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Article ; Online: A knowledge-based, structural-aided discovery of a novel class of 2-phenylimidazo[1,2-a]pyridine-6-carboxamide H-PGDS inhibitors.

Schulte, Christie A / Deaton, David N / Diaz, Elsie / Do, Young / Gampe, Robert T / Guss, Jeffrey H / Hancock, Ashley P / Hobbs, Heather / Hodgson, Simon T / Holt, Jason / Jeune, Michael R / Kahler, Kirsten M / Kramer, H Fritz / Le, Joelle / Mortenson, Paul N / Musetti, Caterina / Nolte, Robert T / Orband-Miller, Lisa A / Peckham, Gregory E /

Petrov, Kim G / Pietrak, Beth L / Poole, Chuck / Price, Daniel J / Saxty, Gordon / Shillings, Anthony / Smalley, Terrence L / Somers, Don O / Stewart, Eugene L / Stuart, J Darren / Thomson, Stephen A

Bioorganic & medicinal chemistry letters

2021 Volume 47, Page(s) 128113

Abstract: ... a]pyridine-6-carboxamide H-PGDS inhibitors were discovered. Careful evaluation of crystal structures and SAR ... led to a novel, potent, and orally active imidazopyridine inhibitor of H-PGDS, 20b. Herein, describes ...

Abstract	Through an internal virtual screen at GlaxoSmithKline a distinct class of 2-phenylimidazo[1,2-a]pyridine-6-carboxamide H-PGDS inhibitors were discovered. Careful evaluation of crystal structures and SAR led to a novel, potent, and orally active imidazopyridine inhibitor of H-PGDS, 20b. Herein, describes the identification of 2 classes of inhibitors, their syntheses, and their challenges.
MeSH term(s)	Dose-Response Relationship, Drug ; Drug Discovery ; Enzyme Inhibitors/chemical synthesis ; Enzyme Inhibitors/chemistry ; Enzyme Inhibitors/pharmacology ; Humans ; Intramolecular Oxidoreductases/antagonists & inhibitors ; Intramolecular Oxidoreductases/metabolism ; Molecular Structure ; Structure-Activity Relationship
Chemical Substances	Enzyme Inhibitors ; Intramolecular Oxidoreductases (EC 5.3.-) ; HPGDS protein, human (EC 5.3.99.2)
Language	English
Publishing date	2021-05-13
Publishing country	England
Document type	Journal Article
ZDB-ID	1063195-1
ISSN	1464-3405 ; 0960-894X
ISSN (online)	1464-3405
ISSN	0960-894X
DOI	10.1016/j.bmcl.2021.128113
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Article: CD38 downregulation modulates NAD+ and NADP(H) levels in thermogenic adipose tissues

Benzi, Andrea / Sturla, Laura / Heine, Markus / Fischer, Alexander W / Spinelli, Sonia / Magnone, Mirko / Sociali, Giovanna / Parodi, Alessia / Fenoglio, Daniela / Emionite, Laura / Koch-Nolte, Friedrich / Mittrücker, Hans-Willi / Guse, Andreas H / De Flora, Antonio / Zocchi, Elena / Heeren, Joerg / Bruzzone, Santina

Biochimica et biophysica acta. 2021 Jan., v. 1866, no. 1

2021

Abstract: ... by a strong increase in NADP(H) levels. Accordingly, NAD kinase and glucose-6-phosphate dehydrogenase ...

Abstract	Different strategies to boost NAD⁺ levels are considered promising means to promote healthy aging and ameliorate dysfunctional metabolism. CD38 is a NAD⁺-dependent enzyme involved in the regulation of different cell functions. In the context of systemic energy metabolism, it has been demonstrated that brown adipocytes, the parenchymal cells of brown adipose tissue (BAT) as well as beige adipocytes that emerge in white adipose tissue (WAT) depots in response to catabolic conditions, are important to maintain metabolic homeostasis. In this study we aim to understand the functional relevance of CD38 for NAD⁺ and energy metabolism in BAT and WAT, also using a CD38⁻/⁻ mouse model.During cold exposure, an increase in NAD⁺ levels occurred in BAT of wild type mice, together with a marked downregulation of CD38, as detected at the mRNA and protein level. CD38 downregulation was observed also in WAT of cold-exposed mice, where it was accompanied by a strong increase in NADP(H) levels. Accordingly, NAD kinase and glucose-6-phosphate dehydrogenase activities were enhanced in WAT (but not in BAT). Increased NAD⁺ levels were observed in BAT/WAT from CD38⁻/⁻ compared with wild type mice, in line with CD38 being a major NAD⁺-consumer in AT. CD38⁻/⁻ mice kept at 6 °C had higher levels of Ucp1 and Pgc-1α in BAT and WAT, and increased levels of phosphorylated hormone-sensitive lipase in BAT, compared with wild type mice.These results demonstrate that CD38, by modulating cellular NAD(P)⁺ levels, is involved in the regulation of thermogenic responses in cold-activated BAT and WAT.
Keywords	NADP-glucose-6-phosphate dehydrogenase ; brown adipocytes ; brown adipose tissue ; carboxylic ester hydrolases ; cold stress ; energy metabolism ; homeostasis ; mice ; protein content ; white adipose tissue
Language	English
Dates of publication	2021-01
Publishing place	Elsevier B.V.
Document type	Article
Note	NAL-AP-2-clean
ISSN	1388-1981
DOI	10.1016/j.bbalip.2020.158819
Database	NAL-Catalogue (AGRICOLA)

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Article: Beschneidung bei Jungen: Unverzichtbare Vorhaut. Stephan H. Nolte fragt, ob Eltern ihren Sohn ohne medizinische Indikation beschneiden lassen dürfen

Nolte, Stephan H.

Deutsche Hebammen-Zeitschrift

2019 Volume 71, Issue 1, Page(s) 34

Language	German
Document type	Article
ZDB-ID	80218-9
ISSN	0012-026x
Database	Current Contents Medicine

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Article: A 24 h Age Difference Causes Twice as Much Gene Expression Divergence as 100 Generations of Adaptation to a Novel Environment.

Hsu, Sheng-Kai / Jakšić, Ana Marija / Nolte, Viola / Barghi, Neda / Mallard, François / Otte, Kathrin A / Schlötterer, Christian

Genes

2019 Volume 10, Issue 2

Abstract: ... h age difference of ...

Abstract	Gene expression profiling is one of the most reliable high-throughput phenotyping methods, allowing researchers to quantify the transcript abundance of expressed genes. Because many biotic and abiotic factors influence gene expression, it is recommended to control them as tightly as possible. Here, we show that a 24 h age difference of
MeSH term(s)	Aging/genetics ; Animals ; Drosophila ; Evolution, Molecular ; Female ; Male ; Thermotolerance/genetics ; Transcriptome
Language	English
Publishing date	2019-01-28
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2527218-4
ISSN	2073-4425
ISSN	2073-4425
DOI	10.3390/genes10020089
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Article ; Online: MRI follow-up after 24 h is an accurate surrogate parameter for treatment success after thrombolysis.

Ostwaldt, Ann-Christin / Galinovic, Ivana / Grosse-Dresselhaus, Florian / Neeb, Lars / Villringer, Kersten / Rocco, Andrea / Nolte, Christian H / Jungehülsing, Gerhard J / Fiebach, Jochen B

Cerebrovascular diseases (Basel, Switzerland)

2013 Volume 36, Issue 5-6, Page(s) 464–465

MeSH term(s)	Aged ; Aged, 80 and over ; Female ; Follow-Up Studies ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Stroke/therapy ; Thrombolytic Therapy ; Time Factors ; Treatment Outcome
Language	English
Publishing date	2013
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	1069462-6
ISSN	1421-9786 ; 1015-9770
ISSN (online)	1421-9786
ISSN	1015-9770
DOI	10.1159/000355498
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Zs.A 3181: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Ad libitum fluid replacement in military personnel during a 4-h route march.

Nolte, Heinrich / Noakes, Timothy D / Van Vuuren, Bernard

Medicine and science in sports and exercise

2010 Volume 42, Issue 9, Page(s) 1675–1680

Abstract: ... sweat rate was 626 +/-122 mL.h-1. Despite an average body mass loss of 1.0 kg (SD = 0.50 kg) TBW, POsm ... Conclusions: A mean ad libitum water intake of 383 mL.h-1, replacing approximately 61% of body mass losses ... during 4 h of exercise, maintained TBW, core temperature, POsm, and serum [Na+] despite a 1.4% body mass ...

Abstract	Introduction: Opportunities to determine optimal rates of fluid ingestion could reduce the mass soldiers might need to carry on military missions. Purpose: The first objective was to evaluate the effects of an ad libitum fluid replacement strategy on total body water (TBW), core temperature, serum sodium concentrations [Na+], and plasma osmolality (POsm). The second objective was to determine if an ad libitum water intake was sufficient to maintain these variables during exercise. A third objective was to determine if changes in body mass are an accurate measure of changes in TBW. Methods: A field study was conducted with 15 soldiers performing a 16.4-km route march. The average age of 15 subjects was 27 yr (SD = 4.6 yr). Results: Their mean hourly ad libitum fluid intake was 383 mL (SD = 150 mL). Predicted sweat rate was 626 +/-122 mL.h-1. Despite an average body mass loss of 1.0 kg (SD = 0.50 kg) TBW, POsm and serum [Na+] did not change significantly during exercise. There was a significant (P < 0.05) linear relationship with a negative slope between postexercise serum [Na+] and changes in both body mass and percentage of TBW. Postexercise POsm and serum [Na+] were significantly related (P < 0.05). Higher postexercise percentage of TBW was associated with lower postexercise POsm and serum [Na+] levels. There was no relation between percent body mass loss and postexercise core temperature (38.1 degrees C +/- 0.6 degrees C). Conclusions: A mean ad libitum water intake of 383 mL.h-1, replacing approximately 61% of body mass losses during 4 h of exercise, maintained TBW, core temperature, POsm, and serum [Na+] despite a 1.4% body mass loss. A reduction in body mass of 1.4% (1.0 kg) was not associated with a reduction in TBW.
MeSH term(s)	Adult ; Body Temperature/physiology ; Body Water/physiology ; Drinking/physiology ; Exercise/physiology ; Humans ; Military Personnel ; Osmolar Concentration ; Sodium/blood ; Sweat/physiology ; Weight Loss/physiology ; Young Adult
Chemical Substances	Sodium (9NEZ333N27)
Language	English
Publishing date	2010-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	603994-7
ISSN	1530-0315 ; 0195-9131 ; 0025-7990
ISSN (online)	1530-0315
ISSN	0195-9131 ; 0025-7990
DOI	10.1249/MSS.0b013e3181d6f9d0
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Article ; Online: Monitoring rFVIIa 90 μg kg⁻¹ dosing in haemophiliacs: comparing laboratory response using various whole blood assays over 6 h.

Brophy, D F / Martin, E J / Christian Barrett, J / Nolte, M E / Kuhn, J G / Gerk, P M / Carr, M E / Pelzer, H / Agersø, H / Ezban, M / Hedner, U

Haemophilia : the official journal of the World Federation of Hemophilia

2011 Volume 17, Issue 5, Page(s) e949–57

Abstract: ... its effect is lacking. To characterize the pharmacokinetics and global coagulation effects of rFVIIa for 6 h ... 4 and 6 h postdose. Global haemostasis was characterized throughout the study utilizing whole ... 8 mL h⁻¹ kg⁻¹ and 2.1 ± 0.2 h respectively. There was good inter-assay agreement with respect ...

Abstract	Recombinant FVIIa is a haemostatic agent administered to patients with severe FVIII or FIX deficiency with inhibitors. Although rFVIIa is effective at stopping bleeding, a reliable assay to monitor its effect is lacking. To characterize the pharmacokinetics and global coagulation effects of rFVIIa for 6 h following a IV dose of 90 μg kg⁻¹. Ten non-bleeding subjects with severe FVIII or FIX deficiency were infused with a single-dose of rFVIIa 90 μg k⁻¹ body weight and blood was collected before and at 0.5, 1, 2, 4 and 6 h postdose. Global haemostasis was characterized throughout the study utilizing whole blood analyses (Hemodyne HAS, TEG, ROTEM). The clearance and half-life of factor FVII:C was estimated as 39.0 ± 8.8 mL h⁻¹ kg⁻¹ and 2.1 ± 0.2 h respectively. There was good inter-assay agreement with respect to clot initiation parameters (R, CT and FOT) and these parameters all fell to a mean of approximately 9 min following rFVIIa dosing. The platelet contractile force (PCF) and clot elastic modulus (CEM) were positively correlated to FVII:C (P < 0.0001), and these parameters were dynamic throughout the 6-h period. The MA and MCF did not correlate to FVII:C nor did they significantly change during the study. Prothrombin F1 + 2 significantly increased following rFVIIa dosing (P < 0.001), but remained steady throughout the study. There was no change in D-dimer concentrations over time. The FOT, R and CT characterized clot initiation following rFVIIa dosing. The PCF and CEM were correlated to FVII:C and characterized the dynamics of platelet function and clot strength over the rFVIIa dosing interval. The clinical significance of these findings needs additional study.
MeSH term(s)	Adult ; Blood Coagulation/drug effects ; Blood Platelets/drug effects ; Blood Platelets/physiology ; Body Weight ; Clot Retraction/drug effects ; Elasticity/drug effects ; Factor VIIa/administration & dosage ; Factor VIIa/pharmacokinetics ; Female ; Half-Life ; Hemophilia A/blood ; Hemophilia A/drug therapy ; Hemophilia B/blood ; Hemophilia B/drug therapy ; Hemostasis/drug effects ; Humans ; Male ; Metabolic Clearance Rate ; Middle Aged ; Platelet Function Tests ; Recombinant Proteins/administration & dosage ; Recombinant Proteins/pharmacokinetics ; Young Adult
Chemical Substances	Recombinant Proteins ; recombinant FVIIa (AC71R787OV) ; Factor VIIa (EC 3.4.21.21)
Language	English
Publishing date	2011-09
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1229713-6
ISSN	1365-2516 ; 1351-8216 ; 1355-0691
ISSN (online)	1365-2516
ISSN	1351-8216 ; 1355-0691
DOI	10.1111/j.1365-2516.2011.02492.x
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Zs.A 4249: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 450: Show issues

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Article ; Online: MRI Follow-Up after 24 h Is an Accurate Surrogate Parameter for Treatment Success after Thrombolysis

Ostwaldt, Ann-Christin / Galinovic, Ivana / Grosse-Dresselhaus, Florian / Neeb, Lars / Villringer, Kersten / Rocco, Andrea / Nolte, Christian H. / Jungehülsing, Gerhard J. / Fiebach, Jochen B.

Cerebrovascular Diseases

2013 Volume 36, Issue 5-6, Page(s) 464–465

Language	English
Publisher	S. Karger AG
Publishing place	Basel
Publishing country	Switzerland
Document type	Article ; Online
ZDB-ID	1069462-6
ISSN	1421-9786 ; 1015-9770 ; 1015-9770
ISSN (online)	1421-9786
ISSN	1015-9770
DOI	10.1159/000355498
Database	Karger publisher's database

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Zs.A 3181: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 226: Show issues

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Article: MRI Follow-Up after 24 h Is an Accurate Surrogate Parameter for Treatment Success after Thrombolysis

Ostwaldt, Ann-Christin / Galinovic, Ivana / Grosse-Dresselhaus, Florian / Neeb, Lars / Villringer, Kersten / Rocco, Andrea / Nolte, Christian H. / Jungehülsing, Gerhard J. / Fiebach, Jochen B.

Cerebrovascular Diseases

2013 Volume 36, Issue 5-6, Page(s) 464–465

Institution	Center for Stroke Research Berlin International Graduate Program Medical Neurosciences, and Department of Neurology, Charité Universitätsmedizin Berlin, Berlin, Germany
Keywords	Outcome after stroke ; Recanalization ; magnetic resonance imaging ; acute ischemic stroke
Language	English
Publishing date	2013-11-28
Publisher	S. Karger AG
Publishing place	Basel, Switzerland
Document type	Article
Note	Stroke Note
ZDB-ID	1069462-6
ISSN	1421-9786 ; 1015-9770
ISSN (online)	1421-9786
ISSN	1015-9770
DOI	10.1159/000355498
Database	Karger publisher's database

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Zs.MO 226: Show issues

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Article ; Online: NAD(P)H:quinone oxidoreductase 1 (NQO1) P187S polymorphism and prostate cancer risk in Caucasians.

Stoehr, Christine G / Nolte, Elke / Wach, Sven / Wieland, Wolf F / Hofstaedter, Ferdinand / Hartmann, Arndt / Stoehr, Robert

International journal of molecular sciences

2012 Volume 13, Issue 9, Page(s) 10959–10969

Abstract: NAD(P)H:quinone oxidoreductase 1 (NQO1) catalyses the reduction of quinoid compounds ...

Abstract	NAD(P)H:quinone oxidoreductase 1 (NQO1) catalyses the reduction of quinoid compounds to hydroquinones, preventing the generation of free radicals and reactive oxygen. A "C" to "T" transversion at position 609 of NQO1, leading to a nonsynonymous amino acid change (Pro187Ser, P187S), results in an altered enzyme activity. No NQO1 protein activity was detected in NQO1(609)TT genotype, and low to intermediate activity was detected in NQO1(609)CT genotype compared with (609)CC genotype. Thus, this polymorphism may result in altered cancer predisposition. For prostate cancer, only sparse data are available. We therefore analyzed the distribution of the NQO1 P187S SNP (single nucleotide polymorphism) in prostate cancer patients and a healthy control group. Allelic variants were determined using RFLP analysis. Overall, 232 patients without any malignancy and 119 consecutive prostate cancer patients were investigated. The genotype distribution in our cohorts followed the Hardy-Weinberg equilibrium in cases and controls. The distribution of the NQO1 codon 187 SNP did not differ significantly between prostate cancer patients and the control group (p = 0.242). There was also no association between the allelic variants and stage or Gleason score of the tumors. The NQO1 P187S SNP was not significantly associated with an increased prostate cancer risk in our cohorts. The SNP has also no influence on histopathological characteristics of the tumors. A combined analysis of all available data from published European studies also showed no significant differences in the genotype distribution between controls and prostate cancer patients. Our data suggest a minor role of the NQO1 nucleotide 609 polymorphism in prostate carcinogenesis.
MeSH term(s)	Aged ; Base Sequence ; Case-Control Studies ; Genetic Predisposition to Disease ; Genotype ; Humans ; Male ; Middle Aged ; NAD(P)H Dehydrogenase (Quinone)/genetics ; Polymorphism, Restriction Fragment Length ; Polymorphism, Single Nucleotide ; Prostate/metabolism ; Prostate/pathology ; Prostatic Neoplasms/diagnosis ; Prostatic Neoplasms/epidemiology ; Prostatic Neoplasms/genetics ; Risk Factors ; Whites/genetics
Chemical Substances	NAD(P)H Dehydrogenase (Quinone) (EC 1.6.5.2) ; NQO1 protein, human (EC 1.6.5.2)
Language	English
Publishing date	2012-07-26
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms130910959
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