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  1. Article ; Online: Impaired circadian rhythm may disturb epithelialization in the wound healing of the skin in diabetic mice.

    Okano, Junko / Katagi, Miwako / Nakagawa, Takahiko / Kojima, Hideto

    Journal of dermatological science

    2023  Volume 110, Issue 1, Page(s) 31–34

    MeSH term(s) Mice ; Animals ; Diabetes Mellitus, Experimental ; Skin ; Wound Healing ; Re-Epithelialization
    Language English
    Publishing date 2023-03-21
    Publishing country Netherlands
    Document type Letter
    ZDB-ID 1024446-3
    ISSN 1873-569X ; 0923-1811
    ISSN (online) 1873-569X
    ISSN 0923-1811
    DOI 10.1016/j.jdermsci.2023.03.005
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2870: Show issues Location:
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  2. Article ; Online: An elevation in serum uric acid precedes the development of preeclampsia.

    Nakagawa, Takahiko / Kang, Duk-Hee / Johnson, Richard J

    Hypertension research : official journal of the Japanese Society of Hypertension

    2023  Volume 46, Issue 3, Page(s) 809–811

    MeSH term(s) Pregnancy ; Female ; Humans ; Pre-Eclampsia/blood ; Pregnancy Trimester, First ; Uric Acid/blood ; Cohort Studies ; Propensity Score ; Hyperuricemia/blood
    Chemical Substances Uric Acid (268B43MJ25)
    Language English
    Publishing date 2023-01-16
    Publishing country England
    Document type Editorial ; Comment
    ZDB-ID 1175297-x
    ISSN 1348-4214 ; 0916-9636
    ISSN (online) 1348-4214
    ISSN 0916-9636
    DOI 10.1038/s41440-023-01181-6
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    Zs.A 3898: Show issues Location:
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  3. Article: Fructose in the kidney: from physiology to pathology.

    Nakagawa, Takahiko / Kang, Duk-Hee

    Kidney research and clinical practice

    2021  Volume 40, Issue 4, Page(s) 527–541

    Abstract: The Warburg effect is a unique property of cancer cells, in which glycolysis is activated instead of mitochondrial respiration despite oxygen availability. However, recent studies found that the Warburg effect also mediates non-cancer disorders, ... ...

    Abstract The Warburg effect is a unique property of cancer cells, in which glycolysis is activated instead of mitochondrial respiration despite oxygen availability. However, recent studies found that the Warburg effect also mediates non-cancer disorders, including kidney disease. Currently, diabetes or glucose has been postulated to mediate the Warburg effect in the kidney, but it is of importance that the Warburg effect can be induced under nondiabetic conditions. Fructose is endogenously produced in several organs, including the kidney, under both physiological and pathological conditions. In the kidney, fructose is predominantly metabolized in the proximal tubules; under normal physiologic conditions, fructose is utilized as a substrate for gluconeogenesis and contributes to maintain systemic glucose concentration under starvation conditions. However, when present in excess, fructose likely becomes deleterious, possibly due in part to excessive uric acid, which is a by-product of fructose metabolism. A potential mechanism is that uric acid suppresses aconitase in the Krebs cycle and therefore reduces mitochondrial oxidation. Consequently, fructose favors glycolysis over mitochondrial respiration, a process that is similar to the Warburg effect in cancer cells. Activation of glycolysis also links to several side pathways, including the pentose phosphate pathway, hexosamine pathway, and lipid synthesis, to provide biosynthetic precursors as fuel for renal inflammation and fibrosis. We now hypothesize that fructose could be the mediator for the Warburg effect in the kidney and a potential mechanism for chronic kidney disease.
    Language English
    Publishing date 2021-11-01
    Publishing country Korea (South)
    Document type Journal Article
    ZDB-ID 2656420-8
    ISSN 2211-9132
    ISSN 2211-9132
    DOI 10.23876/j.krcp.21.138
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  4. Article ; Online: Renal Tubular Handling of Glucose and Fructose in Health and Disease.

    Vallon, Volker / Nakagawa, Takahiko

    Comprehensive Physiology

    2021  Volume 12, Issue 1, Page(s) 2995–3044

    Abstract: The proximal tubule of the kidney is programmed to reabsorb all filtered glucose and fructose. Glucose is taken up by apical sodium-glucose cotransporters SGLT2 and SGLT1 whereas SGLT5 and potentially SGLT4 and GLUT5 have been implicated in apical ... ...

    Abstract The proximal tubule of the kidney is programmed to reabsorb all filtered glucose and fructose. Glucose is taken up by apical sodium-glucose cotransporters SGLT2 and SGLT1 whereas SGLT5 and potentially SGLT4 and GLUT5 have been implicated in apical fructose uptake. The glucose taken up by the proximal tubule is typically not metabolized but leaves via the basolateral facilitative glucose transporter GLUT2 and is returned to the systemic circulation or used as an energy source by distal tubular segments after basolateral uptake via GLUT1. The proximal tubule generates new glucose in metabolic acidosis and the postabsorptive phase, and fructose serves as an important substrate. In fact, under physiological conditions and intake, fructose taken up by proximal tubules is primarily utilized for gluconeogenesis. In the diabetic kidney, glucose is retained and gluconeogenesis enhanced, the latter in part driven by fructose. This is maladaptive as it sustains hyperglycemia. Moreover, renal glucose retention is coupled to sodium retention through SGLT2 and SGLT1, which induces secondary deleterious effects. SGLT2 inhibitors are new anti-hyperglycemic drugs that can protect the kidneys and heart from failing independent of kidney function and diabetes. Dietary excess of fructose also induces tubular injury. This can be magnified by kidney formation of fructose under pathological conditions. Fructose metabolism is linked to urate formation, which partially accounts for fructose-induced tubular injury, inflammation, and hemodynamic alterations. Fructose metabolism favors glycolysis over mitochondrial respiration as urate suppresses aconitase in the tricarboxylic acid cycle, and has been linked to potentially detrimental aerobic glycolysis (Warburg effect). © 2022 American Physiological Society. Compr Physiol 12:2995-3044, 2022.
    MeSH term(s) Diabetes Mellitus/metabolism ; Fructose/metabolism ; Fructose/pharmacology ; Glucose/metabolism ; Humans ; Kidney/metabolism ; Kidney Tubules, Proximal/metabolism ; Sodium/metabolism ; Sodium/pharmacology ; Sodium-Glucose Transporter 2/metabolism ; Sodium-Glucose Transporter 2/pharmacology ; Uric Acid/metabolism ; Uric Acid/pharmacology
    Chemical Substances Sodium-Glucose Transporter 2 ; Uric Acid (268B43MJ25) ; Fructose (30237-26-4) ; Sodium (9NEZ333N27) ; Glucose (IY9XDZ35W2)
    Language English
    Publishing date 2021-12-29
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ISSN 2040-4603
    ISSN (online) 2040-4603
    DOI 10.1002/cphy.c210030
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  5. Article: [Diabetic nephropathy].

    Nakagawa, Takahiko

    Nihon Jinzo Gakkai shi

    2015  Volume 57, Issue 8, Page(s) 1359–1362

    MeSH term(s) Animals ; Diabetic Nephropathies/metabolism ; Diabetic Nephropathies/physiopathology ; Disease Models, Animal ; Energy Metabolism ; Humans ; Mitochondria/metabolism ; Podocytes/metabolism ; Renin-Angiotensin System
    Language Japanese
    Publishing date 2015
    Publishing country Japan
    Document type Journal Article
    ZDB-ID 1195538-7
    ISSN 0385-2385
    ISSN 0385-2385
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    In stock of ZB MED Cologne/Königswinter

    Zs.A 1383: Show issues Location:
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  6. Article: Subclinical Cushing's Disease with High-Molecular-Weight Forms of Adrenocorticotropic Hormone Production.

    Inukai, Takahiko / Harai, Nozomi / Nakagawa, Yukie / Hosokawa, Tadatsugu / Antoku, Airi / Muroi, Yuko / Ogiwara, Masakazu / Tsuchiya, Kyoichiro

    Case reports in endocrinology

    2024  Volume 2024, Page(s) 8721614

    Abstract: Production of the high-molecular-weight forms of adrenocorticotropic hormone (big-ACTH) has been reported in a small number of ectopic ACTH syndrome and ACTH-producing pituitary macroadenoma. However, perioperative changes in big-ACTH in patients with ... ...

    Abstract Production of the high-molecular-weight forms of adrenocorticotropic hormone (big-ACTH) has been reported in a small number of ectopic ACTH syndrome and ACTH-producing pituitary macroadenoma. However, perioperative changes in big-ACTH in patients with subclinical Cushing's disease have not been reported. A 63-year-old woman presented 25 × 20 × 20-mm-sized macroadenoma in the pituitary gland. Her early morning plasma ACTH and cortisol levels were 111 pg/mL and 11.6
    Language English
    Publishing date 2024-03-25
    Publishing country United States
    Document type Case Reports
    ZDB-ID 2627633-1
    ISSN 2090-651X ; 2090-6501
    ISSN (online) 2090-651X
    ISSN 2090-6501
    DOI 10.1155/2024/8721614
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  7. Article ; Online: Association between haemoglobin concentration and intradialytic hypotension in patients undergoing maintenance haemodialysis: a retrospective cohort study.

    Hara, Takashi / Kasahara, Yuto / Nakagawa, Takahiko

    BMJ open

    2022  Volume 12, Issue 8, Page(s) e064026

    Abstract: Objectives: Haemoglobin concentration is a potentially modifiable factor that may help lower the risk of intradialytic hypotension (IDH), but its association with IDH is not well understood. This study aimed to clarify the relationship between ... ...

    Abstract Objectives: Haemoglobin concentration is a potentially modifiable factor that may help lower the risk of intradialytic hypotension (IDH), but its association with IDH is not well understood. This study aimed to clarify the relationship between haemoglobin concentration and IDH.
    Design: Retrospective cohort study.
    Setting: We evaluated patients undergoing maintenance haemodialysis in December 2017 at Rakuwakai Otowa Kinen Hospital.
    Participants: A total of 543 patients were included. We defined exposure according to the following five categories depending on haemoglobin concentrations by 1.0 increments: <9.0, ≥9.0 to <10.0, 10.0 to <11.0, ≥11.0 to <12.0 and ≥12.0 g/dL.
    Primary outcome measure: The primary outcome of interest was the development of IDH, defined as any nadir <100 mm Hg if the pre-dialysis systolic blood pressure (SBP) was ≥160 mm Hg or any nadir <90 mm Hg if the pre-dialysis SBP was <160 mm Hg (IDH
    Results: Overall, IDH
    Conclusion: High haemoglobin concentration is associated with IDH, and thus, the upper limit of haemoglobin concentration should be closely monitored in patients with IDH.
    MeSH term(s) Blood Pressure ; Hemoglobins ; Humans ; Hypotension ; Kidney Failure, Chronic ; Renal Dialysis ; Retrospective Studies
    Chemical Substances Hemoglobins
    Language English
    Publishing date 2022-08-26
    Publishing country England
    Document type Journal Article
    ZDB-ID 2599832-8
    ISSN 2044-6055 ; 2044-6055
    ISSN (online) 2044-6055
    ISSN 2044-6055
    DOI 10.1136/bmjopen-2022-064026
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  8. Article ; Online: Pre-dialysis diastolic blood pressure and intradialytic hypotension in patients undergoing maintenance haemodialysis.

    Hara, Takashi / Kasahara, Yuto / Nakagawa, Takahiko

    Journal of nephrology

    2022  Volume 35, Issue 5, Page(s) 1419–1426

    Abstract: Background: Intradialytic hypotension is a clinically relevant complication in haemodialysis patients. Pre-dialysis diastolic blood pressure is routinely measured. However, the association between pre-dialysis diastolic blood pressure and intradialytic ... ...

    Abstract Background: Intradialytic hypotension is a clinically relevant complication in haemodialysis patients. Pre-dialysis diastolic blood pressure is routinely measured. However, the association between pre-dialysis diastolic blood pressure and intradialytic hypotension is not well understood.
    Methods: Patient-level (N = 545) and haemodialysis session-level (N = 3261) data were collected; the exposure variable was pre-dialysis diastolic blood pressure. The primary outcome of interest was the development of intradialytic hypotension, defined as any nadir < 100 mmHg if the pre-dialysis systolic blood pressure was ≥ 160 mmHg, or any nadir < 90 mmHg if the pre-dialysis systolic blood pressure was < 160 mmHg. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated using mixed-effects logistic regression for the association between pre-dialysis diastolic blood pressure and intradialytic hypotension, after adjusting for potential confounders.
    Results: Intradialytic hypotension occurred in 14.4% of the sessions. All sessions were divided into five categories according to pre-dialysis diastolic blood pressure. The adjusted ORs for intradialytic hypotension were 2.72 (95% CI 1.64-4.51), 1.07 (95% CI 0.68-1.66), 1.68 (95% CI 1.08-2.62), and 1.81 (95% CI 1.05-3.14) in sessions with pre-dialysis diastolic blood pressure of < 60 mmHg, ≥ 60 to < 70 mmHg, ≥ 80 to < 90 mmHg, and ≥ 90 mmHg, respectively, compared with the reference pre-dialysis diastolic blood pressure of ≥ 70 to < 80 mmHg. Cubic spline analyses revealed a reverse J-shaped association between pre-dialysis diastolic blood pressure and intradialytic hypotension.
    Conclusions: Low and high pre-dialysis diastolic blood pressure levels were associated with intradialytic hypotension. This may help identify patients at a high risk of developing intradialytic hypotension.
    MeSH term(s) Blood Pressure ; Dialysis/adverse effects ; Humans ; Hypotension/etiology ; Kidney Failure, Chronic/complications ; Renal Dialysis/adverse effects
    Language English
    Publishing date 2022-03-05
    Publishing country Italy
    Document type Journal Article
    ZDB-ID 1093991-x
    ISSN 1724-6059 ; 1120-3625 ; 1121-8428
    ISSN (online) 1724-6059
    ISSN 1120-3625 ; 1121-8428
    DOI 10.1007/s40620-022-01292-2
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    Zs.A 3369: Show issues Location:
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  9. Article ; Online: Effect of pregnane X receptor and cytochrome P450 oxidoreductase gene polymorphisms on trough concentrations of rivaroxaban and edoxaban in patients with nonvalvular atrial fibrillation.

    Nakagawa, Junichi / Kinjo, Takahiko / Aiuchi, Naoya / Ueno, Kayo / Tomita, Hirofumi / Niioka, Takenori

    European journal of clinical pharmacology

    2023  Volume 79, Issue 5, Page(s) 703–705

    MeSH term(s) Humans ; Rivaroxaban/therapeutic use ; Atrial Fibrillation/drug therapy ; Atrial Fibrillation/genetics ; Pregnane X Receptor/genetics ; Cytochrome P-450 Enzyme System ; Anticoagulants/therapeutic use ; Factor Xa Inhibitors/therapeutic use ; Stroke
    Chemical Substances Rivaroxaban (9NDF7JZ4M3) ; edoxaban (NDU3J18APO) ; Pregnane X Receptor ; Cytochrome P-450 Enzyme System (9035-51-2) ; Anticoagulants ; Factor Xa Inhibitors
    Language English
    Publishing date 2023-03-23
    Publishing country Germany
    Document type Letter ; Comment
    ZDB-ID 121960-1
    ISSN 1432-1041 ; 0031-6970
    ISSN (online) 1432-1041
    ISSN 0031-6970
    DOI 10.1007/s00228-023-03483-7
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    Zs.A 672: Show issues Location:
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  10. Article: The Role of the Left Inferior Frontal Gyrus in Introspection during Verbal Communication.

    Yoshioka, Ayumi / Tanabe, Hiroki C / Nakagawa, Eri / Sumiya, Motofumi / Koike, Takahiko / Sadato, Norihiro

    Brain sciences

    2023  Volume 13, Issue 1

    Abstract: Conversation enables the sharing of our subjective experiences through verbalizing introspected thoughts and feelings. The mentalizing network represents introspection, and successful conversation is characterized by alignment through imitation mediated ... ...

    Abstract Conversation enables the sharing of our subjective experiences through verbalizing introspected thoughts and feelings. The mentalizing network represents introspection, and successful conversation is characterized by alignment through imitation mediated by the mirror neuron system (MNS). Therefore, we hypothesized that the interaction between the mentalizing network and MNS mediates the conversational exchange of introspection. To test this, we performed hyperscanning functional magnetic resonance imaging during structured real-time conversations between 19 pairs of healthy participants. The participants first evaluated their preference for and familiarity with a presented object and then disclosed it. The control was the object feature identification task. When contrasted with the control, the preference/familiarity evaluation phase activated the dorso-medial prefrontal cortex, anterior cingulate cortex, precuneus, left hippocampus, right cerebellum, and orbital portion of the left inferior frontal gyrus (IFG), which represents introspection. The left IFG was activated when the two participants' statements of introspection were mismatched during the disclosure. Disclosing introspection enhanced the functional connectivity of the left IFG with the bilateral superior temporal gyrus and primary motor cortex, representing the auditory MNS. Thus, the mentalizing system and MNS are hierarchically linked in the left IFG during a conversation, allowing for the sharing of introspection of the self and others.
    Language English
    Publishing date 2023-01-07
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2651993-8
    ISSN 2076-3425
    ISSN 2076-3425
    DOI 10.3390/brainsci13010111
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