OAB release more ATP than controls. Here, we compared the urinary ATP concentration in samples collected non-invasively from OAB women with detrusor overactivity and age-matched controls. METHODS: Patients with neurologic diseases, history of malignancy, urinary tract infections or renal impairment (creatinine clearance <70 ml/min were excluded. All patients completed a 3-day voiding diary, a 24 h urine collection and blood sampling to evaluate creatinine clearance. Urine samples collected during voluntary voids were immediately freeze-preserved for ATP determination by the luciferin-luciferase bioluminescence assay; for comparison purposes, samples were also tested for urinary nerve growth factor (NGF by ELISA. RESULTS: The urinary content of ATP, but not of NGF, normalized to patients' urine creatinine levels (ATP/Cr or urinary volume (ATP.Vol were significantly (P<0.05 higher in OAB women with detrusor overactivity (n = 34 than in healthy controls (n = 30. Significant differences between the two groups were still observed by boosting urinary ATP/Cr content after water intake, but these were not detected for NGF/Cr. In OAB patients, urinary ATP/Cr levels correlated inversely with mean voided volumes determined in a 3-day voiding diary. CONCLUSION: A high area under the receiver operator characteristics (ROC curve (0.741; 95% CI 0.62-0.86; P<0.001 is consistent with urinary ATP/Cr being a highly sensitive dynamic biomarker for assessing detrusor overactivity in women with OAB syndrome.

  5. Urinary alpha1-antichymotrypsin: a biomarker of prion infection.

    Directory of Open Access Journals (Sweden)

    Gino Miele

    Full Text Available The occurrence of blood-borne prion transmission incidents calls for identification of potential prion carriers. However, current methods for intravital diagnosis of prion disease rely on invasive tissue biopsies and are unsuitable for large-scale screening. Sensitive biomarkers may help meeting this need. Here we scanned the genome for transcripts elevated upon prion infection and encoding secreted proteins. We found that alpha(1-antichymotrypsin (alpha(1-ACT was highly upregulated in brains of scrapie-infected mice. Furthermore, alpha(1-ACT levels were dramatically increased in urine of patients suffering from sporadic Creutzfeldt-Jakob disease, and increased progressively throughout the disease. Increased alpha(1-ACT excretion was also found in cases of natural prion disease of animals. Therefore measurement of urinary alpha(1-ACT levels may be useful for monitoring the efficacy of therapeutic regimens for prion disease, and possibly also for deferring blood and organ donors that may be at risk of transmitting prion infections.

  6. IL-8 as a urinary biomarker for the detection of bladder cancer

    Directory of Open Access Journals (Sweden)

    Urquidi Virginia

    2012-05-01

    Full Text Available Abstract Background Current urine-based assays for bladder cancer (BCa diagnosis lack accuracy, so the search for improved biomarkers continues. Through genomic and proteomic profiling of urine, we have identified a panel of biomarkers associated with the presence of BCa. In this study, we evaluated the utility of three of these biomarkers, interleukin 8 (IL-8, Matrix metallopeptidase 9 (MMP-9 and Syndecan in the diagnosis of BCa through urinalysis. Methods Voided urines from 127 subjects, cancer subjects (n = 64, non-cancer subjects (n = 63 were analyzed. The protein concentrations of IL-8, MMP-9, and Syndecan were assessed by enzyme-linked immunosorbent assay (ELISA. Data were also compared to a commercial ELISA-based BCa detection assay (BTA-Trak© and urinary cytology. We used the area under the curve of a receiver operating characteristic (AUROC to compare the performance of each biomarker. Results Urinary protein concentrations of IL-8, MMP-9 and BTA were significantly elevated in BCa subjects. Of the experimental markers compared to BTA-Trak©, IL-8 was the most prominent marker (AUC; 0.79; 95% confidence interval [CI], 0.72-0.86. Multivariate regression analysis revealed that only IL-8 (OR; 1.51; 95% CI, 1.16-1.97, p = 0.002 was an independent factor for the detection of BCa. Conclusions These results suggest that the measurement of IL-8 in voided urinary samples may have utility for urine-based detection of BCa. These findings need to be confirmed in a larger, prospective cohort.

  7. Distribution and determinants of urinary biomarkers of exposure to organophosphate insecticides in Puerto Rican pregnant women

    Science.gov (United States)

    Lewis, Ryan C.; Cantonwine, David E.; Anzalota Del Toro, Liza V.; Calafat, Antonia M.; Valentin-Blasini, Liza; Davis, Mark D.; Montesano, M. Angela; Alshawabkeh, Akram N.; Cordero, José F.

    2015-01-01

    Globally, human exposures to organophosphate (OP) insecticides may pose a significant burden to the health of mothers and their developing fetuses. Unfortunately, relevant data is limited in certain areas of the world concerning sources of exposure to OP insecticides in pregnant populations. To begin to address this gap in information for Puerto Rico, we studied repeated measures of urinary concentrations of 10 OP insecticide metabolites among 54 pregnant women from the northern karst region of the island. We also collected demographic data and self-reported information on the consumption of fruits, vegetables, and legumes in the past 48-hr before urine collection and home pest-related issues. We calculated the distributions of the urinary biomarkers and compared them to women of reproductive age from the general U.S. population. We also used statistical models accounting for correlated data to assess within-subject temporal variability of the urinary biomarkers and to identify predictors of exposure. We found that for all but two metabolites (para-nitrophenol [PNP], diethylthiophosphate [DETP]), 50th or 95th percentile urinary concentrations (the metric that was used for comparison was based on the biomarker’s detection frequency) of the other eight metabolites (3,5,6-trichloro-2-pyridinol [TCPY], 2-isopropyl-4-methyl-6-hydroxy-pyrimidine, malathion dicarboxylic acid, diethylphosphate, diethyldithiophosphate, dimethylphosphate, dimethylthiophosphate [DMTP], dimethyldithiophosphate) were somewhat lower in our cohort compared with similarly aged women from the continental United States. TCPY, PNP, DETP, and DMTP, which were the only urinary metabolites detected in greater than 50% of the samples, had poor reproducibility (intraclass correlation coefficient range: 0.19–0.28) during pregnancy. Positive predictors of OP insecticide exposure included: age; marital or employment status; consumption of cherries, grape juice, peanuts, peanut butter, or raisins; and

  8. Urinary peptidomics identifies potential biomarkers for major depressive disorder.

    Science.gov (United States)

    Wang, Ying; Chen, Jianjun; Chen, Liang; Zheng, Peng; Xu, Hong-Bo; Lu, Jia; Zhong, Jiaju; Lei, Yang; Zhou, Chanjuan; Ma, Qingwei; Li, Yan; Xie, Peng

    2014-06-30

    Major depressive disorder (MDD) is a debilitating psychiatric illness with no available objective laboratory-based diagnostic test. In this study, matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS)-based peptidomics was applied to identify potential urinary diagnostic biomarkers for MDD. A training set of 42 first-episode drug-naive MDD patients and 28 age- and gender-matched healthy controls (HC) was used to develop a peptide diagnostic pattern. Then, the diagnostic efficacy of this pattern was assessed in an independent blinded test set consisting of 24 MDD patients and 13 age- and gender-matched HC. A combination of five potential biomarkers was identified, yielding a sensitivity of 91.7% and specificity of 84.6% in the test set. Moreover, the protein precursors of four of the five peptides were identified by tandem mass spectrometric analysis: serum albumin, apolipoprotein A-I, protein AMBP, and basement membrane-specific heparan sulfate proteoglycan core protein. Taken together, the peptide pattern may be valuable for establishing an objective laboratory-based diagnostic test for MDD.

  9. Urinary tobacco smoke-constituent biomarkers for assessing risk of lung cancer.

    Science.gov (United States)

    Yuan, Jian-Min; Butler, Lesley M; Stepanov, Irina; Hecht, Stephen S

    2014-01-15

    Tobacco-constituent biomarkers are metabolites of specific compounds present in tobacco or tobacco smoke. Highly reliable analytic methods, based mainly on mass spectrometry, have been developed for quantitation of these biomarkers in both urine and blood specimens. There is substantial interindividual variation in smoking-related lung cancer risk that is determined in part by individual variability in the uptake and metabolism of tobacco smoke carcinogens. Thus, by incorporating these biomarkers in epidemiologic studies, we can potentially obtain a more valid and precise measure of in vivo carcinogen dose than by using self-reported smoking history, ultimately improving the estimation of smoking-related lung cancer risk. Indeed, we have demonstrated this by using a prospective study design comparing biomarker levels in urine samples collected from smokers many years before their development of cancer versus those in their smoking counterparts without a cancer diagnosis. The following urinary metabolites were associated with lung cancer risk, independent of smoking intensity and duration: cotinine plus its glucuronide, a biomarker of nicotine uptake; 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and its glucuronides (total NNAL), a biomarker of the tobacco carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK); and r-1-,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene (PheT), a biomarker of polycyclic aromatic hydrocarbons (PAH). These results provide several possible new directions for using tobacco smoke-constituent biomarkers in lung cancer prevention, including improved lung cancer risk assessment, intermediate outcome determination in prevention trials, and regulation of tobacco products.

  10. Biomonitoring of concurrent mycotoxin exposure among adults in Sweden through urinary multi-biomarker analysis.

    Science.gov (United States)

    Wallin, S; Gambacorta, L; Kotova, N; Lemming, E Warensjö; Nälsén, C; Solfrizzo, M; Olsen, M

    2015-09-01

    Mycotoxin producing moulds may contaminate numerous agricultural commodities either before harvest or during storage. A varied diet consisting of different foods may therefore be contaminated with a range of mycotoxins. The aim of the present study was to study concurrent exposure to mycotoxins through urinary multi-biomarker analysis, as well as its possible associations with the diet. Urinary samples from 252 adults, participating in the Swedish national dietary survey Riksmaten 2010-11, were collected together with a 4-day diet record. Concurrent mycotoxin exposure was studied using a multi-biomarker LC-MS/MS method. The results revealed that exposure to mycotoxins is common and concurrent exposure to more than one toxin was found in 69% of the study population. However, when comparing the number of toxins detected with the reported consumption data it was difficult to distinguish food patterns which would indicate an increased risk of exposure to many mycotoxins simultaneously. This is the first study to investigate concurrent mycotoxin exposure and urinary levels of fumonisin B1 (FB1), fumonisin B2 (FB2), nivalenol (NIV), ochratoxin A (OTA), zearalenone (ZEA), α-zearalenol (α-ZOL), β-zearalenol (β-ZOL) and de-epoxydeoxynivalenol (DOM-1) among adults in Sweden.

  11. Urinary 1-Hydroxypyrene is Associated with Oxidative Stress and Inflammatory Biomarkers in Acute Myocardial Infarction

    Directory of Open Access Journals (Sweden)

    Fernando Freitas

    2014-09-01

    Full Text Available Several studies have associated exposure to environmental pollutants, especially polycyclic aromatic hydrocarbons (PAHs, with the development of cardiovascular diseases. Considering that 1-hydroxypyrene (1-OHP is the major biomarker of exposure to pyrenes, the purpose of this study was to evaluate the potential association between 1-OHP and oxidative stress/inflammatory biomarkers in patients who had suffered an acute myocardial infarction (AMI. After adopting the exclusion criteria, 58 post-infarction patients and 41 controls were sub-divided into smokers and non-smokers. Urinary 1-OHP, hematological and biochemical parameters, oxidative stress biomarkers (MDA, SOD, CAT, GPx and exogenous antioxidants and the inflammatory biomarker (hs-CRP were analyzed. 1-OHP levels were increased in post-infarct patients compared to controls (p < 0.05 and were correlated to MDA (r = 0.426, p < 0.01, CAT (r = 0.474, p < 0.001 and β-carotene (r = −0.309; p < 0.05 in non-smokers. Furthermore, post-infarction patients had elevated hs-CRP, MDA, CAT and GPx levels compared to controls for both smokers and non-smokers. Besides, β-carotene levels and SOD activity were decreased in post-infarction patients. In summary, our findings indicate that the exposure to pyrenes was associated to lipid damage and alterations of endogenous and exogenous antioxidants, demonstrating that PAHs contribute to oxidative stress and are associated to acute myocardial infarction.

  12. Repeated measures of urinary oxidative stress biomarkers during pregnancy and preterm birth.

    Science.gov (United States)

    Ferguson, Kelly K; McElrath, Thomas F; Chen, Yin-Hsiu; Loch-Caruso, Rita; Mukherjee, Bhramar; Meeker, John D

    2015-02-01

    The purpose of this study was to investigate oxidative stress as a mechanism of preterm birth in human subjects; we examined associations between urinary biomarkers of oxidative stress that were measured at multiple time points during pregnancy and preterm birth. This nested case-control study included 130 mothers who delivered preterm and 352 mothers who delivered term who were originally recruited as part of an ongoing prospective birth cohort at Brigham and Women's Hospital. Two biomarkers that included 8-hydroxydeoxyguanosine (8-OHdG) and 8-isoprostane were measured in urine samples that were collected at up to 4 time points (median 10, 18, 26, and 35 weeks) during gestation. Urinary concentrations of 8-isoprostane and 8-OHdG decreased and increased, respectively, as pregnancy progressed. Average levels of 8-isoprostane across pregnancy were associated with increased odds of spontaneous preterm birth (adjusted odds ratio, 6.25; 95% confidence interval, 2.86-13.7), and associations were strongest with levels measured later in pregnancy. Average levels of 8-OHdG were protective against overall preterm birth (adjusted odds ratio, 0.19; 95% confidence interval, 0.10-0.34), and there were no apparent differences in the protective effect in cases of spontaneous preterm birth compared with cases of placental origin. Odds ratios for overall preterm birth were more protective in association with urinary 8-OHdG concentrations that were measured early in pregnancy. Maternal oxidative stress may be an important contributor to preterm birth, regardless of subtype and timing of exposure during pregnancy. The 2 biomarkers that were measured in the present study had opposite associations with preterm birth; an improved understanding of what each represents may help to identify more precisely important mechanisms in the pathway to preterm birth. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Urinary biomarkers of flame retardant exposure among collegiate U.S. gymnasts.

    Science.gov (United States)

    Carignan, Courtney C; Fang, Mingliang; Stapleton, Heather M; Heiger-Bernays, Wendy; McClean, Michael D; Webster, Thomas F

    2016-09-01

    Flame retardants are widely used in polyurethane foam materials including gymnastics safety equipment such as pit cubes and landing mats. We previously reported elevated concentrations of flame retardants in the air and dust of a U.S. gymnastics training facility and elevated PentaBDE in the serum of collegiate gymnasts. Our objective in this pilot study was to compare urinary biomarkers of exposure to other flame retardants and additives of polyurethane foam including tris(1,3-dichloro-2-propyl) phosphate (TDCIPP), triphenyl phosphate (TPHP) and 2-ethylhexyl- 2,3,4,5-tetrabromobenzoate (EH-TBB) in samples collected from 11 collegiate gymnasts before and after a gymnastics practice (n=53 urine samples total). We identified a 50% increase in the TPHP biomarker (p=0.03) from before to after practice, a non-significant 22% increase in the TDCIPP biomarker (p=0.14) and no change for the EH-TBB biomarker. These preliminary results indicate that the gymnastics training environment can be a source of recreational exposure to flame retardants. Such exposures are likely widespread, as we identified flame retardants in 89% of foam samples collected from gyms across the U.S.

  14. Urinary biomarker concentrations of captan, chlormequat, chlorpyrifos and cypermethrin in UK adults and children living near agricultural land.

    Science.gov (United States)

    Galea, Karen S; MacCalman, Laura; Jones, Kate; Cocker, John; Teedon, Paul; Cherrie, John W; van Tongeren, Martie

    2015-01-01

    There is limited information on the exposure to pesticides experienced by UK residents living near agricultural land. This study aimed to investigate their pesticide exposure in relation to spray events. Farmers treating crops with captan, chlormequat, chlorpyrifos or cypermethrin provided spray event information. Adults and children residing ≤100 m from sprayed fields provided first-morning void urine samples during and outwith the spray season. Selected samples (1-2 days after a spray event and at other times (background samples)) were analysed and creatinine adjusted. Generalised Linear Mixed Models were used to investigate if urinary biomarkers of these pesticides were elevated after spray events. The final data set for statistical analysis contained 1518 urine samples from 140 participants, consisting of 523 spray event and 995 background samples which were analysed for pesticide urinary biomarkers. For captan and cypermethrin, the proportion of values below the limit of detection was greater than 80%, with no difference between spray event and background samples. For chlormequat and chlorpyrifos, the geometric mean urinary biomarker concentrations following spray events were 15.4 μg/g creatinine and 2.5 μg/g creatinine, respectively, compared with 16.5 μg/g creatinine and 3.0 μg/g creatinine for background samples within the spraying season. Outwith the spraying season, concentrations for chlorpyrifos were the same as those within spraying season backgrounds, but for chlormequat, lower concentrations were observed outwith the spraying season (12.3 μg/g creatinine). Overall, we observed no evidence indicative of additional urinary pesticide biomarker excretion as a result of spray events, suggesting that sources other than local spraying are responsible for the relatively low urinary pesticide biomarkers detected in the study population.

  15. Biomarkers identified by urinary metabonomics for noninvasive diagnosis of nutritional rickets.

    Science.gov (United States)

    Wang, Maoqing; Yang, Xue; Ren, Lihong; Li, Songtao; He, Xuan; Wu, Xiaoyan; Liu, Tingting; Lin, Liqun; Li, Ying; Sun, Changhao

    2014-09-01

    Nutritional rickets is a worldwide public health problem; however, the current diagnostic methods retain shortcomings for accurate diagnosis of nutritional rickets. To identify urinary biomarkers associated with nutritional rickets and establish a noninvasive diagnosis method, urinary metabonomics analysis by ultra-performance liquid chromatography/quadrupole time-of-flight tandem mass spectrometry and multivariate statistical analysis were employed to investigate the metabolic alterations associated with nutritional rickets in 200 children with or without nutritional rickets. The pathophysiological changes and pathogenesis of nutritional rickets were illustrated by the identified biomarkers. By urinary metabolic profiling, 31 biomarkers of nutritional rickets were identified and five candidate biomarkers for clinical diagnosis were screened and identified by quantitative analysis and receiver operating curve analysis. Urinary levels of five candidate biomarkers were measured using mass spectrometry or commercial kits. In the validation step, the combination of phosphate and sebacic acid was able to give a noninvasive and accurate diagnostic with high sensitivity (94.0%) and specificity (71.2%). Furthermore, on the basis of the pathway analysis of biomarkers, our urinary metabonomics analysis gives new insight into the pathogenesis and pathophysiology of nutritional rickets.

  16. Urinary Biomarkers in the Assessment of Early Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Cristina Gluhovschi

    2016-01-01

    Full Text Available Diabetic nephropathy (DN is a frequent and severe complication of diabetes mellitus (DM. Its diagnosis in incipient stages may allow prompt interventions and an improved prognosis. Towards this aim, biomarkers for detecting early DN can be used. Microalbuminuria has been proven a remarkably useful biomarker, being used for diagnosis of DN, for assessing its associated condition—mainly cardiovascular ones—and for monitoring its progression. New researches are pointing that some of these biomarkers (i.e., glomerular, tubular, inflammation markers, and biomarkers of oxidative stress precede albuminuria in some patients. However, their usefulness is widely debated in the literature and has not yet led to the validation of a new “gold standard” biomarker for the early diagnosis of DN. Currently, microalbuminuria is an important biomarker for both glomerular and tubular injury. Other glomerular biomarkers (transferrin and ceruloplasmin are under evaluation. Tubular biomarkers in DN seem to be of a paramount importance in the early diagnosis of DN since tubular lesions occur early. Additionally, biomarkers of inflammation, oxidative stress, podocyte biomarkers, and vascular biomarkers have been employed for assessing early DN. The purpose of this review is to provide an overview of the current biomarkers used for the diagnosis of early DN.

  17. Six methods for determining urinary protein compared.

    Science.gov (United States)

    Dilena, B A; Penberthy, L A; Fraser, C G

    1983-03-01

    Inter-laboratory surveys have shown that "routine methods" of urinary protein determination are often unsatisfactory. Therefore, we compared six frequently used methods for determination of protein in urine with respect to linearity, within-batch and between-batch precision, comparative bias, and practicability. We assayed dilutions of human and bovine albumin and serum, and fresh and lyophilized human urine. We find that the AACC Selected Method has poor practicability and poor precision under routine conditions, but good linearity. The sulfosalicylic acid/biuret technique is also impracticable, requires a large sample, and is not linear at low concentrations of urine protein. The Coomassie Brilliant Blue technique has a narrow range of linearity and poor precision. The sulfosalicylic acid/sodium sulfate turbidimetric method is not precise and cannot be standardized with bovine materials. The Ponceau-S technique has good performance characteristics and practicability, and we recommend it for routine laboratory use.

  18. Urinary collagen IV and πGST: potential biomarkers for detecting localized kidney injury in diabetes--a pilot study.

    LENUS (Irish Health Repository)

    Cawood, T J

    2010-01-01

    Urinary biomarkers can identify damage to specific parts of the nephron. We performed a cross-sectional study to characterise the pattern of diabetic nephropathy using urinary biomarkers of glomerular fibrosis (collagen IV), proximal tubular damage (α-glutathione-S-transferase, GST) and distal tubular damage (πGST).

  19. A Comparative Analysis of Biomarker Selection Techniques

    Directory of Open Access Journals (Sweden)

    Nicoletta Dessì

    2013-01-01

    Full Text Available Feature selection has become the essential step in biomarker discovery from high-dimensional genomics data. It is recognized that different feature selection techniques may result in different set of biomarkers, that is, different groups of genes highly correlated to a given pathological condition, but few direct comparisons exist which quantify these differences in a systematic way. In this paper, we propose a general methodology for comparing the outcomes of different selection techniques in the context of biomarker discovery. The comparison is carried out along two dimensions: (i measuring the similarity/dissimilarity of selected gene sets; (ii evaluating the implications of these differences in terms of both predictive performance and stability of selected gene sets. As a case study, we considered three benchmarks deriving from DNA microarray experiments and conducted a comparative analysis among eight selection methods, representatives of different classes of feature selection techniques. Our results show that the proposed approach can provide useful insight about the pattern of agreement of biomarker discovery techniques.

  20. Urinary KIM-1 and AQP-1 in patients with clear renal cell carcinoma: Potential noninvasive biomarkers

    Directory of Open Access Journals (Sweden)

    Mijušković Mirjana

    2016-01-01

    Full Text Available Background/Aim. Kidney injury molecule-1 (KIM-1 and aquaporin-1 (AQP-1 are potential early urinary biomarkers of clear renal cell carcinoma (cRCC. The aim of this study was to ascertain relationship between the urine concentrations KIM-1 and AQP-1 with tumor size, grade, pT stage and type of operation (radical or partial nephrectomy in patients with cRCC. Methods. Urinary concentrations of urinary KIM-1 (uKIM-1 and urinary AQP-1 (uAQP-1 were determined by commercially available ELISA kits. The analysis included 40 patients undergoing partial or radical nephrectomy for cRCC and 40 age- and sex-matched healthy adult volunteers. Results. The median preoperative concentrations of KIM-1 in the cRCC group [0.724 ± 1.120 ng/mg urinary creatinine (Ucr] were significantly greater compared with controls (healthy volunteers (0.210 ± 0.082 ng/mgUcr (p = 0.0227. Postoperatively, uKIM-1 concentration decreased significantly to control values (0.177 ± 0.099 ng/mgUcr vs 0.210 ± 0.082 ng/mgUcr, respectively. The size, grade and stage of tumor were correlated positively with preoperative uKIM-1 concentrations. Contrary to these results, concentrations of uAQP-1 in the cRCC group were significantly lower (0.111 ± 0.092 ng/mgUcr compared with the control group (0.202 ± 0.078 ng/mgUcr (p = 0.0014. Postoperatively, the concentrations of uAQP-1 increased progressively up to control values, approximately. We find no significant correlation between preoperative uAQP-1 concentrations and tumor size, grade and stage. Conclusion. uKIM-1 was found to be a reliable diagnostic marker of cRCC, based on its significantly increased values before and decreased values after the nephrectomy. [Projekat Ministarstva nauke Republike Srbije, br. III41018

  1. Comparison of three methods for isolation of urinary microvesicles to identify biomarkers of nephrotic syndrome.

    NARCIS (Netherlands)

    Rood, I.M.; Deegens, J.K.J.; Merchant, M.L.; Tamboer, W.P.M.; Wilkey, D.W.; Wetzels, J.F.M.; Klein, J.B.

    2010-01-01

    Urinary microvesicles, such as 40-100 nm exosomes and 100-1000 nm microparticles, contain many proteins that may serve as biomarkers of renal disease. Microvesicles have been isolated by ultracentrifugation or nanomembrane ultrafiltration from normal urine; however, little is known about the

  2. Urinary Extracellular Vesicles: Potential Biomarkers of Renal Function in Diabetic Patients

    Directory of Open Access Journals (Sweden)

    Agnieszka Kamińska

    2016-01-01

    Full Text Available The aim of this study was to check the relationship between the density of urinary EVs, their size distribution, and the progress of early renal damage in type 2 diabetic patients (DMt2. Patients were enrolled to this study, and glycated hemoglobin (HbA1c below 7% was a threshold for properly controlled diabetic patients (CD and poorly controlled diabetic patients (UD. Patients were further divided into two groups: diabetic patients without renal failure (NRF and with renal failure (RF according to the Glomerular Filtration Rate. Density and diameter of EVs were determined by Tunable Resistive Pulse Sensing. Additionally, EVs were visualized by means of Transmission and Environmental Scanning Electron Microscopy. Nano-liquid chromatography coupled offline with mass spectrometry (MALDI-TOF-MS/MS was applied for proteomic analysis. RF had reduced density of EVs compared to NRF. The size distribution study showed that CD had larger EVs (mode than UD (115 versus 109 nm; p<0.05; nevertheless the mean EVs diameter was smaller in controls than in the CD group (123 versus 134 nm; p<0.05. It was demonstrated that EVs are abundant in urine. Albumin, uromodulin, and number of unique proteins related to cell stress and secretion were detected in the EVs fraction. Density and size of urinary EVs reflect deteriorated renal function and can be considered as potential renal damage biomarkers.

  3. Urinary Extracellular Vesicles: Potential Biomarkers of Renal Function in Diabetic Patients

    Science.gov (United States)

    Platt, Mark; Kasprzyk, Joanna; Kuśnierz-Cabala, Beata; Gala-Błądzińska, Agnieszka; Woźnicka, Olga; Jany, Benedykt R.; Krok, Franciszek; Piekoszewski, Wojciech; Kuźniewski, Marek

    2016-01-01

    The aim of this study was to check the relationship between the density of urinary EVs, their size distribution, and the progress of early renal damage in type 2 diabetic patients (DMt2). Patients were enrolled to this study, and glycated hemoglobin (HbA1c) below 7% was a threshold for properly controlled diabetic patients (CD) and poorly controlled diabetic patients (UD). Patients were further divided into two groups: diabetic patients without renal failure (NRF) and with renal failure (RF) according to the Glomerular Filtration Rate. Density and diameter of EVs were determined by Tunable Resistive Pulse Sensing. Additionally, EVs were visualized by means of Transmission and Environmental Scanning Electron Microscopy. Nano-liquid chromatography coupled offline with mass spectrometry (MALDI-TOF-MS/MS) was applied for proteomic analysis. RF had reduced density of EVs compared to NRF. The size distribution study showed that CD had larger EVs (mode) than UD (115 versus 109 nm; p < 0.05); nevertheless the mean EVs diameter was smaller in controls than in the CD group (123 versus 134 nm; p < 0.05). It was demonstrated that EVs are abundant in urine. Albumin, uromodulin, and number of unique proteins related to cell stress and secretion were detected in the EVs fraction. Density and size of urinary EVs reflect deteriorated renal function and can be considered as potential renal damage biomarkers. PMID:28105442

  4. Identification and validation of urinary metabolite biomarkers for major depressive disorder.

    Science.gov (United States)

    Zheng, Peng; Wang, Ying; Chen, Liang; Yang, Deyu; Meng, Huaqing; Zhou, Dezhi; Zhong, Jiaju; Lei, Yang; Melgiri, N D; Xie, Peng

    2013-01-01

    Major depressive disorder (MDD) is a widespread and debilitating mental disorder. However, there are no biomarkers available to aid in the diagnosis of this disorder. In this study, a nuclear magnetic resonance spectroscopy-based metabonomic approach was employed to profile urine samples from 82 first-episode drug-naïve depressed subjects and 82 healthy controls (the training set) in order to identify urinary metabolite biomarkers for MDD. Then, 44 unselected depressed subjects and 52 healthy controls (the test set) were used to independently validate the diagnostic generalizability of these biomarkers. A panel of five urinary metabolite biomarkers-malonate, formate, N-methylnicotinamide, m-hydroxyphenylacetate, and alanine-was identified. This panel was capable of distinguishing depressed subjects from healthy controls with an area under the receiver operating characteristic curve (AUC) of 0.81 in the training set. Moreover, this panel could classify blinded samples from the test set with an AUC of 0.89. These findings demonstrate that this urinary metabolite biomarker panel can aid in the future development of a urine-based diagnostic test for MDD.

  5. Urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine as a biomarker in type 2 diabetes

    DEFF Research Database (Denmark)

    Broedbaek, Kasper; Weimann, Allan; Stovgaard, Elisabeth Ida Specht;

    2011-01-01

    . The available epidemiological evidence regarding urinary 8-oxodG and type 2 diabetes is presented. A possible role for DNA oxidation in cancer development in type 2 diabetes patients is discussed, followed by an evaluation of the potential of urinary 8-oxodG as a clinical biomarker in type 2 diabetes....... as a valuable biomarker in diabetes is the DNA oxidation marker 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), which can be assessed noninvasively in the urine, with minimal discomfort for the patient. In this review the analytical validity of 8-oxodG is addressed by highlighting important methodological issues......The increasing prevalence of diabetes together with the associated morbidity and mortality calls for additional preventive and therapeutic strategies. New biomarkers that can be used in therapy control and risk stratification as alternatives to current methods are needed and can facilitate a more...

  6. Comparison and evaluation of urinary biomarkers for occupational exposure to spray adhesives containing 1-bromopropane.

    Science.gov (United States)

    Mathias, Patricia I; Cheever, Kenneth L; Hanley, Kevin W; Marlow, Katherine L; Johnson, Belinda C; B'hymer, Clayton

    2012-09-01

    Three metabolites of 1-bromopropane (1-BP) were measured in urine samples collected from 30 workers exposed to 1-BP at two facilities making furniture seat cushions and evaluated for use as biomarkers of exposure. The mercapturic acid metabolite, N-acetyl-S-(n-propyl)-l-cysteine (AcPrCys), 3-bromopropionic acid (3-BPA), and bromide ion levels (Br(-)) were quantitated for this evaluation. The high exposure group consisted of 13 workers employed as adhesive sprayers who assembled foam cushions using 1-BP containing spray adhesives and the low exposure group consisted of 17 non-sprayers, who worked in various jobs without spraying adhesives. All workers' urine voids were collected over the same 48 h period at work, and at home before bedtime, and upon awakening. Urinary AcPrCys and Br(-) levels were elevated in the sprayers compared to that of non-sprayers. Following HPLC-MS/MS analysis of mercapturic acid metabolite levels, 50 urine samples having the highest levels of AcPrCys were analyzed for 3-BPA. No 3-BPA was detected in any of the samples. The data collected from this study demonstrate that AcPrCys and Br(-) are effective biomarkers of 1-BP exposure, but 3-BPA is not.

  7. Clinical proteomics identifies urinary CD14 as a potential biomarker for diagnosis of stable coronary artery disease.

    Directory of Open Access Journals (Sweden)

    Min-Yi Lee

    Full Text Available Inflammation plays a key role in coronary artery disease (CAD and other manifestations of atherosclerosis. Recently, urinary proteins were found to be useful markers for reflecting inflammation status of different organs. To identify potential biomarker for diagnosis of CAD, we performed one-dimensional SDS-gel electrophoresis followed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS. Among the proteins differentially expressed in urine samples, monocyte antigen CD14 was found to be consistently expressed in higher amounts in the CAD patients as compared to normal controls. Using enzyme-linked immunosorbent assays to analyze the concentrations of CD14 in urine and serum, we confirmed that urinary CD14 levels were significantly higher in patients (n = 73 with multi-vessel and single vessel CAD than in normal control (n = 35 (P < 0.001. Logistic regression analysis further showed that urinary CD14 concentration level is associated with severity or number of diseased vessels and SYNTAX score after adjustment for potential confounders. Concomitantly, the proportion of CD14+ monocytes was significantly increased in CAD patients (59.7 ± 3.6% as compared with healthy controls (14.9 ± 2.1% (P < 0.001, implicating that a high level of urinary CD14 may be potentially involved in mechanism(s leading to CAD pathogenesis. By performing shotgun proteomics, we further revealed that CD14-associated inflammatory response networks may play an essential role in CAD. In conclusion, the current study has demonstrated that release of CD14 in urine coupled with more CD14+ monocytes in CAD patients is significantly correlated with severity of CAD, pointing to the potential application of urinary CD14 as a novel noninvasive biomarker for large-scale diagnostic screening of susceptible CAD patients.

  8. Urinary MicroRNA as Biomarker in Renal Transplantation

    NARCIS (Netherlands)

    Vrie, M. van de; Deegens, J.K.J.; Eikmans, M.; Vlag, J. van der; Hilbrands, L.B.

    2017-01-01

    Urine represents a noninvasive source in which proteins and nucleic acids can be assessed. Such analytes may function as biomarkers to monitor kidney graft pathology at every desired frequency, thereby providing a time window to prevent graft damage by therapeutic intervention. Recently, several

  9. Urinary paraben concentrations among pregnant women and their matching newborn infants of Korea, and the association with oxidative stress biomarkers.

    Science.gov (United States)

    Kang, Sungeun; Kim, Sunmi; Park, Jeongim; Kim, Hae-Joong; Lee, Jeongjae; Choi, Gyuyeon; Choi, Sooran; Kim, Sungjoo; Kim, Su Young; Moon, Hyo-Bang; Kim, Sungkyoon; Kho, Young Lim; Choi, Kyungho

    2013-09-01

    Parabens have been used in multiple products including personal care products, pharmaceuticals, and foods for more than 50 years but increasing numbers of studies have raised concerns on their safety. The present study was designed to determine urinary paraben levels among pregnant women and their matching newborn infants (paraben levels and stress markers. Pregnant women (n=46) and their matching newborn infants were recruited from four university hospitals located in Seoul, Ansan and Jeju of Korea, 2011. Parabens including methyl paraben (MP), ethyl paraben (EP), n-propyl paraben (PP), and n-butyl paraben (BP) were measured in the urine using an automatic, high throughput online SPE-LC-MS/MS method. Urinary concentrations were normalized with specific gravity (SG). Free cortisol, malondealdehyde (MDA) and 8-hydroxydeoxyguanosine (8-OHdG) were measured in the urine as stress marker. Urinary MP was detected as the highest, and BP was detected as the lowest paraben in the urine samples of both pregnant women and their infants. Significant correlations between paraben concentrations of maternal and their newborn infant's urine were observed. The levels of urinary parabens among Korean pregnant women are comparable to those reported elsewhere, except for EP which were 4-9 folds higher than pregnant women of other countries. The ratios of infant to maternal urinary paraben concentrations varied between 0.5 and 0.6 for MP and PP, but approximately 10 fold lower for EP. Urinary MP or EP levels were associated with several oxidative stress related biomarkers such as urinary 8-OHdG and MDA, even after the adjustment of relevant covariates such as maternal age, mode of delivery, pre-pregnancy BMI, gestational age and parity. This is the first study that reported the levels of major parabens in the first urine of newborn infants. Further studies are warranted to understand the implications of paraben exposure among biologically susceptible human populations.

  10. Urinary DNA lesions as a biomarker for assessing male reproductive health

    Directory of Open Access Journals (Sweden)

    Hueiwang Anna Jeng

    2015-06-01

    Full Text Available The study aimed to examine whether urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG could serve as a biomarker for assessing sperm DNA integrity. Urine and semen samples were collected from 124 coke-oven workers, who had chronically been exposed to polycyclic aromatic hydrocarbons (PAHs, from a steel plant in Kaohsiung, Taiwan. The coke-oven workers were divided into two subgroups: topside-oven workers and side-oven workers. Sperm DNA integrity was assessed in terms of DNA fragmentation and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo. Urine samples were used to detect 1-hydroxypyrene (1-OHP and urinary 8-OHdG, which served to assess exposure to PAHs and the whole body oxidative stress, respectively. Urinary 1-OHP concentrations were significantly higher in the topside-oven workers than the side-oven workers (p = 0.02. Sperm 8-oxodGuo concentrations were correlated with percentages of sperm fragmentation (p = 0.044, but urinary 8-OHdG levels failed to correlate with sperm 8-oxodGuo levels and with percentages of fragmentation. In conclusion, exposure to PAHs was linked to increased oxidative stress on sperm. However, urinary 8-OHdG may not be a suitable biomarker for examining sperm DNA damage associated with oxidative stress.

  11. Application of systems biology principles to protein biomarker discovery: Urinary exosomal proteome in renal transplantation

    Science.gov (United States)

    Das, Samarjit; Knepper, Mark A.; Bagnasco, Serena M.

    2013-01-01

    Purpose In MS-based studies to discover urinary protein biomarkers, an important question is how to analyze the data to find the most promising potential biomarkers to be advanced to large-scale validation studies. Here, we describe a ‘systems biology-based’ approach to address this question. Experimental design We analyzed large-scale LC-MS/MS data of urinary exosomes from renal allograft recipients with biopsy-proven evidence of immunological rejection or tubular injury. We asked whether bioinformatic analysis of urinary exosomal proteins can identify protein groups that correlate with biopsy findings and whether the protein groups fit with general knowledge of the pathophysiological mechanisms involved. Results LC-MS/MS analysis of urinary exosomal proteomes identified more than 1000 proteins in each pathologic group. These protein lists were analyzed computationally to identify Biological Process and KEGG Pathway terms that are significantly associated with each pathological group. Among the most informative terms for each group were: “sodium ion transport” for tubular injury; “immune response” for all rejection; “epithelial cell differentiation” for cell-mediated rejection; and “acute inflammatory response” for antibody-mediated rejection. Based on these terms, candidate biomarkers were identified using a novel strategy to allow a dichotomous classification between different pathologic categories. Conclusions and clinical relevance The terms and candidate biomarkers identified make rational connections to pathophysiological mechanisms, suggesting that the described bioinformatic approach will be useful in advancing large-scale biomarker identification studies toward a validation phase. PMID:22641613

  12. Urinary Podocalyxin as a Biomarker to Diagnose Membranous Nephropathy

    Science.gov (United States)

    Nakatochi, Masahiro; Akiyama, Shin’ichi; Yamaguchi, Makoto; Kurosawa, Hiroyuki; Hirayama, Yoshiaki; Katsuno, Takayuki; Tsuboi, Naotake; Hara, Masanori; Maruyama, Shoichi

    2016-01-01

    Background A non-invasive diagnostic marker of membranous nephropathy (MN) is desirable. The urinary level of podocalyxin (PCX) is higher in various glomerular diseases, including MN. The aim of this study was to construct a diagnostic model of MN with the combination of urinary PCX and clinical parameters. Methods We performed this cross-sectional study to construct the diagnostic models for MN by using data and samples from the multicenter kidney biopsy registry of Nagoya University and its affiliated hospitals. Urinary (u-) PCX was measured by sandwich ELISA. We constructed 3 types of diagnostic models in 105 training samples: u-PCX univariate model, the combined model of clinical parameters other than u-PCX (clinical model), and the combined model of both u-PCX and clinical parameters (combined model). We assessed the clinical usefulness of the diagnostic models through the comparison of c-statistics and decision curve analysis (DCA) in 209 validation samples. Results The clinical model consisted of age, glomerular filtration rate, and diabetes mellitus. In the training cohort, the c-statistics were 0.868 [95% CI, 0.799–0.937] in the combined model. In the validation cohort, sensitivity was 80.5% and specificity was 73.5% on the cut-off value. The net benefit of the combined model was better between threshold probabilities of 40–80% in DCA. Conclusions In this study, we demonstrated the utility of u-PCX as a diagnostic marker for MN and the clinical usefulness of the diagnostic models, through the combination of u-PCX and clinical parameters including age, glomerular filtration rate, and diabetes mellitus. PMID:27668430

  13. Urinary Proteomics Pilot Study for Biomarker Discovery and Diagnosis in Heart Failure with Reduced Ejection Fraction

    DEFF Research Database (Denmark)

    Rossing, Kasper; Bosselmann, Helle Skovmand; Gustafsson, Finn

    2016-01-01

    Background Biomarker discovery and new insights into the pathophysiology of heart failure with reduced ejection fraction (HFrEF) may emerge from recent advances in high-throughput urinary proteomics. This could lead to improved diagnosis, risk stratification and management of HFrEF. Methods......EF103 very accurately (area under the curve, AUC = 0.972) discriminated between HFrEF patients (N = 94, sensitivity = 93.6%) and control individuals with and without impaired renal function and hypertension (N = 552, specificity = 92.9%). Interestingly, HFrEF103 showed low sensitivity (12...... to determine a vast array of HFrEF-related urinary peptide biomarkers which might help improving our understanding and diagnosis of heart failure....

  14. Heparin-binding protein: a diagnostic biomarker of urinary tract infection in adults.

    OpenAIRE

    Kjölvmark, Charlott; Påhlman, Lisa; Åkesson, Per; Linder, Adam

    2014-01-01

    Background.  Urinary tract infections (UTIs) are associated with significant morbidity and high frequency of antibiotic prescription. Diagnosing UTI is often difficult, particularly in the critically ill patient and in patients with unspecific and mild symptoms. The standard rapid tests have limited value, and there is a need for more reliable diagnostic tools. Heparin-binding protein (HBP) is released from neutrophils and has previously been studied as a diagnostic and predictive biomarker i...

  15. Urinary Proteomics Pilot Study for Biomarker Discovery and Diagnosis in Heart Failure with Reduced Ejection Fraction.

    Directory of Open Access Journals (Sweden)

    Kasper Rossing

    Full Text Available Biomarker discovery and new insights into the pathophysiology of heart failure with reduced ejection fraction (HFrEF may emerge from recent advances in high-throughput urinary proteomics. This could lead to improved diagnosis, risk stratification and management of HFrEF.Urine samples were analyzed by on-line capillary electrophoresis coupled to electrospray ionization micro time-of-flight mass spectrometry (CE-MS to generate individual urinary proteome profiles. In an initial biomarker discovery cohort, analysis of urinary proteome profiles from 33 HFrEF patients and 29 age- and sex-matched individuals without HFrEF resulted in identification of 103 peptides that were significantly differentially excreted in HFrEF. These 103 peptides were used to establish the support vector machine-based HFrEF classifier HFrEF103. In a subsequent validation cohort, HFrEF103 very accurately (area under the curve, AUC = 0.972 discriminated between HFrEF patients (N = 94, sensitivity = 93.6% and control individuals with and without impaired renal function and hypertension (N = 552, specificity = 92.9%. Interestingly, HFrEF103 showed low sensitivity (12.6% in individuals with diastolic left ventricular dysfunction (N = 176. The HFrEF-related peptide biomarkers mainly included fragments of fibrillar type I and III collagen but also, e.g., of fibrinogen beta and alpha-1-antitrypsin.CE-MS based urine proteome analysis served as a sensitive tool to determine a vast array of HFrEF-related urinary peptide biomarkers which might help improving our understanding and diagnosis of heart failure.

  16. Calcium montmorillonite clay reduces urinary biomarkers of fumonisin B₁ exposure in rats and humans.

    Science.gov (United States)

    Robinson, A; Johnson, N M; Strey, A; Taylor, J F; Marroquin-Cardona, A; Mitchell, N J; Afriyie-Gyawu, E; Ankrah, N A; Williams, J H; Wang, J S; Jolly, P E; Nachman, R J; Phillips, T D

    2012-01-01

    Fumonisin B₁ (FB₁) is often a co-contaminant with aflatoxin (AF) in grains and may enhance AF's carcinogenicity by acting as a cancer promoter. Calcium montmorillonite (i.e. NovaSil, NS) is a possible dietary intervention to help decrease chronic aflatoxin exposure where populations are at risk. Previous studies show that an oral dose of NS clay was able to reduce AF exposure in a Ghanaian population. In vitro analyses from our laboratory indicated that FB₁ (like aflatoxin) could also be sorbed onto the surfaces of NS. Hence, our objectives were to evaluate the efficacy of NS clay to reduce urinary FB₁ in a rodent model and then in a human population highly exposed to AF. In the rodent model, male Fisher rats were randomly assigned to either FB₁ control, FB₁ + 2% NS or absolute control group. FB₁ alone or with clay was given as a single dose by gavage. For the human trial, participants received NS (1.5 or 3 g day⁻¹) or placebo (1.5 g day⁻¹) for 3 months. Urines from weeks 8 and 10 were collected from the study participants for analysis. In rats, NS significantly reduced urinary FB₁ biomarker by 20% in 24 h and 50% after 48 h compared to controls. In the humans, 56% of the urine samples analysed (n = 186) had detectable levels of FB₁. Median urinary FB₁ levels were significantly (p 90% in the high dose NS group (3 g day⁻¹) compared to the placebo. This work indicates that our study participants in Ghana were exposed to FB₁ (in addition to AFs) from the diet. Moreover, earlier studies have shown conclusively that NS reduces the bioavailability of AF and the findings from this study suggest that NS clay also reduces the bioavailability FB₁. This is important since AF is a proven dietary risk factor for hepatocellular carcinoma (HCC) in humans and FB₁ is suspected to be a dietary risk factor for HCC and oesophageal cancer in humans.

  17. Novel automated biomarker discovery work flow for urinary peptidomics

    DEFF Research Database (Denmark)

    Balog, Crina I.; Hensbergen, Paul J.; Derks, Rico

    2009-01-01

    eluted peptides using MALDI-TOF, Fourier transform ion cyclotron resonance, and liquid chromatography-iontrap mass spectrometry. We determined qualitative and quantitative reproducibility of the system and robustness of the method using BSA digests and urine samples, and we used a selected set of urine...... numbers of urine samples, resulting in a broad spectrum of native peptides, as a tool to be used for biomarker discovery. METHODS: Peptide samples were trapped, desalted, pH-normalized, and fractionated on a miniaturized automatic reverse-phase strong cation exchange (RP-SCX) cartridge system. We analyzed...... samples from Schistosoma haematobium-infected individuals to evaluate clinical applicability. RESULTS: The automated RP-SCX sample cleanup and fractionation system exhibits a high qualitative and quantitative reproducibility, with both BSA standards and urine samples. Because of the relatively high...

  18. Kidney injury molecule-1: A urinary biomarker for contrast-induced acute kidney injury

    Directory of Open Access Journals (Sweden)

    M Vijayasimha

    2014-01-01

    Full Text Available Background: Urinary kidney injury molecule 1 (KIM-1 is an early biomarker for renal damage. A few studies have been published analyzing the potential use of urinary KIM-1 as a biomarker for acute kidney injury (AKI. However, no study has been done related to AKI associated with contrast administration. Aim: To search for new markers to identify AKI associated with contrast administration earlier than serum creatinine. Materials and Methods: We studied 100 consecutive patients with normal serum creatinine undergoing angiographic procedure. We assessed urine KIM-1, at 4, 8, and 24 hours after the angiographic procedure. Serum creatinine was measured at basal, 24, and 48 hours after the procedure. Results: There was a significant rise in urinary KIM-1 levels at 24 hours after the angiographic procedure. The presence of contrast induced nephropathy associated with AKI was 12%. Conclusion: The present study highlighted the importance of urinary KIM-1 in detecting AKI associated with contrast administration earlier than Serum creatinine.

  19. Urinary 1-hydroxypyrene as a biomarker of carcinogenic polycyclic aromatic hydrocarbons in Iranian carbon anode plant workers

    Directory of Open Access Journals (Sweden)

    Mehdi Zare

    2012-01-01

    Conclusion: The results confirm urinary 1-hydroxypyrene level as a good biomarker in cPAHs exposed workers. In addition, considering the level of urinary 1-hydroxypyrene, it can be concluded that studied carbon anode plant workers are exposed to substantial risk of cancer and other genotoxic effects which are the result of cPAHs exposure.

  20. Comparison between urinary o-cresol and toluene as biomarkers of toluene exposure.

    Science.gov (United States)

    Fustinoni, Silvia; Mercadante, Rosa; Campo, Laura; Scibetta, Licia; Valla, Carla; Consonni, Dario; Foà, Vito

    2007-01-01

    The characteristics of urinary o-cresol (o-C) and urinary toluene (TOL-U) as biomarkers of occupational exposure to toluene were comparatively evaluated. One hundred healthy male rotogravure printing workers and 161 male and female control subjects were studied. Personal exposure to airborne toluene (TOL-A) during the shift was determined as a time-weighted average. Simple analytical procedures based on solid phase microextraction followed by gas chromatography/mass spectometry analysis were applied to the determination of end-shift o-C and TOL-U. Median TOL-A was 48 (6.0-162.0) mg/m3 in printers and 0.021 (<0.003-0.137) mg/m3 in controls. o-C was 0.185 (0.032-0.948) mg/g creatinine in printers and 0.027 (<0.006-0.330) mg/g creatinine in the controls. TOL-U was 7.6 (1.8-23.9) microg/L in printers and 0.140 (0.094-0.593) microg/L in the controls. According to all indices, exposure to toluene was higher in printers than in the controls. Nevertheless, the distribution of o-C in the two groups partially overlapped, whereas such behavior was not found in TOL-U. Both o-C and TOL-U in printers were correlated with TOL-A (Pearson's on log10-transformed variables r = 0.704 and 0.844, respectively) and with each other (r = 0.683). Smoking habits significantly increased the excretion of o-C but not of TOL-U. From the point of view of sampling conditions and analytical requirements, TOL-U and o-C showed similar properties, but comparison of their intrinsic characteristics showed that TOL-U had higher specificity and sensitivity, lower background values, was better correlated with airborne exposure, and was not influenced by cigarette smoking. Therefore TOL-U may be considered superior to o-C as a biomarker of occupational exposure to toluene.

  1. Urinary C-type natriuretic peptide: an emerging biomarker for heart failure and renal remodeling.

    Science.gov (United States)

    Zakeri, Rosita; Burnett, John C; Sangaralingham, S Jeson

    2015-03-30

    The public health and economic burden of heart failure (HF) is staggering and the need for relevant pathophysiologic and clinical biomarkers to advance the field and improve HF therapy remains high. Renal dysfunction is common among HF patients and is associated with increased HF hospitalization and mortality. It is widely recognized that mechanisms contributing to HF pathogenesis include a complex bidirectional interaction between the kidney and heart, encompassed by the term cardiorenal syndrome (CRS). Among a new wave of urinary biomarkers germane to CRS, C-type natriuretic peptide (CNP) has emerged as an innovative biomarker of renal structural and functional impairment in HF and chronic renal disease states. CNP is a hormone, synthesized in the kidney, and is an important regulator of cell proliferation and organ fibrosis. Hypoxia, cytokines and fibrotic growth factors, which are inherent to both cardiac and renal remodeling processes, are among the recognized stimuli for CNP production and release. In this review we aim to highlight current knowledge regarding the biology and pathophysiological correlates of urinary CNP, and its potential clinical utility as a diagnostic and prognostic biomarker in HF and renal disease states.

  2. Urinary neutrophil gelatinase-associated lipocalin is a biomarker of delayed graft function after kidney transplantation

    Directory of Open Access Journals (Sweden)

    Capelli I

    2017-01-01

    Full Text Available Irene Capelli, Olga Baraldi, Giorgia Comai, Elisa Sala, Maria Cappuccilli, Chiara Donadei, Vania Cuna, Maria Laura Angelini, Gabriele Donati, Gaetano La Manna Department of Experimental Diagnostic and Specialty Medicine (DIMES, Nephrology, Dialysis and Renal Transplant Unit, St Orsola Hospital, University of Bologna, Bologna, Italy Background: Acute kidney injury occurring after kidney transplantation frequently leads to delayed graft function with detrimental long-term effects on graft survival. Neutrophil gelatinase-associated lipocalin (NGAL has been validated as a biomarker for posttransplant acute kidney injury. This observational study aimed to assess the effectiveness of urinary NGAL as a predictive marker of delayed graft function.Materials and methods: Forty-three consecutive patients who received renal transplant were included in the study. Urine samples were collected before transplant (if available and at days 1, 3, 7, 14, and 30 after transplant, and urinary NGAL levels were quantified by enzyme-linked immunosorbent assay.Results: Urinary NGAL progressively decreased after transplant in patients with both delayed and immediate graft function. However, urinary NGAL concentration remained significantly higher in the presence of delayed graft function in the first 14 days after transplant. The area under the receiver operating characteristic curve showed that the ability of urinary NGAL to predict delayed graft function was accurate at 1st and 3rd days after transplant.Conclusion: The relative decrease of urinary NGAL concentration rather than its absolute value may be relevant to predict delayed graft function after renal transplant. In particular, urinary NGAL area under the curve for 3 days seems to be a more valuable parameter of decision making in the early posttransplant period. Keywords: area under the curve, delayed graft function, immediate graft function, kidney transplant, NGAL, acute kidney injury

  3. Urinary aminopeptidase activities as early and predictive biomarkers of renal dysfunction in cisplatin-treated rats.

    Directory of Open Access Journals (Sweden)

    Andrés Quesada

    Full Text Available This study analyzes the fluorimetric determination of alanyl- (Ala, glutamyl- (Glu, leucyl-cystinyl- (Cys and aspartyl-aminopeptidase (AspAp urinary enzymatic activities as early and predictive biomarkers of renal dysfunction in cisplatin-treated rats. Male Wistar rats (n = 8 each group received a single subcutaneous injection of either saline or cisplatin 3.5 or 7 mg/kg, and urine samples were taken at 0, 1, 2, 3 and 14 days after treatment. In urine samples we determined Ala, Glu, Cys and AspAp activities, proteinuria, N-acetyl-β-D-glucosaminidase (NAG, albumin, and neutrophil gelatinase-associated lipocalin (NGAL. Plasma creatinine, creatinine clearance and renal morphological variables were measured at the end of the experiment. CysAp, NAG and albumin were increased 48 hours after treatment in the cisplatin 3.5 mg/kg treated group. At 24 hours, all urinary aminopeptidase activities and albuminuria were significantly increased in the cisplatin 7 mg/kg treated group. Aminopeptidase urinary activities correlated (p0.259 with plasma creatinine, creatinine clearance and/or kidney weight/body weight ratio at the end of the experiment and they could be considered as predictive biomarkers of renal injury severity. ROC-AUC analysis was made to study their sensitivity and specificity to distinguish between treated and untreated rats at day 1. All aminopeptidase activities showed an AUC>0.633. We conclude that Ala, Cys, Glu and AspAp enzymatic activities are early and predictive urinary biomarkers of the renal dysfunction induced by cisplatin. These determinations can be very useful in the prognostic and diagnostic of renal dysfunction in preclinical research and clinical practice.

  4. Development of urinary pseudotargeted LC-MS-based metabolomics method and its application in hepatocellular carcinoma biomarker discovery.

    Science.gov (United States)

    Shao, Yaping; Zhu, Bin; Zheng, Ruiyin; Zhao, Xinjie; Yin, Peiyuan; Lu, Xin; Jiao, Binghua; Xu, Guowang; Yao, Zhenzhen

    2015-02-01

    Hepatocellular carcinoma (HCC) is one of the pestilent malignancies leading to cancer-related death. Discovering effective biomarkers for HCC diagnosis is an urgent demand. To identify potential metabolite biomarkers, we developed a urinary pseudotargeted method based on liquid chromatography-hybrid triple quadrupole linear ion trap mass spectrometry (LC-QTRAP MS). Compared with nontargeted method, the pseudotargeted method can achieve better data quality, which benefits differential metabolites discovery. The established method was applied to cirrhosis (CIR) and HCC investigation. It was found that urinary nucleosides, bile acids, citric acid, and several amino acids were significantly changed in liver disease groups compared with the controls, featuring the dysregulation of purine metabolism, energy metabolism, and amino metabolism in liver diseases. Furthermore, some metabolites such as cyclic adenosine monophosphate, glutamine, and short- and medium-chain acylcarnitines were the differential metabolites of HCC and CIR. On the basis of binary logistic regression, butyrylcarnitine (carnitine C4:0) and hydantoin-5-propionic acid were defined as combinational markers to distinguish HCC from CIR. The area under curve was 0.786 and 0.773 for discovery stage and validation stage samples, respectively. These data show that the established pseudotargeted method is a complementary one of targeted and nontargeted methods for metabolomics study.

  5. Urinary paraben concentrations among pregnant women and their matching newborn infants of Korea, and the association with oxidative stress biomarkers

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Sungeun; Kim, Sunmi [School of Public Health, Seoul National University (Korea, Republic of); Park, Jeongim [College of Natural Sciences, Soonchunhyang University (Korea, Republic of); Kim, Hae-Joong [College of Medicine, Korea University (Korea, Republic of); Lee, Jeongjae; Choi, Gyuyeon [College of Medicine, Soonchunhyang University (Korea, Republic of); Choi, Sooran; Kim, Sungjoo [College of Medicine, Hallym University (Korea, Republic of); Kim, Su Young [College of Medicine, Jeju National University (Korea, Republic of); Moon, Hyo-Bang [College of Science and Technology, Hanyang University (Korea, Republic of); Kim, Sungkyoon [School of Public Health, Seoul National University (Korea, Republic of); Kho, Young Lim [Department of Health, Environment and Safety, Eulji University (Korea, Republic of); Choi, Kyungho, E-mail: kyungho@snu.ac.kr [School of Public Health, Seoul National University (Korea, Republic of)

    2013-09-01

    Parabens have been used in multiple products including personal care products, pharmaceuticals, and foods for more than 50 years but increasing numbers of studies have raised concerns on their safety. The present study was designed to determine urinary paraben levels among pregnant women and their matching newborn infants (< 48 h after delivery), and the association between paraben levels and stress markers. Pregnant women (n = 46) and their matching newborn infants were recruited from four university hospitals located in Seoul, Ansan and Jeju of Korea, 2011. Parabens including methyl paraben (MP), ethyl paraben (EP), n-propyl paraben (PP), and n-butyl paraben (BP) were measured in the urine using an automatic, high throughput online SPE–LC–MS/MS method. Urinary concentrations were normalized with specific gravity (SG). Free cortisol, malondealdehyde (MDA) and 8-hydroxydeoxyguanosine (8-OHdG) were measured in the urine as stress marker. Urinary MP was detected as the highest, and BP was detected as the lowest paraben in the urine samples of both pregnant women and their infants. Significant correlations between paraben concentrations of maternal and their newborn infant's urine were observed. The levels of urinary parabens among Korean pregnant women are comparable to those reported elsewhere, except for EP which were 4–9 folds higher than pregnant women of other countries. The ratios of infant to maternal urinary paraben concentrations varied between 0.5 and 0.6 for MP and PP, but approximately 10 fold lower for EP. Urinary MP or EP levels were associated with several oxidative stress related biomarkers such as urinary 8-OHdG and MDA, even after the adjustment of relevant covariates such as maternal age, mode of delivery, pre-pregnancy BMI, gestational age and parity. This is the first study that reported the levels of major parabens in the first urine of newborn infants. Further studies are warranted to understand the implications of paraben exposure

  6. Urinary 1-Hydroxypyrene as a Biomarker of PAH Exposure in 3-Year-Old Ukrainian Children

    National Research Council Canada - National Science Library

    Amy Pelka Mucha; Daniel Hryhorczuk; Andrij Serdyuk; Joseph Nakonechny; Alexander Zvinchuk; Serap Erdal; Motria Caudill; Peter Scheff; Elena Lukyanova; Zoreslava Shkiryak-Nyzhnyk; Natalia Chislovska

    .... We measured urinary 1-OHP in 48 children 3 years of age in Mariupol, Ukraine, who lived near a steel mill and coking facility and compared these with 1-OHP concentrations measured in 42 children...

  7. Urinary oxidative stress biomarkers among local residents measured 6years after the Hebei Spirit oil spill.

    Science.gov (United States)

    Kim, Jung-Ah; Noh, Su Ryeon; Cheong, Hae-Kwan; Ha, Mina; Eom, Sang-Yong; Kim, Heon; Park, Myung-Sook; Chu, Yeonhee; Lee, Seung-Hwa; Choi, Kyungho

    2017-02-15

    In December 2007, the Hebei Spirit oil spill occurred on the west coast of South Korea. Association between crude oil exposure and the levels of urinary oxidative stress biomarkers was reported among the local residents, 1.5years after the accident. The aim of this study was to follow-up possible longer-term effects of the oil spill among the residents near the oil spill. Six years after the accident, urinary oxidative stress biomarkers of the residents were associated with surrogates of oil exposure. The target subjects were divided into two groups based on the distance of their residence to the spill site, i.e., those near the spill site ('Near' group, n=476), and those far from the spill ('Far' group, n=152). A questionnaire was administered by trained interviewers or self-reporting, and demographic information and other parameters of the participants, such as socioeconomic status, smoking and drinking behaviors, disease history, and duration of clean-up activities after the spill, were collected. The participants' levels of 8-hydroxy-2-deoxyguanosine (8-OHdG) and malondialdehyde (MDA) in 12 h urine samples were measured as indicators of oxidative DNA damage and lipid peroxidation, respectively. A general linear model was used for statistical analysis. Urinary MDA and 8-OHdG levels measured from 'Near' group, i.e., geometric mean of 2.19μmol/g creatinine, and 5.41μg/g creatinine, respectively, were higher than those of 'Far' group. Especially, urinary 8-OHdG levels in the 'Near' group were significantly higher than those of 'Far' after adjusting relevant covariates. In addition, the duration of clean-up activities showed a significant association with both urinary 8-OHdG and MDA levels. Even 6years after the oil spill, positive associations between oxidative stress biomarkers and surrogates of oil exposure were evident. While the present study design lacks biomarkers of exposure, the results of this study suggest that the consequences of oil pollution may last

  8. Mycotoxin exposure in rural residents in northern Nigeria: a pilot study using multi-urinary biomarkers.

    Science.gov (United States)

    Ezekiel, Chibundu N; Warth, Benedikt; Ogara, Isaac M; Abia, Wilfred A; Ezekiel, Victoria C; Atehnkeng, Joseph; Sulyok, Michael; Turner, Paul C; Tayo, Grace O; Krska, Rudolf; Bandyopadhyay, Ranajit

    2014-05-01

    A pilot, cross-sectional, correlational study was conducted in eight rural communities in northern Nigeria to investigate mycotoxin exposures in 120 volunteers (19 children, 20 adolescents and 81 adults) using a modern LC-MS/MS based multi-biomarker approach. First morning urine samples were analyzed and urinary biomarker levels correlated with mycotoxin levels in foods consumed the day before urine collection. A total of eight analytes were detected in 61/120 (50.8%) of studied urine samples, with ochratoxin A, aflatoxin M1 and fumonisin B1 being the most frequently occurring biomarkers of exposure. These mycotoxin biomarkers were present in samples from all age categories, suggestive of chronic (lifetime) exposures. Rough estimates of mycotoxin intake suggested some exposures were higher than the tolerable daily intake. Overall, rural consumer populations from Nasarawa were more exposed to several mixtures of mycotoxins in their diets relative to those from Kaduna as shown by food and urine biomarker data. This study has shown that mycotoxin co-exposure may be a major public health challenge in rural Nigeria; this calls for urgent intervention.

  9. Urinary Levels of IL-1β and GDNF in Preterm Neonates as Potential Biomarkers of Motor Development: A Prospective Study

    Directory of Open Access Journals (Sweden)

    Rafael Coelho Magalhães

    2017-01-01

    Full Text Available Objectives. To evaluate the association between inflammatory biomarkers, neurotrophic factors, birth conditions, and the presence of motor development abnormalities in preterm neonates. Methods. Plasma and urinary levels of cytokines (IL-1β, IL-6, IL-10, TNF, and IL-12p70, chemokines (CXCL8/IL-8, CCL2/MCP-1, CCL5/RANTES, CXCL10/IP-10, and CXCL9/MIG, and neurotrophic factors (BDNF and GDNF were evaluated in 40 preterm neonates born between 28 and 32 incomplete weeks of gestation, at four distinct time points: at birth (umbilical cord blood (T0, at 48 (T1, at 72 hours (T2, and at 3 weeks after birth (T3. Biomarkers levels were compared between different time points and then associated with Test of Infant Motor Performance (TIMP percentiles. Results. Maternal age, plasma, and urinary concentrations of inflammatory molecules and neurotrophic factors were significantly different between groups with normal versus lower than expected motor development. Higher levels of GDNF were found in the group with lower than expected motor development, while IL-1β and CXCL8/IL-8 values were higher in the group with typical motor development. Conclusion. Measurements of cytokines and neurotrophic factors in spot urine may be useful in the follow-up of motor development in preterm neonates.

  10. Urinary kidney injury molecule-1 as an early diagnostic biomarker of obstructive acute kidney injury and development of a rapid detection method

    Science.gov (United States)

    Jin, Yingli; Shao, Xiaona; Sun, Bo; Miao, Chunsheng; Li, Zhengqiang; Shi, Yan

    2017-01-01

    The aim of the present study was to investigate whether urinary kidney injury molecule-1 (KIM-1) presents a suitable early diagnostic biomarker of obstructive nephropathy-induced acute kidney injury (AKI), and to develop a rapid detection method for urinary KIM-1. Obstructive AKI was induced in an experimental rat model by a unilateral ureteral obstruction (UUO) operation. Macro- and micromorphological kidney alterations were determined by visual observation and hematoxylin and eosin (HE) staining, respectively. Kidney functions were evaluated by detecting urea nitrogen and creatinine levels in rat urine and blood. Urinary KIM-1 levels were measured using an enzyme-linked immunosorbent assay, and the protein expression levels of KIM-1, α-smooth muscle actin (α-SMA) and vimentin in kidney tissues were detected using immunohistochemical assays. In order to measure KIM-1 levels, colloidal gold immunochromatographic strips were developed based on the colloidal gold immunochromatographic assay. The results indicated that KIM-1 levels were significantly higher in the UUO group when compared with the Sham group. KIM-1 levels in the urine and kidney tissues exhibited a time-dependent increase, together with increasing obstructive AKI in the UUO group. In addition, KIM-1 levels were demonstrated to be a more sensitive biomarker of early obstructive AKI, when compared with α-SMA and vimentin. A colloidal gold-based immunochromatographic strip was developed, whereby the detection of urinary KIM-1 could be completed within 5–10 min. In conclusion, results of the present study demonstrated that urinary KIM-1 may be a valuable biomarker for the early diagnosis of obstructive AKI, and the use of a colloidal gold immunochromatographic strip may be a promising method for the rapid detection of urinary KIM-1. PMID:28075469

  11. Validation of trichloroacetic acid exposure via drinking water during pregnancy using a urinary TCAA biomarker.

    Science.gov (United States)

    Smith, Rachel B; Nieuwenhuijsen, Mark J; Wright, John; Raynor, Pauline; Cocker, John; Jones, Kate; Kappaostopoulou-Karadanelli, Maria; Toledano, Mireille B

    2013-10-01

    Disinfection by-product (DBP) exposure during pregnancy may be related to reduced fetal growth, but the evidence is inconclusive and improved DBP exposure assessment is required. The authors conducted a nested exposure study on a subset (n=39) of pregnant women in the Born in Bradford cohort to assess validity of TCAA exposure assessment based on tap water sampling and self-reported water-use; water-use questionnaire validity; and use of a one-time urinary TCAA biomarker. TCAA levels in urine and home tap water supply were quantified, and water use was measured via a questionnaire and 7-day diary, at 28 weeks gestation. Diary and urine measures were repeated later in pregnancy (n=14). TCAA level in home tap water supply was not correlated with urinary TCAA (0.18, P=0.29). Cold unfiltered tap water intake at home measured by questionnaire was correlated with urinary TCAA (0.44, P=0.007), but correlation was stronger still for cold unfiltered tap water intake reported over the 3 days prior to urine sampling (0.60, Pwater sampling and self-reported water-use, correlated strongly with urinary TCAA (0.78, Pwater intake is most influential in determining TCAA exposure variability in this cohort, and that TCAA ingestion at home is a valid proxy for TCAA exposure for unemployed women but less satisfactory for employed women.

  12. Urinary zearalenone measured with ELISA as a biomarker of zearalenone exposure in pigs.

    Science.gov (United States)

    Gutzwiller, A; Gafner, J L; Silacci, P

    2014-11-01

    The suitability to assess zearalenone (ZEA) exposure in pigs of a commercial ELISA kit for ZEA analysis in urine was tested. A daily dose of 0, 5, 10, 20 and 40 μg synthetic ZEA per kilogram BW was administered via the feed to four gilts per dose group, and after 3 and after 7 days of ZEA intake, urine samples were assayed with the ELISA which has a relative cross-reactivity of 42% with α-zearalenol. The concentration of urinary ZEA equivalents (ZEA plus 42% of α-zearalenol present) did not differ between day 4 and day 8 (P = 0.50) within each dose group. The urinary ZEA equivalent/creatinine ratio was tightly correlated with ZEA intake (r = 0.95). The urinary ZEA equivalent/creatinine values at 0 and 40 μg/kg BW were distinctly different from those of the intermediate dose levels, whereas there was some overlapping of the individual values at the dose levels 5, 10 and 20 μg/kg BW. The urinary ZEA equivalent/creatinine ratio can be used as a biomarker for ZEA exposure in pigs provided that urine samples of several animals receiving the same diet are assayed, either separately or after pooling.

  13. Reduction in the urinary aflatoxin M1 biomarker as an early indicator of the efficacy of dietary interventions to reduce exposure to aflatoxins.

    Science.gov (United States)

    Mitchell, Nicole J; Kumi, Justice; Johnson, Natalie M; Dotse, Eunice; Marroquin-Cardona, Alicia; Wang, Jia-Sheng; Jolly, Pauline E; Ankrah, Nii-Ayi; Phillips, Timothy D

    2013-08-01

    Aflatoxin B1 is a persistent public health issue in Ghana. Assessment of AFB1 intervention efficacy is currently dependent on long-term biomarkers. This study was designed to determine whether daily AFM1 biomarker levels could be utilized as an early detection method for intervention efficacy. Participants were treated with a refined calcium montmorillonite clay (UPSN) or a placebo (calcium carbonate) in a crossover study. Urine samples were assessed for AFM1 levels daily. UPSN treatment reduced AFM1 biomarkers by 55% compared to the placebo. This is the first study to show that daily urinary AFM1 levels can be used as a biomarker of internal aflatoxin B1 exposure in short-term intervention trials to determine efficacy.

  14. Urinary Biomarkers of Prenatal Atrazine Exposure and Adverse Birth Outcomes in the PELAGIE Birth Cohort

    Science.gov (United States)

    Limon, Gwendolina; Monfort, Christine; Rouget, Florence; Garlantézec, Ronan; Petit, Claire; Durand, Gaël; Cordier, Sylvaine

    2011-01-01

    Background: Despite evidence of atrazine toxicity in developing organisms from experimental studies, few studies—and fewer epidemiologic investigations—have examined the potential effects of prenatal exposure. Objectives: We assessed the association between adverse birth outcomes and urinary biomarkers of prenatal atrazine exposure, while taking into account exposures to other herbicides used on corn crops (simazine, alachlor, metolachlor, and acetochlor). Methods: This study used a case-cohort design nested in a prospective birth cohort conducted in the Brittany region of France from 2002 through 2006. We collected maternal urine samples to examine pesticide exposure biomarkers before the 19th week of gestation. Results: We found quantifiable levels of atrazine or atrazine mercapturate in urine samples from 5.5% of 579 pregnant women, and dealkylated and identified hydroxylated triazine metabolites in 20% and 40% of samples, respectively. The presence versus absence of quantifiable levels of atrazine or a specific atrazine metabolite was associated with fetal growth restriction [odds ratio (OR) = 1.5; 95% confidence interval (CI), 1.0–2.2] and small head circumference for sex and gestational age (OR = 1.7; 95% CI, 1.0–2.7). Associations with major congenital anomalies were not evident with atrazine or its specific metabolites. Head circumference was inversely associated with the presence of quantifiable urinary metolachlor. Conclusions: This study is the first to assess associations of birth outcomes with multiple urinary biomarkers of exposure to triazine and chloroacetanilide herbicides. Evidence of associations with adverse birth outcomes raises particular concerns for countries where atrazine is still in use. PMID:21367690

  15. Kidney injury biomarkers and urinary creatinine variability in nominally healthy adults.

    Science.gov (United States)

    Stiegel, M A; Pleil, J D; Sobus, J R; Angrish, M M; Morgan, M K

    2015-01-01

    Environmental exposure diagnostics use creatinine concentrations in urine aliquots as the internal standard for dilution normalization of all other excreted metabolites when urinary excretion rate data are not available. This is a reasonable approach for healthy adults as creatinine is a human metabolite that is continually produced in skeletal muscles and presumably excreted in the urine at a stable rate. However, creatinine also serves as a biomarker for glomerular filtration rate (efficiency) of the kidneys, so undiagnosed kidney function impairment could affect this commonly applied dilution calculation. The United States Environmental Protection Agency (US EPA) has recently conducted a study that collected approximately 2600 urine samples from 50 healthy adults, aged 19-50 years old, in North Carolina in 2009-2011. Urinary ancillary data (creatinine concentration, total void volume, elapsed time between voids), and participant demographic data (race, gender, height, and body weight) were collected. A representative subset of 280 urine samples from 29 participants was assayed using a new kidney injury panel (KIP). In this article, we investigated the relationships of KIP biomarkers within and between subjects and also calculated their interactions with measured creatinine levels. The aims of this work were to document the analytical methods (procedures, sensitivity, stability, etc.), provide summary statistics for the KIP biomarkers in "healthy" adults without diagnosed disease (distribution, fold range, central tendency, variance), and to develop an understanding as to how urinary creatinine level varies with respect to the individual KIP proteins. Results show that new instrumentation and data reduction methods have sufficient sensitivity to measure KIP levels in nominally healthy urine samples, that linear regression between creatinine concentration and urinary excretion explains only about 68% of variability, that KIP markers are poorly correlated with

  16. Comparative Genomics of Escherichia coli Strains Causing Urinary Tract Infections

    DEFF Research Database (Denmark)

    Vejborg, Rebecca Munk; Hancock, Viktoria; Schembri, Mark A.

    2011-01-01

    The virulence determinants of uropathogenic Escherichia coli have been studied extensively over the years, but relatively little is known about what differentiates isolates causing various types of urinary tract infections. In this study, we compared the genomic profiles of 45 strains from a range...

  17. The diagnostic and prognostic importance of oxidative stress biomarkers and acute phase proteins in Urinary Tract Infection (UTI) in camels.

    Science.gov (United States)

    El-Deeb, Wael M; Buczinski, Sébastien

    2015-01-01

    The present study aimed to investigate the diagnostic and prognostic importance of oxidative stress biomarkers and acute phase proteins in urinary tract infection (UTI) in camels. We describe the clinical, bacteriological and biochemical findings in 89 camels. Blood and urine samples from diseased (n = 74) and control camels (n = 15) were submitted to laboratory investigations. The urine analysis revealed high number of RBCS and pus cells. The concentrations of serum and erythrocytic malondialdehyde (sMDA & eMDA), Haptoglobin (Hp), serum amyloid A (SAA), Ceruloplasmin (Cp), fibrinogen (Fb), albumin, globulin and interleukin 6 (IL-6) were higher in diseased camels when compared to healthy ones. Catalase, super oxide dismutase and glutathione levels were lower in diseased camels when compared with control group. Forty one of 74 camels with UTI were successfully treated. The levels of malondialdehyde, catalase, super oxide dismutase, glutathione, Hp, SAA, Fb, total protein, globulin and IL-6 were associated with the odds of treatment failure. The MDA showed a great sensitivity (Se) and specificity (Sp) in predicting treatment failure (Se 85%/Sp 100%) as well as the SAA (Se 92%/Sp 87%) and globulin levels (Se 85%/Sp 100%) when using the cutoffs that maximizes the sum of Se + Sp. Multivariate logistic regression analysis revealed that two models had a high accuracy to predict failure with the first model including sex, sMDA and Hp as covariates (area under the receiver operating characteristic curve (AUC) = 0.92) and a second model using sex, SAA and Hp (AUC = 0.89). Conclusively, the oxidative stress biomarkers and acute phase proteins could be used as diagnostic and prognostic biomarkers in camel UTI management. Efforts should be forced to investigate such biomarkers in other species with UTI.

  18. Urinary biomarkers of smokers' exposure to tobacco smoke constituents in tobacco products assessment: a fit for purpose approach.

    Science.gov (United States)

    Gregg, Evan O; Minet, Emmanuel; McEwan, Michael

    2013-09-01

    There are established guidelines for bioanalytical assay validation and qualification of biomarkers. In this review, they were applied to a panel of urinary biomarkers of tobacco smoke exposure as part of a "fit for purpose" approach to the assessment of smoke constituents exposure in groups of tobacco product smokers. Clinical studies have allowed the identification of a group of tobacco exposure biomarkers demonstrating a good doseresponse relationship whilst others such as dihydroxybutyl mercapturic acid and 2-carboxy-1-methylethylmercapturic acid - did not reproducibly discriminate smokers and non-smokers. Furthermore, there are currently no agreed common reference standards to measure absolute concentrations and few inter-laboratory trials have been performed to establish consensus values for interim standards. Thus, we also discuss in this review additional requirements for the generation of robust data on urinary biomarkers, including toxicant metabolism and disposition, method validation and qualification for use in tobacco products comparison studies.

  19. Dietary predictors of urinary environmental biomarkers in young girls, BCERP, 2004-7.

    Science.gov (United States)

    Mervish, Nancy; McGovern, Kathleen J; Teitelbaum, Susan L; Pinney, Susan M; Windham, Gayle C; Biro, Frank M; Kushi, Lawrence H; Silva, Manori J; Ye, Xiaoyun; Calafat, Antonia M; Wolff, Mary S

    2014-08-01

    Exposures of children to phthalates, parabens, and bisphenol-A (BPA) are of concern because of their hormonal potential. These agents are found in a wide range of foods and packaging. We investigated whether intake of certain foods predict exposures to these chemicals in young girls. Among 1101 girls (6-8 years at enrollment) from the Breast Cancer and Environment Research Program (BCERP) study, we measured urinary exposure biomarkers for phthalates, parabens, and BPA and assessed dietary intake using 24-h recall 2-4 times. We examined the average daily servings of major and minor food groups categorized as 0 to fish, fruit, single grains, meat, non-poultry meats, pasta, poultry and vegetables. Covariate-adjusted least squares geometric means and 95% confidence intervals of creatinine-corrected phthalate and phenol metabolite concentrations in urine were calculated in relation to food intake. Grains, flour and dry mixes and total fish consumption were positively associated with BPA and the sum of four di-2-ethylhexylphthalate (DEHP) urinary metabolite concentrations. Non-fresh vegetables and poultry were both positively associated with BPA and paraben urinary concentrations. Fats, oils and poultry consumption were positively associated with BPA. Whole-fat dairy consumption was associated with ΣDEHP. Some foods may contribute to child exposures to certain chemicals, and this may constitute modifiable means to reduce these environmental exposures. Copyright © 2014 Elsevier Inc. All rights reserved.

  20. Urinary biomarkers TIMP-2 and IGFBP7 early predict acute kidney injury after major surgery.

    Directory of Open Access Journals (Sweden)

    Ivan Gocze

    Full Text Available To assess the ability of the urinary biomarkers IGFBP7 (insulin-like growth factor-binding protein 7 and TIMP-2 (tissue inhibitor of metalloproteinase 2 to early predict acute kidney injury (AKI in high-risk surgical patients.Postoperative AKI is associated with an increase in short and long-term mortality. Using IGFBP7 and TIMP-2 for early detection of cellular kidney injury, thus allowing the early initiation of renal protection measures, may represent a new concept of evaluating renal function.In this prospective study, urinary [TIMP-2]×[IGFBP7] was measured in surgical patients at high risk for AKI. A predefined cut-off value of [TIMP-2]×[IGFBP7] >0.3 was used for assessing diagnostic accuracy. Perioperative characteristics were evaluated, and ROC analyses as well as logistic regression models of risk assessment were calculated with and without a [TIMP-2]×[IGFBP7] test.107 patients were included in the study, of whom 45 (42% developed AKI. The highest median values of biomarker were detected in septic, transplant and patients after hepatic surgery (1.24 vs 0.45 vs 0.47 ng/l²/1000. The area under receiving operating characteristic curve (AUC for the risk of any AKI was 0.85, for early use of RRT 0.83 and for 28-day mortality 0.77. In a multivariable model with established perioperative risk factors, the [TIMP-2]×[IGFBP7] test was the strongest predictor of AKI and significantly improved the risk assessment (p<0.001.Urinary [TIMP-2]×[IGFBP7] test sufficiently detect patients with risk of AKI after major non-cardiac surgery. Due to its rapid responsiveness it extends the time frame for intervention to prevent development of AKI.

  1. Urinary methyl tert-butyl ether and benzene as biomarkers of exposure to urban traffic.

    Science.gov (United States)

    Campo, Laura; Cattaneo, Andrea; Consonni, Dario; Scibetta, Licia; Costamagna, Paolo; Cavallo, Domenico M; Bertazzi, Pier Alberto; Fustinoni, Silvia

    2011-02-01

    Methyl tert-butyl ether (MTBE) and benzene are added to gasoline to improve the combustion process and are found in the urban environment as a consequence of vehicular traffic. Herein we evaluate urinary MTBE (MTBE-U) and benzene (BEN-U) as biomarkers of exposure to urban traffic. Milan urban policemen (130 total) were investigated in May, July, October, and December for a total of 171 work shifts. Personal exposure to airborne benzene and carbon monoxide (CO), and atmospheric data, were measured during the work shift, while personal characteristics were collected by a questionnaire. A time/activity diary was completed by each subject during the work shift. Spot urine samples were obtained for the determination of MTBE-U and BEN-U. Median personal exposure to CO and airborne benzene were 3.3 mg/m(3) and 9.6 μg/m(3), respectively; median urinary levels in end-of-shift (ES) samples were 147 ng/L (MTBE-U) and 207 ng/L (BEN-U). The time spent on traffic duty at crossing was about 40% of work time. Multiple linear regression models, taking into account within-subject correlations, were applied to investigate the role of urban pollution, atmospheric conditions, job variables and personal characteristics on the level of biomarkers. MTBE-U was influenced by the month of sampling and positively correlated to the time spent in traffic guarding, CO exposure and atmospheric pressure, while negatively correlated to wind speed (R(2) for total model 0.63, P<0.001). BEN-U was influenced by the month and smoking habit, and positively correlated to urinary creatinine; moreover, an interaction between CO and smoking was found (R(2)=0.62, P<0.001). These results suggest that MTBE-U is a reliable marker for assessing urban traffic exposure, while BEN-U is determined mainly by personal characteristics.

  2. Urinary excretion of the acrylonitrile metabolite 2-cyanoethylmercapturic acid is correlated with a variety of biomarkers of tobacco smoke exposure and consumption.

    Science.gov (United States)

    Minet, Emmanuel; Cheung, Francis; Errington, Graham; Sterz, Katharina; Scherer, Gerhard

    2011-02-01

    Acrylonitrile is an IARC class 2B carcinogen present in cigarette smoke. Urinary 2-cyanoethylmercapturic acid (CEMA) is an acrylonitrile metabolite and a potential biomarker for acrylonitrile exposure. The objective of this work was to study the dose response of CEMA in urine of non-smokers and smokers of different ISO tar yield cigarettes. We observed that smokers excreted >100-fold higher amounts of urinary CEMA than non-smokers. The CEMA levels in smokers were significantly correlated with ISO tar yield, daily cigarette consumption, and urinary biomarkers of smoke exposure. In conclusion, urinary CEMA is a suitable biomarker for assessing smoking-related exposure to acrylonitrile.

  3. Urinary excretion of the acrylonitrile metabolite 2-cyanoethylmercapturic acid is correlated with a variety of biomarkers of tobacco smoke exposure and consumption

    Science.gov (United States)

    Minet, Emmanuel; Cheung, Francis; Errington, Graham; Sterz, Katharina; Scherer, Gerhard

    2011-01-01

    Acrylonitrile is an IARC class 2B carcinogen present in cigarette smoke. Urinary 2-cyanoethylmercapturic acid (CEMA) is an acrylonitrile metabolite and a potential biomarker for acrylonitrile exposure. The objective of this work was to study the dose response of CEMA in urine of non-smokers and smokers of different ISO tar yield cigarettes. We observed that smokers excreted >100-fold higher amounts of urinary CEMA than non-smokers. The CEMA levels in smokers were significantly correlated with ISO tar yield, daily cigarette consumption, and urinary biomarkers of smoke exposure. In conclusion, urinary CEMA is a suitable biomarker for assessing smoking-related exposure to acrylonitrile. PMID:21108560

  4. Pharmacogenomic Variants May Influence the Urinary Excretion of Novel Kidney Injury Biomarkers in Patients Receiving Cisplatin.

    Science.gov (United States)

    Chang, Cara; Hu, Yichun; Hogan, Susan L; Mercke, Nickie; Gomez, Madeleine; O'Bryant, Cindy; Bowles, Daniel W; George, Blessy; Wen, Xia; Aleksunes, Lauren M; Joy, Melanie S

    2017-06-22

    Nephrotoxicity is a dose limiting side effect associated with the use of cisplatin in the treatment of solid tumors. The degree of nephrotoxicity is dictated by the selective accumulation of cisplatin in renal tubule cells due to: (1) uptake by organic cation transporter 2 (OCT2) and copper transporter 1 (CTR1); (2) metabolism by glutathione S-transferases (GSTs) and γ-glutamyltransferase 1 (GGT1); and (3) efflux by multidrug resistance-associated protein 2 (MRP2) and multidrug and toxin extrusion protein 1 (MATE1). The purpose of this study was to determine the significance of single nucleotide polymorphisms that regulate the expression and function of transporters and metabolism genes implicated in development of acute kidney injury (AKI) in cisplatin treated patients. Changes in the kidney function were assessed using novel urinary protein biomarkers and traditional markers. Genotyping was conducted by the QuantStudio 12K Flex Real-Time PCR System using a custom open array chip with metabolism, transport, and transcription factor polymorphisms of interest to cisplatin disposition and toxicity. Traditional and novel biomarker assays for kidney toxicity were assessed for differences according to genotype by ANOVA. Allele and genotype frequencies were determined based on Caucasian population frequencies. The polymorphisms rs596881 (SLC22A2/OCT2), and rs12686377 and rs7851395 (SLC31A1/CTR1) were associated with renoprotection and maintenance of estimated glomerular filtration rate (eGFR). Polymorphisms in SLC22A2/OCT2, SLC31A1/CTRI, SLC47A1/MATE1, ABCC2/MRP2, and GSTP1 were significantly associated with increases in the urinary excretion of novel AKI biomarkers: KIM-1, TFF3, MCP1, NGAL, clusterin, cystatin C, and calbindin. Knowledge concerning which genotypes in drug transporters are associated with cisplatin-induced nephrotoxicity may help to identify at-risk patients and initiate strategies, such as using lower or fractionated cisplatin doses or avoiding

  5. Urinary iodine, thyroid function, and thyroglobulin as biomarkers of iodine status.

    Science.gov (United States)

    Pearce, Elizabeth N; Caldwell, Kathleen L

    2016-09-01

    The accurate assessment of population iodine status is necessary to inform public health policies and clinical research on iodine nutrition, particularly the role of iodine adequacy in normal neurodevelopment. Urinary iodine concentration (UIC) directly reflects dietary iodine intake and is the most common indicator used worldwide to assess population iodine status. The CDC established the Ensuring the Quality of Iodine Procedures program in 2001 to provide laboratories that measure urinary iodine with an independent assessment of their analytic performance; this program fosters improvement in the assessment of UIC. Clinical laboratory tests of thyroid function (including serum concentrations of the pituitary hormone thyrotropin and the thyroid hormones thyroxine and triiodothyronine) are sometimes used as indicators of iodine status, although such use is often problematic. Even in severely iodine-deficient regions, there is a great deal of intraindividual variation in the ability of the thyroid to adapt. In most settings and in most population subgroups other than newborns, thyroid function tests are not considered sensitive indicators of population iodine status. However, the thyroid-derived protein thyroglobulin is increasingly being used for this purpose. Thyroglobulin can be measured in either serum or dried blood spot (DBS) samples. The use of DBS samples is advantageous in resource-poor regions. Improved methodologies for ascertaining maternal iodine status are needed to facilitate research on developmental correlates of iodine status. Thyroglobulin may prove to be a useful biomarker for both maternal and neonatal iodine status, but validated assay-specific reference ranges are needed for the determination of iodine sufficiency in both pregnant women and neonates, and trimester-specific ranges are possibly needed for pregnant women. UIC is currently a well-validated population biomarker, but individual biomarkers that could be used for research, patient care

  6. Urinary isoxanthohumol is a specific and accurate biomarker of beer consumption.

    Science.gov (United States)

    Quifer-Rada, Paola; Martínez-Huélamo, Miriam; Chiva-Blanch, Gemma; Jáuregui, Olga; Estruch, Ramon; Lamuela-Raventós, Rosa M

    2014-04-01

    Biomarkers of food consumption are a powerful tool to obtain more objective measurements of dietary exposure and to monitor compliance in clinical trials. In this study, we evaluated the effectiveness of urinary isoxanthohumol (IX) excretion as an accurate biomarker of beer consumption. A dose-response clinical trial, a randomized, crossover clinical trial, and a cohort study were performed. In the dose-response trial, 41 young volunteers (males and females, aged 28 ± 3 y) consumed different doses of beer at night and a spot urine sample was collected the following morning. In the clinical trial, 33 males with high cardiovascular risk (aged 61 ± 7 y) randomly were administered 30 g of ethanol/d as gin or beer, or an equivalent amount of polyphenols as nonalcoholic beer for 4 wk. Additionally, a subsample of 46 volunteers from the PREDIMED (Prevenciόn con Dieta Mediterránea) study (males and females, aged 63 ± 5 y) was also evaluated. Prenylflavonoids were quantified in urine samples by liquid chromatography coupled to mass spectrometry. IX urinary recovery increased linearly with the size of the beer dose in male volunteers. A significant increase in IX excretion (4.0 ± 1.6 μg/g creatinine) was found after consumption of beer and nonalcoholic beer for 4 wk (P beer consumers and abstainers with a sensitivity of 67% and specificity of 100% (positive predictive value = 70%, negative predictive value = 100% in real-life conditions). IX in urine samples was found to be a specific and accurate biomarker of beer consumption and may be a powerful tool in epidemiologic studies.

  7. Recommendations and Standardization of Biomarker Quantification Using NMR-Based Metabolomics with Particular Focus on Urinary Analysis.

    Science.gov (United States)

    Emwas, Abdul-Hamid; Roy, Raja; McKay, Ryan T; Ryan, Danielle; Brennan, Lorraine; Tenori, Leonardo; Luchinat, Claudio; Gao, Xin; Zeri, Ana Carolina; Gowda, G A Nagana; Raftery, Daniel; Steinbeck, Christoph; Salek, Reza M; Wishart, David S

    2016-02-05

    NMR-based metabolomics has shown considerable promise in disease diagnosis and biomarker discovery because it allows one to nondestructively identify and quantify large numbers of novel metabolite biomarkers in both biofluids and tissues. Precise metabolite quantification is a prerequisite to move any chemical biomarker or biomarker panel from the lab to the clinic. Among the biofluids commonly used for disease diagnosis and prognosis, urine has several advantages. It is abundant, sterile, and easily obtained, needs little sample preparation, and does not require invasive medical procedures for collection. Furthermore, urine captures and concentrates many "unwanted" or "undesirable" compounds throughout the body, providing a rich source of potentially useful disease biomarkers; however, incredible variation in urine chemical concentrations makes analysis of urine and identification of useful urinary biomarkers by NMR challenging. We discuss a number of the most significant issues regarding NMR-based urinary metabolomics with specific emphasis on metabolite quantification for disease biomarker applications and propose data collection and instrumental recommendations regarding NMR pulse sequences, acceptable acquisition parameter ranges, relaxation effects on quantitation, proper handling of instrumental differences, sample preparation, and biomarker assessment.

  8. Recommendations and Standardization of Biomarker Quantification Using NMR-based Metabolomics with Particular Focus on Urinary Analysis

    KAUST Repository

    Emwas, Abdul-Hamid M.

    2016-01-08

    NMR-based metabolomics has shown considerable promise in disease diagnosis and biomarker discovery because it allows one to non-destructively identify and quantify large numbers of novel metabolite biomarkers in both biofluids and tissues. Indeed, precise metabolite quantification is a necessary prerequisite to move any chemical biomarker or biomarker panel from the lab into the clinic. Among the many biofluids (urine, serum, plasma, cerebrospinal fluid and saliva) commonly used for disease diagnosis and prognosis, urine has several advantages. It is abundant, sterile, easily obtained, needs little sample preparation and does not require any invasive medical procedures for collection. Furthermore, urine captures and concentrates many “unwanted” or “undesirable” compounds throughout the body, thereby providing a rich source of potentially useful disease biomarkers. However, the incredible variation in urine chemical concentrations due to effects such as gender, age, diet, life style, health conditions, and physical activity make the analysis of urine and the identification of useful urinary biomarkers by NMR quite challenging. In this review, we discuss a number of the most significant issues regarding NMR-based urinary metabolomics with a specific emphasis on metabolite quantification for disease biomarker applications. We also propose a number of data collection and instrumental recommendations regarding NMR pulse sequences, acceptable acquisition parameter ranges, relaxation effects on quantitation, proper handling of instrumental differences, as well as recommendations regarding sample preparation and biomarker assessment.

  9. Identification of human urinary biomarkers of cruciferous vegetable consumption by metabonomic profiling.

    Science.gov (United States)

    Edmands, William M B; Beckonert, Olaf P; Stella, Cinzia; Campbell, Alison; Lake, Brian G; Lindon, John C; Holmes, Elaine; Gooderham, Nigel J

    2011-10-07

    Consumption of cruciferous vegetables (CVs) is inversely correlated to many human diseases including cancer (breast, lung, and bladder), diabetes, and cardiovascular and neurological disease. Presently, there are no readily measurable biomarkers of CV consumption and intake of CVs has relied on dietary recall. Here, biomarkers of CV intake were identified in the urine of 20 healthy Caucasian adult males using (1)H NMR spectroscopy with multivariate statistical modeling. The study was separated into three phases of 14 days: a run-in period with restricted CV consumption (phase I); a high CV phase where participants consumed 250 g/day of both broccoli and Brussels sprouts (phase II); a wash-out phase with a return to restricted CV consumption (phase III). Each study participant provided a complete cumulative urine collection over 48 h at the end of each phase; a spot urine (U0), 0-10 h (U0-10), 10-24 h (U10-24), and 24-48 h (U24-48) urine samples. Urine samples obtained after consumption of CVs were differentiated from low CV diet samples by four singlet (1)H NMR spectroscopic peaks, one of which was identified as S-methyl-l-cysteine sulfoxide (SMCSO) and the three other peaks were tentatively identified as other metabolites structurally related to SMCSO. These stable urinary biomarkers of CV consumption will facilitate future assessment of CVs in nutritional population screening and dietary intervention studies and may correlate to population health outcomes.

  10. Urinary Klotho measured by ELISA as an early biomarker of acute kidney injury in patients after cardiac surgery or coronary angiography

    Directory of Open Access Journals (Sweden)

    Isidro Torregrosa

    2015-03-01

    Results: We found no differences in urinary Klotho levels between AKI patients and those who did not develop AKI. Moreover, there was not significant correlation between urinary Klotho levels and the presence of AKI. Conclusion. Urinary Klotho measured by ELISA does not seem to be a good candidate to be used as an early biomarker of AKI.

  11. Identification of Novel Translational Urinary Biomarkers for Acetaminophen-Induced Acute Liver Injury Using Proteomic Profiling in Mice

    NARCIS (Netherlands)

    van Swelm, Rachel P. L.; Laarakkers, Coby M. M.; van der Kuur, Ellen C.; Morava-Kozicz, Eva; Wevers, Ron A.; Augustijn, Kevin D.; Touw, Daan J.; Sandel, Maro H.; Masereeuw, Rosalinde; Russel, Frans G. M.

    2012-01-01

    Drug-induced liver injury (DILI) is the leading cause of acute liver failure. Currently, no adequate predictive biomarkers for DILI are available. This study describes a translational approach using proteomic profiling for the identification of urinary proteins related to acute liver injury induced

  12. Identification of novel translational urinary biomarkers for acetaminophen-induced acute liver injury using proteomic profiling in mice

    NARCIS (Netherlands)

    Swelm, R.P.L. van; Laarakkers, J.M.M.; Kuur, E.C. van der; Morava, E.; Wevers, R.A.; Augustijn, K.D.; Touw, D.J.; Sandel, M.H.; Masereeuw, R.; Russel, F.G.M.

    2012-01-01

    Drug-induced liver injury (DILI) is the leading cause of acute liver failure. Currently, no adequate predictive biomarkers for DILI are available. This study describes a translational approach using proteomic profiling for the identification of urinary proteins related to acute liver injury induced

  13. Identification of Novel Translational Urinary Biomarkers for Acetaminophen-Induced Acute Liver Injury Using Proteomic Profiling in Mice

    NARCIS (Netherlands)

    van Swelm, Rachel P. L.; Laarakkers, Coby M. M.; van der Kuur, Ellen C.; Morava-Kozicz, Eva; Wevers, Ron A.; Augustijn, Kevin D.; Touw, Daan J.; Sandel, Maro H.; Masereeuw, Rosalinde; Russel, Frans G. M.

    2012-01-01

    Drug-induced liver injury (DILI) is the leading cause of acute liver failure. Currently, no adequate predictive biomarkers for DILI are available. This study describes a translational approach using proteomic profiling for the identification of urinary proteins related to acute liver injury induced

  14. Potential Role of Serum and Urinary Biomarkers in Diagnosis and Prognosis of Diabetic Nephropathy

    Science.gov (United States)

    Campion, Carole G.; Sanchez-Ferras, Oraly; Batchu, Sri N.

    2017-01-01

    Purpose of review: Diabetic nephropathy (DN) is a progressive kidney disease caused by alterations in kidney architecture and function, and constitutes one of the leading causes of end-stage renal disease (ESRD). The purpose of this review is to summarize the state of the art of the DN-biomarker field with a focus on the new strategies that enhance the sensitivity of biomarkers to predict patients who will develop DN or are at risk of progressing to ESRD. Objective: In this review, we provide a description of the pathophysiology of DN and propose a panel of novel putative biomarkers associated with DN pathophysiology that have been increasingly investigated for diagnosis, to predict disease progression or to provide efficient personal treatment. Methods: We performed a review of the literature with PubMed and Google Scholar to collect baseline data about the pathophysiology of DN and biomarkers associated. We focused our research on new and emerging biomarkers of DN. Key findings: In this review, we summarized the critical signaling pathways and biological processes involved in DN and highlighted the pathogenic mediators of this disease. We next proposed a large review of the major advances that have been made in identifying new biomarkers which are more sensitive and reliable compared with currently used biomarkers. This includes information about emergent biomarkers such as functional noncoding RNAs, microRNAs, long noncoding RNAs, exosomes, and microparticles. Limitations: Despite intensive strategies and constant investigation, no current single treatment has been able to reverse or at least mitigate the progression of DN, or reduce the morbidity and mortality associated with this disease. Major difficulties probably come from the renal disease being heterogeneous among the patients. Implications: Expanding the proteomics screening, including oxidative stress and inflammatory markers, along with metabolomics approaches may further improve the prognostic value

  15. Chemometric Evaluation of Urinary Steroid Hormone Levels as Potential Biomarkers of Neuroendocrine Tumors

    Directory of Open Access Journals (Sweden)

    Barbara Seroczyńska

    2013-10-01

    Full Text Available Neuroendocrine tumors (NETs are uncommon tumors which can secrete specific hormone products such as peptides, biogenic amines and hormones. So far, the diagnosis of NETs has been difficult because most NET markers are not specific for a given tumor and none of the NET markers can be used to fulfil the criteria of high specificity and high sensitivity for the screening procedure. However, by combining the measurements of different NET markers, they become highly sensitive and specific diagnostic tests. The aim of the work was to identify whether urinary steroid hormones can be identified as potential new biomarkers of NETs, which could be used as prognostic and clinical course monitoring factors. Thus, a rapid and sensitive reversed-phase high-performance liquid chromatographic method (RP-HPLC with UV detection has been developed for the determination of cortisol, cortisone, corticosterone, testosterone, epitestosterone and progesterone in human urine. The method has been validated for accuracy, precision, selectivity, linearity, recovery and stability. The limits of detection and quantification were 0.5 and 1 ng mL−1 for each steroid hormone, respectively. Linearity was confirmed within a range of 1–300 ng mL−1 with a correlation coefficient greater than 0.9995 for all analytes. The described method was successfully applied for the quantification of six endogenous steroid levels in human urine. Studies were performed on 20 healthy volunteers and 19 patients with NETs. Next, for better understanding of tumor biology in NETs and for checking whether steroid hormones can be used as potential biomarkers of NETs, a chemometric analysis of urinary steroid hormone levels in both data sets was performed.

  16. Chemometric evaluation of urinary steroid hormone levels as potential biomarkers of neuroendocrine tumors.

    Science.gov (United States)

    Plenis, Alina; Miękus, Natalia; Olędzka, Ilona; Bączek, Tomasz; Lewczuk, Anna; Woźniak, Zofia; Koszałka, Patrycja; Seroczyńska, Barbara; Skokowski, Jarosław

    2013-10-16

    Neuroendocrine tumors (NETs) are uncommon tumors which can secrete specific hormone products such as peptides, biogenic amines and hormones. So far, the diagnosis of NETs has been difficult because most NET markers are not specific for a given tumor and none of the NET markers can be used to fulfil the criteria of high specificity and high sensitivity for the screening procedure. However, by combining the measurements of different NET markers, they become highly sensitive and specific diagnostic tests. The aim of the work was to identify whether urinary steroid hormones can be identified as potential new biomarkers of NETs, which could be used as prognostic and clinical course monitoring factors. Thus, a rapid and sensitive reversed-phase high-performance liquid chromatographic method (RP-HPLC) with UV detection has been developed for the determination of cortisol, cortisone, corticosterone, testosterone, epitestosterone and progesterone in human urine. The method has been validated for accuracy, precision, selectivity, linearity, recovery and stability. The limits of detection and quantification were 0.5 and 1 ng mL-1 for each steroid hormone, respectively. Linearity was confirmed within a range of 1-300 ng mL-1 with a correlation coefficient greater than 0.9995 for all analytes. The described method was successfully applied for the quantification of six endogenous steroid levels in human urine. Studies were performed on 20 healthy volunteers and 19 patients with NETs. Next, for better understanding of tumor biology in NETs and for checking whether steroid hormones can be used as potential biomarkers of NETs, a chemometric analysis of urinary steroid hormone levels in both data sets was performed.

  17. Urinary podocalyxin, the novel biomarker for detecting early renal change in obesity.

    Science.gov (United States)

    Suwanpen, Chayanut; Nouanthong, Phonethipsavanh; Jaruvongvanich, Veeravich; Pongpirul, Krit; Pongpirul, Wannarat Amornnimit; Leelahavanichkul, Asada; Kanjanabuch, Talerngsak

    2016-02-01

    The prevalence of obesity is increasing during the past decade along with obesity-related glomerulopathy (ORG), glomeruli injury due to the obesity. The major pathogenesis of ORG is the shedding of podocytes from the glomerular cell barrier into urine. Podocalyxin (PCX), a main surface antigen of podocyte, correlates well with glomerulosclerosis progression and glomerular injury severity, and might be a potential biomarker for early renal alteration in obesity. In addition, vascular endothelial growth factor (VEGF) and alpha-smooth muscle actin (α-SMA) also play a role in promoting glomerulosclerosis. The aim of this study was to explore whether obese subjects without other diseases excrete more PCX-positive (PCX+) cells than non-obese individuals, in comparison with urine protein-creatinine ratio (UPCR) and glomerular filtration rate (GFR) as traditional renal markers. Moreover, the effect of body mass index (BMI) on urinary VEGF, PCX or α-SMA positive cells was also investigated. Forty-eight obese and 13 non-obese adults were included. Exfoliated cells from fresh first void morning urine were harvested, stained with PCX, VEGF, and α-SMA antibody, and quantified by flow cytometry. Correlation between interested urinary biomarkers (cells positive for PCX, VEGF plus PCX and α-SMA), UPCR and GFR with BMI and metabolic risk factors were analyzed. Obese patients had significantly higher PCX+ cells than non-obese [0.62 (0.00-13.13) vs. 0.15 (0.00-0.72) cells/ml × mg cr, p Obese subjects without other diseases and with normal UPCR and GFR showed evidence of renal alteration through the detection of a higher number of PCX+ cells. Increasing BMI also resulted in higher number of PCX+ cells.

  18. Urinary monocyte chemoattractant protein-1 as a biomarker of lupus nephritis activity in children.

    Science.gov (United States)

    Ghobrial, Emad E; El Hamshary, Azza A; Mohamed, Ashraf G; Abd El Raheim, Yomna A; Talaat, Ahmed A

    2015-01-01

    Systemic lupus erythematosus (SLE) is a life-long, life-limiting and multi-systemic autoimmune disease. Glomerulonephritis is one of the most serious manifestations of SLE. Younger children have an increased incidence, severity and morbidity of lupus nephritis (LN) compared with adult-onset disease. Monocyte chemoattractant protein-1 (MCP-1) enhances leukocyte adhesiveness and endothelial permeability in the kidneys of murine and human LN models. Our study aimed to assess the role of urinary MCP-1 in the early diagnosis of LN activity. Sixty children, of whom 45 children aged from six to 12 years old and of both sexes (15 SLE patients without nephritis, 15 active LN and 15 inactive LN) fulfilling the American College of Rheumatology Classification Criteria for SLE were studied in comparison with 15 healthy subjects. We investigated the serum and urinary MCP-1 in all groups using the enzyme-linked immunosorbent assay test. Urinary MCP-1 was significantly higher in active LN in comparison with inactive LN and controls, and also significantly higher in inactive LN in comparison with SLE without nephritis and controls. There was also a significant difference between SLE without nephritis and controls. Serum MCP-1 was significantly higher in the group with active LN in comparison with the inactive group and SLE without nephritis and controls, but there was no significant difference between SLE and controls. The urinary MCP-1 level correlated well with SLE disease activity as measured by the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI). Urinary MCP-1 correlates positively with proteinuria, blood urea nitrogen level and creatinine and negatively with hemoglobin and creatinine clearance. We concluded that measurement of MCP-1 in urine may be useful for monitoring the severity of renal involvement in SLE. We recommend measuring urinary MCP-1 in pediatric SLE for the early diagnosis of LN and for the evaluation of the severity of renal involvement.

  19. H-1 Nuclear Magnetic Resonance Metabolomics Analysis Identifies Novel Urinary Biomarkers for Lung Function

    Energy Technology Data Exchange (ETDEWEB)

    MCClay, Joseph L.; Adkins, Daniel E.; Isern, Nancy G.; O' Connell, Thomas M.; Wooten, Jan B.; Zedler, Barbara K.; Dasika, Madhukar S.; Webb, B. T.; Webb-Robertson, Bobbie-Jo M.; Pounds, Joel G.; Murrelle, Edward L.; Leppert, Mark F.; van den Oord, Edwin J.

    2010-06-04

    Chronic obstructive pulmonary disease (COPD), characterized by chronic airflow limitation, is a serious and growing public health concern. The major environmental risk factor for COPD is tobacco smoking, but the biological mechanisms underlying COPD are not well understood. In this study, we used proton nuclear magnetic resonance (1H-NMR) spectroscopy to identify and quantify metabolites associated with lung function in COPD. Plasma and urine were collected from 197 adults with COPD and from 195 adults without COPD. Samples were assayed using a 600 MHz NMR spectrometer, and the resulting spectra were analyzed against quantitative spirometric measures of lung function. After correcting for false discoveries and adjusting for covariates (sex, age, smoking) several spectral regions in urine were found to be significantly associated with baseline lung function. These regions correspond to the metabolites trigonelline, hippurate and formate. Concentrations of each metabolite, standardized to urinary creatinine, were associated with baseline lung function (minimum p-value = 0.0002 for trigonelline). No significant associations were found with plasma metabolites. Two of the three urinary metabolites positively associated with baseline lung function, i.e. hippurate and formate, are often related to gut microflora. This suggests that the microbiome composition is variable between individuals with different lung function. Alternatively, the nature and origins of all three associated metabolites may reflect lifestyle differences affecting overall health. Our results will require replication and validation, but demonstrate the utility of NMR metabolomics as a screening tool for identifying novel biomarkers of lung disease or disease risk.

  20. Pre-transplant Evaluation of Donor Urinary Biomarkers can Predict Reduced Graft Function After Deceased Donor Kidney Transplantation.

    Science.gov (United States)

    Koo, Tai Yeon; Jeong, Jong Cheol; Lee, Yonggu; Ko, Kwang-Pil; Lee, Kyoung-Bun; Lee, Sik; Park, Suk Joo; Park, Jae Berm; Han, Miyeon; Lim, Hye Jin; Ahn, Curie; Yang, Jaeseok

    2016-03-01

    Several recipient biomarkers are reported to predict graft dysfunction, but these are not useful in decision making for the acceptance or allocation of deceased donor kidneys; thus, it is necessary to develop donor biomarkers predictive of graft dysfunction. To address this issue, we prospectively enrolled 94 deceased donors and their 109 recipients who underwent transplantation between 2010 and 2013 at 4 Korean transplantation centers. We investigated the predictive values of donor urinary neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), and L-type fatty acid binding protein (L-FABP) for reduced graft function (RGF). We also developed a prediction model of RGF using these donor biomarkers. RGF was defined as delayed or slow graft function. Multiple logistic regression analysis was used to generate a prediction model, which was internally validated using a bootstrapping method. Multiple linear regression analysis was used to assess the association of biomarkers with 1-year graft function. Notably, donor urinary NGAL levels were associated with donor AKI (P = 0.014), and donor urinary NGAL and L-FABP were predictive for RGF, with area under the receiver-operating characteristic curves (AUROC) of 0.758 and 0.704 for NGAL and L-FABP, respectively. The best-fit model including donor urinary NGAL, L-FABP, and serum creatinine conveyed a better predictive value for RGF than donor serum creatinine alone (P = 0.02). In addition, we generated a scoring method to predict RGF based on donor urinary NGAL, L-FABP, and serum creatinine levels. Diagnostic performance of the RGF prediction score (AUROC 0.808) was significantly better than that of the DGF calculator (AUROC 0.627) and the kidney donor profile index (AUROC 0.606). Donor urinary L-FABP levels were also predictive of 1-year graft function (P = 0.005). Collectively, these findings suggest donor urinary NGAL and L-FABP to be useful biomarkers for RGF, and support the use of

  1. Pharmacogenomic Variants May Influence the Urinary Excretion of Novel Kidney Injury Biomarkers in Patients Receiving Cisplatin

    Directory of Open Access Journals (Sweden)

    Cara Chang

    2017-06-01

    Full Text Available Nephrotoxicity is a dose limiting side effect associated with the use of cisplatin in the treatment of solid tumors. The degree of nephrotoxicity is dictated by the selective accumulation of cisplatin in renal tubule cells due to: (1 uptake by organic cation transporter 2 (OCT2 and copper transporter 1 (CTR1; (2 metabolism by glutathione S-transferases (GSTs and γ-glutamyltransferase 1 (GGT1; and (3 efflux by multidrug resistance-associated protein 2 (MRP2 and multidrug and toxin extrusion protein 1 (MATE1. The purpose of this study was to determine the significance of single nucleotide polymorphisms that regulate the expression and function of transporters and metabolism genes implicated in development of acute kidney injury (AKI in cisplatin treated patients. Changes in the kidney function were assessed using novel urinary protein biomarkers and traditional markers. Genotyping was conducted by the QuantStudio 12K Flex Real-Time PCR System using a custom open array chip with metabolism, transport, and transcription factor polymorphisms of interest to cisplatin disposition and toxicity. Traditional and novel biomarker assays for kidney toxicity were assessed for differences according to genotype by ANOVA. Allele and genotype frequencies were determined based on Caucasian population frequencies. The polymorphisms rs596881 (SLC22A2/OCT2, and rs12686377 and rs7851395 (SLC31A1/CTR1 were associated with renoprotection and maintenance of estimated glomerular filtration rate (eGFR. Polymorphisms in SLC22A2/OCT2, SLC31A1/CTRI, SLC47A1/MATE1, ABCC2/MRP2, and GSTP1 were significantly associated with increases in the urinary excretion of novel AKI biomarkers: KIM-1, TFF3, MCP1, NGAL, clusterin, cystatin C, and calbindin. Knowledge concerning which genotypes in drug transporters are associated with cisplatin-induced nephrotoxicity may help to identify at-risk patients and initiate strategies, such as using lower or fractionated cisplatin doses or avoiding

  2. 4-Methoxymethyl-2,3,5,6-tetrafluorobenzyl alcohol as a urinary biomarker for monitoring of metofluthrin, a fluorine-containing pyrethroid, in exposed rats.

    Science.gov (United States)

    Yoshida, Toshiaki

    2015-02-01

    A fluorine-containing pyrethroid metofluthrin is widely used recently in mosquito repellents. The urinary excretion kinetics of its metabolites was evaluated in rats to establish an optimal biomarker for monitoring metofluthrin exposure of the general population. After metofluthrin had been administered intraperitoneally to rats, the urinary excretion kinetics of the major metofluthrin metabolites was evaluated by moment analysis. The urinary excretion amounts of 4-methoxymethyl-2,3,5,6-tetrafluorobenzyl alcohol were estimated to be proportional to the absorption amounts over a wide exposure range. Urinary 4-methoxymethyl-2,3,5,6-tetrafluorobenzyl alcohol was considered to be an optimal biomarker for metofluthrin exposure.

  3. Development of urinary biomarkers for internal exposure by cesium-137 using a metabolomics approach in mice.

    Science.gov (United States)

    Goudarzi, Maryam; Weber, Waylon; Mak, Tytus D; Chung, Juijung; Doyle-Eisele, Melanie; Melo, Dunstana; Brenner, David J; Guilmette, Raymond A; Fornace, Albert J

    2014-01-01

    Cesium-137 is a fission product of uranium and plutonium in nuclear reactors and is released in large quantities during nuclear explosions or detonation of an improvised device containing this isotope. This environmentally persistent radionuclide undergoes radioactive decay with the emission of beta particles as well as gamma radiation. Exposure to (137)Cs at high doses can cause acute radiation sickness and increase risk for cancer and death. The serious health risks associated with (137)Cs exposure makes it critical to understand how it affects human metabolism and whether minimally invasive and easily accessible samples such as urine and serum can be used to triage patients in case of a nuclear disaster or a radiologic event. In this study, we have focused on establishing a time-dependent metabolomic profile for urine collected from mice injected with (137)CsCl. The samples were collected from control and exposed mice on days 2, 5, 20 and 30 after injection. The samples were then analyzed by ultra-performance liquid chromatography coupled to time-of-flight mass spectrometry (UPLC/TOFMS) and processed by an array of informatics and statistical tools. A total of 1,412 features were identified in ESI(+) and ESI(-) modes from which 200 were determined to contribute significantly to the separation of metabolomic profiles of controls from those of the different treatment time points. The results of this study highlight the ease of use of the UPLC/TOFMS platform in finding urinary biomarkers for (137)Cs exposure. Pathway analysis of the statistically significant metabolites suggests perturbations in several amino acid and fatty acid metabolism pathways. The results also indicate that (137)Cs exposure causes: similar changes in the urinary excretion levels of taurine and citrate as seen with external-beam gamma radiation; causes no attenuation in the levels of hexanoylglycine and N-acetylspermidine; and has unique effects on the levels of isovalerylglycine and

  4. Identification of novel translational urinary biomarkers for acetaminophen-induced acute liver injury using proteomic profiling in mice.

    Directory of Open Access Journals (Sweden)

    Rachel P L van Swelm

    Full Text Available Drug-induced liver injury (DILI is the leading cause of acute liver failure. Currently, no adequate predictive biomarkers for DILI are available. This study describes a translational approach using proteomic profiling for the identification of urinary proteins related to acute liver injury induced by acetaminophen (APAP. Mice were given a single intraperitoneal dose of APAP (0-350 mg/kg bw followed by 24 h urine collection. Doses of ≥275 mg/kg bw APAP resulted in hepatic centrilobular necrosis and significantly elevated plasma alanine aminotransferase (ALT values (p<0.0001. Proteomic profiling resulted in the identification of 12 differentially excreted proteins in urine of mice with acute liver injury (p<0.001, including superoxide dismutase 1 (SOD1, carbonic anhydrase 3 (CA3 and calmodulin (CaM, as novel biomarkers for APAP-induced liver injury. Urinary levels of SOD1 and CA3 increased with rising plasma ALT levels, but urinary CaM was already present in mice treated with high dose of APAP without elevated plasma ALT levels. Importantly, we showed in human urine after APAP intoxication the presence of SOD1 and CA3, whereas both proteins were absent in control urine samples. Urinary concentrations of CaM were significantly increased and correlated well with plasma APAP concentrations (r = 0.97; p<0.0001 in human APAP intoxicants, who did not present with elevated plasma ALT levels. In conclusion, using this urinary proteomics approach we demonstrate CA3, SOD1 and, most importantly, CaM as potential human biomarkers for APAP-induced liver injury.

  5. Periostin as a tissue and urinary biomarker of renal injury in type 2 diabetes mellitus.

    Directory of Open Access Journals (Sweden)

    Bancha Satirapoj

    Full Text Available Improving the early detection of diabetic nephropathy remains a great challenge in disease management. Periostin is a marker of renal tubular injury and related to progressive kidney injury in animal models of chronic kidney disease. The clinical implications of urinary periostin activities in patients with type 2 diabetes have not been evaluated.Urine samples were obtained from 30 healthy volunteers and 328 type 2 diabetic patients with normoalbuminuria (n=114, microalbuminuria (n=100 and macroalbuminuria (n=114. The excretion levels of urinary periostin were quantified with enzyme-linked immunosorbent assay. Immunohistochemical periostin expression was determined in kidney tissues from overt diabetic nephropathy.Increased periostin expression in glomeruli and tubular epithelium in diabetic renal pathology was observed. Urinary periostin levels were significantly elevated in the patients of the normoalbuminuria [3.06 (IQR: 1.12, 6.77 ng/mgCr], microalbuminuria [8.71 (IQR: 5.09, 19.29 ng/mgCr] and macroalbuminuria [13.58 (IQR: 3.99, 16.19 ng/mgCr] compared with healthy controls [1.15 (IQR: 0.60, 1.63 ng/mgCr] (P<0.01.Increased urine periostin level significantly correlated with aging, high albuminuria and decline of GFR. Urine periostin ELISA also demonstrated high performance for the diagnosis of established normoalbuminuric, microalbuminuric and macroalbuminuric type 2 diabetes (AUC 0.78 (95%CI, 0.71 to 0.86, 0.99 (95%CI, 0.98 to 1.00 and 0.95 (95%CI, 0.91 to 0.98, respectively.The study indicates that increased urine periostin levels can be detected in patients with type 2 diabetes before the onset of significant albuminuria. Urinary periostin is an associated renal derangement in patients with established diabetic nephropathy and it may be used as an early marker of diabetic renal injury.

  6. Assessing variability and comparing short-term biomarkers of styrene exposure using a repeated measurements approach.

    Science.gov (United States)

    Fustinoni, S; Manini, P; Campo, L; De Palma, G; Andreoli, R; Mutti, A; Bertazzi, P A; Rappaport, S M

    2010-01-15

    The aim of this work is to compare several short-term biomarkers of styrene exposure, namely urinary styrene (StyU), mercapturic acids (M1+M2), mandelic acid (MA), phenylglyoxylic acid (PGA), phenylglycine (PHG), and 4-vinylphenol conjugates (VP), for use as biomarkers of exposure in epidemiologic studies. A repeated measurements protocol (typically 4 measurements per worker over 6 weeks) was applied to measure airborne styrene (StyA) and urinary biomarkers in 10 varnish and 8 fiberglass reinforced plastic workers. Estimated geometric mean personal exposures to StyA were 2.96mg/m(3) in varnish workers and 15.7mg/m(3) in plastic workers. The corresponding levels of StyU, M1+M2, MA, PGA, MA+PGA, PHG and VP were 5.13microg/L, 0.111, 38.2, 22.7, 62.6, 0.978, and 3.97mg/g creatinine in varnish workers and 8.38microg/L, 0.303, 146, 83.4, 232, 2.85 and 3.97mg/g creatinine in plastic workers. Within-worker (sigma(wY)(2)) and between-worker (sigma(bY)(2)) variance components were estimated from the log-transformed data as were the corresponding fold ranges containing 95% of the respective lognormal distributions of daily levels ((w)R(0.95)) and subject-specific mean levels ((b)R(0.95)). Estimates of (w)R(0.95) (range: 4-26) were generally smaller than those of (b)R(0.95) (range: 5-790) for both environmental and biological markers; this indicates that exposures varied much more between workers than within workers in these groups. Since attenuation bias in an estimated exposure-response relationship increases with the variance ratio lambda=sigma(wY)(2)/sigma(bY)(2), we estimated values of lambda for all exposure measures in our study. Values of lambda were typically much less than one (median=0.220) and ranged from 0.089 for M1+M2 in plastic workers to 1.38 for PHG in varnish workers. Since values of lambda were 0.147 and 0.271 for StyA in varnish workers and plastic workers, respectively, compared to 0.178 and 0.210 for MA in the same groups, our results suggest that either

  7. Urinary t,t-muconic acid, S-phenylmercapturic acid and benzene as biomarkers of low benzene exposure.

    Science.gov (United States)

    Fustinoni, Silvia; Buratti, Marina; Campo, Laura; Colombi, Antonio; Consonni, Dario; Pesatori, Angela C; Bonzini, Matteo; Farmer, Peter; Garte, Seymour; Valerio, Federico; Merlo, Domenico F; Bertazzi, Pier A

    2005-05-30

    This research compared the capability of urinary trans,trans-muconic acid (t,t-MA), S-phenylmercapturic acid (S-PMA) and benzene excreted in urine (U-benzene) to monitor low benzene exposure and evaluated the influence of smoking habit on these indices. Gasoline attendants, urban policemen, bus drivers and two groups of referents working in two large Italian cities (415 people) were studied. Median benzene exposure was 61, 22, 21, 9 and 6 microg/m3, respectively, with higher levels in workers than in referents. U-benzene, but not t,t-MA and S-PMA, showed an exposure-related increase. All the biomarkers were strongly influenced by cigarette smoking, with values up to five-fold higher in smokers compared to non-smokers. In conclusion, in the range of investigated benzene exposure (<478 microg/m3 or <0.15 ppm), the smoking habit may be regarded as a major source of benzene intake; among the study indices, U-benzene is the marker of choice for the biological monitoring of occupational and environmental exposure.

  8. Proteomic analysis of urinary biomarker candidates for nonmuscle invasive bladder cancer.

    Science.gov (United States)

    Lindén, Mårten; Lind, Sara Bergström; Mayrhofer, Corina; Segersten, Ulrika; Wester, Kenneth; Lyutvinskiy, Yaroslav; Zubarev, Roman; Malmström, Per-Uno; Pettersson, Ulf

    2012-01-01

    Nonmuscle invasive tumors of the bladder often recur and thereby bladder cancer patients need regular re-examinations which are invasive, unpleasant, and expensive. A noninvasive and less expensive method, e.g. a urine dipstick test, for monitoring recurrence would thus be advantageous. In this study, the complementary techniques mass spectrometry (MS) and Western blotting (WB)/dot blot (DB) were used to screen the urine samples from bladder cancer patients. High resolving MS was used to analyze and quantify the urinary proteome and 29 proteins had a significantly higher abundance (pblot for four selected proteins; fibrinogen β chain precursor, apolipoprotein E, α-1-antitrypsin, and leucine-rich α-2-glycoprotein 1. Dot blot analysis of an independent urine sample set pointed out fibrinogen β chain and α-1-antitrypsin as most interesting biomarkers having sensitivity and specificity values in the range of 66-85%. Exploring the Human Protein Atlas (HPA) also revealed that bladder cancer tumors are the likely source of these proteins. They have the potential of being useful in diagnosis, monitoring of recurrence and thus may improve the treatment of bladder tumors, especially nonmuscle invasive tumors.

  9. [Urinary L-type fatty acid binding protein (L-FABP) as a new urinary biomarker promulgated by the Ministry of Health, Labour and Welfare in Japan].

    Science.gov (United States)

    Kamijo-Ikemori, Atsuko; Ichikawa, Daisuke; Matsui, Katsuomi; Yokoyama, Takeshi; Sugaya, Takeshi; Kimura, Kenjiro

    2013-07-01

    Liver-type fatty acid binding protein (L-FABP) is a 14kDa protein found in the cytoplasm of human renal proximal tubules. Fatty acids are bound with L-FABP and transported to the mitochondria or peroxisomes, where fatty acids are beta-oxidized, and this may play a role in fatty acid homeostasis. Moreover, L-FABP has high affinity and capacity to bind long-chain fatty acid oxidation products, and may be an effective endogenous antioxidant. Renal L-FABP is rarely expressed in the kidneys of rodents. In order to evaluate the pathological dynamics of renal L-FABP in kidney disease, human L-FABP chromosomal transgenic mice were generated. Various stress, such as massive proteinuria, hyperglycemia, hypertension, and toxins overloaded in the proximal tubules were revealed to up-regulate the gene expression of renal L-FABP and increase the excretion of L-FABP derived from the proximal tubules into urine. In clinical studies of chronic kidney disease (CKD), urinary L-FABP accurately reflected the degree of tubulointerstitial damage and correlated with the rate of CKD progression. Furthermore, a multicenter trial has shown that urinary L-FABP is more sensitive than urinary protein in predicting the progression of CKD. With respect to diabetic nephropathy and acute kidney disease (AKI), urinary L-FABP is an early diagnostic of kidney disease or a predictive marker for renal prognosis. After many clinical studies, urinary L-FABP was approved as a new tubular biomarker promulgated by the Ministry of Health, Labour and Welfare in Japan.

  10. Clinical relevance of urinary angiotensinogen and renin as potential biomarkers in patients with overt proteinuria.

    Science.gov (United States)

    Jang, Hye Ryoun; Jeon, Junseok; Park, Ji Hyeon; Lee, Jung Eun; Huh, Wooseong; Oh, Ha Young; Kim, Yoon-Goo

    2014-11-01

    Urinary angiotensinogen (AGT) and renin have been reported to reflect the intrarenal renin-angiotensin system (RAS) activity. However, the adequacy and clinical significance of these markers have not been evaluated in overtly proteinuric patients. In patients with biopsy-proven glomerulonephritis, plasma and urinary AGT and renin were analyzed. A cohort of 75 patients treated with RAS inhibitors was followed for 1 year. Among the 207 patients, 105 had subnephrotic and 102 had nephrotic-range proteinuria. Mean age, estimated glomerular filtration rate (eGFR), and urinary protein-to-creatinine ratio (P/Cr) of all patients were 48 years, 79.7 mL/min/1.73 m(2), and 5.66 mg/mg, respectively. Both natural logarithm of urinary AGT/creatinine (ln [urinary AGT/Cr]) and ln (urinary renin/Cr) showed positive correlations with urinary P/Cr. There was a positive correlation between ln (urinary AGT/Cr) and ln (urinary renin/Cr). Ln (urinary renin/Cr) was not affected by ln (plasma renin) regardless of the degree of proteinuria. The treatment response to RAS inhibitors was greatest in patients with high urinary AGT and renin. However, the predictive value of those parameters was no longer present when the values were adjusted by the degree of proteinuria. Ln (urinary renin/Cr) and initial eGFR were independently associated with the changes in renal function for 1 year. Ln (urinary AGT/Cr) was associated with persistent overt proteinuria after 1 year. Our study suggests that urinary renin may be a better marker in heavy proteinuria, and the treatment response to RAS inhibitors may be enhanced in patients with high urinary renin and AGT. Further studies will be necessary to explore the value of urinary AGT and renin.

  11. Urinary Microvesicle-Bound Uromodulin: A Potential Molecular Biomarker in Diabetic Kidney Disease

    Science.gov (United States)

    Lou, Neng-jun; Ni, Yi-hong; Jia, Hong-ying; Deng, Jing-ti; Jiang, Lu; Zheng, Feng-jie

    2017-01-01

    This study was designed to investigate the changes of urinary microvesicle-bound uromodulin and total urinary uromodulin levels in human urine and the correlations with the severity of diabetic kidney disease (DKD). 31 healthy subjects without diabetes and 100 patients with type 2 diabetes mellitus (T2DM) were included in this study. The patients with T2DM were divided into three groups based on the urinary albumin/creatinine ratio (UACR): normoalbuminuria group (DM, n = 46); microalbuminuria group (DN1, n = 32); and macroalbuminuria group (DN2, n = 22). We use a specific monoclonal antibody AD-1 to capture the urinary microvesicles. Urinary microvesicle-bound uromodulin and total urinary uromodulin levels were determined by enzyme-linked immunosorbent assay (ELISA). Our results showed that the levels of urinary microvesicle-bound uromodulin in DN1 and DN2 groups were significantly higher than those in control group and DM group (P < 0.01). Multiple stepwise linear regression analysis showed that UACR was independent determinant for urinary microvesicle-bound uromodulin (P < 0.05) but not for total urinary uromodulin. These findings suggest that the levels of urinary microvesicle-bound uromodulin are associated with the severity of DKD. The uromodulin in urinary microvesicles may be a specific marker of DKD and potentially may be used to predict the onset and/or monitor the progression of DKD. PMID:28182086

  12. Alkyl protocatechuates as novel urinary biomarkers of exposure to p-hydroxybenzoic acid esters (parabens).

    Science.gov (United States)

    Wang, Lei; Kannan, Kurunthachalam

    2013-09-01

    Human exposure to p-hydroxybenzoic acid esters (parabens) is a concern, owing to adverse health effects of these compounds. Parabens are metabolized and eliminated from the human bodies within a few hours of exposure. In this study, for the first time, methyl- and ethyl-protocatechuates (OH-MeP and OH-EtP) and their parent compounds, methyl- (MeP) and ethyl-parabens (EtP), were determined in urine samples collected from U.S. children and adults. Alkyl protocatechuates were found in almost all urine samples, with median concentrations of 11.8 (OH-MeP) and 2.90ng/mL (OH-EtP) in adults, and 5.43 (OH-MeP) and 0.85ng/mL (OH-EtP) in children. In adults, the concentrations of urinary OH-MeP and OH-EtP were higher than the corresponding concentrations of MeP and EtP. Significant correlation between OH-MeP/OH-EtP and MeP/EtP was observed. This is the first report to document hydroxylation of parabens in humans, and to propose hydroxylated metabolites (i.e., alkyl protocatechuates) as alternative biomarkers of exposure to parabens in human biomonitoring studies. The rates of transformation of parabens between children and adults appeared to be different, as evidenced from the slopes of regression between alkyl protocatechuates and parabens. In addition to alkyl protocatechuates, hydroxybenzoic acid (4-HB) and 3,4-dihydroxybenzoic acid (3,4-DHB) were found at considerable levels in the urine samples. The occurrence of a significant proportion of alkyl protocatechuates and 3,4-DHB suggests the need for inclusion of these derivatives in accurate estimation of human exposure to parabens and in epidemiological studies that associate paraben exposure to health outcomes in populations. Copyright © 2013 Elsevier Ltd. All rights reserved.

  13. Human urinary biomarkers of dioxin exposure: analysis by metabolomics and biologically driven data dimensionality reduction.

    Science.gov (United States)

    Jeanneret, Fabienne; Boccard, Julien; Badoud, Flavia; Sorg, Olivier; Tonoli, David; Pelclova, Daniela; Vlckova, Stepanka; Rutledge, Douglas N; Samer, Caroline F; Hochstrasser, Denis; Saurat, Jean-Hilaire; Rudaz, Serge

    2014-10-15

    Untargeted metabolomic approaches offer new opportunities for a deeper understanding of the molecular events related to toxic exposure. This study proposes a metabolomic investigation of biochemical alterations occurring in urine as a result of dioxin toxicity. Urine samples were collected from Czech chemical workers submitted to severe dioxin occupational exposure in a herbicide production plant in the late 1960s. Experiments were carried out with ultra-high pressure liquid chromatography (UHPLC) coupled to high-resolution quadrupole time-of-flight (QTOF) mass spectrometry. A chemistry-driven feature selection was applied to focus on steroid-related metabolites. Supervised multivariate data analysis allowed biomarkers, mainly related to bile acids, to be highlighted. These results supported the hypothesis of liver damage and oxidative stress for long-term dioxin toxicity. As a second step of data analysis, the information gained from the urine analysis of Victor Yushchenko after his poisoning was examined. A subset of relevant urinary markers of acute dioxin toxicity from this extreme phenotype, including glucuro- and sulfo-conjugated endogenous steroid metabolites and bile acids, was assessed for its ability to detect long-term effects of exposure. The metabolomic strategy presented in this work allowed the determination of metabolic patterns related to dioxin effects in human and the discovery of highly predictive subsets of biologically meaningful and clinically relevant compounds. These results are expected to provide valuable information for a deeper understanding of the molecular events related to dioxin toxicity. Furthermore, it presents an original methodology of data dimensionality reduction by using extreme phenotype as a guide to select relevant features prior to data modeling (biologically driven data reduction).

  14. Urinary follicle stimulating hormone can be used as a biomarker to assess male reproductive function

    Institute of Scientific and Technical Information of China (English)

    Xin-RuWANG; JamesWOverstreet; HeatherTodd; QingQIU; Jiang-HuaYANG; Shu-YiWANG; Xi-PingXU; BillLLasley

    1999-01-01

    Aim: To develop an algorithm for use in population-based studies to assess testicniar function by measurements of total urinary follicle stimulating hormone (FSH). Methods: Total concentrations of unnary FSH were measured in a group of 44 men at the University of Califomia, Davis (UCD) and were compared to FSH measurements in serum. On the basis of these and other published data, a urinary FSH value of>2 ng/mg creatinine (Cr) was selected as the cutoffpoint to identify men with elevated serum FSH ( > 12 IU/L) or low sperm counts ( < 20 million/mL). Results: Thesensitivity and specificity of this algorithm for detecting elevated serum FSH in a group of 58 agricultural workers in thePeople' s Republic of China were 100 % and 50 %, respectively. The sensitivity and specificity of this algorithm fordetecting low sperm counts in a population of 105 infertility patients at UCD were 58 % and 76 %, respectavely.Conclusion: This test may have particular value in identifying populations with no evidence of testicular toxicity, andin which labor-intensive semen studies may not be feasible. (As/an JAndrol 1999; 1 : 67 - 72)

  15. Urinary exosomal activating transcriptional factor 3 as the early diagnostic biomarker for sepsis-induced acute kidney injury.

    Science.gov (United States)

    Panich, Tanaporn; Chancharoenthana, Wiwat; Somparn, Poorichaya; Issara-Amphorn, Jiraphorn; Hirankarn, Nattiya; Leelahavanichkul, Asada

    2017-01-07

    An early sepsis-induced acute kidney injury (sepsis-AKI) biomarker is currently in needed. Urinary neutrophil gelatinase-associated lipocalin (uNGAL) is a candidate of sepsis-AKI biomarker but with different cut-point values. Urinary exosomal activating transcriptional factor 3 (uATF3) has been mentioned as an interesting biomarker. We conducted experiments in mice and a prospective, multicenter study in patients as a proof of concept that urine exosome is an interesting biomarker. An early expression of ATF3 in kidney of CD-1 mice at 6 h after cecal ligation and puncture implied the possibility of uATF3 as an early sepsis-AKI biomarker. Increase serum creatinine (Scr) ≥0.3 mg/dL from the baseline was used as an AKI diagnosis and urine was analyzed for uATF3 and uNGAL. Patients with baseline Scr at admission ≥1.5 mg/dL were excluded. The analysis showed higher Scr, uNGAL and uATF3 in patients with sepsis-AKI in comparison with patients with sepsis-non-AKI and healthy volunteers. A fair correlation, r(2) = 0.47, between uATF3 and uNGAL was showed in sepsis-AKI group with Scr ≥2 mg/dL. To see if uATF3 could be an early sepsis-AKI biomarker, urine sample was collected daily during the first week of the admission. In sepsis-AKI and sepsis-non-AKI groups, uNGAL were 367 ± 43 ng/mL and 183 ± 23 ng/mL, respectively; and uATF3 were 19 ± 4 ng/mL and 1.4 ± 0.8 ng/mL, respectively. With the mean value of uNGAL and uATF3 in sepsis AKI as a cut-off level, AUROC of uNGAL and uATF3 were 64% (95% CI 0.54 to 0.74) and 84% (95% CI 0.77 to 0.91), respectively. Urine exosome is an interesting source of urine biomarker and uATF3 is an interesting sepsis-AKI biomarker.

  16. Evaluation of urinary metabolites of 1-nitropyrene as biomarkers for exposure to diesel exhaust in taxi drivers of Shenyang, China.

    Science.gov (United States)

    Miller-Schulze, Justin P; Paulsen, Michael; Kameda, Takayuki; Toriba, Akira; Tang, Ning; Tamura, Kenji; Dong, Lijun; Zhang, Xuemei; Hayakawa, Kazuichi; Yost, Michael G; Simpson, Christopher D

    2013-03-01

    Diesel exhaust (DE) is a significant contributor to the toxicity associated with particulate matter (PM). 1-Nitropyrene (1-NP) has been used as a molecular marker for DE, and the urinary metabolites of 1-NP have been proposed as biomarkers for exposure to DE. In this study, several urinary 1-NP metabolites were evaluated for their utility as markers of short-term exposures to DE. The study population was a cohort of 24 taxi drivers from Shenyang, China, who submitted urine samples collected before, after, and the next morning following their workshifts. The urinary metabolites studied were isomers of hydroxy-1-nitropyrene (3-, 6-, 8- OHNPs) and hydroxy-N-acetyl-1-aminopyrene (3-,6-, 8-OHNAAPs). Exposure to DE was estimated based on exposure to 1-NP in air samples collected during and after the driver's workshift; 6- and 8-OHNP, and 8-OHNAAP were consistently detected in the drivers' urine. Concentrations of the metabolites in the taxi drivers' urine were greater than metabolite levels previously reported in non-occupationally exposed subjects; however no associations were observed between subject-specific exposures to 1-NP and urinary metabolites measured at the end of the workshift or in the next morning void. Significant autocorrelation was observed in metabolite levels in successive urine samples, from which half-lives for urinary elimination of ~10-12 h were estimated. These observations suggest that, in an occupational setting, urinary 1-NP metabolites may be more suitable as markers of ongoing exposure (timescales of several days) rather than indicators of acute exposure associated with single workshifts.

  17. Globin s-propyl cysteine and urinary N-acetyl-S-propylcysteine as internal biomarkers of 1-bromopropane exposure.

    Science.gov (United States)

    Valentine, Holly; Amarnath, Kalyani; Amarnath, Venkataraman; Li, Weihua; Ding, Xuncheng; Valentine, William M; Ichihara, Gaku

    2007-08-01

    1-Bromopropane (1-BP), an alternative to ozone-depleting solvents, is a neuro and reproductive toxicant in animals and humans. In this study, the dose responses for urinary AcPrCys and S-propylcysteine (PrCys) adducts on globin and neurofilaments were determined as a function of 1-BP exposure level and duration in the rat; and globin PrCys adducts and urinary AcPrCys were quantified in samples obtained from workers in a 1-BP production facility. Rats were exposed to 1-BP by inhalation for 2 weeks at 0, 50, 200, or 800 ppm and to 1-BP at 0 or 50 ppm for 4 weeks. After the 4-week exposures ended, half of the animals were euthanized immediately and half euthanized 8 days later. Urinary AcPrCys was measured using liquid chromatography-tandem mass spectrometry (LC/MS/MS) and gas chromatograph-mass spectrometry (GC/MS); and PrCys adducts were determined on globin and neurofilaments using LC/MS/MS. In rats, PrCys adduct and urinary AcPrCys levels demonstrated a linear dose response relative to exposure level. PrCys globin adducts demonstrated a linear cumulative dose response over the 4-week exposure period. Elimination of AcPrCys appeared biphasic with detectable levels still present in urine up to 8 days postexposure. A significant increase in globin PrCys adducts was observed in the 1-BP workers relative to control workers; and urinary AcPrCys increased with increasing 1-BP ambient exposure levels. The results of these studies demonstrate the ability of 1-BP to covalently modify proteins in vivo and support the potential of urinary AcPrCys and globin PrCys adducts to serve as biomarkers of 1-BP exposure in humans.

  18. Urinary monocyte chemoattractant protein-1 and vitamin D-binding protein as biomarkers for early detection of diabetic nephropathy in type 2 diabetes mellitus.

    Science.gov (United States)

    Shoukry, Amira; Bdeer, Shereen El-Arabi; El-Sokkary, Rehab H

    2015-10-01

    Diabetic nephropathy is a serious complication of both type 1 and type 2 diabetes and, unless arrested, leads to end-stage renal disease. Therefore, early prediction and detection of DN would greatly benefit the disease management and delay its progression. The aim of this study is to evaluate the levels of urinary monocyte chemoattractant protein-1 (uMCP-1) and urinary vitamin D-binding protein (uVDBP) in type 2 diabetic patients with different degrees of diabetic nephropathy (DN) and to assess the value of uMCP-1 and uVDBP in the early detection of DN. Seventy-five type 2 diabetic patients with normoalbuminuria (n = 25), microalbuminuria (n = 25), macroalbuminuria (n = 25), and 25 healthy controls were included in this study. Urinary MCP-1 and VDBP levels were evaluated by enzyme-linked immunosorbent assay. A significant elevation in the uMCP-1 and uVDBP levels was found in macroalbuminuric (p diabetic patients compared to that in normoalbuminuric diabetic patients and control subjects (p diagnosis and detection of DN revealed that the cut-off value of uMCP-1 was 110 pg/mg with 92% sensitivity and 100% specificity; whereas, the cut-off value of uVDBP was 550 ng/mg with 96% sensitivity and 84% specificity. The findings of the present study suggest that uMCP-1 and uVDBP may be considered as novel potential diagnostic biomarkers for the early detection of diabetic nephropathy.

  19. Use of urinary renal biomarkers to evaluate the nephrotoxic effects of melamine or cyanuric acid in non-pregnant and pregnant rats.

    Science.gov (United States)

    Bandele, O J; Stine, C B; Ferguson, M; Black, T; Olejnik, N; Keltner, Z; Evans, E R; Crosby, T C; Reimschuessel, R; Sprando, R L

    2014-12-01

    Although traditional assessments of renal damage detect loss of kidney function, urinary renal biomarkers are proposed to indicate early changes in renal integrity. The recent adulteration of infant formula and other milk-based foods with melamine revealed a link between melamine ingestion and nephropathy. Thus, the effects of melamine and related analogs (e.g., cyanuric acid) should be assessed in other potentially sensitive groups. We evaluated whether urinary Kim-1, clusterin, and osteopontin could detect the effects of high doses of melamine or cyanuric acid in pregnant and non-pregnant female rats gavaged with 1000 mg/kg bw/day for 10 days. We demonstrate that these biomarkers can differentiate the severity of effects induced by melamine or cyanuric acid. All melamine-treated animals experienced adverse effects; however, pregnant rats were most sensitive as indicated by increased SCr, BUN, and kidney weights, decreased body weight, and presence of renal crystals. These effects coincided with elevated urinary biomarker levels as early as day 2 of exposure. One cyanuric acid-treated rat displayed effects similar to melamine, including increased urinary biomarker levels. This work illustrates that these biomarkers can detect early effects of melamine or cyanuric acid crystal-induced nephropathy and further supports the use of urinary protein immunoassays as a powerful, non-invasive method to assess nephrotoxicity.

  20. Metabolic profiling in Maturity-onset diabetes of the young (MODY and young onset type 2 diabetes fails to detect robust urinary biomarkers.

    Directory of Open Access Journals (Sweden)

    Anna L Gloyn

    Full Text Available 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

  1. Metabolic profiling in Maturity-onset diabetes of the young (MODY) and young onset type 2 diabetes fails to detect robust urinary biomarkers.

    Science.gov (United States)

    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

  2. Urinary Excretion of Kidney Aquaporins as Possible Diagnostic Biomarker of Diabetic Nephropathy.

    Science.gov (United States)

    Rossi, Luigi; Nicoletti, Maria Celeste; Carmosino, Monica; Mastrofrancesco, Lisa; Di Franco, Antonella; Indrio, Francesca; Lella, Rossella; Laviola, Luigi; Giorgino, Francesco; Svelto, Maria; Gesualdo, Loreto; Procino, Giuseppe

    2017-01-01

    Diabetic nephropathy (DN) is a microangiopathic complication of diabetes mellitus (DM) affecting one-third of diabetic patients. The large variability in the clinical presentation of renal involvement in patients with DM makes kidney biopsy a prerequisite for a correct diagnosis. However, renal biopsy is an invasive procedure associated with risk of major complications. Numerous studies aimed to identify a noninvasive biomarker of DN but, so far, none of these is considered to be sufficiently specific and sensitive. Water channel aquaporins (AQPs), expressed at the plasma membrane of epithelial tubular cells, are often dysregulated during DN. In this work, we analyzed the urine excretion of AQP5 and AQP2 (uAQP5 and uAQP2), via exosomes, in 35 diabetic patients: 12 normoalbuminuric with normal renal function (DM), 11 with proteinuric nondiabetic nephropathy (NDN), and 12 with histological diagnosis and classification of DN. ELISA and WB analysis independently showed that uAQP5 was significantly increased in DN patients. Interestingly, linear regression analysis showed a positive correlation between uAQP5 and the histological class of DN. The same analysis, focusing on uAQP2, showed comparable results. Taken together, these data suggest a possible use of AQP5 and AQP2 as novel noninvasive biomarkers to help in classifying the clinical stage of DN.

  3. Urinary Excretion of Kidney Aquaporins as Possible Diagnostic Biomarker of Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Luigi Rossi

    2017-01-01

    Full Text Available Diabetic nephropathy (DN is a microangiopathic complication of diabetes mellitus (DM affecting one-third of diabetic patients. The large variability in the clinical presentation of renal involvement in patients with DM makes kidney biopsy a prerequisite for a correct diagnosis. However, renal biopsy is an invasive procedure associated with risk of major complications. Numerous studies aimed to identify a noninvasive biomarker of DN but, so far, none of these is considered to be sufficiently specific and sensitive. Water channel aquaporins (AQPs, expressed at the plasma membrane of epithelial tubular cells, are often dysregulated during DN. In this work, we analyzed the urine excretion of AQP5 and AQP2 (uAQP5 and uAQP2, via exosomes, in 35 diabetic patients: 12 normoalbuminuric with normal renal function (DM, 11 with proteinuric nondiabetic nephropathy (NDN, and 12 with histological diagnosis and classification of DN. ELISA and WB analysis independently showed that uAQP5 was significantly increased in DN patients. Interestingly, linear regression analysis showed a positive correlation between uAQP5 and the histological class of DN. The same analysis, focusing on uAQP2, showed comparable results. Taken together, these data suggest a possible use of AQP5 and AQP2 as novel noninvasive biomarkers to help in classifying the clinical stage of DN.

  4. Urinary Excretion of Kidney Aquaporins as Possible Diagnostic Biomarker of Diabetic Nephropathy

    Science.gov (United States)

    Rossi, Luigi; Nicoletti, Maria Celeste; Mastrofrancesco, Lisa; Di Franco, Antonella; Indrio, Francesca; Lella, Rossella; Laviola, Luigi; Giorgino, Francesco; Svelto, Maria; Gesualdo, Loreto

    2017-01-01

    Diabetic nephropathy (DN) is a microangiopathic complication of diabetes mellitus (DM) affecting one-third of diabetic patients. The large variability in the clinical presentation of renal involvement in patients with DM makes kidney biopsy a prerequisite for a correct diagnosis. However, renal biopsy is an invasive procedure associated with risk of major complications. Numerous studies aimed to identify a noninvasive biomarker of DN but, so far, none of these is considered to be sufficiently specific and sensitive. Water channel aquaporins (AQPs), expressed at the plasma membrane of epithelial tubular cells, are often dysregulated during DN. In this work, we analyzed the urine excretion of AQP5 and AQP2 (uAQP5 and uAQP2), via exosomes, in 35 diabetic patients: 12 normoalbuminuric with normal renal function (DM), 11 with proteinuric nondiabetic nephropathy (NDN), and 12 with histological diagnosis and classification of DN. ELISA and WB analysis independently showed that uAQP5 was significantly increased in DN patients. Interestingly, linear regression analysis showed a positive correlation between uAQP5 and the histological class of DN. The same analysis, focusing on uAQP2, showed comparable results. Taken together, these data suggest a possible use of AQP5 and AQP2 as novel noninvasive biomarkers to help in classifying the clinical stage of DN. PMID:28246612

  5. Urinary peptidomics in a rodent model of diabetic nephropathy highlights epidermal growth factor as a biomarker for renal deterioration in patients with type 2 diabetes.

    Science.gov (United States)

    Betz, Boris B; Jenks, Sara J; Cronshaw, Andrew D; Lamont, Douglas J; Cairns, Carolynn; Manning, Jonathan R; Goddard, Jane; Webb, David J; Mullins, John J; Hughes, Jeremy; McLachlan, Stela; Strachan, Mark W J; Price, Jackie F; Conway, Bryan R

    2016-05-01

    Many diabetic patients suffer from declining renal function without developing albuminuria. To identify alternative biomarkers for diabetic nephropathy (DN) we performed urinary peptidomic analysis in a rodent model in which hyperglycemia and hypertension synergize to promote renal pathologic changes consistent with human DN. We identified 297 increased and 15 decreased peptides in the urine of rats with DN compared with controls, including peptides derived from proteins associated with DN and novel candidate biomarkers. We confirmed by ELISA that one of the parent proteins, urinary epidermal growth factor (uEGF), was more than 2-fold reduced in rats with DN in comparison with controls. To assess the clinical utility of uEGF we examined renal outcomes in 642 participants from the Edinburgh Type 2 Diabetes Study who were normoalbuminuric and had preserved renal function at baseline. After adjustment for established renal risk factors, a lower uEGF to creatinine ratio was associated with new-onset estimated glomerular filtration rate less than 60 ml/min per 1.73m(2) (odds ratio 0.48; 95% confidence interval, 0.26-0.90), rapid (over 5% per annum) decline in renal function (odds ratio 0.44; 95% confidence interval, 0.27-0.72) or the composite of both outcomes (odds ratio 0.38; 95% confidence interval, 0.24-0.62). Thus, the utility of a low uEGF to creatinine ratio as a biomarker of progressive decline in renal function in normoalbuminuric patients should be assessed in additional populations.

  6. New perspectives on bioactivity of olive oil: evidence from animal models, human interventions and the use of urinary proteomic biomarkers.

    Science.gov (United States)

    Silva, S; Combet, E; Figueira, M E; Koeck, T; Mullen, W; Bronze, M R

    2015-08-01

    Olive oil (OO) is the primary source of fat in the Mediterranean diet and has been associated with longevity and a lower incidence of chronic diseases, particularly CHD. Cardioprotective effects of OO consumption have been widely related with improved lipoprotein profile, endothelial function and inflammation, linked to health claims of oleic acid and phenolic content of OO. With CVD being a leading cause of death worldwide, a review of the potential mechanisms underpinning the impact of OO in the prevention of disease is warranted. The current body of evidence relies on mechanistic studies involving animal and cell-based models, epidemiological studies of OO intake and risk factor, small- and large-scale human interventions, and the emerging use of novel biomarker techniques associated with disease risk. Although model systems are important for mechanistic research nutrition, methodologies and experimental designs with strong translational value are still lacking. The present review critically appraises the available evidence to date, with particular focus on emerging novel biomarkers for disease risk assessment. New perspectives on OO research are outlined, especially those with scope to clarify key mechanisms by which OO consumption exerts health benefits. The use of urinary proteomic biomarkers, as highly specific disease biomarkers, is highlighted towards a higher translational approach involving OO in nutritional recommendations.

  7. Proteome Profiling of Urinary Exosomes Identifies Alpha 1-Antitrypsin and H2B1K as Diagnostic and Prognostic Biomarkers for Urothelial Carcinoma

    Science.gov (United States)

    Lin, Shih-Yi; Chang, Chao-Hsiang; Wu, His-Chin; Lin, Ching-Chan; Chang, Kai-Po; Yang, Chi-Rei; Huang, Chi-Ping; Hsu, Wu-Huei; Chang, Chiz-Tzung; Chen, Chao-Jung

    2016-01-01

    MALDI-TOF spectrometry has not been used for urinary exosome analysis. We used it for determining UC biomarkers. From 2012 to 2015, we enrolled 129 consecutive patients with UC and 62 participants without UC. Exosomes from their urine were isolated, and analyzed through MALDI-TOF spectrometry. Immunohistochemical (IHC) analysis of another 122 UC and 26 non-UC tissues was conducted to verify the discovered biomarkers. Two peaks at m/z 5593 (fragmented peptide of alpha-1-antitrypsin; sensitivity, 50.4%; specificity, 96.9%) and m/z 5947 (fragmented peptide of histone H2B1K sensitivity, 62.0%; specificity, 92.3%) were identified as UC diagnosis exosome biomarkers. UC patients with detectable histone H2B1K showed 2.29- and 3.11-fold increased risks of recurrence and progression, respectively, compared with those with nondetectable histone H2B1K. Verification results of IHC staining revealed significantly higher expression of alpha 1-antitrypsin (p = 0.038) and H2B1K (p = 0.005) in UC tissues than in normal tissues. The expression of alpha 1-antitrypsin and H2B1K in UC tissues was significantly correlated with UC grades (p exosome proteins alpha 1-antitrypsin and histone H2B1K, which are identified through MALDI-TOF analysis, could facilitate rapid diagnosis and prognosis of UC. PMID:27686150

  8. Urinary biomarkers are associated with incident cardiovascular disease, all-cause mortality and deterioration of kidney function in type 2 diabetic patients with microalbuminuria

    DEFF Research Database (Denmark)

    von Scholten, Bernt Johan; Reinhard, Henrik; Hansen, Tine W;

    2016-01-01

    AIMS/HYPOTHESIS: We evaluated two urinary biomarkers reflecting different aspects of renal pathophysiology as potential determinants of incident cardiovascular disease (CVD), all-cause mortality and a reduced estimated GFR (eGFR) in patients with type 2 diabetes and microalbuminuria but without...... diabetes and microalbuminuria receiving multifactorial treatment, higher urinary HGF was associated with incident CVD and all-cause mortality, and higher adiponectin was associated with CVD and deterioration in renal function....

  9. Identification of β2-microglobulin as a urinary biomarker for chronic allograft nephropathy using proteomic methods.

    LENUS (Irish Health Repository)

    Johnston, Olwyn

    2011-08-01

    Chronic allograft nephropathy (CAN) remains the leading cause of renal graft loss after the first year following renal transplantation. This study aimed to identify novel urinary proteomic profiles, which could distinguish and predict CAN in susceptible individuals.

  10. Hydroxy-fipronil is a new urinary biomarker of exposure to fipronil

    Science.gov (United States)

    Occupational medical surveillance is highly desirable in manufacturing facilities where exposure to chemicals is significant. The insecticide fipronil is generally considered safe for humans but with increasing use, exposure to fipronil is of concern. Identification of urinary me...

  11. Kidney injury biomarkers and urinary creatinine variability in nominally healthy adults

    Science.gov (United States)

    Environmental exposure diagnostics use creatinine concentrations in urine aliquots as the internal standard for dilution normalization of all other excreted metabolites when urinary excretion rate data are not available. This is a reasonable approach for healthy adults as creati...

  12. Organic Anion Transporter 5 (Oat5) Urinary Excretion Is a Specific Biomarker of Kidney Injury: Evaluation of Urinary Excretion of Exosomal Oat5 after N-Acetylcysteine Prevention of Cisplatin Induced Nephrotoxicity.

    Science.gov (United States)

    Bulacio, Romina Paula; Anzai, Naohiko; Ouchi, Motoshi; Torres, Adriana Mónica

    2015-08-17

    Cisplatin is a commonly used chemotherapeutic agent. Its main side-effect is nephrotoxicity. It was reported that the organic anion transporter 5 (Oat5) urinary excretion is elevated, implying renal perturbation, when no modifications of traditional markers of renal damage are still observed in cisplatin-induced acute kidney injury (AKI). It was also demonstrated that Oat5 is excreted in urine by the exosomal pathway. This study was designated to demonstrate the specific response of the urinary excretion of exosomal Oat5 to kidney injury independently of other cisplatin toxic effects, in order to strengthen Oat5 urinary levels as a specific biomarker of AKI. To accomplish that aim, we evaluated if urinary excretion of exosomal Oat5 returns to its basal levels when cisplatin renal damage is prevented by the coadministration of the renoprotective compound N-acetylcysteine. Four days after cisplatin administration, AKI was induced in cisplatin-treated male Wistar rats (Cis group), as it was corroborated by increased urea and creatinine plasma levels. Tubular damage was also observed. In cotreated animals (Cis + NAC group), plasma urea and creatinine concentrations tended to return to their basal values, and tubular damage was improved. Urinary excretion of exosomal Oat5 was notably increased in the Cis group, but when renal injury was ameliorated by N-acetylcysteine coadministration, that increase was undetected. So, in this work we observed that urinary excretion of exosomal Oat5 was only increased if renal insult is produced, demonstrating its specificity as a renal injury biomarker.

  13. Effect of parsley (Petroselinum crispum) intake on urinary apigenin excretion, blood antioxidant enzymes and biomarkers for oxidative stress in human subjects.

    Science.gov (United States)

    Nielsen, S E; Young, J F; Daneshvar, B; Lauridsen, S T; Knuthsen, P; Sandström, B; Dragsted, L O

    1999-06-01

    Seven men and seven women participated in a randomized crossover trial to study the effect of intake of parsley (Petroselinum crispum), containing high levels of the flavone apigenin, on the urinary excretion of flavones and on biomarkers for oxidative stress. The subjects received a strictly controlled diet low in flavones and other naturally occurring antioxidants during the 2 weeks of intervention. This basic diet was supplemented with parsley providing 3.73-4.49 mg apigenin/MJ in one of the intervention weeks. Urinary excretion of apigenin was 1.59-409.09 micrograms/MJ per 24 h during intervention with parsley and 0-112.27 micrograms/MJ per 24 h on the basic diet (P < 0.05). The fraction of apigenin intake excreted in the urine was 0.58 (SE 0.16)% during parsley intervention. Erythrocyte glutathione reductase (EC 1.6.4.1; GR) and superoxide dismutase (EC 1.15.1.1; SOD) activities increased during intervention with parsley (P < 0.005) as compared with the levels on the basic diet, whereas erythrocyte catalase (EC 1.11.1.6) and glutathione peroxidase (EC 1.11.1.9) activities did not change. No significant changes were observed in plasma protein 2-adipic semialdehyde residues, a biomarker of plasma protein oxidation. In this short-term investigation, an overall decreasing trend in the activity of antioxidant enzymes was observed during the 2-week study. The decreased activity of SOD was strongly correlated at the individual level with an increased oxidative damage to plasma proteins. However, the intervention with parsley seemed, partly, to overcome this decrease and resulted in increased levels of GR and SOD.

  14. Linking Biomarker and Comparative Omics to Pathogens in Legumes.

    Science.gov (United States)

    Diapari, Marwan

    2016-01-01

    It is envisioned that a more precise study of the association between the traits and biomarkers will dramatically decrease the time and costs required to bring new improved disease resistance lines to market. The field of omics has an enormous potential to assess diseases more precise, including the identification and understanding of pathogenic mechanisms in legume crops, and have been exemplified by a relatively large number of studies. Recently, molecular genetic studies have accumulated a huge amount of genotypic data, through a more affordable next generation sequencing (NGS) technology, causing the omics approaches to fall behind. In this paper I provide an overview of genomics and proteomics and their use in legume crops, including the use of comparative genomics to identify homologous markers within legume crops.

  15. Urinary deoxynivalenol (DON) and zearalenone (ZEA) as biomarkers of DON and ZEA exposure of pigs.

    Science.gov (United States)

    Thanner, S; Czeglédi, L; Schwartz-Zimmermann, H E; Berthiller, F; Gutzwiller, A

    2016-05-01

    Four diets contaminated with 1.1 to 5.0 mg/kg deoxynivalenol (DON) and 0.4 to 2.4 mg/kg zearalenone (ZEA) were fed to four groups of six growing Large White pigs. Urine samples were collected after 3 to 4 days and again after 6 to 7 days on the diets. On each sampling day, half of the animals were sampled in the morning, after an 8-h fast, and the other half were sampled in the afternoon, after 7 h of ad libitum access to feed. The urinary concentrations of DON, DON-glucuronide, DON-3-sulphate, de-epoxy-DON, as well as of ZEA, ZEA-14-glucuronide, α-zearalenol and α-zearalenol-14-glucuronide, analysed using LC-MS/MS, were used to calculate urinary DON and ZEA equivalent concentrations (DONe and ZEAe). The urinary concentration of DONe (P < 0.001), but not of ZEAe (P = 0.31), was lower in the fasted than that in the fed animals. The urinary DONe/creatinine and ZEAe/creatinine ratios were highly correlated with DON and ZEA intake per kg body weight the day preceding sampling (r = 0.76 and 0.77; P < 0.001). The correlations between DON intake during the 7 h preceding urine sampling in the afternoon and urinary DONe/creatinine ratio (r = 0.88) as well as between mean ZEA intake during 3 days preceding urine sampling and urinary ZEAe/creatinine ratio (r = 0.84) were even higher, reflecting the plasma elimination half-time of several hours for DON and of more than 3 days for ZEA. ZEAe analysed in enzymatically hydrolysed urine using an ELISA kit was highly correlated with the LC-MS/MS data (r = 0.94). The urinary DONe and ZEAe to creatinine ratios, analysed in pooled urine samples of several pigs fed the same diet, can be used to estimate their exposure to DON and ZEA.

  16. Global metabolomics reveals potential urinary biomarkers of esophageal squamous cell carcinoma for diagnosis and staging

    Science.gov (United States)

    Xu, Jing; Chen, Yanhua; Zhang, Ruiping; He, Jiuming; Song, Yongmei; Wang, Jingbo; Wang, Huiqing; Wang, Luhua; Zhan, Qimin; Abliz, Zeper

    2016-10-01

    We performed a metabolomics study using liquid chromatography-mass spectrometry (LC-MS) combined with multivariate data analysis (MVDA) to discriminate global urine profiles in urine samples from esophageal squamous cell carcinoma (ESCC) patients and healthy controls (NC). Our work evaluated the feasibility of employing urine metabolomics for the diagnosis and staging of ESCC. The satisfactory classification between the healthy controls and ESCC patients was obtained using the MVDA model, and obvious classification of early-stage and advanced-stage patients was also observed. The results suggest that the combination of LC-MS analysis and MVDA may have potential applications for ESCC diagnosis and staging. We then conducted LC-MS/MS experiments to identify the potential biomarkers with large contributions to the discrimination. A total of 83 potential diagnostic biomarkers for ESCC were screened out, and 19 potential biomarkers were identified; the variations between the differences in staging using these potential biomarkers were further analyzed. These biomarkers may not be unique to ESCCs, but instead result from any malignant disease. To further elucidate the pathophysiology of ESCC, we studied related metabolic pathways and found that ESCC is associated with perturbations of fatty acid β-oxidation and the metabolism of amino acids, purines, and pyrimidines.

  17. Impact of the improved patsari biomass stove on urinary polycyclic aromatic hydrocarbon biomarkers and carbon monoxide exposures in rural Mexican women.

    Science.gov (United States)

    Riojas-Rodriguez, Horacio; Schilmann, Astrid; Marron-Mares, Adriana Teresa; Masera, Omar; Li, Zheng; Romanoff, Lovisa; Sjödin, Andreas; Rojas-Bracho, Leonora; Needham, Larry L; Romieu, Isabelle

    2011-09-01

    Cooking with biomass fuels on open fires results in exposure to health-damaging pollutants such as carbon monoxide (CO), polycyclic aromatic hydrocarbons (PAHs), and particulate matter. We compared CO exposures and urinary PAH biomarkers pre- and postintervention with an improved biomass stove, the Patsari stove. In a subsample of 63 women participating in a randomized controlled trial in central Mexico, we measured personal CO exposure for 8 hr during the day using continuous monitors and passive samplers. In addition, first-morning urine samples obtained the next day were analyzed for monohydroxylated PAH metabolites by gas chromatography/isotope dilution/high-resolution mass spectrometry. Exposure data were collected during the use of an open fire (preintervention) and after installation of the improved stove (postintervention) for 47 women, enabling paired comparisons. Median pre- and postintervention values were 4 and 1 ppm for continuous personal CO and 3 and 1 ppm for passive sampler CO, respectively. Postintervention measurements indicated an average reduction of 42% for hydroxylated metabolites of naphthalene, fluorene, phenanthrene, and pyrene on a whole-weight concentration basis (micrograms per liter of urine), and a 34% reduction on a creatinine-adjusted basis (micrograms per gram of creatinine). Pre- and postintervention geometric mean values for 1-hydroxypyrene were 3.2 and 2.0 μg/g creatinine, respectively. Use of the Patsari stove significantly reduced CO and PAH exposures in women. However, levels of many PAH biomarkers remained higher than those reported among smokers.

  18. Urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine as a biomarker in type 2 diabetes

    DEFF Research Database (Denmark)

    Broedbaek, Kasper; Weimann, Allan; Stovgaard, Elisabeth Ida Specht;

    2011-01-01

    The increasing prevalence of diabetes together with the associated morbidity and mortality calls for additional preventive and therapeutic strategies. New biomarkers that can be used in therapy control and risk stratification as alternatives to current methods are needed and can facilitate a more...... as a valuable biomarker in diabetes is the DNA oxidation marker 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), which can be assessed noninvasively in the urine, with minimal discomfort for the patient. In this review the analytical validity of 8-oxodG is addressed by highlighting important methodological issues...

  19. Epilepsy as a pyridoxine-dependent condition: quantified urinary biomarkers for status evaluation and monitoring antiepileptic treatment.

    Science.gov (United States)

    Dolina, Svetlana; Margalit, Dov; Malitsky, Sergey; Pressman, Eugeny; Rabinkov, Aharon

    2012-08-01

    The study testifies an assumption on epilepsy as an inborn error of pyridoxine metabolism and suggests non-invasive quantitative biomarkers for clarified evaluation of clinical status and monitoring an individual treatment by antiepileptic drugs. Urinary parameters of pyridoxal-phosphate (PLP)-dependent tryptophan degradation and the level of 4-pyridoxic acid, the end product of pyridoxine metabolism, were measured by HPLC method with simultaneous ultraviolet and fluorimetric detection in children with different forms of epilepsy and matched healthy controls. The concentrations of compounds formed or metabolized in the course of tryptophan degradation (kynurenines, indoxyl-sulfate) along with correlations between them turned out to be quantitative biomarkers useful for both clarifying patient's clinical state and monitoring antiepileptic treatment. In particular, the value of the ratio of 4-pyridoxic acid to kynurenine appears to be an index of an experienced seizure attack, while the ratio of 3-hydroxyanthranilic acid to 3-hydroxykynurenine reflects activity of kynureninase, the enzyme of critical sensitivity to PLP supply. Growing progressively worse, epilepsy is accompanied by aggravation of PLP-dependent disturbances of tryptophan metabolism and expanding inhibition of kynureninase. The affected pyridoxine metabolism is discussed as an inborn genetic trait in epilepsy in general, rather than a specific sign of pyridoxine-dependent epilepsy solely.

  20. Application of Holistic Liquid Chromatography-High Resolution Mass Spectrometry Based Urinary Metabolomics for Prostate Cancer Detection and Biomarker Discovery.

    Directory of Open Access Journals (Sweden)

    Tong Zhang

    Full Text Available Human exhibit wide variations in their metabolic profiles because of differences in genetic factors, diet and lifestyle. Therefore in order to detect metabolic differences between individuals robust analytical methods are required. A protocol was produced based on the use of Liquid Chromatography- High Resolution Mass Spectrometry (LC-HRMS in combination with orthogonal Hydrophilic Interaction (HILIC and Reversed Phase (RP liquid chromatography methods for the analysis of the urinary metabolome, which was then evaluated as a diagnostic tool for prostate cancer (a common but highly heterogeneous condition. The LC-HRMS method was found to be robust and exhibited excellent repeatability for retention times (0.9. In addition, using the receiver operator characteristics (ROC test, the area under curve (AUC for the combination of the four best characterised biomarker compounds was 0.896. The four biomarker compounds were also found to differ significantly (P<0.05 between an independent patient cohort and controls. This is the first time such a rigorous test has been applied to this type of model. If validated, the established protocol provides a robust approach with a potentially wide application to metabolite profiling of human biofluids in health and disease.

  1. Effect of fruit juice intake on urinary quercetin excretion and biomarkers of antioxidative status

    DEFF Research Database (Denmark)

    Young, J. F.; Nielsen, S. E.; Haraldsdottir, J.

    1999-01-01

    Background: Epidemiologic studies suggest that foods rich in flavonoids might reduce the risk of cardiovascular disease. Objective: Our objective was to investigate the effect of intake of flavonoid-containing black currant and apple juice on urinary excretion of quercetin and on markers of oxida......Background: Epidemiologic studies suggest that foods rich in flavonoids might reduce the risk of cardiovascular disease. Objective: Our objective was to investigate the effect of intake of flavonoid-containing black currant and apple juice on urinary excretion of quercetin and on markers...... of oxidative status. Design: This was a crossover study with 3 doses of juice (750, 1000, and 1500 mL) consumed for 1 wk by 4 women and 1 man corresponding to an intake of 4.8, 6.4, and 9.6 mg quercetin/d. Results: Urinary excretion of quercetin increased significantly with dose and with time. The fraction...... excreted in urine was 0.29-0.47%. Plasma quercetin did not change with juice inter vention, Plasma ascorbate increased during intervention because of the ascorbate in the juice. Total plasma malondialdehyde decreased with time during the 1500-mL juice intervention, indicating reduced lipid oxidation...

  2. Urinary levels of thymine dimer as a biomarker of exposure to ultraviolet radiation in humans during outdoor activities in the summer.

    Science.gov (United States)

    Liljendahl, Tove Sandberg; Blomqvist, Anna; Andersson, Eva M; Barregard, Lars; Segerbäck, Dan

    2013-05-01

    The incidence of skin cancer is rising rapidly in many countries, presumably due to increased leisure time exposure to solar ultraviolet radiation (UVR). UVR causes DNA lesions, such as the thymine dimer (T=T), which have been causatively linked to the development of skin cancer. T=T is clearly detectable in urine and may, thereby, be a potentially valuable biomarker of UVR exposure. The objective of this study was to evaluate the relationship between UVR exposure and urinary levels of T=T in a field study involving outdoor workers. Daily ambient and personal exposure of 52 beach lifeguards and agricultural workers to UVR were determined (employing 656 personal polysulphone dosimeters). In 22 of these subjects, daily urinary T=T levels (120 samples) were measured, the area of skin exposed calculated and associations assessed utilizing mixed statistical models. The average daily UVR dose was approximately 600 J/m(2) (7.7 standard erythemal doses), i.e. about 20% of ambient UVR. T=T levels were correlated to UVR dose, increasing by about 6 fmol/µmol creatinine for each 100 J/m(2) increase in dose (average of the three preceding days). This is the first demonstration of a relationship between occupational UVR exposure and urinary levels of a biomarker of DNA damage. On a population level, urinary levels of T=T can be used as a biomarker for UVR exposure in the field.

  3. Urinary p75ECD

    Science.gov (United States)

    Shepheard, Stephanie R.; Wuu, Joanne; Cardoso, Michell; Wiklendt, Luke; Dinning, Phil G.; Chataway, Tim; Schultz, David

    2017-01-01

    Objective: To evaluate urinary neurotrophin receptor p75 extracellular domain (p75ECD) levels as disease progression and prognostic biomarkers in amyotrophic lateral sclerosis (ALS). Methods: The population in this study comprised 45 healthy controls and 54 people with ALS, 31 of whom were sampled longitudinally. Urinary p75ECD was measured using an enzyme-linked immunoassay and validation included intra-assay and inter-assay coefficients of variation, effect of circadian rhythm, and stability over time at room temperature, 4°C, and repeated freeze-thaw cycles. Longitudinal changes in urinary p75ECD were examined by mixed model analysis, and the prognostic value of baseline p75ECD was explored by survival analysis. Results: Confirming our previous findings, p75ECD was higher in patients with ALS (5.6 ± 2.2 ng/mg creatinine) compared to controls (3.6 ± 1.4 ng/mg creatinine, p analysis, bulbar onset (hazard ratio [HR] 3.0, p = 0.0035), rate of disease progression from onset to baseline (HR 4.4, p survival. Conclusions: The assay for urinary p75ECD is analytically robust and shows promise as an ALS biomarker with prognostic, disease progression, and potential pharmacodynamic application. Baseline urinary p75ECD provides prognostic information and is currently the only biological fluid–based biomarker of disease progression. PMID:28228570

  4. Bio-monitoring of mycotoxin exposure in Cameroon using a urinary multi-biomarker approach.

    Science.gov (United States)

    Abia, Wilfred A; Warth, Benedikt; Sulyok, Michael; Krska, Rudolf; Tchana, Angele; Njobeh, Patrick B; Turner, Paul C; Kouanfack, Charles; Eyongetah, Mbu; Dutton, Mike; Moundipa, Paul F

    2013-12-01

    Bio-monitoring of human exposure to mycotoxin has mostly been limited to a few individually measured mycotoxin biomarkers. This study aimed to determine the frequency and level of exposure to multiple mycotoxins in human urine from Cameroonian adults. 175 Urine samples (83% from HIV-positive individuals) and food frequency questionnaire responses were collected from consenting Cameroonians, and analyzed for 15 mycotoxins and relevant metabolites using LC-ESI-MS/MS. In total, eleven analytes were detected individually or in combinations in 110/175 (63%) samples including the biomarkers aflatoxin M1, fumonisin B1, ochratoxin A and total deoxynivalenol. Additionally, important mycotoxins and metabolites thereof, such as fumonisin B2, nivalenol and zearalenone, were determined, some for the first time in urine following dietary exposures. Multi-mycotoxin contamination was common with one HIV-positive individual exposed to five mycotoxins, a severe case of co-exposure that has never been reported in adults before. For the first time in Africa or elsewhere, this study quantified eleven mycotoxin biomarkers and bio-measures in urine from adults. For several mycotoxins estimates indicate that the tolerable daily intake is being exceeded in this study population. Given that many mycotoxins adversely affect the immune system, future studies will examine whether combinations of mycotoxins negatively impact Cameroonian population particularly immune-suppressed individuals.

  5. Urinary excretion of biomarkers of oxidatively damaged DNA and RNA in hereditary hemochromatosis

    DEFF Research Database (Denmark)

    Broedbaek, Kasper; Poulsen, Henrik E; Weimann, Allan

    2009-01-01

    to measure the urinary excretion of oxidatively generated 8-oxo-7,8-dihydroguanine and related 2'-deoxyribonucleoside and ribonucleoside derivatives in hereditary hemochromatosis patients, and we investigated the effect of treatment on the levels of these modifications. The study was carried out......, and after phlebotomy treatment the excretion of the RNA oxidation product 8-oxoGuo returned to control values and the excretion of the DNA product 8-oxo-7,8-dihydro-2'-deoxyguanosine was reduced by 30%. In patients with hereditary hemochromatosis oxidative stress on nucleic acids is an important feature...

  6. Measurement of Urinary Biomarkers of Parabens, Benzophenone-3, and Phthalates in a Belgian Population

    Directory of Open Access Journals (Sweden)

    Lucas Dewalque

    2014-01-01

    Full Text Available Parabens, benzophenone-3 (BP3, and phthalates are commonly used as antimicrobial conservator, UV-filter, and plasticizer, respectively, and are thought to exhibit endocrine disrupting properties. These endocrine disrupting activities have been recently assumed to lead to cutaneous malignant melanoma. Humans are exposed to these chemicals through different sources such as food, personal care products, or cosmetics. In this study, we measured urinary levels of 4 parabens, BP3, and 7 metabolites of phthalates in samples collected from 261 participants living in and around Liege (Belgium. The analyses were carried out by liquid chromatography tandem mass spectrometry (LC-MS/MS using isotopic dilution. To the best of our knowledge, this is the first time that the urinary levels of these 3 classes of chemicals are reported for the same general population in Belgium. Most of the parabens, the BP3, and all the phthalate metabolites were detected in 82.8 to 100.0% of the samples. For most of these chemicals, the exposure patterns significantly differ not only between children and adults, but also between males and females, especially with higher concentrations of parabens and phthalate metabolites in female and children subjects, respectively.

  7. Measurement of urinary biomarkers of parabens, benzophenone-3, and phthalates in a Belgian population.

    Science.gov (United States)

    Dewalque, Lucas; Pirard, Catherine; Charlier, Corinne

    2014-01-01

    Parabens, benzophenone-3 (BP3), and phthalates are commonly used as antimicrobial conservator, UV-filter, and plasticizer, respectively, and are thought to exhibit endocrine disrupting properties. These endocrine disrupting activities have been recently assumed to lead to cutaneous malignant melanoma. Humans are exposed to these chemicals through different sources such as food, personal care products, or cosmetics. In this study, we measured urinary levels of 4 parabens, BP3, and 7 metabolites of phthalates in samples collected from 261 participants living in and around Liege (Belgium). The analyses were carried out by liquid chromatography tandem mass spectrometry (LC-MS/MS) using isotopic dilution. To the best of our knowledge, this is the first time that the urinary levels of these 3 classes of chemicals are reported for the same general population in Belgium. Most of the parabens, the BP3, and all the phthalate metabolites were detected in 82.8 to 100.0% of the samples. For most of these chemicals, the exposure patterns significantly differ not only between children and adults, but also between males and females, especially with higher concentrations of parabens and phthalate metabolites in female and children subjects, respectively.

  8. Hydroxy-fipronil is a new urinary biomarker of exposure to ...

    Science.gov (United States)

    Occupational medical surveillance is highly desirable in manufacturing facilities where exposure to chemicals is significant. The insecticide fipronil is generally considered safe for humans but with increasing use, exposure to fipronil is of concern. Identification of urinary metabolites of fipronil may allow development of affordable, cheap and rapid procedures for human exposure evaluation. In this study we developed a fast and easy approach for synthesis of hydroxy-fipronil, a potential urinary metabolite of fipronil. This standard was used to develop a sensitive analytical LC-MS/MS method with a limit of quantification (LOQ) of 0.4 ng/mL. Fipronil sulfone, a known metabolite, and hydroxy-fipronil were quantified in urine samples from rats treated with a fipronil containing diet. Fipronil sulfone concentration centered around 20 ng/mL, while the concentration of hydroxy-fipronil was dose-dependent ranging in 10–10,000 ng/mL and thus being a more sensitive marker of fipronil exposure. A fipronil immunoassay with cross-reactivity to hydroxy-fipronil showed a good correlation in signal intensity with LC-MS data. It was also used to demonstrate the applicability of the method for sample screening in the evaluation of exposure levels. Fipronil is a broad spectrum insecticide from the phenylpyrazole family. It is often used in four major domains: pest control in a wide variety of field crops, urban pest management, veterinary applications (especially in topical

  9. Urinary apolipoprotein M as a biomarker of acute kidney injury in children undergoing heart surgery

    DEFF Research Database (Denmark)

    Svarrer, Eva Martha Madsen; Andersen, Henrik Ørbæk; Helvind, Morten

    2016-01-01

    by gel filtration chromatography and western blotting. RESULTS: ApoM was excreted into the urine 0-4 h postoperatively as the full-length apoM in particles smaller than plasma HDL. At 0 h, U-apoM predicted AKI with an area under the receiver-operating characteristics curve of 0.70 (p ....018). Sensitivity was 0.71 and specificity was 0.68 at a cutoff level at 1.45 nmol/l. CONCLUSION: ApoM is excreted in the urine of children after cardiac surgery. Its potential as biomarker of AKI deserves exploration....

  10. Challenges of liver cancer:Future emerging tools in imaging and urinary biomarkers

    Institute of Scientific and Technical Information of China (English)

    Francesca; M; Trovato; Joshua; M; Tognarelli; Mary; ME; Crossey; Daniela; Catalano; Simon; D; Taylor-Robinson; Guglielmo; M; Trovato

    2015-01-01

    Chronic liver disease has become a global health problem as a result of the increasing incidence of viral hepatitis, obesity and alcohol misuse. Over the past three decades, in the United Kingdom alone, deaths from chronic liver disease have increased both in men and in women. Currently, 2.5% of deaths worldwide are attributed to liver disease and projected figures suggest a doubling in hospitalisation and associated mortality by 2020. Chronic liver diseases vary for clinical manifestations and natural history, with some individuals having relatively indolent disease and others with a rapidly progressive course. About 30% of patients affected by hepatitis C has a progressive disease and develop cirrhosis over a 20 years period from the infection, usually 5-10 years after initial medical presentation. The aim of the current therapeutic strategies is preventing the progression from hepatitis to fibrosis and subsequently, cirrhosis. Hepatic steatosis is a risk factor for chronic liver disease and is affecting about the half of patients who abuse alcohol. Moreover non-alcoholic fatty liver disease is part of the metabolic syndrome, associated with obesity, hypertension, type Ⅱ diabetes mellitus and dyslipidaemia, and a subgroup of patients develops non-alcoholic steatohepatitis and fibrosis with subsequent cirrhosis. The strengths and pitfalls of liver biopsy are discussed and a variety of new techniques to assess liver damage from transient elastography to experimental techniques, such as in vitro urinary nuclear magnetic resonance spectroscopy. Some of the techniques and tests described are already suitable for more widespread clinical application, as is the case with ultrasound-based liver diagnostics, but others, such as urinary metabonomics, requires a period of critical evaluation or development to take them from the research arena to clinical practice.

  11. Urinary Biomarkers KIM-1 and NGAL for Detection of Chronic Kidney Disease of Uncertain Etiology (CKDu) among Agricultural Communities in Sri Lanka.

    Science.gov (United States)

    De Silva, Pallagae Mangala C S; Mohammed Abdul, Khaja Shameem; Eakanayake, Eakanayake M D V; Jayasinghe, Sudheera Sammanthi; Jayasumana, Channa; Asanthi, Hewa Bandulage; Perera, Hettiarachigae S D; Chaminda, Gamage G Tushara; Chandana, Ediriweera P S; Siribaddana, Sisira H

    2016-09-01

    Chronic Kidney Disease of uncertain etiology (CKDu) is an emerging epidemic among farming communities in rural Sri Lanka. Victims do not exhibit common causative factors, however, histopathological studies revealed that CKDu is a tubulointerstitial disease. Urine albumin or albumin-creatinine ratio is still being used as a traditional diagnostic tool to identify CKDu, but accuracy and prevalence data generated are questionable. Urinary biomarkers have been used in similar nephropathy and are widely recognised for their sensitivity, specificity and accuracy in determining CKDu and early renal injury. However, these biomarkers have never been used in diagnosing CKDu in Sri Lanka. Male farmers (n = 1734) were recruited from 4 regions in Sri Lanka i.e. Matara and Nuwara Eliya (farming locations with no CKDu prevalence) and two CKDu emerging locations from Hambantota District in Southern Sri Lanka; Angunakolapelessa (EL1) and Bandagiriya (EL2). Albuminuria (ACR ≥ 30mg/g); serum creatinine based estimation of glomerular filtration rate (eGFR); creatinine normalized urinary kidney injury molecule (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) were measured. Fourteen new CKDu cases (18%) from EL1 and nine CKDu cases (9%) from EL2 were recognized for the first time from EL1, EL2 locations, which were previously considered as non-endemic of the disease and associated with persistent albuminuria (ACR ≥ 30mg/g Cr). No CKDu cases were identified in non-endemic study locations in Matara (CM) and Nuwara Eliya (CN). Analysis of urinary biomarkers showed urinary KIM-1 and NGAL were significantly higher in new CKDu cases in EL1 and EL2. However, we also reported significantly higher KIM-1 and NGAL in apparently healthy farmers in EL 1 and EL 2 with comparison to both control groups. These observations may indicate possible early renal damage in absence of persistent albuminuria and potential capabilities of urinary KIM-1 and NGAL in early detection of renal injury

  12. Urinary Biomarkers KIM-1 and NGAL for Detection of Chronic Kidney Disease of Uncertain Etiology (CKDu) among Agricultural Communities in Sri Lanka

    OpenAIRE

    De Silva, Pallagae Mangala C. S.; Khaja Shameem Mohammed Abdul; Eakanayake M D V Eakanayake; Sudheera Sammanthi Jayasinghe; Channa Jayasumana; Hewa Bandulage Asanthi; Perera, Hettiarachigae S. D.; Gamage G Tushara Chaminda; Ediriweera P S Chandana; Siribaddana, Sisira H.

    2016-01-01

    Chronic Kidney Disease of uncertain etiology (CKDu) is an emerging epidemic among farming communities in rural Sri Lanka. Victims do not exhibit common causative factors, however, histopathological studies revealed that CKDu is a tubulointerstitial disease. Urine albumin or albumin-creatinine ratio is still being used as a traditional diagnostic tool to identify CKDu, but accuracy and prevalence data generated are questionable. Urinary biomarkers have been used in similar nephropathy and are ...

  13. Stress Urinary lncontinence : Comparative Study of Perineal Sonography in Erect Position and Chain Cystourethrograpy

    Energy Technology Data Exchange (ETDEWEB)

    Han, Gi Seok; Kim, Seung Hyup; Yeon, Kyung Mo; Han, Man Chung; Paick, Jae Seung [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    1995-06-15

    Authors investigated the diagnostic value of perineal sonography in erect position for patients with stress urinary incontinence. Perineal sonography and chain cystourethrography were performed in 18 female patients(mean age 51.2) with stress urinary incontinence. The posterior are throvesical angles in stress and rest states were measured in both studies and compared with each other. Mean posteriorurethrovesical angles({+-}2 standard error) in rest and stress states were 136.3({+-}7.2) .deg. , and 145.9({+-}7.0) .deg. for chain cystourethrography and 131.4({+-}5.6) .deg. and 143.4({+-}5.9) .deg. for perineal sonography, respectively. The data frorm both studies correlated well with cach other. Perineal sonography inerect position is easy,non-invasive technique and may substitute the chain cystourethrography in the evaluation of the patients with stress urinary in continece

  14. The effects of physiotherapy for female urinary incontinence: Individual compared with group treatment

    NARCIS (Netherlands)

    Janssen, C.C.M.; Lagro-Janssen, A.L.M.; Felling, A.J.A.

    2001-01-01

    OBJECTIVES: To compare, in a randomized trial, the effects of individual and group physiotherapy for urinary incontinence in women referred by their general practitioner (GP). PATIENTS AND METHODS: The study included women of all ages (mean 47.8 years) with stress, urge or mixed incontinence; 126

  15. The effects of physiotherapy for female urinary incontinence: individual compared with group treatment

    NARCIS (Netherlands)

    Janssen, C.C.M.; Lagro-Janssen, A.L.M.; Felling, A.J.A.

    2001-01-01

    OBJECTIVES: To compare, in a randomized trial, the effects of individual and group physiotherapy for urinary incontinence in women referred by their general practitioner (GP). PATIENTS AND METHODS: The study included women of all ages (mean 47.8 years) with stress, urge or mixed incontinence; 126

  16. The effects of physiotherapy for female urinary incontinence: individual compared with group treatment

    NARCIS (Netherlands)

    Janssen, C.C.M.; Lagro-Janssen, A.L.M.; Felling, A.J.A.

    2001-01-01

    OBJECTIVES: To compare, in a randomized trial, the effects of individual and group physiotherapy for urinary incontinence in women referred by their general practitioner (GP). PATIENTS AND METHODS: The study included women of all ages (mean 47.8 years) with stress, urge or mixed incontinence; 126 re

  17. The effects of physiotherapy for female urinary incontinence: Individual compared with group treatment

    NARCIS (Netherlands)

    Janssen, C.C.M.; Lagro-Janssen, A.L.M.; Felling, A.J.A.

    2001-01-01

    OBJECTIVES: To compare, in a randomized trial, the effects of individual and group physiotherapy for urinary incontinence in women referred by their general practitioner (GP). PATIENTS AND METHODS: The study included women of all ages (mean 47.8 years) with stress, urge or mixed incontinence; 126 re

  18. Strong Associations Exist among Oxidative Stress and Antioxidant Biomarkers in the Circulating, Cellular and Urinary Anatomical Compartments in Guatemalan Children from the Western Highlands.

    Directory of Open Access Journals (Sweden)

    María J Soto-Méndez

    Full Text Available A series of antioxidant enzymes and non-enzymatic compounds act to protect cells from uncontrolled propagation of free radicals. It is poorly understood, though, to what extent and how their interaction is harmonized.To explore associative interactions among a battery of urinary and blood biomarkers of oxidative stress and enzymatic and non-enzymatic markers of the antioxidant defense system in children from low income households.For this cross-sectional descriptive study, urine, red cells, and plasma were sampled in 82 preschool children attending three daycare centers in Quetzaltenango Guatemala. The urinary oxidative stress biomarkers studied were F2-isoprostanes and 8-hydroxy-deoxy-guanosine. Red cell enzyme activities measured were: catalase, superoxide dismutase, glutathione peroxidase and glutathione reductase. Circulating non-enzymatic antioxidants selected were: retinol, tocopherols, β-carotene and coenzymes Q9 and Q10.In a Spearman rank-order correlation hemi-matrix, of 55 paired combinations of the 11 biomarkers, 28 (51% were significantly correlated among each other (p ≤ 0.05, with the strongest association being retinol and tocopherols (r = 0.697, p 0.5 to ≤ 0.10. F2-isoprostanes showed the greatest number of cross-associations, having significant interactions with 8 of the 10 remaining biomarkers. Goodness-of-fit modeling improved or maintained the r value for 24 of the significant interactions and for one of the 5 borderline associations. Multiple regression backward stepwise analysis indicated that plasma retinol, β-carotene and coenzyme Q10 were independent predictors of urinary F2-isoprostanes.Numerous significant associations resulted among biomarkers of oxidation and responders to oxidation. Interesting findings were the apparent patterns of harmonious interactions among the elements of the oxidation-antioxidation systems in this population.

  19. Urinary biomarkers of exposure to 57 xenobiotics and its association with oxidative stress in a population in Jeddah, Saudi Arabia.

    Science.gov (United States)

    Asimakopoulos, Alexandros G; Xue, Jingchuan; De Carvalho, Bruno Pereira; Iyer, Archana; Abualnaja, Khalid Omer; Yaghmoor, Soonham Sami; Kumosani, Taha Abdullah; Kannan, Kurunthachalam

    2016-10-01

    Oxidative stress arises from excessive free radicals in the body and is a trigger for numerous diseases, such as cancer and atherosclerosis. Elevated exposure to environmental chemicals can contribute to oxidative stress. The association between exposure to xenobiotics and oxidative stress, however, has rarely been studied. In this study, urinary concentrations of 57 xenobiotics (antimicrobials, parabens, bisphenols, benzophenones, and phthalates metabolites) were determined in a population from Jeddah, Saudi Arabia, to delineate association with the oxidative stress biomarker, 8-hydroxy-2'-deoxyguanosine (8OHDG). We collected 130 urine samples and analyzed for 57 xenobiotics using liquid chromatography-tandem mass spectrometry (LC/MS/MS) methods. The association between unadjusted and creatinine- or specific gravity-adjusted concentrations of xenobiotics and 8OHDG was examined by Pearson correlations and multiple regression analysis. High concentrations of mCPP (a metabolite of di-n-octyl phthalate; DnOP) and mCMHP (a metabolite of diethylhexyl phthalate; DEHP) were found in urine. In addition, the concentrations of bisphenol S (BPS) were higher than those of bisphenol A (BPA). The concentrations of metabolites of DEHP, phthalic acid, BPA, BPS, and methyl-protocatechuic acid were significantly associated with 8OHDG. This is the first biomonitoring study to report exposure of the Saudi population to a wide range of environmental chemicals and provides evidence that environmental chemical exposures contribute to oxidative stress.

  20. Determination of urinary biomarkers for assessment of short-term human exposure to aflatoxins in São Paulo, Brazil.

    Science.gov (United States)

    Jager, Alessandra V; Tonin, Fernando G; Souto, Pollyana C M C; Privatti, Rafaela T; Oliveira, Carlos A F

    2014-07-08

    In the present study, a longitudinal assessment was carried out to evaluate the short-term human exposure to aflatoxins in Pirassununga region, São Paulo, Brazil, by determination of urinary aflatoxins by a liquid chromatography coupled to mass sprectrometry (UPLC-MS/MS) method. Sixteen volunteers with ages ranging from 14 to 55 years old were instructed to collect the early morning first urine four times every three months, from June 2011 to March 2012, totaling 64 samples. Aflatoxin M1 (AFM1) was found in 39 samples (61%) at levels ranging from 0.19 to 12.7 pg·mg-1 creatinine (mean: 1.2 ± 2.0 pg·mg-1 creatinine). Residues of aflatoxins B1, B2, G1, G2 and aflatoxicol were not identified in any urine sample. No significant difference was found among the AFM1 mean levels in urine samples collected in the four sampling periods. The levels of AFM1 found in urine samples indicate a low short-term exposure of the population studied to aflatoxins through the diet, although further investigations are needed to assess other long-term biomarkers of exposure to AFB1.

  1. A vitamin B-12 supplement of 500 μg/d for eight weeks does not normalize urinary methylmalonic acid or other biomarkers of vitamin B-12 status in elderly people with moderately poor vitamin B-12 status.

    Science.gov (United States)

    Hill, Marilyn H; Flatley, Janet E; Barker, Margo E; Garner, Clare M; Manning, Nigel J; Olpin, Simon E; Moat, Stuart J; Russell, Jean; Powers, Hilary J

    2013-02-01

    Plasma vitamin B-12 is the most commonly used biomarker of vitamin B-12 status, but the predictive value for low vitamin B-12 status is poor. The urinary methylmalonic acid (uMMA) concentration has potential as a functional biomarker of vitamin B-12 status, but the response to supplemental vitamin B-12 is uncertain. A study was conducted to investigate the responsiveness of uMMA to supplemental vitamin B-12 in comparison with other biomarkers of vitamin B-12 status [plasma vitamin B-12, serum holotranscobalamin (holoTC), plasma MMA] in elderly people with moderately poor vitamin B-12 status. A double-blind, placebo-controlled, randomized 8-wk intervention study was carried out using vitamin B-12 supplements (500 μg/d, 100 μg/d, and 10 μg/d cyanocobalamin) in 100 elderly people with a combined plasma vitamin B-12 1.5. All biomarkers had a dose response to supplemental vitamin B-12. Improvements in plasma vitamin B-12 and serum holoTC were achieved at cobalamin supplements of 10 μg/d, but even 500 μg/d for 8 wk did not normalize plasma vitamin B-12 in 8% and serum holoTC in 12% of people. The response in uMMA was comparable with plasma MMA; 15-25% of people still showed evidence of metabolic deficiency after 500 μg/d cobalamin for 8 wk. There was a differential response in urinary and plasma MMA according to smoking behavior; the response was enhanced in ex-smokers compared with never-smokers. uMMA offers an alternative marker of metabolic vitamin-B12 status, obviating the need for blood sampling.

  2. Urinary metabolomic profiling to identify biomarkers of a flavonoid-rich and flavonoid-poor fruits and vegetables diet in adults

    DEFF Research Database (Denmark)

    Ulaszewska, Maria M.; Trost, Kajetan; Stanstrup, Jan

    2016-01-01

    The present study aims to investigate the dose dependent effects of consuming diets enriched in flavonoid-rich and flavonoid-poor fruits and vegetables on the urine metabolome of adults who had a ≥1.5 fold increased risk of cardiovascular diseases. A single-blind, dose-dependent, parallel...... an Orbitrap mass spectrometer. Putative biomarkers which characterize diets with high and low flavonoid content were selected by state-of-the-art data analysis strategies and identified by HR-MS and HR-MS/MS assays. Discrimination between diets was observed by application of two linear mixed models: one....... For the first time abscisic acid glucuronide was reported as a biomarker after a dietary intake, however its origins have to be examined by future hypothesis driven experiments using a more targeted approach. This metabolomic analysis has identified a number of dose dependent urinary biomarkers (i.e. proline...

  3. Associations between Urinary Excretion of Cadmium and Renal Biomarkers in Nonsmoking Females: A Cross-Sectional Study in Rural Areas of South China

    Directory of Open Access Journals (Sweden)

    Yun-rui Zhang

    2015-09-01

    Full Text Available Objectives: The aim of this study was to systematically evaluate the relationship between urinary excretion of cadmium (U-Cd and biomarkers of renal dysfunction. Methods: One hundred eighty five non-smoking female farmers (aged from 44 to 71 years were recruited from two rural areas with different cadmium levels of exposure in southern China. Morning spot urine samples were collected for detecting U-Cd, urinary creatinine (U-cre, β2-microglobulin (β2-MG, α1-microglobulin (α1-MG, metallothionein (MT, retinol binding protein (RBP, albumin (AB, N-acetyl-β-D-glucosaminidase (NAG, alkaline phosphatase (ALP, γ-glutamyl transpeptidase (GGT and kidney injury molecule-1 (KIM-1. Spearman’s rank correlation was carried out to assess pairwise bivariate associations between continuous variables. Three different models of multiple linear regression (the cre-corrected, un-corrected and cre-adjusted model were used to model the dose-response relationships between U-Cd and nine urine markers. Results: Spearman’s rank correlation showed that NAG, ALP, RBP, β2-MG and MT were significantly associated with U-Cd for both cre-corrected and observed data. Generally, NAG correlated best with U-Cd among the nine biomarkers studied, followed by ALP and MT. In the un-corrected model and cre-adjusted model, the regression coefficients and R2 of nine biomarkers were larger than the corresponding values in the cre-corrected model, indicating that the use of observed data was better for investigating the relationship between biomarkers and U-Cd than cre-corrected data. Conclusions: Our results suggest that NAG, MT and ALP in urine were better biomarkers for long-term environmental cadmium exposure assessment among the nine biomarkers studied. Further, data without normalization with creatinine show better relationships between cadmium exposure and renal dysfunction.

  4. Snapshot situation of oxidative degradation of the nervous system, kidney, and adrenal glands biomarkers-neuroprostane and dihomo-isoprostanes-urinary biomarkers from infancy to elderly adults

    Directory of Open Access Journals (Sweden)

    Libia Alejandra García-Flores

    2017-04-01

    Full Text Available We analyzed biomarkers of lipid peroxidation of the nervous system -F2-dihomo-isoprostanes, F3-neuroprostanes, and F4-neuroprostanes- in urine samples from 158 healthy volunteers ranging from 4 to 88 years old with the aim of analyzing possible associations between their excretion values and age (years. Ten biomarkers were screened in the urine samples by UHPLC-QqQ-MS/MS. Four F2-dihomo-isoprostanes (ent−7-(R−7-F2t-dihomo-isoprostane, ent−7-epi−7-F2t-dihomo-isoprostane, 17-F2t-dihomo-isoprostane, 17-epi−17-F2t-dihomo-isoprostane, and one DPA-neuroprostane (4-F3t-neuroprostane were detected in the samples. On the one hand, we found a significant, positive correlation (Rho: 0.197, P=0.015 between the age increase and the amount of total F2-dihomo-IsoPs. On the other hand, the values were significantly higher in the childhood group (4–12 years old, when compared to the adolescence group (13–17 years old and the young adult group (18–35 years old. Surprisingly, no significant differences were found between the middle-aged adults (36–64 years old and the elderly adults (65–88 years old. We display a snapshot situation of excretory values of oxidative stress biomarkers of the nervous system, using healthy volunteers representative of the different stages of human growth and development. The values reported in this study could be used as a basal or starting point in clinical interventions related to aging processes and/or pathologies associated with the nervous system.

  5. Increased urinary levels of podocyte glycoproteins, matrix metallopeptidases, inflammatory cytokines, and kidney injury biomarkers in women with preeclampsia.

    Science.gov (United States)

    Wang, Yuping; Gu, Yang; Loyd, Susan; Jia, Xiuyue; Groome, Lynn J

    2015-12-15

    To investigate kidney injury in preeclampsia, we analyzed 14 biomarkers in urine specimen from 4 groups of pregnant women (normotensive pregnant women and those with pregnancy complicated with chronic hypertension or mild or severe preeclampsia). These biomarkers included 1) podocyte glycoproteins nephrin and podocalyxin, 2) matrix metallopeptidase (MMP)-2 and MMP-9 and their inhibitor tissue inhibitor of metalloproteinase-2, 3) inflammatory molecules and cytokines soluble VCAM-1, TNF-α, soluble TNF receptor receptor-1, IL-6, IL-8, IL-10, and IL-18, and 4) kidney injury biomarkers neutrophil gelatinase-associated lipocalin and kidney injury molecule-1. Postpartum urine specimens (6-8 wk) from normotensive women and those with severe preeclampsia were also evaluated. We found that, first, urine levels of nephrin, MMP-2, MMP-9, and kidney injury molecule-1 were significantly higher before delivery in severe preeclampsia than normotensive groups. The increased levels were all reduced to levels similar to those of the normotensive control group in postpartum specimens from the severe preeclampsia group. Second, soluble VCAM-1, soluble TNF receptor-1, and neutrophil gelatinase-associated lipocalin levels were significantly increased in the severe preeclampsia group compared with the normotensive control group before delivery, but levels of these molecules were significantly reduced in postpartum specimens in both groups. Third, IL-6 and IL-8 levels were not different between preeclampsia and normotensive groups but significantly increased in pregnancy complicated with chronic hypertension. Finally, tissue inhibitor of metalloproteinase-2 and IL-18 levels were not different among the study groups before delivery but were significantly reduced in postpartum specimens from normotensive controls. Our results indicate that the kidney experiences an increased inflammatory response during pregnancy. Most interestingly, tubular epithelial cell injury may also occur in severe

  6. Urinary neutrophil-gelatinase associated lipocalin is a more prognostic biomarker to distinguish antenatal hydronephrosis in neonates

    Directory of Open Access Journals (Sweden)

    Hamid MohammadJafari

    2013-09-01

    Results: There was a significant difference in uNGAL concentration between AH patients and controls (0.80 ± 0.26 and 0.29 ± 0.27 ng/ml, p<0.0001. However, the levels of uNGAL was not significantly deviated between AH patients with VUR compared to those without VUR (0.84 ± 0.34 vs. 0.75 ± 0.13, p=0.419. Standardization of NGAL based on urinary creatinine (uNGAL/uCr showed a significantly difference between AH neonates with VUR compared to those without VUR (2.43±1.61 vs. 1.91±0.79, p<0.0001. Receiver operator characteristic (ROC analysis revealed higher prognostic power of uNGAL for identifying AH with a sensitivity 95.7%, and specificity 84.2%. Meanwhile, the levels of uNGAL or NGAL/uCr ratio did not correlate with reflux grade or laterality. Conclusion: The urinary level of NGAL and NGAL/uCr ratio might be a surrogate non invasive, reliable tool to distinguish hydronephrosis.

  7. Efficacy of voided urinary cytology and ultrasonography compared to cystoscopy in the detection of urinary bladder cancer

    Directory of Open Access Journals (Sweden)

    N. Kumar

    2017-09-01

    Conclusions: Voided urinary cytology can be omitted as a screening test. Ultrasonography can be recommended as the initial imaging investigation for detection of bladder carcinoma in patients presenting with hematuria and for follow up of bladder carcinoma patients.

  8. Effect of parsley (Petroselinum crispum) intake on urinary apigenin excretion, blood antioxidant enzymes and biomarkers for oxidative stress in human subjects

    DEFF Research Database (Denmark)

    Nielsen, S. E.; Young, J.F.; Daneshvar, B.

    1999-01-01

    . In this short-term investigation, an overall decreasing trend in the activity of antioxidant enzymes was observed during the 2-week study. The decreased activity of SOD was strongly correlated at the individual level with an increased oxidative damage to plasma proteins. However, the intervention with parsley......Seven men and seven women participated in a randomized crossover trial to study the effect of intake of parsley (Petroselinum crispum), containing high levels of the flavone apigenin, on the urinary excretion of flavones and on biomarkers for oxidative stress. The subjects received a strictly...... controlled diet low in flavones and other naturally occurring antioxidants during the 2 weeks of intervention. This basic diet was supplemented with parsley providing 3.73-4.49 mg apigenin/MJ in one of the intervention weeks. Urinary excretion of apigenin was 1.59-409.09 mu g/MJ per 24 h during intervention...

  9. Dose response and time course studies on superoxide dismutase as a urinary biomarker of carbon tetrachloride-induced hepatic injury in the Hanover Wistar rat.

    Science.gov (United States)

    Smyth, Rosemary; Munday, Michael R; York, Malcolm J; Clarke, Christopher J; Dare, Theo; Turton, John A

    2009-10-01

    Previous studies have shown that the enzyme copper/zinc superoxide dismutase (SOD-1) is increased in the urine of rats with carbon tetrachloride (CCl(4))-induced hepatotoxicity. The present experiments aimed to investigate further the usefulness of urinary SOD-1 as a non-invasive biomarker of liver injury. Two investigations were carried out, a dose response study and a time course study. In the dose response study, rats were given a single dose of CCl(4) at 0 (control), 0.10, 0.15, 0.20, 0.25, 0.30, 0.35, 0.40 and 0.80 ml/kg and urine samples collected from 12 to 36 h postdosing. In the time course study, rats were dosed at 0.80 ml/kg CCl(4) and urine sampled at 4, 12, 24 and 36 h postdosing. In both studies, the presence of SOD-1 in the urine was confirmed by Western blotting with an SOD-1 antibody. In the dose response study, serum SOD activity was elevated in all CCl(4)-treated animals and urinary SOD-1 activity was increased 2.2 times at the lowest dose (0.10 ml/kg) and 60.4 times at the highest CCl(4) dose level (0.80 ml/kg). In the time course study, urinary SOD-1 was first detected in samples collected from 4 to 12 h postdosing. We conclude that urinary SOD-1 has potential as a sensitive non-invasive biomarker of CCl(4)-induced hepatocellular injury.

  10. A detailed urinary excretion time course study of captan and folpet biomarkers in workers for the estimation of dose, main route-of-entry and most appropriate sampling and analysis strategies.

    Science.gov (United States)

    Berthet, Aurélie; Heredia-Ortiz, Roberto; Vernez, David; Danuser, Brigitta; Bouchard, Michèle

    2012-08-01

    Captan and folpet are two fungicides largely used in agriculture, but biomonitoring data are mostly limited to measurements of captan metabolite concentrations in spot urine samples of workers, which complicate interpretation of results in terms of internal dose estimation, daily variations according to tasks performed, and most plausible routes of exposure. This study aimed at performing repeated biological measurements of exposure to captan and folpet in field workers (i) to better assess internal dose along with main routes-of-entry according to tasks and (ii) to establish most appropriate sampling and analysis strategies. The detailed urinary excretion time courses of specific and non-specific biomarkers of exposure to captan and folpet were established in tree farmers (n = 2) and grape growers (n = 3) over a typical workweek (seven consecutive days), including spraying and harvest activities. The impact of the expression of urinary measurements [excretion rate values adjusted or not for creatinine or cumulative amounts over given time periods (8, 12, and 24 h)] was evaluated. Absorbed doses and main routes-of-entry were then estimated from the 24-h cumulative urinary amounts through the use of a kinetic model. The time courses showed that exposure levels were higher during spraying than harvest activities. Model simulations also suggest a limited absorption in the studied workers and an exposure mostly through the dermal route. It further pointed out the advantage of expressing biomarker values in terms of body weight-adjusted amounts in repeated 24-h urine collections as compared to concentrations or excretion rates in spot samples, without the necessity for creatinine corrections.

  11. Urinary Biomarkers KIM-1 and NGAL for Detection of Chronic Kidney Disease of Uncertain Etiology (CKDu among Agricultural Communities in Sri Lanka.

    Directory of Open Access Journals (Sweden)

    Pallagae Mangala C S De Silva

    2016-09-01

    Full Text Available Chronic Kidney Disease of uncertain etiology (CKDu is an emerging epidemic among farming communities in rural Sri Lanka. Victims do not exhibit common causative factors, however, histopathological studies revealed that CKDu is a tubulointerstitial disease. Urine albumin or albumin-creatinine ratio is still being used as a traditional diagnostic tool to identify CKDu, but accuracy and prevalence data generated are questionable. Urinary biomarkers have been used in similar nephropathy and are widely recognised for their sensitivity, specificity and accuracy in determining CKDu and early renal injury. However, these biomarkers have never been used in diagnosing CKDu in Sri Lanka. Male farmers (n = 1734 were recruited from 4 regions in Sri Lanka i.e. Matara and Nuwara Eliya (farming locations with no CKDu prevalence and two CKDu emerging locations from Hambantota District in Southern Sri Lanka; Angunakolapelessa (EL1 and Bandagiriya (EL2. Albuminuria (ACR ≥ 30mg/g; serum creatinine based estimation of glomerular filtration rate (eGFR; creatinine normalized urinary kidney injury molecule (KIM-1 and neutrophil gelatinase-associated lipocalin (NGAL were measured. Fourteen new CKDu cases (18% from EL1 and nine CKDu cases (9% from EL2 were recognized for the first time from EL1, EL2 locations, which were previously considered as non-endemic of the disease and associated with persistent albuminuria (ACR ≥ 30mg/g Cr. No CKDu cases were identified in non-endemic study locations in Matara (CM and Nuwara Eliya (CN. Analysis of urinary biomarkers showed urinary KIM-1 and NGAL were significantly higher in new CKDu cases in EL1 and EL2. However, we also reported significantly higher KIM-1 and NGAL in apparently healthy farmers in EL 1 and EL 2 with comparison to both control groups. These observations may indicate possible early renal damage in absence of persistent albuminuria and potential capabilities of urinary KIM-1 and NGAL in early detection of renal

  12. UHPLC-MS/MS bioanalysis of urinary DHEA, cortisone and their hydroxylated metabolites as potential biomarkers for CYP3A-mediated drug-drug interactions.

    Science.gov (United States)

    Zheng, Naiyu; Christopher, Lisa J; Ma, Xuewen; Ji, Qin C; Buzescu, Adela; Kandoussi, Hamza; Garonzik, Samira M; LaCreta, Frank; Aubry, Anne-Francoise; Arnold, Mark E; Zeng, Jianing

    2016-12-01

    A UHPLC-MS/MS assay was developed to quantify urinary dehydroepiandrosterone (DHEA), 7β-hydroxy-DHEA, cortisone and 6β-hydroxycortisone as potential biomarkers to predict CYP3A activity. A sensitive assay at LLOQ of 0.500 ng/ml with good accuracy and precision was developed for the four analytes in human urine. This UHPLC-MS/MS assay was optimized by eliminating nonspecific loss of the analytes in urine, ensuring complete hydrolysis of the conjugates to unconjugated forms and use of the product ions of [M+H-H2O](+) for multiple reaction monitoring detection of DHEA and 7β-hydroxy-DHEA. This assay was successfully applied to a pilot clinical study. It is also suitable for future drug-drug interaction studies to continue evaluating the potential of these steroids as biomarkers for CYP3A inhibition and induction.

  13. Urinary total flavonoid excretion but not 4-pyridoxic acid or potassium can be used as a biomarker for the intake of fruits and vegetables

    DEFF Research Database (Denmark)

    Krogholm, Kirstine Suszkiewicz; Haraldsdottir, J.; Knuthsen, Pia;

    2004-01-01

    in fruit and vegetable consumption. Furthermore, the urinary excretions of 4-pyridoxic acid (4-PA) and potassium were investigated as other potential biomarkers of fruit and vegetable intake. The study was designed as a 5-d randomized, controlled crossover study. On d 1-3, the men (n = 12) consumed a self......To gain better insight into the potential health effects of fruits and vegetables, reliable biomarkers of intake are needed. The main purpose of this study was to investigate the ability of flavonoid excretion in both 24-h and morning urine samples to reflect a low intake and moderate changes......-restricted flavonoid-free diet. On d 4, they were provided a strictly controlled diet containing no fruits or vegetables (basic diet). On d 5, they consumed the basic diet supplemented with 300 or 600 g of fruits and vegetables. The total excretion of flavonoids in 24-h urine samples increased linearly with increasing...

  14. Captan fungicide exposures of strawberry harvesters using THPI as a urinary biomarker.

    Science.gov (United States)

    Krieger, R I; Dinoff, T M

    2000-04-01

    Clothing affords harvesters considerable protection against the elements and can retain substantial amounts of pesticide residue from treated crops. Normal work clothing of female harvesters was supplemented with rubber latex gloves and facial scarves to determine whether those measures reduced exposure. Captan fungicide exposures in female strawberry harvesters were assessed by determining urine clearance rates of tetrahydrophalimide (THPI). Clean rubber gloves were supplied to the 41 harvesters for the 3 days of the study period in October 1995. The workers were divided into two groups consisting of either bare-handed or gloved workers, and 24-h urine specimens were collected each day. Female harvesters who worked bare-handed cleared 5.3 microg captan equivalents as THPI with a range of 0.4 to 13.8 microg/person/day. Harvesters who worked wearing rubber latex gloves cleared only 2.0 microg captan equivalents with a range of 0.9 to 4.3 microg/person/day. In this case clean rubber latex gloves reduced absorbed dose by 38%, compared to the dose absorbed by bare-handed workers. These results additionally indicate that when a pesticide is avidly retained by rubber latex gloves and not readily absorbed dermally as captan, estimates of absorbed dose based on passive dosimetry data may be less reliable than exposure estimates derived from urine biomonitoring.

  15. First Post-Operative Urinary Kidney Injury Biomarkers and Association with the Duration of AKI in the TRIBE-AKI Cohort

    Science.gov (United States)

    Coca, Steven G.; Nadkarni, Girish N.; Garg, Amit X.; Koyner, Jay; Thiessen-Philbrook, Heather; McArthur, Eric; Shlipak, Michael G.; Parikh, Chirag R.

    2016-01-01

    Background We previously demonstrated that assessment of the duration of AKI, in addition to magnitude of rise in creatinine alone, adds prognostic information for long-term survival. We evaluated whether post-operative kidney injury biomarkers in urine collected immediately after cardiac surgery associate with duration of serum creatinine elevation. Methods We studied 1199 adults undergoing cardiac surgery in a prospective cohort study (TRIBE-AKI) and examined the association between the levels of five urinary biomarkers individually at 0–6 hours after surgery: interleukin-18 (IL-18), neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver fatty acid binding protein (L-FABP) and albumin with duration of serum creatinine-based AKIN criteria for AKI (0 (no AKI), 1–2, 3–6, ≥7 days). Results Overall, 407 (34%) patients had at least stage 1 AKI, of whom 251 (61.7%) had duration of 1–2 days, 118 (28.9%) had duration 3–6 days, and 38 (9.3%) had duration of ≥7 days. Higher concentrations of all biomarkers (per log increase) were independently associated with a greater odds of a longer duration of AKI; odds ratios and 95% confidence intervals using ordinal logistic regression were the following: IL-18: 1.22, 1.13–1.32; KIM-1: 1.36, 1.21–1.52; albumin 1.20, 1.09–1.32; L-FABP 1.11, 1.04–1.19; NGAL 1.06, 1.00–1.14). AKI duration of 7 days or longer was associated with a 5-fold adjusted risk of mortality at 3 years. Conclusions There was an independent dose-response association between urinary levels of injury biomarkers immediately after cardiac surgery and longer duration of AKI. Duration of AKI was also associated with long term mortality. Future studies should explore the potential utility of these urinary kidney injury biomarkers to enrich enrollment of patients at risk for longer duration of AKI into trials of interventions to prevent or treat post-operative AKI. PMID:27537050

  16. Urinary Vitamin D Binding Protein and KIM-1 Are Potent New Biomarkers of Major Adverse Renal Events in Patients Undergoing Coronary Angiography.

    Directory of Open Access Journals (Sweden)

    Lyubov Chaykovska

    Full Text Available Vitamin-D-binding protein (VDBP is a low molecular weight protein that is filtered through the glomerulus as a 25-(OH vitamin D 3/VDBP complex. In the normal kidney VDBP is reabsorbed and catabolized by proximal tubule epithelial cells reducing the urinary excretion to trace amounts. Acute tubular injury is expected to result in urinary VDBP loss. The purpose of our study was to explore the potential role of urinary VDBP as a biomarker of an acute renal damage.We included 314 patients with diabetes mellitus or mild renal impairment undergoing coronary angiography and collected blood and urine before and 24 hours after the CM application. Patients were followed for 90 days for the composite endpoint major adverse renal events (MARE: need for dialysis, doubling of serum creatinine after 90 days, unplanned emergency rehospitalization or death.Increased urine VDBP concentration 24 hours after contrast media exposure was predictive for dialysis need (no dialysis: 113.06 ± 299.61 ng/ml, n = 303; need for dialysis: 613.07 ± 700.45 ng/ml, n = 11, Mean ± SD, p<0.001, death (no death during follow-up: 121.41 ± 324.45 ng/ml, n = 306; death during follow-up: 522.01 ± 521.86 ng/ml, n = 8; Mean ± SD, p<0.003 and MARE (no MARE: 112.08 ± 302.00 ng/ml, n = 298; MARE: 506.16 ± 624.61 ng/ml, n = 16, Mean ± SD, p<0.001 during the follow-up of 90 days after contrast media exposure. Correction of urine VDBP concentrations for creatinine excretion confirmed its predictive value and was consistent with increased levels of urinary Kidney Injury Molecule-1 (KIM-1 and baseline plasma creatinine in patients with above mentioned complications. The impact of urinary VDBP and KIM-1 on MARE was independent of known CIN risk factors such as anemia, preexisting renal failure, preexisting heart failure, and diabetes.Urinary VDBP is a promising novel biomarker of major contrast induced nephropathy-associated events 90 days after contrast media exposure.

  17. Comparison of protein, microRNA, and mRNA yields using different methods of urinary exosome isolation for the discovery of kidney disease biomarkers.

    Science.gov (United States)

    Alvarez, M Lucrecia; Khosroheidari, Mahdieh; Kanchi Ravi, Rupesh; DiStefano, Johanna K

    2012-11-01

    Urinary exosomes are 40-100 nm vesicles containing protein, mRNA, and microRNA that may serve as biomarkers of renal dysfunction and structural injury. Currently, there is a need for more sensitive and specific biomarkers of renal injury and disease progression. Here we sought to identify the best exosome isolation methods for both proteomic analysis and RNA profiling as a first step for biomarker discovery. We used six different protocols; three were based on ultracentrifugation, one used a nanomembrane concentrator-based approach, and two utilized a commercial exosome precipitation reagent. The highest yield of exosomes was obtained using a modified exosome precipitation protocol, which also yielded the highest quantities of microRNA and mRNA and, therefore, is ideal for subsequent RNA profiling. This method is likewise suitable for downstream proteomic analyses if an ultracentrifuge is not available and/or a large number of samples are to be processed. Two of the ultracentrifugation methods, however, are better options for exosome isolation if an ultracentrifuge is available and few samples will be processed for proteomic analysis. Thus, our modified exosome precipitation method is a simple, fast, highly scalable, and effective alternative for the isolation of exosomes, and may facilitate the identification of exosomal biomarkers from urine.

  18. Low Levels of a Urinary Biomarker of Dietary Polyphenol Are Associated with Substantial Cognitive Decline over a 3-Year Period in Older Adults: The Invecchiare in Chianti Study.

    Science.gov (United States)

    Rabassa, Montserrat; Cherubini, Antonio; Zamora-Ros, Raul; Urpi-Sarda, Mireia; Bandinelli, Stefania; Ferrucci, Luigi; Andres-Lacueva, Cristina

    2015-05-01

    To investigate the association between total urinary polyphenols (TUPs) and total dietary polyphenols (TDPs) and cognitive decline in an older population. The Invecchiare in Chianti (InCHIANTI) study, a cohort study with 3 years of follow-up. Tuscany, Italy. Individuals without dementia aged 65 and older (N=652). TUP and TDP concentrations were analyzed at baseline using the Folin-Ciocalteu assay and a validated food frequency questionnaire, respectively. Cognition was assessed using the Mini-Mental State Examination (MMSE) and Trail-Making Test (TMT) at baseline and after 3 years of follow-up. Substantial cognitive decline was defined as a reduction in MMSE score of three or more points and an increase of at least 29 seconds on the TMT Part A (TMT-A) and 68 seconds on the TMT Part B (TMT-B) (the worst 10% of the distribution of decline) or as test discontinued because of multiple mistakes on the TMT A and B at follow-up. Higher TUP levels were associated with lower risk of substantial cognitive decline on the MMSE (odds ratio (OR) comparing extreme tertiles=0.53, 95% confidence interval (CI)=0.34-0.85, P-trend=.008) and on the TMT-A (OR=0.52, 95% CI=0.28-0.96, P-trend=.03), but not on TMT-B in a logistic regression model that adjusted for baseline cognitive score and potential confounding factors. TDP did not affect the development of substantial cognitive decline in either test. High concentrations of polyphenols, a nutritional biomarker of polyphenol intake, were associated with lower risk of substantial cognitive decline in an older population studied over a 3-year period, suggesting a protective effect against cognitive impairment. © 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.

  19. Bis-butanediol-mercapturic acid (bis-BDMA) as a urinary biomarker of metabolic activation of butadiene to its ultimate carcinogenic species.

    Science.gov (United States)

    Kotapati, Srikanth; Sangaraju, Dewakar; Esades, Amanda; Hallberg, Lance; Walker, Vernon E; Swenberg, James A; Tretyakova, Natalia Y

    2014-06-01

    Human carcinogen 1,3-butadiene (BD) undergoes metabolic activation to 3,4-epoxy-1-butene (EB), hydroxymethylvinyl ketone (HMVK), 3,4-epoxy-1,2-butanediol (EBD) and 1,2,3,4-diepoxybutane (DEB). Among these, DEB is by far the most genotoxic metabolite and is considered the ultimate carcinogenic species of BD. We have shown previously that BD-exposed laboratory mice form 8- to 10-fold more DEB-DNA adducts than rats exposed at the same conditions, which may be responsible for the enhanced sensitivity of mice to BD-mediated cancer. In the present study, we have identified 1,4-bis-(N-acetyl-L-cystein-S-yl)butane-2,3-diol (bis-BDMA) as a novel DEB-specific urinary biomarker. Isotope dilution high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry was employed to quantify bis-BDMA and three other BD-mercapturic acids, 2-(N-acetyl-L-cystein-S-yl)-1-hydroxybut-3-ene/1-(N-acetyl-L-cystein-S-yl)-2-hydroxy-but-3-ene (MHBMA, from EB), 4-(N-acetyl-L-cystein-S-yl)-1,2-dihydroxybutane (DHBMA, from HMVK) and 4-(N-acetyl-L-cystein-S-yl)-1,2,3-trihydroxybutane (THBMA, from EBD), in urine of confirmed smokers, occupationally exposed workers and BD-exposed laboratory rats. Bis-BDMA was formed in a dose-dependent manner in urine of rats exposed to 0-200 p.p.m. BD by inhalation, although it was a minor metabolite (1%) as compared with DHBMA (47%) and THBMA (37%). In humans, DHBMA was the most abundant BD-mercapturic acid excreted (93%), followed by THBMA (5%) and MHBMA (2%), whereas no bis-BDMA was detected. These results reveal significant differences in metabolism of BD between rats and humans.

  20. Evaluation of urinary resveratrol as a biomarker of dietary resveratrol intake in the European Prospective Investigation into Cancer and Nutrition (EPIC) study.

    Science.gov (United States)

    Zamora-Ros, Raul; Rothwell, Joseph A; Achaintre, David; Ferrari, Pietro; Boutron-Ruault, Marie-Christine; Mancini, Francesca R; Affret, Aurelie; Kühn, Tilman; Katzke, Verena; Boeing, Heiner; Küppel, Sven; Trichopoulou, Antonia; Lagiou, Pagona; La Vecchia, Carlo; Palli, Domenico; Contiero, Paolo; Panico, Salvatore; Tumino, Rosario; Ricceri, Fulvio; Noh, Hwayoung; Freisling, Heinz; Romieu, Isabelle; Scalbert, Augustin

    2017-06-01

    In vitro studies have shown several beneficial properties of resveratrol. Epidemiological evidence is still scarce, probably because of the difficulty in estimating resveratrol exposure accurately. The current study aimed to assess the relationships between acute and habitual dietary resveratrol and wine intake and urinary resveratrol excretion in a European population. A stratified random subsample of 475 men and women from four countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) cross-sectional study, who had provided 24-h urine samples and completed a 24-h dietary recall (24-HDR) on the same day, were included. Acute and habitual dietary data were collected using standardised 24-HDR software and a validated country-specific dietary questionnaire, respectively. Phenol-Explorer was used to estimate the intake of resveratrol and other stilbenes. Urinary resveratrol was analysed using tandem MS. Spearman's correlation coefficients between estimated dietary intakes of resveratrol and other stilbenes and consumption of wine, their main food source, were very high (r>0·9) when measured using dietary questionnaires and were slightly lower with 24-HDR (r>0·8). Partial Spearman's correlations between urinary resveratrol excretion and intake of resveratrol, total stilbenes or wine were found to be higher when using the 24-HDR (R 2 partial approximately 0·6) than when using the dietary questionnaires (R 2 partial approximately 0·5). Moderate to high correlations between dietary resveratrol, total stilbenes and wine, and urinary resveratrol concentrations were observed. These support the earlier findings that 24-h urinary resveratrol is an effective biomarker of both resveratrol and wine intakes. These correlations also support the validity of the estimation of resveratrol intake using the dietary questionnaire and Phenol-Explorer.

  1. Quantification of urinary o,o'-dityrosine, a biomarker for oxidative damage to proteins, by high performance liquid chromatography with triple quadrupole tandem mass spectrometry. A comparison with ion-trap tandem mass spectrometry.

    Science.gov (United States)

    Orhan, Hilmi; Coolen, Stefan; Meerman, John H N

    2005-11-15

    We recently described an isotope dilution reversed-phase liquid chromatography-atmospheric pressure chemical ionization-ion-trap-tandem mass spectrometry (HPLC-APCI-MS/MS) method for the quantitative determination of oxidized amino acids in human urine, including o,o'-dityrosine, a specific marker of protein oxidation. In the present study, we investigated the possibility to use a triple quadrupole instrument for the analysis of this biomarker in urine. The two instruments were compared in terms of sensitivity, specificity and reproducibility. Results showed that the triple quadrupole instrument reaches 2.5-fold higher sensitivity (LOD=0.01 microM) compared to the previously used ion-trap instrument. Precision of the present assay is as follows: in-day variation is 4.6% and inter-day variation is 17%. The currently developed method was applied to a group of smoker urine samples. The mean urinary o,o'-dityrosine concentration was 0.08+/-0.01 microM. Expressed per urinary creatinine concentration, this corresponds to 10.1+/-0.4 micromol/mol creatinine. This is comparable to the previously reported values of 5.8+/-0.3 micromol/mol creatinine in non-smokers night-time urines, and 12.3+/-5 micromol/mol creatinine in day-time urines measured by the ion-trap instrument.

  2. Urinary Biomarker Panel to Improve Accuracy in Predicting Prostate Biopsy Result in Chinese Men with PSA 4–10 ng/mL

    Directory of Open Access Journals (Sweden)

    Yongqiang Zhou

    2017-01-01

    Full Text Available This study aims to evaluate the effectiveness and clinical performance of a panel of urinary biomarkers to diagnose prostate cancer (PCa in Chinese men with PSA levels between 4 and 10 ng/mL. A total of 122 patients with PSA levels between 4 and 10 ng/mL who underwent consecutive prostate biopsy at three hospitals in China were recruited. First-catch urine samples were collected after an attentive prostate massage. Urinary mRNA levels were measured by quantitative real-time polymerase chain reaction (qRT-PCR. The predictive accuracy of these biomarkers and prediction models was assessed by the area under the curve (AUC of the receiver-operating characteristic (ROC curve. The diagnostic accuracy of PCA3, PSGR, and MALAT-1 was superior to that of PSA. PCA3 performed best, with an AUC of 0.734 (95% CI: 0.641, 0.828 followed by MALAT-1 with an AUC of 0.727 (95% CI: 0.625, 0.829 and PSGR with an AUC of 0.666 (95% CI: 0.575, 0.749. The diagnostic panel with age, prostate volume, % fPSA, PCA3 score, PSGR score, and MALAT-1 score yielded an AUC of 0.857 (95% CI: 0.780, 0.933. At a threshold probability of 20%, 47.2% of unnecessary biopsies may be avoided whereas only 6.2% of PCa cases may be missed. This urinary panel may improve the current diagnostic modality in Chinese men with PSA levels between 4 and 10 ng/mL.

  3. Identification of novel biomarkers for sepsis prognosis via urinary proteomic analysis using iTRAQ labeling and 2D-LC-MS/MS.

    Directory of Open Access Journals (Sweden)

    Longxiang Su

    Full Text Available OBJECTIVES: Sepsis is the major cause of death for critically ill patients. Recent progress in proteomics permits a thorough characterization of the mechanisms associated with critical illness. The purpose of this study was to screen potential biomarkers for early prognostic assessment of patients with sepsis. METHODS: For the discovery stage, 30 sepsis patients with different prognoses were selected. Urinary proteins were identified using isobaric tags for relative and absolute quantitation (iTRAQ coupled with LC-MS/MS. Mass spec instrument analysis were performed with Mascot software and the International Protein Index (IPI; bioinformatic analyses were used by the algorithm of set and the Gene Ontology (GO Database. For the verification stage, the study involved another 54 sepsis-hospitalized patients, with equal numbers of patients in survivor and non-survivor groups based on 28-day survival. Differentially expressed proteins were verified by Western Blot. RESULTS: A total of 232 unique proteins were identified. Proteins that were differentially expressed were further analyzed based on the pathophysiology of sepsis and biomathematics. For sepsis prognosis, five proteins were significantly up-regulated: selenium binding protein-1, heparan sulfate proteoglycan-2, alpha-1-B glycoprotein, haptoglobin, and lipocalin; two proteins were significantly down-regulated: lysosome-associated membrane proteins-1 and dipeptidyl peptidase-4. Based on gene ontology clustering, these proteins were associated with the biological processes of lipid homeostasis, cartilage development, iron ion transport, and certain metabolic processes. Urinary LAMP-1 was down-regulated, consistent with the Western Blot validation. CONCLUSION: This study provides the proteomic analysis of urine to identify prognostic biomarkers of sepsis. The seven identified proteins provide insight into the mechanism of sepsis. Low urinary LAMP-1 levels may be useful for early prognostic

  4. Urinary Biomarker Panel to Improve Accuracy in Predicting Prostate Biopsy Result in Chinese Men with PSA 4–10 ng/mL

    Science.gov (United States)

    Zhou, Yongqiang; Li, Yun; Li, Xiangnan

    2017-01-01

    This study aims to evaluate the effectiveness and clinical performance of a panel of urinary biomarkers to diagnose prostate cancer (PCa) in Chinese men with PSA levels between 4 and 10 ng/mL. A total of 122 patients with PSA levels between 4 and 10 ng/mL who underwent consecutive prostate biopsy at three hospitals in China were recruited. First-catch urine samples were collected after an attentive prostate massage. Urinary mRNA levels were measured by quantitative real-time polymerase chain reaction (qRT-PCR). The predictive accuracy of these biomarkers and prediction models was assessed by the area under the curve (AUC) of the receiver-operating characteristic (ROC) curve. The diagnostic accuracy of PCA3, PSGR, and MALAT-1 was superior to that of PSA. PCA3 performed best, with an AUC of 0.734 (95% CI: 0.641, 0.828) followed by MALAT-1 with an AUC of 0.727 (95% CI: 0.625, 0.829) and PSGR with an AUC of 0.666 (95% CI: 0.575, 0.749). The diagnostic panel with age, prostate volume, % fPSA, PCA3 score, PSGR score, and MALAT-1 score yielded an AUC of 0.857 (95% CI: 0.780, 0.933). At a threshold probability of 20%, 47.2% of unnecessary biopsies may be avoided whereas only 6.2% of PCa cases may be missed. This urinary panel may improve the current diagnostic modality in Chinese men with PSA levels between 4 and 10 ng/mL.

  5. CONTEMPORARY APPROACHES TO MALE URINARY INCONTINENCE: A CONTROLLED RANDOMIZED COMPARATIVE STUDY

    Directory of Open Access Journals (Sweden)

    Hany M. I. Elgohary

    2015-12-01

    Full Text Available Background: Urinary incontinence UI is an involuntary leakage of urine due to loss of bladder control which is a common and often embarrassing problem that may cause tremendous emotional distress. Prevalence and risk factors depend on baseline physiological mechanisms, including weakness of pelvic floor muscles, hyperactive bladder that may result in urge UI, poor urethral sphincter function associated with stress UI, and impaired structural and functional integrity of pudendal nerve activity, associated with Pelvic floor muscle weakness plays an important role in UI etiology. Pelvic floor muscles work to support the bladder neck in the intra- abdominal cavity and maintain urinary continence. Weakness of these muscles leads the bladder to shift to the extra-abdominal cavity and thus a change in the urethra-vesicle angle occurs. Methods: Group (A twenty participants who received behavioral training (BT pelvic floor exercises (PFE and interferential current, group (B twenty participants who received BT, PFE and posterior tibial nerve stimulation, and group (C twenty participants who received BT, PFE and placebo interferential current. Urodynamic and cystometric measures including bladder volume at first desire to void, maximum cystometric capacity, and pressure at maximum flow rate were measured before and after intervention. Results: Results of this study revealed that there was a statistical significant difference in bladder volume at first desire to void, maximum cystometric capacity, and pressure at maximum flow rate in favor of participants who received a combination of BT, PFE and interferential current compared with those who received a combination of BH and PFE with either posterior tibial nerve stimulation or placebo interferential current. Conclusion: Interferential current is better than posterior tibial nerve stimulation in the rehabilitation of urinary incontinence.

  6. A comparative study of n-alkane biomarker and pollen records: an example from southern China

    Institute of Scientific and Technical Information of China (English)

    ZHENG YanHong; ZHOU WeiJian; XIE ShuCheng; YU XueFeng

    2009-01-01

    We report the results of a comparative study of n-alkane biomarkers and pollens in lacustrine and peat deposits at Dingnan, Jiangxi Province in southern China, and discuss the likely causes for the discrepancy in the interpretations of the n-alkane biomarker and pollen records in terms of climate and vegetation change. The results show that past changes in climate and vegetation revealed by the n-alkane record are not always consistent with the pollen assemblage record in the whole section.Biomarkers do not permit direct identification of the plant family and/or genus and mainly record compositions of local plant remains, while pollens mainly reflect the regional vegetation change. Biomarkers and pollen records complement each other, providing a better picture of local and regional environments. Furthermore, biomarkers are more sensitive than pollen to climatic and vegetational change. Several climatic events are clearly identified by the n-alkane biomarker proxies, such as C31/(C27+C29+C31) ratio and can be correlated to the North Atlantic Heinrich event, B/A, YD and two dry-cool events during the early Holocene such as the periods of 9850 to 9585 cal a B.P. and 8590 to 7920 cal a B.P. These events are consistent with those found in the surrounding regions, suggesting that the regional climate was coupled with global-scale abrupt climatic events. Our results suggest that biomarker and pollen data can record the more detailed climate and vegetation information, thus improving the resolution and precision of vegetation and climate reconstruction.

  7. Comparing Seminal Plasma Biomarkers between Normospermic and Azoospermic Men

    Science.gov (United States)

    Sabetian, Soudabeh; Ardekani, Ali M.; Hodjat, Mahshid; Akhondi, Mohammad Mehdi; Soltanghoraee, Haleh; Amirjannati, Naser; Lakpour, Niknam; Sadeghi, Mohammad Reza

    2010-01-01

    Introduction Azoospermia affects more than 10% - 15% of infertile male subjects attending infertilty clinics. At present, testicular biopsy is the golden standard procedure for evaluating spermatogenesis status in men with azoospermia. Semen collection and analysis is a non-invasive method and has proven to be valuable in the evaluation of spermatogenesis. Identification of seminal plasma markers with testicular or extra-testicular origins have a great value in predicting the prescence of sperm in testicular tissue and presumptive cause of azoospermia. The aim of this study was to find such markers by comparing the content of seminal plasma using different methods in normospermic and azoospermic men. Materials and Methods Semen samples were collected from 200 men attending Avicenna Infertility Clinic (AIC) in Tehran, Iran. Semen samples were analysed according to WHO guidlines. The subjects were divided into two groups: normospermic (n = 100; group one) and azoospermic men (n = 100; group two) according to semen analysis results. Seminal plasma was separated by high speed centrifuagation and stored in -20° C. Four markers including fructose, neutral alpha glucosidase (NαG), inhibin B and anti-Müllerian hormone (AMH) were measured in seminal plasma. Fructose and NαG were evaluated by spectrophotometry, while inhibin B and AMH were assessed by ELISA method. The spermatogenesis status in the azoospermic group was evaluated by histopathological method following testicular biopsy. Results Fructose concentration showed no difference between the two groups. However, it was significantly correlated with sperm count (p < 0.01, r = -0.408). Seminal plasma inhibin B (OR: 1.01; 95%: CI: 1.005 - 1.016), AMH (OR: 1.63; 95% CI: 1.17 - 2.28) and NαG, (OR: 1.07; 95% CI: 1.04 - 1.1) levels were higher in normospermic subjects compared to azoospermic men. There were significant differences in inhibin B and AMH concentrations between the two groups based on the presence or

  8. Urinary albumin and 8-oxo-7,8-dihydroguanosine as markers of mortality and cardiovascular disease during 19 years after diagnosis of type 2 diabetes – A comparative study of two markers to identify high risk patients

    DEFF Research Database (Denmark)

    Broedbaek, Kasper; Køster-Rasmussen, Rasmus; Siersma, Volkert

    2017-01-01

    Urinary albumin is an important biomarker used to identify high risk patients with diabetes, but there is a need for new biomarkers that alone or in combination with urinary albumin could give an even better prediction of clinical patient outcomes. One promising biomarker is 8-oxo-7......-up. At diagnosis only urinary albumin was associated with CVD. In contrast, only 8-oxoGuo was associated with CVD at 6-year follow-up. When investigating test performance, we found that by combining information from MA and 8-oxoGuo the ability to correctly identify patients at risk could be improved. The findings...... suggest that measurement of urinary 8-oxoGuo provides additional information about risk to that obtained from urinary albumin, and that the combined use of 8-oxoGuo and urinary albumin could be useful for a better identification of patients at risk of CVD and death....

  9. Urinary proteomics to support diagnosis of stroke.

    Directory of Open Access Journals (Sweden)

    Jesse Dawson

    Full Text Available Accurate diagnosis in suspected ischaemic stroke can be difficult. We explored the urinary proteome in patients with stroke (n = 69, compared to controls (n = 33, and developed a biomarker model for the diagnosis of stroke. We performed capillary electrophoresis online coupled to micro-time-of-flight mass spectrometry. Potentially disease-specific peptides were identified and a classifier based on these was generated using support vector machine-based software. Candidate biomarkers were sequenced by liquid chromatography-tandem mass spectrometry. We developed two biomarker-based classifiers, employing 14 biomarkers (nominal p-value <0.004 or 35 biomarkers (nominal p-value <0.01. When tested on a blinded test set of 47 independent samples, the classification factor was significantly different between groups; for the 35 biomarker model, median value of the classifier was 0.49 (-0.30 to 1.25 in cases compared to -1.04 (IQR -1.86 to -0.09 in controls, p<0.001. The 35 biomarker classifier gave sensitivity of 56%, specificity was 93% and the AUC on ROC analysis was 0.86. This study supports the potential for urinary proteomic biomarker models to assist with the diagnosis of acute stroke in those with mild symptoms. We now plan to refine further and explore the clinical utility of such a test in large prospective clinical trials.

  10. Correlation of histopathology, urinary biomarkers, and gene expression responses following hexachloro-1:3-butadiene-induced acute nephrotoxicity in male Hanover Wistar rats: a 28-day time course study.

    Science.gov (United States)

    Maguire, David P; Turton, John A; Scudamore, Cheryl L; Swain, Aubrey J; McClure, Fiona J; Smyth, Rosemary; Pereira, Ines B; Munday, Michael R; York, Malcolm J

    2013-07-01

    Hexachloro-1:3-butadiene (HCBD) causes segment-specific injury to the proximal renal tubule. A time course study of traditional and more recently proposed urinary biomarkers was performed in male Hanover Wistar rats receiving a single intraperitoneal (ip) injection of 45 mg/kg HCBD. Animals were killed on days 1, 2, 3, 4, 5, 6, 7, 10, 14, and 28 postdosing and the temporal response of renal biomarkers was characterized using kidney histopathology, urinary and serum biochemistry, and gene expression. Histopathologic evidence of tubular degeneration was seen from day 1 until day 3 postdosing and correlated with increased urinary levels of α-glutathione S-transferase (α-GST), albumin, glucose, and kidney injury molecule-1 (KIM-1), and increased gene expression of KIM-1, NAD(P)H dehydrogenase, quinone 1, and heme oxygenase (decycling) 1. Histopathologic evidence of tubular regeneration was seen from day 2 postdosing and correlated with raised levels of urinary KIM-1 and osteopontin and increased gene expression of KIM-1 and annexin A7. Traditional renal biomarkers generally demonstrated low sensitivity. It is concluded that in rat proximal tubular injury, measurement of a range of renal biomarkers, in conjunction with gene expression analysis, provides an understanding of the extent of degenerative changes induced in the kidney and the process of regeneration.

  11. Comparative analysis of urinary N7-(2-hydroxyethyl)guanine for ethylene oxide- and non-exposed workers.

    Science.gov (United States)

    Huang, Chih-Chun Jean; Wu, Chia-Fang; Shih, Wei-Chung; Chen, Ming-Feng; Chen, Chang-Yuh; Chien, Yeh-Chung; Liou, Saou-Hsing; Chiang, Su-Yin; Wu, Kuen-Yuh

    2011-05-10

    Ethylene oxide (EO), a direct alkylating agent and a carcinogen, can attack the nucleophilic sites of DNA bases to form a variety of DNA adducts. The most abundant adduct, N7-(2-hydroxyethyl)guanine (N7-HEG), can be depurinated spontaneously or enzymatically from DNA backbone to form abasic sites. Molecular dosimetry of the excised N7-HEG in urine can serve as an EO exposure and potential risk-associated biomarker. This study was to analyze N7-HEG in urine collected from 89 EO-exposed and 48 nonexposed hospital workers and 20 exposed and 10 nonexposed factory workers by using our newly developed on-line solid-phase extraction isotope-dilution LC-MS/MS method. Statistical analysis of data shows that the exposed factory workers excreted significantly greater concentrations of N7-HEG than both the nonexposed factory workers and hospital workers. Multiple linear regression analysis reveals that the EO-exposed factory workers had a significantly greater post-shift urinary N7-HEG than their nonexposed coworkers and hospital workers. These results demonstrate that analysis of urinary N7-HEG can serve as a biomarker of EO exposure for future molecular epidemiology studies to better understand the role of the EO-induced DNA adduct formation in EO carcinogenicity and certainly for routine surveillance of occupational EO exposure for the study of potential health impacts on workers. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  12. Plasma concentrations and urinary excretion of the antioxidant flavonols quercetin and kaempferol as biomarkers for dietary intake.

    NARCIS (Netherlands)

    Vries, de J.H.M.; Hollman, P.C.H.; Meyboom, S.; Buysman, M.N.C.P.; Zock, P.L.; Staveren, van W.A.; Katan, M.B.

    1998-01-01

    Flavonols are antioxidants that may reduce the risk of heart disease. Two major flavonols in the diet are quercetin and kaempferol, and their main sources in The Netherlands are tea and onions. We investigated whether plasma concentrations and urinary excretion of quercetin and kaempferol in humans

  13. Use of urinary biomarkers of ovarian function and altrenogest supplementation to enhance captive breeding success in the Indian rhinoceros (Rhinoceros unicornis).

    Science.gov (United States)

    Stoops, Monica A; West, Gary D; Roth, Terri L; Lung, Nancy P

    2014-01-01

    Urinary hormone analysis was conducted on two adult female Indian rhinoceroses (Rhinoceros unicornis) that exhibited minimal or no estrual behaviors traditionally used to time breeding. Urine was collected throughout two consecutive estrous cycles to establish preliminary data on each individual's pattern and concentration of estrogen conjugates (EC) and progesterone metabolites (PdG) during follicular and luteal phases. Following preliminary endocrine analysis, urine samples were shipped on a frequent basis to verify when each female was off baseline in EC. Estrus and breeding dates were then predicted. Females were introduced to fresh male rhinoceros fecal samples daily throughout the follicular phase to potentially stimulate estrous behaviors. Despite successful assessment of follicular phase dynamics, females sometimes failed to exhibit estrus. Both females conceived following mating introductions that were timed using hormone analysis. Pregnancy was diagnosed either by endocrine analysis or rectal ultrasonography. Progestational support (altrenogest) occurred after pregnancy confirmation and varied for each female (21 and 66 days post-breeding). One female experienced early pregnancy loss and the other successfully completed a term pregnancy. These results demonstrate that a science based management strategy that relies on urinary biomarkers of ovarian function can facilitate naturally breeding captive Indian rhinoceroses.

  14. Urinary 1-hydroxypyrene concentration as an exposure biomarker to polycyclic aromatic hydrocarbons (PAHs) in Mexican women from different hot spot scenarios and health risk assessment.

    Science.gov (United States)

    Pruneda-Álvarez, Lucia G; Pérez-Vázquez, Francisco J; Ruíz-Vera, Tania; Ochoa-Martínez, Ángeles C; Orta-García, Sandra T; Jiménez-Avalos, Jorge A; Pérez-Maldonado, Iván N

    2016-04-01

    Recently, in developing countries, polycyclic aromatic hydrocarbons (PAHs) have been considered contaminants of grave concern for women and children. Therefore, the aim of this study was twofold: (1) evaluate exposure assessment to PAHs using urinary 1-hydroxypyrene (1-OHP) as an exposure biomarker and (2) perform a health risk assessment in women from four different high risk scenarios in Mexico. From 2012 to 2013, in a cross-sectional study, we evaluated a total of 184 healthy women from the following scenarios: (A) indoor biomass combustion site (n = 50); (B) brick manufacturing site using different materials such as fuel sources (n = 70); (C) industrial site (n = 44); and (D) high vehicular traffic site (n = 20). 1-hydroxypyrene (1-OHP) was quantified using a high-performance liquid chromatography (HPLC) technique. Afterward, a probabilistic health risk assessment was performed (Monte Carlo analysis). Mean urinary 1-OHP levels found were 0.92 ± 0.92; 0.91 ± 0.83; 0.22 ± 0.19; and 0.14 ± 0.17 μg/L for scenario A, B, C, and D, respectively. Then, based on the measured urinary 1-OHP levels, the estimated median daily intake doses of pyrene were calculated: 659, 623, 162, and 77.4 ng/kg/day for the women participating in the study living in areas A, B, C, and D, respectively, and finally, the hazard quotient (HQ) was calculated (22 ± 21, 21 ± 20, 5.5 ± 5.5, and 2.6 ± 3.5; for areas A, B, C, and D, respectively), high health risk was noted for the women living in the studied communities. The data shown in this study (exposure levels to PAHs and health risk assessment) made it reasonable to conclude that the exposure levels found have a significant potential for generating adverse effects on human health in the studied scenarios.

  15. Echinocandins Compared to Fluconazole for Candidemia of a Urinary Tract Source: A Propensity Score Analysis.

    Science.gov (United States)

    Cuervo, Guillermo; Garcia-Vidal, Carolina; Puig-Asensio, Mireia; Vena, Antonio; Meije, Yolanda; Fernández-Ruiz, Mario; González-Barberá, Eva; Blanco-Vidal, María José; Manzur, Adriana; Cardozo, Celia; Gudiol, Carlota; Montejo, José Miguel; Pemán, Javier; Ayats, Josefina; Aguado, Jose María; Muñoz, Patricia; Marco, Francesc; Almirante, Benito; Carratalà, Jordi

    2017-05-15

    Whether echinocandins could be used to treat candidemia of a urinary tract source (CUTS) is unknown. We aimed to provide current epidemiological information of CUTS and to compare echinocandin to fluconazole treatment on CUTS outcomes. A multicenter study of adult patients with candidemia was conducted in 9 hospitals. CUTS was defined as a candidemia with concomitant candiduria by the same organism associated with significant urological comorbidity. The primary outcome assessed was clinical failure (defined by 7-day mortality or persistent candidemia) in patients treated with either an echinocandin or fluconazole. A propensity score was calculated and then entered into a regression model. Of 2176 episodes of candidemia, 128 were CUTS (5.88%). Most CUTS cases were caused by Candida albicans (52.7%), followed by Candida glabrata (25.6%) and Candida tropicalis (16.3%). Clinical failure occurred in 7 patients (20%) treated with an echinocandin and in 15 (17.1%) treated with fluconazole (P = .730). Acute renal failure (adjusted odds ratio [AOR], 3.01; 95% confidence interval [CI], 1.01-8.91; P = .047) was the only independent factor associated with clinical failure, whereas early urinary tract drainage procedures (surgical, percutaneous, or endoscopic) were identified as protective (AOR, 0.08; 95% CI, .02-.31; P < .001). Neither univariate nor multivariate analysis showed that echinocandin therapy altered the risk of clinical failure. Initial echinocandin therapy was not associated with clinical failure in patients with CUTS. Notably, acute renal failure predicted worse outcomes and performing an early urologic procedure was a protective measure.

  16. Urinary Elimination of Coproporphyrins Is Dependent on ABCC2 Polymorphisms and Represents a Potential Biomarker of MRP2 Activity in Humans

    Directory of Open Access Journals (Sweden)

    Isabelle Benz-de Bretagne

    2011-01-01

    Full Text Available MRP2 encoded by ABCC2 gene is involved in the secretion of numerous drugs and endogenous substrates. Patients with Dubin-Johnson syndrome due to mutation in ABCC2 gene have elevated urinary coproporphyrin ratio (UCP I/(I + III. Here we investigated whether this ratio could serve as a biomarker of MRP2 function. Phenotype-genotype relationships were studied in 74 healthy subjects by measuring individual UCP I/(I + III ratio obtained on 24-hour urine and by analyzing five common SNPs in ABCC2 gene. The UCP I/(I + III ratio varied from 14.7% to 46.0% in our population. Subjects with 3972TT genotype had a higher ratio (=.04 than those carrying the C allele. This higher UCP I/(I + III ratio was correlated with a higher level of isomer I excretion. This study provides a proof of concept that UCP I/(I + III ratio can be used as a biomarker of MRP2 function in clinical studies as it provides quantitative information about the in vivo activity of MRP2 in a given patient.

  17. Urinary (1)H Nuclear Magnetic Resonance Metabolomic Fingerprinting Reveals Biomarkers of Pulse Consumption Related to Energy-Metabolism Modulation in a Subcohort from the PREDIMED study.

    Science.gov (United States)

    Madrid-Gambin, Francisco; Llorach, Rafael; Vázquez-Fresno, Rosa; Urpi-Sarda, Mireia; Almanza-Aguilera, Enrique; Garcia-Aloy, Mar; Estruch, Ramon; Corella, Dolores; Andres-Lacueva, Cristina

    2017-04-07

    Little is known about the metabolome fingerprint of pulse consumption. The study of robust and accurate biomarkers for pulse dietary assessment has great value for nutritional epidemiology regarding health benefits and their mechanisms. To characterize the fingerprinting of dietary pulses (chickpeas, lentils, and beans), spot urine samples from a subcohort from the PREDIMED study were stratified using a validated food frequency questionnaire. Urine samples of nonpulse consumers (≤4 g/day of pulse intake) and habitual pulse consumers (≥25 g/day of pulse intake) were analyzed using a (1)H nuclear magnetic resonance (NMR) metabolomics approach combined with multi- and univariate data analysis. Pulse consumption showed differences through 16 metabolites coming from (i) choline metabolism, (ii) protein-related compounds, and (iii) energy metabolism (including lower urinary glucose). Stepwise logistic regression analysis was applied to design a combined model of pulse exposure, which resulted in glutamine, dimethylamine, and 3-methylhistidine. This model was evaluated by a receiver operating characteristic curve (AUC > 90% in both training and validation sets). The application of NMR-based metabolomics to reported pulse exposure highlighted new candidates for biomarkers of pulse consumption and the impact on energy metabolism, generating new hypotheses on energy modulation. Further intervention studies will confirm these findings.

  18. The Evolution of Self-Reported Urinary and Sexual Dysfunction over the Last Two Decades: Implications for Comparative Effectiveness Research.

    Science.gov (United States)

    Resnick, Matthew J; Barocas, Daniel A; Morgans, Alicia K; Phillips, Sharon E; Koyama, Tatsuki; Albertsen, Peter C; Cooperberg, Matthew R; Goodman, Michael; Greenfield, Sheldon; Hamilton, Ann S; Hoffman, Karen E; Hoffman, Richard M; Kaplan, Sherrie H; McCollum, Dan; Paddock, Lisa E; Stanford, Janet L; Stroup, Antoinette M; Wu, Xiao-Cheng; Penson, David F

    2015-06-01

    Despite the paramount importance of patient-reported outcomes, little is known about the evolution of patient-reported urinary and sexual function over time. To evaluate differences in pretreatment urinary and sexual function in two population-based cohorts of men with prostate cancer enrolled nearly 20 yr apart. Patients were enrolled in the Prostate Cancer Outcomes Study (PCOS) or the Comparative Effectiveness Analysis of Surgery and Radiation (CEASAR) study, two population-based cohorts that enrolled patients with incident prostate cancer from 1994 to 1995 and from 2011 to 2012, respectively. Participants completed surveys at baseline and various time points thereafter. We performed multivariable logistic and linear regression analysis to investigate differences in pretreatment function between studies. The study comprised 5469 men of whom 2334 (43%) were enrolled in PCOS and 3135 (57%) were enrolled in CEASAR. Self-reported urinary incontinence was higher in CEASAR compared with PCOS (7.7% vs 4.7%; adjusted odds ratio [OR]: 1.83; 95% confidence interval [CI], 1.39-2.43). Similarly, self-reported erectile dysfunction was more common among CEASAR participants (44.7% vs 24.0%) with an adjusted OR of 3.12 (95% CI, 2.68-3.64). Multivariable linear regression models revealed less favorable self-reported baseline function among CEASAR participants in the urinary incontinence and sexual function domains. The study is limited by its observational design and possibility of unmeasured confounding. Reporting of pretreatment urinary incontinence and erectile dysfunction has increased over the past two decades. These findings may reflect sociological changes including heightened media attention and direct-to-consumer marketing, among other potential explanations. Patient reporting of urinary and sexual function has evolved and is likely contingent on continually changing societal norms. Recognizing the evolving nature of patient reporting is essential in efforts to conduct

  19. A new strategy for faster urinary biomarkers identification by Nano-LC-MALDI-TOF/TOF mass spectrometry

    Directory of Open Access Journals (Sweden)

    Le Meur Y

    2008-11-01

    Full Text Available Abstract Background LC-MALDI-TOF/TOF analysis is a potent tool in biomarkers discovery characterized by its high sensitivity and high throughput capacity. However, methods based on MALDI-TOF/TOF for biomarkers discovery still need optimization, in particular to reduce analysis time and to evaluate their reproducibility for peak intensities measurement. The aims of this methodological study were: (i to optimize and critically evaluate each step of urine biomarker discovery method based on Nano-LC coupled off-line to MALDI-TOF/TOF, taking full advantage of the dual decoupling between Nano-LC, MS and MS/MS to reduce the overall analysis time; (ii to evaluate the quantitative performance and reproducibility of nano-LC-MALDI analysis in biomarker discovery; and (iii to evaluate the robustness of biomarkers selection. Results A pool of urine sample spiked at increasing concentrations with a mixture of standard peptides was used as a specimen for biological samples with or without biomarkers. Extraction and nano-LC-MS variabilities were estimated by analyzing in triplicates and hexaplicates, respectively. The stability of chromatographic fractions immobilised with MALDI matrix on MALDI plates was evaluated by successive MS acquisitions after different storage times at different temperatures. Low coefficient of variation (CV%: 10–22% and high correlation (R2 > 0.96 values were obtained for the quantification of the spiked peptides, allowing quantification of these peptides in the low fentomole range, correct group discrimination and selection of "specific" markers using principal component analysis. Excellent peptide integrity and stable signal intensity were found when MALDI plates were stored for periods of up to 2 months at +4°C. This allowed storage of MALDI plates between LC separation and MS acquisition (first decoupling, and between MS and MSMS acquisitions while the selection of inter-group discriminative ions is done (second decoupling

  20. Time profiles and toxicokinetic parameters of key biomarkers of exposure to cypermethrin in orally exposed volunteers compared with previously available kinetic data following permethrin exposure.

    Science.gov (United States)

    Ratelle, Mylène; Coté, Jonathan; Bouchard, Michèle

    2015-12-01

    Biomonitoring of pyrethroid exposure is largely conducted but human toxicokinetics has not been fully documented. This is essential for a proper interpretation of biomonitoring data. Time profiles and toxicokinetic parameters of key biomarkers of exposure to cypermethrin in orally exposed volunteers have been documented and compared with previously available kinetic data following permethrin dosing. Six volunteers ingested 0.1 mg kg(-1) bodyweight of cypermethrin acutely. The same volunteers were exposed to permethrin earlier. Blood samples were taken over 72 h after treatment and complete timed urine voids were collected over 84 h postdosing. Cis- and trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane-1-carboxylic acids (trans- and cis-DCCA) and 3-phenoxybenzoic acid (3-PBA) metabolites, common to both cypermethrin and permethrin, were quantified. Blood and urinary time courses of all three metabolites were similar following cypermethrin and permethrin exposure. Plasma levels of metabolites reached peak values on average ≈ 5-7 h post-dosing; the elimination phase showed mean apparent half-lives (t½ ) for trans-DCCA, cis-DCCA and 3-PBA of 5.1, 6.9 and 9.2 h, respectively, following cypermethrin treatment as compared to 7.1, 6.2 and 6.5 h after permethrin dosing. Corresponding mean values obtained from urinary rate time courses were peak values at ≈ 9 h post-dosing and apparent elimination t½ of 6.3, 6.4 and 6.4 h for trans-DCCA, cis-DCCA and 3-PBA, respectively, following cypermethrin treatment as compared to 5.4, 4.5 and 5.7 h after permethrin dosing. These data confirm that the kinetics of cypermethrin is similar to that of permethrin in humans and that their common biomarkers of exposure may be used for an overall assessment of exposure.

  1. Novel multimetabolite prediction of walnut consumption by a urinary biomarker model in a free-living population: the PREDIMED study.

    Science.gov (United States)

    Garcia-Aloy, Mar; Llorach, Rafael; Urpi-Sarda, Mireia; Tulipani, Sara; Estruch, Ramon; Martínez-González, Miguel A; Corella, Dolores; Fitó, Montserrat; Ros, Emilio; Salas-Salvadó, Jordi; Andres-Lacueva, Cristina

    2014-07-03

    The beneficial impact of walnuts on human health has been attributed to their unique chemical composition. In order to characterize the dietary walnut fingerprinting, spot urine samples from two sets of 195 (training) and 186 (validation) individuals were analyzed by an HPLC-q-ToF-MS untargeted metabolomics approach, selecting the most discriminating metabolites by multivariate data analysis (VIP ≥ 1.5). Stepwise logistic regression analysis was used to design a multimetabolite prediction biomarker model. The global performance of the model and each included metabolite in it was evaluated by receiver operating characteristic curves, using the area under the curve (AUC) values. Dietary exposure to walnuts was characterized by 18 metabolites, including markers of fatty acid metabolism, ellagitannin-derived microbial compounds, and intermediate metabolites of the tryptophan/serotonin pathway. The predictive model of walnut exposure included at least one compound of each class. The AUC (95% CI) for the combined biomarker model was 93.4% (90.1-96.8%) in the training set and 90.2% (85.9-94.6%) in the validation set. The AUCs for individual metabolites were ≤85%. As far as we know, this is the first study proposing a combination of biomarkers of walnut exposure in a population under free-living conditions, as considered in epidemiological studies examining associations between diet and health outcomes.

  2. Usefulness of the UBC{sup TM} (urinary bladder cancer) test compared to urinary cytology for transitional cell carcinoma of the bladder in patients with hematuria

    Energy Technology Data Exchange (ETDEWEB)

    Gil, Myung Cheol; Kang, Do Young; Seong, Youl Koon [School of Medicine, Donaga Univ., Busan (Korea, Republic of)] [and others

    2001-06-01

    Urinary cytology and cystoscopic exam are effective methods for diagnosis of transitional cell carcinoma (TCC). But the former shows drawbacks such as the need for a well-trained examiner, and wide imprecision related to the variability of microscopic exam; the latter is a invasive method. UBC{sup TM} test detects the epitope on specific cytokeratin fragments released from epithelium of bladder cancer by immunoradiometric assay. We compared UBC{sup TM} test with urinary cytology for diagnosis of TCC to evaluate the utility of UBC{sup TM} test. Eighty-four patients with hematuria were included in our study, UBC{sup TM} tests (IDL Biotech, Sweden) were assayed in mid-stream urine according to the ordinary assay protocol. Nineteen patients were confirmed as TCC by cystoscopic examination and underwent transurethral resection (Group A). Other patients had various benign urinary tract conditions (Group B). Samples were considered positive as the UBC{sup TM} concentration was greater than 12 {mu}g/L. UBC{sup TM} levels were significantly different between group A (95.9 {+-}166.4 {mu}g/L) and group B (19.2 {+-} 85.6 {mu}g/L)(p<0.001). Sensitivity for diagnosis of TCC was 89.5% (17/19) in UBC test and 47.4% (9/19) in cytology (p<0.05). Specificity for diagnosis of TCC was 81.5% (53/65) in UBC{sup TM} test and 100% (65/65) in cytology. UBC{sup TM} test was significantly more sensitive in stage Ta, T{sub 1} tumors (84.6 vs 38.5%, p<0.05) and in grade I (83.3% vs 16.7%, p<005) than cytology. UBC{sup TM} test showed a tendency to be more sensitive as the grade was higher (83.3% in Grade 1, 90% in Grade II and 100% in Grade III). UBC{sup TM} test could be a useful method in distinguishing TCC from other benign genitourinary diseases. Moreover, UBC{sup TM} test could be an especially valuable marker for diagnosis of TCC in patients with early TCC of low grade TCC compared to urinary cytology. Therefore, mbined use of UBC{sup TM} test in association with cytology is helpful to

  3. Urinary Phthalate Metabolites and Biomarkers of Oxidative Stress in a Mexican-American Cohort: Variability in Early and Late Pregnancy

    Directory of Open Access Journals (Sweden)

    Nina Holland

    2016-03-01

    Full Text Available People are exposed to phthalates through their wide use as plasticizers and in personal care products. Many phthalates are endocrine disruptors and have been associated with adverse health outcomes. However, knowledge gaps exist in understanding the molecular mechanisms associated with the effects of exposure in early and late pregnancy. In this study, we examined the relationship of eleven urinary phthalate metabolites with isoprostane, an established marker of oxidative stress, among pregnant Mexican-American women from an agricultural cohort. Isoprostane levels were on average 20% higher at 26 weeks than at 13 weeks of pregnancy. Urinary phthalate metabolite concentrations suggested relatively consistent phthalate exposures over pregnancy. The relationship between phthalate metabolite concentrations and isoprostane levels was significant for the sum of di-2-ethylhexyl phthalate and the sum of high molecular weight metabolites with the exception of monobenzyl phthalate, which was not associated with oxidative stress at either time point. In contrast, low molecular weight metabolite concentrations were not associated with isoprostane at 13 weeks, but this relationship became stronger later in pregnancy (p-value = 0.009 for the sum of low molecular weight metabolites. Our findings suggest that prenatal exposure to phthalates may influence oxidative stress, which is consistent with their relationship with obesity and other adverse health outcomes.

  4. Comparative structural study of N-linked oligosaccharides of urinary and recombinant erythropoietins

    Energy Technology Data Exchange (ETDEWEB)

    Tsuda, E.; Goto, M.; Murakami, A.; Akia, K.; Ueda, M.; Kawanishi, G.; Takahashi, N.; Sasaki, R.; Chiba, H.; Ishihara, H.; Mori, M.

    1988-07-26

    The structures of the N-linked oligosaccharides of the urinary erythropoietin (u-EPOI) purified from urine of aplastic anemic patients were analyzed and compared with those for recombinant erythropoietin (r-EPO) prepared with baby hamster kidney (BHK) cells. Asparagine-linked neutral oligosaccharides were released from each EPO protein by N-oligosaccharide glycopeptidase (almond) digestion. The reducing ends of the oligosaccharide chains thus obtained were aminated with a fluorescent reagent, 2-aminopyridine, and the mixture of pyridylamino derivatives of the oligosaccharides was separated by high-performance liquid chromatography (HPLC) on an ODS silica column. More than 8 and 13 kinds of oligosaccharide fractions for u-EPO and r-EPO (BHK), respectively, were completely separated by the one-step HPLC procedure. The structure of each oligosaccharide thus isolated was analyzed by a combination of sequential exoglycosidase digestion and another kind of HPLC with an amide-silica column. Furthermore, high-resolution proton nuclear magnetic resonance (/sup 1/H NMR) spectroscopy and methylation analyses were carried out in the case of r-EPO (BHK).

  5. Comparative analysis of selected exhaled breath biomarkers obtained with two different temperature-controlled devices

    Directory of Open Access Journals (Sweden)

    Brüning Thomas

    2009-11-01

    Full Text Available Abstract Background The collection of exhaled breath condensate (EBC is a suitable and non-invasive method for evaluation of airway inflammation. Several studies indicate that the composition of the condensate and the recovery of biomarkers are affected by physical characteristics of the condensing device and collecting circumstances. Additionally, there is an apparent influence of the condensing temperature, and often the level of detection of the assay is a limiting factor. The ECoScreen2 device is a new, partly single-use disposable system designed for studying different lung compartments. Methods EBC samples were collected from 16 healthy non-smokers by using the two commercially available devices ECoScreen2 and ECoScreen at a controlled temperature of -20°C. EBC volume, pH, NOx, LTB4, PGE2, 8-isoprostane and cys-LTs were determined. Results EBC collected with ECoScreen2 was less acidic compared to ECoScreen. ECoScreen2 was superior concerning condensate volume and detection of biomarkers, as more samples were above the detection limit (LTB4 and PGE2 or showed higher concentrations (8-isoprostane. However, NOx was detected only in EBC sampled by ECoScreen. Conclusion ECoScreen2 in combination with mediator specific enzyme immunoassays may be suitable for measurement of different biomarkers. Using this equipment, patterns of markers can be assessed that are likely to reflect the complex pathophysiological processes in inflammatory respiratory disease.

  6. Identification of novel serum peptide biomarkers for high-altitude adaptation: a comparative approach

    Science.gov (United States)

    Yang, Juan; Li, Wenhua; Liu, Siyuan; Yuan, Dongya; Guo, Yijiao; Jia, Cheng; Song, Tusheng; Huang, Chen

    2016-05-01

    We aimed to identify serum biomarkers for screening individuals who could adapt to high-altitude hypoxia at sea level. HHA (high-altitude hypoxia acclimated; n = 48) and HHI (high-altitude hypoxia illness; n = 48) groups were distinguished at high altitude, routine blood tests were performed for both groups at high altitude and at sea level. Serum biomarkers were identified by comparing serum peptidome profiling between HHI and HHA groups collected at sea level. Routine blood tests revealed the concentration of hemoglobin and red blood cells were significantly higher in HHI than in HHA at high altitude. Serum peptidome profiling showed that ten significantly differentially expressed peaks between HHA and HHI at sea level. Three potential serum peptide peaks (m/z values: 1061.91, 1088.33, 4057.63) were further sequence identified as regions of the inter-α trypsin inhibitor heavy chain H4 fragment (ITIH4 347-356), regions of the inter-α trypsin inhibitor heavy chain H1 fragment (ITIH1 205-214), and isoform 1 of fibrinogen α chain precursor (FGA 588-624). Expression of their full proteins was also tested by ELISA in HHA and HHI samples collected at sea level. Our study provided a novel approach for identifying potential biomarkers for screening people at sea level who can adapt to high altitudes.

  7. Increased urinary excretion of 8-oxo-2'-deoxyguanosine, a biomarker of oxidative DNA damage, in urban bus drivers

    DEFF Research Database (Denmark)

    Loft, S; Poulsen, H E; Vistisen, K

    1999-01-01

    '-deoxyguanosine (8-oxodG), a repair product of the highly mutagenic oxidation of guanine in DNA or the cellular pool of GTP. CYP1A2 activity was estimated from the urinary excretion of metabolites of dietary caffeine. The DNA repair was estimated by unscheduled DNA synthesis (UDS) in mononuclear cells isolated......Oxidative damage to DNA could be involved in the increased risk of cancer associated with exposure to polluted urban air, which contains a number of oxidants. CYP1A2 is induced by and metabolizes polyaromatic hydrocarbons (PAH) and aromatic amines and could modify effects of exposure to ambient air...... pollution. Similarly, DNA repair may be influenced by occupational and other exposures as well as modify the effect of DNA damaging agents. As part of a large investigation of the genotoxic burden to diesel exposed workers in transport sectors we studied oxidative DNA damage in 57 non-smoking bus drivers...

  8. Oxidative DNA damage and repair in children exposed to low levels of arsenic in utero and during early childhood: Application of salivary and urinary biomarkers

    Energy Technology Data Exchange (ETDEWEB)

    Hinhumpatch, Pantip; Navasumrit, Panida [Laboratory of Environmental Toxicology, Chulabhorn Research Institute, Laksi, Bangkok (Thailand); Chulabhorn Graduate Institute, Laksi, Bangkok (Thailand); Center of Excellence on Environmental Health and Toxicology, CHE, Ministry of Education (Thailand); Chaisatra, Krittinee; Promvijit, Jeerawan [Laboratory of Environmental Toxicology, Chulabhorn Research Institute, Laksi, Bangkok (Thailand); Mahidol, Chulabhorn [Laboratory of Chemical Carcinogenesis, Chulabhorn Research Institute, Laksi, Bangkok (Thailand); Ruchirawat, Mathuros, E-mail: mathuros@cri.or.th [Laboratory of Environmental Toxicology, Chulabhorn Research Institute, Laksi, Bangkok (Thailand); Chulabhorn Graduate Institute, Laksi, Bangkok (Thailand); Center of Excellence on Environmental Health and Toxicology, CHE, Ministry of Education (Thailand); Department of Pharmacology, Faculty of Science, Mahidol University, Phayathai, Bangkok (Thailand)

    2013-12-15

    The present study aimed to assess arsenic exposure and its effect on oxidative DNA damage and repair in young children exposed in utero and continued to live in arsenic-contaminated areas. To address the need for biological specimens that can be acquired with minimal discomfort to children, we used non-invasive urinary and salivary-based assays for assessing arsenic exposure and early biological effects that have potentially serious health implications. Levels of arsenic in nails showed the greatest magnitude of difference between exposed and control groups, followed by arsenic concentrations in saliva and urine. Arsenic levels in saliva showed significant positive correlations with other biomarkers of arsenic exposure, including arsenic accumulation in nails (r = 0.56, P < 0.001) and arsenic concentration in urine (r = 0.50, P < 0.05). Exposed children had a significant reduction in arsenic methylation capacity indicated by decreased primary methylation index and secondary methylation index in both urine and saliva samples. Levels of salivary 8-OHdG in exposed children were significantly higher (∼ 4-fold, P < 0.01), whereas levels of urinary 8-OHdG excretion and salivary hOGG1 expression were significantly lower in exposed children (∼ 3-fold, P < 0.05), suggesting a defect in hOGG1 that resulted in ineffective cleavage of 8-OHdG. Multiple regression analysis results showed that levels of inorganic arsenic (iAs) in saliva and urine had a significant positive association with salivary 8-OHdG and a significant negative association with salivary hOGG1 expression. - Highlights: • The effects of arsenic exposure in utero and through early childhood were studied. • Arsenic-exposed children had a reduction in arsenic methylation capacity. • Exposed children had more DNA damage, observed as elevated salivary 8-OHdG. • Lower salivary hOGG1 in exposed children indicated impairment of 8-OHdG repair. • Salivary and urinary 8-OHdG levels were discordant.

  9. Urinary biomarkers in hexachloro-1:3-butadiene-induced acute kidney injury in the female Hanover Wistar rat; correlation of α-glutathione S-transferase, albumin and kidney injury molecule-1 with histopathology and gene expression.

    Science.gov (United States)

    Swain, Aubrey; Turton, John; Scudamore, Cheryl L; Pereira, Ines; Viswanathan, Neeti; Smyth, Rosemary; Munday, Michael; McClure, Fiona; Gandhi, Mitul; Sondh, Surjit; York, Malcolm

    2011-05-01

    Hexachloro-1:3-butadiene (HCBD) causes kidney injury specific to the pars recta of the proximal tubule. In the present studies, injury to the nephron was characterized at 24 h following a single dose of HCBD, using a range of quantitative urinary measurements, renal histopathology and gene expression. Multiplexed renal biomarker measurements were performed using both the Meso Scale Discovery (MSD) and Rules Based Medicine platforms. In a second study, rats were treated with a single nephrotoxic dose of HCBD and the time course release of a range of traditional and newer urinary biomarkers was followed over a 25 day period. Urinary albumin (a marker of both proximal tubular function and glomerular integrity) and α-glutathione S-transferase (α-GST, a proximal tubular cell marker of cytoplasmic leakage) showed the largest fold change at 24 h (day 1) after dosing. Most other markers measured on either the MSD or RBM platforms peaked on day 1 or 2 post-dosing, whereas levels of kidney injury molecule-1 (KIM-1), a marker of tubular regeneration, peaked on day 3/4. Therefore, in rat proximal tubular nephrotoxicity, the measurement of urinary albumin, α-GST and KIM-1 is recommended as they potentially provide useful information about the function, degree of damage and repair of the proximal tubule. Gene expression data provided useful confirmatory information regarding exposure of the kidney and liver to HCBD, and the response of these tissues to HCBD in terms of metabolism, oxidative stress, inflammation, and regeneration and repair.

  10. Microfluidic paper-based analytical devices for colorimetric detection of urinary tract infection biomarkers on adult diapers.

    Science.gov (United States)

    Chaohao Chen; Tao Dong

    2015-08-01

    Urinary tract infections (UTI) are common infection diseases in elderly patients. The conventional method of detecting UTI involves the collection of significant urine samples from the elderly patients. However, this is a very difficult and time-consuming procedure. This paper addresses the development of a microfluidic paper-based analytical device (μPAD) to detect UTI from urine collected from adult diapers. The design and fabrication for the μPAD is shown. The fabrication process involves melting solid wax on top of filter paper using a hot plate, followed by pattern transfer using a mold with rubbed wax. To demonstrate the feasibility of the proposed method, the μPAD with deposited nitrite reagent had detected different concentrations of nitrite solutions from 0.5 ppm to 100 ppm spiked in urine samples. A calibration curve was obtained by plotting the gray scale intensity values against the various nitrite concentrations. The results showed that the proposed paper-based device holds great potential as low-cost, disposable solution to sensitively detect UTI markers in urine sampled from diapers.

  11. Urinary incontinence during pregnancy and 1 year after delivery in primiparous women compared with a control group of nulliparous women

    DEFF Research Database (Denmark)

    Hansen, Bent Brandt; Svare, Jens; Viktrup, Lars

    2012-01-01

    AIMS: To investigate the impact of the first pregnancy and delivery on the prevalence and types of urinary incontinence during pregnancy and 1 year after delivery. METHODS: The study was a prospective cohort study with a control group. Primiparous women, who delivered in our department from June......, the prevalence of any type of urinary incontinence in the primiparous group was 32.1%, compared to 13.8% in the control group. Adjusted OR¿=¿3.3 (95%CI¿=¿2.4-4.4). One year after delivery, the prevalence in the primiparous group was 29.3%, compared to 16.6% in the control group. Adjusted OR¿=¿2.5 (95%CI¿=¿1...... in the primiparous group. The symptoms and impact on quality of life seemed to be mild to moderate in both groups. Neurourol. Urodynam. © 2011 Wiley Periodicals, Inc....

  12. Investigating the biomarker potential of glycoproteins using comparative glycoprofiling - application to tissue inhibitor of metalloproteinases-1

    DEFF Research Database (Denmark)

    Thøgersen, Ida; Lademann, Ulrik Axel; Offenberg, Hanne Kjær;

    2008-01-01

    Cancer-induced alterations of protein glycosylations are well-known phenomena. Hence, the glycoprofile of certain glycoproteins can potentially be used as biomarkers for early diagnosis. However, there are a substantial number of candidates and the techniques for measuring their biomarker potential...... tool for biomarker investigation of low-abundant glycoproteins....

  13. Racial/ethnic residential segregation, neighborhood poverty and urinary biomarkers of diet in New York City adults.

    Science.gov (United States)

    Yi, Stella S; Ruff, Ryan R; Jung, Molly; Waddell, Elizabeth Needham

    2014-12-01

    Consuming less sodium and more potassium are components of a healthy diet and reduced cardiovascular disease risk. Racial/ethnic segregation and poverty are both associated with dietary habits, but data linking dietary intake to neighborhood characteristics are limited, particularly in Hispanic and Asian American ethnic enclaves. This study presents relationships between neighborhood-level segregation, poverty and biologic indicators of sodium and potassium consumption. Data were from the 2010 Heart Follow-Up Study, a cross-sectional health survey, which included 24-h urine collections and self-reported health status (n = 1656). Black, Hispanic, and Asian segregated areas and neighborhood poverty were defined for aggregated zip-code areas. Multivariable models assessed the association between neighborhood segregation and poverty and sodium and potassium intake, after adjustment for individual-level covariates. In unadjusted models, potassium intake (a marker of fruit and vegetable consumption) was lower in high-versus low-Hispanic segregated neighborhoods, and the sodium-potassium ratio was higher in high-versus low black and Hispanic segregated neighborhoods, and in high-versus low-poverty neighborhoods; the sodium-potassium ratio was lower in high-versus low Asian segregated neighborhoods. Segregation and poverty were not independently associated with nutrition biomarkers after adjustment for demographics and for each other; however, practical consideration of neighborhood race/ethnic composition may be useful to understand differences in consumption.

  14. Liquid chromatography-mass spectrometry methods for urinary biomarker detection in metabonomic studies with application to nutritional studies.

    Science.gov (United States)

    Legido-Quigley, Cristina; Stella, Cinzia; Perez-Jimenez, Francisco; Lopez-Miranda, Jose; Ordovas, Jose; Powell, Jonathan; van-der-Ouderaa, Frans; Ware, Lisa; Lindon, John C; Nicholson, Jeremy K; Holmes, Elaine

    2010-07-01

    The effects of sample preparation and chromatographic method differences on the classification and recovery of metabolic biomarkers from UPLC-MS measurements on urine samples of humans exposed to different dietary interventions have been investigated. Eight volunteers consumed three high-fat meals (rich in saturated, monounsaturated and polyunsaturated fatty acids, respectively) in randomized order with a washout period in between. For each participant, urine samples were obtained prior to and at three timed intervals after each meal. Samples were processed either by dilution (1 : 4) or by liquid-liquid extraction and then run under two different gradient conditions. For each analysis method, a total of 96 observations (eight participants, four time points, three diets) were measured. The total ion count chromatograms were analyzed using partial-least-squares discriminant analysis. All three dietary classes could be discriminated irrespective of sample preparation and chromatographic method. However, the main discriminating metabolites varied according to sample preparation, indicating that sample treatment and chromatographic conditions influence the ability to extract biomolecular information. Diluted samples showed higher m/z compounds (ca 400 u) while liquid-liquid extraction samples showed low m/z at the same retention time span. Optimized methods for metabolite identification (e.g. organic acids) were statistically inferior to global screening for mixed compound identification, confirming that multiple compound class-based metabolic profiles are likely to give superior metabonomic (diagnostic) classification, although great care has to be taken in the interpretation in relation to matrix effects.

  15. Randomized clinical trial comparing TVT Secur system and trans vaginal obturator tape for the surgical management of stress urinary incontinence.

    Science.gov (United States)

    Maslow, Ken; Gupta, Chander; Klippenstein, Peter; Girouard, Lise

    2014-07-01

    This prospective randomized study aimed to compare the safety and efficacy of the TVT-Secur (TVT-S) with the trans vaginal obturator tape (TVT-O) for the treatment of stress urinary incontinence. We set out to enroll 136 patients in our study. 106 patients with stress urinary incontinence were randomized to either the TVT-S (n = 56) or TVT-O (n = 50) procedure. Patients were evaluated postoperatively at 2 months and 1 year. Our primary outcome was objective cure measured by the cough test. Secondary outcomes of subjective symptoms, questionnaires, pain scores, complications, and urodynamic studies were also included. Statistical analysis was by Chi-squared, Kruskal-Wallis, Wilcoxon, and Fisher's exact tests as appropriate. P values of <0.05 were considered significant. Objective cure rates were better for TVT-O compared with TVT-S at 1 year (86 % and 63 % respectively, p = 0.01). Subjective cure rates were 88 % for TVT-O and 63 % for TVT-S. Quality of life scores through questionnaires improved in both groups and were not statistically different. Initial post-operative groin pain was more prevalent in the TVT-O group; however, this resolved quickly with time. TVT-O was superior to TVT-S in the objective cure of stress urinary incontinence at 1-year follow-up.

  16. An Inter-Laboratory Comparison for the Urinary Acrolein Biomarker 3-Hydroxypropyl-Mercapturic Acid (3-HPMA

    Directory of Open Access Journals (Sweden)

    Scherer Gerhard

    2017-01-01

    Full Text Available An inter-laboratory comparison study on the acrolein biomarker of exposure 3-hydroxypropyl-mercapturic acid (3-HPMA with 12 laboratories from 7 globally distributed countries was performed. The laboratories received coded triplicates of 4 spiked and lyophilized urine samples (LU, 12 samples as well as 5 authentic urine pool samples (PU, 15 samples covering the 3-HPMA concentration range from background (non-smoking to heavy smoking levels for analysis by using their own (in-house analytical method. All laboratories applied liquid chromatography with tandem mass spectrometry (LC-MS/MS, with most of them (10 of 12 using solid phase extraction (SPE as sample work-up procedure. The intra-laboratory variation (indicating repeatability was determined by calculating the standard deviation (sr and the coefficient of variation (CVr of the triplicates, whereas the inter-laboratory variation (indicating reproducibility was determined by calculating the standard deviation between laboratories (sR and the corresponding coefficient of variation (CVR. After removal of outlier samples or laboratories, the mean CVr values for LU and PU test samples ranged from 2.1–3.6% (mean: 2.8% and 2.4–3.7% (mean: 3.3%, respectively, indicating good repeatability for the determination of 3-HPMA in both sample types. CVR for LU and PU test samples ranged from 9.1–31.9% (mean: 18.8% and 13.9–27.0% (mean: 18.5%, respectively, indicating limited reproducibility in 3-HPMA analysis for both sample types. Re-calculation of the PU results by applying an embedded calibration (EC, derived from the reported peak areas for the LU test samples, somewhat improved the CVR values (range: 9.6–28.8%, mean: 16.7%.

  17. A newly developed kit for the measurement of urinary liver-type fatty acid-binding protein as a biomarker for acute kidney injury in patients with critical care.

    Science.gov (United States)

    Sato, Ryo; Suzuki, Yasushi; Takahashi, Gaku; Kojika, Masahiro; Inoue, Yoshihiro; Endo, Shigeatsu

    2015-03-01

    In recent years, it has been reported that the urinary level of Liver-type fatty acid-binding protein (L-FABP) serves as a useful biomarker for diagnosing acute kidney injury (AKI) or sepsis complicated by AKI. However, because the urinary level of L-FABP is currently measured by enzyme-linked immunosorbent assay (ELISA), several days may elapse before the results of the measurement become available. We have newly developed a simplified kit, the Dip-test, for measuring the urinary level of L-FABP. The Dip-test was measured at 80 measurement points (22 points in noninfectious disease, 13 points in SIRS, 20 points in infectious disease, and 25 points in sepsis) in 20 patients. The urinary L-FABP levels as determined by ELISA in relation to the results of the Dip-test were as follows: 10.10 ± 12.85 ng/ml in patients with a negative Dip-test ([-] group), 41.93 ± 50.51 ng/ml in patients with a ± test ([±] group), 70.36 ± 73.70 ng/ml in patients with a positive test ([+] group), 1048.96 ± 2117.68 ng/ml in patients with a 2 + test ([2+] group), and 23,571.55 ± 21,737.45 ng/ml in patients with a 3 + test ([3+] group). The following tendency was noted: the stronger the positive Dip-test reaction, the higher the urinary L-FABP level. Multigroup comparison revealed a significant differences in the urinary L-FABP levels between the Dip-test (-) group and each of the other groups. In this study, the usefulness of the Dip-test, our newly developed simplified kit for measuring the urinary L-FABP level, is suggested.

  18. A new and fast methodology to assess oxidative damage in cardiovascular diseases risk development through eVol-MEPS-UHPLC analysis of four urinary biomarkers.

    Science.gov (United States)

    Mendes, Berta; Silva, Pedro; Mendonça, Isabel; Pereira, Jorge; Câmara, José S

    2013-11-15

    In this work, a new, fast and reliable methodology using a digitally controlled microextraction by packed sorbent (eVol(®)-MEPS) followed by ultra-high pressure liquid chromatography (UHPLC) analysis with photodiodes (PDA) detection, was developed to establish the urinary profile levels of four putative oxidative stress biomarkers (OSBs) in healthy subjects and patients evidencing cardiovascular diseases (CVDs). This data was used to verify the suitability of the selected OSBs (uric acid-UAc, malondialdehyde-MDA, 5-(hydroxymethyl)uracil-5-HMUra and 8-hydroxy-2'-deoxyguanosine-8-oxodG) as potential biomarkers of CVDs progression. Important parameters affecting the efficiency of the extraction process were optimized, particularly stationary phase selection, pH influence, sample volume, number of extraction cycles and washing and elution volumes. The experimental conditions that allowed the best extraction efficiency, expressed in terms of total area of the target analytes and data reproducibility, includes a 10 times dilution and pH adjustment of the urine samples to 6.0, followed by a gradient elution through the C8 adsorbent with 5 times 50 µL of 0.01% formic acid and 3×50 µL of 20% methanol in 0.01% formic acid. The chromatographic separation of the target analytes was performed with a HSS T3 column (100 mm × 2.1 mm, 1.7 µm in particle size) using 0.01% formic acid 20% methanol at 250 µL min(-1). The methodology was validated in terms of selectivity, linearity, instrumental limit of detection (LOD), method limit of quantification (LOQ), matrix effect, accuracy and precision (intra-and inter-day). Good results were obtained in terms of selectivity and linearity (r(2)>0.9906), as well as the LOD and LOQ, whose values were low, ranging from 0.00005 to 0.72 µg mL(-1) and 0.00023 to 2.31 µg mL(-1), respectively. The recovery results (91.1-123.0%), intra-day (1.0-8.3%), inter-day precision (4.6-6.3%) and the matrix effect (60.1-110.3%) of e

  19. Present Situation and Prospect of Urinary Biomarkers For Bladder Cancer%膀胱癌尿液生物标记物的现状与展望

    Institute of Scientific and Technical Information of China (English)

    刘彩树; 蔡森; 张亚萍; 闫合燕; 李宏杰

    2015-01-01

    膀胱癌是世界上最常见的肿瘤之一,膀胱肿瘤的早期检测对改善病人预后至关重要。目前检测和监视膀胱肿瘤的常规方法是膀胱镜检查联合应用尿细胞学检查,但其局限性已经表明膀胱癌需要更好的诊断方法。理想中的诊断方法应该是非侵袭性的,既能够诊断,也能监测疾病的复发,并且能够为治疗提供依据。因此,以尿液为基础的非侵袭性方法将会给患者和医院带来福音。本文综述了近年来报道的膀胱癌尿液生物标记物及相关新技术。%Bladder cancer is one of the most common cancers in the world.Early detection of bladder cancer is critical to improve the prognosis of the patient.The conventional method for the detection and monitoring of bladder cancer at present is cystoscopy with urinary cytology.Limitations of cystoscopy and urinary cytology have shown the need for better diagnostic method for bladder cancer.Ideally,such as-says would be applicable to noninvasively obtained,and be designed not only for diagnosis,but also for monitoring disease recurrence and providing basis for therapy.Consequently,the development of a nonin-vasive urine-based assay would bring the gospel to both patients and healthcare systems.This article re-views some of the more prominent urine-based biomarkers and related new technologies reported in the lit-erature in recent years.

  20. Urinary delta-ALA: a potential biomarker of exposure and neurotoxic effect in rats co-treated with a mixture of lead, arsenic and manganese.

    Science.gov (United States)

    Andrade, Vanda; Mateus, M Luísa; Batoréu, M Camila; Aschner, Michael; dos Santos, A P Marreilha

    2013-09-01

    Lead (Pb), arsenic (As) and manganese (Mn) are neurotoxic elements that often occur in mixtures for which practically no information is available on biomarkers (BMs) for the evaluation of exposure/effects. Exposures to these metals may increase delta-aminolevulinic acid (delta-ALA), which in itself may potentiate neurotoxicity. The objective of this study was to investigate the utility of urinary delta-ALA (delta-ALA-U) levels as BM of exposure and/or neurotoxic effects induced by this mixture. Five groups of Wistar rats were treated for 8 days with Pb (5mg/kg), As (60mg/L), Mn (10mg/kg), the 3-metal mixture (same doses of the single metals), and control group. Motor activity was evaluated and 24-h urine collected before and after the treatment. 24-hours (h) after the last dose, the rats were sacrificed and the brains removed for analyses. Delta-ALA and metal levels were determined in brain and urine. Co-treated rats showed a significant (p<0.05) correlation between increased Pb, As, Mn and delta-ALA levels in the brain and decreased motor activity. Delta-ALA-U concentrations were higher in the mixture-treated group than the sum of the delta-ALA-U levels in each single-treated groups and discriminated (p<0.05) between the mixture and untreated rats. Moreover, delta-ALA-U was correlated (p<0.05) with brain delta-ALA levels. These results establish that treatments with this metal mixture exacerbate behavioral dysfunction, increasing most prominently brain Pb levels. This study is the first to establish that delta-ALA-U levels represent a sensitive BM of exposure/neurotoxic effect to this metal mixture.

  1. Detection of urinary stones at reduced radiation exposure: a phantom study comparing computed radiography and a low-dose digital radiography linear slit scanning system

    Science.gov (United States)

    Szucs-Farkas, Zsolt; Chakraborty, D. P.; Thoeny, Harriet C.; Loupatatzis, Christos; Vock, Peter; Harald, Bonel

    2010-01-01

    Objective In this experimental study we assessed the diagnostic performance of linear slit scanning radiography (LSSR) compared to conventional computed radiography (CR) in the detection of urinary calculi in an anthropomorphic phantom imitating patients weighing approximately 58 to 88 kg. Conclusion Compared to computed radiography, LSSR is superior in the detection of urinary stones and may be used for pretreatment localization and follow-up at a lower patient exposure. PMID:19457787

  2. Urinary l-type fatty acid-binding protein is a predictor of early renal function after partial nephrectomy.

    Science.gov (United States)

    Yanishi, Masaaki; Kinoshita, Hidefumi; Mishima, Takao; Taniguchi, Hisanori; Yoshida, Kenji; Komai, Yoshihiro; Yasuda, Kaneki; Watanabe, Masato; Sugi, Motohiko; Matsuda, Tadashi

    2017-11-01

    Urinary biomarkers of renal injury urinary may identify loss of renal function following nephron-sparing surgery (NSS). This study was designed to evaluate whether urinary l-type fatty acid-binding protein (l-FABP) is an early biomarker of loss of renal function after NSS. Specifically, the kinetics of urinary l-FABP level after NSS and its correlation with factors related to ischemic renal injury were analyzed. This study prospectively evaluated 18 patients who underwent NSS between July and December 2014, including 12 who underwent laparoscopic and six who underwent robot-assisted partial nephrectomy. Urinary l-FABP concentrations were measured preoperatively and 1, 2, 3, 6, 12, 24, 48, and 72 h after renal artery declamping. Loss of renal function loss was calculated by comparing the effective renal plasma flow, as determined by (99m)Tc-mercaptoacetyltriglycine (MAG3) clearance, on the operated and normal sides. The decrease in estimated glomerular filtration rate from before surgery to six months after surgery was also measured. Urinary l-FABP concentration peaked within 2 h of declamping, which may quantify nephron damage caused by ischemia. The decrease in MAG3 reduction ratio correlated with both the ischemia time and peak urinary l-FABP concentration. Peak urinary l-FABP concentration showed a significant correlation with MAG3 reduction ratio. l-FABP is a suitable urinary biomarker for predicting the extent of ischemic renal injury.

  3. Urinary markers in bladder cancer.

    NARCIS (Netherlands)

    Vrooman, O.P.; Witjes, J.A.

    2008-01-01

    OBJECTIVES: Many markers for the detection of bladder cancers have been tested. Almost all urinary markers reported are better than cytology with regard to sensitivity, but they score lower in specificity. The purpose of this review is to highlight the most important urinary biomarkers studied and

  4. Randomized comparative study of amoxicillin-clavulanic acid and co-trimoxazole in the treatment of acute urinary tract infections in adults.

    OpenAIRE

    Karachalios, G N

    1985-01-01

    The efficacy and safety of amoxicillin-clavulanic acid were compared with those of co-trimoxazole in the treatment of acute urinary tract infections. A total of 104 patients (mean age, 52 years) with clinical and laboratory evidence of acute urinary tract infection were enrolled in the study. Characteristics and infecting organisms were equivalent in both groups of patients. Escherichia coli was the predominant bacteria pathogen in both groups. Both drugs resulted in clinical improvement in 1...

  5. Comparative analysis of the symptomatology of children with lower urinary tract dysfunction in relation to objective data

    Directory of Open Access Journals (Sweden)

    Ubirajara Barroso Jr

    2006-02-01

    Full Text Available OBJECTIVES: To assess the clinical presentation of children with lower urinary tract dysfunction (LUTD relating to objective examination data. MATERIALS AND METHODS: Forty-four children (36 girls and 8 boys with mean age of 6.8 years with LUTD were prospectively assessed through a specific questionnaire that analyzed clinical presentation of those patients. These data were then compared to objective data, such as micturition diary and uroflowmetry with electromyography. RESULTS: A urinary tract infection (UTI antecedent was observed in 31 cases (70.5%, and of those, 24 cases of UTI were accompanied by fever. All children presented micturition urgency. Daily urinary incontinence was observed in 33 cases (75% and nocturnal enuresis in 23 (52.3%. As for micturition frequency, 15 (34.1% had normal frequency 19 (43.2% presented more than 10 daily micturition episodes and 10 (22.7% thought they urinated less than 5 times a day. In the uroflowmetry and electromyography examination, 14 (31.8% experienced lack of coordination during micturition. Of 10 children with infrequent micturition, 5 confirmed this in their micturition diaries and 2 listed more than 5 micturition episodes per day in the diary. Of 19 patients presenting polaciuria, only 5 confirmed this in their micturition diaries, while 7 had less than 10 micturition episodes per day. CONCLUSION: Most children with LUTD presented a previous UTI, and daily incontinence was verified in around 75% of the patients. Complaints of polaciuria or infrequent micturition are not noted completely in the micturition diaries and there is no parameter in the clinical history that offers good sensitivity or specificity for the diagnosis of lack of perineal coordination.

  6. Immediate versus conditional treatment of uncomplicated urinary tract infection - a randomized-controlled comparative effectiveness study in general practices

    Directory of Open Access Journals (Sweden)

    Gágyor Ildikó

    2012-06-01

    Full Text Available Abstract Background Uncomplicated urinary tract infections (UTI are usually treated with antibiotics as recommended by primary care guidelines. Antibiotic treatment supports clinical cure in individual patients but also leads to emerging resistance rates in the population. We designed a comparative effectiveness study to investigate whether the use of antibiotics for uncomplicated UTI could be reduced by initial treatment with ibuprofen, reserving antibiotic treatment to patients who return due to ongoing or recurrent symptoms. Methods/design This is a randomized-controlled, double-blind, double dummy multicentre trial assessing the comparative effectiveness of immediate vs. conditional antibiotic therapy in uncomplicated UTI. Women > 18 and  Discussion This study aims at investigating whether the use of antibiotics for uncomplicated UTI could be reduced by initial treatment with ibuprofen. The comparative effectiveness design was chosen to prove the effectiveness of two therapeutic strategies instead of the pure drug efficacy. Trial registration Clinicaltrials.Gov: NCT01488955

  7. Triggered Urine Interleukin-6 Correlates to Severity of Symptoms in Nonfebrile Lower Urinary Tract Infections.

    Science.gov (United States)

    Sundén, Fredrik; Butler, Daniel; Wullt, Björn

    2017-07-01

    Objective diagnosis of symptomatic urinary tract infections in patients prone to asymptomatic bacteriuria is compromised by local host responses that are already present and the positive urine culture. We investigated interleukin-6 as a biomarker for nonfebrile urinary tract infection severity and diagnostic thresholds for interleukin-6 and 8, and neutrophils to differentiate between asymptomatic bacteriuria and urinary tract infection. Patients with residual urine and neurogenic bladders due to spinal lesions included in a long-term Escherichia coli 83972 asymptomatic bacteriuria inoculation trial were monitored for 2 years. Symptom scoring and urine sampling to estimate interleukin-6 and 8, and neutrophils were performed regularly monthly and at urinary tract infection episodes. Patients were followed in the complete study for a mean of 19 months (range 10 to 27) and those with asymptomatic bacteriuria with E. coli 83972 were followed a mean of 11 months (range 4 to 19). A total of 37 nonfebrile urinary tract infection episodes with complete data on interleukin-6 and 8, neutrophils and symptom scoring were documented. Interleukin-6 was the only marker that persistently increased during urinary tract infection compared to asymptomatic bacteriuria in pooled and paired intra-individual comparisons (p urinary tract infection symptoms (p urinary tract infection episodes. However, in urinary tract infections with worse symptoms interleukin-6 and neutrophils demonstrated equal good/excellent outcomes. Triggered interleukin-6 correlated to urinary tract infection symptom severity and demonstrated a promising differential diagnostic capacity to discriminate urinary tract infection from asymptomatic bacteriuria. Future studies should explore interleukin-6 as a biomarker of urinary tract infection severity and assess the treatment indication in nonfebrile urinary tract infections. Copyright © 2017 American Urological Association Education and Research, Inc. Published by

  8. Proteomic analysis of urinary exosomes from patients of early IgA nephropathy and thin basement membrane nephropathy.

    Science.gov (United States)

    Moon, Pyong-Gon; Lee, Jeong-Eun; You, Sungyong; Kim, Taek-Kyun; Cho, Ji-Hoon; Kim, In-San; Kwon, Tae-Hwan; Kim, Chan-Duck; Park, Sun-Hee; Hwang, Daehee; Kim, Yong-Lim; Baek, Moon-Chang

    2011-06-01

    To identify biomarker candidates associated with early IgA nephropathy (IgAN) and thin basement membrane nephropathy (TBMN), the most common causes presenting isolated hematuria in childhood, a proteomic approach of urinary exosomes from early IgAN and TBMN patients was introduced. The proteomic results from the patients were compared with a normal group to understand the pathophysiological processes associated with these diseases at the protein level. The urinary exosomes, which reflect pathophysiological processes, collected from three groups of young adults (early IgAN, TBMN, and normal) were trypsin-digested using a gel-assisted protocol, and quantified by label-free LC-MS/MS, using an MS(E) mode. A total of 1877 urinary exosome proteins, including cytoplasmic, membrane, and vesicle trafficking proteins, were identified. Among the differentially expressed proteins, four proteins (aminopeptidase N, vasorin precursor, α-1-antitrypsin, and ceruloplasmin) were selected as biomarker candidates to differentiate early IgAN from TBMN. We confirmed the protein levels of the four biomarker candidates by semi-quantitative immunoblot analysis in urinary exosomes independently prepared from other patients, including older adult groups. Further clinical studies are needed to investigate the diagnostic and prognostic value of these urinary markers for early IgAN and TBMN. Taken together, this study showed the possibility of identifying biomarker candidates for human urinary diseases using urinary exosomes and might help to understand the pathophysiology of early IgAN and TBMN at the protein level.

  9. Comparing efficiency of micro-RNA and mRNA biomarker liberation with microbubble-enhanced ultrasound exposure.

    Science.gov (United States)

    Forbrich, Alex; Paproski, Robert; Hitt, Mary; Zemp, Roger

    2014-09-01

    Blood biomarkers are potentially powerful diagnostic tools that are limited clinically by low concentrations, the inability to determine biomarker origin and unknown patient baseline. Recently, ultrasound has been shown to liberate proteins and large mRNA biomarkers, overcoming many of these limitations. We have since demonstrated that adding lipid-stabilized microbubbles elevates mRNA concentration an order of magnitude compared with ultrasound without microbubbles, in vitro. Unfortunately the large size of some mRNA molecules may limit efficiency of release and hinder efficacy as an ultrasound-liberated biomarker. We hypothesize that smaller molecules will be released more efficiently with ultrasound than larger molecules. Although investigation of large libraries of biomarkers should be performed to fully validate this hypothesis, we focus on a small subset of mRNA and micro-RNAs. Specifically, we focus on miR-21 (22 base pairs [bp]), which is upregulated in certain forms of cancer, compared with previously investigated mammaglobin mRNA (502 bp). We also report release of micro-RNA miR-155 (22 bp) and housekeeping rRNA S18 (1869 bp). More than 10 million additional miR-21 copies per 100,000 cells are released with ultrasound-microbubble exposure. The low- molecular-weight miR-21 proved to be liberated 50 times more efficiently than high-molecular-weight mammaglobin mRNA, releasing orders of magnitude more miR-21 than mammaglobin mRNA under comparable conditions. Copyright © 2014 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

  10. Urinary Biomarkers IGFBP7 and TIMP-2 for the Diagnostic Assessment of Transient and Persistent Acute Kidney Injury in Critically Ill Patients.

    Science.gov (United States)

    Daubin, Delphine; Cristol, Jean Paul; Dupuy, Anne Marie; Kuster, Nils; Besnard, Noémie; Platon, Laura; Buzançais, Aurèle; Brunot, Vincent; Garnier, Fanny; Jonquet, Olivier; Klouche, Kada

    2017-01-01

    The capability of urinary TIMP-2 (tissue inhibitor of metalloproteinase) and IGFBP7 (insulin-like growth factor binding protein)-NephroCheck Test (NC) = ([TIMP-2] x [IGFBP7]) / 1000)-to predict renal recovery from acute kidney injury (AKI) has been poorly studied. The aim of this study was to assess the performance of measurements of ([TIMP-2] x [IGFBP7]) / 1000) over 24 hours to differentiate transient from persistent AKI. Of 460 consecutive adult patients admitted to the ICU, 101 were prospectively studied: 56 men, 62 (52-71) years old. A fresh urine sample was collected at H0, H4, H12 and H24 to determine ([TIMP-2] x [IGFBP7]) / 1000) levels. Areas under the curves of Delta NC H4-Ho and H12-H4 and serum creatinine (sCr) for detection of AKI recovery were compared. Forty-one (40.6%) patient were diagnosed with AKI: 27 transient and 14 persistent AKI. At admission (H0), AKI patients had a significantly higher NC score than patients without AKI (0.43 [0.07-2.06] vs 0.15 [0.07-0.35], p = 0.027). In AKI groups, transient AKI have a higher NC, at H0 and H4, than persistent AKI (0.87 [0.09-2.82] vs 0.13 [0.05-0.66] p = 0.035 and 0.13 [0.07-0.61] vs 0.05 [0.02-0.13] p = 0.013). Thereafter, NC level decreased in both AKI groups with a Delta NC score H4-H0 and H12-H4 significantly more important in transient AKI. Roc curves showed however that delta NC scores did not discriminate between transient and persistent AKI. In our population, absolute urinary levels of NC score were higher at early hours after ICU admission (H0 and H4) in transient AKI as compared to persistent AKI patients. NC variations (Delta NC scores) over the first 12 hours may indicate the AKI's evolving nature with a more significant decrease in case of transient AKI but were not able to differentiate transient from persistent AKI.

  11. A Comparative Study of Ultrasound Examination of Urinary Tract Performed on Spinal Cord Injury Patients with No Urinary Symptoms and Spinal Cord Injury Patients with Symptoms Related to Urinary Tract: Do Findings of Ultrasound Examination Lead to Changes in Clinical Management?

    Directory of Open Access Journals (Sweden)

    Subramanian Vaidyanathan

    2006-01-01

    Full Text Available Findings of ultrasound examination of the urinary tract and changes in clinical management, which were instituted on the basis of ultrasound examination, were compared between two groups of spinal cord injury patients. Group 1 had no urinary symptoms when they underwent the scan, whereas group 2 was comprised of patients with symptoms pertaining to the urinary tract. Between 2000 and 2006, ultrasound examination of the urinary tract was performed in 87 spinal cord injury patients who had no urinary symptoms when they underwent the ultrasound scan. No abnormality was found in 63 patients. The ultrasound scan showed some abnormality of the urinary tract in 24 patients (simple cyst in the kidney: 4; reduced size of a kidney: 3; increased echogenicity of left kidney: 1; prominent extrarenal pelvis and mild calyceal dilatation: 1; slightly dilated renal pelvis and calyceal system: 1; pelvic kidney showing mild hydronephrosis: 1; foetal lobulation of kidney: 2; multicystic kidney with no interval change in the appearance since last examination: 1; 2-cm-diameter parapelvic cyst: 1; small renal calyceal calculus: 5; a little cortical scarring bilaterally: 1; focal renal scar: 2; generalised thinning of renal cortex: 3; increase in renal sinus fat: 3; trabeculated bladder: 2; small vesical diverticulum: 1; mild generalised bladder wall thickening: 1; small residual urine in postvoid scan; 2. No specific interventions were performed in these patients on the basis of ultrasound findings. In Group 2, ultrasound examination revealed serious abnormalities such as hydronephrosis, pyonephrosis, vesical calculi, vesical polyp in 20 of 21 patients, and all 20 patients required therapeutic intervention on the basis of ultrasound scan findings.In conclusion, routine ultrasound examination of the urinary tract in spinal cord injury patients who have no urinary symptoms may not be justifiable in terms of cost effectiveness; limited hospital resources should be

  12. Urinary Exosomes

    Directory of Open Access Journals (Sweden)

    Irena Dimov

    2009-01-01

    Full Text Available Exosomes are nanovesicles of endocytic origin that are secreted into the extracellular space or body fluids when a multivesicular body (MVB fuses with the cell membrane. Interest in exosomes intensified after their description in antigen-presenting cells and the observation that they can significantly moderate immune responses in vivo. In the past few years, several groups have reported on the secretion of exosomes by almost all cell types in an organism. In addition to a common set of membrane and cytosolic molecules, exosomes harbor unique subsets of proteins, reflecting their cellular source. Major research efforts were put into their surprisingly various biological functions and in translating knowledge into clinical practice. Urine provides an exciting noninvasive alternative to blood or tissue samples as a potential source of disease biomarkers. Urinary exosomes (UE became the subject of serious studies just a few years ago. A recent large-scale proteomics-based study of normal UE revealed a myriad of proteins, including disease-related gene products. Thus, UE have valuable potential as a source of biomarkers for early detection of various types of diseases, monitoring the disease evolution and/or response to therapy. As a relatively new field of research, it still faces many challenges, but UE have already shown some straightforward potential.

  13. Urinary Incontinence

    Science.gov (United States)

    ... It may begin around the time of menopause. Urgency urinary incontinence happens when people have a sudden need ... urinary incontinence is a mix of stress and urgency urinary incontinence. You may leak urine with a laugh ...

  14. Urinary excretion of total isothiocyanates from cruciferous vegetables shows high dose-response relationship and may be a useful biomarker for isothiocyanate exposure

    DEFF Research Database (Denmark)

    Kristensen, Mette; Krogholm, Kirstine Suszkiewicz; Frederiksen, Hanne

    2007-01-01

    Background Isothiocyanates (ITCs), hydrolysis products from glucosinolates, are a family of biologically active compounds originating from cruciferous vegetables. Many ITCs are assumed to have cancer preventive effects and to further evaluate these potential health effects, reliable biomarkers...

  15. Health-related quality of life after radical cystectomy for bladder cancer in elderly patients with an ileal conduit, ureterocutaneostomy, or orthotopic urinary reservoir: a comparative questionnaire survey

    Directory of Open Access Journals (Sweden)

    Saika,Takashi

    2007-08-01

    Full Text Available To compare the health-related quality of life of elderly patients after radical cystectomy for bladder cancer in urinary diversion groups: ileal conduit, ureterocutaneostomy, or orthotopic urinary reservoir. The 109 participating elderly patients aged 75 or older completed self-reporting questionnaires: the QLQ-C30, and on satisfaction with urinary diversion methods. Fifty-six patients had undergone constructions for ileal conduit diversion, 31 for ureterocutaneostomy, and 22 for orthotopic urinary reservoir (OUR. The median follow-up period for each group was 4.0 years (range 0.3-11.2, 4.5 years (range 0.3-18.0, and 3.3 years (range 0.3-6.7, respectively. Regardless of the type of urinary diversion, the majority of patients reported having good overall quality of life, although with some problem of pain. No significant differences among urinary diversion subgroups were found in any quality of life area in the QLQ-C30 questionnaire. More patients in the OUR sub-group felt disappointment than those in the ileal conduit or cutaneostomy sub-groups. However, a questionnaire which asked which diversion method would be preferable showed a trend that more patients in the OUR subgroup would have chosen the same one. Health-related quality of life appeared relatively good in these 3 groups. Patient demands and expectations may be so different from the results that the details of each urinary diversion method should be explained thoroughly. OUR construction could be a candidate even for elderly patients.

  16. A seven day running training period increases basal urinary hepcidin levels as compared to cycling

    NARCIS (Netherlands)

    Sim, M.; Dawson, B.; Landers, G.J.; Swinkels, D.W.; Tjalsma, H.; Wiegerinck, E.T.G.; Trinder, D.; Peeling, P.

    2014-01-01

    BACKGROUND: This investigation compared the effects of an extended period of weight-bearing (running) vs. non-weight-bearing (cycling) exercise on hepcidin production and its implications for iron status. METHODS: Ten active males performed two separate exercise training blocks with either running (

  17. A seven day running training period increases basal urinary hepcidin levels as compared to cycling

    NARCIS (Netherlands)

    Sim, M.; Dawson, B.; Landers, G.J.; Swinkels, D.W.; Tjalsma, H.; Wiegerinck, E.T.G.; Trinder, D.; Peeling, P.

    2014-01-01

    BACKGROUND: This investigation compared the effects of an extended period of weight-bearing (running) vs. non-weight-bearing (cycling) exercise on hepcidin production and its implications for iron status. METHODS: Ten active males performed two separate exercise training blocks with either running

  18. Randomized comparative study of amoxicillin-clavulanic acid and co-trimoxazole in the treatment of acute urinary tract infections in adults.

    Science.gov (United States)

    Karachalios, G N

    1985-01-01

    The efficacy and safety of amoxicillin-clavulanic acid were compared with those of co-trimoxazole in the treatment of acute urinary tract infections. A total of 104 patients (mean age, 52 years) with clinical and laboratory evidence of acute urinary tract infection were enrolled in the study. Characteristics and infecting organisms were equivalent in both groups of patients. Escherichia coli was the predominant bacteria pathogen in both groups. Both drugs resulted in clinical improvement in 100% of the patients; bacteriological cure after the termination of therapy was 95% with amoxicillin-clavulanic acid and 83% with co-trimoxazole (P less than 0.001). Side effects were not severe enough to necessitate discontinuation of the antimicrobial agents. Amoxicillin-clavulanic acid is effective and safe therapy for acute urinary tract infections caused by susceptible bacteria. PMID:3911880

  19. Direct concurrent measurement of urinary vanillylmandelic acid, 5-hydroxyindoleacetic acid and homovanillic acid by HPLC. Three methodologies compared.

    Science.gov (United States)

    van Haard, P M; Wielders, J P; Wikkerink, J B

    1987-01-01

    Three different direct HPLC methods for the determination of 3-methoxy-4-hydroxymandelic acid (VMA, vanillylmandelic acid), 5-hydroxyindoleacetic acid (5-HIAA) and 3-methoxy-4-hydroxyphenylacetic acid (HVA, homovanillic acid) in urine were compared: two spectrofluorometric methods, applying discontinuous gradients, and one serial coulometric linear gradient method. The imprecision study (n = 6) revealed comparable coefficients of variation (CV), intra-assay ranging 1.4-11.1%, and inter-assay ranging 5.9-11.8% for physiological and moderately elevated levels of VMA, 5-HIAA and HVA. All methods showed good linearities up to 100 mumol/L for each of the three compounds studied. Analytical recoveries were 97-114% for VMA, 87-103% for 5-HIAA, and 80-95% for HVA. Recoveries were not dependent on urinary relative densities in the range 1.010-1.030 kg/L or on protein content (prior to acidification) in the range 0.1-3 g/L, or on the pH of conservation in the range 2-5 or on storage temperature in the range -20 - +22 degrees C for three weeks. The distributed-sample comparison revealed acceptable correlations and clinically unimportant accuracy differences between the methods. It is concluded that direct fluorometric and electrochemical HPLC methods can be used in the determination of major catecholamine and serotonin metabolites in human urine for clinical diagnosis and follow-up of neural crest and carcinoid tumours.

  20. Aspirin-Intolerant Asthma (AIA Assessment Using the Urinary Biomarkers, Leukotriene E4 (LTE4 and Prostaglandin D2 (PGD2 Metabolites

    Directory of Open Access Journals (Sweden)

    Noritaka Higashi

    2012-01-01

    Full Text Available The clinical syndrome of aspirin-intolerant asthma (AIA is characterized by aspirin/nonsteroidal antiinflammatory drug intolerance, bronchial asthma, and chronic rhinosinusitis with nasal polyposis. AIA reactions are evidently triggered by pharmacological effect of cyclooxygenase-1 inhibitors. Urine sampling is a non-invasive research tool for time-course measurements in clinical investigations. The urinary stable metabolite concentration of arachidonic acid products provides a time-integrated estimate of the production of the parent compounds in vivo. AIA patients exhibits significantly higher urinary concentrations of leukotriene E4 (LTE4 and 1,15-dioxo-9α-hydroxy-2,3,4,5-tetranorprostan-1,20-dioic acid (tetranor-PGDM, a newly identified metabolite of PGD2, at baseline. This finding suggests the possibility that increased mast cell activation is involved in the pathophysiology of AIA even in a clinically stable condition. In addition, lower urinary concentrations of primary prostaglandin E2 and 15-epimer of lipoxin A4 at baseline in the AIA patients suggest that the impaired anti-inflammatory elements may also contribute to the severe clinical outcome of AIA. During the AIA reaction, the urinary concentrations of LTE4 and PGD2 metabolites, including tetranor-PGDM significantly and correlatively increase. It is considered that mast cell activation probably is a pathophysiologic hallmark of AIA. However, despite the fact that cyclooxygenease-1 is the dominant in vivo PGD2 biosynthetic pathway, the precise mechanism underlying the PGD2 overproduction resulting from the pharmacological effect of cyclooxygenease-1 inhibitors in AIA remains unknown. A comprehensive analysis of the urinary concentration of inflammatory mediators may afford a new research target in elucidating the pathophysiology of AIA.

  1. Shed urinary ALCAM is an independent prognostic biomarker of three-year overall survival after cystectomy in patients with bladder cancer

    Science.gov (United States)

    Egloff, Shanna A. Arnold; Du, Liping; Loomans, Holli A.; Starchenko, Alina; Su, Pei-Fang; Ketova, Tatiana; Knoll, Paul B.; Wang, Jifeng; Haddad, Ahmed Q.; Fadare, Oluwole; Cates, Justin M.; Lotan, Yair; Shyr, Yu; Clark, Peter E.; Zijlstra, Andries

    2017-01-01

    Proteins involved in tumor cell migration can potentially serve as markers of invasive disease. Activated Leukocyte Cell Adhesion Molecule (ALCAM) promotes adhesion, while shedding of its extracellular domain is associated with migration. We hypothesized that shed ALCAM in biofluids could be predictive of progressive disease. ALCAM expression in tumor (n = 198) and shedding in biofluids (n = 120) were measured in two separate VUMC bladder cancer cystectomy cohorts by immunofluorescence and enzyme-linked immunosorbent assay, respectively. The primary outcome measure was accuracy of predicting 3-year overall survival (OS) with shed ALCAM compared to standard clinical indicators alone, assessed by multivariable Cox regression and concordance-indices. Validation was performed by internal bootstrap, a cohort from a second institution (n = 64), and treatment of missing data with multiple-imputation. While ALCAM mRNA expression was unchanged, histological detection of ALCAM decreased with increasing stage (P = 0.004). Importantly, urine ALCAM was elevated 17.0-fold (P cancer controls, correlated positively with tumor stage (P = 0.018), was an independent predictor of OS after adjusting for age, tumor stage, lymph-node status, and hematuria (HR, 1.46; 95% CI, 1.03–2.06; P = 0.002), and improved prediction of OS by 3.3% (concordance-index, 78.5% vs. 75.2%). Urine ALCAM remained an independent predictor of OS after accounting for treatment with Bacillus Calmette-Guerin, carcinoma in situ, lymph-node dissection, lymphovascular invasion, urine creatinine, and adjuvant chemotherapy (HR, 1.10; 95% CI, 1.02–1.19; P = 0.011). In conclusion, shed ALCAM may be a novel prognostic biomarker in bladder cancer, although prospective validation studies are warranted. These findings demonstrate that markers reporting on cell motility can act as prognostic indicators. PMID:27894096

  2. Comparative spectroscopic analysis of urinary calculi inhibition by Larrea Tridentata infusion and NDGA chemical extract

    Science.gov (United States)

    Manciu, Felicia

    2012-10-01

    In the present comparative spectroscopic study we try to understand calcium oxalate kidney stone formation as well as its inhibition by using a traditional medicine approach with Larrea Tridentata (LT) herbal extracts and nordihydroguaiaretic acid (NDGA), which is a chemical extract of the LT bush. The samples were synthesized without and with LT or NDGA using a simplified single diffusion gel growth technique. While the use of infusion from LT decreases the sizes of calcium oxalate crystals and also changes their structure from monohydrate for pure crystals to dihydrate for crystals grown with different amounts of inhibitor, both Raman and infrared absorption spectroscopic techniques, which are the methods of analysis employed in this work, reveal that NDGA is not responsible for the change in the morphology of calcium oxalate crystals and does not contribute significantly to the inhibition process. The presence of NDGA slightly affects the structure of the crystals by modifying the strength of the C-C bonds as seen in the Raman data. Also, the current infrared absorption results demonstrate the presence of NDGA in the samples through a vibrational line that corresponds to the double bond between carbon atoms of the ester group of NDGA.

  3. Comparative Study of Seven Commercial Kits for Human DNA Extraction from Urine Samples Suitable for DNA Biomarker-Based Public Health Studies

    Science.gov (United States)

    El Bali, Latifa; Diman, Aurélie; Bernard, Alfred; Roosens, Nancy H. C.; De Keersmaecker, Sigrid C. J.

    2014-01-01

    Human genomic DNA extracted from urine could be an interesting tool for large-scale public health studies involving characterization of genetic variations or DNA biomarkers as a result of the simple and noninvasive collection method. These studies, involving many samples, require a rapid, easy, and standardized extraction protocol. Moreover, for practicability, there is a necessity to collect urine at a moment different from the first void and to store it appropriately until analysis. The present study compared seven commercial kits to select the most appropriate urinary human DNA extraction procedure for epidemiological studies. DNA yield has been determined using different quantification methods: two classical, i.e., NanoDrop and PicoGreen, and two species-specific real-time quantitative (q)PCR assays, as DNA extracted from urine contains, besides human, microbial DNA also, which largely contributes to the total DNA yield. In addition, the kits giving a good yield were also tested for the presence of PCR inhibitors. Further comparisons were performed regarding the sampling time and the storage conditions. Finally, as a proof-of-concept, an important gene related to smoking has been genotyped using the developed tools. We could select one well-performing kit for the human DNA extraction from urine suitable for molecular diagnostic real-time qPCR-based assays targeting genetic variations, applicable to large-scale studies. In addition, successful genotyping was possible using DNA extracted from urine stored at −20°C for several months, and an acceptable yield could also be obtained from urine collected at different moments during the day, which is particularly important for public health studies. PMID:25365790

  4. Comparative study of seven commercial kits for human DNA extraction from urine samples suitable for DNA biomarker-based public health studies.

    Science.gov (United States)

    El Bali, Latifa; Diman, Aurélie; Bernard, Alfred; Roosens, Nancy H C; De Keersmaecker, Sigrid C J

    2014-12-01

    Human genomic DNA extracted from urine could be an interesting tool for large-scale public health studies involving characterization of genetic variations or DNA biomarkers as a result of the simple and noninvasive collection method. These studies, involving many samples, require a rapid, easy, and standardized extraction protocol. Moreover, for practicability, there is a necessity to collect urine at a moment different from the first void and to store it appropriately until analysis. The present study compared seven commercial kits to select the most appropriate urinary human DNA extraction procedure for epidemiological studies. DNA yield has been determined using different quantification methods: two classical, i.e., NanoDrop and PicoGreen, and two species-specific real-time quantitative (q)PCR assays, as DNA extracted from urine contains, besides human, microbial DNA also, which largely contributes to the total DNA yield. In addition, the kits giving a good yield were also tested for the presence of PCR inhibitors. Further comparisons were performed regarding the sampling time and the storage conditions. Finally, as a proof-of-concept, an important gene related to smoking has been genotyped using the developed tools. We could select one well-performing kit for the human DNA extraction from urine suitable for molecular diagnostic real-time qPCR-based assays targeting genetic variations, applicable to large-scale studies. In addition, successful genotyping was possible using DNA extracted from urine stored at -20°C for several months, and an acceptable yield could also be obtained from urine collected at different moments during the day, which is particularly important for public health studies.

  5. Comparative Study for the Effect of Tamsulosin on Biomarkers between Renal and Urethral Stone Lithotripsy

    Directory of Open Access Journals (Sweden)

    Mohammed Khalid Abood

    2015-10-01

    Full Text Available Nephrolithiasis are multi-factorial diseases that result from the combined influence of epidemiological, biochemical and genetically risk factors. Defective drainage due to urinary tract obstruction at the narrowest part (ureterovesical junction, ureteropelvic junction, and near the pelvic brim via stones will eventually cause the agonizing renal colic pain. Therapeutic managements of nephrolithiasis to relief acute colic pain are the primary objective. Non-steroidal anti-inflammatory drugs are the most commonly used drugs as suggested by many studies. It is very important to consider side effects of the drugs used in the treatment of colic pain. In order to preserve renal function and to relief obstruction, medical expulsion therapy are used for urethral calculi as a conservative management. These medications will aid the passage urethral calculi, an area that currently seems to be a field for continuous investigation.

  6. Earth Mover's Distance (EMD: A True Metric for Comparing Biomarker Expression Levels in Cell Populations.

    Directory of Open Access Journals (Sweden)

    Darya Y Orlova

    Full Text Available Changes in the frequencies of cell subsets that (coexpress characteristic biomarkers, or levels of the biomarkers on the subsets, are widely used as indices of drug response, disease prognosis, stem cell reconstitution, etc. However, although the currently available computational "gating" tools accurately reveal subset frequencies and marker expression levels, they fail to enable statistically reliable judgements as to whether these frequencies and expression levels differ significantly between/among subject groups. Here we introduce flow cytometry data analysis pipeline which includes the Earth Mover's Distance (EMD metric as solution to this problem. Well known as an informative quantitative measure of differences between distributions, we present three exemplary studies showing that EMD 1 reveals clinically-relevant shifts in two markers on blood basophils responding to an offending allergen; 2 shows that ablative tumor radiation induces significant changes in the murine colon cancer tumor microenvironment; and, 3 ranks immunological differences in mouse peritoneal cavity cells harvested from three genetically distinct mouse strains.

  7. The Human Urinary Proteome Fingerprint Database UPdb

    Directory of Open Access Journals (Sweden)

    Holger Husi

    2013-01-01

    Full Text Available The use of human urine as a diagnostic tool has many advantages, such as ease of sample acquisition and noninvasiveness. However, the discovery of novel biomarkers, as well as biomarker patterns, in urine is hindered mainly by a lack of comparable datasets. To fill this gap, we assembled a new urinary fingerprint database. Here, we report the establishment of a human urinary proteomic fingerprint database using urine from 200 individuals analysed by SELDI-TOF (surface enhanced laser desorption ionisation-time of flight mass spectrometry (MS on several chip surfaces (SEND, HP50, NP20, Q10, CM10, and IMAC30. The database currently lists 2490 unique peaks/ion species from 1172 nonredundant SELDI analyses in the mass range of 1500 to 150000. All unprocessed mass spectrometric scans are available as “.xml” data files. Additionally, 1384 peaks were included from external studies using CE (capillary electrophoresis-MS, MALDI (matrix assisted laser desorption/ionisation, and CE-MALDI hybrids. We propose to use this platform as a global resource to share and exchange primary data derived from MS analyses in urinary research.

  8. Assessment of DNA Damage and Telomerase Activity in Exfoliated Urinary Cells as Sensitive and Noninvasive Biomarkers for Early Diagnosis of Bladder Cancer in Ex-Workers of a Rubber Tyres Industry

    Directory of Open Access Journals (Sweden)

    Delia Cavallo

    2014-01-01

    Full Text Available The aim of the present study was to identify sensitive and noninvasive biomarkers of early carcinogenic effect at target organ to use in biomonitoring studies of workers at risk for previous occupational exposure to potential carcinogens. Standard urine cytology (Papanicolaou staining test, comet assay, and quantitative telomerase repeat amplification protocol (TRAP assay were performed in 159 ex-rubber workers employed in tyres production and 97 unexposed subjects. In TRAP positive cases, a second level analysis using FISH (Urovysion was done. Cystoscopy results were available for 11 individuals whose 6 FISH/TRAP/comet positive showed in 3 cases a dysplastic condition confirmed by biopsy, 1 comet positive resulted in infiltrating UBC to the biopsy and with hyperplasia and slight dysplasia to the urinary cytology, 1 comet positive resulted in papillary superficial UBC to the biopsy, 1 FISH/TRAP positive showed a normal condition, and 2 TRAP positive showed in one case a phlogosis condition. The results evidenced good concordance of TRAP, comet, and FISH assays as early biomarkers of procarcinogenic effect confirmed by the dysplastic condition and UBC found by cystoscopy-biopsy analysis. The analysis of these markers in urine cells could be potentially more accurate than conventional cytology in monitoring workers exposed to mixture of bladder potential carcinogens.

  9. Assessment of DNA Damage and Telomerase Activity in Exfoliated Urinary Cells as Sensitive and Noninvasive Biomarkers for Early Diagnosis of Bladder Cancer in Ex-Workers of a Rubber Tyres Industry

    Science.gov (United States)

    Pira, Enrico; Romano, Canzio; Fresegna, Anna Maria; Ciervo, Aureliano; Buresti, Giuliana; Zoli, Wainer; Calistri, Daniele

    2014-01-01

    The aim of the present study was to identify sensitive and noninvasive biomarkers of early carcinogenic effect at target organ to use in biomonitoring studies of workers at risk for previous occupational exposure to potential carcinogens. Standard urine cytology (Papanicolaou staining test), comet assay, and quantitative telomerase repeat amplification protocol (TRAP) assay were performed in 159 ex-rubber workers employed in tyres production and 97 unexposed subjects. In TRAP positive cases, a second level analysis using FISH (Urovysion) was done. Cystoscopy results were available for 11 individuals whose 6 FISH/TRAP/comet positive showed in 3 cases a dysplastic condition confirmed by biopsy, 1 comet positive resulted in infiltrating UBC to the biopsy and with hyperplasia and slight dysplasia to the urinary cytology, 1 comet positive resulted in papillary superficial UBC to the biopsy, 1 FISH/TRAP positive showed a normal condition, and 2 TRAP positive showed in one case a phlogosis condition. The results evidenced good concordance of TRAP, comet, and FISH assays as early biomarkers of procarcinogenic effect confirmed by the dysplastic condition and UBC found by cystoscopy-biopsy analysis. The analysis of these markers in urine cells could be potentially more accurate than conventional cytology in monitoring workers exposed to mixture of bladder potential carcinogens. PMID:24877087

  10. Liquid chromatography with tandem mass spectrometry quantification of urinary proanthocyanin A2 dimer and its potential use as a biomarker of cranberry intake

    Science.gov (United States)

    The lack of a biomarker for the consumption of cranberries has confounded the interpretation of several studies investigating the effect of cranberry products, especially juices, on health outcomes. The objectives of this pilot study were to develop a liquid chromatography tandem mass spectrometric ...

  11. Urinary Concentrations of Bisphenols and Their Association with Biomarkers of Oxidative Stress in People Living Near E-Waste Recycling Facilities in China.

    Science.gov (United States)

    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.

  12. Measurement of biomarkers in juvenile idiopathic arthritis patients and their significant association with disease severity: a comparative study.

    Science.gov (United States)

    Gilliam, B E; Chauhan, A K; Low, J M; Moore, T L

    2008-01-01

    To evaluate in juvenile idiopathic arthritis (JIA) patients a biomarker panel of anti-cyclic citrullinated peptide (anti-CCP) antibodies, cartilage oligomeric matrix protein (COMP), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), IgM rheumatoid factor (RF), IgG RF, and IgA RF and compare to the presence of joint erosions (JE), joint space narrowing (JSN), and synovitis in order to evaluate aggressive disease. Sixty-eight JIA patients (19 RF positive polyarthritis, 23 RF negative polyarthritis, 17 persistent oligoarthritis, and 9 systemic-onset) were evaluated using the biomarker panel and compared to 18 healthy controls. All RF isotypes, anti-CCP antibodies, and COMP were measured by enzyme-linked immunosorbent assays (ELISA). Statistically significant differences and associations were assessed for each biomarker in relation to JE, JSN, and synovitis. Multiple regression analysis was used to find the variables associated with joint damage and synovitis. Patients with JE and JSN had significantly elevated levels of IgA RF, IgM RF, and anti-CCP antibodies. COMP levels were higher in early disease, but also later in disease in patients with no JE or JSN. ESR, CRP, and IgA RF were significantly elevated in patients with active synovitis. Regression analysis showed IgM RF and disease duration to be associated with JE and JSN. Anti-CCP antibodies and COMP were also associated with JSN. CRP and IgA RF were associated with synovitis. Our findings demonstrate the importance of measuring IgM RF and IgA RF by ELISA and anti-CCP antibodies by ELISA, in addition to COMP in the assessment of JIA patients to determine severity of disease.

  13. A metabolomics strategy to explore urinary biomarkers and metabolic pathways for assessment of interaction between Danhong injection and low-dose aspirin during their synergistic treatment.

    Science.gov (United States)

    Li, Jianping; Guo, Jianming; Shang, Erxin; Zhu, Zhenhua; Zhu, Kevin Yue; Li, Shujiao; Zhao, Buchang; Jia, Lifu; Zhao, Jing; Tang, Zhishu; Duan, Jinao

    2016-07-15

    The drug combination of Danhong injection (DHI) and low-dose aspirin (ASA) was frequently applied for the treatment of cardiovascular and cerebrovascular diseases. Due to the drug interactions, a lot of potential benefits and risks might exist side by side in the course of combination therapy. However, there had been no studies of interaction between DHI and ASA. Metabolomics was a powerful tool to explore endogenous biomarkers and metabolic pathways. In present study, metabolic profiling with ultra-high-performance liquid chromatography coupled to quadrupole time of flight mass spectrometry (UHPLC-QTOF/MS) coupled with multivariate statistical analysis was performed to provide insight into understanding the interaction between DHI and low-dose ASA. Eleven potential biomarkers of three types were identified and seven metabolic pathways were constructed. The results showed that the interaction between DHI and low-dose ASA during synergistic treatment indeed affected some key endogenous biomarkers and metabolic pathways, which could not happen when DHI or low-dose ASA was used alone. The quality and quantity of endogenous metabolite were both influenced by interaction between DHI and low-dose ASA. In details, the amount of flavin mononucleotide, L-2, 4-diaminobutyric acid (DABA) and 4-aminohippuric acid were significantly increased. On the contrary, the amount of 3-methyluridine, 4, 6-dihydroxyquinoline, cortolone-3-glucuronide, and serotonin were significantly decreased. Furthermore, O-phosphotyrosine, 3-methyl-2-butenal, indoxyl sulfate and dolichyl diphosphate were disappeared in urine. As to metabolic pathways, riboflavin metabolism, pentose and glucuronate interconversions, and tryptophan metabolism were all significantly influenced. The emerging alterations of biomarkers and metabolic pathways were associated with a lot of drugs and diseases based on literature researches, which might influence the co-administration of other drugs or the treatments of relevant

  14. The Pharmacogenomic HLA Biomarker Associated to Adverse Abacavir Reactions: Comparative Analysis of Different Genotyping Methods

    Science.gov (United States)

    Stocchi, Laura; Cascella, Raffaella; Zampatti, Stefania; Pirazzoli, Antonella; Novelli, Giuseppe; Giardina, Emiliano

    2012-01-01

    Many pharmacogenomic biomarkers (PGBM) were identified and translated into clinical practice, affecting the usage of drugs via label updates. In this context, abacavir is one of the most brilliant examples of pharmacogenetic studies translated into clinical practice. Pharmacogenetic studies have revealed that abacavir HSRs are highly associated with the major histocompatibility complex class I. Large studies established the effectiveness of prospective HLA-B*57:01 screening to prevent HSRs to abacavir. Accordingly to these results the abacavir label has been modified: the European Medicines Agency (EMA) and the FDA recommend/suggested that the administration of abacavir must be preceded by a specific genotyping test. The HLA locus is extremely polymorphic, exhibiting many closely related alleles, making it difficult to discriminate HLA-B*57:01 from other related alleles, and a number of different molecular techniques have been developed recently to detect the presence of HLA-B*57:01. In this review, we provide a summary of the available techniques used by laboratories to genotype HLA-B*57:01, outlining the scientific and pharmacoeconomics pros and cons. PMID:23204921

  15. Differential characteristics of healthcare-associated compared to community-acquired febrile urinary tract infections in males.

    Science.gov (United States)

    Smithson, A; Ramos, J; Bastida, M T; Bernal, S; Jove, N; Niño, E; Msabri, N; Porrón, R

    2015-12-01

    The objective of this study was to analyse the characteristics of healthcare-associated febrile urinary tract infection (HCA-FUTI) compared to community-acquired FUTI (CA-FUTI) in men. An ambispective cross-sectional study in which we recorded clinical and microbiology data and outcomes from males with FUTI attended in the Emergency Department was carried out. A total of 479 males with FUTI, 162 (33.8%) HCA-FUTI and 317 (66.2%) CA-FUTI, were included. HCA-FUTI patients were older (p < 0.001), had higher Charlson scores (p < 0.001) and received previous antimicrobial treatment more frequently (p < 0.001) compared to CA-FUTI patients. HCA-FUTI was less likely caused by Escherichia coli (p < 0.001) and more frequently by Klebsiella spp. (p = 0.02), Enterobacter spp. (p < 0.001) and Pseudomonas aeruginosa (p < 0.001). Resistance to ceftriaxone (p = 0.006), gentamicin (p < 0.001), quinolones (p < 0.001), co-trimoxazole (p = 0.001) and fosfomycin (p = 0.009) was higher among E. coli strains isolated from males with HCA-FUTI and so was the prevalence of extended-spectrum beta-lactamase and AmpC E. coli and Klebsiella spp.-producing strains (p = 0.012). Inadequate antimicrobial treatment and all-cause in-hospital mortality was associated with HCA-FUTI (p < 0.001 and p = 0.004, respectively). Independent factors for mortality were severe sepsis or septic shock [odds ratio (OR) 29; 95% confidence interval (CI): 3.9-214] and cirrhosis (OR 23.7; 95% CI: 1.6-350.6). Male patients with HCA-FUTI have different clinical characteristics, outcomes and microbiological features compared to CA-FUTI patients. Previous contact with the healthcare system has to be taken into consideration when deciding the optimal antimicrobial treatment in males with FUTI.

  16. Amino Acid Medical Foods Provide a High Dietary Acid Load and Increase Urinary Excretion of Renal Net Acid, Calcium, and Magnesium Compared with Glycomacropeptide Medical Foods in Phenylketonuria

    Directory of Open Access Journals (Sweden)

    Bridget M. Stroup

    2017-01-01

    Full Text Available Background. Skeletal fragility is a complication of phenylketonuria (PKU. A diet containing amino acids compared with glycomacropeptide reduces bone size and strength in mice. Objective. We tested the hypothesis that amino acid medical foods (AA-MF provide a high dietary acid load, subsequently increasing urinary excretion of renal net acid, calcium, and magnesium, compared to glycomacropeptide medical foods (GMP-MF. Design. In a crossover design, 8 participants with PKU (16–35 y provided food records and 24-hr urine samples after consuming a low-Phe diet in combination with AA-MF and GMP-MF for 1–3 wks. We calculated potential renal acid load (PRAL of AA-MF and GMP-MF and determined bone mineral density (BMD measurements using dual X-ray absorptiometry. Results. AA-MF provided 1.5–2.5-fold higher PRAL and resulted in 3-fold greater renal net acid excretion compared to GMP-MF (p=0.002. Dietary protein, calcium, and magnesium intake were similar. GMP-MF significantly reduced urinary excretion of calcium by 40% (p=0.012 and magnesium by 30% (p=0.029. Two participants had low BMD-for-age and trabecular bone scores, indicating microarchitectural degradation. Urinary calcium with AA-MF negatively correlated with L1–L4 BMD. Conclusion. Compared to GMP-MF, AA-MF increase dietary acid load, subsequently increasing urinary calcium and magnesium excretion, and likely contributing to skeletal fragility in PKU. The trial was registered at clinicaltrials.gov as NCT01428258.

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

    Science.gov (United States)

    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

    2013-05-01

    Elevated levels of 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 nonsteroidal anti-inflammatory drugs (NSAIDs) had the highest PGE-M levels. PGE-M levels were increased in association with elevated body mass index (BMI; P 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 cancer, especially in overweight and obese women.

  18. Urinary tract infections caused by community-acquired extended-spectrum β-lactamase-producing and nonproducing bacteria: a comparative study.

    Science.gov (United States)

    Dayan, Noam; Dabbah, Husein; Weissman, Irith; Aga, Ibrahim; Even, Lea; Glikman, Daniel

    2013-11-01

    To study the clinical characteristics and associated risk factors of urinary tract infections (UTIs) caused by community-acquired extended-spectrum β-lactamase (CA-ESBL)-producing Enterobacteriaceae. A case-control study at a large community hospital in northern Israel, comparing children who had UTI due to CA-ESBL (n = 25) and CA non-ESBL (n = 125) in 2008-2011. Data were collected from medical charts, telephonic questionnaires administered to all participants, and groups were compared. During the study period, the yearly incidence of CA-ESBL UTI increased significantly. There were no significant differences between the CA-ESBL and CA non-ESBL groups in demographics and clinical outcome. Compared with CA non-ESBL UTI, children with CA-ESBL UTI had a longer hospital stay (5.9 ± 3.3 vs 3.9 ± 2.3 days; P = .003) and higher rates of recent hospitalization (28% vs 4%; P = .001), previous UTI (40% vs 13%; P = .003), urinary tract anomalies (32% vs 5%; P urinary tract anomalies or recurrent UTI) with cephalexin and those with previous hospitalizations are at increased risk for CA-ESBL UTI. Although not associated with higher rates of complications, the multidrug resistant phenotype of CA-ESBL isolates poses a challenge in choosing appropriate empiric and definitive therapy and prolongs hospital stay. Copyright © 2013 Mosby, Inc. All rights reserved.

  19. A Randomized Controlled Trial to Compare 2 Scalable Interventions for Lower Urinary Tract Symptom Prevention: Main Outcomes of the TULIP Study.

    Science.gov (United States)

    Sampselle, Carolyn M; Newman, Diane K; Miller, Janis M; Kirk, Keri; DiCamillo, Mary Ann; Wagner, Todd H; Raghunathan, Trivellor E; Diokno, Ananias C

    2017-06-01

    We compared 2-year urinary incontinence and urgency scores of older women who attended a 2-hour bladder health class vs those who viewed a 20-minute abbreviated class video for the purpose of urinary incontinence prevention. A randomized, 2-arm, parallel design study was done to test the superiority of the 20-minute video over the 2-hour class. Outcomes at baseline, and 3, 12 and 24 months were the scores on questions 1 to 3 of ICIQ-SF (International Consultation on Incontinence Short Form) as the primary outcome and on IUSS (Indevus Urgency Severity Scale). Intent to treat analysis was done to compare the change from baseline in each intervention group across time and also with each other. Multiple imputation was used for missing data. A total of 647 women participated in the study. Mean age was 63 years and approximately 28% of the participants were African American, primarily from an urban setting. The 2 arms were balanced on body mass index at baseline, age, race/ethnicity, education, employment status, income and marital status. No differences in primary or secondary outcomes were demonstrated between the 2 groups from baseline to the 3, 12 or 24-month visits. The absence of significant differences in the outcome measures of ICIQ-SF and IUSS between the 2-hour class and the 20-minute video groups demonstrates that the 2 interventions were comparable. As urinary incontinence and urgency tend to rise annually in older women, instruction in bladder health self-care provided through either the 2-hour class or the 20-minute video format is a useful intervention to prevent urinary incontinence in older women. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  20. An individual urinary proteome analysis in normal human beings to define the minimal sample number to represent the normal urinary proteome

    National Research Council Canada - National Science Library

    Liu, Xuejiao; Shao, Chen; Wei, Lilong; Duan, Jindan; Wu, Shuzhen; Li, Xuewang; Li, Mingxi; Sun, Wei

    2012-01-01

    The urinary proteome has been widely used for biomarker discovery. A urinary proteome database from normal humans can provide a background for discovery proteomics and candidate proteins/peptides for targeted proteomics...

  1. Congenital Upper Urinary Tract Obstruction

    African Journals Online (AJOL)

    2007-10-10

    Oct 10, 2007 ... 1110-5704 179-187. Review Arllele Role of Urinary Biomarkers in the Diagnosis of .... plasma flow and glomerular filtration rate in rats subjected to ..... Chemical characterization and biological properties. J.Biol.Chem. 1990 ...

  2. Randomized comparative study of moxalactam and cefazolin in the treatment of acute urinary tract infections in adults.

    Science.gov (United States)

    Lea, A S; Sudan, A W; Wood, B A; Gentry, L O

    1982-01-01

    Eighty-nine patients with clinical and laboratory evidence of acute urinary tract infection were randomized to therapy with either moxalactam (500 mg) or cefazolin (1 g) every 12 h. Escherichia coli was the predominant pathogen in both groups (92.6 versus 90.2%). Therapy was continued for 3 days after the patient defervesced. The minimum hospital stay was 5 days. Sequential urine cultures were obtained on day 3, at discharge, and 5 to 10 days after the cessation of therapy. THe average duration of hospital stay was 5.6 days for both groups of patients. THe incidence of recurrent infection was similar in uncomplicated patients (9.1 versus 10%) and in complicated patients with a condition predisposing them to urinary tract infections (43 versus 42%). Moxalactam-treated patients had a higher incidence of reversible hepatic enzyme elevation (36%) and Streptococcus faecalis superinfections (12.2%). Moxalactam is as effective as cefazolin for the elimination of gram-negative pathogens from the urine of patients with acute urinary tract infections, but it is associated with a higher incidence of reversible side effects. PMID:6214996

  3. [Proteomic analysis of urinary exosomes].

    Science.gov (United States)

    Nakayama, Aki

    2014-07-01

    Exosomes are 40-100-nm membrane vesicles secreted into the extracellular space by various types of cell in many biological fluids, including serum, saliva, breast milk, amniotic fluid, and urine. Exosomes, which contain several key proteins, lipids, mRNAs, and microRNAs, were considered as an alternative secretion pathway. In addition, recent findings suggest that the exosome itself is a functional biomolecule involved in intracellular communication; thus, its components can be transferred to recipient cells by fusion, changing the function of the target cell. Recently, urinary exosomes have attracted much attention because some of their proteins have been identified as biomarkers related to certain physiological events and disease-related metabolism of the kidney. This review provides an overview of urinary exosomes, including methods of isolation and associated problems, and focuses on urinary exosomes as protein biomarker sources involved in numerous physiological and pathophysiological processes.

  4. Diagnostic accuracy of urinary prostate protein glycosylation profiling in prostatitis diagnosis

    Science.gov (United States)

    Vermassen, Tijl; Van Praet, Charles; Poelaert, Filip; Lumen, Nicolaas; Decaestecker, Karel; Hoebeke, Piet; Van Belle, Simon; Rottey, Sylvie

    2015-01-01

    Introduction Although prostatitis is a common male urinary tract infection, clinical diagnosis of prostatitis is difficult. The developmental mechanism of prostatitis is not yet unraveled which led to the elaboration of various biomarkers. As changes in asparagine-linked-(N-)-glycosylation were observed between healthy volunteers (HV), patients with benign prostate hyperplasia and prostate cancer patients, a difference could exist in biochemical parameters and urinary N-glycosylation between HV and prostatitis patients. We therefore investigated if prostatic protein glycosylation could improve the diagnosis of prostatitis. Materials and methods Differences in serum and urine biochemical markers and in total urine N-glycosylation profile of prostatic proteins were determined between HV (N = 66) and prostatitis patients (N = 36). Additionally, diagnostic accuracy of significant biochemical markers and changes in N-glycosylation was assessed. Results Urinary white blood cell (WBC) count enabled discrimination of HV from prostatitis patients (P < 0.001). Urinary bacteria count allowed for discriminating prostatitis patients from HV (P < 0.001). Total amount of biantennary structures (urinary 2A/MA marker) was significantly lower in prostatitis patients compared to HV (P < 0.001). Combining the urinary 2A/MA marker and urinary WBC count resulted in an AUC of 0.79, 95% confidence interval (CI) = (0.70–0.89) which was significantly better than urinary WBC count (AUC = 0.70, 95% CI = [0.59–0.82], P = 0.042) as isolated test. Conclusions We have demonstrated the diagnostic value of urinary N-glycosylation profiling, which shows great potential as biomarker for prostatitis. Further research is required to unravel the developmental course of prostatic inflammation. PMID:26526330

  5. Determination of urinary biogenic amines' biomarker profile in neuroblastoma and pheochromocytoma patients by MEKC method with preceding dispersive liquid-liquid microextraction.

    Science.gov (United States)

    Miękus, Natalia; Olędzka, Ilona; Plenis, Alina; Kowalski, Piotr; Bień, Ewa; Miękus, Aleksandra; Krawczyk, Małgorzata Anna; Adamkiewicz-Drożyńska, Elżbieta; Bączek, Tomasz

    2016-11-15

    The unbalanced secretion of biogenic amines (BAs) is considered to be a relevant biochemical biomarker in the screening for neuroendocrine tumors, such as: neuroblastoma and pheochromocytoma. However, there is still a need to improve the bioanalytical procedures for BA determination in biological samples due to their instability (photo- and thermosensitivity, easy oxidation) and low concentration in the body fluids. In this study, the primary analytical challenge was to optimize the method of extraction of seven compounds from among BAs and their precursors from urine samples. Several methods based on liquid-liquid extraction (LLE) or solid phase extraction (SPE) techniques were tested. By optimization of the extraction and data analysis using chemometric tool, the dispersive liquid-liquid microextraction (DLLME) has been chosen due to its low solvents consumption, high efficiency of isolation, preconcentration and suitable clean-up of biological matrix. Further, α-cyclodextrin-modified micellar electrokinetic chromatography (MEKC) with ultraviolet detection (UV) has been applied for quantification of the analyzed biologically active compounds with limits of detection (LOD) and limits of quantification (LOQ) at 0.15 and 0.5μgmL(-1), respectively. Finally, the optimized and validated DLLME-MEKC-UV method has been employed for the analysis of real urine samples, obtained from 6 children with neuroendocrine tumors and 6 healthy children. It was stated that concentrations of BA could serve to differentiate between the patients and healthy children. This pilot study indicates that the elaborated fast and sensitive DLLME-MEKC-UV method for determination of panel of biomarkers could be successfully applied in everyday clinical practice to help to confirm the clinical diagnosis of neuroendocrine tumors in children.

  6. Quantification of urinary 5-hydroxyindoleacetic acid by in-house nitrosonaphthol reaction compared with nitrosonaphthol micro column chromatography and enzyme-linked immunosorbent assay

    Directory of Open Access Journals (Sweden)

    Joyce Matie Kinoshita da Silva

    2014-06-01

    Full Text Available The aim of this study was to compare the colorimetric "kit" and enzyme-linked immunosorbent assay (ELISA methods to quantify urinary 5-hydroxyindoleacetic acid through the Goldenberg's technique, exploring the potential of replacing it. 24-hour urine samples were tested by Goldenberg's assay and compared with kits. The agreement was almost perfect for the comparison of Goldenberg's assay with both colorimetric kit, and with ELISA kit, considering ≤ 7.5 mg/24h normal cutoff value. Therefore, both "kits" would be good alternatives to Goldenberg's technique due to practicality and agreement between values.

  7. Comparison of Plasma and Urine Biomarker Performance in Acute Kidney Injury

    Science.gov (United States)

    Schley, Gunnar; Köberle, Carmen; Manuilova, Ekaterina; Rutz, Sandra; Forster, Christian; Weyand, Michael; Formentini, Ivan; Kientsch-Engel, Rosemarie; Eckardt, Kai-Uwe; Willam, Carsten

    2015-01-01

    Background New renal biomarkers measured in urine promise to increase specificity for risk stratification and early diagnosis of acute kidney injury (AKI) but concomitantly may be altered by urine concentration effects and chronic renal insufficiency. This study therefore directly compared the performance of AKI biomarkers in urine and plasma. Methods This single-center, prospective cohort study included 110 unselected adults undergoing cardiac surgery with cardiopulmonary bypass between 2009 and 2010. Plasma and/or urine concentrations of creatinine, cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), liver fatty acid-binding protein (L-FABP), kidney injury molecule 1 (KIM1), and albumin as well as 15 additional biomarkers in plasma and urine were measured during the perioperative period. The primary outcome was AKI defined by AKIN serum creatinine criteria within 72 hours after surgery. Results Biomarkers in plasma showed markedly better discriminative performance for preoperative risk stratification and early postoperative (within 24h after surgery) detection of AKI than urine biomarkers. Discriminative power of urine biomarkers improved when concentrations were normalized to urinary creatinine, but urine biomarkers had still lower AUC values than plasma biomarkers. Best diagnostic performance 4h after surgery had plasma NGAL (AUC 0.83), cystatin C (0.76), MIG (0.74), and L-FAPB (0.73). Combinations of multiple biomarkers did not improve their diagnostic power. Preoperative clinical scoring systems (EuroSCORE and Cleveland Clinic Foundation Score) predicted the risk for AKI (AUC 0.76 and 0.71) and were not inferior to biomarkers. Preexisting chronic kidney disease limited the diagnostic performance of both plasma and urine biomarkers. Conclusions In our cohort plasma biomarkers had higher discriminative power for risk stratification and early diagnosis of AKI than urine biomarkers. For preoperative risk stratification of AKI clinical models showed

  8. Comparison of Plasma and Urine Biomarker Performance in Acute Kidney Injury.

    Directory of Open Access Journals (Sweden)

    Gunnar Schley

    Full Text Available New renal biomarkers measured in urine promise to increase specificity for risk stratification and early diagnosis of acute kidney injury (AKI but concomitantly may be altered by urine concentration effects and chronic renal insufficiency. This study therefore directly compared the performance of AKI biomarkers in urine and plasma.This single-center, prospective cohort study included 110 unselected adults undergoing cardiac surgery with cardiopulmonary bypass between 2009 and 2010. Plasma and/or urine concentrations of creatinine, cystatin C, neutrophil gelatinase-associated lipocalin (NGAL, liver fatty acid-binding protein (L-FABP, kidney injury molecule 1 (KIM1, and albumin as well as 15 additional biomarkers in plasma and urine were measured during the perioperative period. The primary outcome was AKI defined by AKIN serum creatinine criteria within 72 hours after surgery.Biomarkers in plasma showed markedly better discriminative performance for preoperative risk stratification and early postoperative (within 24h after surgery detection of AKI than urine biomarkers. Discriminative power of urine biomarkers improved when concentrations were normalized to urinary creatinine, but urine biomarkers had still lower AUC values than plasma biomarkers. Best diagnostic performance 4h after surgery had plasma NGAL (AUC 0.83, cystatin C (0.76, MIG (0.74, and L-FAPB (0.73. Combinations of multiple biomarkers did not improve their diagnostic power. Preoperative clinical scoring systems (EuroSCORE and Cleveland Clinic Foundation Score predicted the risk for AKI (AUC 0.76 and 0.71 and were not inferior to biomarkers. Preexisting chronic kidney disease limited the diagnostic performance of both plasma and urine biomarkers.In our cohort plasma biomarkers had higher discriminative power for risk stratification and early diagnosis of AKI than urine biomarkers. For preoperative risk stratification of AKI clinical models showed similar discriminative performance

  9. Randomized comparative study of moxalactam and cefazolin in the treatment of acute urinary tract infections in adults.

    OpenAIRE

    Lea, A.S.; Sudan, A W; Wood, B A; Gentry, L O

    1982-01-01

    Eighty-nine patients with clinical and laboratory evidence of acute urinary tract infection were randomized to therapy with either moxalactam (500 mg) or cefazolin (1 g) every 12 h. Escherichia coli was the predominant pathogen in both groups (92.6 versus 90.2%). Therapy was continued for 3 days after the patient defervesced. The minimum hospital stay was 5 days. Sequential urine cultures were obtained on day 3, at discharge, and 5 to 10 days after the cessation of therapy. THe average durati...

  10. Treatment duration of febrile urinary tract infection (FUTIRST trial: a randomized placebo-controlled multicenter trial comparing short (7 days antibiotic treatment with conventional treatment (14 days

    Directory of Open Access Journals (Sweden)

    Kuijper Ed J

    2009-08-01

    clinical cure rate 70- to 84-day post-treatment, relapse rate of UTI and adverse events or complications during 90 days of follow-up. Discussion This study aims to demonstrate that 7 days of antimicrobial treatment is non-inferior as compared with 14 days of treatment in patients with febrile urinary tract infection. In addition, it will generate insights into the side-effects of antimicrobial treatment in relation to its duration. The study population will also include men, the elderly and patients with significant co-morbidity. Reflecting daily practice of primary health care and emergency departments, the results of this study can be generalized to other locations. Trial registration (Trial registration at clinicaltrials.gov: NCT00809913 and trialregister.nl: NTR01583

  11. Effect of hyperbaric oxygen and vitamin C and E supplementation on biomarkers of oxidative stress in healthy men

    DEFF Research Database (Denmark)

    Bader, Nicolle; Bosy-Westphal, Anja; Koch, Andreas

    2007-01-01

    biomarkers were collected before and immediately after each treatment. The present results showed that when compared with 'control', a single exposure to HBO resulted in a decrease of plasma vitamin C (P = 0.027) and an increase of lipid peroxides (P = 0.0008) and urinary 8-oxo-deoxyguanosine (8-oxod...

  12. Comparative analysis of urinary schistosomiasis among primary school children and rural farmers in Obollo-Eke, Enugu State, Nigeria:Implications for control

    Institute of Scientific and Technical Information of China (English)

    Celestine Chidi Ogbonna; Geme Urge Dori; Emeka Innocent Nweze; Gilbert Muoneke; Innocent Ejike Nwankwo; Nkiru Akputa

    2012-01-01

    Objective:To determine the prevalence, sex-age related intensity of urinary schistosomiasis and to compare such parameters among rural school children and rural farmers in selected communities in Obollo-Eke located in Southeast, Nigeria. Methods: A cross-sectional survey involving 1 337 school children and farmers was conducted in Obollo-Eke community between September 2006 and July 2007. Demographic data of subjects was collected using a questionnaire prepared for this purpose. Urine samples were collected and examined for haematuria and ova of Schistosoma haematobium (S. haematobium) using Medi-test Combi 9 and sedimentation technique respectively. Results:The prevalence of urinary schistosomiasis based on microscopic examination of the urine sediment for the ova of S. haematobium was 17.5%while the prevalence of haematuria was 15.6%. Infection intensity varied from light to heavy. In general, the prevalence was higher among males (20.8%) than females (14.6%;P>0.05) and was slightly higher among primary school children (18.0%;n=762) than farmers (16.9%;n=575;P>0.05).The age-specific prevalence of schistosomiasis among the study subjects ranged from 8.3%to 21.2%in 0-5 years and 11-15 years age groups respectively. Conclusions:Haematuria and mean egg/10 mL urine (r= 0.95;P<0.01) showed that both procedures are reliable for the diagnosis of the disease and can be used to ascertain the prevalence of the disease in any community. The comparative analysis of urinary bilharziasis among primary school children and rural farmers demonstrated that the infection is moderately high in these two risk population groups at Obollo-Eke. A robust intervention strategy is clearly needed.

  13. Comparison of arsenic levels in fingernails with urinary As species as biomarkers of arsenic exposure in residents living close to a coal-burning power plant in Prievidza District, Slovakia

    Energy Technology Data Exchange (ETDEWEB)

    Wilhelm, M.; Pesch, B.; Wittsiepe, R.; Jakubis, P.; Miskovic, P.; Keegan, T.; Nieuwenhuijsen, M.J.; Ranft, U. [Ruhr University of Bochum, Bochum (Germany)

    2005-01-01

    The associations between As levels in fingernails with both As concentrations in urine and environmental samples are reported. The participants (aged 20 - 80 years, mean 66 years) lived in the vicinity of a coal-burning power plant with high As emissions in the Prievidza District, Slovakia. Samples were taken in 1999 and 2000. The As levels in fingernails (n = 524) were measured after washing and digestion with microwave heating by hydride generation atomic absorption spectrometry. The spot urine samples (n = 436) were speciated for inorganic As (As{sub inorg}), monomethylarsonic (MMA) and dimethylarsinic acid (DMA) by hydride-cryogenic trap-atomic absorption spectrometry. The geometric mean As level in fingernails was 0.10 {mu}g/g (range, {lt}0.01-2.94 {mu}g/g). There was a clear association between As in fingernails and the distance of the home to the power plant (P {lt}0.001). The association between the distance to the power plant and total urinary As (As{sub sum}) (n = 436, no fish consumption during the last 3 days before sample collection) was less pronounced (P = 0.018). The As levels in fingernails were positively correlated to As in soil (n = 207, r = 0.23, P{lt}0.001) and to As in house dust (n = 209, r = 0.30, P{lt}0.001). The associations between urinary As{sub sum} and As concentrations in soil (n = 159, r = 0.13, P{lt}0.105) and in house dust (n = 162, r = 0.14, P{lt}0.081) were quite similar. It is concluded that As levels in fingernails are a reliable marker of environmental As exposure, and that As concentrations in fingernails reflect the As exposure in a similar manner compared with urinary As-sum and As species.

  14. Tissue polypeptide antigen in the follow-up of patients with urinary bladder cancer compared with conventional urine cytology.

    Science.gov (United States)

    Bantis, Athanasios; Zissimopoulos, Athanasios; Sountoulides, Petros; Giannakopoulos, Stilianos; Kalaitzis, Christos; Athanassiadou, Paulina; Agelonidou, Eleni; Touloupidis, Stavros

    2010-01-01

    The incidence of bladder cancer has demonstrated a rapid increase during the last decades. The aim of this study is to determine the clinical value of serum tissue polypeptide antigen (TPA) as a tumour marker for urinary bladder cancer in comparison with conventional urine cytology. Urine and blood samples were obtained from a total of 108 patients (group A) with a known history of bladder cancer, who presented for their routine 3 month follow-up. These 108 patients included 45 patients with high grade and 63 patients with low grade bladder cancer, and 30 patients with lower urinary tract symptoms (LUTS) and no history of bladder cancer (group B). Urine and blood samples from fifty healthy adults (group C) were also tested; this group served as the control group for estimating the normal range of serum TPA values. In all group A patients cystoscopy and/or bladder biopsies were performed. All blood and urine samples were tested for TPA and conventional urine cytology respectively. Results showed that the upper normal range for TPA was 1.0 ng/mL(0.9 ± 0.04) in the control group. For the subgroups of patients with high and low grade bladder cancer elevated serum TPA levels were found in 52% and 40% of the patients respectively. The overall serum TPA sensitivity and specificity were 50% and 85% respectively for patients with known bladder cancer (group A). We found the sensitivity of cytology for high grade bladder (GIII) carcinomas to be 72%; however when urine cytology was combined with serum TPA the overall sensitivity reached 80%. We conclude that serum TPA combined with urine cytology may be used as a prognostic marker for bladder cancer.

  15. Perturbations in the Urinary Exosome in Transplant Rejection

    Energy Technology Data Exchange (ETDEWEB)

    Sigdel, Tara K.; NG, Yolanda; Lee, Sangho; Nicora, Carrie D.; Qian, Weijun; Smith, Richard D.; Camp, David G.; Sarwal, Minnie M.

    2015-01-05

    Background: Urine exosomes, vesicles exocytosed into urine by all renal epithelial cell types, occur under normal physiologic and disease states. Exosome contents may mirror disease-specific proteome perturbations in kidney injury. Analysis methodologies for the exosomal fraction of the urinary proteome were developed and for comparing the urinary exosomal fraction versus unfractionated proteome for biomarker discovery. Methods: Urine exosomes were isolated by centrifugal filtration from mid-stream, second morning void, urine samples collected from kidney transplant recipients with and without biopsy matched acute rejection. The proteomes of unfractionated whole urine (Uw) and urine exosomes (Uexo) underwent mass spectrometry-based quantitative proteomics analysis. The proteome data were analyzed for significant differential protein abundances in acute rejection (AR). Results: Identifications of 1018 and 349 proteins, Uw and Uexo fractions, respectively, demonstrated a 279 protein overlap between the two urinary compartments with 25%(70) of overlapping proteins unique to Uexoand represented membrane bound proteins (p=9.31e-7). Of 349 urine exosomal proteins identified in transplant patients 220 were not previously identified in the normal urine exosomal fraction. Uexo proteins (11), functioning in the inflammatory / stress response, were more abundant in patients with biopsy-confirmed acute rejection, 3 of which were exclusive to Uexo. Uexo AR-specific biomarkers (8) were also detected in Uw, but since they were observed at significantly lower abundances in Uw, they were not significant for AR in Uw. Conclusions: A rapid urinary exosome isolation method and quantitative measurement of enriched Uexo proteins was applied. Urine proteins specific to the exosomal fraction were detected either in unfractionated urine (at low abundances) or by Uexo fraction analysis. Perturbed proteins in the exosomal compartment of urine collected from kidney transplant patients were

  16. Perturbations in the Urinary Exosome in Transplant Rejection

    Directory of Open Access Journals (Sweden)

    Tara eSigdel

    2015-01-01

    Full Text Available Urine exosomes are small vesicles exocytosed into the urine by all renal epithelial cell types under normal physiologic and disease states. Urine exosomal proteins may mirror disease specific proteome perturbations in kidney injury. Analysis methodologies for the exosomal fraction of the urinary proteome were developed for comparing the urinary exosomal fraction versus unfractionated proteome for biomarker discovery. Urine exosomes were isolated by centrifugal filtration of urine samples collected from kidney transplant patients with and without acute rejection, which were biopsy matched. The proteomes of unfractionated whole urine (Uw and urine exosomes (Ue underwent mass spectroscopy-based quantitative proteonomics analysis. The proteome data were analyzed for significant differential protein abundances in acute rejection (AR. A total of 1018 proteins were identified in Uw and 349 proteins in Ue. 279 overlapped between the two urinary compartments and 70 proteins were unique to the Ue compartment. Of 349 exosomal proteins identified from transplant patients,220 had not been previously identified in the normal Ue fraction. 11 Ue proteins, functionally involved in an inflammatory and stress response, were more abundant in urine samples from patients with acute rejection, 3 of which are exclusive to the Ue fraction. Ue AR-specific biomarkers(8 were also detected in Uw, but since they were observed at significantly lower abundances in Uw, they were not significant for AR in Uw. A rapid urinary exosome isolation method and quantitative measurement of enriched Ue proteins was applied. Perturbed proteins in the exosomal compartment of urine collected from kidney transplant patients were specific to inflammatory responses, and were not observed in the Ue fraction from normal healthy subjects. Ue specific protein alterations in renal disease provide potential mechanistic insights and offer a unique panel of sensitive biomarkers for monitoring AR.

  17. A micro-extraction technique using a new digitally controlled syringe combined with UHPLC for assessment of urinary biomarkers of oxidatively damaged DNA.

    Directory of Open Access Journals (Sweden)

    Berta Mendes

    Full Text Available The formation of reactive oxygen species (ROS within cells causes damage to biomolecules, including membrane lipids, DNA, proteins and sugars. An important type of oxidative damage is DNA base hydroxylation which leads to the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG and 5-hydroxymethyluracil (5-HMUra. Measurement of these biomarkers in urine is challenging, due to the low levels of the analytes and the matrix complexity. In order to simultaneously quantify 8-oxodG and 5-HMUra in human urine, a new, reliable and powerful strategy was optimised and validated. It is based on a semi-automatic microextraction by packed sorbent (MEPS technique, using a new digitally controlled syringe (eVol(®, to enhance the extraction efficiency of the target metabolites, followed by a fast and sensitive ultrahigh pressure liquid chromatography (UHPLC. The optimal methodological conditions involve loading of 250 µL urine sample (1:10 dilution through a C8 sorbent in a MEPS syringe placed in the semi-automatic eVol(® syringe followed by elution using 90 µL of 20% methanol in 0.01% formic acid solution. The obtained extract is directly analysed in the UHPLC system using a binary mobile phase composed of aqueous 0.1% formic acid and methanol in the isocratic elution mode (3.5 min total analysis time. The method was validated in terms of selectivity, linearity, limit of detection (LOD, limit of quantification (LOQ, extraction yield, accuracy, precision and matrix effect. Satisfactory results were obtained in terms of linearity (r(2 > 0.991 within the established concentration range. The LOD varied from 0.00005 to 0.04 µg mL(-1 and the LOQ from 0.00023 to 0.13 µg mL(-1. The extraction yields were between 80.1 and 82.2 %, while inter-day precision (n = 3 days varied between 4.9 and 7.7 % and intra-day precision between 1.0 and 8.3 %. This approach presents as main advantages the ability to easily collect and store urine samples for further processing

  18. A micro-extraction technique using a new digitally controlled syringe combined with UHPLC for assessment of urinary biomarkers of oxidatively damaged DNA.

    Science.gov (United States)

    Mendes, Berta; Silva, Pedro; Aveiro, Fernando; Pereira, Jorge; Câmara, José S

    2013-01-01

    The formation of reactive oxygen species (ROS) within cells causes damage to biomolecules, including membrane lipids, DNA, proteins and sugars. An important type of oxidative damage is DNA base hydroxylation which leads to the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 5-hydroxymethyluracil (5-HMUra). Measurement of these biomarkers in urine is challenging, due to the low levels of the analytes and the matrix complexity. In order to simultaneously quantify 8-oxodG and 5-HMUra in human urine, a new, reliable and powerful strategy was optimised and validated. It is based on a semi-automatic microextraction by packed sorbent (MEPS) technique, using a new digitally controlled syringe (eVol(®)), to enhance the extraction efficiency of the target metabolites, followed by a fast and sensitive ultrahigh pressure liquid chromatography (UHPLC). The optimal methodological conditions involve loading of 250 µL urine sample (1:10 dilution) through a C8 sorbent in a MEPS syringe placed in the semi-automatic eVol(®) syringe followed by elution using 90 µL of 20% methanol in 0.01% formic acid solution. The obtained extract is directly analysed in the UHPLC system using a binary mobile phase composed of aqueous 0.1% formic acid and methanol in the isocratic elution mode (3.5 min total analysis time). The method was validated in terms of selectivity, linearity, limit of detection (LOD), limit of quantification (LOQ), extraction yield, accuracy, precision and matrix effect. Satisfactory results were obtained in terms of linearity (r(2) > 0.991) within the established concentration range. The LOD varied from 0.00005 to 0.04 µg mL(-1) and the LOQ from 0.00023 to 0.13 µg mL(-1). The extraction yields were between 80.1 and 82.2 %, while inter-day precision (n = 3 days) varied between 4.9 and 7.7 % and intra-day precision between 1.0 and 8.3 %. This approach presents as main advantages the ability to easily collect and store urine samples for further processing

  19. COMPARATIVE STUDY ON THE EFFECTS OF PRETREATMENT WITH MAGNESIUM SULPHATE AND PROPOFOL INDUCTION ON SERUM CREATINE PHOSPHOKINASE AND URINARY MYOGLOBIN LEVELS ASSOCIATED WITH THE USE OF SUCCINYLCHOLINE

    Directory of Open Access Journals (Sweden)

    Sadhana

    2015-07-01

    Full Text Available Succinyl Choline posses s unique properties of rapid onset and short duration of action to facilitate endo tracheal intubation but myalgias, hyperkalemia, increase in serum myoglobin, creatine phosphokinase and masseter spasm are adverse effe cts associated with its use in apparently healthy population. The aim of present study is to compare the effects of with and without pretreatment with magnesium sulphate and propofol induction on serum creatine phosphokinase and urinary myoglobin levels as sociated with use of succinyl choline. 60 patients aged between 18 - 60 years of both sexes of ASA Grade – I and II undergoing elective Surgery with minimal or no muscle damage were divided into two groups randomly. After taking informed consent, patient was shifting to operation table, monitors were connected, vital parameters recorded, intravenous line secured and 2ml of blood was collected in plain bottle and 10 - 15 ml of urine sample was collected and set to lab for serum creatine phosphokinase and urinary myoglobin estimation. Patients of both groups were preoxygenated for 5 minutes, premedicated with Inj. Gycopyrolate ( 0 .2mg iv, Inj. Fentanyl 2 Micro Grams per Kg iv and induced with Inj. Propofol 2mg/kg and succinyl choline 2mg./kg was given to facilitat e endotracheal intubation. One group was pretreated with 10cc of 0.9% Normal saline and other group with magnesium sulphate 40mg/kg in 10ml slowly over 10 minutes before induction with propofol. The occurrence of fassiculations was noted. 10 - 15 ml of urine was collected in both groups for myoglobin estimation 20 minutes after intubation. At the end of surgery patients was revered with neostigmine (0.07 mg/kg and Inj. Glycopyrdate (0.01 mg/kg. After complete recovery extubation was done and patient shifted to postoperative ward 2ml of blood was collected 20 - 24 hours post - surgery for serum creatine phosphokinare estimations and results tabulated. The study found that there was raise in

  20. A comparative study of pelvic floor muscle training in women with multiple sclerosis: its impact on lower urinary tract symptoms and quality of life

    Directory of Open Access Journals (Sweden)

    Adélia Correia Lúcio

    2011-01-01

    Full Text Available OBJECTIVE: To compare pelvic floor muscle training and a sham procedure for the treatment of lower urinary tract symptoms and quality of life in women with multiple sclerosis. METHODS: Thirty-five female patients with multiple sclerosis were randomized into two groups: a treatment group (n = 18 and a sham group (n = 17. The evaluation included use of the Overactive Bladder Questionnaire, Medical Outcomes Study Short Form 36, International Consultation on Incontinence Questionnaire Short Form, and Qualiveen questionnaire. The intervention was performed twice per week for 12 weeks in both groups. The treatment group underwent pelvic floor muscle training with assistance from a vaginal perineometer and instructions to practice the exercises daily at home. The sham group received a treatment consisting of introducing a perineometer inside the vagina with no exercises required. Pre- and post-intervention data were recorded. RESULTS: The evaluation results of the two groups were similar at baseline. At the end of the treatment, the treatment group reported fewer storage and voiding symptoms than the sham group. Furthermore, the differences found between the groups were significant improvements in the following scores in the treatment group: Overactive Bladder Questionnaire, International Consultation on Incontinence Questionnaire Short Form, and the General Quality of Life, and Specific Impact of Urinary Problems domains of the Qualiveen questionnaire. CONCLUSIONS: The improvement of lower urinary tract symptoms had a positive effect on the quality of life of women with multiple sclerosis who underwent pelvic floor muscle training, as the disease-specific of quality of life questionnaires demonstrated. This study reinforces the importance of assessing quality of life to judge the effectiveness of a treatment intervention.

  1. Urinary Incontinence

    Science.gov (United States)

    ... you to restrict your activities and limit your social interactions Increase the risk of falls in older adults ... increase your risk of developing urinary incontinence include: Gender. Women are more likely to have stress incontinence. ...

  2. Urinary Incontinence

    Science.gov (United States)

    ... Alcohol Caffeine Decaffeinated tea and coffee Carbonated drinks Artificial sweeteners Corn syrup Foods that are high in spice, sugar or acid, especially citrus fruits Heart and blood pressure ... surgery. Artificial urinary sphincter. In men, a small, fluid-filled ...

  3. Exploratory urinary metabolomics of type 1 leprosy reactions.

    Science.gov (United States)

    Mayboroda, Oleg A; van Hooij, Anouk; Derks, Rico; van den Eeden, Susan J F; Dijkman, Karin; Khadge, Saraswoti; Thapa, Pratibha; Kunwar, Chhatra B; Hagge, Deanna A; Geluk, Annemieke

    2016-04-01

    Leprosy is an infectious disease caused by Mycobacterium leprae that affects the skin and nerves. Although curable with multidrug therapy, leprosy is complicated by acute inflammatory episodes called reactions, which are the major causes of irreversible neuropathy in leprosy that occur before, during, and even after treatment. Early diagnosis and prompt treatment of reactions reduces the risk of permanent disability. This exploratory study investigated whether urinary metabolic profiles could be identified that correlate with early signs of reversal reactions (RR). A prospective cohort of leprosy patients with and without reactions and endemic controls was recruited in Nepal. Urine-derived metabolic profiles were measured longitudinally. Thus, a conventional area of biomarker identification for leprosy was extended to non-invasive urine testing. It was found that the urinary metabolome could be used to discriminate endemic controls from untreated patients with mycobacterial disease. Moreover, metabolic signatures in the urine of patients developing RR were clearly different before RR onset compared to those at RR diagnosis. This study indicates that urinary metabolic profiles are promising host biomarkers for the detection of intra-individual changes during acute inflammation in leprosy and could contribute to early treatment and prevention of tissue damage. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  4. Investigating the emerging role of comparative proteomics in the search for new biomarkers of metal contamination under varying abiotic conditions

    Energy Technology Data Exchange (ETDEWEB)

    Vellinger, Céline, E-mail: celine.vellinger@gmail.com [Laboratoire Interdisciplinaire des Environnements Continentaux (LIEC), CNRS UMR 7360, Université de Lorraine – Metz (France); Sohm, Bénédicte, E-mail: benedicte.sohm@univ-lorraine.fr [Laboratoire Interdisciplinaire des Environnements Continentaux (LIEC), CNRS UMR 7360, Université de Lorraine – Metz (France); Parant, Marc, E-mail: marc.parant@univ-lorraine.fr [Laboratoire Interdisciplinaire des Environnements Continentaux (LIEC), CNRS UMR 7360, Université de Lorraine – Metz (France); Immel, Françoise, E-mail: Francoise.Immel@u-bourgogne.fr [Biogéosciences, CNRS UMR 6282, Université de Bourgogne – Dijon (France); Usseglio-Polatera, Philippe, E-mail: philippe.usseglio-polatera@univ-lorraine.fr [Laboratoire Interdisciplinaire des Environnements Continentaux (LIEC), CNRS UMR 7360, Université de Lorraine – Metz (France)

    2016-08-15

    mixture previously observed on G. pulex mortality at 10 °C. - Highlights: • We tested comparative proteomics for identifying new biomarkers of chemical exposure. • Both metal interactions and temperature confounding effects were taken into account. • 129 spots have been highlighted as potential Protein Expression Signatures at 10 °C. • Proteomics has high potential but a long way still to go to efficient multi-marker. • Recommendations and precautions for future studies have been presented.

  5. Comprehensive MR Urography Protocol: Equally Good Diagnostic Performance and Enhanced Visibility of the Upper Urinary Tract Compared to Triple-Phase CT Urography.

    Science.gov (United States)

    Sudah, Mazen; Masarwah, Amro; Kainulainen, Sakari; Pitkänen, Marja; Matikka, Hanna; Dabravolskaite, Vaiva; Aaltomaa, Sirpa; Vanninen, Ritva

    2016-01-01

    To prospectively compare the diagnostic performance and the visualization of the upper urinary tract (UUT) using a comprehensive 3.0T- magnetic resonance urography (MRU) protocol versus triple-phase computed tomography urography (CTU). During the study period (January-2014 through December-2015), all consecutive patients in our tertiary university hospital scheduled by a urologist for CTU to exclude UUT malignancy were invited to participate. Diagnostic performance and visualization scores of 3.0T-MRU were compared to CTU using Wilcoxon matched-pairs test. Twenty patients (39 UUT excreting units) were evaluated. 3.0T-MRU and CTU achieved equal diagnostic performances. The benign etiology of seven UUT obstructions was clarified equally with both methods. Another two urinary tract malignant tumors and one benign extraurinary tumor were detected and confirmed. Diagnostic visualization was slightly better in the intrarenal cavity areas with CTU but worsened towards distal ureter. MRU showed consistently slightly better visualization of the ureter. In the comparison, full 100% visualizations were detected in all areas in 93.6% (with 3.0T-MRU) and 87.2% (with CTU) and >75% visualization in 100% (3.0T-MRU) and 93.6% (CTU). Mean CTU effective radiation dose was 9.2 mSv. Comprehensive 3.0T-MRU is an accurate imaging modality achieving comparable performance with CTU; since it does not entail exposure to radiation, it has the potential to become the primary investigation technique in selected patients. ClinicalTrials.gov NCT02606513.

  6. Comprehensive MR Urography Protocol: Equally Good Diagnostic Performance and Enhanced Visibility of the Upper Urinary Tract Compared to Triple-Phase CT Urography.

    Directory of Open Access Journals (Sweden)

    Mazen Sudah

    Full Text Available To prospectively compare the diagnostic performance and the visualization of the upper urinary tract (UUT using a comprehensive 3.0T- magnetic resonance urography (MRU protocol versus triple-phase computed tomography urography (CTU.During the study period (January-2014 through December-2015, all consecutive patients in our tertiary university hospital scheduled by a urologist for CTU to exclude UUT malignancy were invited to participate. Diagnostic performance and visualization scores of 3.0T-MRU were compared to CTU using Wilcoxon matched-pairs test.Twenty patients (39 UUT excreting units were evaluated. 3.0T-MRU and CTU achieved equal diagnostic performances. The benign etiology of seven UUT obstructions was clarified equally with both methods. Another two urinary tract malignant tumors and one benign extraurinary tumor were detected and confirmed. Diagnostic visualization was slightly better in the intrarenal cavity areas with CTU but worsened towards distal ureter. MRU showed consistently slightly better visualization of the ureter. In the comparison, full 100% visualizations were detected in all areas in 93.6% (with 3.0T-MRU and 87.2% (with CTU and >75% visualization in 100% (3.0T-MRU and 93.6% (CTU. Mean CTU effective radiation dose was 9.2 mSv.Comprehensive 3.0T-MRU is an accurate imaging modality achieving comparable performance with CTU; since it does not entail exposure to radiation, it has the potential to become the primary investigation technique in selected patients.ClinicalTrials.gov NCT02606513.

  7. Improved sleep quality in older adults with insomnia reduces biomarkers of disease risk: pilot results from a randomized controlled comparative efficacy trial.

    Science.gov (United States)

    Carroll, Judith E; Seeman, Teresa E; Olmstead, Richard; Melendez, Gerson; Sadakane, Ryan; Bootzin, Richard; Nicassio, Perry; Irwin, Michael R

    2015-05-01

    Sleep disturbances have been linked to increased morbidity and mortality, yet it is unknown whether improving sleep quality in older adult patients with insomnia alters biomarkers of diabetes and cardiovascular disease risk. Determine the comparative efficacy of cognitive behavioral therapy (CBT), tai chi chih (TCC), and a sleep seminar control (SS) to reduce multisystem biomarkers of disease risk in older adults with insomnia. Randomized controlled comparative efficacy trial. Los Angeles community. A population-based sample of 109 older adults with chronic and primary insomnia. Random assignment to CBT, TCC, or SS for 2-h group sessions weekly over 4 months with a 16-month evaluation (1 year after follow-up). Multisystem biological risk comprised of 8 biomarkers: high-density lipoprotein, low-density lipoprotein, triglycerides, hemoglobinA1c, glucose, insulin, C-reactive protein, and fibrinogen. Using clinical laboratory cutoffs defined as abnormal, a multisystem risk score was computed representing a sum of the deviation around the cutoffs across the 8 biomarkers. In addition, high risk grouping was classified if subjects exhibited 4 or more biomarkers in the abnormal laboratory range. An interaction of time-by-treatment-by-high risk group was found (F(4, 197.2)=3.14, p=.02) in which both TCC (p=.04) and CBT (p=.001) showed significantly lower risk scores as compared to SS at 16-months. CBT reduced risk of being in the high risk group at 4-months (odds ratio [OR]=.21 [95% CI, .03-1.47], psleep quality, as defined by a clinical severity threshold, reduced the likelihood of being in the high risk group at 16-months, OR=.08 (95% CI, .008-.78); p=.01. Participants classified as having high multisystem biological risk at entry and assigned to CBT or TCC show improvements in risk scores after one year follow-up. Given that these clinical biomarkers are associated with cardiovascular, metabolic, and inflammatory disease risk, improving sleep quality has the potential to

  8. Immune biomarker differences and changes comparing HCV mono-infected, HIV/HCV co-infected, and HCV spontaneously cleared patients.

    Directory of Open Access Journals (Sweden)

    Lauren E Kushner

    Full Text Available BACKGROUND: Immune biomarkers are implicated in HCV treatment response, fibrosis, and accelerated pathogenesis of comorbidities, though only D-dimer and C-reactive protein have been consistently studied. Few studies have evaluated HIV/HCV co-infection, and little longitudinal data exists describing a broader antiviral cytokine response. METHODS: Fifty immune biomarkers were analyzed at baseline (BL and HCV end of treatment follow-up(FU time point using the Luminex 50-plex assay in plasma samples from 15 HCV-cleared, 24 HCV mono- and 49 HIV/HCV co-infected patients receiving antiretroviral treatment, who either did or did not receive pegylated-interferon/ribavirin HCV treatment. Biomarker levels were compared among spontaneous clearance patients, mono- and co-infected, untreated and HCV-treated, and sustained virologic responders (SVR and non-responders (NR at BL and FU using nonparametric analyses. A Bonferroni correction, adjusting for tests of 50 biomarkers, was used to reduce Type I error. RESULTS: Compared to HCV patients at BL, HIV/HCV patients had 22 significantly higher and 4 significantly lower biomarker levels, following correction for multiple testing. There were no significantly different BL levels when comparing SVR and NR in mono- or co-infected patients; however, FU levels changed considerably in co-infected patients, with seven becoming significantly higher and eight becoming significantly lower in SVR patients. Longitudinally between BL and FU, 13 markers significantly changed in co-infected SVR patients, while none significantly changed in co-infected NR patients. There were also no significant changes in longitudinal analyses of mono-infected patients achieving SVR or mono-infected and co-infected groups deferring treatment. CONCLUSIONS: Clear differences exist in pattern and quantity of plasma immune biomarkers among HCV mono-infected, HIV/HCV co-infected, and HCV-cleared patients; and with SVR in co-infected patients treated

  9. Carcinogen derived biomarkers: applications in studies of human exposure to secondhand tobacco smoke

    OpenAIRE

    Hecht, S

    2004-01-01

    Objective: To review the literature on carcinogen derived biomarkers of exposure to secondhand tobacco smoke (SHS). These biomarkers are specifically related to known carcinogens in tobacco smoke and include urinary metabolites, DNA adducts, and blood protein adducts.

  10. Increased urinary orosomucoid excretion predicts preeclampsia in pregnant women with pregestational type 1 diabetes

    DEFF Research Database (Denmark)

    2010-01-01

    We evaluated the urinary orosomucoid excretion (UOE) as a biomarker of preeclampsia and preterm delivery in pregnant women with type 1 diabetes.......We evaluated the urinary orosomucoid excretion (UOE) as a biomarker of preeclampsia and preterm delivery in pregnant women with type 1 diabetes....

  11. Consumption of wholemeal rye bread increases serum concentrations and urinary excretion of enterolactone compared with consumption of white wheat bread in healthy Finnish men and women.

    Science.gov (United States)

    Juntunen, K S; Mazur, W M; Liukkonen, K H; Uehara, M; Poutanen, K S; Adlercreutz, H C; Mykkänen, H M

    2000-12-01

    Rye is an important source of plant lignans in Finland. In the present crossover trial we wanted to study the effect of rye bread as part of the usual diet on serum and urine enterolactone (ENL) concentrations in healthy volunteers. Eighteen men aged 43 (sem 2.0) years and twenty-one women aged 43 (sem 1.6) years consumed wholemeal rye bread and white wheat bread in random order for 4 weeks. The bread periods were separated by a 4 week wash-out period. The breads provided at least 20% of the daily energy intake. The mean intakes of rye bread were 219 (sem 14.6) and 162 (sem 5.3) g/d and those of wheat bread were 200 (sem 9.6) and 153 (sem 5.8) g/d for men and women respectively. Blood samples were collected from all subjects and three 24 h urine samples were collected from ten men and twelve women at the end of both bread periods for the determination of serum concentration and urinary excretion of ENL. The mean serum ENL concentrations in both men and women at the beginning of baseline period and at the end of the rye-bread period remained constant and were significantly higher than those at the end of the wheat-bread period. Correspondingly, daily urinary ENL excretion increased significantly during the rye-bread period compared with the wheat-bread period and was 5- and 10-fold higher in men and women respectively in comparison with the amount of plant lignan precursors measured in the rye bread. These data indicate the presence of other precursors for ENL in rye which are not detected by the current method of measuring plant lignans in food. The possible role of fibre in enhancement of the formation of mammalian lignans from their plant precursors in the gut also remains to be determined.

  12. Criteria to interpret cancer biomarker increments crossing the recommended cut-off compared in a simulation model focusing on false positive signals and tumour detection time

    DEFF Research Database (Denmark)

    Lund, Flemming; Hyltoft Petersen, Per; Pedersen, Merete Frejstrup;

    2014-01-01

    BACKGROUND: Several criteria have been proposed to interpret increments in serological cancer biomarker concentrations starting from low baseline concentrations crossing the cut-off. None of the criteria have been compared for their ability to signal tumour growth when ≤2% false positive results...... are accepted. METHODS: The cancer biomarker Tissue Polypeptide Antigen was used as an example. Seven criteria to interpret increments in concentrations were investigated by computer simulations. Firstly, for each criterion, we identified a baseline concentration stratified for three levels of biological...... that different types of criteria should be used within different intervals of below cut-off level concentrations if the rate of false positive signals of marker increments should be kept ≤2%....

  13. Comparative effectiveness of oral drug therapies for lower urinary tract symptoms due to benign prostatic hyperplasia: a systematic review and network meta-analysis.

    Directory of Open Access Journals (Sweden)

    Xinghuan Wang

    Full Text Available Lower urinary tract symptoms (LUTS due to benign prostatic hyperplasia (BPH are common in elder men and a number of drugs alone or combined are clinically used for this disorder. But available studies investigating the comparative effects of different drug therapies are limited. This study was aimed to compare the efficacy of different drug therapies for LUTS/BPH with network meta-analysis.An electronic search of PubMed, Cochrane Library and Embase was performed to identify randomized controlled trials (RCTs comparing different drug therapies for LUTS/BPH within 24 weeks. Comparative effects were calculated using Aggregate Data Drug Information System. Consistency models of network meta-analysis were created and cumulative probability was used to rank different therapies.A total 66 RCTs covering seven different therapies with 29384 participants were included. We found that α-blockers (ABs plus phosphodiesterase 5 inhibitors (PDE5-Is ranked highest in the test of IPSS total score, storage subscore and voiding subscore. The combination therapy of ABs plus 5α-reductase inhibitors was the best for increasing maximum urinary flow rate (Qmax with a mean difference (MD of 1.98 (95% CI, 1.12 to 2.86 as compared to placebo. ABs plus muscarinic receptor antagonists (MRAs ranked secondly on the reduction of IPSS storage subscore, although monotherapies including MRAs showed no effect on this aspect. Additionally, PDE5-Is alone showed great effectiveness for LUTS/BPH except Qmax.Based on our novel findings, combination therapy, especially ABs plus PDE5-Is, is recommended for short-term treatment for LUTS/BPH. There was also evidence that PDE5-Is used alone was efficacious except on Qmax. Additionally, it should be cautious when using MRAs. However, further clinical studies are required for longer duration which considers more treatment outcomes such as disease progression, as well as basic research investigating mechanisms involving PDE5-Is and other

  14. Urinary catheters

    Science.gov (United States)

    ... incontinence. There is no tube placed inside the penis. Instead, a condom-like device is placed over the penis. A tube leads from this device to a ... too small Bladder spasms Constipation The wrong balloon size Urinary tract infections POSSIBLE COMPLICATIONS Complications of catheter ...

  15. CT urography in the urinary bladder: To compare excretory phase images using a low noise index and a high noise index with adaptive noise reduction filter

    Energy Technology Data Exchange (ETDEWEB)

    Takeyama, Nobuyuki; Hayashi, Takaki (Dept. of Radiology, Showa Univ. Fujigaoka Hospital, Yokohama (Japan)), email: momiji@mtc.biglobe.ne.jp; Ohgiya, Yoshimitsu (Dept. of Radiology, Showa Univ. School of Medicine, Tokyo (Japan)) (and others)

    2011-07-15

    Background: Although CT urography (CTU) is widely used for the evaluation of the entire urinary tract, the most important drawback is the radiation exposure. Purpose: To evaluate the effect of a noise reduction filter (NRF) using a phantom and to quantitatively and qualitatively compare excretory phase (EP) images using a low noise index (NI) with those using a high NI and postprocessing NRF (pNRF). Material and Methods: Each NI value was defined for a slice thickness of 5 mm, and reconstructed images with a slice thickness of 1.25 mm were assessed. Sixty patients who were at high risk of developing bladder tumors (BT) were divided into two groups according to whether their EP images were obtained using an NI of 9.88 (29 patients; group A) or an NI of 20 and pNRF (31 patients; group B). The CT dose index volume (CTDI{sub vol}) and the contrast-to-noise ratio (CNR) of the bladder with respect to the anterior pelvic fat were compared in both groups. Qualitative assessment of the urinary bladder for image noise, sharpness, streak artifacts, homogeneity, and the conspicuity of polypoid or sessile-shaped BTs with a short-axis diameter greater than 10 mm was performed using a 3-point scale. Results: The phantom study showed noise reduction of approximately 40% and 76% dose reduction between group A and group B. CTDI{sub vol} demonstrated a 73% reduction in group B (4.6 +- 1.1 mGy) compared with group A (16.9 +- 3.4 mGy). The CNR value was not significantly different (P = 0.60) between group A (16.1 +- 5.1) and group B (16.6 +- 7.6). Although group A was superior (P < 0.01) to group B with regard to image noise, other qualitative analyses did not show significant differences. Conclusion: EP images using a high NI and pNRF were quantitatively and qualitatively comparable to those using a low NI, except with regard to image noise

  16. Renal proximal tubular dysfunction is a major determinant of urinary connective tissue growth factor excretion.

    NARCIS (Netherlands)

    Gerritsen, K.G.; Peters, H.P.E.; Nguyen, T.Q.; Koeners, M.P.; Wetzels, J.F.M.; Joles, J.A.; Christensen, E.I.; Verroust, P.J.; Li, D.; Oliver, N.; Xu, L.; Kok, R.J.; Goldschmeding, R.

    2010-01-01

    Connective tissue growth factor (CTGF) plays a key role in renal fibrosis. Urinary CTGF is elevated in various renal diseases and may have biomarker potential. However, it is unknown which processes contribute to elevated urinary CTGF levels. Thus far, urinary CTGF was considered to reflect renal ex

  17. Regulation of urinary ACE2 in diabetic mice.

    Science.gov (United States)

    Wysocki, Jan; Garcia-Halpin, Laura; Ye, Minghao; Maier, Christoph; Sowers, Kurt; Burns, Kevin D; Batlle, Daniel

    2013-08-15

    Angiotensin-converting enzyme-2 (ACE2) enhances the degradation of ANG II and its expression is altered in diabetic kidneys, but the regulation of this enzyme in the urine is unknown. Urinary ACE2 was studied in the db/db model of type 2 diabetes and stretozotocin (STZ)-induced type 1 diabetes during several physiological and pharmacological interventions. ACE2 activity in db/db mice was increased in the serum and to a much greater extent in the urine compared with db/m controls. Neither a specific ANG II blocker, telmisartan, nor an ACE inhibitor, captopril, altered the levels of urinary ACE2 in db/db or db/m control mice. High-salt diet (8%) increased whereas low-salt diet (0.1%) decreased urinary ACE2 activity in the urine of db/db mice. In STZ mice, urinary ACE2 was also increased, and insulin decreased it partly but significantly after several weeks of administration. The increase in urinary ACE2 activity in db/db mice reflected an increase in enzymatically active protein with two bands identified of molecular size at 110 and 75 kDa and was associated with an increase in kidney cortex ACE2 protein at 110 kDa but not at 75 kDa. ACE2 activity was increased in isolated tubular preparations but not in glomeruli from db/db mice. Administration of soluble recombinant ACE2 to db/m and db/db mice resulted in a marked increase in serum ACE2 activity, but no gain in ACE2 activity was detectable in the urine, further demonstrating that urinary ACE2 is of kidney origin. Increased urinary ACE2 was associated with more efficient degradation of exogenous ANG II (10(-9) M) in urine from db/db compared with that from db/m mice. Urinary ACE2 could be a potential biomarker of increased metabolism of ANG II in diabetic kidney disease.

  18. Evaluation of cadmium-induced nephrotoxicity using urinary metabolomic profiles in sprague-dawley male rats.

    Science.gov (United States)

    Lee, Yu Kyung; Park, Eun Young; Kim, Shiwon; Son, Ji Yeon; Kim, Tae Hyung; Kang, Won Gu; Jeong, Tae Chun; Kim, Kyu-Bong; Kwack, Seung Jun; Lee, Jaewon; Kim, Suhkmann; Lee, Byung-Mu; Kim, Hyung Sik

    2014-01-01

    The aim of this study was to investigate urinary metabolomic profiles associated with cadmium (Cd)-induced nephrotoxicity and their potential mechanisms. Metabolomic profiles were measured by high-resolution (1)H-nuclear magnetic resonance (NMR) spectroscopy in the urine of rats after oral exposure to CdCl2 (1, 5, or 25 mg/kg) for 6 wk. The spectral data were further analyzed by a multivariate analysis to identify specific urinary metabolites. Urinary excretion levels of protein biomarkers were also measured and CdCl2 accumulated dose-dependently in the kidney. High-dose (25 mg/kg) CdCl2 exposure significantly increased serum blood urea nitrogen (BUN), but serum creatinine (sCr) levels were unchanged. High-dose CdCl2 (25 mg/kg) exposure also significantly elevated protein-based urinary biomarkers including osteopontin, monocyte chemoattractant protein-1 (MCP-1), kidney injury molecules-1 (Kim-1), and selenium-binding protein 1 (SBP1) in rat urine. Under these conditions, six urinary metabolites (citrate, serine, 3-hydroxyisovalerate, 4-hydroxyphenyllactate, dimethylamine, and betaine) were involved in mitochondrial energy metabolism. In addition, a few number of amino acids such as glycine, glutamate, tyrosine, proline, or phenylalanine and carbohydrate (glucose) were altered in urine after CdCl2 exposure. In particular, the metabolites involved in the glutathione biosynthesis pathway, including cysteine, serine, methionine, and glutamate, were markedly decreased compared to the control. Thus, these metabolites are potential biomarkers for detection of Cd-induced nephrotoxicity. Our results further indicate that redox metabolomics pathways may be associated with Cd-mediated chronic kidney injury. These findings provide a biochemical pathway for better understanding of cellular mechanism underlying Cd-induced renal injury in humans.

  19. Comparing biomarker responses during thermal acclimation: A lethal vs non-lethal approach in a tropical reef clownfish.

    Science.gov (United States)

    Madeira, Carolina; Madeira, Diana; Diniz, Mário S; Cabral, Henrique N; Vinagre, Catarina

    2017-02-01

    Knowledge of thermal stress biology for most tropical fish species in reef ecosystems under climate change is still quite limited. Thus, the objective of this study was to measure the time-course changes of thermal stress biomarkers in the commercially exploited coral reef fish Amphiprion ocellaris, during a laboratory simulated event of increased temperature. Heat shock protein 70kDa (Hsp70) and total ubiquitin (Ub) were determined in the muscle (lethal method) and in the fin (non-lethal alternative method) under two temperature treatments (control - 26°C and elevated temperature - 30°C) throughout one month with weekly samplings. Results suggest that biomarker basal levels are tissue-specific and influence the degree of response under temperature exposure. Responses were highly inducible in the muscle but not in fin tissue, indicating that the latter is not reliable for monitoring purposes. Thermal stress was observed in the muscle after one week of exposure (both biomarkers increased significantly) and Ub levels then decreased, suggesting the animals were able to acclimate by maintaining high levels of Hsp70 and through an effective protein turnover. In addition, the results show that mortality rates did not differ between treatments. This indicates that A. ocellaris is capable of displaying a plastic response to elevated temperature by adjusting the protein quality control system to protect cell functions, without decreasing survival. Thus, this coral reef fish species presents a significant acclimation potential under ocean warming scenarios of +4°C. Monitoring of thermal stress through a non-lethal method, fin-clipping, although desirable proved to be inadequate for this species. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Naturally Occurring Human Urinary Peptides for Use in Diagnosis of Chronic Kidney Disease*

    Science.gov (United States)

    Good, David M.; Zürbig, Petra; Argilés, Àngel; Bauer, Hartwig W.; Behrens, Georg; Coon, Joshua J.; Dakna, Mohammed; Decramer, Stéphane; Delles, Christian; Dominiczak, Anna F.; Ehrich, Jochen H. H.; Eitner, Frank; Fliser, Danilo; Frommberger, Moritz; Ganser, Arnold; Girolami, Mark A.; Golovko, Igor; Gwinner, Wilfried; Haubitz, Marion; Herget-Rosenthal, Stefan; Jankowski, Joachim; Jahn, Holger; Jerums, George; Julian, Bruce A.; Kellmann, Markus; Kliem, Volker; Kolch, Walter; Krolewski, Andrzej S.; Luppi, Mario; Massy, Ziad; Melter, Michael; Neusüss, Christian; Novak, Jan; Peter, Karlheinz; Rossing, Kasper; Rupprecht, Harald; Schanstra, Joost P.; Schiffer, Eric; Stolzenburg, Jens-Uwe; Tarnow, Lise; Theodorescu, Dan; Thongboonkerd, Visith; Vanholder, Raymond; Weissinger, Eva M.; Mischak, Harald; Schmitt-Kopplin, Philippe

    2010-01-01

    Because of its availability, ease of collection, and correlation with physiology and pathology, urine is an attractive source for clinical proteomics/peptidomics. However, the lack of comparable data sets from large cohorts has greatly hindered the development of clinical proteomics. Here, we report the establishment of a reproducible, high resolution method for peptidome analysis of naturally occurring human urinary peptides and proteins, ranging from 800 to 17,000 Da, using samples from 3,600 individuals analyzed by capillary electrophoresis coupled to MS. All processed data were deposited in an Structured Query Language (SQL) database. This database currently contains 5,010 relevant unique urinary peptides that serve as a pool of potential classifiers for diagnosis and monitoring of various diseases. As an example, by using this source of information, we were able to define urinary peptide biomarkers for chronic kidney diseases, allowing diagnosis of these diseases with high accuracy. Application of the chronic kidney disease-specific biomarker set to an independent test cohort in the subsequent replication phase resulted in 85.5% sensitivity and 100% specificity. These results indicate the potential usefulness of capillary electrophoresis coupled to MS for clinical applications in the analysis of naturally occurring urinary peptides. PMID:20616184

  1. Cost-effectiveness of involving nurse specialists for adult patients with urinary incontinence in primary care compared to care-as-usual: an economic evaluation alongside a pragmatic randomized controlled trial.

    NARCIS (Netherlands)

    Albers-Heitner, C.P.; Joore, M.A.; Winkens, R.A.G.; Lagro-Janssen, A.L.M.; Severens, J.L.; Berghmans, L.C.M.

    2012-01-01

    AIMS: To determine the 12-month, societal cost-effectiveness of involving urinary incontinence (UI) nurse specialists in primary care compared to care-as-usual by general practitioners (GPs). METHODS: From 2005 until 2008 an economic evaluation was performed alongside a pragmatic multicenter randomi

  2. Tension-Free Vaginal Tape, Transobturator Tape, and Own Modification of Transobturator Tape in the Treatment of Female Stress Urinary Incontinence: Comparative Analysis

    Directory of Open Access Journals (Sweden)

    Marcin Zyczkowski

    2014-01-01

    Full Text Available Introduction. This study is a comparative evaluation of the TVT, TOT, and our own modification of TOT (mTOT in the treatment of female stress urinary incontinence from a single center experience. Material and Methods. The study was conducted on 527 patients with SUI diagnosed on the basis of urodynamic studies. They were divided into three groups—TVT: n=142, (TOT: n=129, and mTOT: n=256. All of the patients underwent evaluation at 1, 3, and 6 months after surgery. Results were statistically analysed and compared. Results. Objective and subjective effectiveness after the surgery were not significantly different in the study groups and ranged from 90.1% to 96.4%. Mean surgery time was 32.3, 28.2, and 26.4 in the TVT, TOT, and mTOT, respectively. Mean hospitalization time was 2.51 days. Mean catheter maintenance time was significantly higher in the TVT than in other groups. In the TVT group total incidence of complications was 13.4%, and it was significantly higher than that in TOT and mTOT (9.3% and 8.6%, resp.. Conclusions. TVT, TOT, and mTOT are highly effective and safe methods in the treatment of SUI. There are no differences in the efficacy between the methods with a little higher percentage of complications in the TVT group.

  3. Human inhalation exposures to toluene, ethylbenzene, and m-xylene and physiologically based pharmacokinetic modeling of exposure biomarkers in exhaled air, blood, and urine.

    Science.gov (United States)

    Marchand, Axelle; Aranda-Rodriguez, Rocio; Tardif, Robert; Nong, Andy; Haddad, Sami

    2015-04-01

    Urinary biomarkers of exposure are used widely in biomonitoring studies. The commonly used urinary biomarkers for the aromatic solvents toluene (T), ethylbenzene (E), and m-xylene (X) are o-cresol, mandelic acid, and m-methylhippuric acid. The toxicokinetics of these biomarkers following inhalation exposure have yet to be described by physiologically based pharmacokinetic (PBPK) modeling. Five male volunteers were exposed for 6 h in an inhalation chamber to 1/8 or 1/4 of the time-weighted average exposure value (TWAEV) for each solvent: toluene, ethylbenzene, and m-xylene were quantified in blood and exhaled air and their corresponding urine biomarkers were measured in urine. Published PBPK model for parent compounds was used and simulations were compared with experimental blood and exhaled air concentration data. If discrepancies existed, Vmax and Km were optimized. Urinary excretion was modeled using parameters found in literature assuming simply stoichiometric yields from parent compound metabolism and first-order urinary excretion rate. Alternative models were also tested for (1) the possibility that CYP1A2 is the only enzyme implicated in o-cresol and (2) a 2-step model for describing serial metabolic steps for mandelic acid. Models adapted in this study for urinary excretion will be further used to interpret urinary biomarker kinetic data from mixed exposures of these solvents. © The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  4. Comparing intra-abdominal pressures in different body positions via a urinary catheter and nasogastric tube: a pilot study.

    Science.gov (United States)

    Rooban, Nirooshan; Regli, Adrian; Davis, Wendy A; De Keulenaer, Bart L

    2012-07-05

    Intra-abdominal pressure (IAP) is most commonly measured via the bladder with the patient in the supine position. In the ICU, patients are nursed with the head of the bed elevated at 30° (HOB30) to reduce the risk of ventilator-associated pneumonia. This study investigated whether gastric pressure at HOB30 can be used as a surrogate measure of IAP via the bladder in the supine position. A prospective observational study was conducted in a single-centre intensive care unit. A total of 20 patients were included. IAP was recorded simultaneously via the bladder catheter (bladder pressure, IBP) and via nasogastric tube (gastric pressures, IGP) in the supine and HOB30 position. Each patient had three sets of IAP measurements performed at least 4 h apart. In the supine position, mean IBP was 12.3 ± 4.5 mmHg compared to IGP of 11.8 ± 4.7 mmHg. The bias between the two groups was 0.5 and precision of 3.7 (LA, -6.8 to 7.5 mmHg). At 30 degrees, mean IBP was 15.8 ± 4.9 mmHg compared to IGP of 13.1 ± 6.1 mmHg. The bias between both groups was 2.7 with a precision of 5.5 (LA, -8.0 to 13.5). Comparing IBP in the supine position with IGP at 30° showed a bias of -0.8 and precision of 5.6 (LA, -10.1 to 11.6 mmHg). IAP measured via a nasogastric tube was less influenced by changing the body position from supine to HOB30 than was bladder pressure.

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

    Energy Technology Data Exchange (ETDEWEB)

    Swaddiwudhipong, Witaya, E-mail: swaddi@hotmail.com [Department of Community and Social Medicine, Mae Sot General Hospital, Tak 63110 (Thailand); Mahasakpan, Pranee [Department of Community and Social Medicine, Mae Sot General Hospital, Tak 63110 (Thailand); Limpatanachote, Pisit; Krintratun, Somyot [Department of Internal Medicine, Mae Sot General Hospital, Tak 63110 (Thailand)

    2011-05-15

    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 urinary 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.

  6. DW-MRI as a biomarker to compare therapeutic outcomes in radiotherapy regimens incorporating temozolomide or gemcitabine in glioblastoma.

    Directory of Open Access Journals (Sweden)

    Stefanie Galbán

    Full Text Available The effectiveness of the radiosensitizer gemcitabine (GEM was evaluated in a mouse glioma along with the imaging biomarker diffusion-weighted magnetic resonance imaging (DW-MRI for early detection of treatment effects. A genetically engineered murine GBM model [Ink4a-Arf(-/- Pten(loxP/loxP/Ntv-a RCAS/PDGF(+/Cre(+] was treated with gemcitabine (GEM, temozolomide (TMZ +/- ionizing radiation (IR. Therapeutic efficacy was quantified by contrast-enhanced MRI and DW-MRI for growth rate and tumor cellularity, respectively. Mice treated with GEM, TMZ and radiation showed a significant reduction in growth rates as early as three days post-treatment initiation. Both combination treatments (GEM/IR and TMZ/IR resulted in improved survival over single therapies. Tumor diffusion values increased prior to detectable changes in tumor volume growth rates following administration of therapies. Concomitant GEM/IR and TMZ/IR was active and well tolerated in this GBM model and similarly prolonged median survival of tumor bearing mice. DW-MRI provided early changes to radiosensitization treatment warranting evaluation of this imaging biomarker in clinical trials.

  7. Wilm's tumor-1 protein levels in urinary exosomes from diabetic patients with or without proteinuria.

    Directory of Open Access Journals (Sweden)

    Anuradha Kalani

    Full Text Available BACKGROUND: Podocyte injury is an early feature of diabetic nephropathy (DN. Recently, urinary exosomal Wilm's tumor-1 protein (WT1, shed by renal epithelial cells, has been proposed as a novel biomarker for podocyte injury. However, its usefulness as biomarker for early diabetic nephropathy has not been verified yet. We investigated urinary exosomal WT1 in type-1 diabetic patients to confirm its role as a non-invasive biomarker for predicting early renal function decline. METHODS: The expression of WT1 protein in urinary exosomes from spot urine samples of type-1 diabetes mellitus patients (n = 48 and healthy controls (n = 25 were analyzed. Patients were divided based on their urinary albumin excretion, ACR (mg/g creatinine into non- proteinuria group (ACR30 mg/g, n = 18. Regression analysis was used to assess the association between urinary exosomal levels of WT1 with parameters for renal function. Receiver Operating Characteristic (ROC curve analysis was used to determine the diagnostic performance of exosomal WT-1. RESULTS: WT1 protein was detected in 33 out of 48 diabetic patients and in only 1 healthy control. The levels of urinary exosomal WT1 protein is significantly higher (p = 0.001 in patients with proteinuria than in those without proteinuria. In addition, all the patients with proteinuria but only half of the patients without proteinuria were positive for exosomal WT1. We found that the level of exosomal WT1 were associated with a significant increase in urine protein-to-creatinine ratio, albumin-to-creatinine ratio, and serum creatinine as well as a decline in eGFR. Furthermore, patients exhibiting WT1-positive urinary exosomes had decreased renal function compared to WT1-negative patients. ROC analysis shows that WT-1 effectively predict GFR<60 ml. min-1/1.73 m(2. CONCLUSION: The predominant presence of WT1 protein in urinary exosomes of diabetic patients and increase in its expression level with decline in renal

  8. Diagnosis and Prediction of CKD Progression by Assessment of Urinary Peptides

    Science.gov (United States)

    Schanstra, Joost P.; Alkhalaf, Alaa; Argiles, Angel; Bakker, Stephan J.L.; Beige, Joachim; Bilo, Henk J.G.; Chatzikyrkou, Christos; Dakna, Mohammed; Dawson, Jesse; Delles, Christian; Haller, Hermann; Haubitz, Marion; Husi, Holger; Jankowski, Joachim; Jerums, George; Kleefstra, Nanne; Kuznetsova, Tatiana; Maahs, David M.; Menne, Jan; Mullen, William; Ortiz, Alberto; Persson, Frederik; Rossing, Peter; Ruggenenti, Piero; Rychlik, Ivan; Serra, Andreas L.; Siwy, Justyna; Snell-Bergeon, Janet; Spasovski, Goce; Staessen, Jan A.; Vlahou, Antonia; Mischak, Harald; Vanholder, Raymond

    2015-01-01

    Progressive CKD is generally detected at a late stage by a sustained decline in eGFR and/or the presence of significant albuminuria. With the aim of early and improved risk stratification of patients with CKD, we studied urinary peptides in a large cross-sectional multicenter cohort of 1990 individuals, including 522 with follow-up data, using proteome analysis. We validated that a previously established multipeptide urinary biomarker classifier performed significantly better in detecting and predicting progression of CKD than the current clinical standard, urinary albumin. The classifier was also more sensitive for identifying patients with rapidly progressing CKD. Compared with the combination of baseline eGFR and albuminuria (area under the curve [AUC]=0.758), the addition of the multipeptide biomarker classifier significantly improved CKD risk prediction (AUC=0.831) as assessed by the net reclassification index (0.303±−0.065; P<0.001) and integrated discrimination improvement (0.058±0.014; P<0.001). Correlation of individual urinary peptides with CKD stage and progression showed that the peptides that associated with CKD, irrespective of CKD stage or CKD progression, were either fragments of the major circulating proteins, suggesting failure of the glomerular filtration barrier sieving properties, or different collagen fragments, suggesting accumulation of intrarenal extracellular matrix. Furthermore, protein fragments associated with progression of CKD originated mostly from proteins related to inflammation and tissue repair. Results of this study suggest that urinary proteome analysis might significantly improve the current state of the art of CKD detection and outcome prediction and that identification of the urinary peptides allows insight into various ongoing pathophysiologic processes in CKD. PMID:25589610

  9. A comparative study on the efficacy of solifenacin succinate in patients with urinary frequency with or without urgency.

    Directory of Open Access Journals (Sweden)

    Ji-Yeon Han

    Full Text Available OBJECTIVES: Patients with overactive bladder (OAB often have trouble perceiving urgency because of difficulties in distinguishing between urgency and desire to void. Empirical antimuscarinic treatment of patients with frequency only may be reasonable if conservative management has failed. We compared the efficacy of solifenacin in patients with frequency with or without urgency. MATERIALS AND METHODS: This multicenter, 12-week, open-label, comparative, non-inferiority clinical trial assessed whether the solifenacin efficacy for frequency without urgency is non-inferior to its efficacy for frequency with urgency. All patients had micturition frequency ≥ 8 voids/day with or without urgency. Primary efficacy variable: daily frequency change at 12 weeks relative to baseline. Secondary efficacy variables: change at 12 weeks relative to baseline in Patients' Perception of Bladder Condition (PPBC, OAB Symptom Score (OABSS, and Benefit, Satisfaction, Willingness to continue (BSW questionnaire. RESULTS: Of the 286 enrolled patients, 240 (83.9% completed the study (without urgency n = 115; with urgency n = 125. Full dataset analysis revealed that the groups without and with urgency exhibited significant reductions in daily micturition frequency of -2.49 ± 0.35 (mean ± standard error and -2.63 ± 0.37, respectively. The lower limit of the 95% two-sided CI of the comparison of the two group means was -1.14, which is smaller than the -0.8 margin of clinical equivalence. The two groups did not differ in improvement in PPBC, OABSS, or BSW scores. Both tolerated the treatment well. CONCLUSIONS: It was not possible to verify that the solifenacin efficacy for frequency alone was non-inferior to its efficacy for OAB. Nevertheless, solifenacin tended to be effective for frequency regardless of urgency. TRIAL REGISTRATION: ClinicalTrials.gov NCT00979472.

  10. Alterations of urinary metabolite profile in model diabetic nephropathy

    Energy Technology Data Exchange (ETDEWEB)

    Stec, Donald F. [Vanderbilt Institute of Chemical Biology, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Wang, Suwan; Stothers, Cody [Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Avance, Josh [Berea College, 1916 CPO, Berea, KY 40404 (United States); Denson, Deon [Choctaw Central High School, Philadelphia, MS 39350 (United States); Harris, Raymond [Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232 (United States); Voziyan, Paul, E-mail: paul.voziyan@vanderbilt.edu [Department of Medicine, Vanderbilt University Medical Center, Nashville, TN 37232 (United States)

    2015-01-09

    Highlights: • {sup 1}H NMR spectroscopy was employed to study urinary metabolite profile in diabetic mouse models. • Mouse urinary metabolome showed major changes that are also found in human diabetic nephropathy. • These models can be new tools to study urinary biomarkers that are relevant to human disease. - Abstract: Countering the diabetes pandemic and consequent complications, such as nephropathy, will require better understanding of disease mechanisms and development of new diagnostic methods. Animal models can be versatile tools in studies of diabetic renal disease when model pathology is relevant to human diabetic nephropathy (DN). Diabetic models using endothelial nitric oxide synthase (eNOS) knock-out mice develop major renal lesions characteristic of human disease. However, it is unknown whether they can also reproduce changes in urinary metabolites found in human DN. We employed Type 1 and Type 2 diabetic mouse models of DN, i.e. STZ-eNOS{sup −/−} C57BLKS and eNOS{sup −/−} C57BLKS db/db, with the goal of determining changes in urinary metabolite profile using proton nuclear magnetic resonance (NMR). Six urinary metabolites with significantly lower levels in diabetic compared to control mice have been identified. Specifically, major changes were found in metabolites from tricarboxylic acid (TCA) cycle and aromatic amino acid catabolism including 3-indoxyl sulfate, cis-aconitate, 2-oxoisocaproate, N-phenyl-acetylglycine, 4-hydroxyphenyl acetate, and hippurate. Levels of 4-hydroxyphenyl acetic acid and hippuric acid showed the strongest reverse correlation to albumin-to-creatinine ratio (ACR), which is an indicator of renal damage. Importantly, similar changes in urinary hydroxyphenyl acetate and hippurate were previously reported in human renal disease. We demonstrated that STZ-eNOS{sup −/−} C57BLKS and eNOS{sup −/−} C57BLKS db/db mouse models can recapitulate changes in urinary metabolome found in human DN and therefore can be

  11. Biomarker analysis of Morquio syndrome: identification of disease state and drug responsive markers

    Directory of Open Access Journals (Sweden)

    Martell Lisa

    2011-12-01

    Full Text Available Abstract Background This study was conducted to identify potential biomarkers that could be used to evaluate disease progression and monitor responses to enzyme replacement therapy (ERT in patients with mucopolysaccharidosis (MPS IVA. Methods Levels of 88 candidate biomarkers were compared in plasma samples from 50 healthy controls and 78 MPSIVA patients not receiving ERT to test for significant correlations to the presence of MPSIVA. MPSIVA samples were also tested for correlations between candidate biomarkers and age, endurance, or urinary keratin sulfate (KS levels. Then, levels of the same 88 analytes were followed over 36 weeks in 20 MPSIVA patients receiving ERT to test for significant correlations related to ERT, age, or endurance. Results Nineteen candidate biomarkers were significantly different between MPSIVA and unaffected individuals. Of these, five also changed significantly in response to ERT: alpha-1-antitrypsin, eotaxin, lipoprotein(a, matrix metalloprotein (MMP-2, and serum amyloid P. Three of these were significantly lower in MPSIVA individuals versus unaffected controls and were increased during ERT: alpha-1-antitrypsin, lipoprotein(a, and serum amyloid P. Conclusions Candidate biomarkers alpha-1-antitrypsin, lipoprotein(a, and serum amyloid P may be suitable markers, in addition to urinary KS, to follow the response to ERT in MPSIVA patients.

  12. Virtual non-contrast dual-energy CT compared to single-energy CT of the urinary tract: a prospective study

    Energy Technology Data Exchange (ETDEWEB)

    Lundin, Margareta; Liden, Mats; Geijer, Haakan; Andersson, Torbjoern [Dept. of Radiology, Oerebro Univ. Hospital, Oerebro Univ., Oerebro (Sweden)], E-mail: margareta.lundin@orebroll.se; Magnuson, Anders [Clinical Epidemiology and Biostatistic Unit, Oerebro Univ. Hospital, Oerebro (Sweden); Mohammed, Ahmed Abdulilah [Dept. of Radiology, Linkoeping Univ. Hospital, Linkoeping (Sweden); Persson, Anders [CMIV Center for Medical Image Science and Visualization, Linkoeping (Sweden)

    2012-07-15

    Background. Dual-energy computed tomography (DECT) has been shown to be useful for subtracting bone or calcium in CT angiography and gives an opportunity to produce a virtual non-contrast-enhanced (VNC) image from a series where contrast agents have been given intravenously. High noise levels and low resolution have previously limited the diagnostic value of the VNC images created with the first generation of DECT. With the recent introduction of a second generation of DECT, there is a possibility of obtaining VNC images with better image quality at hopefully lower radiation dose compared to the previous generation. Purpose. To compare the image quality of the single-energy series to a VNC series obtained with a two generations of DECT scanners. CT of the urinary tract was used as a model. Material and Methods. Thirty patients referred for evaluation of hematuria were examined with an older system (Somatom Definition) and another 30 patients with a new generation (Somatom Definition Flash). One single-energy series was obtained before and one dual-energy series after administration of intravenous contrast media. We created a VNC series from the contrast-enhanced images. Images were assessed concerning image quality with a visual grading scale evaluation of the VNC series with the single-energy series as gold standard. Results. The image quality of the VNC images was rated inferior to the single-energy variant for both scanners, OR 11.5-67.3 for the Definition and OR 2.1-2.8 for the Definition Flash. Visual noise and overall quality were regarded as better with Flash than Definition. Conclusion. Image quality of VNC images obtained with the new generation of DECT is still slightly inferior compared to native images. However, the difference is smaller with the new compared to the older system.

  13. Liquid-Liquid Extraction and Solid Phase Extraction for Urinary Organic Acids: A Comparative Study from a Resource Constraint Setting.

    Science.gov (United States)

    Kumari, Chandrawati; Varughese, Bijo; Ramji, Siddarth; Kapoor, Seema

    2016-10-01

    Pre analytical process of extraction for accurate detection of organic acids is a crucial step in diagnosis of organic acidemias by GCMS analysis. This process is accomplished either by solid phase extraction (SPE) or by liquid-liquid extraction (LLE). Both extraction procedures are used in different metabolic laboratories all over the world. In this study we compared these two extraction procedures in respect of precision, accuracy, percent recovery of metabolites, number of metabolites isolated, time and cost in a resource constraint setup. We observed that the mean recovery from SPE was 84.1 % and by LLE it was 77.4 % (p value <0.05). Moreover, the average number of metabolites isolated by SPE and LLE was 161.8 ± 18.6 and 140.1 ± 20.4 respectively. The processing cost of LLE was economical. In a cost constraint setting using LLE may be the practical option if used for organic acid analysis.

  14. Comparing Catheter-Associated Urinary Tract Infection Prevention Programs Between Veterans Affairs Nursing Homes and Non-Veterans Affairs Nursing Homes.

    Science.gov (United States)

    Mody, Lona; Greene, M Todd; Saint, Sanjay; Meddings, Jennifer; Trautner, Barbara W; Wald, Heidi L; Crnich, Christopher; Banaszak-Holl, Jane; McNamara, Sara E; King, Beth J; Hogikyan, Robert; Edson, Barbara S; Krein, Sarah L

    2017-03-01

    OBJECTIVE The impact of healthcare system integration on infection prevention programs is unknown. Using catheter-associated urinary tract infection (CAUTI) prevention as an example, we hypothesize that US Department of Veterans Affairs (VA) nursing homes have a more robust infection prevention infrastructure due to integration and centralization compared with non-VA nursing homes. SETTING VA and non-VA nursing homes participating in the AHRQ Safety Program for Long-Term Care collaborative. METHODS Nursing homes provided baseline information about their infection prevention programs to assess strengths and gaps related to CAUTI prevention via a needs assessment questionnaire. RESULTS A total of 353 of 494 nursing homes from 41 states (71%; 47 VA and 306 non-VA facilities) responded. VA nursing homes reported more hours per week devoted to infection prevention-related activities (31 vs 12 hours; Phomes reported tracking CAUTI rates (94% vs 66%; Phomes reported having policies for appropriate catheter use (64% vs 81%; P=.004) and catheter insertion (83% vs 94%; P=.004). CONCLUSIONS Among nursing homes participating in an AHRQ-funded collaborative, VA and non-VA nursing homes differed in their approach to CAUTI prevention. Best practices from both settings should be applied universally to create an optimal infection prevention program within emerging integrated healthcare systems. Infect Control Hosp Epidemiol 2017;38:287-293.

  15. Protein Complexes in Urine Interfere with Extracellular Vesicle Biomarker Studies

    OpenAIRE

    Magda Wachalska; Danijela Koppers-Lalic; Monique van Eijndhoven; Michiel Pegtel; Geldof, Albert A.; Lipinska, Andrea D.; R. Jeroen van Moorselaar; Irene V. Bijnsdorp

    2016-01-01

    Urine exosomes (extracellular vesicles; EVs) contain (micro)RNA (miRNA) and protein biomarkers that are useful for the non-invasive diagnosis of various urological diseases. However, the urinary Tamm-Horsfall protein (THP) complex, which forms at reduced temperatures, may affect EV isolation and may also lead to contamination by other molecules including microRNAs (miRNAs). There‐ fore, we compared the levels of three miRNAs within the purified EV fraction and THP- protein-network. Urine was ...

  16. Comparing illicit drug use in 19 European cities through sewage analysis

    NARCIS (Netherlands)

    K.V. Thomas; L. Bijlsma; S. Castiglioni; A. Covaci; E. Emke; R. Grabic; F. Hernández; S. Karolak; B. Kasprzyk-Hordern; R.H. Lindberg; A. Meierjohann; C. Ort; Y. Pico; J. Quintana; M. Reid; J. Rieckermann; S. Terzic; A.L.N. van Nuijs; P. de Voogt

    2012-01-01

    The analysis of sewage for urinary biomarkers of illicit drugs is a promising and complementary approach for estimating the use of these substances in the general population. For the first time, this approach was simultaneously applied in 19 European cities, making it possible to directly compare il

  17. Comparing illicit drug use in 19 European cities through sewage analysis

    NARCIS (Netherlands)

    Thomas, K.V.; Bijlsma, L.; Castiglioni, S.; Covaci, A.; Emke, E.; Grabic, R.; Hernández, F.; Karolak, S.; Kasprzyk-Hordern, B.; Lindberg, R.H.; Meierjohann, A.; Ort, C.; Pico, Y.; Quintana, J.; Reid, M.; Rieckermann, J.; Terzic, S.; van Nuijs, A.L.N.; de Voogt, P.

    2012-01-01

    The analysis of sewage for urinary biomarkers of illicit drugs is a promising and complementary approach for estimating the use of these substances in the general population. For the first time, this approach was simultaneously applied in 19 European cities, making it possible to directly compare

  18. Concentrations versus amounts of biomarkers in urine: a comparison of approaches to assess pyrethroid exposure

    Directory of Open Access Journals (Sweden)

    Bouchard Michèle

    2008-11-01

    Full Text Available Abstract Background Assessment of human exposure to non-persistent pesticides such as pyrethroids is often based on urinary biomarker measurements. Urinary metabolite levels of these pesticides are usually reported in volume-weighted concentrations or creatinine-adjusted concentrations measured in spot urine samples. It is known that these units are subject to intra- and inter-individual variations. This research aimed at studying the impact of these variations on the assessment of pyrethroid absorbed doses at individual and population levels. Methods Using data obtained from various adult and infantile populations, the intra and inter-individual variability in the urinary flow rate and creatinine excretion rate was first estimated. Individual absorbed doses were then calculated using volume-weighted or creatinine-adjusted concentrations according to published approaches and compared to those estimated from the amounts of biomarkers excreted in 15- or 24-h urine collections, the latter serving as a benchmark unit. The effect of the units of measurements (volume-weighted or creatinine adjusted concentrations or 24-h amounts on results of the comparison of pyrethroid biomarker levels between two populations was also evaluated. Results Estimation of daily absorbed doses of permethrin from volume-weighted or creatinine-adjusted concentrations of biomarkers was found to potentially lead to substantial under or overestimation when compared to doses reconstructed directly from amounts excreted in urine during a given period of time (-70 to +573% and -83 to +167%, respectively. It was also shown that the variability in creatinine excretion rate and urinary flow rate may introduce a bias in the case of between population comparisons. Conclusion The unit chosen to express biomonitoring data may influence the validity of estimated individual absorbed dose as well as the outcome of between population comparisons.

  19. [Microalbuminuria and urinary albumin excretion in clinical practice].

    Science.gov (United States)

    Tagle, Rodrigo; González, Fernando; Acevedo, Mónica

    2012-06-01

    Microalbuminuria is a new tool in the management of patients with diabetes mellitus or hypertension. Microalbuminuria is an easily measured biomarker in a urine sample. Urinary albumin to creatinine ratio in first morning urine sample correlates with 24 hours urinary albumin excretion, but it is easier to obtain, and can identify hypertensive or diabetic patients with high risk for cardiovascular events. Therapeutic interventions such as renin angiotensin system blockade have demonstrated their usefulness in reducing urinary albumin excretion in clinical studies. It would be advisable to incorporate urinary albumin to creatinine ratio to the routine clinical monitoring of patients with cardiovascular risk, such as those with hypertension and diabetes mellitus.

  20. Urinary tract infection - adults

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000521.htm Urinary tract infection - adults To use the sharing features on this page, please enable JavaScript. A urinary tract infection, or UTI, is an infection of the urinary ...

  1. Urinary tract infection - children

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/000505.htm Urinary tract infection - children To use the sharing features on this page, please enable JavaScript. A urinary tract infection is an infection of the urinary tract. This ...

  2. Urinary Tract Infection

    Science.gov (United States)

    Urinary tract infection (UTI) Overview By Mayo Clinic Staff A urinary tract infection (UTI) is an infection in any part of ... UTI spreads to your kidneys. Doctors typically treat urinary tract infections with antibiotics. But you can take steps to ...

  3. Laparoscopic versus open nephroureterectomy for the treatment of upper urinary tract urothelial carcinoma: a systematic review and cumulative analysis of comparative studies.

    Science.gov (United States)

    Ni, Shaobin; Tao, Weiyang; Chen, Qiyin; Liu, Lianxin; Jiang, Hongchi; Hu, Hailong; Han, Ruifa; Wang, Chunyang

    2012-06-01

    Laparoscopic nephroureterectomy (LNU) has increasingly been used as a minimally invasive alternative to open nephroureterectomy (ONU), but studies comparing the efficacy and safety of the two surgical procedures are still limited. Evaluate the oncologic and perioperative outcomes of LNU versus ONU in the treatment of upper urinary tract urothelial carcinoma. A systematic review and cumulative analysis of comparative studies reporting both oncologic and perioperative outcomes of LNU and ONU was performed through a comprehensive search of the Medline, Embase, and the Cochrane Library electronic databases. All analyses were performed using the Review Manager (RevMan) v.5 (Nordic Cochrane Centre, Copenhagen, Denmark) and Meta-analysis In eXcel (MIX) 2.0 Pro (BiostatXL) software packages. Twenty-one eligible studies (1235 cases and 3093 controls) were identified. A significantly higher proportion of pTa/Tis was observed in LNU compared to ONU (27.52% vs 22.59%; p = 0.047), but there were no significant differences in other stages and pathologic grades (all p>0.05). For patients who underwent LNU, the 5-yr cancer-specific survival (CSS) rate was significantly higher, at 9% (p = 0.03), compared to those who underwent ONU, while the overall recurrence rate and bladder recurrence rate were notably lower, at 15% (p = 0.01) and 17% (p = 0.02), respectively. However, there were no statistically significant differences in 2-yr CSS, 5-yr recurrence-free survival (RFS), 5-yr overall survival (OS), 2-yr OS, and metastasis rates between LNU and ONU (all p>0.05). Moreover, there were no significant differences between LNU and ONU in terms of intraoperative complications, postoperative complications, and perioperative mortality (all p>0.05). The results of our study were mainly limited by the retrospective design of most of the individual studies included as well as selection biases based on different management of regional lymph nodes and pathologic characteristics. Our data suggest

  4. Clinical efficacy and tolerability of praziquantel for intestinal and urinary schistosomiasis-a meta-analysis of comparative and non-comparative clinical trials.

    Directory of Open Access Journals (Sweden)

    Julien Zwang

    Full Text Available Extensive use of praziquantel for treatment and control of schistosomiasis requires a comprehensive understanding of efficacy and safety of various doses for different Schistosoma species.A systematic review and meta-analysis of comparative and non-comparative trials of praziquantel at any dose for any Schistosoma species assessed within two months post-treatment. Of 273 studies identified, 55 were eligible (19,499 subjects treated with praziquantel, control treatment or placebo. Most studied were in school-aged children (64%, S. mansoni (58%, and the 40 mg/kg dose (56%; 68% of subjects were in Africa. Efficacy was assessed as cure rate (CR, n=17,017 and egg reduction rate (ERR, n=13,007; safety as adverse events (AE incidence. The WHO-recommended dose of praziquantel 40 mg/kg achieved CRs of 94.7% (95%CI 92.2-98.0 for S. japonicum, 77.1% (68.4-85.1 for S. haematobium, 76.7% (95%CI 71.9-81.2 for S. mansoni, and 63.5% (95%CI 48.2-77.0 for mixed S. haematobium/S. mansoni infections. Using a random-effect meta-analysis regression model, a dose-effect for CR was found up to 40 mg/kg for S. mansoni and 30 mg/kg for S. haematobium. The mean ERR was 95% for S. japonicum, 94.1% for S. haematobium, and 86.3% for S. mansoni. No significant relationship between dose and ERR was detected. Tolerability was assessed in 40 studies (12,435 subjects. On average, 56.9% (95%CI 47.4-67.9 of the subjects receiving praziquantel 40 mg/kg experienced an AE. The incidence of AEs ranged from 2.3% for urticaria to 31.1% for abdominal pain.The large number of subjects allows generalizable conclusions despite the inherent limitations of aggregated-data meta-analyses. The choice of praziquantel dose of 40 mg/kg is justified as a reasonable compromise for all species and ages, although in a proportion of sites efficacy may be lower than expected and age effects could not be fully explored.

  5. [Novel biomarkers for diabetic nephropathy].

    Science.gov (United States)

    Araki, Shin-ichi

    2014-02-01

    Diabetic nephropathy is a leading cause of end-stage renal disease worldwide. An early clinical sign of this complication is an increase of urinary albumin excretion, called microalbuminuria, which is not only a predictor of the progression of nephropathy, but also an independent risk factor for cardiovascular disease. Although microalbuminuria is clinically important to assess the prognosis of diabetic patients, it may be insufficient as an early and specific biomarker of diabetic nephropathy because of a large day-to-day variation and lack of a good correlation of microalbuminuria with renal dysfunction and pathohistological changes. Thus, more sensitive and specific biomarkers are needed to improve the diagnostic capability of identifying patients at high risk. The factors involved in renal tubulo-interstitial damage, the production and degradation of extracellular matrix, microinflammation, etc., are investigated as candidate molecules. Despite numerous efforts so far, the assessment of these biomarkers is still a subject of ongoing investigations. Recently, a variety of omics and quantitative techniques in systems biology are rapidly emerging in the field of biomarker discovery, including proteomics, transcriptomics, and metabolomics, and they have been applied to search for novel putative biomarkers of diabetic nephropathy. Novel biomarkers or their combination with microalbuminuria provide a better diagnostic accuracy than microalbuminuria alone, and may be useful for establishing personal medicine. Furthermore, the identification of novel biomarkers may provide insight into the mechanisms underlying diabetic nephropathy.

  6. Determination of Urinary Neopterin/Creatinine Ratio to Distinguish Active Tuberculosis from Latent Mycobacterium tuberculosis Infection

    Directory of Open Access Journals (Sweden)

    Michael Eisenhut

    2016-01-01

    Full Text Available Background. Biomarkers to distinguish latent from active Mycobacterium (M. tuberculosis infection in clinical practice are lacking. The urinary neopterin/creatinine ratio can quantify the systemic interferon-gamma effect in patients with M. tuberculosis infection. Methods. In a prospective observational study, urinary neopterin levels were measured by enzyme linked immunosorbent assay in patients with active tuberculosis, in people with latent M. tuberculosis infection, and in healthy controls and the urinary neopterin/creatinine ratio was calculated. Results. We included a total of 44 patients with M. tuberculosis infection and nine controls. 12 patients had active tuberculosis (8 of them culture-confirmed. The median age was 15 years (range 4.5 to 49. Median urinary neopterin/creatinine ratio in patients with active tuberculosis was 374.1 micromol/mol (129.0 to 1072.3, in patients with latent M. tuberculosis infection it was 142.1 (28.0 to 384.1, and in controls it was 146.0 (40.3 to 200.0, with significantly higher levels in patients with active tuberculosis (p<0.01. The receiver operating characteristics curve had an area under the curve of 0.84 (95% CI 0.70 to 0.97 (p<0.01. Conclusions. Urinary neopterin/creatinine ratios are significantly higher in patients with active tuberculosis compared to patients with latent infection and may be a significant predictor of active tuberculosis in patients with M. tuberculosis infection.

  7. Urinary miR-29 correlates with albuminuria and carotid intima-media thickness in type 2 diabetes patients.

    Directory of Open Access Journals (Sweden)

    Hui Peng

    Full Text Available BACKGROUND: Cell-free microRNAs stably and abundantly exist in body fluids and emerging evidence suggests cell-free microRNAs as novel and non-invasive disease biomarker. Deregulation of miR-29 is involved in the pathogenesis of diabetic nephropathy and insulin resistance thus may be implicated in diabetic vascular complication. Therefore, we investigated the possibility of urinary miR-29 as biomarker for diabetic nephropathy and atherosclerosis in patients with type 2 diabetes. METHODS: 83 patients with type 2 diabetes were enrolled in this study, miR-29a, miR-29b and miR-29c levels in urine supernatant was determined by TaqMan qRT-PCR, and a synthetic cel-miR-39 was added to the urine as a spike-in control before miRNAs extraction. Urinary albumin excretion rate and urine albumin/creatinine ratio, funduscopy and carotid ultrasound were used for evaluation of diabetic vascular complication. The laboratory parameters indicating blood glucose level, renal function and serum lipids were also collected. RESULTS: Patients with albuminuria (n = 42, age 60.62 ± 12.00 yrs showed significantly higher comorbidity of diabetic retinopathy (p = 0.015 and higher levels of urinary miR-29a (p = 0.035 compared with those with normoalbuminuria (n = 41, age 58.54 ± 14.40 yrs. There was no significant difference in urinary miR-29b (p = 0.148 or miR-29c level (p = 0.321 between groups. Urinary albumin excretion rate significantly correlated with urinary miR-29a level (r = 0.286, p = 0.016, while urinary miR-29b significantly correlated with carotid intima-media thickness (cIMT (r = 0.286, p = 0.046. CONCLUSION: Urinary miR-29a correlated with albuminuria while urinary miR-29b correlated with carotid intima-media thickness (cIMT in patients with type 2 diabetes. Therefore, they may have the potential to serve as alternative biomarker for diabetic nephropathy and atherosclerosis in type 2 diabetes.

  8. Urine biomarkers of tubular injury do not improve on the clinical model predicting chronic kidney disease progression.

    Science.gov (United States)

    Hsu, Chi-Yuan; Xie, Dawei; Waikar, Sushrut S; Bonventre, Joseph V; Zhang, Xiaoming; Sabbisetti, Venkata; Mifflin, Theodore E; Coresh, Josef; Diamantidis, Clarissa J; He, Jiang; Lora, Claudia M; Miller, Edgar R; Nelson, Robert G; Ojo, Akinlolu O; Rahman, Mahboob; Schelling, Jeffrey R; Wilson, Francis P; Kimmel, Paul L; Feldman, Harold I; Vasan, Ramachandran S; Liu, Kathleen D

    2017-01-01

    Few investigations have evaluated the incremental usefulness of tubular injury biomarkers for improved prediction of chronic kidney disease (CKD) progression. As such, we measured urinary kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, N-acetyl-ß-D-glucosaminidase and liver fatty acid binding protein under highly standardized conditions among 2466 enrollees of the prospective Chronic Renal Insufficiency Cohort Study. During 9433 person-years of follow-up, there were 581 cases of CKD progression defined as incident end-stage renal disease or halving of the estimated glomerular filtration rate. Levels of the urine injury biomarkers, normalized for urine creatinine, were strongly associated with CKD progression in unadjusted Cox proportional hazard models with hazard ratios in the range of 7 to 15 comparing the highest with the lowest quintiles. However, after controlling for the serum creatinine-based estimated glomerular filtration rate and urinary albumin/creatinine ratio, none of the normalized biomarkers was independently associated with CKD progression. None of the biomarkers improved on the high (0.89) C-statistic for the base clinical model. Thus, among patients with CKD, risk prediction with a clinical model that includes the serum creatinine-based estimated glomerular filtration rate and the urinary albumin/creatinine ratio is not improved on with the addition of renal tubular injury biomarkers. Copyright © 2016 International Society of Nephrology. All rights reserved.

  9. Relationship of urinary isoprostanes to prostate cancer occurrence.

    Science.gov (United States)

    Brys, Magdalena; Morel, Agnieszka; Forma, Ewa; Krzeslak, Anna; Wilkosz, Jacek; Rozanski, Waldemar; Olas, Beata

    2013-01-01

    To estimate the oxidative stress in patients with prostate cancer and in a control group, we used the biomarker of lipid peroxidation-isoprostanes (8-isoPGF(2)) and the level of selected antioxidants (glucose and uric acid [UA]). The level of urinary isoprostanes was determined in patients and controls using an immunoassay kit according to the manufacturer's instruction. The levels of UA and glucose were also determined in serum by the use of UA Assay Kit and Glucose Assay Kit. We observed a statistically increased the level of isoprostanes in urine of patients with prostate cancer in compared with a control group. The concentration of tested antioxidants in blood from patients with prostate cancer was also higher than in healthy subjects. Moreover, our experiments indicate that the correlation between the increased amount of UA and the lipid peroxidation exists in prostate cancer patients (in all tested groups). Prostate cancer risk by urinary isoprostanes level was analyzed, and a positive association was found (relative risk for highest vs. lowest quartile of urinary isoprostanes = 1.6; 95 % confidence interval 1.2-2.4; p for trend = 0.03). We suggest that reactive oxygen species induce peroxidation of unsaturated fatty acid in patients with prostate cancer, and the level of isoprostanes may be used as a non-invasive marker for determination of oxidative stress. We also propose that UA may enhance the oxidative stress in patients with prostate cancer.

  10. Urinary neutrophil gelatinase-associated lipocalin and cystatin C compared to the estimated glomerular filtration rate to predict risk in patients with suspected acute myocardial infarction.

    Science.gov (United States)

    von Jeinsen, Beatrice; Kraus, Daniel; Palapies, Lars; Tzikas, Stergios; Zeller, Tanja; Schauer, Anne; Drechsler, Christiane; Bickel, Christoph; Baldus, Stephan; Lackner, Karl J; Münzel, Thomas; Blankenberg, Stefan; Zeiher, Andreas M; Keller, Till

    2017-10-15

    Impaired renal function, reflected by estimated glomerular filtration rate (eGFR) or cystatin C, is a strong risk predictor in the presence of acute myocardial infarction (AMI). Urinary neutrophil gelatinase-associated lipocalin (uNGAL) is an early marker of acute kidney injury. uNGAL might also be a good predictor of outcome in patients with cardiovascular disease. Aim of the present study was to evaluate the prognostic value of uNGAL compared to eGFR and cystatin C in patients with suspected AMI. 1818 patients were enrolled with suspected AMI. Follow-up information on the combined endpoint of death or non-fatal myocardial infarction was obtained 6months after enrolment and was available in 1804 patients. 63 events (3.5%) were registered. While cystatin C and eGFR were strong risk predictors for the primary endpoint even adjusted for several variables, uNGAL was not independently associated with outcome: When applied continuously uNGAL was associated with outcome but did not remain a statistically significant predictor after several adjustments (i.e. eGFR). By adding cystatin C or uNGAL to GRACE risk score variables, only cystatin C could improve the predictive value while uNGAL showed no improvement. We could show that cystatin C is an independent risk predictor in patients with suspected AMI and cystatin C can add improvement to the commonly used GRACE risk score. In contrast uNGAL is not independently associated with outcome and seems not to add further prognostic information to GRACE risk score. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Biomarkers of mercury exposure in two eastern Ukraine cities

    Science.gov (United States)

    Gibb, H.; Haver, C.; Kozlov, K.; Centeno, J.A.; Jurgenson, V.; Kolker, A.; Conko, K.M.; Landa, E.R.; Xu, H.

    2011-01-01

    This study evaluates biomarkers of mercury exposure among residents of Horlivka, a city in eastern Ukraine located in an area with geologic and industrial sources of environmental mercury, and residents of Artemivsk, a nearby comparison city outside the mercury-enriched area. Samples of urine, blood, hair, and nails were collected from study participants, and a questionnaire was administered to obtain data on age, gender, occupational history, smoking, alcohol consumption, fish consumption, tattoos, dental amalgams, home heating system, education, source of drinking water, and family employment in mines. Median biomarker mercury concentrations in Artemivsk were 0.26 ??g/g-Cr (urine), 0.92 ??g/L (blood), 0.42 ??g/g (hair), 0.11 ??g/g (toenails), and 0.09 ??g/g (fingernails); median concentrations in Horlivka were 0.15 ??g/g-Cr (urine), 1.01 ??g/L (blood), 0.14 ??g/g (hair), 0.31 ??g/g (toenails), and 0.31 ??g/g (fingernails). Biomarkers of mercury exposure for study participants from Horlivka and Artemivsk are low in comparison with occupationally exposed workers at a mercury recycling facility in Horlivka and in comparison with exposures known to be associated with clinical effects. Blood and urinary mercury did not suggest a higher mercury exposure among Horlivka residents as compared with Artemivsk; however, three individuals living in the immediate vicinity of the mercury mines had elevated blood and urinary mercury, relative to overall results for either city. For a limited number of residents from Horlivka (N = 7) and Artemivsk (N = 4), environmental samples (vacuum cleaner dust, dust wipes, soil) were collected from their residences. Mercury concentrations in vacuum cleaner dust and soil were good predictors of blood and urinary mercury. Copyright ?? 2011 JOEH, LLC.

  12. Biomarkers of mercury exposure in two eastern Ukraine cities.

    Science.gov (United States)

    Gibb, Herman; Haver, Cary; Kozlov, Kostj; Centeno, Jose A; Jurgenson, Vera; Kolker, Allan; Conko, Kathryn M; Landa, Edward R; Xu, Hanna

    2011-04-01

    This study evaluates biomarkers of mercury exposure among residents of Horlivka, a city in eastern Ukraine located in an area with geologic and industrial sources of environmental mercury, and residents of Artemivsk, a nearby comparison city outside the mercury-enriched area. Samples of urine, blood, hair, and nails were collected from study participants, and a questionnaire was administered to obtain data on age, gender, occupational history, smoking, alcohol consumption, fish consumption, tattoos, dental amalgams, home heating system, education, source of drinking water, and family employment in mines. Median biomarker mercury concentrations in Artemivsk were 0.26 μg/g-Cr (urine), 0.92 μg/L (blood), 0.42 μg/g (hair), 0.11 μg/g (toenails), and 0.09 μg/g (fingernails); median concentrations in Horlivka were 0.15 μg/g-Cr (urine), 1.01 μg/L (blood), 0.14 μg/g (hair), 0.31 μg/g (toenails), and 0.31 μg/g (fingernails). Biomarkers of mercury exposure for study participants from Horlivka and Artemivsk are low in comparison with occupationally exposed workers at a mercury recycling facility in Horlivka and in comparison with exposures known to be associated with clinical effects. Blood and urinary mercury did not suggest a higher mercury exposure among Horlivka residents as compared with Artemivsk; however, three individuals living in the immediate vicinity of the mercury mines had elevated blood and urinary mercury, relative to overall results for either city. For a limited number of residents from Horlivka (N = 7) and Artemivsk (N = 4), environmental samples (vacuum cleaner dust, dust wipes, soil) were collected from their residences. Mercury concentrations in vacuum cleaner dust and soil were good predictors of blood and urinary mercury.

  13. Comparative effectiveness of biomarkers and clinical indicators for predicting outcomes of SSRI treatment in Major Depressive Disorder: results of the BRITE-MD study.

    Science.gov (United States)

    Leuchter, Andrew F; Cook, Ian A; Marangell, Lauren B; Gilmer, William S; Burgoyne, Karl S; Howland, Robert H; Trivedi, Madhukar H; Zisook, Sidney; Jain, Rakesh; McCracken, James T; Fava, Maurizio; Iosifescu, Dan; Greenwald, Scott

    2009-09-30

    Patients with Major Depressive Disorder (MDD) may not respond to antidepressants for 8 weeks or longer. A biomarker that predicted treatment effectiveness after only 1 week could be clinically useful. We examined a frontal quantitative electroencephalographic (QEEG) biomarker, the Antidepressant Treatment Response (ATR) index, as a predictor of response to escitalopram, and compared ATR with other putative predictors. Three hundred seventy-five subjects meeting DSM-IV criteria for MDD had a baseline QEEG study. After 1 week of treatment with escitalopram, 10 mg, a second QEEG was performed, and the ATR was calculated. Subjects then were randomly assigned to continue with escitalopram, 10 mg, or change to alternative treatments. Seventy-three evaluable subjects received escitalopram for a total of 49days. Response and remission rates were 52.1% and 38.4%, respectively. The ATR predicted both response and remission with 74% accuracy. Neither serum drug levels nor 5HTTLPR and 5HT2a genetic polymorphisms were significant predictors. Responders had larger decreases in Hamilton Depression Rating Scale (Ham-D(17)) scores at day 7 (P=0.005), but remitters did not. Clinician prediction based upon global impression of improvement at day 7 did not predict outcome. Logistic regression showed that the ATR and early Ham-D(17) changes were additive predictors of response, but the ATR was the only significant predictor of remission. Future studies should replicate these results prior to clinical use.

  14. Diagnostic performance of the urinary canine calgranulins in dogs with lower urinary or urogenital tract carcinoma.

    Science.gov (United States)

    Heilmann, Romy M; McNiel, Elizabeth A; Grützner, Niels; Lanerie, David J; Suchodolski, Jan S; Steiner, Jörg M

    2017-04-21

    Onset of canine transitional cell carcinoma (TCC) and prostatic carcinoma (PCA) is usually insidious with dogs presenting at an advanced stage of the disease. A biomarker that can facilitate early detection of TCC/PCA and improve patient survival would be useful. S100A8/A9 (calgranulin A/B or calprotectin) and S100A12 (calgranulin C) are expressed by cells of the innate immune system and are associated with several inflammatory disorders. S100A8/A9 is also expressed by epithelial cells after malignant transformation and is involved in the regulation of cell proliferation and metastasis. S100A8/A9 is up-regulated in human PCA and TCC, whereas the results for S100A12 have been ambiguous. Also, the urine S100A8/A9-to-S100A12 ratio (uCalR) may have potential as a marker for canine TCC/PCA. Aim of the study was to evaluate the diagnostic accuracy of the urinary S100/calgranulins to detect TCC/PCA in dogs by using data and urine samples from 164 dogs with TCC/PCA, non-neoplastic urinary tract disease, other neoplasms, or urinary tract infections, and 75 healthy controls (nested case-control study). Urine S100A8/A9 and S100A12 (measured by species-specific radioimmunoassays and normalized against urine specific gravity [S100A8/A9USG; S100A12USG], urine creatinine concentration, and urine protein concentration and the uCalR were compared among the groups of dogs. S100A8/A9USG had the highest sensitivity (96%) and specificity (66%) to detect TCC/PCA, with specificity reaching 75% after excluding dogs with a urinary tract infection. The uCalR best distinguished dogs with TCC/PCA from dogs with a urinary tract infection (sensitivity: 91%, specificity: 60%). Using a S100A8/A9USG ≥ 109.9 to screen dogs ≥6 years of age for TCC/PCA yielded a negative predictive value of 100%. S100A8/A9USG and uCalR may have utility for diagnosing TCC/PCA in dogs, and S100A8/A9USG may be a good screening test for canine TCC/PCA.

  15. Urinary Angiotensinogen Is Elevated in Patients with Nephrolithiasis

    Directory of Open Access Journals (Sweden)

    Wei Sun

    2014-01-01

    Full Text Available Background. Elevated urinary angiotensinogen (UA was identified as novel prognostic biomarker capable of predicting chronic kidney disease, and in the present study, we will investigate the diagnostic value of UA in the patients of nephrolithiasis. Methods. Urine angiotensinogen levels and α1-microglobulin were measured by enzyme-linked immunosorbent assay (ELISA in 60 patients presenting with nephrolithiasis and 50 sex- and age-matched healthy volunteers. Estimated glomerular filtration (eGFR was calculated and, by simple regression analysis, the correlation of UA/α1-microglobulin levels and the decline of eGFR were analyzed as well. Results. Median UA levels was significantly increased in the nephrolithiasis patients compared with normal control (1250.78 ± 439.27 versus 219.34 ± 45.27 pg/mL; P1250 pg/mL was significantly higher than those with lower UA levels (<1250 pg/mL [92.23 ± 18.13 μmol/L versus 70.07 ± 11.17 μmol/L; P<0.05]. According to the single variate analysis, UA levels were significantly and positively correlated with urinary α1-microglobulin (r=0.733; P=1.33×10-15, while they were significantly and negatively correlated with eGFR (r=-0.343; P=1.03×10-4. Conclusion. Urinary UA is a novel biomarker for patients with nephrolithiasis, which indicates renal tubular injury. Further study on the molecular pathogenic mechanism of UA and larger scale of clinical trial is required.

  16. A Comparative Study of the Predictive Values of Urinary Acute Kidney Injury Markers Angiogenin and Kidney Injury Molecule 1 for the Outcomes of Kidney Allografts

    Directory of Open Access Journals (Sweden)

    Quentin Tavernier, PhD

    2017-09-01

    Conclusions. Together, our results indicate that, in a cohort of 244 kidney transplant recipients, urinary ANG and KIM-1 levels in a single measurement 10 days after transplantation reflect the severity of IRI after kidney transplantation, but are neither independent predictors of renal function, histological changes and graft survival.

  17. Postcircumcision urinary tract infection.

    Science.gov (United States)

    Cohen, H A; Drucker, M M; Vainer, S; Ashkenasi, A; Amir, J; Frydman, M; Varsano, I

    1992-06-01

    The possible association of urinary tract infection (UTI) with ritual circumcision on the eighth day of life was studied by analyzing the epidemiology of urinary tract infections during the first year of life in 169 children with UTI (56 males and 113 females) born in Israel from 1979 to 1984. Forty-eight percent of the episodes of UTI occurring in males appeared during the 12 days following circumcision, and the increased incidence during that period was highly significant. The median age of the males at the time of the UTI was 16 days, compared with seven months in females. Ritual Jewish circumcision as practiced in Israel may be a predisposing factor for UTI during the 12-day period following that procedure.

  18. Elevation of urinary liver-type fatty acid binding protein after cardiac catheterization related to cardiovascular events

    Directory of Open Access Journals (Sweden)

    Kamijo-Ikemori A

    2015-08-01

    Full Text Available Atsuko Kamijo-Ikemori,1,3 Nobuyuki Hashimoto,2 Takeshi Sugaya,1 Katsuomi Matsui,1 Mikako Hisamichi,1 Yugo Shibagaki,1 Fumihiko Miyake,2 Kenjiro Kimura1 1Department of Nephrology and Hypertension, 2Department of Cardiology, 3Department of Anatomy, St Marianna University School of Medicine, Kawasaki, Kanagawa, Japan Purpose: Contrast medium (CM induces tubular hypoxia via endothelial damage due to direct cytotoxicity or viscosity. Urinary liver-type fatty acid binding protein (L-FABP increases along with tubular hypoxia and may be a detector of systemic circulation injury. The aim of this study was to evaluate the clinical usefulness of detecting increases in urinary L-FABP levels due to administration of CM, as a prognostic biomarker for cardiovascular disease in patients without occurrence of CM-induced nephropathy undergoing cardiac catheterization procedure (CCP. Methods: Retrospective longitudinal analyses of the relationship between urinary L-FABP levels and occurrence of cardiovascular events were performed (n=29. Urinary L-FABP was measured by ELISA before CCP, and at 6, 12, 24, and 48 hours after CCP. Results: Urinary L-FABP levels were significantly higher at 12 hours (P<0.05 and 24 hours (P<0.005 after CCP compared with before CCP, only in the patients with occurrence of cardiovascular events (n=17, but not in those without cardiovascular events (n=12. The parameter with the largest area under the curve (0.816 for predicting the occurrence of cardiovascular events was the change in urinary L-FABP at 24 hours after CCP. The difference in urinary L-FABP levels (ΔL-FABP ≥11.0 µg/g creatinine between before CCP and at 24 hours after CCP was a risk factor for the occurrence of cardiovascular events (hazard ratio, 4.93; 95% confidence interval, 1.27–19.13; P=0.021. Conclusion: Measurement of urinary L-FABP before CCP and at 24 hours after CCP in patients with mild to moderate renal dysfunction may be an important indicator for risk

  19. 粪便及尿液生物标记物用于早期诊断新生儿坏死性小肠结肠炎研究进展%Research progress of fecal and urinary biomarkers for early diagnosis of neonatal necrotizing enterocolitis

    Institute of Scientific and Technical Information of China (English)

    罗丽娟; 李禄全

    2014-01-01

    Necrotizing enterocolitis (NEC) is the most common severe gastrointestinal emergency in neonatal period. Searching biomarkers to identify infants at greatest risk of developing NEC might be of importance for early diagnosis, effective treatment and better prognosis of NEC. Biomarkers from stool and urine attract great attention due to non-invasiveness and easy availability of fecal and urinary sampling. This article reviews the latest research progress of non-invasive biomarkers including intestinal fatty acid binding protein, serum amyloid A, complement C3a and C5a in urine;fecal lactoferrin, intestinal bacteria spectrum, fecal calprotectin, S100A12 and high mobility group box-1 protein.%新生儿坏死性小肠结肠炎(NEC)是新生儿期常见的危重胃肠道疾病。积极探寻早期诊断NEC的生物标记物,对于及时诊断NEC,并采取有效措施改善患儿预后具有重要意义。粪便及尿液生物标记物监测具备无创性的特点,因而受到广泛关注。标志物包括尿液源性的肠源性脂肪酸结合蛋白、血清淀粉样蛋白A、补体C3a和C5a;粪便源性的乳铁蛋白、肠道菌群谱变化、钙卫蛋白、S100A12蛋白及高迁移率族蛋白B1等。文章对这些标志物在应用于早期诊断NEC方面的研究进展作一综述。

  20. Comparative Immunohistochemical Analysis of Ochratoxin A Tumourigenesis in Rats and Urinary Tract Carcinoma in Humans; Mechanistic Significance of p-S6 Ribosomal Protein Expression

    Directory of Open Access Journals (Sweden)

    Sarah Pinder

    2012-09-01

    Full Text Available Ochratoxin A (OTA is considered to be a possible human urinary tract carcinogen, based largely on a rat model, but no molecular genetic changes in the rat carcinomas have yet been defined. The phosphorylated-S6 ribosomal protein is a marker indicating activity of the mammalian target of rapamycin, which is a serine/threonine kinase with a key role in protein biosynthesis, cell proliferation, transcription, cellular metabolism and apoptosis, while being functionally deregulated in cancer. To assess p-S6 expression we performed immunohistochemistry on formalin-fixed and paraffin-embedded tumours and normal tissues. Marked intensity of p-S6 expression was observed in highly proliferative regions of rat renal carcinomas and a rare angiosarcoma, all of which were attributed to prolonged exposure to dietary OTA. Only very small OTA-generated renal adenomas were negative for p-S6. Examples of rat subcutaneous fibrosarcoma and testicular seminoma, as well as of normal renal tissue, showed no or very weak positive staining. In contrast to the animal model, human renal cell carcinoma, upper urinary tract transitional cell carcinoma from cases of Balkan endemic nephropathy, and a human angiosarcoma were negative for p-S6. The combined findings are reminiscent of constitutive changes in the rat tuberous sclerosis gene complex in the Eker strain correlated with renal neoplasms, Therefore rat renal carcinogenesis caused by OTA does not obviously mimic human urinary tract tumourigenesis.

  1. Urinary Peptide Levels in Patients with Chronic Renal Failure

    Directory of Open Access Journals (Sweden)

    Mungli Prakash

    2010-10-01

    Full Text Available Introduction: Peptide levels in urine are found to be decreased in renal failure. In the current study urinary peptide levels were determined in chronic renal failure (CRF patients. Method: 86 CRF patients and 80 healthy controls were selected for the study. Urinary proteins and peptide levels were determined by spectrophotometer based Lowry and Bradford methods. Urinary creatinine levels were determined by clinical chemistry analyzer. Results: There was significant decrease in urinary peptide levels in CRF patients and Urinary % peptides were significantly decreased in CRF patients as compared to healthy controls. Urinary % peptides correlated negatively with proteinuria. Conclusion: we have found decrease in urinary peptides and % urinary peptides in CRF patients and possibly measurement of % urinary peptides may possibly serve as better indicator in early detection of impairment in renal function.

  2. Urinary proteomic diagnosis of coronary artery disease: identification and clinical validation in 623 individuals

    DEFF Research Database (Denmark)

    Delles, Christian; Schiffer, Eric; von Zur Muhlen, Constantin

    2010-01-01

    We studied the urinary proteome in a total of 623 individuals with and without coronary artery disease (CAD) in order to characterize multiple biomarkers that enable prediction of the presence of CAD....

  3. Urinary proteomic diagnosis of coronary artery disease: identification and clinical validation in 623 individuals

    DEFF Research Database (Denmark)

    Delles, Christian; Schiffer, Eric; von Zur Muhlen, Constantin

    2010-01-01

    We studied the urinary proteome in a total of 623 individuals with and without coronary artery disease (CAD) in order to characterize multiple biomarkers that enable prediction of the presence of CAD....

  4. Evaluation of the urinary microbiota of women with uncomplicated stress urinary incontinence.

    Science.gov (United States)

    Thomas-White, Krystal J; Kliethermes, Stephanie; Rickey, Leslie; Lukacz, Emily S; Richter, Holly E; Moalli, Pamela; Zimmern, Philippe; Norton, Peggy; Kusek, John W; Wolfe, Alan J; Brubaker, Linda

    2017-01-01

    Female urinary microbiota are associated with urgency urinary incontinence and response to medication. The urinary microbiota of women with stress urinary incontinence has not been described. We sought to study the cross-sectional relationships between urinary microbiota features and demographic and clinical characteristics of women undergoing stress urinary incontinence surgery. Preoperative urine specimens were collected from women without urinary tract infection and were available from 197 women (174 voided, 23 catheterized) enrolled in a multicenter prospective randomized trial, the Value of Urodynamic Evaluation study. Demographic and clinical variables were obtained including stress and urgency urinary incontinence symptoms, menopausal status, and hormone use. The bacterial composition of the urine was qualitatively assessed by sequencing the bacterial 16S ribosomal RNA gene. Phylogenetic relatedness and microbial alpha diversity were compared to demographics and symptoms using generalized estimating equation models. The majority of 197 urine samples (86%) had detectable bacterial DNA. Bacterial diversity was significantly associated with higher body mass index (P = .02); increased Medical, Epidemiologic, and Social Aspects of Aging urge index score (P = .04); and hormonal status (P microbiota. This cross-sectional analysis revealed that increased diversity of the microbiota was associated with urgency urinary incontinence symptoms, hormonal status, and body mass index. In contrast, the female urinary microbiota were not associated with stress urinary incontinence symptoms. Published by Elsevier Inc.

  5. Urinary acidification and urinary excretion of calcium and citrate in women with bilateral medullary sponge kidney

    DEFF Research Database (Denmark)

    Osther, P J; Mathiasen, Helle; Hansen, A B

    1994-01-01

    Urinary acidification ability, acid-base status and urinary excretion of calcium and citrate were evaluated in 10 women with bilateral medullary sponge kidney (MSK) and in 10 healthy women. Patients with MSK had higher fasting urine pH compared to normal controls (p ....32 +/- 1.45 mmol) compared to patients with normal urinary acidification (3.83 +/- 0.12 mmol) (p normal urinary acidification (23.8 +/- 0.8) and healthy women (22.7 +/- 0.......6) (p urinary excretion of citrate (0.93 +/- 0.25 mmol) compared to patients with normal urinary acidification (3.58 +/- 0.51) and healthy women (2.78 +/- 0.49) (p

  6. Cancer Biomarkers

    OpenAIRE

    Kamel, Hala Fawzy Mohamed; Al-Amodi, Hiba Saeed Bagader

    2016-01-01

    Biomarkers have many potential applications in oncology, including risk assessment, screening, differential diagnosis, determination of prognosis, prediction of response to treatment, and monitoring of progression of disease. Because of the critical role that biomarkers play at all stages of disease, it is important that they undergo rigorous evaluation, including analytical validation, clinical validation, and assessment of clinical utility, prior to incorporation into routine clinical care....

  7. Urinary N-acetyl-beta -D-glucosaminidase and its isoenzymes A & B in workers exposed to cadmium at cadmium plating

    Directory of Open Access Journals (Sweden)

    Rajan BK

    2007-07-01

    Full Text Available Abstract Objective The present study was carried out to determine the effect of cadmium exposure on Urinary N-acetyl-beta -D-glucosaminidase and its isoenzymes A and B in workers exposed at cadmium plating. Methods 50 subjects using cadmium during cadmium plating formed the study group. An equal number of age-sex matched subjects working in administrative section formed the control group. Urinary cadmium levels were determined by using a flameless atomic absorption spectrophotometer. Urinary N-acetyl-beta -D-glucosaminidase and its isoenzymes A and B were determined by using spectrophotmetric method. Results A significant increase of urinary total N-acetyl-beta -D-glucosaminidase and its isoenzymes A and B profiles were noted in study as compared to controls. The levels of urinary N-acetyl-beta -D-glucosaminidase and its isoenzymes A and B profiles were positively and significantly correlated with cadmium levels in urine. Multiple regression analysis was used to assess the effect of urinary cadmium or life style confounding factors (age, BMI, smoking and alcohol consumption on urinary N-acetyl-beta -D-glucosaminidase and its isoenzymes A and B. The analysis showed that the study subjects who had urine cadmium levels greater than 5 μg/g of creatinine, work duration >15 years, smoking and body mass index variables were significantly associated with urinary total N-acetyl-beta -D-glucosaminidase but not on isoenzymes A&B. Conclusion The results presented in this study shows that the increased levels of urinary N-acetyl-beta -D-glucosaminidase observed in cadmium-exposed workers could be used as biomarkers for suggesting preventive measure.

  8. Urinary Tract Infections (For Kids)

    Medline Plus

    Full Text Available ... Urinary Tract? Your urinary tract is actually a system made up of these main parts: two kidneys ... ON THIS TOPIC Chronic Kidney Diseases Movie: Urinary System Your Urinary System Bedwetting Contact Us Print Resources ...

  9. A Comparative Study of Lipid Profile and Cardiovascular Risk Biomarkers Among Chronic Haemodialysis Patients and Healthy Individuals

    Science.gov (United States)

    Kadavanu, Tony Mathew; Green, Siva Ranganathan; Dutta, Tarun Kumar; Hemachandar, Radhakrishnan; Ramachandrappa, Arun Kumar; Tiwari, Shashank Rakesh; Govindasamy, Ezhumalai

    2016-01-01

    Introduction Lipid abnormalities and increase in inflammatory markers are common among patients with End Stage Renal Disease (ESRD) and it tends to persist/worsen even after initiating Intermittent Haemodialysis (IHD). The cardiovascular mortality and morbidity remains significantly high in this population. Aim The present study was carried out to assess the pattern of lipid abnormality in our population and to find its association with inflammatory markers. Materials and Methods It was a cross-sectional, observational study on ESRD patients undergoing Haemodialysis (HD) in comparison with age and sex matched healthy individuals in a tertiary care hospital. About 40 adult male and female patients aged >18 years, undergoing chronic HD for more than 6 months were enrolled in Group A. Patients who were alcoholics, tobacco consumers and those on steroids and hypolipidemic drugs were excluded. Group B consisted of healthy, age and sex matched controls. Serum lipid profile, lipoprotein A, apolipoprotein A1, apolipoprotein B and apo B/A1 ratio, serum uric acid, homocysteine, hs-CRP and testosterone levels were estimated among patients undergoing intermittent HD and healthy individuals. Chi-square/Fisher’s-exact test was used for comparing ratios. A p-value of <0.05 was considered statistically significant. Results The mean Total Cholesterol (TC), Low Density Lipoprotein (LDL) and Non-HDL High Density Lipoprotein cholesterol was significantly lower in HD patients as compared to control group with all the three parameters attaining statistical significance (p<0.005). The mean lipoprotein A level was significantly higher (p=0.037), while Apo A1 was found to be significantly lower (p=0.001) in patients receiving HD. Inflammatory markers like uric acid was high (p<0.005) and serum testotsterone level in male HD patient was significantly low (p<0.005). Conclusion The mean values of traditional serum lipid profile remained lower in HD patients than the control group. The

  10. [Male urinary incontinence

    NARCIS (Netherlands)

    Boer, TA de; Heesakkers, J.P.F.A.

    2008-01-01

    *Urinary incontinence in males is gaining increasingly more attention. *Male urinary incontinence can be classified as storage incontinence due to overactive bladder syndrome or stress incontinence due to urethral sphincter dysfunction. *Most patients benefit from the currently available treatment o

  11. Variation across the agricultural season in organophosphorus pesticide urinary metabolite levels for Latino farmworkers in eastern North Carolina: project design and descriptive results.

    Science.gov (United States)

    Arcury, Thomas A; Grzywacz, Joseph G; Chen, Haiying; Vallejos, Quirina M; Galván, Leonardo; Whalley, Lara E; Isom, Scott; Barr, Dana B; Quandt, Sara A

    2009-07-01

    Community Participatory Approach to Measuring Farmworker Pesticide Exposure, PACE3, used a longitudinal design to document pesticide biomarkers among farmworkers. This article presents an overview of PACE3 and provides a descriptive analysis of participant characteristics and one set of pesticide biomarkers, the dialkylphosphate (DAP) urinary metabolites of organophosphorus (OP) pesticides. Two hundred eighty seven farmworkers were recruited during 2007 from 44 farmworker camps in 11 eastern North Carolina counties. Participants provided interviews, urine samples, blood samples, and saliva samples up to four times at monthly intervals beginning in May. A total of 939 data points were collected. Farmworkers were largely men (91.3%) from Mexico (94.8%) with a mean age of 33.7 years (SE 0.82); 23.3% spoke an indigenous language. Across all data points, frequencies of detection and median urinary concentrations were 41.3% and 0.96 microg/L for dimethylphosphate (DMP), 78.3% and 3.61 microg/L for dimethylthiophosphate (DMTP), 33.3% and 0.04 microg/L for dimethyldithiophosphate (DMDTP), 40.5% and 0.87 microg/L for diethylphosphate (DEP), 32.3% and 0.17 microg/L for diethylthiophosphate (DETP), and 8.09% and 0.00 microg/L for diethyldithiophosphate (DEDTP). The frequencies of detection and urinary concentrations of the DAP metabolites increased during the season. More PACE3 participants were from Mexico, male, migrant workers, and spoke an indigenous language compared to national data. PACE3 participants had comparable frequencies of detection and urinary metabolite concentrations with participants in other studies. Variability in the frequencies of detection and urinary concentrations of the DAP metabolites indicates the importance of longitudinal studies of biomarkers of currently used pesticides in farmworker populations.

  12. Comparative plasma lipidome between human and cynomolgus monkey: are plasma polar lipids good biomarkers for diabetic monkeys?

    Directory of Open Access Journals (Sweden)

    Guanghou Shui

    Full Text Available BACKGROUND: Non-human primates (NHP are now being considered as models for investigating human metabolic diseases including diabetes. Analyses of cholesterol and triglycerides in plasma derived from NHPs can easily be achieved using methods employed in humans. Information pertaining to other lipid species in monkey plasma, however, is lacking and requires comprehensive experimental analysis. METHODOLOGIES/PRINCIPAL FINDINGS: We examined the plasma lipidome from 16 cynomolgus monkey, Macaca fascicularis, using liquid chromatography coupled with mass spectrometry (LC/MS. We established novel analytical approaches, which are based on a simple gradient elution, to quantify polar lipids in plasma including (i glycerophospholipids (phosphatidylcholine, PC; phosphatidylethanolamine, PE; phosphatidylinositol, PI; phosphatidylglycerol, PG; phosphatidylserine, PS; phosphatidic acid, PA; (ii sphingolipids (sphingomyelin, SM; ceramide, Cer; Glucocyl-ceramide, GluCer; ganglioside mannoside 3, GM3. Lipidomic analysis had revealed that the plasma of human and cynomolgus monkey were of similar compositions, with PC, SM, PE, LPC and PI constituting the major polar lipid species present. Human plasma contained significantly higher levels of plasmalogen PE species (p<0.005 and plasmalogen PC species (p<0.0005, while cynomolgus monkey had higher levels of polyunsaturated fatty acyls (PUFA in PC, PE, PS and PI. Notably, cynomolgus monkey had significantly lower levels of glycosphingolipids, including GluCer (p<0.0005 and GM(3 (p<0.0005, but higher level of Cer (p<0.0005 in plasma than human. We next investigated the biochemical alterations in blood lipids of 8 naturally occurring diabetic cynomolgus monkeys when compared with 8 healthy controls. CONCLUSIONS: For the first time, we demonstrated that the plasma of human and cynomolgus monkey were of similar compositions, but contained different mol distribution of individual molecular species. Diabetic monkeys

  13. The ischemic/nephrotoxic acute kidney injury and the use of renal biomarkers in clinical practice.

    Science.gov (United States)

    Andreucci, Michele; Faga, Teresa; Pisani, Antonio; Perticone, Maria; Michael, Ashour

    2017-04-01

    The term Acute Renal Failure (ARF) has been replaced by the term Acute Kidney Injury (AKI). AKI indicates an abrupt (within 24-48h) decrease in Glomerular Filtraton Rate, due to renal damage, that causes fluid and metabolic waste retention and alteration of electrolyte and acid-base balance. The renal biomarkers of AKI are substances or processes that are indicators of normal or impaired function of the kidney. The most used renal biomarker is still serum creatinine that is inadequate for several reasons, one of which is its inability to differentiate between hemodynamic changes of renal function ("prerenal azotemia") from intrinsic renal failure or obstructive nephropathy. Cystatin C is no better in this respect. After the description of the pathophysiology of "prerenal azotemia" and of Acute Kidney Injury (AKI) due to ischemia or nephrotoxicity, the renal biomarkers are listed and described: urinary NAG, urinary and serum KIM-1, serum and urinary NGAL, urinary IL-18, urinary L-FABP, serum Midkine, urinary IGFBP7 and TIMP2, urinary α-GST and π-GST, urinary ɣGT and AP, urinary β2M, urinary RBP, serum and urinary miRNA. All have been shown to appear much earlier than the rise of serum Creatinine. Some of them have been demonstrated to predict the clinical outcomes of AKI, such as the need for initiation of dialysis and mortality.

  14. NASA Astronaut Urinary Conditions Associated with Spaceflight

    Science.gov (United States)

    Law, Jennifer; Cole, Richard; Young, Millennia H.; Mason, Sara

    2016-01-01

    INTRODUCTION: Spaceflight is associated with many factors which may promote kidney stone formation, urinary retention, and/or Urinary Tract Infection (UTI). According to ISS mission predictions supplied by NASA's Integrated Medical Model, kidney stone is the second and sepsis (urosepsis as primary driver) the third most likely reason for emergent medical evacuation from the International Space Station (ISS). METHODS: Inflight and postflight medical records of NASA astronauts were reviewed for urinary retention, UTI and kidney stones during Mercury, Gemini, Apollo, Mir, Shuttle, and ISS expeditions 1-38. RESULTS: NASA astronauts have had 7 cases of kidney stones in the 12 months after flight. Three of these cases occurred within 90 to 180 days after landing and one of the seven cases occurred in the first 90 days after flight. There have been a total of 16 cases (0.018 events per person-flights) of urinary retention during flight. The event rates per mission are nearly identical between Shuttle and ISS flights (0.019 vs 0.021 events per person-flights). In 12 of the 16 cases, astronauts had taken at least one space motion sickness medication. Upon further analysis, it was determined that the odds of developing urinary retention in spaceflight is 3 times higher among astronauts who took promethazine. The female to male odds ratio for inflight urinary retention is 11:14. An astronaut with urinary retention is 25 times more likely to have a UTI with a 17% infection rate per mission. There have been 9 reported UTIs during spaceflight. DISCUSSION: It is unclear if spaceflight carries an increased post-flight risk of kidney stones. Regarding urinary retention, the female to male odds ratio is higher during flight compared to the general population where older males comprise almost all cases due to prostatic hypertrophy. This female prevalence in spaceflight is even more concerning given the fact that there have been many more males in space than females. Terrestrial

  15. Comparing biomarker measurements to a normal range: when to use standard error of the mean (SEM) or standard deviation (SD) confidence intervals tests

    Science.gov (United States)

    This commentary is the second of a series outlining one specific concept in interpreting biomarkers data. In the first, an observational method was presented for assessing the distribution of measurements before making parametric calculations. Here, the discussion revolves around...

  16. Prediction of acute coronary syndromes by urinary proteome analysis

    Science.gov (United States)

    Htun, Nay M.; Magliano, Dianna J.; Zhang, Zhen-Yu; Lyons, Jasmine; Petit, Thibault; Nkuipou-Kenfack, Esther; Ramirez-Torres, Adela; von zur Muhlen, Constantin; Maahs, David; Schanstra, Joost P.; Pontillo, Claudia; Pejchinovski, Martin; Snell-Bergeon, Janet K.; Delles, Christian; Mischak, Harald; Staessen, Jan A.; Shaw, Jonathan E.

    2017-01-01

    Identification of individuals who are at risk of suffering from acute coronary syndromes (ACS) may allow to introduce preventative measures. We aimed to identify ACS-related urinary peptides, that combined as a pattern can be used as prognostic biomarker. Proteomic data of 252 individuals enrolled in four prospective studies from Australia, Europe and North America were analyzed. 126 of these had suffered from ACS within a period of up to 5 years post urine sampling (cases). Proteomic analysis of 84 cases and 84 matched controls resulted in the discovery of 75 ACS-related urinary peptides. Combining these to a peptide pattern, we established a prognostic biomarker named Acute Coronary Syndrome Predictor 75 (ACSP75). ACSP75 demonstrated reasonable prognostic discrimination (c-statistic = 0.664), which was similar to Framingham risk scoring (c-statistics = 0.644) in a validation cohort of 42 cases and 42 controls. However, generating by a composite algorithm named Acute Coronary Syndrome Composite Predictor (ACSCP), combining the biomarker pattern ACSP75 with the previously established urinary proteomic biomarker CAD238 characterizing coronary artery disease as the underlying aetiology, and age as a risk factor, further improved discrimination (c-statistic = 0.751) resulting in an added prognostic value over Framingham risk scoring expressed by an integrated discrimination improvement of 0.273 ± 0.048 (P < 0.0001) and net reclassification improvement of 0.405 ± 0.113 (P = 0.0007). In conclusion, we demonstrate that urinary peptide biomarkers have the potential to predict future ACS events in asymptomatic patients. Further large scale studies are warranted to determine the role of urinary biomarkers in clinical practice. PMID:28273075

  17. Utility and Cutoff Value of Hair Nicotine as a Biomarker of Long-Term Tobacco Smoke Exposure, Compared to Salivary Cotinine

    Directory of Open Access Journals (Sweden)

    Sungroul Kim

    2014-08-01

    Full Text Available While hair samples are easier to collect and less expensive to store and transport than biological fluids, and hair nicotine characterizes tobacco exposure over a longer time period than blood or urine cotinine, information on its utility, compared with salivary cotinine, is still limited. We conducted a cross-sectional study with 289 participants (107 active smokers, 105 passive smokers with self-reported secondhand smoke (SHS exposure, and 77 non-smokers with no SHS exposure in Baltimore (Maryland, USA. A subset of the study participants (n = 52 were followed longitudinally over a two-month interval.  Median baseline hair nicotine concentrations for active, passive and non-smokers were 16.2, 0.36, and 0.23 ng/mg, respectively, while those for salivary cotinine were 181.0, 0.27, and 0.27 ng/mL, respectively. Hair nicotine concentrations for 10% of passive or non-smokers were higher than the 25th percentile value for active smokers while all corresponding salivary cotinine concentrations for them were lower than the value for active smokers. This study showed that hair nicotine concentration values could be used to distinguish active or heavy passive adult smokers from non-SHS exposed non-smokers. Our results indicate that hair nicotine is a useful biomarker for the assessment of long-term exposure to tobacco smoke.

  18. Biomarkers in Vasculitis

    Science.gov (United States)

    Monach, Paul A.

    2014-01-01

    Purpose of review Better biomarkers are needed for guiding management of patients with vasculitis. Large cohorts and technological advances had led to an increase in pre-clinical studies of potential biomarkers. Recent findings The most interesting markers described recently include a gene expression signature in CD8+ T cells that predicts tendency to relapse or remain relapse-free in ANCA-associated vasculitis, and a pair of urinary proteins that are elevated in Kawasaki disease but not other febrile illnesses. Both of these studies used “omics” technologies to generate and then test hypotheses. More conventional hypothesis-based studies have indicated that the following circulating proteins have potential to improve upon clinically available tests: pentraxin-3 in giant cell arteritis and Takayasu’s arteritis; von Willebrand factor antigen in childhood central nervous system vasculitis; eotaxin-3 and other markers related to eosinophils or Th2 immune responses in eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome); and MMP-3, TIMP-1, and CXCL13 in ANCA-associated vasculitis. Summary New markers testable in blood and urine have the potential to assist with diagnosis, staging, assessment of current disease activity, and prognosis. However, the standards for clinical usefulness, in particular the demonstration of either very high sensitivity or very high specificity, have yet to be met for clinically relevant outcomes. PMID:24257367

  19. Monitoring of urinary L-type fatty acid-binding protein predicts histological severity of acute kidney injury.

    Science.gov (United States)

    Negishi, Kousuke; Noiri, Eisei; Doi, Kent; Maeda-Mamiya, Rui; Sugaya, Takeshi; Portilla, Didier; Fujita, Toshiro

    2009-04-01

    The present study aimed to evaluate whether levels of urinary L-type fatty acid-binding protein (L-FABP) could be used to monitor histological injury in acute kidney injury (AKI) induced by cis-platinum (CP) injection and ischemia reperfusion (IR). Different degrees of AKI severity were induced by several renal insults (CP dose and ischemia time) in human L-FABP transgenic mice. Renal histological injury scores increased with both CP dose and ischemic time. In CP-induced AKI, urinary L-FABP levels increased exponentially even in the lowest dose group as early as 2 hours, whereas blood urea nitrogen (BUN) levels increased at 48 hours. In IR-induced AKI, BUN levels increased only in the 30-minute ischemia group 24 hours after reperfusion; however, urinary L-FABP levels increased more than 100-fold, even in the 5-minute ischemia group after 1 hour. In both AKI models, urinary L-FABP levels showed a better correlation with final histological injury scores and glomerular filtration rates measured by fluorescein isothiocyanate-labeled inulin injection than with levels of BUN and urinary N-acetyl-D-glucosaminidase, especially at earlier time points. Receiver operating characteristic curve analysis demonstrated that urinary L-FABP was superior to other biomarkers for the detection of significant histological injuries and functional declines. In conclusion, urinary L-FABP levels are better suited to allow the accurate and earlier detection of both histological and functional insults in ischemic and nephrotoxin-induced AKI compared with conventional renal markers.

  20. Assessment of Urinary Osteopontin in Association with Podocyte for Early Predication of Nephropathy in Diabetic Patients

    Directory of Open Access Journals (Sweden)

    Abdulrahman L. Al-Malki

    2014-01-01

    Full Text Available Objectives. Microalbuminuria has been clinically used for noninvasive evaluation of renal dysfunctions. However, it is a nonspecific marker of diabetic nephropathy (DN. Methods. This study was conducted from March 2012 to April 2013 at Biochemistry Unit, King Fahd Medical Research Center (KFMRC. In this study, urinary osteopontin, podocytes number, and levels of immunoglobulin M (IgM were determined in 60 patients (diabetic normoalbuminuria, diabetic microalbuminuria, and nephritic syndrome compared with healthy subjects. Results. It was found that in diabetic microalbuminuria patients have a highly significant increase in urinary IgM, osteopontin, and podocyte levels as compared to other groups. Nephrotic syndrome patients showed a moderate significant elevation of these parameters compared to control subjects. At a given specificity of 97%, podocytes yielded the highest sensitivity of all markers, 95.5%. The sensitivity was considerably higher compared to IgM and osteopontin. Podocyte number was positively correlated with serum IgM and osteopontin (r=0.63 and 0.56, respectively. Its cutoff corresponding to the 10% coefficient of variation was most appropriate for early diagnosis of DN. Conclusion. Monitoring urinary podocyte may provide a noninvasive tool that is a sensitive, accurate, and specific biomarker of glomerular injury and can be used in combination with osteopontin and IgM to more reliably detect and monitor prognosis.

  1. 两台 Sysm ex U F-1000i 全自动尿沉渣分析仪检测结果的比对研究%Comparative analysis of two Sysmex UF-1000i automated urinary sediment analyzers

    Institute of Scientific and Technical Information of China (English)

    熊志刚; 黄小天; 余洋; 曾瑾忱

    2013-01-01

    Objective To compare the test results from the different Sysmex UF-1000i automated urinary sed-iment analyzers ,and to explore whether the variance of the results were within the permitted range for improving the accuracy and consistency .Methods Under the condition that two urinary sediment analyzers were normal ,two fresh urine samples were examined in duplicate ,and the test data of RBC/μL、WBC/μL、EC/μL、CAST/μL and BACT/μL were compared with the results determined by traceable urinary sediment analyzer ,and regression equations were es-tablished ,then the passing rate was counted and test results were evaluated with the reference provided by SYSMEX company .Results The verification analyzers and the reference analyzer showed that RBC ,WBC ,EC ,CAST and BACT passing rates were 88 .09% ,88 .09% ,92 .86% ,52 .38% ,35 .71% ,coefficients of correlation (r) exceeded 0 .998 ,0 .997 ,0 .993 ,0 .417 ,0 .971 ,and there was no statistical significance of CAST and BACT between two analyz-ers (P>0 .05) ,but statistical differences of RBC ,WBC and EC were observed(P0.05),RBC、WBC、EC结果比较差异有统计学意义(P<0.05).结论临床实验室应加强对所有检测项目结果的可靠性进行验证,做好尿沉渣分析仪室内质控的同时定期进行仪器比对试验,以保证不同仪器上的检测结果具有可比性、准确性、一致性、持续性的质量保证.

  2. Effects of a supplement combining Pycnogenol(®) and l-arginine aspartate on lower urinary dysfunction compared with saw palmetto extract.

    Science.gov (United States)

    Yagi, Hiroshi; Sato, Ryo; Nishio, Kojiro; Arai, Gaku; Soh, Shigehiro; Okada, Hiroshi

    2017-01-01

    Lower urinary tract symptoms (LUTS) and sexual dysfunction (SDys) are common problems that affect quality of life (QOL) in elderly men. In addition to prescribed drugs, many over-the-counter medications including supplements are used to treat QOL diseases. Phosphodiesterase inhibitors are reported to be effective for both LUTS and SDys by increasing nitric oxide levels. French maritime pine bark extract Pycnogenol(®), which is a potent nitric oxide donor, is reported to be effective for SDys. However, no reports have been published on whether it ameliorates LUTS. Open-labeled, randomized study. The effects of two supplements, Nokogiriyashi EX(®) containing 160 mg saw palmetto (SP) extract per tablet and Edicare(®) containing 10 mg of Pycnogenol(®), 115 mg of l-arginine and 92 mg of aspartate (PAA) per tablet on International Prostate Symptom Score (IPSS), IPSS-QOL, Overactive Bladder Symptom Score (OABSS), International Index of Erectile Function 5 (IIEF5), Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF), urinary 8-OHdG and uroflowmetry (UFM) of total 40 men with LUTS and SDys were examined. 19 subjects were instructed to take two tablets of SP, on the other 20 were on four tablets of PAA for 16 weeks. IPSS and IPSS-QOL showed statistically significant improvements in both groups. OABSS and IIEF5 were significantly improved in the PAA group. Conversely, ICIQ-SF, 8-OHdG and UFM did not change in either group. PAA might be an effective therapeutic alternative for elderly patients with LUTS and SDys.

  3. Microfiltration isolation of human urinary exosomes for characterization by MS.

    NARCIS (Netherlands)

    Merchant, M.L.; Powell, D.W.; Wilkey, D.W.; Cummins, T.D.; Deegens, J.K.J.; Rood, I.M.; McAfee, K.J.; Fleischer, C.; Klein, E.; Klein, J.B.

    2010-01-01

    PURPOSE: The purpose of this study was to address the hypothesis that small vesicular urinary particles known as exosomes could be selectively microfiltered using low protein-binding size exclusion filters, thereby simplifying their use in clinical biomarker discovery studies. EXPERIMENTAL DESIGN: W

  4. Inflammatory biomarkers and cancer

    DEFF Research Database (Denmark)

    Rasmussen, Line Jee Hartmann; Schultz, Martin; Gaardsting, Anne

    2017-01-01

    In Denmark, patients with serious nonspecific symptoms and signs of cancer (NSSC) are referred to the diagnostic outpatient clinics (DOCs) where an accelerated cancer diagnostic program is initiated. Various immunological and inflammatory biomarkers have been associated with cancer, including...... soluble urokinase plasminogen activator receptor (suPAR) and the pattern recognition receptors (PRRs) pentraxin-3, mannose-binding lectin, ficolin-1, ficolin-2 and ficolin-3. We aimed to evaluate these biomarkers and compare their diagnostic ability to classical biomarkers for diagnosing cancer...... in patients with NSSC. Patients were included from the DOC, Department of Infectious Diseases, Copenhagen University Hospital Hvidovre. Patients were given a final diagnosis based on the combined results from scans, blood work and physical examination. Weight loss, Charlson score and previous cancer were...

  5. Imaging Biomarkers or Biomarker Imaging?

    Directory of Open Access Journals (Sweden)

    Markus Mitterhauser

    2014-06-01

    Full Text Available Since biomarker imaging is traditionally understood as imaging of molecular probes, we highly recommend to avoid any confusion with the previously defined term “imaging biomarkers” and, therefore, only use “molecular probe imaging (MPI” in that context. Molecular probes (MPs comprise all kinds of molecules administered to an organism which inherently carry a signalling moiety. This review highlights the basic concepts and differences of molecular probe imaging using specific biomarkers. In particular, PET radiopharmaceuticals are discussed in more detail. Specific radiochemical and radiopharmacological aspects as well as some legal issues are presented.

  6. Hypercalciuria in children with urinary tract symptoms

    Directory of Open Access Journals (Sweden)

    Fallahzadeh M

    2010-01-01

    Full Text Available We performed this prospective study to determine the urinary calcium to creatinine ratio (Ca/Cr in children with different urinary symptoms. We studied 523 children in our neph-rology clinic with an age range of 3 to 14 years (mean= 8 and male to female ratio of 0.61. All the children had at least one of the urinary tract symptoms (dysuria, frequency, urgency, abdo-minal and/or flank pain, diurnal incontinence or enuresis, microscopic hematuria, urinary tract infection or urolithiasis. Fasting urine was collected for measuring calcium and creatinine and the results were compared to the values for the normal Iranian children. Ca/Cr ratio of more than 0.2 (mg/mg was considered as hypercalciuria. Of all the patients, 166 (31.3% were hypercalciuric. Urine Ca/Cr ratio was significantly higher in all the subgroups with one or more of the urinary symptoms (P< 0.001. We conclude that urine Ca/Cr ratio is significantly increased in children with all types of urinary symptoms. We recommend measuring urinary calcium in all children with urinary tract symptoms, especially if unexplained.

  7. Effects of Three Commonly-used Diuretics on the Urinary Proteome

    Science.gov (United States)

    Li, Xundou; Zhao, Mindi; Li, Menglin; Jia, Lulu; Gao, Youhe

    2014-01-01

    Biomarker is the measurable change associated with a physiological or pathophysiological process. Unlike blood which has mechanisms to keep the internal environment homeostatic, urine is more likely to reflect changes of the body. As a result, urine is likely to be a better biomarker source than blood. However, since the urinary proteome is affected by many factors, including diuretics, careful evaluation of those effects is necessary if urinary proteomics is used for biomarker discovery. Here, we evaluated the effects of three commonly-used diuretics (furosemide, F; hydrochlorothiazide, H; and spirolactone, S) on the urinary proteome in rats. Urine samples were collected before and after intragastric administration of diuretics at therapeutic doses and the proteomes were analyzed using label-free liquid chromatography–tandem mass spectrometry (LC–MS/MS). Based on the criteria of P ⩽ 0.05, a fold change ⩾2, a spectral count ⩾5, and false positive rate (FDR) ⩽1%, 14 proteins (seven for F, five for H, and two for S) were identified by Progenesis LC–MS. The human orthologs of most of these 14 proteins are stable in the healthy human urinary proteome, and ten of them are reported as disease biomarkers. Thus, our results suggest that the effects of diuretics deserve more attention in future urinary protein biomarker studies. Moreover, the distinct effects of diuretics on the urinary proteome may provide clues to the mechanisms of diuretics. PMID:24508280

  8. Effects of Three Commonly-used Diuretics on the Urinary Proteome

    Institute of Scientific and Technical Information of China (English)

    Xundou Li; Mindi Zhao; Menglin Li; Lulu Jia; Youhe Gao

    2014-01-01

    Biomarker is the measurable change associated with a physiological or pathophysiolog-ical process. Unlike blood which has mechanisms to keep the internal environment homeostatic, urine is more likely to reflect changes of the body. As a result, urine is likely to be a better biomarker source than blood. However, since the urinary proteome is affected by many factors, including diuretics, careful evaluation of those effects is necessary if urinary proteomics is used for biomarker discovery. Here, we evaluated the effects of three commonly-used diuretics (furosemide, F;hydro-chlorothiazide, H; and spirolactone, S) on the urinary proteome in rats. Urine samples were col-lected before and after intragastric administration of diuretics at therapeutic doses and the proteomes were analyzed using label-free liquid chromatography-tandem mass spectrometry (LC-MS/MS). Based on the criteria of P 6 0.05, a fold change P2, a spectral count P5, and false positive rate (FDR) 61%, 14 proteins (seven for F, five for H, and two for S) were identified by Progenesis LC-MS. The human orthologs of most of these 14 proteins are stable in the healthy human urinary proteome, and ten of them are reported as disease biomarkers. Thus, our results suggest that the effects of diuretics deserve more attention in future urinary protein biomarker studies. Moreover, the distinct effects of diuretics on the urinary proteome may provide clues to the mechanisms of diuretics.

  9. Effects of Three Commonly-used Diuretics on the Urinary Proteome

    Directory of Open Access Journals (Sweden)

    Xundou Li

    2014-06-01

    Full Text Available Biomarker is the measurable change associated with a physiological or pathophysiological process. Unlike blood which has mechanisms to keep the internal environment homeostatic, urine is more likely to reflect changes of the body. As a result, urine is likely to be a better biomarker source than blood. However, since the urinary proteome is affected by many factors, including diuretics, careful evaluation of those effects is necessary if urinary proteomics is used for biomarker discovery. Here, we evaluated the effects of three commonly-used diuretics (furosemide, F; hydrochlorothiazide, H; and spirolactone, S on the urinary proteome in rats. Urine samples were collected before and after intragastric administration of diuretics at therapeutic doses and the proteomes were analyzed using label-free liquid chromatography–tandem mass spectrometry (LC–MS/MS. Based on the criteria of P ⩽ 0.05, a fold change ⩾2, a spectral count ⩾5, and false positive rate (FDR ⩽1%, 14 proteins (seven for F, five for H, and two for S were identified by Progenesis LC–MS. The human orthologs of most of these 14 proteins are stable in the healthy human urinary proteome, and ten of them are reported as disease biomarkers. Thus, our results suggest that the effects of diuretics deserve more attention in future urinary protein biomarker studies. Moreover, the distinct effects of diuretics on the urinary proteome may provide clues to the mechanisms of diuretics.

  10. Biomarkers of environmental benzene exposure

    Energy Technology Data Exchange (ETDEWEB)

    Weisel, C.; Yu, R.; Roy, A.; Georgopoulos, P. [Environmental and Occupational Health Sciences Institute, Piscataway, NJ (United States)

    1996-12-01

    Environmental exposures to benzene result in increases in body burden that are reflected in various biomarkers of exposure, including benzene in exhaled breath, benzene in blood and urinary trans-trans-muconic acid and S-phenylmercapturic acid. A review of the literature indicates that these biomarkers can be used to distinguish populations with different levels of exposure (such as smokers from nonsmokers and occupationally exposed from environmentally exposed populations) and to determine differences in metabolism. Biomarkers in humans have shown that the percentage of benzene metabolized by the ring-opening pathway is greater at environmental exposures than that at higher occupational exposures, a trend similar to that found in animal studies. This suggests that the dose-response curve is nonlinear; that potential different metabolic mechanisms exist at high and low doses; and that the validity of a linear extrapolation of adverse effects measured at high doses to a population exposed to lower, environmental levels of benzene is uncertain. Time-series measurements of the biomarker, exhaled breath, were used to evaluate a physiologically based pharmacokinetic (PBPK) model. Biases were identified between the PBPK model predictions and experimental data that were adequately described using an empirical compartmental model. It is suggested that a mapping of the PBPK model to a compartmental model can be done to optimize the parameters in the PBPK model to provide a future framework for developing a population physiologically based pharmacokinetic model. 44 refs., 3 figs., 1 tab.

  11. Urinary acidification and urinary excretion of calcium and citrate in women with bilateral medullary sponge kidney

    DEFF Research Database (Denmark)

    Osther, P J; Mathiasen, Helle; Hansen, A B

    1994-01-01

    Urinary acidification ability, acid-base status and urinary excretion of calcium and citrate were evaluated in 10 women with bilateral medullary sponge kidney (MSK) and in 10 healthy women. Patients with MSK had higher fasting urine pH compared to normal controls (p ... in the mechanism of hypercalciuria and hypocitraturia in patients with medullary sponge kidney.(ABSTRACT TRUNCATED AT 250 WORDS)...

  12. Urinary proteomic profiling in severe obesity and obstructive sleep apnoea with CPAP treatment

    Directory of Open Access Journals (Sweden)

    Ian W Seetho

    2015-04-01

    Conclusions: The urinary proteome is compared in OSA with CPAP and without OSA in severe obesity. The effects of CPAP on OSA may lead to changes in the urinary peptides but further research work is needed to investigate the potential role for urinary proteomics in characterising urinary peptide profiles in OSA.

  13. Cost effectiveness analysis of fesoterodine compared to mirabegron in first-line therapy setting for overactive bladder with urge urinary incontinence, from the Spanish National Health System perspective.

    Science.gov (United States)

    Angulo, J C; Sánchez-Ballester, F; Peral, C; Rejas, J; Ramos, J; Snedecor, S J; Sudharshan, L; Liu, S; Luo, X

    2016-10-01

    To evaluate the cost-effectiveness of first-line treatment of Overactive Bladder (OAB) with fesoterodine relative to mirabegron, from the Spanish National Health System (NHS) perspective. A decision tree model was developed to represent a typical clinical process of 52-week of treatment for an OAB patient with urge urinary incontinence (UUI) initiating first-line therapy with fesoterodine 4mg, including optional titration to 8mg, vs.mirabegron 50mg. Efficacy data were obtained from a Bayesian indirect treatment meta-analysis. Patients with UUI of less than one episode/day were defined as treatment responder and persistence was assessed at weeks 4, 12 and 24. At week 12, non-responders discontinued treatment permanently. Quality-adjusted life years (QALYs) were calculated based on time spent in responder and non-responder states. OAB-related drug and medical care costs including physician visits, laboratory tests, incontinence pads, and comorbidities (fracture, skin infection, urinary tract infections and depression) were modeled and expressed in €2015. At week 52, the percentage of responders was 20.8% for patients starting on fesoterodine 4mg who optionally titrated to 8mg and 19.4% for patients treated with mirabegron. QALYs were slightly higher with fesoterodine than mirabegron (0.7703vs. 0.7668, difference=0.0035). Fesoterodine treatment also had slightly higher total costs than mirabegron (3,296€vs. 3,217, difference=79€), resulting in a cost of 22,523/QALY€ gained for fesoterodine versus mirabegron. Probabilistic sensitivity analysis confirmed the slight advantage of fesoterodine with a 61.1% probability of being cost-effective at the 30,000€ willingness-to-pay for 1QALY threshold. Given the relatively small 1-year cost difference between the two treatments, fesoterodine can be considered a cost-effective option relative to mirabegron for the first-line management of OAB with UUI in Spain. Copyright © 2016 AEU. Publicado por Elsevier España, S

  14. Interpreting biomarker data from the COPHES/DEMOCOPHES twin projects: Using external exposure data to understand biomarker differences among countries

    Energy Technology Data Exchange (ETDEWEB)

    Smolders, R., E-mail: roel.smolders@vito.be [Flemish Institute of Technological Research (VITO), Environmental Risks and Health Unit, Boeretang 200, 2400 Mol (Belgium); Den Hond, E.; Koppen, G.; Govarts, E.; Willems, H. [Flemish Institute of Technological Research (VITO), Environmental Risks and Health Unit, Boeretang 200, 2400 Mol (Belgium); Casteleyn, L. [KU LEUVEN (Belgium); Kolossa-Gehring, M.; Fiddicke, U. [Federal Environment Agency (UBA) (Germany); Castaño, A. [Instituto de Salud Carlos III (Spain); Koch, H.M.; Angerer, J. [Institute for Prevention and Occupational Medicine of the German Social Accident Insurance - Institute of the Ruhr-Universität Bochum (IPA) (Germany); Esteban, M. [Instituto de Salud Carlos III (Spain); Sepai, O.; Exley, K. [Public Health England (United Kingdom); Bloemen, L. [Environmental Health Sciences International (Netherlands); Horvat, M. [Jožef Stefan Institute (Slovenia); Knudsen, L.E. [University of Copenhagen (Denmark); Joas, A.; Joas, R. [BiPRO (Germany); Biot, P. [FPS Health, Food Chain Safety and Environment (Belgium); and others

    2015-08-15

    In 2011 and 2012, the COPHES/DEMOCOPHES twin projects performed the first ever harmonized human biomonitoring survey in 17 European countries. In more than 1800 mother–child pairs, individual lifestyle data were collected and cadmium, cotinine and certain phthalate metabolites were measured in urine. Total mercury was determined in hair samples. While the main goal of the COPHES/DEMOCOPHES twin projects was to develop and test harmonized protocols and procedures, the goal of the current paper is to investigate whether the observed differences in biomarker values among the countries implementing DEMOCOPHES can be interpreted using information from external databases on environmental quality and lifestyle. In general, 13 countries having implemented DEMOCOPHES provided high-quality data from external sources that were relevant for interpretation purposes. However, some data were not available for reporting or were not in line with predefined specifications. Therefore, only part of the external information could be included in the statistical analyses. Nonetheless, there was a highly significant correlation between national levels of fish consumption and mercury in hair, the strength of antismoking legislation was significantly related to urinary cotinine levels, and we were able to show indications that also urinary cadmium levels were associated with environmental quality and food quality. These results again show the potential of biomonitoring data to provide added value for (the evaluation of) evidence-informed policy making. - Highlights: • External data was collected to interpret HBM data from DEMOCOPHES. • Hg in hair could be related to fish consumption across different countries. • Urinary cotinine was related to strictness of anti-smoking legislation. • Urinary Cd was borderline significantly related to air and food quality. • Lack of comparable data among countries hampered the analysis.

  15. Elevated urinary levels of 8-oxo-2'-deoxyguanosine, (5'R)- and (5'S)-8,5'-cyclo-2'-deoxyadenosines, and 8-iso-prostaglandin F2α as potential biomarkers of oxidative stress in patients with prediabetes.

    Science.gov (United States)

    Kant, Melis; Akış, Merve; Çalan, Mehmet; Arkan, Tuğba; Bayraktar, Fırat; Dizdaroglu, Miral; İşlekel, Hüray

    2016-12-01

    Prediabetes is the preclinical stage of type 2 diabetes mellitus (T2DM) with intermediate state of hyperglycemia. Hyperglycemia results in a state of oxidative stress, which may contribute to the production of insulin resistance, β-cell dysfunction and long-term complications of diabetes. Novel approaches are required for prevention and treatment of diabetes. New biomarkers that can be used in risk stratification and therapy control as supplementary to current parameters are needed. These biomarkers may facilitate a more individualized and sufficient treatment of diabetes. Therefore, the aim of this study was to investigate the levels of oxidatively induced DNA damage products, 8-oxo-2'-deoxyguanosine (8-oxo-dG) (also known as 8-OH-dG), (5'R)- and (5'S)-8,5'-cyclo-2'-deoxyadenosines (R-cdA and S-cdA), and the lipid peroxidation product 8-iso-prostaglandin F2α (8-iso-PGF2α) as reliable oxidative stress markers in patients with prediabetes or T2DM in comparison with healthy volunteers. Urine samples were collected from these subjects. Absolute quantification of 8-oxo-dG, R-cdA, S-cdA and 8-iso-PGF2α was achieved by liquid chromatography-isotope dilution tandem mass spectrometry. The levels of 8-oxo-dG, S-cdA and 8-iso-PGF2α were significantly greater in prediabetes patients than those in healthy volunteers. T2DM patients also had higher levels of 8-oxo-dG than healthy volunteers. No statistically significant difference was observed for R-cdA levels. 8-Oxo-dG levels positively correlated with R-cdA and S-cdA levels for prediabetes and newly diagnosed T2DM. S-cdA levels and HbA1c were found negatively correlated in prediabetes patients. Also 8-iso-PGF2α levels and HbA1c were found negatively correlated in prediabetes patients. These results indicate that oxidatively induced macromolecular damage appears before the establishment of T2DM. Thus, our data suggest that oxidatively induced DNA damage and lipid peroxidation products that were found to be elevated in

  16. STUDY OF URINARY CALCIUM AND URINARY CREATININE LEVELS AND URINARY CALCIUM/CREATININE RATIO IN GESTATIONAL HYPERTENSIVE PATIENTS

    Directory of Open Access Journals (Sweden)

    Swapna

    2015-06-01

    Full Text Available BACKGROUND: Gestational hypertension (BP>140/90mmHg or pregnancy induced hypertension usually precedes pre - eclampsia (BP>140/90mmHg associated with proteniuria. Many tests to predict pre - eclampsia are coming up on the horizon. Hypocalciuria is one such test to predict pre - eclampsia which may be present before other clinical signs and symptoms. AIM: To determine urinary calcium, urinary creatinine and urinary calcium/creatinine ratio in pregnancy induced hypertension and in normal pregnant women. MATERIAL AND METHODS: The study included 100 subjects with gestational age between 24 - 38 weeks and divided into two groups’ viz. control group and study group . The control group included 50 subjects who were normal pregnant women and study group included 50 subjects who were gestational hypertensive patients. Urinary calcium was estimated by Ortho - Cresolphthalein Complexone (CPC method, urinary creatinine was estimated by Jaffe’s method in all the subjects. RESULTS: The estimated mean levels (Mean±SD of urinary calcium, creatinine in control group were 263.0±80.3, 0.95±0.16 respectively and in patients with gestational hypertension they were 86.2±19.5, 1.21±0. 37 respectively. The statistical analysis by unpaired t - test shows that the levels of urinary calcium were significantly decreased (p<0.001 and the urinary creatinine were significantly increased (p <0.001 in gestational hypertensive patients when compar ed to healthy controls. The mean urinary calcium/creatinine ratio in control group were 0.28±0.08 and in gestational hypertensive patients were 0.07±0.03.The statistical analysis by unpaired t - test shows that the levels of urinary calcium/creatinine ratio were significantly decreased (p<0.001 in gestational hypertensive patients when compared to healthy controls. CONCLUSION: This study suggests that a regular evaluation of urinary calcium/creatinine ratio after 20wks of gestation may be an effective screen ing method for

  17. The female urinary microbiota, urinary health and common urinary disorders

    Science.gov (United States)

    Wolfe, Alan J.

    2017-01-01

    This review provides the clinical context and updated information regarding the female urinary microbiota (FUM), a resident microbial community within the female bladder of many adult women. Microbial communities have variability and distinct characteristics in health, as well as during community disruption (dysbiosis). Information concerning characteristics of the FUM in health and disease is emerging. Sufficient data confirms that the microbes that compose the FUM are not contaminants and are cultivatable under appropriate conditions. Common clinical conditions, including urinary tract infection (UTI) and urgency urinary incontinence (UUI), a common form of urinary incontinence (UI), may be usefully reconsidered to determine the role of the FUM. Knowledge of FUM characteristics may help advance prevention, diagnosis and treatment of these conditions and other common lower urinary disorders in women. The FUM appears related to UTI and UUI in adult women. The specific role of the FUM remains to be clarified and requires significant additional work in describing FUM variability and resilience in health. Unique aspects of the FUM prompt re-evaluation of existing nomenclature to more appropriately define health and disease; the concept of dysbiosis may be useful for understanding the interaction of the FUM with other aspects of lower urinary tract physiology, including urothelial signaling. Clinicians, through their clinical laboratories, can adopt enhanced urine culture techniques that more fully describe the living microbes within the FUM. This additional information may provide clinicians and their patients an opportunity to impact clinical care without antibiotic use, if the FUM can be appropriately modified to improve treatment precision for UTI and UUI. PMID:28217699

  18. Urinary incontinence in women.

    Science.gov (United States)

    Norton, Peggy; Brubaker, Linda

    2006-01-07

    Urinary incontinence is common in women, but is under-reported and under-treated. Urine storage and emptying is a complex coordination between the bladder and urethra, and disturbances in the system due to childbirth, aging, or other medical conditions can lead to urinary incontinence. The two main types of incontinence in women, stress urinary incontinence and urge urinary incontinence, can be evaluated by history and simple clinical assessment available to most primary care physicians. There is a wide range of therapeutic options, but the recent proliferation of new drug treatments and surgical devices for urinary incontinence have had mixed results; direct-to-consumer advertising has increased public awareness of the problem of urinary incontinence, but many new products are being introduced without long-term assessment of their safety and efficacy.

  19. Urinary calprotectin and posttransplant renal allograft injury.

    Directory of Open Access Journals (Sweden)

    Martin Tepel

    Full Text Available OBJECTIVE: Current methods do not predict the acute renal allograft injury immediately after kidney transplantation. We evaluated the diagnostic performance of urinary calprotectin for predicting immediate posttransplant allograft injury. METHODS: In a multicenter, prospective-cohort study of 144 incipient renal transplant recipients, we postoperatively measured urinary calprotectin using an enzyme-linked immunosorbent assay and estimated glomerular filtration rate (eGFR after 4 weeks, 6 months, and 12 months. RESULTS: We observed a significant inverse association of urinary calprotectin concentrations and eGFR 4 weeks after transplantation (Spearman r =  -0.33; P<0.001. Compared to the lowest quartile, patients in the highest quartile of urinary calprotectin had an increased risk for an eGFR less than 30 mL/min/1.73 m(2 four weeks after transplantation (relative risk, 4.3; P<0.001; sensitivity, 0.92; 95% CI, 0.77 to 0.98; specificity, 0.48; 95% CI, 0.31 to 0.66. Higher urinary calprotectin concentrations predicted impaired kidney function 4 weeks after transplantation, as well as 6 months and 12 months after transplantation. When data were analyzed using the urinary calprotectin/creatinine-ratio similar results were obtained. Urinary calprotectin was superior to current use of absolute change of plasma creatinine to predict allograft function 12 months after transplantation. Urinary calprotectin predicted an increased risk both in transplants from living and deceased donors. Multivariate linear regression showed that higher urinary calprotectin concentrations and older donor age predicted lower eGFR four weeks, 6 months, and 12 months after transplantation. CONCLUSIONS: Urinary calprotectin is an early, noninvasive predictor of immediate renal allograft injury after kidney transplantation.

  20. Urinary Kidney Injury Molecule-1 (KIM-1 in Early Diagnosis of Acute Kidney Injury in Pediatric Critically Ill

    Directory of Open Access Journals (Sweden)

    Irma Lestari Paramastuty

    2016-04-01

    Full Text Available Acute kidney injury (AKI often associated with a high hospital morbi-mortality rate in the intensive care unit patients. Kidney injury molecule-1 (KIM-1, has many characteristics of ideal biomarker for kidney injury. The aim of this study was to compared the temporal pattern of elevation urinary KIM-1 level following critically ill children with SCr as standart biomarker of AKI. Prospective analytic observational study was conducted during October to March 2014 in the Saiful Anwar General Hospital and Physiology Laboratory Brawijaya University. There were 13 critically ill as subjects. SCr and KIM-1 levels from all subjects were measured three times ( at admission, after 1st and 6th hour. Subjects were devided into AKI - non-AKI groups by SCr level and survivor - non survivor group at the and of the observations. Results showed that there were significantly increased levels of KIM-1 in the AKI and non-AKI and survivor-non survivor group at time point. However, we found that delta KIM-1 at time point increased significant in non AKI group and survivor group. KIM-1 at admission can diagnosed AKI in critically ill children. We conclude that urinary KIM-1 is a sensitive non-invasive biomarker to diagnosed acute kidney injury in critically ill children. Increase level of KIM-1 by time shows protective and good outcome in critically ill children.

  1. Potential urinary aging markers of 20-month-old rats

    Directory of Open Access Journals (Sweden)

    Xundou Li

    2016-06-01

    Full Text Available Urine is a very good source for biomarker discovery because it accumulates changes in the body. However, a major challenge in urinary biomarker discovery is the fact that the urinary proteome is influenced by various elements. To circumvent these problems, simpler systems, such as animal models, can be used to establish associations between physiological or pathological conditions and alterations in the urinary proteome. In this study, the urinary proteomes of young (two months old and old rats (20 months old; nine in each group were analyzed using LC-MS/MS and quantified using the Progenesis LC-MS software. A total of 371 proteins were identified, 194 of which were shared between the young and old rats. Based on criteria of a fold change ≥2, P < 0.05 and identification in each rat of the high-abundance group, 33 proteins were found to be changed (15 increased and 18 decreased in old rats. By adding a more stringent standard (protein spectral counts from every rat in the higher group greater than those in the lower group, eight proteins showed consistent changes in all rats of the groups; two of these proteins are also altered in the urinary proteome of aging humans. However, no shared proteins between our results and the previous aging plasma proteome were identified. Twenty of the 33 (60% altered proteins have been reported to be disease biomarkers, suggesting that aging may share similar urinary changes with some diseases. The 33 proteins corresponded to 28 human orthologs which, according to the Human Protein Atlas, are strongly expressed in the kidney, intestine, cerebellum and lung. Therefore, the urinary proteome may reflect aging conditions in these organs.

  2. Circulating angiogenic factors and urinary prolactin as predictors of adverse outcomes in women with preeclampsia.

    Science.gov (United States)

    Leaños-Miranda, Alfredo; Campos-Galicia, Inova; Ramírez-Valenzuela, Karla Leticia; Chinolla-Arellano, Zarela Lizbeth; Isordia-Salas, Irma

    2013-05-01

    Preeclampsia is characterized by an imbalance in angiogenic factors. Urinary prolactin (PRL) levels and its antiangiogenic PRL fragments have been associated with disease severity. In this study, we assessed whether these biomarkers are associated with an increased risk of adverse maternal and perinatal outcomes in preeclamptic women. We studied 501 women with preeclampsia attended at a tertiary care hospital. Serum concentrations of soluble fms-like tyrosine kinase-1 (sFlt-1), placental growth factor (PlGF), and soluble endoglin (sEng), as well as urinary PRL levels, were measured by enzymed-linked immunosorbent assay. Antiangiogenic PRL fragments were determined by immunoblotting. The risk for any adverse maternal outcome and for having a small-for-gestational-age infant was higher among women with sFlt-1/PlGF ratios, sEng, and urinary PRL level values in the highest quartile (odds ratios ≥ 2.7), compared with the lowest quartile. Both urinary PRL levels and the presence of antiangiogenic PRL fragments were more closely associated with the risk of specific adverse maternal outcomes (placental abruption, hepatic hematoma or rupture, acute renal failure, pulmonary edema, maternal death, and need for endotracheal intubation, positive inotropic drug support, and hemodialysis; odds ratios ≥ 5.7 and ≥ 4.7, respectively) than either sFlt-1/PlGF ratio or sEng alone. We concluded that in preeclamptic women at the time of initial evaluation, sFlt-1/PlGF ratio and sEng are associated with increased risk of combined adverse maternal outcomes. However, urinary PRL concentrations and its antiangiogenic fragments appear to be better predictors of an adverse maternal outcome and may be useful for risk stratification in preeclampsia.

  3. Which biomarkers reveal neonatal sepsis?

    Directory of Open Access Journals (Sweden)

    Kun Wang

    Full Text Available We address the identification of optimal biomarkers for the rapid diagnosis of neonatal sepsis. We employ both canonical correlation analysis (CCA and sparse support vector machine (SSVM classifiers to select the best subset of biomarkers from a large hematological data set collected from infants with suspected sepsis from Yale-New Haven Hospital's Neonatal Intensive Care Unit (NICU. CCA is used to select sets of biomarkers of increasing size that are most highly correlated with infection. The effectiveness of these biomarkers is then validated by constructing a sparse support vector machine diagnostic classifier. We find that the following set of five biomarkers capture the essential diagnostic information (in order of importance: Bands, Platelets, neutrophil CD64, White Blood Cells, and Segs. Further, the diagnostic performance of the optimal set of biomarkers is significantly higher than that of isolated individual biomarkers. These results suggest an enhanced sepsis scoring system for neonatal sepsis that includes these five biomarkers. We demonstrate the robustness of our analysis by comparing CCA with the Forward Selection method and SSVM with LASSO Logistic Regression.

  4. Urinary proteins, vitamin D and genetic polymorphisms as risk factors for febrile urinary tract infection and relation with bacteremia: a case control study.

    Directory of Open Access Journals (Sweden)

    Willize E van der Starre

    Full Text Available Febrile urinary tract infection (UTI is a common bacterial disease that may lead to substantial morbidity and mortality especially among the elderly. Little is known about biomarkers that predict a complicated course. Our aim was to determine the role of certain urinary cytokines or antimicrobial proteins, plasma vitamin D level, and genetic variation in host defense of febrile UTI and its relation with bacteremia.A case-control study. Out of a cohort of consecutive adults with febrile UTI (n = 787 included in a multi-center observational cohort study, 46 cases with bacteremic E.coli UTI and 45 cases with non-bacteremic E.coli UTI were randomly selected and compared to 46 controls. Urinary IL-6, IL-8, LL37, β-defensin 2 and uromodulin as well as plasma 25-hydroxyvitamin D were measured. In 440 controls and 707 UTI patients polymorphisms were genotyped in the genes CXCR1, DEFA4, DEFB1, IL6, IL8, MYD88, UMOD, TIRAP, TLR1, TLR2, TLR5 and TNF.IL-6, IL-8, and LL37 are different between controls and UTI patients, although these proteins do not distinguish between patients with and without bacteremia. While uromodulin did not differ between groups, inability to produce uromodulin is more common in patients with bacteremia. Most participants in the study, including the controls, had insufficient vitamin D and, at least in winter, UTI patients have lower vitamin D than controls. Associations were found between the CC genotype of IL6 SNP rs1800795 and occurrence of bacteremia and between TLR5 SNP rs5744168 and protection from UTI. The rare GG genotype of IL6 SNP rs1800795 was associated with higher β-defensin 2 production.Although no biomarker was able to distinguish between UTI with or without bacteremia, two risk factors for bacteremia were identified. These were inability to produce uromodulin and an IL6 rs1800795 genotype.

  5. Biomarkers of acute kidney injury in neonatal encephalopathy.

    LENUS (Irish Health Repository)

    Sweetman, D U

    2013-03-01

    Acute kidney injury (AKI) is a common complication of neonatal encephalopathy (NE). The accurate diagnosis of neonatal AKI, irrespective of the cause, relies on suboptimal methods such as identification of rising serum creatinine, decreased urinary output and glomerular filtration rate. Studies of AKI biomarkers in adults and children have shown that biomarkers can improve the early diagnosis of AKI. Hypoxia-ischaemia is the proposed aetiological basis of AKI in both NE and cardiopulmonary bypass (CPB). However, there is a paucity of studies examining the role of AKI biomarkers specifically in NE. Urinary cystatin C (CysC), neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18, kidney injury molecule-1, liver-type fatty acid-binding protein, serum CysC and serum NGAL all show good ability to predict early AKI in a heterogeneous critically ill neonatal population including infants post-CPB. Moreover, serum and urinary NGAL and urinary CysC are early predictors of AKI secondary to NE. These findings are promising and open up the possibility of biomarkers playing a significant role in the early diagnosis and treatment of NE-related AKI. There is an urgent need to explore the role of AKI biomarkers in infants with NE as establishing the diagnosis of AKI earlier may allow more timely intervention with potential for improving long-term outcome.

  6. Hypotheses, rationale, design, and methods for prognostic evaluation of cardiac biomarker elevation after percutaneous and surgical revascularization in the absence of manifest myocardial infarction. A comparative analysis of biomarkers and cardiac magnetic resonance. The MASS-V Trial

    Directory of Open Access Journals (Sweden)

    Hueb Whady

    2012-08-01

    Full Text Available Abstract Background Although the release of cardiac biomarkers after percutaneous (PCI or surgical revascularization (CABG is common, its prognostic significance is not known. Questions remain about the mechanisms and degree of correlation between the release, the volume of myocardial tissue loss, and the long-term significance. Delayed-enhancement of cardiac magnetic resonance (CMR consistently quantifies areas of irreversible myocardial injury. To investigate the quantitative relationship between irreversible injury and cardiac biomarkers, we will evaluate the extent of irreversible injury in patients undergoing PCI and CABG and relate it to postprocedural modifications in cardiac biomarkers and long-term prognosis. Methods/Design The study will include 150 patients with multivessel coronary artery disease (CAD with left ventricle ejection fraction (LVEF and a formal indication for CABG; 50 patients will undergo CABG with cardiopulmonary bypass (CPB; 50 patients with the same arterial and ventricular condition indicated for myocardial revascularization will undergo CABG without CPB; and another 50 patients with CAD and preserved ventricular function will undergo PCI using stents. All patients will undergo CMR before and after surgery or PCI. We will also evaluate the release of cardiac markers of necrosis immediately before and after each procedure. Primary outcome considered is overall death in a 5-year follow-up. Secondary outcomes are levels of CK-MB isoenzyme and I-Troponin in association with presence of myocardial fibrosis and systolic left ventricle dysfunction assessed by CMR. Discussion The MASS-V Trial aims to establish reliable values for parameters of enzyme markers of myocardial necrosis in the absence of manifest myocardial infarction after mechanical interventions. The establishments of these indices have diagnostic value and clinical prognosis and therefore require relevant and different therapeutic measures. In daily practice

  7. Comparing non contrast computerized tomography criteria versus dual X-ray absorptiometry as predictors of radio-opaque upper urinary tract stone fragmentation after electromagnetic shockwave lithotripsy.

    Science.gov (United States)

    Hameed, Diaa A; Elgammal, Mohammed A; ElGanainy, Ehab O; Hageb, Adel; Mohammed, Khaled; El-Taher, Ahmed Mohamed; Mostafa, Mostafa Mohamed; Ahmed, Abdelfatah Ibrahim

    2013-11-01

    The objective of this study was to assess the value of dual X-ray absorptiometry (DXA) in comparison to non contrast computed tomography (NCCT) density as possible predictors of upper urinary tract stone disintegration by shock wave lithotripsy (SWL). This study included 100 consecutive patients, with solitary renal stone 0.5-2 cm or upper ureteral stone up to 1 cm. DXA to calculate stone mineral density (SMD) and stone mineral content (SMC) was done. NCCT was performed to measure Hounsfield units (HU). SWL was performed with an electromagnetic lithotripsy, plain X-ray documented disintegration after SWL. Successful treatment was defined as stone free or complete fragmentation after 1 or 2 sessions of SWL. The impact of patients age, sex, body mass index, stone laterality, location, volume, length, mean SMC and SMD, HU and Hounsfield density (HD), skin to stone distance (SSD) and number of shock waves were evaluated by univariate and multivariate analysis. Only 76 patients were available for follow-up. Success of disintegration was observed in 50 out of 76 patients (65.8 %). On multivariate analysis, SMC and number of shock wave were the significant independent factors affecting SWL outcome (p = 0.04 and p = 0.000, respectively). SMC as detected by DXA is a significant predictor of success of stone disintegration by SWL. SMC measured by DXA is more accurate than HU measured by CT. Patients with high stone mineral content (SMC greater than 0.65 g) should be directly offered another treatment option.

  8. Long-term comparative outcomes of open versus laparoscopic nephroureterectomy for upper urinary tract urothelial-cell carcinoma after a median follow-up of 13 years*.

    Science.gov (United States)

    Stewart, Grant D; Humphries, Katie J; Cutress, Mark L; Riddick, Antony C P; McNeill, S Alan; Tolley, David A

    2011-08-01

    Open nephroureterectomy (ONU) rather than laparoscopic nephroureterectomy (LNU) is still regarded as the standard of care for extirpative surgical management of upper urinary tract urothelial-cell carcinoma (UUT-UCC). The longest published follow-up of LNU is 7 years. We report outcomes for patients having surgery ≥10 years ago. Consecutive patients with UUT-UCC who were treated with ONU (n=39) or LNU (n=23) between April 1992 to September 2000 were included. Preoperative, tumor, operative and postoperative characteristics, recurrence, and outcomes were collated. Survival was estimated using the Kaplan-Meier method. Median follow-up of censored patients was 163 months (13.6 y). Estimated mean overall survival (OS) was 111 months for ONU and 103 months for LNU. Mean progression free survival (PFS) was 175 months for ONU and 143 months for LNU. Probability of PFS at 10 years was 79% for ONU and 76% for LNU and was unchanged at 15 years. There was no significant difference between ONU and LNU in terms of OS (P=0.51, log-rank test), PFS (P=0.70) or cancer-specific survival (CSS; P=0.43). There were no prognostic differences between ONU and LNU after correcting for confounding variables. There was no increase in the probability of a bladder cancer recurrence from 10 to 15 years postoperation. Long-term follow-up of patients who were operated on more than 10 years ago suggests that LNU has oncologic equivalence to ONU because there were no significant differences in OS, PFS, or CSS between ONU and LNU patients followed for a median of 13 years.

  9. Urinary 1H-NMR Metabolomics Can Distinguish Pancreatitis Patients from Healthy Controls

    Science.gov (United States)

    Lusczek, Elizabeth R; Paulo, Joao A; Saltzman, John R; Kadiyala, Vivek; Banks, Peter A; Beilman, Greg; Conwell, Darwin L

    2015-01-01

    Context The characterization of the urinary metabolome may yield biomarkers indicative of pancreatitis. Objectives We establish a non-invasive technique to compare urinary metabolic profiles in patients with acute and chronic pancreatitis to healthy controls. Methods Urine was obtained from healthy controls (HC, n=5), in patients with mild acute pancreatitis (AP, n=5), and outpatients with chronic pancreatitis (CP, n=5). Proton nuclear magnetic resonance spectra were obtained for each sample. Metabolites were identified and quantified in each spectrum; resulting concentrations were normalized to account for differences in dilution among samples. Kruskal-Wallis test, post-hoc Mann-Whitney U tests, and principal component analysis were performed to identify metabolites that discriminate healthy controls, acute pancreatitis, and chronic pancreatitis. Results Sixty metabolites were identified and quantified; five were found to differ significantly (P<0.05) among the three groups. Of these, citrate and adenosine remained significant after validation by random permutation. Principal component analysis demonstrated that healthy control urine samples can be differentiated from patients with chronic pancreatitis or acute pancreatitis; chronic pancreatitis patients could not be distinguished from acute pancreatitis patients. Conclusions This metabolomic investigation demonstrates that this non-invasive technique offers insight into the metabolic states of pancreatitis. Although the identified metabolites cannot conclusively be defined as biomarkers of disease, future studies will validate our findings in larger patient cohorts. PMID:23474563

  10. Surgery for Stress Urinary Incontinence

    Science.gov (United States)

    ... Management Education & Events Advocacy For Patients About ACOG Surgery for Stress Urinary Incontinence Home For Patients Search ... Stress Urinary Incontinence FAQ166, July 2014 PDF Format Surgery for Stress Urinary Incontinence Special Procedures What is ...

  11. Flavonoids as fruit and vegetable intake biomarkers

    DEFF Research Database (Denmark)

    Krogholm, Kirstine Suszkiewicz

    Most validation studies show that the food frequency questionnaire (FFQ) is rather low in precision and accuracy, and there is an ongoing debate regarding the applicability of such self-reported data with regard to diet-disease relationships. However, no other method has so far been able to replace...... of fruit and vegetable intakes. In Paper I, the urinary recovery of the 7 flavonoids in morning spot urine (i.e. all urine voids from midnight including the first morning void) was also found to respond to moderate increases in the intake of fruits and vegetables. However, the association was somewhat...... weaker than in 24h urine samples, indicating that the 24h urinary recovery of the 7 flavonoids is a stronger biomarker of the intake of fruit and vegetables than the urinary recovery of the 7 flavonoids in morning spot urine. In Paper II, the biokinetic profiles of some of the most important dietary...

  12. The extracellular domain of neurotrophin receptor p75 as a candidate biomarker for amyotrophic lateral sclerosis.

    Directory of Open Access Journals (Sweden)

    Stephanie R Shepheard

    Full Text Available Objective biomarkers for amyotrophic lateral sclerosis would facilitate the discovery of new treatments. The common neurotrophin receptor p75 is up regulated and the extracellular domain cleaved from injured neurons and peripheral glia in amyotrophic lateral sclerosis. We have tested the hypothesis that urinary levels of extracellular neurotrophin receptor p75 serve as a biomarker for both human motor amyotrophic lateral sclerosis and the SOD1(G93A mouse model of the disease. The extracellular domain of neurotrophin receptor p75 was identified in the urine of amyotrophic lateral sclerosis patients by an immuno-precipitation/western blot procedure and confirmed by mass spectrometry. An ELISA was established to measure urinary extracellular neurotrophin receptor p75. The mean value for urinary extracellular neurotrophin receptor p75 from 28 amyotrophic lateral sclerosis patients measured by ELISA was 7.9±0.5 ng/mg creatinine and this was significantly higher (p<0.001 than 12 controls (2.6±0.2 ng/mg creatinine and 19 patients with other neurological disease (Parkinson's disease and Multiple Sclerosis; 4.1±0.2 ng/mg creatinine. Pilot data of disease progression rates in 14 MND patients indicates that p75NTR(ECD levels were significantly higher (p = 0.0041 in 7 rapidly progressing patients as compared to 7 with slowly progressing disease. Extracellular neurotrophin receptor p75 was also readily detected in SOD1(G93A mice by immuno-precipitation/western blot before the onset of clinical symptoms. These findings indicate a significant relation between urinary extracellular neurotrophin receptor p75 levels and disease progression and suggests that it may be a useful marker of disease activity and progression in amyotrophic lateral sclerosis.

  13. The extracellular domain of neurotrophin receptor p75 as a candidate biomarker for amyotrophic lateral sclerosis.

    Science.gov (United States)

    Shepheard, Stephanie R; Chataway, Tim; Schultz, David W; Rush, Robert A; Rogers, Mary-Louise

    2014-01-01

    Objective biomarkers for amyotrophic lateral sclerosis would facilitate the discovery of new treatments. The common neurotrophin receptor p75 is up regulated and the extracellular domain cleaved from injured neurons and peripheral glia in amyotrophic lateral sclerosis. We have tested the hypothesis that urinary levels of extracellular neurotrophin receptor p75 serve as a biomarker for both human motor amyotrophic lateral sclerosis and the SOD1(G93A) mouse model of the disease. The extracellular domain of neurotrophin receptor p75 was identified in the urine of amyotrophic lateral sclerosis patients by an immuno-precipitation/western blot procedure and confirmed by mass spectrometry. An ELISA was established to measure urinary extracellular neurotrophin receptor p75. The mean value for urinary extracellular neurotrophin receptor p75 from 28 amyotrophic lateral sclerosis patients measured by ELISA was 7.9±0.5 ng/mg creatinine and this was significantly higher (pSclerosis; 4.1±0.2 ng/mg creatinine). Pilot data of disease progression rates in 14 MND patients indicates that p75NTR(ECD) levels were significantly higher (p = 0.0041) in 7 rapidly progressing patients as compared to 7 with slowly progressing disease. Extracellular neurotrophin receptor p75 was also readily detected in SOD1(G93A) mice by immuno-precipitation/western blot before the onset of clinical symptoms. These findings indicate a significant relation between urinary extracellular neurotrophin receptor p75 levels and disease progression and suggests that it may be a useful marker of disease activity and progression in amyotrophic lateral sclerosis.

  14. Urinary tract infection in pregnancy.

    Science.gov (United States)

    MacLean, A B

    2001-04-01

    Urinary tract infection is one of the most frequently seen 'medical' complications in pregnancy. The pioneering work of Edward Kass discovered that 6% of pregnant women had asymptomatic bacteriuria associated with increased prematurity and perinatal mortality compared to women with sterile urine. Screening for bacteriuria in pregnancy has become routine. The prevalence of asymptomatic bacteriuria as well as the associated complications described by Kass in 1962 are higher compared to most data collected in the 1980s and late 1990s in different populations in various parts of the world. Other factors such as vaginal colonization have been recognized as important contributors to preterm labour. The value of screening for bacteriuria has to be re-addressed considering methods, significance and costs. Treatment of urinary tract infection in pregnancy is critically reviewed.

  15. Pediatric Urinary Tract Infection

    Science.gov (United States)

    SBA National Resource Center: 800-621-3141 Pediatric Urinary Tract Infections and Catheterization in Children with Neurogenic Bladder and ... To protect the kidneys from damage – By preventing urinary tract infections (UTI) – By identifying and treating vesicoureteral remux (VUR). ...

  16. Biomarkers of occupational exposure to air pollution, inflammation and oxidative damage in taxi drivers.

    Science.gov (United States)

    Brucker, Natália; Moro, Angela M; Charão, Mariele F; Durgante, Juliano; Freitas, Fernando; Baierle, Marília; Nascimento, Sabrina; Gauer, Bruna; Bulcão, Rachel P; Bubols, Guilherme B; Ferrari, Pedro D; Thiesen, Flávia V; Gioda, Adriana; Duarte, Marta M M F; de Castro, Iran; Saldiva, Paulo H; Garcia, Solange C

    2013-10-01

    Exposure to environmental pollutants has been recognised as a risk factor for cardiovascular events. 1-hydroxypyrene (1-OHP) is a biomarker of exposure to polycyclic aromatic hydrocarbons (PAHs) from traffic-related air pollution. Experimental studies indicate that PAH exposure could be associated with inflammation and atherogenesis. Thus, the purpose of this study was to evaluate whether the biomarker of PAH exposure is associated with biomarkers of inflammation and oxidative stress and if these effects modulate the risk of developing cardiovascular diseases in workers exposed to air pollution. This study included 60 subjects, comprising 39 taxi drivers and 21 non-occupationally exposed persons. Environmental PM2.5 and benzo[a]pyrene (BaP) levels, in addition to biomarkers of exposure and oxidative damage, were determined. Inflammatory cytokines (IL-1β, IL-6, IL-10, TNF-α, IFN-γ and hs-CRP) and serum levels of oxidised LDL (ox-LDL), auto-antibodies (ox-LDL-Ab) and homocysteine (Hcy) were also evaluated. PM2.5 and BaP exhibited averages of 12.4±6.9 μg m(-3) and 1.0±0.6 ng m(-3), respectively. Urinary 1-OHP levels were increased in taxi drivers compared to the non-occupationally exposed subjects (ptaxi drivers had elevated pro-inflammatory cytokines, biomarkers of oxidative damage, and ox-LDL, ox-LDL-Ab and Hcy levels, although antioxidant enzymes were decreased compared to the non-occupationally exposed subjects (ptaxi drivers showed major exposure to pollutants, such as PAHs, in relation to non-occupationally exposed subjects. This finding was associated with higher inflammatory biomarkers and Hcy, which represent important predictors for cardiovascular events. These data suggest a contribution of PAHs to cardiovascular diseases upon occupational exposure. © 2013.

  17. Biomarkers in Barrett's esophagus.

    Science.gov (United States)

    Reid, Brian J; Blount, Patricia L; Rabinovitch, Peter S

    2003-04-01

    future. Biopsy repositories are now readily available for phase 3 studies that can evaluate and compare biomarkers. There are initiatives for multi-institutional Barrett's Centers of Excellence that could provide rapid progress in biomarker evaluation. In addition to new candidate biomarkers, the human genome project has provided high-throughput methodologies and methods for computer analysis of data, which can provide the volume and quality control required for clinically useful biomarkers. Currently, 17p (p53) LOH has progressed the furthest among molecular biomarkers. The authors do not recommend its routine clinical use at the present time, however. Finally, it is likely that clinicians will want to follow the results of clinical treatment-response studies and epidemiologic studies that evaluate relationship between clinical interventions or environmental risk and protective factors and surrogate endpoints, especially if the endpoints are progessing well along the phases of biomarker validation. These studies are likely to be of clinical interest because they may becoming the basis for randomized clinical trials to prevent cancer in BE.

  18. 尿甲酸在职业病危害评价中作为甲醛生物标志物的意义%Urinary formaldehyde as a biomarker for evaluation of occupational hazards

    Institute of Scientific and Technical Information of China (English)

    冯斌; 邵华; 单永乐

    2012-01-01

    目的 对车间空气中甲醛浓度和作业环境人群尿中甲酸含量进行测定,验证甲酸作为生物代谢物在接触甲醛的职业危害评价中的意义.方法 对山东省生产人造板的某集团车间空气中甲醛浓度和作业人群尿中甲酸含量进行同步测定,采用Spearman法进行相关分析.结果 车间空气中甲醛浓度与作业职工班末尿中甲酸含量呈正相关(r=0.46,P<0.05),与班末尿中甲酸增加量呈正相关(r=0.48,P<0.05).推测与甲醛的MAC值相配套的甲醛接触工人班末尿中甲酸的生物阈限值,为尿中甲酸含量34.8 mg/g肌酐或甲酸增加量24.0 mg/g肌酐.结论 尿甲酸可以作为接触甲醛职业危害评价中特征性较强的生物标志物.%[Objective]To determine the level of air formaldehyde concentration in workplace and formic acid content in urine of workers with formaldehyde exposure , and verify the value of formic acid in occupational hazard assessment of formaldehyde as biological metabolites. [ Methods] Air concentration of formaldehyde and formic acid content in the urine of workers were simultaneously determined in workplace of a wood-based panels manufacturer in Shandong Province. Spearman method was adopted for correlation analysis. [Results] Air concentration of formaldehyde in workplace was positively correlated with fotmic acid content (r = 0.46,P<0.05) and the increasing amount of formic acid (r=0.48,P<0.05) in workers' urine of shift end. The speculated biological threshold limit value of formic acid content in workers' urine of shift end which matched the MAC value of formaldehyde was urine formic acid content of 34.8 mg/g creatinine or formic acid increasing amount of 24.0 mg/g creatinine. [ Conclusion] Formic acid in urine can be taken as biomarker with obvious characteristic in occupational hazard evaluation of formaldehyde exposure.

  19. Comparative Study of Effectiveness of Long Term Low Dose of Naldixic Acid and Cotrimoxazole in Patients with Recurrent Urinary Tract Infections

    Directory of Open Access Journals (Sweden)

    Sh. Amirhassani

    2012-04-01

    Full Text Available Introduction & Objective: Urinary tract infections (UTI are a common cause of morbidity and its diagnosis and treatment can lead to health. In this study we evaluated the efficacy of the long- term low-dose antibiotic prophylaxis with Cotrimoxazole and Nalidixic-acid in the patients with recurrent UTI.Materials & Methods: This study is a before and after clinical trial without control group done on 100 patients with recurrent UTI who had referred to Ekbatan Hospital. These patients had no urologic findings in clinical and para-clinical evaluations. These patients were treated by Cotrimoxazole or Nalidixic-acid in long term-low dose Antibiotic prophylaxis method according to urine culture and antibiogram. These patients followed with urine cultures in the therapeutic and 6 month follow-up periods. Also, we evaluated the differences between age, gender, type of microorganism, marital status, re-infection time and number of recurrences before treatment.Results: Our study includes 100 patients (83% female and 17% male. The mean+/-SD age of the patients in the group treated with Cotrimoxazole (group A was 15.57+/-13.03 and in the patients treated with Nalidixic-acid (group B was 13.67+/-10.9 years. 74% of the patients who were treated with Cotrimoxazole were single and this number was 66% for the nalidixic-acid group. E.coli, kelebsiella and proteous account for 80%, 18% and 2% of infections in the Cotrimoxazole group, respectively. These microorganisms account for 62%, 34% and 4% of infections in the nalidixic-acid group respectively. The re-infection rate for the Cotrimoxazole group was 18% which 82% of them were successfully treated. The re-infection rate for nalidixic-acid was 12% which 88% of them showed a good response to nalidixic-acid. In fact, in this study Nalidixic-acid was as effective as Cotrimoxazole. Conclusion: The long term-low dose antibiotic prophylaxis is very effective in the treatment of recurrent UTI and in our study Nalidixic

  20. Significance of urinary proteome pattern in renal allograft recipients.

    Science.gov (United States)

    Suhail, Sufi M

    2014-01-01

    Urinary proteomics is developing as a platform of urinary biomarkers of immense potential in recent years. The definition of urinary proteome in the context of renal allograft and characterization of different proteome patterns in various graft dysfunctions have led to the development of a distinct science of this noninvasive tool. Substantial numbers of studies have shown that different renal allograft disease states, both acute and chronic, could portray unique urinary proteome pattern enabling early diagnosis of graft dysfunction and proper manipulation of immunosuppressive strategy that could impact graft prognosis. The methodology of the urinary proteome is nonetheless not more complex than that of other sophisticated assays of conventional urinary protein analysis. Moreover, the need for a centralized database is also felt by the researchers as more and more studies have been presenting their results from different corners and as systems of organizing these newly emerging data being developed at international and national levels. In this context concept of urinary proteomics in renal allograft recipients would be of significant importance in clinical transplantation.

  1. Biomarkers of internal dose for the assessment of environmental exposure to benzene.

    Science.gov (United States)

    Lovreglio, Piero; D'Errico, Maria Nicolà; Fustinoni, Silvia; Drago, Ignazio; Barbieri, Anna; Sabatini, Laura; Carrieri, Mariella; Apostoli, Pietro; Soleo, Leonardo

    2011-10-01

    The urinary excretion of t,t-muconic acid (t,t-MA), S-phenylmercapturic acid (SPMA) and urinary benzene and the influence of a smoking habit and of exposure to urban traffic on the urinary excretion of these biomarkers were investigated in 137 male adults from the general population. All subjects were not occupationally exposed to benzene and resident in two cities in Puglia (Southern-Italy). Environmental exposure to benzene was measured using passive personal samplers. The biomarkers t,t-MA, SPMA and urinary benzene were determined in urine samples collected from each subject at the end of the environmental sampling. The percentage of cases above the limit of detection was higher for SPMA and urinary benzene in smokers than in non-smokers, and for airborne benzene and urinary benzene in subjects exposed to urban traffic. Airborne benzene was correlated with the time spent in urban traffic during the environmental sampling. Among the biomarkers, urinary benzene was found to be correlated with airborne benzene only in non-smokers, and with the time spent in urban traffic, both in smokers and non-smokers considered together, and in non-smokers only. Finally, multiple regression analysis showed that the urinary excretion of all the biomarkers was dependent on the number of cigarettes smoked per day and, for urinary benzene, also on the time spent in urban traffic. In conclusion, urinary benzene seems to be a more valid biomarker than t,t-MA and SPMA to assess environmental exposure to extremely low concentrations of benzene. Cigarette smoking prevailed over traffic exhaust fumes in determining the internal dose of benzene.

  2. Application of urine proteomics for biomarker discovery in drug-induced liver injury

    NARCIS (Netherlands)

    van Swelm, Rachel P L; Kramers, Cornelis; Masereeuw, R.; Russel, Frans G M

    2014-01-01

    Abstract The leading cause of hepatic damage is drug-induced liver injury (DILI), for which currently no adequate predictive biomarkers are available. Moreover, for most drugs related to DILI, the mechanisms underlying the adverse reaction have not yet been elucidated. Urinary protein biomarker cand

  3. Curriculum integration of urinary system

    Institute of Scientific and Technical Information of China (English)

    Min WANG; Li WANG; Wen-xie XU

    2015-01-01

    As the organ-system oriented integration of medical education has been carried out in many domestic medical schools for years,an urgent need of discussions on various problems of integrated medical education emerges.This paper reviews the urinary integrated educational work in Shanghai Jiao Tong University School of Medicine(SJTU-MS)and introduces the contents of the integrated curriculum of urinary system.We focus on whether we should apply the single cycle integration mode or dual cycle mode,and compare the vocational medical education and elite medical education,and demonstrate the importance of inter-system integration and the ideal integrated textbooks.Multifarious teaching methods and other issues are also mentioned.The future development of integrated medical education is prospected positively.

  4. Dynamics of Urinary Calprotectin after Renal Ischaemia.

    Directory of Open Access Journals (Sweden)

    Jan Ebbing

    Full Text Available Urinary calprotectin has been identified as a promising biomarker for acute kidney injury. To date, however, the time-dependent changes of this parameter during acute kidney injury remain elusive. The aim of the present work was to define the time-course of urinary calprotectin secretion after ischaemia/reperfusion-induced kidney injury in comparison to neutrophil gelatinase-associated lipocalin, thereby monitoring the extent of tubular damage in nephron sparing surgery for kidney tumours.The study population consisted of 42 patients. Thirty-two patients underwent either open or endoscopic nephron sparing surgery for kidney tumours. During the surgery, the renal arterial pedicle was clamped with a median ischaemic time of 13 minutes (interquartile range, 4.5-20.3 minutes in 26 patients. Ten retro-peritoneoscopic living donor nephrectomy patients and 6 nephron sparing surgery patients in whom the renal artery was not clamped served as controls. Urinary calprotectin and neutrophil gelatinase-associated lipocalin concentrations were repeatedly measured by enzyme-linked immunosorbent assay and assessed according to renal function parameters.Urinary concentrations of calprotectin and neutrophil gelatinase-associated lipocalin increased significantly after ischaemia/reperfusion injury, whereas concentrations remained unchanged after nephron sparing surgery without ischaemia/reperfusion injury and after kidney donation. Calprotectin and neutrophil gelatinase-associated lipocalin levels were significantly increased 2 and 8 hours, respectively, post-ischaemia. Both proteins reached maximal concentrations after 48 hours, followed by a subsequent persistent decrease. Maximal neutrophil gelatinase-associated lipocalin and calprotectin concentrations were 9-fold and 69-fold higher than their respective baseline values. The glomerular filtration rate was only transiently impaired at the first post-operative day after ischaemia/reperfusion injury (p = 0

  5. Biomarkers in Parkinson's disease (recent update).

    Science.gov (United States)

    Sharma, Sushil; Moon, Carolyn Seungyoun; Khogali, Azza; Haidous, Ali; Chabenne, Anthony; Ojo, Comfort; Jelebinkov, Miriana; Kurdi, Yousef; Ebadi, Manuchair

    2013-09-01

    Parkinson's disease (PD) is the second most common neurodegenerative disorder mostly affecting the aging population over sixty. Cardinal symptoms including, tremors, muscle rigidity, drooping posture, drooling, walking difficulty, and autonomic symptoms appear when a significant number of nigrostriatal dopaminergic neurons are already destroyed. Hence we need early, sensitive, specific, and economical peripheral and/or central biomarker(s) for the differential diagnosis, prognosis, and treatment of PD. These can be classified as clinical, biochemical, genetic, proteomic, and neuroimaging biomarkers. Novel discoveries of genetic as well as nongenetic biomarkers may be utilized for the personalized treatment of PD during preclinical (premotor) and clinical (motor) stages. Premotor biomarkers including hyper-echogenicity of substantia nigra, olfactory and autonomic dysfunction, depression, hyposmia, deafness, REM sleep disorder, and impulsive behavior may be noticed during preclinical stage. Neuroimaging biomarkers (PET, SPECT, MRI), and neuropsychological deficits can facilitate differential diagnosis. Single-cell profiling of dopaminergic neurons has identified pyridoxal kinase and lysosomal ATPase as biomarker genes for PD prognosis. Promising biomarkers include: fluid biomarkers, neuromelanin antibodies, pathological forms of α-Syn, DJ-1, amyloid β and tau in the CSF, patterns of gene expression, metabolomics, urate, as well as protein profiling in the blood and CSF samples. Reduced brain regional N-acetyl-aspartate is a biomarker for the in vivo assessment of neuronal loss using magnetic resonance spectroscopy and T2 relaxation time with MRI. To confirm PD diagnosis, the PET biomarkers include [(18)F]-DOPA for estimating dopaminergic neurotransmission, [(18)F]dG for mitochondrial bioenergetics, [(18)F]BMS for mitochondrial complex-1, [(11)C](R)-PK11195 for microglial activation, SPECT imaging with (123)Iflupane and βCIT for dopamine transporter, and urinary

  6. Urinary Tract Infections (For Teens)

    Science.gov (United States)

    ... Can I Help Someone Who's Being Bullied? Volunteering Urinary Tract Infections KidsHealth > For Teens > Urinary Tract Infections Print A ... especially girls — visit a doctor. What Is a Urinary Tract Infection? A bacterial urinary tract infection (UTI) is the ...

  7. Urinary metabolomics revealed arsenic exposure related to metabolic alterations in general Chinese pregnant women.

    Science.gov (United States)

    Li, Han; Wang, Mu; Liang, Qiande; Jin, Shuna; Sun, Xiaojie; Jiang, Yangqian; Pan, Xingyun; Zhou, Yanqiu; Peng, Yang; Zhang, Bin; Zhou, Aifen; Zhang, Yiming; Chen, Zhong; Cao, Jiangxia; Zhang, Hongling; Xia, Wei; Zheng, Tongzhang; Cai, Zongwei; Li, Yuanyuan; Xu, Shunqing

    2017-01-06

    Arsenic exposure is considered a major environmental threat to human health. It is already known that high-level arsenic exposure has adverse effects on human health. Since the pregnant women are known to be more susceptible to some chemical exposures than ordinary people, the understanding regarding the health effects of low-level arsenic exposure on pregnant women is critical and remains unclear. The aim of this study is to investigate the urinary metabolic changes of pregnant women exposed to low-dose arsenic, and to identify biomarkers from metabolomics analysis. Urine samples of 246 pregnant women were collected in the first trimester of pregnancy and were divided into three groups based on the tertile distribution of urinary arsenic concentrations which were determined using inductively coupled plasma mass spectrometry (ICP-MS). Changes in the metabolite profile were measured using ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC/Q-TOF MS). Arsenic- related metabolic biomarkers were investigated by comparing the samples of the first and third tertiles of arsenic exposure classifications using a partial least-squares discriminant model (PLS-DA). Nine urine potential biomarkers were putatively identified, including LysoPC (14:0), glutathione, 18-carboxy-dinor-LTE4, 20-COOH-LTE4, cystathionine ketimin, 1-(beta-d-ribofuranosyl)-1,4-dihydronicotinamide, thiocysteine, p-cresol glucuronide and vanillactic acid. The obtained results showed that environmental arsenic exposure, even at low levels, could cause metabolite alterations in pregnant women which might be associated with adverse health outcomes. This is the first report on metabolic changes in pregnant women for arsenic exposure. The findings may be valuable for the arsenic risk assessment for pregnant women. Copyright © 2016 Elsevier B.V. All rights reserved.

  8. Defective urinary crystallization inhibition and urinary stone formation

    Directory of Open Access Journals (Sweden)

    Mauricio Carvalho

    2006-06-01

    Full Text Available INTRODUCTION: Nephrocalcin (NC is a glycoprotein produced in the kidney and inhibits calcium oxalate crystal formation. It has been separated into 4 isoforms (A, B, C, and D and found that (A + B are more abundant than (C + D in urine of healthy subjects, but the reverse is seen in human urine of kidney stone patients. To further examine the role of this protein in inhibition of urinary crystallization, nephrocalcin isoforms were purified from 2 genetically pure dog species. MATERIALS AND METHODS: We studied healthy Beagles, known to be non-stone forming dogs, and Mini-Schnauzers, known to be calcium oxalate stone formers. NC was isolated and purified from each group. Urinary biochemistry and calcium oxalate crystal growth inhibition were measured. RESULTS: Specific crystal growth inhibition activity was significantly higher in non-stone forming dogs (9.79 ± 2.25 in Beagles vs. 2.75 ± 1.34 of Mini-Schnauzers, p < 0.005. Dissociation constants toward calcium oxalate monohydrate were 10-fold different, with Beagles' isoforms being 10 times stronger inhibitors compare to those of Mini-Schnauzers'. Isoforms C + D of NC were the main isoforms isolated in stone-forming dogs. CONCLUSION: NC of these two species of dogs differently affects calcium oxalate crystallization and might have a role in determining ulterior urinary stone formation.

  9. HAND WIPE SUBSAMPLING METHOD FOR USE WITH BIOMARKER MEASUREMENTS IN THE AGRICULTURAL HEALTH STUDY/PESTICIDE EXPOSURE STUDY

    Science.gov (United States)

    Dermal exposure studies incorporating urinary biomarker measurements are complicated because dermal sampling may intercept or remove the target chemical before it is absorbed. A hand wipe subsampling method has been developed using polyurethane foam-tipped (PUF) swabs to minim...

  10. Urinary incontinence - collagen implants

    Science.gov (United States)

    ... gov/ency/article/007373.htm Urinary incontinence - injectable implant To use the sharing features on this page, please enable JavaScript. Injectable implants are injections of material into the urethra to ...

  11. 2-Furoylglycine as a Candidate Biomarker of Coffee Consumption.

    Science.gov (United States)

    Heinzmann, Silke S; Holmes, Elaine; Kochhar, Sunil; Nicholson, Jeremy K; Schmitt-Kopplin, Philippe

    2015-09-30

    Specific and sensitive food biomarkers are necessary to support dietary intake assessment and link nutritional habits to potential impact on human health. A multistep nutritional intervention study was conducted to suggest novel biomarkers for coffee consumption. (1)H NMR metabolic profiling combined with multivariate data analysis resolved 2-furoylglycine (2-FG) as a novel putative biomarker for coffee consumption. We relatively quantified 2-FG in the urine of coffee drinkers and investigated its origin, metabolism, and excretion kinetics. When searching for its potential precursors, we found different furan derivatives in coffee products, which are known to get metabolized to 2-FG. Maximal urinary excretion of 2-FG occurred 2 h after consumption (p = 0.0002) and returned to baseline after 24 h (p = 0.74). The biomarker was not excreted after consumption of coffee substitutes such as tea and chicory coffee and might therefore be a promising acute biomarker for the detection of coffee consumption in human urine.

  12. Urinary Tract Infections

    OpenAIRE

    Bjerklund Johansen, Truls E.; Naber, Kurt G.

    2014-01-01

    Urinary tract infections (UTI) are among the most frequently acquired infections in the community, but also in hospitals and other health care institutions, causing a huge amount of antibiotic consumption. During the last decade we have seen significant changes in the field of urinary tract infections regarding causative pathogens and antibiotic treatment calling for an update of current trends. The worldwide increase of uropathogens resistant to former first line antibiotics, such as cotrim...

  13. Urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL in Patients with Obstructive Sleep Apnea.

    Directory of Open Access Journals (Sweden)

    Manish R Maski

    Full Text Available Obstructive sleep apnea (OSA is a well-established risk factor for hypertension and cardiovascular morbidity and mortality. More recently, OSA has been implicated as an independent risk factor for chronic kidney disease. Urinary neutrophil gelatinase-associated lipocalin (NGAL is a well-accepted early biomarker of subclinical kidney tubular injury, preceding an increase in serum creatinine. The goal of this study was to determine if an association exists between OSA and increased urinary NGAL levels.We prospectively enrolled adult patients from the sleep clinic of an academic medical center. Each underwent polysomnography and submitted a urine specimen upon enrollment. We measured NGAL and creatinine levels on all urine samples before participants received treatment with continuous positive airway pressure (CPAP, and, in a subset of OSA patients, after CPAP therapy. We compared the urinary NGAL/creatinine ratio between untreated participants with and without OSA, and within a subset of 11 OSA patients also after CPAP therapy.A total of 49 subjects were enrolled: 16 controls based on an apnea-hypopnea index (events with at least 4% oxygen desaturation; AHI-4% 5 events/hour (mean AHI-4% = 43.3 +/- 28.1. OSA patients had a higher mean body-mass index than the control group (36.58 +/- 11.02 kg/m2 vs. 26.81 +/- 6.55 kg/m2, respectively; p = 0.0005 and were more likely to be treated for hypertension (54.5% vs. 6.25% of group members, respectively; p = 0.0014. The groups were otherwise similar in demographics, and there was no difference in the number of diabetic subjects or in the mean serum creatinine concentration (control = 0.86 +/- 0.15 mg/dl, OSA = 0.87 +/- 0.19 mg/dl; p = 0.7956. We found no difference between the urinary NGAL-to-creatinine ratios among untreated OSA patients versus control subjects (median NGAL/creatinine = 6.34 ng/mg vs. 6.41 ng/mg, respectively; p = 0.4148. Furthermore, CPAP therapy did not affect the urinary NGAL

  14. Association between Oxidative DNA Damage and Risk of Colorectal Cancer: Sensitive Determination of Urinary 8-Hydroxy-2‧-deoxyguanosine by UPLC-MS/MS Analysis

    Science.gov (United States)

    Guo, Cheng; Li, Xiaofen; Wang, Rong; Yu, Jiekai; Ye, Minfeng; Mao, Lingna; Zhang, Suzhan; Zheng, Shu

    2016-09-01

    Oxidative DNA damage plays crucial roles in the pathogenesis of numerous diseases including cancer. 8-hydroxy-2‧-deoxyguanosine (8-OHdG) is the most representative product of oxidative modifications of DNA, and urinary 8-OHdG is potentially the best non-invasive biomarker of oxidative damage to DNA. Herein, we developed a sensitive, specific and accurate method for quantification of 8-OHdG in human urine. The urine samples were pretreated using off-line solid-phase extraction (SPE), followed by ultrahigh performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis. By the use of acetic acid as an additive to the mobile phase, we improved the UPLC-MS/MS detection of 8-OHdG by 2.7-5.3 times. Using the developed strategy, we measured the contents of 8-OHdG in urine samples from 142 healthy volunteers and 84 patients with colorectal cancer (CRC). We observed increased levels of urinary 8-OHdG in patients with CRC and patients with tumor metastasis, compared to healthy controls and patients without tumor metastasis, respectively. Additionally, logistic regression analysis and receiver operator characteristic (ROC) curve analysis were performed. Our findings implicate that oxidative stress plays important roles in the development of CRC and the marked increase of urinary 8-OHdG may serve as a potential liquid biomarker for the risk estimation, early warning and detection of CRC.

  15. Association between Oxidative DNA Damage and Risk of Colorectal Cancer: Sensitive Determination of Urinary 8-Hydroxy-2‧-deoxyguanosine by UPLC-MS/MS Analysis

    Science.gov (United States)

    Guo, Cheng; Li, Xiaofen; Wang, Rong; Yu, Jiekai; Ye, Minfeng; Mao, Lingna; Zhang, Suzhan; Zheng, Shu

    2016-09-01

    Oxidative DNA damage plays crucial roles in the pathogenesis of numerous diseases including cancer. 8-hydroxy-2‧-deoxyguanosine (8-OHdG) is the most representative product of oxidative modifications of DNA, and urinary 8-OHdG is potentially the best non-invasive biomarker of oxidative damage to DNA. Herein, we developed a sensitive, specific and accurate method for quantification of 8-OHdG in human urine. The urine samples were pretreated using off-line solid-phase extraction (SPE), followed by ultrahigh performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis. By the use of acetic acid as an additive to the mobile phase, we improved the UPLC-MS/MS detection of 8-OHdG by 2.7‑5.3 times. Using the developed strategy, we measured the contents of 8-OHdG in urine samples from 142 healthy volunteers and 84 patients with colorectal cancer (CRC). We observed increased levels of urinary 8-OHdG in patients with CRC and patients with tumor metastasis, compared to healthy controls and patients without tumor metastasis, respectively. Additionally, logistic regression analysis and receiver operator characteristic (ROC) curve analysis were performed. Our findings implicate that oxidative stress plays important roles in the development of CRC and the marked increase of urinary 8-OHdG may serve as a potential liquid biomarker for the risk estimation, early warning and detection of CRC.

  16. Biomarker analyses from a randomized, placebo-controlled, phase IIIb trial comparing bevacizumab with or without erlotinib as maintenance therapy for the treatment of advanced non-small-cell lung cancer (ATLAS).

    Science.gov (United States)

    Kabbinavar, Fairooz; Fehrenbacher, Louis; Hainsworth, John; Kasubhai, Saifuddin; Kressel, Bruce; Marsland, Thomas; Patel, Taral; Rubin, Mark; White, Leonard; Yang, James Chih-Hsin; Klughammer, Barbara; Colburn, Dawn; Miller, Vincent; Johnson, Bruce E

    2014-09-01

    ATLAS compared bevacizumab plus erlotinib (B+E) with bevacizumab plus placebo (B+P) as maintenance therapy after first-line bevacizumab plus chemotherapy (B+C) for advanced non-small-cell lung cancer (NSCLC). Prespecified biomarkers were prospectively evaluated. Tumor samples were analyzed for: epidermal growth factor receptor (EGFR) expression (immunohistochemistry [IHC]); EGFR gene copy number (fluorescence in-situ hybridization [FISH]); EGFR mutations (exon 19 deletions/L858R mutations); and KRAS mutations (exons 2/3). Progression-free survival (PFS) and overall survival (OS) were estimated. Of 743 patients randomized to receive maintenance treatment (after four cycles of B+C without progression), 190 (B+E) and 177 (B+P) were evaluable for biomarker status. Median PFS (from randomization) was 4.4 months (B+E) versus 3.7 months (B+P; hazard ratio [HR], 0.75; 95% confidence interval [CI], 0.57-0.99), which was numerically similar to the intent-to-treat PFS. PFS benefit of B+E was observed across most biomarker subgroups. EGFR IHC, EGFR FISH, and EGFR/KRAS mutation status were not predictive of outcome. B+E-treated patients with EGFR mutation-positive NSCLC had longer PFS compared with B+P-treated patients (HR, 0.44; 95% CI, 0.22-0.86; p = 0.0139). Patients with KRAS wild-type disease had significant PFS improvements with B+E, compared with B+P (HR, 0.66; 95% CI, 0.485-0.914; p = 0.0105). No OS benefit of B+E was observed. Patients with KRAS wild-type or EGFR mutation-positive NSCLC derived PFS benefits from B+E. However, EGFR IHC, EGFR FISH, and EGFR or KRAS mutation status were not strongly predictive of survival. A larger sample size would be needed to confirm the initial trends observed in this study.

  17. Assessing adrenocortical activity by determining levels of urinary free cortisol and urinary 6 beta-hydroxycortisol.

    Science.gov (United States)

    Nakamura, J; Yakata, M

    1989-03-01

    A comparative study of urinary free cortisol and urinary 6 beta-hydroxycortisol levels as a diagnostic test for hypercortisolemic states was carried out by measuring the excretion in 24-h specimens from 289 apparently healthy subjects and 10 Cushing patients. The diurnal variations of both variables were examined in normal subjects and subjects with altered adrenal activities. Two of the 289 apparently normal subjects had high values of urinary free cortisol; one had a high, the other a normal 6 beta-hydroxycortisol level; they were later diagnosed as having Cushing's syndrome and infertility, respectively. Three other subjects had high values of the urinary variables, but during 5 years of follow-up did not show any clinical evidence of hypercortisolism. The two urinary variables gave no false-negative results in the Cushing patients. The diurnal variation revealed that levels of 6 beta-hydroxycortisol change in parallel with those of free cortisol in normal subjects and in subjects with altered adrenal activities. However, the ratio of 6 beta-hydroxycortisol to free cortisol during the diurnal variation varied from low values when free cortisol levels were high to high values when free cortisol levels were low. In normal subjects, 1 mg of dexamethasone taken orally at 23.00 h completely suppressed the levels of both variables on the following day. It is concluded that urinary 6 beta-hydroxycortisol is correlated to urinary free cortisol so that measurement of urinary 6 beta-hydroxycortisol levels can be used as a diagnostic test for hypercortisolism in a way comparable to the method using urinary free cortisol.

  18. Characterization of renal biomarkers for use in clinical trials: biomarker evaluation in healthy volunteers

    Directory of Open Access Journals (Sweden)

    Brott DA

    2014-02-01

    Full Text Available David A Brott,1 Scott H Adler,1 Ramin Arani,2 Susan C Lovick,3 Mark Pinches,4 Stephen T Furlong1 1Translational Patient Safety and Enabling Sciences, AstraZeneca Pharmaceuticals, 2AstraZeneca Pharmaceuticals, Wilmington, DE, USA; 3AstraZeneca Pharmaceuticals, 4Global Safety Assessment, AstraZeneca Pharmaceuticals, Macclesfield, Cheshire, UK Background: Several preclinical urinary biomarkers have been qualified and accepted by the health authorities (US Food and Drug Administration, European Medicines Agency, and Pharmaceuticals and Medical Devices Agency for detecting drug-induced kidney injury during preclinical toxicologic testing. Validated human assays for many of these biomarkers have become commercially available, and this study was designed to characterize some of the novel clinical renal biomarkers. The objective of this study was to evaluate clinical renal biomarkers in a typical Phase I healthy volunteer population to determine confidence intervals (pilot reference intervals, intersubject and intrasubject variability, effects of food intake, effect of sex, and vendor assay comparisons. Methods: Spot urine samples from 20 male and 19 female healthy volunteers collected on multiple days were analyzed using single analyte and multiplex assays. The following analytes were measured: α-1-microglobulin, β-2-microglobulin, calbindin, clusterin, connective tissue growth factor, creatinine, cystatin C, glutathione S-transferase-α, kidney injury marker-1, microalbumin, N-acetyl-β-(D glucosaminidase, neutrophil gelatinase-associated lipocalin, osteopontin, Tamm-Horsfall urinary glycoprotein, tissue inhibitor of metalloproteinase 1, trefoil factor 3, and vascular endothelial growth factor. Results: Confidence intervals were determined from the single analyte and multiplex assays. Intersubject and intrasubject variability ranged from 38% to 299% and from 29% to 82% for biomarker concentration, and from 24% to 331% and from 10% to 67% for

  19. Randomized trial of glucosamine and chondroitin supplementation on inflammation and oxidative stress biomarkers and plasma proteomics profiles in healthy humans.

    Directory of Open Access Journals (Sweden)

    Sandi L Navarro

    Full Text Available Glucosamine and chondroitin are popular non-vitamin dietary supplements used for osteoarthritis. Long-term use is associated with lower incidence of colorectal and lung cancers and with lower mortality; however, the mechanism underlying these observations is unknown. In vitro and animal studies show that glucosamine and chondroitin inhibit NF-kB, a central mediator of inflammation, but no definitive trials have been done in healthy humans.We conducted a randomized, double-blind, placebo-controlled, cross-over study to assess the effects of glucosamine hydrochloride (1500 mg/d plus chondroitin sulfate (1200 mg/d for 28 days compared to placebo in 18 (9 men, 9 women healthy, overweight (body mass index 25.0-32.5 kg/m2 adults, aged 20-55 y. We examined 4 serum inflammatory biomarkers: C-reactive protein (CRP, interleukin 6, and soluble tumor necrosis factor receptors I and II; a urinary inflammation biomarker: prostaglandin E2-metabolite; and a urinary oxidative stress biomarker: F2-isoprostane. Plasma proteomics on an antibody array was performed to explore other pathways modulated by glucosamine and chondroitin.Serum CRP concentrations were 23% lower after glucosamine and chondroitin compared to placebo (P = 0.048. There were no significant differences in other biomarkers. In the proteomics analyses, several pathways were significantly different between the interventions after Bonferroni correction, the most significant being a reduction in the "cytokine activity" pathway (P = 2.6 x 10-16, after glucosamine and chondroitin compared to placebo.Glucosamine and chondroitin supplementation may lower systemic inflammation and alter other pathways in healthy, overweight individuals. This study adds evidence for potential mechanisms supporting epidemiologic findings that glucosamine and chondroitin are associated with reduced risk of lung and colorectal cancer.ClinicalTrials.gov NCT01682694.

  20. A pilot trial assessing urinary gene expression profiling with an mRNA array for diabetic nephropathy.

    Directory of Open Access Journals (Sweden)

    Min Zheng

    Full Text Available BACKGROUND: The initiation and progression of diabetic nephropathy (DN is complex. Quantification of mRNA expression in urinary sediment has emerged as a novel strategy for studying renal diseases. Considering the numerous molecules involved in DN development, a high-throughput platform with parallel detection of multiple mRNAs is needed. In this study, we constructed a self-assembling mRNA array to analyze urinary mRNAs in DN patients with aims to reveal its potential in searching novel biomarkers. METHODS: mRNA array containing 88 genes were fabricated and its performance was evaluated. A pilot study with 9 subjects including 6 DN patients and 3 normal controls were studied with the array. DN patients were assigned into two groups according to their estimate glomerular rate (eGFR: DNI group (eGFR>60 ml/min/1.73 m(2, n = 3 and DNII group (eGFR<60 ml/min/1.73 m(2, n = 3. Urinary cell pellet was collected from each study participant. Relative abundance of these target mRNAs from urinary pellet was quantified with the array. RESULTS: The array we fabricated displayed high sensitivity and specificity. Moreover, the Cts of Positive PCR Controls in our experiments were 24±0.5 which indicated high repeatability of the array. A total of 29 mRNAs were significantly increased in DN patients compared with controls (p<0.05. Among these genes, α-actinin4, CDH2, ACE, FAT1, synaptopodin, COL4α, twist, NOTCH3 mRNA expression were 15-fold higher than those in normal controls. In contrast, urinary TIMP-1 mRNA was significantly decreased in DN patients (p<0.05. It was shown that CTGF, MCP-1, PAI-1, ACE, CDH1, CDH2 mRNA varied significantly among the 3 study groups, and their mRNA levels increased with DN progression (p<0.05. CONCLUSION: Our pilot study demonstrated that mRNA array might serve as a high-throughput and sensitive tool for detecting mRNA expression in urinary sediment. Thus, this primary study indicated that mRNA array probably could be a

  1. Studies of biomarkers in aluminum workers occupationally exposed to polycyclic aromatic hydrocarbons.

    Science.gov (United States)

    Ovrebø, S; Haugen, A; Hemminki, K; Szyfter, K; Drabløs, P A; Skogland, M

    1995-01-01

    Evaluation of biomarkers for genotoxic exposure are important for future use of such biomarkers in cancer prevention. We have studied a group of aluminum plant workers for a period of 2.5 years. The level of polycyclic aromatic hydrocarbons (PAHs) has been monitored at the work place (cathode relining). During the study period, urine and blood were sampled up to seven times from the same workers. Mean level of urinary 1-hydroxypyrene varied from 1.08 to 2.44 mumol/mol creatinine in the exposed groups compared with 0.36 and 0.20 mumol/mol creatinine in the two reference groups. For a group of 14 workers the intraindividual variation of urinary 1-hydroxypyrene was analyzed. The relative standard deviation of the values was < or = 0.50 for half of the workers; the relative standard deviation was calculated for individual values divided by mean of each time point. Polycyclic aromatic hydrocarbon-DNA adducts in white blood cells from exposed and nonexposed workers were measured by both immunoassay and 32P-postlabeling. By 32P-postlabeling mean values of 12.0 adducts/10(8) and 10.8 adducts/10(8) nucleotides were found in a PAH-exposed group and a reference group, respectively. Intraindividual variation of PAH-DNA adducts was also analyzed.

  2. Human urinary mutagenicity after wood smoke exposure during traditional temazcal use

    OpenAIRE

    Long, Alexandra S.; Lemieux, Christine L.; Yousefi, Paul; Ruiz-Mercado, Ilse; Lam, Nicholas L.; Orellana, Carolina Romero; White, Paul A.; Smith, Kirk R.; Holland, Nina

    2014-01-01

    In Central America, the traditional temazcales or wood-fired steam baths, commonly used by many Native American populations, are often heated by wood fires with little ventilation, and this use results in high wood smoke exposure. Urinary mutagenicity has been previously employed as a non-invasive biomarker of human exposure to combustion emissions. This study examined the urinary mutagenicity in 19 indigenous Mayan families from the highlands of Guatemala who regularly use temazcales (N = 32...

  3. A Prospective Study of Comparing Multi-Gene Biomarker Chip and Serum Carcinoembryonic Antigen in the Postoperative Surveillance for Patients with Stage I-III Colorectal Cancer.

    Science.gov (United States)

    Chang, Yu-Tang; Huang, Ming-Yii; Yeh, Yung-Sung; Huang, Ching-Wen; Tsai, Hsiang-Lin; Cheng, Tian-Lu; Wang, Jaw-Yuan

    2016-01-01

    Circulating biomarkers can predict clinical outcomes in colorectal cancer patients. The aim of the study was to evaluate the feasibility of our multigene biomarker chip for detecting circulating tumor cells for postoperative surveillance of stage I-III colorectal cancer patients. In total, 298 stage I-III colorectal cancer patients were analyzed after curative resection between June 2010 and October 2014. During each follow-up, a postoperative surveillance strategy, including ESMO Guidelines Working Group recommendations and the biochip, was used. After a 28.4-month median follow-up, 48 (16.1%) patients had postoperative relapse. Univariate analysis revealed that the postoperative relapse risk factors were rectal tumor, perineural invasion, elevated preoperative and postoperative serum carcinoembryonic antigen levels, and positive biochip results (all P postoperative relapse correlated significantly with elevated postoperative serum carcinoembryonic antigen levels (odds ratio = 4.136, P = 0.008) and positive biochip results (odds ratio = 66.878, P sensitivity (P = 0.003), specificity (P = 0.003), positive (P = 0.002) and negative (P = 0.006) predictive values, and accuracy (P postoperative relapse were significantly higher than those of elevated postoperative serum carcinoembryonic antigen levels. Moreover, the median lead time between positive biochip result and postoperative relapse detection was significantly earlier than that between elevated postoperative serum carcinoembryonic antigen level and postoperative relapse detection (10.7 vs. 2.8 months, P postoperative relapse during stage I-III colorectal cancer patient surveillance. In clinical practice, this biochip may facilitate early postoperative relapse diagnosis in colorectal cancer patients.

  4. Artificial urinary sphincters for male stress urinary incontinence: current perspectives

    Directory of Open Access Journals (Sweden)

    Cordon BH

    2016-07-01

    Full Text Available Billy H Cordon,1 Nirmish Singla,1 Ajay K Singla2 1Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, 2Department of Urology, University of Toledo College of Medicine, Toledo, OH, USA Abstract: The artificial urinary sphincter (AUS, which has evolved over many years, has become a safe and reliable treatment for stress urinary incontinence and is currently the gold standard. After 4 decades of existence, there is substantial experience with the AUS. Today AUS is most commonly placed for postprostatectomy stress urinary incontinence. Only a small proportion of urologists routinely place AUS. In a survey in 2005, only 4% of urologists were considered high-volume AUS implanters, performing >20 per year. Globally, ~11,500 AUSs are placed annually. Over 400 articles have been published regarding the outcomes of AUS, with a wide variance in success rates ranging from 61% to 100%. Generally speaking, the AUS has good long-term outcomes, with social continence rates of ~79% and high patient satisfaction usually between 80% and 90%. Despite good outcomes, a substantial proportion of patients, generally ~25%, will require revision surgery, with the rate of revision increasing with time. Complications requiring revision include infection, urethral atrophy, erosion, and mechanical failure. Most infections are gram-positive skin flora. Urethral atrophy and erosion lie on a spectrum resulting from the same problem, constant urethral compression. However, these two complications are managed differently. Mechanical failure is usually a late complication occurring on average later than infection, atrophy, or erosions. Various techniques may be used during revisions, including cuff relocation, downsizing, transcorporal cuff placement, or tandem cuff placement. Patient satisfaction does not appear to be affected by the need for revision as long as continence is restored. Additionally, AUS following prior sling surgery has comparable

  5. Urinary liver-type fatty acid-binding protein change in gestational diabetes mellitus.

    Science.gov (United States)

    Fu, Wen-Jin; Wang, Du-Juan; Deng, Ren-Tang; Huang, Zhi-Hong; Chen, Mei-Lian; Jang, You-Ming; Wen, Shu; Yang, Hong-Ling; Huang, Xian-zhang

    2015-09-01

    We compared urinary liver-type fatty acid-binding protein (L-FABP) among non-pregnant and pregnant women with and without gestational diabetes mellitus (GDM). Higher urinary L-FABP was found in pregnant with and without GDM, and considerably higher urinary L-FABP was found in the GDM group compared with the non-GDM group. Hyperglycemia and anemia were related with high urinary L-FABP expression.

  6. Urinary KIM-1, NGAL and L-FABP for the diagnosis of AKI in patients with acute coronary syndrome or heart failure undergoing coronary angiography.

    Science.gov (United States)

    Torregrosa, Isidro; Montoliu, Carmina; Urios, Amparo; Andrés-Costa, María Jesús; Giménez-Garzó, Carla; Juan, Isabel; Puchades, María Jesús; Blasco, María Luisa; Carratalá, Arturo; Sanjuán, Rafael; Miguel, Alfonso

    2015-11-01

    Acute kidney injury (AKI) is a common complication after coronary angiography. Early biomarkers of this disease are needed since increase in serum creatinine levels is a late marker. To assess the usefulness of urinary kidney injury molecule-1 (uKIM-1), neutrophil gelatinase-associated lipocalin (uNGAL) and liver-type fatty acid-binding protein (uL-FABP) for early detection of AKI in these patients, comparing their performance with another group of cardiac surgery patients. Biomarkers were measured in 193 patients, 12 h after intervention. In the ROC analysis, AUC for KIM-1, NGAL and L-FABP was 0.713, 0.958 and 0.642, respectively, in the coronary angiography group, and 0.716, 0.916 and 0.743 in the cardiac surgery group. Urinary KIM-1 12 h after intervention is predictive of AKI in adult patients undergoing coronary angiography, but NGAL shows higher sensitivity and specificity. L-FABP provides inferior discrimination for AKI than KIM-1 or NGAL in contrast to its performance after cardiac surgery. This is the first study showing the predictive capacity of KIM-1 for AKI after coronary angiography. Further studies are still needed to answer relevant questions about the clinical utility of biomarkers for AKI in different clinical settings.

  7. Urinary microRNA-29 correlates with urinary albumin in type 2 diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    钟美容

    2014-01-01

    Objective To investigate the possibility of urinary microRNA-29(miR-29)as biomarker for diabetic nephropathy in patients with type 2 diabetes.Methods Sixty-one patients with type 2 diabetes were divided into 2groups:diabetes with normoalbuminuria[n=25,(58.88±11.75)years old]and diabetes with albuminuria[n=36,(62.19±13.11)years old].There were no significant differences in age and gender between groups.The

  8. Evaluation of Exposures to Diesel Particulate Matter Utilizing Ambient Air Monitoring and Urinary Biomarkers Among Pedestrian Commuters who Cross the U.S.-Mexico Border at San Ysidro, CA

    Science.gov (United States)

    Galaviz, Vanessa Eileen

    Background: Walk-in-line pedestrians crossing the U.S.-Mexico border northbound at the San Ysidro, CA Port of Entry ("Border Commuters") may be at an increased risk of experiencing elevated traffic-related air pollution, including diesel exhaust (DE). DE exposure has been associated with numerous adverse health effects, particularly cardiovascular and respiratory problems, including as lung cancer. Pedestrian crossers wait in line for extended periods and stand within 10 feet of highly concentrated traffic, particularly to diesel buses. Understanding the magnitude of traffic-related exposures is important for this vulnerable population. It was hypothesized that subjects who reside in Tijuana, Baja California, Mexico and cross the border as a pedestrian will experience higher exposure to traffic-related pollutants than those who live and work in South San Diego, CA, USA and do not cross the border. Methods: Ninety-one participants were enrolled for this study; 80% were "Border Commuters" and 20% were "Non-Border Commuters". "Non-Border Commuters" served as the comparison group and were defined as residents who lived in or near and worked or went to school in San Ysidro, CA but did not cross the border. Questionnaires, time activity diaries, and urine samples were collected from all participants. Of the "Border Commuters", 56 personal 24-hour PM2.5 and 1-nitropyrene (1-NP) - a marker for diesel exhaust - samples were collected. There were 22 at-home indoor and 14 at-home outdoor 1-NP samples collected. Additionally, area samples collected at the border included 35 days of 1-NP, black carbon (BC), carbon monoxide (CO), fine particulate matter (PM2.5) and ultrafine particulate matter (UFP). Of the "Non-Border Commuters", 15 personal 24-hour PM2.5 and 1-NP samples were collected. Additonally, 3 at-home indoor and outdoor 24-hour 1-NP samples were collected. Results: Personal exposure to PM2.5 was nearly 2-fold higher among "Border Commuters" compared to "Non

  9. Urinary cadmium levels in active and retired coal miners.

    Science.gov (United States)

    Isermann, Julia; Prager, Hans-Martin; Ebbinghaus, Rainer; Janasik, Beata; Wasowicz, Wojciech; Dufaux, Bertinus; Meyer, Hans-Friedrich; Widera, Agata; Selinski, Silvia; Hengstler, Jan G; Golka, Klaus

    2017-01-01

    A meta-analysis, based upon 24 publications, showed a significantly elevated risk for urinary bladder cancer amongst miners. In European underground hard coal mining areas, an increased risk for urinary bladder cancer development was noted among hard coal miners, in particular in three investigations in the greater Dortmund area. However, the cause remains unclear. As cadmium (Cd), which was reported to be a bladder carcinogen in humans and is a constituent of coal, the aim of this study was to determine urinary Cd levels in active and retired hard coal miners and assess whether hard coal miners demonstrated elevated metal levels. In total, 103 retired and 25 active hard coal miners as well as 18 controls without any history of hard coal mining were investigated for urinary Cd levels. Urinary Cd concentrations, in addition to other elements, were analyzed in spot urines by ICP-MS-based multi-element analysis in a Department for Forensic and Clinical Toxicology. Limit of detection (LOD) for Cd was 0.5 μg/L. Reference value for occupationally non-exposed working age population was 0.8 μg/L. In total, 49% of all underground coal miners were exposed to coal dust, 12% to grinded rock, and 39% to both. Urinary Cd levels in retired as well as active coal miners and controls were clearly below the Biological Exposure Index. Urinary Cd concentration is a suitable biomarker to evaluate the metallic load of the body, as the half-life is > than 10 years. The detected urinary Cd levels in retired and active coal miners indicated underground hard coal miners were not apparently exposed to Cd to a occupationally-relevant concentration.

  10. Fasting and Urinary Stones

    Directory of Open Access Journals (Sweden)

    Ali Shamsa

    2013-11-01

    Full Text Available Introduction: Fasting is considered as one of the most important practices of Islam, and according to Prophet Mohammad, fasting is obligatory upon Muslims. The aim of this study is to evaluate the effects of fasting on urinary stones. Materials and Methods: Very few studies have been carried out on urinary stones and the effect of Ramadan fasting. The sources of the present study are Medline and articles presented by local and Muslim researchers. Meanwhile, since we are acquainted with three well-known researchers in the field of urology, we contacted them via email and asked for their professional opinions. Results: The results of studies about the relationship of urinary stones and their incidence in Ramadan are not alike, and are even sometimes contradictory. Some believe that increased incidence of urinary stones in Ramadan is related not to fasting, but to the rise of weather temperature in hot months, and an increase in humidity. Conclusion: Numerous biological and behavioral changes occur in people who fast in Ramadan and some researchers believe that urinary stone increases during this month.

  11. Fasting and urinary stones

    Directory of Open Access Journals (Sweden)

    Ali Shamsa

    2013-12-01

    Full Text Available Introduction: Fasting is considered as one of the most important practices of Islam, and according to Prophet Mohammad, fasting is obligatory upon Muslims. The aim of this study is to evaluate the effects of fasting on urinary stones. Materials and Methods:Very few studies have been carried out on urinary stones and the effect of Ramadan fasting. The sources of the present study are Medline and articles presented by local and Muslim researchers. Meanwhile, since we are acquainted with three well-known researchers in the field  of urology, we contacted them via email and asked for their professional opinions. Results:The results of studies about the relationship of urinary stones and their incidence in Ramadan are not alike, and are even sometimes contradictory. Some believe that increased incidence of urinary stones in Ramadan is related not to fasting, but to the rise of weather temperature in hot months, and an increase in humidity. Conclusion: Numerous biological and behavioral changes occur in people who fast in Ramadan and some researchers believe that urinary stone increases during this month.

  12. Pediatric urinary tract infection

    Energy Technology Data Exchange (ETDEWEB)

    Blickman, J.G.

    1991-02-06

    Acute urinary tract infection (UTI) is an important cause of morbidity in children and may be complicated by congenital urinary tract abnormalities of a functional or anatomic nature which, predispose to recurrent UTI's that in turn may lead to renal failure and hypertension. Early radiologic and ultrasonographic investigations may reveal these anatomic anomalies in particular because the urinary tract, specifically in children, is not readily accessible to adequate clinical examinations Excretory urography (EU) has been considered as the 'gold standard' of upper urinary tract visualization, while the voiding cystourethrogram (VCUG) was thought to be the preferential method of imaging of the lower urinary tract. Recently, major technical advances have altered this commonly accepted diagnostic workup. Although ultrasonography, radio-nuclide scanning and urodynamics have become important contributors to the understanding of pathophysiology of UTI's their value and place in assessment of the sequence of imaging has not been comprehensively studied. This thesis deals about the optimization of the choice and the order of the different imaging techniques used in the evaluation of children, younger than six year with UTI. (author). 243 refs.; 23 figs.; 8 tabs.

  13. Prophylactic ciprofloxacin for catheter-associated urinary-tract infection

    NARCIS (Netherlands)

    Wall, E. van der; Verkooyen, R.P.; Mintjes-de Groot, J.; Oostinga, J.; Dijk, Arie van; Hustinx, W.N.M.; Verbrugh, H.A.

    1992-01-01

    Patients receiving antibiotics during bladder drainage have a lower incidence of urinary-tract infections compared with similar patients not on antibiotics. However, antibiotic prophylaxis in patients with a urinary catheter is opposed because of the fear of inducing resistant bacterial strains. We

  14. Distribution, variability, and predictors of urinary concentrations of phenols and parabens among pregnant women in Puerto Rico.

    Science.gov (United States)

    Meeker, John D; Cantonwine, David E; Rivera-González, Luis O; Ferguson, Kelly K; Mukherjee, Bhramar; Calafat, Antonia M; Ye, Xiaoyun; Anzalota Del Toro, Liza V; Crespo-Hernández, Noé; Jiménez-Vélez, Braulio; Alshawabkeh, Akram N; Cordero, José F

    2013-04-02

    Puerto Rico has higher rates of a range of endocrine-related diseases and disorders compared to the United States. However, little is known to date about human exposures to known or potential endocrine disrupting chemicals (EDCs) in Puerto Rico. We recruited 105 pregnant women in Northern Puerto Rico who provided urine samples and questionnaire data at three times (18 ± 2, 22 ± 2, and 26 ± 2 weeks) during gestation. We measured the urinary concentrations of five phenols and three parabens: 2,4-dichlorophenol (24-DCP), 2,5-dichlorophenol (25-DCP), benzophenone-3 (BP-3), bisphenol A (BPA), triclosan (TCS), butyl paraben (B-PB), methyl paraben (M-PB), and propyl paraben (P-PB). The frequent detection of these chemicals suggests that exposure is highly prevalent among these Puerto Rican pregnant women. Urinary concentrations of TCS, BP-3, and 25-DCP were higher than among women of reproductive age in the US general population, while concentrations of BPA, 24-DCP, and parabens were similar. Intraclass correlation coefficients (ICC) varied widely between biomarkers; BPA had the lowest ICC (0.24) and BP-3 had the highest (0.62), followed by 25-DCP (0.49) and TCS (0.47). We found positive associations between biomarker concentrations with self-reported use of liquid soap (TCS), sunscreen (BP-3), lotion (BP-3 and parabens), and cosmetics (parabens). Our results can inform future epidemiology studies and strategies to reduce exposure to these chemicals or their precursors.

  15. Distribution, variability and predictors of urinary concentrations of phenols and parabens among pregnant women in Puerto Rico

    Science.gov (United States)

    Meeker, John D.; Cantonwine, David E.; Rivera-González, Luis O.; Ferguson, Kelly K.; Mukherjee, Bhramar; Calafat, Antonia M.; Ye, Xiaoyun; Anzalota Del Toro, Liza V.; Crespo, Noe; Jiménez-Vélez, Braulio; Alshawabkeh, Akram N.; Cordero, José F.

    2013-01-01

    Puerto Rico has higher rates of a range of endocrine-related diseases and disorders compared to the United States. However, little is known to date about human exposures to known or potential endocrine disrupting chemicals (EDCs) in Puerto Rico. We recruited 105 pregnant women in Northern Puerto Rico who provided urine samples and questionnaire data at three times (20±2, 24±2, and 28±2 weeks) during gestation. We measured the urinary concentrations of five phenols and three parabens: 2,4-dichlorophenol (24-DCP), 2,5-dichlorophenol (25-DCP), benzophenone-3 (BP-3), bisphenol A (BPA), triclosan (TCS), butyl paraben (B-PB), methyl paraben (M-PB), and propyl paraben (P-PB). The frequent detection of these chemicals suggests that exposure is highly prevalent among these Puerto Rican pregnant women. Urinary concentrations of TCS, BP-3 and 25-DCP were higher than among women of reproductive age in the US general population, while concentrations of BPA, 24-DCP and parabens were similar. Intraclass correlation coefficients (ICC) varied widely between biomarkers; BPA had the lowest ICC (0.24) and BP-3 had highest (0.62), followed by 25-DCP (0.49) and TCS (0.47). We found positive associations between biomarker concentrations with self-reported use of liquid soap (TCS), sunscreen (BP-3), lotion (BP-3 and parabens), and cosmetics (parabens). Our results can inform future epidemiology studies and strategies to reduce exposure to these chemicals or their precursors. PMID:23469879

  16. Differentiation of acute pyelonephritis from other febrile states in children using urinary neutrophil gelatinase-associated lipocalin (uNGAL).

    Science.gov (United States)

    Arambašić, Jadranka; Mandić, Sanja; Debeljak, Željko; Mandić, Dario; Horvat, Vesna; Šerić, Vatroslav

    2016-01-01

    Acute pyelonephritis is a severe disease which is sometimes difficult to recognize based on clinical symptoms and routinely available diagnostic tests, especially in young children. The aim of this study was to assess the diagnostic value of urinary neutrophil gelatinase-associated lipocalin (uNGAL) as a biomarker of acute pyelonephritis. In this case-control study we analyzed 134 children (median age 2.5 years) who were admitted to the Pediatric Clinic of University Hospital Centre Osijek, Croatia. Eighty of them had acute pyelonephritis, while 54 children had febrile state of different etiology including cystitis and they represented the control group. uNGAL, white blood cells, C-reactive protein, urinanalysis, urine culture, kidney ultrasound and a dimercaptosuccinic acid scintigraphic scan were done for each child. uNGAL was measured using chemiluminiscent microparticle immunoassay on ARHITECT i1000SR (Abbott Diagnostics, IL, USA). uNGAL values were significantly higher in children with acute pyelonephritis compared to the control groups (113.6 ng/mL vs. 10.2 ng/mL, ppyelonephritis from cystitis (cut-off 38.5 ng/mL), and for differentiation of cystitis from febrile states with etiology other than urinary tract infection (UTI) (cut-off 20.4 ng/mL). uNGAL can be a useful diagnostic biomarker in acute pyelonephritis in children, but also in differentiating cystitis from febrile states other than UTI.

  17. The Economic Burden of Urinary Tract Infection and Pressure Ulceration in Acute Traumatic Spinal Cord Injury Admissions: Evidence for Comparative Economics and Decision Analytics from a Matched Case-control Study.

    Science.gov (United States)

    White, Barry; Dea, Nicolas; Street, John; Cheng, Christiana L; Rivers, Carly S; Attabib, Najmedden; Kwon, Brian K; Fisher, Charles G; Dvorak, Marcel F

    2017-08-09

    Secondary complications of spinal cord injury (SCI) are a burden to afflicted individuals and the rest of society. However, there is limited evidence of the economic burden or cost of complications in SCI populations in Canada, which is necessary for comparative economic analyses and decision analytic modeling of possible solutions to these common health problems. Comparative economic analyses can inform resource allocation decisions, but the outputs are only as good as the inputs. In this article, new evidence of the excess or incremental costs of urinary tract infection (UTI) and pressure ulceration (PU) in acute traumatic SCI from an exploratory case series analysis of admissions to a Level I specialized Canadian spine facility (2008-2013) is presented. Participants in a national SCI registry were case-control matched (1:1) on the predicted probability of experiencing UTI or PU during initial acute SCI admission. The excess costs of UTI and PU are estimated as the mean of the differences in total direct acute SCI admission costs (length of stay, accommodation, nursing, pharmacy) from the perspective of the admitting facility between participants matched or paired on demographic and SCI characteristics. Even relatively minor UTI and PU, respectively, added an average of $7,790 (SD $6,267) and $18,758 (SD $27,574) to the direct cost of acute SCI admission in 2013 Canadian dollars (CAD). This case series showed that UTI and PU in acute SCI admission are associated with excess cost and will facilitate comparative economic analyses and decision analytic modeling in SCI.

  18. Female urinary incontinence and sexuality.

    Science.gov (United States)

    Mota, Renato Lains

    2017-01-01

    Urinary incontinence is a common problem among women and it is estimated that between 15 and 55% of them complain of lower urinary symptoms. The most prevalent form of urinary incontinence is associated with stress, followed by mixed urinary incontinence and urge urinary incontinence. It is a symptom with several effects on quality of life of women mainly in their social, familiar and sexual domains. Female reproductive and urinary systems share anatomical structures, which promotes that urinary problems interfere with sexual function in females. This article is a review of both the concepts of female urinary incontinence and its impact on global and sexual quality of life. Nowadays, it is assumed that urinary incontinence, especially urge urinary incontinence, promotes anxiety and several self-esteem damages in women. The odour and the fear of incontinence during sexual intercourse affect female sexual function and this is related with the unpredictability and the chronicity of incontinence, namely urge urinary incontinence. Female urinary incontinence management involves conservative (pelvic floor muscle training), surgical and pharmacological treatment. Both conservative and surgical treatments have been studied about its benefit in urinary incontinence and also the impact among female sexual function. Unfortunately, there are sparse articles that evaluate the benefits of female sexual function with drug management of incontinence.

  19. Female urinary incontinence and sexuality

    Science.gov (United States)

    Mota, Renato Lains

    2017-01-01

    ABSTRACT Urinary incontinence is a common problem among women and it is estimated that between 15 and 55% of them complain of lower urinary symptoms. The most prevalent form of urinary incontinence is associated with stress, followed by mixed urinary incontinence and urge urinary incontinence. It is a symptom with several effects on quality of life of women mainly in their social, familiar and sexual domains. Female reproductive and urinary systems share anatomical structures, which promotes that urinary problems interfere with sexual function in females. This article is a review of both the concepts of female urinary incontinence and its impact on global and sexual quality of life. Nowadays, it is assumed that urinary incontinence, especially urge urinary incontinence, promotes anxiety and several self-esteem damages in women. The odour and the fear of incontinence during sexual intercourse affect female sexual function and this is related with the unpredictability and the chronicity of incontinence, namely urge urinary incontinence. Female urinary incontinence management involves conservative (pelvic floor muscle training), surgical and pharmacological treatment. Both conservative and surgical treatments have been studied about its benefit in urinary incontinence and also the impact among female sexual function. Unfortunately, there are sparse articles that evaluate the benefits of female sexual function with drug management of incontinence. PMID:28124522

  20. Urinary arsenic profiles and the risks of cancer mortality: A population-based 20-year follow-up study in arseniasis-endemic areas in Taiwan

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Chi-Jung [Department of Health Risk Management, College of Public Health, China Medical University, Taichung, Taiwan (China); Department of Medical Research, China Medical Hospital, Taichung, Taiwan (China); Huang, Ya-Li [Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); Huang, Yung-Kai [School of Oral Hygiene, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan (China); Wu, Meei-Maan [School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan (China); Chen, Shu-Yuan [Department of Public Health, Tzu-Chi University, Hualien, Taiwan (China); Hsueh, Yu-Mei, E-mail: ymhsueh@tmu.edu.tw [Department of Public Health, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan (China); School of Public Health, College of Public Health and Nutrition, Taipei Medical University, Taipei, Taiwan (China); Chen, Chien-Jen [Genomics Research Center, Academia Sinica, Taipei, Taiwan (China)

    2013-04-15

    Few studies investigated the association between chronic arsenic exposure and the mortality of cancers by estimating individual urinary arsenic methylation profiles. Therefore, we compared with the general population in Taiwan to calculate the standardized mortality ratio (SMR) in arseniasis-endemic area of Taiwan from 1996 to 2010 and evaluated the dose-response relationships between environmental arsenic exposure indices or urinary arsenic profiles and the mortality of cause-specific cancer. A cohort of 1563 residents was conducted and collected their urine sample and information regarding arsenic exposure from a questionnaire. All-cause death was identified using the National Death Registry of Taiwan. Urinary arsenic profiles were measured using high performance liquid chromatography–hydride generator–atomic absorption spectrometry. We used Cox proportional hazard models to evaluate the mortality risks. In results, 193 all-site cancer deaths, and 29, 71, 43 deaths respectively for liver, lung and bladder cancers were ascertained. The SMRs were significantly high in arseniasis-endemic areas for liver, lung, and bladder cancers. People with high urinary InAs% or low DMA% or low secondary methylation index (SMI) were the most likely to suffer bladder cancer after adjusting other risk factors. Even stopping exposure to arsenic from the artesian well water, the mortality rates of the residents were higher than general population. Finally, urinary InAs%, DMA% and SMI could be the potential biomarkers to predict the mortality risk of bladder cancer. -- Highlights: ► The SMRs were significantly high in arseniasis-endemic areas for liver, lung, and bladder cancers. ► People with high urinary InAs% were the most likely to suffer bladder cancer. ► People with low DMA% or low SMI were the most likely to suffer bladder cancer.

  1. Stability of miR-126 in Urine and Its Potential as a Biomarker for Renal Endothelial Injury with Diabetic Nephropathy

    Directory of Open Access Journals (Sweden)

    Yang Liu

    2014-01-01

    Full Text Available Background. The purpose of the present study was to assess the feasibility of using miR-126 in the urine as a biomarker for diabetic nephropathy. Methods. miRNAs were extracted from the urine samples of T2DM patients with diabetic nephropathy (DN; n=92, T2DM without DN (n=86, and 85 healthy volunteers using quantitative reverse transcriptase polymerase chain reaction (real-time polymerase chain reaction analysis. Stability of urinary miR-126 and factors that affected the stability were assessed. A subgroup analysis was also carried out to compare the urinary miR-126 level in T2DM patients well controlled by the treatment versus those who were not well controlled. Results. Urinary miR-126 was stable when the urine samples were kept at room temperature for extended period of time, 4°C, −20°C, and −80°C for up to 12 hours or subjected to 10 freeze-and-thaw cycle. Urinary miR-126 was significantly higher in T2DM patients with DN (5.76±0.33 versus 3.25±0.45 in T2DM patients without DN. Successful treatment significantly reduced urinary miR-126 in T2DM patients with DN to 3.89±0.52 (P<0.05. Conclusion. miR-126 in the urine is stable and it could be used as a biomarker of DN and to monitor the treatment response.

  2. Detecting the presence of an indwelling urinary catheter and urinary symptoms in hospitalized patients using natural language processing.

    Science.gov (United States)

    Gundlapalli, Adi V; Divita, Guy; Redd, Andrew; Carter, Marjorie E; Ko, Danette; Rubin, Michael; Samore, Matthew; Strymish, Judith; Krein, Sarah; Gupta, Kalpana; Sales, Anne; Trautner, Barbara W

    2017-07-01

    To develop a natural language processing pipeline to extract positively asserted concepts related to the presence of an indwelling urinary catheter in hospitalized patients from the free text of the electronic medical note. The goal is to assist infection preventionists and other healthcare professionals in determining whether a patient has an indwelling urinary catheter when a catheter-associated urinary tract infection is suspected. Currently, data on indwelling urinary catheters is not consistently captured in the electronic medical record in structured format and thus cannot be reliably extracted for clinical and research purposes. We developed a lexicon of terms related to indwelling urinary catheters and urinary symptoms based on domain knowledge, prior experience in the field, and review of medical notes. A reference standard of 1595 randomly selected documents from inpatient admissions was annotated by human reviewers to identify all positively and negatively asserted concepts related to indwelling urinary catheters. We trained a natural language processing pipeline based on the V3NLP framework using 1050 documents and tested on 545 documents to determine agreement with the human reference standard. Metrics reported are positive predictive value and recall. The lexicon contained 590 terms related to the presence of an indwelling urinary catheter in various categories including insertion, care, change, and removal of urinary catheters and 67 terms for urinary symptoms. Nursing notes were the most frequent inpatient note titles in the reference standard document corpus; these also yielded the highest number of positively asserted concepts with respect to urinary catheters. Comparing the performance of the natural language processing pipeline against the human reference standard, the overall recall was 75% and positive predictive value was 99% on the training set; on the testing set, the recall was 72% and positive predictive value was 98%. The performance on

  3. Upper urinary tract tumors

    DEFF Research Database (Denmark)

    Gandrup, Karen L; Nordling, Jørgen; Balslev, Ingegerd

    2014-01-01

    BACKGROUND: Computed tomography urography (CTU) is used widely in the work-up of patients with symptoms of urinary tract lesions. Preoperative knowledge of whether a tumor is invasive or non-invasive is important for the choice of surgery. So far there are no studies about the distinction...... of invasive and non-invasive tumors in ureter and renal pelvis based on the enhancement measured with Hounsfield Units. PURPOSE: To examine the value of CTU using split-bolus technique to distinguish non-invasive from invasive urothelial carcinomas in the upper urinary tract. MATERIAL AND METHODS: Patients...... obtained at CTU could distinguish between invasive and non-invasive lesions. No patients had a CTU within the last year before the examination that resulted in surgery. CONCLUSION: A split-bolus CTU cannot distinguish between invasive and non-invasive urothelial tumors in the upper urinary tract...

  4. Urinary 1-hydroxypyrene, a PAH biomarker in foundry workers

    DEFF Research Database (Denmark)

    Omland, Øyvind; Sherson, D; Hansen, Åse Marie

    1996-01-01

    hygienic samples, consisting of 16 selected PAH compounds. Mean total PAH concentration (SD) was 10.40 (4.04) mu g/m3. A multiple regression model of tobacco consumption, age, airborne PAH-exposure and foundry work on log HPU showed a significant correlation, p

  5. Parabens as Urinary Biomarkers of Exposure in Humans

    OpenAIRE

    Ye, Xiaoyun; Bishop, Amber M.; Reidy, John A; Needham, Larry L.; Calafat, Antonia M

    2006-01-01

    Background Parabens appear frequently as antimicrobial preservatives in cosmetic products, in pharmaceuticals, and in food and beverage processing. In vivo and in vitro studies have revealed weak estrogenic activity of some parabens. Widespread use has raised concerns about the potential human health risks associated with paraben exposure. Objectives Assessing human exposure to parabens usually involves measuring in urine the conjugated or free species of parabens or their metabolites. In ani...

  6. Validation of APF as a Urinary Biomarker for Interstitial Cystitis

    Science.gov (United States)

    2016-12-01

    104 cells per well in MEM medium containing 10% heat-inactivated fetal calf serum, 1% glutamine and 1% antibiotic/antimycotic solution onto Corning ...issue, we contacted our original supplier to provide additional APF peptide. Despite a delay, they were able to synthesize more peptide for us

  7. Urinary metalloproteinases: noninvasive biomarkers for breast cancer risk assessment

    DEFF Research Database (Denmark)

    Pories, Susan E; Zurakowski, David; Roy, Roopali

    2008-01-01

    in women with atypical hyperplasia and LCIS from normal controls, with receiver operating characteristic curve analysis showing an area under the curve of 0.914 and 0.950, respectively. To assess clinical applica