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Article: [Identification of the old and new lipid mediator, 12-HHT and the role in skin wound healing].

Okuno, Toshiaki

Seikagaku. The Journal of Japanese Biochemical Society

2015 Volume 87, Issue 1, Page(s) 125–128

MeSH term(s)	Animals ; Fatty Acids, Unsaturated/metabolism ; Fatty Acids, Unsaturated/pharmacology ; Humans ; Lipid Metabolism/physiology ; Lipids ; Skin/drug effects ; Skin/metabolism ; Skin Diseases/drug therapy ; Skin Diseases/metabolism ; Wound Healing/physiology
Chemical Substances	Fatty Acids, Unsaturated ; Lipids ; 12-hydroxy-5,8,10-heptadecatrienoic acid (50683-78-8)
Language	Japanese
Publishing date	2015-02
Publishing country	Japan
Document type	Journal Article ; Review
ZDB-ID	282319-6
ISSN	0037-1017
ISSN	0037-1017
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Article: Metabolism and biological functions of 12(S)-hydroxyheptadeca-5Z,8E,10E-trienoic acid.

Okuno, Toshiaki / Yokomizo, Takehiko

Prostaglandins & other lipid mediators

2020 Volume 152, Page(s) 106502

Abstract: 12(S)-hydroxyheptadeca-5Z,8E,10E-trienoic acid (12-HHT) is a 17-carbon hydroxy fatty acid that is biosynthesized either by enzymatic pathways, like thromboxane synthase (TXAS) and cytochrome P450 or a non-enzymatic pathway. TXAS catalyzes the ... ...

Abstract	12(S)-hydroxyheptadeca-5Z,8E,10E-trienoic acid (12-HHT) is a 17-carbon hydroxy fatty acid that is biosynthesized either by enzymatic pathways, like thromboxane synthase (TXAS) and cytochrome P450 or a non-enzymatic pathway. TXAS catalyzes the isomerization reaction from PGH
MeSH term(s)	Animals ; Cell Movement ; Epithelial Cells/metabolism ; Fatty Acids, Unsaturated ; Leukotriene B4 ; Mice ; Rats ; Receptors, Leukotriene B4
Chemical Substances	Fatty Acids, Unsaturated ; Receptors, Leukotriene B4 ; Leukotriene B4 (1HGW4DR56D) ; 12-hydroxy-5,8,10-heptadecatrienoic acid (50683-78-8)
Language	English
Publishing date	2020-10-16
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1426962-4
ISSN	2212-196X ; 1098-8823 ; 0090-6980
ISSN (online)	2212-196X
ISSN	1098-8823 ; 0090-6980
DOI	10.1016/j.prostaglandins.2020.106502
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Zs.A 815: Show issues

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Article ; Online: Identification and characterization of bioactive metabolites of 12-hydroxyheptadecatrienoic acid, a ligand for leukotriene B4 receptor 2.

Yasukawa, Ken / Okuno, Toshiaki / Ogawa, Narihito / Kobayashi, Yuichi / Yokomizo, Takehiko

Journal of biochemistry

2022 Volume 173, Issue 4, Page(s) 293–305

Abstract: 12(S)-hydroxyheptadecatrienoic acid (12-HHT) is a bioactive fatty acid synthesized from arachidonic acid via the cyclooxygenase pathway and serves as an endogenous ligand for the low-affinity leukotriene B4 receptor 2 (BLT2). Although the 12-HHT/BLT2 ... ...

Abstract	12(S)-hydroxyheptadecatrienoic acid (12-HHT) is a bioactive fatty acid synthesized from arachidonic acid via the cyclooxygenase pathway and serves as an endogenous ligand for the low-affinity leukotriene B4 receptor 2 (BLT2). Although the 12-HHT/BLT2 axis contributes to the maintenance of epithelial homeostasis, 12-HHT metabolism under physiological conditions is unclear. In this study, 12-keto-heptadecatrienoic acid (12-KHT) and 10,11-dihydro-12-KHT (10,11dh-12-KHT) were detected as 12-HHT metabolites in the human megakaryocytic cell line MEG01s. We found that 12-KHT and 10,11dh-12-KHT are produced from 12-HHT by 15-hydroxyprostaglandin dehydrogenase (15-PGDH) and prostaglandin reductase 1 (PTGR1), key enzymes in the degradation of prostaglandins, respectively. The 15-PGDH inhibitor SW033291 completely suppressed the production of 12-KHT and 10,11dh-12-KHT in MEG01s cells, resulting in a 9-fold accumulation of 12-HHT. 12-KHT and 10,11dh-12-KHT were produced in mouse skin wounds, and the levels were significantly suppressed by SW033291. Surprisingly, the agonistic activities of 12-KHT and 10,11dh-12-KHT on BLT2 were comparable to that of 12-HHT. Taken together, 12-HHT is metabolized into 12-KHT by 15-PGDH, and then 10,11dh-12-KHT by PTGR1 without losing the agonistic activity.
MeSH term(s)	Mice ; Humans ; Animals ; Receptors, Leukotriene B4/metabolism ; Ligands ; Fatty Acids, Unsaturated/metabolism ; Leukotriene B4/metabolism
Chemical Substances	12-hydroxy-5,8,10-heptadecatrienoic acid (50683-78-8) ; SW033291 ; Receptors, Leukotriene B4 ; Ligands ; Fatty Acids, Unsaturated ; Leukotriene B4 (1HGW4DR56D)
Language	English
Publishing date	2022-11-30
Publishing country	England
Document type	Journal Article
ZDB-ID	218073-x
ISSN	1756-2651 ; 0021-924X
ISSN (online)	1756-2651
ISSN	0021-924X
DOI	10.1093/jb/mvac105
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Article ; Online: Isoflurane attenuates sepsis-associated lung injury.

Koutsogiannaki, Sophia / Okuno, Toshiaki / Kobayashi, Yuichi / Ogawa, Narihito / Yuki, Koichi

Biochemical and biophysical research communications

2022 Volume 599, Page(s) 127–133

Abstract: Acute lung injury is one of major complications associated with sepsis, responsible for morbidity and mortality. Patients who suffer from acute lung injury often require respiratory support under sedations, and it would be important to know the role of ... ...

Abstract	Acute lung injury is one of major complications associated with sepsis, responsible for morbidity and mortality. Patients who suffer from acute lung injury often require respiratory support under sedations, and it would be important to know the role of sedatives in lung injury. We examined volatile anesthetic isoflurane, which is commonly used in surgical setting, but also used as an alternative sedative in intensive care settings in European countries and Canada. We found that isoflurane exposure attenuated neutrophil recruitment to the lungs in mice suffering from experimental polymicrobial abdominal sepsis. We found that isoflurane attenuated one of major neutrophil chemoattractants LTB
MeSH term(s)	Acute Lung Injury/drug therapy ; Acute Lung Injury/etiology ; Anesthetics, Inhalation/pharmacology ; Animals ; Chemotaxis/drug effects ; Disease Models, Animal ; Eicosanoids/metabolism ; Isoflurane/chemistry ; Isoflurane/metabolism ; Isoflurane/pharmacology ; Leukotriene B4/metabolism ; Lung/drug effects ; Lung/pathology ; Male ; Mice, Inbred C57BL ; Neutrophil Infiltration/drug effects ; Receptors, Leukotriene B4/antagonists & inhibitors ; Receptors, Leukotriene B4/chemistry ; Receptors, Leukotriene B4/metabolism ; Sepsis/complications ; Sepsis/physiopathology ; Mice
Chemical Substances	Anesthetics, Inhalation ; Eicosanoids ; Receptors, Leukotriene B4 ; Leukotriene B4 (1HGW4DR56D) ; Isoflurane (CYS9AKD70P)
Language	English
Publishing date	2022-02-13
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	205723-2
ISSN	1090-2104 ; 0006-291X ; 0006-291X
ISSN (online)	1090-2104 ; 0006-291X
ISSN	0006-291X
DOI	10.1016/j.bbrc.2022.02.028
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Zs.A 116: Show issues

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Article: Biological functions of 12(

Okuno, Toshiaki / Yokomizo, Takehiko

Inflammation and regeneration

2018 Volume 38, Page(s) 29

Abstract: Although 12( ...

Abstract	Although 12(
Language	English
Publishing date	2018-10-29
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2051471-2
ISSN	1880-9693 ; 0389-4290
ISSN	1880-9693 ; 0389-4290
DOI	10.1186/s41232-018-0087-4
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Article: Isoflurane attenuates sepsis-associated lung injury

Koutsogiannaki, Sophia / Okuno, Toshiaki / Kobayashi, Yuichi / Ogawa, Narihito / Yuki, Koichi

Biochemical and biophysical research communications. 2022 Apr. 09, v. 599

2022

Abstract	Acute lung injury is one of major complications associated with sepsis, responsible for morbidity and mortality. Patients who suffer from acute lung injury often require respiratory support under sedations, and it would be important to know the role of sedatives in lung injury. We examined volatile anesthetic isoflurane, which is commonly used in surgical setting, but also used as an alternative sedative in intensive care settings in European countries and Canada. We found that isoflurane exposure attenuated neutrophil recruitment to the lungs in mice suffering from experimental polymicrobial abdominal sepsis. We found that isoflurane attenuated one of major neutrophil chemoattractants LTB₄ mediated response via its receptor BLT1 in neutrophils. Furthermore, we have shown that isoflurane directly bound to BLT1 by a competition assay using newly developed labeled BLT1 antagonist, suggesting that isoflurane would be a BLT1 antagonist.
Keywords	antagonists ; chemoattractants ; isoflurane ; lungs ; morbidity ; mortality ; neutrophils ; research ; sedatives ; Canada
Language	English
Dates of publication	2022-0409
Size	p. 127-133.
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	205723-2
ISSN	0006-291X ; 0006-291X
ISSN (online)	0006-291X
ISSN	0006-291X
DOI	10.1016/j.bbrc.2022.02.028
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Article ; Online: Eicosanoids in Skin Wound Healing.

Yasukawa, Ken / Okuno, Toshiaki / Yokomizo, Takehiko

International journal of molecular sciences

2020 Volume 21, Issue 22

Abstract: Wound healing is an important process in the human body to protect against external threats. A dysregulation at any stage of the wound healing process may result in the development of various intractable ulcers or excessive scar formation. Numerous ... ...

Abstract	Wound healing is an important process in the human body to protect against external threats. A dysregulation at any stage of the wound healing process may result in the development of various intractable ulcers or excessive scar formation. Numerous factors such as growth factors, cytokines, and chemokines are involved in this process and play vital roles in tissue repair. Moreover, recent studies have demonstrated that lipid mediators derived from membrane fatty acids are also involved in the process of wound healing. Among these lipid mediators, we focus on eicosanoids such as prostaglandins, thromboxane, leukotrienes, and specialized pro-resolving mediators, which are produced during wound healing processes and play versatile roles in the process. This review article highlights the roles of eicosanoids on skin wound healing, especially focusing on the biosynthetic pathways and biological functions, i.e., inflammation, proliferation, migration, angiogenesis, remodeling, and scarring.
MeSH term(s)	Animals ; Biosynthetic Pathways ; Cytochrome P-450 Enzyme System/metabolism ; Eicosanoids/physiology ; Humans ; Lipids/physiology ; Lipoxygenases/metabolism ; Models, Biological ; Prostaglandin-Endoperoxide Synthases/metabolism ; Skin/injuries ; Skin/physiopathology ; Wound Healing/physiology
Chemical Substances	Eicosanoids ; Lipids ; Cytochrome P-450 Enzyme System (9035-51-2) ; Lipoxygenases (EC 1.13.11.-) ; Prostaglandin-Endoperoxide Synthases (EC 1.14.99.1)
Language	English
Publishing date	2020-11-10
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms21228435
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Article ; Online: αDβ2 as a novel target of experimental polymicrobial sepsis.

Koutsogiannaki, Sophia / Hou, Lifei / Okuno, Toshiaki / Shibamura-Fujiogi, Miho / Luo, Hongbo R / Yuki, Koichi

Frontiers in immunology

2022 Volume 13, Page(s) 1059996

Abstract: Since sepsis was defined three decades ago, it has been a target of intensive study. However, there is no specific sepsis treatment available, with its high mortality and morbidity. αDβ2 (CD11d/CD18) is one of the four β2 integrin members. Its role in ... ...

Abstract	Since sepsis was defined three decades ago, it has been a target of intensive study. However, there is no specific sepsis treatment available, with its high mortality and morbidity. αDβ2 (CD11d/CD18) is one of the four β2 integrin members. Its role in sepsis has been limitedly studied. Using an experimental polymicrobial sepsis model, we found that the deficiency of αDβ2 was associated with less lung injury and better outcome, which was in sharp contrast to other β2 integrin member αLβ2 (CD11a/CD18), and αMβ2 (CD11b/CD18). This phenotype was supported by a reduction of bacterial loads in αDβ2 knockout mice. Further analysis showed that the deficiency of αDβ2 led to a reduction of neutrophil cell death as well as an increase in neutrophil phagocytosis in both murine and human systems. Our data showed a unique role of αDβ2 among the β2 integrin members, which would serve as a potential target to improve the outcome of sepsis.
MeSH term(s)	Humans ; Animals ; Mice ; CD18 Antigens/genetics ; Sepsis ; Neutrophils ; Macrophage-1 Antigen ; Lung Injury ; Lymphocyte Function-Associated Antigen-1 ; Mice, Knockout
Chemical Substances	CD18 Antigens ; Macrophage-1 Antigen ; Lymphocyte Function-Associated Antigen-1
Language	English
Publishing date	2022-11-18
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.1059996
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Article ; Online: The leukotriene B

Shioda, Ryotaro / Jo-Watanabe, Airi / Okuno, Toshiaki / Saeki, Kazuko / Nakayama, Maiko / Suzuki, Yusuke / Yokomizo, Takehiko

FASEB journal : official publication of the Federation of American Societies for Experimental Biology

2023 Volume 37, Issue 2, Page(s) e22789

Abstract: Crescent formation is the most important pathological finding that defines the prognosis of nephritis. Although neutrophils are known to play an important role in the progression of crescentic glomerulonephritis, such as anti-neutrophil cytoplasmic ... ...

Abstract	Crescent formation is the most important pathological finding that defines the prognosis of nephritis. Although neutrophils are known to play an important role in the progression of crescentic glomerulonephritis, such as anti-neutrophil cytoplasmic antibody (ANCA)-associated glomerulonephritis, the key chemoattractant for neutrophils in ANCA-associated glomerulonephritis has not been identified. Here, we demonstrate that a lipid chemoattractant, leukotriene B
MeSH term(s)	Animals ; Mice ; Antibodies, Antineutrophil Cytoplasmic ; Antigen-Antibody Complex ; Chemotactic Factors ; Glomerulonephritis/pathology ; Leukotriene B4 ; Neutrophils/pathology ; Receptors, Leukotriene B4/metabolism
Chemical Substances	Antibodies, Antineutrophil Cytoplasmic ; Antigen-Antibody Complex ; Chemotactic Factors ; Leukotriene B4 (1HGW4DR56D) ; Receptors, Leukotriene B4 ; Ltb4r1 protein, mouse
Language	English
Publishing date	2023-01-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	639186-2
ISSN	1530-6860 ; 0892-6638
ISSN (online)	1530-6860
ISSN	0892-6638
DOI	10.1096/fj.202201936R
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Zs.A 2266: 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 296: Show issues

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Article ; Online: The impact of cyclooxygenase inhibitor use on urinary prostaglandin metabolites in preterm infants.

Ohkawa, Natsuki / Shoji, Hiromichi / Ikeda, Naho / Murano, Yayoi / Okuno, Toshiaki / Kantake, Masato / Yokomizo, Takehiko / Shimizu, Toshiaki

Pediatrics and neonatology

2023 Volume 65, Issue 2, Page(s) 123–126

Abstract: Background: There is limited evidence on the association between the clinical course of patent ductus arteriosus (PDA) and prostaglandin (PG) metabolites. This study aimed to determine the influence of PDA treatment on urinary PG metabolite excretion in ...

Abstract	Background: There is limited evidence on the association between the clinical course of patent ductus arteriosus (PDA) and prostaglandin (PG) metabolites. This study aimed to determine the influence of PDA treatment on urinary PG metabolite excretion in very-low-birth-weight (VLBW) infants. Methods: Urine samples were collected from 25 VLBW infants at 1, 3, and 7 days of age. Infants were separated into two groups: a PDA-treated group that received a cyclooxygenase-2 (COX) inhibitor (n = 12) and a control group that did not receive a COX inhibitor during the first 7 days after birth (n = 13). Urinary PG metabolite tetranor prostaglandin E Results: Urinary t-PGEM excretion levels were not significantly different between the groups at 1, 3, and 7 days of age. Urinary t-PGDM excretion levels at 1 day of age were higher in PDA-treated infants than in control infants (median [interquartile range]: 5.5 [2.6, 12.2] versus 2.1 [1.0, 3.9] ng/mg creatinine; p = 0.017); however, among PDA-treated infants, the levels were significantly lower at 3 and 7 days than at 1 day of age (5.5 [2.6, 12.2] versus 3.4 [1.7, 4.5] and 4.0 [1.7, 5.3] ng/mg creatinine, respectively; p < 0.05). The urinary t-PGDM excretion level in the control group did not significantly differ among the time points. Conclusion: PDA and COX inhibitor administration affected PG metabolism in VLBW infants. Our results indicated that urinary t-PGDM excretion was significantly associated with PDA-treatment in preterm infants.
MeSH term(s)	Infant ; Infant, Newborn ; Humans ; Cyclooxygenase Inhibitors/therapeutic use ; Infant, Premature ; Indomethacin/therapeutic use ; Prostaglandins/therapeutic use ; Creatinine ; Ibuprofen/therapeutic use ; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; Ductus Arteriosus, Patent/drug therapy ; Infant, Very Low Birth Weight
Chemical Substances	Cyclooxygenase Inhibitors ; Indomethacin (XXE1CET956) ; Prostaglandins ; Creatinine (AYI8EX34EU) ; Ibuprofen (WK2XYI10QM) ; Anti-Inflammatory Agents, Non-Steroidal
Language	English
Publishing date	2023-08-23
Publishing country	Singapore
Document type	Journal Article
ZDB-ID	2441816-X
ISSN	2212-1692 ; 1875-9572
ISSN (online)	2212-1692
ISSN	1875-9572
DOI	10.1016/j.pedneo.2023.08.002
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