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Article ; Online: The complexity of kidney disease and diagnosing it - cystatin C, selective glomerular hypofiltration syndromes and proteome regulation.

Malmgren, Linnea / Öberg, Carl / den Bakker, Emil / Leion, Felicia / Siódmiak, Joanna / Åkesson, Anna / Lindström, Veronica / Herou, Erik / Dardashti, Alain / Xhakollari, Liana / Grubb, Gabriel / Strevens, Helena / Abrahamson, Magnus / Helmersson-Karlqvist, Johanna / Magnusson, Martin / Björk, Jonas / Nyman, Ulf / Ärnlöv, Johan / Ridefelt, Peter /

Åkerfeldt, Torbjörn / Hansson, Magnus / Sjöström, Anna / Mårtensson, Johan / Itoh, Yoshihisa / Grubb, David / Tenstad, Olav / Hansson, Lars-Olov / Olafsson, Isleifur / Campos, Araceli Jarquin / Risch, Martin / Risch, Lorenz / Larsson, Anders / Nordin, Gunnar / Pottel, Hans / Christensson, Anders / Bjursten, Henrik / Bökenkamp, Arend / Grubb, Anders

Journal of internal medicine

2022 Volume 293, Issue 3, Page(s) 293–308

Abstract: ... the endogenous glomerular filtration rate (GFR)-markers creatinine or cystatin C. A recommendation to use ... by a selective reduction in the glomerular filtration of 5-30 kDa molecules, such as cystatin C, compared ... modalities. Presently, the KDIGO guidelines for diagnosing kidney disorders do not recommend cystatin C ...

Abstract	Estimation of kidney function is often part of daily clinical practice, mostly done by using the endogenous glomerular filtration rate (GFR)-markers creatinine or cystatin C. A recommendation to use both markers in parallel in 2010 has resulted in new knowledge concerning the pathophysiology of kidney disorders by the identification of a new set of kidney disorders, selective glomerular hypofiltration syndromes. These syndromes, connected to strong increases in mortality and morbidity, are characterized by a selective reduction in the glomerular filtration of 5-30 kDa molecules, such as cystatin C, compared to the filtration of small molecules <1 kDa dominating the glomerular filtrate, for example water, urea and creatinine. At least two types of such disorders, shrunken or elongated pore syndrome, are possible according to the pore model for glomerular filtration. Selective glomerular hypofiltration syndromes are prevalent in investigated populations, and patients with these syndromes often display normal measured GFR or creatinine-based GFR-estimates. The syndromes are characterized by proteomic changes promoting the development of atherosclerosis, indicating antibodies and specific receptor-blocking substances as possible new treatment modalities. Presently, the KDIGO guidelines for diagnosing kidney disorders do not recommend cystatin C as a general marker of kidney function and will therefore not allow the identification of a considerable number of patients with selective glomerular hypofiltration syndromes. Furthermore, as cystatin C is uninfluenced by muscle mass, diet or variations in tubular secretion and cystatin C-based GFR-estimation equations do not require controversial race or sex terms, it is obvious that cystatin C should be a part of future KDIGO guidelines.
MeSH term(s)	Humans ; Cystatin C ; Proteome ; Creatinine ; Proteomics ; Glomerular Filtration Rate/physiology ; Kidney Diseases/diagnosis ; Biomarkers
Chemical Substances	Cystatin C ; Proteome ; Creatinine (AYI8EX34EU) ; Biomarkers
Language	English
Publishing date	2022-12-07
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	96274-0
ISSN	1365-2796 ; 0954-6820
ISSN (online)	1365-2796
ISSN	0954-6820
DOI	10.1111/joim.13589
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Article ; Online: Etiologic and Diagnostic Implications of Morbidity and Mortality Associations When Cystatin C-Based Estimated GFR Is Lower Than Creatinine-Based Estimated GFR.

Grubb, Anders O / Magnusson, Martin / Christensson, Anders

American journal of kidney diseases : the official journal of the National Kidney Foundation

2023 Volume 82, Issue 5, Page(s) 509–511

Language	English
Publishing date	2023-09-20
Publishing country	United States
Document type	Editorial
ZDB-ID	604539-x
ISSN	1523-6838 ; 0272-6386
ISSN (online)	1523-6838
ISSN	0272-6386
DOI	10.1053/j.ajkd.2023.08.001
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Zs.A 1669: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Rare functional variants in the CRP and G6PC genes modify the relationship between obesity and serum C-reactive protein in white British population.

Li, Xia / Ploner, Alexander / Wang, Yunzhang / Mak, Jonathan K L / Lu, Yi / Magnusson, Patrik K E / Jylhävä, Juulia / Hägg, Sara

Molecular genetics & genomic medicine

2023 Volume 11, Issue 12, Page(s) e2255

Abstract: Background: C-reactive protein (CRP) is a sensitive biomarker of inflammation with moderate ...

Abstract	Background: C-reactive protein (CRP) is a sensitive biomarker of inflammation with moderate heritability. The role of rare functional genetic variants in relation to serum CRP is understudied. We aimed to examine gene mutation burden of protein-altering (PA) and loss-of-function (LOF) variants in association with serum CRP, and to further explore the clinical relevance. Methods: We included 161,430 unrelated participants of European ancestry from the UK Biobank. Of the rare (minor allele frequency <0.1%) and functional variants, 1,776,249 PA and 266,226 LOF variants were identified. Gene-based burden tests, linear regressions, and logistic regressions were performed to identify the candidate mutations at the gene and variant levels, to estimate the potential interaction effect between the identified PA mutation and obesity, and to evaluate the relative risk of 16 CRP-associated diseases. Results: At the gene level, PA mutation burdens of the CRP (β = -0.685, p = 2.87e-28) and G6PC genes (β = 0.203, p = 1.50e-06) were associated with reduced and increased serum CRP concentration, respectively. At the variant level, seven PA alleles in the CRP gene decreased serum CRP, of which the per-allele effects were approximately three to seven times greater than that of a common variant in the same locus. The effects of obesity and central obesity on serum CRP concentration were smaller among the PA mutation carriers in the CRP (p Conclusion: PA mutation burdens in the CRP and G6PC genes are strongly associated with decreased serum CRP concentrations. As serum CRP and obesity are important predictors of cardiovascular risks in clinics, our observations suggest taking rare genetic factors into consideration might improve the delivery of precision medicine.
MeSH term(s)	Humans ; C-Reactive Protein/genetics ; C-Reactive Protein/analysis ; Gene Frequency ; Obesity/genetics ; Polymorphism, Single Nucleotide ; White People/genetics ; Glucose-6-Phosphatase/genetics
Chemical Substances	C-Reactive Protein (9007-41-4) ; Glucose-6-Phosphatase (EC 3.1.3.9)
Language	English
Publishing date	2023-07-26
Publishing country	United States
Document type	Journal Article
ZDB-ID	2734884-2
ISSN	2324-9269 ; 2324-9269
ISSN (online)	2324-9269
ISSN	2324-9269
DOI	10.1002/mgg3.2255
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Article ; Online: Hyperpolarized (13)C MR Angiography.

Lipsø, Kasper W / Magnusson, Peter / Ardenkjaer-Larsen, Jan Henrik

Current pharmaceutical design

2015 Volume 22, Issue 1, Page(s) 90–95

Abstract: Magnetic resonance angiography (MRA) is a non-invasive technology that can be used for diagnosis and monitoring of cardiovascular disease; the number one cause of mortality worldwide. Hyperpolarized imaging agents provide signal enhancement of more than ... ...

Abstract	Magnetic resonance angiography (MRA) is a non-invasive technology that can be used for diagnosis and monitoring of cardiovascular disease; the number one cause of mortality worldwide. Hyperpolarized imaging agents provide signal enhancement of more than 10, 000 times, which implies large reduction in acquisition time and improved spatial resolution. We review the role of hyperpolarized 13C agents for MR angiography and present the literature in the field. Furthermore, we present a study of the benefit of intra-arterial injection over intravenous injection of hyperpolarized agent for cerebral angiography in the rat, and compare the performance of two standard angiographic pulse sequences, the gradient echo (GRE) sequence and the balanced steady-state free precession (bSSFP). 2D coronal cerebral angiographies using intra-arterial injections were acquired with a GRE sequence with in-plane resolution of 0.27 mm and matrix size 256x128, and 2D coronal cerebral angiographies were acquired with a bSSFP sequence with in-plane resolution of 0.55 mm and matrix size 128x64. The bSSFP sequence provides higher SNR in phantoms than the GRE sequence. Similarly, intravenous injections are imaged with higher SNR with the bSSFP sequence, where the signal destruction of the GRE sequence is avoided. However, for intra-arterial injections, the bSSFP sequence results in strong artefacts, and the GRE sequence is preferred. Hyperpolarized MRA presents many challenges and cannot currently compete with conventional contrast enhanced MRA. Further research may change this since hyperpolarization is still an immature methodology.
MeSH term(s)	Animals ; Carbon Isotopes/administration & dosage ; Cardiovascular Diseases/pathology ; Cerebrum/diagnostic imaging ; Cerebrum/pathology ; Contrast Media/administration & dosage ; Humans ; Image Processing, Computer-Assisted ; Injections, Intra-Arterial ; Injections, Intravenous ; Magnetic Resonance Angiography ; Male ; Radionuclide Imaging ; Rats ; Rats, Sprague-Dawley
Chemical Substances	Carbon Isotopes ; Contrast Media
Language	English
Publishing date	2015-11-06
Publishing country	United Arab Emirates
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1304236-1
ISSN	1873-4286 ; 1381-6128
ISSN (online)	1873-4286
ISSN	1381-6128
DOI	10.2174/1381612822666151109112415
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Article ; Online: Cystatin C and Cardiovascular Disease: A Mendelian Randomization Study.

van der Laan, Sander W / Fall, Tove / Soumaré, Aicha / Teumer, Alexander / Sedaghat, Sanaz / Baumert, Jens / Zabaneh, Delilah / van Setten, Jessica / Isgum, Ivana / Galesloot, Tessel E / Arpegård, Johannes / Amouyel, Philippe / Trompet, Stella / Waldenberger, Melanie / Dörr, Marcus / Magnusson, Patrik K / Giedraitis, Vilmantas / Larsson, Anders / Morris, Andrew P /

Felix, Janine F / Morrison, Alanna C / Franceschini, Nora / Bis, Joshua C / Kavousi, Maryam / O'Donnell, Christopher / Drenos, Fotios / Tragante, Vinicius / Munroe, Patricia B / Malik, Rainer / Dichgans, Martin / Worrall, Bradford B / Erdmann, Jeanette / Nelson, Christopher P / Samani, Nilesh J / Schunkert, Heribert / Marchini, Jonathan / Patel, Riyaz S / Hingorani, Aroon D / Lind, Lars / Pedersen, Nancy L / de Graaf, Jacqueline / Kiemeney, Lambertus A L M / Baumeister, Sebastian E / Franco, Oscar H / Hofman, Albert / Uitterlinden, André G / Koenig, Wolfgang / Meisinger, Christa / Peters, Annette / Thorand, Barbara / Jukema, J Wouter / Eriksen, Bjørn Odvar / Toft, Ingrid / Wilsgaard, Tom / Onland-Moret, N Charlotte / van der Schouw, Yvonne T / Debette, Stéphanie / Kumari, Meena / Svensson, Per / van der Harst, Pim / Kivimaki, Mika / Keating, Brendan J / Sattar, Naveed / Dehghan, Abbas / Reiner, Alex P / Ingelsson, Erik / den Ruijter, Hester M / de Bakker, Paul I W / Pasterkamp, Gerard / Ärnlöv, Johan / Holmes, Michael V / Asselbergs, Folkert W

Journal of the American College of Cardiology

2016 Volume 68, Issue 9, Page(s) 934–945

Abstract: Background: Epidemiological studies show that high circulating cystatin C is associated with risk ... Objectives: The aim of this study was to use Mendelian randomization to investigate whether cystatin C is ... prospective cohorts (n = 76,481) with 37,126 measures of cystatin C and added genetic data from 43 studies (n ...

Abstract	Background: Epidemiological studies show that high circulating cystatin C is associated with risk of cardiovascular disease (CVD), independent of creatinine-based renal function measurements. It is unclear whether this relationship is causal, arises from residual confounding, and/or is a consequence of reverse causation. Objectives: The aim of this study was to use Mendelian randomization to investigate whether cystatin C is causally related to CVD in the general population. Methods: We incorporated participant data from 16 prospective cohorts (n = 76,481) with 37,126 measures of cystatin C and added genetic data from 43 studies (n = 252,216) with 63,292 CVD events. We used the common variant rs911119 in CST3 as an instrumental variable to investigate the causal role of cystatin C in CVD, including coronary heart disease, ischemic stroke, and heart failure. Results: Cystatin C concentrations were associated with CVD risk after adjusting for age, sex, and traditional risk factors (relative risk: 1.82 per doubling of cystatin C; 95% confidence interval [CI]: 1.56 to 2.13; p = 2.12 × 10(-14)). The minor allele of rs911119 was associated with decreased serum cystatin C (6.13% per allele; 95% CI: 5.75 to 6.50; p = 5.95 × 10(-211)), explaining 2.8% of the observed variation in cystatin C. Mendelian randomization analysis did not provide evidence for a causal role of cystatin C, with a causal relative risk for CVD of 1.00 per doubling cystatin C (95% CI: 0.82 to 1.22; p = 0.994), which was statistically different from the observational estimate (p = 1.6 × 10(-5)). A causal effect of cystatin C was not detected for any individual component of CVD. Conclusions: Mendelian randomization analyses did not support a causal role of cystatin C in the etiology of CVD. As such, therapeutics targeted at lowering circulating cystatin C are unlikely to be effective in preventing CVD.
MeSH term(s)	Aged ; Alleles ; Cardiovascular Diseases/blood ; Cardiovascular Diseases/epidemiology ; Cardiovascular Diseases/genetics ; Cystatin C/blood ; Cystatin C/genetics ; Genotype ; Global Health ; Humans ; Incidence ; Mendelian Randomization Analysis/methods ; Middle Aged ; Polymorphism, Single Nucleotide ; Prospective Studies ; Risk Factors
Chemical Substances	Cystatin C
Language	English
Publishing date	2016-08-25
Publishing country	United States
Document type	Journal Article ; Multicenter Study ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	605507-2
ISSN	1558-3597 ; 0735-1097
ISSN (online)	1558-3597
ISSN	0735-1097
DOI	10.1016/j.jacc.2016.05.092
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Zs.A 1846: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 196: Show issues

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Article ; Online: Cystatin C Predicts Incident Cardiovascular Disease in Twins.

Arpegård, Johannes / Magnusson, Patrik K E / Chen, Xu / Ridefelt, Peter / Pedersen, Nancy L / De Faire, Ulf / Svensson, Per

Journal of the American Heart Association

2016 Volume 5, Issue 6

Abstract: Background: Cystatin C is associated with both renal function and atherosclerotic ... cardiovascular disease (ASCVD). We have previously shown a genetic correlation between cystatin C and prevalent ASCVD ... The objective of this article is to study whether variation in cystatin C or creatinine predicts incident ASCVD ...

Abstract	Background: Cystatin C is associated with both renal function and atherosclerotic cardiovascular disease (ASCVD). We have previously shown a genetic correlation between cystatin C and prevalent ASCVD. The objective of this article is to study whether variation in cystatin C or creatinine predicts incident ASCVD when controlled for genetic factors. Methods and results: The predictive value of cystatin C and creatinine for incident ASCVD was studied in 11 402 Swedish twins, free of CVD at baseline, in an adjusted Cox-regression model during a median follow-up of 71 months. Twin pairs discordant for incident stroke, myocardial infarction and ASCVD during follow-up were identified and within-pair comparisons regarding cystatin C and creatinine levels were performed. We also investigated whether contact frequency and degree of shared environment influences were associated with similarity in cystatin C levels. In univariate analysis, cystatin C predicted incident ASCVD hazard ratio 1.57, 95% CI 1.47-1.67. When adjusted for traditional Framingham risk factors as covariates, cystatin C remained a predictor of incident stroke hazard ratio 1.45, 95% CI (1.25-1.70), ASCVD hazard ratio 1.26, 95% CI (1.13-1.41), and myocardial infarction hazard ratio 1.16, 95% CI (1.01-1.33). In twins discordant for incident stroke, cystatin C at baseline was higher in the twin who experienced a stroke compared to the healthy co-twin (1.11±0.3 mg/L versus 1.06±0.3 mg/L), whereas creatinine was lower in the twin who developed CVD compared to their healthy co-twins (76.1±16.9 μmol/L versus 79.4±20.3 μmol/L). Conclusions: Variation in cystatin C relates to incident ASCVD and to stroke when adjusted for genetic confounding. In identical twins, cystatin C may be a sensitive marker of early hypertensive end-organ damage and small-vessel disease, whereas creatinine level may reflect nutritional status. The findings in disease-discordant monozygotic twins indicate that unique, possibly preventable, environmental factors are important.
MeSH term(s)	Angina, Unstable/blood ; Angina, Unstable/diagnosis ; Angina, Unstable/epidemiology ; Atherosclerosis/blood ; Atherosclerosis/diagnosis ; Atherosclerosis/epidemiology ; Cystatin C/metabolism ; Epidemiologic Methods ; Female ; Humans ; Male ; Middle Aged ; Myocardial Infarction/blood ; Myocardial Infarction/diagnosis ; Myocardial Infarction/epidemiology ; Stroke/blood ; Stroke/diagnosis ; Stroke/epidemiology ; Sweden/epidemiology ; Twins, Dizygotic ; Twins, Monozygotic
Chemical Substances	Cystatin C
Language	English
Publishing date	2016-06-27
Publishing country	England
Document type	Comparative Study ; Journal Article ; Twin Study ; Research Support, Non-U.S. Gov't
ZDB-ID	2653953-6
ISSN	2047-9980 ; 2047-9980
ISSN (online)	2047-9980
ISSN	2047-9980
DOI	10.1161/JAHA.115.003085
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Article ; Online: Endothelial protein C receptor (EPCR) expression marks human fetal liver hematopoietic stem cells.

Subramaniam, Agatheeswaran / Talkhoncheh, Mehrnaz Safaee / Magnusson, Mattias / Larsson, Jonas

Haematologica

2018 Volume 104, Issue 2, Page(s) e47–e50

MeSH term(s)	Biomarkers ; Endothelial Protein C Receptor/genetics ; Endothelial Protein C Receptor/metabolism ; Gene Expression ; Hematopoietic Stem Cells/metabolism ; Humans ; Immunophenotyping ; Liver/cytology ; Liver/metabolism
Chemical Substances	Biomarkers ; Endothelial Protein C Receptor ; PROCR protein, human
Language	English
Publishing date	2018-07-19
Publishing country	Italy
Document type	Letter ; Research Support, Non-U.S. Gov't
ZDB-ID	2333-4
ISSN	1592-8721 ; 0017-6567 ; 0390-6078
ISSN (online)	1592-8721
ISSN	0017-6567 ; 0390-6078
DOI	10.3324/haematol.2018.198515
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Article ; Online: The Safety and Antiviral Activity of BZF961 with or without Ritonavir in Patients Infected with Hepatitis C Virus: A Randomized, Multicenter Trial.

Lawitz, Eric / Bidair, Mohamed / Marbury, Thomas / Jones, Christopher T / Barve, Avantika / Magnusson, Baldur / Barkan, David T / Bodendorf, Ursula / Bracken, Kathryn / Canino, Erica / Chen, Darlene / Dabovic, Kristina / Heimbach, Tycho / Ison, Marjorie / Jones, Catherine L / Kovacs, Steven J / Lakshman, Jay P / Li, Bin / Raman, Prakash /

Steiner-Swiat, Rachael / Thohan, Sanjeev / Wong, Kelly A / Zhong, Weidong / Colvin, Richard A

Clinical therapeutics

2018 Volume 40, Issue 9, Page(s) 1567–1581.e4

Abstract: Purpose: Infection with hepatitis C virus is the leading cause of infectious disease mortality ... in the United States. BZF961 is a novel small molecule inhibitor of the hepatitis C virus NS3-4A protease. Here ... naïve patients with chronic hepatitis C virus genotype-1 infection.: Methods: Patients were enrolled ...

Abstract	Purpose: Infection with hepatitis C virus is the leading cause of infectious disease mortality in the United States. BZF961 is a novel small molecule inhibitor of the hepatitis C virus NS3-4A protease. Here we present the results of a randomized, double-blinded, placebo-controlled, multicentered study in treatment-naïve patients with chronic hepatitis C virus genotype-1 infection. Methods: Patients were enrolled sequentially in 2 parts and treated for 3days. BZF961 was administered as monotherapy (500mg BID for 3 days) or in combination with the cytochrome P450 3A4 inhibitor ritonavir to boost its exposure (BZF961 10, 20, or 50mg QD or BID). Findings: BZF961 was safe and well tolerated in the patients studied with no serious adverse events. There were no appreciable differences in adverse events among patients who received BZF961, BZF961 with ritonavir, or placebo. There was a significant, clinically meaningful reduction in viral load from baseline in patients treated either with BZF961 500mg every 12hours alone or BZF961 50mg every 12hours in combination with ritonavir. Activity against the hepatitis C virus of the lower-dose regimens was apparent but more modest. There were no relevant changes from baseline viral loads in placebo-treated patients. Implications: Coadministration of ritonavir with BZF961 boosted BZF961 exposure (including C
MeSH term(s)	Adult ; Antiviral Agents/administration & dosage ; Antiviral Agents/adverse effects ; Antiviral Agents/therapeutic use ; Double-Blind Method ; Drug Therapy, Combination ; Female ; Genotype ; Hepacivirus/genetics ; Hepatitis C, Chronic/drug therapy ; Humans ; Male ; Middle Aged ; Organic Chemicals/administration & dosage ; Organic Chemicals/adverse effects ; Organic Chemicals/therapeutic use ; Ritonavir/therapeutic use ; United States ; Viral Load/drug effects ; Viral Nonstructural Proteins/antagonists & inhibitors
Chemical Substances	Antiviral Agents ; BZF961 ; NS3 protein, hepatitis C virus ; Organic Chemicals ; Viral Nonstructural Proteins ; Ritonavir (O3J8G9O825)
Language	English
Publishing date	2018-09-02
Publishing country	United States
Document type	Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	603113-4
ISSN	1879-114X ; 0149-2918
ISSN (online)	1879-114X
ISSN	0149-2918
DOI	10.1016/j.clinthera.2018.07.019
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Zs.A 1435: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 404: Show issues

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Article ; Online: Safety, tolerability, and pharmacokinetics of ribavirin in hepatitis C virus-infected patients with various degrees of renal impairment.

Brennan, B J / Wang, K / Blotner, S / Magnusson, M O / Wilkins, J J / Martin, P / Solsky, J / Nieforth, K / Wat, C / Grippo, J F

Antimicrobial agents and chemotherapy

2013 Volume 57, Issue 12, Page(s) 6097–6105

Abstract: Ribavirin (RBV) is an integral part of standard-of-care hepatitis C virus (HCV) treatments and ...

Abstract	Ribavirin (RBV) is an integral part of standard-of-care hepatitis C virus (HCV) treatments and many future regimens under investigation. The pharmacokinetics (PK), safety, and tolerability of RBV in chronically HCV-infected patients with renal impairment are not well defined and were the focus of an open-label PK study in HCV-infected patients receiving RBV plus pegylated interferon. Serial RBV plasma samples were collected over 12 h on day 1 of weeks 1 and 12 from patients with moderate renal impairment (creatinine clearance [CLCR], 30 to 50 ml/min; RBV, 600 mg daily), severe renal impairment (CLCR, <30 ml/min; RBV, 400 mg daily), end-stage renal disease (ESRD) (RBV, 200 mg daily), or normal renal function (CLCR, >80 ml/min; RBV, 800 to 1,200 mg daily). Of the 44 patients, 9 had moderately impaired renal function, 10 had severely impaired renal function, 13 had ESRD, and 12 had normal renal function. The RBV dose was reduced because of adverse events (AEs) in 71% and 53% of severe and moderate renal impairment groups, respectively. Despite this modification, patients with moderate and severe impairment had 12-hour (area under the concentration-time curve from 0 to 12 h [AUC0-12]) values 36% (38,452 ng · h/ml) and 25% (35,101 ng · h/ml) higher, respectively, than those with normal renal function (28,192 ng · h/ml). Patients with ESRD tolerated a 200-mg daily dose, and AUC0-12 was 20% lower (22,629 ng · h/ml) than in patients with normal renal function. PK modeling and simulation (M&S) indicated that doses of 200 mg or 400 mg alternating daily for patients with moderate renal impairment and 200 mg daily for patients with severe renal impairment were the most appropriate dose regimens in these patients.
MeSH term(s)	Adult ; Aged ; Antiviral Agents/blood ; Antiviral Agents/pharmacokinetics ; Antiviral Agents/pharmacology ; Area Under Curve ; Drug Administration Schedule ; Drug Dosage Calculations ; Female ; Hepacivirus/drug effects ; Hepacivirus/physiology ; Hepatitis C, Chronic/blood ; Hepatitis C, Chronic/complications ; Hepatitis C, Chronic/drug therapy ; Hepatitis C, Chronic/virology ; Humans ; Interferon-alpha/blood ; Interferon-alpha/pharmacokinetics ; Interferon-alpha/pharmacology ; Male ; Metabolic Clearance Rate ; Middle Aged ; Polyethylene Glycols/pharmacokinetics ; Polyethylene Glycols/pharmacology ; Recombinant Proteins/blood ; Recombinant Proteins/pharmacokinetics ; Recombinant Proteins/pharmacology ; Renal Insufficiency/blood ; Renal Insufficiency/complications ; Renal Insufficiency/drug therapy ; Renal Insufficiency/virology ; Ribavirin/blood ; Ribavirin/pharmacokinetics ; Ribavirin/pharmacology ; Severity of Illness Index
Chemical Substances	Antiviral Agents ; Interferon-alpha ; Recombinant Proteins ; Polyethylene Glycols (3WJQ0SDW1A) ; Ribavirin (49717AWG6K) ; peginterferon alfa-2a (Q46947FE7K)
Language	English
Publishing date	2013-09-30
Publishing country	United States
Document type	Clinical Trial ; Journal Article ; Multicenter Study ; Research Support, Non-U.S. Gov't
ZDB-ID	217602-6
ISSN	1098-6596 ; 0066-4804
ISSN (online)	1098-6596
ISSN	0066-4804
DOI	10.1128/AAC.00608-13
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Zs.A 809: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Einzelsignatur: Show issues

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Book ; Online: Icelandic grasslands as long-term C sinks under elevated N inputs

Leblans, Niki I. W. / Sigurdsson, Bjarni D. / Aerts, Rien / Vicca, Sara / Magnússon, Borgthór / Janssens, Ivan A.

eISSN: 1726-4189

2016

Abstract: ... terrestrial ecosystems during the past decades. It has been hypothesized that part of this increasing carbon (C) sink is ... However, little is known about this N-dependent C sink. Here, we studied the effect of chronic seabird-derived N ... inputs (47–67 kg N ha −1 yr −1 ) on the net soil organic C (SOC) storage rate of unmanaged Icelandic ...

Abstract	About 10 % of the anthropogenic CO 2 emissions have been absorbed by northern terrestrial ecosystems during the past decades. It has been hypothesized that part of this increasing carbon (C) sink is caused by the alleviation of nitrogen (N) limitation by increasing anthropogenic N inputs. However, little is known about this N-dependent C sink. Here, we studied the effect of chronic seabird-derived N inputs (47–67 kg N ha −1 yr −1 ) on the net soil organic C (SOC) storage rate of unmanaged Icelandic grasslands on the volcanic Vestmannaeyjar archipelago by using a stock change approach in combination with soil dating. We studied both early developmental soils (50 years) and mature soils (1,600 years), and for the latter we separated between decadal (topsoil) and millennial (total soil profile) responses, where the SOC stocks in the topsoil accorded to 40–50 years of net SOC storage and those in the total soil to 1,600 years of net SOC storage. We found that enhanced N availability – either from accumulation over time, or seabird derived – increased the net SOC storage rate. Under low N inputs, the early developmental soils were weak decadal C sinks (0.018 ton SOC ha −1 yr −1 ), but this increased quickly under elevated N inputs to 0.29 ton SOC ha −1 yr −1 , thereby equaling the decadal SOC storage rate of the unfertilized mature site. Furthermore, at the mature site, chronic N inputs not only stimulated the decadal SOC storage rate, but also the millennial SOC storage was consistently higher at the high N input site. Hence, our study suggests that Icelandic grasslands, if not disturbed, can remain C sinks for many centuries under current climatic conditions and that chronically elevated N inputs can induce a permanent strengthening of this sink.
Subject code	333 ; 550
Language	English
Publishing date	2016-04-04
Publishing country	de
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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