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Sample records for gelatinase-associated lipocalin ngal

  1. Urine neutrophil gelatinase-associated lipocalin (NGAL as a biomarker for acute canine kidney injury

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    Lee Ya-Jane

    2012-12-01

    Full Text Available Abstract Background Biomarkers for the early prediction of canine acute kidney injury (AKI are clinically important. Recently, neutrophil gelatinase-associated lipocalin (NGAL was found to be a sensitive biomarker for the prediction of human AKI at a very early stage and the development of AKI after surgery. However, NGAL has not yet been studied with respect to dog kidney diseases. The application of NGAL canine AKI was investigated in this study. Results The canine NGAL gene was successfully cloned and expressed. Polyclonal antibodies against canine NGAL were generated and used to develop an ELISA for measuring NGAL protein in serum and urine samples that were collected from 39 dogs at different time points after surgery. AKI was defined by the standard method, namely a serum creatinine increase of greater than or equal to 26.5 μmol/L from baseline within 48 h. At 12 h after surgery, compared to the group without AKI (12 dogs, the NGAL level in the urine of seven dogs with AKI was significantly increased (median 178.4 pg/mL vs. 88.0 pg/mL, and this difference was sustained to 72 h. Conclusion As the increase in NGAL occurred much earlier than the increase in serum creatinine, urine NGAL seems to be able to serve as a sensitive and specific biomarker for the prediction of AKI in dogs.

  2. Plasma neutrophil gelatinase associated lipocalin (NGAL) is associated with kidney function in uraemic patients before and after kidney transplantation

    DEFF Research Database (Denmark)

    Magnusson, Nils E; Hornum, Mads; Jørgensen, Kaj Anker;

    2012-01-01

    Neutrophil gelatinase associated lipocalin (NGAL) is a biomarker of kidney injury. We examined plasma levels of NGAL in a cohort of 57 kidney allograft recipients (Tx group, 39 ± 13 years), a uraemic group of 40 patients remaining on the waiting list (47 ± 11 years) and a control group of 14 heal...

  3. Urinary Neutrophil Gelatinase-Associated Lipocalin (NGAL in Patients with Obstructive Sleep Apnea.

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    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

  4. Neutrophil Gelatinase-Associated Lipocalin (NGAL), Pro-Matrix Metalloproteinase-9 (pro-MMP-9) and Their Complex Pro-MMP-9/NGAL in Leukaemias

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    Bouchet, Sandrine; Bauvois, Brigitte, E-mail: brigitte.bauvois@crc.jussieu.fr [INSERM U1138, Université Pierre et Marie Curie, Université Paris-Descartes, Centre de Recherche des Cordeliers, Paris 75006 (France)

    2014-04-04

    Matrix metalloproteinase (MMP)-9 and neutrophil gelatinase-associated lipocalin (NGAL) have gained attention as cancer biomarkers. The inactive zymogen form of MMP-9 (pro-MMP-9) also exists as a disulphide-linked heterodimer bound to NGAL in humans. Leukaemias represent a heterogeneous group of neoplasms, which vary in their clinical behavior and pathophysiology. In this review, we summarize the current literature on the expression profiles of pro-MMP-9 and NGAL as prognostic factors in leukaemias. We also report the expression of the pro-MMP-9/NGAL complex in these diseases. We discuss the roles of (pro)-MMP-9 (active and latent forms) and NGAL in tumour development, and evaluate the mechanisms by which pro-MMP-9/NGAL may influence the actions of (pro)-MMP-9 and NGAL in cancer. Emerging knowledge about the coexpression and the biology of (pro)-MMP-9, NGAL and their complex in cancer including leukaemia may improve treatment outcomes.

  5. Neutrophil Gelatinase Associated Lipocalin (NGAL) as a Biomarker. Does It Apply in Abdominal Aortic Aneurysms? A Review of Literature.

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    Karaolanis, Georgios; Moris, Demetrios; Palla, Viktoria-Varvara; Karanikola, Euridiki; Bakoyiannis, Chris; Georgopoulos, Sotirios

    2015-12-01

    Neutrophil gelatinase associated lipocalin (NGAL) as a protein derived from neutrophils has recently been the field of investigation in a wide range of diseases (renal disease, coronary artery disease, etc). The MEDLINE/PubMed database was searched for publications with the medical subject heading "NGAL" and keywords "Abdominal aortic aneurysm (AAA)," "biomarker," and "growth". We restricted our search to date. In this review, we included 38 articles and abstracts that were accessible and available in English. An effort to further explain the role of NGAL within AAA has been made. NGAL seems to be a hopeful marker for the pathogenesis and the progression of abdominal aortic aneurysms (AAAs), which has significant morbidity and mortality rates.

  6. Neutrophil Gelatinase-Associated Lipocalin (NGAL) and Kidney Injury Molecule 1 (KIM1) in patients with diabetic nephropathy: a cross-sectional study and the effects of lisinopril

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    Nielsen, S E; Schjoedt, K J; Astrup, A S

    2010-01-01

    Our aim was to evaluate the markers of tubulointerstitial damage, neutrophil gelatinase-associated lipocalin (NGAL) and kidney injury molecule1 (KIM1) in Type 1 diabetic patients with different levels of albuminuria and in control subjects. In addition, the effect of renoprotective treatment...... on urinary NGAL was evaluated in diabetic nephropathy....

  7. Relationship of neutrophil gelatinase-associated lipocalin (NGAL) and procalcitonin levels with the presence and severity of the preeclampsia.

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    Artunc-Ulkumen, Burcu; Guvenc, Yesim; Goker, Asli; Gozukara, Ceyhun

    2015-11-01

    The aim of the present study was to evaluate changes in maternal serum neutrophil gelatinase-associated lipocalin (NGAL) and procalcitonin (PCT) concentrations in preeclampsia. This case-control study consisted of 40 preeclamptic and 40 healthy singleton pregnancies matched for age and body mass index. Serum NGAL and PCT levels were compared between the groups. Diagnostic performance and clinical association of these markers were evaluated. NGAL and PCT concentrations were significantly higher in preeclamptic group (p preeclampsia. There were significant positive correlation between these markers and mean arterial pressure (MAP) and spot urine protein excretion. There was negative correlation between NGAL and apgar scores and fetal birth weight. Pregnancies with higher NGAL (OR: 4.89; 95% CI: 1.81-13.21) and higher PCT (OR: 6.67; 95% CI: 2.44-18.21) concentrations had higher risk for preeclampsia. NGAL and PCT may be potential biomarkers for preeclampsia. Their levels increase significantly in preeclampsia and they are related to the severity of the disease. These results are in agreement with the generalized endothelial damage and persistant inflammatory status in preeclampsia. NGAL may also be an indicator for adverse neonatal outcomes with decreased placental hypoperfusion.

  8. Differentiation of acute pyelonephritis from other febrile states in children using urinary neutrophil gelatinase-associated lipocalin (uNGAL).

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    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.

  9. Circulating levels of matrix metalloproteinase-9 (MMP-9, neutrophil gelatinase-associated lipocalin (NGAL and their complex MMP-9/NGAL in breast cancer disease

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    Nonni Afroditi

    2009-11-01

    Full Text Available Abstract Background Recent evidence suggests that neutrophil gelatinase-associated lipocalin (NGAL expression is induced in many types of human cancer, while detection of its complex with matrix metalloproteinase-9 (MMP-9 is correlated with cancer disease status. We aim to evaluate the serum expression of MMP-9, NGAL and their complex (MMP-9/NGAL during the diagnostic work-up of women with breast abnormalities and investigate their correlation with disease severity. Methods The study included 113 women with non-palpable breast lesions undergoing vacuum-assisted breast biopsy for histological diagnosis, and 30 healthy women, which served as controls. Expression levels of MMP-9, NGAL and their complex MMP-9/NGAL were determined in peripheral blood samples with immunoenzymatic assays. Results Women with invasive ductal carcinoma exhibited significantly increased levels of MMP-9, NGAL and MMP-9/NGAL compared to healthy controls (MMP-9: p Conclusion These findings suggest that the serum measurement of MMP-9 and NGAL may be useful in non-invasively monitoring breast cancer progression, while supporting their potential role as early biomarkers of breast disease status.

  10. Neutrophil Gelatinase-Associated Lipocalin (NGAL, Pro-Matrix Metalloproteinase-9 (pro-MMP-9 and Their Complex Pro-MMP-9/NGAL in Leukaemias

    Directory of Open Access Journals (Sweden)

    Sandrine Bouchet

    2014-04-01

    Full Text Available Matrix metalloproteinase (MMP-9 and neutrophil gelatinase-associated lipocalin (NGAL have gained attention as cancer biomarkers. The inactive zymogen form of MMP-9 (pro-MMP-9 also exists as a disulphide-linked heterodimer bound to NGAL in humans. Leukaemias represent a heterogeneous group of neoplasms, which vary in their clinical behavior and pathophysiology. In this review, we summarize the current literature on the expression profiles of pro-MMP-9 and NGAL as prognostic factors in leukaemias. We also report the expression of the pro-MMP-9/NGAL complex in these diseases. We discuss the roles of (pro-MMP-9 (active and latent forms and NGAL in tumour development, and evaluate the mechanisms by which pro-MMP-9/NGAL may influence the actions of (pro-MMP-9 and NGAL in cancer. Emerging knowledge about the coexpression and the biology of (pro-MMP-9, NGAL and their complex in cancer including leukaemia may improve treatment outcomes.

  11. Neutrophil Gelatinase Associated Lipocalin (NGAL) in Leptospirosis Acute Kidney Injury: A Multicenter Study in Thailand.

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    Srisawat, Nattachai; Praditpornsilpa, Kearkiat; Patarakul, Kanitha; Techapornrung, Malee; Daraswang, Tinnapop; Sukmark, Theerapon; Khositrangsikun, Kamol; Fakthongyoo, Apinya; Oranrigsupak, Petchdee; Praderm, Laksamon; Suwattanasilpa, Ummarit; Peerapornratana, Sadudee; Loahaveeravat, Passisd; Suwachittanont, Nattachai; Wirotwan, Thaksa-on; Phonork, Chayanat; Kumpunya, Sarinya; Tiranathanagul, Khajohn; Chirathaworn, Chintana; Eiam-ong, Somchai; Tungsanga, Kriang; Sitprija, Visith; Kellum, John A; Townamchai, Natavudh

    2015-01-01

    AKI is one of the most serious complications of leptospirosis, an important zoonosis in the tropics. Recently, NGAL, one of the novel AKI biomarkers, is extensively studied in various specific settings such as sepsis, cardiac surgery, and radiocontrast nephropathy. In this multicenter study, we aimed to study the role of NGAL as an early marker and an outcome predictor of leptospirosis associated AKI. Patients who presented with clinical suspiciousness of leptospirosis were prospectively enrolled in 9 centers from August 2012 to November 2014. The first day of enrollment was the first day of clinical suspicious leptospirosis. Blood and urine samples were serially collected on the first three days and day 7 after enrollment. We used three standard techniques (microscopic agglutination test, direct culture, and PCR technique) to confirm the diagnosis of leptospirosis. KDIGO criteria were used for AKI diagnosis. Recovery was defined as alive and not requiring dialysis during hospitalization or maintaining maximum KDIGO stage at hospital discharge. Of the 221 recruited cases, 113 cases were leptospirosis confirmed cases. Thirty seven percent developed AKI. Median uNGAL and pNGAL levels in those developing AKI were significantly higher than in patients not developing AKI [253.8 (631.4) vs 24.1 (49.6) ng/ml, p leptospirosis associated AKI. However, both of them did not show the potential role to be the predictor of renal recovery in this specific setting.

  12. Neutrophil gelatinase-associated lipocalin (NGAL/Lcn2) is upregulated in gastric mucosa infected with Helicobacter pylori

    DEFF Research Database (Denmark)

    Alpízar-Alpízar, Warner; Laerum, Ole Didrik; Illemann, Martin

    2009-01-01

    characterized here the pattern of expression of NGAL/Lcn2 in gastric mucosa (45 non-neoplastic and 38 neoplastic tissue samples) and explored the connection between NGAL/Lcn2 expression and H. pylori infection. Immunohistochemical analysis showed high NGAL/Lcn2 expression in normal and gastritis-affected mucosa...... compared to low expression in intestinal metaplasia, dysplasia, and gastric cancer. In normal and gastritis-affected mucosa (n=36 tissue samples), NGAL/Lcn2 was more frequently seen in epithelial cells located at the neck and base of the glands in H. pylori-positive cases than in similar epithelial cells...... of noninfected cases (Fisher's exact test, p=0.04). In conclusion, the high expression of NGAL/Lcn2 in normal and gastritis-affected mucosa infected with H. pylori suggests that NGAL/Lcn2 is upregulated locally in response to this bacterial infection. It is discussed whether this may have a causal relation...

  13. Serum and Plasma Neutrophil Gelatinase Associated Lipocalin (NGAL) Levels are Not Equivalent in Patients Admitted to Intensive Care

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    Itenov, Theis Skovsgaard; Bangert, Kristian; Christensen, Per Hjort

    2014-01-01

    and EDTA plasma NGAL concentrations in patients admitted to intensive care units (ICUs) and whether these determinations are directly comparable in this setting. METHODS: NGAL was measured in 40 paired samples of serum and EDTA plasma from 25 patients admitted to intensive care with a commercial particle.......8-106). CONCLUSION: NGAL concentration values measured in serum and EDTA plasma cannot be directly compared and should not be used as equivalents in studies of patients admitted to intensive care....... and EDTA plasma values were correlated (Spearman's r = 0.95, P unity (95% confidence interval (CI) 1.0-1.1) and a highly significant intercept of 67.9 ng/ml with a wide confidence interval (95% CI 29...

  14. of Matrix Metalloproteinase-9 and Neutrophil Gelatinase-Associated Lipocalin

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    De Caridi Giovanni

    2015-01-01

    Full Text Available The association of an axillary artery aneurysm and an abdominal aortic aneurysm is extremely rare. In this study, we describe this association in a 69 year-old-man. We measured this patient’s metalloproteinases (MMPs and Neutrophil Gelatinase - Associated Lipocalin (NGAL levels over a three years period before the abdominal aortic aneurysm rupture. We speculate that high serium levels of MMPs and NGAL may have a prognostic role and may predict aneurysm rupture in patients with an uncommon association of arterial aneurysms.

  15. Expression of NRL/NGAL (neu-related lipocalin/neutrophil gelatinase-associated lipocalin) during mammalian embryonic development and in inflammation.

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    Zerega, B; Cermelli, S; Michelis, B; Cancedda, R; Cancedda, F D

    2000-03-01

    The neu-related lipocalin (NRL) is a protein overexpressed in rat mammary cancer induced by activated neu (HER-2/c-erbB2). This protein belongs to the family of the lipocalins or low molecular weight proteins able to bind and transport small hydrophobic molecules. The NRL homologue in mouse is SIP24, an acute phase protein induced in the animal by turpentine injection; the human homologous protein is NGAL expressed in granulocytes and epithelial cells in pathological conditions, such as inflammation and malignancy. We have investigated NRL expression in developing rat embryos. By immunolocalization we have shown localization of the protein in the hypertrophic region of growth plate cartilage. NRL was particularly enriched in prehypertrophic chondrocytes. In addition, we observed localization of the protein in forming skeletal muscle fibres and in the myocardium of developing heart. In agreement with the immunolocalization data, by in situ hybridization we have demonstrated the presence of the specific mRNA in the same tissues. At an early stage of differentiation, cultured rat embryo-derived chondrocytes did not express NRL; nevertheless expression of the protein was induced in these cells by treatment with an inflammatory agent, such as LPS. By Western blot analysis with specific antibodies we showed protein synthesis by cultured myoblasts also in the absence of LPS treatment, but only when forming myotubes were observed in culture. Stimulation of myoblast cultures with LPS resulted in an enhancement of the NRL expression in well formed myotubes. Our data suggest a role of NRL in cartilage and muscle differentiation. NRL expression was induced by inflammatory agents. We wish to propose that the expression of NRL in hypertrophic chondrocytes and forming myotubes is part of a "physiological" acute phase response occurring during cartilage and muscle development. In this manuscript we also report that NRL is not detectable by immunolocalization in adult cartilage

  16. Experimental and Human Evidence for Lipocalin-2 (Neutrophil Gelatinase-Associated Lipocalin [NGAL]) in the Development of Cardiac Hypertrophy and heart failure.

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    Marques, Francine Z; Prestes, Priscilla R; Byars, Sean G; Ritchie, Scott C; Würtz, Peter; Patel, Sheila K; Booth, Scott A; Rana, Indrajeetsinh; Minoda, Yosuke; Berzins, Stuart P; Curl, Claire L; Bell, James R; Wai, Bryan; Srivastava, Piyush M; Kangas, Antti J; Soininen, Pasi; Ruohonen, Saku; Kähönen, Mika; Lehtimäki, Terho; Raitoharju, Emma; Havulinna, Aki; Perola, Markus; Raitakari, Olli; Salomaa, Veikko; Ala-Korpela, Mika; Kettunen, Johannes; McGlynn, Maree; Kelly, Jason; Wlodek, Mary E; Lewandowski, Paul A; Delbridge, Lea M; Burrell, Louise M; Inouye, Michael; Harrap, Stephen B; Charchar, Fadi J

    2017-06-14

    Cardiac hypertrophy increases the risk of developing heart failure and cardiovascular death. The neutrophil inflammatory protein, lipocalin-2 (LCN2/NGAL), is elevated in certain forms of cardiac hypertrophy and acute heart failure. However, a specific role for LCN2 in predisposition and etiology of hypertrophy and the relevant genetic determinants are unclear. Here, we defined the role of LCN2 in concentric cardiac hypertrophy in terms of pathophysiology, inflammatory expression networks, and genomic determinants. We used 3 experimental models: a polygenic model of cardiac hypertrophy and heart failure, a model of intrauterine growth restriction and Lcn2-knockout mouse; cultured cardiomyocytes; and 2 human cohorts: 114 type 2 diabetes mellitus patients and 2064 healthy subjects of the YFS (Young Finns Study). In hypertrophic heart rats, cardiac and circulating Lcn2 was significantly overexpressed before, during, and after development of cardiac hypertrophy and heart failure. Lcn2 expression was increased in hypertrophic hearts in a model of intrauterine growth restriction, whereas Lcn2-knockout mice had smaller hearts. In cultured cardiomyocytes, Lcn2 activated molecular hypertrophic pathways and increased cell size, but reduced proliferation and cell numbers. Increased LCN2 was associated with cardiac hypertrophy and diastolic dysfunction in diabetes mellitus. In the YFS, LCN2 expression was associated with body mass index and cardiac mass and with levels of inflammatory markers. The single-nucleotide polymorphism, rs13297295, located near LCN2 defined a significant cis-eQTL for LCN2 expression. Direct effects of LCN2 on cardiomyocyte size and number and the consistent associations in experimental and human analyses reveal a central role for LCN2 in the ontogeny of cardiac hypertrophy and heart failure. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  17. Early detection and intervention using neutrophil gelatinase-associated lipocalin (NGAL may improve renal outcome of acute contrast media induced nephropathy: A randomized controlled trial in patients undergoing intra-arterial angiography (ANTI-CIN Study

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    Stiegler Philipp

    2011-08-01

    Full Text Available Abstract Background Patients with pre-existing impaired renal function are prone to develop acute contrast media induced nephropathy (CIN. Neutrophil gelatinase-associated lipocalin (NGAL, a new biomarker predictive for acute kidney injury (AKI, has been shown to be useful for earlier diagnosis of CIN; however, urinary NGAL values may be markedly increased in chronic renal failure at baseline. Results from those studies suggested that urinary NGAL values may not be helpful for the clinician. An intravenous volume load is a widely accepted prophylactic measure and possibly a reasonable intervention to prevent deterioration of renal function. The aim of our study is to evaluate NGAL as an early predictor of CIN and to investigate the clinical benefit of early post-procedural i.v. hydration. Methods/Design The study will follow a prospective, open-label, randomized controlled design. Patients requiring intra-arterial contrast media (CM application will be included and receive standardized, weight-based, intravenous hydration before investigation. Subjects with markedly increased urinary NGAL values after CM application will be randomized into one of two study groups. Group A will receive 3-4 ml/kg BW/h 0.9% saline intravenously for 6 hours. Group B will undergo only standard treatment consisting of unrestricted oral fluid intake. The primary outcome measure will be CIN defined by an increase greater than 25% of baseline serum creatinine. Secondary outcomes will include urinary NGAL values, cystatin C values, contrast media associated changes in cardiac parameters such as NT-pro-BNP/troponin T, changes in urinary cytology, need for renal replacement treatment, length of stay in hospital and death. We assume that 20% of the included patients will show a definite rise in urinary NGAL. Prospective statistical power calculations indicate that the study will have 80% statistical power to detect a clinically significant decrease of CIN of 40% in the

  18. Early detection and intervention using neutrophil gelatinase-associated lipocalin (NGAL) may improve renal outcome of acute contrast media induced nephropathy: a randomized controlled trial in patients undergoing intra-arterial angiography (ANTI-CIN Study).

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    Schilcher, Gernot; Ribitsch, Werner; Otto, Ronald; Portugaller, Rupert H; Quehenberger, Franz; Truschnig-Wilders, Martini; Zweiker, Robert; Stiegler, Philipp; Brodmann, Marianne; Weinhandl, Klemens; Horina, Joerg H

    2011-08-17

    Patients with pre-existing impaired renal function are prone to develop acute contrast media induced nephropathy (CIN). Neutrophil gelatinase-associated lipocalin (NGAL), a new biomarker predictive for acute kidney injury (AKI), has been shown to be useful for earlier diagnosis of CIN; however, urinary NGAL values may be markedly increased in chronic renal failure at baseline. Results from those studies suggested that urinary NGAL values may not be helpful for the clinician. An intravenous volume load is a widely accepted prophylactic measure and possibly a reasonable intervention to prevent deterioration of renal function. The aim of our study is to evaluate NGAL as an early predictor of CIN and to investigate the clinical benefit of early post-procedural i.v. hydration. The study will follow a prospective, open-label, randomized controlled design. Patients requiring intra-arterial contrast media (CM) application will be included and receive standardized, weight-based, intravenous hydration before investigation. Subjects with markedly increased urinary NGAL values after CM application will be randomized into one of two study groups. Group A will receive 3-4 ml/kg BW/h 0.9% saline intravenously for 6 hours. Group B will undergo only standard treatment consisting of unrestricted oral fluid intake. The primary outcome measure will be CIN defined by an increase greater than 25% of baseline serum creatinine. Secondary outcomes will include urinary NGAL values, cystatin C values, contrast media associated changes in cardiac parameters such as NT-pro-BNP/troponin T, changes in urinary cytology, need for renal replacement treatment, length of stay in hospital and death.We assume that 20% of the included patients will show a definite rise in urinary NGAL. Prospective statistical power calculations indicate that the study will have 80% statistical power to detect a clinically significant decrease of CIN of 40% in the treatment arm if 1200 patients are recruited into the

  19. Renal neutrophil gelatinase associated lipocalin expression in lipopolysaccharide-induced acute kidney injury in the rat

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    Han Mei

    2012-06-01

    Full Text Available Abstract Background Neutrophil gelatinase associated lipocalin (NGAL is a highly predictive biomarker of acute kidney injury. To understand the role of NGAL in renal injury during sepsis, we investigated the temporal changes and biological sources of NGAL in a rat model of acute kidney injury, and explored the relationship between renal inflammation, humoral NGAL and NGAL expression during endotoxemia. Methods To induce acute renal injury, rats were treated with lipopolysaccharide (LPS, 3.5 mg/kg, ip, and the location of NGAL mRNA was evaluated by in situ hybridization. Quantitative RT-PCR was also used to determine the dynamic changes in NGAL, tumor necrosis factor α (TNFα and interleukin (IL-6 mRNA expression 1, 3, 6, 12, and 24 hours following LPS treatment. The correlation among NGAL, TNFα and IL-6 was analyzed. Urinary and plasma NGAL (u/pNGAL levels were measured, and the relationship between humoral NGAL and NGAL expression in the kidney was investigated. Results Renal function was affected 3–12 hours after LPS. NGAL mRNA was significantly upregulated in tubular epithelia at the same time (P P P P Conclusions NGAL upregulation is sensitive to LPS-induced renal TNFα increase and injury, which are observed in the tubular epithelia. Urinary NGAL levels accurately reflect changes in NGAL in the kidney.

  20. Systemic and urinary neutrophil gelatinase-associated lipocalins are poor predictors of acute kidney injury in unselected critically ill patients.

    NARCIS (Netherlands)

    Royakkers, A.A.; Bouman, C.S.; Stassen, P.M.; Korevaar, J.C.; Binnekade, J.M.; Hoek, W. van der; Kuiper, M.A.; Spronk, P.E.; Schultz, M.J.

    2012-01-01

    Background. Neutrophil gelatinase-associated lipocalin (NGAL) in serum and urine have been suggested as potential early predictive biological markers of acute kidney injury (AKI) in selected critically ill patients. Methods. We performed a secondary analysis of a multicenter prospective observationa

  1. Association between plasma neutrophil gelatinase associated lipocalin level and obstructive sleep apnea or nocturnal intermittent hypoxia.

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    Kimihiko Murase

    Full Text Available BACKGROUND: Both obstructive sleep apnea (OSA and a novel lipocalin, neutrophil gelatinase associated lipocalin (Ngal, have been reported to be closely linked with cardiovascular disease and loss of kidney function through chronic inflammation. However, the relationship between OSA and Ngal has never been investigated. OBJECTIVES: To evaluate the relationship between Ngal and OSA in clinical practice. METHODS: In 102 patients, polysomnography was performed to diagnose OSA and plasma Ngal levels were measured. The correlations between Ngal levels and OSA severity and other clinical variables were evaluated. Of the 46 patients who began treatment with continuous positive airway pressure (CPAP, Ngal levels were reevaluated after three months of treatment in 25 patients. RESULTS: The Ngal level correlated significantly with OSA severity as determined by the apnea hypopnea index (r = 0.24, p = 0.01 and 4% oxygen desaturation index (ODI (r = 0.26, p = 0.01. Multiple regression analysis showed that the Ngal level was associated with 4%ODI independently of other clinical variables. Compliance was good in 13 of the 25 patients who used CPAP. Although the OSA (4%ODI: 33.1±16.7 to 1.1±1.9/h, p<0.01 had significantly improved in those with good compliance, the Ngal levels were not significantly changed (60.5±18.1 before CPAP vs 64.2±13.9 ng/ml after CPAP, p = 0.27. CONCLUSIONS: Plasma Ngal levels were positively associated with the severity of OSA. However, the contribution rate of OSA to systemic Ngal secretion was small and changes in Ngal levels appeared to be influenced largely by other confounding factors. Therefore, it does not seem reasonable to use the Ngal level as a specific biomarker of OSA in clinical practice.

  2. Plasma Neutrophil Gelatinase-Associated Lipocalin Is Primarily Related to Inflammation during Sepsis: A Translational Approach

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    Otto, Gordon P.; Hurtado-Oliveros, Jorge; Chung, Ha-Yeun; Knoll, Kristin; Neumann, Thomas; Müller, Hans J.; Herbsleb, Marco; Kohl, Matthias; Busch, Martin; Sossdorf, Maik; Claus, Ralf A.

    2015-01-01

    Acute kidney injury (AKI) during sepsis is common and underestimated. Plasma neutrophil gelatinase-associated lipocalin (plasma-NGAL) is discussed as new biomarker for AKI diagnosis, but during inflammation its function and diagnostic impact remain unclear. The association between plasma-NGAL and inflammatory markers in septic patients, but also in healthy controls and patients with chronic inflammation before and after either maximum exercise test or treatment with an anti-TNF therapy were investigated. In-vitro blood stimulations with IL-6, lipopolysaccharide, NGAL or its combinations were performed to investigate cause-effect-relationship. Plasma-NGAL levels were stronger associated with inflammation markers including IL-6 (Sepsis: r=0.785 PSepsis: r=0.714 Pdetection during severe inflammation - indeed it has to be interpreted carefully within this setting - but additionally might offer therapeutic potential. PMID:25893429

  3. Urinary Neutrophil Gelatinase-Associated Lipocalin and Progression of Diabetic Nephropathy in Type 1 Diabetic Patients in a Four-Year Follow-Up Study

    DEFF Research Database (Denmark)

    Nielsen, Stine Elkjaer; Hansen, Henrik Post; Jensen, Berit Ruud;

    2010-01-01

    Background: Neutrophil gelatinase-associated lipocalin (NGAL), a marker of renal tubular damage, predicts progression in non-diabetic chronic kidney. We evaluated urinary (u)-NGAL as a predictor of progression in diabetic nephropathy in type 1 diabetic (T1D) patients. Methods: As a substudy of a ...

  4. Neutrophil Gelatinase-Associated Lipocalin and its Receptors in Alzheimer's Disease (AD) Brain Regions: Differential Findings in AD with and without Depression

    NARCIS (Netherlands)

    Dekens, D.W.; Naude, P.J.; Engelborghs, S.; Vermeiren, Y.; Dam, D. Van; Oude Voshaar, R.C.; Eisel, U.L.; De Deyn, P.P.

    2016-01-01

    Co-existing depression worsens Alzheimer's disease (AD) pathology. Neutrophil gelatinase-associated lipocalin (NGAL) is a newly identified (neuro)inflammatory mediator in the pathophysiologies of both AD and depression. This study aimed to compare NGAL levels in healthy controls, AD without depressi

  5. Correlation of serum neutrophil gelatinase associated lipocalin with disease severity in hypertensive disorders of pregnancy

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    Rekha Sachan

    2014-01-01

    Full Text Available Background: Vascular endothelial dysfunction is considered central to the pathogenesis of hypertensive disorders of pregnancy (HDP. Serum level of neutrophil gelatinase-associated lipocalin (NGAL is closely related to endothelial injury. The aim of this study was to examine the correlation of serum NGAL with disease severity in HDP. Materials and Methods: This prospective case-control study was carried out for one year. After informed consent, ethical clearance, total 1,850 pregnant women were screened. Analysis was performed on 142 cases of HDP and 31 healthy controls. Quantitative measurement of serum NGAL levels was done by the enzyme linked immunosorbent assay (ELISA technique, by using sandwich ELISA kit. Results: Mean serum NGAL value in patients with oliguria was significantly higher when compared with non-oliguric patients (P < 0.001. Serum NGAL had a positive correlation with systolic blood pressure (r ~ 0.5973, diastolic blood pressure (r ~ 0.6195, blood urea (r ~ 0.4392, serum creatinine (r ~ 0.6112, serum uric acid (r ~ 0.3878. Sensitivity and specificity of serum NGAL using a cut-off value of 545 pg/ml, for the diagnosis of HDP, was 97.89% and 93.55% respectively, using 95% confidence interval. Conclusion: Between the two groups, we found that serum NGAL had a positive correlation with disease severity and better sensitivity and specificity in the evaluation of HDP.

  6. Hubungan Kadar Albumin Serum dengan Neutrophil Gelatinase-Associated Lipocalin Urine pada Penderita Sindrom Nefrotik Anak

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    Deasy Nurisya

    2014-09-01

    Full Text Available Neutrophil gelatinase-associated lipocalin (NGAL is a biological marker found in kidney damage that increases in proximal tubular damage. The purpose of this study was to analyze the correlation between serum albumin and urine NGAL (uNGAL levels in children with NS at initial presentation or relapse. Subjects in this study were 1−14 year-old children with NS. An observational analytical study with cross sectional design was conducted in the Pediatric Department of Dr. Hasan Sadikin General Hospital Bandung and Bandung City Public Hospital from September 2011 to March 2012. The serum albumin level and uNGAL level were measured using bromcresol green method and enzyme-linked immunosorbent assay (ELISA, respectively. Data were analyzed using Pearson correlation test on normal distribution data. Subjects consisted of 14 boys and 10 girls. Mean serum albumin and uNGAL levels were 1.37 (SD 0.33 g/dL and 2,719.37 (SD 3,781.82 ng/mL, respectively. There was a significant correlation between decreased albumin level and elevated uNGAL level (r=−0.519, p=0.009. In conclusion, the lower the albumin level, the higher the uNGAL level. An awareness should be developed towards the possibility that hypoalbuminemia in children with NS might decrease renal function.

  7. Is neutrophil gelatinase associated lipocalin useful in hepatitis C virus infection?

    Institute of Scientific and Technical Information of China (English)

    Alessio; Strazzulla; Giuseppe; Coppolino; Concetta; Di; Fatta; Francesca; Giancotti; Giuseppina; D’Onofrio; Maria; Concetta; Postorino; Maria; Mazzitelli; Selma; Valerie; Mammone; Innocenza; Gentile; Laura; Rivoli; Eleonora; Palella; Tiziana; Gravina; Chiara; Costa; Vincenzo; Pisani; Vincenzo; De; Maria; Giorgio; Settimo; Barreca; Nadia; Marascio; Alfredo; Focà; Giorgio; Fuiano; Elio; Gulletta; Carlo; Torti

    2016-01-01

    AIM: To evaluate neutrophil gelatinase associated lipocalin(NGAL) in patients infected by hepatitis C virus(HCV) before and during treatment with directly acting antivirals(DAAs).METHODS: NGAL was measured in a group of patients with chronic HCV infection ranked, at baseline, by age, gender, anti-hypertensive therapy, HCV viral load, liver fibrosis stage and, either at baseline or after 1 year, estimated glomerular filtration rate(e GFR). Then, NGAL and e GFR evolutions were monitored in a subgroup of patients who started antiviral therapy with DAAs. Differences of median NGAL levels were evaluated through Wilcoxon-Mann-Whitney test for nonparametric data. Differences in dichotomous variables were evaluated through χ~2 test. At baseline, a univariate regression analysis was conducted to verify if NGAL values correlated with other quantitative variables [age, fibrosis four(FIB-4), AST to platelet ratio index(APRI), and e GFR]. RESULTS: Overall, 48 patients were enrolled, 8 of them starting HCV treatment. At baseline, statistically significant differences were found in median NGAL values only between patients with e GFR 118.11 ng/d L were compared with those of NGAL ≤ 118.11 ng/d L, not statistically significant differences were present for age, gender, chronic kidney disease classification and liver fibrosis(P > 0.05). Linear correlation was found between NGAL and both age(P = 0.0475) and e GFR(P = 0.0282) values. Not statistically significant predictions of NGAL at baseline were demonstrated for e GFR evolution 1 year later. Interestingly, in the 8 patients treated with DAAs, median NGAL significantly increased at week 12 compared to baseline(P = 0.0239).CONCLUSION: Our results suggest that NGAL should be further evaluated as an adjunct marker of kidney function in these patients.

  8. Neutrophil Gelatinase-Associated Lipocalin Concentration in Vaginal Fluid: Relation to Bacterial Vaginosis and Vulvovaginal Candidiasis.

    Science.gov (United States)

    Beghini, Joziani; Giraldo, Paulo C; Linhares, Iara M; Ledger, William J; Witkin, Steven S

    2015-08-01

    Neutrophil gelatinase-associated lipocalin (NGAL) is a component of innate immunity that prevents iron uptake by microorganisms. We evaluated whether NGAL was present in vaginal fluid and whether concentrations were altered in women with bacterial vaginosis (BV) or vulvovaginal candidiasis (VVC). Vaginal secretions from 52 women with VVC, 43 with BV, and 77 healthy controls were assayed by enzyme-linked immunosorbent assay for NGAL and for concentrations of L-lactic acid. The median concentration of NGAL in vaginal fluid was significantly higher in control women (561 pg/mL) than in women with BV (402 pg/mL; P = .0116) and lower in women with VVC (741 pg/mL; P = .0017). Median lactic acid levels were similar in controls (0.11 mmol/L) and women with VVC (0.13 mmol/L) and were lower in women with BV (0.02 mmol/L; P < .0001). The NGAL and lactic acid concentrations were highly correlated (P < .0001). A decrease in Lactobacilli and/or lactic acid plus the absence of leukocytes results in lower vaginal NGAL levels that might facilitate the growth of bacteria associated with BV. © The Author(s) 2015.

  9. Serum cystatin C and neutrophil gelatinase-associated lipocalin in predicting the severity of coronary artery disease in diabetic patients

    OpenAIRE

    OKYAY, Kaan; Y?ld?r?r, Aylin; ?i?ek, Mutlu; Ayd?nalp, Alp; M?derriso?lu, Haldun

    2015-01-01

    Objective: Cystatin C and neutrophil gelatinase-associated lipocalin (NGAL) are biomarkers of renal functions. We evaluated their roles in predicting the severity of coronary artery disease (CAD). Methods: Fifty-two consecutive type 2 diabetic patients (32 males, 65.7?8.6 years) who underwent coronary angiography (CAG) for stable CAD were included in this single-center, prospective, cross-sectional study. Patients with an estimated glomerular filtration rate

  10. 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

  11. Urinary Excretion of Neutrophil Gelatinase-Associated Lipocalin in Diabetic Rats

    Science.gov (United States)

    Arellano-Buendía, Abraham Said; García-Arroyo, Fernando Enrique; Cristóbal-García, Magdalena; Loredo-Mendoza, María Lilia; Tapia-Rodríguez, Edilia; Sánchez-Lozada, Laura Gabriela; Osorio-Alonso, Horacio

    2014-01-01

    Recent studies suggest that tubular damage precedes glomerular damage in the progression of diabetic nephropathy. Therefore, we evaluated oxidative stress and urinary excretion of tubular proteins as markers of tubular dysfunction. Methods. Diabetes was induced in rats by streptozotocin administration (50 mg/kg). Oxidative stress was assessed by measuring the activity of catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD); additionally, expression levels of 3-nitrotyrosine (3-NT), 4-hydroxynonenal (4-HNE), and oxidized protein (OP) were quantified. Whole glomerular filtration rate (GFR) was measured. Urinary excretion of neutrophil gelatinase-associated lipocalin (uNGAL), osteopontin (uOPN), and N-acetyl-β-D-glucosaminidase (uNAG) was also determined. Results. Diabetic rats showed an increase in uNGAL excretion 7 days following induction of diabetes. Diuresis, proteinuria, albuminuria, creatinine clearance, and GFR were significantly increased by 30 days after induction. Furthermore, there was an increase in both CAT and SOD activity, in addition to 3-NT, 4-HNE, and OP expression levels. However, GPx activity was lower. Serum levels of NGAL and OPN, as well as excretion levels of uNGAL, uOPN, and uNAG, were increased in diabetics. Tubular damage was observed by 7 days after diabetes induction and was further aggravated by 30 days after induction. Conclusion. The tubular dysfunction evidenced by urinary excretion of NGAL precedes oxidative stress during diabetes. PMID:25243053

  12. Urinary Excretion of Neutrophil Gelatinase-Associated Lipocalin in Diabetic Rats

    Directory of Open Access Journals (Sweden)

    Abraham Said Arellano-Buendía

    2014-01-01

    Full Text Available Recent studies suggest that tubular damage precedes glomerular damage in the progression of diabetic nephropathy. Therefore, we evaluated oxidative stress and urinary excretion of tubular proteins as markers of tubular dysfunction. Methods. Diabetes was induced in rats by streptozotocin administration (50 mg/kg. Oxidative stress was assessed by measuring the activity of catalase (CAT, glutathione peroxidase (GPx, and superoxide dismutase (SOD; additionally, expression levels of 3-nitrotyrosine (3-NT, 4-hydroxynonenal (4-HNE, and oxidized protein (OP were quantified. Whole glomerular filtration rate (GFR was measured. Urinary excretion of neutrophil gelatinase-associated lipocalin (uNGAL, osteopontin (uOPN, and N-acetyl-β-D-glucosaminidase (uNAG was also determined. Results. Diabetic rats showed an increase in uNGAL excretion 7 days following induction of diabetes. Diuresis, proteinuria, albuminuria, creatinine clearance, and GFR were significantly increased by 30 days after induction. Furthermore, there was an increase in both CAT and SOD activity, in addition to 3-NT, 4-HNE, and OP expression levels. However, GPx activity was lower. Serum levels of NGAL and OPN, as well as excretion levels of uNGAL, uOPN, and uNAG, were increased in diabetics. Tubular damage was observed by 7 days after diabetes induction and was further aggravated by 30 days after induction. Conclusion. The tubular dysfunction evidenced by urinary excretion of NGAL precedes oxidative stress during diabetes.

  13. Plasma Neutrophil Gelatinase-Associated Lipocalin and Acute Postoperative Kidney Injury in Adult Cardiac Surgical Patients

    Science.gov (United States)

    Perry, Tjörvi E.; Muehlschlegel, Jochen D.; Liu, Kuang-Yu; Fox, Amanda A.; Collard, Charles D.; Shernan, Stanton K.; Body, Simon C.

    2010-01-01

    BACKGROUND Acute kidney injury (AKI) after coronary artery bypass graft (CABG) surgery is associated with increased postoperative morbidity and mortality. We hypothesized that increased plasma neutrophil gelatinase-associated lipocalin (NGAL) measured immediately after separating from cardiopulmonary bypass (CPB) would predict AKI after CABG surgery. METHODS In a retrospective observational study, we examined the value of plasma NGAL measured after CPB for predicting the risk of developing AKI (defined as a ≥50% increase in serum creatinine from preoperative levels) in 879 patients after CABG surgery using multivariable logistic regression. Area under the curve of receiver operating characteristic curves was analyzed to assess sensitivities, specificities, and cutoff points for postoperative plasma NGAL levels to predict AKI. RESULTS Seventy-five patients (8.6%) developed postoperative AKI. Plasma NGAL levels measured after CPB were higher in patients who subsequently developed AKI than in those who did not (AKI: 268.8 ng/mL [207.5–459.5 ng/mL], median [interquartile range], vs no AKI: 238.4 ng/mL [172.0–319.1 ng/mL]; P postoperative day 4. An optimal serum plasma NGAL cutoff of 353.5 ng/mL at the post-CPB time point had a sensitivity of 38.7%, specificity of 81.5%, and a positive predictive value of 16.3% for predicting AKI. In our multivariate regression model, post-CPB plasma NGAL levels >353.5 ng/mL were independently associated with postoperative AKI (odds ratio, 2.3; 95% confidence interval, 1.5–6.5; P = 0.002). CONCLUSION An early increase of post-CPB plasma NGAL is associated with AKI in adult patients undergoing CABG surgery, although the sensitivity is low. Therefore, assessing early plasma NGAL alone has limited utility for predicting AKI in this patient population. PMID:20435938

  14. Serum Levels of Gelatinase Associated Lipocalin as Indicator of the Inflammatory Status in Coronary Artery Disease

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    Nikolaos Kafkas

    2012-01-01

    Full Text Available Background. Atherosclerosis is a chronic inflammatory disease and the acute clinical manifestations represent acute on chronic inflammation. Neutrophil gelatinase-associated lipocalin (NGAL is found in the granules of human neutrophils, with many diverse functions. The aim of this study was to evaluate the hypothesis that levels NGAL in blood may reflect the inflammatory process in various stages of coronary artery disease. Methods. We studied 140 patients, with SA 40, UA 35, NSTEMI 40, and STEMI 25, and 20 healthy controls. Serum NGAL was measured upon admission and before coronary angiography. Results. Significant differences were observed in median serum-NGAL(ng/mL between patients with SA (79.23 (IQR, 37.50–100.32, when compared with UA (108.00 (68.34–177.59, NSTEMI (166.49 (109.24–247.20, and STEMI (178.63 (111.18–305.92 patients and controls (50.31 (44.30–69.78 with significant incremental value from SA to STEMI. We observed a positive and significant correlation between serum-NGAL and hs-CRP (spearman coefficient rho = 0.685, <0.0001 as well as with neutrophil counts (r = 0.511, <0.0001. Conclusions. In patients with coronary artery disease serum levels of NGAL increase and reflect the degree of inflammatory process. In patients with acute coronary syndromes, serum levels of NGAL have high negative predictive value and reflecting the inflammatory status could show the severity of coronary clinical syndrome.

  15. Neutrophil Gelatinase-Associated Lipocalin: Its Response to Hypoxia and Association with Acute Mountain Sickness

    Directory of Open Access Journals (Sweden)

    Adrian Mellor

    2013-01-01

    Full Text Available Acute Mountain Sickness (AMS is a common clinical challenge at high altitude (HA. A point-of-care biochemical marker for AMS could have widespread utility. Neutrophil gelatinase-associated lipocalin (NGAL rises in response to renal injury, inflammation and oxidative stress. We investigated whether NGAL rises with HA and if this rise was related to AMS, hypoxia or exercise. NGAL was assayed in a cohort (n=22 undertaking 6 hours exercise at near sea-level (SL; a cohort (n=14 during 3 hours of normobaric hypoxia (FiO2 11.6% and on two trekking expeditions (n=52 to over 5000 m. NGAL did not change with exercise at SL or following normobaric hypoxia. During the trekking expeditions NGAL levels (ng/ml, mean ± sd, range rose significantly (P<0.001 from 68 ± 14 (60–102 at 1300 m to 183 ± 107 (65–519; 143 ± 66 (60–315 and 150 ± 71 (60–357 at 3400 m, 4270 m and 5150 m respectively. At 5150 m there was a significant difference in NGAL between those with severe AMS (n=7, mild AMS (n=16 or no AMS (n=23: 201 ± 34 versus 171 ± 19 versus 124 ± 12 respectively (P=0.009 for severe versus no AMS; P=0.026 for mild versus no AMS. In summary, NGAL rises in response to prolonged hypobaric hypoxia and demonstrates a relationship to the presence and severity of AMS.

  16. PLASMA NEUTROPHIL GELATINASE ASSOCIATED LIPOCALIN AS AN EARLY BIOMARKER OF ACUTE KIDNEY INJURY IN SNAKE BITE

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    Thamarai

    2014-12-01

    Full Text Available INTRODUCTION: Acute kidney injury due to snake bite represents a frequent and devastating problem. Currently, Acute Kidney Injury is diagnosed by biochemical monitoring of increase in serum creatinine. Increase in serum creatinine represents a late indication of a functional change in glomerular function rate. Studies have shown that Neutrophil Gelatinase Associated Lipocalin has been found to be very useful for the detection of acute kidney injury within few hours of nephrotoxic insult. Limited information, however, is available regarding the study of plasma Neutrophil Gelatinase-Associated Lipocalin in snake bite. AIM: The purpose of the study was to estimate the diagnostic accuracy of plasma Neutrophil Gelatinase-Associated Lipocalin as an early biomarker of Acute Kidney Injury in patients with snake bite and to correlate with serum creatinine. If early detection of Acute Kidney Injury occurs, it can be followed by effective treatment modalities to abort the development or limit the severity of AKI. Therefore this study was designed to explore the importance of pNGAL in cases of snake bite induced AKI. MATERIALS AND METHODS: A prospective observational study was designed to study the patients admitted for the treatment of snakebite within 6 hours in a tertiary care hospital. Patients admitted for snake bite were followed by estimation of pNGAL on day 1 and serum creatinine from the period of admission for up to 5 days. A total of 130 snake bite patients were enrolled and 100 were included in the final study. Snake bite patients were classified into two groups based on the occurrence and absence of AKI. Plasma NGAL and serum creatinine was estimated by solid phase Enzyme Linked Immunosorbent Assay method and Jaffe`s method respectively. Data were entered into the excel sheet and analyzed statistically using statistical package for the social sciences (SPSS version 17. RESULTS:Among 100 snake bite patients 64 individuals had elevated pNGAL

  17. Proenkephalin, Neutrophil Gelatinase-Associated Lipocalin, and Estimated Glomerular Filtration Rates in Patients With Sepsis.

    Science.gov (United States)

    Kim, Hanah; Hur, Mina; Lee, Seungho; Marino, Rossella; Magrini, Laura; Cardelli, Patrizia; Struck, Joachim; Bergmann, Andreas; Hartmann, Oliver; Di Somma, Salvatore

    2017-09-01

    Proenkephalin (PENK) has been suggested as a novel biomarker for kidney function. We investigated the diagnostic and prognostic utility of plasma PENK in comparison with neutrophil gelatinase-associated lipocalin (NGAL) and estimated glomerular filtration rates (eGFR) in septic patients. A total of 167 septic patients were enrolled: 99 with sepsis, 37 with septic shock, and 31 with suspected sepsis. PENK and NGAL concentrations were measured and GFR was estimated by using the isotope dilution mass spectrometry traceable-Modification of Diet in Renal Disease (MDRD) Study and three Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations: CKD-EPI(Cr), CDK-EPI(CysC), and CKD-EPI(Cr-CysC). The PENK, NGAL, and eGFR results were compared according to sepsis severity, presence or absence of acute kidney injury (AKI), and clinical outcomes. The PENK, NGAL, and eGFR results were significantly associated with sepsis severity and differed significantly between patients with and without AKI only in the sepsis group (all P<0.05). PENK was superior to NGAL in predicting AKI (P=0.022) and renal replacement therapy (RRT) (P=0.0085). Regardless of the variable GFR category by the different eGFR equations, PENK showed constant and significant associations with all eGFR equations. Unlike NGAL, PENK was not influenced by inflammation and predicted the 30-day mortality. PENK is a highly sensitive and objective biomarker of AKI and RRT and is useful for prognosis prediction in septic patients. With its diagnostic robustness and predictive power for survival, PENK constitutes a promising biomarker in critical care settings including sepsis.

  18. Induction of neutrophil gelatinase-associated lipocalin expression by co-stimulation with interleukin-17 and tumor necrosis factor-alpha is controlled by IkappaB-zeta but neither by C/EBP-beta nor C/EBP-delta

    DEFF Research Database (Denmark)

    Karlsen, Joachim R; Borregaard, Niels; Cowland, Jack B

    2010-01-01

    Neutrophil gelatinase-associated lipocalin (NGAL) is a siderophore-binding antimicrobial protein that is up-regulated in epithelial tissues during inflammation. We demonstrated previously that the gene encoding NGAL (LCN2) is strongly up-regulated by interleukin (IL)-1beta in an NF-kappaB-depende...

  19. Plasma Neutrophil Gelatinase-Associated Lipocalin Is Primarily Related to Inflammation during Sepsis: A Translational Approach.

    Directory of Open Access Journals (Sweden)

    Gordon P Otto

    Full Text Available Acute kidney injury (AKI during sepsis is common and underestimated. Plasma neutrophil gelatinase-associated lipocalin (plasma-NGAL is discussed as new biomarker for AKI diagnosis, but during inflammation its function and diagnostic impact remain unclear. The association between plasma-NGAL and inflammatory markers in septic patients, but also in healthy controls and patients with chronic inflammation before and after either maximum exercise test or treatment with an anti-TNF therapy were investigated. In-vitro blood stimulations with IL-6, lipopolysaccharide, NGAL or its combinations were performed to investigate cause-effect-relationship. Plasma-NGAL levels were stronger associated with inflammation markers including IL-6 (Sepsis: r = 0.785 P < 0.001; chronic inflammation after anti-TNF: r = 0.558 P < 0.001, IL-8 (Sepsis: r = 0.714 P<0.004; healthy controls after exercise r = 0.786 P < 0.028; chronic inflammation before anti-TNF: r = 0.429 P < 0.041 and IL-10 (healthy controls before exercise: r = 0.791 P < 0.028 than with kidney injury or function. Correlation to kidney injury or function was found only in septic patients (for creatinine: r = 0.906 P < 0.001; for eGFR: r = -0.686 P = 0.005 and in patients with rheumatic disease after anti-TNF therapy (for creatinine: r = 0.466 P < 0.025. In stimulation assays with IL-6 and lipopolysaccharide plasma-NGAL was increased. Co-stimulation of lipopolysaccharide with plasma-NGAL decreased cellular injury (P < 0.05 and in trend IL-10 levels (P = 0.057. Septic mice demonstrated a significantly improved survival rate after NGAL treatment (P < 0.01. Plasma-NGAL seams to be strongly involved in inflammation. For clinical relevance, it might not only be useful for AKI detection during severe inflammation - indeed it has to be interpreted carefully within this setting - but additionally might offer therapeutic potential.

  20. Urinary Neutrophil Gelatinase-Associated Lipocalin and Progression of Diabetic Nephropathy in Type 1 Diabetic Patients in a Four-Year Follow-Up Study

    DEFF Research Database (Denmark)

    Nielsen, Stine Elkjaer; Hansen, Henrik Post; Jensen, Berit Ruud

    2010-01-01

    Background: Neutrophil gelatinase-associated lipocalin (NGAL), a marker of renal tubular damage, predicts progression in non-diabetic chronic kidney. We evaluated urinary (u)-NGAL as a predictor of progression in diabetic nephropathy in type 1 diabetic (T1D) patients. Methods: As a substudy of a 4......-year randomized, intervention study evaluating low-protein diet in T1D patients with diabetic nephropathy, 78 patients were studied with yearly measurements of u-NGAL (ELISA, BioPorto). Outcome: Decline in glomerular filtration rate (GFR) ((51)Cr-EDTA), and end-stage renal disease (ESRD) or death...

  1. The diagnostic value of neutrophil gelatinase-associated lipocalin and hepcidin in bacteria translocation of liver cirrhosis.

    Science.gov (United States)

    Zhang, Jiangguo; Gong, Fengyun; Li, Ling; Zhao, Manzhi; Wu, Zhuhua; Song, Jianxin

    2015-01-01

    Bacterial translocation (BT) or bacterial DNA (bactDNA) translocation is a critical pathogenesis mechanism of spontaneous bacterial peritonitis. Studies of BT or bactDNA translocation are limited in humans. Neutrophil gelatinase associated lipocalin (NGAL) can efficiently distinguish bacterial and nonbacterial ascites in ascitic patients. Hepcidin is a useful marker of bacterial infection in the late-onset sepsis. However, the relationship between NGAL, hepcidin and BT was still unclear. In present study, the levels of NGAL, hepcidin and their relationship with BT or bactDNA translocation were investigated. Weekly doses of carbon tetrachloride (CCl4) were given to induce liver cirrhosis in Sprague-Dawley rats. Trypticase (blood) soy agars were used to culture bacteria. BactDNA was sequenced by ABIPRISM 310 automated sequencer. The levels of NGAL and hepcidin were assessed by ELISA. Receiver operating characteristic (ROC) curve was used to determine the cut-off values and compare the diagnostic performance of NGAL and hepcidin. 56 cirrhotic and 10 normal rats were included in this study. The levels of both two biomarkers were significantly higher in BT or bactDNA translocation group compared to non-translocation group. The area under ROC curve for the diagnosis of BT was 0.910 for serum NGAL, 0.858 for serum hepcidin and 0.940 for their combination, whereas that for the diagnosis of bactDNA translocation was 0.906 for NGAL, 0.779 for hepcidin and 0.950 for their combination, respectively. The combination of NGAL and hepcidin improved the ability to detect BT or bactDNA presence in MLNs and ascites. BT and the presence of bactDNA in MLNs were observed in a rat cirrhotic model. Serum NGAL and hepcidin can serve as sensitive and specific tests for diagnosis of BT or bactDNA translocation. NGAL in combination with hepcidin can improve the accuracy of diagnosis.

  2. Plasma neutrophil gelatinase-associated lipocalin as an early biomarker for prediction of acute kidney injury after cardio-pulmonary bypass in pediatric cardiac surgery

    OpenAIRE

    Fatina I Fadel; Abdel Rahman, Azza M.O.; Mohamed, Mohamed Farouk; Habib, Sonia A.; Ibrahim, Mona H.; Sleem, Zeinab S.; Bazaraa, Hafez M; Soliman, Mohamed M.A.

    2012-01-01

    Introduction Cardiopulmonary bypass (CPB) surgery is considered one of the most frequent surgical procedures in which acute kidney injury (AKI) represents a frequent and serious complication. The aim of the present study was to evaluate the efficiency of neutrophil gelatinase-associated lipocalin (NGAL) as an early AKI biomarker after CPB in pediatric cardiac surgery. Material and methods The study included forty children aged 2 to 78 months undergoing CPB. They were divided into group I: pat...

  3. Neutrophil Gelatinase-Associated Lipocalin: Ready for Routine Clinical Use? An International Perspective

    Science.gov (United States)

    Ronco, Claudio; Legrand, Matthieu; Goldstein, Stuart L.; Hur, Mina; Tran, Nam; Howell, Eric C.; Cantaluppi, Vincenzo; Cruz, Dinna N.; Damman, Kevin; Bagshaw, Sean M.; Di Somma, Salvatore; Lewington, Andrew

    2016-01-01

    Acute kidney injury (AKI) remains a challenge in terms of diagnosis and classification, its morbidity and mortality remaining high in the face of improving clinical protocols. Current clinical criteria use serum creatinine (sCr) and urine output to classify patients. Ongoing research has identified novel biomarkers that may improve the speed and accuracy of patient evaluation and prognostication, yet the route from basic science to clinical practice remains poorly paved. International evidence supporting the use of plasma neutrophil gelatinase-associated lipocalin (NGAL) as a valuable biomarker of AKI and chronic kidney disease (CKD) for a number of clinical scenarios was presented at the 31st International Vicenza Course on Critical Care Nephrology, and these data are detailed in this review. NGAL was shown to be highly useful alongside sCr, urinary output, and other biomarkers in assessing kidney injury; in patient stratification and continuous renal replacement therapy (CRRT) selection in paediatric AKI; in assessing kidney injury in conjunction with sCr in sepsis; in guiding resuscitation protocols in conjunction with brain natriuretic peptide in burn patients; as an early biomarker of delayed graft function and calcineurin inhibitor nephrotoxicity in kidney transplantation from extended criteria donors; as a biomarker of cardiovascular disease and heart failure, and in guiding CRRT selection in the intensive care unit and emergency department. While some applications require further clarification by way of larger randomised controlled trials, NGAL nevertheless demonstrates promise as an independent biological marker with the potential to improve earlier diagnosis and better assessment of risk groups in AKI and CKD. This is a critical element in formulating quick and accurate decisions for individual patients, both in acute scenarios and in long-term care, in order to improve patient prognostics and outcomes. PMID:25012891

  4. Urinary Neutrophil Gelatinase-Associated Lipocalin Levels in Neonates

    Directory of Open Access Journals (Sweden)

    Chi-Nien Chen

    2016-06-01

    Conclusion: This study presents preliminary data on uNGAL levels in neonates in Taiwan. A large-scale study investigating the correlations between uNGAL and with gestational age, birth body weight, sex, and PNA is recommended.

  5. Neutrophil gelatinase-associated lipocalin and albuminuria as predictors of acute kidney injury in patients treated with goal-directed haemodynamic therapy after major abdominal surgery.

    LENUS (Irish Health Repository)

    Cullen, Mr

    2013-10-11

    Neutrophil gelatinase-associated lipocalin (NGAL) is emerging as a new biomarker for the early identification of acute kidney injury (AKI). There is also increasing evidence of an association between urinary albumin\\/creatinine ratio (ACR) and AKI. The primary aim of this study was to evaluate the clinical utility of these biomarkers to predict AKI in a population of perioperative patients treated with goal-directed haemodynamic therapy (GDHT). Secondary aims were to examine NGAL and ACR as sensitive biomarkers to detect the effects of GDHT and to investigate the association of these biomarkers with secondary outcomes.

  6. Predict value of monitoring changes of urinary neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 after coronary angiography and percutaneous coronary intervention on early diagnosis of contrast-induced nephropathy

    Institute of Scientific and Technical Information of China (English)

    王磊

    2014-01-01

    Objective To explore the predict value of monitoring changes of urinary neutrophil gelatinase-associated lipocalin(NGAL)and kidney injury molecule-1(KIM-1)after coronary angiography(CAG)and percutaneous coronary intervention(PCI)on the early diagnosis of contrast-induced nephropathy(CIN).Methods One hundred and sixty patients underwent CAG and PCI were en-

  7. No increase in kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin excretion following intravenous contrast enhanced-CT

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    Kooiman, Judith [Leiden University Medical Center, Department of Thrombosis and Haemostasis, Leiden (Netherlands); Leiden University Medical Center, Department of Nephrology, Leiden (Netherlands); Peppel, Wilke R. van de; Huisman, Menno V. [Leiden University Medical Center, Department of Thrombosis and Haemostasis, Leiden (Netherlands); Sijpkens, Yvo W.J. [Bronovo Hospital, Department of Nephrology, The Hague (Netherlands); Brulez, Harald F.H. [Sint Lucas Andreas Hospital, Department of Nephrology, Amsterdam (Netherlands); Vries, P.M. de [St. Antonius Hospital, Department of Vascular Surgery, Nieuwegein (Netherlands); Nicolaie, Mioara A.; Putter, H. [Leiden University Medical Center, Department of Medical Statistics and Bioinformatics, Leiden (Netherlands); Kooij, W. van der; Kooten, Cees van; Rabelink, Ton J. [Leiden University Medical Center, Department of Nephrology, Leiden (Netherlands)

    2015-07-15

    To analyze kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (N-GAL) excretion post-intravenous contrast enhanced-CT (CE-CT) in patients with chronic kidney disease (CKD). Patients were enrolled in a trial on hydration regimes to prevent contrast-induced acute kidney injury (CI-AKI). Blood and urine samples were taken at baseline, 4 - 6, and 48 - 96 h post CE-CT. Urinary KIM-1 and N-GAL values were normalized for urinary creatinine levels, presented as medians with 2.5 - 97.5 percentiles. Of the enrolled 511 patients, 10 (2 %) were lost to follow-up. CI-AKI occurred in 3.9 % of patients (20/501). Median KIM-1 values were 1.2 (0.1 - 7.7) at baseline, 1.3 (0.1 - 8.6) at 4 - 6 h, and 1.3 ng/mg (0.1 - 8.1) at 48 - 96 h post CE-CT (P = 0.39). Median N-GAL values were 41.0 (4.4 - 3,174.4), 48.9 (5.7 - 3,406.1), and 37.8 μg/mg (3.5 - 3,200.4), respectively (P = 0.07). The amount of KIM-1 and N-GAL excretion in follow-up was similar for patients with and without CI-AKI (P-value KIM-1 0.08, P-value N-GAL 0.73). Neither patient characteristics at baseline including severe CKD, medication use, nor contrast dose were associated with increased excretion of KIM-1 or N-GAL during follow-up. KIM-1 and N-GAL excretion were unaffected by CE-CT both in patients with and without CI-AKI, suggesting that CI-AKI was not accompanied by tubular injury. (orig.)

  8. The potential of lipocalin-2/NGAL as biomarker for inflammatory and metabolic diseases.

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    Abella, Vanessa; Scotece, Morena; Conde, Javier; Gómez, Rodolfo; Lois, Ana; Pino, Jesús; Gómez-Reino, Juan J; Lago, Francisca; Mobasheri, Ali; Gualillo, Oreste

    2015-01-01

    Lipocalin-2 (LCN2), also known as neutrophil gelatinase-associated lipocalin (NGAL), is a secreted glycoprotein that belongs to a group of transporters of small lipophilic molecules in circulation. LCN2 has been recently characterized as an adipose-derived cytokine. This adipokine is believed to bind small substances, such as steroids and lipopolysaccharides, and has been reported to have roles in the induction of apoptosis in hematopoietic cells, transport of fatty acids and iron, modulation of inflammation, and metabolic homeostasis. Recently, LCN2 has emerged as a useful biomarker and rheumatic diseases. This review provides an overview of LCN2 in inflammation, immunity, and metabolism.

  9. Plasma neutrophil gelatinase-associated lipocalin as a marker for the prediction of worsening renal function in children hospitalized for acute heart failure.

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    Elsharawy, Sahar; Raslan, Lila; Morsy, Saed; Hassan, Basheir; Khalifa, Naglaa

    2016-01-01

    Acute heart failure (AHF) is frequently associated with worsening renal function in adult patients. Neutrophil gelatinase-associated lipocalin (NGAL) serves as an early marker for acute renal tubular injury. To assess the role of plasma NGAL in predicting worsening renal function (WRF) in children with AHF, we studied 30 children hospitalized for AHF; children with history of chronic renal disease or on nephrotoxic drugs were excluded. Twenty age- and sex-matched healthy children were included in the study as a control group. Echocardiographic examination was performed on admission. Blood urea nitrogen (BUN), serum creatinine, estimated glomerular filtration rate (eGFR) and plasma NGAL levels were measured on admission and 72 h later. Seventeen (56.6%) patients developed WRF within the three-day follow-up period. At presentation, plasma NGAL level was significantly elevated in children who developed WRF. Admission plasma NGAL level correlated with renal parameters (BUN, creatinine and eGFR) as well as with left ventricular systolic parameters (ejection fraction and fractional shortening). For prediction of WRF, admission plasma, NGAL level>27.5 μg/L had sensitivity and specificity of 90% and 68%, respectively. The area under the receiver-operator curve was higher for NGAL (0.869) than for BUN (0.569) or eGFR (0.684). We conclude that admission plasma NGAL level can predict WRF in children hospitalized for AHF.

  10. Serum neutrophil gelatinase-associated lipocalin concentration reflects severity of coronary artery disease in patients without heart failure and chronic kidney disease.

    Science.gov (United States)

    Katagiri, Mikako; Takahashi, Masao; Doi, Kent; Myojo, Masahiro; Kiyosue, Arihiro; Ando, Jiro; Hirata, Yasunobu; Komuro, Issei

    2016-10-01

    Serum neutrophil gelatinase-associated lipocalin (NGAL) is recognized as a useful biomarker for acute kidney injury. Recently, elevated NGAL levels were reported in patients with heart failure and cardiac events, but the association between serum NGAL and severity of coronary artery disease (CAD) has not been investigated adequately. This study aimed to evaluate the association between serum NGAL concentration and CAD severity in patients without heart failure and chronic kidney disease. Two-hundred thirteen patients [mean age: 66.2 ± 9.2 (SD)] without heart failure and chronic kidney disease (estimated glomerular filtration rate >60 mL/min/1.73 m(2)) who underwent coronary angiography were retrospectively analyzed using the SYNTAX score. The mean concentration of serum NGAL was 134.3 ± 111.3 ng/mL. A statistically significant correlation was observed between serum NGAL levels and the SYNTAX score (R = 0.18, P = 0.0091). Multivariable analysis also showed elevated serum NGAL as an independent risk factor for a high SYNTAX score (P 100 ng/mL) and high levels of BNP (>25 pg/mL) had a higher SYNTAX score (low-low vs. high-high: 13.8 ± 13.4 vs. 20.8 ± 18.9, P heart failure. Serum NGAL might be a biomarker for CAD severity.

  11. Waist circumference and neutrophil gelatinase-associated lipocalin in late-life depression.

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    Marijnissen, Radboud M; Naudé, Petrus J W; Comijs, Hannie C; Schoevers, Robert A; Oude Voshaar, Richard C

    2014-03-01

    Both visceral obesity and depression are associated with impaired health and excess mortality, possibly through overlapping pathophysiological mechanisms like adipose tissue derived inflammatory markers. These results, however, are primarily based on population-based surveys, often restricted to a young population and depression severity scales instead of patients with established diagnosis of depressive disorder. We examined the relation between waist circumference and late-life depression using the baseline data of The Netherlands Study of Depression in Older people (NESDO). Psychopathology has been assessed with Composite International Diagnostic Interview version 2.1. Adjusted for age, sex, education, lifestyle (smoking, alcohol, physical activity), drug use, cognition and chronic diseases as well as adjusted for body mass index (BMI), analysis of covariance showed that depressed older patients (n=376) had a significantly lower waist circumference (WC) compared to their non-depressed comparisons (n=130): estimated marginal mean (SE)=93.9 (0.5) versus 97.8 (0.8) cm (F=15.9; df=1467; p<.001). Multiple linear regression analyses within the depressed group showed that both, depression severity (Inventory of Depressive Symptoms) as well as duration-related depression characteristics (age of onset, duration of illness, life-time comorbid dysthymia), were associated with the WC. Only the severity of depressive symptoms remained significant after further adjusted for the BMI. Interestingly, a recently discovered adipokine, Neutrophil Gelatinase-Associated Lipocalin (NGAL), was associated with late-life depression, but only in the subgroup of patients with a pathologically increased WC. Population-based findings on the positive association between obesity and depressive symptoms can thus not be generalised to a clinical sample of depressed older patients. The impact of the WC on course and treatment outcome of late-life depression should be examined in clinical samples

  12. Discrepancy between mRNA and Protein Expression of Neutrophil Gelatinase-Associated Lipocalin in Bronchial Epithelium Induced by Sulfur Mustard

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    Majid Ebrahimi

    2010-01-01

    Full Text Available Sulfur mustard (SM is a potent vesicant that has been employed as a chemical weapon in various conflicts during the 20th century. More recently, mustard was used in the Iraq conflict against Iranian troops and civilians. At the present time there are more than 40.000 people suffering from pulmonary lesions special bronchiolitis obliterans (BOs due to mustard gas. SM increases the endogenous production of reactive oxygen species (ROS. Neutrophil Gelatinase-associated Lipocalin 2 (Lcn2, NGAL is a member of the lipocalin superfamily for which a variety of functions such as cellular protection against oxidative stress have been reported. Ten normal and Twenty SM-induced COPD patient individuals were studied. Assessment of NGAL expressions in healthy and the patients endobrinchial biopsies were performed by semiquantitative RT-PCR, real-time RT-PCR, and Immunohistochemistry analysis. While Normal control samples expressed same level of mRNA NGAL, expression level of mRNA-NGAL was upregulated about 1.4- to 9.8-folds compared to normal samples. No significant immunoreactivity was revealed in both samples. As we are aware this is the first report of induction of NGAL in patients exposed to SM. NGAL may play an important role in cellular protection against oxidative stress toxicity induced by mustard gas in airway wall of patients.

  13. Correlation of serum neutrophil gelatinase-associated lipocalin with acute kidney injury in hypertensive disorders of pregnancy

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    Patel ML

    2013-10-01

    Full Text Available ML Patel,1 Rekha Sachan,2 Radheyshyam Gangwar,3 Pushpalata Sachan,4 SM Natu51Department of Medicine, King George's Medical University, Lucknow, Uttar Pradesh, India; 2Department of Obstetrics and Gynaecology, King George's Medical University, Lucknow, Uttar Pradesh, India; 3Department of Critical Care, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India; 4Department of Physiology, King George's Medical University, Lucknow, Uttar Pradesh, India; 5Department of Pathology, King George's Medical University, Lucknow, Uttar Pradesh, IndiaAbstract: Hypertensive disorders of pregnancy (HDP remain one of the largest single causes of maternal and fetal morbidity and mortality, accounting for 16.1% of maternal deaths in developed countries. The aim of the study was to evaluate acute kidney injury (AKI in hypertensive disorders of pregnancy and to examine the correlation of serum neutrophil gelatinase-associated lipocalin (NGAL with acute kidney injury. This prospective case control study was carried out over a period of 1 year. After written, informed consent and ethical clearance, 149 cases of hypertensive disorders of pregnancy were screened, and seven were lost to follow-up. Acute kidney injury was detected in 88 cases and acute renal failure in 30 cases of HDP. Thirty-one healthy pregnant nonhypertensive women were enrolled as controls. Quantitative measurement of serum NGAL levels was done by enzyme linked immunosorbent assay technique using a sandwich enzyme-linked immunosorbent assay kit. As per the Kidney Diseases Improving Global Outcomes International guidelines acute kidney injury network (AKIN, 50 cases (42.37% of AKI stage I, 38 (32.2% cases of AKI stage II, and 30 (25.42% cases of renal failure were detected. Serum NGAL had a positive association with increasing proteinuria. It also had a positive correlation with systolic blood pressure (r~0.36, diastolic blood pressure (r~0.37, and serum creatinine (r~0

  14. Low Serum Neutrophil Gelatinase-associated Lipocalin Level as a Marker of Malnutrition in Maintenance Hemodialysis Patients.

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    Hirotaka Imamaki

    Full Text Available Neutrophil gelatinase-associated lipocalin (NGAL or LCN2 is an iron-transporting factor which possesses various activities such as amelioration of kidney injury and host defense against pathogens. Its circulating concentrations are elevated in acute and chronic kidney diseases and show a positive correlation with poor renal outcome and mortality, but its clinical significance in maintenance hemodialysis (HD patients remains elusive.Serum NGAL levels were determined by enzyme-linked immunosorbent assay in out-patient, Japanese HD subjects. Their correlation to laboratory findings and morbidity (as development of severe infection or serum albumin reduction was investigated using linear regression analysis and χ2 test.Pre-dialysis serum NGAL levels in HD patients were elevated by 13-fold compared to healthy subjects (n=8, P<0.001. In a cross-sectional study of 139 cases, serum NGAL concentrations were determined independently by % creatinine generation rate (an indicator of muscle mass, standardized coefficient β=0.40, P<0.001, peripheral blood neutrophil count (β=0.38, P<0.001 and anion gap (which likely reflects dietary protein intake, β=0.16, P<0.05. Iron administration to anemic HD patients caused marked elevation of peripheral blood hemoglobin, serum ferritin and iron-regulatory hormone hepcidin-25 levels, but NGAL levels were not affected. In a prospective study of 87 cases, increase in serum albumin levels a year later was positively associated to baseline NGAL levels by univariate analysis (r=0.36, P<0.01. Furthermore, within a year, patients with the lowest NGAL tertile showed significantly increased risk for marked decline in serum albumin levels (≥0.4 g/dl; odds ratio 5.5, 95% confidence interval 1.5-20.3, P<0.05 and tendency of increased occurrence of severe infection requiring admission (odds ratio 3.1, not significant compared to the middle and highest tertiles.Low serum NGAL levels appear to be associated with current

  15. Increased Neutrophil Gelatinase-Associated Lipocalin is Associated with Mortality and Multiple Organ Dysfunction Syndrome in Severe Sepsis and Septic Shock.

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    Wang, Biao; Chen, Gang; Zhang, Jun; Xue, Jiping; Cao, Yifei; Wu, Yunfu

    2015-09-01

    This study examines the clinical utility of increased neutrophil gelatinase-associated lipocalin (NGAL) as an indicator of mortality and multiple organ dysfunction syndrome (MODS) in severe sepsis and septic shock. We designed a prospective cohort study in an intensive care unit, and 123 patients with severe sepsis or septic shock were included. Data were used to determine a relationship between NGAL and the development of MODS and mortality. These associations were determined by the Mann-Whitney U test, log-rank test, Cox proportional hazards regression analyses, and plotting the receiver operating characteristic curve. Patients with high NGAL (75th percentile) had increased risk of mortality and MODS compared with patients with low NGAL (log-rank test, P MODS on day 1, and 37 patients (30%) on day 7. The area under the receiver operating characteristic curve showed that high NGAL could predict mortality (0.6385) during intensive care unit stay. After adjustment for confounding risk factors chosen by backward elimination by Cox regression analysis, high NGAL remained an independent predictor of mortality and MODS (hazard ratios, 2.128 [95% confidence interval, 1.078-4.203; P = 0.030] and 1.896 [95% confidence interval, 1.012-3.552; P = 0.046], respectively). High plasma NGAL independently predicts mortality and MODS in severe sepsis and septic shock.

  16. Correlation of serum neutrophil gelatinase-associated lipocalin with acute kidney injury in hypertensive disorders of pregnancy.

    Science.gov (United States)

    Patel, Ml; Sachan, Rekha; Gangwar, Radheyshyam; Sachan, Pushpalata; Natu, Sm

    2013-01-01

    Hypertensive disorders of pregnancy (HDP) remain one of the largest single causes of maternal and fetal morbidity and mortality, accounting for 16.1% of maternal deaths in developed countries. The aim of the study was to evaluate acute kidney injury (AKI) in hypertensive disorders of pregnancy and to examine the correlation of serum neutrophil gelatinase-associated lipocalin (NGAL) with acute kidney injury. This prospective case control study was carried out over a period of 1 year. After written, informed consent and ethical clearance, 149 cases of hypertensive disorders of pregnancy were screened, and seven were lost to follow-up. Acute kidney injury was detected in 88 cases and acute renal failure in 30 cases of HDP. Thirty-one healthy pregnant nonhypertensive women were enrolled as controls. Quantitative measurement of serum NGAL levels was done by enzyme linked immunosorbent assay technique using a sandwich enzyme-linked immunosorbent assay kit. As per the Kidney Diseases Improving Global Outcomes International guidelines acute kidney injury network (AKIN), 50 cases (42.37%) of AKI stage I, 38 (32.2%) cases of AKI stage II, and 30 (25.42%) cases of renal failure were detected. Serum NGAL had a positive association with increasing proteinuria. It also had a positive correlation with systolic blood pressure (r∼0.36), diastolic blood pressure (r∼0.37), and serum creatinine (r∼0.4). NGAL was found to be significantly correlated with creatinine in the cases with the value of the correlation coefficient being 0.4. This direct correlation might be a consequence of endothelial dysfunction on which hypertension and proteinuria probably depends.

  17. Neutrophil gelatinase-associated lipocalin as a biomarker for acute kidney injury in children after cardiac surgery

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    Meta Herdiana Hanindita

    2016-08-01

    Full Text Available Background Acute kidney injury (AKI is still diagnosed by measuring the estimated creatinine clearance (eCCl, despite the fact that it may not change until 50% or more of kidney function has been lost. AKI after cardiac surgery is related to prolonged intensive care, decreased quality of life, and increased long term mortality. Neutrophil gelatinase-associated lipocalin (NGAL represents an early biomarker of AKI, which may be useful for assessing AKI in cardiac patients. Objective To determine the validity of urinary and plasma NGAL as biomarkers for AKI in children after cardiac surgery. Methods Subjects were children who underwent cardiac surgery in Dr. Soetomo Hospital, Surabaya, Indonesia from August 2013 to January 2014. Serial urine and blood samples were analyzed for NGAL before surgery, as well as at 2h, 4h, 12h, and 24h after surgery. The AKI was established based on pRIFLE criteria. Estimated creatinine clearance (eCCl was calculated from the estimated glomerular filtration rate (eGFR, according to age by the traditional Schwartz formula. Serum creatinine was assayed by the Jaffe method before surgery, as well as at 12h, 24h, 48h, and 72h after surgery. Results Of 20 subjects, 5 developed AKI. Urinary and plasma NGAL increased markedly at 2h postoperatively, as compared to eGFR which showed a rise at 12-48 h after cardiac surgery. Analysis of 2h post-operative urinary NGAL at a cut off value of 11.270ng/mL yielded an area under the curve (AUC of 1.00 (95%CI 2.63 to 12.13, with sensitivity and specificity of 100% each for AKI. In addition, 2h post-operative plasma NGAL at a cut off value of 8.385 ng/mL yielded an AUC of 1.00 (95%CI 3.71 to 12.15 with sensitivity and specificity of 100% each for AKI. Conclusion Urinary and plasma NGAL are valid as early biomarkers for AKI in children after cardiac surgery.

  18. The Predictivity of Neutrophil Gelatinase Associated Lipocaline in the Development of Radiocontrast-Induced Nephropathy in the Intensive Care Unit Patients

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    Funda TÜRKMEN

    2013-05-01

    Full Text Available OBJECTIVE: The aim of this study is to investigate the predictive value of neutrophil gelatinase associated lipocaline (NGAL levels in the development of radiocontrast-induced nephropathy (rin in intensive care unit patients. MATERIAL and METHODS: Forty patients (female: male was 23:17 with a mean age of 73.7± 9.7 yrs (range= 60-94 yrs were included in the study. Lopromide 623mg/dl (ultravist 300 (iv was administered at a dose of 1.5 ml/kg. NGAL measurements were performed with the ELISA method on serum samples (cut-off >25 ng/ml. RESULTS: Eight patients were diagnosed as RIN. Five of these had 20% or more increases in NGAL levels. Cases who developed RIN had a statistically significant and direct correlation between the increases in NGAL and serum creatinine levels (p= 0.02. When the means of NGAL levels were compared before and six hours after the procedure, there was a significant increase after the procedure (p0.05. CONCLUSION: When compared to creatinine, plasma NGAL levels help to establish the diagnosis of RIN at a much earlier stage.

  19. Impact of clinical context on acute kidney injury biomarker performances: differences between neutrophil gelatinase-associated lipocalin and L-type fatty acid-binding protein.

    Science.gov (United States)

    Asada, Toshifumi; Isshiki, Rei; Hayase, Naoki; Sumida, Maki; Inokuchi, Ryota; Noiri, Eisei; Nangaku, Masaomi; Yahagi, Naoki; Doi, Kent

    2016-01-01

    Application of acute kidney injury (AKI) biomarkers with consideration of nonrenal conditions and systemic severity has not been sufficiently determined. Herein, urinary neutrophil gelatinase-associated lipocalin (NGAL), L-type fatty acid-binding protein (L-FABP) and nonrenal disorders, including inflammation, hypoperfusion and liver dysfunction, were evaluated in 249 critically ill patients treated at our intensive care unit. Distinct characteristics of NGAL and L-FABP were revealed using principal component analysis: NGAL showed linear correlations with inflammatory markers (white blood cell count and C-reactive protein), whereas L-FABP showed linear correlations with hypoperfusion and hepatic injury markers (lactate, liver transaminases and bilirubin). We thus developed a new algorithm by combining urinary NGAL and L-FABP with stratification by the Acute Physiology and Chronic Health Evaluation score, presence of sepsis and blood lactate levels to improve their AKI predictive performance, which showed a significantly better area under the receiver operating characteristic curve [AUC-ROC 0.940; 95% confidential interval (CI) 0.793-0.985] than that under NGAL alone (AUC-ROC 0.858, 95% CI 0.741-0.927, P = 0.03) or L-FABP alone (AUC-ROC 0.837, 95% CI 0.697-0.920, P = 0.007) and indicated that nonrenal conditions and systemic severity should be considered for improved AKI prediction by NGAL and L-FABP as biomarkers.

  20. The changes of neutrophil gelatinase-associated lipocalin in plasma and its expression in adipose tissue in pregnant women with gestational diabetes.

    Science.gov (United States)

    Lou, Yanqin; Wu, Chaoying; Wu, Min; Xie, Cui; Ren, Lirong

    2014-04-01

    To investigate plasma levels and the expression of neutrophil gelatinase-associated lipocalin (NGAL) in subcutaneous adipose tissue (SAT) in patients with gestational diabetes mellitus (GDM). The study recruited 260 Chinese women divided into three groups: 96 were healthy pregnant women with pre-pregnancy body mass index (pre-pregnancy BMI) below 25kg/m(2) (GROUP 1), 84 were women with GDM with pre-pregnancy BMI below 25kg/m(2) (GROUP 2) and 80 were women with GDM with pre-pregnancy BMI over 25kg/m(2) (GROUP 3). Laboratory and anthropometric measurements were recorded and NGAL plasma levels were determined by ELISA for subjects in all groups. Real-time RT-PCR and Western blotting were used to assess the relative mRNA and protein expression of NGAL and tumor necrosis factor-α (TNF-α) in SAT (30 cases in each group). Our results demonstrated statistically significant elevation in plasma NGAL concentrations in GROUP 2 and GROUP 3 compared with GROUP 1 (p<0.001 for both group comparisons). Moreover, SAT NGAL mRNA (p<0.001 and p<0.001, respectively) and protein (p<0.001 and p<0.001, respectively) expression levels were higher in GROUP 3 than in both GROUP 1 and GROUP 2. Correlations were noted between the plasma NGAL concentration and various parameters of insulin resistance. Plasma NGAL may play a role in the development of insulin resistance in GDM, and the high levels of NGAL expression in SAT in overweight women with GDM suggests that NGAL in SAT is associated with obesity in women with GDM. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  1. A comparison of neutrophil gelatinase-associated lipocalin and immature to total neutrophil ratio for diagnosing early-onset neonatal sepsis

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    Rocky Wilar

    2016-07-01

    Full Text Available Background Neonatal sepsis is a clinical syndrome caused by the invasion of microorganisms into the bloodstream. Early diagnosis of early-onset neonatal sepsis (EONS is difficult. Laboratory tests with high sensitivity and specificity are needed in order to make early diagnoses in newborns.Objective To compare the sensitivity and specificity of neutrophil gelatinase-associated lipocalin (NGAL and immature to total (IT neutrophil ratio for the diagnosis of early-onset neonatal sepsis.Methods This observational study with cross-sectional design was conducted in the Neonatology Division, Prof. R. D. Kandou General Hospital from November 2012 to April 2014. Consecutive sampling was applied. There were 103 newborns with suspected EONS who fulfilled the inclusion criteria. Complete blood counts, blood cultures, as well as NGAL and IT ratio measurements were performed.Results NGAL was not significantly more sensitive than IT ratio [80.4% vs. 67.3%, respectively; (P=0.058]. However, NGAL had lower specificity than IT ratio (27.7% vs. 50.0%, respectively; P=0.016. The positive predictive values (57.0% vs. 64.9%, respectively; P=0.176, and negative predictive values (54.2% vs. 52.6%, respectively; P=0.451 were similar in both diagnostic tests.Conclusion Immature to total neutrophil (IT ratio has higher specificity compared to NGAL for early diagnosis of EONS. However, the difference in sensitivity between the two test is not statistically significant.

  2. 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.

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    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.

  3. Diagnostic and prognostic value of neutrophil gelatinase associated lipocalin and cancer antigen 15-3 serum levels in benign and malignant breast disease

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    Tunc Eren

    2016-03-01

    Full Text Available Purpose: Increased neutrophil gelatinase-associated lipocalin (NGAL serum levels have been shown in studies for colorectal, gastric, esophageal, liver, thyroid and lung cancer. The aim of this study was to demonstrate the differences of NGAL and cancer antigen 15-3 (CA15-3 serum levels between the groups of patients diagnosed with either breast cancer, or benign breast disorders in order to investigate the diagnostic and prognostic value of these biomarkers. Material and Methods: The patients were divided into three groups as the malignancy group, the benign group, and the control group. Serum NGAL/CA15-3 levels, the presence of a breast lesion, and the type of the lesion were recorded. In the malignancy group; parameters including tumor type, invasion degree, T/N stages, lymphovascular/perineural invasion, histological grade, c-erbB2, e-cadherin, estrogen and progesteron reseptor levels were recorded, and compared between the three groups. Results: Eighty four patients were enrolled to the study. The mean NGAL level was higher in the benign group. CA15-3 detection did not reveal significant difference between the study groups. In the malignant group; increased serum NGAL levels were associated with higher histological grade, while elevated CA15-3 levels were associated with positive lymph node count. Conclusion: The association of elevated CA15-3 levels with metastatic lymph node counts proves that the prognostic value of this marker is higher than its diagnostic accuracy. On the other hand, serum NGAL detection results reveal that the diagnostic value of NGAL for breast cancer is lower when compared to other cancer types. [Cukurova Med J 2016; 41(1.000: 87-96

  4. Correlation of plasma osteopontin and neutrophil gelatinase-associated lipocalin levels with the severity and clinical outcome of pelvic inflammatory disease.

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    Tee, Yi-Torng; Wang, Po-Hui; Yang, Shun-Fa; Tsai, Hsiu-Ting; Lee, Shu-Kuei; Ko, Jiunn-Liang; Lin, Long-Yau; Chen, Shiuan-Chih

    2014-06-01

    To investigate the correlation of two important inflammatory biomarkers, plasma osteopontin and neutrophil gelatinase-associated lipocalin (NGAL), with the severity and outcome of pelvic inflammatory disease (PID). Sixty-one patients with PID, including 25 patients with tubo-ovarian abscess (TOA), were consecutively recruited. Their blood samples were tested for the concentrations of plasma osteopontin and NGAL using enzyme-linked immunosorbent assay. The associations of these biomarkers with TOA, length of hospitalization, and incidence of surgery were also analyzed. Plasma osteopontin level was significantly increased in PID patients with TOA compared to PID patients without TOA (median 107.77 ng/mL vs. 72.39 ng/mL, p = 0.004). However, there was no significant difference for plasma NGAL. If the cutoff level of plasma osteopontin was set at 81.1 ng/mL, there was a 76.0% sensitivity and a 24.0% false negative rate in predicting TOA in PID patients. Plasma osteopontin significantly correlated with length of hospital stay (r = 0.467, p < 0.001), and this correlation was better than that of NGAL. However, neither biomarker was associated with incidence of surgery. Plasma osteopontin has a better correlation with TOA and length of hospitalization compared to NGAL. If plasma osteopontin level falls below 81.1 ng/mL, PID patients will have about a 20% chance of developing TOA. Incorporating plasma osteopontin, but not NGAL, will allow for an adjuvant diagnostic biomarker for TOA and predictor of length of hospital stay. Copyright © 2014. Published by Elsevier B.V.

  5. Urine Neutrophil Gelatinase-Associated Lipocalin and Risk of Cardiovascular Disease and Death in CKD: Results From the Chronic Renal Insufficiency Cohort (CRIC) Study

    Science.gov (United States)

    Liu, Kathleen D.; Yang, Wei; Go, Alan S.; Anderson, Amanda H.; Feldman, Harold I.; Fischer, Michael J.; He, Jiang; Kallem, Radhakrishna R.; Kusek, John W.; Master, Stephen R.; Miller, Edgar R.; Rosas, Sylvia E.; Steigerwalt, Susan; Tao, Kaixiang; Weir, Matthew R.; Hsu, Chi-yuan

    2015-01-01

    Background Chronic kidney disease is common and associated with increased cardiovascular disease risk. Currently, markers of renal tubular injury are not used routinely to describe kidney health and little is known about risk of cardiovascular events and death associated with these biomarkers independent of glomerular filtration—based markers (such as serum creatinine or albuminuria). Study Design Cohort study, Chronic Renal Insufficiency Cohort (CRIC) Study. Setting & Participants 3386 participants with estimated glomerular filtration rate of 20-70 mL/min/1.73 m2 enrolled from June 2003 through August 2008. Predictor Urine neutrophil gelatinase-associated lipocalin (NGAL) concentration. Outcomes Adjudicated heart failure event, ischemic atherosclerotic event (myocardial infarction, ischemic stroke or peripheral artery disease) and death through March 2011. Measurements Urine NGAL concentration measured at baseline with a two-step assay using chemiluminescent microparticle immunoassay technology on an ARCHITECT i2000SR (Abbott Laboratories). Results There were 428 heart failure events (during 16383 person-years of follow-up), 361 ischemic atherosclerotic events (during 16584 person-years of follow-up) and 522 deaths (during 18214 person-years of follow-up). In Cox regression models adjusted for estimated glomerular filtration rate, albuminuria, demographics, traditional cardiovascular disease risk factors and cardiac medications, higher urine NGAL levels remained independently associated with ischemic atherosclerotic events (adjusted HR for the highest [>49.5 ng/ml] vs. lowest [≤6.9 ng/ml] quintile, 1.83 [95% CI, 1.20-2.81]; HR, per 0.1-unit increase in log urine NGAL, 1.012 [95% CI, 1.001-1.023]), but not heart failure events or deaths. Limitations Urine NGAL was measured only once. Conclusions Among patients with chronic kidney disease, urine levels of NGAL, a marker of renal tubular injury, were independently associated with future ischemic atherosclerotic

  6. Decreased circulating 25-(OH) Vitamin D concentrations in obese female children and adolescents: positive associations with Retinol Binding Protein-4 and Neutrophil Gelatinase-associated Lipocalin.

    Science.gov (United States)

    Metheniti, Dimitra; Sakka, Sophia; Dracopoulou, Maria; Margeli, Alexandra; Papassotiriou, Ioannis; Kanaka-Gantenbein, Christina; Chrousos, George P; Pervanidou, Panagiota

    2013-01-01

    Hypovitaminosis D has been associated with adult as well as childhood obesity. Retinol-binding-protein-4 (RBP-4) and Neutrophil Gelatinase-associated Lipocalin (NGAL) are altered in obese individuals. The aim of this study was to examine circulating 25-(OH) Vitamin D (25-(OH) D) concentrations according to BMI and its associations with RBP-4 and NGAL in female children and adolescents. Seventy-nine (79) children, aged 8-16 years, were studied and divided into four groups: 19 control (BMI z-score range -2.15 - 1.24), 20 overweight (1.34 - 2.49), 20 obese (2.50 - 2.87) and 20 ultra-obese (3 - 4.37). Patients were derived from a Pediatric Obesity Clinic. Plasma 25-(OH) D, RBP-4 and NGAL concentrations were measured with specific assays. Plasma 25-(OH) D concentrations were decreased significantly in the ultra-obese (p=0.005) and marginally in the obese group (p=0.05) compared to the control group. In the entire BMI range, Spearman correlations revealed strong positive associations between 25-(OH) D and RBP-4 (r=0.349, p=0.002) and between 25-(OH) D and NGAL (r=0.338, p=0.003). 25-(OH) D is deficient in a clinical population of obese female children and adolescents, whereas in the entire BMI range 25-(OH) D is associated with RBP4 and NGAL concentrations. Longitudinal studies are needed to reveal the role of these associations in metabolic alterations related to childhood and adolescent obesity and associated metabolic morbidities.

  7. Early predictors of acute kidney injury in patients with cirrhosis and bacterial infection: urinary neutrophil gelatinase-associated lipocalin and cardiac output as reliable tools

    Science.gov (United States)

    Ximenes, Rafael O.; Farias, Alberto Q.; Helou, Claudia M.B.

    2015-01-01

    Background Hemodynamic abnormalities and acute kidney injury (AKI) are often present in infected cirrhotic patients. Hence, an early diagnosis of AKI is necessary, which might require the validation of new predictors as the determinations of urinary neutrophil gelatinase-associated lipocalin (uNGAL) and cardiac output. Methods We evaluated 18 infected cirrhotic patients subdivided into two groups at admission (0 hours). In Group I, we collected urine samples at 0 hours, 6 hours, 24 hours, and 48 hours for uNGAL and fractional excretion of sodium determinations. In Group II, we measured cardiac output using echocardiography. Results The age of patients was 55.0±1.9 years, and 11 patients were males. The Model for End-Stage Liver Disease score was 21±1, whereas the Child–Pugh score was C in 11 patients and B in 7 patients. Both patients in Group I and Group II showed similar baseline characteristics. In Group I, we diagnosed AKI in 5 of 9 patients, and the mean time to this diagnosis by measuring serum creatinine was 5.4 days. Patients with AKI showed higher uNGAL levels than those without AKI from 6 hours to 48 hours. The best accuracy using the cutoff values of 68 ng uNGAL/mg creatinine was achieved at 48 hours when we distinguished patients with and without AKI in all cases. In Group II, we diagnosed AKI in 4 of 9 patients, and cardiac output was significantly higher in patients who developed AKI at 0 hours. Conclusion Both uNGAL and cardiac output determinations allow the prediction of AKI in infected cirrhotic patients earlier than increments in serum creatinine. PMID:26484038

  8. Serum neutrophil gelatinase associated lipocalin during the early postoperative period predicts the recovery of graft function after kidney transplantation from donors after cardiac death.

    Science.gov (United States)

    Kusaka, Mamoru; Iwamatsu, Fumi; Kuroyanagi, Yoko; Nakaya, Miho; Ichino, Manabu; Marubashi, Shigeru; Nagano, Hiroaki; Shiroki, Ryoichi; Kurahashi, Hiroki; Hoshinaga, Kiyotaka

    2012-06-01

    Kidneys procured from donors after cardiac death hold great potential to expand the donor pool. However, they have not yet been fully used, in part due to the high incidence of delayed graft function. Although urine neutrophil gelatinase-associated lipocalin is a well-known early biomarker for renal injury after kidney transplantation, its usefulness is limited in cases with delayed graft function because of the unavailability of a urine sample. We evaluated serum neutrophil gelatinase-associated lipocalin as a potential biomarker to predict the functional recovery of kidneys transplanted from donors after cardiac death. Consecutive patients transplanted with a kidney from a living related (39), brain dead (1) or post-cardiac death (27) donor were retrospectively enrolled in the study. Serum samples were collected serially before and after kidney transplantation. Serum neutrophil gelatinase-associated lipocalin was measured using the ARCHITECT® assay. Average serum neutrophil gelatinase-associated lipocalin was markedly high during the pre transplantation period. It decreased rapidly after transplantation. The slope of the decrease correlated well with the recovery period. By analyzing ROC curves we determined cutoffs to predict immediate, slow or delayed graft function requiring hemodialysis for longer than 1 week with high sensitivity and specificity. These data suggest that serial monitoring of serum neutrophil gelatinase-associated lipocalin may allow us to predict graft recovery and the need for hemodialysis after kidney transplantation from a donor after cardiac death. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

  9. Assessment of Plasma and NGAL for the Early Prediction of Acute Kidney Injury After Cardiac Surgery in Adults Study

    Science.gov (United States)

    2016-04-11

    Acute Kidney Injury (AKI); Chronic Kidney Disease (CKD); End Stage Renal Disease (ESRD); Estimated Glomerular Filtration Rate (eGFR); Neutrophil Gelatinase-associated Lipocalin (NGAL); Serum Creatinine (SCr); Urine Creatinine (UCr); Urine Albumin (UAlb)

  10. Molecularly Imprinted Polymer (MIP) Film with Improved Surface Area Developed by Using Metal-Organic Framework (MOF) for Sensitive Lipocalin (NGAL) Determination.

    Science.gov (United States)

    Iskierko, Zofia; Sharma, Piyush Sindhu; Prochowicz, Daniel; Fronc, Krzysztof; D'Souza, Francis; Toczydłowska, Diana; Stefaniak, Filip; Noworyta, Krzysztof

    2016-08-10

    Electropolymerizable functional and cross-linking monomers were used to prepare conducting molecularly imprinted polymer film with improved surface area with the help of a sacrificial metal-organic framework (MOF). Subsequent dissolution of the MOF layer resulted in a surface developed MIP film. This surface enlargement increased the analyte accessibility to imprinted molecular cavities. Application of the porous MIP film as a recognition unit of an extended-gate field effect transistor (EG-FET) chemosensor effectively enhanced analytical current signals of determination of recombinant human neutrophil gelatinase-associated lipocalin (NGAL).

  11. Urinary neutrophil gelatinase-associated lipocalin time course during cardiac surgery

    Directory of Open Access Journals (Sweden)

    Elena Bignami

    2015-01-01

    Full Text Available Background: NGAL is one of the most promising AKI biomarkers in cardiac surgery. However, the best timing to dose it and the reference values are still matter of discussion. Aim of the Study: We performed a uNGAL perioperative time course, to better understand its perioperative kinetics and its role in AKI diagnosis. Setting of the Study: San Raffaele University Hospital, cardiac surgery department. Material and Methods: We enrolled in this prospective observational study 19 patients undergoing cardiac surgery with cardiopulmonary bypass (CPB. Based on preoperative characteristics, they were divided in low-risk and high-risk patients. uNGAL measurements were collected at pre-defined times before, during, and up to 24 hours after surgery. Statistical Analysis: Data were analysed by use of SAS 1999-2001 program or IBM SPSS Statistics. Results: In low-risk patients, uNGAL had the highest value immediately after general anesthesia induction (basal dosage: uNGAL: 12.20ng×ml -1 , IQR 14.00. It later decreased significantly (3.40 ng×ml -1 , IQR 4.80; P = 0.006 during CPB, and finally return to its original value 24 hours after surgery. In high-risk patients, uNGAL increased immediately after surgery; it had the highest value on ICU arrival (38,20 ng×ml -1 ; IQR 133,10 and remained high for several hours. A difference in uNGAL levels between the two groups was already observed at the end of surgery, but it became statistically significant on ICU arrival (P = 0.002. Conclusion: This study helps to better understand the different kinetics of this new biomarker in low-risk and high-risk cardiac patients.

  12. Urinary neutrophil gelatinase-associated lipocalin and acute kidney injury after cardiac surgery

    DEFF Research Database (Denmark)

    Wagener, G.; Gubitosa, G.; Wang, S.

    2008-01-01

    adult cardiac surgery. STUDY DESIGN: Diagnostic test accuracy. SETTING & PARTICIPANTS: Adult cardiac surgical patients (n = 426) in a single center from 2004 to 2006. INDEX TEST: Urinary NGAL immediately and 3, 18, and 24 hours after cardiac surgery, using an enzyme-linked immunosorbent assay. REFERENCE...... TEST OR OUTCOME: Serum creatinine-based definition for AKI (increase in serum creatinine from preoperative values by >50% or >0.3 mg/dL within 48 hours). RESULTS: Mean urinary NGAL level was 165 +/- 663 (SD) ng/mL preoperatively, peaked immediately after cardiac surgery at 1,490 +/- 102 ng...... to predict AKI defined by change in serum creatinine after cardiac surgery Udgivelsesdato: 2008/9...

  13. Neutrophil gelatinase-associated lipocalin and cystatin C in cirrhosis and portal hypertension

    DEFF Research Database (Denmark)

    Hurry, Preete Kapisha; Poulsen, Jørgen Hjelm; Bendtsen, Flemming

    2017-01-01

    and kinetics are sparsely studied in cirrhosis. In patients with cirrhosis and portal hypertension, we studied plasma levels and renal, hepatic, and peripheral extraction of NGAL and cystatin C and relations to patients characteristics, liver dysfunction, and hemodynamics. METHODS: Forty-five cirrhotic...... have the potential of being both valuable in diagnosing renal failure and reflecting the degree of portal hypertension and systemic haemodynamic changes....

  14. General anesthesia type does not influence serum levels of neutrophil gelatinase-associated lipocalin during the perioperative period in video laparoscopic bariatric surgery.

    Science.gov (United States)

    Fernandes, Adriano; Ettinger, João; Amaral, Fabiano; Ramalho, Maria José; Alves, Rodrigo; Módolo, Norma Sueli Pinheiro

    2014-12-01

    Video laparoscopic bariatric surgery is the preferred surgical technique for treating morbid obesity. However, pneumoperitoneum can pose risks to the kidneys by causing a decrease in renal blood flow. Furthermore, as in other surgical procedures, laparoscopic bariatric surgery triggers an acute inflammatory response. Neutrophil gelatinase-associated lipocalin is an early and accurate biomarker of renal injury, as well as of the inflammatory response. Anesthetic drugs could offer some protection for the kidneys and could attenuate the acute inflammatory response from surgical trauma. The objective of this study was to compare the effects of two types of anesthetics, propofol and sevoflurane, on the serum levels of neutrophil gelatinase-associated lipocalin during the perioperative period in laparoscopic bariatric surgery. Sixty-four patients scheduled for laparoscopic bariatric surgery were randomized into two anesthesia groups and were administered either total intravenous anesthesia (propofol) or inhalation anesthesia (sevoflurane). In the perioperative period, blood samples were collected at three time points (before anesthesia, 6 hours after pneumoperitoneum and 24 hours after pneumoperitoneum) and urine output was measured for 24 hours. Acute kidney injuries were evaluated by examining both the clinical and laboratory parameters during the postoperative period. The differences between the groups were compared using non-parametric tests. ReBEC (http://www.ensaiosclinicos.gov.br/rg/recruiting/): RBR-8wt2fy None of the patients developed an acute kidney injury during the study and no significant differences were found between the serum neutrophil gelatinase-associated lipocalin levels of the groups during the perioperative period. The choice of anesthetic drug, either propofol or sevoflurane, did not affect the serum levels of neutrophil gelatinase-associated lipocalin during the perioperative period in laparoscopic bariatric surgery.

  15. The role of neutrophil gelatinase associated lipocalin (NGAL) as biological constituent linking depression and cardiovascular disease

    NARCIS (Netherlands)

    Gouweleeuw, Leonie; Naudé, Petrus; Rots, Marianne; de Jongste, Michel; Eisel, Ulrich; Schoemaker, Regina

    2015-01-01

    Depression is more common in patients with cardiovascular disease than in the general population. Conversely, depression is a risk factor for developing cardiovascular disease. Comorbidity of these two pathologies worsens prognosis. Several mechanisms have been indicated in the link between cardiova

  16. Cardiac, renal, and neurological benefits of preoperative levosimendan administration in patients with right ventricular dysfunction and pulmonary hypertension undergoing cardiac surgery: evaluation with two biomarkers neutrophil gelatinase-associated lipocalin and neuronal enolase

    Science.gov (United States)

    Guerrero-Orriach, José Luis; Ariza-Villanueva, Daniel; Florez-Vela, Ana; Garrido-Sánchez, Lourdes; Moreno-Cortés, María Isabel; Galán-Ortega, Manuel; Ramírez-Fernández, Alicia; Alcaide Torres, Juan; Fernandez, Concepción Santiago; Navarro Arce, Isabel; Melero-Tejedor, José María; Rubio-Navarro, Manuel; Cruz-Mañas, José

    2016-01-01

    Purpose To evaluate if the preoperative administration of levosimendan in patients with right ventricular (RV) dysfunction, pulmonary hypertension, and high perioperative risk would improve cardiac function and would also have a protective effect on renal and neurological functions, assessed using two biomarkers neutrophil gelatinase-associated lipocalin (N-GAL) and neuronal enolase. Methods This is an observational study. Twenty-seven high-risk cardiac patients with RV dysfunction and pulmonary hypertension, scheduled for cardiac valve surgery, were prospectively followed after preoperative administration of levosimendan. Levosimendan was administered preoperatively on the day before surgery. All patients were considered high risk of cardiac and perioperative renal complications. Cardiac function was assessed by echocardiography, renal function by urinary N-GAL levels, and the acute kidney injury scale. Neuronal damage was assessed by neuron-specific enolase levels. Results After surgery, no significant variations were found in mean and SE levels of N-GAL (14.31 [28.34] ng/mL vs 13.41 [38.24] ng/mL), neuron-specific enolase (5.40 [0.41] ng/mL vs 4.32 [0.61] ng/mL), or mean ± SD creatinine (1.06±0.24 mg/dL vs 1.25±0.37 mg/dL at 48 hours). RV dilatation decreased from 4.23±0.7 mm to 3.45±0.6 mm and pulmonary artery pressure from 58±18 mmHg to 42±19 mmHg at 48 hours. Conclusion Preoperative administration of levosimendan has shown a protective role against cardiac, renal, and neurological damage in patients with a high risk of multiple organ dysfunctions undergoing cardiac surgery. PMID:27143905

  17. Plasma Neutrophil Gelatinase-Associated Lipocalin Reflects Both Inflammation and Kidney Function in Patients with Myocardial Infarction

    DEFF Research Database (Denmark)

    Lindberg, Søren; Jensen, Jan S; Hoffmann, Søren;

    2016-01-01

    cohorts. RESULTS: Estimated glomerular filtration rate (eGFR) was associated significantly more strongly with plasma NGAL when eGFR was abnormal compared to normal eGFR: a decrease in eGFR of 10 ml/min was associated with an increase in NGAL of 27% (18-36%) versus 4% (1-7%), respectively (p ....001). Leukocyte count and C-reactive protein were the main determinants of plasma NGAL in patients with normal eGFR, whereas eGFR was the main determinant at reduced kidney function. CONCLUSIONS: eGFR determines the association of NGAL with either inflammation or kidney function; in patients with normal eGFR......, plasma NGAL reflects inflammation but when eGFR is reduced, plasma NGAL reflects kidney function, highlighting the dual perception of plasma NGAL. From a clinical perspective, eGFR may be used to guide the interpretation of elevated NGAL levels in patients with STEMI....

  18. 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.

  19. Analyis of changes in the serum concentration of cystatin c, creatinine and renal neutrophil gelatinase-associated lipocalin in patients with hemorrhagic fever with renal syndrome

    Directory of Open Access Journals (Sweden)

    E. M. Mingazova

    2015-01-01

    Full Text Available Introduction. Acute kidney injury is a frequent complication of hemorrhagic fever with renal syndrome. The objective evaluation of аcute kidney injury severity degree is significant in determining the amount of medical actions at hemorrhagic fever with renal syndrome.Objective. Тhe shifts of acute kidney injury biomarkers’ levels (urine neutrophil gelatinase-associated lipocalin, serum cystatin C and serum creatinine at different periods of hemorrhagic fever with renal syndrome were evaluated.Methods. Depending to hemorrhagic fever with renal syndrome severity the patients were divided into groups with severe (n=16 and moderate form of hemorrhagic fever with renal syndrome (n=10; the control group included 10 healthy individuals. The levels of biomarkers were measured by ELISA.Results. Тhe serum concentration of creatinine and cystatin C – markers of glomerular pathology – increased significantly in hemorrhagic fever with renal syndrome, peaking at oligouric period; while changes of cystatin C were more rapid. Urine neutrophil gelatinase-associated lipocalin level – marker of renal tubular damage – increased 30 to 96 times compared to the control group in fever period of hemorrhagic fever with renal syndrome and gradually decreased thereafter.Conclusion. Тhe use of modern biochemical markers of renal pathology (sCystatin C, urine neutrophil gelatinaseassociated lipocalin in hemorrhagic fever with renal syndrome, along with traditional indicators, allows a more differentiated approach to the assessment of renal pathology and gives additional evidence to highlight stage and severity of the disease.

  20. 儿童血清中性粒细胞明胶酶相关脂质运载蛋白与维生素A代谢指标相关性研究%Relationship between serum neutrophil gelatinase-associated lipocalin and vitamin A metabolic index in preschool children

    Institute of Scientific and Technical Information of China (English)

    陈科; 章岚; 程昕然; 罗红裔; 高宁; 王劲; 傅桂英; 毛萌

    2012-01-01

    [Objective] To explore the correlation of neutrophil gelatinase-associated lipocalin (NGAL) and vitamin A metabolic index,including serum retinol,serum retinol binding protein (RBP) ,serum transthyretin (TTR) and the molar ratio of RBP to TTR[R-T index,RBP(mol/L)/TTR(mol/L)]. [Methods] About 473 preschool children with 2~7 years old were randomly selected from eight kindergartens,including 223 boys and 250 girls with (47. 8 ± 14. 5) months. Serum retinol was measured by HPLC method,NGAL and RBP by ELISA and TTR by immunoturbidimetric method. [Results] There were significant negative correlations between NGAL and retinol and R-T index(The partial correlation coefficients were - 0. 21 and - 0. 25 ;P aLL0. 05). The serum retinol and R-T index levels in children with Q1 RBP value group (cut by RBP 4 quartile level) was significantly higher than those of children with Q4 RBP value group (P0. 05). [Conclusion] There is close relation between serum NGAL and vitamin A status in preschool children and vitamin A may be able to inhibit the expression of NGAL which against the inhibition of NGAL on hematopoietic system.%[目的]初步分析中性粒细胞明胶酶相关脂质运载蛋白(neutrophil gelatinase-associated lipocalin,NGAL)水平与维生素A代谢指标血清视黄醇、视黄醇结合蛋白(retinol-binding protein,RBP)、甲状腺素运载蛋白(transthyretin,TTR)的关系. [方法]随机抽取研究现场8所幼儿园473名2~7岁(不足7岁)学龄前儿童纳入.分别利用HPLC法测血清视黄醇;采用ELISA法测NGAL与RBP,采用免疫比浊法测TTR,并计算R-T指数[RBP (mol/L)/TTR(mol/L)]. [结果]血清NGAL与血清视黄醇和R-T指数存在明显负相关关系(偏相关系数r分别为-0.21和-0.25;P均<0.000 1).维生素A正常组儿童NGAL水平显著低于维生素A不正常组儿童(P<0.05).以指标中位数为界,低R-T指数组儿童血清NGAL水平明显高于高R-T组儿童(P<0.05),但是高与低RBP组儿童之间

  1. Sex-specific associations between Neutrophil Gelatinase-Associated Lipocalin (NGAL) and cognitive domains in late-life depression

    NARCIS (Netherlands)

    Naude, P.J.; Boer, J.A. den; Comijs, H.C.; Bosker, F.J.; Zuidersma, M.; Groenewold, N.A.; Deyn, P.P. de; Luiten, P.G.M.; Eisel, U.L.; Oude Voshaar, R.C.

    2014-01-01

    BACKGROUND: Although it is well established that late-life depression is associated with both systemic low-graded inflammation and cognitive impairment, the relation between inflammation and cognition in depressed older persons is still equivocal. The objective of this study is to examine the associ

  2. Cardiac, renal, and neurological benefits of preoperative levosimendan administration in patients with right ventricular dysfunction and pulmonary hypertension undergoing cardiac surgery: evaluation with two biomarkers neutrophil gelatinase-associated lipocalin and neuronal enolase

    Directory of Open Access Journals (Sweden)

    Guerrero-Orriach JL

    2016-04-01

    Full Text Available José Luis Guerrero-Orriach,1 Daniel Ariza-Villanueva,1 Ana Florez-Vela,1 Lourdes Garrido-Sánchez,2,3 María Isabel Moreno-Cortés,1 Manuel Galán-Ortega,1 Alicia Ramírez-Fernández,1 Juan Alcaide Torres,3 Concepción Santiago Fernandez,3 Isabel Navarro Arce,1 José María Melero-Tejedor,4 Manuel Rubio-Navarro,1 José Cruz-Mañas1 1Department of Cardio-Anaesthesiology, University Hospital Virgen de la Victoria, Málaga, Spain; 2CIBER Fisiología de la Obesidad y Nutrición (CIBEROBN, Instituto de Salud Carlos III, Málaga, Spain; 3Department of Nutrition and Endocrinology, Instituto de Investigaciones Biomédicas de Málaga (IBIMA, University Hospital Virgen de la Victoria, Málaga, Spain; 4Department of Cardiovascular Surgery, University Hospital Virgen de la Victoria, Málaga, Spain Purpose: To evaluate if the preoperative administration of levosimendan in patients with right ventricular (RV dysfunction, pulmonary hypertension, and high perioperative risk would improve cardiac function and would also have a protective effect on renal and neurological functions, assessed using two biomarkers neutrophil gelatinase-associated lipocalin (N-GAL and neuronal enolase. Methods: This is an observational study. Twenty-seven high-risk cardiac patients with RV dysfunction and pulmonary hypertension, scheduled for cardiac valve surgery, were prospectively followed after preoperative administration of levosimendan. Levosimendan was administered preoperatively on the day before surgery. All patients were considered high risk of cardiac and perioperative renal complications. Cardiac function was assessed by echocardiography, renal function by urinary N-GAL levels, and the acute kidney injury scale. Neuronal damage was assessed by neuron-specific enolase levels. Results: After surgery, no significant variations were found in mean and SE levels of N-GAL (14.31 [28.34] ng/mL vs 13.41 [38.24] ng/mL, neuron-specific enolase (5.40 [0.41] ng/mL vs 4.32 [0.61] ng

  3. Accuracy of plasma and urine neutrophil gelatinase-associated lipocalin concentrations in predicting postoperative delirium in elderly patients%血浆和尿NGAL浓度预测老年患者术后谵妄的准确性

    Institute of Scientific and Technical Information of China (English)

    郝学超; 闵苏; 彭丽桦; 任力; 魏珂

    2016-01-01

    Objective To evaluate the accuracy of plasma and urine neutrophil gelatinase-associated lipocalin (NGAL) concentrations in predicting postoperative delirium in elderly patients.Methods From November 2014 to March 2015,70 patients of either sex who underwent total unilateral hip or knee replacement,aged 65-85 yr,with body mass index of 18-25 kg/m2,of American Society of Anesthesiologists physical status Ⅱ or Ⅲ,were selected.The Confusion Assessment Method for the Intensive Care Unit was used to assess the development of postoperative delirium at 24,48 and 72 h after operation.The patients were divided into either delirium group or non-delirium group according to whether or not postoperative delirium occurred.At 5 min before anesthesia induction,immediately after extubation,and at 24 and 72 h after operation,the midstream urine samples and peripheral venous blood samples were collected for determination of the urine and plasma NGAL concentrations by immuno-enhanced turbidimetry.At 5 min before anesthesia induction,and 24 and 48 h after operation,the serum creatinine and cystatin C concentrations were detected,and the development of postoperative acute kidney injury was recorded.The receiver operating characteristic curve for urine and plasma NGAL concentrations in diagnosing postoperative delirium was plotted,and the area under the curve and 95% confidence interval were calculated.The critical value and sensitivity and specificity were calculated according to the corresponding concentrations of NGAL in urine and plasma when Youden index reached the maximal value.Results The incidence of postoperative delirium was 15%.Compared with non-delirium group,the plasma NGAL concentrations were significantly increased immediately after extubation,and the urine NGAL concentrations were significantly increased immediately after extubation and at 24 h after operation in delirium group (P<0.01).There was no significant difference in the serum creatinine and cystatin C

  4. Relationship between serum neutrophil gelatinase-associated lipocalin and iron metabolic index in preschool children%学龄前儿童血清中性粒细胞明胶酶相关脂质运载蛋白与铁代谢指标相关性及其意义

    Institute of Scientific and Technical Information of China (English)

    陈科; 程昕然; 章岚; 罗红裔; 高宁; 王劲; 傅桂英; 毛萌

    2012-01-01

    [目的]初步分析中性粒细胞明胶酶相关脂质运载蛋白(neutrophil gelatinase associated lipocalin,NGAL)水平对铁代谢指标血红蛋白(hemoglobin,HB)、铁蛋白(serum ferritin,SF)、血清转铁蛋白受体(serum transferrin receptor,sTfR)、转铁蛋白/铁蛋白指数(transferritin receptor-ferritin index,TFR-F)以及机体铁含量(body iron content,BIC)的关系. [方法]随机抽取473名3~6岁(不足7岁)学龄前儿童纳入本研究,利用氰化高铁血红蛋白法测定HB、ELISA 法测定血清NGAL、SF及sTfR,并根据相关公式计算TRFI和BIC指数. [结果]血清NGAL与sTfR、TFR F和BIC均呈显著相关关系(偏相关系数r=0.23、0.24、-0.15,P<0.01或<0.05).贫血儿童血清NGAL水平显著低于非贫血儿童[(152.8±33.4)vs(220.7士25.4)pg/mL] (P<0.05);以指标中位数为界,低sTfR组儿童血清NGAL水平明显低于高sTfR组[(181.05±41.1)vs(257.6±47.8)pg/mL](P<0.05),低BIC组儿童血清NGAL水平明显高于高BIC组[(269.1±49.4)vs(181.3±30.8) pg/mL] (P<0.05).低NGAL组儿童血清sTfR水平及TFR-F指数显著低于高NGAL组(P<0.05),而HB、SF以及BIC组间差异无统计学意义(P>0.05). [结论] NGAL可能主要通过阻止红系统增殖参与调节儿童铁代谢稳态,而与机体铁储备过程无关.%[Objective] To explore the correlation of neutrophil gelatinase-associated lipocalin (NGAL) and iron metabolic index,including hemoglobin (HB),serum ferritin (SF), serum transferrin receptor (sTfR) , transferritin receptor-fer-ritin index (TFR-F) and body iron content (B1C). [Methods] About 473 preschool children with 2~7 years old were randomly selected from eight kindergartens,including 223 boys and 250 girls with (47. 8 ± 14. 5) months. HB was measured by HiCN method,NGAL,SF and sTfR by ELISA. TFR-F index and BIC were calculated according to the relevant index formula. [Result] There were significant correlation between NGAL and sTfR,TFR-F and BIC (the partial correlation

  5. Clinical significance of levels of serum osteopontin and neutrophil gelatinase -associated lipocalin in patients with polycystic ovary syndrome%血清骨桥蛋白及中性粒细胞明胶酶相关脂质运载蛋白水平在多囊卵巢综合征中的临床意义

    Institute of Scientific and Technical Information of China (English)

    莫轶晖; 张进; 杨丽丽

    2015-01-01

    目的:探讨多囊卵巢综合征(PCOS)患者血清骨桥蛋白(OPN)与中性粒细胞明胶酶相关脂质运载蛋白(NGAL)的水平及其临床意义。方法:62例 PCOS 患者及同期健康体检的30例正常对照者分别采用酶联免疫法(ELISA)检测血清 OPN 和 NGAL 的水平,同时根据体重指数(BMI)将 PCOS 患者分为肥胖组32例(BMI≥25kg/m2)和非肥胖组30例(BMI <25kg/m2)。结果:与正常对照组相比较,所有 PCOS 患者血清中 OPN 和 NGAL 含量均显著偏高;肥胖 PCOS 患者血清中的 OPN 和 NGAL 水平也均明显高于非肥胖 P-COS 患者,差异具有统计学意义(P <0.05)。此外,Pearson 相关分析结果显示血清 OPN 及 NGAL 均与 BMI、胰岛素抵抗指数(HOMA -IR)呈正相关性,与胰岛素敏感指数(ISI)呈负相关性,差异具有统计学意义(P <0.05)。结论:多囊卵巢综合征患者血清中 OPN 和 NGAL 水平均处于升高状态,提示 PCOS 患者机体处于一种慢性炎性状态,未来可将减缓机体炎性状态作为治疗 PCOS 患者的策略之一。%Objectives:To investigate clinical significance of levels of serum osteopontin and neutrophil ge-latinase -associated lipocalin in patients with polycystic ovary syndrome.Methods:The levels of serum levels of OPN and NGAL of 62 PCOS patients and 30 healthy people as normal control were detected by using enzyme -linked immunoassay (ELISA).According to body mass index (BMI),patients with PCOS were divided into two groups:32 cases in obese group (BMI≥25kg/m)2 and 30 cases in non -obese group (BMI <25kg/m2 ).Results:Compared with normal control group,OPN and NGAL content in all PCOS patients were significantly higher.And OPN and NGAL levels of PCOS patients with obese were significantly higher than these of non -obese PCOS patients (P <0.05).In addition,Pearson correlation analysis results showed that there was a positive correlation between the

  6. Lipocalin 2 regulation by thermal stresses: Protective role of Lcn2/NGAL against cold and heat stresses

    Energy Technology Data Exchange (ETDEWEB)

    Roudkenar, Mehryar Habibi, E-mail: roudkenar@ibto.ir [Research Center, Iranian Blood Transfusion Organization, Tehran (Iran, Islamic Republic of); Halabian, Raheleh [Research Center, Iranian Blood Transfusion Organization, Tehran (Iran, Islamic Republic of); Roushandeh, Amaneh Mohammadi [Department of Anatomy, Faculty of Medicine, Medical University of Tabriz, Tabriz (Iran, Islamic Republic of); Nourani, Mohammad Reza [Chemical Injury Research Center, Baqiyatallah Medical Science University, Tehran (Iran, Islamic Republic of); Masroori, Nasser [Research Center, Iranian Blood Transfusion Organization, Tehran (Iran, Islamic Republic of); Ebrahimi, Majid [Research Center, Iranian Blood Transfusion Organization, Tehran (Iran, Islamic Republic of); Chemical Injury Research Center, Baqiyatallah Medical Science University, Tehran (Iran, Islamic Republic of); Nikogoftar, Mahin; Rouhbakhsh, Mehdi; Bahmani, Parisa [Research Center, Iranian Blood Transfusion Organization, Tehran (Iran, Islamic Republic of); Najafabadi, Ali Jahanian [Department of Molecular Biology, Pasteur Institute of Iran, Tehran (Iran, Islamic Republic of); Shokrgozar, Mohammad Ali [National Cell Bank of Iran, Pasteur institute of Iran, Tehran (Iran, Islamic Republic of)

    2009-11-01

    Environmental temperature variations are the most common stresses experienced by a wide range of organisms. Lipocalin 2 (Lcn2/NGAL) is expressed in various normal and pathologic conditions. However, its precise functions have not been fully determined. Here we report the induction of Lcn2 by thermal stresses in vivo, and its role following exposure to cold and heat stresses in vitro. Induction of Lcn2 in liver, heart and kidney was detected by RT-PCR, Western blot and immunohistochemistry following exposure of mice to heat and cold stresses. When CHO and HEK293T cells overexpressing NGAL were exposed to cold stress, cell proliferation was higher compared to controls. Down-regulatrion of NGAL by siRNA in A549 cells resulted in less proliferation when exposed to cold stress compared to control cells. The number of apoptotic cells and expression of pro-apoptotic proteins were lower in the NGAL overexpressing CHO and HEK293T cells, but were higher in the siRNA-transfected A549 cells compared to controls, indicating that NGAL protects cells against cold stress. Following exposure of the cells to heat stress, ectopic expression of NGAL protected cells while addition of exogenous recombinant NGAL to the cell culture medium exacerbated the toxicity of heat stress specially when there was low or no endogenous expression of NGAL. It had a dual effect on apoptosis following heat stress. NGAL also increased the expression of HO-1. Lcn2/NGAL may have the potential to improve cell proliferation and preservation particularly to prevent cold ischemia injury of transplanted organs or for treatment of some cancers by hyperthermia.

  7. Urine/Plasma Neutrophil Gelatinase Associated Lipocalin Ratio Is a Sensitive and Specific Marker of Subclinical Acute Kidney Injury in Mice.

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    Tamás Kaucsár

    Full Text Available Detection of acute kidney injury (AKI is still a challenge if conventional markers of kidney function are within reference range. We studied the sensitivity and specificity of NGAL as an AKI marker at different degrees of renal ischemia.Male C57BL/6J mice were subjected to 10-, 20- or 30-min unilateral renal ischemia, to control operation or no operation, and AKI was evaluated 1 day later by histology, immunohistochemistry, BUN, creatinine, NGAL (plasma and urine and renal NGAL mRNA expression.A short (10-min ischemia did not alter BUN or kidney histology, but elevated plasma and urinary NGAL level and renal NGAL mRNA expression although to a much smaller extent than longer ischemia. Surprisingly, control operation elevated plasma NGAL and renal NGAL mRNA expression to a similar extent as 10-min ischemia. Further, the ratio of urine to plasma NGAL was the best parameter to differentiate a 10-min ischemic injury from control operation, while it was similar in the non and control-operated groups.These results suggest that urinary NGAL excretion and especially ratio of urine to plasma NGAL are sensitive and specific markers of subclinical acute kidney injury in mice.

  8. NGAL (Lcn2) monomer is associated with tubulointerstitial damage in chronic kidney disease.

    Science.gov (United States)

    Nickolas, Thomas L; Forster, Catherine S; Sise, Meghan E; Barasch, Nicholas; Solá-Del Valle, David; Viltard, Melanie; Buchen, Charles; Kupferman, Shlomo; Carnevali, Maria Luisa; Bennett, Michael; Mattei, Silvia; Bovino, Achiropita; Argentiero, Lucia; Magnano, Andrea; Devarajan, Prasad; Mori, Kiyoshi; Erdjument-Bromage, Hediye; Tempst, Paul; Allegri, Landino; Barasch, Jonathan

    2012-09-01

    The type and the extent of tissue damage inform the prognosis of chronic kidney disease (CKD), but kidney biopsy is not a routine test. Urinary tests that correlate with specific histological findings might serve as surrogates for the kidney biopsy. We used immunoblots and ARCHITECT-NGAL assays to define the immunoreactivity of urinary neutrophil gelatinase-associated lipocalin (NGAL) in CKD, and we used mass spectroscopy to identify associated proteins. We analyzed kidney biopsies to determine whether specific pathological characteristics associated with the monomeric NGAL species. Advanced CKD urine contained the NGAL monomer as well as novel complexes of NGAL. When these species were separated, we found a significant correlation between the NGAL monomer and glomerular filtration rate (r=-0.53, Phistology that typifies progressive, severe CKD.

  9. No Effect of NGAL/lipocalin-2 on Aggressiveness of Cancer in the MMTV-PyMT/FVB/N Mouse Model for Breast Cancer

    DEFF Research Database (Denmark)

    Cramer, Elisabeth P; Glenthøj, Andreas; Häger, Mattias;

    2012-01-01

    NGAL/lipocalin-2 is a siderophore-binding protein that is highly expressed in several cancers. It is suggested to confer a proliferative advantage to cancer cells. Its expression has been correlated with aggressiveness of breast cancer as determined both in patients and in mouse breast cancer...... tumor volume, or to the number of metastases. Histology and gelatinolytic activity of the mammary tumors did not differ between wild-type and lipocalin-2-deficient mice. We conclude that NGAL/lipocalin-2 does not invariably affect the aggressiveness of breast cancers as assessed in mouse models, thus...

  10. The endocytic receptor megalin binds the iron transporting neutrophil-gelatinase-associated lipocalin with high affinity and mediates its cellular uptake

    DEFF Research Database (Denmark)

    Hvidberg, Vibeke; Jacobsen, Christian; Strong, Roland K

    2005-01-01

    in delivering iron to cells during formation of the tubular epithelial cells of the primordial kidney. No cellular receptor for NGAL has been described. We show here that megalin, a member of the low-density lipoprotein receptor family expressed in polarized epithelia, binds NGAL with high affinity, as shown...

  11. Expression and function of the lipocalin-2 (24p3/NGAL receptor in rodent and human intestinal epithelia.

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    Christian Langelueddecke

    Full Text Available The lipocalin 2//NGAL/24p3 receptor (NGAL-R/24p3-R is expressed in rodent distal nephron where it mediates protein endocytosis. The mechanisms of apical endocytosis and transcytosis of proteins and peptides in the intestine are poorly understood. In the present study, the expression and localization of rodent 24p3-R (r24p3-R and human NGAL-R (hNGAL-R was investigated in intestinal segments by immunofluorescence and confocal laser scanning microscopy, immunohistochemistry and immunoblotting. r24p3-R/hNGAL-R was also studied in human Caco-2 BBE cells and CHO cells transiently transfected with r24p3-R by immunofluorescence microscopy, RT-PCR and immunoblotting of plasma membrane enriched vesicles (PM. To assay function, endocytosis/transcytosis of putative ligands phytochelatin (PC₃, metallothionein (MT and transferrin (Tf was assayed by measuring internalization of fluorescence-labelled ligands in Caco-2 BBE cells grown on plastic or as monolayers on Transwell inserts. The binding affinity of Alexa 488-PC₃ to colon-like Caco-2 BBE PM was quantified by microscale thermophoresis (MST. r24p3-R/hNGAL-R expression was detected apically in all intestinal segments but showed the highest expression in ileum and colon. Colon-like, but not duodenum-like, Caco-2 BBE cells expressed hNGAL-R on their surface. Colon-like Caco-2 BBE cells or r24p3-R transfected CHO cells internalized fluorescence-labelled PC₃ or MT with half-maximal saturation at submicromolar concentrations. Uptake of PC₃ and MT (0.7 µM by Caco-2 BBE cells was partially blocked by hNGAL (500 pM and an EC₅₀ of 18.6 ± 12.2 nM was determined for binding of Alexa 488-PC₃ to PM vesicles by MST. Transwell experiments showed rapid (0.5-2 h apical uptake and basolateral delivery of fluorescent PC₃/MT/Tf (0.7 µM. Apical uptake of ligands was significantly blocked by 500 pM hNGAL. hNGAL-R dependent uptake was more prominent with MT but transcytosis efficiency was reduced compared to

  12. Clinical research on plasma and urine neutrophil gelatinase-associated lipocalin of lupus nephritis%狼疮性肾炎患者检测血、尿中性粒细胞明胶酶相关脂质运载蛋白的临床研究

    Institute of Scientific and Technical Information of China (English)

    谢伟基; 张夏兰; 张丽玲; 洪楷; 肖再雄; 陈东晓; 耿义群

    2010-01-01

    目的 测定狼疮性肾炎(LN)患者和健康成年人的血、尿中性粒细胞明胶酶相关脂质运载蛋白(NGAL)并分析其临床意义.方法 选取符合1997年美国风湿病学会修订的系统性红斑狼疮的诊断标准,同时合并有不同程度肾损害而确诊合并LN患者35例作为研究组,选取年龄、性别相匹配的健康成年人30例作为对照组,采用酶联免疫吸附技术(ELISA)分别测定血、尿NGAL的水平.另依据SLEDAI-2K的肾病活动指数将研究组患者分为肾病活动组(25例)与非肾病活动组(10例),并比较血、尿NGAL水平.结果 研究组患者尿NGAL水平为(78.94±81.97)μg/L,明显高于对照组的(28.50±18.08)μg/L,差异有统计学意义(P=0.002).肾病活动组尿NGAL水平为(92.90±94.88)μg/L,明显高于非肾病活动组的(48.20±24.77)μg/L,差异有统计学意义(P=0.049),两组血NGAL水平比较差异无统计学意义(P>0.05).结论 LN患者尿NGAL可作为肾病活动性的指标,其升高原因可能与肾小管病变有关.%Objective To study the clinical significance ofneutrophil gelatinase-associated lipocalin (NGAL), which in serial plasma and urine samples was measured in participants with lupus nephritis (LN)and healthy persons. Methods NGAL in serial plasma and urine samples was measured by enzyme-linked immunosorbent assay (EL.ISA) in 35 patients with LN by 1997 ACR systemic lupus erythematosus (SLE)standard with varied degree of kidney damage and 30 healthy persons with matching sex and age in physical examination center. Disease activity was measured by the SLE disease activity index (SLEDAI-2K),and 35LN patients were classified in active group and (25 cases) non-active group (10 cases) according to the SLEDAI-2K. Results Urinary NGAL were significantly increased in LN patients [(78.94 ± 81.97) μg/L]compared with healthy persons[(28.50 ± 18.08) μ g/L] (P = 0.002). And urinary NGAL were significantly increased in active group [(92.90 ± 94.88)

  13. Accuracy of Neutrophil Gelatinase-Associated Lipocalin in Detecting Acute Kidney Injury after Urogenital Robotic Assisted Laparoscopic Surgery under General Anesthesia

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    Orsolya MIHÁLY

    2012-06-01

    Full Text Available The aim of this study was to demonstrate the accuracy of NGAL in detecting acute kidney injury (AKI after urogenital robotic surgery in general anesthesia. Methods: A prospective longitudinal observational study, which included patients scheduled for elective robotic surgery under general anesthesia. The serum and urine NGAL at induction, 6 hours and 12 hours were determined. Serum creatinine was measured preoperatively and daily 4 days postoperatively. AKI was defined as the absolute growth of serum creatinine by 0.3 mg/dl over baseline within 48 hours postoperatively. Results: 24 patients were enrolled in the study. AKI occurred in 38% of patients. Serum NGAL increased significantly at 6 hours and 12h, compared to baseline, with a higher increase in the group of patents without AKI. There were no significant results for urine NGAL. A link was observed between the values of serum NGAL, with associated significance p<0.0001. The correlations between urine NGAL were not significant. The predictive value of NGAL, analyzed by cross-tabulation, OR was 3 for baseline value and 5.33 for the values measured at 6 hours and 12 hours, but with no statistical significance. Conclusions: The modifications of the NGAL levels, measured at 6 hours and 12 hours from the induction of anesthesia, were significant with more importance at 6 hours and in patients without AKI. Serum NGAL had no predictive value for AKI, but the risk to develop AKI was 3 times higher for baseline determination and 5 times at 6 and 12 hours.

  14. A comparison of neutrophil gelatinase-associated lipocalin and immature to total neutrophil ratio for diagnosing early-onset neonatal sepsis

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    Rocky Wilar

    2016-07-01

    Conclusion Immature to total neutrophil (IT ratio has higher specificity compared to NGAL for early diagnosis of EONS. However, the difference in sensitivity between the two test is not statistically significant.

  15. Serum and urinary neutrophil gelatinase-associated lipocalin as a predictor of rat kidney histopathology in an early ischemia-reperfusion model

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    Sahala Panggabean

    2012-11-01

    Full Text Available Background: The severity of ischemia-reperfusion (I/R kidney injury is highly correlated with mortality and morbidity rate. Research on human and animal prove that NGAL predicts kidney injury at early phase. The objective of this study is to prove that the increase in serum and urinary NGAL are correlated with kidney tubular epithelial damage, and this increase has occurred in initiation phase, indicated by rat kidney histopathology in an early I/R model.Methods: Twenty eight male Sprague-Dawley rats were divided into 4 groups: 4 hour sham (Sham 4, 8 hour sham (Sham 8, 10 minute ischemia 4 hour reperfusion (I/R 4 and 10 minute ischemia 8 hour reperfusion (I/R 8. Blood, urine and kidney samples were collected. Serum creatinine level was analyzed with Jaffe method, while serum and urinary NGAL level were analyzed with direct sandwich ELISA method. Evaluation of kidney damage were measured semi quantitatively in tissue stained with HE. Further evaluation to confirm cellular changes on kidney was performed by electron microscope and immunohistochemistry.Results: Serum NGAL was found significantly correlated with degree of kidney tissue damage (ρSpearman NGAL serum = 0.701, p < 0.001, also urinary NGAL (ρSpearman = 0.689, p < 0.001. NGAL expression differs significantly between I/R group and sham (t-test, t = -26635.056, p < 0.001, also kidney damage (t-test, t = -5.028, p < 0.001, and serum and urinary NGAL levels (Mann-Whitney, U = 0, p < 0.001. With cutoff points of 136.95 ng/mL and 58.69 ng/mL subsequently for serum and urinary NGAL , it is found that sensitivity = 1, specificity = 1.Conclusion: Elevation of serum and urinary NGAL are significantly correlated with epithelial tubular kidney damage on rat undergoing early ischaemia reperfusion. (Med J Indones. 2012;21:208-13Keywords: Early I/R kidney injury, kidney histopathology, NGAL

  16. Pyoverdine, the Major Siderophore in Pseudomonas aeruginosa, Evades NGAL Recognition

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    Mary E. Peek

    2012-01-01

    Full Text Available Pseudomonas aeruginosa is the most common pathogen that persists in the cystic fibrosis lungs. Bacteria such as P. aeruginosa secrete siderophores (iron-chelating molecules and the host limits bacterial growth by producing neutrophil-gelatinase-associated lipocalin (NGAL that specifically scavenges bacterial siderophores, therefore preventing bacteria from establishing infection. P. aeruginosa produces a major siderophore known as pyoverdine, found to be important for bacterial virulence and biofilm development. We report that pyoverdine did not bind to NGAL, as measured by tryptophan fluorescence quenching, while enterobactin bound to NGAL effectively causing a strong response. The experimental data indicate that pyoverdine evades NGAL recognition. We then employed a molecular modeling approach to simulate the binding of pyoverdine to human NGAL using NGAL’s published crystal structures. The docking of pyoverdine to NGAL predicted nine different docking positions; however, neither apo- nor ferric forms of pyoverdine docked into the ligand-binding site in the calyx of NGAL where siderophores are known to bind. The molecular modeling results offer structural support that pyoverdine does not bind to NGAL, confirming the results obtained in the tryptophan quenching assay. The data suggest that pyoverdine is a stealth siderophore that evades NGAL recognition allowing P. aeruginosa to establish chronic infections in CF lungs.

  17. The Usefulness of Determining Neutrophil Gelatinase-Associated Lipocalin Concentration Excreted in the Urine in the Evaluation of Cyclosporine A Nephrotoxicity in Children with Nephrotic Syndrome

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    Ewa Gacka

    2016-01-01

    Full Text Available Introduction. The use of cyclosporine (CsA in the treatment of nephrotic syndrome (NS contributed to a significant reduction in the amount of corticosteroids used in therapy and its cumulative side effects. One of the major drawbacks of CsA therapy is its nephrotoxicity. Prolonged CsA treatment protocols require sensitive, easily available, and simple to measure biomarkers of nephrotoxicity. NGAL is an antibacterial peptide, excreted by cells of renal tubules in response to their toxic or inflammatory damage. Aim of the Study. The aim of this study was to assess the suitability of the NGAL concentration in the urine as a potential biomarker of the CsA nephrotoxicity. Material and Methods. The study was performed on a group of 31 children with NS treated with CsA. The control group consisted of 23 children diagnosed with monosyptomatic enuresis. The relationship between NGAL excreted in urine and the time of CsA treatment, concentration of CsA in blood serum, and other biochemical parameters was assessed. Results. The study showed a statistically significant positive correlation between urine NGAL concentration and serum triglycerides concentration and no correlation between C0 CsA concentration and other observed parameters of NS. The duration of treatment had a statistically significant influence on the NGAL to creatinine ratio. Conclusions. NGAL cannot be used alone as a simple CsA nephrotoxicity marker during NS therapy. Statistically significant correlation between NGAL urine concentration and the time of CsA therapy indicates potential benefits of using this biomarker in the monitoring of nephrotoxicity in case of prolonged CsA therapy.

  18. Increased incidence of acute kidney injury with aprotinin use during cardiac surgery detected with urinary NGAL

    DEFF Research Database (Denmark)

    Wagener, G.; Gubitosa, G.; Wang, S.;

    2008-01-01

    BACKGROUND: Use of aprotinin has been associated with acute kidney injury after cardiac surgery. Neutrophil gelatinase-associated lipocalin (NGAL) is a novel, very sensitive marker for renal injury. Urinary NGAL may be able to detect renal injury caused by aprotinin. This study determined...... if the use of aprotinin is associated with an increased incidence of acute kidney injury and increased levels of urinary NGAL. METHODS: In this prospective, observational study 369 patients undergoing cardiac surgery were enrolled. 205 patients received aprotinin and 164 received epsilon amino-caproic acid...... intraoperatively. Urinary NGAL was measured before and immediately after cardiac surgery and 3, 18 and 24 h later. The association of aprotinin use with the incidence of acute kidney injury (increase of serum creatinine >0.5 mg/dl) and NGAL levels was determined using logistic and linear regression models. RESULTS...

  19. The role of neutrophil gelatinase-associated lipocalin in predicting acute kidney injury in patients undergoing off-pump coronary artery bypass graft: A pilot study

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    Vishal Jain

    2016-01-01

    Full Text Available Objective: Acute kidney injury (AKI is a commonly encountered postoperative complication after cardiac surgery especially in high risk patients. AKI though seen more commonly after conventional on pump coronary artery bypass surgery (CCABG, is not uncommon after off pump coronary bypass surgery (OPCAB. Various biomarkers have shown promise over last one decade as an early marker for predicting AKI postoperatively. NGAL is one such biomarker whose concentration is increased in urine after any nephrotoxic and ischemic insult. The objective of this study was to assess the role of urine NGAL in predicting AKI after OPCAB in patients with increased risk of developing AKI. Design: A prospective cohort study. Setting: A clinical study in a multi specialty hospital. Participants: Eighty patients. Materials and Methods: study was approved by the hospital research ethics committee. 80 patients posted for OPCAB with an increased risk of developing AKI defined as having a Cleveland Clinic Foundation Acute renal failure scoring System score of ≥6 were included in the study. Patients with coronary angiography (CAG within 48 hrs prior to surgery, pre-existing AKI, preoperative renal replacement therapy (RRT and CKD stage 5 were excluded. Urine NGAL level before the start of surgery baseline and at 4 hrs post surgery were done. Renal function tests were assessed on the day of surgery (4 hrs post surgery and on the next three days. Result: Seven patients developed AKI as defined by acute kidney infection network (AKIN and risk injury failure loss end stage (RIFLE criteria for AKI. NGAL value at 4 hrs in patients who developed AKI was significantly higher than in those patients who did not develop AKI (P < 0.05. Conclusion: urine NGAL is an early biomarker of acute kidney injury in patients undergoing OPCAB surgeries. However, large multicentre studies may be needed to confirm it.

  20. 中性粒细胞明胶酶相关载脂蛋白在非小细胞肺癌组织的表达%Expression of neutrophil gelatinase-associated lipocalin in non-small cell lung cancer tissues

    Institute of Scientific and Technical Information of China (English)

    李岩; 任淑华; 刘立新; 周海英; 李欣

    2016-01-01

    Objective To investigate the neutrophil gelatinase-associated lipocalin (NGAL) expression and clinical significance in non-small cell lung cancer (NSCLC) tissues.Methods The surgical treatment of non-small cell lung cancer patients resected tumor specimens of 130 cases of the experimental group,the distance of the cut edge of tumor more than 5cm much cancerous tissue as a control group,60 cases of adenocarcinoma,squamous cell carcinoma and 70 cases.By real-time fluorescent quantitative polymerase chain reaction (FQ-PCR) method to detect NGAL mRNA expression in NSCLC tissues;the protein was detected by immunohistochemistry NSCLC tissues NGAL,NGAL expression and analysis and clinical characteristics of patients with protein relationship.Results (1) Adenocarcinoma NGAL mRNA real-time fluorescence quantitative results and ACt difference of β-actin (-2.9 ± 1.4),and squamous cell carcinoma (-2.4 ± 1.1) compared to no significant difference (P > 0.05);Adjacent tissues (-1.5 ± 1.4) compared with adenocarcinoma and squamous cell carcinomas (P < 0.05).(2) Non-small cell lung cancer,squamous cell carcinoma NGAL protein positive rate 55.71% (39/70),adenocarcinoma positive rate was 78.33% (47/60),adjacent tissues was 31.53% (41/130),three positive expression rate difference was statistically significant (x2 =5.942,P < 0.05).(3) Non-small cell lung cancer NAGL protein expression and patient' s age,sex,smoking and lymph node metastasis was no significant correlation (P > 0.05).Conclusion NGAL in the non-small cell lung cancer was highly expressed,and the classification of non-small cell lung cancer-related,may be an early diagnosis of non-small cell lung cancer a marker.%目的 探讨中性粒细胞明胶酶相关载脂蛋白(NGAL)在非小细胞肺癌(NSCLC)组织中的表达及意义.方法 以130例NSCLC患者切除肿块标本作为实验组,肿块边缘5 cm以上的远癌组织作为对照组,其中腺癌60例,鳞癌70例.通过实时荧光定量聚合酶

  1. Predictive value of NGAL for use of renal replacement therapy in patients with severe sepsis

    DEFF Research Database (Denmark)

    Hjortrup, P B; Haase, N; Treschow, F;

    2015-01-01

    BACKGROUND: The predictive value of plasma and urine neutrophil gelatinase-associated lipocalin (NGAL) for use of renal replacement therapy (RRT) and acute kidney injury (AKI) is not established in patients with severe sepsis. METHODS: This was a prospective observational study in three general...... intensive care units (ICUs) in adult ICU patients with severe sepsis needing fluid resuscitation and a sub-study of the 6S trial. Plasma and urine were sampled at baseline and NGAL was measured using particle-enhanced turbidimetric immunoassay (The NGAL Test). Outcome measures were use of RRT in ICU......ROCs. CONCLUSION: In ICU patients with severe sepsis, plasma and urine NGAL had low predictive power for use of RRT, AKI and 90-day mortality. These results were supported by sensitivity and exploratory analyses....

  2. The expression and significance of matrix metalloproteinases and neutrophil gelatinase-associated lipocalin in serum and placental tissue of preeclampsia maternal%子痫前期患者血清基质金属蛋白酶-9、中性粒细胞明胶酶相关脂质运载蛋白水平及其在胎盘组织中的表达

    Institute of Scientific and Technical Information of China (English)

    王卉

    2013-01-01

    目的 探讨子痫前期患者血清基质金属蛋白酶-9(MMP-9)、中性粒细胞明胶酶相关脂质运载蛋白(NGAL)水平及其在胎盘组织中的表达变化.方法 74例子痫前期患者作为研究对象,其中重度39例、轻度35例;同时选取正常足月妊娠产妇30例作为对照组,应用酶联免疫吸附法测定三组血清MMP-9、NGAL水平,应用RT-PCR测定三组胎盘组织中MMP-9mRNA及NGALmRNA水平.结果 轻度子痫前期组、重度子痫前期组血清MMP-9、NGAL水平均明显高于对照组(t=3.127、2.846、3.508、3.284,均P<0.05),胎盘组织中MMP-9 mRNA、NGAL mRNA水平均明显低于对照组(t=-2.842、-2.728、-3.532、-3.276,均P<0.05);重度子痫前期患者血清MMP-9、NGAL水平显著高于轻度子痫前期患者(t=2.732、2.741,均P<0.05),重度子痫前期组胎盘组织中MMP-9 mRNA、NGAL mRNA水平明显低于轻度子痫前期组(t=-2.681、-2.587,均P<0.05);子痫前期血清MMP-9水平与NGAL水平呈正相关(r=0.606,P<0.05),胎盘组织中MMP-9 mRNA表达水平与NGAL mRNA表达水平呈正相关(r=0.532,P<0.05).结论 子痫前期患者血清MMP-9、NGAL水平显著升高,胎盘组织MMP-9 mRNA、NGAL mRNA水平显著下降,提示两者可能参与子痫的发病过程.%Objective To investigate expression and significance of matrix metalloproteinase-9 (MMP-9) and neutrophil gelatinase-associated lipocalin (NGAL) in serum and placental tissue of preeclampsia maternal.Methods 74 cases of preeclampsia pregnant women as research subjects,which 39 cases of severe preeclampsia,35 cases of mild preeclampsia,selected 30 cases of normal late maternal as the control group.Three groups of maternal serum levels of MMP-9 and of NGAL were detected by enzyme-linked immunosorbent assay.RT-PCR was used to test placenta MMP-9 mRNA,and NGAL mRNA level.Results Preeclampsia maternal serum levels of MMP-9 and NGAL level were significantly higher than those of severe preeclampsia pregnant women serum

  3. Expression and significance of neutrophil gelatinase-associated lipocalin in renal interstitial fibrosis in rats%NGAL在大鼠肾间质纤维化中的表达及其意义

    Institute of Scientific and Technical Information of China (English)

    张桦; 朱晔; 贾宁; 张慧涛; 郑晶; 朱伟平; 周文英; 林宇静; 王晓鸿

    2012-01-01

    目的 探讨中性粒细胞明胶酶相关脂质运载蛋白(NGAL)在肾间质纤维化(RIF)中的表达变化及其意义.方法 60只SD雄性大鼠随机分为假手术(SOR)组、单侧输尿管梗阻(UUO)组和血管紧张素转换酶抑制剂(ACEI)组.ELISA法检测血清NGAL、肿瘤坏死因子(TNF)-α含量,免疫组化法检测肾组织NGAL、转化生长因子(TGF)-β1、基质金属蛋白酶-9(MMP-9)的表达水平.结果 (1)UUO组大鼠血清NGAL、TNF-α水平均显著高于ACEI组和SOR组[NGAL:( 69.2±5.6) pg/ml比(41.0±10.4)pg/ml、( 10.8 ±3.8) pg/ml,TNF-α:( 116.2±9.2)ng/ml比(99.8±14.0) ng/ml、(29.2±5.7) ng/ml,均P<0.05],SOR组最低.(2)NGAL、TGF-β1、MMP-9在UUO组大鼠肾小管间质内表达明显增强;在ACEI组,TGF-β1表达量低于UUO组,而NGAL、MMP-9表达量在术后14 d内均少于UUO组,但在术后21和28 d其表达量高于UUO组.(3)相关关系:在UUO组,血清NGAL水平与TNF-α、血清肌酐呈显著正相关(r=0.910、0.673,P<0.01);肾脏NGAL表达量与MMP-9表达水平呈显著正相关(r =0.913,P<0.01),与肾小管间质损伤指数、TGF-β1表达阳性程度在术后3~7d呈显著正相关(r=0.937、0.847,P<0.01),在术后14 ~ 28 d呈显著负相关(r=-0.945、-0.944,P<0.01).结论 NGAL在UUO大鼠血清与肾组织中的表达显著增加,并与MMP-9、TNF-α、TGF-β1等因子密切相关,而ACEI可通过多种机制影响NGAL在RIF中的生物学作用.%Objective To explore the expression and significance of neutrophil gelatina(s)e-associated lipocalin(NGAL)in renal interstitial fibrosis (RIF) in rats.Methods A total of 60 male Sprague-Dawley rats were randomly divided into 3 groups of sham operation (SOR),unilateral ureteral obstruction (UUO)and angiotensin-converting enzyme inhibitor (ACEI).The serum concentrations of NGAL and tumor necrosis factor-alpha (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA).And the expressions of NGAL,matrix metalloproteinase-9 (MMP-9) and

  4. Correlation of neutrophil gelatinase - associated lipocalin with dialysis adequacy,microinflammation and iron metabolism in maintenance hemodialysis patients%维持性血液透析患者血清中性粒细胞明胶酶相关载脂蛋白水平与透析充分性、铁代谢及微炎性反应状态的相关性

    Institute of Scientific and Technical Information of China (English)

    李占园; 黄文; 郑育; 叶菡洋; 金领微; 叶白如; 周志宏

    2012-01-01

    目的 研究维持性血液透析(MHD)患者血清中性粒细胞明胶酶相关载脂蛋白(NGAL)水平与透析充分性、微炎性反应状态及铁代谢的关系;探讨NGAL对判断透析充分性的价值.方法 从2010年10月开始,纳入我院MHD患者150例为对象,同时以50例健康人为对照.收集MHD患者的人口学资料、临床表现及检测参试者血清NGAL、C反应蛋白( CRP)、转铁蛋白饱和度(TSAT)、铁蛋白等水平.根据单室尿素清除指数(spKt/V)值将MHD 患者分为透析充分组和不充分组,比较组间血清NGAL差异.用Pearson相关法、多元线性回归模型和受试者工作特征(ROC)曲线分析NAGL与Kt/V、炎性因子和铁代谢指标等相关性.患者随访3个月,对比两组随访前后NAGL、Kt/V及炎性因子变化,进一步评估血清NGAL与透析充分性、炎性指标的关系.结果 MHD患者血清NGAL为(445.45±50.34) μg/L,显著高于健康对照的(50.02±6.45) μg/L(P<0.01).150例MHD患者中,95例为充分组,55例为不充分组.充分组与不充分组NGAL分别为(589.14±56.34) μg/L和(360.13±46.23)μg/L,差异有统计学意义(P<0.05).MHD患者血清NGAL与spKt/V、CRP、TSAT呈正相关(r=0.652、0.825、0.785,均P<0.05).多元线性回归模型结果显示,NGAL与CRP、spKt/V、TSAT有相关关系.ROC曲线下面积(AUC)表明,NGAL水平能较好地反映透析充分性.随诊后结果显示,所有充分组患者均维持透析充分状态;经干预后,不充分组中38例达透析充分,另17例仍未达到透析充分.在这38例中,未达充分和达充分时的NGAL分别为(368.14±56.21) μg/L和( 360.56±46.23) μg/L,差异无统计学意义.CRP水平达充分后有所下降,但差异无统计学意义.结论 MHD透析充分患者血清NGAL显著高于不充分患者.MHD患者血清NGAL与spKt/V、CRP及TSAT均呈正相关.血清NGAL能较好地反映透析充分性.%Objective To examine the correlation of serum neutrophil gelatinase-associated

  5. Serum level of neutrophii gelatinase-associated lipocalin in preeclampsia with gestational diabetes mellitus%中性粒细胞明胶酶相关脂质运载蛋白与子痫前期及妊娠期糖尿病孕妇糖代谢和脂代谢指标的相关性

    Institute of Scientific and Technical Information of China (English)

    段冬梅; 牛建民; 朱斌; 林小红

    2012-01-01

    =0.427,P<0.01),systolic blood pressure (r=0.648,P<0.01),diastolic blood pressure (r=0.664,P<0.01),fasting blood glucose (r=0.320,P<0.01),fasting insulin level (r=0.381,P<0.01),HOMA-IR (r=0.399,P<0.01),triglyceride level (r=0.405,P<0.01),total cholesterol (r=0.145,P<0.05),free fatty acids (r=0.335,P<0.01),uric acid (r =0.292,P<0.01),creatinine (r =0.226,P < 0.01),and 24-hour urine protein content (r =0.436,P<0.01),and negatively correlated with high density lipoprotein-cholesterol (r=-0.189,P =0.008).Stepwise regression analysis showed that systolic blood pressure (β =0.251,P < 0.01),diastolic blood pressure (β=0.351,P<0.01),HOMA-IR (β=0.265,P<0.01) and 24-hour urine protein content (β=0.140,P=0.011) were independent factors of NGAL. Conclusions Serum NGAL levels increase significantly in patients with preeclampsia or GDM,and are correlated with parameters of glycolipid metabolism end endothelial dysfunction,which might play a role in the pathogenesis of preeclampsia and GDM.%目的 通过测定正常妊娠孕妇、子痫前期糖代谢正常患者、妊娠期糖尿病( gestational diabetes mellitus,GDM)患者及子痫前期合并GDM患者血清中性粒细胞明胶酶相关脂质运载蛋白(neutrophil gelatinase-associated lipocalin,NGAL)水平,探讨NGAL与子痫前期、GDM孕妇糖代谢和脂代谢的相关性. 方法 选取2009年12月至2010年11月在广州医学院附属广东省妇女儿童医院定期产前检查并分娩的单胎正常妊娠孕妇、子痫前期糖代谢正常患者及GDM患者各77例,子痫前期合并GDM患者32例.测定所有研究对象血清NGAL、空腹血精、空腹胰岛素、脂代谢参数、尿酸、肌酐、乳酸脱氢酶及24 h尿蛋白等指标,测量血压,计算体重指数(body mass index,BMI),用稳态模型评估法计算胰岛素抵抗指数(homeostasis model assessment for insulin resistance,HOMA-IR)评价胰岛索敏感性.正态分布资料用单因素方差分析及Student's t

  6. Does NGAL reduce costs? A cost analysis of urine NGAL (uNGAL) & serum creatinine (sCr) for acute kidney injury (AKI) diagnosis.

    Science.gov (United States)

    Parikh, Amay; Rizzo, John A; Canetta, Pietro; Forster, Catherine; Sise, Meghan; Maarouf, Omar; Singer, Eugenia; Elger, Antje; Elitok, Saban; Schmidt-Ott, Kai; Barasch, Jonathon; Nickolas, Thomas L

    2017-01-01

    Urine neutrophil gelatinase-associated lipocalin (uNGAL) is a sensitive and specific diagnostic test for acute kidney injury (AKI) in the Emergency Department (ED), but its economic impact has not been investigated. We hypothesized that uNGAL used in combination with serum creatinine (sCr) would reduce costs in the management of AKI in patients presenting to the ED in comparison to using sCr alone. A cost simulation model was developed for clinical algorithms to diagnose AKI based on sCr alone vs. uNGAL plus sCr (uNGAL+sCr). A cost minimization analysis was performed to determine total expected costs for patients with AKI. uNGAL test characteristics were validated with eight-hundred forty-nine patients with sCr ≥1.5 from a completed study of 1635 patients recruited from EDs at two U.S. hospitals from 2007-8. Biomarker test, AKI work-up, and diagnostic imaging costs were incorporated. For a hypothetical cohort of 10,000 patients, the model predicted that the expected costs were $900 per patient (pp) in the sCr arm and $950 in the uNGAL+sCr arm. uNGAL+sCr resulted in 1,578 fewer patients with delayed diagnosis and treatment than sCr alone (2,013 vs. 436 pts) at center 1 and 1,973 fewer patients with delayed diagnosis and treatment than sCr alone at center 2 (2,227 vs. 254 patients). Although initial evaluation costs at each center were $50 pp higher in with uNGAL+sCr, total costs declined by $408 pp at Center 1 and by $522 pp at Center 2 due to expected reduced delays in diagnosis and treatment. Sensitivity analyses confirmed savings with uNGAL + sCr for a range of cost inputs. Using uNGAL with sCr as a clinical diagnostic test for AKI may improve patient management and reduce expected costs. Any cost savings would likely result from avoiding delays in diagnosis and treatment and from avoidance of unnecessary testing in patients given a false positive AKI diagnosis by use of sCr alone.

  7. 中性粒细胞明胶酶相关脂质运载蛋白鉴别革兰阳性菌与革兰阴性菌感染的实验研究%Value of neutrophil gelatinase-associated lipocalin in differential diagnosis of gram-positive and gram-negative bacterial infections:an animal experimental study

    Institute of Scientific and Technical Information of China (English)

    谢尹晶; 段晋燕; 张洪瑞; 刘一凡; 吴小利; 唐红卫; 杨继勇; 罗燕萍; 王成彬

    2015-01-01

    目的:通过建立全身感染性疾病小鼠模型,探讨中性粒细胞明胶酶相关脂质运载蛋白(NGAL )在鉴别诊断革兰阳性菌感染和革兰阴性菌感染方面的价值。方法选择216只IC R小鼠,每组8只,通过尾静脉分别注射金黄色葡萄球菌和大肠埃希菌,建立革兰阳性菌和革兰阴性菌所致的小鼠全身感染模型,分别在感染后1、3、6、12 h及1、2、3、5、7 d处死各组小鼠,检测其血清NGAL浓度。结果金黄色葡萄球菌感染组的小鼠NGAL浓度在感染后3 h明显升高,为(926.84±245.76)ng/ml ,大肠埃希菌感染组的小鼠NGAL浓度在感染后1 h明显升高,为(554.34±47.63)ng/ml;ROC曲线分析显示,金黄色葡萄球菌感染组和大肠埃希菌感染组 NGAL 的ROC曲线下面积(AUC)分别为0.908、0.979,两者差异无统计学意义。结论 NGAL在感染早期即明显升高,但其变化在金黄色葡萄球菌和大肠埃希菌引发的小鼠感染模型之间并无差异。%OBJECTIVE To explore the value of neutrophil gelatinase‐associated lipocalin(NGAL) in differential di‐agnosis of gram‐positive and gram‐negative bacteria infections by establishing systemic infectious mouse model . METHODS Totally 216 ICR mice were grouped ,with 8 mice in each group;the Staphylococcus aureus and Esche‐richia coli were respectively injected through tail vein so as to establish the gram‐positive bacteria‐and gram‐nega‐tive bacteria‐induced mice systemic infection model .The mice in each group were killed at 1 ,3 ,6 ,and 12 hours as well as at 1 ,2 ,3 ,5 ,and 7 days of being infected ,and the concentrations of serum NGAL were determined . RESULTS The concentration of NGAL of the mice infected with S .aureus was significantly elevated at 3 hours af‐ter being infected ,which was (926 .84 ± 245 .76)ng/ml;the concentration of NGAL of the mice infected with E .coli was remarkably elevated at 1 hour

  8. Hypertension and hyperglycemia synergize to cause incipient renal tubular alterations resulting in increased NGAL urinary excretion in rats.

    Directory of Open Access Journals (Sweden)

    Ana M Blázquez-Medela

    Full Text Available Hypertension and diabetes are the two leading causes of chronic kidney disease (CKD eventually leading to end stage renal disease (ESRD and the need of renal replacement therapy. Mortality among CKD and ESRD patients is high, mostly due to cardiovascular events. New early markers of risk are necessary to better anticipate the course of the disease, to detect the renal affection of additive risk factors, and to appropriately handle patients in a pre-emptive and personalized manner.Renal function and NGAL urinary excretion was monitored in rats with spontaneous (SHR or L-NAME induced hypertension rendered hyperglycemic (or not as controls.Combination of hypertension and hyperglycemia (but not each of these factors independently causes an increased urinary excretion of neutrophil gelatinase-associated lipocalin (NGAL in the rat, in the absence of signs of renal damage. Increased NGAL excretion is observed in diabetic animals with two independent models of hypertension. Elevated urinary NGAL results from a specific alteration in its tubular handling, rather than from an increase in its renal expression. In fact, when kidneys of hyperglycaemic-hypertensive rats are perfused in situ with Krebs-dextran solution containing exogenous NGAL, they excrete more NGAL in the urine than hypertensive rats. We also show that albuminuria is not capable of detecting the additive effect posed by the coexistence of these two risk factors.Our results suggest that accumulation of hypertension and hyperglycemia induces an incipient and quite specific alteration in the tubular handling of NGAL resulting in its increased urinary excretion.

  9. 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.

  10. Importance of urinary NGAL, serum creatinine standardization and estimated glomerular filtration rate in resistant hypertension.

    Science.gov (United States)

    Prkacin, Ingrid; Ozvald, Ivan; Cavrić, Gordana; Balenović, Diana; Bulum, Tomislav; Flegar-Mestrić, Zlata

    2013-09-01

    In patients with resistant hypertension (RH) we investigated the importance of urinary neutrophil gelatinase-associated lipocalin (uNGAL- a chemiluminescent microparticle immunoassay (CMIA) method became using (Abbott Diagnostics) for the measurement of NGAL in urine samples) and incidence of chronic kidney disease using the Modification of Diet in Renal Disease Study (MDRD) and Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations in estimating glomerular filtration rate (eGFR) based on standardised serum creatinine method traceable to isotope dilution mass spectrometry (IDMS) method. It would have been difficult to predict that levels of these biomarker would perform better organ damage than traditional measurements of kidney function such as standardised serum creatinine, MDRD, or CKD-EPI equations in special population such as RH. Serum creatinine concentrations were measured in 50 patients (24M:26F from RH Registar in Clinical Hospital Merkur) by the kinetic Jaffe method. There were no significant differences between the GFR values derived by MDRD and CKD-EPI equations in the group of patients with RH. 62% of patients have eGFR > 60 mL/minl/1.73 m2, while a 38% of patients have eGFR < 60 mL/min/1.73 m2. The measurement of NGAL in urine samples of 40 patients with RH showed no difference and seems to be of no use in further determination of renal impairement. Higher value of uNGAL in some resistant hypertension patients could have link in the repair stage after AKI and would reveal pathways that could link AKI and CKD.

  11. Clinical value of NGAL, L-FABP and albuminuria in predicting GFR decline in type 2 diabetes mellitus patients.

    Directory of Open Access Journals (Sweden)

    Kuei-Mei Chou

    Full Text Available OBJECTIVES: Neutrophil gelatinase-associated lipocalin (NGAL and liver-type fatty acid binding protein (L-FABP are emerging as excellent biomarkers in the urine and plasma for the early prediction of acute and chronic kidney injury. The aims of this prospective study were to determine the role of albuminuria, and that of serum and urine levels of NGAL and L-FABP as predictors of a decline in the glomerular filtration rate (GFR in patients with type 2 diabetes. METHODS: A longitudinal cohort study with one hundred forty type 2 diabetic patients was conducted. Serum and urine levels of NGAL and L-FABP, and the urine albumin excretion rate were determined. The correlation between the kidney injury biomarkers and rate of GFR decline was analyzed. RESULTS: The eGFR of study subjects decreased significantly as the study progressed (86.4±31.1 vs. 74.4±27.3 ml/min/1.73 m(2, P<0.001, and the urine albumin excretion rate increased significantly (264.9±1060.3 vs. 557.7±2092.5 mg/day, P = 0.009. The baseline urine albumin excretion rate and serum L-FABP level were significantly correlated with baseline eGFR (P<0.05. The results of regression analysis for the correlations between the rate of eGFR change and the baseline levels of NGAL and L-FABP, and the urine albumin excretion rate showed that only the urine albumin excretion rate was significantly correlated with the rate of eGFR change (standardized coefficients: -0.378; t: -4.298; P<0.001. CONCLUSIONS: Tubular markers, such as NGAL and L-FABP, may not be predictive factors associated with GFR decline in type 2 diabetic patients.

  12. The Role of NGAL in Peritoneal Dialysis Effluent in Early Diagnosis of Peritonitis: Case-Control Study in Peritoneal Dialysis Patients.

    Science.gov (United States)

    Martino, Francesca; Scalzotto, Elisa; Giavarina, Davide; Rodighiero, Maria Pia; Crepaldi, Carlo; Day, Sonya; Ronco, Claudio

    2015-01-01

    Peritoneal dialysis (PD) is frequently complicated by high rates of peritonitis, which result in hospitalization, technique failure, transfer to hemodialysis, and increased mortality. Early diagnosis, and identification of contributing factors are essential components to increasing effectiveness of care. In previous reports, neutrophil gelatinase-associated lipocalin (NGAL), a lipocalin which is a key player in innate immunity and rapidly detectable in peritoneal dialysis effluent (PDE), has been demonstrated to be a useful tool in the early diagnosis of peritonitis. This study investigates predictive value of PDE NGAL concentration as a prognostic indicator for PD-related peritonitis. A case-control study with 182 PD patients was conducted. Plasma and PDE were analyzed for the following biomarkers: C-reactive protein (CRP), blood procalcitonin (PCT), leucocytes and NGAL in PDE. The cases consisted of patients with suspected peritonitis, while controls were the patients who came to our ambulatory clinic for routine visits without any sign of peritonitis. The episodes of peritonitis were defined in agreement with International Society for Peritoneal Dialysis guidelines. Continuous variables were presented as the median values and interquartile range (IQR). Mann-Whitney U test was used to compare continuous variables. Univariate and multivariate logistic regression were used to evaluate the association of biomarkers with peritonitis. Receiver operating characteristic (ROC) curve analysis was used to calculate area under curve (AUC) for biomarkers. Finally we evaluated sensitivity, and specificity for each biomarker. All statistical analyses were performed with SPSS version 17.0 (SPSS Inc., Chicago, IL, USA). During the 19-month study, of the 182 patients, 80 had a clinical diagnosis of peritonitis. C-reactive protein levels (p peritonitis. In univariate analysis, CRP (odds ratio [OR] 1,339; p = 0.001), PCT (OR 2,473; p peritonitis. In multivariate regression analysis

  13. Interleukin-17-induced protein lipocalin 2 is dispensable for immunity to oral candidiasis.

    Science.gov (United States)

    Ferreira, Maria Carolina; Whibley, Natasha; Mamo, Anna J; Siebenlist, Ulrich; Chan, Yvonne R; Gaffen, Sarah L

    2014-03-01

    Oropharyngeal candidiasis (OPC; thrush) is an opportunistic fungal infection caused by the commensal microbe Candida albicans. Immunity to OPC is strongly dependent on CD4+ T cells, particularly those of the Th17 subset. Interleukin-17 (IL-17) deficiency in mice or humans leads to chronic mucocutaneous candidiasis, but the specific downstream mechanisms of IL-17-mediated host defense remain unclear. Lipocalin 2 (Lcn2; 24p3; neutrophil gelatinase-associated lipocalin [NGAL]) is an antimicrobial host defense factor produced in response to inflammatory cytokines, particularly IL-17. Lcn2 plays a key role in preventing iron acquisition by bacteria that use catecholate-type siderophores, and lipocalin 2(-/-) mice are highly susceptible to infection by Escherichia coli and Klebsiella pneumoniae. The role of Lcn2 in mediating immunity to fungi is poorly defined. Accordingly, in this study, we evaluated the role of Lcn2 in immunity to oral infection with C. albicans. Lcn2 is strongly upregulated following oral infection with C. albicans, and its expression is almost entirely abrogated in mice with defective IL-17 signaling (IL-17RA(-/-) or Act1(-/-) mice). However, Lcn2(-/-) mice were completely resistant to OPC, comparably to wild-type (WT) mice. Moreover, Lcn2 deficiency mediated protection from OPC induced by steroid immunosuppression. Therefore, despite its potent regulation during C. albicans infection, Lcn2 is not required for immunity to mucosal candidiasis.

  14. Plasma Neutrophil Gelatinase-Associated Lipocalinin in the General Population

    DEFF Research Database (Denmark)

    Lindberg, Søren; Jensen, Jan S; Mogelvang, Rasmus;

    2014-01-01

    , when both markers were added to the Framingham risk score, NGAL conferred 3× to 4× the risk. CONCLUSIONS: Plasma NGAL is strongly associated with inflammation in the general population. NGAL independently associated with 10-year outcome, and when added to the Framingham risk score, NGAL both improves c...

  15. 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

  16. Clinical Significance of Urinary Kidney Injury Molecule-1,Serum Cystatin C and Urinary Neutrophil Gelatinase-associated Lipocalin in the Prediction of Early Kidney Damage in Preeclampsia%尿肾损伤分子1、血清胱抑素C和尿中性粒细胞明胶酶相关性脂质运载蛋白预测子痫前期发病和早期肾损伤的价值

    Institute of Scientific and Technical Information of China (English)

    黄菁; 郑美玲; 王玉珏; 于庭

    2016-01-01

    目的:探讨新型生物学标志物尿肾损伤分子1(KIM⁃1)、血清胱抑素C和尿中性粒细胞明胶酶相关性脂质运载蛋白(NGAL)与子痫前期的关系及预测子痫前期发病和早期肾损伤的价值。方法选择2014年10月至2015年7月在吉林大学第二医院住院的30例重度子痫前期孕妇、30例轻度子痫前期孕妇作为子痫前期组,并选取同期住院足月分娩的60例健康孕妇作为对照组。采用ELISA法测定尿KIM⁃1和尿NGAL,采用免疫浊度法测定血清胱抑素C。结果子痫前期组孕妇的尿KIM⁃1、尿NGAL、血清胱抑素C水平明显高于对照组(均P<0.05),随着病情进展各指标均逐渐升高。体质量指数(BMI)、肾小球滤过率(eGFR)、尿蛋白/肌酐比值、尿KIM⁃1、血清胱抑素C和尿NGAL是子痫前期发生的危险因素;尿KIM⁃1、血清胱抑素C、尿NGAL及联合预测因子作为子痫前期早期肾损伤筛查指标的灵敏度分别为83.3%、75.0%、88.9%、96.8%;特异度分别为72.7%、70.0%、75.6%、86.4%。结论尿KIM⁃1、血清胱抑素C和尿NGAL的水平可反映子痫前期的病情进展和子痫前期肾损伤的程度。尿KIM⁃1、血清胱抑素C、尿NGAL联合检测对子痫前期早期肾损伤有更高的预测价值。%Objective To investigate the relationship between serum cystain C,urinary neutrophil gelatinase⁃associated lipocalin(NGAL),uri⁃nary kidney injury molecule⁃1(KIM⁃1)and preeclampsia,and explore the value in predicting preeclampsia and early kidney damage. Methods A total of 30 cases of pregnant women with severe preeclampsia,30 cases of mild preeclampsia and 60 cases of healthy pregnant women admitted in the Second Hospital of Jilin University from October 2014 to July 2015 were enrolled for the study. ELISA was performed to check urinary KIM⁃1 and urinary NGAL,and the serum cystatin C was detected by immune turbidity method. Results KIM⁃1,NGAL,serum cystatin C

  17. The significance of urine microscopy and urinary kidney injury molecular 1 and neutrophil gelatinase associated lipocalin in patients with primary kidney disease complicated with acute tubular interstitial lesion%尿沉渣联合尿KIM-1、NGAL在诊断原发性肾脏病合并急性肾小管间质病变中的意义

    Institute of Scientific and Technical Information of China (English)

    刘亚红; 苑丽华

    2015-01-01

    目的 观察原发性慢性肾脏病(CKD)合并急性肾小管间质病变(ATIL)时尿沉渣积分情况和尿肾损伤因子1(KIM-1)、中性粒细胞明胶酶相关脂质运载蛋白(NGAL)水平的变化,以期早期、准确发现ATIL.方法 经临床和病理确诊为CKD并发ATIL病例52例,对照组为无急性肾损伤(AKI)的原发性CKD患者33例,15例健康人为正常对照组.比较三组尿KIM-1、NGAL水平与尿沉渣积分的不同.结果 ①三组的尿KIM-1、NGAL水平和尿沉渣积分相比较,原发性CKD并发ATIL患者均高于其他两组(P<0.05),无AKI的CKD患者高于健康对照组(P<0.05);②尿KIM-1、NGAL水平与尿沉渣评分呈正相关(r=0.711,0.683,P<0.05),三者又均与CKD患者的ATIL严重程度呈正相关(r=0.892,0.735,0.745,P<0.05);③N-乙酰-β-D-氨基葡萄糖苷酶(NAG)、视黄醇结合蛋白(RBP)和α1-微球蛋白(α1-MG)尚在正常范围的患者尿KIM-1、NGAL水平已有升高,肾脏组织病理证实存在不同程度的ATIL;④尿KIM-1、NGAL、光抑素C(CysC)、NAG诊断ATIL的ROC曲线下面积大于尿RBP、α1-MG.尿沉渣诊断ATIL的受试者工作(ROC)曲线下面积为84%.尿KIM-1、NGAL联合尿沉渣积分诊断ATIL的准确性达100%.结论 尿沉渣联合尿KIM-1、NGAL可作为诊断原发性CKD并发ATIL的早期、无创、敏感的指标.%Objectives We explored urinary sediment scoring on the basis of the number of renal tubular epithelial cells and granular casts and the urinary level of KIM-1 and NGAL in patients with primary and chronic kidney disease (CKD) complicated with acute tubular interstitial lesion(ATIL),in order to find tubular interstitial injury early and accurately.Methods Data of 52 cases of primary CKD with ATIL and of 33 cases of CKD without acute kidney injury (AKI)admitted to Second Affiliated Hospital of Xingtai Medical College from February 2012 to February 2013 were analyzed.Urinary sediment scoring on the basis of the number of renal tubular epithelial

  18. High Frequency Electromagnetic Field Induces Lipocalin 2 Expression in

    Directory of Open Access Journals (Sweden)

    Amaneh Mohammadi Roushandeh

    2010-06-01

    Full Text Available Objective(sNeutrophil gelatinase-associated lipocalin (NGAL/Lcn2, comprise a group of small extracellular proteins with a common β-sheet-dominated 3-dimensional structure. In the past, it was assumed that the predominant role of lipocalin was acting as transport proteins. Recently it has been found that oxidative stress induces Lcn2 expression. It has been also proved that electromagnetic field (EMF produces reactive oxygen species (ROS in different tissues. Expression of Lcn2 following exposure to electromagnetic field has been investigated in this study. Materials and MethodsBalb/c mice (8 weeks old were exposed to 3 mT, 50 HZ EMF for 2 months, 4 hr/day. Afterwards, the mice were sacrificed by cervical dislocation and livers were removed. The liver specimens were stained with Haematoxylin- Eosin (H&E and analyzed under an optical microscope. Total RNA was extracted from liver and reverse transcription was performed by SuperScript III reverse transcriptase with 1 µg of total RNA. Assessment of Lcn2 expression was performed by semiquantitative and real time- PCR.ResultsThe light microscopic studies revealed that the number of lymphocyte cells was increased compared to control and dilation of sinosoids was observed in the liver. Lcn2 was up-regulated in the mice exposed to EMF both in mRNA and protein levels.ConclusionTo the extent of our knowledge, this is the first report dealing with up-regulation of Lcn2 in liver after exposure to EMF. The up-regulation might be a compensatory response that involves cell defense pathways and protective effects against ROS. However, further and complementary studies are required in this regards.

  19. Effect of compound chinese herbal medicine 861 on NGAL in serum and urine in diabetic rats%复方861对糖尿病大鼠血、尿ngal的影响

    Institute of Scientific and Technical Information of China (English)

    刘凤华; 张咪; 刘奇; 陈海平; 史振伟

    2015-01-01

    目的 探讨糖尿病肾病大鼠血、尿中性粒细胞明胶酶相关脂笼蛋白(neutrophil gelatinase associated lipocalin,ngal)的水平及复方861对其的影响.方法 采用一次性腹腔注射链脲佐菌素溶液制备糖尿病大鼠模型,随机分为正常对照组(N)、糖尿病组(D)、糖尿病中药治疗组(T)[中药复方861合剂1.5g·(kg·d)-1灌胃],于实验第2、4、8、12周处死,应用酶联免疫吸附法检测血清ngal(sngal)、尿ngal浓度(ungal).结果 糖尿病组较正常组2周起血、尿ngal明显升高(P<0.01);治疗组较糖尿病组2周起尿ngal降低(P<0.01),4周血ngal明显降低(P<0.01).结论 血、尿ngal可作为糖尿病大鼠肾损伤的早期标记物.复方861可降低糖尿病大鼠血、尿ngal浓度而起到肾保护作用.%Objectives To study the neutrophil gelatinase associated lipocalin (NGAL)in the serum and urine of diabetic rats and the efficacy of compound chinese? herbal medicine 861 (ccm) on NGAL.Methods Diabetic rats were induced by intraperitoneal injection of streptozotocin (STZ),and were randomly divided into three groups:normal control group (n =24),d iabete group (n =24),ccm [1.5 g · (kg · d)-1] treatment group (n =24).The concentration of NGAL in serum(sngal) and urine(ungal) was measured by euzymelinked immunosorbent assay at the 2nd,4th,8th and 12th week of experiment.Results NGAL in serum,urine was increased significantly at the 2nd week in diabetic group;In the ccm group sngal and ungal were decreased at the 4th and 2th week respectively compared with the diabetes group.Conclusions NGAL in the serum,urine increases in the early time in diabetic rats and on the increase over time.Ccm can decrease ngal in serum,urine and alleviates the renal tubular ultramicrostructural injury to protect the kidney.

  20. Transcriptional analysis of kidneys during repair from AKI reveals possible roles for NGAL and KIM-1 as biomarkers of AKI-to-CKD transition.

    Science.gov (United States)

    Ko, Gang Jee; Grigoryev, Dmitry N; Linfert, Douglas; Jang, Hye Ryoun; Watkins, Tonya; Cheadle, Chris; Racusen, Lorraine; Rabb, Hamid

    2010-06-01

    Acute kidney injury (AKI) is being increasingly shown to be a risk factor for chronic kidney disease (CKD), but little is known about the possible mechanistic links. We hypothesized that analysis of the genomic signature in the repair stage after AKI would reveal pathways that could link AKI and CKD. Unilateral renal pedicle clamping for 45 min was performed in male C57BL/6J mice. Mice were euthanized at 3, 10, and 28 days after ischemia-reperfusion injury (IRI). Total RNA was isolated from kidney and analyzed using an Illumina mouse array. Among 24,600 tested genes, 242, 146, and 46 genes were upregulated at days 3, 10, and 28 after IRI, and 85, 35, and 0 genes were downregulated, respectively. Gene ontology analysis showed that gene expression changes were primarily related to immune and inflammatory pathways both early and late after AKI. The most highly upregulated genes late after AKI were hepatitis A virus cellular receptor 1 (Havcr1) and lipocalin 2 (Lcn2), which code for kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL), respectively. This was unexpected since they are both primarily potential biomarkers of the early stage of AKI. Furthermore, increases observed in gene expression in amiloride binding protein 1, vascular cell adhesion molecule-1, and endothelin 1 could explain the salt-sensitive hypertension that can follow AKI. These data suggested that 1) persistent inflammation and immune responses late after AKI could contribute to the pathogenesis of CKD, 2) late upregulation of KIM-1 and NGAL could be a useful marker for sustained renal injury after AKI, and 3) hypertension-related gene changes could underlie mechanisms for persistent renal and vascular injury after AKI.

  1. 内毒素休克所致急性肾损伤家兔血和尿中性粒细胞明胶酶相关脂质运载蛋白变化%Changes of plasma and urine neutrophil gelatinase-associated lipocalin in septic acute kidney injury in rabbits

    Institute of Scientific and Technical Information of China (English)

    王海霞; 薛露; 张敏; 颜培夏; 郑瑞强

    2016-01-01

    小,上皮细胞空泡样变性较模型组程度轻。结论尿和血清NGAL在内毒性休克所致AKI中明显升高,NGAL可能是早期诊断内毒素性休克所致AKI较好的生物学标志物。早期充分液体复苏可能有助于肾功能的改善。%Objective To investigate the significance of the changes in NGAL during septic shock induced AKI and the impact of fluid resuscitation on NGAL. Methods Rabits were used to establish animal model of septic shock by ear vein infusing LPS. The animals were randomized into blank control group, septic shock group, Ringer’s solution resuscitation group (n=6 each). The data of systemic hemodynamic parameters, uNGAL, sNGAL and Scr were collected at baseline (Tx), septic shock (T0), resuscitation 3 hours (T3) and resuscitation 6 hours (T6), renal tissue pathology was observed by optical microscopy and transmission electron microscopy. Results No significant difference existed in the basic status among 3 groups. There was no significant difference among different time-points in the blank control group. In septic shock group, compared with basic status, the level of MAP and SVRI were reduced at 0 h, 3 h and 6 h;Compared with basic status, the level of HR and SVV were elevated and CI, SVRI, GEDVI, ITBI were lowered at 3 h and 6 h (P0.05);there was no correlation between sNGAL and uNGAL whether at T3 or at T6 time point (r=0.767, P=0.075; r=0.698, P=0.302). Observing kidney tissue by optical microscopy and transmission electron microscopy showed: the kidney from control group showed normal glomeruli and tubules, complete and clear cells and organelles, and dyeing uniform cytoplasm;in contrast, in model group the kidney showed edema in glomerular capillary endothelial cells, vacuoles in cytoplasmic, and inflammatory cells in the mesangial stroma and renal interstitium, but there were no obvious abnormal in basement membrane, foot cells, and foot process. Although renal tubule of model group appeared edema, smaller

  2. Differential transcytosis and toxicity of the hNGAL receptor ligands cadmium-metallothionein and cadmium-phytochelatin in colon-like Caco-2 cells: implications for in vivo cadmium toxicity.

    Science.gov (United States)

    Langelueddecke, Christian; Lee, Wing-Kee; Thévenod, Frank

    2014-04-21

    The environmental toxicant cadmium (Cd) enters the food chain. A substantial proportion of Cd in nutrients of plant origin is present as Cd-metallothionein (CdMT) and Cd-phytochelatin (CdPC) complexes, which may be absorbed and transcytosed intact by colonic enterocytes following bacterial fermentation and contribute to systemic Cd toxicity, e.g. in liver and kidneys. We have recently demonstrated that the receptor for human neutrophil gelatinase-associated lipocalin (hNGAL) is expressed in human colon and colon-like Caco-2 BBE cells where it mediates transcytosis of MT and PC. Here we show in colon-like Caco-2 BBE cells that hNGAL receptor (hNGAL-R) dependent toxicity is significantly higher with CdMT than with CdPC3 (2.5-50μM Cd(2+) complexed to MT or PC3 for ≤24h), using MTT assay. Fluorescence-labelled A546-MT, but not A488-PC3 (both 700nM), co-localizes with the lysosomal marker cathepsin-B, as determined by confocal microscopy. In transwell experiments with confluent monolayers, transcytosis efficiency (i.e. the ratio of basal delivery to apical decrease) of A546-MT is decreased compared to A488-PC3 (both 700nM). The tubulin polymerization disruptor nocodazole (16.7μM) almost abolished CdMT and CdPC3 toxicity, reduced apical uptake of both A546-MT and A488-PC3, but increased transcytosis efficiency of A546-MT compared to that of A488-PC3 by preventing trafficking of A546-MT to lysosomes. Hence, following hNGAL-R dependent endocytosis of CdMT/CdPC3 in colonic epithelia, a nocodazole-sensitive trafficking pathway may preferentially target CdMT, but not CdPC3, to lysosomes, causing increased colonic epithelial toxicity but reduced systemic toxicity.

  3. Potentials of plasma NGAL and MIC-1 as biomarker(s in the diagnosis of lethal pancreatic cancer.

    Directory of Open Access Journals (Sweden)

    Sukhwinder Kaur

    Full Text Available Pancreatic cancer (PC is lethal malignancy with very high mortality rate. Absence of sensitive and specific marker(s is one of the major factors for poor prognosis of PC patients. In pilot studies using small set of patients, secreted acute phase proteins neutrophil gelatinase associated lipocalin (NGAL and TGF-β family member macrophage inhibitory cytokine-1 (MIC-1 are proposed as most potential biomarkers specifically elevated in the blood of PC patients. However, their performance as diagnostic markers for PC, particularly in pre-treatment patients, remains unknown. In order to evaluate the diagnostic efficacy of NGAL and MIC-1, their levels were measured in plasma samples from patients with pre-treatment PC patients (n = 91 and compared it with those in healthy control (HC individuals (n = 24 and patients with chronic pancreatitis (CP, n = 23. The diagnostic performance of these two proteins was further compared with that of CA19-9, a tumor marker commonly used to follow PC progression. The levels of all three biomarkers were significantly higher in PC compared to HCs. The mean (± standard deviation, SD plasma NGAL, CA19-9 and MIC-1 levels in PC patients was 111.1 ng/mL (2.2, 219.2 U/mL (7.8 and 4.5 ng/mL (4.1, respectively. In comparing resectable PC to healthy patients, all three biomarkers were found to have comparable sensitivities (between 64%-81% but CA19-9 and NGAL had a higher specificity (92% and 88%, respectively. For distinguishing resectable PC from CP patients, CA19-9 and MIC-1 were most specific (74% and 78% respectively. CA19-9 at an optimal cut-off of 54.1 U/ml is highly specific in differentiating resectable (stage 1/2 pancreatic cancer patients from controls in comparison to its clinical cut-off (37.1 U/ml. Notably, the addition of MIC-1 to CA19-9 significantly improved the ability to distinguish resectable PC cases from CP (p = 0.029. Overall, MIC-1 in combination with CA19-9 improved the diagnostic

  4. 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

  5. Waist circumference and neutrophil gelatinase-associated lipocalin in late-life depression

    NARCIS (Netherlands)

    Marijnissen, Radboud M.; Naude, Petrus J. W.; Comijs, Hannie C.; Schoevers, Robert A.; Oude Voshaar, Richard

    Both visceral obesity and depression are associated with impaired health and excess mortality, possibly through overlapping pathophysiological mechanisms like adipose tissue derived inflammatory markers. These results, however, are primarily based on population-based surveys, often restricted to a

  6. Neutrophil Gelatinase-Associated Lipocalin : Ready for Routine Clinical Use? An International Perspective

    NARCIS (Netherlands)

    Ronco, Claudio; Legrand, Matthieu; Goldstein, Stuart L.; Hur, Mina; Nam Tran, [No Value; Howell, Eric C.; Cantaluppi, Vincenzo; Cruz, Dinna N.; Damman, Kevin; Bagshaw, Sean M.; Di Somma, Salvatore; Lewington, Andrew

    2014-01-01

    Acute kidney injury (AKI) remains a challenge in terms of diagnosis and classification, its morbidity and mortality remaining high in the face of improving clinical protocols. Current clinical criteria use serum creatinine (sCr) and urine output to classify patients. Ongoing research has identified

  7. Waist circumference and neutrophil gelatinase-associated lipocalin in late-life depression

    NARCIS (Netherlands)

    Marijnissen, Radboud M.; Naude, Petrus J. W.; Comijs, Hannie C.; Schoevers, Robert A.; Oude Voshaar, Richard

    2014-01-01

    Both visceral obesity and depression are associated with impaired health and excess mortality, possibly through overlapping pathophysiological mechanisms like adipose tissue derived inflammatory markers. These results, however, are primarily based on population-based surveys, often restricted to a y

  8. Serum NGAL is Associated with Distinct Plasma Amyloid-beta Peptides According to the Clinical Diagnosis of Dementia in Down Syndrome

    NARCIS (Netherlands)

    Naude, P.J.; Dekker, A.D.; Coppus, A.M.W.; Vermeiren, Y.; Eisel, U.L.; Duijn, C.M. van; Dam, D. Van; Deyn, P.P. De

    2015-01-01

    BACKGROUND: The majority of people with Down syndrome (DS) develop dementia due to Alzheimer's disease (AD). Neuropathological features are characterized by an accumulation of amyloid-beta (Abeta) deposits and the presence of an activated immune response. Neutrophil Gelatinase-Associated Lipocalin

  9. 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.

  10. a慢性阻塞性肺疾病患者血浆中性粒细胞明胶酶蛋白及内皮素-1水平与认知功能障碍的相关性%Correlation between plasma NGAL and ET-1 levels and cognitive dysfunction in patients with chronic obstructive pulmonary disease

    Institute of Scientific and Technical Information of China (English)

    胡玲玲; 戈艳蕾; 黄超; 李丽蕊; 王红阳

    2016-01-01

    Objective To investigate the relationship between the plasma neutrophil gelatinase-associated lipocalin (NGAL)and endothelin-1 (ET-1) levels and cognitive dysfunction in chronic obstructive pulmonary disease (COPD) patients.Methods A case-control study was performed,consisting of 128 patients with COPD(68 patients without cognitive dysfunction and 60 patients with cognitive dysfunction) and 70 normal controls.All patients with COPD were diagnosed by pulmonary function tests and plasma levels of NGAL and ET-1 were determined by enzyme immunoassay.The cognitive function was evaluated by the MMSE and MoCA.Results ①Compared with normal control,the levels of plasma NGAL and ET-1 were increased(NGAL:(2.20±0.60) μg/L vs (1.69±0.73) μg/L,P<0.05;ET-1:(26.19± 10.55)pg/ml vs (13.05±2.37) pg/ml,P<0.05) in COPD patients without cognitive dysfunction and in COPD patients with cognitive dysfunction(NGAL:(3.80±2.75) μg/L vs (1.69±0.73) μg/L,P<0.01;ET-1:(37.82±0.29) pg/ml vs (13.05±2.37) pg/ml,P<0.01).Compared with the COPD patients without cognitive dysfunction,the levels of plasma NGAL and ET-1 were also increased in COPD patients with cognitive dysfunction (all P<0.05).②The plasma NGAL levels were correlated negatively with MMSE scores(r=-0.524,P<0.05),and negatively correlated with MoCA scores (r=-0.527,P<0.05).The plasma ET-1 levels were negatively correlated with MMSE scores(r=-0.549,P<0.05),and negatively correlated with MoCA scores(r=-0.558,P<0.05).The levels of NGAL and ET-1 were positively correlated(r=0.564,P<0.05).Conclusion NGAL and ET-1 may be involved in the pathophysiological process of cognitive dysfunction in patients with COPD,which provides a certain clinical value for the assessment of cognitive dysfunction in patients with COPD.%目的 探讨慢性阻塞性肺疾病(chronic obstructive pulmonary disease,COPD)患者血浆中性粒细胞明胶酶蛋白(neutrophil gelatinase-associated lipocalin,NGAL)及内皮素-1(endothelin-1

  11. Value of urine NGAL and N - acetyl - β - D - glucosaminidase in early diagnosis of IgA nephropathy%尿NGAL和N-乙酰-β-D-氨基葡萄糖苷酶对IgA肾病早期诊断的价值研究

    Institute of Scientific and Technical Information of China (English)

    王寅; 童俊容; 何凤; 罗正茂; 张虹

    2011-01-01

    Objective:To explore the value of urine NGAL and N - acetyl - p - D - glucosaminidase in diagnosing early injury of IgA nephropathy. Methods: 85 patients with lgA nephropathy were categorized into two groups ( Hass I - II group and Hass III~ V group). 30 healthy subjects were recruited as controls. Ungal and Unag were detected by commercial available ELISA kit according to the manufacturer's instructions. And the ratio of Ungal/Cr and Unag/Cr were calculated. Receiver operating characteristic (ROC) curve analysis was used to evaluat the two on the sensitivity and specificity of diagnosis on IgA nephropathy. The area under the ROC curve and the best diagnostic cut -off value were calculated. Results: The levels of Ungal,Unag,Un-GAL/Cr and Unag/Cr are significantly higher in IgAN patients than in control group. The area under ROC curve of Ungal/Cr and Unag/Cr were 0.941 and 0.846 respectively. The best diagnostic cut - off value were 3.50 g /mmol Cr and 1.20 U /mmol Cr. Taking the boundary value to diagnose IgA nephropathy, the sensitivity and specificity for Ungal/Cr and Unag/Cr were 91.2% , 93.7% and 83.3% , 84.9% respectively. Conclusion: Ungal is an objective indicator of early renal damage in IgA nephropathy. Ungal/Cr has higher sensitivity and specificity for the diagnosis of IgA nephropathy than Unag /Cr,and it is expected to be diagnostic indicator for IgA nephropathy.%目的:探讨尿中性粒细胞明胶酶相关脂蛋白(neutrophil gelatinase associated lipocalin,NGAL)和N-乙酰-β-D-氨基葡萄糖苷酶(N - acetyl -β-D - glucosaminidase,NAG)对IgA肾病早期诊断价值.方法:选择IgA肾病患者85例,根据Hass分级Hass Ⅰ~Ⅱ(A组)40例、Hass Ⅲ~V(B组)45例;正常对照组30例.应用ELISA法检测尿液NGAL(uNGAL)和uNAG的浓度,并计算uNGAL/Cr比值和uNAG/Cr比值,进而对uNGAL/Cr和uNAG/Cr进行受试者工作特征(ROC)曲线分析,计算ROC曲线下面积和最佳诊断界值.结果:IgA肾病患者的uNGAL、uNAG、uNGAL/Cr

  12. 抗衰老蛋白 Klotho 阻断高糖培养的大鼠肾小球系膜细胞 TLR4/NF-kB p65/NGAL 通路的激活及其作用机制%Klotho, an aging-suppression protein, inhib its TLR4/NF-kB p65/NGAL pathways in rat mesangial cells cultured with high glucose and its mechanism

    Institute of Scientific and Technical Information of China (English)

    吴灿; 吕川; 周月宏; 邵滢; 秦宁宁; 王秋月

    2015-01-01

    目的探讨体外高糖培养的大鼠肾小球系膜细胞(RMCs)中抗衰老蛋白 Klotho 及中性粒细胞明胶酶相关脂质运载蛋白(NGAL)两者表达水平的变化及其相关作用,同时观察 Toll 样受体-4(TLR4)/核因子-kB(NF-kB) p65通路在此过程中的作用。方法设计并合成针对 NGAL 基因的3个特异性 siRNA序列转入 RMCs,筛选抑制效率最佳的 siRNA 用于后续实验;以吡咯烷二硫基甲酸盐(PDTC)或 Klotho 重组蛋白干预体外高糖培养的 RMCs;采用实时定量 PCR 检测 Klotho、TLR4、NGAL mRNA 的表达,Western 印迹检测 Klotho、TLR4、NF-kB p65、NGAL、纤连蛋白、结缔组织生长因子(CTGF)的表达,ELISA 检测单核细胞趋化因子-1(MCP-1)、趋化因子配体5(CXCL5)的分泌。结果高糖抑制 Klotho 表达(P<0.05)并激活 TLR4/NF-kB p65通路促进 NGAL、纤连蛋白、CTGF、MCP-1、CXCL5表达,基因沉默 NGAL 表达后纤连蛋白、CTGF、MCP-1、CXCL5表达明显下降(P<0.01),PDTC 干预后 NGAL 蛋白表达明显下降(P<0.01),Klotho 重组蛋白干预可抑制 TLR4/ NF-kB p65通路活性,下调 NGAL、纤连蛋白、CTGF、MCP-1、CXCL5的表达(P<0.01)。结论在 RMCs 中,Klotho 可通过抑制高糖刺激的 TLR4/ NF-kB p65通路活性下调 NGAL 的表达,从而抑制纤连蛋白、CTGF、MCP-1、CXCL5的表达,可能对糖尿病肾脏组织起保护作用。%Objective To explore the changes in expression of Klotho, an aging-suppression protein, and neutrophil gelatinase associated lipocalin ( NGAL) and their relationship with rat mesangial cells ( RMCs) cultured with high glucose in vitro, and to explore the role played by Toll-like receptor-4 (TLR4) / nuclear factor-kB(NF-kB) p65 pathways in this process. Methods Three NGAL-siRNA sequences were designed and synthesized. The effective sequence in subsequent experiments was chosen. RMCs were preincubated with pyrrolidinedithiocarbamate (PDTC)or exogenously added Klotho prior to high glucose treatment

  13. Assessment of neutrophil gelatinase-associated lipocalin and lactate dehydrogenase in ascities for the screening of spontaneous bacterial peritonitis in cirrhosis%腹水中的中性粒细胞明胶酶相关脂质运载蛋白和乳酸脱氢酶检测在诊断肝硬化自发性腹膜炎中的价值

    Institute of Scientific and Technical Information of China (English)

    王军; 彭浩; 王哲; 宋建新

    2016-01-01

    目的:腹水中有核细胞计数及分类仍然是目前诊断肝硬化自发性细菌性腹膜炎(SBP)的标准.然而,这种方法有其缺点,因此使用其他腹水中可检测指标可能是诊断SBP的有益的选择.方法:测定肝硬化患者腹水中的中性粒细胞明胶酶相关脂质运载蛋白(NGAL)、乳酸脱氢酶(LDH),评估NGAL、LDH对SBP的诊断价值.结果:共对52例肝硬化腹水标本进行检测分析,其中13例(25%)中性粒细胞数≥250/μl诊断为SBP,患者腹水中NGAL和LDH的中位浓度分别为243ng/ml和565 U/L,分别是非SBP患者的2.7和3倍(P<0.05).NGAL诊断SBP的ROC曲线下的面积是0.87,LDH的曲线下面积为0.86,两者联合检测(均高于临界值)的曲线下的面积为0.87.NGAL≥122.5ng/ml时其敏感性和特异性分别为1.00和0.77,LDH≥120U/L时其敏感性和特异性分别为0.92和0.69,两者检测均高于临界值的敏感性和特异性分别为0.85和0.90.结论:通过本次研究表明,检测腹水中NGAL和LDH有可能成为筛查肝硬化腹水患者并发SBP的有效手段之一.

  14. Prediction and early diagnosis on cisplatin induced acute kidney injury through NGAL%NGAL预测和早期诊断顺铂所致急性肾损伤的研究

    Institute of Scientific and Technical Information of China (English)

    张立元; 朱振红; 王敏; 刘剑华; 李玉; 朱正秋

    2013-01-01

    目的:研究顺铂所致急性肾损伤(AKI)患者中粒细胞明胶酶相关脂质运载蛋白(NGAL)水平的变化,探讨其对AKI的预测和早期诊断价值.方法:动态检测60例化疗患者应用顺铂前后的肌酐和NGAL水平,根据肌酐水平上升值将患者分为AKI组和非AKI组,研究尿NGAL水平与AKI发生的关系.结果:AKI组血清肌酐升高峰值出现在12~48 h,NGAL升高峰值出现在2~8 h.AKI发生率为18.33% (11/60).与化疗前相比,化疗后AKI组2、4和8h尿NGAL水平升高,差异有统计学意义,P<0.01;化疗后12 h水平与化疗前相比差异无统计学意义,P>0.05;与非AKI组比较,AKI组化疗后2、4、6和8h的尿NGAL水平都明显升高,差异有统计学意义,P<0.01.化疗后两组患者2~4h尿液中NGAL水平都有所升高,6h后尿NGAL水平AKI组仍较高,而非AKI组降至正常参考值范围内,以非AKI尿NGAL水平的((X)±s)值作为诊断AKI的限定值,以6~8 h尿NGAL水平为诊断依据,诊断特异性为100%(49/49),敏感性为100%(11/11),诊断符合率为100% (60/60).AKI组化疗后24 h Scr水平与化疗后2h尿NGAL水平间存在线性相关,r=0.864 4.结论:检测尿NGAL水平可早期预测和诊断顺铂化疗后AKI的发生,方法准确、灵敏,可作为顺铂引起的AKI的早期诊断方法.%OBJECTIVE:This study was to show that neutrophil gelatinase-associated lipocalin (NGAL) has an early predictive value of acute kidney injury (AKI) obtained by using cisplatin.METHODS:Serum creatinine(Scr),and NGAL levels of 60 chemotherapy patients were dynamically measured before and after cisplatin administration.Patients were divided into AKI group and non-AKI group by AKI diagnostic standard.The relationship of urinary NGAL level with AKI were studied.RESULTS:Scr peak value increased from 12 to 48 h,AKI was observed in 11 cases of 60 patients and the rate was 18.33%,NGAL increased peak within 2~8 h.In contrast with urinary NGAL levels before chemotherapy

  15. Involvement of TSP1 and MMP9/NGAL in Angiogenesis during Orthodontic Periodontal Remodeling

    Directory of Open Access Journals (Sweden)

    Petra Surlin

    2014-01-01

    Full Text Available In the present study the aim was to measure the levels of Thrombospondin-1 (TSP1 and Lipocalin-2/matrix metalloproteinase 9 (MMP9/NGAL complex in gingival crevicular fluid (GCF at different time points of orthodontic treatment, to determine the relationship between these values and those of total-matrix metalloproteinase 9 (MMP9 and theirs implication in angiogenesis balance, in the situation of a good control of the bacterial plaque, emphasizing the role of TSP1 and MMP9/NGAL complex. GCF samples were collected from 16 young orthodontic patients requiring upper canine distalization (test tooth with first premolar extraction. The contralateral canine (control tooth was free from orthodontic force. For the orthodontic appliance, brackets Roth 0.018 inch with 0.012 inch NiTi archwire and a laceback were used. TSP1, MMP9/NGAL, and MMP9 increased from 1 hour before activation of orthodontic appliance to a maximum at 8 hours for MMP9 and 72 hours for MMP9/NGAL and TSP1. The results show a change in time of TSP1, MMP9/NGAL, and MMP9 levels in GCF of patients with this method of orthodontic treatment. The powerful correlation of MMP9/NGAL with TSP1 suggests their stronger involvement in angiogenesis processes in PDL during orthodontic periodontal remodeling, in the situation of a healthy periodontium and a good control of the bacterial plaque.

  16. Correlation of serum neutrophil gelatinase-associated lipocalin with acute kidney injury in hypertensive disorders of pregnancy

    OpenAIRE

    Patel ML; Sachan R; Gangwar R; Sachan P; Natu SM

    2013-01-01

    ML Patel,1 Rekha Sachan,2 Radheyshyam Gangwar,3 Pushpalata Sachan,4 SM Natu51Department of Medicine, King George's Medical University, Lucknow, Uttar Pradesh, India; 2Department of Obstetrics and Gynaecology, King George's Medical University, Lucknow, Uttar Pradesh, India; 3Department of Critical Care, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India; 4Department of Physiology, King George's Medical University, Lucknow, Uttar Pra...

  17. 原发性肾病综合征并发急性肾损伤患者血清及肾组织中NGAL的表达及意义%Expression of NGAL in serum and renal tissues of patients with primary nephrotic syndrome and acute kidney injury

    Institute of Scientific and Technical Information of China (English)

    刘静; 李绍梅; 薛雯; 温文龙; 杨林; 杨万霞; 王建荣

    2012-01-01

    目的:检测原发性肾病综合征(PNS)患者血清及肾组织中中性粒细胞明胶酶相关脂质运载蛋白(NGAL)的水平,探讨PNS合并急性肾损伤(AKI)时患者血清及肾组织中NGAL浓度的变化.方法:72例PNS患者根据病理结果分为:(1)PNS合并急性肾小管坏死(ATN)组 15例,其中微小病变(MCD)合并ATN 10例,系膜增生(MsPGN)合并ATN 5例;(2)PNS不合并ATN组 57例,其中MCD组 24例,膜性肾病(MN)组23例和MsPGN 组10例.15例健康体检者的血液及5例正常肾组织作为正常对照组.采用ELISA检测血清NGAL的水平;采用免疫组化法检测肾组织中NGAL的表达.结果:(1)PNS患者血清NGAL水平及肾组织中NGAL表达明显高于正常对照组(P0.05);血清中NGAL与肾组织NGAL的表达呈正相关(P<0.01).结论:血清NGAL可能作为判断原发性肾病综合征并发急性肾损伤的早期、无创、敏感指标.%AIM; To observe the changes of neutrophil gelatinase -associated lipocalin (NGAL) level in ser-um and renal tissues of the patients with primary nephrotic syndrome (PNS) and acute kidney injury (AKI). METH-ODS : Seventy - two PNS patients were selected in the study and divided into 2 groups according to the pathological results of renal biopsy. The patients in PNS + AKI group included 15 cases of PNS with acute tubular necrosis ( ATN) , in which there were 10 cases of minimal change disease ( MCD) with ATN and 5 cases of mesangial proliferative glomerulonephritis ( MsPGN) with ATN. The patients in PNS alone group included 57 cases of PNS without ATN. According to the pathologi-cal types, they were divided into MCD group (24 cases) , membranous nephropathy (MN) group (23 cases) and MsPGN group (10 cases). Serum samples from 15 healthy persons and 5 cases of normal renal tissues were used as controls. The serum levels of NGAL were detected by ELISA. The distribution and expression of NGAL in the renal tissues were observed by immunohistochemical method. RESULTS: ( 1) The serum

  18. Matrix metalloproteinases 2 and 9 and MMP9/NGAL complex activity in women with PCOS.

    Science.gov (United States)

    Ranjbaran, Javad; Farimani, Marzieh; Tavilani, Heidar; Ghorbani, Marzieh; Karimi, Jamshid; Poormonsefi, Faranak; Khodadadi, Iraj

    2016-04-01

    It is believed that matrix metalloproteinases (MMPs) play important roles in follicular development and pathogenesis of polycystic ovary syndrome (PCOS). However, conflicting results are available about the alteration of MMP2 and MMP9 concentrations or activities in PCOS. In fact, there is no study entirely investigating both concentration and activity of these MMPs and serum levels of their tissue inhibitors TIMP2 and TIMP1, as well as lipocalin-bound form of MMP9 (MMP9/NGAL). Therefore, the thoroughness of previous studies is questionable. This study was conducted to determine circulatory concentration of MMP2, MMP9, MMP9/NGAL complex, TIMP1 and TIMP2 as well as gelatinase activities of MMP2, MMP9 and MMP9/NGAL complex in women with PCOS and controls. Mean age and BMI as well as serum levels of total cholesterol, triacylglycerol, HDL-C, LDL-C, fasting blood sugar (FBS), insulin, estradiol and sex hormone-binding globulin did not differ between groups, whereas a marked decrease in FSH and significant increases in LH, LH/FSH ratio, testosterone and free androgen index were observed. Women with PCOS and controls showed closed concentrations of MMP2, MMP9, MMP9/NGAL, TIMP1 and TIMP2. Gelatinase activity of MMP9 was found significantly higher in PCOS than in controls (64.53±15.32 vs 44.61±18.95 respectively) while patients and healthy subjects showed similar activities of MMP2 and MMP9/NGAL complex. Additionally, PCOS patients showed a higher MMP9/TIMP1 ratio compared with control women. Direct correlations were also observed between circulatory MMP9 level and the concentration and activity of MMP9/NGAL complex. In conclusion, based on the results of present study, we believe that MMP9 may be involved in the pathogenesis of PCOS.

  19. The bacterial lipocalins.

    Science.gov (United States)

    Bishop, R E

    2000-10-18

    The lipocalins were once regarded as a eukaryotic protein family, but new members have been recently discovered in bacteria. The first bacterial lipocalin (Blc) was identified in Escherichia coli as an outer membrane lipoprotein expressed under conditions of environmental stress. Blc is distinguished from most lipocalins by the absence of intramolecular disulfide bonds, but the presence of a membrane anchor is shared with two of its closest homologues, apolipoprotein D and lazarillo. Several common features of the membrane-anchored lipocalins suggest that each may play an important role in membrane biogenesis and repair. Additionally, Blc proteins are implicated in the dissemination of antibiotic resistance genes and in the activation of immunity. Recent genome sequencing efforts reveal the existence of at least 20 bacterial lipocalins. The lipocalins appear to have originated in Gram-negative bacteria and were probably transferred horizontally to eukaryotes from the endosymbiotic alpha-proteobacterial ancestor of the mitochondrion. The genome sequences also reveal that some bacterial lipocalins exhibit disulfide bonds and alternative modes of subcellular localization, which include targeting to the periplasmic space, the cytoplasmic membrane, and the cytosol. The relationships between bacterial lipocalin structure and function further illuminate the common biochemistry of bacterial and eukaryotic cells.

  20. Independent associations of urine neutrophil gelatinase–associated lipocalin and serum uric acid with interstitial fibrosis and tubular atrophy in primary glomerulonephritis

    Directory of Open Access Journals (Sweden)

    Lertrit A

    2016-04-01

    Full Text Available Amornpan Lertrit,1 Suchin Worawichawong,2 Somlak Vanavanan,2 Anchalee Chittamma,2 Dittapol Muntham,3 Piyanuch Radinahamed,1 Aumporn Nampoon,4 Chagriya Kitiyakara1 1Department of Medicine, 2Department of Pathology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, 3Section for Mathematics, Faculty of Science and Technology, Rajamangala University of Technology Suvarnabhumi, Phranakhon Si Ayutthaya, 4Research Center, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand Abstract: The degree of interstitial fibrosis and tubular atrophy (IFTA is one of the strongest prognostic factors in glomerulonephritis (GN. In experimental models, high serum uric acid (UA could contribute to IFTA through direct effects on the renal tubules, but the significance of this process has not been evaluated in patients. Urine neutrophil gelatinase–associated lipocalin (NGAL is produced by renal tubules following acute or chronic damage. We investigated the relationship between UA and NGAL excretion in primary GN and tested whether these biomarkers are independently associated with IFTA. Urine and blood were collected from patients on the day of kidney biopsy. IFTA was assessed semi-quantitatively. Fifty-one patients with primary GN were enrolled. NGAL/creatinine correlated significantly with proteinuria but not with glomerular filtration rate (GFR. By contrast, UA correlated with GFR but not with proteinuria. NGAL/creatinine did not correlate with UA. Both NGAL/creatinine and UA increased with the severity of IFTA. By multivariate analysis, GFR, NGAL/creatinine, and UA were independently associated with moderate-to-severe IFTA. Combining UA and NGAL/creatinine with classical predictors (proteinuria and GFR tended to improve discrimination for moderate-to-severe IFTA. Findings that UA was unrelated to urinary NGAL excretion suggest that the two biomarkers reflect different pathways related to the development of IFTA in

  1. Parenteral iron formulations differentially affect MCP-1, HO-1, and NGAL gene expression and renal responses to injury.

    Science.gov (United States)

    Johnson, Ali C M; Becker, Kirsten; Zager, Richard A

    2010-08-01

    Despite their prooxidant effects, ferric iron compounds are routinely administered to patients with renal disease to correct Fe deficiency. This study assessed relative degrees to which three clinically employed Fe formulations [Fe sucrose (FeS); Fe gluconate (FeG); ferumoxytol (FMX)] impact renal redox- sensitive signaling, cytotoxicity, and responses to superimposed stress [endotoxin; glycerol-induced acute renal failure (ARF)]. Cultured human proximal tubule (HK-2) cells, isolated proximal tubule segments (PTS), or mice were exposed to variable, but equal, amounts of FeS, FeG, or FMX. Oxidant-stimulated signaling was assessed by heme oxygenase-1 (HO-1) or monocyte chemoattractant protein (MCP)-1 mRNA induction. Cell injury was gauged by MTT assay (HK-2 cells), %LDH release (PTS), or renal cortical neutrophil gelatinase-associated lipoprotein (NGAL) protein/mRNA levels. Endotoxin sensitivity and ARF severity were assessed by TNF-alpha and blood urea nitrogen concentrations, respectively. FeS and FeG induced lethal cell injury (in HK-2 cells, PTS), increased HO-1 and MCP-1 mRNAs (HK-2 cells; in vivo), and markedly raised plasma ( approximately 10 times), and renal cortical ( approximately 3 times) NGAL protein levels. Both renal and extrarenal (e.g., hepatic) NGAL production likely contributed to these results, based on assessments of tissue and HK-2 cell NGAL mRNA. FeS pretreatment exacerbated endotoxemia. However, it conferred marked protection against the glycerol model of ARF (halving azotemia). FMX appeared to be "bioneutral," as it exerted none of the above noted FeS/FeG effects. We conclude that 1) parenteral iron formulations that stimulate redox signaling can evoke cyto/nephrotoxicity; 2) secondary adaptive responses to this injury (e.g., HO-1/NGAL induction) can initiate a renal tubular cytoresistant state; this suggests a potential new clinical application for intravenous Fe therapy; and 3) FMX is bioneutral regarding these responses. The clinical

  2. 冠心病患者血清中性粒细胞明胶酶相关脂质运载蛋白的表达及其临床意义%Expression of serum NGAL in coronary heart disease patients and its clinical significance

    Institute of Scientific and Technical Information of China (English)

    贾方; 王彦军; 朱琳; 俞天虹; 孙建辉

    2015-01-01

    目的:探讨冠心病患者血清中性粒细胞明胶酶相关脂质运载蛋白(neutrophil gelatinase-associated lipocalin,NGAL)的表达及临床意义.方法:选取因胸闷、胸痛入住心内科患者110例,根据冠脉造影结果及临床表现分为急性冠脉综合征(ACS)组33例、稳定型心绞痛(SAP)组32例和对照组45例.比较3组间的临床资料、血清NGAL水平,分析NGAL与冠心病相关性,并观察其与冠脉病变支数及Gensini积分的关系.结果:ACS组、SAP组血清NGAL水平均明显高于对照组(P<0.05),ACS组血清NGAL水平明显高于SAP组(P<0.05).随着冠脉病变支数增加,冠心病患者血清NGAL水平增高(F=17.468,P<0.05),且与Gensini积分呈正相关(r=0.327,P<0.01).简单及偏相关分析均显示,血清NGAL水平与冠心病呈正相关性;多因素Logistic回归分析显示,NGAL是冠心病发生的独立危险因素(OR=1.059,P<0.01).结论:NGAL不仅能对粥样斑块稳定性具有提示性,且与冠脉病变程度呈正相关,可作为冠心病发生的独立危险因素.

  3. Changes of urinary L-FABP, KIM-1, NGAL and serum cystatin C in diabetic nephropathy and its clinical value%尿L-FABP、KIM-1、NGAL和血清cystatin C在糖尿病肾病中的变化及意义

    Institute of Scientific and Technical Information of China (English)

    梁雅灵; 杨茂君; 李衍辉; 黎秋晗; 黄炜; 徐勇

    2016-01-01

    Objective To investigate the changes of urinary liver-type fatty acid binding protein (L-FABP),kidney injury molecule-1 (KIM-1),neutrophil gelatinase-associated lipocalin (NGAL) and serum cystatin C in diabetic nephropathy and its clinical value.Methods A total of 118 patients diagnosed with type 2 diabetes in the Department of Endocrinology of Affiliated Hospital of Sichuan Medical University from October 2011 to October 2012 were recruited in this study.According to their urinary albumin-to-creatinine ratio(UACR),patients were divided into normal albuminuria group(n =45),microalbuminuria group (n =42),and macroalbuminuria group (n =43).A total of 41 healthy subjects were enrolled as normal control group(n =41).Enzyme-linked immunosorbent assays were used to measure the levels of urinary L-FABP,KIM-1 and NGAL.Turbidimetric inhibition immuno-assay was used to measure the expression of serum cystatin C.All the urinary indicators were adjusted by the level of urine creatinine.Changes of biomarkers in each group and their crrelations between UACR,eGFR were also compared.Results Compared with normal control group,urinary L-FABP and serum cystatin C were significantly increased in diabetic groups (x2 =77.959,104.003,all P < 0.05);urinary KIM-1 was also significantly increased (x2 =29.711,P < 0.05).Urinary NGAL was increased in microalbuminuria group and macroalbuminuria group compared with normal control group and normal albuminuria group(x2 =23.833,P < 0.05),but there were no significant difference between normal albuminuria group and normal control group.Urinary L-FABP,KIM-1,NGAL and serum cystatin C were positively correlated with UACR (r =0.719,0.427,0.327,0.726,all P < 0.01);while L-FABP and serum cystatin C were negatively correlated with eGFR (r =-0.301,-0.791,all P < 0.01).Conclusion Urinary L-FABP,KIM-1,NGAL and serum cystatin C are increased in early diabetic nephropathy,while urinary L-FABP and serum cystatin C may be the better biomarkers to

  4. 尿L-FABP和NGAL在梗阻性肾病所致急性肾损伤诊断及其肾脏预后预测中的价值%Value of urinary L-FABP and NGAL in the diagnosis of acute kidney injury caused by obstructive nephropathy and the prediction of renal outcome

    Institute of Scientific and Technical Information of China (English)

    谢园园; 倪兆慧; 薛蔚; 蒋晨; 徐维佳; 牟姗

    2013-01-01

    目的 探讨尿肝型脂肪酸结合蛋白(uL-FABP)、尿中性粒细胞明胶酶相关脂质运载蛋白(uNGAL)诊断梗阻性肾病所致急性肾损伤(AKI)和预测肾脏预后的价值.方法 前瞻性收集30例梗阻性肾病患者解除梗阻前后不同时相的尿液标本,应用ELISA法检测uL-FABP、uNGAL水平.对不同时相、是否发生AKI等情况进行分析比较.对这2个指标与其他临床指标进行相关分析.随访1年,评估uL-FABP、uNGAL对梗阻性肾病肾脏的预后价值.结果 与非AKI患者相比,AKI患者的uL-FABP和uNGAL水平显著升高[700.00(154.62~1216.14) μg/g·Cr比26.90(16.77~41.38) μg/g·Cr;1266.69(671.57~3396.07) μg/g· Cr比179.12(90.98~215.16) μg/g· Cr,均P<0.01].uL-FABP、uNGAL与Scr呈正相关(r=0.552,0.553,均P< 0.01);两者预测AKI的受试者工作特征(ROC)曲线下面积(AUC)分别为0.925和0.900.随访1年时肾功能未恢复患者各时间点uL-FABP水平均显著高于肾功能恢复组(均P<0.01).术前uL-FABP水平在肾脏预后判断中的AUC为0.948,敏感度为85.7%,特异度为90.9%;术后72 h uL-FABP在肾脏预后判断中的AUC为0.935,敏感度为85.7%,特异度为90.9%.Kaplan-Meier生存曲线分析显示,术前uL-FABP> 366.57 μg/g· Cr或术后72 h uL-FABP>223.60 μg/g· Cr,与不良预后呈明显相关性.结论 uL-FABP、uNGAL对诊断梗阻性肾病所致AKI有较高的准确性.术前及术后72 h uL-FABP有助于判断梗阻性肾病的肾脏预后.%Objective To evaluate the values of urinary liver-fatty acid binding protein (uL-FABP) and urinary neutrophil gelatinase-associated lipocalin (uNGAL) in diagnosis of acute kidney injury (AKI) caused by obstructive nephropathy and in the prediction of renal prognosis.Methods Clinical data of 30 patients with obstructive nephropathy were collected prospectively.uL-FABP and uNGAL were measured by ELISA at various time points.Risk factors of the renal outcome were evaluated.The patients were

  5. Urinary neutrophil gelatinase-associated lipocalin identifies critically ill young children with acute kidney injury following intensive care admission: A prospective cohort study

    NARCIS (Netherlands)

    A.J.M. Zwiers (Alexandra); S.N. de Wildt (Saskia); J.M. van Rosmalen (Joost); Y.B. de Rijke (Yolanda); E.A.B. Buijs (Erik ); D. Tibboel (Dick); K. Cransberg (Karlien)

    2015-01-01

    textabstractIntroduction: Children admitted to a pediatric intensive care unit (ICU) are at high risk of developing acute kidney injury (AKI). Although serum creatinine (SCr) levels are used in clinical practice, they are insensitive for early diagnosis of AKI. Urinary neutrophil gelatinase-associat

  6. Urinary neutrophil gelatinase-associated lipocalin identifies critically ill young children with acute kidney injury following intensive care admission: A prospective cohort study

    NARCIS (Netherlands)

    A.J.M. Zwiers (Alexandra); S.N. de Wildt (Saskia); J.M. van Rosmalen (Joost); Y.B. de Rijke (Yolanda); E.A.B. Buijs (Erik ); D. Tibboel (Dick); K. Cransberg (Karlien)

    2015-01-01

    markdownabstract#### Introduction Children admitted to a pediatric intensive care unit (ICU) are at high risk of developing acute kidney injury (AKI). Although serum creatinine (SCr) levels are used in clinical practice, they are insensitive for early diagnosis of AKI. Urinary neutrophil gelatinase

  7. Venous aneurysm complicating arteriovenous fistula access and matrix metalloproteinases

    Directory of Open Access Journals (Sweden)

    Serra Raffaele

    2015-01-01

    Full Text Available Introduction: An arteriovenous fistula (AVF for placed for hemodialysis may be burdened by one particular complication-the formation of a venous aneurysm. It has been shown that matrix metalloproteinases (MMPs and neutrophil gelatinase-associated lipocalin (NGAL could represent markers of disease in both venous and arterial vessels.

  8. ProHNPs are specific markers of normal myelopoiesis

    DEFF Research Database (Denmark)

    Emmertsen, F; Glenthøj, A; Sønderskov, J;

    2014-01-01

    =16) stem cell transplantations (SCTs) and patients receiving chemotherapy for acute leukemia (n=14). To compare proHNPs with previously suggested myeloid markers, myeloperoxidase (MPO), lysozyme and neutrophil gelatinase-associated lipocalin (NGAL) were also assayed. In all but one patient...

  9. The NGAL Concentration and its Significance in the Urine of Pa-tients with Mercury Poisoning%汞中毒患者尿中性粒细胞明胶酶脂质相关运载蛋白的含量及其意义

    Institute of Scientific and Technical Information of China (English)

    张明香; 王汉斌; 刘晓玲; 熊锡山; 韩博; 孙世惠; 周育森

    2013-01-01

      目的:检测汞中毒患者尿中性粒细胞明胶酶脂质相关运载蛋白(U-NGAL)的含量,探讨其在汞中毒早期肾损伤中的意义。方法:以24例我科收住院患者为汞中毒组、无汞接触史的15例健康成人为对照组,分别进行临床体检并测定尿-N-乙酰-D-葡萄糖苷酶(U-NAG)、24 h尿蛋白定量(UPQ)、尿β2微球蛋白(U-β2-MG)、尿α1微球蛋白(U-α1-MG)、尿汞(U-Hg)、血汞(B-Hg)、血肌酐(Scr)、血尿素氮(BUN),排除既往肾脏病史,ELISA法测定U-NGAL含量,并分析上述结果。结果:汞中毒组B-Hg、U-Hg、U-NAG、UPQ、U-β2-MG、U-α1-MG、U-NGAL与对照组相比均有统计学差异(P<0.05),传统指标Scr、BUN与对照组相比无统计学差异;U-α1-MG、U-β2-MG、U-NAG、UPQ、U-NGAL与B-Hg均有相关性,且相关系数逐渐递增。结论:长期汞接触可造成肾功能损害,U-α1-MG、U-β2-MG、U-NAG、UPQ、U-NGAL可作为汞中毒肾早期损害的敏感指标,且灵敏性依次递增;U-NGAL可能比U-NAG早出现。%  Objective: Detecting the concentration of the urinary neutrophil gelatinase-associated lipocalin (U-NGAL), to explore its significance in the early renal damage of the patients with mercury poisoning. Meth⁃ods: 24 cases inpatient were assigned as the mercury poisoning group, 15 health adults with no mercury exposure history were assigned as the control group, any subjects with history of renal diseases were excluded. The results from physical examinations and measurements of urine-N-acetyl-D-glucosaminidase(U-NAG), 24 h urine protein quantities(UPQ), urinary β2-microglobulin(U-β2-MG), urinary α1-microglobulin(U-α1-MG), urinary mercury (U-Hg), blood mercury(B-Hg), serum creatinine(Scr), blood urea nitrogen(BUN) in all the groups were ana⁃lyzed. Results: The levels of B-Hg, U-Hg, U-NAG, UPQ, U-β2-MG, U-α1-MG and U-NGAL were significantly higher in the mercury poisoning

  10. Evaluation of NGAL TestTM on Cobas 6000

    DEFF Research Database (Denmark)

    Hansen, Young B L; Damgaard, Anette; Poulsen, Jørgen H

    2014-01-01

    analyzed for method, anticoagulant, and freeze-thaw comparisons. Linearity was assessed using high NGAL samples diluted in urine, EDTA, and Li-Hep plasma. Commercial internal controls were used for the imprecision study. RESULTS: The Cobas 6000 measured identically with the Hitachi 917, however...... the Hitachi 917 in EDTA plasma. Though clinically insignificant, we found that the freeze-thaw process had a reduced effect. NGAL results were higher in Li-Hep tubes than in EDTA tubes. Thus, for blood samples we recommend use of EDTA tubes for NGAL measurements....

  11. 血清和尿液NGAL在急、慢性肾损伤中的变化及临床价值%Expression and significance of serum NGAL and urine NGAL in kidney diseases

    Institute of Scientific and Technical Information of China (English)

    赵元明

    2013-01-01

    Objective To investigate the clinical change and significance of neutrophil gelatinasc-associatcd lipocalin (NGAL) in patients with acute and chronic renal damage and the comparison with scrum creatinine (Scr) and glomeru-lar filtration rate(GRF). Methods the NGAL concentration in scrum and urine were detected by ELISA in 95 Acute kidney injury (AKI) patients and 40 primary chronic kidney disease (CKD) patients, 50 healthy subjects as control group. The changes of NGAL in scrum and urine and relationship to glomerular filtration rate (GFR) were analyzed. The scrum and urine NGAL AKI in each group divided by clinical staging criteria were also observed. Results NGAL level in the scrum of the AKI group,CKD group and healthy control group were:678. 6 ± 45. 3 μg/L,374. 5 ± 63. 1 μg/ L,49. 6 ± 8. 3 μg/L;75. 5 ± 10. 2 μg/L,44. 3 ± 9. 8 μg/L,7. 45 ± 0. 66 μg/L in urine. The NGAL in scrum and urine in AKI and CKD group scrum were higher than in control, the differences were statistically significant (P<0. 05) ; NGAL levels in scrum and urine increased accompany with AKI phase,and NGAL levels were negatively correlated with GFR (in scrum:r= —0 867 , P<0. 05 ;in urine:r= —0. 756 , P<0. 05). Conclusion NGAL can be used as indicators of acute kidney injury,and the early and continuous detection of scrum or urine NGAL level in critically ill patients and chronic kidney disease complicated with AKI,have great significance in the understanding of the progress of renal damage and the early development of appropriate intervention measures.%目的 探讨急、慢性肾损伤患者血清和尿液中中性粒细胞明胶酶相关脂质运载蛋白(NGAL)的变化及其临床价值,并与血肌酐(Scr)浓度、肾小球滤过率(GRF)做比较.方法 选择急性肾损伤(AKI)患者95例,原发性慢性肾脏疾病(CKD)患者40例,用ELISA法检测血清和尿液中NGAL的浓度,并与50例健康体检正常者作比较,分析血清和尿液中NGAL的变化以及与肾

  12. Epididymis-specific lipocalin promoters

    Institute of Scientific and Technical Information of China (English)

    Kichiya Suzuki; Xiuping Yu; Pierre Chaurand; Yoshihiko Araki; Jean-Jacques Lareyre; Richard M. Caprioli; Marie-Claire Orgebin-Crist; Robert J. Matusik

    2007-01-01

    Our goal is to decipher which DNA sequences are required for tissue-specific expression of epididymal genes. At least 6 epididymis-specific lipocalin genes are known. These are differently regulated and regionalized in the epididymis.Lipocalin 5 (Lcn5 or mE-RABP) and Lipocalin 8 (Lcn8 or mEP17) are homologous genes belonging to the epididymis-specific lipocalin gene cluster. Both the 5 kb promoter fragment of the Lcn5 gene and the 5.3 kb promoter fragment of the Lcn8 gene can direct transgene expression in the epididymis (Lcn5 to the distal caput and Lcn8 to the initial segment), indicating that these promoter fragments contain important cis-regulatory element(s) for epididymisspecific gene expression. To define further the fragments regulating gene expression, the Lcn5 promoter was examined in transgenic mice and immortalized epididymal cell lines. After serial deletion, the 1.8 kb promoter fragment of the Lcn5 gene was sufficient for tissue-specific and region-specific gene expression in transgenic mice. Transient transfection analysis revealed that a transcription factor forkhead box A2 (Foxa2) interacts with androgen receptor and binds to the 100 bp fragment of the Lcn5 promoter between 1.2 kb and 1.3 kb and that Foxa2 expression inhibitsandrogen-dependent induction of the Lcn5 promoter activity. Immunohistochemistry indicated a restricted expression of Foxa2 in the epididymis where endogenous Lcn5 gene expression is suppressed and that the Foxa2 inhibition of the Lcn5 promoter is consistent with the lack of expression of Lcn5 in the corpus and cauda. Our approach provides a basic strategy for further analysis of the epididymal lipocalin gene regulation and flexible control of epididymal function.

  13. Value of joint detecion of multiple biomarkers on early diagnosis of acute kidney injury in critical patients

    Institute of Scientific and Technical Information of China (English)

    许光银

    2014-01-01

    Objective To assess the value of joint detection of serum cysteine proteinase inhibitors C(sCys-C),urinary kidney injury molecule 1(uKIM-1),urinary neutrophil gelatinase-associated lipocalin(uNGAL)and urinary interleukin 18(uIL-18)for early diagnosis of acute kidney injury(AKI)in critically ill patients.Methods A total of256 adult patients who stayed in Intensive Care Unit for

  14. Prognostic significance of urinary NGAL in chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Patel ML

    2015-10-01

    Full Text Available Munna Lal Patel,1 Rekha Sachan,2 Ravi Misra,3 Ritul Kamal,4 Radhey Shyam,5 Pushpalata Sachan6 1Department of Medicine, King George Medical University, Lucknow, India; 2Department of Obstetrics and Gynaecology, King George Medical University, Lucknow, India; 3Department of Internal Medicine, King George Medical University, Lucknow, India; 4Epidemiology Division, Council of Scientific and Industrial Research-Indian Institute of Toxicology Research (CSIR-IITR, Lucknow, India; 5Department of Geriatric Intensive Care Unit, King George Medical University, Lucknow, India; 6Department of Physiology, Career Institute of Medical Sciences, Lucknow, India Background: Chronic kidney disease (CKD is a worldwide public health problem. Recently urinary NGAL (uNGAL has been proven to be a useful (potentially ideal biomarker for early detection of CKD. The aim of the present study was to examine the correlation of uNGAL with severity of renal impairment in CKD and to evaluate its prognostic value in these subjects. Methods: This was a prospective study carried out over a period of 24 months in subjects with CKD due to primary chronic glomerulonephritis. New cases of CKD stage II, III, IV aged between 18 and 65 years were enrolled as per KDIGO (Kidney Disease: Improving Global Outcomes guidelines 2012. A total of 90 subjects completed the study up to the end-point. The primary follow-up end-point was 18 months, or decreased glomerular filtration rate of less than 15 mL/min. Secondary follow-up end-point was the number of subjects who expired during this period. Results: Multiple regression model of estimated glomerular filtration rate showed significant associations with log uNGAL (β=0.38, P<0.001, Ca×PO4 (β=0.60, P<0.001, hemoglobin (β=0.37, P<0.001, urine protein (β=0.34, P<0.001, serum albumin (β=0.48, P<0.001, and systolic blood pressure (β=0.76, P<0.001. Receiver operator curve for uNGAL considering the progression of CKD showed area under the curve

  15. Siderocalin/Lcn2/NGAL/24p3 does not drive apoptosis through gentisic acid mediated iron withdrawal in hematopoietic cell lines.

    Directory of Open Access Journals (Sweden)

    Colin Correnti

    Full Text Available Siderocalin (also lipocalin 2, NGAL or 24p3 binds iron as complexes with specific siderophores, which are low molecular weight, ferric ion-specific chelators. In innate immunity, siderocalin slows the growth of infecting bacteria by sequestering bacterial ferric siderophores. Siderocalin also binds simple catechols, which can serve as siderophores in the damaged urinary tract. Siderocalin has also been proposed to alter cellular iron trafficking, for instance, driving apoptosis through iron efflux via BOCT. An endogenous siderophore composed of gentisic acid (2,5-dihydroxybenzoic acid substituents was proposed to mediate cellular efflux. However, binding studies reported herein contradict the proposal that gentisic acid forms high-affinity ternary complexes with siderocalin and iron, or that gentisic acid can serve as an endogenous siderophore at neutral pH. We also demonstrate that siderocalin does not induce cellular iron efflux or stimulate apoptosis, questioning the role siderocalin plays in modulating iron metabolism.

  16. Identification, Expression, and Evolutionary Analyses of Plant Lipocalins1[W

    Science.gov (United States)

    Frenette Charron, Jean-Benoit; Ouellet, François; Pelletier, Mélanie; Danyluk, Jean; Chauve, Cédric; Sarhan, Fathey

    2005-01-01

    Lipocalins are a group of proteins that have been characterized in bacteria, invertebrate, and vertebrate animals. However, very little is known about plant lipocalins. We have previously reported the cloning of the first true plant lipocalins. Here we report the identification and characterization of plant lipocalins and lipocalin-like proteins using an integrated approach of data mining, expression studies, cellular localization, and phylogenetic analyses. Plant lipocalins can be classified into two groups, temperature-induced lipocalins (TILs) and chloroplastic lipocalins (CHLs). In addition, violaxanthin de-epoxidases (VDEs) and zeaxanthin epoxidases (ZEPs) can be classified as lipocalin-like proteins. CHLs, VDEs, and ZEPs possess transit peptides that target them to the chloroplast. On the other hand, TILs do not show any targeting peptide, but localization studies revealed that the proteins are found at the plasma membrane. Expression analyses by quantitative real-time PCR showed that expression of the wheat (Triticum aestivum) lipocalins and lipocalin-like proteins is associated with abiotic stress response and is correlated with the plant's capacity to develop freezing tolerance. In support of this correlation, data mining revealed that lipocalins are present in the desiccation-tolerant red algae Porphyra yezoensis and the cryotolerant marine yeast Debaryomyces hansenii, suggesting a possible association with stress-tolerant organisms. Considering the plant lipocalin properties, tissue specificity, response to temperature stress, and their association with chloroplasts and plasma membranes of green leaves, we hypothesize a protective function of the photosynthetic system against temperature stress. Phylogenetic analyses suggest that TIL lipocalin members in higher plants were probably inherited from a bacterial gene present in a primitive unicellular eukaryote. On the other hand, CHLs, VDEs, and ZEPs may have evolved from a cyanobacterial ancestral gene

  17. Identification, expression, and evolutionary analyses of plant lipocalins.

    Science.gov (United States)

    Charron, Jean-Benoit Frenette; Ouellet, François; Pelletier, Mélanie; Danyluk, Jean; Chauve, Cédric; Sarhan, Fathey

    2005-12-01

    Lipocalins are a group of proteins that have been characterized in bacteria, invertebrate, and vertebrate animals. However, very little is known about plant lipocalins. We have previously reported the cloning of the first true plant lipocalins. Here we report the identification and characterization of plant lipocalins and lipocalin-like proteins using an integrated approach of data mining, expression studies, cellular localization, and phylogenetic analyses. Plant lipocalins can be classified into two groups, temperature-induced lipocalins (TILs) and chloroplastic lipocalins (CHLs). In addition, violaxanthin de-epoxidases (VDEs) and zeaxanthin epoxidases (ZEPs) can be classified as lipocalin-like proteins. CHLs, VDEs, and ZEPs possess transit peptides that target them to the chloroplast. On the other hand, TILs do not show any targeting peptide, but localization studies revealed that the proteins are found at the plasma membrane. Expression analyses by quantitative real-time PCR showed that expression of the wheat (Triticum aestivum) lipocalins and lipocalin-like proteins is associated with abiotic stress response and is correlated with the plant's capacity to develop freezing tolerance. In support of this correlation, data mining revealed that lipocalins are present in the desiccation-tolerant red algae Porphyra yezoensis and the cryotolerant marine yeast Debaryomyces hansenii, suggesting a possible association with stress-tolerant organisms. Considering the plant lipocalin properties, tissue specificity, response to temperature stress, and their association with chloroplasts and plasma membranes of green leaves, we hypothesize a protective function of the photosynthetic system against temperature stress. Phylogenetic analyses suggest that TIL lipocalin members in higher plants were probably inherited from a bacterial gene present in a primitive unicellular eukaryote. On the other hand, CHLs, VDEs, and ZEPs may have evolved from a cyanobacterial ancestral gene

  18. A novel lipocalin homologue from the venom gland of Deinagkistrodon acutus similar to mammalian lipocalins

    Directory of Open Access Journals (Sweden)

    CB Wei

    2012-01-01

    Full Text Available Lipocalins are involved in a variety of functions including retinol transport, cryptic coloration, olfaction, pheromone transport, prostaglandin synthesis, regulation of the immune response and cell homeostatic mediation. A full-length cDNA clone (named d-lipo, isolated from the venom gland cDNA library of Deinagkistrodon acutus, contained an insert of 664 bp including an open reading frame that encodes a lipocalin homologue of 177 amino acids. Comparison of d-lipo and other related proteins revealed an overall amino acid identity of less than 21.5%. Primary structures of d-lipo carried three structurally conserved regions (SCR showing homologies to those of lipocalins. The first conserved Cys residue - the essential amino acid residue for the catalytic activity and unique to lipocalin-type prostaglandin D synthase (L-PGDS in the lipocalin protein family - was identified in d-lipo at amino acid position 58. Phylogenetic tree analysis showed that d-lipo was in-between the large L-PGDS cluster and the small von Ebner's-gland proteins (VEGP cluster. Moreover, d-lipo gene presented a high-level expression in the venom gland and a low-level expression in the brain and its expression was significantly increased under pathological conditions, suggesting a possible relationship between d-lipo mRNA expression and the venom gland inflammatory disease. This is also the first report of a lipocalin homologous gene identified in the venom gland of a snake.

  19. Structure-Based Phylogenetic Analysis of the Lipocalin Superfamily.

    Directory of Open Access Journals (Sweden)

    Balasubramanian Lakshmi

    Full Text Available Lipocalins constitute a superfamily of extracellular proteins that are found in all three kingdoms of life. Although very divergent in their sequences and functions, they show remarkable similarity in 3-D structures. Lipocalins bind and transport small hydrophobic molecules. Earlier sequence-based phylogenetic studies of lipocalins highlighted that they have a long evolutionary history. However the molecular and structural basis of their functional diversity is not completely understood. The main objective of the present study is to understand functional diversity of the lipocalins using a structure-based phylogenetic approach. The present study with 39 protein domains from the lipocalin superfamily suggests that the clusters of lipocalins obtained by structure-based phylogeny correspond well with the functional diversity. The detailed analysis on each of the clusters and sub-clusters reveals that the 39 lipocalin domains cluster based on their mode of ligand binding though the clustering was performed on the basis of gross domain structure. The outliers in the phylogenetic tree are often from single member families. Also structure-based phylogenetic approach has provided pointers to assign putative function for the domains of unknown function in lipocalin family. The approach employed in the present study can be used in the future for the functional identification of new lipocalin proteins and may be extended to other protein families where members show poor sequence similarity but high structural similarity.

  20. LCN6, a novel human epididymal lipocalin

    Directory of Open Access Journals (Sweden)

    Soundararajan Rama

    2003-11-01

    Full Text Available Abstract Background The lipocalin (LCN family of structurally conserved hydrophobic ligand binding proteins is represented in all major taxonomic groups from prokaryotes to primates. The importance of lipocalins in reproduction and the similarity to known epididymal lipocalins prompted us to characterize the novel human epididymal LCN6. Methods and Results LCN6 cDNA was identified by database analysis in a comprehensive human library sequencing program. Macaca mulatta (rhesus monkey cDNA was obtained from an epididymis cDNA library and is 93% homologous to the human. The gene is located on chromosome 9q34 adjacent LCN8 and LCN5. LCN6 amino acid sequence is most closely related to LCN5, but the LCN6 beta-barrel structure is best modeled on mouse major urinary protein 1, a pheromone binding protein. Northern blot analysis of RNAs isolated from 25 human tissues revealed predominant expression of a 1.0 kb mRNA in the epididymis. No other transcript was detected except for weak expression of a larger hybridizing mRNA in urinary bladder. Northern hybridization analysis of LCN6 mRNA expression in sham-operated, castrated and testosterone replaced rhesus monkeys suggests mRNA levels are little affected 6 days after castration. Immunohistochemical staining revealed that LCN6 protein is abundant in the caput epithelium and lumen. Immunofluorescent staining of human spermatozoa shows LCN6 located on the head and tail of spermatozoa with the highest concentration of LCN6 on the post-acrosomal region of the head, where it appeared aggregated into large patches. Conclusions LCN6 is a novel lipocalin closely related to Lcn5 and Lcn8 and these three genes are likely products of gene duplication events that predate rodent-primate divergence. Predominant expression in the epididymis and location on sperm surface are consistent with a role for LCN6 in male fertility.

  1. The provision of thromboprophylaxis and the prediction of renal recovery in critically ill patients with acute kidney injury

    DEFF Research Database (Denmark)

    Robinson, Sian; Larsen, Ulla L.; Zincuk, Aleksander

    2015-01-01

    Background: It is unknown whether the dose of enoxaparin can be optimised, without increasing the risk of bleeding, in critically ill patients with acute kidney injury (AKI). Neutrophil gelatinase-associated lipocalin (NGAL) is associated with AKI, and the subsequent need for continuous renal rep...... be able to predict renal recovery in critically ill patients, and allow proper utilization of resources. (EU Clinical Trials Register EudraCT Number: 2012-004368-23; URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2012-004368-23/DK)....

  2. Heart-Kidney Biomarkers in Patients Undergoing Cardiac Stress Testing

    Directory of Open Access Journals (Sweden)

    Mikko Haapio

    2011-01-01

    Full Text Available We examined association of inducible myocardial perfusion defects with cardiorenal biomarkers, and of diminished left ventricular ejection fraction (LVEF with kidney injury marker plasma neutrophil gelatinase-associated lipocalin (NGAL. Patients undergoing nuclear myocardial perfusion stress imaging were divided into 2 groups. Biomarkers were analyzed pre- and poststress testing. Compared to the patients in the low ischemia group (n=16, the patients in the high ischemia group (n=18 demonstrated a significantly greater rise in cardiac biomarkers plasma BNP, NT-proBNP and cTnI. Subjects were also categorized based on pre- or poststress test detectable plasma NGAL. With stress, the group with no detectable NGAL had a segmental defect score 4.2 compared to 8.2 (P=.06 in the detectable NGAL group, and 0.9 vs. 3.8 (P=.03 at rest. BNP rose with stress to a greater degree in patients with detectable NGAL (10.2 vs. 3.5 pg/mL, P=.03. LVEF at rest and with stress was significantly lower in the detectable NGAL group; 55.8 versus 65.0 (P=.03 and 55.1 vs. 63.8 (P=.04, respectively. Myocardial perfusion defects associate with biomarkers of cardiac stress, and detectable plasma NGAL with significantly lower LVEF, suggesting a specific heart-kidney link.

  3. Lipocalin 2 is protective against E. coli pneumonia

    DEFF Research Database (Denmark)

    Wu, Hong; Santoni-Rugiu, Eric; Ralfkiaer, Elisabeth

    2010-01-01

    Lipocalin 2 is a bacteriostatic protein that binds the siderophore enterobactin, an iron-chelating molecule produced by Escherichia coli (E. coli) that is required for bacterial growth. Infection of the lungs by E. coli is rare despite a frequent exposure to this commensal bacterium. Lipocalin 2...... is an effector molecule of the innate immune system and could therefore play a role in hindering growth of E. coli in the lungs....

  4. Molecular and structural analyses of a novel temperature stress-induced lipocalin from wheat and Arabidopsis.

    Science.gov (United States)

    Frenette Charron, Jean Benoit; Breton, Ghislain; Badawi, Mohamed; Sarhan, Fathey

    2002-04-24

    Two cDNAs corresponding to a novel lipocalin were identified from wheat and Arabidopsis. The two cDNAs designated Tatil for Triticum aestivum L. temperature-induced lipocalin and Attil for Arabidopsis thaliana temperature-induced lipocalin encode polypeptides of 190 and 186 amino acids respectively. Structure analyses indicated the presence of the three structurally conserved regions that characterize lipocalins. Sequence analyses revealed that this novel class of plant lipocalin shares homology with three evolutionarily related lipocalins: the mammalian apolipoprotein D (ApoD), the bacterial lipocalin and the insect Lazarillo. The comparison of the putative tertiary structures of both the human ApoD and the wheat TaTIL suggest that the two proteins differ in membrane attachment and ligand interaction. Northern analyses demonstrated that Tatil and Attil transcripts are upregulated during cold acclimation and heat-shock treatment. The putative functions of this novel class of plant lipocalins during temperature stresses are discussed.

  5. Plasma NGAL and glomerular filtration rate in cardiac transplant recipients treated with standard or reduced calcineurin inhibitor levels

    DEFF Research Database (Denmark)

    Gustafsson, Finn; Gude, Einar; Sigurdardottir, Vilborg

    2014-01-01

    GFR) at baseline (R(2) = 0.21; p year (median [25-75 % percentiles]: ΔmGFR 5.5 [-0.5-11.5] vs -1 [-7-4] ml/min/1.73 m(2); p = 0.006). Baseline P-NGAL predicted mGFR after 1 year (R(2) = 0.18; p ...: P-NGAL was measured in 88 cardiac transplantation patients (median 5 years post-transplant) with renal dysfunction randomized to continuation of conventional calcineurin inhibitor-based immunosuppression or switching to an everolimus-based regimen. RESULTS: P-NGAL correlated with measured GFR (m...

  6. Accumulation of 23 kDa lipocalin during brain development and injury in Hyphantria cunea.

    Science.gov (United States)

    Kim, Hong Ja; Je, Hyun Jeong; Cheon, Hyang Mi; Kong, Sun Young; Han, JikHyun; Yun, Chi Young; Han, Yeon Su; Lee, In Hee; Kang, Young Jin; Seo, Sook Jae

    2005-10-01

    The cDNA corresponding to a novel lipocalin was identified from the fall webworm, Hyphantria cunea. This lipocalin cDNA encodes a 194 residue protein with a calculated molecular mass of 23 kDa. Sequence analyses revealed that the 23 kDa lipocalin cDNA is most similar to Drosophila lazarillo, human apolipoprotein D, and Bombyrin. Northern blot analyses showed that 23 kDa lipocalin transcript is expressed in the whole body only in 4- and 6-day-old pupae. By Western blot analysis it was confirmed that 23 kDa lipocalin is mainly accumulated in brain and subesophageal ganglion, though it is detected in a small amount in fat body and epidermis of Hyphantria cunea. The accumulation of 23 kDa lipocalin in brain tissue was upregulated in response to injury. The putative function of 23 kDa lipocalin in brain is discussed.

  7. Role of New Biomarkers: Functional and Structural Damage

    Directory of Open Access Journals (Sweden)

    Evdoxia Tsigou

    2013-01-01

    Full Text Available Traditional diagnosis of acute kidney injury (AKI depends on detection of oliguria and rise of serum creatinine level, which is an unreliable and delayed marker of kidney damage. Delayed diagnosis of AKI in the critically ill patient is related to increased morbidity and mortality, prolonged length of stay, and cost escalation. The discovery of a reliable biomarker for early diagnosis of AKI would be very helpful in facilitating early intervention, evaluating the effectiveness of therapy, and eventually reducing cost and improving outcome. Innovative technologies such as genomics and proteomics have contributed to the discovery of new biomarkers, such as neutrophil gelatinase-associated lipocalin (NGAL, cystatin C (Cys C, kidney injury molecule-1 (KIM-1, interleukin-18 (IL-18, and liver-type fatty acid binding protein (L-FABP. The current status of the most promising of these novel AKI biomarkers, including NGAL, Cys C, KIM-1, L-FABP, and IL-18, is reviewed.

  8. Estimation of tissue and serum lipocalin-2 in psoriasis vulgaris and its relation to metabolic syndrome.

    Science.gov (United States)

    El-Hadidi, H; Samir, N; Shaker, O G; Otb, S

    2014-04-01

    Adipose tissue is now considered an endocrine organ secreting different cytokines known as adipocytokines. Lipocalin-2 has been recently identified as an adipokine present in the circulation, it is related to insulin resistance, obesity, atherosclerotic diseases and type 2 diabetes. Lipocalin-2 and psoriasis are assumed to be closely associated with the metabolic syndrome. The aim of the present study is to estimate the level of lipocalin-2 in the serum and tissue of psoriatic patients and to correlate these levels with markers of metabolic syndrome, CRP and disease severity. This study was done on 30 patients of psoriasis and 30 healthy controls. All patients and controls were subjected to clinical examination. Serum, tissue levels of lipocalin-2 and C-reactive protein (CRP) were measured by enzyme linked immunosorbent assay technique. Metabolic syndrome parameters including anthropometric measures, lipid profiles, blood sugar and blood pressure were studied. Patients with psoriasis showed significant association with metabolic syndrome parameters than controls. Tissue lipocalin-2 was significantly higher than serum levels in psoriasis patients. A significant difference was detected in tissue levels of lipocalin-2 and not in the serum between patients and controls. Both tissue and serum lipocalin-2 correlated with CRP. Although there was a correlation between tissue and serum levels of lipocalin-2 in patients, there was no correlation between both of them with metabolic syndrome and related disorders. Our results revealed that patients with psoriasis are at increased risk of metabolic and cardiovascular complications, tissue lipocalin-2 is more specific to psoriasis than serum lipocalin-2. Lipocalin-2 has no role in determining severity of the disease. Neither tissue nor serum lipocalin-2 conveys cardiovascular risk in psoriasis patients.

  9. Lipocalin 2 is present in the EAE brain and is modulated by natalizumab

    DEFF Research Database (Denmark)

    Marques, Fernanda; Mesquita, Sandro D; Sousa, João C

    2012-01-01

    characterized the transcriptome of the choroid plexus (CP), which is part of the blood-brain barriers (BBBs) and the major site of cerebrospinal fluid production, in the experimental autoimmune encephalomyelitis (EAE) mouse model of MS. In addition, cerebrospinal fluid samples from two cohorts of patients...... for lipocalin 2 was the most up-regulated; notably, the cerebrospinal fluid lipocalin 2 levels coincided with the active phases of the disease. Immunostaining revealed that neutrophils infiltrating the CP were the source of the increased lipocalin 2 expression in this structure. However, within the brain......, lipocalin 2 was also detected in astrocytes, particularly in regions typically affected in patients with MS. The increase of lipocalin 2 in the cerebrospinal fluid and in astrocytes was reverted by natalizumab treatment. Most importantly, the results obtained in the murine model were translatable...

  10. Lipocalin 2, a new GADD153 target gene, as an apoptosis inducer of endoplasmic reticulum stress in lung cancer cells

    Energy Technology Data Exchange (ETDEWEB)

    Hsin, I-Lun; Hsiao, Yueh-Chieh [Institute of Medical and Molecular Toxicology, Chung Shan Medical University, Taichung 40201, Taiwan (China); Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan (China); Wu, Ming-Fang [Division of Chest Medicine, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung 40201, Taiwan (China); School of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan (China); Jan, Ming-Shiou [Institute of Microbiology and Immunology, Chung Shan Medical University, Taichung 40201, Taiwan (China); Tang, Sheau-Chung; Lin, Yu-Wen [Institute of Medical and Molecular Toxicology, Chung Shan Medical University, Taichung 40201, Taiwan (China); Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan (China); Hsu, Chung-Ping, E-mail: cliff@vghtc.com.tw [Department of Thoracic Surgery, Veterans General Hospital—Taichung, Taichung 40705, Taiwan (China); Department of Surgery, National Yang-Ming University School of Medicine and Taipei Veterans General Hospital, Taipei 11221, Taiwan (China); Ko, Jiunn-Liang, E-mail: jlko@csmu.edu.tw [Institute of Medical and Molecular Toxicology, Chung Shan Medical University, Taichung 40201, Taiwan (China); Institute of Medicine, Chung Shan Medical University, Taichung 40201, Taiwan (China); Division of Chest Medicine, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung 40201, Taiwan (China)

    2012-09-15

    Endoplasmic reticulum (ER) stress is activated under severe cellular conditions. GADD153, a member of the C/EBP family, is an unfolded protein response (UPR) responsive transcription factor. Increased levels of lipocalin 2, an acute phase protein, have been found in several epithelial cancers. The aim of this study is to investigate the function of lipocalin 2 in lung cancer cells under ER stress. Treatment with thapsigargin, an ER stress activator, led to increases in cytotoxicity, ER stress, apoptosis, and lipocalin 2 expression in A549 cells. GADD153 silencing decreased lipocalin 2 expression in A549 cells. On chromatin immunoprecipitation assay, ER stress increased GADD153 DNA binding to lipocalin 2 promoter. Furthermore, silencing of lipocalin 2 mitigated ER stress-mediated apoptosis in A549 cells. Our findings demonstrated that lipocalin 2 is a new GADD153 target gene that mediates ER stress-induced apoptosis. Highlights: ► We demonstrate that Lipocalin 2 is a new GADD153 target gene. ► Lipocalin 2 mediates ER stress-induced apoptosis. ► ER stress-induced lipocalin 2 expression is calcium-independent in A549 cells. ► Lipocalin 2 dose not play a major role in ER stress-induced autophagy.

  11. Evaluation of the usefulness of novel biomarkers for drug-induced acute kidney injury in beagle dogs

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Xiaobing [National Center for Safety Evaluation of Drugs, National Institutes for Food and Drug Control, A8 Hongda Middle Street, Beijing Economic-Technological Development Area, Beijing 100176 (China); Graduate School of Peking Union Medical College, Dongcheng District, Beijing, 100730 (China); Ma, Ben; Lin, Zhi; Qu, Zhe; Huo, Yan; Wang, Jufeng [National Center for Safety Evaluation of Drugs, National Institutes for Food and Drug Control, A8 Hongda Middle Street, Beijing Economic-Technological Development Area, Beijing 100176 (China); Li, Bo, E-mail: libo@nifdc.org.cn [National Center for Safety Evaluation of Drugs, National Institutes for Food and Drug Control, A8 Hongda Middle Street, Beijing Economic-Technological Development Area, Beijing 100176 (China); Graduate School of Peking Union Medical College, Dongcheng District, Beijing, 100730 (China)

    2014-10-01

    As kidney is a major target organ affected by drug toxicity, early detection of renal injury is critical in preclinical drug development. In past decades, a series of novel biomarkers of drug-induced nephrotoxicity were discovered and verified in rats. However, limited data regarding the performance of novel biomarkers in non-rodent species are publicly available. To increase the applicability of these biomarkers, we evaluated the performance of 4 urinary biomarkers including neutrophil gelatinase-associated lipocalin (NGAL), clusterin, total protein, and N-acetyl-β-D-glucosaminidase (NAG), relative to histopathology and traditional clinical chemistry in beagle dogs with acute kidney injury (AKI) induced by gentamicin. The results showed that urinary NGAL and clusterin levels were significantly elevated in dogs on days 1 and 3 after administration of gentamicin, respectively. Gene expression analysis further provided mechanistic evidence to support that NGAL and clusterin are potential biomarkers for the early assessment of drug-induced renal damage. Furthermore, the high area (both AUCs = 1.000) under receiver operator characteristics (ROC) curve also indicated that NGAL and clusterin were the most sensitive biomarkers for detection of gentamicin-induced renal proximal tubular toxicity. Our results also suggested that NAG may be used in routine toxicity testing due to its sensitivity and robustness for detection of tissue injury. The present data will provide insights into the preclinical use of these biomarkers for detection of drug-induced AKI in non-rodent species. - Highlights: • Urinary NGAL, clusterin and NAG levels were significantly elevated in canine AKI. • NGAL and clusterin gene expression were increased following treatment with gentamicin. • NGAL and clusterin have high specificity and sensitivity for detection of AKI.

  12. Substrate prediction of Ixodes ricinus salivary lipocalins differentially expressed during Borrelia afzelii infection

    Science.gov (United States)

    Valdés, James J.; Cabezas-Cruz, Alejandro; Sima, Radek; Butterill, Philip T.; Růžek, Daniel; Nuttall, Patricia A.

    2016-09-01

    Evolution has provided ticks with an arsenal of bioactive saliva molecules that counteract host defense mechanisms. This salivary pharmacopoeia enables blood-feeding while enabling pathogen transmission. High-throughput sequencing of tick salivary glands has thus become a major focus, revealing large expansion within protein encoding gene families. Among these are lipocalins, ubiquitous barrel-shaped proteins that sequester small, typically hydrophobic molecules. This study was initiated by mining the Ixodes ricinus salivary gland transcriptome for specific, uncharacterized lipocalins: three were identified. Differential expression of these I. ricinus lipocalins during feeding at distinct developmental stages and in response to Borrelia afzelii infection suggests a role in transmission of this Lyme disease spirochete. A phylogenetic analysis using 803 sequences places the three I. ricinus lipocalins with tick lipocalins that sequester monoamines, leukotrienes and fatty acids. Both structural analysis and biophysical simulations generated robust predictions showing these I. ricinus lipocalins have the potential to bind monoamines similar to other tick species previously reported. The multidisciplinary approach employed in this study characterized unique lipocalins that play a role in tick blood-feeding and transmission of the most important tick-borne pathogen in North America and Eurasia.

  13. Effect of psoriasis activity and topical treatment on serum lipocalin-2 levels.

    Science.gov (United States)

    Baran, A; Świderska, M; Myśliwiec, H; Flisiak, I

    2017-03-01

    Psoriasis has been considered as systemic disorder. Lipocalin-2 might be a link between psoriasis and its comorbidities. Aim of the study was to investigate the associations between serum lipocalin-2 levels and the disease activity, markers of inflammation or metabolic disturbances and changes after topical treatment in psoriatic patients. Thirty-seven individuals with active plaque-type psoriasis and 15 healthy controls were recruited. Blood samples were collected before and after 14 days of therapy. Serum lipocalin-2 concentrations were examined by enzyme-linked immunosorbent assay. The results were correlated with Psoriasis Area and Severity Index (PASI), body mass index (BMI), inflammatory and biochemical markers, lipid profile and with effectiveness of topical treatment. Lipocalin-2 serum levels were significantly increased in psoriatic patients in comparison to the controls (p = 0.023). No significant correlations with indicators of inflammation, nor BMI or PASI were noted. A statistical association between lipocalin-2 and low-density lipoprotein-cholesterol was shown. After topical treatment serum lipocalin-2 level did not significantly change (p = 0.9), still remaining higher than in the controls, despite clinical improvement. Lipocalin-2 might be a marker of psoriasis and convey cardiovascular or metabolic risk in psoriatic patients, but may not be a reliable indicator of inflammation, severity of psoriasis nor efficacy of antipsoriatic treatment.

  14. Evaluation of the usefulness of novel biomarkers for drug-induced acute kidney injury in beagle dogs.

    Science.gov (United States)

    Zhou, Xiaobing; Ma, Ben; Lin, Zhi; Qu, Zhe; Huo, Yan; Wang, Jufeng; Li, Bo

    2014-10-01

    As kidney is a major target organ affected by drug toxicity, early detection of renal injury is critical in preclinical drug development. In past decades, a series of novel biomarkers of drug-induced nephrotoxicity were discovered and verified in rats. However, limited data regarding the performance of novel biomarkers in non-rodent species are publicly available. To increase the applicability of these biomarkers, we evaluated the performance of 4 urinary biomarkers including neutrophil gelatinase-associated lipocalin (NGAL), clusterin, total protein, and N-acetyl-β-D-glucosaminidase (NAG), relative to histopathology and traditional clinical chemistry in beagle dogs with acute kidney injury (AKI) induced by gentamicin. The results showed that urinary NGAL and clusterin levels were significantly elevated in dogs on days 1 and 3 after administration of gentamicin, respectively. Gene expression analysis further provided mechanistic evidence to support that NGAL and clusterin are potential biomarkers for the early assessment of drug-induced renal damage. Furthermore, the high area (both AUCs=1.000) under receiver operator characteristics (ROC) curve also indicated that NGAL and clusterin were the most sensitive biomarkers for detection of gentamicin-induced renal proximal tubular toxicity. Our results also suggested that NAG may be used in routine toxicity testing due to its sensitivity and robustness for detection of tissue injury. The present data will provide insights into the preclinical use of these biomarkers for detection of drug-induced AKI in non-rodent species.

  15. Lazarillo, a neuronal lipocalin in grasshoppers with a role in axon guidance.

    Science.gov (United States)

    Sánchez, D; Ganfornina, M D; Bastiani, M J

    2000-10-18

    In this report we present a review on the grasshopper lipocalin Lazarillo with special emphasis on how its molecular properties could account for its known function: the guidance of pioneer neurons during nervous system development. The expression and function of Lazarillo in a subset of developing neurons, its heavy glycosylation and its glycosylphosphatidylinositol linkage to the plasma membrane, make Lazarillo a unique member of the lipocalin family. We have built a model of the tertiary structure of Lazarillo in which we have studied the exposed surfaces in search for clues about ligand and protein interactions with Lazarillo. Our hypotheses about how this lipocalin can exert its function are discussed.

  16. The cat lipocalin Fel d 7 and its cross-reactivity with the dog lipocalin Can f 1.

    Science.gov (United States)

    Apostolovic, D; Sánchez-Vidaurre, S; Waden, K; Curin, M; Grundström, J; Gafvelin, G; Cirkovic Velickovic, T; Grönlund, H; Thomas, W R; Valenta, R; Hamsten, C; van Hage, M

    2016-10-01

    We investigated the prevalence of sensitization to the cat lipocalin Fel d 7 among 140 cat-sensitized Swedish patients and elucidated its allergenic activity and cross-reactivity with the dog lipocalin Can f 1. Sixty-five of 140 patients had IgE to rFel d 7 whereof 60 also had IgE to rCan f 1. A moderate correlation between IgE levels to rFel d 7 and rCan f 1 was found. rFel d 7 activated basophils in vitro and inhibited IgE binding to rCan f 1 in 4 of 13 patients, whereas rCan f 1 inhibited IgE binding to rFel d 7 in 7 of 13 patients. Fel d 7 and Can f 1 showed high similarities in protein structure and epitopes in common were found using cross-reactive antisera. Fel d 7 is a common allergen in a Swedish cat-sensitized population that cross-reacts with Can f 1, and may contribute to symptoms in cat- but also in dog-allergic patients.

  17. Antibiotic Capture by Bacterial Lipocalins Uncovers an Extracellular Mechanism of Intrinsic Antibiotic Resistance.

    Science.gov (United States)

    El-Halfawy, Omar M; Klett, Javier; Ingram, Rebecca J; Loutet, Slade A; Murphy, Michael E P; Martín-Santamaría, Sonsoles; Valvano, Miguel A

    2017-03-14

    The potential for microbes to overcome antibiotics of different classes before they reach bacterial cells is largely unexplored. Here we show that a soluble bacterial lipocalin produced by Burkholderia cenocepacia upon exposure to sublethal antibiotic concentrations increases resistance to diverse antibiotics in vitro and in vivo These phenotypes were recapitulated by heterologous expression in B. cenocepacia of lipocalin genes from Pseudomonas aeruginosa, Mycobacterium tuberculosis, and methicillin-resistant Staphylococcus aureus Purified lipocalin bound different classes of bactericidal antibiotics and contributed to bacterial survival in vivo Experimental and X-ray crystal structure-guided computational studies revealed that lipocalins counteract antibiotic action by capturing antibiotics in the extracellular space. We also demonstrated that fat-soluble vitamins prevent antibiotic capture by binding bacterial lipocalin with higher affinity than antibiotics. Therefore, bacterial lipocalins contribute to antimicrobial resistance by capturing diverse antibiotics in the extracellular space at the site of infection, which can be counteracted by known vitamins.IMPORTANCE Current research on antibiotic action and resistance focuses on targeting essential functions within bacterial cells. We discovered a previously unrecognized mode of general bacterial antibiotic resistance operating in the extracellular space, which depends on bacterial protein molecules called lipocalins. These molecules are highly conserved in most bacteria and have the ability to capture different classes of antibiotics outside bacterial cells. We also discovered that liposoluble vitamins, such as vitamin E, overcome in vitro and in vivo antibiotic resistance mediated by bacterial lipocalins, providing an unexpected new alternative to combat resistance by using this vitamin or its derivatives as antibiotic adjuvants. Copyright © 2017 El-Halfawy et al.

  18. Urine Levels of Defensin α1 Reflect Kidney Injury in Leptospirosis Patients

    Directory of Open Access Journals (Sweden)

    Haorile Chagan-Yasutan

    2016-09-01

    Full Text Available Leptospirosis is a zoonotic disease whose severe forms are often accompanied by kidney dysfunction. In the present study, urinary markers were studied for potential prediction of disease severity. Urine samples from 135 patients with or without leptospirosis at San Lazaro Hospital, the Philippines, were analyzed. Urine levels of defensin α1 (uDA1 were compared with those of neutrophil gelatinase-associated lipocalin (uNGAL and N-acetyl-β-d-glucosidase (uNAG. Serum creatinine (Cr was used as a marker of kidney injury. The levels of uDA1/Cr, uNGAL/Cr, and uNAG/Cr were positive in 46%, 90%, and 80% of leptospirosis patients, and 69%, 70%, and 70% of non-leptospirosis patients, respectively. In leptospirosis patients, the correlation of uDA1/Cr, uNGAL/Cr and uNAG/Cr levels with serum Cr were r = 0.3 (p < 0.01, r = 0.29 (p < 0.01, and r = 0.02 (p = 0.81, respectively. uDA1/Cr levels were correlated with uNGAL/Cr levels (r = 0.49, p < 0.01 and uNAG/Cr levels (r = 0.47, p < 0.0001 in leptospirosis patients. These findings suggest that uDA1, uNGAL, and uNAG were elevated in leptospirosis patients and reflected various types of kidney damage. uDA1 and uNGAL can be used to track kidney injury in leptospirosis patients because of their correlation with the serum Cr level.

  19. Effect of fluorescein angiography on renal functions in type 2 diabetes patients: A pilot study

    Directory of Open Access Journals (Sweden)

    Waleed H Almalki

    2017-01-01

    Full Text Available Fluorescein angiography (FA is an important tool for the diagnosis and management of diabetic retinopathy. However, the safety of fluorescein sodium on renal functions is not fully understood. One hundred type 2 diabetes patients, within the Ophthalmology Outpatient Clinic at Alexandria Main University Hospital, Egypt, were enrolled in this prospective observational study to determine the safety of FA on renal function. Serum creatinine and cystatin C were measured pre- and 2 days post-FA. Urinary neutrophil gelatinase-associated lipocalin (uNGAL was measured pre- and 4 hours post-FA. Renal injury was defined as a 25% increase in serum creatinine, cystatin C, or uNGAL. The study included 71 females and 29 males, with a mean age of 55.73 ± 7.29 years. Baseline serum cystatin C and uNGAL were 0.89 ± 0.34 mg/L and 21.7 ± 2.39 ng/mL, respectively. Serum cystatin C and uNGAL significantly increased after FA to 0.95 ± 0.36 and 27 ± 2.81, respectively (P <0.001. Eleven patients (11% experienced more than a 25% rise in serum cystatin C from baseline, whereas 40 patients (40% experienced more than a 25% increase in uNGAL levels after FA. However, the mean serum creatinine level did not change significantly after FA (P = 0.061. Only one patient experienced more than a 25% rise in serum creatinine from baseline. FA showed a significant increase in early sensitive acute kidney injury biomarkers (as serum cystatin C and uNGAL in substantial number of patients, suggesting but still not proving, a potential harmful effect of FA on kidney functions. These findings were not demonstrated using ordinary serum creatinine.

  20. Urinary levels of early kidney injury molecules in children with vitamin B12 deficiency.

    Science.gov (United States)

    Güneş, Ali; Aktar, Fesih; Tan, İlhan; Söker, Murat; Uluca, Ünal; Balık, Hasan; Mete, Nuriye

    2016-10-01

    The aim of this study was to investigate urine early kidney injury molecules, including human kidney injury molecule-1 (KIM-1), liver-type fatty-acid binding protein (L-FABP), N-acetyl-b-D-glucosaminidase A (NAG), and neutrophil gelatinase-associated lipocalin (NGAL) in children with vitamin B12 (cobalamin) deficiency (CD). Twelve children with vitamin B12 deficiency and 20 healthy matched controls were included. Hematologic parameters, serum urea, creatinine (Cr), electrolytes, B12 and folate levels were recorded. Estimated glomerular filtration rate (eGFR) was calculated. Urine protein, electrolytes, andurinary early markers were measured. Patients with CD had significantly higher urine electrolyte/Cr ratios (p B12 and urinary markers in the patients (p B12 deficiency suggest a possible subclinical renal dysfunction, which cannot be determined by conventional kidney function tests.

  1. Tubular markers do not predict the decline in glomerular filtration rate in type 1 diabetic patients with overt nephropathy

    DEFF Research Database (Denmark)

    Nielsen, Stine E; Andersen, Steen; Zdunek, Dietmar

    2011-01-01

    Recent studies have shown that both glomerular and tubulointerstitial damage are important factors in the pathophysiology and progression of diabetic nephropathy. To examine whether markers of tubular damage are useful in monitoring the progression of disease, we measured urinary levels...... associated with a faster decline in GFR, but not after adjustment for known promoters of progression. Urinary LFABP was not related to decline in GFR. Losartan treatment (100 mg/day) reduced urinary KIM-1 by 43% over a 12-month period. Thus, urine biomarker measurements in patients with type 1 diabetic...... of neutrophil gelatinase-associated lipocalin (NGAL), liver-fatty acid-binding protein (LFABP), and kidney injury molecule-1 (KIM-1) in a 3-year intervention study of 63 type 1 diabetic patients with kidney disease. The baseline mean glomerular filtration rate (GFR) was 87 ml/min per 1.73 m(2) and urinary...

  2. Sphingosine-1-phosphate signalling induces the production of Lcn-2 by macrophages to promote kidney regeneration

    DEFF Research Database (Denmark)

    Sola, Anna; Weigert, Andreas; Jung, Michaela;

    2011-01-01

    the kidney. The present study describes a mechanism for renal tissue regeneration after ischaemia/reperfusion injury. Following injury, apoptotic cell-derived sphingosine-1-phosphate (S1P) or exogenously administered sphingosine analogue FTY720 activates macrophages to support the proliferation and healing......Inflammatory reactions are initiated to eliminate pathogens, but also to promote repair of damaged tissue after acute inflammation is terminated. In this regard, macrophages play a prominent role during induction as well as resolution of inflammation and injury in various organs including...... of renal epithelium, once inflammatory conditions are terminated. Both suppression of inflammation and renal regeneration might require S1P receptor 3 (S1P3) signalling and downstream release of neutrophil gelatinase-associated lipocalin (NGAL/Lcn-2) from macrophages. Overall, our data point...

  3. Distantly related lipocalins share two conserved clusters of hydrophobic residues: use in homology modeling

    Directory of Open Access Journals (Sweden)

    Brasseur Robert

    2008-01-01

    Full Text Available Abstract Background Lipocalins are widely distributed in nature and are found in bacteria, plants, arthropoda and vertebra. In hematophagous arthropods, they are implicated in the successful accomplishment of the blood meal, interfering with platelet aggregation, blood coagulation and inflammation and in the transmission of disease parasites such as Trypanosoma cruzi and Borrelia burgdorferi. The pairwise sequence identity is low among this family, often below 30%, despite a well conserved tertiary structure. Under the 30% identity threshold, alignment methods do not correctly assign and align proteins. The only safe way to assign a sequence to that family is by experimental determination. However, these procedures are long and costly and cannot always be applied. A way to circumvent the experimental approach is sequence and structure analyze. To further help in that task, the residues implicated in the stabilisation of the lipocalin fold were determined. This was done by analyzing the conserved interactions for ten lipocalins having a maximum pairwise identity of 28% and various functions. Results It was determined that two hydrophobic clusters of residues are conserved by analysing the ten lipocalin structures and sequences. One cluster is internal to the barrel, involving all strands and the 310 helix. The other is external, involving four strands and the helix lying parallel to the barrel surface. These clusters are also present in RaHBP2, a unusual "outlier" lipocalin from tick Rhipicephalus appendiculatus. This information was used to assess assignment of LIR2 a protein from Ixodes ricinus and to build a 3D model that helps to predict function. FTIR data support the lipocalin fold for this protein. Conclusion By sequence and structural analyzes, two conserved clusters of hydrophobic residues in interactions have been identified in lipocalins. Since the residues implicated are not conserved for function, they should provide the minimal

  4. Characterization of two novel lipocalins expressed in the Drosophila embryonic nervous system.

    Science.gov (United States)

    Sánchez, D; Ganfornina, M D; Torres-Schumann, S; Speese, S D; Lora, J M; Bastiani, M J

    2000-06-01

    We have found two novel lipocalins in the fruit fly Drosophila melanogaster that are homologous to the grasshopper Lazarillo, a singular lipocalin within this protein family which functions in axon guidance during nervous system development. Sequence analysis suggests that the two Drosophila proteins are secreted and possess peptide regions unique in the lipocalin family. The mRNAs of DNLaz (for Drosophila neural Lazarillo) and DGLaz (for Drosophila glial Lazarillo) are expressed with different temporal patterns during embryogenesis. They show low levels of larval expression and are highly expressed in pupa and adult flies. DNLaz mRNA is transcribed in a subset of neurons and neuronal precursors in the embryonic CNS. DGLaz mRNA is found in a subset of glial cells of the CNS: the longitudinal glia and the medial cell body glia. Both lipocalins are also expressed outside the nervous system in the developing gut, fat body and amnioserosa. The DNLaz protein is detected in a subset of axons in the developing CNS. Treatment with a secretion blocker enhances the antibody labeling, indicating the DNLaz secreted nature. These findings make the embryonic nervous system expression of lipocalins a feature more widespread than previously thought. We propose that DNLaz and DGLaz may have a role in axonal outgrowth and pathfinding, although other putative functions are also discussed.

  5. Down-Regulation of Lipocalin 2 Expression in Mouse Testis after Exposure to Electromagnetic Field

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    Amaneh Mohammadi Roushandeh

    2009-12-01

    Full Text Available Background: The effects of electromagnetic field (EMF onreproductive system have been of critical concern for a longtime. It has been shown that the EMF can adversely affect testicularcells and tissue and decrease male fertility. The mostimportant determinants of male fertility are sperm developmentand motility, which are affected by changes in several factorsincluding lipocalin 2 proteins. In the present study, we investigatedthe effects of exposure to EMF on testis tissue and expressionof lipocalin 2 gene.Methods: Male BALB/c mice (8 weeks old were exposed to 3mT EMF for 8 weeks, 4 hours/day. Control group (10 micedid not receive EMF exposure. After the experimental period,the mice were sacrificed, and their testis tissues were examinedby using light microscopy after hematoxylin-eosin staining.Additionally, total RNA and proteins were extracted from testistissue and used to study the lipocalin 2 expression by realtime RT-PCR and Western blot analysis.Results: The histological changes observed in the testes of experimentalgroup included increased number of spermatocytesand Leydig cells, and increased thickness of basement membranecompared with the control group. The mRNA and proteinstudies showed that expression of lipocalin 2 gene wasdown regulated in testes of the mice exposed to EMF.Conclusion: Our study showed that EMF down regulates theexpression of lipocalin 2, a cytoprotective molecule, in testis tissue.This down regulation can be one of the mechanisms that contributeto the decreased fertility observed after exposure to EMF

  6. Graphene-based immunoassay for human lipocalin-2.

    Science.gov (United States)

    Vashist, Sandeep Kumar

    2014-02-01

    We have developed a highly sensitive immunoassay using graphene nano platelets (GNPs) for the rapid detection of human lipocalin-2 (LCN2) in plasma, serum, and whole blood. It has the dynamic range, linear range, limit of detection, and analytical sensitivity of 0.6 to 5120, 80 to 2560, 0.7, and 1pg/ml, respectively. It is the most sensitive assay for the detection of LCN2, which has 80-fold higher analytical sensitivity and 3-fold lesser immunoassay duration than the commercially available sandwich enzyme-linked immunosorbent assay (ELISA) kit. The functionalization of microtiter plate (MTP) with GNPs, dispersed in 3-aminopropyltriethoxysilane (APTES), provided the increased surface area that leads to higher immobilization density of capture antibodies. Moreover, the generation of free amino groups on MTP and GNPs by APTES enables the leach-proof covalent crosslinking of anti-human LCN2 capture antibody by its carboxyl groups using 1-ethyl-3-[3-dimethylaminopropyl]carbodiimide hydrochloride (EDC) as the heterobifunctional crosslinker. The anti-LCN2 antibody-bound MTPs were highly stable given that they did not show any significant decrease in their functional activity when stored at 4°C in 0.1M phosphate-buffered saline (PBS) for 8weeks. The developed immunoassay correlated well with the conventional ELISA, thereby demonstrating its high precision and potential utility for highly sensitive analyte detection in industrial and clinical settings.

  7. Lipocalin-2 protects the brain during inflammatory conditions.

    Science.gov (United States)

    Kang, S S; Ren, Y; Liu, C-C; Kurti, A; Baker, K E; Bu, G; Asmann, Y; Fryer, J D

    2017-01-10

    Sepsis is a prevalent health issue that can lead to central nervous system (CNS) inflammation with long-term behavioral and cognitive alterations. Using unbiased proteomic profiling of over 100 different cytokines, we found that Lipocalin-2 (LCN2) was the most substantially elevated protein in the CNS after peripheral administration of lipopolysaccharide (LPS). To determine whether the high level of LCN2 in the CNS is protective or deleterious, we challenged Lcn2(-/-) mice with peripheral LPS and determined effects on behavior and neuroinflammation. At a time corresponding to peak LCN2 induction in wild-type (WT) mice injected with LPS, Lcn2(-/-) mice challenged with LPS had exacerbated levels of pro-inflammatory cytokines and exhibited significantly worsened behavioral phenotypes. To determine the extent of global inflammatory changes dependent upon LCN2, we performed an RNAseq transcriptomic analysis. Compared with WT mice injected with LPS, Lcn2(-/-) mice injected with LPS had unique transcriptional profiles and significantly elevated levels of multiple pro-inflammatory molecules. Several LCN2-dependent pathways were revealed with this analysis including, cytokine and chemokine signaling, nucleotide-binding oligomerization domain-like receptor signaling and Janus kinase-signal transducer and activator of transcription signaling. These findings demonstrate that LCN2 serves as a potent protective factor in the CNS in response to systemic inflammation and may be a potential candidate for limiting sepsis-related CNS sequelae.Molecular Psychiatry advance online publication, 10 January 2017; doi:10.1038/mp.2016.243.

  8. Lipocalin signaling controls unicellular tube development in the Caenorhabditis elegans excretory system.

    Science.gov (United States)

    Stone, Craig E; Hall, David H; Sundaram, Meera V

    2009-05-15

    Unicellular tubes or capillaries composed of individual cells with a hollow lumen perform important physiological functions including fluid or gas transport and exchange. These tubes are thought to build intracellular lumina by polarized trafficking of apical membrane components, but the molecular signals that promote luminal growth and luminal connectivity between cells are poorly understood. Here we show that the lipocalin LPR-1 is required for luminal connectivity between two unicellular tubes in the Caenorhabditis elegans excretory (renal) system, the excretory duct cell and pore cell. Lipocalins are a large family of secreted proteins that transport lipophilic cargos and participate in intercellular signaling. lpr-1 is required at a time of rapid luminal growth, it is expressed by the duct, pore and surrounding cells, and it can function cell non-autonomously. These results reveal a novel signaling mechanism that controls unicellular tube formation, and provide a genetic model system for dissecting lipocalin signaling pathways.

  9. 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.

  10. Impact of Iodinated Contrast on Renal Function and Hemodynamics in Rats with Chronic Hyperglycemia and Chronic Kidney Disease.

    Science.gov (United States)

    Fernandes, Sheila Marques; Martins, Daniel Malisani; da Fonseca, Cassiane Dezoti; Watanabe, Mirian; Vattimo, Maria de Fátima Fernandes

    2016-01-01

    Iodinated contrast (IC) is clinically used in diagnostic and interventional procedures, but its use can result in contrast-induced acute kidney injury (CI-AKI). Chronic kidney disease (CKD) and chronic hyperglycemia (CH) are important predisposing factors to CI-AKI. The aim of this study was to investigate the impact of iodinated contrast on the renal function and hemodynamics in rats with chronic hyperglycemia and chronic kidney disease. A total of 30 rats were divided into six groups; Sham: control of chronic renal disease; Citrate: control of chronic hyperglycemia (CH); Nx5/6: rats with 5/6 nephrectomy; Chronic Hyperglycemia: rats receiving Streptozotocin 65 mg/kg; Nx5/6 + IC: rats Nx5/6 received 6 mL/kg of IC; CH + IC: Chronic hyperglycemia rats receiving 6 mL/kg of IC. Renal function (inulin clearance; urinary neutrophil gelatinase-associated lipocalin, NGAL) and hemodynamics (arterial blood pressure; renal blood flow; renal vascular resistance) were evaluated. Iodinated contrast significantly increased urinary NGAL and reduced inulin clearance, while the hemodynamics parameters showed changes in arterial blood pressure, renal blood flow, and renal vascular resistance in both CKD and CH groups. The results suggest that the iodinated contrast in risk factors models has important impact on renal function and hemodynamics. NGAL was confirmed to play a role of highlight in diagnosis of CI-AKI.

  11. Effect on renal function of an iso-osmolar contrast agent in patients with monoclonal gammopathies

    Energy Technology Data Exchange (ETDEWEB)

    Preda, Lorenzo [Division of Radiology, European Institute of Oncology, IRCCS, Milan (Italy); Agazzi, Alberto; Martinelli, Giovanni [Division of Haematology, European Institute of Oncology, IRCCS, Milan (Italy); Raimondi, Sara [Division of Epidemiology and Biostatistics, European Institute of Oncology, IRCCS, Milan (Italy); University of Milan, Department of Occupational Medicin ' ' Clinica del Lavoro Luigi Devoto' ' Section of Medical Statistics and Biometry ' ' GA Maccacaro' ' , Milan (Italy); Lanfranchi, Carla Federica [University of Milan, IRCCS, School of Medicine, Milan (Italy); Passerini, Rita [Unit of Laboratory Medicine, European Institute of Oncology, IRCCS, Milan (Italy); Calvetta, Albania [Nephrology and Dialysis Unit, Istituto Clinico Humanitas, IRCCS, Rozzano, Milan (Italy); Bellomi, Massimo [Division of Radiology, European Institute of Oncology, IRCCS, Milan (Italy); University of Milan, IRCCS, School of Medicine, Milan (Italy)

    2011-01-15

    To assess the safety of the non-ionic iso-osmolar contrast agent iodixanol on renal function in patients with monoclonal gammopathies undergoing CT. We explored the effect of iodixanol on renal function in 30 patients with monoclonal gammopathies and 20 oncological patients with a normal electrophoretic profile (control group). The parameters used to estimate renal function were: serum creatinine, eGFR (determined 24 h before and 48 h after the administration of iodixanol), and urinary excretion of Neutrophil Gelatinase-Associated Lipocalin (NGAL) determined 2 h and 24 h after. Serum creatinine was also determined 1 month after the administration of iodixanol. No significant increase in serum creatinine values were observed in the monoclonal gammopathies group and in 19/20 patients in the control group. Only 1 patient in the control group developed a transient contrast agent-induced nephropathy. We found no statistically significant difference between the two groups regarding the percentage variation from baseline values of serum creatinine, creatinine clearance, NGAL 2 h after, and eGFR. Whereas NGAL at 24 h showed a statistically significant increase in patients with Monoclonal gammopathies. The use of iodixanol appears to be safe in patients with monoclonal gammopathies and an eGFR {>=} 60 ml/min/1.73 mq. (orig.)

  12. Early Biomarkers of Renal Damage in Relation to Arterial Stiffness and Inflammation in Male Coronary Artery Disease Patients

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    Kaido Paapstel

    2016-07-01

    Full Text Available Background/Aims: Plasma neutrophil gelatinase-associated lipocalin (NGAL, urinary liver-type fatty acid-binding protein (L-FABP and urinary kidney injury molecule-1 (KIM-1 have emerged as promising biomarkers for both acute and chronic kidney injury that also provide prognostic value for cardiovascular morbidity and mortality. Our aim was to evaluate their relationships with arterial stiffness and inflammation in coronary artery disease (CAD patients and in clinically healthy controls. Methods: We studied 52 patients with CAD (age 63.2 ± 9.2 years and 41 healthy controls (age 60.1 ± 7.2 years. Urinary L-FABP and KIM-1 as well as serum NGAL, adiponectin and resistin levels were measured using the enzyme-linked immunosorbent assay method. The technique of applanation tonometry was used for non-invasive pulse wave analysis and pulse wave velocity assessments. Results: Urinary L-FABP and KIM-1 were independent determinants of cf-PWV for the CAD patients (R2=0.584, Pr=0.31, P=0.028 only for the patients, while NGAL correlated with WBC count (rho=0.29, P=0.038; r=0.35, P=0.029 and resistin (rho=0.60, PConclusion: Our findings suggest that urinary L-FABP and KIM-1 may be independently associated with aortic stiffness in individuals with CAD.

  13. Rosiglitazone Did Not Induce Acute Kidney Injury in Normocholesterolemic Rats Despite Reduction in Glomerular Filtration Rate

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    Cristiano Dias

    2014-04-01

    Full Text Available Background/Aims: Rosiglitazone (RGL has been used to ameliorate lipids homeostasis and also to treat inflammatory diseases. However, RGL may reduce renal blood flow and glomerular filtration rate (GFR predisposing to acute kidney injury (AKI. We investigated whether the treatment with RGL induces AKI in normocholesterolemic (NC and hypercholesterolemic (HC rats. Methods: We measured GFR by inulin clearance technique and we quantified urinary neutrophil gelatinase-associated lipocalin (uNGAL in all groups at baseline and during Ang II-stimulated vasoconstriction. Moreover, we evaluated the presence of renal damaged by histologic examination. Results: At baseline, NC and HC had normal and similar GFR. RGL treatment reduced GFR only in NC+RGL. Unexpectedly, HC+RGL showed high levels of uNGAL although GFR was at normal range. During Ang II-stimulated vasoconstriction, all groups showed reduction in GFR to the same range and we found high levels of uNGAL and high score of renal damage in HC and HC+RGL. Conclusion: RGL acts distinctly in normocholesterolemia and in hypercholesterolemia. Reduction in GFR provoked by RGL treatment did not allow the diagnosis of AKI in NC even in the presence of ANG II-stimulated vasoconstriction. However, AKI was diagnosed in HC+RGL at baseline although GFR was within normal range.

  14. Lipocalins Are Required for Apical Extracellular Matrix Organization and Remodeling in Caenorhabiditis elegans.

    Science.gov (United States)

    Forman-Rubinsky, Rachel; Cohen, Jennifer D; Sundaram, Meera V

    2017-08-25

    A lipid and glycoprotein-rich apical extracellular matrix (aECM) or glycocalyx lines exposed membranes in the body, and is particularly important to protect narrow tube integrity. Lipocalins ("fat cups") are small, secreted, cup-shaped proteins that bind and transport lipophilic cargo and are often found in luminal or aECM compartments such as mammalian plasma, urine, or tear film. Although some lipocalins can bind known aECM lipids and/or matrix metalloproteinases, it is not known if and how lipocalins affect aECM structure due to challenges in visualizing the aECM in most systems. Here we show that two C. elegans lipocalins, LPR-1 and LPR-3, have distinct functions in the pre-cuticular glycocalyx of developing external epithelia. LPR-1 moves freely through luminal compartments, while LPR-3 stably localizes to a central layer of the membrane-anchored glycocalyx, adjacent to the transient zona pellucida domain protein LET-653. Like LET-653 and other C. elegans glycocalyx components, these lipocalins are required to maintain the patency of the narrow excretory duct tube, and also affect multiple aspects of later cuticle organization. lpr-1 mutants cannot maintain a continuous excretory duct apical domain and have misshapen cuticle ridges (alae) and abnormal patterns of cuticular surface lipid staining. lpr-3 mutants cannot maintain a passable excretory duct lumen, properly degrade the eggshell, or shed old cuticle during molting, and they lack cuticle barrier function. Based on these phenotypes, we infer that both LPR-1 and LPR-3 are required to build a properly organized aECM, while LPR-3 additionally is needed for aECM clearance and remodeling. The C. elegans glycocalyx provides a powerful system, amenable to both genetic analysis and live imaging, for investigating how lipocalins and lipids impact aECM structure. Copyright © 2017, Genetics.

  15. Mammal-derived respiratory lipocalin allergens do not exhibit dendritic cell-activating capacity.

    Science.gov (United States)

    Parviainen, S; Kinnunen, T; Rytkönen-Nissinen, M; Nieminen, A; Liukko, A; Virtanen, T

    2013-03-01

    Most mammal-derived respiratory allergens belong to the lipocalin family of proteins. Determinants of their allergenic capacity are still unknown. Innate immune cells, in particular dendritic cells, have been shown to be involved in the allergenicity of some proteins. As recognition by dendritic cells is one of the few plausible mechanisms for the allergenicity of proteins, we wanted to investigate their role in the allergenicity of lipocalin allergens. Therefore, we first incubated human monocyte-derived dendritic cells with immunologically functional recombinant allergens mouse Mus m 1, dog Can f 1 and 2, cow Bos d 2, horse Equ c 1 and natural Bos d 2. Then, the surface marker expression and cytokine production of dendritic cells and their capacity to promote T cell proliferation and Th2 immune deviation in naïve CD4(+) T cells were examined in vitro. We found that near to endotoxin-free lipocalin allergens had no effect on the activation, allostimulatory capacity or cytokine production of dendritic cells. The dendritic cells could not induce immune deviation in naïve CD4(+) T cells. In contrast, lipopolysaccharide activated the dendritic cells efficiently. However, lipocalin allergens were not able to modify the lipopolysaccharide-induced responses. We conclude that an important group of mammal-derived respiratory allergens, lipocalins, appear not to be able to activate dendritic cells, a major component involved in the allergenicity of some proteins. It is conceivable that this incapacity of lipocalin allergens to arouse innate immunity may be associated with their poor capacity to induce a strong T cell response, verified in several studies.

  16. Lipocalin-2 Deficiency Attenuates Insulin Resistance Associated With Aging and Obesity

    Science.gov (United States)

    Law, Ivy K.M.; Xu, Aimin; Lam, Karen S.L.; Berger, Thorsten; Mak, Tak W.; Vanhoutte, Paul M.; Liu, Jacky T.C.; Sweeney, Gary; Zhou, Mingyan; Yang, Bo; Wang, Yu

    2010-01-01

    OBJECTIVE The proinflammatory cytokines/adipokines produced from adipose tissue act in an autocrine and/or endocrine manner to perpetuate local inflammation and to induce peripheral insulin resistance. The present study investigates whether lipocalin-2 deficiency or replenishment with this adipokine has any impact on systemic insulin sensitivity and the underlying mechanisms. METHODS AND RESULTS Under conditions of aging or dietary-/genetic-induced obesity, lipocalin-2 knockout (Lcn2-KO) mice show significantly decreased fasting glucose and insulin levels and improved insulin sensitivity compared with their wild-type littermates. Despite enlarged fat mass, inflammation and the accumulation of lipid peroxidation products are significantly attenuated in the adipose tissues of Lcn2-KO mice. Adipose fatty acid composition of these mice varies significantly from that in wild-type animals. The amounts of arachidonic acid (C20:4 n6) are elevated by aging and obesity and are paradoxically further increased in adipose tissue, but not skeletal muscle and liver of Lcn2-KO mice. On the other hand, the expression and activity of 12-lipoxygenase, an enzyme responsible for metabolizing arachidonic acid, and the production of tumor necrosis factor-α (TNF-α), a critical insulin resistance–inducing factor, are largely inhibited by lipocalin-2 deficiency. Lipocalin-2 stimulates the expression and activity of 12-lipoxygenase and TNF-α production in fat tissues. Cinnamyl-3,4-dihydroxy-α-cyanocinnamate (CDC), an arachidonate lipoxygenase inhibitor, prevents TNF-α expression induced by lipocalin-2. Moreover, treatment with TNF-α neutralization antibody or CDC significantly attenuated the differences of insulin sensitivity between wild-type and Lcn2-KO mice. CONCLUSIONS Lipocalin-2 deficiency protects mice from developing aging- and obesity-induced insulin resistance largely by modulating 12-lipoxygenase and TNF-α levels in adipose tissue. PMID:20068130

  17. Lipocalin 2: a new mechanoresponding gene regulating bone homeostasis.

    Science.gov (United States)

    Rucci, Nadia; Capulli, Mattia; Piperni, Sara Gemini; Cappariello, Alfredo; Lau, Patrick; Frings-Meuthen, Petra; Heer, Martina; Teti, Anna

    2015-02-01

    Mechanical loading represents a crucial factor in the regulation of skeletal homeostasis. Its reduction causes loss of bone mass, eventually leading to osteoporosis. In a previous global transcriptome analysis performed in mouse calvarial osteoblasts subjected to simulated microgravity, the most upregulated gene compared to unit gravity condition was Lcn2, encoding the adipokine Lipocalin 2 (LCN2), whose function in bone metabolism is poorly known. To investigate the mechanoresponding properties of LCN2, we evaluated LCN2 levels in sera of healthy volunteers subjected to bed rest, and found a significant time-dependent increase of this adipokine compared to time 0. We then evaluated the in vivo LCN2 regulation in mice subjected to experimentally-induced mechanical unloading by (1) tail suspension, (2) muscle paralysis by botulin toxin A (Botox), or (3) genetically-induced muscular dystrophy (MDX mice), and observed that Lcn2 expression was upregulated in the long bones of all of them, whereas physical exercise counteracted this increase. Mechanistically, in primary osteoblasts transfected with LCN2-expression-vector (OBs-Lcn2) we observed that Runx2 and its downstream genes, Osterix and Alp, were transcriptionally downregulated, and alkaline phosphatase (ALP) activity was less prominent versus empty-vector transduced osteoblasts (OBs-empty). OBs-Lcn2 also exhibited an increase of the Rankl/Opg ratio and IL-6 mRNA, suggesting that LCN2 could link poor differentiation of osteoblasts to enhanced osteoclast stimulation. In fact, incubation of purified mouse bone marrow mononuclear cells with conditioned media from OBs-Lcn2 cultures, or their coculture with OBs-Lcn2, improved osteoclastogenesis compared to OBs-empty, whereas treatment with recombinant LCN2 had no effect. In conclusion, our data indicate that LCN2 is a novel osteoblast mechanoresponding gene and that its regulation could be central to the pathological response of the bone tissue to low mechanical forces

  18. Molecular interactions of the neuronal GPI-anchored lipocalin Lazarillo.

    Science.gov (United States)

    Sanchez, Diego; Ortega-Cubero, Sara; Akerström, Bo; Herrera, Macarena; Bastiani, Michael J; Ganfornina, Maria D

    2008-01-01

    Lazarillo, a glycoprotein involved in axon growth and guidance in the grasshopper embryo, is the only member of the lipocalin family that is attached to the cell surface by a GPI anchor. Recently, the study of Lazarillo homologous genes in Drosophila and mouse has revealed new functions in the regulation of lifespan, stress resistance and neurodegeneration. Here we report an analysis of biochemical properties of Lazarillo to gain insight into the molecular basis of its physiological function. Recombinant forms of the grasshopper protein were expressed in two different systems to test: (1) potential binding of several hydrophobic ligands; (2) protein-protein homophilic interactions; and (3) whether interaction with the function-blocking mAb 10E6 interferes with ligand binding. We tested 10 candidate ligands (retinoic acid, heme, bilirubin, biliverdin, ecdysterone, juvenile hormone, farnesol, arachidonic acid, linoleic acid and palmitic acid), and monitored binding using electrophoretic mobility shift, absorbance spectrum, and fluorimetry assays. Our work indicates binding to heme and retinoic acid, resulting in increased electrophoretic mobility, as well as to fatty acids, resulting in multimerization. Retinoic acid and fatty acids binding were confirmed by fluorescence titration, and heme binding was confirmed with absorbance spectrum assays. We demonstrate that Lazarillo oligomerizes in solution and can form clusters in the plasma membrane when expressed and GPI-anchored to the cell surface, however it is unable to mediate cell-cell adhesion. Finally, by ligand-mAb competition experiments we show that ligand-binding alone cannot be the key factor for Lazarillo to perform its function during axonal growth in the grasshopper embryo.

  19. Lipocalin-7 is a matricellular regulator of angiogenesis.

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    Leslie J Brown

    Full Text Available BACKGROUND: Matricellular proteins are extracellular regulators of cellular adhesion, signaling and performing a variety of physiological behaviors such as proliferation, migration and differentiation. Within vascular microenvironments, matricellular proteins exert both positive and negative regulatory cues to vascular endothelium. The relative balance of these matricellular cues is believed to be critical for vascular homeostasis, angiogenesis activation or angiogenesis resolution. However, our knowledge of matricellular proteins within vascular microenvironments and the mechanisms by which these proteins impact vascular function remain largely undefined. The matricellular protein lipocalin-7 (LCN7 is found throughout vascular microenvironments, and circumstantial evidence suggests that LCN7 may be an important regulator of angiogenesis. Therefore, we hypothesized that LCN7 may be an important regulator of vascular function. METHODOLOGY AND PRINCIPAL FINDINGS: To test this hypothesis, we examined the effect of LCN7 overexpression, recombinant protein and gene knockdown in a series of in vitro and in vivo models of angiogenesis. We found that overexpression of LCN7 in MB114 and SVEC murine endothelial cell lines or administration of highly purified recombinant LCN7 protein increased endothelial cell invasion. Similarly, LCN7 increased angiogenic sprouting from quiescent endothelial cell monolayers and ex vivo aortic rings. Moreover, LCN7 increased endothelial cell sensitivity to TGF-β but did not affect sensitivity to other pro-angiogenic growth factors including bFGF and VEGF. Finally, morpholino based knockdown of LCN7 in zebrafish embryos specifically inhibited angiogenic sprouting but did not affect vasculogenesis within injected embryos. CONCLUSIONS AND SIGNIFICANCE: No functional analysis has previously been performed to elucidate the function of LCN7 in vascular or other cellular processes. Collectively, our results show for the first

  20. Persistent serum creatinine increase following contrast-induced acute kidney injury.

    Science.gov (United States)

    Briguori, Carlo; Quintavalle, Cristina; De Micco, Francesca; Visconti, Gabriella; Di Palma, Vito; Napolitano, Giovanni; Focaccio, Amelia; Condorelli, Gerolama

    2017-08-11

    Contrast-induced acute kidney injury (CI-AKI) may led to both a transient and a persistent serum creatinine (sCr) increase. To assess whether serum cystatin C (sCyC) and urine and serum neutrophil gelatinase-associated lipocalin (uNGAL, sNGAL) are useful in the early identification of persistent sCr increase following CI-AKI. One hundred and eighteen patients who developed CI-AKI were included into the study. Persistent sCr elevation was defined as a persistent increase ≥0.3 mg dL(-1) at 1 month after contrast media (CM) administration. sCr levels recovered in 87 patients (74%; Transient group), whereas a persistent elevation of sCr was observed in the remaining 31 patients (26%; Persistent group). By multivariable logistic regression analysis, independent predictors of persistent sCr increase were insulin therapy, uNGAL at 48 hr and absolute sCr difference between 48 and 72 hr. On the contrary, sCyC assessment did not help in the early identification of this subset of patients. By receiver operating curve analysis, the best cutoff values for predicting persistent sCr increase were uNGAL ≥0.50 ng dL(-1) at 48 hr, and the absolute sCr increase ≥0.20 mg dL(-1) between 48 and 72 hr. uNGAL ≥0.50 ng dL(-1) at 48 hr and absolute sCr increase ≥0.20 mg dL(-1) between 48 and 72 hr but not sCyC are useful in the early identification of patients developing persistent sCr increase after CM administration. © 2017 Wiley Periodicals, Inc.

  1. Acute kidney injury biomarkers for patients in a coronary care unit: a prospective cohort study.

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    Tien-Hsing Chen

    Full Text Available BACKGROUND: Renal dysfunction is an established predictor of all-cause mortality in intensive care units. This study analyzed the outcomes of coronary care unit (CCU patients and evaluated several biomarkers of acute kidney injury (AKI, including neutrophil gelatinase-associated lipocalin (NGAL, interleukin-18 (IL-18 and cystatin C (CysC on the first day of CCU admission. METHODOLOGY/PRINCIPAL FINDINGS: Serum and urinary samples collected from 150 patients in the coronary care unit of a tertiary care university hospital between September 2009 and August 2010 were tested for NGAL, IL-18 and CysC. Prospective demographic, clinical and laboratory data were evaluated as predictors of survival in this patient group. The most common cause of CCU admission was acute myocardial infarction (80%. According to Acute Kidney Injury Network criteria, 28.7% (43/150 of CCU patients had AKI of varying severity. Cumulative survival rates at 6-month follow-up following hospital discharge differed significantly (p<0.05 between patients with AKI versus those without AKI. For predicting AKI, serum CysC displayed an excellent areas under the receiver operating characteristic curve (AUROC (0.895 ± 0.031, p < 0.001. The overall 180-day survival rate was 88.7% (133/150. Multiple Cox logistic regression hazard analysis revealed that urinary NGAL, serum IL-18, Acute Physiology, Age and Chronic Health Evaluation II (APACHE II and sodium on CCU admission day one were independent risk factors for 6-month mortality. In terms of 6-month mortality, urinary NGAL had the best discriminatory power, the best Youden index, and the highest overall correctness of prediction. CONCLUSIONS: Our data showed that serum CysC has the best discriminative power for predicting AKI in CCU patients. However, urinary NGAL and serum IL-18 are associated with short-term mortality in these critically ill patients.

  2. Lipocalin-2 is increased in progressive multiple sclerosis and inhibits remyelination

    DEFF Research Database (Denmark)

    Al Nimer, Faiez; Elliott, Christina; Bergman, Joakim

    2016-01-01

    OBJECTIVE: We aimed to examine the regulation of lipocalin-2 (LCN2) in multiple sclerosis (MS) and its potential functional relevance with regard to myelination and neurodegeneration. METHODS: We determined LCN2 levels in 3 different studies: (1) in CSF and plasma from a case-control study compar...

  3. Lipocalin-type prostaglandin D synthase is not a biomarker of atherosclerotic manifestations

    DEFF Research Database (Denmark)

    Hosbond, Susanne E; Diederichsen, Axel C P; Pedersen, Lise

    2014-01-01

    OBJECTIVE: Over the last decades Lipocalin-type prostaglandin D synthase (L-PGDS), Osteoprotegerin (OPG), Osteopontin (OPN) and Pregnancy associated plasma protein A (PAPP-A) have been reported to be associated with coronary artery disease, and L-PGDS has been proposed as a potential new diagnostic...

  4. The menagerie of human lipocalins: a natural protein scaffold for molecular recognition of physiological compounds.

    Science.gov (United States)

    Schiefner, André; Skerra, Arne

    2015-04-21

    While immunoglobulins are well-known for their characteristic ability to bind macromolecular antigens (i.e., as antibodies during an immune response), the lipocalins constitute a family of proteins whose role is the complexation of small molecules for various physiological processes. In fact, a number of low-molecular-weight substances in multicellular organisms show poor solubility, are prone to chemical decomposition, or play a pathophysiological role and thus require specific binding proteins for transport through body fluids, storage, or sequestration. In many cases, lipocalins are involved in such tasks. Lipocalins are small, usually monomeric proteins with 150-180 residues and diameters of approximately 40 Å, adopting a compact fold that is dominated by a central eight-stranded up-and-down β-barrel. At the amino-terminal end, this core is flanked by a coiled polypeptide segment, while its carboxy-terminal end is followed by an α-helix that leans against the β-barrel as well as an amino acid stretch in a more-or-less extended conformation, which finally is fixed by a disulfide bond. Within the β-barrel, the antiparallel strands (designated A to H) are arranged in a (+1)7 topology and wind around a central axis in a right-handed manner such that part of strand A is hydrogen-bonded to strand H again. Whereas the lower region of the β-barrel is closed by short loops and densely packed hydrophobic side chains, including many aromatic residues, the upper end is usually open to solvent. There, four long loops, each connecting one pair of β-strands, together form the entrance to a cup-shaped cavity. Depending on the individual structure of a lipocalin, and especially on the lengths and amino acid sequences of its four loops, this pocket can accommodate chemical ligands of various sizes and shapes, including lipids, steroids, and other chemical hormones as well as secondary metabolites such as vitamins, cofactors, or odorants. While lipocalins are ubiquitous in

  5. Renal failure

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    2010357 Urinary neutrophil gelatinase-associated lipocalin and urinary interleukin-18 in early diagnosis of acute kidney injury in critically ill patients. ZANG Zhidong(臧芝栋),et al. Dept Critical Care Med,Zhongda Hosp,Southeast University,Nanjing 210009. Chin J Intern Med 2010;49(5):396-399. Objective To determine whether urinary neutrophil gelatinase-associated

  6. Roborovskin, a lipocalin in the urine of the Roborovski hamster, Phodopus roborovskii.

    Science.gov (United States)

    Turton, Michael J; Robertson, Duncan H L; Smith, Julia R; Hurst, Jane L; Beynon, Robert J

    2010-10-01

    Many rodents are now known to exhibit an obligate proteinuria that delivers urine-mediated chemosignals. In this paper, we explore the urinary proteins of the Roborovski hamster (Phodopus roborovskii). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of urine from individual male and female Roborovski hamsters revealed 2 proteins, with approximate masses of 6 and 17 kDa, the expression pattern of which showed little variation between individuals or between sexes. Peptide mass fingerprints obtained from these 2 proteins revealed a number of features: 1) the proteins of a given mass were the same in all individuals regardless of sex, 2) the 6 kDa protein was not a fragment of the 21 kDa protein, and 3) neither protein was a fragment of a larger, conserved protein such as serum albumin. Electrospray mass spectrometry of purified protein preparations established the mass of the larger protein as invariant, at 17144 ± 2 Da in all samples. This protein has been termed roborovskin. The primary structure of roborovskin was determined by tandem mass spectrometry of peptides derived from independent and overlapping digestion with 3 proteases, supported by Edman degradation of the protein N-terminus. Roborovskin shared significant homology with olfactory-binding proteins from Myodes glareolus (bank vole) and with aphrodisin and submandibular protein from the golden hamster Mesocricetus auratus, all of which belong to the lipocalin superfamily. Lower levels of homology were also indicated between a variety of other lipocalins including the major urinary proteins from house mice and Norway rats. A model of the tertiary structure of roborovskin was constructed from the primary sequence by homology modeling. This model structure resembled other 8-stranded beta barrel lipocalins. Thus, the Roborovski hamster may demonstrate another variant of urinary lipocalin expression, as for the animals studied here, there appears to be no polymorphism in expression either

  7. Ligand binding-dependent functions of the lipocalin NLaz: an in vivo study in Drosophila.

    Science.gov (United States)

    Ruiz, Mario; Ganfornina, Maria D; Correnti, Colin; Strong, Roland K; Sanchez, Diego

    2014-04-01

    Lipocalins are small extracellular proteins mostly described as lipid carriers. The Drosophila lipocalin NLaz (neural Lazarillo) modulates the IIS pathway and regulates longevity, stress resistance, and behavior. Here, we test whether a native hydrophobic pocket structure is required for NLaz to perform its functions. We use a point mutation altering the binding pocket (NLaz(L130R)) and control mutations outside NLaz binding pocket. Tryptophan fluorescence titration reveals that NLaz(L130R) loses its ability to bind ergosterol and the pheromone 7(z)-tricosene but retains retinoic acid binding. Using site-directed transgenesis in Drosophila, we test the functionality of the ligand binding-altered lipocalin at the organism level. NLaz-dependent life span reduction, oxidative stress and starvation sensitivity, aging markers accumulation, and deficient courtship are rescued by overexpression of NLaz(WT), but not of NLaz(L130R). Transcriptional responses to aging and oxidative stress show a large set of age-responsive genes dependent on the integrity of NLaz binding pocket. Inhibition of IIS activity and modulation of oxidative stress and infection-responsive genes are binding pocket-dependent processes. Control of energy metabolites on starvation appears to be, however, insensitive to the modification of the NLaz binding pocket.

  8. Extracellular Matrix Markers for Disease Progression and Follow-Up of Therapies in Familial Amyloid Polyneuropathy V30M TTR-Related

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    I. Cardoso

    2008-01-01

    Full Text Available Familial Amyloidotic Polyneuropathy (FAP is a disorder characterized by the extracellular deposition of fibrillar Transthyretin (TTR amyloid, with a special involvement of the peripheral nerve. Several extracellular matrix proteins have been found elevated in tissues from FAP patients, namely metalloproteinase-9 (MMP-9, neutrophil gelatinase associated lipocalin (NGAL and biglycan. In this work we assessed the levels of MMP-9, tissue inhibitor of metalloproteinase 1 (TIMP-1, NGAL, biglycan and chondroitin sulphate (CSPG in an FAP V30M TTR-related transgenic mouse model at different stages of TTR deposition and after two different treatment approaches to remove fibrillar deposits. Immunohistochemistry or RT-PCR analysis showed that biglycan was already increased in animals presenting TTR deposited in a non-fibrillar state, whereas MMP-9, TIMP-1, NGAL and CSPG were elevated only in mice with TTR amyloid deposits. Mice treated with doxycycline, a TTR fibril disrupter, presented lower levels of MMP-9, TIMP-1 and NGAL, suggestive of matrix recovery. Mice immunized with TTR Y78F to remove TTR deposition showed significantly lower levels of all the five tested markers, suggesting removal of fibrillar and non-fibrillar deposits. Cellular studies using oligomeric TTR showed induction of MMP-9 when compared to soluble TTR, large aggregates or fibrils. Furthermore, this induction was neutralized by an anti-receptor for advanced glycation end products (RAGE antibody, indicating RAGE engagement in this process. Further studies in a larger number of tissue samples will indicate the application of these ECM markers in parallel with Congo Red staining in tissue characterization of pre-clinical and clinical stages in FAP and other amyloidoses.

  9. Novel and conventional serum biomarkers predicting acute kidney injury in adult cardiac surgery--a prospective cohort study.

    Science.gov (United States)

    Haase-Fielitz, Anja; Bellomo, Rinaldo; Devarajan, Prasad; Story, David; Matalanis, George; Dragun, Duska; Haase, Michael

    2009-02-01

    To compare the value of novel with conventional serum biomarkers in the prediction of acute kidney injury (AKI) in adult cardiac surgical patients according to preoperative renal function. Single-center, prospective observational study. Tertiary hospital. One hundred adult cardiac surgical patients. We measured concentrations of plasma neutrophil gelatinase-associated lipocalin (NGAL), and serum cystatin C, and creatinine and urea at baseline, on arrival in the intensive care unit (ICU) and at 24 hours postoperatively. We assessed such biomarkers in relation to the development of AKI (>50% increase in creatinine from baseline) and to a composite end point (need for renal replacement therapy and in-hospital mortality). We defined an area under the receiver operating characteristic curve of 0.60-0.69 as poor, 0.70-0.79 as fair, 0.80-0.89 as good, and 0.90-1.00 as excellent in terms of predictive value. On arrival in ICU, plasma NGAL and serum cystatin C were of good predictive value, but creatinine and urea were of poor predictive value. After exclusion of patients with preoperative renal impairment (estimated glomerular filtration rate fair value in such patients. At 24 hours postoperatively, all renal biomarkers were of good predictive value. On arrival in ICU, novel biomarkers were superior to conventional biomarkers (p value in the prediction of the composite end point. Early postoperative measurement of plasma NGAL was of good value in identifying patients who developed AKI after adult cardiac surgery. Plasma NGAL and serum cystatin C were superior to conventional biomarkers in the prediction of AKI and were also of prognostic value in this setting.

  10. Ixodes ricinus tick lipocalins: identification, cloning, phylogenetic analysis and biochemical characterization.

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    Jérôme Beaufays

    Full Text Available BACKGROUND: During their blood meal, ticks secrete a wide variety of proteins that interfere with their host's defense mechanisms. Among these proteins, lipocalins play a major role in the modulation of the inflammatory response. METHODOLOGY/PRINCIPAL FINDINGS: Screening a cDNA library in association with RT-PCR and RACE methodologies allowed us to identify 14 new lipocalin genes in the salivary glands of the Ixodes ricinus hard tick. A computational in-depth structural analysis confirmed that LIRs belong to the lipocalin family. These proteins were called LIR for "Lipocalin from I. ricinus" and numbered from 1 to 14 (LIR1 to LIR14. According to their percentage identity/similarity, LIR proteins may be assigned to 6 distinct phylogenetic groups. The mature proteins have calculated pM and pI varying from 21.8 kDa to 37.2 kDa and from 4.45 to 9.57 respectively. In a western blot analysis, all recombinant LIRs appeared as a series of thin bands at 50-70 kDa, suggesting extensive glycosylation, which was experimentally confirmed by treatment with N-glycosidase F. In addition, the in vivo expression analysis of LIRs in I. ricinus, examined by RT-PCR, showed homogeneous expression profiles for certain phylogenetic groups and relatively heterogeneous profiles for other groups. Finally, we demonstrated that LIR6 codes for a protein that specifically binds leukotriene B4. CONCLUSIONS/SIGNIFICANCE: This work confirms that, regarding their biochemical properties, expression profile, and sequence signature, lipocalins in Ixodes hard tick genus, and more specifically in the Ixodes ricinus species, are segregated into distinct phylogenetic groups suggesting potential distinct function. This was particularly demonstrated by the ability of LIR6 to scavenge leukotriene B4. The other LIRs did not bind any of the ligands tested, such as 5-hydroxytryptamine, ADP, norepinephrine, platelet activating factor, prostaglandins D2 and E2, and finally leukotrienes B4 and C

  11. The Effects of 8 Eight Weeks Resistance Versus Endurance Training on Lipocalin-2 level in Non-Athlete Male Students

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    A Mohammadi Domiyeh

    2012-12-01

    Resistance training performed 3 three d/wk at an intensity corresponding to 65–80% of one-repetition maximum, 8-12 repetitions and 2-4 sets for 8 weeks. Endurance training group, underwent an 8-week intervention with a frequency of 3 d/wk at an intensity corresponding to 65, – 80% maximum heart rate for 20- – 38 minutes. Expressing lipocalin-2 plasma levels in samples were measured before and after intervention. Data were analyzed by one-way ANOVA. Results: Plasma expressing level of lipocalin 2 in the control group before and after intervention, were respectively 11./1 ± 4./5 & 13./05 ± 2/.04, µg/L, respectively. The plasma level of lipocalin 2 and in the endurance training group, were 22./7 ± 8/.3 & and 17/.7 ± 6/.8 , and while these level werein the resistance training group 22/.2 ± 6/.2 & 19/.9 ± 6/.5 in the resistance training group. micrograms per liter, which was not statistically different.The differences between three groups were not statistically significant (p>0/.05. Conclusion: This study showed that 8 eight weeks of endurance & and resistance exercise training has no effect on lipocalin-2 plasma levels. Key words: Resistance training, Endurance training, Lipocalin-2, Insulin Resistance

  12. A Meta-Analysis of Renal Function After Adult Cardiac Surgery With Pulsatile Perfusion.

    Science.gov (United States)

    Nam, Myung Ji; Lim, Choon Hak; Kim, Hyun-Jung; Kim, Yong Hwi; Choi, Hyuk; Son, Ho Sung; Lim, Hae Ja; Sun, Kyung

    2015-09-01

    The aim of this meta-analysis was to determine whether pulsatile perfusion during cardiac surgery has a lesser effect on renal dysfunction than nonpulsatile perfusion after cardiac surgery in randomized controlled trials. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were used to identify available articles published before April 25, 2014. Meta-analysis was conducted to determine the effects of pulsatile perfusion on postoperative renal functions, as determined by creatinine clearance (CrCl), serum creatinine (Cr), urinary neutrophil gelatinase-associated lipocalin (NGAL), and the incidences of acute renal insufficiency (ARI) and acute renal failure (ARF). Nine studies involving 674 patients that received pulsatile perfusion and 698 patients that received nonpulsatile perfusion during cardiopulmonary bypass (CPB) were considered in the meta-analysis. Stratified analysis was performed according to effective pulsatility or unclear pulsatility of the pulsatile perfusion method in the presence of heterogeneity. NGAL levels were not significantly different between the pulsatile and nonpulsatile groups. However, patients in the pulsatile group had a significantly higher CrCl and lower Cr levels when the analysis was restricted to studies on effective pulsatile flow (P < 0.00001, respectively). The incidence of ARI was significantly lower in the pulsatile group (P < 0.00001), but incidences of ARF were similar. In conclusion, the meta-analysis suggests that the use of pulsatile flow during CPB results in better postoperative renal function.

  13. Effects of Schizolobium parahyba extract on experimental Bothrops venom-induced acute kidney injury.

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    Monique Silva Martines

    Full Text Available BACKGROUND: Venom-induced acute kidney injury (AKI is a frequent complication of Bothrops snakebite with relevant morbidity and mortality. The aim of this study was to assess the effects of Schizolobium parahyba (SP extract, a natural medicine with presumed anti-Bothrops venom effects, in an experimental model of Bothrops jararaca venom (BV-induced AKI. METHODOLOGY: Groups of 8 to 10 rats received infusions of 0.9% saline (control, C, SP 2 mg/kg, BV 0.25 mg/kg and BV immediately followed by SP (treatment, T in the doses already described. After the respective infusions, animals were assessed for their glomerular filtration rate (GFR, inulin clearance, renal blood flow (RBF, Doppler, blood pressure (BP, intra-arterial transducer, renal vascular resistance (RVR, urinary osmolality (UO, freezing point, urinary neutrophil gelatinase-associated lipocalin (NGAL, enzyme-linked immunosorbent assay [ELISA], lactate dehydrogenase (LDH, kinetic method, hematocrit (Hct, microhematocrit, fibrinogen (Fi, Klauss modified and blinded renal histology (acute tubular necrosis score. PRINCIPAL FINDINGS: BV caused significant decreases in GFR, RBF, UO, HcT and Fi; significant increases in RVR, NGAL and LDH; and acute tubular necrosis. SP did not prevent these changes; instead, it caused a significant decrease in GFR when used alone. CONCLUSION: SP administered simultaneously with BV, in an approximate 10∶1 concentration, did not prevent BV-induced AKI, hemolysis and fibrinogen consumption. SP used alone caused a decrease in GFR.

  14. Evidence of Uncoupling between Renal Dysfunction and Injury in Cardiorenal Syndrome: Insights from the BIONICS Study

    Science.gov (United States)

    Legrand, Matthieu; De Berardinis, Benedetta; Gaggin, Hanna K.; Magrini, Laura; Belcher, Arianna; Zancla, Benedetta; Femia, Alexandra; Simon, Mandy; Motiwala, Shweta; Sambhare, Rasika; Di Somma, Salvatore; Mebazaa, Alexandre; Vaidya, Vishal S.; Januzzi, James L.; (GREAT), from the Global Research on Acute Conditions Team

    2014-01-01

    Objective The objective of the study was to assess urinary biomarkers of renal injury for their individual or collective ability to predict Worsening renal function (WRF) in patients with acutely decompensated heart failure (ADHF). Methods In a prospective, blinded international study, 87 emergency department (ED) patients with ADHF were evaluated with biomarkers of cardiac stretch (B type natriuretic peptide [BNP] and its amino terminal equivalent [NT-proBNP], ST2), biomarkers of renal function (creatinine, estimated glomerular filtration rate [eGFR]) and biomarkers of renal injury (plasma neutrophil gelatinase associated lipocalin [pNGAL], urine kidney injury molecule-1 [KIM-1], urine N-acetyl-beta-D-glucosaminidase [NAG], urine Cystatin C, urine fibrinogen). The primary endpoint was WRF. Results 26% developed WRF; baseline characteristics of subjects who developed WRF were generally comparable to those who did not. Biomarkers of renal function and urine biomarkers of renal injury were not correlated, while urine biomarkers of renal injury correlated between each other. Biomarker concentrations were similar between patients with and without WRF except for baseline BNP. Although plasma NGAL was associated with the combined endpoint, none of the biomarker showed predictive accuracy for WRF. Conclusions In ED patients with ADHF, urine biomarkers of renal injury did not predict WRF. Our data suggest that a weak association exists between renal dysfunction and renal injury in this setting (Clinicaltrials.gov NCT#0150153). PMID:25386851

  15. Evidence of uncoupling between renal dysfunction and injury in cardiorenal syndrome: insights from the BIONICS study.

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    Matthieu Legrand

    Full Text Available The objective of the study was to assess urinary biomarkers of renal injury for their individual or collective ability to predict Worsening renal function (WRF in patients with acutely decompensated heart failure (ADHF.In a prospective, blinded international study, 87 emergency department (ED patients with ADHF were evaluated with biomarkers of cardiac stretch (B type natriuretic peptide [BNP] and its amino terminal equivalent [NT-proBNP], ST2, biomarkers of renal function (creatinine, estimated glomerular filtration rate [eGFR] and biomarkers of renal injury (plasma neutrophil gelatinase associated lipocalin [pNGAL], urine kidney injury molecule-1 [KIM-1], urine N-acetyl-beta-D-glucosaminidase [NAG], urine Cystatin C, urine fibrinogen. The primary endpoint was WRF.26% developed WRF; baseline characteristics of subjects who developed WRF were generally comparable to those who did not. Biomarkers of renal function and urine biomarkers of renal injury were not correlated, while urine biomarkers of renal injury correlated between each other. Biomarker concentrations were similar between patients with and without WRF except for baseline BNP. Although plasma NGAL was associated with the combined endpoint, none of the biomarker showed predictive accuracy for WRF.In ED patients with ADHF, urine biomarkers of renal injury did not predict WRF. Our data suggest that a weak association exists between renal dysfunction and renal injury in this setting (Clinicaltrials.gov NCT#0150153.

  16. Glycemic Variability Assessed by Continuous Glucose Monitoring and Short-Term Outcome in Diabetic Patients Undergoing Percutaneous Coronary Intervention: An Observational Pilot Study

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    Annunziata Nusca

    2015-01-01

    Full Text Available Poor glycemic control is associated with unfavorable outcome in patients undergoing percutaneous coronary intervention (PCI, irrespective of diabetes mellitus. However a complete assessment of glycemic status may not be fully described by glycated hemoglobin or fasting blood glucose levels, whereas daily glycemic fluctuations may influence cardiovascular risk and have even more deleterious effects than sustained hyperglycemia. Thus, this paper investigated the effectiveness of a continuous glucose monitoring (CGM, registering the mean level of glycemic values but also the extent of glucose excursions during coronary revascularization, in detecting periprocedural outcome such as renal or myocardial damage, assessed by serum creatinine, neutrophil gelatinase-associated lipocalin (NGAL, and troponin I levels. High glycemic variability (GV has been associated with worse postprocedural creatinine and NGAL variations. Moreover, GV, and predominantly hypoglycemic variations, has been observed to increase in patients with periprocedural myocardial infarction. Thus, our study investigated the usefulness of CGM in the setting of PCI where an optimal glycemic control should be achieved in order to prevent complications and improve outcome.

  17. 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

  18. 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.

  19. Lazarillo, a new GPI-linked surface lipocalin, is restricted to a subset of neurons in the grasshopper embryo.

    Science.gov (United States)

    Ganfornina, M D; Sánchez, D; Bastiani, M J

    1995-01-01

    Lazarillo, a protein recognized by the monoclonal antibody 10E6, is expressed by a subset of neurons in the developing nervous system of the grasshopper. It is a glycoprotein of 45x10(3) M(r) with internal disulfide bonds and linked to the extracellular side of the plasma membrane by a glycosylphosphatidylinositol moiety. Peptide sequences obtained from affinity purified adult protein were used to identify an embryonic cDNA clone, and in situ hybridizations confirmed that the distribution of the Lazarillo mRNA paralleled that of the monoclonal antibody labeling on embryos. Sequence analysis defines Lazarillo as a member of the lipocalin family, extracellular carriers of small hydrophobic ligands, and most related to the porphyrin- and retinol-binding lipocalins. Lazarillo is the first example of a lipocalin anchored to the plasma membrane, highly glycosylated, and restricted to a subset of developing neurons.

  20. Molecular Markers of Tubulointerstitial Fibrosis and Tubular Cell Damage in Patients with Chronic Kidney Disease.

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    Shunsaku Nakagawa

    Full Text Available In chronic kidney disease (CKD, progressive nephron loss causes glomerular sclerosis, as well as tubulointerstitial fibrosis and progressive tubular injury. In this study, we aimed to identify molecular changes that reflected the histopathological progression of renal tubulointerstitial fibrosis and tubular cell damage. A discovery set of renal biopsies were obtained from 48 patients with histopathologically confirmed CKD, and gene expression profiles were determined by microarray analysis. The results indicated that hepatitis A virus cellular receptor 1 (also known as Kidney Injury Molecule-1, KIM-1, lipocalin 2 (also known as neutrophil gelatinase-associated lipocalin, NGAL, SRY-box 9, WAP four-disulfide core domain 2, and NK6 homeobox 2 were differentially expressed in CKD. Their expression levels correlated with the extent of tubulointerstitial fibrosis and tubular cell injury, determined by histopathological examination. The expression of these 5 genes was also increased as kidney damage progressed in a rodent unilateral ureteral obstruction model of CKD. We calculated a molecular score using the microarray gene expression profiles of the biopsy specimens. The composite area under the receiver operating characteristics curve plotted using this molecular score showed a high accuracy for diagnosing tubulointerstitial fibrosis and tubular cell damage. The robust sensitivity of this score was confirmed in a validation set of 5 individuals with CKD. These findings identified novel molecular markers with the potential to contribute to the detection of tubular cell damage and tubulointerstitial fibrosis in the kidney.

  1. Control of metabolic homeostasis by stress signaling is mediated by the lipocalin NLaz.

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    Julie Hull-Thompson

    2009-04-01

    Full Text Available Metabolic homeostasis in metazoans is regulated by endocrine control of insulin/IGF signaling (IIS activity. Stress and inflammatory signaling pathways--such as Jun-N-terminal Kinase (JNK signaling--repress IIS, curtailing anabolic processes to promote stress tolerance and extend lifespan. While this interaction constitutes an adaptive response that allows managing energy resources under stress conditions, excessive JNK activity in adipose tissue of vertebrates has been found to cause insulin resistance, promoting type II diabetes. Thus, the interaction between JNK and IIS has to be tightly regulated to ensure proper metabolic adaptation to environmental challenges. Here, we identify a new regulatory mechanism by which JNK influences metabolism systemically. We show that JNK signaling is required for metabolic homeostasis in flies and that this function is mediated by the Drosophila Lipocalin family member Neural Lazarillo (NLaz, a homologue of vertebrate Apolipoprotein D (ApoD and Retinol Binding Protein 4 (RBP4. Lipocalins are emerging as central regulators of peripheral insulin sensitivity and have been implicated in metabolic diseases. NLaz is transcriptionally regulated by JNK signaling and is required for JNK-mediated stress and starvation tolerance. Loss of NLaz function reduces stress resistance and lifespan, while its over-expression represses growth, promotes stress tolerance and extends lifespan--phenotypes that are consistent with reduced IIS activity. Accordingly, we find that NLaz represses IIS activity in larvae and adult flies. Our results show that JNK-NLaz signaling antagonizes IIS and is critical for metabolic adaptation of the organism to environmental challenges. The JNK pathway and Lipocalins are structurally and functionally conserved, suggesting that similar interactions represent an evolutionarily conserved system for the control of metabolic homeostasis.

  2. Control of metabolic homeostasis by stress signaling is mediated by the lipocalin NLaz.

    Science.gov (United States)

    Hull-Thompson, Julie; Muffat, Julien; Sanchez, Diego; Walker, David W; Benzer, Seymour; Ganfornina, Maria D; Jasper, Heinrich

    2009-04-01

    Metabolic homeostasis in metazoans is regulated by endocrine control of insulin/IGF signaling (IIS) activity. Stress and inflammatory signaling pathways--such as Jun-N-terminal Kinase (JNK) signaling--repress IIS, curtailing anabolic processes to promote stress tolerance and extend lifespan. While this interaction constitutes an adaptive response that allows managing energy resources under stress conditions, excessive JNK activity in adipose tissue of vertebrates has been found to cause insulin resistance, promoting type II diabetes. Thus, the interaction between JNK and IIS has to be tightly regulated to ensure proper metabolic adaptation to environmental challenges. Here, we identify a new regulatory mechanism by which JNK influences metabolism systemically. We show that JNK signaling is required for metabolic homeostasis in flies and that this function is mediated by the Drosophila Lipocalin family member Neural Lazarillo (NLaz), a homologue of vertebrate Apolipoprotein D (ApoD) and Retinol Binding Protein 4 (RBP4). Lipocalins are emerging as central regulators of peripheral insulin sensitivity and have been implicated in metabolic diseases. NLaz is transcriptionally regulated by JNK signaling and is required for JNK-mediated stress and starvation tolerance. Loss of NLaz function reduces stress resistance and lifespan, while its over-expression represses growth, promotes stress tolerance and extends lifespan--phenotypes that are consistent with reduced IIS activity. Accordingly, we find that NLaz represses IIS activity in larvae and adult flies. Our results show that JNK-NLaz signaling antagonizes IIS and is critical for metabolic adaptation of the organism to environmental challenges. The JNK pathway and Lipocalins are structurally and functionally conserved, suggesting that similar interactions represent an evolutionarily conserved system for the control of metabolic homeostasis.

  3. Lipocalin 2 deficiency dysregulates iron homeostasis and exacerbates endotoxin-induced sepsis

    DEFF Research Database (Denmark)

    Srinivasan, Gayathri; Aitken, Jesse D; Zhang, Benyue

    2012-01-01

    Various states of inflammation, including sepsis, are associated with hypoferremia, which limits iron availability to pathogens and reduces iron-mediated oxidative stress. Lipocalin 2 (Lcn2; siderocalin, 24p3) plays a central role in iron transport. Accordingly, Lcn2-deficient (Lcn2KO) mice exhib...... mortality, suggesting that Lcn2 may act as an antioxidant in vivo by regulating iron homeostasis. Thus, Lcn2-mediated regulation of labile iron protects the host against sepsis. Its small size and simple structure may make Lcn2 a deployable treatment for sepsis....

  4. Multiple apoptotic defects in hematopoietic cells from mice lacking lipocalin 24p3.

    Science.gov (United States)

    Liu, Zhuoming; Yang, Amy; Wang, Zhengqi; Bunting, Kevin D; Davuluri, Gangarao; Green, Michael R; Devireddy, Laxminarayana R

    2011-06-10

    The lipocalin mouse 24p3 has been implicated in diverse physiological processes, including apoptosis, iron trafficking, development and innate immunity. Studies from our laboratory as well as others demonstrated the proapoptotic activity of 24p3 in a variety of cultured models. However, a general role for the lipocalin 24p3 in the hematopoietic system has not been tested in vivo. To study the role of 24p3, we derived 24p3 null mice and back-crossed them onto C57BL/6 and 129/SVE backgrounds. Homozygous 24p3(-/-) mice developed a progressive accumulation of lymphoid, myeloid, and erythroid cells, which was not due to enhanced hematopoiesis because competitive repopulation and recovery from myelosuppression were the same as for wild type. Instead, apoptotic defects were unique to many mature hematopoietic cell types, including neutrophils, cytokine-dependent mast cells, thymocytes, and erythroid cells. Thymocytes isolated from 24p3 null mice also displayed resistance to apoptosis-induced by dexamethasone. Bim response to various apoptotic stimuli was attenuated in 24p3(-/-) cells, thus explaining their resistance to the ensuing cell death. The results of these studies, in conjunction with those of previous studies, reveal 24p3 as a regulator of the hematopoietic compartment with important roles in normal physiology and disease progression. Interestingly, these functions are limited to relatively mature blood cell compartments.

  5. Lipocalin-2 inhibits osteoclast formation by suppressing the proliferation and differentiation of osteoclast lineage cells

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hyun-Ju, E-mail: biohjk@knu.ac.kr [Department of Molecular Medicine, Cell and Matrix Research Institute, Clinical Trial Center, BK21 Plus KNU Biomedical Convergence Program, School of Medicine, Kyungpook National University, Daegu 700-422 (Korea, Republic of); Yoon, Hye-Jin [Department of Molecular Medicine, Cell and Matrix Research Institute, Clinical Trial Center, BK21 Plus KNU Biomedical Convergence Program, School of Medicine, Kyungpook National University, Daegu 700-422 (Korea, Republic of); Yoon, Kyung-Ae [Department of Orthopedic Surgery, Skeletal Diseases Genome Research Center, School of Medicine, Kyungpook National University, Daegu 700-422 (Korea, Republic of); Gwon, Mi-Ri; Jin Seong, Sook [Department of Molecular Medicine, Cell and Matrix Research Institute, Clinical Trial Center, BK21 Plus KNU Biomedical Convergence Program, School of Medicine, Kyungpook National University, Daegu 700-422 (Korea, Republic of); Suk, Kyoungho [Department of Pharmacology, School of Medicine, Kyungpook National University, Daegu 700-422 (Korea, Republic of); Kim, Shin-Yoon [Department of Orthopedic Surgery, Skeletal Diseases Genome Research Center, School of Medicine, Kyungpook National University, Daegu 700-422 (Korea, Republic of); Yoon, Young-Ran, E-mail: yry@knu.ac.kr [Department of Molecular Medicine, Cell and Matrix Research Institute, Clinical Trial Center, BK21 Plus KNU Biomedical Convergence Program, School of Medicine, Kyungpook National University, Daegu 700-422 (Korea, Republic of)

    2015-06-10

    Lipocalin-2 (LCN2) is a member of the lipocalin superfamily and plays a critical role in the regulation of various physiological processes, such as inflammation and obesity. In this study, we report that LCN2 negatively modulates the proliferation and differentiation of osteoclast precursors, resulting in impaired osteoclast formation. The overexpression of LCN2 in bone marrow-derived macrophages or the addition of recombinant LCN2 protein inhibits the formation of multinuclear osteoclasts. LCN2 suppresses macrophage colony-stimulating factor (M-CSF)-induced proliferation of osteoclast precursor cells without affecting their apoptotic cell death. Interestingly, LCN2 decreases the expression of the M-CSF receptor, c-Fms, and subsequently blocks its downstream signaling cascades. In addition, LCN2 inhibits RANKL-induced osteoclast differentiation and attenuates the expression of c-Fos and nuclear factor of activated T cells c1 (NFATc1), which are important modulators in osteoclastogenesis. Mechanistically, LCN2 inhibits NF-κB signaling pathways, as demonstrated by the suppression of IκBα phosphorylation, nuclear translocation of p65, and NF-κB transcriptional activity. Thus, LCN2 is an anti-osteoclastogenic molecule that exerts its effects by retarding the proliferation and differentiation of osteoclast lineage cells. - Highlights: • LCN2 expression is regulated during osteoclast development. • LCN2 suppresses M-CSF-mediated osteoclast precursor proliferation. • LCN2 inhibits RANKL-induced osteoclast differentiation.

  6. Clinical Value of uNGAL and uCys-C for Early Renal Impairment in Multiple Myeloma Patients%尿 NGAL 与 Cys-C 用于诊断多发性骨髓瘤早期肾损伤的临床价值研究

    Institute of Scientific and Technical Information of China (English)

    袁新科; 黄映红; 李萌; 李大勇; 吴运斗; 肖平

    2016-01-01

    目的:探讨尿中性粒细胞明胶酶相关载脂蛋白(uNGAL)与胱抑素 C(uCys-C)对多发性骨髓瘤(MM)患者早期肾损伤的诊断价值。方法根据肾小球滤过率估计值(eGFR)将 MM 患者分为两组:A 组(肾功能正常组)38例,eGFR ≥90 ml·min-1;B组(肾功能损伤组)34例,eGFR<90 ml·min-1。对照组为同期76例健康体检者。检测并比较各组尿液中 uNGAL、uCys-C 水平和血清 Scr 水平。结果A组 uNGAL、uCys-C 水平高于对照组,差异有统计学意义(P<0.01),B组 uNGAL、uCys-C、Scr 水平均显著高于对照组(P<0.01)。A组 uNGAL、uCys-C 联合检测的阳性率为52.38%,明显高于单项检测(P<0.05)。结论与传统指标相比较, uNGAL、uCys-C 能更有效地诊断 MM 患者早期肾损伤,联合检测更有价值。%Objective To discuss the diagnostic value of urinary NGAL (uNGAL) and urinary Cystatin C (uCys-C) for the early renal impairment in multiple myeloma (MM) patients. Methods According to the estimated glomerular filtration rate (eGFR), the MM patients were divided into two groups, group A (eGFR≥90 ml·min-1, n=38), the normal renal function group, and group B (eGFR<90 ml·min-1, n=34), the renal impairment group. Another 76 healthy subjects were selected as control group. The concentrations of uNGAL, uCys-C and Scr were measured and compared. Results The levels of uNGAL and uCys-C in group A were significantly higher than those in the control group (P<0.01). The levels of uNGAL, uCys-C and Scr in group B were also significantly higher than those in the control group (P<0.01). The positive rate of the combined detection of uNGAL and uCys-C was 52.38%, significantly higher than single index detection (P<0.05). Conclusion Com-pared with the traditional biomarkers, uNGAL and uCys-C were more sensitive and effective indexes for the diagnosis of early renal impairment in multiple myeloma patients. Jointed detection of the two had

  7. Stent Revascularization Restores Cortical Blood Flow and Reverses Tissue Hypoxia in Atherosclerotic Renal Artery Stenosis, But Fails To Reverse Inflammatory Pathways or GFR

    Science.gov (United States)

    Saad, Ahmed; Herrmann, Sandra M.S.; Crane, John; Glockner, James F; Mckusick, Michael A; Misra, Sanjay; Eirin, Alfonso; Ebrahimi, Behzad; Lerman, Lilach O.; Textor, Stephen C.

    2013-01-01

    Background Atherosclerotic renal artery stenosis (ARAS) is known to reduce renal blood flow (RBF), glomerular filtration rate (GFR) and amplify kidney hypoxia, but the relationships between these factors and tubulo-interstitial injury in the post-stenotic kidney are poorly understood. The purpose of this study was to examine the effect of renal revascularization in ARAS on renal tissue hypoxia and renal injury. Methods and Results Inpatient studies performed in ARAS patients (n = 17), more than 60% occlusion) before and 3 months after stent revascularization, or patients with essential hypertension (EH) (n = 32), during fixed Na+ intake and ACE/ARB Rx. Single-kidney (SK) cortical, medullary perfusion and RBF measured using multidetector CT, and GFR by iothalamate clearance. Tissue deoxyhemoglobin levels (R2*) measured by Blood Oxygen Level Dependent (BOLD) MRI at 3T, as was fractional kidney hypoxia (% of axial area with R2* > 30/s). In addition, we measured renal vein levels of Neutrophil gelatinase-associated lipocalin (NGAL), monocyte chemotactic protein-1 (MCP-1) and Tumor necrosis factor (TNF-α). Pre-stent SK-RBF, perfusion, and GFR were reduced in the post-stenotic kidney. Renal vein NGAL, TNF-α, MCP-1 and fractional hypoxia were higher in untreated ARAS than EH. After stent revascularization, fractional hypoxia fell (p < 0.002) with increased cortical perfusion and blood flow, while GFR and NGAL, MCP-1 and TNF-α remained unchanged. Conclusions These data demonstrate that despite reversal of renal hypoxia and partial restoration of RBF after revascularization, inflammatory cytokines and injury biomarkers remained elevated and GFR failed to recover in ARAS. Restoration of vessel patency alone failed to reverse tubulointerstitial damage and partly explains the limited clinical benefit of renal stenting. These results identify potential therapeutic targets for recovery of kidney function in renovascular disease. PMID:23899868

  8. Adding 75 mg pregabalin to analgesic regimen reduces pain scores and opioid consumption in adults following percutaneous nephrolithotomy

    Directory of Open Access Journals (Sweden)

    Harun Aydoğan

    2014-09-01

    Full Text Available Background and objectives: Adding novel adjunctive drugs like gabapentinoids to multimodal analgesic regimen might be reasonable for lessening postoperative pain scores, total opioid consumption and side effects after percutaneous nephrolithotomy. We aimed to evaluate the effect of pregabalin on postoperative pain scores, analgesic consumption and renal functions expressed by creatinine clearance (CrCl and blood neutrophil gelatinase-associated lipocalin (NGAL and cystatin C (Cys C levels in patients undergoing percutaneous nephrolithotomy (PCNL. Methods: 60 patients undergoing elective PCNL were enrolled in the study. Patients were randomized to oral single dose 75 mg pregabalin group and a control group. Visual Analog Scale pain scores (VAS, postoperative intravenous morphine consumption during the first 24 postoperative hours, serum NGAL, Cys C levels and creatinine clearance (CrCl was measured preoperatively and post-operatively at 2nd and 24th hour. Results: Postoperative VAS scores were significantly decreased in the pregabalin group at the postoperative 30th min, 1st, and 2nd hour (p = 0.002, p = 0.001 and p = 0.027, respectively. Postoperative mean morphine consumption was statistically significantly decreased for all time intervals in the pregabalin group (p = 0.002, p = 0.001, p = 0.001, p = 0.001, p < 0.001, respectively. No statistically significant differences were found between the two groups with regard to CrCl, or Cys C at preoperative and postoperative 2nd and 24th hour. Postoperative 24th hour NGAL levels were significantly decreased in the pregabalin group (p = 0.027. Conclusions: Oral single-dose preemptive 75 mg pregabalin was effective in reducing early postoperative pain scores and total analgesic consumption in patients undergoing PCNL without leading to hemodynamic instability and side effects.

  9. Urinary L-FABP predicts poor outcomes in critically ill patients with early acute kidney injury.

    Science.gov (United States)

    Parr, Sharidan K; Clark, Amanda J; Bian, Aihua; Shintani, Ayumi K; Wickersham, Nancy E; Ware, Lorraine B; Ikizler, T Alp; Siew, Edward D

    2015-03-01

    Biomarker studies for early detection of acute kidney injury (AKI) have been limited by nonselective testing and uncertainties in using small changes in serum creatinine as a reference standard. Here we examine the ability of urine L-type fatty acid-binding protein (L-FABP), neutrophil gelatinase-associated lipocalin (NGAL), interleukin-18 (IL-18), and kidney injury molecule-1 (KIM-1) to predict injury progression, dialysis, or death within 7 days in critically ill adults with early AKI. Of 152 patients with known baseline creatinine examined, 36 experienced the composite outcome. Urine L-FABP demonstrated an area under the receiver-operating characteristic curve (AUC-ROC) of 0.79 (95% confidence interval 0.70-0.86), which improved to 0.82 (95% confidence interval 0.75-0.90) when added to the clinical model (AUC-ROC of 0.74). Urine NGAL, IL-18, and KIM-1 had AUC-ROCs of 0.65, 0.64, and 0.62, respectively, but did not significantly improve discrimination of the clinical model. The category-free net reclassification index improved with urine L-FABP (total net reclassification index for nonevents 31.0%) and urine NGAL (total net reclassification index for events 33.3%). However, only urine L-FABP significantly improved the integrated discrimination index. Thus, modest early changes in serum creatinine can help target biomarker measurement for determining prognosis with urine L-FABP, providing independent and additive prognostic information when combined with clinical predictors.

  10. MART-10 represses cholangiocarcinoma cell growth and high vitamin D receptor expression indicates better prognosis for cholangiocarcinoma

    Science.gov (United States)

    Chiang, Kun-Chun; Yeh, Ta-Sen; Huang, Cheng-Cheng; Chang, Yu-Chan; Juang, Horng-Heng; Cheng, Chi-Tung; Pang, Jong-Hwei S.; Hsu, Jun-Te; Takano, Masashi; Chen, Tai C.; Kittaka, Atsushi; Hsiao, Michael; Yeh, Chun-Nan

    2017-01-01

    Cholangiocarcinoma (CCA) is a devastating disease due to no effective treatments available. Since the non-mineral functions of vitamin D emerges, 1α,25(OH)2D3, the active form of vitamin D, has been applied in anti-cancer researches. In this study, we demonstrated that both the 1α,25(OH)2D3 analog, MART-10, and 1α,25(OH)2D3 possessed anti-growth effect on human CCA cells with MART-10 much more potent than 1α,25(OH)2D3. The growth inhibition of both drugs were mediated by induction of G0/G1 cell cycle arrest through upregulation of p27 and downregulation of CDK4, CDK6, and cyclin D3. Human neutrophil gelatinase associated lipocalin (NGAL) was found to be involved in 1α,25(OH)2D3 and MART-10 meditated growth inhibition for CCA as knockdown of NGAL decreased Ki-67 expression in SNU308 cells and rendered SNU308 cells less responsive to 1α,25(OH)2D3 and MART-10 treatment. Vitamin D receptor (VDR) knockdown partly abolished MART-10-induced inhibition of NGAL and cell growth in SNU308 cells. The xenograft animal study demonstrated MART-10 could effectively repressed CCA growth in vivo without inducing obvious side effects. The IHC examination of human CCA specimen for VDR revealed that higher VDR expression was linked with better prognosis. Collectively, our results suggest that MART-10 could be a promising regimen for CCA treatment. PMID:28256614

  11. Testing Danegaptide Effects on Kidney Function after Ischemia/Reperfusion Injury in a New Porcine Two Week Model

    Science.gov (United States)

    Keller, Anna K.; Hansen, Rie Schultz; Nørregaard, Rikke; Krag, Søren Palmelund; Møldrup, Ulla; Pedersen, Michael; Jespersen, Bente; Birn, Henrik

    2016-01-01

    Introduction Ischemia/reperfusion injury (I/R-I) is a leading cause of acute kidney injury (AKI) and is associated with increased mortality. Danegaptide is a selective modifier of the gap junction protein connexion 43. It has cytoprotective as well as anti-arrhythmic properties and has been shown to reduce the size of myocardial infarct in pigs. The aim of this study was to investigate the ischemia-protective effect of Danegaptide in a porcine renal I/R-I model with two weeks follow up. Methods Unilateral renal I/R-I was induced in pigs by clamping the left renal artery over a two hour period. The model allowed examination of renal blood flow by magnetic resonance imaging (MRI) and the measurement of single kidney GFR two weeks after injury. Eleven animals were randomized to Danegaptide-infusion while nine animals received placebo. Kidney histology and urinary neutrophil gelatinase-associated lipocalin (NGAL) excretion were included as markers of AKI. Results Unilateral kidney I/R-I resulted in an immediate ~50% GFR reduction, associated with a four-fold increase in urinary NGAL-excretion. Fourteen days after I/R-I, the total GFR was ~75% of baseline with a significantly lower GFR in the injured left kidney compared to the right kidney. No differences in GFR were observed between the treated and non-treated animals immediately after I/R-I or at Day 14. Furthermore, no differences were observed in the urinary excretion of NGAL, renal blood flow or other markers of renal function. Conclusions As expected this porcine renal I/R-I model was associated with reduced GFR two weeks after injury. Danegaptide did not improve renal function after I/R-I. PMID:27760220

  12. Renoprotective effect of alprostadil in combination with statins in patients with mild to moderate renal failure undergoing coronary angiography

    Institute of Scientific and Technical Information of China (English)

    LIU Wei-jing; ZHANG Bu-chun; GUO Rong; WEI Yi-dong; LI Wei-ming; XU Ya-wei

    2013-01-01

    Background The role of alprostadil and statins in contrast-induced acute kidney injury (CI-AKI) is controversial.The purpose of this study was to explore the efficacy of combined therapy with alprostadil and statins in protecting renal function and preventing contrast-induced nephropathy (CIN) in patients undergoing coronary angiography.Methods A total of 156 consecutive patients with mild to moderate renal failure who underwent coronary angiography were enrolled in our study,and randomly categorized into two groups.In the statins group,80 patients were treated with statins before and after coronary angiography.in the alprostadil plus statins group,76 patients were treated with statins and alprostadil before and after coronary angiography.Serum creatinine (SCr),serum cystatin (CysC) and neutrophil gelatinase-associated lipocalin (NGAL) were detected after administration of contrast media,and adverse events were evaluated within six months.Results In both groups,the SCr,CysC and NGAL significantly increased after coronary angiography and peaked at 48,24 and 6 hours,respectively.SCr,CysC and NGAL were significantly lower in the alprostadil plus statins group than in the statins group (P<0.05).The incidence of CIN in the alprostadil plus statins group was slightly lower than in the statins group.The incidence of adverse events within six months in the alprostadil plus statins group was significantly lower than in the statins group (P=0.034).Conclusions Intravenous alprostadil in combination with oral statins is superior to statins alone for protecting renal function in patients with mild to moderate renal dysfunction who undergo coronary angiography,and can reduce the incidence of adverse events seen within six months.

  13. 机体脱水对Lipocalin-2基因影响的时效关系研究%The effects of dehydration on gene transcription of lipocalin-2 in rats

    Institute of Scientific and Technical Information of China (English)

    王宇; 曾婷婷

    2013-01-01

    OBJECTIVE To study the gene expression change of Lipocalin-2 in normal and water deprivated SD rat brain. METHODS 40 60d-old male SD rats were detached to control and three experimental groups randomly. Normal rat food and water was administrated to control group while experimental group was deprivated for normal water intake for 1d, 2d and 3d. All animals were sacrificed in 4h, and SONs were taken from the whole brain. The amount of mRNA and protein expression of Iipocalin-2 was detected. RESULTS Gene transcription and protein expression of Iipocalin-2 in 2d and 3d experimental groups were obviously stronger than control group (P< 0.05). CONCLUSION In chronic dehydration model, expression of Iipocalin-2 is obviously up-regulated which indicates that exclusive role of Iipocalin-2 in serum osmoregulation, a significant time-efficiency relation is found and the results are further verified by previous proteomic study.%目的 研究在不同的脱水时间下,大鼠脑组织视上核中Lipocalin-2基因的变化情况.方法 60日龄雄性SD大鼠40只,随机分为脱水1d、2d、3d组和正常饮水对照组.脱水期满后处死动物,取脑组织视上核部分,采用RT-PCR和Western-blot检测Lipocalin-2的表达.结果 与对照组相比,脱水2d、3d组视上核组织中Lipocalin-2的mRNA和蛋白表达水平都显著升高(P<0.05).结论 随着脱水时间的延长,Lipocalin-2在视上核组织中的含量逐渐增加,具有明显的时间-效应关系.提示了在机体脱水等原因导致的体液代谢混乱情况下,Lipocalin-2可能具有重要的生物学功能.

  14. Circulating lipocalin-2 and retinol-binding protein 4 are associated with intima-media thickness and subclinical atherosclerosis in patients with type 2 diabetes.

    Directory of Open Access Journals (Sweden)

    Yang Xiao

    Full Text Available BACKGROUND: The lipocalin family proteins, including lipocalin-2 and retinol-binding protein 4 (RBP4, are adipokines closely associated with obesity-related metabolic disorders. In this study, we evaluated the association of serum lipocalin-2 and RBP4 with intima-media thickness (IMT and subclinical atherosclerosis in type 2 diabetic patients. METHODS AND RESULTS: Serum levels of lipocalin-2 and RBP4 were measured in 284 type 2 diabetic patients. Subclinical atherosclerosis was assessed by IMT at carotid, femoral and iliac arteries with ultrasound. Patients with subclinical atherosclerosis showed significantly higher circulating concentrations of lipocalin-2 and RBP4 when compared to those without [112.9 (86.4 to 202.1 µg/L versus 77.2(55.0-150.4 µg/L, 37.1(32.3-40.8 mg/L versus 23.2(20.1-29.2 mg/L, respectively; P = 0.002, P<0.001, respectively]. Moreover, positive correlations were observed between carotid IMT and lipocalin-2 (r = 0.170, P = 0.018 or RBP4 (r = 0.132, P = 0.040, femoral IMT and lipocalin-2 (r = 0.160, P = 0.027, as well as between iliac IMT and RBP4 (r = 0.241, P<0.001. Multiple logistic regression analysis further demonstrated that these two adipokines were independent risk factors for subclinical atherosclerosis in type 2 diabetes. CONCLUSION: Circulating levels of lipocalin-2 and RBP4 are positively correlated with carotid IMT and subclinical atherosclerosis in type 2 diabetes, which suggests a potential role of these two lipid-binding chaperones in the pathogenesis of vascular complications of diabetes.

  15. Developmental expression of the lipocalin Lazarillo and its role in axonal pathfinding in the grasshopper embryo.

    Science.gov (United States)

    Sánchez, D; Ganfornina, M D; Bastiani, M J

    1995-01-01

    This article describes the expression pattern and functional analysis of Lazarillo, a novel cell surface glycoprotein expressed in the embryonic grasshopper nervous system, and a member of the lipocalin family. Lazarillo is expressed by a subset of neuroblasts, ganglion mother cells and neurons of the central nervous system, by all sensory neurons of the peripheral nervous system, and by a subset of neurons of the enteric nervous system. It is also present in a few non neuronal cells associated mainly with the excretory system. A monoclonal antibody raised against Lazarillo perturbs the extent and direction of growth of identified commissural pioneer neurons. We propose that Lazarillo is the receptor for a midline morphogen involved in the outgrowth and guidance of these neurons.

  16. Papel da lipocalina associada à gelatinase neutrofílica (NGAL urinária na nefrotoxicidade da cisplatina em pacientes com câncer de cabeça e pescoço

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    Luis Alberto Batista Peres

    2014-09-01

    Full Text Available Introdução: A injúria renal aguda (IRA em pacientes que recebem a cisplatina é comum, portanto, a avaliação da função renal em pacientes utilizando drogas nefrotóxicas é fundamental. Objetivo: Avaliar a incidência da IRA e o papel da lipocalina associada à gelatinase neutrofílica (NGAL na avaliação da função renal em pacientes com câncer de cabeça e pescoço (CCP que receberam a cisplatina. Métodos: Foram avaliados prospectivamente 50 pacientes com CCP, tratados com três sessões de cisplatina. Foram coletados sangue e urina 24 horas antes da cisplatina, 24 horas após a infusão, 48 horas após cada aplicação e 35 dias após o término do tratamento (NGAL urinária, proteína C reativa, creatinina e taxa de filtração glomerular, desidrogenase lática e magnésio plasmáticos. Resultados: A IRA foi observada em 78% dos pacientes. Houve aumento na creatinina, ureia e queda na TFG após cada ciclo de cisplatina, e aumento da NGAL urinária. Foi observada associação positiva entre os níveis de NGAL e a creatinina e PCR. Evidenciou-se um aumento dos níveis de creatinina, NGAL, PCR e diminuição da TFG nos pacientes com IRA em relação aos pacientes sem IRA. Conclusão: Observamos IRA em 78% dos pacientes avaliados com CCP tratados com a cisplatina e correlação da NGAL com a creatinina e a TFG em demonstrar lesão renal. Os níveis de NGAL podem estar elevados em relação aos níveis basais, mesmo antes da utilização da cisplatina.

  17. Biomarkers in predicting renal replacement therapy in acute septic kidney injury%不同生物学标志物对感染性急性肾损伤肾脏替代治疗的预测作用

    Institute of Scientific and Technical Information of China (English)

    蒋波; 姜利; 席修明

    2013-01-01

    Objective To evaluate whether the serum neutrophil gelatinase associated lipocalin ( sNGAL) , urinary neutrophil gelatinase lipocalin(uNGAL) , urinary interleukin-18 ( uIL-18) or urinary kidney injury molecule-1 ( uKIM-1 ) can predict the need for renal replacement therapy ( RRT) in patients with septic acute kidney injury (AKI). Methods A prospective observational study was conducted in patients with septic AKI whose expected ICU stay ^ 24 h. AKI was defined by American Kidney Injury (AKIN) criteria during the 48 h after admission, while sNGAL, uNGAL, uIL-18 and uKIM-1 were determined at the enrollment. Test characteristics were calculated to assess the diagnostic performance of these biomarkers. Results Forty-five patients were studied, RRT was initiated in 12 patients with septic AKI in the first 7 days. Two groups were defined according to the need of RRT; RRT group(ra=12) and non-RRT group(n=33). RRT group had higher median uNGAL level compared to non-RRT group(912. 0 vs 218. 0 ng/mL, P<0. 001). The predicting performance for uNGAL was good( AUC 0. 88), and that of sNGAL, uIL-18 and uKIM-1 was poor( AUC 0. 68,0. 69,0. 67, respectively). Conclusion uNGAL might be a good biomarker for predicting the need of RRT in patients with septic AKI.%目的 通过测定感染性急性肾损伤患者血清中性粒细胞胶原酶相关脂质运载蛋白(serum neutrophil gelatinase associated lipocalin,sNGAL)、尿中性粒细胞胶原酶相关脂质运载蛋白(urinary neutrophil gelatinase lipocalin,uNGAL)、尿肾损伤因子-1(urinary kidney injury molecule-1,uKIM-1)、尿白细胞介素-18(urinary interleukin-18,uIL-18)浓度,评价上述生物学标志物对感染性急性肾损伤患者接受肾脏替代治疗(renal replacement therapy,RRT)的预测作用.方法 预计入住重症监护病房(intensive care unit,ICU)时间≥24 h的全身性感染患者,并于入组48 h内存在或出现急性肾损伤.测定患者入组时sNGAL、uNGAL、uIL-18、uKIM-1

  18. The Lipocalin LPR-1 Cooperates with LIN-3/EGF Signaling To Maintain Narrow Tube Integrity in Caenorhabditis elegans.

    Science.gov (United States)

    Pu, Pu; Stone, Craig E; Burdick, Joshua T; Murray, John I; Sundaram, Meera V

    2016-12-30

    Lipocalins are secreted cup-shaped glycoproteins that bind sterols, fatty acids, and other lipophilic molecules. Lipocalins have been implicated in a wide array of processes related to lipophilic cargo transport, sequestration and signaling, and several are used as biomarkers for human disease, but the functions of most lipocalins remain poorly understood. Here we show that the C. elegans lipocalin LPR-1 is required to maintain apical membrane integrity and a continuous lumen in two narrow, unicellular tubes, the excretory duct and pore, during a period of rapid lumen elongation. LPR-1 fusion protein is expressed by the duct and pore and accumulates both intracellularly and in apical extracellular compartments, but it can also function cell non-autonomously when provided from outside of the excretory system. lpr-1 mutant defects can be rescued by increased signaling through the Epidermal growth factor (EGF) - Ras - Extracellular signal regulated kinase (ERK) pathway, which promotes the more elongated duct vs. less elongated pore tube fate. Spatial and temporal rescue experiments indicate that Ras signaling acts within the duct and pore tubes during or prior to cell fate determination to bypass the requirement for LPR-1. lpr-1 mutations did not disrupt LIN-3/EGF-dependent duct fate specification, prevent functioning of any specific LIN-3/EGF isoform, or alter LET-23/EGFR localization, and reduced signaling did not phenocopy or enhance lpr-1 mutant defects. These data suggest that LPR-1 protects lumen integrity through a LIN-3/EGF-independent mechanism, but that increased signaling upregulates some target(s) that can compensate for lpr-1 absence.

  19. Molecular characterization and developmental expression pattern of the chicken apolipoprotein D gene: implications for the evolution of vertebrate lipocalins.

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    Ganfornina, María D; Sánchez, Diego; Pagano, Aldo; Tonachini, Laura; Descalzi-Cancedda, Fiorella; Martínez, Salvador

    2005-01-01

    The insect Lazarillo and the mammalian apolipoprotein D (ApoD) are orthologous members of the lipocalin protein family. We report the cloning and embryonic expression of chicken ApoD, the first molecularly characterized nonmammalian ApoD. We also report the ApoD expression in mouse during postnatal development and some novel aspects of the expression of the paralogous lipocalin prostaglandin D-synthase (PGDS) and discuss these results in view of the lipocalin family evolution in vertebrates. ApoD is expressed in subsets of central nervous system (CNS) neurons and glia during late chicken embryogenesis. Contrary to mouse ApoD, no expression appears in neural crest-derived cephalic mesenchyme and blood vessel pericytes. Also, ApoD is expressed in developing chicken feathers. These expressions are corroborated by quantitative reverse transcriptase-polymerase chain reaction profiles. ApoD is expressed during mouse postnatal development in a subset of CNS neurons, astrocytes and oligodendrocytes, but also in meninges and pericytes. Chicken PGDS is expressed in brain meninges and perivascular cells. Our results suggest that the amniote last common ancestor expressed ApoD and PGDS in the brain during embryogenesis. ApoD appears restricted to ectodermal derivatives, whereas PGDS is expressed by derivatives of the three germ layers.

  20. Short-Term Regulation of Lipocalin-2 but not RBP-4 During Oral Lipid Tolerance Test and Oral Glucose Tolerance Test.

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    Schmid, A; Leszczak, S; Ober, I; Schäffler, A; Karrasch, T

    2016-02-01

    The postprandial regulation of lipocalin-2 and retinol binding protein-4 (RBP-4) by oral uptake of lipids and carbohydrates in healthy individuals has not yet been investigated. The regulation of lipocalin-2 and RBP-4 in 2 large cohorts of healthy volunteers during oral lipid tolerance test (OLTT; n=100) and oral glucose tolerance test (OGTT; n=100) was analyzed. One hundred healthy volunteers underwent OLTT and OGTT in an outpatient setting. Venous blood was drawn after 0, 2, 4, and 6 h in OLTT and after 0, 1, and 2 h in OGTT. In order to dissect carbohydrate-induced from lipid-induced effects, a novel OLTT solution completely free of carbohydrates and protein was applied. Subjects were characterized by anthropometric and laboratory parameters. Serum concentrations of lipocalin-2 and RBP-4 were measured by enzyme-linked immunosorbent assay (ELISA). Whereas RBP-4 levels remained unchanged during OGTT, lipocalin-2 concentrations significantly decreased during OGTT. During OLTT, RBP-4 levels were not influenced, whereas lipocalin-2 levels decreased significantly and stepwise. Fasting concentrations of RBP-4 were negatively correlated with BMI and waist-hip ratio, whereas lipocalin-2 levels were positively associated with BMI and waist-hip ratio. Female users of hormonal contraception had higher RBP-4 levels than females not on contraceptives. There is no significant short-term regulation of RBP-4 by orally ingested lipids or carbohydrates. Lipocalin-2 is downregulated after lipid and carbohydrate ingestion and this kind of regulation was not predicted by age, sex, triglycerides, glucose, or insulin levels.

  1. Increased serum levels of lipocalin-1 and -2 in patients with stable chronic obstructive pulmonary disease

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    Wang XR

    2014-05-01

    Full Text Available Xiao-ru Wang,1,* Yong-pu Li,2,* Shui Gao,2 Wei Xia,2 Kun Gao,1 Qing-hua Kong,1 Hui Qi,1 Ling Wu,1 Jing Zhang,3 Jie-ming Qu,4 Chun-xue Bai3 1Department of Pulmonary Medicine, Dahua Hospital, Xuhui District, Shanghai, 2Department of Pulmonary Medicine, People's Hospital of Changshou, Chongqing, 3Department of Pulmonary Medicine, Zhongshan Hospital, 4Department of Pulmonary Medicine, Huadong Hospital, Fudan University, Shanghai, People's Republic of China *These two authors contributed to this paper equally Abstract: Despite a number of studies on biomarkers in chronic obstructive pulmonary disease (COPD, only a few disease-related markers have been identified, yet we still have no satisfactory markers specific to innate immune system and neutrophil activation, which is essential in airway inflammation in COPD. Recent biological studies indicated that lipocalins (LCNs might be involved in airway inflammation and innate immunity; however, results from available studies on the association of LCNs with COPD are not consistent. We carried out a multicenter prospective observational cohort study to investigate the differences in serum levels of LCN1 and LCN2 between subjects with COPD (n=58 and healthy controls (n=29. Several validated inflammatory markers, including C-reactive protein, tumor necrosis factor-a, interleukin-6, and interleukin-8, were measured. The correlation of LCN1 and LCN2 with clinical features such as smoking habits, lung function, symptoms, and disease category was also analyzed. When comparing with healthy controls, serum levels of LCN1 (66.35±20.26 ng/mL versus 41.16±24.19 ng/mL, P<0.001 and LCN2 (11.29±3.92 ng/mL versus 6.09±5.13 ng/mL, P<0.001 were both elevated in subjects with COPD after adjusting for age, sex, smoking habits, and inflammatory biomarkers. Smoking history and tobacco exposure, as quantified by pack-year, had no impact on systemic expressions of LCN1 and LCN2 in our study. Blood levels of LCN1 and LCN2

  2. NGAL和血清胱抑素C在预测妊高征肾脏损伤中的诊断价值%Diagnostic Value of NGAL and Serum Cystatin C in Predicting Hypertensive Disease of Pregnancy Renal Injury

    Institute of Scientific and Technical Information of China (English)

    陈小英; 贾海红; 李晓丽

    2016-01-01

    Objective To investigate the diagnostic value of NGAL and serum cystatin C in predicting hypertensive disease of pregnancy renal injury. Method 100 patients with hypertensive disorder complicating pregnancy as the experimental group,select the same period admitted in our hospital and pregnancy outcome of normal pregnant women 50 cases as the control group. Detection of two serum NGAL and serum cystatin C levels within 24 h after admission and pregnancy after 72 h. Results Within 24 hours after admission,the experimental group in patients with serum NGAL levels,which was significantly higher than that in the control group,the two groups compared with statistical significance. Patients in the experimental group serum Cys-C levels was significantly higher than that in the control group, the two groups compared with statistical significance ( t=2. 256,P0. 05). Using the diagnostic value of ROC curve in the evaluation of NGAL and Cys-C. Among them,the area under the ROC curve of NGAL value is 0. 841,showed that NGAL is high diagnostic accuracy rate,Cys-C under the ROC curve area of 0. 810,showed that Cys-C diagnosis accurate medium,NGAL diagnosis accurate rate is higher than that of Cys-C. Conclusion NGAL and cystatin C may be as a predictor of pregnancy hypertension disease early renal damage index,in the disease early detection of pregnancy women with stage renal function, early detection of early treatment,can effectively reduce the maternal and perinatal mortality,improve maternal and child quality,worthy of clinical promotion.%目的:研究NGAL和血清胱抑素C在预测妊娠高血压疾病肾脏损伤中的诊断价值.方法选取妊娠高血压疾病患者100例作为实验组,另选取同期住院且妊娠结局正常的孕妇50例作为对照组.入院24 h内及产后72 h后检测两组血清NGAL和血清胱抑素C水平,并进行比较.结果入院24 h内,实验组患者血NGAL水平、血Cys-C水平显著高于对照组,两组比较

  3. Characterization of sputum biomarkers for asthma–COPD overlap syndrome

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    Gao J

    2016-09-01

    Full Text Available Jing Gao,1 Hiroshi Iwamoto,2 Jukka Koskela,3 Harri Alenius,4 Noboru Hattori,2 Nobuoki Kohno,5 Tarja Laitinen,6 Witold Mazur,1 Ville Pulkkinen1 1Heart and Lung Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland; 2Department of Molecular and Internal Medicine, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan; 3Clinical Research Unit of Pulmonary Diseases and Division of Pulmonology, Heart and Lung Center, University of Helsinki and Helsinki University Hospital, 4Unit of Systems Toxicology, Finnish Institute of Occupational Health, Helsinki, Finland; 5Hiroshima Cosmopolitan University, Hiroshima, Japan; 6Department of Pulmonary Diseases and Clinical Allergology, Turku University Hospital, University of Turku, Turku, Finland Abstract: Asthma–COPD overlap syndrome (ACOS is a commonly encountered chronic airway disease. However, ACOS is still a consensus-based clinical phenotype and the underlying inflammatory mechanisms are inadequately characterized. To clarify the inflammatory mediatypical for ACOS, five biomarkers, namely interleukin (IL-13, myeloperoxidase (MPO, neutrophil gelatinase-associated lipocalin (NGAL, chitinase-like protein (YKL-40, and IL-6, were selected. This study hypothesized that sputum biomarkers relevant for airway inflammation in asthma (IL-13, COPD (MPO, NGAL, or in both asthma and COPD (YKL-40, IL-6 could be used to differentiate ACOS from COPD and asthma. The aim of this study was to characterize the inflammatory profile and improve the recognition of ACOS. Induced sputum levels of IL-13, MPO, NGAL, YKL-40, and IL-6 were measured by enzyme-linked immunosorbent assay/Luminex assay in a Finnish discovery cohort (n=90 of nonsmokers, smokers, and patients with asthma, COPD, and ACOS and validated in a Japanese cohort (n=135. The classification accuracy of potential biomarkers was compared with area under the receiver operating characteristic curves. Only sputum NGAL

  4. Raised plasma Robo4 and cardiac surgery-associated acute kidney injury.

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    Anne Burke-Gaffney

    Full Text Available OBJECTIVE: Endothelial dysfunction associated with systemic inflammation can contribute to organ injury/failure following cardiac surgery requiring cardiopulmonary bypass (CPB. Roundabout protein 4 (Robo4, an endothelial-expressed transmembrane receptor and regulator of cell activation, is an important inhibitor of endothelial hyper-permeability. We investigated the hypothesis that plasma levels of Robo4 are indicative of organ injury, in particular acute kidney injury (AKI, after cardiac surgery. METHODS: Patients (n = 32 undergoing elective cardiac surgery with CPB were enrolled, prospectively. Plasma Robo4 concentrations were measured pre-, 2 and 24 h post-operatively, using a commercially available ELISA. Plasma and endothelial markers of inflammation [interleukin (IL -6, -8, -10: von Willibrand factor (vWF and angiopoeitin-2 (Ang-2] and the AKI marker, neutrophil gelatinase-associated lipocalin (NGAL, were also measured by ELISA. RESULTS: Plasma Robo4 increased significantly (p<0.001 from pre-operative levels of 2515 ± 904 pg/ml to 4473 ± 1915 pg/ml, 2 h after surgery; and returned to basal levels (2682 ± 979 pg/ml by 24 h. Plasma cytokines, vWF and NGAL also increased 2 h post-operatively and remained elevated at 24 h. Ang-2 increased 24 h post-operatively, only. There was a positive, significant correlation (r = 0.385, p = 0.0298 between Robo-4 and IL-10, but not other cytokines, 2 h post-operatively. Whilst raised Robo4 did not correlate with indices of lung dysfunction or other biomarkers of endothelial activation; there was a positive, significant correlation between raised (2 h plasma NGAL and Robo4 (r = 0.4322, p = 0.0135. When patients were classed as AKI or non-AKI either using NGAL cut-off of 150 ng/ml, or the AKI Network (AKIN clinical classification; plasma Robo4 was significantly higher (p = 0.0073 and 0.003, respectively in AKI vs. non-AKI patients (NGAL cut-off: 5350 ± 2191 ng/ml, n = 16 vs. 3595 ± 1068 pg/ml, n = 16

  5. Hyperglycemia and acute kidney injury in critically ill children

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    Gordillo R

    2016-08-01

    Full Text Available Roberto Gordillo,1 Tania Ahluwalia,2 Robert Woroniecki3 1Department of Pediatrics, Division of Nephrology, 2Department of Pediatrics, University of Illinois College of Medicine, Peoria, IL, USA; 3Division of Pediatric Nephrology and Hypertension, Stony Brook Children’s Hospital, Stony Brook, NY, USA Background: Hyperglycemia and acute kidney injury (AKI are common in critically ill children and have been associated with higher morbidity and mortality. The incidence of AKI in children is difficult to estimate because of the lack of a standard definition for AKI. The pediatric RIFLE (Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease criteria can be used to define AKI in children. Various biomarkers in urine and blood have been studied to detect AKI in critically ill children. However, it is not clear whether hyperglycemia is associated with AKI. Our objective was to evaluate the effect of hyperglycemia on kidney function and its effect on neutrophil gelatinase-associated lipocalin (NGAL in children. Methods: We studied retrospective and prospective cohorts of pediatric critically ill subjects admitted to the pediatric intensive care unit (PICU. We analyzed data from admission that included estimated glomerular filtration rate, plasma and urine NGAL, serum glucose and peak glycemia (highest glycemia during PICU admission, and length of hospital and PICU stay from two different institutions. Results: We found that the prevalence of hyperglycemia was 89% in the retrospective cohort and 86% in the prospective cohort, P=0.99. AKI was associated with peak glycemia, P=0.03. There was a statistically significant correlation between peak glycemia and hospital and PICU stays, P=<0.001 and P<0.001, respectively. Urine NGAL and plasma NGAL were not statistically different in subjects with and without hyperglycemia, P=0.99 and P=0.85, respectively. Subjects on vasopressors had lower estimated glomerular filtration rate and higher

  6. Temperature-induced lipocalin (TIL): a shield against stress-inducing environmental shocks in Saccharomyces cerevisiae.

    Science.gov (United States)

    Berterame, Nadia Maria; Bertagnoli, Stefano; Codazzi, Vera; Porro, Danilo; Branduardi, Paola

    2017-09-01

    The yeast Saccharomyces cerevisiae is a well-established workhorse, either for recombinant or natural products, thanks to its natural traits and easily editable metabolism. However, during a bio-based industrial process it meets multiple stresses generated by operative conditions such as non-optimal temperature, pH, oxygenation and product accumulation. The development of tolerant strains is therefore indispensable for the improvement of production, yield and productivity of fermentative processes. In this regard, plants as resilient organisms are a generous source for fishing genes and/or metabolites that can help the cell factory to counteract environmental constraints. Plants possess proteins named temperature-induced lipocalins, TIL, whose levels in the cells correlates with the tolerance to sudden temperature changes and with the scavenging of reactive oxygen species. In this work, the gene encoding for the Arabidopsis thaliana TIL protein was for the first time expressed in S. cerevisiae. The recombinant strain was compared and analysed against the parental counterpart under heat shock, freezing, exposure to organic acid and oxidative agents. In all the tested conditions, TIL expression conferred a higher tolerance to the stress imposed, making this strain a promising candidate for the development of robust cell factories able to overtake the major impairments of industrial processes. © FEMS 2017. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  7. Under pressure that splits a family in two. The case of lipocalin family.

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    Marchal, Stephane; Marabotti, Anna; Staiano, Maria; Varriale, Antonio; Domaschke, Thomas; Lange, Reinhard; D'Auria, Sabato

    2012-01-01

    The lipocalin family is typically composed of small proteins characterized by a range of different molecular recognition properties. Odorant binding proteins (OBPs) are a class of proteins of this family devoted to the transport of small hydrophobic molecules in the nasal mucosa of vertebrates. Among OBPs, bovine OBP (bOBP) is of great interest for its peculiar structural organization, characterized by a domain swapping of its two monomeric subunits. The effect of pressure on unfolding and refolding of native dimeric bOBP and of an engineered monomeric form has been investigated by theoretical and experimental studies under pressure. A coherent model explains the pressure-induced protein structural changes: i) the substrate-bound protein stays in its native configuration up to 330 MPa, where it loses its substrate; ii) the substrate-free protein dissociates into monomers at 200 MPa; and iii) the monomeric substrate-free form unfolds at 120 MPa. Molecular dynamics simulations showed that the pressure-induced tertiary structural changes that accompany the quaternary structural changes are mainly localized at the interface between the monomers. Interestingly, pressure-induced unfolding is reversible, but dimerization and substrate binding can no longer occur. The volume of the unfolding kinetic transition state of the monomer has been found to be similar to that of the folded state. This suggests that its refolding requires relatively large structural and/or hydrational changes, explaining thus the relatively low stability of the monomeric form of this class of proteins.

  8. A cell-surface receptor for lipocalin 24p3 selectively mediates apoptosis and iron uptake.

    Science.gov (United States)

    Devireddy, Laxminarayana R; Gazin, Claude; Zhu, Xiaochun; Green, Michael R

    2005-12-29

    The lipocalin mouse 24p3 has been implicated in diverse physiological processes, including apoptosis due to interleukin-3 (IL-3) deprivation and iron transport. Here we report cloning of the 24p3 cell-surface receptor (24p3R). Ectopic 24p3R expression confers on cells the ability to undergo either iron uptake or apoptosis, dependent upon the iron content of the ligand: Iron-loaded 24p3 increases intracellular iron concentration without promoting apoptosis; iron-lacking 24p3 decreases intracellular iron levels, which induces expression of the proapoptotic protein Bim, resulting in apoptosis. Intracellular iron delivery blocks Bim induction and suppresses apoptosis due to 24p3 addition or IL-3 deprivation. We find, unexpectedly, that the BCR-ABL oncoprotein activates expression of 24p3 and represses 24p3R expression, rendering BCR-ABL(+) cells refractory to secreted 24p3. By inhibiting BCR-ABL, imatinib induces 24p3R expression and, consequently, apoptosis. Our results reveal an unanticipated role for intracellular iron regulation in an apoptotic pathway relevant to BCR-ABL-induced myeloproliferative disease and its treatment.

  9. Under pressure that splits a family in two. The case of lipocalin family.

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    Stephane Marchal

    Full Text Available The lipocalin family is typically composed of small proteins characterized by a range of different molecular recognition properties. Odorant binding proteins (OBPs are a class of proteins of this family devoted to the transport of small hydrophobic molecules in the nasal mucosa of vertebrates. Among OBPs, bovine OBP (bOBP is of great interest for its peculiar structural organization, characterized by a domain swapping of its two monomeric subunits. The effect of pressure on unfolding and refolding of native dimeric bOBP and of an engineered monomeric form has been investigated by theoretical and experimental studies under pressure. A coherent model explains the pressure-induced protein structural changes: i the substrate-bound protein stays in its native configuration up to 330 MPa, where it loses its substrate; ii the substrate-free protein dissociates into monomers at 200 MPa; and iii the monomeric substrate-free form unfolds at 120 MPa. Molecular dynamics simulations showed that the pressure-induced tertiary structural changes that accompany the quaternary structural changes are mainly localized at the interface between the monomers. Interestingly, pressure-induced unfolding is reversible, but dimerization and substrate binding can no longer occur. The volume of the unfolding kinetic transition state of the monomer has been found to be similar to that of the folded state. This suggests that its refolding requires relatively large structural and/or hydrational changes, explaining thus the relatively low stability of the monomeric form of this class of proteins.

  10. Absence of intestinal PPARγ aggravates acute infectious colitis in mice through a lipocalin-2-dependent pathway.

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    Parag Kundu

    2014-01-01

    Full Text Available To be able to colonize its host, invading Salmonella enterica serovar Typhimurium must disrupt and severely affect host-microbiome homeostasis. Here we report that S. Typhimurium induces acute infectious colitis by inhibiting peroxisome proliferator-activated receptor gamma (PPARγ expression in intestinal epithelial cells. Interestingly, this PPARγ down-regulation by S. Typhimurium is independent of TLR-4 signaling but triggers a marked elevation of host innate immune response genes, including that encoding the antimicrobial peptide lipocalin-2 (Lcn2. Accumulation of Lcn2 stabilizes the metalloproteinase MMP-9 via extracellular binding, which further aggravates the colitis. Remarkably, when exposed to S. Typhimurium, Lcn2-null mice exhibited a drastic reduction of the colitis and remained protected even at later stages of infection. Our data suggest a mechanism in which S. Typhimurium hijacks the control of host immune response genes such as those encoding PPARγ and Lcn2 to acquire residence in a host, which by evolution has established a symbiotic relation with its microbiome community to prevent pathogen invasion.

  11. Lipocalin2 promotes invasion, tumorigenicity and gemcitabine resistance in pancreatic ductal adenocarcinoma.

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    Lisa Leung

    Full Text Available Lipocalin 2 (LCN2 is a small secreted protein and its elevated expression has been observed in pancreatic as well as other cancer types. LCN2 has been reported to promote resistance to drug-induced apoptosis, enhance invasion through its physical association with matrix metalloproteinase-9, and promote in vivo tumor growth. LCN2 was found to be commonly expressed in patient PDAC samples and its pattern of immunohistochemical staining intensified with increasing severity in high-grade precursor lesions. Downregulation of LCN2 in two pancreatic ductal adenocarcinoma cell lines (BxPC3 and HPAF-II with high LCN2 expression significantly reduced attachment, invasion, and tumour growth in vivo, but not proliferation or motility. Downregulation of LCN2 in two pancreatic ductal adenocarcinoma cell lines (BxPC3 and HPAF-II with high expression significantly reduced attachment, invasion, and tumour growth in vivo. In contrast, LCN2 overexpression in PANC1, with low endogenous expression, significantly increased invasion, attachment, and enhanced tumor growth. Suppression of LCN2 in BxPC3 and HPAF-II cells increased their sensitivity to gemcitabine in vitro, and in vivo when BxPC3 was tested. Furthermore, LCN2 promotes expression of VEGF and HIF1A which contribute to enhanced vascularity. These overall results demonstrate that LCN2 plays an important role in the malignant progression of pancreatic ductal carcinoma and is a potential therapeutic target for this disease.

  12. Lipocalin2 promotes invasion, tumorigenicity and gemcitabine resistance in pancreatic ductal adenocarcinoma.

    Science.gov (United States)

    Leung, Lisa; Radulovich, Nikolina; Zhu, Chang-Qi; Organ, Shawna; Bandarchi, Bizhan; Pintilie, Melania; To, Christine; Panchal, Devang; Tsao, Ming Sound

    2012-01-01

    Lipocalin 2 (LCN2) is a small secreted protein and its elevated expression has been observed in pancreatic as well as other cancer types. LCN2 has been reported to promote resistance to drug-induced apoptosis, enhance invasion through its physical association with matrix metalloproteinase-9, and promote in vivo tumor growth. LCN2 was found to be commonly expressed in patient PDAC samples and its pattern of immunohistochemical staining intensified with increasing severity in high-grade precursor lesions. Downregulation of LCN2 in two pancreatic ductal adenocarcinoma cell lines (BxPC3 and HPAF-II) with high LCN2 expression significantly reduced attachment, invasion, and tumour growth in vivo, but not proliferation or motility. Downregulation of LCN2 in two pancreatic ductal adenocarcinoma cell lines (BxPC3 and HPAF-II) with high expression significantly reduced attachment, invasion, and tumour growth in vivo. In contrast, LCN2 overexpression in PANC1, with low endogenous expression, significantly increased invasion, attachment, and enhanced tumor growth. Suppression of LCN2 in BxPC3 and HPAF-II cells increased their sensitivity to gemcitabine in vitro, and in vivo when BxPC3 was tested. Furthermore, LCN2 promotes expression of VEGF and HIF1A which contribute to enhanced vascularity. These overall results demonstrate that LCN2 plays an important role in the malignant progression of pancreatic ductal carcinoma and is a potential therapeutic target for this disease.

  13. Induction of Lipocalin2 in a Rat Model of Lung Irradiation

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    Sadaf Sultan

    2016-04-01

    Full Text Available Previously, we showed that lipocalin2 (LCN2 serum levels increased after liver irradiation and during acute-phase conditions. Here, we evaluate LCN2 expression and serum levels after single-dose lung irradiation with 25 Gy, percutaneously administered to the lung of randomly-paired male Wistar rats. Due to the concave anatomy of the lung recesses, the irradiation field included the upper part of the liver. No rat died due to irradiation. In control tissue, lung immunohistochemistry showed a high constitutive expression of LCN2+ granulocytes. LCN2 mRNA levels in lung tissue increased up to 24 h (9 ± 2.3-fold after irradiation. However, serum LCN2 levels remained undetectable after lung irradiation. LCN2 expression in the upper part of the liver increased up to 4.2-fold after lung irradiation, but the lower liver showed an early decrease. Acute-phase cytokines (IL-1β and TNF-α showed a significant increase on transcript level in both lung and upper liver, whilst the lower liver did not show any considerable increase. In conclusion, constitutive expression of LCN2 in local immune cells demonstrates its local role during stress conditions in the lung. The absence of LCN2 in the serum strengthens our previous findings that the liver is the key player in secreting LCN2 during stress conditions with liver involvement.

  14. Diverse functional roles of lipocalin-2 in the central nervous system.

    Science.gov (United States)

    Jha, Mithilesh Kumar; Lee, Shinrye; Park, Dong Ho; Kook, Hyun; Park, Keun-Gyu; Lee, In-Kyu; Suk, Kyoungho

    2015-02-01

    Lipocalin-2 (LCN2) is an acute phase protein with multiple functions that has garnered a great deal of interest over the last decade. However, its precise role in the pathophysiology of the central nervous system (CNS) remains to be outlined. Emerging evidence indicates that LCN2 is synthesized and secreted as an inducible factor from activated microglia, reactive astrocytes, neurons, and endothelial cells in response to inflammatory, infectious, or injurious insults. More recently, it has been recognized as a modulatory factor for diverse cellular phenotypes in the CNS, such as cell death, survival, morphology, migration, invasion, differentiation, and functional polarization. LCN2 induces chemokine production in the CNS in response to inflammatory challenges, and actively participates in the innate immune response, cellular influx of iron, and regulation of neuroinflammation and neurodegeneration. LCN2 also modulates several biobehavioral responses including pain hypersensitivity, cognitive functions, emotional behaviors, depression, neuronal excitability, and anxiety. This review covers recent advances in our knowledge regarding functional roles of LCN2 in the CNS, and discusses how LCN2 acts as an autocrine mediator of astrocytosis, a chemokine inducer, and a modulator of various cellular phenotypes in the CNS. We finally explore the possibilities and challenges of employing LCN2 as a signature of several CNS anomalies.

  15. Lipocalin prostaglandin D synthase and PPARγ2 coordinate to regulate carbohydrate and lipid metabolism in vivo.

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    Sam Virtue

    Full Text Available Mice lacking Peroxisome Proliferator-Activated Receptor γ2 (PPARγ2 have unexpectedly normal glucose tolerance and mild insulin resistance. Mice lacking PPARγ2 were found to have elevated levels of Lipocalin prostaglandin D synthase (L-PGDS expression in BAT and subcutaneous white adipose tissue (WAT. To determine if induction of L-PGDS was compensating for a lack of PPARγ2, we crossed L-PGDS KO mice to PPARγ2 KO mice to generate Double Knock Out mice (DKO. Using DKO mice we demonstrated a requirement of L-PGDS for maintenance of subcutaneous WAT (scWAT function. In scWAT, DKO mice had reduced expression of thermogenic genes, the de novo lipogenic program and the lipases ATGL and HSL. Despite the reduction in markers of lipolysis in scWAT, DKO mice had a normal metabolic rate and elevated serum FFA levels compared to L-PGDS KO alone. Analysis of intra-abdominal white adipose tissue (epididymal WAT showed elevated expression of mRNA and protein markers of lipolysis in DKO mice, suggesting that DKO mice may become more reliant on intra-abdominal WAT to supply lipid for oxidation. This switch in depot utilisation from subcutaneous to epididymal white adipose tissue was associated with a worsening of whole organism metabolic function, with DKO mice being glucose intolerant, and having elevated serum triglyceride levels compared to any other genotype. Overall, L-PGDS and PPARγ2 coordinate to regulate carbohydrate and lipid metabolism.

  16. Dynamics of Urinary Calprotectin after Renal Ischaemia.

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    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

  17. Grasshopper Lazarillo, a GPI-anchored Lipocalin, increases Drosophila longevity and stress resistance, and functionally replaces its secreted homolog NLaz.

    Science.gov (United States)

    Ruiz, Mario; Wicker-Thomas, Claude; Sanchez, Diego; Ganfornina, Maria D

    2012-10-01

    Lazarillo (Laz) is a glycosyl-phosphatidylinositol (GPI)-linked glycoprotein first characterized in the developing nervous system of the grasshopper Schistocerca americana. It belongs to the Lipocalins, a functionally diverse family of mostly secreted proteins. In this work we test whether the protective capacity known for Laz homologs in flies and vertebrates (NLaz, GLaz and ApoD) is evolutionarily conserved in grasshopper Laz, and can be exerted from the plasma membrane in a cell-autonomous manner. First we demonstrate that extracellular forms of Laz have autocrine and paracrine protecting effects for oxidative stress-challenged Drosophila S2 cells. Then we assay the effects of overexpressing GPI-linked Laz in adult Drosophila and whether it rescues both known and novel phenotypes of NLaz null mutants. Local effects of GPI-linked Laz inside and outside the nervous system promote survival upon different stress forms, and extend lifespan and healthspan of the flies in a cell-type dependent manner. Outside the nervous system, expression in fat body cells but not in hemocytes results in protection. Within the nervous system, glial cell expression is more effective than neuronal expression. Laz actions are sexually dimorphic in some expression domains. Fat storage promotion and not modifications in hydrocarbon profiles or quantities explain the starvation-desiccation resistance caused by Laz overexpression. This effect is exerted when Laz is expressed ubiquitously or in dopaminergic cells, but not in hemocytes. Grasshopper Laz functionally restores the loss of NLaz, rescuing stress-sensitivity as well as premature accumulation of aging-related damage, monitored by advanced glycation end products (AGEs). However Laz does not rescue NLaz courtship behavioral defects. Finally, the presence of two new Lipocalins with predicted GPI-anchors in mosquitoes shows that the functional advantages of GPI-linkage have been commonly exploited by Lipocalins in the arthropodan lineage.

  18. Lipid-binding properties of human ApoD and Lazarillo-related lipocalins: functional implications for cell differentiation.

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    Ruiz, Mario; Sanchez, Diego; Correnti, Colin; Strong, Roland K; Ganfornina, Maria D

    2013-08-01

    Lipocalins are a family of proteins characterized by a conserved eight-stranded β-barrel structure with a ligand-binding pocket. They perform a wide range of biological functions and this functional multiplicity must relate to the lipid partner involved. Apolipoprotein D (ApoD) and its insect homologues, Lazarillo (Laz) and neural Lazarillo (NLaz), share common ancestral functions like longevity, stress resistance and lipid metabolism regulation, coexisting with very specialized functions, like courtship behavior. Using tryptophan fluorescence titration, we screened the binding of 15 potential lipid partners for NLaz, ApoD and Laz and uncovered several novel ligands with apparent dissociation constants in the low micromolar range. Retinoic acid (RA), retinol, fatty acids and sphingomyelin are shared ligands. Sterols, however, showed a species-specific binding pattern: cholesterol did not show strong binding to human ApoD, whereas NLaz and Laz did bind ergosterol. Among the lipocalin-specific ligands, we found that ApoD selectively binds the endocannabinoid anandamide but not 2-acylglycerol, and that NLaz binds the pheromone 7-tricosene, but not 7,11-heptacosadiene or 11-cis-vaccenyl acetate. To test the functional relevance of lipocalin ligand binding at the cellular level, we analyzed the effect of ApoD, Laz and NLaz preloaded with RA on neuronal differentiation. Our results show that ApoD is necessary and sufficient to allow for RA differentiating activity. Both human ApoD and Drosophila NLaz successfully deliver RA to immature neurons, driving neurite outgrowth. We conclude that ApoD, NLaz and Laz bind selectively to a different but overlapping set of lipid ligands. This multispecificity can explain their varied physiological functions.

  19. Ischemic Postconditioning and Subanesthetic S(+)-Ketamine Infusion: Effects on Renal Function and Histology in Rats

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    de Resende, Marco A. C.; Pantoja, Alberto V.; Barcellos, Bruno M.; Reis, Eduardo P.; Consolo, Thays D.; Módolo, Renata P.; Domingues, Maria A. C.; Assad, Alexandra R.; Cavalcanti, Ismar L.; Castiglia, Yara M. M.; Módolo, Norma S. P.

    2015-01-01

    Background. Ischemic postconditioning (IP) in renal Ischemia reperfusion injury (IRI) models improves renal function after IRI. Ketamine affords significant benefits against IRI-induced acute kidney injury (AKI). The present study investigated the effects of IP and IP associated with subanesthetic S(+)-ketamine in ischemia-reperfusion-induced AKI. Methods. Forty-one Wistar rats were randomized into four groups: CG (10), control; KG (10), S(+)-ketamine infusion; IPG (10), IP; and KIPG (11), S(+)-ketamine infusion + IP. All rats underwent right nephrectomy. IRI and IP were induced only in IPG and KIPG by left kidney arterial occlusion for 30 min followed by reperfusion for 24 h. Complete reperfusion was preceded by three cycles of 2 min of reocclusion followed by 2 min of reperfusion. Renal function was assessed by measuring serum neutrophil gelatinase-associated lipocalin (NGAL), creatinine, and blood urea nitrogen (BUN). Tubular damage was evaluated by renal histology. Results. Creatinine and BUN were significantly increased. Severe tubular injury was only observed in the groups with IRI (IPG and KIPG), whereas no injury was observed in CG or KG. No significant differences were detected between IPG and KIPG. Conclusions. No synergic effect of the use of subanesthetic S(+)-ketamine and IP on AKI was observed in this rat model. PMID:26413552

  20. Protection of the Transplant Kidney from Preservation Injury by Inhibition of Matrix Metalloproteinases.

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    Michael A J Moser

    Full Text Available Matrix metalloproteinases (MMPs, particularly MMP-2 and MMP-9, play an important role in ischemic injury to the heart, yet it is not known if these MMPs are involved in the injury that occurs to the transplant kidney. We therefore studied the pharmacologic protection of transplant kidneys during machine cold perfusion.Human kidney perfusates were analyzed for the presence of injury markers such as cytochrome c oxidase, lactate dehydrogenase, and neutrophil-gelatinase associated lipocalin (NGAL, and MMP-2 and MMP-9 were measured. The effects of MMP inhibitors MMP-2 siRNA and doxycycline were studied in an animal model of donation after circulatory determination of death (DCDD.Markers of injury were present in all analyzed perfusates, with higher levels seen in perfusates from human kidneys donated after controlled DCDD compared to brain death and in perfusate from kidneys with delayed graft function. When rat kidneys were perfused at 4°C for 22 hours with the addition of MMP inhibitors, this resulted in markedly reduced levels of MMP-2, MMP-9 and analyzed injury markers.Based on our study, MMPs are involved in preservation injury and the supplementation of preservation solution with MMP inhibitors is a potential novel strategy in protecting the transplant kidney from preservation injury.

  1. Opinion paper on innovative approach of biomarkers for infectious diseases and sepsis management in the emergency department.

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    Di Somma, Salvatore; Magrini, Laura; Travaglino, Francesco; Lalle, Irene; Fiotti, Nicola; Cervellin, Grianfranco; Avanzi, Gian Carlo; Lupia, Enrico; Maisel, Alan; Hein, Frauke; Wagner, Florian; Lippi, Giuseppe

    2013-06-01

    Sepsis is a leading healthcare problem, accounting for the vast majority of fatal events in critically ill patients. Beyond early diagnosis and appropriate treatment, this condition requires a multifaceted approach for monitoring the severity, the potential organ failure as well as the risk of death. Monitoring of the efficacy of treatment is also a major issue in the emergency department (ED). The assessment of critically ill conditions and the prognosis of patients with sepsis is currently based on some scoring systems, which are, however, inefficient to provide definite clues about organ failure and prognosis in general. The discretionary and appropriate use of some selected biomarkers such as procalcitonin, inducible protein 10 (IP10), Group IV phospholipase A2 type II (PLA2 II), neutrophil gelatinase-associated lipocalin (NGAL), natriuretic peptides, mature adrenomedullin (ADM), mid-regional pro-adrenomedullin (MR-proADM), copeptin, thrombopoietin, Mer receptor and even red blood cell distribution width (RDW) represent thereby an appealing perspective in the diagnosis and management of patients with sepsis. Nevertheless, at the moment, it is not still clear if it is better to use a multimarkers approach or if a single, most appropriate, biomarker exists. This collective opinion paper is aimed at providing an overview about the potential clinical usefulness of some innovative biomarkers of sepsis in its diagnosis and prognosis, but also in the treatment management of the disease. This manuscript represents a synopsis of the lectures of Third Italian GREAT Network Congress, that was hold in Rome, 15-19 October 2012.

  2. Endothelial glycocalyx damage is associated with leptospirosis acute kidney injury.

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    Libório, Alexandre Braga; Braz, Marcelo Boecker Munoz; Seguro, Antonio Carlos; Meneses, Gdayllon C; Neves, Fernanda Macedo de Oliveira; Pedrosa, Danielle Carvalho; Cavalcanti, Luciano Pamplona de Góes; Martins, Alice Maria Costa; Daher, Elizabeth de Francesco

    2015-03-01

    Leptospirosis is a common disease in tropical countries, and the kidney is one of the main target organs. Membrane proteins of Leptospira are capable of causing endothelial damage in vitro, but there have been no studies in humans evaluating endothelial glycocalyx damage and its correlation with acute kidney injury (AKI). We performed a cohort study in an outbreak of leptospirosis among military personnel. AKI was diagnosed in 14 of 46 (30.4%) patients. Leptospirosis was associated with higher levels of intercellular adhesion molecule-1 (ICAM-1; 483.1 ± 31.7 versus 234.9 ± 24.4 mg/L, P leptospirosis-associated AKI had increased level of syndecan-1 (112.1 ± 45.4 versus 41.5 ± 11.7 ng/mL, P = 0.021) and ICAM-1 (576.9 ± 70.4 versus 434.9 ± 35.3, P = 0.034) compared with leptospirosis patients with no AKI. Association was verified between syndecan-1 and ICAM-1 with serum creatinine elevation and neutrophil gelatinase-associated lipocalin (NGAL) levels. This association remained even after multivariate analysis including other AKI-associated characteristics. Endothelial injury biomarkers are associated with leptospirosis-associated renal damage.

  3. Urinary Markers of Tubular Injury in Early Diabetic Nephropathy

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    Temesgen Fiseha

    2016-01-01

    Full Text Available Diabetic nephropathy (DN is a common and serious complication of diabetes associated with adverse outcomes of renal failure, cardiovascular disease, and premature mortality. Early and accurate identification of DN is therefore of critical importance to improve patient outcomes. Albuminuria, a marker of glomerular involvement in early renal damage, cannot always detect early DN. Thus, more sensitive and specific markers in addition to albuminuria are needed to predict the early onset and progression of DN. Tubular injury, as shown by the detection of tubular injury markers in the urine, is a critical component of the early course of DN. These urinary tubular markers may increase in diabetic patients, even before diagnosis of microalbuminuria representing early markers of normoalbuminuric DN. In this review we summarized some new and important urinary markers of tubular injury, such as neutrophil gelatinase associated lipocalin (NGAL, kidney injury molecule-1 (KIM-1, liver-type fatty acid binding protein (L-FABP, N-acetyl-beta-glucosaminidase (NAG, alpha-1 microglobulin (A1M, beta 2-microglobulin (B2-M, and retinol binding protein (RBP associated with early DN.

  4. Diagnostic and predictive biomarkers for pre-eclampsia in patients with established hypertension and chronic kidney disease.

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    Bramham, Kate; Seed, Paul T; Lightstone, Liz; Nelson-Piercy, Catherine; Gill, Carolyn; Webster, Philip; Poston, Lucilla; Chappell, Lucy C

    2016-04-01

    Women with chronic kidney disease (CKD) and chronic hypertension (CHT) frequently develop superimposed pre-eclampsia, but distinction from pre-existing disease is challenging. Plasma placental growth factor (PlGF), B-type natriuretic peptide (BNP), neutrophil gelatinase-associated lipocalin (NGAL), and serum relaxin concentrations were quantified in a longitudinal prospective cohort of 121 women with CKD: 44 with chronic hypertension, and 79 healthy controls. Biomarker concentrations were compared with 32 women with pre-eclampsia without pre-existing disease. Test performance was evaluated for diagnosis of superimposed pre-eclampsia requiring delivery within 14 days of sampling. PlGF was evaluated as a promising marker in a validation cohort of women with suspected pre-eclampsia (29 with CKD; 94 with chronic hypertension; 29 with superimposed pre-eclampsia requiring delivery within 14 days) and compared with women without pre-existing disease (290 with no pre-eclampsia and 176 with pre-eclampsia requiring delivery within 14 days). From 20 and up to 42 weeks of gestation, lower maternal PlGF concentrations had high diagnostic accuracy for superimposed pre-eclampsia requiring delivery within 14 days (receiver operator characteristic 0.85) and confirmed in the validation cohort. The other plasma and serum biomarkers were not discriminatory. Thus, plasma PlGF concentrations could potentially help guide clinical decision making regarding admission and delivery for superimposed pre-eclampsia.

  5. Once daily administration of the SGLT2 inhibitor, empagliflozin, attenuates markers of renal fibrosis without improving albuminuria in diabetic db/db mice.

    Science.gov (United States)

    Gallo, Linda A; Ward, Micheal S; Fotheringham, Amelia K; Zhuang, Aowen; Borg, Danielle J; Flemming, Nicole B; Harvie, Ben M; Kinneally, Toni L; Yeh, Shang-Ming; McCarthy, Domenica A; Koepsell, Hermann; Vallon, Volker; Pollock, Carol; Panchapakesan, Usha; Forbes, Josephine M

    2016-05-26

    Blood glucose control is the primary strategy to prevent complications in diabetes. At the onset of kidney disease, therapies that inhibit components of the renin angiotensin system (RAS) are also indicated, but these approaches are not wholly effective. Here, we show that once daily administration of the novel glucose lowering agent, empagliflozin, an SGLT2 inhibitor which targets the kidney to block glucose reabsorption, has the potential to improve kidney disease in type 2 diabetes. In male db/db mice, a 10-week treatment with empagliflozin attenuated the diabetes-induced upregulation of profibrotic gene markers, fibronectin and transforming-growth-factor-beta. Other molecular (collagen IV and connective tissue growth factor) and histological (tubulointerstitial total collagen and glomerular collagen IV accumulation) benefits were seen upon dual therapy with metformin. Albuminuria, urinary markers of tubule damage (kidney injury molecule-1, KIM-1 and neutrophil gelatinase-associated lipocalin, NGAL), kidney growth, and glomerulosclerosis, however, were not improved with empagliflozin or metformin, and plasma and intra-renal renin activity was enhanced with empagliflozin. In this model, blood glucose lowering with empagliflozin attenuated some molecular and histological markers of fibrosis but, as per treatment with metformin, did not provide complete renoprotection. Further research to refine the treatment regimen in type 2 diabetes and nephropathy is warranted.

  6. Urinary Markers of Tubular Injury in Early Diabetic Nephropathy

    Science.gov (United States)

    Fiseha, Temesgen; Tamir, Zemenu

    2016-01-01

    Diabetic nephropathy (DN) is a common and serious complication of diabetes associated with adverse outcomes of renal failure, cardiovascular disease, and premature mortality. Early and accurate identification of DN is therefore of critical importance to improve patient outcomes. Albuminuria, a marker of glomerular involvement in early renal damage, cannot always detect early DN. Thus, more sensitive and specific markers in addition to albuminuria are needed to predict the early onset and progression of DN. Tubular injury, as shown by the detection of tubular injury markers in the urine, is a critical component of the early course of DN. These urinary tubular markers may increase in diabetic patients, even before diagnosis of microalbuminuria representing early markers of normoalbuminuric DN. In this review we summarized some new and important urinary markers of tubular injury, such as neutrophil gelatinase associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), liver-type fatty acid binding protein (L-FABP), N-acetyl-beta-glucosaminidase (NAG), alpha-1 microglobulin (A1M), beta 2-microglobulin (B2-M), and retinol binding protein (RBP) associated with early DN. PMID:27293888

  7. Role of markers for acute kidney injury in surgical management of patients with renal cancer

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    O. I. Kit

    2015-01-01

    Full Text Available The paper gives the results of studying the urinary levels of markers of acute kidney injury (AKI in 46 patients with renal cancer during separate ureteral catheterization before the surgery and 24 hours after laparoscopic partial nephrectomy performed due to elective indications under warm ischemia. The levels of cystatin C, neutrophil gelatinase-associated lipocalin (NGAL, liver-type fatty acid-binding protein (L-FABP, and interleukin-18 were examined by enzyme immunoassay. It has been established that the risk of early postoperative AKI may be predicted from the baseline urinary levels of cystatin C and LFABP in patients with renal cancer resulting from 15-20-min warm ischemia time during the partial nephrectomy. An approach based on estimation of the baseline urinary levels of cystatin C and L-FABP to be incorporated into a preoperative examination scheme is proposed for surgical treatment policy choosing in patients with renal cancer. A scheme for examining patients with renal cancer is also suggested for the risk of complications and the degree of AKI assessing in the early post-operative period.

  8. Ischemic Postconditioning and Subanesthetic S(+-Ketamine Infusion: Effects on Renal Function and Histology in Rats

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    Marco A. C. de Resende

    2015-01-01

    Full Text Available Background. Ischemic postconditioning (IP in renal Ischemia reperfusion injury (IRI models improves renal function after IRI. Ketamine affords significant benefits against IRI-induced acute kidney injury (AKI. The present study investigated the effects of IP and IP associated with subanesthetic S(+-ketamine in ischemia-reperfusion-induced AKI. Methods. Forty-one Wistar rats were randomized into four groups: CG (10, control; KG (10, S(+-ketamine infusion; IPG (10, IP; and KIPG (11, S(+-ketamine infusion + IP. All rats underwent right nephrectomy. IRI and IP were induced only in IPG and KIPG by left kidney arterial occlusion for 30 min followed by reperfusion for 24 h. Complete reperfusion was preceded by three cycles of 2 min of reocclusion followed by 2 min of reperfusion. Renal function was assessed by measuring serum neutrophil gelatinase-associated lipocalin (NGAL, creatinine, and blood urea nitrogen (BUN. Tubular damage was evaluated by renal histology. Results. Creatinine and BUN were significantly increased. Severe tubular injury was only observed in the groups with IRI (IPG and KIPG, whereas no injury was observed in CG or KG. No significant differences were detected between IPG and KIPG. Conclusions. No synergic effect of the use of subanesthetic S(+-ketamine and IP on AKI was observed in this rat model.

  9. Sepsis and Acute Kidney Injury.

    Science.gov (United States)

    Bilgili, Beliz; Haliloğlu, Murat; Cinel, İsmail

    2014-12-01

    Acute kindney injury (AKI) is a clinical syndrome which is generally defined as an abrupt decline in glomerular filtration rate, causing accumulation of nitrogenous products and rapid development of fluid, electrolyte and acid base disorders. In intensive care unit sepsis and septic shock are leading causes of AKI. Sepsis-induced AKI literally acts as a biologic indicator of clinical deterioration. AKI triggers variety of immune, inflammatory, metabolic and humoral patways; ultimately leading distant organ dysfunction and increases morbidity and mortality. Serial mesurements of creatinine and urine volume do not make it possible to diagnose AKI at early stages. Serum creatinine influenced by age, weight, hydration status and become apparent only when the kidneys have lost 50% of their function. For that reason we need new markers, and many biomarkers in the diagnosis of early AKI activity is assessed. Historically "Risk-Injury-Failure-Loss-Endstage" (RIFLE), "Acute Kidney Injury Netwok" (AKIN) and "The Kidney Disease/ Improving Global Outcomes" (KDIGO) classification systems are used for diagnosing easily in clinical practice and research and grading disease. Classifications including diagnostic criteria are formed for the identification of AKI. Neutrophil gelatinase associated lipocalin (NGAL), cystatin-C (Cys-C), kidney injury molecule-1 (KIM-1) and also "cell cycle arrest" molecules has been concerned for clinical use. In this review the pathophysiology of AKI, with the relationship of sepsis and the importance of early diagnosis of AKI is evaluated.

  10. Effect of copper on extracellular levels of key pro-inflammatory molecules in hypothalamic GN11 and primary neurons.

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    Spisni, Enzo; Valerii, Maria Chiara; Manerba, Marcella; Strillacci, Antonio; Polazzi, Elisabetta; Mattia, Toni; Griffoni, Cristiana; Tomasi, Vittorio

    2009-07-01

    Copper dyshomeostasis is responsible for the neurological symptoms observed in the genetically inherited copper-dependent disorders (e.g., Menkes' and Wilson's diseases), but it has been also shown to have an important role in neurodegenerative diseases such as Alzheimer disease, prion diseases, Parkinson's disease and amyotrophic lateral sclerosis. It is widely accepted that increased extracellular copper levels contribute to neuronal pathogenic process by increasing the production of dangerous radical oxygen species, but the existence of other molecular mechanisms explaining copper neurotoxicity has not been investigated yet. By using a cellular model based on hypothalamic GN11 cultured neurons exposed to copper supplementation and by analysing the cell conditioned media, we try here to identify new molecular events explaining the association between extracellular copper accumulation and neuronal damages. We show here that increased extracellular copper levels produce a wide complex of alterations in the neuronal extracellular environment. In particular, copper affects the secretion of molecules involved in the protection of neurons against oxidative stress, such as cyclophilin A (CypA), or of molecules capable of shifting neuronal cells towards a pro-inflammatory state, such as IL-1alpha, IL-12, Rantes, neutrophil gelatinase-associated lipocalin (NGAL) and secreted protein acidic and rich in cysteine (SPARC). Copper pro-inflammatory properties have been confirmed by using primary neurons.

  11. Fecal lipocalin 2, a sensitive and broadly dynamic non-invasive biomarker for intestinal inflammation.

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    Benoit Chassaing

    Full Text Available Inflammation has classically been defined histopathologically, especially by the presence of immune cell infiltrates. However, more recent studies suggest a role for "low-grade" inflammation in a variety of disorders ranging from metabolic syndrome to cancer, which is defined by modest elevations in pro-inflammatory gene expression. Consequently, there is a need for cost-effective, non-invasive biomarkers that, ideally, would have the sensitivity to detect low-grade inflammation and have a dynamic range broad enough to reflect classic robust intestinal inflammation. Herein, we report that, for assessment of intestinal inflammation, fecal lipocalin 2 (Lcn-2, measured by ELISA, serves this purpose. Specifically, using a well-characterized mouse model of DSS colitis, we observed that fecal Lcn-2 and intestinal expression of pro-inflammatory cytokines (IL-1β, CXCL1, TNFα are modestly but significantly induced by very low concentrations of DSS (0.25 and 0.5%, and become markedly elevated at higher concentrations of DSS (1.0 and 4.0%. As expected, careful histopathologic analysis noted only modest immune infiltrates at low DSS concentration and robust colitis at higher DSS concentrations. In accordance, increased levels of the neutrophil product myeloperoxidase (MPO was only detected in mice given 1.0 and 4.0% DSS. In addition, fecal Lcn-2 marks the severity of spontaneous colitis development in IL-10 deficient mice. Unlike histopathology, MPO, and q-RT-PCR, the assay of fecal Lcn-2 requires only a stool sample, permits measurement over time, and can detect inflammation as early as 1 day following DSS administration. Thus, assay of fecal Lcn-2 by ELISA can function as a non-invasive, sensitive, dynamic, stable and cost-effective means to monitor intestinal inflammation in mice.

  12. Lipocalin 2 Enhances Migration and Resistance against Cisplatin in Endometrial Carcinoma Cells.

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    Tsutomu Miyamoto

    Full Text Available Lipocalin 2 (LCN2 is a secretory protein that is involved in various physiological processes including iron transport. We previously identified LCN2 as an up-regulated gene in endometrial carcinoma, and found that the overexpression of LCN2 and its receptor, SLC22A17, was associated with a poor prognosis. However, the functions and mechanism of action of LCN2 currently remain unclear.The LCN2-overexpressing endometrial carcinoma cell lines, HHUA and RL95-2, and LCN2-low-expressing one, HEC1B, were used. The effects of LCN2 on cell migration, cell viability, and apoptosis under various stresses, including ultraviolet (UV irradiation and cisplatin treatment, were examined using the scratch wound healing assay, WST-1 assay, and Apostrand assay, respectively.LCN2-silencing using shRNA method significantly reduced the migration ability of cells (p<0.05. Cytotoxic stresses significantly decreased the viability of LCN2-silenced cells more than that of control cells. In contrast, LCN2 overexpression was significantly increased cisplatin resistance. These effects were canceled by the addition of the iron chelator, deferoxamine. After UV irradiation, the expression of phosphorylated Akt (pAkt was decreased in LCN2-silenced cells, and the PI3K inhibitor canceled the difference induced in UV sensitivity by LCN2. The cisplatin-induced expression of pAkt was not affected by LCN2; however, the expression of p53 and p21 was increased by LCN2-silencing.These results indicated that LCN2 was involved in the migration and survival of endometrial carcinoma cells under various stresses in an iron-dependent manner. The survival function of LCN2 may be exerted through the PI3K pathway and suppression of the p53-p21 pathway. These functions of LCN2 may increase the malignant potential of endometrial carcinoma cells.

  13. High sugar-induced insulin resistance in Drosophila relies on the lipocalin Neural Lazarillo.

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    Matthieu Y Pasco

    Full Text Available In multicellular organisms, insulin/IGF signaling (IIS plays a central role in matching energy needs with uptake and storage, participating in functions as diverse as metabolic homeostasis, growth, reproduction and ageing. In mammals, this pleiotropy of action relies in part on a dichotomy of action of insulin, IGF-I and their respective membrane-bound receptors. In organisms with simpler IIS, this functional separation is questionable. In Drosophila IIS consists of several insulin-like peptides called Dilps, activating a unique membrane receptor and its downstream signaling cascade. During larval development, IIS is involved in metabolic homeostasis and growth. We have used feeding conditions (high sugar diet, HSD that induce an important change in metabolic homeostasis to monitor possible effects on growth. Unexpectedly we observed that HSD-fed animals exhibited severe growth inhibition as a consequence of peripheral Dilp resistance. Dilp-resistant animals present several metabolic disorders similar to those observed in type II diabetes (T2D patients. By exploring the molecular mechanisms involved in Drosophila Dilp resistance, we found a major role for the lipocalin Neural Lazarillo (NLaz, a target of JNK signaling. NLaz expression is strongly increased upon HSD and animals heterozygous for an NLaz null mutation are fully protected from HSD-induced Dilp resistance. NLaz is a secreted protein homologous to the Retinol-Binding Protein 4 involved in the onset of T2D in human and mice. These results indicate that insulin resistance shares common molecular mechanisms in flies and human and that Drosophila could emerge as a powerful genetic system to study some aspects of this complex syndrome.

  14. High sugar-induced insulin resistance in Drosophila relies on the lipocalin Neural Lazarillo.

    Science.gov (United States)

    Pasco, Matthieu Y; Léopold, Pierre

    2012-01-01

    In multicellular organisms, insulin/IGF signaling (IIS) plays a central role in matching energy needs with uptake and storage, participating in functions as diverse as metabolic homeostasis, growth, reproduction and ageing. In mammals, this pleiotropy of action relies in part on a dichotomy of action of insulin, IGF-I and their respective membrane-bound receptors. In organisms with simpler IIS, this functional separation is questionable. In Drosophila IIS consists of several insulin-like peptides called Dilps, activating a unique membrane receptor and its downstream signaling cascade. During larval development, IIS is involved in metabolic homeostasis and growth. We have used feeding conditions (high sugar diet, HSD) that induce an important change in metabolic homeostasis to monitor possible effects on growth. Unexpectedly we observed that HSD-fed animals exhibited severe growth inhibition as a consequence of peripheral Dilp resistance. Dilp-resistant animals present several metabolic disorders similar to those observed in type II diabetes (T2D) patients. By exploring the molecular mechanisms involved in Drosophila Dilp resistance, we found a major role for the lipocalin Neural Lazarillo (NLaz), a target of JNK signaling. NLaz expression is strongly increased upon HSD and animals heterozygous for an NLaz null mutation are fully protected from HSD-induced Dilp resistance. NLaz is a secreted protein homologous to the Retinol-Binding Protein 4 involved in the onset of T2D in human and mice. These results indicate that insulin resistance shares common molecular mechanisms in flies and human and that Drosophila could emerge as a powerful genetic system to study some aspects of this complex syndrome.

  15. Differential role of lipocalin-2 during immune-complex mediated acute and chronic inflammation

    Science.gov (United States)

    Shashidharamurthy, Rangaiah; Machiah, Deepa; Aitken, Jesse D; Putty, Kalyani; Srinivasan, Gayathri; Chassaing, Benoit; Parkos, Charles A; Selvaraj, Periasamy; Vijay-Kumar, Matam

    2013-01-01

    Objectives Lipocalin-2 (Lcn2) is an innate immune protein expressed by a variety of cells and is highly upregulated during several pathological conditions including immune-complex (IC) mediated inflammatory/autoimmune disorders. However, the function of Lcn2 during IC-mediated inflammation is largely unknown. Therefore our objective was to investigate the role of Lcn2 in IC-mediated diseases. Methods The upregulation of Lcn2 was determined by ELISA in three different mouse models of IC-mediated autoimmune disease: systemic lupus erythematosus, collagen-induced arthritis and serum-induced arthritis. The in vivo role of Lcn2 during IC-mediated inflammation was investigated using Lcn2 knockout (Lcn2KO) mice and their wild type (WT) littermates. Results Lcn2 levels were significantly elevated in all the three autoimmune disease models. Further, in an acute skin inflammation model, Lcn2KO mice demonstrated a 50% reduction in inflammation with histopathological analysis revealing strikingly reduced immune cell infiltration compared to WT mice. Administration of recombinant Lcn2 to Lcn2KO mice restored inflammation to levels observed in WT mice. Neutralization of Lcn2 using a monoclonal antibody significantly reduced inflammation in WT mice. In contrast, Lcn2KO mice developed more severe serum-induced arthritis compared to WT mice. Histological analysis revealed extensive tissue and bone destruction with significantly reduced neutrophil infiltration but considerably more macrophage migration in Lcn2KO mice when compared to WT. Conclusion These results demonstrate that Lcn2 may regulate immune cell recruitment to the site of inflammation, a process essential for the controlled initiation, perpetuation and resolution of inflammatory processes. Thus, Lcn2 may present a promising target in the treatment of IC-mediated inflammatory/autoimmune diseases. PMID:23280250

  16. Lipocalin-2-induced cytokine production enhances endometrial carcinoma cell survival and migration

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    Hsiu-Hsia Lin, Chi-Jr Liao, Ying-Chu Lee, Keng-Hsun Hu, Hsien-Wei Meng, Sin-Tak Chu

    2011-01-01

    Full Text Available Lipocalin-2 (Lcn-2 is an acute-phase protein that has been implicated in diverse physiological processes in mice, including: apoptosis, ion transport, inflammation, cell survival, and tumorigenesis. This study characterized the biological activity of Lcn-2 in human endometrial carcinoma cells (RL95-2. Exposure of RL95-2 cells to Lcn-2 for >24 h reduced Lcn-2-induced cell apoptosis, changed the cell proliferation and up-regulated cytokine secretions, including: interleukin-8 (IL-8, inteleukin-6 (IL-6, monocyte chemotatic protein-1 (MCP-1 and growth-related oncogene (GRO. However, IL-8 mRNA and protein levels were dramatically increased in Lcn-2-treated RL95-2 cells. To determine the IL-8 effect on Lcn-2-treated RL95-2 cells was our major focus. Adding recombinant IL-8 (rIL-8 resulted in decreased caspase-3 activity in Lcn-2-treated cells, whereas the addition of IL-8 antibodies resulted in significantly increased caspase-3 activity and decreased cell migration. Data indicate that IL-8 plays a crucial role in the induction of cell migration. Interestingly, Lcn-2-induced cytokines, secretion from RL95-2 cells, could not show the potent cell migration ability with the exception of IL-8. We conclude that Lcn-2 triggered cytokine secretions to prevent RL95-2 cells from undergoing apoptosis and subsequently increased cell migration. We hypothesize that Lcn-2 increased cytokine secretion by RL95-2 cells, which in turn activated a cellular defense system. This study suggests that Lcn-2 may play a role in the human female reproductive system or in endometrial cancer.

  17. The effects of sulodexide on both clinical and molecular parameters in patients with mixed arterial and venous ulcers of lower limbs

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    Serra R

    2014-05-01

    Full Text Available Raffaele Serra,1,2,* Luca Gallelli,3,* Angela Conti,1 Giovanni De Caridi,4 Mafalda Massara,4 Francesco Spinelli,4 Gianluca Buffone,1 Francesco Giuseppe Caliò,5 Bruno Amato,6 Simona Ceglia,7 Giuseppe Spaziano,8 Luca Scaramuzzino,9 Alessia Giovanna Ferrarese,10 Raffaele Grande,1 Stefano de Franciscis1,2 1Interuniversity Center of Phlebolymphology (CIFL, International Research and Educational Program in Clinical and Experimental Biotechnology, University Magna Graecia of Catanzaro, Catanzaro, Italy; 2Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy; 3Department of Health Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy; 4Cardiovascular and Thoracic Department, University of Messina, Messina, Italy; 5Unit of Vascular Surgery, S Anna Hospital, Catanzaro, Italy; 6Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy; 7Department of Experimental and Clinical Medicine, University Magna Graecia of Catanzaro, Catanzaro, Italy; 8Department of Experimental Medicine, Second University of Naples, Naples, Italy; 9University Campus BioMedico of Rome, Rome, Italy; 10Department of General Surgery, University of Turin, Turin, Italy *These authors contributed equally to this work Background: Mixed venous and arterial ulcers account for approximately 15%–30% of all venous leg ulcerations. Several studies have shown that matrix metalloproteinases (MMPs and neutrophil gelatinase-associated lipocalin (NGAL play a central role in the pathophysiology of venous and arterial diseases. Some studies have shown the efficacy of glycosaminoglycans, such as sulodexide (SDX, in treating patients with leg ulcers. The aim of this study was to evaluate clinical effects of SDX and its correlation with MMPs and NGAL expression in patients with mixed arterial and venous leg ulcers. Methods: Patients eligible for this study were of both sexes, older than 20 years, and with a

  18. Comparative Study of Serum NGAL and Cystatin C Detection in the Early Diagnosis of Diabetic Nephropathy%血清NGAL和Cystatin C检测对糖尿病肾病早期诊断的对比研究

    Institute of Scientific and Technical Information of China (English)

    罗莹

    2016-01-01

    Objective:To compare the effect of serum NGAL and Cystatin C detection in the early diagnosis of diabetic nephropathy.Method:88 patients with type 2 diabetes were selected as the observation group,88 healthy people were selected as the control group,serum NGAL and Cystatin C content were measured rseparately,the two groups were compared and made the relevant analysis.Result:(1)The serum NGAL and Cystatin C of the observation group were significantly better than the control group,the eGFR index was significantly lower than the control group,the differences were statistically significant(P<0.01);(2) lnNGAL negative correlation with eGFR,correlation coefficient was -0.8412,superior Cystatin C(correlation coefficient of -0.7189).Conclusion:Serum NGAL in the early diagnosis of diabetic nephropathy is better than Cystatin C,and it can be used for early diagnosis of clinical.%目的:比较血清NGAL和Cystatin C检测对糖尿病肾病早期诊断效果。方法:选取88例2型糖尿病患者为观察组,88例健康人为对照组,分别测量其血清NGAL和Cystatin C含量,对两组进行比较和相关性分析。结果:(1)观察组患者血清NGAL和Cystatin C均显著高于对照组, eGFR指标显著低于对照组,两组比较差异均有统计学意义(P<0.01);(2)lnNGAL与eGFR成负相关,相关系数为-0.8412,优于Cystatin C(相关系数为-0.7189)。结论:血清NGAL对糖尿病肾病早期诊断效果优于Cystatin C,可用于临床上的早期诊断。

  19. The effect of RAAS blockade on markers of renal tubular damage in diabetic nephropathy

    DEFF Research Database (Denmark)

    Nielsen, Stine; Rossing, Kasper; Hess, Georg

    2012-01-01

    Blockade of the renin-angiotensin-aldosterone system (RAAS) affects both the glomerulus and tubules. We aimed to investigate the effect of irbesartan on the tubular markers: urinary (u) neutrophil gelatinase associated protein (NGAL), Kidney injury molecule 1 (KIM1) and liver-fatty acid-binding p...

  20. The Piezo Actuator-Driven Pulsed Water Jet System for Minimizing Renal Damage after Off-Clamp Laparoscopic Partial Nephrectomy.

    Science.gov (United States)

    Kamiyama, Yoshihiro; Yamashita, Shinichi; Nakagawa, Atsuhiro; Fujii, Shinji; Mitsuzuka, Koji; Kaiho, Yasuhiro; Ito, Akihiro; Abe, Takaaki; Tominaga, Teiji; Arai, Yoichi

    2017-01-01

    In the setting of partial nephrectomy (PN) for renal cell carcinoma, postoperative renal dysfunction might be caused by surgical procedure. The aim of this study was to clarify the technical safety and renal damage after off-clamp laparoscopic PN (LPN) with a piezo actuator-driven pulsed water jet (ADPJ) system. Eight swine underwent off-clamp LPN with this surgical device, while off-clamp open PN was also performed with radio knife or soft coagulation. The length of the removed kidney was 40 mm, and the renal parenchyma was dissected until the renal calyx became clearly visible. The degree of renal degeneration from the resection surface was compared by Hematoxylin-Eosin staining and immunostaining for 1-methyladenosine, a sensitive marker for the ischemic tissue damage. The mRNA levels of neutrophil gelatinase-associated lipocalin (Ngal), a biomarker for acute kidney injury, were measured by quantitative real-time PCR. Off-clamp LPN with ADPJ system was successfully performed while preserving fine blood vessels and the renal calix with little bleeding. In contrast to other devices, the resection surface obtained with the ADPJ system showed only marginal degree of ischemic changes. Indeed, the expression level of Ngal mRNA was lower in the resection surface obtained with the ADPJ system than that with soft coagulation (p = 0.02). Furthermore, using the excised specimens of renal cell carcinoma, we measured the breaking strength at each site of the human kidney, suggesting the applicability of this ADPJ to clinical trials. In conclusion, off-clamp LPN with the ADPJ system could be safely performed with attenuated renal damage.

  1. Comparison of bone and renal effects in HIV-infected adults switching to abacavir or tenofovir based therapy in a randomized trial.

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    Thomas A Rasmussen

    Full Text Available INTRODUCTION: Our objective was to compare the bone and renal effects among HIV-infected patients randomized to abacavir or tenofovir-based combination anti-retroviral therapy. METHODS: In an open-label randomized trial, HIV-infected patients were randomized to switch from zidovudine/lamivudine (AZT/3TC to abacavir/lamivudine (ABC/3TC or tenofovir/emtricitabine (TDF/FTC. We measured bone mass density (BMD and bone turnover biomarkers (osteocalcin, osteocalcin, procollagen type 1 N-terminal propeptide (P1NP, alkaline phosphatase, type I collagen cross-linked C-telopeptide (CTx, and osteoprotegerin. We assessed renal function by estimated creatinine clearance, plasma cystatin C, and urinary levels of creatinine, albumin, cystatin C, and neutrophil gelatinase-associated lipocalin (NGAL. The changes from baseline in BMD and renal and bone biomarkers were compared across study arms. RESULTS: Of 40 included patients, 35 completed 48 weeks of randomized therapy and follow up. BMD was measured in 33, 26, and 27 patients at baseline, week 24, and week 48, respectively. In TDF/FTC-treated patients we observed significant reductions from baseline in hip and lumbar spine BMD at week 24 (-1.8% and -2.5% and week 48 (-2.1% and -2.1%, whereas BMD was stable in patients in the ABC/3TC arm. The changes from baseline in BMD were significantly different between study arms. All bone turnover biomarkers except osteoprotegerin increased in the TDF/FTC arm compared with the ABC/3TC arm, but early changes did not predict subsequent loss of BMD. Renal function parameters were similar between study arms although a small increase in NGAL was detected among TDF-treated patients. CONCLUSION: Switching to TDF/FTC-based therapy led to decreases in BMD and increases in bone turnover markers compared with ABC/3TC-based treatment. No major difference in renal function was observed. TRIAL REGISTRATION: Clinicaltrials.gov NCT00647244.

  2. Effects of captopril, telmisartan and bardoxolone methyl (CDDO-Me) in ischemia-reperfusion-induced acute kidney injury in rats: an experimental comparative study.

    Science.gov (United States)

    Kocak, Cengiz; Kocak, Fatma Emel; Akcilar, Raziye; Bayat, Zeynep; Aras, Bekir; Metineren, Mehmet Huseyin; Yucel, Mehmet; Simsek, Hasan

    2016-02-01

    Renal ischemia-reperfusion (IR) injury is one of the most common causes of acute kidney injury. This study investigated the effects of captopril (CAP), telmisartan (TEL) and bardoxolone methyl (BM) in animals with renal IR injury. Adult male Wistar-Albino rats were divided into six groups: control, vehicle, IR, IR with CAP, IR with TEL and IR with BM. Before IR was induced, drugs were administered by oral gavage. After a 60-min ischemia and a 120-min reperfusion period, bilateral nephrectomies were performed. Serum urea, creatinine, neutrophil gelatinase-associated lipocalin (NGAL) levels, tissue total oxidant status (TOS), total antioxidant status (TAS), total thiol (TT), asymmetric dimethylarginine (ADMA) levels, superoxide dismutase (SOD) activity and glutathione peroxidase (GSH-Px) activity were measured. Tissue mRNA expression levels of peroxisome proliferator-activated receptor-ɣ (PPAR-ɣ), nuclear factor erythroid 2-related factor 2 (Nrf2) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) were analyzed. In addition, renal tissues were evaluated histopathologically and immunohistochemically. All tested drugs reduced renal damage, apoptosis, urea, creatinine, NGAL, TOS, nitric oxide (NO) and ADMA levels, NF-κB, inducible nitric oxide synthase (iNOS) and endothelin-1 (ET-1) expressions (P < 0.001). All tested drugs increased SOD activity, GSH-Px activity, TAS levels, TT levels, endothelial nitric oxide synthase (eNOS) expression, dimethylarginine dimethylaminohydrolases (DDAHs) expression, Nrf2 expression and PPAR-ɣ expression (P < 0.001, P < 0.003). These results suggest that CAP, TEL and BM pretreatment could reduce renal IR injury via anti-inflammatory, antioxidant and anti-apoptotic effects. © 2016 John Wiley & Sons Australia, Ltd.

  3. 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

  4. 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

  5. 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

  6. Relationship between Fractional Exhaled Nitric Oxide Level and Efficacy of Inhaled Corticosteroid in Asthma-COPD Overlap Syndrome Patients with Different Disease Severity

    Science.gov (United States)

    2017-01-01

    This study explored the relationship between the fractional exhaled nitric oxide (FeNO) level and the efficacy of inhaled corticosteroid (ICS) in asthma-chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS) patients with different disease severity. A total of 127 ACOS patients with ACOS (case group) and 131 healthy people (control group) were enrolled in this study. Based on the severity of COPD, the ACOS patients were divided into: mild ACOS; moderate ACOS; severe ACOS; and extremely severe ACOS groups. We compared FeNO levels, pulmonary function parameters including percentage of forced expiratory volume in 1 second (FEV1) to predicted value (FEV1%pred), ratio of FEV1 to forced vital capacity (FEV1/FVC), inspiratory capacity to total lung capacity (IC/TLC) and residual volume to total lung capacity (RV/TLC), arterial blood gas parameters, including PH, arterial partial pressure of oxygen (PaO2) and arterial partial pressure of carbon dioxide (PaCO2), total serum immunoglobulin E (IgE), induced sputum eosinophil (EOS), plasma surfactant protein A (SP-A), plasma soluble receptor for advanced glycation end products (sRAGE), sputum myeloperoxidase (MPO), sputum neutrophil gelatinase-associated lipocalin (NGAL) and Asthma Control Test (ACT) scores, and COPD Assessment Test (CAT) scores. Compared with pre-treatment parameters, the FeNO levels, RV/TLC, PaCO2, total serum IgE, induced sputum EOS, plasma SP-A, sputum MPO, sputum NGAL, and CAT scores were significantly decreased after 6 months of ICS treatment, while FEV1%pred, FEV1/FVC, IC/TLC, PH, PaO2, plasma sRAGE, and ACT scores were significantly increased in ACOS patients with different disease severity after 6 months of ICS treatment. This finding suggests that the FeNO level may accurately predict the efficacy of ICS in the treatment of ACOS patients. PMID:28145647

  7. Effects of Maternal Exposure to Cadmium Oxide Nanoparticles During Pregnancy on Maternal and Offspring Kidney Injury Markers Using a Murine Model.

    Science.gov (United States)

    Blum, Jason L; Edwards, Joshua R; Prozialeck, Walter C; Xiong, Judy Q; Zelikoff, Judith T

    2015-01-01

    Nanoparticles (NP) are pervasive in many areas of modern life, with little known about their potential toxicities. One commercially important NP is cadmium oxide (CdO), which is used to synthesize other Cd-containing NP, such as quantum dots. Cadmium (Cd) is a well-known nephrotoxicant, but the nephrotoxic potential of CdO NP remains unknown, particularly when exposure occurs during pregnancy. Therefore, pregnant CD-1 mice were used to examine the effects of inhaled CdO NP (230 μg CdO NP/m(3)) on maternal and neonatal renal function by examining urinary creatinine and urinary biomarkers of kidney injury, including kidney injury molecule-1 (Kim-1) and neutrophil gelatinase-associated lipocalin (NGAL). Inhalation of CdO NP by dams produced a fivefold increase in urinary Kim-1 with no marked effect on urinary creatinine levels. Kim-1 mRNA expression peaked by gestational day (GD) 10.5, and NGAL expression increased from GD 10.5 to 17.5. In addition, histological analyses revealed proximal tubular pathology at GD 10.5. Neonatal Kim-1 mRNA expression rose between postnatal days (PND) 7 and 14, with mammary glands/milk being the apparent source of Cd for offspring. These studies demonstrate that, similar to what is seen with other Cd forms, Cd associated with inhaled CdO NP results in renal injury to both directly exposed dam and offspring. As commercial uses for nanotechnology continue to expand throughout the world, risks for unintentional exposure in the workplace increase. Given the large number of women in the industrial workforce, care needs to be taken to protect these already vulnerable populations.

  8. Significance of CD163-Positive Macrophages in Proliferative Glomerulonephritis.

    Science.gov (United States)

    Li, Jun; Liu, Chang-Hua; Xu, Dao-Liang; Gao, Bo

    2015-11-01

    CD163, a marker of M2 macrophages, possesses anti-inflammatory properties. This study aims to investigate the clinicopathological significance of CD163-positive macrophages in proliferative glomerulonephritis. Renal tissue samples from patients with lupus nephritis (LN, n = 22), antineutrophil cytoplasmic autoantibody (ANCA)-associated pauci-immune necrotizing glomerulonephritis (PNGN, n = 10), type 1 membranoproliferative glomerulonephritis (n = 5), minimal change disease (n = 8) and normal control kidneys (n = 3) were included in this study. The expression of CD163, CD68, CD20 and CD3 in renal tissues was detected by immunohistochemistry or immunofluorescence. The level of urinary neutrophil gelatinase-associated lipocalin (NGAL) was determined by enzyme-linked immunosorbent assay. CD163 was mainly expressed in active crescentic glomerulonephritis, proliferative glomerular lesions and areas of tubulointerstitial injury. Patients with LN-IV and PNGN had numerous CD163-positive cells in glomerular and acute tubulointerstitial lesions. CD163-positive cells in glomeruli positively correlated to proteinuria yet negatively correlated to estimated glomerular filtration rate. There was a positive correlation between the number of CD163 cells in acute tubulointerstitial lesions and NGAL levels, whereas a negative correlation between CD163 numbers and estimated glomerular filtration rate. The number of CD163-positive cells in crescentic glomerulonephritis was more than other groups. In LN, the number of CD163 cells in the tubulointerstitial and glomerular lesions had a positive correlation with activity index. Dual staining showed that CD163-positive cells also expressed CD68, although they did not show any staining for CD20 or CD3. CD163-positive macrophages were involved in the pathogenesis of proliferative glomerular lesions, active crescentic glomerulonephritis and acute tubular injury of patients with PNGN and active LN.

  9. Galectin-3 Blockade Reduces Renal Fibrosis in Two Normotensive Experimental Models of Renal Damage

    Science.gov (United States)

    Martinez-Martinez, Ernesto; Ibarrola, Jaime; Calvier, Laurent; Fernandez-Celis, Amaya; Leroy, Celine; Cachofeiro, Victoria; Rossignol, Patrick; Lopez-Andres, Natalia

    2016-01-01

    Background Galectin-3 (Gal-3), a β-galactoside-binding lectin, is increased in kidney injury and its pharmacological blockade reduces renal damage in acute kidney injury, hyperaldosteronism or hypertensive nephropathy. We herein investigated the effects of pharmacological Gal-3 inhibition by modified citrus pectin (MCP) in early renal damage associated with obesity and aortic stenosis (AS). Results Gal-3 was upregulated in kidneys from high fat diet (HFD) rats and in animals with partial occlusion of ascending aorta (AS). Urinary and plasma neutrophil gelatinase-associated lipocalin (NGAL) and urinary albumin were enhanced in HFD and AS rats. In kidney from obese rats, fibrotic markers (collagen, TFG-β), epithelial-mesenchymal transition molecules (α-smooth muscle actin, E-cadherin), inflammatory mediator (osteopontin) and kidney injury marker (kidney injury molecule-1) were modified. In kidney from AS rats, fibrotic markers (collagen, CTGF), epithelial-mesenchymal transition molecules (fibronectin, α-smooth muscle actin, β-catenin, E-cadherin) and kidney injury markers (NGAL, kidney injury molecule-1) were altered. Histologic observations of obese and AS rat kidneys revealed tubulointerstitial fibrosis. The pharmacological inhibition of Gal-3 with MCP normalized renal Gal-3 levels as well as functional, histological and molecular alterations in obese and AS rats. Conclusions In experimental models of mild kidney damage, the increase in renal Gal-3 expression paralleled with renal fibrosis, inflammation and damage, while these alterations were prevented by Gal-3 blockade. These data suggest that Gal-3 could be a new player in renal molecular, histological and functional alterations at early stages of kidney damage. PMID:27829066

  10. Levels of protein C and soluble thrombomodulin in critically ill patients with acute kidney injury: a multicenter prospective observational study.

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    Josée Bouchard

    Full Text Available Endothelial dysfunction contributes to the development of acute kidney injury (AKI in animal models of ischemia reperfusion injury and sepsis. There are limited data on markers of endothelial dysfunction in human AKI. We hypothesized that Protein C (PC and soluble thrombomodulin (sTM levels could predict AKI. We conducted a multicenter prospective study in 80 patients to assess the relationship of PC and sTM levels to AKI, defined by the AKIN creatinine (AKI Scr and urine output criteria (AKI UO. We measured marker levels for up to 10 days from intensive care unit admission. We used area under the curve (AUC and time-dependent multivariable Cox proportional hazard model to predict AKI and logistic regression to predict mortality/non-renal recovery. Protein C and sTM were not different in patients with AKI UO only versus no AKI. On intensive care unit admission, as PC levels are usually lower with AKI Scr, the AUC to predict the absence of AKI was 0.63 (95%CI 0.44-0.78. The AUC using log10 sTM levels to predict AKI was 0.77 (95%CI 0.62-0.89, which predicted AKI Scr better than serum and urine neutrophil gelatinase-associated lipocalin (NGAL and cystatin C, urine kidney injury molecule-1 and liver-fatty acid-binding protein. In multivariable models, PC and urine NGAL levels independently predicted AKI (p=0.04 and 0.02 and PC levels independently predicted mortality/non-renal recovery (p=0.04. In our study, PC and sTM levels can predict AKI Scr but are not modified during AKI UO alone. PC levels could independently predict mortality/non-renal recovery. Additional larger studies are needed to define the relationship between markers of endothelial dysfunction and AKI.

  11. Lipocalin 2 in the central nervous system host response to systemic lipopolysaccharide administration

    Directory of Open Access Journals (Sweden)

    Müller Marcus

    2011-09-01

    Full Text Available Abstract Background Lipocalin 2 (Lcn2 is a bacteriostatic factor that may also modulate cellular function, however, little is known concerning the expression or role of Lcn2 in CNS inflammation. Therefore, here we investigated the regulation and possible function of Lcn2 in the CNS following peripheral lipopolysaccharide (LPS injection in mice. Methods A murine model for systemic endotoxemia was used in this study. Wild type or Lcn2 KO mice (both genotypes C57BL/6 strain were given either a single or dual, staggered intraperitoneal injections of purified E. coli LPS or vehicle alone. The brain was examined for the expression and location of Lcn2 mRNA and protein and various markers for neuroinflammation were analyzed. Results Although undetectable under physiological conditions, both Lcn2 mRNA and protein were induced to high levels in the brain after LPS injection. By contrast, RNA corresponding to the putative Lcn2 (termed 24p3R receptor was present at high levels in the normal brain and remained unaltered by LPS injection. Differences between Lcn2 and 24p3R mRNA expression were found at the anatomic and cellular level. Endothelial cells, microglia and the choroid plexus but not neurons were identified as the main cellular sources for Lcn2 mRNA in the CNS. By contrast, 24p3R mRNA was detected in neurons and the choroid plexus only. Lcn2 protein was found to have a similar cellular localization as the corresponding RNA transcripts with the exception that subsets of neurons were also strongly positive. Various inflammatory, glial, and iron handling markers were analyzed and found to have similar alterations between WT and Lcn2 KO animals. Conclusions 1 Lcn2 production is strongly induced in the CNS by systemic LPS injection, 2 in addition to Lcn2 production at key gateways of bacterial entry to the CNS, neurons may be a target for the actions of Lcn2, which is apparently taken up by these cells, and 3 the cellular functions of Lcn2 in the CNS

  12. Maximizing lipocalin prediction through balanced and diversified training set and decision fusion.

    Science.gov (United States)

    Nath, Abhigyan; Subbiah, Karthikeyan

    2015-12-01

    Lipocalins are short in sequence length and perform several important biological functions. These proteins are having less than 20% sequence similarity among paralogs. Experimentally identifying them is an expensive and time consuming process. The computational methods based on the sequence similarity for allocating putative members to this family are also far elusive due to the low sequence similarity existing among the members of this family. Consequently, the machine learning methods become a viable alternative for their prediction by using the underlying sequence/structurally derived features as the input. Ideally, any machine learning based prediction method must be trained with all possible variations in the input feature vector (all the sub-class input patterns) to achieve perfect learning. A near perfect learning can be achieved by training the model with diverse types of input instances belonging to the different regions of the entire input space. Furthermore, the prediction performance can be improved through balancing the training set as the imbalanced data sets will tend to produce the prediction bias towards majority class and its sub-classes. This paper is aimed to achieve (i) the high generalization ability without any classification bias through the diversified and balanced training sets as well as (ii) enhanced the prediction accuracy by combining the results of individual classifiers with an appropriate fusion scheme. Instead of creating the training set randomly, we have first used the unsupervised Kmeans clustering algorithm to create diversified clusters of input patterns and created the diversified and balanced training set by selecting an equal number of patterns from each of these clusters. Finally, probability based classifier fusion scheme was applied on boosted random forest algorithm (which produced greater sensitivity) and K nearest neighbour algorithm (which produced greater specificity) to achieve the enhanced predictive performance

  13. Lipocalina associada à gelatinase de neutrófilos (NGAL e calprotectina no tecido laminar de equinos após obstrução jejunal, tratados ou não com hidrocortisona

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    Luciane M. Laskoski

    2012-09-01

    Full Text Available A laminite é uma doença podal grave que acomete os equídeos, sendo responsável por intenso sofrimento. Neste estudo foram pesquisadas a presença de calprotectina por meio da imunoistoquímica, e de lipocalina associada à gelatinase de neutrófilos (NGAL, por zimografia, no tecido laminar do casco de equinos após obstrução intestinal. Os animais foram divididos em quatro grupos: Grupo controle (Gc, contendo sete animais normais, sem procedimento cirúrgico; Grupo Instrumentado (Gi, contendo cinco animais, os quais passaram por todo o procedimento cirúrgico sem sofrerem obstrução intestinal; Grupo Não Tratado (Gnt, contendo quatro equinos submetidos a obstrução intestinal do jejuno por distensão de balão intraluminal, sem tratamento; e Grupo Tratado (Gt, contendo quatro equinos submetidos a obstrução intestinal, e tratados preventivamente com hidrocortisona. Houve imunomarcação de calprotectina em todos os grupos experimentais, com aumento nos equinos do grupo distendido em relação ao Gc. Com relação ao NGAL, houve aumento também do Gnt e do Gi em relação ao Gc. O Gt não diferiu dos demais. Conclui-se que a distensão do intestino delgado pode promover acúmulos de leucócitos nos cascos de equinos e que o NGAL é um método viável para se detectar infiltração neutrofílica em equinos. Novos estudos deverão ser realizados para se verificar possível benefício anti-inflamatório da hidrocortisona no casco de equinos com obstrução intestinal.

  14. Molecular and immunological characterization of the first allergenic lipocalin in hamster: the major allergen from Siberian hamster (Phodopus sungorus).

    Science.gov (United States)

    Torres, José Alberto; de Las Heras, Manuel; Maroto, Aroa Sanz; Vivanco, Fernando; Sastre, Joaquín; Pastor-Vargas, Carlos

    2014-08-22

    The most frequent pet allergy is to cat and dog, but in recent years, it has become increasingly popular to have other pets, and the risk of exposure to new allergens is more prevalent. The list of new pets includes hamsters, and one of the most popular hamsters is the Siberian hamster (Phodopus sungorus). The aim of this study was the characterization and cloning of the major allergen from this hamster. The study of its allergenicity and cross-reactivity could improve the specific diagnosis and treatment for hamster-allergic patients. Thirteen Siberian hamster-allergic patients were recruited at the outpatient clinic. Protein extracts were prepared from the hair, urine, and salivary glands of four hamster species (European, golden, Siberian, and Roborovski). IgE-binding proteins were detected by immunoblotting and identified by mass spectrometry. The recombinant protein was produced in Escherichia coli and then purified by metal chelate affinity chromatography. The allergenic properties of the recombinant protein were tested by ELISA and immunoblotting, and biological activity was tested according to capacity for basophil activation. Three IgE-binding proteins were identified in extracts obtained from Siberian hamster hair, urine, and salivary glands. All proteins corresponded to the same protein, which was identified as a lipocalin. This lipocalin had no cross-reactivity with common and golden hamsters. The recombinant allergen was cloned and purified, showing similar IgE reactivity in vitro to Siberian hamster protein extracts. Also, the recombinant allergen was capable of producing biological activation in vivo. The major Siberian hamster allergen was cloned, and allergenic properties were characterized, providing a new tool for specific diagnosis of allergy to Siberian hamster.

  15. Effects of TNF-α on expression of NGAL in HK-2 cells after ischemia reperfusion injury%TNF-α对缺氧复氧损伤的肾小管上皮HK-2细胞NGAL表达的影响

    Institute of Scientific and Technical Information of China (English)

    杨硕; 崔丽艳; 张捷

    2011-01-01

    Objective To investigate the effects of TNF-α on the expression of NGAL in HK-2 cells after ischemia reperfusion injury. Methods The ischemia reperfusion model of HK-2 cells was established in vitro. The expressions of NGAL gene with different ischemic time and concentration of TNF-α were detected by using RT-PCR. Results Our datas showed that the NGAL level in cells significantly increased,and ischemia for 1 h,2 h,4 h before reperfusion was higer than 0.5 h. The expression of NGAL gene could enhance with the increased concentration of TNF-α.Conclusion The expression of NGAL enhanced significantly after ischemia reperfusion,and the production of TNFα can increase the NGAL gene level.%目的 研究TNF-α对缺氧复氧损伤的HK-2细胞中NGAL表达的影响,探讨NGAL作为早期AKI标志的意义.方法 模拟缺氧复氧模型,RT-PCR法检测不同缺氧时间和不同浓度TNF-α作用后NGAL表达水平.结果 缺氧复氧后NGAL表达上调,1、2、4 h组均高于0.5 h组.随TNF-α浓度增高NGAL表达增加.缺氧1 h,同时200 μg/L TNF-α刺激后,NGAL明显提高.结论 缺氧复氧后,NGAL表达明显增强,TNF-α的大量产生,可能是NGAL表达增加的直接原因之一.

  16. Early Prediction of Lupus Nephritis Using Advanced Proteomics

    Science.gov (United States)

    2008-06-01

    neutrophil gelatinase- associated lipocalin in atherosclerosis and myocardial infarction . Arterioscler Thromb Vasc Biol 26:136–142 29. Mori K, Lee HT...the detection of drug metabolites in biological fluids. Rapid Commun Mass Spectrom. 17, 2632-2638. 11. Idborg-Björkman H, Edlund PO, Kvalheim OM

  17. Stable expression of lipocalin-type prostaglandin D synthase in cultured preadipocytes impairs adipogenesis program independently of endogenous prostanoids

    Energy Technology Data Exchange (ETDEWEB)

    Hossain, Mohammad Salim; Chowdhury, Abu Asad; Rahman, Mohammad Sharifur [Department of Life Science and Biotechnology, Shimane University, 1060 Nishikawatsu-cho, Matsue, Shimane 690-8504 (Japan); Nishimura, Kohji [Department of Molecular and Functional Genomics, Center for Integrated Research in Science, Shimane University, 1060 Nishikawatsu-cho, Matsue, Shimane 690-8504 (Japan); Jisaka, Mitsuo; Nagaya, Tsutomu [Department of Life Science and Biotechnology, Shimane University, 1060 Nishikawatsu-cho, Matsue, Shimane 690-8504 (Japan); Shono, Fumiaki [Department of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, 180 Yamashiro-cho, Tokushima-shi, Tokushima 770-8514 (Japan); Yokota, Kazushige, E-mail: yokotaka@life.shimane-u.ac.jp [Department of Life Science and Biotechnology, Shimane University, 1060 Nishikawatsu-cho, Matsue, Shimane 690-8504 (Japan)

    2012-02-15

    Lipocalin-type prostaglandin D synthase (L-PGDS) expressed preferentially in adipocytes is responsible for the synthesis of PGD{sub 2} and its non-enzymatic dehydration products, PGJ{sub 2} series, serving as pro-adipogenic factors. However, the role of L-PGDS in the regulation of adipogenesis is complex because of the occurrence of several derivatives from PGD{sub 2} and their distinct receptor subtypes as well as other functions such as a transporter of lipophilic molecules. To manipulate the expression levels of L-PGDS in cultured adipocytes, cultured preadipogenic 3T3-L1 cells were transfected stably with a mammalian expression vector having cDNA encoding murine L-PGDS oriented in the sense direction. The isolated cloned stable transfectants with L-PGDS expressed higher levels of the transcript and protein levels of L-PGDS, and synthesized PGD{sub 2} from exogenous arachidonic acid at significantly higher levels. By contrast, the synthesis of PGE{sub 2} remained unchanged, indicating no influence on the reactions of cyclooxygenase (COX) and PGE synthase. Furthermore, the ability of those transfectants to synthesize {Delta}{sup 12}-PGJ{sub 2} increased more greatly during the maturation phase. The sustained expression of L-PGDS in cultured stable transfectants hampered the storage of fats during the maturation phase of adipocytes, which was accompanied by the reduced gene expression of adipocyte-specific markers reflecting the down-regulation of the adipogenesis program. The suppressed adipogenesis was not rescued by either exogenous aspirin or peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}) agonists including troglitazone and {Delta}{sup 12}-PGJ{sub 2}. Taken together, the results indicate the negative regulation of the adipogenesis program by the enhanced expression of L-PGDS through a cellular mechanism involving the interference of the PPAR{gamma} signaling pathway without the contribution of endogenous pro-adipogenic prostanoids

  18. Klotho and S100A8/A9 as Discriminative Markers between Pre-Renal and Intrinsic Acute Kidney Injury.

    Directory of Open Access Journals (Sweden)

    Ae Jin Kim

    Full Text Available Early detection and accurate differentiation of the cause of AKI may improve the prognosis of the patient. However, to date, there are few reliable biomarkers that can discriminate between pre-renal and intrinsic AKI. In this study, we determined whether AKI is associated with altered serum and urinary levels of Klotho, S100A8/A9 (an endogenous ligand of toll-like receptor 4, and neutrophil gelatinase-associated lipocalin (NGAL, which may allow differentiation between pre-renal and intrinsic AKI. A volume-depleted pre-renal AKI model was induced in male Sprague Dawley rats fed a low-salt diet (0.03% without water 96 h before two intraperitoneal (IP injections of furosemide (20 mg/kg at a 24 h interval. In contrast, in the cisplatin-induced intrinsic AKI model, animals were given a single IP injection of cisplatin (5 mg/kg. All of the animals were euthanized 72 h after the first IP injection. Serum and urinary levels of Klotho, S100A8/A9, and NGAL were measured using an enzyme-linked immunosorbent assay. We also performed a proof-of-concept cross-sectional study to measure serum and urinary biomarkers in 61 hospitalized patients with established AKI. Compared to the intrinsic AKI group, the pre-renal AKI group showed a marked depression in urinary Klotho levels (13.21 ± 17.32 vs. 72.97 ± 17.96 pg/mL; P = 0.002. In addition, the intrinsic AKI group showed marked elevation of S100A8/A9 levels compared to the pre-renal AKI group (2629.97 ± 598.05 ng/mL vs. 685.09 ± 111.65 ng/mL; P = 0.002 in serum; 3361.11 ± 250.86 ng/mL vs. 741.72 ± 101.96 ng/mL; P = 0.003 in urine. There was no difference in serum and urinary NGAL levels between the pre-renal and intrinsic AKI groups. The proof-of-concept study with the hospitalized AKI patients also demonstrated decreased urinary Klotho in pre-renal AKI patients and increased urinary S100A8/A9 concentrations in intrinsic AKI patients. The attenuation of urinary Klotho and increase in urinary S100A8/A9 may

  19. Adipose-derived lipocalin 14 alleviates hyperglycaemia by suppressing both adipocyte glycerol efflux and hepatic gluconeogenesis in mice.

    Science.gov (United States)

    Lee, Jimmy Tsz Hang; Huang, Zhe; Pan, Kewu; Zhang, Herbert Jialiang; Woo, Connie Waihong; Xu, Aimin; Wong, Chi-Ming

    2016-03-01

    Growing evidence supports that dysregulation of adipose tissue-derived factors contributes to the pathogenesis of diabetes and its complications. Since our global gene profiling analysis has identified lipocalin-14 (LCN14)-a secretory protein with lipid-binding properties-as a potential adipokine highly expressed in white adipose tissue (WAT), this study aims to explore the metabolic roles of LCN14 in obese mice, and to investigate the functional mechanisms involved. Immunoassays and western blotting were performed to determine the circulating level and tissue distribution of LCN14, respectively. Recombinant adeno-associated virus (rAAV)-mediated gene delivery was used to overexpress LCN14 in diet-induced obese (DIO) mice and the effects on glucose and lipid metabolism were examined. LCN14 is expressed predominantly in WAT. Both circulating levels of LCN14 and its expression in adipose tissues are repressed in DIO and genetically inherited diabetic (db/db) mice. Overexpression of LCN14 by rAAV-mediated gene delivery in DIO mice significantly increased insulin sensitivity in major metabolic tissues and ameliorated hyperglycaemia by inhibiting hepatic gluconeogenesis. The reduced hepatic glucose production is attributed to the suppressive effects of LCN14 on the expression of gluconeogenic genes and on glycerol efflux in adipocytes, possibly by reducing the expression of aquaporin-7. Reduced LCN14 expression is involved in the pathogenesis of obesity-related metabolic dysregulation. LCN14 exerts its beneficial effects on glucose homeostasis and insulin sensitivity via its actions in both adipocytes and hepatocytes.

  20. Aptamer-based Sandwich Assay and its Clinical Outlooks for Detecting Lipocalin-2 in Hepatocellular Carcinoma (HCC)

    Science.gov (United States)

    Lee, Kyeong-Ah; Ahn, Ji-Young; Lee, Sang-Hee; Singh Sekhon, Simranjeet; Kim, Dae-Ghon; Min, Jiho; Kim, Yang-Hoon

    2015-01-01

    We validated a single-stranded, DNA aptamer-based, diagnostic method capable of detecting Lipocalin-2 (LCN2), a biomarker from clinically relevant hepatocellular carcinoma (HCC) patient serum, in the sandwich assay format. Nine aptamers (LCN2_apta1 to LCN2_apta9) for LCN2 were screened with SELEX processes, and a sandwich pair (LCN2_apta2 and LCN2_apta4) was finally chosen using surface plasmon resonance (SPR) and dot blotting analysis. The result of the proposed aptamer sandwich construction shows that LCN2 was sensitively detected in the concentration range of 2.5–500 ng mL−1 with a limit of detection of 0.6 ng mL−1. Quantitative measurement tests in HCC patients were run on straight serum and were compared with the performance of the conventional antibody-based ELISA kit. The aptamer sandwich assay demonstrated an excellent dynamic range for LCN2 at clinically relevant serum levels, covering sub-nanogram per mL concentrations. The new approach offers a simple and robust method for detecting serum biomarkers that have low and moderate abundance. It consists of functionalization, hybridization and signal read-out, and no dilution is required. The results of the study demonstrate the capability of the aptamer sandwich assay platform for diagnosing HCC and its potential applicability to the point-of-care testing (POCT) system. PMID:26039737

  1. Lipocalin 2 imparts selective pressure on bacterial growth in the bladder and is elevated in women with urinary tract infection.

    Science.gov (United States)

    Steigedal, Magnus; Marstad, Anne; Haug, Markus; Damås, Jan K; Strong, Roland K; Roberts, Pacita L; Himpsl, Stephanie D; Stapleton, Ann; Hooton, Thomas M; Mobley, Harry L T; Hawn, Thomas R; Flo, Trude H

    2014-12-15

    Competition for iron is a critical component of successful bacterial infections, but the underlying in vivo mechanisms are poorly understood. We have previously demonstrated that lipocalin 2 (LCN2) is an innate immunity protein that binds to bacterial siderophores and starves them for iron, thus representing a novel host defense mechanism to infection. In the present study we show that LCN2 is secreted by the urinary tract mucosa and protects against urinary tract infection (UTI). We found that LCN2 was expressed in the bladder, ureters, and kidneys of mice subject to UTI. LCN2 was protective with higher bacterial numbers retrieved from bladders of Lcn2-deficient mice than from wild-type mice infected with the LCN2-sensitive Escherichia coli strain H9049. Uropathogenic E. coli mutants in siderophore receptors for salmochelin, aerobactin, or yersiniabactin displayed reduced fitness in wild-type mice, but not in mice deficient of LCN2, demonstrating that LCN2 imparts a selective pressure on bacterial growth in the bladder. In a human cohort of women with recurrent E. coli UTIs, urine LCN2 levels were associated with UTI episodes and with levels of bacteriuria. The number of siderophore systems was associated with increasing bacteriuria during cystitis. Our data demonstrate that LCN2 is secreted by the urinary tract mucosa in response to uropathogenic E. coli challenge and acts in innate immune defenses as a colonization barrier that pathogens must overcome to establish infection. Copyright © 2014 by The American Association of Immunologists, Inc.

  2. Absence of Intestinal PPARγ Aggravates Acute Infectious Colitis in Mice through a Lipocalin-2–Dependent Pathway

    Science.gov (United States)

    Kundu, Parag; Ling, Teo Wei; Korecka, Agata; Li, Yinghui; D'Arienzo, Rossana; Bunte, Ralph M.; Berger, Thorsten; Arulampalam, Velmurugesan; Chambon, Pierre; Mak, Tak Wah; Wahli, Walter; Pettersson, Sven

    2014-01-01

    To be able to colonize its host, invading Salmonella enterica serovar Typhimurium must disrupt and severely affect host-microbiome homeostasis. Here we report that S. Typhimurium induces acute infectious colitis by inhibiting peroxisome proliferator-activated receptor gamma (PPARγ) expression in intestinal epithelial cells. Interestingly, this PPARγ down-regulation by S. Typhimurium is independent of TLR-4 signaling but triggers a marked elevation of host innate immune response genes, including that encoding the antimicrobial peptide lipocalin-2 (Lcn2). Accumulation of Lcn2 stabilizes the metalloproteinase MMP-9 via extracellular binding, which further aggravates the colitis. Remarkably, when exposed to S. Typhimurium, Lcn2-null mice exhibited a drastic reduction of the colitis and remained protected even at later stages of infection. Our data suggest a mechanism in which S. Typhimurium hijacks the control of host immune response genes such as those encoding PPARγ and Lcn2 to acquire residence in a host, which by evolution has established a symbiotic relation with its microbiome community to prevent pathogen invasion. PMID:24465207

  3. Modulation of lipocalin-type prostaglandin D2 synthase expression in catfish seminal vesicles by thyroid disrupting agents and hormones.

    Science.gov (United States)

    Sreenivasulu, Gunti; Pavani, Ayinampudi; Sudhakumari, Cheni-Chery; Dutta-Gupta, Aparna; Senthilkumaran, Balasubramanian

    2013-11-01

    Thyroid hormones play crucial role in several biological processes including reproduction. Disruption of normal thyroid status by environmental contaminants can cause severe impairment in reproductive functions. In our previous study, we reported down-regulation of a protein in seminal vesicular fluid of air-breathing catfish, Clarias gariepinus during experimentally induced hyperthyroidism. N-terminal amino acid sequence analysis followed by search in sequence database denoted it to be lipocalin-type prostaglandin D2 synthase (ptgds-b). In the present study, we cloned full-length cDNA of ptgds-b based on the N-terminal amino acid sequence. Surprisingly, Northern blot as well as RT-PCR analysis demonstrated the presence of ptgds-b transcript predominantly in seminal vesicles and developing testis. Further, ptgds-b mRNA significantly decreased in seminal vesicles following L-thyroxine overdose while there was an increased expression of ptgds-b after depletion of thyroid hormone by thiourea and withdrawal of the treatments reverted this effect. Treatment of catfish with human chorionic gonadotropin and estradiol significantly reduced ptgds-b expression. Taken together, we report ptgds-b as a thyroid hormone regulated protein in the seminal vesicles in addition to gonadotropin and estradiol. Further studies might explain the exclusive presence of ptgds-b in seminal vesicles and developing testis yet present data evaluated it as a putative biomarker for thyroid hormone disruption.

  4. Cloning and primary characterizations of rLcn9, a new member of epididymal lipocalins in rat

    Institute of Scientific and Technical Information of China (English)

    Xiangqi Li; Xiaoni Zhan; Shigui Liu; Shuanggang Hu; Chunfang Zhu; Susan H.Hall; Frank S.French; Qiang Liu; Yonglian Zhang

    2012-01-01

    Lipocalins are a structurally conserved and diversely functional family of proteins that are of potential importance in epididymis functions.The rat Lcn9 gene was cloned by in silico methods and genome walking based on homology to the rhesus monkey epididymal ESC513 and its polyclonal antisera were prepared.The rat Lcn9 gene is located on chromosome 3p13 spanning 7 exons,contains 2.3 kb and encodes 179 amino acids with a 17-amino acid signal peptide.Northern blot,western blot,and immunohistochemical staining analysis revealed that rat Lcn9 was a novel epididymis-specific gene,expressed selectively in the proximal caput region,influenced by luminal fluid testicular factors.Moreover,Lcn9 protein was modified by N-glycosylation and bound on the postacrosomal domain of caput sperm.In conclusion,the rat Lcn9 exhibited tissue-,region-,and temporal-specific expression patterns and its expression was regulated by luminal testicular factors.Its potential roles in sperm maturation are discussed.

  5. Lipocalin (LCN 2 Mediates Pro-Atherosclerotic Processes and Is Elevated in Patients with Coronary Artery Disease.

    Directory of Open Access Journals (Sweden)

    Raghav Oberoi

    Full Text Available Lipocalin (LCN 2 is associated with multiple acute and chronic inflammatory diseases but the underlying molecular and cellular mechanisms remain unclear. Here, we investigated whether LCN2 is released from macrophages and contributes to pro-atherosclerotic processes and whether LCN2 plasma levels are associated with the severity of coronary artery disease progression in humans.In an autocrine-paracrine loop, tumor necrosis factor (TNF-α promoted the release of LCN2 from murine bone-marrow derived macrophages (BMDM and vice versa. Moreover, LCN2 stimulation of BMDM led to up-regulation of M1 macrophage markers. In addition, enhanced migration of monocytic J774A.1 cells towards LCN2 was observed. Furthermore, LCN2 increased the expression of the scavenger receptors Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1 as well as scavenger receptor class A-1 (SRA-1 and induced the conversion of macrophages to foam cells. In atherosclerotic lesions of low density lipoprotein receptor-deficient (ldlr-/- mice fed a high fat, high cholesterol diet, LCN2 was found to be co-localized with macrophages in the shoulder region of the atherosclerotic plaque. In addition, LCN2 plasma levels were significantly increased in plasma samples of these mice. Finally, LCN2 plasma levels correlated with the severity of coronary artery disease (CAD in patients as determined by coronary angiography.Here we demonstrated that LCN2 plays a pivotal role in processes involved in atherogenesis by promoting polarization and migration of monocytic cells and development of macrophages towards foam cells. Moreover, LCN2 may be used as a prognostic marker to determine the status of CAD progression.

  6. Mucosal lipocalin 2 has pro-inflammatory and iron-sequestering effects in response to bacterial enterobactin.

    Directory of Open Access Journals (Sweden)

    Michael A Bachman

    2009-10-01

    Full Text Available Nasal colonization by both gram-positive and gram-negative pathogens induces expression of the innate immune protein lipocalin 2 (Lcn2. Lcn2 binds and sequesters the iron-scavenging siderophore enterobactin (Ent, preventing bacterial iron acquisition. In addition, Lcn2 bound to Ent induces release of IL-8 from cultured respiratory cells. As a countermeasure, pathogens of the Enterobacteriaceae family such as Klebsiella pneumoniae produce additional siderophores such as yersiniabactin (Ybt and contain the iroA locus encoding an Ent glycosylase that prevents Lcn2 binding. Whereas the ability of Lcn2 to sequester iron is well described, the ability of Lcn2 to induce inflammation during infection is unknown. To study each potential effect of Lcn2 on colonization, we exploited K. pneumoniae mutants that are predicted to be susceptible to Lcn2-mediated iron sequestration (iroA ybtS mutant or inflammation (iroA mutant, or to not interact with Lcn2 (entB mutant. During murine nasal colonization, the iroA ybtS double mutant was inhibited in an Lcn2-dependent manner, indicating that the iroA locus protects against Lcn2-mediated growth inhibition. Since the iroA single mutant was not inhibited, production of Ybt circumvents the iron sequestration effect of Lcn2 binding to Ent. However, colonization with the iroA mutant induced an increased influx of neutrophils compared to the entB mutant. This enhanced neutrophil response to Ent-producing K. pneumoniae was Lcn2-dependent. These findings suggest that Lcn2 has both pro-inflammatory and iron-sequestering effects along the respiratory mucosa in response to bacterial Ent. Therefore, Lcn2 may represent a novel mechanism of sensing microbial metabolism to modulate the host response appropriately.

  7. Estrogen receptor (ER)α-regulated lipocalin 2 expression in adipose tissue links obesity with breast cancer progression.

    Science.gov (United States)

    Drew, Brian G; Hamidi, Habib; Zhou, Zhenqi; Villanueva, Claudio J; Krum, Susan A; Calkin, Anna C; Parks, Brian W; Ribas, Vicent; Kalajian, Nareg Y; Phun, Jennifer; Daraei, Pedram; Christofk, Heather R; Hewitt, Sylvia C; Korach, Kenneth S; Tontonoz, Peter; Lusis, Aldons J; Slamon, Dennis J; Hurvitz, Sara A; Hevener, Andrea L

    2015-02-27

    Obesity is associated with increased breast cancer (BrCA) incidence. Considering that inactivation of estrogen receptor (ER)α promotes obesity and metabolic dysfunction in women and female mice, understanding the mechanisms and tissue-specific sites of ERα action to combat metabolic-related disease, including BrCA, is of clinical importance. To study the role of ERα in adipose tissue we generated fat-specific ERα knock-out (FERKO) mice. Herein we show that ERα deletion increased adipocyte size, fat pad weight, and tissue expression and circulating levels of the secreted glycoprotein, lipocalin 2 (Lcn2), an adipokine previously associated with BrCA development. Chromatin immunoprecipitation and luciferase reporter studies showed that ERα binds the Lcn2 promoter to repress its expression. Because adipocytes constitute an important cell type of the breast microenvironment, we examined the impact of adipocyte ERα deletion on cancer cell behavior. Conditioned medium from ERα-null adipocytes and medium containing pure Lcn2 increased proliferation and migration of a subset of BrCA cells in culture. The proliferative and promigratory effects of ERα-deficient adipocyte-conditioned medium on BrCA cells was reversed by Lcn2 deletion. BrCA cell responsiveness to exogenous Lcn2 was heightened in cell types where endogenous Lcn2 expression was minimal, but components of the Lcn2 signaling pathway were enriched, i.e. SLC22A17 and 3-hydroxybutyrate dehydrogenase (BDH2). In breast tumor biopsies from women diagnosed with BrCA we found that BDH2 expression was positively associated with adiposity and circulating Lcn2 levels. Collectively these data suggest that reduction of ERα expression in adipose tissue promotes adiposity and is linked with the progression and severity of BrCA via increased adipocyte-specific Lcn2 production and enhanced tumor cell Lcn2 sensitivity. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

  8. Estrogen Receptor (ER)α-regulated Lipocalin 2 Expression in Adipose Tissue Links Obesity with Breast Cancer Progression*

    Science.gov (United States)

    Drew, Brian G.; Hamidi, Habib; Zhou, Zhenqi; Villanueva, Claudio J.; Krum, Susan A.; Calkin, Anna C.; Parks, Brian W.; Ribas, Vicent; Kalajian, Nareg Y.; Phun, Jennifer; Daraei, Pedram; Christofk, Heather R.; Hewitt, Sylvia C.; Korach, Kenneth S.; Tontonoz, Peter; Lusis, Aldons J.; Slamon, Dennis J.; Hurvitz, Sara A.; Hevener, Andrea L.

    2015-01-01

    Obesity is associated with increased breast cancer (BrCA) incidence. Considering that inactivation of estrogen receptor (ER)α promotes obesity and metabolic dysfunction in women and female mice, understanding the mechanisms and tissue-specific sites of ERα action to combat metabolic-related disease, including BrCA, is of clinical importance. To study the role of ERα in adipose tissue we generated fat-specific ERα knock-out (FERKO) mice. Herein we show that ERα deletion increased adipocyte size, fat pad weight, and tissue expression and circulating levels of the secreted glycoprotein, lipocalin 2 (Lcn2), an adipokine previously associated with BrCA development. Chromatin immunoprecipitation and luciferase reporter studies showed that ERα binds the Lcn2 promoter to repress its expression. Because adipocytes constitute an important cell type of the breast microenvironment, we examined the impact of adipocyte ERα deletion on cancer cell behavior. Conditioned medium from ERα-null adipocytes and medium containing pure Lcn2 increased proliferation and migration of a subset of BrCA cells in culture. The proliferative and promigratory effects of ERα-deficient adipocyte-conditioned medium on BrCA cells was reversed by Lcn2 deletion. BrCA cell responsiveness to exogenous Lcn2 was heightened in cell types where endogenous Lcn2 expression was minimal, but components of the Lcn2 signaling pathway were enriched, i.e. SLC22A17 and 3-hydroxybutyrate dehydrogenase (BDH2). In breast tumor biopsies from women diagnosed with BrCA we found that BDH2 expression was positively associated with adiposity and circulating Lcn2 levels. Collectively these data suggest that reduction of ERα expression in adipose tissue promotes adiposity and is linked with the progression and severity of BrCA via increased adipocyte-specific Lcn2 production and enhanced tumor cell Lcn2 sensitivity. PMID:25468909

  9. Epigallocatechin-3-Gallate Inhibition of Myeloperoxidase and Its Counter-Regulation by Dietary Iron and Lipocalin 2 in Murine Model of Gut Inflammation.

    Science.gov (United States)

    Yeoh, Beng San; Aguilera Olvera, Rodrigo; Singh, Vishal; Xiao, Xia; Kennett, Mary J; Joe, Bina; Lambert, Joshua D; Vijay-Kumar, Matam

    2016-04-01

    Green tea-derived polyphenol (-)-epigallocatechin-3-gallate (EGCG) has been extensively studied for its antioxidant and anti-inflammatory properties in models of inflammatory bowel disease, yet the underlying molecular mechanism is not completely understood. Herein, we demonstrate that EGCG can potently inhibit the proinflammatory enzyme myeloperoxidase in vitro in a dose-dependent manner over a range of physiologic temperatures and pH values. The ability of EGCG to mediate its inhibitory activity is counter-regulated by the presence of iron and lipocalin 2. Spectral analysis indicated that EGCG prevents the peroxidase-catalyzed reaction by reverting the reactive peroxidase heme (compound I:oxoiron) back to its native inactive ferric state, possibly via the exchange of electrons. Further, administration of EGCG to dextran sodium sulfate-induced colitic mice significantly reduced the colonic myeloperoxidase activity and alleviated proinflammatory mediators associated with gut inflammation. However, the efficacy of EGCG against gut inflammation is diminished when orally coadministered with iron. These findings indicate that the ability of EGCG to inhibit myeloperoxidase activity is one of the mechanisms by which it exerts mucoprotective effects and that counter-regulatory factors such as dietary iron and luminal lipocalin 2 should be taken into consideration for optimizing clinical management strategies for inflammatory bowel disease with the use of EGCG treatment.

  10. Lipocalin-2基因表达产物对人胚肾细胞增殖的影响%Effect of Expressed Product of Lipocalin-2 Gene on Proliferation of Human Embryonic Kidney Cells

    Institute of Scientific and Technical Information of China (English)

    帖儒修; 朱道银; 李娜; 王爽

    2008-01-01

    目的 构建Lipocalin-2(Lcn-2)基凶真核表达质粒PL-2,并榆测其及前期原核表达的重组Lcn-2蛋白对人胚肾细胞HEK293增殖的影响.方法 利用RT-PCR从鼠巨噬细胞RAW264.7中扩增tcn-2基因,克隆人真核表达质粒pEGFP-C1中,构建蓖组质粒PL-2.转染HEK293细胞,通过荧光观察和RT-PCR鉴定Lcn-2基凶的表达.将重组质粒PL-2和前期原核表达的重组Lcn-2蛋白作用于HEK293细胞,通过MTT法检测细胞增殖情况,Western blot法检测细胞增殖核抗原(PCNA)的表达.结果 重组真核表达质粒PL-2经酶切和测序鉴定,证明构建正确.经荧光观察和RT-PCR鉴定,转染重组质粒PL-2的HEK293细胞中有Lcn-2基因的表达.加入重组Lcn-2蛋白后,HEK293细胞较对照组明显增殖,细胞中PCNA的表达也较对照组明显升高,而重组质粒PL-2对HEK293细胞增殖以及细胞中PCNA的表达均无影响.结论 已成功构建了Lcn-2基凶真核表达质粒,其对HEK293细胞的增殖无影响,而原核表达的重组Lcn-2蛋门对HEK293细胞的增殖有一定的促进作用,推测Lcn-2基因的表达产物可能通过与细胞膜受体结合促进HEK293细胞的增殖.

  11. Clinical characteristics of chronic kidney disease of non-traditional causes in women of agricultural communities in El Salvador.

    Science.gov (United States)

    Herrera Valdés, Raúl; Orantes, Carlos M; Almaguer López, Miguel; López Marín, Laura; Arévalo, Pedro Alfonso; Smith González, Magaly J; Morales, Fabrizio E; Bacallao, Raymed; Bayarre, Héctor D; Vela Parada, Xavier F

    2015-01-01

    A chronic kidney disease of non-traditional causes (CKDu) has emerged in Central America and elsewhere, predominantly affecting male farmworkers. In El Salvador (2009), it was the second cause of death in men > 18 years old. Causality has not been determined. Most available research focused on men and there is scarce data on women. Describe the clinical and histopathologic characteristics of CKDu in women of agricultural communities in El Salvador. A descriptive study was carried out in 10 women with CKDu stages 2, 3a, and 3b. Researchers studied demographics, clinical examination; hematological and biochemical analyses, urine sediment, renal injury markers, and assessed renal, cardiac, and peripheral arteries, liver, pancreas, and lung anatomy and functions. Kidney biopsy was performed in all. Data was collected on the Lime Survey platform and exported to SPSS 19.0. Patient distribution by stages: 2 (70%), 3a (10%), 3b (20%). Occupation: agricultural 7; non-agricultural 3. agrochemical exposure 100%; farmworkers 70%; incidental malaria 50%, NSAIDs use 40%; hypertension 40%. nocturia 50%; dysuria 50%; arthralgia 70%; asthenia 50%; cramps 30%, profuse sweating 20%. Renal markers: albumin creatinine ratio (ACR) > 300 mg/g 90%; β microglobulin and neutrophil gelatinase- associated lipocalin (NGAL) presence in 40%. Kidney function: hypermagnesuria 100%; hyperphosphaturia 50%, hypercalciuria 40%; hypernatriuria 30%; hyponatremia 60%, hypocalcemia 50%. Doppler: tibial artery damage 40%. Neurological: reflex abnormalities 30%; Babinski and myoclonus 20%. Neurosensorial hypoacusis 70%. Histopathology: damage restricted mostly to the tubulo-interstitium, urine was essentially bland. CKDu in women is a chronic tubulointerstitial nephropathy with varied extrarenal symptoms.

  12. Role of TRPV1 channels in ischemia/reperfusion-induced acute kidney injury.

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    Lan Chen

    Full Text Available OBJECTIVES: Transient receptor potential vanilloid 1 (TRPV1 -positive sensory nerves are widely distributed in the kidney, suggesting that TRPV1-mediated action may participate in the regulation of renal function under pathophysiological conditions. Stimulation of TRPV1 channels protects against ischemia/reperfusion (I/R-induced acute kidney injury (AKI. However, it is unknown whether inhibition of these channels is detrimental in AKI or not. We tested the role of TRPV1 channels in I/R-induced AKI by modulating these channels with capsaicin (TRPV1 agonist, capsazepine (TRPV1 antagonist and using Trpv1-/- mice. METHODS AND RESULTS: Anesthetized C57BL/6 mice were subjected to 25 min of renal ischemia and 24 hrs of reperfusion. Mice were pretreated with capsaicin (0.3 mg/kg body weight or capsazepine (50 mg/kg body weight. Capsaicin ameliorated the outcome of AKI, as measured by serum creatinine levels, tubular damage,neutrophil gelatinase-associated lipocalin (NGAL abundance and Ly-6B.2 positive polymorphonuclear inflammatory cells in injured kidneys. Neither capsazepine nor deficiency of TRPV1 did deteriorate renal function or histology after AKI. Measurements of endovanilloids in kidney tissue indicate that 20-hydroxyeicosatetraeonic acid (20-HETE or epoxyeicosatrienoic acids (EETs are unlikely involved in the beneficial effects of capsaicin on I/R-induced AKI. CONCLUSIONS: Activation of TRPV1 channels ameliorates I/R-induced AKI, but inhibition of these channels does not affect the outcome of AKI. Our results may have clinical implications for long-term safety of renal denervation to treat resistant hypertension in man, with respect to the function of primary sensory nerves in the response of the kidney to ischemic stimuli.

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

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    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.

  14. Deregulated Renal Calcium and Phosphate Transport during Experimental Kidney Failure.

    Science.gov (United States)

    Pulskens, Wilco P; Verkaik, Melissa; Sheedfar, Fareeba; van Loon, Ellen P; van de Sluis, Bart; Vervloet, Mark G; Hoenderop, Joost G; Bindels, René J

    2015-01-01

    Impaired mineral homeostasis and inflammation are hallmarks of chronic kidney disease (CKD), yet the underlying mechanisms of electrolyte regulation during CKD are still unclear. Here, we applied two different murine models, partial nephrectomy and adenine-enriched dietary intervention, to induce kidney failure and to investigate the subsequent impact on systemic and local renal factors involved in Ca(2+) and Pi regulation. Our results demonstrated that both experimental models induce features of CKD, as reflected by uremia, and elevated renal neutrophil gelatinase-associated lipocalin (NGAL) expression. In our model kidney failure was associated with polyuria, hypercalcemia and elevated urinary Ca(2+) excretion. In accordance, CKD augmented systemic PTH and affected the FGF23-αklotho-vitamin-D axis by elevating circulatory FGF23 levels and reducing renal αklotho expression. Interestingly, renal FGF23 expression was also induced by inflammatory stimuli directly. Renal expression of Cyp27b1, but not Cyp24a1, and blood levels of 1,25-dihydroxy vitamin D3 were significantly elevated in both models. Furthermore, kidney failure was characterized by enhanced renal expression of the transient receptor potential cation channel subfamily V member 5 (TRPV5), calbindin-D28k, and sodium-dependent Pi transporter type 2b (NaPi2b), whereas the renal expression of sodium-dependent Pi transporter type 2a (NaPi2a) and type 3 (PIT2) were reduced. Together, our data indicates two different models of experimental kidney failure comparably associate with disturbed FGF23-αklotho-vitamin-D signalling and a deregulated electrolyte homeostasis. Moreover, this study identifies local tubular, possibly inflammation- or PTH- and/or FGF23-associated, adaptive mechanisms, impacting on Ca(2+)/Pi homeostasis, hence enabling new opportunities to target electrolyte disturbances that emerge as a consequence of CKD development.

  15. Balanced Hydroxyethylstarch (HES 130/0.4 Impairs Kidney Function In-Vivo without Inflammation.

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    Martin Alexander Schick

    Full Text Available Volume therapy is a standard procedure in daily perioperative care, and there is an ongoing discussion about the benefits of colloid resuscitation with hydroxyethylstarch (HES. In sepsis HES should be avoided due to a higher risk for acute kidney injury (AKI. Results of the usage of HES in patients without sepsis are controversial. Therefore we conducted an animal study to evaluate the impact of 6% HES 130/0.4 on kidney integrity with sepsis or under healthy conditions Sepsis was induced by standardized Colon Ascendens Stent Peritonitis (sCASP. sCASP-group as well as control group (C remained untreated for 24 h. After 18 h sCASP+HES group (sCASP+VOL and control+HES (C+VOL received 50 ml/KG balanced 6% HES (VOL 130/0.4 over 6 h. After 24 h kidney function was measured via Inulin- and PAH-Clearance in re-anesthetized rats, and serum urea, creatinine (crea, cystatin C and Neutrophil gelatinase-associated lipocalin (NGAL as well as histopathology were analysed. In vitro human proximal tubule cells (PTC were cultured +/- lipopolysaccharid (LPS and with 0.1-4.0% VOL. Cell viability was measured with XTT-, cell toxicity with LDH-test. sCASP induced severe septic AKI demonstrated divergent results regarding renal function by clearance or creatinine measure focusing on VOL. Soleley HES (C+VOL deteriorated renal function without sCASP. Histopathology revealed significantly derangements in all HES groups compared to control. In vitro LPS did not worsen the HES induced reduction of cell viability in PTC cells. For the first time, we demonstrated, that application of 50 ml/KG 6% HES 130/0.4 over 6 hours induced AKI without inflammation in vivo. Severity of sCASP induced septic AKI might be no longer susceptible to the way of volume expansion.

  16. Sensitivitas dan Spesifisitas Cystatin C dan Kreatinin Serum dalam Mendiagnosis Cedera Ginjal Akut pada Pasien Sepsis yang Dirawat di Ruang Rawat Intensif RSUP H. Adam Malik Medan

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    Hasanul Arifin

    2016-08-01

    Full Text Available Serum creatinine has many limitations when being used to diagnose acute kidney injury (AKI, especially in the scope of intensive care unit due to its low sensitivity to depict the kidney dysfunctional level of critically-ill patients. Out of numerous new available biological markers, four biological markers are widely used all over the world to detect AKI, e.g. neutrophil gelatinase-associated lipocalin (NGAL, cystatin C, KIM-1, and interleukin-18. The purpose of this study was to determine the sensitivity and specificity of serum cystatin C and creatinine in establishing the diagnosis of acute kidney injury in sepsis patients treated in intensive care room. This study was a diagnostic test to 24 patients and conducted in intensive care room of H. Adam Malik Hospital during the period of February–March 2014. Population in this study is all adult patients with sepsis, severe sepsis, and septic shock in the intensive care room. A statistical test was conducted using receiving operator characteristics (ROC method using SPSS 17 software. The result of this study showed that serum cystatin C was more superior than serum creatinine in detecting acute kidney injury in sepsis patients treated in intensive care room. In this study, cystatin C had higher sensitivity, positive prediction score, negative prediction score, and area under curve-receiving operator characteristics (AUC-ROC than serum creatinine. As of specificity, there was no significant difference between these two biological markers. In conclusion, cystatin C can be an alternative biological marker to detect AKI in sepsis patients treated in intensive care room with a better diagnostic value.

  17. Protective Effects of Quercetin Against HgCl₂-Induced Nephrotoxicity in Sprague-Dawley Rats.

    Science.gov (United States)

    Shin, Yu Jin; Kim, Jeong Jun; Kim, Ye Ji; Kim, Won Hee; Park, Eun Young; Kim, In Young; Shin, Han-Seung; Kim, Kyeong Seok; Lee, Eui-Kyung; Chung, Kyu Hyuck; Lee, Byung Mu; Kim, Hyung Sik

    2015-05-01

    Mercury is a well-known environmental pollutant that can cause nephropathic diseases, including acute kidney injury (AKI). Although quercetin (QC), a natural flavonoid, has been reported to have medicinal properties, its potential protective effects against mercury-induced AKI have not been evaluated. In this study, the protective effect of QC against mercury-induced AKI was investigated using biochemical parameters, new protein-based urinary biomarkers, and a histopathological approach. A 250 mg/kg dose of QC was administered orally to Sprague-Dawley male rats for 3 days before administration of mercury chloride (HgCl2). All animals were sacrificed at 24 h after HgCl2 treatment, and biomarkers associated with nephrotoxicity were measured. Our data showed that QC absolutely prevented HgCl2-induced AKI, as indicated by biochemical parameters such as blood urea nitrogen (BUN) and serum creatinine (sCr). In particular, QC markedly decreased the accumulation of Hg in the kidney. Urinary excretion of protein-based biomarkers, including clusterin, kidney injury molecule-1 (KIM-1), neutrophil gelatinase-associated lipocalin (NGAL), monocyte chemoattractant protein-1 (MCP-1), tissue inhibitor of metalloproteinases 1 (TIMP-1), and vascular endothelial growth factor (VEGF) in response to HgCl2 administration were significantly decreased by QC pretreatment relative to that in the HgCl2-treated group. Furthermore, urinary excretion of metallothionein and Hg were significantly elevated by QC pretreatment. Histopathological examination indicated that QC protected against HgCl2-induced proximal tubular damage in the kidney. A TUNEL assay indicated that QC pretreatment significantly reduced apoptotic cell death in the kidney. The administration of QC provided significant protective effects against mercury-induced AKI.

  18. Phosphodiesterase-5 inhibition preserves renal hemodynamics and function in mice with diabetic kidney disease by modulating miR-22 and BMP7

    Science.gov (United States)

    Pofi, Riccardo; Fiore, Daniela; De Gaetano, Rita; Panio, Giuseppe; Gianfrilli, Daniele; Pozza, Carlotta; Barbagallo, Federica; Xiang, Yang Kevin; Giannakakis, Konstantinos; Morano, Susanna; Lenzi, Andrea; Naro, Fabio; Isidori, Andrea M.; Venneri, Mary Anna

    2017-01-01

    Diabetic Nephropathy (DN) is the leading cause of end-stage renal disease. Preclinical and experimental studies show that PDE5 inhibitors (PDE5is) exert protective effects in DN improving perivascular inflammation. Using a mouse model of diabetic kidney injury we investigated the protective proprieties of PDE5is on renal hemodynamics and the molecular mechanisms involved. PDE5i treatment prevented the development of DN-related hypertension (P < 0.001), the increase of urine albumin creatinine ratio (P < 0.01), the fall in glomerular filtration rate (P < 0.001), and improved renal resistive index (P < 0.001) and kidney microcirculation. Moreover PDE5i attenuated the rise of nephropathy biomarkers, soluble urokinase-type plasminogen activator receptor, suPAR and neutrophil gelatinase-associated lipocalin, NGAL. In treated animals, blood vessel perfusion was improved and vascular leakage reduced, suggesting preserved renal endothelium integrity, as confirmed by higher capillary density, number of CD31+ cells and pericyte coverage. Analysis of the mechanisms involved revealed the induction of bone morphogenetic protein-7 (BMP7) expression, a critical regulator of angiogenesis and kidney homeostasis, through a PDE5i-dependent downregulation of miR-22. In conclusion PDE5i slows the progression of DN in mice, improving hemodynamic parameters and vessel integrity. Regulation of miR-22/BMP7, an unknown mechanism of PDE5is in nephrovascular protection, might represent a novel therapeutic option for treatment of diabetic complications. PMID:28294194

  19. Deregulated Renal Calcium and Phosphate Transport during Experimental Kidney Failure.

    Directory of Open Access Journals (Sweden)

    Wilco P Pulskens

    Full Text Available Impaired mineral homeostasis and inflammation are hallmarks of chronic kidney disease (CKD, yet the underlying mechanisms of electrolyte regulation during CKD are still unclear. Here, we applied two different murine models, partial nephrectomy and adenine-enriched dietary intervention, to induce kidney failure and to investigate the subsequent impact on systemic and local renal factors involved in Ca(2+ and Pi regulation. Our results demonstrated that both experimental models induce features of CKD, as reflected by uremia, and elevated renal neutrophil gelatinase-associated lipocalin (NGAL expression. In our model kidney failure was associated with polyuria, hypercalcemia and elevated urinary Ca(2+ excretion. In accordance, CKD augmented systemic PTH and affected the FGF23-αklotho-vitamin-D axis by elevating circulatory FGF23 levels and reducing renal αklotho expression. Interestingly, renal FGF23 expression was also induced by inflammatory stimuli directly. Renal expression of Cyp27b1, but not Cyp24a1, and blood levels of 1,25-dihydroxy vitamin D3 were significantly elevated in both models. Furthermore, kidney failure was characterized by enhanced renal expression of the transient receptor potential cation channel subfamily V member 5 (TRPV5, calbindin-D28k, and sodium-dependent Pi transporter type 2b (NaPi2b, whereas the renal expression of sodium-dependent Pi transporter type 2a (NaPi2a and type 3 (PIT2 were reduced. Together, our data indicates two different models of experimental kidney failure comparably associate with disturbed FGF23-αklotho-vitamin-D signalling and a deregulated electrolyte homeostasis. Moreover, this study identifies local tubular, possibly inflammation- or PTH- and/or FGF23-associated, adaptive mechanisms, impacting on Ca(2+/Pi homeostasis, hence enabling new opportunities to target electrolyte disturbances that emerge as a consequence of CKD development.

  20. Acute kidney injury in children

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    Peco-Antić Amira

    2014-01-01

    Full Text Available Acute kidney injury (AKI is a clinical condition considered to be the consequence of a sudden decrease (>25% or discontinuation of renal function. The term AKI is used instead of the previous term acute renal failure, because it has been demonstrated that even minor renal lesions may cause far-reaching consequences on human health. Contemporary classifications of AKI (RIFLE and AKIN are based on the change of serum creatinine and urinary output. In the developed countries, AKI is most often caused by renal ischemia, nephrotoxins and sepsis, rather than a (primary diffuse renal disease, such as glomerulonephritis, interstitial nephritis, renovascular disorder and thrombotic microangiopathy. The main risk factors for hospital AKI are mechanical ventilation, use of vasoactive drugs, stem cell transplantation and diuretic-resistant hypervolemia. Prerenal and parenchymal AKI (previously known as acute tubular necrosis jointly account for 2/3 of all AKI causes. Diuresis and serum creatinine concentration are not early diagnostic markers of AKI. Potential early biomarkers of AKI are neutrophil gelatinase-associated lipocalin (NGAL, cystatin C, kidney injury molecule-1 (KIM-1, interleukins 6, 8 and 18, and liver-type fatty acid-binding protein (L-FABP. Early detection of kidney impairment, before the increase of serum creatinine, is important for timely initiated therapy and recovery. The goal of AKI treatment is to normalize the fluid and electrolyte status, as well as the correction of acidosis and blood pressure. Since a severe fluid overload resistant to diuretics and inotropic agents is associated with a poor outcome, the initiation of dialysis should not be delayed. The mortality rate of AKI is highest in critically ill children with multiple organ failure and hemodynamically unstable patients.

  1. Curcumin prevents maleate-induced nephrotoxicity: relation to hemodynamic alterations, oxidative stress, mitochondrial oxygen consumption and activity of respiratory complex I.

    Science.gov (United States)

    Tapia, E; Sánchez-Lozada, L G; García-Niño, W R; García, E; Cerecedo, A; García-Arroyo, F E; Osorio, H; Arellano, A; Cristóbal-García, M; Loredo, M L; Molina-Jijón, E; Hernández-Damián, J; Negrette-Guzmán, M; Zazueta, C; Huerta-Yepez, S; Reyes, J L; Madero, M; Pedraza-Chaverrí, J

    2014-11-01

    The potential protective effect of the dietary antioxidant curcumin (120 mg/Kg/day for 6 days) against the renal injury induced by maleate was evaluated. Tubular proteinuria and oxidative stress were induced by a single injection of maleate (400 mg/kg) in rats. Maleate-induced renal injury included increase in renal vascular resistance and in the urinary excretion of total protein, glucose, sodium, neutrophil gelatinase-associated lipocalin (NGAL) and N-acetyl β-D-glucosaminidase (NAG), upregulation of kidney injury molecule (KIM)-1, decrease in renal blood flow and claudin-2 expression besides of necrosis and apoptosis of tubular cells on 24 h. Oxidative stress was determined by measuring the oxidation of lipids and proteins and diminution in renal Nrf2 levels. Studies were also conducted in renal epithelial LLC-PK1 cells and in mitochondria isolated from kidneys of all the experimental groups. Maleate induced cell damage and reactive oxygen species (ROS) production in LLC-PK1 cells in culture. In addition, maleate treatment reduced oxygen consumption in ADP-stimulated mitochondria and diminished respiratory control index when using malate/glutamate as substrate. The activities of both complex I and aconitase were also diminished. All the above-described alterations were prevented by curcumin. It is concluded that curcumin is able to attenuate in vivo maleate-induced nephropathy and in vitro cell damage. The in vivo protection was associated to the prevention of oxidative stress and preservation of mitochondrial oxygen consumption and activity of respiratory complex I, and the in vitro protection was associated to the prevention of ROS production.

  2. High-resolution structures of mutants of residues that affect access to the ligand-binding cavity of human lipocalin-type prostaglandin D synthase.

    Science.gov (United States)

    Perduca, Massimiliano; Bovi, Michele; Bertinelli, Mattia; Bertini, Edoardo; Destefanis, Laura; Carrizo, Maria E; Capaldi, Stefano; Monaco, Hugo L

    2014-08-01

    Lipocalin-type prostaglandin D synthase (L-PGDS) catalyzes the isomerization of the 9,11-endoperoxide group of PGH2 (prostaglandin H2) to produce PGD2 (prostaglandin D2) with 9-hydroxy and 11-keto groups. The product of the reaction, PGD2, is the precursor of several metabolites involved in many regulatory events. L-PGDS, the first member of the important lipocalin family to be recognized as an enzyme, is also able to bind and transport small hydrophobic molecules and was formerly known as β-trace protein, the second most abundant protein in human cerebrospinal fluid. Previous structural work on the mouse and human proteins has focused on the identification of the amino acids responsible and the proposal of a mechanism for catalysis. In this paper, the X-ray structures of the apo and holo forms (bound to PEG) of the C65A mutant of human L-PGDS at 1.40 Å resolution and of the double mutant C65A/K59A at 1.60 Å resolution are reported. The apo forms of the double mutants C65A/W54F and C65A/W112F and the triple mutant C65A/W54F/W112F have also been studied. Mutation of the lysine residue does not seem to affect the binding of PEG to the ligand-binding cavity, and mutation of a single or both tryptophans appears to have the same effect on the position of these two aromatic residues at the entrance to the cavity. A solvent molecule has also been identified in an invariant position in the cavity of virtually all of the molecules present in the nine asymmetric units of the crystals that have been examined. Taken together, these observations indicate that the residues that have been mutated indeed appear to play a role in the entrance-exit process of the substrate and/or other ligands into/out of the binding cavity of the lipocalin.

  3. The protein scaffold of the lipocalin odorant-binding protein is suitable for the design of new biosensors for the detection of explosive components

    Energy Technology Data Exchange (ETDEWEB)

    Ramoni, Roberto [Dipartimento di Produzioni Animali, Universita degli Studi di Parma (Italy); Bellucci, Stefano [INFN-Laboratori Nazionali di Frascati, Frascati (Italy); Grycznyski, Ignacy [University of North Texas, Forth Worth, TX (United States); Grycznyski, Zigmunt [University of North Texas, Forth Worth, TX (United States); Grolli, Stefano [Dipartimento di Produzioni Animali, Universita degli Studi di Parma (Italy); Staiano, Maria [Istituto di Biochimica della Proteine, CNR, Naples (Italy); Bellis, Giovanni De [INFN-Laboratori Nazionali di Frascati, Frascati (Italy); Micciulla, Federico [INFN-Laboratori Nazionali di Frascati, Frascati (Italy); Pastore, Roberto [INFN-Laboratori Nazionali di Frascati, Frascati (Italy); Tiberia, Alessandra [INFN-Laboratori Nazionali di Frascati, Frascati (Italy); Conti, Virna [Dipartimento di Produzioni Animali, Universita degli Studi di Parma (Italy); Merli, Elisa [Dipartimento di Produzioni Animali, Universita degli Studi di Parma (Italy); Varriale, Antonio [Istituto di Biochimica della Proteine, CNR, Naples (Italy); Rossi, Mose' [Istituto di Biochimica della Proteine, CNR, Naples (Italy); D' Auria, Sabato [Istituto di Biochimica della Proteine, CNR, Naples (Italy)

    2007-10-03

    The detection of hazard exposure is a current priority, including the detection of traces of explosive molecules in different environments like luggage storage rooms and public places, and is becoming a major requirement for homeland security. In the present study we carried out a preliminary investigation on the binding capacities of four forms of the lipocalin odorant-binding protein (OBP) for the detection of explosive components such as diphenylamine, dimethyl-phthalate, resorcinol and dinitrotoluene. The experimental results, showing that OBP binds these compounds with affinity constants ranging between 80 nM and 10.6 mM, indicate that this protein can be used as a probe for the realization of a biosensor to sense explosive compounds.

  4. Lipocalin 2 binds to membrane phosphatidylethanolamine to induce lipid raft movement in a PKA-dependent manner and modulates sperm maturation.

    Science.gov (United States)

    Watanabe, Hitomi; Takeo, Toru; Tojo, Hiromasa; Sakoh, Kazuhito; Berger, Thorsten; Nakagata, Naomi; Mak, Tak W; Kondoh, Gen

    2014-05-01

    Mammalian sperm undergo multiple maturation steps after leaving the testis in order to become competent for fertilization, but the molecular mechanisms underlying this process remain unclear. In terms of identifying factors crucial for these processes in vivo, we found that lipocalin 2 (Lcn2), which is known as an innate immune factor inhibiting bacterial and malarial growth, can modulate sperm maturation. Most sperm that migrated to the oviduct of wild-type females underwent lipid raft reorganization and glycosylphosphatidylinositol-anchored protein shedding, which are signatures of sperm maturation, but few did so in Lcn2 null mice. Furthermore, we found that LCN2 binds to membrane phosphatidylethanolamine to reinforce lipid raft reorganization via a PKA-dependent mechanism and promotes sperm to acquire fertility by facilitating cholesterol efflux. These observations imply that mammals possess a mode for sperm maturation in addition to the albumin-mediated pathway.

  5. Human Lipocalin-Type Prostaglandin D Synthase-Based Drug Delivery System for Poorly Water-Soluble Anti-Cancer Drug SN-38.

    Science.gov (United States)

    Nakatsuji, Masatoshi; Inoue, Haruka; Kohno, Masaki; Saito, Mayu; Tsuge, Syogo; Shimizu, Shota; Ishida, Atsuko; Ishibashi, Osamu; Inui, Takashi

    2015-01-01

    Lipocalin-type prostaglandin D synthase (L-PGDS) is a member of the lipocalin superfamily, which is composed of secretory transporter proteins, and binds a wide variety of small hydrophobic molecules. Using this function, we have reported the feasibility of using L-PGDS as a novel drug delivery vehicle for poorly water-soluble drugs. In this study, we show the development of a drug delivery system using L-PGDS, one that enables the direct clinical use of 7-ethyl-10-hydroxy-camptothecin (SN-38), a poorly water-soluble anti-cancer drug. In the presence of 2 mM L-PGDS, the concentration of SN-38 in PBS increased 1,130-fold as compared with that in PBS. Calorimetric experiments revealed that L-PGDS bound SN-38 at a molecular ratio of 1:3 with a dissociation constant value of 60 μM. The results of an in vitro growth inhibition assay revealed that the SN-38/L-PGDS complexes showed high anti-tumor activity against 3 human cancer cell lines, i.e., Colo201, MDA-MB-231, and PC-3 with a potency similar to that of SN-38 used alone. The intravenous administration of SN-38/L-PGDS complexes to mice bearing Colo201 tumors showed a pronounced anti-tumor effect. Intestinal mucositis, which is one of the side effects of this drug, was not observed in mice administered SN-38/L-PGDS complexes. Taken together, L-PGDS enables the direct usage of SN-38 with reduced side effects.

  6. Human Lipocalin-Type Prostaglandin D Synthase-Based Drug Delivery System for Poorly Water-Soluble Anti-Cancer Drug SN-38.

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    Masatoshi Nakatsuji

    Full Text Available Lipocalin-type prostaglandin D synthase (L-PGDS is a member of the lipocalin superfamily, which is composed of secretory transporter proteins, and binds a wide variety of small hydrophobic molecules. Using this function, we have reported the feasibility of using L-PGDS as a novel drug delivery vehicle for poorly water-soluble drugs. In this study, we show the development of a drug delivery system using L-PGDS, one that enables the direct clinical use of 7-ethyl-10-hydroxy-camptothecin (SN-38, a poorly water-soluble anti-cancer drug. In the presence of 2 mM L-PGDS, the concentration of SN-38 in PBS increased 1,130-fold as compared with that in PBS. Calorimetric experiments revealed that L-PGDS bound SN-38 at a molecular ratio of 1:3 with a dissociation constant value of 60 μM. The results of an in vitro growth inhibition assay revealed that the SN-38/L-PGDS complexes showed high anti-tumor activity against 3 human cancer cell lines, i.e., Colo201, MDA-MB-231, and PC-3 with a potency similar to that of SN-38 used alone. The intravenous administration of SN-38/L-PGDS complexes to mice bearing Colo201 tumors showed a pronounced anti-tumor effect. Intestinal mucositis, which is one of the side effects of this drug, was not observed in mice administered SN-38/L-PGDS complexes. Taken together, L-PGDS enables the direct usage of SN-38 with reduced side effects.

  7. Renal Doppler and Novel Biomarkers to Assess Acute Kidney Injury in a Swine Model of Ventricular Fibrillation Cardiac Arrest

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    Xue Mei

    2015-01-01

    Full Text Available Background: Majority of the research on cardiac arrest (CA have focused on post-CA brain injury and myocardial dysfunction, the renal dysfunction and acute kidney injury (AKI in other critical illnesses after CA have not been well described. This study was designed to assess AKI with renal Doppler and novel AKI biomarkers in a swine model of ventricular fibrillation cardiac arrest (VFCA. Methods: Thirty healthy piglets were divided into VFCA group (n = 22 and Sham group (n = 8 in a blinded manner. Mean arterial pressure, heart rate, and cardiac output were recorded continuously. Cardiac arrest (CA was induced by programmed electric stimulation in the VFCA group, and then cardiopulmonary resuscitation was performed. Twenty piglets returned of spontaneous circulation (ROSC and received intensive care. Blood and urine samples were collected for AKI biomarkers testing, and Color Doppler flow imaging was performed at baseline, 6 h, 12 h, and 24 h, respectively after ROSC. At ROSC 24 h, the animals were sacrificed and a semi-quantitative evaluation of pathologic kidney injury was performed. Results: In the VFCA group, corrected resistive index (cRI increased from 0.47 ± 0.03 to 0.64 ± 0.06, and pulsatility index (PI decreased from 0.82 ± 0.03 to 0.68 ± 0.04 after ROSC. Cystatin C (CysC in both serum and urine samples increased at ROSC 6 h, but neutrophil gelatinase-associated lipocalin (NGAL in serum increased to 5.34 ± 1.68 ng/ml at ROSC 6 h, and then decreased to 3.16 ± 0.69 ng/ml at ROSC 24 h while CysC increasing constantly. According to the renal histopathology, 18 of 20 animals suffered from kidney injury. The grade of renal injury was highly correlated with RI, cRI, NGAL, and CysC. Linear regression equation was established: Grade of renal injury = 0.002 × serum CysC + 6.489 × PI + 4.544 × cRI - 8.358 (r2 = 0.698, F = 18.506, P < 0.001. Conclusions: AKI is common in post-CA syndrome. Renal Doppler and novel AKI biomarkers in serum and

  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. Renal Doppler and Novel Biomarkers to Assess Acute Kidney Injury in a Swine Model of Ventricular Fibrillation Cardiac Arrest

    Institute of Scientific and Technical Information of China (English)

    Xue Mei; Chen-Chen Hang; Shuo Wang; Chun-Sheng Li; Ze-Xing Yu

    2015-01-01

    Background: Majority of the research on cardiac arrest (CA) have focused on post-CA brain injury and myocardial dysfunction, the renal dysfunction and acute kidney injury (AKI) in other critical illnesses after CA have not been well described.This study was designed to assess AKI with renal Doppler and novel AKI biomarkers in a swine model ofventricular fibrillation cardiac arrest (VFCA).Methods: Thirty healthy piglets were divided into VFCA group (n =22) and Sham group (n =8) in a blinded manner.Mean arterial pressure, heart rate, and cardiac output were recorded continuously.Cardiac arrest (CA) was induced by programmed electric stimulation in the VFCA group, and then cardiopulmonary resuscitation was performed.Twenty piglets retumed of spontaneous circulation (ROSC) and received intensive care.Blood and urine samples were collected for AKI biomarkers testing, and Color Doppler flow imaging was performed at baseline, 6 h, 12 h, and 24 h,respectively after ROSC.At ROSC 24 h, the animals were sacrificed and a semi-quantitative evaluation of pathologic kidney injury was performed.Results: In the VFCA group, corrected resistive index (cRI) increased from 0.47 ± 0.03 to 0.64 ± 0.06, and pulsatility index (PI) decreased from 0.82 ± 0.03 to 0.68 ± 0.04 after ROSC.Cystatin C (CysC) in both serum and urine samples increased at ROSC 6 h, but neutrophil gelatinase-associated lipocalin (NGAL) in serum increased to 5.34 ± 1.68 ng/ml at ROSC 6 h, and then decreased to 3.16 ± 0.69 ng/ml at ROSC 24 h while CysC increasing constantly.According to the renal histopathology, 18 of 20 animals suffered from kidney injury.The grade of renal injury was highly correlated with RI, cRI, NGAL, and CysC.Linear regression equation was established: Grade of renal injury =0.002 × serum CysC + 6.489 × PI + 4.544 × cRI-8.358 (r2 =0.698, F =18.506, P < 0.001).Conclusions: AKI is common in post-CA syndrome.Renal Doppler and novel AKI biomarkers in serum and urine are of significant

  10. 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

  11. 热缺血损伤大鼠肾脏中中性粒细胞明胶酶脂质运载蛋白的表达及意义%The Expression of NGAL in the Kidney of Rat after Warm Ischemia Injury and Its Clinical Significance

    Institute of Scientific and Technical Information of China (English)

    刘树荣; 刘勋; 程颖; 焦保平; 刘永锋

    2013-01-01

    Objective To verify whether NGAL can be used to reflect the function of rat kidney undergoing different warm ischemia time. Methods Male SD rats were used to establish an ischemia reperfusion model. According to the length of warm ischemia time,rats were divided into control group (warm ischemia time for 0 minute), 15 minutes group (warm ischemia time for 15 minutes),30 minutes group( warm ischemia time for 30 minutnes),45 minutes group( warm ischemia time for 45 minutnes),60 minutes group (warm ischemia time for 60 minutes) . After reperfusion for 8 hours,allograft samples were collected and sectioned for HE,immunohistochemistry and Western blot, respectively. Blood were collected from the inferior vena cava for further tests. Results With the extension of the warm ischemia time,the kidney tubular became swollen and more necrotic. The expression of NGAL became stronger, serum Cr levels got higher. The difference of NGAL expression was found among control group, 15 minutes group,and 30 minutes group. Conclusion To reflect the rat renal function within 30 minutes of warm ischemia injury NGAL is more sensitive than Cr. Combines with pathological examination, NGAL could reflect function of kidney under warm ischemia injury better.%目的 建立大鼠肾脏缺血再灌注损伤模型,测定肾组织中中性粒细胞明胶酶脂质运载蛋白(NGAL)的表达情况,探讨其在反映肾脏热缺血损伤程度方面的应用价值.方法 建立大鼠肾脏的缺血再灌注损伤模型,根据热缺血时间将大鼠分为对照组(热缺血0 min组)、热缺血15 min、30 min、45 min和60 min组.再灌注8h后,HE染色观察肾脏病理学变化,免疫组化检测肾组织NGAL的表达,免疫印迹法检测胞质中NGAL的含量,下腔静脉抽血并测定血清肌酐(Cr)含量.结果 随着热缺血时间的延长,肾小管肿胀坏死程度加重,肾组织NGAL表达增强,血清Cr增高.对照组、热缺血15 min组和30 min组肾组织NGAL的表

  12. NUEVOS BIOMARCADORES PARA LA DETECCIÓN DE LA INSUFICIENCIA RENAL AGUDA

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    Medina Ayala AE

    2013-05-01

    Full Text Available Acute renal failure (ARF is one of the main renal disorders, which is characterized by deterioration (in hours or days of the glomerular filtration rate. Serum creatinine is the marker typically used in clinical practice for the diagnosis and monitoring of the IRA. However, it has the disadvantage of being a late marker and influenced by multiple variables. In order to overcome this limitation new biomarkers of AKI were obtained, such as interleukin 18 (Interleukin 18, gelatinase-associated lipocalin neutrophil (neutrophil gelatinase-associated lipocalin, kidney injury molecule (kidney injury molecule and cystatin C (cystatin-C, which have higher sensitivity, specificity and ability to determine the location of the damage and the IRA evolution respect to serum creatinine.

  13. 早期液体复苏对脓毒性休克患者肾功能的影响%Effect of early fluid resuscitation on the renal function of patients with septic shock

    Institute of Scientific and Technical Information of China (English)

    王澜涛; 刘红娟; 胡振杰

    2012-01-01

    Objective To study the effect of early fluid resuscitation on renal function of the patients with septic shock by determining the neutrophil gelatinase - associated lipocalin ( NGAL) and cystatin C. Methods 48 patients with septic shock were admitted into the ICU of the 4th Affiliated Hospital of the Hebei Medical University during March 1 and November 11, 2010. According to the 2004 international guideline for the treatment of sepsis, fluid resuscitation was conducted through the emplaced deep venous catheter following the early goal directed therapy (EGDT). Blood samples were taken at 0 h before the fluid loading, and at 6, 24, 48 h after the fluid loading. The plasma NGAL and cystatin C were detected by the ELISA method. Meanwhile, the temperature, heart rate, respiration rate, mean arterial pressure, hourly - and 24 - hour urine volume, ScvO2 and the APACHE II score were simultaneously recorded. The subjects were further divided into survival and non - survival groups. The controls were 20 healthy volunteers. Results The plasma NGAL and cystatin C levels before fluid loading were statistically higher than those in the control ( P 0. 05 ) . The correlation between the plasma NGAL, cystatin C levels and Scr was very good, and the plasma NGAL, Cystatin C levels step up earlier than Scr. Conclusion ①The plasma concentration of NGAL and cystatin C are clearly elevated in the patients with septic shock, which indicates the occurrence of acute kidney injury ( AKI). ② Early and complete fluid loading may markedly improve the renal function in the studied patients. ③The correlation between the plasma NGAL, cystatin C and Scr is very good, but the plasma NGAL and cystatin C could reflect the damage of the renal earlier, and the plasma concentration of the NGAL and cystatin C are positive correlation with damage of the renal.%目的 通过检测早期肾损伤监测指标血浆胱抑素C(Cystatin C)、中性粒细胞明胶酶脂质转运蛋白(NGAL),探讨早期液

  14. 过度运动对大鼠肾损伤敏感标志物的影响及人参总皂苷的干预研究%Excessive-exercise Induced Kidney Injury Sensitive Biomarker Change in Rats and the Effects of Ginsenoside

    Institute of Scientific and Technical Information of China (English)

    王会玲; 李俊彦; 许烨; 张金元

    2011-01-01

    Objective : We investigate the changes of some sensitive hiomarkers in rats undertaking excessive - exercise, and the effects of Ginsenoside ( GS ) which was a product from a plant herb - Ginsen.Methods : Male Sprague - Dawley rats divided into five groups: control group( CTL ), over - exercise group( two sub - group : M2 and M24 ); Ginsenoside group ( two sub - group: G2 and C24 ).The animal model of excessive - exercise induced AKI was established by exhaustively running on the treadmill according protocol.We administrated with GS ( 100g/kg· d ) intragastric ahead the G2 and G24 rats took exhausting running.We collected urine 2h or 24h after excessive - exercise , and measured their albumin, neutrophil gelatinase - associated lipocalin ( NGAL ) and N - acetyl - d - glucosaminidase( NAG ).We collected blood to test the renal function ( BUN, serum creatinine ), superoxide dismutase ( SOD ) and malondialdehyde ( MDA ).The hlood and kidney Angiotensin Ⅱ ( Ang Ⅱ ) were measured by radioimmunoassay ( RIA ).We observed the renal pathology by Microscope after HE staining.Results : Over - exercise induced the urine albumin and NAG excretion increasing, the BUN and blood NGAL increased too.Compared with the blood and kidney Ang Ⅱ increased, the serum and kidney tissue SOD decreased, but MDA increased at the same time.We ohserved a part of the renal tuhular epithelial cells swelling and ablating.After treatment by GS, the excretion of urine albumin and NAC reduced.BUN and NGAL in hlood decreased.GS decreased the kidney Angiotensin Ⅱ and MDA level, but increased the SOD level in blood or kidney tissue, thus, ameliorate the tubular injury.Conclusion : Ginsenoside protect the tuhular injury induced by the over - exercise in rats, which mechanism might reduce the Ang Ⅱ and anti - oxidative stress in the kidney.%目的:探讨过度运动对大鼠肾组织及肾损伤敏感标志物的影响,及人参总皂苷的防治作用.方法:SD大鼠随机分为对

  15. Bacterial siderophores that evade or overwhelm lipocalin 2 induce hypoxia inducible factor 1α and proinflammatory cytokine secretion in cultured respiratory epithelial cells.

    Science.gov (United States)

    Holden, Victoria I; Lenio, Steven; Kuick, Rork; Ramakrishnan, Sadeesh K; Shah, Yatrik M; Bachman, Michael A

    2014-09-01

    Iron is essential for many cellular processes and is required by bacteria for replication. To acquire iron from the host, pathogenic Gram-negative bacteria secrete siderophores, including enterobactin (Ent). However, Ent is bound by the host protein lipocalin 2 (Lcn2), preventing bacterial reuptake of aferric or ferric Ent. Furthermore, the combination of Ent and Lcn2 (Ent+Lcn2) leads to enhanced secretion of interleukin-8 (IL-8) compared to that induced by either stimulus alone. Modified or structurally distinct siderophores, including yersiniabactin (Ybt) and glycosylated Ent (GlyEnt, or salmochelin), deliver iron to bacteria despite the presence of Lcn2. We hypothesized that the robust immune response to Ent and Lcn2 requires iron chelation rather than the Ent+Lcn2 complex itself and also can be stimulated by Lcn2-evasive siderophores. To test this hypothesis, cultured respiratory epithelial cells were stimulated with combinations of purified siderophores and Lcn2 and analyzed by gene expression microarrays, quantitative PCR, and cytokine immunoassays. Ent caused HIF-1α protein stabilization, induced the expression of genes regulated by hypoxia-inducible factor 1α (HIF-1α), and repressed genes involved in cell cycle and DNA replication, whereas Lcn2 induced expression of proinflammatory cytokines. Iron chelation by excess Ent or Ybt significantly increased Lcn2-induced secretion of IL-8, IL-6, and CCL20. Stabilization of HIF-1α was sufficient to enhance Lcn2-induced IL-6 secretion. These data indicate that respiratory epithelial cells can respond to bacterial siderophores that evade or overwhelm Lcn2 binding by increasing proinflammatory cytokine production.

  16. Dendritic cell-secreted lipocalin2 induces CD8+ T-cell apoptosis, contributes to T-cell priming and leads to a TH1 phenotype.

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    Melanie Floderer

    Full Text Available Lipocalin 2 (LCN2, which is highly expressed by dendritic cells (DCs when treated with dexamethasone (Dex and lipopolysaccharide (LPS, plays a key role in the defence against bacteria and is also involved in the autocrine apoptosis of T-cells. However, the function of LCN2 when secreted by DCs is unknown: this is a critical gap in our understanding of the regulation of innate and adaptive immune systems. Tolerance, stimulation and suppression are functions of DCs that facilitate the fine-tuning of the immune responses and which are possibly influenced by LCN2 secretion. We therefore examined the role of LCN2 in DC/T-cell interaction. WT or Lcn2-/- bone marrow-derived DCs were stimulated with LPS or LPS+IFN-γ with and without Dex and subsequently co-cultured with T-cells from ovalbumin-specific TCR transgenic (OT-I and OT-II mice. We found that CD8+ T-cell apoptosis was highly reduced when Lcn2-/- DCs were compared with WT. An in vivo CTL assay, using LPS-treated DCs, showed diminished killing ability in mice that had received Lcn2-/- DCs compared with WT DCs. As a consequence, we analysed T-cell proliferation and found that LCN2 participates in T-cell-priming in a dose-dependent manner and promotes a TH1 microenvironment. DC-secreted LCN2, whose function has previously been unknown, may in fact have an important role in regulating the balance between TH1 and TH2. Our results yield insights into DC-secreted LCN2 activity, which could play a pivotal role in cellular immune therapy and in regulating immune responses.

  17. Contrast-induced acute kidney injury in children with cardiovascular defects – results of a pilot study

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    Daria Tomczyk

    2016-12-01

    Full Text Available Introduction: Contrast-induced nephropathy – acute kidney injury is an acquired kidney injury that is an important factor in short- and long-term cardiovascular complications. Contrast-induced nephropathy – acute kidney injury continues to be diagnosed based on serum creatinine level. Serum creatinine, however, is a delayed indicator of contrast-induced nephropathy, as its levels typically peak between 1 and 3 days following contrast exposure. Currently, more sensitive biomarkers of kidney injury are sought, with human neutrophil lipocalin (also known as neutrophil gelatinase-associated lipocalin highlighted in literature as a troponin-like biomarker of early nephropathy. Aim of the study: Changes in serum and urine neutrophil gelatinase-associated lipocalin levels were assessed in children with congenital heart diseases, following a scheduled cardiac catheterization procedure. Material and methods: The group studied comprised 16 patients. The neutrophil gelatinaseassociated lipocalin and creatinine levels, along with urine and serum neutrophil gelatinase-associated lipocalin/creatinine ratio were evaluated five times at different time intervals from the procedure. The group did not vary in respect of kidney function, preprocedure management, and volume expansion (hydration therapy prior to the procedure. Results: In the assessed material, median neutrophil gelatinase-associated lipocalin rose as early as 2 hours after exposure to contrast as compared with baseline [median = 28.2 ng/mL (Quartile 1 = 22.8 – Quartile 3 = 33.77 vs. median = 25.87 ng/mL (Quartile 1 = 19.4 – Quartile 3 = 29.6]. Serum neutrophil gelatinase-associated lipocalin level peaked in hour 6 of our study: median – 30.6 ng/mL (Quartile 1 = 22.32 – Quartile 3 = 42.17, then reverting to normal. Urine neutrophil gelatinaseassociated lipocalin peaked in hour 24 of the study, subsequently dropping below baseline in hour 48

  18. Proteomic Studies of Cholangiocarcinoma and Hepatocellular Carcinoma Cell Secretomes

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    Chantragan Srisomsap

    2010-01-01

    Full Text Available Cholangiocarcinoma (CCA and hepatocellular carcinoma (HCC occur with relatively high incidence in Thailand. The secretome, proteins secreted from cancer cells, are potentially useful as biomarkers of the diseases. Proteomic analysis was performed on the secreted proteins of cholangiocarcinoma (HuCCA-1 and hepatocellular carcinoma (HCC-S102, HepG2, SK-Hep-1, and Alexander cell lines. The secretomes of the five cancer cell lines were analyzed by SDS-PAGE combined with LC/MS/MS. Sixty-eight proteins were found to be expressed only in HuCCA-1. Examples include neutrophil gelatinase-associated lipocalin (lipocalin 2, laminin 5 beta 3, cathepsin D precursor, desmoplakin, annexin IV variant, and annexin A5. Immunoblotting was used to confirm the presence of lipocalin 2 in conditioned media and cell lysate of 5 cell lines. The results showed that lipocalin 2 was a secreted protein which is expressed only in the conditioned media of the cholangiocarcinoma cell line. Study of lipocalin 2 expression in different types of cancer and normal tissues from cholangiocarcinoma patients showed that lipocalin 2 was expressed only in the cancer tissues. We suggest that lipocalin 2 may be a potential biomarker for cholangiocarcinoma.

  19. Total protein, albumin and low-molecular-weight protein excretion in HIV-positive patients

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    Campbell Lucy J

    2012-08-01

    Full Text Available Abstract Background Chronic kidney disease is common in HIV positive patients and renal tubular dysfunction has been reported in those receiving combination antiretroviral therapy (cART. Tenofovir (TFV in particular has been linked to severe renal tubular disease as well as proximal tubular dysfunction. Markedly elevated urinary concentrations of retinal-binding protein (RBP have been reported in patients with severe renal tubular disease, and low-molecular-weight proteins (LMWP such as RBP may be useful in clinical practice to assess renal tubular function in patients receiving TFV. We analysed 3 LMWP as well as protein and albumin in the urine of a sample of HIV positive patients. Methods In a cross-sectional fashion, total protein, albumin, RBP, cystatin C, and neutrophil gelatinase-associated lipocalin (NGAL were quantified in random urine samples of 317 HIV positive outpatients and expressed as the ratio-to-creatinine (RBPCR, CCR and NGALCR. Exposure to cART was categorised as none, cART without TFV, and cART containing TFV and a non-nucleoside reverse-transcriptase-inhibitor (TFV/NNRTI or TFV and a protease-inhibitor (TFV/PI. Results Proteinuria was present in 10.4 % and microalbuminuria in 16.7 % of patients. Albumin accounted for approximately 10 % of total urinary protein. RBPCR was within the reference range in 95 % of patients while NGALCR was elevated in 67 % of patients. No overall differences in urine protein, albumin, and LMWP levels were observed among patients stratified by cART exposure, although a greater proportion of patients exposed to TFV/PI had RBPCR >38.8 μg/mmol (343 μg/g (p = 0.003. In multivariate analyses, black ethnicity (OR 0.43, 95 % CI 0.24, 0.77 and eGFR 2 (OR 3.54, 95 % CI 1.61, 7.80 were independently associated with upper quartile (UQ RBPCR. RBPCR correlated well to CCR (r2 = 0.71, but not to NGALCR, PCR or ACR. Conclusions In HIV positive patients, proteinuria was predominantly of

  20. Candidate inflammatory biomarkers display unique relationships with alpha-synuclein and correlate with measures of disease severity in subjects with Parkinson's disease.

    Science.gov (United States)

    Eidson, Lori N; Kannarkat, George T; Barnum, Christopher J; Chang, Jianjun; Chung, Jaegwon; Caspell-Garcia, Chelsea; Taylor, Peggy; Mollenhauer, Brit; Schlossmacher, Michael G; Ereshefsky, Larry; Yen, Mark; Kopil, Catherine; Frasier, Mark; Marek, Kenneth; Hertzberg, Vicki S; Tansey, Malú G

    2017-08-18

    Efforts to identify fluid biomarkers of Parkinson's disease (PD) have intensified in the last decade. As the role of inflammation in PD pathophysiology becomes increasingly recognized, investigators aim to define inflammatory signatures to help elucidate underlying mechanisms of disease pathogenesis and aid in identification of patients with inflammatory endophenotypes that could benefit from immunomodulatory interventions. However, discordant results in the literature and a lack of information regarding the stability of inflammatory factors over a 24-h period have hampered progress. Here, we measured inflammatory proteins in serum and CSF of a small cohort of PD (n = 12) and age-matched healthy control (HC) subjects (n = 6) at 11 time points across 24 h to (1) identify potential diurnal variation, (2) reveal differences in PD vs HC, and (3) to correlate with CSF levels of amyloid β (Aβ) and α-synuclein in an effort to generate data-driven hypotheses regarding candidate biomarkers of PD. Despite significant variability in other factors, a repeated measures two-way analysis of variance by time and disease state for each analyte revealed that serum IFNγ, TNF, and neutrophil gelatinase-associated lipocalin (NGAL) were stable across 24 h and different between HC and PD. Regression analysis revealed that C-reactive protein (CRP) was the only factor with a strong linear relationship between CSF and serum. PD and HC subjects showed significantly different relationships between CSF Aβ proteins and α-synuclein and specific inflammatory factors, and CSF IFNγ and serum IL-8 positively correlated with clinical measures of PD. Finally, linear discriminant analysis revealed that serum TNF and CSF α-synuclein discriminated between PD and HC with a minimum of 82% sensitivity and 83% specificity. Our findings identify a panel of inflammatory factors in serum and CSF that can be reliably measured, distinguish between PD and HC, and monitor inflammation as disease

  1. Effect of oleic acid-induced acute lung injury and conventional mechanical ventilation on renal function in piglets

    Institute of Scientific and Technical Information of China (English)

    LIU Ai-jun; LING Feng; LI Zhi-qiang; LI Xiao-feng; LIU Ying-long; DU Jie; HAN Ling

    2013-01-01

    Background Animal models that demonstrate changes of renal function in response to acute lung injury (ALl) and mechanical ventilation (MV) are few.The present study was performed to examine the effect of ALl induced by oleic acid (OA) in combination with conventional MV strategy on renal function in piglets.Methods Twelve Chinese mini-piglets were randomly divided into two groups:the OA group (n=6),animals were ventilated with a conventional MV strategy of 12 ml/kg and suffered an ALl induced by administration of OA,and the control group (n=6),animals were ventilated with a protective MV strategy of 6 ml/kg and received the same amount of sterile saline.Results Six hours after OA injection a severe lung injury and a mild-moderate degree of renal histopathological injury were seen,while no apparent histological abnormalities were observed in the control group.Although we observed an increase in the plasma concentrations of creatinine and urea after ALl,there was no significant difference compared with the control group.Plasma concentrations of neutrophil gelatinase-associated lipocalin (NGAL) and cystatin C increased (5.6±1.3) and (7.4±1.5) times in the OA group compared to baseline values,and were significantly higher than the values in the control group.OA injection in combination with conventional MV strategy resulted in a dramatic aggravation of hemodynamic and blood gas exchange parameters,while these parameters remained stable during the experiment in the control group.The plasma expression of TNF-α and IL-6 in the OA group were significantly higher than that in the control group.Compared with high expression in the lung and renal tissue in the OA group,TNF-α and IL-6 were too low to be detected in the lung and renal tissue in the control group.Conclusions OA injection in combination with conventional MV strategy not only resulted in a severe lung injury but also an apparent renal injury.The potential mechanisms involved a cytokine response of TNF-α and

  2. Oxidative/Nitrative Stress and Inflammation Drive Progression of Doxorubicin-Induced Renal Fibrosis in Rats as Revealed by Comparing a Normal and a Fibrosis-Resistant Rat Strain.

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    Csaba Imre Szalay

    Full Text Available Chronic renal fibrosis is the final common pathway of end stage renal disease caused by glomerular or tubular pathologies. Genetic background has a strong influence on the progression of chronic renal fibrosis. We recently found that Rowett black hooded rats were resistant to renal fibrosis. We aimed to investigate the role of sustained inflammation and oxidative/nitrative stress in renal fibrosis progression using this new model. Our previous data suggested the involvement of podocytes, thus we investigated renal fibrosis initiated by doxorubicin-induced (5 mg/kg podocyte damage. Doxorubicin induced progressive glomerular sclerosis followed by increasing proteinuria and reduced bodyweight gain in fibrosis-sensitive, Charles Dawley rats during an 8-week long observation period. In comparison, the fibrosis-resistant, Rowett black hooded rats had longer survival, milder proteinuria and reduced tubular damage as assessed by neutrophil gelatinase-associated lipocalin (NGAL excretion, reduced loss of the slit diaphragm protein, nephrin, less glomerulosclerosis, tubulointerstitial fibrosis and matrix deposition assessed by periodic acid-Schiff, Picro-Sirius-red staining and fibronectin immunostaining. Less fibrosis was associated with reduced profibrotic transforming growth factor-beta, (TGF-β1 connective tissue growth factor (CTGF, and collagen type I alpha 1 (COL-1a1 mRNA levels. Milder inflammation demonstrated by histology was confirmed by less monocyte chemotactic protein 1 (MCP-1 mRNA. As a consequence of less inflammation, less oxidative and nitrative stress was obvious by less neutrophil cytosolic factor 1 (p47phox and NADPH oxidase-2 (p91phox mRNA. Reduced oxidative enzyme expression was accompanied by less lipid peroxidation as demonstrated by 4-hydroxynonenal (HNE and less protein nitrosylation demonstrated by nitrotyrosine (NT immunohistochemistry and quantified by Western blot. Our results demonstrate that mediators of fibrosis

  3. Central nervous system lipocalin-type prostaglandin D2-synthase is correlated with orexigenic neuropeptides, visceral adiposity and markers of the hypothalamic-pituitary-adrenal axis in obese humans.

    Science.gov (United States)

    Elias, E; Benrick, A; Behre, C J; Ekman, R; Zetterberg, H; Stenlöf, K; Wallenius, V

    2011-06-01

    Lipocalin-type prostaglandin D2-synthase (L-PGDS) is the main producer of prostaglandin D2 (PGD2) in the central nervous system (CNS). Animal data suggest effects of central nervous L-PGDS in the regulation of food intake and obesity. No human data are available. We hypothesised that a role for CNS L-PGDS in metabolic function in humans would be reflected by correlations with known orexigenic neuropeptides. Cerebrospinal fluid (CSF) and serum samples were retrieved from 26 subjects in a weight loss study, comprising a 3-week dietary lead-in followed by 12-weeks of leptin or placebo treatment. At baseline, CSF L-PGDS was positively correlated with neuropeptide Y (NPY) (ρ = 0.695, P obesity by interaction with the neuroendocrine circuits regulating appetite and fat distribution. Further interventional studies will be needed to characterise these interactions in more detail.

  4. The Potential Utility of Urinary Biomarkers for Risk Prediction in Combat Casualties: A Prospective Observational Cohort Study

    Science.gov (United States)

    2015-06-16

    Separate models were run for each of the five UBs. A two- tailed p value ɘ.05 was considered significant. Statistics were performed using SAS...ICU admission predict adverse clinical outcomes. Clin J Am Soc Nephrol. 2010;5:1497–505. 10. Parikh CR, Coca SG, Thiessen-Philbrook H, Shlipak MG...serum cystatin-C, plasma and urine neutrophil gelatinase-associated lipocalin. Crit Care. 2014;18:R151. 24. Coca SG, Garg AX, Thiessen-Philbrook H, Koyner

  5. Effects of glucocorticoids and tumor necrosis factor-alpha inhibitors on both clinical and molecular parameters in patients with Takayasu arteritis

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    Raffaele Serra

    2014-01-01

    Full Text Available Objective: To explore the effect of sequential treatment with glucocorticoid and tumor necrosis factor-alpha inhibitors in patients with Takayasu arteritis (TA. Materials and Methods: In five patients with TA, the effects of the sequential treatment with prednisone for 5-7 months and then with adalimumab (ADA + methotrexate (MTX or infliximab + MTX, or with ADA only, for 12 months on both clinical and laboratory findings were evaluated. Results: All treatments improved both symptoms and laboratory parameters without the development of side-effects. Conclusions: It was hypothesized that MMP-9 and neutrophil gelatinase-associated lipocalin could be markers of the response to the treatments.

  6. Effect of reduced Glutathione onserum and urinary concentration of NGAL in the rodent model of Cisplatin induced acute kidney injury%顺铂致大鼠急性肾损伤血、尿NGAL变化及还原型谷胱甘肽干预的研究

    Institute of Scientific and Technical Information of China (English)

    孟晓燕; 郑妮; 张敏; 宋雪霞; 刘倩; 黄向阳

    2014-01-01

    目的 研究顺铂致大鼠急性肾损伤(AKI)模型中AKI标志物中性粒细胞明胶酶相关脂质运载蛋白(NGAL)变化及还原型谷胱甘肽干预疗效.方法 66只健康雄性Wistar大鼠为研究对象,随机数字法随机分为盐水对照组(CN组),顺铂模型组(CP组)及还原型谷胱甘肽干预组(GI组),CP组为腹腔单次注射顺铂10mg/kg,据给药后各时间点不同分为5组;GI组为应用顺铂前腹腔注射还原型谷胱甘肽800 mg/kg,同样据给药时间不同分为5组;CN组为腹腔注射同顺铂组等容量生理盐水.观察用药后12、24、48、96 h及144 h各组大鼠血清肌酐(Scr)及用ELISA法检测血、尿NGAL变化情况.结果 同CN组相比,CP组12h血、尿NGAL开始升高,48 h达峰值,Scr 48 h开始升高,144 h达峰值.GI组同CP组比较,减轻了血、尿NGAL的升高.结论 CDDP致大鼠AKI早期存在血、尿NGAL的升高,还原型谷胱甘肽可一定程度上减轻NGAL的升高,可能为防治顺铂致急性肾损伤的有效药物.

  7. Overexpression of lipocalins and pro-inflammatory chemokines and altered methylation of PTGS2 and APC2 in oral squamous cell carcinomas induced in rats by 4-nitroquinoline-1-oxide.

    Directory of Open Access Journals (Sweden)

    Xinjian Peng

    Full Text Available Oral squamous cell carcinomas (OSCC induced in F344 rats by 4-nitroquinoline-1-oxide (4-NQO demonstrate considerable phenotypic similarity to human oral cancers. Gene expression studies (microarray and PCR were coupled with methylation analysis of selected genes to identify molecular markers of carcinogenesis in this model and potential biochemical and molecular targets for oral cancer chemoprevention. Microarray analysis of 11 pairs of OSCC and site-matched phenotypically normal oral tissues from 4-NQO-treated rats identified more than 3500 differentially expressed genes; 1735 genes were up-regulated in rat OSCC versus non-malignant tissues, while 1803 genes were down-regulated. In addition to several genes involved in normal digestion, genes demonstrating the largest fold increases in expression in 4-NQO-induced OSCC include three lipocalins (VEGP1, VEGP2, LCN2 and three chemokines (CCL, CXCL2, CXCL3; both classes are potentially druggable targets for oral cancer chemoprevention and/or therapy. Down-regulated genes in 4-NQO-induced OSCC include numerous keratins and keratin-associated proteins, suggesting that alterations in keratin expression profiles may provide a useful biomarker of oral cancer in F344 rats treated with 4-NQO. Confirming and extending our previous results, PTGS2 (cyclooxygenase-2 and several cyclooxygenase-related genes were significantly up-regulated in 4-NQO-induced oral cancers; up-regulation of PTGS2 was associated with promoter hypomethylation. Rat OSCC also demonstrated increased methylation of the first exon of APC2; the increased methylation was correlated with down-regulation of this tumor suppressor gene. Overexpression of pro-inflammatory chemokines, hypomethylation of PTGS2, and hypermethylation of APC2 may be causally linked to the etiology of oral cancer in this model.

  8. A feasible strategy for preventing blood clots in critically ill patients with acute kidney injury (FBI)

    DEFF Research Database (Denmark)

    Robinson, Sian I.; Zincuk, A.; Larsen, U. L.;

    2014-01-01

    urine output prior to discontinuing dialysis, and low neutrophil gelatinase-associated lipocalin in dialysis-free intervals, as markers of renal recovery. METHODS/DESIGN: In a multicenter, double-blind randomized controlled trial in progress at three intensive care units across Denmark, we randomly......BACKGROUND: Previous pharmacokinetic trials suggested that 40 mg subcutaneous enoxaparin once daily provided inadequate thromboprophylaxis for intensive care unit patients. Critically ill patients with acute kidney injury are at increased risk of venous thromboembolism and yet are often excluded...... from these trials. We hypothesized that for critically ill patients with acute kidney injury receiving continuous renal replacement therapy, a dose of 1 mg/kg enoxaparin subcutaneously once daily would improve thromboprophylaxis without increasing the risk of bleeding. In addition, we seek to utilize...

  9. Novel biomarkers for cardiac surgery-associated acute kidney injury: a skeptical assessment of their role.

    Science.gov (United States)

    Sidebotham, David

    2012-12-01

    Cardiac surgery-associated acute kidney injury (AKI) is common and is associated with a high mortality rate. Traditional biomarkers of AKI (creatinine and urea) increase slowly in response to renal injury, are insensitive to mild degrees of AKI, and are influenced by nonrenal factors. There is considerable interest in novel biomarkers of AKI such as neutrophil gelatinase-associated lipocalin that increase rapidly after renal injury, detect mild degrees of AKI, and are less subject to nonrenal factors. It has been postulated that the early diagnosis of cardiac surgery-associated AKI using novel biomarkers will result in improved outcomes. However, there is little evidence that interventions started early in the course of evolving AKI enhance renal recovery. Until effective therapies are developed that significantly improve the outcome from AKI, there is little benefit from early diagnosis using novel biomarkers.

  10. Early biomarkers for acute kidney injury%早期诊断急性肾损伤的生物学标志物研究现状

    Institute of Scientific and Technical Information of China (English)

    侯玲

    2010-01-01

    急性肾损伤(AKI)是一种常见的严重疾病.由于缺乏诊断AKI的早期生物学标志物,往往导致早期有效治疗的延误.目前对于诊断AKI新的生物学标志物的研究已发展到了临床研究阶段,最有希望成为早期诊断AKI的生物学标志物包括中性粒细胞明胶酶相关脂质运载蛋白、IL-18、肾损伤分子-1和L-脂肪酸结合蛋白.本文就近年来关于上述几种生物学标志物的研究作一综述,为应用早期诊断AKI的生物学标志物提供理论依据.%Acute kidney injury (AKI) represents a common and devastating problem in clinical medicine. The lack of early biomarkers for AKI has led to a delay in initiating potentially effective therapies.Identification of novel biomarkers for AKI has progressed to the clinical phase of the biomarker discovery process. The most promising AKI biomarkers include neutrophil gelatinase-associated lipocalin, IL-18, kidney injury molecule-1 and liver-type fatty acid binding protein. In this article, we review the study of neutrophil gelatinase-associated lipocalin,IL-18, kidney injury molecule-1 and liver-type fatty acid binding protein in recent years,in order to provide the theory basis for the clinical application of the early biomarkers for AKI.

  11. Performance of kidney injury molecule-1 and liver fatty acid-binding protein and combined biomarkers of AKI after cardiac surgery.

    Science.gov (United States)

    Parikh, Chirag R; Thiessen-Philbrook, Heather; Garg, Amit X; Kadiyala, Deepak; Shlipak, Michael G; Koyner, Jay L; Edelstein, Charles L; Devarajan, Prasad; Patel, Uptal D; Zappitelli, Michael; Krawczeski, Catherine D; Passik, Cary S; Coca, Steven G

    2013-07-01

    AKI is common and novel biomarkers may help provide earlier diagnosis and prognosis of AKI in the postoperative period. This was a prospective, multicenter cohort study involving 1219 adults and 311 children consecutively enrolled at eight academic medical centers. Performance of two urine biomarkers, kidney injury molecule-1 (KIM-1) and liver fatty acid-binding protein (L-FABP), alone or in combination with other injury biomarkers during the perioperative period was evaluated. AKI was defined as doubling of serum creatinine or need for acute dialysis. KIM-1 peaked 2 days after surgery in adults and 1 day after surgery in children, whereas L-FABP peaked within 6 hours after surgery in both age groups. In multivariable analyses, the highest quintile of the first postoperative KIM-1 level was associated with AKI compared with the lowest quintile in adults, whereas the first postoperative L-FABP was not associated with AKI. Both KIM-1 and L-FABP were not significantly associated with AKI in adults or children after adjusting for other kidney injury biomarkers (neutrophil gelatinase-associated lipocalin and IL-18). The highest area under the curves achievable for discrimination for AKI were 0.78 in adults using urine KIM-1 from 6 to 12 hours, urine IL-18 from day 2, and plasma neutrophil gelatinase-associated lipocalin from day 2 and 0.78 in children using urine IL-18 from 0 to 6 hours and urine L-FABP from day 2. Postoperative elevations of KIM-1 associate with AKI and adverse outcmes in adults but were not independent of other AKI biomarkers. A panel of multiple biomarkers provided moderate discrimination for AKI.

  12. Remote ischemic conditioning enhanced the early recovery of renal function in recipients after kidney transplantation: a randomized controlled trial.

    Science.gov (United States)

    Wu, Jianyong; Feng, Xiaoxiao; Huang, Hongfeng; Shou, Zhangfei; Zhang, Xiaohui; Wang, Rending; Chen, Yanyan; Chen, Jianghua

    2014-05-01

    To investigate whether remote ischemic conditioning (RIC) can attenuate ischemic reperfusion injury (IRI) in recipients after kidney transplantation using donation after cardiac death. Forty-eight recipients referred for kidney transplantation were recruited. The paired recipients who received the kidneys from the same donor were randomly assigned (one received RIC and the other did not). RIC was induced by three 5-min cycles of brief repetitive ischemia and reperfusion by clamping the exposed external iliac artery. Blood samples were withdrawn at hour 2, hour 12, days 1-7, day 14, and day 30 to measure serum creatinine level and estimated glomerular filtration rate after transplantation. Urine samples were collected at hours 2, 12, 24, and 48 to measure urine neutrophil gelatinase-associated lipocalin after transplantation. Renal tissues were obtained at 30 min for histologic changes after transplantation. There were no significant differences in clinical characteristics of the recipients and donors between RIC and control groups. The serum creatinine level was lower in the RIC group compared with that of the control group (12 h, days 1-14, P  0.05); the estimated glomerular filtration rate was higher in the RIC group compared with that of the control group (12 h, days 1-14, P 0.05); urine neutrophil gelatinase-associated lipocalin, an early marker of IRI, was lower in the RIC group at hours 2, 12, 24, and 48 (2 h, 48 h, P > 0.05; 12 h, 24 h, P control group. The graft pathology showed no differences between RIC and control groups. RIC enhanced the early recovery of renal function in recipients after kidney transplantation. Our results provide a novel potential approach to attenuate transplantation-associated IRI. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Complement activation and kidney injury molecule-1-associated proximal tubule injury in severe preeclampsia.

    Science.gov (United States)

    Burwick, Richard M; Easter, Sarah Rae; Dawood, Hassan Y; Yamamoto, Hidemi S; Fichorova, Raina N; Feinberg, Bruce B

    2014-10-01

    Kidney injury with proteinuria is a characteristic feature of preeclampsia, yet the nature of injury in specific regions of the nephron is incompletely understood. Our study aimed to use existing urinary biomarkers to describe the pattern of kidney injury and proteinuria in pregnancies affected by severe preeclampsia. We performed a case-control study of pregnant women from Brigham and Women's Hospital from 2012 to 2013. We matched cases of severe preeclampsia (n=25) 1:1 by parity and gestational age to 2 control groups with and without chronic hypertension. Urinary levels of kidney injury molecule-1 and complement components (C3a, C5a, and C5b-9) were measured by enzyme-linked immunosorbent assay, and other markers (albumin, β2 microglobulin, cystatin C, epithelial growth factor, neutrophil gelatinase-associated lipocalin, osteopontin, and uromodulin) were measured simultaneously with a multiplex electrochemiluminescence assay. Median values between groups were compared with the Wilcoxon signed-rank test and correlations with Spearman correlation coefficient. Analysis of urinary markers revealed higher excretion of albumin and kidney injury molecule-1 and lower excretion of neutrophil gelatinase-associated lipocalin and epithelial growth factor in severe preeclampsia compared with chronic hypertension and healthy controls. Among subjects with severe preeclampsia, urinary excretion of complement activation products correlated most closely with kidney injury molecule-1, a specific marker of proximal tubule injury (C5a: r=0.60; P=0.001; and C5b-9: r=0.75; Pkidney injury in severe preeclampsia that is characterized by glomerular impairment and complement-mediated inflammation and injury, possibly localized to the proximal tubule in association with kidney injury molecule-1.

  14. 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

  15. 不同缺血后处理方案对家兔挤压综合征损伤保护效应的实验研究%Experimental study on the protective effect of different ischemic postconditioning scheme in rabbits with crush syndrome

    Institute of Scientific and Technical Information of China (English)

    王金墙; 刘子泉; 丁辉; 樊毫军; 董文龙; 宋美娟; 侯世科

    2015-01-01

    目的:筛选不同缺血后处理(ischemic postconditioning,IPost)方案对家兔挤压综合征(crush syndrome,CS)损伤保护效应的最佳时间窗。方法选取48只家兔随机分为对照组( S组)及5个不同IPost方案组( IPA~IPE组),每组8只。建立CS模型,并于解压前游离双下肢股动、静脉,解压后IPA组给予阻断下肢血流5 s,再灌注5 s,共5个循环(即5×5 s/5 s),IPB组5×30 s/30 s,IPC组5×1 min/1 min,IPD组5×5 min/5 min,IPE组3×10 min/10 min,继续观察至解压后24 h。分别于建模前,解压即刻及解压后2、6、12、18、24 h时间点检测家兔血液中肌酸激酶( creatine kinase,CK)、肌红蛋白( myoglo-bin,Mb)、中性粒细胞明胶酶相关脂质运载蛋白( neutrophil gelatinase-associated lipocalin,NGAL)的含量。结果与S组相比,各IPost组均可降低解压后CS家兔血清CK、Mb和NGAL的含量。在解压后6、12、18、24 h,IPC、IPD组各指标与S组相比,差异均具有统计学意义( P<0.005);IPC组各指标较IPD组低,但解压后各时间点两组之间比较无显著差异。结论 CS家兔再灌注前给予1~5 min的肢体远隔IPost对损伤具有保护作用,其中给予5个循环的1 min缺血,1 min再灌后处理具有最佳保护效应。%Objective To screen the best time-window of the protective effect of different ischemia postconditioning ( IPost) scheme on rabbits with crush syndrome ( CS) injury.Methods 48 healthy Japanese white rabbits were selected and randomly divided into control group ( S group) and 5 groups of different IPost scheme ( IPA~IPE group) , 8 rabbits each.CS model was established, and femoral arteries and veins were separated in the groin of both lower limbs before releasing of pressure.After decompression, the ar-teries of IPA group were treated with bulldog climp clamping for 5 s, then releasing 5 s, and repeated for 5 cycles (5 ×5 s/5 s), IPB

  16. The role of Lipocalin 2 in Alzheimer's disease and depression

    NARCIS (Netherlands)

    Naudé, Petrus Johan Wichardt

    2012-01-01

    De meeste mensen, zo niet alle mensen die deze samenvatting lezen, hebbcn persoonlijk iemand onrmoet of weten van iemand die gediagnosticeerd is met de ziekte van Alzheimer. De ziekte van Alzheimer is een neurodegeneratieve ziekte die voornamelijk voorkomt bij oudere mensen. De eerste tekenen van de

  17. Expression analysis of lipocalin 2 in patients with diabetes mellitus complicated with preeclampsia and its relationship with the disease%妊娠期糖尿病并发子痫前期患者血清 LCN-2水平及其与疾病严重程度的相关性

    Institute of Scientific and Technical Information of China (English)

    刘益华; 陈秀琴; 何燕

    2015-01-01

    Objective To test the level of human lipocalin 2 ( LCN-2 ) in gestational diabetes ( GDM) complicated with preeclampsia(PE) , and explore the relationship between LCN-2 and related indicators and disease.Methods From January 2010 to December 2013 , 60 patients with GDM merger PE were enrolled , including 30 patients with mild PE ( GDM combined with mild PE group ) , 30 cases of patients with severe PE ( GDM with severe PE group ) , 30 cases of patients with simple GDM (GDM group) and 30 patients with PE (PE group) as the disease control, selected normal pregnant women as normal pregnancy group.All subjects’ serum triglyceride (TG), free fatty acids (FFAs), uric acid (UA),24 -hour urine protein, LCN-2 levels, insulin resistance and homeostasis model assessment index (HOMA-IR) were analyzed.Results There were statistically significant differences of FFAs , LCN-2 level in each group ( P =0.000), GDM merger PE group with the highest level , the lowest level was in normal pregnancy group .PE group and GDM group ’ s HOMA-IR merger PE were higher than normal pregnancy group and the GDM group ( P 0.05), No difference was statistically significant between nor-mal pregnancy group and GDM group ( P >0.05);PE group, GDM group’s TG was higher than the GDM combined with PE group and normal pregnancy group ( P 0 .05 ); PE group, GDM combined with PE group’s UA were higher than normal pregnancy group ( P 0 .05);GDM combined with PE group's 24 h urinary protein levels was higher than the PE group , the difference was statistically significant ( P <0.01), while the normal pregnancy group and the GDM group was not detected in urine pro-tein.GDM with severe PE group’s FFAs, HOMA-IR, TG, LCN-2,24 h urinary protein and UA levels were significantly high-er than those with GDM combined with mild PE group , the difference were statistically significant ( P <0.05, P <0.01);LCN-2 and FFAs, HOMA-IR, TG, 24 h urinary protein and UA were positively correlated ( r =0.598, r =0.602, r

  18. A Nitric Oxide-Donor Furoxan Moiety Improves the Efficacy of Edaravone against Early Renal Dysfunction and Injury Evoked by Ischemia/Reperfusion

    Directory of Open Access Journals (Sweden)

    Fausto Chiazza

    2015-01-01

    Full Text Available Edaravone (5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one, EDV is a free-radical scavenger reduces organ ischemic injury. Here we investigated whether the protective effects of EDV in renal ischemia/reperfusion (I/R injury may be enhanced by an EDV derivative bearing a nitric oxide- (NO- donor furoxan moiety (NO-EDV. Male Wistar rats were subjected to renal ischemia (45 minutes, followed by reperfusion (6 hours. Administration of either EDV (1.2–6–30 µmol/kg, i.v. or NO-EDV (0.3–1.2–6 µmol/kg, i.v. dose-dependently attenuated markers of renal dysfunction (serum urea and creatinine, creatinine clearance, urine flow, urinary N-acetyl-β-D-glucosaminidase, and neutrophil gelatinase-associated lipocalin/lipocalin-2. NO-EDV exerted protective effects in the dose-range 1.2–6 µmol/kg, while a higher dose (30 µmol/kg was needed to obtain protection by EDV. Both EDV and NO-EDV modulated tissue markers of oxidative stress and lipid peroxidation. NO-EDV, but not EDV, activated endothelial NO synthase (NOS and blunted I/R-induced upregulation of inducible NOS, secondary to modulation of Akt and NF-κB activation, respectively. Besides NO-EDV administration inhibited I/R-induced IL-1β, IL-18, IL-6, and TNF-α overproduction. Overall, these findings demonstrate that the NO-donor moiety contributes to the protection against early renal I/R injury and suggest that NO-donor EDV codrugs are worthy of additional study as innovative pharmacological tools.

  19. 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.

  20. Hepatorenal syndrome: Update on diagnosis and therapy

    Science.gov (United States)

    Acevedo, Juan G; Cramp, Matthew E

    2017-01-01

    Hepatorenal syndrome (HRS) is a manifestation of extreme circulatory dysfunction and entails high morbidity and mortality. A new definition has been recently recommended by the International Club of Ascites, according to which HRS diagnosis relies in serum creatinine changes instead that on a fixed high value. Moreover, new data on urinary biomarkers has been recently published. In this sense, the use of urinary neutrophil gelatinase-associated lipocalin seems useful to identify patients with acute tubular necrosis and should be employed in the diagnostic algorithm. Treatment with terlipressin and albumin is the current standard of care. Recent data show that terlipressin in intravenous continuous infusion is better tolerated than intravenous boluses and has the same efficacy. Terlipressin is effective in reversing HRS in only 40%-50% of patients. Serum bilirubin and creatinine levels along with the increase in blood pressure and the presence of systemic inflammatory response syndrome have been identified as predictors of response. Clearly, there is a need for further research in novel treatments. Other treatments have been assessed such as noradrenaline, dopamine, transjugular intrahepatic portosystemic shunt, renal and liver replacement therapy, etc. Among all of them, liver transplant is the only curative option and should be considered in all patients. HRS can be prevented with volume expansion with albumin during spontaneous bacterial peritonitis and after post large volume paracentesis, and with antibiotic prophylaxis in patients with advanced cirrhosis and low proteins in the ascitic fluid. This manuscript reviews the recent advances in the diagnosis and management of this life-threatening condition.

  1. Emerging risk factors and markers of chronic kidney disease progression.

    Science.gov (United States)

    Kronenberg, Florian

    2009-12-01

    Chronic kidney disease (CKD) is a common condition with an increasing prevalence. A number of comorbidities are associated with CKD and prognosis is poor, with many patients experiencing disease progression. Recognizing the factors associated with CKD progression enables high-risk patients to be identified and given more intensive treatment if necessary. The identification of new predictive markers might improve our understanding of the pathogenesis and progression of CKD. This Review discusses a number of emerging factors and markers for which epidemiological evidence from prospective studies indicates an association with progression of CKD. The following factors and markers are discussed: asymmetric dimethylarginine, factors involved in calcium-phosphate metabolism, adrenomedullin, A-type natriuretic peptide, N-terminal pro-brain natriuretic peptide, liver-type fatty acid binding protein, kidney injury molecule 1, neutrophil gelatinase-associated lipocalin, apolipoprotein A-IV, adiponectin and some recently identified genetic polymorphisms. Additional epidemiological and experimental data are required before these markers can be broadly used for the prediction of CKD progression and before the risk factors can be considered as potential drug targets in clinical interventional trials.

  2. The effect of activated charcoal on adenine-induced chronic renal failure in rats.

    Science.gov (United States)

    Ali, Badreldin H; Alza'abi, Mohamed; Ramkumar, Aishwarya; Al-Lawati, Intisar; Waly, Mostafa I; Beegam, Sumaya; Nemmar, Abderrahim; Brand, Susanne; Schupp, Nicole

    2014-03-01

    Activated charcoal (AC) is a sorbent that has been shown to remove urinary toxins like urea and indoxyl sulfate. Here, the influence of AC on kidney function of rats with experimental chronic renal failure (CRF) is investigated. CRF was induced in rats by feeding adenine (0.75%) for four weeks. As an intervention, AC was added to the feed at concentrations of 10%, 15% or 20%. Adenine treatment impaired kidney function: it lowered creatinine clearance and increased plasma concentrations of creatinine, urea, neutrophil gelatinase-associated lipocalin and vanin-1. Furthermore, it raised plasma concentrations of the uremic toxins indoxyl sulfate, phosphate and uric acid. Renal morphology was severely damaged and histopathological markers of inflammation and fibrosis were especially increased. In renal homogenates, antioxidant indices, including superoxide dismutase and catalase activity, total antioxidant capacity and reduced glutathione were adversely affected. Most of these changes were significantly ameliorated by dietary administration of AC at a concentration of 20%, while effects induced by lower doses of dietary AC on adenine nephrotoxicity were not statistically significant. The results suggest that charcoal is a useful sorbent agent in dietary adenine-induced CRF in rats and that its usability as a nephroprotective agent in human kidney disease should be studied.

  3. Clinical utility of biomarkers in chronic kidney disease and chronic heart failure.

    Science.gov (United States)

    Zachariah, Donah; Olechowski, Bartosz; Kalra, Paul R

    2013-09-01

    Biomarkers have an increasingly important clinical role in managing patients with heart failure as well as those with kidney disease, both common conditions with generally poor prognostic outcomes and huge impacts on healthcare economics. For patients with chronic heart failure, biomarkers have become centre place in streamlining diagnostic pathways as well as identifying those with worse prognosis. There is much interest in the role for biomarkers in identifying patients at risk of acute kidney injury, although a number of these currently remain as research tools or are in the early stages of evaluation in clinical practice. Patients with cardiorenal syndrome represent a particular challenge to the clinician, and recent studies have suggested a valuable clinical role for certain biomarkers in this setting, either on their own or in combination. This paper will focus on biomarkers with a current clinical role in patients with cardiorenal disease (natriuretic peptides and neutrophil gelatinase-associated lipocalin), although brief reference will be made to other biomarkers with potential future application.

  4. Fetal Kidney Cells Can Ameliorate Ischemic Acute Renal Failure in Rats through Their Anti-Inflammatory, Anti-Apoptotic and Anti-Oxidative Effects.

    Science.gov (United States)

    Gupta, Ashwani Kumar; Jadhav, Sachin H; Tripathy, Naresh Kumar; Nityanand, Soniya

    2015-01-01

    Fetal kidney cells may contain multiple populations of kidney stem cells and thus appear to be a suitable cellular therapy for the treatment of acute renal failure (ARF) but their biological characteristics and therapeutic potential have not been adequately explored. We have culture expanded fetal kidney cells derived from rat fetal kidneys, characterized them and evaluated their therapeutic effect in an ischemia reperfusion (IR) induced rat model of ARF. The fetal kidney cells grew in culture as adherent spindle shaped/polygonal cells and expressed CD29, CD44, CD73, CD90, CD105, CD24 and CD133 markers. Administration of PKH26 labeled fetal kidney cells in ARF rats resulted in a significant decrease in the levels of blood urea nitrogen, creatinine, and neutrophil gelatinase-associated lipocalin and decreased tubular necrosis in the kidney tissues (pkidney cells were observed to engraft around injured tubular cells, and there was increased proliferation and decreased apoptosis of tubular cells in the kidneys (pkidney tissues of ARF rats treated with fetal kidney cells had a higher gene expression of renotropic growth factors (VEGF-A, IGF-1, BMP-7 and bFGF) and anti-inflammatory cytokine (IL10); up regulation of anti-oxidative markers (HO-1 and NQO-1); and a lower Bax/Bcl2 ratio as compared to saline treated rats (pkidney cells express mesenchymal and renal progenitor markers, and ameliorate ischemic ARF predominantly by their anti-apoptotic, anti-inflammatory and anti-oxidative effects.

  5. New biomarkers of acute kidney injury

    Directory of Open Access Journals (Sweden)

    Ruya Ozelsancak

    2013-04-01

    Full Text Available Acute kidney injury is a clinical syndrome which is generally defined as an abrupt decline in glomerular filtration rate causing accumulation of nitrogenous products and rapid development of fluid, electrolyte and acid-base disorders. It is an important clinical problem increasing mortality in patient with several co-morbid conditions. The frequency of acute kidney injury occurrence varies from 5% on the inpatients wards to 30-50% in patients from intensive care units. Serial measurement of creatinine and urine volume do not make it possible to diagnose acute kidney injury at early stages. Serum creatinine may be influenced by age, weight, hydration status and become apparent only when the kidneys have lost 50% of their function. For that reasons we need new markers. Here, we are reviewing the most promising new acute kidney injury markers, neutrophil gelatinase associated lipocalin, cystatin-C, kidney injury molecule-1, liver fatty acid binding proteins and IL-18. [Archives Medical Review Journal 2013; 22(2.000: 221-229

  6. Renocardiovascular Biomarkers: from the Perspective of Managing Chronic Kidney Disease and Cardiovascular Disease

    Science.gov (United States)

    Niizuma, Shinichiro; Iwanaga, Yoshitaka; Yahata, Takaharu; Miyazaki, Shunichi

    2017-01-01

    Mortality among the patients with chronic kidney disease (CKD) and end-stage renal disease (ESRD) remains high because of the very high incidence of cardiovascular disease (CVD) such as coronary artery disease, cardiac hypertrophy, and heart failure. Identifying CVD in patients with CKD/ESRD remains a significant hurdle and the early diagnosis and therapy for CVD is crucial in these patients. Therefore, it is necessary for the better management to identify and utilize cardiovascular (CV) biomarkers in profiling CVD risk and enabling stratification of early mortality. This review summarizes current evidence about renocardiovascular biomarkers: CV biomarkers in patients with CKD as well as with ESRD, emphasizing on the emerging biomarkers: B-type natriuretic peptide, cardiac troponins, copeptin, the biomarker of renal injury (neutrophil gelatinase-associated lipocalin), and the mineral and bone disorder hormone/marker (fibroblast growth factor-23). Furthermore, it discusses their potential roles especially in ESRD and in future diagnostic and therapeutic strategies for CVD in the context of managing cardiorenal syndrome.

  7. Vitamin D depletion aggravates hypertension and target-organ damage

    DEFF Research Database (Denmark)

    Andersen, Louise Bjørkholt; Przybyl, Lukasz; Haase, Nadine

    2015-01-01

    BACKGROUND: We tested the controversial hypothesis that vitamin D depletion aggravates hypertension and target-organ damage by influencing renin. METHODS AND RESULTS: Four-week-old double-transgenic rats (dTGR) with excess angiotensin (Ang) II production due to overexpression of the human renin (h......REN) and angiotensinogen (hAGT) genes received vitamin D-depleted (n=18) or standard chow (n=15) for 3 weeks. The depleted group had very low serum 25-hydroxyvitamin D levels (mean±SEM; 3.8±0.29 versus 40.6±1.19 nmol/L) and had higher mean systolic BP at week 5 (158±3.5 versus 134.6±3.7 mm Hg, P....6±3.3 versus 162.3±3.8 mm Hg, PVitamin D depletion led to increased relative heart weights and increased serum creatinine concentrations. Furthermore, the mRNAs of natriuretic peptides, neutrophil gelatinase-associated lipocalin, hREN, and r...

  8. Pediatric acute kidney injury: Appraisal of predictors and prognostic indicators

    Directory of Open Access Journals (Sweden)

    Samuel Nkachukwu Uwaezuoke

    2017-01-01

    Full Text Available Acute kidney injury (AKI is a major contributor to childhood morbidity and mortality worldwide. In spite of the advances in renal replacement therapy, there has been a minimal reduction in AKI-related morbidity and mortality. Identifying the prognostic indicators and the risk factors that predict disease onset and progression, and instituting appropriate measures will lead to better survival outcomes. This narrative review seeks to appraise the predictors and prognostic indicators of pediatric AKI. Several biomarkers clearly stand out as predictors and prognostic indicators of the acute disease. Some of them are urine angiotensinogen, fibroblast growth factor-23, cystacin C, neutrophil gelatinase-associated lipocalin, tissue inhibitor of metalloproteinase-2 and insulin-like growth factor-binding protein 7. Combining few of these biomarkers with clinical prediction models has improved their predictive and prognostic utility for AKI. Hemodynamic parameters such as indexed systemic oxygen delivery and mean arterial blood pressure have been proved to be reliable in predicting the occurrence and progression of the disease and its outcomes. Miscellaneous predictors and prognostic indicators like AKI definition criteria, presence of co-morbidities, and health-related quality of life assessment have also been documented from evidence-based studies. An understanding and application of these indices will obviously help to reduce AKI mortality in children.

  9. Diannexin protects against renal ischemia reperfusion injury and targets phosphatidylserines in ischemic tissue.

    Directory of Open Access Journals (Sweden)

    Kimberley E Wever

    Full Text Available Renal ischemia/reperfusion injury (IRI frequently complicates shock, renal transplantation and cardiac and aortic surgery, and has prognostic significance. The translocation of phosphatidylserines to cell surfaces is an important pro-inflammatory signal for cell-stress after IRI. We hypothesized that shielding of exposed phosphatidylserines by the annexin A5 (ANXA5 homodimer Diannexin protects against renal IRI. Protective effects of Diannexin on the kidney were studied in a mouse model of mild renal IRI. Diannexin treatment before renal IRI decreased proximal tubule damage and leukocyte influx, decreased transcription and expression of renal injury markers Neutrophil Gelatinase Associated Lipocalin and Kidney Injury Molecule-1 and improved renal function. A mouse model of ischemic hind limb exercise was used to assess Diannexin biodistribution and targeting. When comparing its biodistribution and elimination to ANXA5, Diannexin was found to have a distinct distribution pattern and longer blood half-life. Diannexin targeted specifically to the ischemic muscle and its affinity exceeded that of ANXA5. Targeting of both proteins was inhibited by pre-treatment with unlabeled ANXA5, suggesting that Diannexin targets specifically to ischemic tissues via phosphatidylserine-binding. This study emphasizes the importance of phosphatidylserine translocation in the pathophysiology of IRI. We show for the first time that Diannexin protects against renal IRI, making it a promising therapeutic tool to prevent IRI in a clinical setting. Our results indicate that Diannexin is a potential new imaging agent for the study of phosphatidylserine-exposing organs in vivo.

  10. The nano-TiO2 exposure can induce hepatic inflammation involving in a JAK-STAT signalling pathway

    Science.gov (United States)

    Hong, Jie; Hong, Fashui; Ze, Yuguan; Zhang, Yu-Qing

    2016-06-01

    TiO2 nanoparticles (TiO2 NPs) have unique physiochemical properties and thus are widely used in daily life. However, these nanoparticles also have potential toxic effects in humans and animals, and the issue of the security TiO2 NPs has also gained prominence. In this article, mice were administered a gavage instillation of 2.5, 5, or 10 mg/kg body weight TiO2 NPs (5-6 nm) for 90 days. We investigated whether TiO2 NPs activate the JAK-STAT signalling pathway, causing nano-TiO2-induced hepatic toxicity. The results demonstrated that with increasing doses of TiO2 NPs the body weights of the mice body decreased, and the liver index, liver dysfunction, infiltration of inflammatory cells, and hepatocyte apoptosis and necrosis increased. Moreover, liver inflammation was accompanied by increased expression of Janus kinase 2, the signal transducers and activators of transcription 3, interleukin-6, cyclooxygenase-2, neutrophil gelatinase-associated lipocalin, purinergic receptor-7, and epithelial neutrophil-activating protein-78 and decreased expression of suppressors of cytokine signalling-1, peroxisome proliferator-activated receptor-γ, and peroxisome proliferator-activated receptor gamma coactivator-1 alpha. In summary, the activation of the JAK-STAT pathway may be involved in the hepatic inflammation induced by chronic nano-TiO2 toxicity.

  11. The use of biomarkers for assessing HAART-associated renal toxicity in HIV-infected patients.

    Science.gov (United States)

    del Palacio, María; Romero, Sara; Casado, Jose L

    2012-09-01

    Renal toxicity has become an important issue in HIV-infected patients receiving highly active antiretroviral therapy (HAART). Several biomarkers are available for monitoring renal function, although no consensus exists on how best to apply these tools in HIV infection. The best biomarker is the glomerular filtration rate (GFR), and several creatinine-based estimates equations of GFR are widely used in HIV infection, with clinical advantages for the equation developed by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI). Although serum cystatin C has been proposed as a more sensitive marker of renal dysfunction in HIV infection, it may be affected by ongoing inflammation. Tubular dysfunction can be simple or complex, depending on whether the tubular transport of one or more substances is affected. Multiple renal tubular dysfunction or Fanconi syndrome is characterized by alterations in the reabsorption of glucose, amino acids, phosphate and often also bicarbonate. Therefore, Fanconi syndrome would be the tip of the iceberg, and the most unusual and severe manifestation. In the last years, several low molecular weight proteins as markers of tubular alteration, including retinol-binding protein, b2-microglobulin, and neutrophil gelatinase associated lipocalin have become available. Different studies have shown differences in urine concentrations of these proteins in patients receiving tenofovir, but again, no consistent data have shown their clinical usefulness in predicting the clinical consequences of tubular alteration. Thus, we review findings from recent studies performed in this area to describe the performance of new biomarkers for renal damage in HIV-infected patients.

  12. Perioperative acute renal failure.

    LENUS (Irish Health Repository)

    Mahon, Padraig

    2012-02-03

    PURPOSE OF REVIEW: Recent biochemical evidence increasingly implicates inflammatory mechanisms as precipitants of acute renal failure. In this review, we detail some of these pathways together with potential new therapeutic targets. RECENT FINDINGS: Neutrophil gelatinase-associated lipocalin appears to be a sensitive, specific and reliable biomarker of renal injury, which may be predictive of renal outcome in the perioperative setting. For estimation of glomerular filtration rate, cystatin C is superior to creatinine. No drug is definitively effective at preventing postoperative renal failure. Clinical trials of fenoldopam and atrial natriuretic peptide are, at best, equivocal. As with pharmacological preconditioning of the heart, volatile anaesthetic agents appear to offer a protective effect to the subsequently ischaemic kidney. SUMMARY: Although a greatly improved understanding of the pathophysiology of acute renal failure has offered even more therapeutic targets, the maintenance of intravascular euvolaemia and perfusion pressure is most effective at preventing new postoperative acute renal failure. In the future, strategies targeting renal regeneration after injury will use bone marrow-derived stem cells and growth factors such as insulin-like growth factor-1.

  13. Ferric Carboxymaltose-Mediated Attenuation of Doxorubicin-Induced Cardiotoxicity in an Iron Deficiency Rat Model

    Directory of Open Access Journals (Sweden)

    Jorge Eduardo Toblli

    2014-01-01

    Full Text Available Since anthracycline-induced cardiotoxicity (AIC, a complication of anthracycline-based chemotherapies, is thought to involve iron, concerns exist about using iron for anaemia treatment in anthracycline-receiving cancer patients. This study evaluated how intravenous ferric carboxymaltose (FCM modulates the influence of iron deficiency anaemia (IDA and doxorubicin (3–5 mg per kg body weight [BW] on oxidative/nitrosative stress, inflammation, and cardiorenal function in spontaneously hypertensive stroke-prone (SHR-SP rats. FCM was given as repeated small or single total dose (15 mg iron per kg BW, either concurrent with or three days after doxorubicin. IDA (after dietary iron restriction induced cardiac and renal oxidative stress (markers included malondialdehyde, catalase, Cu,Zn-superoxide dismutase, and glutathione peroxidase, nitrosative stress (inducible nitric oxide synthase and nitrotyrosine, inflammation (tumour necrosis factor-alpha and interleukin-6, and functional/morphological abnormalities (left ventricle end-diastolic and end-systolic diameter, fractional shortening, density of cardiomyocytes and capillaries, caveolin-1 expression, creatinine clearance, and urine neutrophil gelatinase-associated lipocalin that were aggravated by doxorubicin. Notably, iron treatment with FCM did not exacerbate but attenuated the cardiorenal effects of IDA and doxorubicin independent of the iron dosing regimen. The results of this model suggest that intravenous FCM can be used concomitantly with an anthracycline-based chemotherapy without increasing signs of AIC.

  14. 对比剂肾病诊断进展%Progress of Diagnosis of Contrast-induced Nephropathy

    Institute of Scientific and Technical Information of China (English)

    周炳凤

    2011-01-01

    The contrast - induced nephropathy( CIN )is a common reason to obtain acute renal injury,of-ten leading to short and long term renal injury, the key solution is in time diagnosis. The current clinical ap-plication of diagnosis of renal insufficiency methods such as serum creatinine, creatinine clearance rate in CIN early diagnosis has obvious limitations. Therefore, looking for early diagnosis of CIN becomes the focus of clinical research. Research shows that cystatin C, neutrophil gelatinase associated lipocalin, liver type fatty acid binding protein in CIN play an important role in the diagnosis.%对比剂肾病(CIN)是医院内获得性急性肾功能不全的常见原因,常导致短期和长期肾功能损害,而及时诊断是有效处理CIN的关键.目前临床上应用诊断肾功能不全的方法(血肌酐水平、肌酐清除率等)在CIN的早期诊断中具有明显的局限性.因此,寻找早期诊断CIN的方法成为临床研究重点.研究表明胱抑素C、中性粒细胞明胶酶相关载脂蛋白、肝脏型脂肪酸结合蛋白等在CIN的诊断中具有重要作用.

  15. Biomarkers in bile-complementing advanced endoscopicimaging in the diagnosis of indeterminate biliary strictures

    Institute of Scientific and Technical Information of China (English)

    Vennisvasanth Lourdusamy; Benjamin Tharian; Udayakumar Navaneethan

    2015-01-01

    Biliary strictures present a diagnostic challenge and aconundrum, particularly when an initial work up includingabdominal imaging and endoscopic retrogradecholangiopancreatography based sampling are nondiagnostic.Advances in endoscopic imaging have helpedus diagnose these strictures better. However, even withmodern technology, some strictures remain a diagnosticchallenge. The proximity of bile fluid to the bile ductepithelia makes it an attractive option to investigatefor bio-markers, which might be representative of thefunctions/abnormal changes taking place in the biliarysystem. A number of biomarkers in bile have beendiscovered recently in approaching biliary strictureswith their potential future diagnostic utility, furthersupported by the immunohistochemical analysis of theresected tissue specimens. Novel biliary biomarkersespecially carcinoembryonic cell adhesion molecule 6and neutrophil gelatinase-associated lipocalin seempromising in differentiating malignant from benign biliarystrictures. Recent developments in lipidomic profiling ofbile are also very promising. Biliary biomarkers appearto complement endoscopic imaging in diagnosingmalignant etiologies of biliary stricture. Future studiesaddressing these biomarkers need to be incorporatedto the current endoscopic techniques to determine thebest approach in determining the etiology of biliarystrictures.

  16. The potential use of biomarkers in predicting contrast-induced acute kidney injury

    Science.gov (United States)

    Andreucci, Michele; Faga, Teresa; Riccio, Eleonora; Sabbatini, Massimo; Pisani, Antonio; Michael, Ashour

    2016-01-01

    Contrast-induced acute kidney injury (CI-AKI) is a problem associated with the use of iodinated contrast media, causing kidney dysfunction in patients with preexisting renal failure. It accounts for 12% of all hospital-acquired kidney failure and increases the length of hospitalization, a situation that is worsening with increasing numbers of patients with comorbidities, including those requiring cardiovascular interventional procedures. So far, its diagnosis has relied upon the rise in creatinine levels, which is a late marker of kidney damage and is believed to be inadequate. Therefore, there is an urgent need for biomarkers that can detect CI-AKI sooner and more reliably. In recent years, many new biomarkers have been characterized for AKI, and these are discussed particularly with their use in known CI-AKI models and studies and include neutrophil gelatinase-associated lipocalin, cystatin C (Cys-C), kidney injury molecule-1, interleukin-18, N-acetyl-β-d-glucosaminidase, and L-type fatty acid-binding protein (L-FABP). The potential of miRNA and metabolomic technology is also mentioned. Early detection of CI-AKI may lead to early intervention and therefore improve patient outcome, and in future any one or a combination of several of these markers together with development in technology for their analysis may prove effective in this respect. PMID:27672338

  17. Acute kidney injury after using contrast during cardiac catheterization in children with heart disease.

    Science.gov (United States)

    Hwang, Young Ju; Hyun, Myung Chul; Choi, Bong Seok; Chun, So Young; Cho, Min Hyun

    2014-08-01

    Acute kidney injury (AKI) is closely associated with the mortality of hospitalized patients and long-term development of chronic kidney disease, especially in children. The purpose of our study was to assess the evidence of contrast-induced AKI after cardiac catheterization in children with heart disease and evaluate the clinical usefulness of candidate biomarkers in AKI. A total of 26 children undergoing cardiac catheterization due to various heart diseases were selected and urine and blood samples were taken at 0 hr, 6 hr, 24 hr, and 48 hr after cardiac catheterization. Until 48 hr after cardiac catheterization, there was no significant increase in serum creatinine level in all patients. Unlike urine kidney injury molecule-1, IL-18 and neutrophil gelatinase-associated lipocalin, urine liver-type fatty acid-binding protein (L-FABP) level showed biphasic pattern and the significant difference in the levels of urine L-FABP between 24 and 48 hr. We suggest that urine L-FABP can be one of the useful biomarkers to detect subclinical AKI developed by the contrast before cardiac surgery.

  18. Serum Soluble Fms-Like Tyrosine Kinase 1 (sFlt-1) Predicts the Severity of Acute Pancreatitis

    Science.gov (United States)

    Dumnicka, Paulina; Sporek, Mateusz; Mazur-Laskowska, Małgorzata; Ceranowicz, Piotr; Kuźniewski, Marek; Drożdż, Ryszard; Ambroży, Tadeusz; Olszanecki, Rafał; Kuśnierz-Cabala, Beata

    2016-01-01

    Organ failure is the most important determinant of the severity of acute pancreatitis (AP). Soluble fms-like tyrosine kinase 1 (sFlt-1) is positively associated with organ failure in sepsis. Our aim was to evaluate the diagnostic utility of automated sFlt-1 measurements for early prediction of AP severity. Adult patients (66) with AP were recruited, including 46 with mild (MAP), 15 with moderately-severe (MSAP) and 5 with severe AP (SAP). Serum and urine samples were collected twice. Serum sFlt-1 was measured with automated electrochemiluminescence immunoassay. Serum concentrations of sFlt-1 were significantly higher in patients with MSAP and SAP as compared to MAP. SAP patients had the highest concentrations. At 24 and 48 h, sFlt-1 positively correlated with inflammatory markers (leukocyte count, C-reactive protein), kidney function (creatinine, urea, cystatin C, serum and urine neutrophil gelatinase-associated lipocalin, urine albumin/creatinine ratio), D-dimer and angiopoietin-2. sFlt-1 positively correlated with the bedside index of severity in AP (BISAP) score and the duration of hospital stay. Serum sFlt-1 above 139 pg/mL predicted more severe AP (MSAP + SAP). In the early phase of AP, sFlt-1 is positively associated with the severity of AP and predicts organ failure, in particular kidney failure. Serum sFlt-1 may be a practical way to improve early assessment of AP severity. PMID:27929426

  19. Mild systemic thermal therapy ameliorates renal dysfunction in a rodent model of chronic kidney disease.

    Science.gov (United States)

    Iwashita, Yoshihiro; Kuwabara, Takashige; Hayata, Manabu; Kakizoe, Yutaka; Izumi, Yuichiro; Iiyama, Junichi; Kitamura, Kenichiro; Mukoyama, Masashi

    2016-06-01

    Thermal therapy has become a nonpharmacological therapy in clinical settings, especially for cardiovascular diseases. However, the practical role of thermal therapy on chronic kidney disease remains elusive. We performed the present study to investigate whether a modified thermal protocol, repeated mild thermal stimulation (MTS), could affect renal damages in chronic kidney disease using a mouse renal ablation model. Mice were subjected to MTS or room temperature (RT) treatment once daily for 4 wk after subtotal nephrectomy (Nx) or sham operation (Sh). We revealed that MTS alleviated renal impairment as indicated by serum creatinine and albuminuria in Nx groups. In addition, the Nx + MTS group showed attenuated tubular histological changes and reduced urinary neutrophil gelatinase-associated lipocalin excretion approximately by half compared with the Nx + RT group. Increased apoptotic signaling, such as TUNEL-positive cell count and cleavage of caspase 3, as well as enhanced oxidative stress were significantly reduced in the Nx + MTS group compared with the Nx + RT group. These changes were accompanied with the restoration of kidney Mn-SOD levels by MTS. Heat shock protein 27, a key molecular chaperone, was phosphorylated by MTS only in Nx kidneys rather than in Sh kidneys. MTS also tended to increase the phosphorylation of p38 MAPK and Akt in Nx kidneys, possibly associated with the activation of heat shock protein 27. Taken together, these results suggest that modified MTS can protect against renal injury in a rodent model of chronic kidney disease.

  20. Update on clinical and research application of fecal biomarkers for gastrointestinal diseases

    Science.gov (United States)

    Siddiqui, Imran; Majid, Hafsa; Abid, Shahab

    2017-01-01

    Gastrointestinal (GI) diseases comprise a large spectrum of clinical conditions ranging from indigestion to inflammatory bowel diseases (IBDs) and carcinomas. Endoscopy is the usual method employed to diagnose these condition. Another noninvasive way to assess and diagnose GI conditions are fecal biomarkers. Fecal biomarkers provide information regarding a specific disease process and are perhaps more acceptable to clinicians and patients alike because of their non-invasivity compared to endoscopy. Aim of this review was to evaluate the current status of the fecal biomarkers in clinical and research for in GI diseases. Multiple types of fecal biomarkers are discussed in this review including; markers to assess IBD, which are released as a results of an inflammatory insults to intestinal epithelia such as antimicrobial peptides (lactoferrin) or inflammation related proteins (calprotectin). While markers related to function of digestion are primarily related to partially digested food or mucosal proteins such as abnormal amount of fecal fat α1-antitrypsin, elastase and secretary IgA. The upcoming fecal biomarker like M2 pyruvate kinase and neutrophil gelatinase associated lipocalin are discussed as well. Apart from above mention, the fecal biomarkers under exploration for possible clinical use in future are also discussed. These include cathelicidins, osteoprotegerin, β-glucuronidase, Eosinophil proteins, etc. PMID:28217373

  1. The Effects of Vitamin D on Gentamicin-Induced Acute Kidney Injury in Experimental Rat Model

    Directory of Open Access Journals (Sweden)

    Ender Hur

    2013-01-01

    Full Text Available Introduction. Acute kidney injury (AKI pathogenesis is complex. Findings of gentamicin nephrotoxicity are seen in 30% of the AKI patients. Vitamin D has proven to be effective on renin expression, inflammatory response, oxidative stress, apoptosis, and atherosclerosis. We aimed to investigate the effect of vitamin D in an experimental rat model of gentamicin-induced AKI. Methods. Thirty nonuremic Wistar albino rats were divided into 3 groups: Control group, 1 mL saline intramuscular (im daily; Genta group, gentamicin 100 mg/kg/day (im; Genta + vitamin D, gentamicin 100 mg/kg/day (im in addition to 1α, 25 (OH2D3 0.4 mcg/kg/day subcutaneously for 8 days. Blood pressures and 24-hour urine were measured. Blood urea and creatinine levels and urine tubular injury markers were measured. Renal histology was semiquantitatively assessed. Results. Urea, creatinine and urine neutrophil gelatinase-associated lipocalin, and kidney injury molecule-1 were all increased in Genta group indicating AKI model. Systolic blood pressure decreased, but urine volume and glutathione increased in Genta + Vit D group compared to Control group. Histological scores indicating tubular injury increased in Genta and Genta + Vit D groups. Conclusions. Vitamin D does not seem to be effective on histological findings although it has some beneficial effects via RAS system and a promising effect on antioxidant system.

  2. Application of quantitative proteomic analysis using tandem mass tags for discovery and identification of novel biomarkers in periodontal disease.

    Science.gov (United States)

    Tsuchida, Sachio; Satoh, Mamoru; Kawashima, Yusuke; Sogawa, Kazuyuki; Kado, Sayaka; Sawai, Setsu; Nishimura, Motoi; Ogita, Mayumi; Takeuchi, Yasuo; Kobyashi, Hiroaki; Aoki, Akira; Kodera, Yoshio; Matsushita, Kazuyuki; Izumi, Yuichi; Nomura, Fumio

    2013-08-01

    Periodontal disease is a bacterial infection that destroys the gingiva and surrounding tissues of the oral cavity. Gingival crevicular fluid (GCF) is extracted from the gingival sulcus and pocket. Analysis of biochemical markers in GCF, which predict the progression of periodontal disease, may facilitate disease diagnosis. However, no useful GCF biochemical markers with high sensitivity for detecting periodontal disease have been identified. Thus, the search for biochemical markers of periodontal disease is of continued interest in experimental and clinical periodontal disease research. Using tandem mass tag (TMT) labeling, we analyzed GCF samples from healthy subjects and patients with periodontal disease, and identified a total of 619 GCF proteins based on proteomic analysis. Of these, we focused on two proteins, matrix metalloproteinase (MMP)-9 and neutrophil gelatinase-associated lipocalin (LCN2), which are involved in the progression of periodontal disease. Western blot analysis revealed that the levels of MMP-9 and LCN2 were significantly higher in patients with periodontal disease than in healthy subjects. In addition, ELISA also detected significantly higher levels of LCN2 in patients with periodontal disease than in healthy subjects. Thus, LC-MS/MS analyses of GCF using TMT labeling led to the identification of LCN2, which may be a promising GCF biomarker for the detection of periodontal disease.

  3. Biomarkers of Renal Disease and Progression in Patients with Diabetes

    Directory of Open Access Journals (Sweden)

    Radovan Hojs

    2015-05-01

    Full Text Available Diabetes prevalence is increasing worldwide, mainly due to the increase in type 2 diabetes. Diabetic nephropathy occurs in up to 40% of people with type 1 or type 2 diabetes. It is important to identify patients at risk of diabetic nephropathy and those who will progress to end stage renal disease. In clinical practice, most commonly used markers of renal disease and progression are serum creatinine, estimated glomerular filtration rate and proteinuria or albuminuria. Unfortunately, they are all insensitive. This review summarizes the evidence regarding the prognostic value and benefits of targeting some novel risk markers for development of diabetic nephropathy and its progression. It is focused mainly on tubular biomarkers (neutrophil-gelatinase associated lipocalin, kidney injury molecule 1, liver-fatty acid-binding protein, N-acetyl-beta-d-glucosaminidase, markers of inflammation (pro-inflammatory cytokines, tumour necrosis factor-α and tumour necrosis factor-α receptors, adhesion molecules, chemokines and markers of oxidative stress. Despite the promise of some of these new biomarkers, further large, multicenter prospective studies are still needed before they can be used in everyday clinical practice.

  4. A Novel Biomarker Panel to Identify Steroid Resistance in Childhood Idiopathic Nephrotic Syndrome

    Directory of Open Access Journals (Sweden)

    Michael R Bennett

    2017-03-01

    Full Text Available Idiopathic nephrotic syndrome (NS is the most common glomerular disorder of childhood. Response to initial treatment with corticosteroids is an indicator of prognosis, as resistant patients often present more progressive disease. In this cross-sectional pilot study, we set out to discover a panel of noninvasive biomarkers that could distinguish steroid-resistant nephrotic syndrome (SRNS from steroid-sensitive nephrotic syndrome (SSNS. Information gleaned from such a panel could yield more individualized treatment plans and prevent unnecessary steroid exposure in patients unlikely to respond. Urine was collected from 50 pediatric patients diagnosed with idiopathic NS at Cincinnati Children’s Hospital Medical Center. Isobaric tags for relative and absolute quantitation (iTRAQ was used to discover 13 proteins that were differentially expressed in SSNS vs SRNS in a small 5 × 5 discovery cohort. Suitable assays were found for 9 of the 13 markers identified by iTRAQ and were used in a 25 SRNS × 25 SSNS validation cohort. Vitamin D–binding protein (VDBP, alpha-1 acid glycoprotein 1 (AGP1, alpha-1 acid glycoprotein 2 (AGP2, alpha-1-B glycoprotein (A1BG, fetuin-A, prealbumin, thyroxine-binding globulin and hemopexin, and alpha-2 macroglobulin were measured and combined with urine neutrophil gelatinase–associated lipocalin (NGAL, which had been previously shown to distinguish patients with SRNS. Urinary VDBP, prealbumin, NGAL, fetuin-A, and AGP2 were found to be significantly elevated in SRNS using univariate analysis, with area under the receiver operating characteristic curves (AUCs ranging from 0.65 to 0.81. Multivariate analysis revealed a panel of all 10 markers that yielded an AUC of 0.92 for identification of SRNS. A subset of 5 markers (including VDBP, NGAL, fetuin-A, prealbumin, and AGP2 showed significant associations with SRNS and yielded an AUC of 0.85.

  5. Lipocalin2 protects against airway inflammation and hyperresponsiveness in a murine model of allergic airway disease

    DEFF Research Database (Denmark)

    Dittrich, A M; Krokowski, M; Meyer, H-A;

    2010-01-01

    Allergen-induced bronchial asthma is a chronic airway disease that involves the interplay of various genes with environmental factors triggering different inflammatory pathways.......Allergen-induced bronchial asthma is a chronic airway disease that involves the interplay of various genes with environmental factors triggering different inflammatory pathways....

  6. Interplay between enterobactin, myeloperoxidase and lipocalin 2 regulates E. coli survival in the inflamed gut

    DEFF Research Database (Denmark)

    Singh, Vishal; Yeoh, Beng San; Xiao, Xia

    2015-01-01

    . Glycosylated Ent (salmochelin) and non-catecholate siderophores (yersiniabactin and ferrichrome) fail to inhibit MPO activity. An E. coli mutant (ΔfepA) that overproduces Ent, but not an Ent-deficient double mutant (ΔaroB/ΔfepA), inhibits MPO activity and exhibits enhanced survival in inflamed guts...

  7. The small fibrinopeptide Bβ15-42 as renoprotective agent preserving the endothelial and vascular integrity in early ischemia reperfusion injury in the mouse kidney.

    Directory of Open Access Journals (Sweden)

    Anja Urbschat

    Full Text Available Disruption of the renal endothelial integrity is pivotal for the development of a vascular leak, tissue edema and consequently acute kidney injury. Kidney ischemia amplifies endothelial activation and up-regulation of pro-inflammatory mechanisms. After restoring a sufficient blood flow, the kidney is damaged through complex pathomechanisms that are classically referred to as ischemia and reperfusion injury, where the disruption of the inter-endothelial connections seems to be a crucial step in this pathomechanism. Focusing on the molecular cell-cell interaction, the fibrinopeptide Bβ15-42 prevents vascular leakage by stabilizing these inter-endothelial junctions. The peptide associates with vascular endothelial-cadherin, thus preventing early kidney dysfunction by preserving blood perfusion efficacy, edema formation and thus organ dysfunction. We intended to demonstrate the early therapeutic benefit of intravenously administered Bβ15-42 in a mouse model of renal ischemia and reperfusion. After 30 minutes of ischemia, the fibrinopeptide Bβ15-42 was administered intravenously before reperfusion was commenced for 1 and 3 hours. We show that Bβ15-42 alleviates early functional and morphological kidney damage as soon as 1 h and 3 h after ischemia and reperfusion. Mice treated with Bβ15-42 displayed a significantly reduced loss of VE-cadherin, indicating a conserved endothelial barrier leading to less neutrophil infiltration which in turn resulted in significantly reduced structural renal damage. The significant reduction in tissue and serum neutrophil gelatinase-associated lipocalin levels reinforced our findings. Moreover, renal perfusion analysis by color duplex sonography revealed that Bβ15-42 treatment preserved resistive indices and even improved blood velocity. Our data demonstrate the efficacy of early therapeutic intervention using the fibrinopeptide Bβ15-42 in the treatment of acute kidney injury resulting from ischemia and

  8. Acute kidney injury and inflammatory response of sepsis following cecal ligation and puncture in d-galactose-induced aging rats.

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    Liu, Chao; Hu, Jie; Mao, Zhi; Kang, Hongjun; Liu, Hui; Fu, Wanlei; Lv, Yangfan; Zhou, Feihu

    2017-01-01

    Recently, the d-galactose (d-gal)-induced mimetic aging rat model has been widely used in studies of age-associated diseases, which have shown that chronic d-gal exposure induces premature aging similar to natural aging in rats. With the increasing rate of sepsis in the geriatric population, an easy-access animal model for preclinical studies of elderly sepsis is urgently needed. This study investigates whether a sepsis model that is established in d-gal-induced aging rats can serve as a suitable model for preclinical studies of elderly patients with sepsis. To investigate the acute kidney injury (AKI) and inflammatory response of sepsis following cecal ligation and puncture (CLP) in d-gal-induced aging rats. Twelve-week-old male Sprague Dawley rats were divided into low-dose d-gal (L d-gal, 125 mg/kg/d), high-dose d-gal (H d-gal, 500 mg/kg/d), and control groups. After daily subcutaneous injection of d-gal for 6 weeks, the CLP method was used to establish a sepsis model. The mortality was 73.3%, 40%, and 33.3% in the H d-gal, L d-gal, and control groups, respectively. Blood urea nitrogen, creatinine, plasma neutrophil gelatinase-associated lipocalin, interleukin-6, interleukin-10, and tumor necrosis factor-α were markedly increased in the H d-gal group after establishment of the sepsis model (H d-gal vs control, Paging rats are more likely to die from sepsis than are young rats, and probably this is associated with increased severity of septic AKI and an increased inflammatory response. Therefore, use of the high-dose- d-gal-induced aging rat model of sepsis for preclinical studies can provide more useful information for the treatment of sepsis in elderly patients.

  9. Association of Kidney Tissue Barrier Disrupture and Renal Dysfunction in Resuscitated Murine Septic Shock.

    Science.gov (United States)

    Stenzel, Tatjana; Weidgang, Clair; Wagner, Katja; Wagner, Florian; Gröger, Michael; Weber, Sandra; Stahl, Bettina; Wachter, Ulrich; Vogt, Josef; Calzia, Enrico; Denk, Stephanie; Georgieff, Michael; Huber-Lang, Markus; Radermacher, Peter; McCook, Oscar

    2016-10-01

    Septic shock-related kidney failure is characterized by almost normal morphological appearance upon pathological examination. Endothelial barrier disrupture has been suggested to be of crucial importance for septic shock-induced organ dysfunction. Therefore, in murine resuscitated cecal ligation and puncture (CLP)-induced septic shock, we tested the hypothesis whether there is a direct relationship between the kidney endothelial barrier injury and renal dysfunction. Anesthetized mice underwent CLP, and 15 h later, were anesthetized again and surgically instrumented for a 5-h period of intensive care comprising lung-protective mechanical ventilation, fluid resuscitation, continuous i.v. norepinephrine to maintain target hemodynamics, and measurement of creatinine clearance (CrCl). Animals were stratified according to low or high CrCl. Nitrotyrosine formation, expression of the inducible isoform of the nitric oxide synthase, and blood cytokine (tumor necrosis factor, interleukin-6, interleukin-10) and chemokine (monocyte chemoattractant protein-1, keratinocyte-derived chemokine) levels were significantly higher in animals with low CrCl. When plotted against CrCl and neutrophil gelatinase-associated lipocalin levels, extravascular albumin accumulation, and tissue expression of the vascular endothelial growth factor and angiopoietin-1 showed significant mathematical relationships related to kidney (dys)function. Preservation of the constitutive expression of the hydrogen sulfide producing enzyme cystathione-γ-lyase was associated with maintenance of organ function. The direct quantitative relation between microvascular leakage and kidney (dys)function may provide a missing link between near-normal tissue morphology and septic shock-related renal failure, thus further highlighting the important role of vascular integrity in septic shock-related renal failure.

  10. Disrupted Renal Mitochondrial Homeostasis after Liver Transplantation in Rats.

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    Qinlong Liu

    Full Text Available Suppressed mitochondrial biogenesis (MB contributes to acute kidney injury (AKI after many insults. AKI occurs frequently after liver transplantation (LT and increases mortality. This study investigated whether disrupted mitochondrial homeostasis plays a role in AKI after LT.Livers were explanted from Lewis rats and implanted after 18 h cold storage. Kidney and blood were collected 18 h after LT.In the kidney, oxidative phosphorylation (OXPHOS proteins ATP synthase-β and NADH dehydrogenase-3 decreased 44% and 81%, respectively, with marked reduction in associated mRNAs. Renal PGC-1α, the major regulator of MB, decreased 57% with lower mRNA and increased acetylation, indicating inhibited synthesis and suppressed activation. Mitochondrial transcription factor-A, which controls mtDNA replication and transcription, protein and mRNA decreased 66% and 68%, respectively, which was associated with 64% decreases in mtDNA. Mitochondrial fission proteins Drp-1 and Fis-1 and mitochondrial fusion protein mitofusin-1 all decreased markedly. In contrast, PTEN-induced putative kinase 1 and microtubule-associated protein 1A/1B-light chain 3 increased markedly after LT, indicating enhanced mitophagy. Concurrently, 18- and 13-fold increases in neutrophil gelatinase-associated lipocalin and cleaved caspase-3 occurred in renal tissue. Both serum creatinine and blood urea nitrogen increased >2 fold. Mild to moderate histological changes were observed in the kidney, including loss of brush border, vacuolization of tubular cells in the cortex, cast formation and necrosis in some proximal tubular cells. Finally, myeloperoxidase and ED-1 also increased, indicating inflammation.Suppression of MB, inhibition of mitochondrial fission/fusion and enhancement of mitophagy occur in the kidneys of recipients of liver grafts after long cold storage, which may contribute to the occurrence of AKI and increased mortality after LT.

  11. Correlation study of podocyte injur y and kidney function in patients with acute kidney injur y

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    You-Gang Feng

    2016-11-01

    Full Text Available Objective: To investigate the correlation between the podocyte injury indexes in urine such as nephrin, desmin, P-cadherin, podocin, podocalyxin and CD2-associated protein (CD2AP and the kidney function in patients with acute kidney injury (AKI. Methods: A total of 120 severe postsurgical patients treated in the Intensive Care Unit of our hospital from May 2012 to October 2015 were selected and divided into AKI group (n = 38 and non-AKI group (n = 82 according to the diagnostic criteria of AKI. After admission to the Intensive Care Unit for 24 h, their blood samples were collected to detect the contents of serum creatinine (Scr, serum urea (SUrea, b2-microglobulin (b2-MG and cystatin C (Cys-C, and urine samples were collected to detect the contents of kidney injury molecule-1 (KIM-1, liver-type fatty acid binding protein (L-FABP, Netrin-1, nephrin, desmin, P-cadherin, podocin, podocalyxin and CD2AP. Results: For patients in AKI group, the contents of Scr, SUrea, b2-MG and Cys-C in their blood samples and the contents of KIM-1, L-FABP, Netrin-1, nephrin, desmin, Pcadherin, podocin, podocalyxin and CD2AP in their urine samples were both significantly higher than those in non-AKI group. The contents of nephrin, desmin, P-cadherin, podocin, podocalyxin and CD2AP in urine samples and contents of Scr, SUrea, b2-MG, Cys-C and neutrophil gelatinase associated lipocalin in blood samples were positively correlated with the contents of KIM-1, L-FABP, and Netrin-1 in urine. Conclusions: Contents of podocyte injury molecules in urine of patients with acute kidney injury such as nephrin, desmin, P-cadherin, podocin, podocalyxin and CD2AP raised remarkably and the changes were consistent with the changes of kidney function indexes in the blood and urine samples.

  12. Acute hepatic ischemic-reperfusion injury induces a renal cortical "stress response," renal "cytoresistance," and an endotoxin hyperresponsive state.

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    Zager, Richard A; Johnson, Ali C M; Frostad, Kirsten B

    2014-10-01

    Hepatic ischemic-reperfusion injury (HIRI) is considered a risk factor for clinical acute kidney injury (AKI). However, HIRI's impact on renal tubular cell homeostasis and subsequent injury responses remain ill-defined. To explore this issue, 30-45 min of partial HIRI was induced in CD-1 mice. Sham-operated or normal mice served as controls. Renal changes and superimposed injury responses (glycerol-induced AKI; endotoxemia) were assessed 2-18 h later. HIRI induced mild azotemia (blood urea nitrogen ∼45 mg/dl) in the absence of renal histologic injury or proteinuria, implying a "prerenal" state. However, marked renal cortical, and isolated proximal tubule, cytoprotective "stress protein" gene induction (neutrophil gelatinase-associated lipocalin, heme oxygenase-1, hemopexin, hepcidin), and increased Toll-like receptor 4 (TLR4) expression resulted (protein/mRNA levels). Ischemia caused release of hepatic heme-based proteins (e.g., cytochrome c) into the circulation. This corresponded with renal cortical oxidant stress (malondialdehyde increases). That hepatic derived factors can evoke redox-sensitive "stress protein" induction was implied by the following: peritoneal dialysate from HIRI mice, soluble hepatic extract, or exogenous cytochrome c each induced the above stress protein(s) either in vivo or in cultured tubule cells. Functional significance of HIRI-induced renal "preconditioning" was indicated by the following: 1) HIRI conferred virtually complete morphologic protection against glycerol-induced AKI (in the absence of hyperbilirubinemia) and 2) HIRI-induced TLR4 upregulation led to a renal endotoxin hyperresponsive state (excess TNF-α/MCP-1 gene induction). In conclusion, HIRI can evoke "renal preconditioning," likely due, in part, to hepatic release of pro-oxidant factors (e.g., cytochrome c) into the systemic circulation. The resulting renal changes can impact subsequent AKI susceptibility and TLR4 pathway-mediated stress.

  13. The potential use of biomarkers in predicting contrast-induced acute kidney injury

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    Andreucci M

    2016-09-01

    Full Text Available Michele Andreucci,1 Teresa Faga,1 Eleonora Riccio,2 Massimo Sabbatini,2 Antonio Pisani,2 Ashour Michael,1 1Department of Health Sciences, University “Magna Graecia” of Catanzaro, Catanzaro, 2Department of Public Health, University of Naples Federico II, Naples, Italy Abstract: Contrast-induced acute kidney injury (CI-AKI is a problem associated with the use of iodinated contrast media, causing kidney dysfunction in patients with preexisting renal failure. It accounts for 12% of all hospital-acquired kidney failure and increases the length of hospitalization, a situation that is worsening with increasing numbers of patients with comorbidities, including those requiring cardiovascular interventional procedures. So far, its diagnosis has relied upon the rise in creatinine levels, which is a late marker of kidney damage and is believed to be inadequate. Therefore, there is an urgent need for biomarkers that can detect CI-AKI sooner and more reliably. In recent years, many new biomarkers have been characterized for AKI, and these are discussed particularly with their use in known CI-AKI models and studies and include neutrophil gelatinase-associated lipocalin, cystatin C (Cys-C, kidney injury molecule-1, interleukin-18, N-acetyl-β-d-glucosaminidase, and L-type fatty acid-binding protein (L-FABP. The potential of miRNA and metabolomic technology is also mentioned. Early detection of CI-AKI may lead to early intervention and therefore improve patient outcome, and in future any one or a combination of several of these markers together with development in technology for their analysis may prove effective in this respect. Keywords: radiocontrast media, acute renal failure, markers, renal injury

  14. Remote ischemic preconditioning in cyanosed neonates undergoing cardiopulmonary bypass: a randomized controlled trial.

    Science.gov (United States)

    Jones, Bryn O; Pepe, Salvatore; Sheeran, Freya L; Donath, Susan; Hardy, Pollyanna; Shekerdemian, Lara; Penny, Daniel J; McKenzie, Ian; Horton, Stephen; Brizard, Christian P; d'Udekem, Yves; Konstantinov, Igor E; Cheung, Michael M H

    2013-12-01

    The myocardial protective effect of remote ischemic preconditioning has been demonstrated in heterogeneous groups of patients undergoing cardiac surgery. No studies have examined this technique in neonates. The present study was performed to examine the remote ischemic preconditioning efficacy in this high-risk patient group. A preliminary, randomized, controlled trial was conducted to investigate whether remote ischemic preconditioning in cyanosed neonates undergoing cardiac surgery confers protection against cardiopulmonary bypass. Two groups of neonates undergoing cardiac surgery were recruited for the present study: patients with transposition of the great arteries undergoing the arterial switch procedure and patients with hypoplastic left heart syndrome undergoing the Norwood procedure. The subjects were randomized to the remote ischemic preconditioning or sham control groups. Remote ischemic preconditioning was induced by four 5-minute cycles of lower limb ischemia and reperfusion using a blood pressure cuff. Troponin I and the biomarkers for renal and cerebral injury were measured pre- and postoperatively. A total of 39 neonates were recruited-20 with transposition of the great arteries and 19 with hypoplastic left heart syndrome. Of the 39 neonates, 20 were randomized to remote ischemic preconditioning and 19 to the sham control group. The baseline demographics appeared similar between the randomized groups. The cardiopulmonary bypass and crossclamp times were not significantly different between the 2 groups. The troponin I levels were not significantly different at 6 hours after cardiopulmonary bypass nor were the postoperative inotrope requirements. Markers of renal (neutrophil gelatinase-associated lipocalin) and cerebral injury (S100b, neuron-specific enolase) were not significantly different between the 2 groups. Our data suggest that remote ischemic preconditioning in hypoxic neonates undergoing cardiopulmonary bypass surgery does not provide

  15. Effect of remote ischemic preconditioning on renal dysfunction after complex valvular heart surgery: a randomized controlled trial.

    Science.gov (United States)

    Choi, Yong Seon; Shim, Jae Kwang; Kim, Jong Chan; Kang, Kyu-Sik; Seo, Yong Han; Ahn, Ki-Ryang; Kwak, Young Lan

    2011-07-01

    Acute kidney injury after cardiac surgery with cardiopulmonary bypass is closely related to systemic inflammatory reactions and oxidative stresses. Remote ischemic preconditioning is a systemic protective strategy whereby brief limb ischemia confers systemic protection against prolonged ischemia and inflammatory reactions in distant organs. This study investigated whether remote ischemic preconditioning provides systemic protective effect on kidneys that are not directly exposed to ischemia-reperfusion injury during complex valvular heart surgery. Seventy-six adult patients undergoing complex valvular heart surgery were randomly assigned to either remote ischemic preconditioning group (n = 38) or control group (n = 38). Remote ischemic preconditioning consisted of 3 10-minute cycles of lower limb ischemia and reperfusion with an automated cuff inflator. Primary end points were comparisons of biomarkers of renal injury including serum creatinine, cystatin C and neutrophil gelatinase-associated lipocalin, and incidence of acute kidney injury. Secondary end points were comparisons of myocardial enzyme release and pulmonary parameters. There were no significant differences in serum levels of biomarkers of renal injury between groups throughout the study period. The incidence of acute kidney injury did not differ between groups. Creatine kinase isoenzyme MB at 24 hours after surgery was lower, and intensive care unit stay was shorter in the remote ischemic preconditioning group than in the control group. In patients undergoing complex valvular heart surgery, remote ischemic preconditioning did not reduce degree of renal injury or incidence of acute kidney injury whereas it did reduce myocardial injury and intensive care unit stay. Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

  16. Serum metalloproteinases 2 and 9 as predictors of gait status, pressure ulcer and mortality after hip fracture.

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    David N Gumieiro

    Full Text Available INTRODUCTION: The aim of this study is to evaluate the serum activity of metalloproteinases (MMPs -2 and -9 as predictors of pressure ulcer (PU, gait status and mortality 6 months after hip fracture. METHODS: Eighty-seven patients over the age of 65 admitted to the orthopedic unit from January to December 2010 with hip fracture were prospectively evaluated. Upon admission, patient demographic information, including age, gender and concomitant diseases, was recorded. Blood samples were taken for analysis of MMP -2 and -9 activity by gel zymography and for biochemical examination within the first 72 hours of the patient's admission, after clinical stabilization. The fracture pattern (neck, trochanteric or subtrochanteric, time from admission to surgery, surgery duration and length of hospital stay were also recorded. RESULTS: Two patients were excluded due to the presence of pathological fractures (related to cancer, and three patients were excluded due to the presence of PU before admission. Eighty-two patients, with a mean age of 80.4 ± 7.3 years, were included in the analysis. Among these patients, 75.6% were female, 59.8% had PU, and 13.4% died 6 months after hip fracture. All patients underwent hip fracture repair. In a univariate analysis, there were no differences in serum MMP activity between hip fracture patients with or without PU. In addition, the multiple logistic regression analysis models, which were adjusted by age, gender, length of hospital stay and C-reactive protein, showed that the pro-MMP-9 complexed with neutrophil gelatinase-associated lipocalin form (130 kDa was associated with gait status recovery 6 months after hip fracture. CONCLUSIONS: In conclusion, serum pro-MMP-9 is a predictor of gait status recovery 6 months after hip fracture.

  17. Preventing autoimmunity protects against the development of hypertension and renal injury.

    Science.gov (United States)

    Mathis, Keisa W; Wallace, Kedra; Flynn, Elizabeth R; Maric-Bilkan, Christine; LaMarca, Babbette; Ryan, Michael J

    2014-10-01

    Several studies suggest a link between autoimmunity and essential hypertension in humans. However, whether autoimmunity can drive the development of hypertension remains unclear. The autoimmune disease systemic lupus erythematosus is characterized by autoantibody production, and the prevalence of hypertension is increased markedly in this patient population compared with normal healthy women. We hypothesized that preventing the development of autoimmunity would prevent the development of hypertension in a mouse model of lupus. Female lupus (NZBWF1) and control mice (NZW) were treated weekly with anti-CD20 or immunoglobulin G antibodies (both 10 mg/kg, IV) starting at 20 weeks of age for 14 weeks. Anti-CD20 therapy markedly attenuated lupus disease progression as evidenced by reduced CD45R+ B cells and lower double-stranded DNA autoantibody activity. In addition, renal injury in the form of urinary albumin, glomerulosclerosis, and tubulointerstitial fibrosis, as well as tubular injury (indicated by renal cortical expression of neutrophil gelatinase-associated lipocalin) was prevented by anti-CD20 therapy in lupus mice. Finally, lupus mice treated with anti-CD20 antibody did not develop hypertension. The protection against the development of hypertension was associated with lower renal cortical tumor necrosis factor-α expression, a cytokine that has been previously reported by us to contribute to the hypertension in this model, as well as renal cortical monocyte chemoattractant protein-1 expression and circulating T cells. These data suggest that the development of autoimmunity and the resultant increase in renal inflammation are an important underlying factor in the prevalent hypertension that occurs during systemic lupus erythematosus.

  18. Delivery of interleukin-10 via injectable hydrogels improves renal outcomes and reduces systemic inflammation following ischemic acute kidney injury in mice.

    Science.gov (United States)

    Soranno, Danielle E; Rodell, Christopher B; Altmann, Christopher; Duplantis, Jane; Andres-Hernando, Ana; Burdick, Jason A; Faubel, Sarah

    2016-08-01

    Injectable hydrogels can be used to deliver drugs in situ over a sustained period of time. We hypothesized that sustained delivery of interleukin-10 (IL-10) following acute kidney injury (AKI) would mitigate the local and systemic proinflammatory cascade induced by AKI and reduce subsequent fibrosis. Wild-type C57BL/6 mice underwent ischemia-reperfusion AKI with avertin anesthesia. Three days later, mice were treated with either hyaluronic acid injectable hydrogel with or without IL-10, or IL-10 suspended in saline, injected under the capsule of the left kidney, or hydrogel with IL-10 injected subcutaneously. Untreated AKI served as controls. Serial in vivo optical imaging tracked the location and degradation of the hydrogel over time. Kidney function was assessed serially. Animals were killed 28 days following AKI and the following were evaluated: serum IL-6, lung inflammation, urine neutrophil gelatinase-associated lipocalin, and renal histology for fibroblast activity, collagen type III deposition and fibrosis via Picrosirius Red staining and second harmonic imaging. Our model shows persistent systemic inflammation, and renal inflammation and fibrosis 28 days following AKI. The hydrogels are biocompatible and reduced serum IL-6 and renal collagen type III 28 days following AKI even when delivered without IL-10. Treatment with IL-10 reduced renal and systemic inflammation, regardless of whether the IL-10 was delivered in a sustained manner via the injectable hydrogel under the left kidney capsule, as a bolus injection via saline under the left kidney capsule, or via the injectable hydrogel subcutaneously. Injectable hydrogels are suitable for local drug delivery following renal injury, are biocompatible, and help mitigate local and systemic inflammation. Copyright © 2016 the American Physiological Society.

  19. Differential expression of cancer associated proteins in breast milk based on age at first full term pregnancy

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    Qin Wenyi

    2012-03-01

    Full Text Available Abstract Background First full term pregnancy (FFTP completed at a young age has been linked to low long term breast cancer risk, whereas late FFTP pregnancy age confers high long term risk, compared to nulliparity. Our hypothesis was that proteins linked to breast cancer would be differentially expressed in human milk collected at three time points during lactation based on age at FFTP. Methods We analyzed breast milk from 72 lactating women. Samples were collected within 10 days of the onset of lactation (baseline-BL, two months after lactation started and during breast weaning (W. We measured 16 proteins (11 kallikreins (KLKs, basic fibroblast growth factor, YKL-40, neutrophil gelatinase-associated lipocalin and transforming growth factor (TGF β-1 and -2 associated with breast cancer, most known to be secreted into milk. Results During lactation there was a significant change in the expression of 14 proteins in women = 26 at FFTP. The most significant (p = 26 were in KLK3,6, 8, and TGFβ2 in women = 26. There was a significant increase (p = .022 in KLK8 expression from BL to W depending on FFTP age. Examination of DNA methylation in the promoter region of KLK6 revealed high levels of methylation that did not explain the observed changes in protein levels. On the other hand, KLK6 and TGFβ1 expression were significantly associated (r2 = .43, p = .0050. Conclusions The expression profile of milk proteins linked to breast cancer is influenced by age at FFTP. These proteins may play a role in future cancer risk.

  20. Acute kidney injury in patients undergoing cardiac surgery.

    Science.gov (United States)

    Coppolino, Giuseppe; Presta, Piera; Saturno, Laura; Fuiano, Giorgio

    2013-01-01

    The incidence of postoperative acute kidney injury (AKI) in patients undergoing cardiac surgery ranges from 7.7% to 28.1% in different studies, probably in relation to the criteria adopted to define AKI. AKI markedly increases mortality risk. However, despite the development of less invasive techniques, cardiac surgery remains the first option in many conditions such as severe coronary artery disease, valve diseases and complex interventions. The risk of postsurgery AKI can be reduced by adopting less invasive approaches, such as off-pump coronary artery bypass grafting or transcatheter aortic valve implantation, but these options cannot be employed in all cases. Thus, since traditional cardiac surgery remains the only option in many cases, it is important to adopt strategies helping the clinician to prevent AKI or diagnose it early. Old age, preprocedural chronic kidney disease, obesity, some comorbidities, wide pulse pressure and some pharmacological regimens represent risk factors for postsurgery AKI and mortality. Important intraoperative factor are use and duration of cardiopulmonary bypass. Postoperative efforts should be aimed toward maximizing cardiac output, avoiding drugs vasoconstricting the renal artery, providing adequate crystalloid infusion and alkalinizing urine. Fluid management should not be based on the measurements for cardiac filling pressures, which are mostly unreliable in these patients. Novel biomarkers such as cystatin C, kidney injury molecule-1 and human neutrophil gelatinase-associated lipocalin have been found to change earlier than creatinine, particularly when measured in combination, so their use in clinical practice can facilitate early diagnosis and treatment of AKI. The occurrence of oliguria despite adequate cardiovascular therapy can be managed with furosemide, possibly using continuous infusion, or renal replacement therapy.

  1. Environmental exposure to arsenic and chromium in children is associated with kidney injury molecule-1.

    Science.gov (United States)

    Cárdenas-González, M; Osorio-Yáñez, C; Gaspar-Ramírez, O; Pavković, M; Ochoa-Martínez, A; López-Ventura, D; Medeiros, M; Barbier, O C; Pérez-Maldonado, I N; Sabbisetti, V S; Bonventre, J V; Vaidya, V S

    2016-10-01

    Environmental hazards from natural or anthropological sources are widespread, especially in the north-central region of Mexico. Children represent a susceptible population due to their unique routes of exposure and special vulnerabilities. In this study we evaluated the association of exposure to environmental kidney toxicants with kidney injury biomarkers in children living in San Luis Potosi (SLP), Mexico. A cross-sectional study was conducted with 83 children (5-12 years of age) residents of Villa de Reyes, SLP. Exposure to arsenic, cadmium, chromium, fluoride and lead was assessed in urine, blood and drinking water samples. Almost all tap and well water samples had levels of arsenic (81.5%) and fluoride (100%) above the permissible levels recommended by the World Health Organization. Mean urine arsenic (45.6ppb) and chromium (61.7ppb) were higher than the biological exposure index, a reference value in occupational settings. Using multivariate adjusted models, we found a dose-dependent association between kidney injury molecule-1 (KIM-1) across chromium exposure tertiles [(T1: reference, T2: 467pg/mL; T3: 615pg/mL) (p-trend=0.001)]. Chromium upper tertile was also associated with higher urinary miR-200c (500 copies/μl) and miR-423 (189 copies/μL). Arsenic upper tertile was also associated with higher urinary KIM-1 (372pg/mL). Other kidney injury/functional biomarkers such as serum creatinine, glomerular filtration rate, albuminuria, neutrophil gelatinase-associated lipocalin and miR-21 did not show any association with arsenic, chromium or any of the other toxicants evaluated. We conclude that KIM-1 might serve as a sensitive biomarker to screen children for kidney damage induced by environmental toxic agents.

  2. Clinical review

    DEFF Research Database (Denmark)

    Hjortrup, Peter Buhl; Haase, Nicolai; Wetterslev, Mik

    2013-01-01

    ROC) for NGAL to predict study outcomes. Eleven studies with a total of 2,875 (range of 20 to 632) participants were included: seven studies assessed urinary NGAL and six assessed plasma NGAL. The included studies varied in design, including observation period from NGAL sampling to AKI follow-up (range of 12...

  3. Design and Methods of the Pan-Canadian Applying Biomarkers to Minimize Long-Term Effects of Childhood/Adolescent Cancer Treatment (ABLE) Nephrotoxicity Study

    Science.gov (United States)

    McMahon, Kelly R.; Rod Rassekh, Shahrad; Schultz, Kirk R.; Pinsk, Maury; Blydt-Hansen, Tom; Mammen, Cherry; Tsuyuki, Ross T.; Devarajan, Prasad; Cuvelier, Geoff D. E.; Mitchell, Lesley G.; Baruchel, Sylvain; Palijan, Ana; Carleton, Bruce C.; Ross, Colin J. D.; Zappitelli, Michael

    2017-01-01

    Background: Childhood cancer survivors experience adverse drug events leading to lifelong health issues. The Applying Biomarkers to Minimize Long-Term Effects of Childhood/Adolescent Cancer Treatment (ABLE) team was established to validate and apply biomarkers of cancer treatment effects, with a goal of identifying children at high risk of developing cancer treatment complications associated with thrombosis, graft-versus-host disease, hearing loss, and kidney damage. Cisplatin is a chemotherapy well known to cause acute and chronic nephrotoxicity. Data on biomarkers of acute kidney injury (AKI) and late renal outcomes in children treated with cisplatin are limited. Objective: To describe the design and methods of the pan-Canadian ABLE Nephrotoxicity study, which aims to evaluate urine biomarkers (neutrophil gelatinase–associated lipocalin [NGAL] and kidney injury molecule-1 [KIM-1]) for AKI diagnosis, and determine whether they predict risk of long-term renal outcomes (chronic kidney disease [CKD], hypertension). Design: This is a 3-year observational prospective cohort study. Setting: The study includes 12 Canadian pediatric oncology centers. Patients: The target recruitment goal is 150 patients aged less than 18 years receiving cisplatin. Exclusion criteria: Patients with an estimated glomerular filtration rate (eGFR) renal transplantation at baseline. Measurements: Serum creatinine (SCr), urine NGAL, and KIM-1 are measured during cisplatin infusion episodes (pre-infusion, immediate post-infusion, discharge sampling). At follow-up visits, eGFR, microalbuminuria, and blood pressure are measured and outcomes are collected. Methods: Outcomes: AKI is defined as per SCr criteria of the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. CKD is defined as eGFR cancer treatment complications. The Nephrotoxicity study is a novel study of AKI biomarkers in children treated with cisplatin that will greatly inform on late cisplatin renal outcomes and follow

  4. 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 ...

  5. A Case Study: Review of an Indigenous Digital Resource as a Potential Medium for Dance Undergraduate Teaching and Learning: "Cassie's Story: Dyan Ngal" (Wiradjuri for "Fix Me")

    Science.gov (United States)

    Jefferson-Buchanan, Rachael

    2015-01-01

    The following article comprises a case study that considers the potential for an Indigenous digital resource to be used within a dance undergraduate context. In this manner, suggestions for dance pedagogy and practice are offered in relation to the Indigenous Education Strategy at Charles Sturt University, together with a university digital…

  6. Nasal Levels of Antimicrobial Peptides in Allergic Asthma Patients and Healthy Controls: Differences and Effect of a Short 1,25(OH2 Vitamin D3 Treatment.

    Directory of Open Access Journals (Sweden)

    Willemien Thijs

    Full Text Available Allergy is often accompanied by infections and lower levels of antimicrobial peptides (AMPs. Vitamin D has been shown to increase expression of selected AMPs. In this study we investigated whether antimicrobial peptide levels in nasal secretions of allergic asthma patients are lower than in healthy controls, and whether administration of the active form of vitamin D (1,25(OH2D3 affects these antimicrobial peptide levels.The levels of antimicrobial peptides in nasal secretions were compared between 19 allergic asthma patients and 23 healthy controls. The effect of seven days daily oral treatment with 2 μg 1,25(OH2D3 on antimicrobial peptides in nasal secretions was assessed in a placebo-controlled cross-over clinical study.Levels of neutrophil α-defensins (human neutrophil peptides 1-3; HNP1-3 and lipocalin 2 (LCN2; also known as NGAL were significantly lower in asthmatics, but no differences in LL-37 and SLPI were detected. Treatment with a short-term 1,25(OH2D3 caused a small increase in HNP1-3, but not when the asthma and control groups were analyzed separately. LL-37, LCN2 and SLPI did not change after treatment with 1,25(OH2D3.Levels of the antimicrobial peptides HNP1-3 and LCN2 are lower in nasal secretions in asthmatics and are not substantially affected by a short-term treatment with active vitamin D.

  7. Liver is the major source of elevated serum lipocalin-2 levels after bacterial infection or partial hepatectomy

    DEFF Research Database (Denmark)

    Xu, Ming-Jiang; Feng, Dechun; Wu, Hailong;

    2015-01-01

    knockout (Lcn2(Hep-/-)) mice were generated and subjected to bacterial infection (with Klesbsiella pneumoniae or Escherichia coli) or partial hepatectomy (PHx). Studies of Lcn2(Hep-/-) mice revealed that hepatocytes contributed to 25% of the low basal serum level of LCN2 protein (∼ 62 ng/mL) but were...... responsible for more than 90% of the highly elevated serum LCN2 protein level (∼ 6,000 ng/mL) postinfection and more than 60% post-PHx (∼ 700 ng/mL). Interestingly, both Lcn2(Hep-/-) and global Lcn2 knockout (Lcn2(-/-)) mice demonstrated comparable increases in susceptibility to infection with K. pneumoniae...

  8. Expression of the genes dual oxidase 2, lipocalin 2 and regenerating islet-derived 1 alpha in Crohn's disease

    DEFF Research Database (Denmark)

    Csillag, C.; Nielsen, O.H.; Vainer, Ben

    2007-01-01

    colonoscopically from 33 CD patients and from 17 control subjects. All controls and 10 CD patients were medication-free at the time of colonoscopy. The Human Genome U133 Plus 2.0 GeneChip Array was used for gene profiling. Hybridization data were analysed with dChip software. Results were confirmed by real......, fold change 3.9), codes for a mitogenic protein; this could not be confirmed by RT-PCR. Medication-free patients had no differentially expressed genes as compared with controls. Immunohistochemistry indicated that these proteins were produced by epithelial cells (REG1A, LCN2) and leucocytes (DUOX2...... and LCN2). CONCLUSIONS: As compared with controls, non-inflamed colonic mucosal cells contain two up-regulated genes related to the innate immune system. Up-regulation of these genes, known to be induced by microorganisms, suggests either increased microflora antigenicity or an altered function in mucosal...

  9. Association of Kidney Function and Early Kidney Injury With Incident Hypertension in HIV-Infected Women.

    Science.gov (United States)

    Ascher, Simon B; Scherzer, Rebecca; Peralta, Carmen A; Tien, Phyllis C; Grunfeld, Carl; Estrella, Michelle M; Abraham, Alison; Gustafson, Deborah R; Nowicki, Marek; Sharma, Anjali; Cohen, Mardge H; Butch, Anthony W; Young, Mary A; Bennett, Michael R; Shlipak, Michael G

    2017-02-01

    Subclinical kidney disease is associated with developing hypertension in the general population, but data are lacking among HIV-infected people. We examined associations of kidney function and injury with incident hypertension in 823 HIV-infected and 267 HIV-uninfected women in the Women's Interagency HIV Study, a multicenter, prospective cohort of HIV-infected and uninfected women in the United States. Baseline kidney biomarkers included estimated glomerular filtration rate using cystatin C, urine albumin-to-creatinine ratio, and 7 urine biomarkers of tubular injury: α-1-microglobulin, interleukin-18, kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, liver fatty acid-binding protein, N-acetyl-β-d-glucosaminidase, and α1-acid-glycoprotein. We used multivariable Poisson regression to evaluate associations of kidney biomarkers with incident hypertension, defined as 2 consecutive visits of antihypertensive medication use. During a median follow-up of 9.6 years, 288 HIV-infected women (35%) developed hypertension. Among the HIV-infected women, higher urine albumin-to-creatinine ratio was independently associated with incident hypertension (relative risk =1.13 per urine albumin-to-creatinine ratio doubling, 95% confidence interval, 1.07-1.20), as was lower estimated glomerular filtration rate (relative risk =1.10 per 10 mL/min/1.73 m(2) lower estimated glomerular filtration rate; 95% confidence interval, 1.04-1.17). No tubular injury and dysfunction biomarkers were independently associated with incident hypertension in HIV-infected women. In contrast, among the HIV-uninfected women, urine albumin-to-creatinine ratio was not associated with incident hypertension, whereas higher urine interleukin-18, α1-acid-glycoprotein, and N-acetyl-β-d-glucosaminidase levels were significantly associated with incident hypertension. These findings suggest that early glomerular injury and kidney dysfunction may be involved in the pathogenesis of hypertension in

  10. Clinical Factors Associated with Dose of Loop Diuretics After Pediatric Cardiac Surgery: Post Hoc Analysis.

    Science.gov (United States)

    Haiberger, Roberta; Favia, Isabella; Romagnoli, Stefano; Cogo, Paola; Ricci, Zaccaria

    2016-06-01

    A post hoc analysis of a randomized controlled trial comparing the clinical effects of furosemide and ethacrynic acid was conducted. Infants undergoing cardiac surgery with cardiopulmonary bypass were included in order to explore which clinical factors are associated with diuretic dose in infants with congenital heart disease. Overall, 67 patients with median (interquartile range) age of 48 (13-139) days were enrolled. Median diuretic dose was 0.34 (0.25-0.4) mg/kg/h at the end of postoperative day (POD) 0 and it significantly decreased (p = 0.04) over the following PODs; during this period, the ratio between urine output and diuretic dose increased significantly (p = 0.04). Age (r -0.26, p = 0.02), weight (r -0.28, p = 0.01), cross-clamp time (r 0.27, p = 0.03), administration of ethacrynic acid (OR 0.01, p = 0.03), and, at the end of POD0, creatinine levels (r 0.3, p = 0.009), renal near-infrared spectroscopy saturation (-0.44, p = 0.008), whole-blood neutrophil gelatinase-associated lipocalin levels (r 0.30, p = 0.01), pH (r -0.26, p = 0.02), urinary volume (r -0.2755, p = 0.03), and fluid balance (r 0.2577, p = 0.0266) showed a significant association with diuretic dose. At multivariable logistic regression cross-clamp time (OR 1.007, p = 0.04), use of ethacrynic acid (OR 0.2, p = 0.01) and blood pH at the end of POD0 (OR 0.0001, p = 0.03) was independently associated with diuretic dose. Early resistance to loop diuretics continuous infusion is evident in post-cardiac surgery infants: Higher doses are administered to patients with lower urinary output. Independently associated variables with diuretic dose in our population appeared to be cross-clamping time, the administration of ethacrynic acid, and blood pH.

  11. Identification of potential saliva and tear biomarkers in primary Sjögren's syndrome, utilising the extraction of extracellular vesicles and proteomics analysis.

    Science.gov (United States)

    Aqrawi, Lara A; Galtung, Hilde Kanli; Vestad, Beate; Øvstebø, Reidun; Thiede, Bernd; Rusthen, Shermin; Young, Alix; Guerreiro, Eduarda M; Utheim, Tor Paaske; Chen, Xiangjun; Utheim, Øygunn Aass; Palm, Øyvind; Jensen, Janicke Liaaen

    2017-01-25

    There is a long-lasting need for non-invasive, more accurate diagnostic techniques when evaluating primary Sjögren's syndrome (pSS) patients. Incorporation of additional diagnostics involving screening for disease-specific biomarkers in biological fluid is a promising concept that requires further investigation. In the current study we aimed to explore novel disease biomarkers in saliva and tears from pSS patients. Liquid chromatography-mass spectrometry (LC-MS) was performed on stimulated whole saliva and tears from 27 pSS patients and 32 healthy controls, and salivary and tear proteomic biomarker profiles were generated. LC-MS was also combined with size exclusion chromatography to isolate extracellular vesicles (EVs) from both fluids. Nanoparticle tracking analysis was conducted on joint fractions from the saliva and tears to determine size distribution and concentration of EVs. Further EV characterisation was performed by immunoaffinity capture of CD9-positive EVs using magnetic beads, detected by flow cytometry. The LC-MS data were analysed for quantitative differences between patient and control groups using Scaffold, and the proteins were further analysed using the Database for Annotation, Visualization and Integrated Discovery (DAVID), for gene ontology overrepresentation, and the Search Tool for the Retrieval of Interacting Genes/Proteins for protein-protein interaction network analysis. Upregulation of proteins involved in innate immunity (LCN2), cell signalling (CALM) and wound repair (GRN and CALML5) were detected in saliva in pSS. Saliva EVs also displayed biomarkers critical for activation of the innate immune system (SIRPA and LSP1) and adipocyte differentiation (APMAP). Tear analysis indicated overexpression of proteins involved in TNF-α signalling (CPNE1) and B cell survival (PRDX3). Moreover, neutrophil gelatinase-associated lipocalin was upregulated in saliva and tears in pSS. Consistently, DAVID analysis demonstrated pathways of the adaptive

  12. A software application for comparing large numbers of high resolution MALDI-FTICR MS spectra demonstrated by searching candidate biomarkers for glioma blood vessel formation

    Directory of Open Access Journals (Sweden)

    Smitt Peter

    2008-03-01

    Full Text Available Abstract Background A Java™ application is presented, which compares large numbers (n > 100 of raw FTICR mass spectra from patients and controls. Two peptide profile matrices can be produced simultaneously, one with occurrences of peptide masses in samples and another with the intensity of common peak masses in all the measured samples, using the peak- and background intensities of the raw data. In latter way, more significantly differentially expressed peptides are found between groups than just using the presence or absence in samples of common peak masses. The software application is tested by searching angiogenesis related proteins in glioma by comparing laser capture micro dissected- and enzymatic by trypsin digested tissue sections. Results By hierarchical clustering of the presence-absence matrix, it appears that proteins, such as hemoglobin alpha and delta subunit, fibrinogen beta and gamma chain precursor, tubulin specific chaperone A, epidermal fatty acid binding protein, neutrophil gelatinase-associated lipocalin precursor, peptidyl tRNA hydrolase 2 mitochondrial precursor, placenta specific growth hormone, and zinc finger CCHC domain containing protein 13 are significantly different expressed in glioma vessels. The up-regulated proteins in the glioma vessels with respect to the normal vessels determined by the Wilcoxon-Mann-Whitney test on the intensity matrix are vimentin, glial fibrillary acidic protein, serum albumin precursor, annexin A5, alpha cardiac and beta actin, type I cytoskeletal 10 keratin, calcium binding protein p22, and desmin. Peptide masses of calcium binding protein p22, Cdc42 effector protein 3, fibronectin precursor, and myosin-9 are exclusively present in glioma vessels. Some peptide fragments of non-muscular myosin-9 at the C-terminus are strongly up-regulated in the glioma vessels with respect to the normal vessels. Conclusion The less rigorous than in general used commercial propriety software de

  13. Green Tea Polyphenols Stimulate Mitochondrial Biogenesis and Improve Renal Function after Chronic Cyclosporin A Treatment in Rats

    Science.gov (United States)

    Rehman, Hasibur; Krishnasamy, Yasodha; Haque, Khujista; Lemasters, John J.; Schnellmann, Rick G.; Zhong, Zhi

    2013-01-01

    Our previous studies showed that an extract from Camellia sinenesis (green tea), which contains several polyphenols, attenuates nephrotoxicity caused by cyclosporine A (CsA). Since polyphenols are stimulators of mitochondrial biogenesis (MB), this study investigated whether stimulation of MB plays a role in green tea polyphenol protection against CsA renal toxicity. Rats were fed a powdered diet containing green tea polyphenolic extract (0.1%) starting 3 days prior to CsA treatment (25 mg/kg, i.g. daily for 3 weeks). CsA alone decreased renal nuclear DNA-encoded oxidative phosphorylation (OXPHOS) protein ATP synthase-β (AS-β) by 42%, mitochondrial DNA (mtDNA)-encoded OXPHOS protein NADH dehydrogenase-3 (ND3) by 87% and their associated mRNAs. Mitochondrial DNA copy number was also decreased by 78% by CsA. Immunohistochemical analysis showed decreased cytochrome c oxidase subunit IV (COX-IV), an OXPHOS protein, in tubular cells. Peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α, the master regulator of MB, and mitochondrial transcription factor-A (Tfam), the transcription factor that regulates mtDNA replication and transcription, were 42% and 90% lower, respectively, in the kidneys of CsA-treated than in untreated rats. These results indicate suppression of MB by chronic CsA treatment. Green tea polyphenols alone and following CsA increased AS-β, ND3, COX-IV, mtDNA copy number, PGC-1α mRNA and protein, decreased acetylated PGC-1α, and increased Tfam mRNA and protein. In association with suppressed MB, CsA increased serum creatinine, caused loss of brush border and dilatation of proximal tubules, tubular atrophy, vacuolization, apoptosis, calcification, and increased neutrophil gelatinase-associated lipocalin expression, leukocyte infiltration, and renal fibrosis. Green tea polyphenols markedly attenuated CsA-induced renal injury and improved renal function. Together, these results demonstrate that green tea polyphenols attenuate Cs

  14. 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

  15. Characterization of renal biomarkers for use in clinical trials: effect of preanalytical processing and qualification using samples from subjects with diabetes

    Directory of Open Access Journals (Sweden)

    Brott DA

    2015-06-01

    Full Text Available David A Brott,1 Stephen T Furlong,1 Scott H Adler,1 James W Hainer,2 Ramin B Arani,2 Mark Pinches,3 Peter Rossing,4–6 Nish Chaturvedi7 On behalf of the DIRECT Programme Steering Committee1Enabling Safety Sciences, 2AstraZeneca Pharmaceuticals, Wilmington, DE, USA; 3Drug Safety and Metabolism, AstraZeneca Pharmaceuticals, Alderley Park, UK; 4Steno Diabetes Center, Gentofte, Denmark; 5Aarhus University, Aarhus, Denmark, 6University of Copenhagen, Denmark; 7Institute of Cardiovascular Sciences, University College London, London, UK Background: Identifying the potential for drug-induced kidney injury is essential for the successful research and development of new drugs. Newer and more sensitive preclinical drug-induced kidney injury biomarkers are now qualified for use in rat toxicology studies, but biomarkers for clinical studies are still undergoing qualification. The current studies investigated biomarkers in healthy volunteer (HV urine samples with and without the addition of stabilizer as well as in urine from patients with normoalbuminuric diabetes mellitus (P-DM.Methods: Urine samples from 20 male HV with stabilizer, 69 male HV without stabilizer, and 95 male DM without stabilizer (39 type 1 and 56 type 2 were analyzed for the following biomarkers using multiplex assays: α-1-microglobulin (A1M, β-2-microglobulin, calbindin, clusterin, connective tissue growth factor (CTGF, creatinine, cystatin-C, glutathione s-transferase α (GSTα, kidney injury marker-1 (KIM-1, microalbumin, neutrophil gelatinase-associated lipocalin, osteopontin, Tamm–Horsfall urinary glycoprotein (THP, tissue inhibitor of metalloproteinase 1, trefoil factor 3 (TFF3, and vascular endothelial growth factor.Results: CTGF and GSTα assays on nonstabilized urine were deemed nonoptimal (>50% of values below assay lower limits of quantification. “Expected values” were determined for HV with stabilizer, HV without stabilizer, and P-DM without stabilizer. There was a

  16. Gut Microbiota Conversion of Dietary Ellagic Acid into Bioactive Phytoceutical Urolithin A Inhibits Heme Peroxidases.

    Directory of Open Access Journals (Sweden)

    Piu Saha

    Full Text Available Numerous studies signify that diets rich in phytochemicals offer many beneficial functions specifically during pathologic conditions, yet their effects are often not uniform due to inter-individual variation. The host indigenous gut microbiota and their modifications of dietary phytochemicals have emerged as factors that greatly influence the efficacy of phytoceutical-based intervention. Here, we investigated the biological activities of one such active microbial metabolite, Urolithin A (UA or 3,8-dihydroxybenzo[c]chromen-6-one, which is derived from the ellagic acid (EA. Our study demonstrates that UA potently inhibits heme peroxidases i.e. myeloperoxidase (MPO and lactoperoxidase (LPO when compared to the parent compound EA. In addition, chrome azurol S (CAS assay suggests that EA, but not UA, is capable of binding to Fe3+, due to its catechol-like structure, although its modest heme peroxidase inhibitory activity is abrogated upon Fe3+-binding. Interestingly, UA-mediated MPO and LPO inhibition can be prevented by innate immune protein human NGAL or its murine ortholog lipocalin 2 (Lcn2, implying the complex nature of host innate immunity-microbiota interactions. Spectral analysis indicates that UA inhibits heme peroxidase-catalyzed reaction by reverting the peroxidase back to its inactive native state. In support of these in vitro results, UA significantly reduced phorbol myristate acetate (PMA-induced superoxide generation in neutrophils, however, EA failed to block the superoxide generation. Treatment with UA significantly reduced PMA-induced mouse ear edema and MPO activity compared to EA treated mice. Collectively, our results demonstrate that microbiota-mediated conversion of EA to UA is advantageous to both host and microbiota i.e. UA-mediated inhibition of pro-oxidant enzymes reduce tissue inflammation, mitigate non-specific killing of gut bacteria, and abrogate iron-binding property of EA, thus providing a competitive edge to the

  17. Gut Microbiota Conversion of Dietary Ellagic Acid into Bioactive Phytoceutical Urolithin A Inhibits Heme Peroxidases.

    Science.gov (United States)

    Saha, Piu; Yeoh, Beng San; Singh, Rajbir; Chandrasekar, Bhargavi; Vemula, Praveen Kumar; Haribabu, Bodduluri; Vijay-Kumar, Matam; Jala, Venkatakrishna R

    2016-01-01

    Numerous studies signify that diets rich in phytochemicals offer many beneficial functions specifically during pathologic conditions, yet their effects are often not uniform due to inter-individual variation. The host indigenous gut microbiota and their modifications of dietary phytochemicals have emerged as factors that greatly influence the efficacy of phytoceutical-based intervention. Here, we investigated the biological activities of one such active microbial metabolite, Urolithin A (UA or 3,8-dihydroxybenzo[c]chromen-6-one), which is derived from the ellagic acid (EA). Our study demonstrates that UA potently inhibits heme peroxidases i.e. myeloperoxidase (MPO) and lactoperoxidase (LPO) when compared to the parent compound EA. In addition, chrome azurol S (CAS) assay suggests that EA, but not UA, is capable of binding to Fe3+, due to its catechol-like structure, although its modest heme peroxidase inhibitory activity is abrogated upon Fe3+-binding. Interestingly, UA-mediated MPO and LPO inhibition can be prevented by innate immune protein human NGAL or its murine ortholog lipocalin 2 (Lcn2), implying the complex nature of host innate immunity-microbiota interactions. Spectral analysis indicates that UA inhibits heme peroxidase-catalyzed reaction by reverting the peroxidase back to its inactive native state. In support of these in vitro results, UA significantly reduced phorbol myristate acetate (PMA)-induced superoxide generation in neutrophils, however, EA failed to block the superoxide generation. Treatment with UA significantly reduced PMA-induced mouse ear edema and MPO activity compared to EA treated mice. Collectively, our results demonstrate that microbiota-mediated conversion of EA to UA is advantageous to both host and microbiota i.e. UA-mediated inhibition of pro-oxidant enzymes reduce tissue inflammation, mitigate non-specific killing of gut bacteria, and abrogate iron-binding property of EA, thus providing a competitive edge to the microbiota in

  18. Gut Microbiota Conversion of Dietary Ellagic Acid into Bioactive Phytoceutical Urolithin A Inhibits Heme Peroxidases

    Science.gov (United States)

    Saha, Piu; Yeoh, Beng San; Singh, Rajbir; Chandrasekar, Bhargavi; Vemula, Praveen Kumar; Haribabu, Bodduluri; Vijay-Kumar, Matam; Jala, Venkatakrishna R.

    2016-01-01

    Numerous studies signify that diets rich in phytochemicals offer many beneficial functions specifically during pathologic conditions, yet their effects are often not uniform due to inter-individual variation. The host indigenous gut microbiota and their modifications of dietary phytochemicals have emerged as factors that greatly influence the efficacy of phytoceutical-based intervention. Here, we investigated the biological activities of one such active microbial metabolite, Urolithin A (UA or 3,8-dihydroxybenzo[c]chromen-6-one), which is derived from the ellagic acid (EA). Our study demonstrates that UA potently inhibits heme peroxidases i.e. myeloperoxidase (MPO) and lactoperoxidase (LPO) when compared to the parent compound EA. In addition, chrome azurol S (CAS) assay suggests that EA, but not UA, is capable of binding to Fe3+, due to its catechol-like structure, although its modest heme peroxidase inhibitory activity is abrogated upon Fe3+-binding. Interestingly, UA-mediated MPO and LPO inhibition can be prevented by innate immune protein human NGAL or its murine ortholog lipocalin 2 (Lcn2), implying the complex nature of host innate immunity-microbiota interactions. Spectral analysis indicates that UA inhibits heme peroxidase-catalyzed reaction by reverting the peroxidase back to its inactive native state. In support of these in vitro results, UA significantly reduced phorbol myristate acetate (PMA)-induced superoxide generation in neutrophils, however, EA failed to block the superoxide generation. Treatment with UA significantly reduced PMA-induced mouse ear edema and MPO activity compared to EA treated mice. Collectively, our results demonstrate that microbiota-mediated conversion of EA to UA is advantageous to both host and microbiota i.e. UA-mediated inhibition of pro-oxidant enzymes reduce tissue inflammation, mitigate non-specific killing of gut bacteria, and abrogate iron-binding property of EA, thus providing a competitive edge to the microbiota in

  19. [In silico analysis of the identity of lipocalin of dog, cat, horse, cow, hamster and hen. Possible role in allergic diseases].

    Science.gov (United States)

    Sánchez, Andrés; Cardona, Ricardo; Sánchez, Jorge

    2016-01-01

    Antecedentes: las lipocalinas parecen explicar la reactividad cruzada entre animales como gato y perro, pero poco se ha estudiado acerca de su papel en la reactividad cruzada con otros animales y su efecto clínico. Objetivos: analizar por técnicas bioinformáticas la identidad entre lipocalinas de diferentes especies y explorar la utilidad de estas técnicas en el estudio de las alergias. Material y método: estudio in silico en el que se buscaron las secuencias de lipocalinas utilizando el programa BLAST. Las secuencias de proteínas se alinearon con el programa CLUSTAL Omega versión 1.2.1 de UniProt. Las secuencias base de los alineamientos fueron las lipocalinas de perros y gatos. La identidad entre las lipocalinas se comparó con la frecuencia de sensibilización a animales en una población de 284 pacientes alérgicos. Resultados: las secuencias mostraron identidades entre 10 y 70%. Los valores más altos se encontraron entre Can f 6-Fel d 4 (68%) y Fel d 4-Equ c 1 (68%). La identidad más baja fue con las lipocalinas purpurina y proteína de unión al retinol del gallo (menor de 20%). Observamos una relación entre el patrón de sensibilización y el grado de identidad entre las especies estudiadas. Conclusiones: a partir de los estudios bioinformáticos y los patrones de sensibilización encontrados se propone que Fel d 4 y Equ c 1 son posibles alergenos mayores para gato y caballo en la población del trópico y comparten alta reactividad cruzada con Can f 6. Debido a que estos resultados provienen de modelos predictivos, deben confirmarse con estudios in vitro e in vivo.

  20. Perioperative utility of goal-directed therapy in high-risk cardiac patients undergoing coronary artery bypass grafting: “A clinical outcome and biomarker-based study”

    Science.gov (United States)

    Kapoor, Poonam Malhotra; Magoon, Rohan; Rawat, Rajinder; Mehta, Yatin

    2016-01-01

    significantly more in the GDT group. The two groups did not differ in duration of inotropic use, mortality, and other complications. The perioperative continuation of GDT affected the early decline in the lactate levels after 6 h in ICU, whereas the control group demonstrated a settling lactate only after 12 h. Similarly, the GDT group had significantly lower levels of brain natriuretic peptide, neutrophil gelatinase-associated lipocalin levels as compared to the control. The study clearly depicts the advantage of GDT for a favorable postoperative outcome in high-risk cardiac surgical patients. PMID:27716694

  1. Perioperative utility of goal-directed therapy in high-risk cardiac patients undergoing coronary artery bypass grafting: “A clinical outcome and biomarker-based study”

    Directory of Open Access Journals (Sweden)

    Poonam Malhotra Kapoor

    2016-01-01

    significantly more in the GDT group. The two groups did not differ in duration of inotropic use, mortality, and other complications. The perioperative continuation of GDT affected the early decline in the lactate levels after 6 h in ICU, whereas the control group demonstrated a settling lactate only after 12 h. Similarly, the GDT group had significantly lower levels of brain natriuretic peptide, neutrophil gelatinase-associated lipocalin levels as compared to the control. The study clearly depicts the advantage of GDT for a favorable postoperative outcome in high-risk cardiac surgical patients.

  2. Review Study of Renal Tubular Injury Markers in the Acute Kidney Injury%急性肾损伤中肾小管损伤标志物的研究进展

    Institute of Scientific and Technical Information of China (English)

    李一飞; 姚广涛

    2011-01-01

    The reports concerned with renal injury markers in recent 10 years were consulted through Science Direct database, and literature related to specific markers of renal tubular injury were compiled and analyzed. Some biomarkers have been partially verified the good sensitivity and high specificity in experimental studies and clinical observations. For example, Kidney injury molecule-1 .which would over express in the kidney injury in renal tubular epithelial cells,is sensitive to the early diagnosis of kidney cancer, ischemic and renal toxic renal injury,and detected with high stability. Liver-type fatty acid binding protein involved in local lipid metabolism of renal,with high specificity to renal proximal tubule. Its content in urine were of great value for early evaluation of various types of acute kidney injury. As a diagnostic indicator,sensitivity and specificity of Interleukin-18 were more than 90%. It could distinguish acute tubular necrosis from other types of kidney diseases, also predict the renal injury occurrence and renal function recovery. Neutrophil gelatinase-associated lipocalin was often detected as the first expressed product in the injury kidney,which changed earlier than creatinine and other markers, with obvious time advantage. All biomarkers have different characteristics and respective shortage. So joint detection were better to wider and sensitive evaluation of renal injury.%通过Science Direct数据库查阅了近10年有关肾损伤标志物的报道,对肾小管损伤特异性标志物方面的文献进行了整理和分析.一些敏感性好、特异性高的肾小管损伤标志物已在实验研究和临床观察得到了部分验证,如肾损伤分子-1,肾损伤时在肾小管上皮细胞过度表达,对肾肿瘤、缺血性和肾毒性肾损伤的早期诊断敏感性好,且检测稳定性高;肝型脂肪酸结合蛋白,参与肾局部的脂质代谢,对肾近端小管的特异性很高,其尿液含量变化在多种类型的急

  3. Acute kidney injury and inflammatory response of sepsis following cecal ligation and puncture in D-galactose-induced aging rats

    Directory of Open Access Journals (Sweden)

    Liu C

    2017-03-01

    Full Text Available Chao Liu,1,* Jie Hu,1,* Zhi Mao,1,* Hongjun Kang,1 Hui Liu,1 Wanlei Fu,2 Yangfan Lv,2 Feihu Zhou1 1Department of Critical Care Medicine, Chinese People’s Liberation Army General Hospital, Beijing, People’s Republic of China; 2Department of Pathology, Xinqiao Hospital, Third Military Medical University, Chongqing, People’s Republic of China *These authors contributed equally to this work Background: Recently, the D-galactose (D-gal-induced mimetic aging rat model has been widely used in studies of age-associated diseases, which have shown that chronic D-gal exposure induces premature aging similar to natural aging in rats. With the increasing rate of sepsis in the geriatric population, an easy-access animal model for preclinical studies of elderly sepsis is urgently needed. This study investigates whether a sepsis model that is established in D-gal-induced aging rats can serve as a suitable model for preclinical studies of elderly patients with sepsis.Objective: To investigate the acute kidney injury (AKI and inflammatory response of sepsis following cecal ligation and puncture (CLP in D-gal-induced aging rats.Methods: Twelve-week-old male Sprague Dawley rats were divided into low-dose D-gal (L D-gal, 125 mg/kg/d, high-dose D-gal (H D-gal, 500 mg/kg/d, and control groups. After daily subcutaneous injection of D-gal for 6 weeks, the CLP method was used to establish a sepsis model.Results: The mortality was 73.3%, 40%, and 33.3% in the H D-gal, L D-gal, and control groups, respectively. Blood urea nitrogen, creatinine, plasma neutrophil gelatinase-associated lipocalin, interleukin-6, interleukin-10, and tumor necrosis factor-α were markedly increased in the H D-gal group after establishment of the sepsis model (H D-gal vs control, P<0.05 at 12 h and 24 h post-CLP. The rate of severe AKI (RIFLE-F at 24 h post-CLP was 43% for both the control and L D-gal groups and 80% for the H D-gal group.Conclusion: High-dose-D-gal-induced aging rats are

  4. Tubular markers are associated with decline in kidney function in proteinuric type 2 diabetic patients

    DEFF Research Database (Denmark)

    Nielsen, Stine; Reinhard, Henrik; Zdunek, Dietmar

    2012-01-01

    Our aim was to investigate u-NGAL, u-KIM1 and p-FGF23 and prediction of decline in kidney function in type 2 diabetic patients with proteinuria.......Our aim was to investigate u-NGAL, u-KIM1 and p-FGF23 and prediction of decline in kidney function in type 2 diabetic patients with proteinuria....

  5. AcEST: DK944553 [AcEST

    Lifescience Database Archive (English)

    Full Text Available n OS=Oryza... 45 0.002 tr|Q38JD4|Q38JD4_SOLLC Temperature-induced lipocalin OS=So...lanum ... 43 0.007 tr|Q38JC7|Q38JC7_SOLTU Temperature-induced lipocalin OS=Solanum ... 43 0.007 tr|Q38JE2|Q38JE2_SORBI Temperature...-induced lipocalin-2 OS=Sorghu... 42 0.012 tr|Q38JC6|Q38JC6_BRANA Temperature-induced ...lipocalin OS=Brassica... 42 0.016 tr|Q8S9H0|Q8S9H0_WHEAT Temperature stress-induced lipocalin OS=T... 42 0.0...20 tr|Q38JE7|Q38JE7_MAIZE Temperature-induced lipocalin-1 (Putative... 42 0.020 tr|Q38JE6|Q38JE6_SORBI Tem

  6. AcEST: DK945226 [AcEST

    Lifescience Database Archive (English)

    Full Text Available icea... 46 0.001 tr|Q38JD0|Q38JD0_PINTA Temperature-induced lipocalin OS=Pinus ta... 45 0.001 tr|Q38JE2|Q38JE2_SORBI Temperature...-induced lipocalin-2 OS=Sorghu... 45 0.002 tr|Q38JD4|Q38JD4_SOLLC Temperature...-induced lipocalin OS=Solanum ... 44 0.003 tr|Q38JC7|Q38JC7_SOLTU Temperature-induced lipoca...lin OS=Solanum ... 44 0.003 tr|Q8S9H0|Q8S9H0_WHEAT Temperature stress-induced lipocalin OS=T... 44 0.004 tr|Q38JB1|Q38JB1_TORRU Tempe...rature-induced lipocalin OS=Tortula ... 44 0.005 tr|Q38JE7|Q38JE7_MAIZE Temperatu

  7. AcEST: BP915349 [AcEST

    Lifescience Database Archive (English)

    Full Text Available d Q38JC5 Definition tr|Q38JC5|Q38JC5_PRUPE Temperature-induced lipocalin OS=Prunus persica Align length 131 ...cant alignments: (bits) Value tr|Q38JC5|Q38JC5_PRUPE Temperature-induced lipocalin OS=Prunus p... 184 2e-45 ...tr|Q38JC4|Q38JC4_PRUAR Temperature-induced lipocalin OS=Prunus a... 184 2e-45 tr|Q38JB9|Q38JB9_POPTM Temperature...-induced lipocalin OS=Populus ... 184 2e-45 tr|Q38JD5|Q38JD5_POPBA Temperature...-induced lipocalin' OS=Populus... 183 4e-45 tr|B6V700|B6V700_9ROSI Temperature-induced lipocalin OS=Populus

  8. Co-culture of bone marrow-derived mesenchymal stem cells overexpressing lipocalin 2 with HK-2 and HEK293 cells protects the kidney cells against cisplatin-induced injury.

    Science.gov (United States)

    Halabian, Raheleh; Roudkenar, Mehryar Habibi; Jahanian-Najafabadi, Ali; Hosseini, Kamran Mousavi; Tehrani, Hossein Abdul

    2015-02-01

    Conditioned medium of mesenchymal stem cells (MSCs) is now being used for its cytoprotective effects, especially when the cells are equipped with cytoprotective factors to strengthen them against unfavorable microenvironments. Overexpression of Lcn2 in MSCs mimics in vivo kidney injury. Hence, unraveling how Lcn2-engineered MSCs affect kidney cells has been investigated. Cisplatin treated HK-2 or HEK293 kidney cells were co-cultivated with Lcn2 overexpressing MSCs in upper and lower chambers of transwell plates. Proliferation, apoptosis, and expression of growth factors and cytokines were assessed in the kidney cells. Co-cultivation with the MSCs-Lcn2 not only inhibited cisplatin-induced cytotoxicity in the HK-2 and HEK293 cells, but increased proliferation rate, prevented cisplatin-induced apoptosis, and increased expression of growth factors and the amount of antioxidants in the kidney cells. Thus Lcn2-engineered MSCs can ameliorate and repair injured kidney cells in vitro, which strongly suggests there are beneficial effects of the MSCs-Lcn2 in cell therapy of kidney injury.

  9. Overexpression of lipocalins and pro-inflammatory che