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Article ; Online: Possible Regulation of P-Glycoprotein Function by Adrenergic Agonists II: Study with Isolated Rat Jejunal Sheets and Caco-2 Cell monolayers.

Mukai, Hironori / Takanashi, Masashi / Ogawara, Ken-Ichi / Maruyama, Masato / Higaki, Kazutaka

2023 Volume 113, Issue 5, Page(s) 1209–1219

Abstract: To clarify the regulation of drug absorption by the enteric nervous system, we investigated how adrenergic agonists (adrenaline (ADR), clonidine (CLO), dobutamine (DOB)) and dibutyryl cAMP (DBcAMP) affected P-glycoprotein (P-gp) function by utilizing ... ...

Abstract	To clarify the regulation of drug absorption by the enteric nervous system, we investigated how adrenergic agonists (adrenaline (ADR), clonidine (CLO), dobutamine (DOB)) and dibutyryl cAMP (DBcAMP) affected P-glycoprotein (P-gp) function by utilizing isolated rat jejunal sheets and Caco-2 cell monolayers. ADR and CLO significantly decreased the secretory transport (P
MeSH term(s)	Humans ; Rats ; ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism ; Caco-2 Cells ; Adrenergic Agonists ; Bucladesine/metabolism ; Biological Transport/physiology ; ATP Binding Cassette Transporter, Subfamily B/metabolism ; Epinephrine ; Intestinal Absorption
Chemical Substances	ATP Binding Cassette Transporter, Subfamily B, Member 1 ; Adrenergic Agonists ; Bucladesine (63X7MBT2LQ) ; ATP Binding Cassette Transporter, Subfamily B ; Epinephrine (YKH834O4BH)
Language	English
Publishing date	2023-11-19
Publishing country	United States
Document type	Journal Article
ZDB-ID	3151-3
ISSN	1520-6017 ; 0022-3549
ISSN (online)	1520-6017
ISSN	0022-3549
DOI	10.1016/j.xphs.2023.11.010
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Article ; Online: Effect of Excessive Serotonin on Pharmacokinetics of Cephalexin after Oral Administration: Studies with Serotonin-Excessive Model Rats.

Nakashima, Shun / Iwamoto, Takeharu / Takanashi, Masashi / Ogawara, Ken-Ichi / Maruyama, Masato / Higaki, Kazutaka

Pharmaceutical research

2022 Volume 39, Issue 9, Page(s) 2163–2178

Abstract: Purpose: Serotonin (5-HT) is important for gastrointestinal functions, but its role in drug absorption remains to be clarified. Therefore, the pharmacokinetics and oral absorption of cephalexin (CEX) were examined under 5-HT-excessive condition to ... ...

Abstract	Purpose: Serotonin (5-HT) is important for gastrointestinal functions, but its role in drug absorption remains to be clarified. Therefore, the pharmacokinetics and oral absorption of cephalexin (CEX) were examined under 5-HT-excessive condition to understand the role of 5-HT. Methods: 5-HT-excessive rats were prepared by multiple intraperitoneal dosing of 5-HT and clorgyline, an inhibitor for 5-HT metabolism, and utilized to examine the pharmacokinetics, absorption behavior and the intestinal permeability for CEX. Results: Higher levels of 5-HT in brain, plasma and small intestines were recognized in 5-HT-excessive rats, where the oral bioavailability of CEX was significantly enhanced. The intestinal mucosal transport via passive diffusion of CEX was significantly increased, while its transport via PEPT1 was markedly decreased specifically in the jejunal segment, which was supported by the decrease in PEPT1 expression on brush border membrane (BBM) of intestinal epithelial cells. Since no change in antipyrine permeability and significant increase in FITC dextran-4 permeability were observed in 5-HT-excessive rats, the enhanced permeability for CEX would be attributed to the opening of tight junction, which was supported by the significant decrease in transmucosal electrical resistance. In 5-HT-excessive rats, furthermore, total body clearance of CEX tended to be larger and the decrease in PEPT2 expression on BBM in kidneys was suggested to be one of the reasons for it. Conclusions: 5-HT-excessive condition enhanced the oral bioavailability of CEX in rats, which would be attributed to the enhanced permeability across the intestinal mucosa via passive diffusion through the paracellular route even though the transport via PEPT1 was decreased.
MeSH term(s)	Administration, Oral ; Animals ; Antipyrine/metabolism ; Cephalexin/metabolism ; Clorgyline/metabolism ; Intestinal Absorption ; Intestinal Mucosa/metabolism ; Rats ; Serotonin/metabolism
Chemical Substances	Serotonin (333DO1RDJY) ; Clorgyline (LYJ16FZU9Q) ; Cephalexin (OBN7UDS42Y) ; Antipyrine (T3CHA1B51H)
Language	English
Publishing date	2022-07-08
Publishing country	United States
Document type	Journal Article
ZDB-ID	843063-9
ISSN	1573-904X ; 0724-8741 ; 0739-0742
ISSN (online)	1573-904X
ISSN	0724-8741 ; 0739-0742
DOI	10.1007/s11095-022-03325-8
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Article ; Online: Association between Genetic Variation in the

Aoki, Kyoko / Mori, Kanetaka / Iijima, Shohei / Sakon, Masato / Matsuura, Nariaki / Kobayashi, Tsuneto / Takanashi, Masashi / Yoshimura, Takeshi / Mori, Norio / Katayama, Taiichi

Nutrients

2023 Volume 15, Issue 10

Abstract: Individual taste sensitivity influences food preferences, nutritional control, and health, and differs greatly between individuals. The purpose of this study was to establish a method of measuring and quantifying an individual's taste sensitivity and to ... ...

Abstract	Individual taste sensitivity influences food preferences, nutritional control, and health, and differs greatly between individuals. The purpose of this study was to establish a method of measuring and quantifying an individual's taste sensitivity and to evaluate the relationship between taste variation and genetic polymorphisms in humans using agonist specificities of the bitter taste receptor gene,
MeSH term(s)	Adult ; Humans ; Taste/genetics ; Taste Threshold/genetics ; Propylthiouracil ; Japan ; Bayes Theorem ; Receptors, G-Protein-Coupled/genetics ; Taste Perception/genetics ; Genotype ; Polymorphism, Genetic ; Genetic Variation
Chemical Substances	Propylthiouracil (721M9407IY) ; Receptors, G-Protein-Coupled
Language	English
Publishing date	2023-05-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2518386-2
ISSN	2072-6643 ; 2072-6643
ISSN (online)	2072-6643
ISSN	2072-6643
DOI	10.3390/nu15102415
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Article: Cerebral hemorrhage due to amyloid angiopathy that was difficult to differentiate from breast cancer metastasis: a case report.

Uomori, Toshitaka / Horimoto, Yoshiya / Takanashi, Masashi / Shikanai, Ayana / Nakai, Katsuya / Arakawa, Astushi / Saito, Mitsue

Surgical case reports

2021 Volume 7, Issue 1, Page(s) 150

Abstract: Background: Breast cancer patients are known to develop brain metastasis at a relatively high frequency. However, imaging findings of brain metastases vary, and it is sometimes very difficult to distinguish these from other tumorous lesions and non- ... ...

Abstract	Background: Breast cancer patients are known to develop brain metastasis at a relatively high frequency. However, imaging findings of brain metastases vary, and it is sometimes very difficult to distinguish these from other tumorous lesions and non-neoplastic lesions, such as cerebral hemorrhage. Meanwhile, there are various causes of cerebral hemorrhage; a major one is cerebral amyloid angiopathy (CAA). With the advancement of imaging technology, CAA-related cerebral hemorrhage can be more precisely diagnosed with magnetic resonance imaging (MRI), but definitive diagnosis of CAA can only be made based on pathological assessment. Herein, we report a case of consciousness disorder appearing during adjuvant therapy for breast cancer. We initially considered that the patient's cerebral hemorrhage was due to a metastatic tumor, but based on excisional biopsy, she was diagnosed with CAA. Case presentation: A 73-year-old Japanese woman underwent curative surgery for left breast cancer. Her disease was hormone receptor-positive and human epidermal growth factor receptor 2 (HER2)-positive invasive ductal carcinoma (pStage IIB). While receiving adjuvant treatment, she developed disorientation, and emergent imaging revealed multiple cerebral hemorrhages. There was no apparent enhancement in the cerebral parenchyma on MRI, and differential diagnosis included hemorrhage due to a metastatic tumor, intravascular large B-cell lymphoma, CAA and thrombotic intracranial bleeding. After hospitalization, the bleeding lesion enlarged, resulting in cerebral hernia, and she needed emergency drainage surgery. The tissue surrounding the hemorrhage was pathologically assessed, and she was diagnosed with CAA. Although we initially suspected the lesion to be a metastatic tumor from breast cancer, there were no tumorous cells. Conclusion: Atypical MRI findings made diagnosis difficult in this case, but it should be considered for differential diagnosis when multiple cerebral hemorrhages in elderly patients are observed, especially in cases with symptoms such as transient multifocal neurological deficits and dementia.
Language	English
Publishing date	2021-06-27
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2809613-7
ISSN	2198-7793
ISSN	2198-7793
DOI	10.1186/s40792-021-01225-4
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Article ; Online: Possible Regulation of P-glycoprotein Function by Adrenergic Agonists in a Vascular-luminal Perfused Preparation of Small Intestine.

Mukai, Hironori / Takanashi, Masashi / Ogawara, Ken-Ichi / Maruyama, Masato / Higaki, Kazutaka

Journal of pharmaceutical sciences

2021 Volume 110, Issue 12, Page(s) 3889–3895

Abstract: Although the functions of small intestine are largely regulated by enteric nervous system (ENS), an independent intrinsic innervation, as well as central nervous system (CNS), the neural regulation of drug absorption from the small intestine still ... ...

Abstract	Although the functions of small intestine are largely regulated by enteric nervous system (ENS), an independent intrinsic innervation, as well as central nervous system (CNS), the neural regulation of drug absorption from the small intestine still remains to be clarified. To obtain some information on it, the effect of adrenergic agonists on P-glycoprotein (P-gp) function was investigated by utilizing a vascular-luminal perfused rat small intestine. Adrenaline significantly decreased the secretion of rhodamine-123 (R-123) into the intestinal lumen, but dibutyryl cAMP (DBcAMP) significantly enhanced R-123 secretion. The inhibition study with quinidine clearly indicated that the decrease in secretory clearance of R-123 by adrenaline or the increase by DBcAMP would be attributed to the decrease or increase in P-gp activity, respectively. Expression levels of P-gp in whole mucosal homogenates were not changed at all by any chemicals examined, but those on brush border membrane (BBM) of intestinal epithelial cells were significantly decreased or increased by adrenaline or DBcAMP, respectively. Furthermore, changes in P-gp activity caused by adrenergic agonists and DBcAMP were significantly correlated with changes in expression level of P-gp in BBM, suggesting that the trafficking of P-gp from cytosolic pool to BBM would be regulated by adrenergic agonists and DBcAMP.
MeSH term(s)	ATP Binding Cassette Transporter, Subfamily B/metabolism ; ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism ; Adrenergic Agonists/metabolism ; Adrenergic Agonists/pharmacology ; Animals ; Biological Transport/physiology ; Intestinal Absorption ; Intestine, Small/metabolism ; Rats
Chemical Substances	ATP Binding Cassette Transporter, Subfamily B ; ATP Binding Cassette Transporter, Subfamily B, Member 1 ; Adrenergic Agonists
Language	English
Publishing date	2021-09-13
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3151-3
ISSN	1520-6017 ; 0022-3549
ISSN (online)	1520-6017
ISSN	0022-3549
DOI	10.1016/j.xphs.2021.09.014
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Article ; Online: Graphic Summary of Movement Disorders Society Criteria for Progressive Supranuclear Palsy and Multiple Allocations eXtinction Rules.

Ogawa, Takashi / Hatano, Taku / Oyama, Genko / Takanashi, Masashi / Taniguchi, Daisuke / Hattori, Nobutaka

Movement disorders clinical practice

2020 Volume 7, Issue 2, Page(s) 240–242

Language	English
Publishing date	2020-01-20
Publishing country	United States
Document type	Journal Article
ISSN	2330-1619
ISSN (online)	2330-1619
DOI	10.1002/mdc3.12894
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Article: Radiation-Induced Myopathy Developing in a Hodgkin Lymphoma Patient: An Autopsy Case with Systemic Muscle Sampling.

Ando, Jun / Ueno, Yuji / Yasuda, Hajime / Ando, Miki / Edahiro, Yoko / Honda, Tadahiro / Takanashi, Masashi / Taniguchi, Daisuke / Hattori, Nobutaka / Komatsu, Norio

Case reports in oncology

2021 Volume 14, Issue 1, Page(s) 338–342

Abstract: Radiation-induced myopathy (RIM) is a rare complication occurring years after radiotherapy. RIM basically occurs within the irradiation field, but some cases have been reported to be accommodated by myopathy outside the irradiation field, and the actual ... ...

Abstract	Radiation-induced myopathy (RIM) is a rare complication occurring years after radiotherapy. RIM basically occurs within the irradiation field, but some cases have been reported to be accommodated by myopathy outside the irradiation field, and the actual extent of RIM is obscure. The presented case also showed decreased MMT scores and abnormal needle electromyography results in the muscles outside the irradiated field, and the patient was initially thought to have RIM both within and outside the irradiated field. However, while systemic postmortem muscle sampling revealed prominent myopathy in line with RIM in the irradiated muscles, only mild myogenic changes that could be explained by other causes such as age-related sarcopenia, radiculopathy, and disuse atrophy were observed in the non-irradiated muscles. The number of biopsy sites in live patients is limited due to the invasive nature of the procedure, but we were privileged to systemically evaluate the extent of myopathy through multiple muscle sampling including muscles both inside and outside of the irradiation field because this was an autopsy case. Through the presented case, we conclude that RIM is a phenomenon most probably limited to the muscles within the irradiated field, and myopathy outside the irradiation is due to other causes.
Language	English
Publishing date	2021-03-08
Publishing country	Switzerland
Document type	Case Reports
ZDB-ID	2458961-5
ISSN	1662-6575
ISSN	1662-6575
DOI	10.1159/000512070
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Article: Relapse of Herpes Simplex Encephalitis by Epilepsy Surgery 35 Years after the First Infection: A Case Report and Literature Review.

Iimura, Yasushi / Sugano, Hidenori / Ueda, Tetsuya / Matsuda, Shimpei / Karagiozov, Kostadin / Tsunemi, Taiji / Takanashi, Masashi / Shimada, Tomoyo / Maruyama, Shinsuke / Otsubo, Hiroshi

NMC case report journal

2021 Volume 8, Issue 1, Page(s) 235–240

Abstract: Late relapse of herpes simplex encephalitis (HSE) is defined as the recurrence of HSE more than 3 months after the initial exposure. The postoperative diagnosis of HSE following neurosurgery is complicated because the clinical presentation can mimic ... ...

Abstract	Late relapse of herpes simplex encephalitis (HSE) is defined as the recurrence of HSE more than 3 months after the initial exposure. The postoperative diagnosis of HSE following neurosurgery is complicated because the clinical presentation can mimic other common complications of neurosurgery. Cerebrospinal fluid polymerase chain reactions (CSF-PCR) is the gold standard for the diagnosis of HSE. We describe a case of late HSE relapse after epilepsy surgery in a patient who required a brain biopsy due to repeated negative CSF-PCR results. A 38-year-old woman had a history of HSE from the age of 3 years. She had intractable epilepsy from the age of 20 years and underwent right posterior quadrant disconnection (PQD) at the age of 38 years. Postoperatively, she had a right hemispheric intracerebral hemorrhage (ICH) and her consciousness was gradually worsening. Her consciousness improved after removal of the ICH. However, her consciousness gradually deteriorated again. Fluid-attenuated inversion recovery (FLAIR) revealed bilateral hyperintensity in the frontal lobes, including the white matter. CSF-PCR for herpes simplex virus (HSV) was performed twice, but yielded negative results. We performed a brain biopsy to target FLAIR hyperintensity in the right frontal lobe. PCR of the brain specimen was positive for HSV. Her consciousness improved with acyclovir, methylprednisolone, and cyclophosphamide. To our knowledge, this is a case of HSE induced by epilepsy surgery which had the longest duration until relapse after the initial HSE episode. A brain biopsy can be used to confirm the diagnosis of suspected HSE when CSF-PCR results are negative.
Language	English
Publishing date	2021-06-11
Publishing country	Japan
Document type	Case Reports
ISSN	2188-4226
ISSN	2188-4226
DOI	10.2176/nmccrj.cr.2020-0180
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Article ; Online: High-fat diet-induced activation of SGK1 promotes Alzheimer's disease-associated tau pathology.

Elahi, Montasir / Motoi, Yumiko / Shimonaka, Shotaro / Ishida, Yoko / Hioki, Hiroyuki / Takanashi, Masashi / Ishiguro, Koichi / Imai, Yuzuru / Hattori, Nobutaka

Human molecular genetics

2021 Volume 30, Issue 18, Page(s) 1693–1710

Abstract: Type 2 diabetes mellitus (T2DM) has long been considered a risk factor for Alzheimer's disease (AD). However, the molecular links between T2DM and AD remain obscure. Here, we reported that serum-/glucocorticoid-regulated kinase 1 (SGK1) is activated by ... ...

Abstract	Type 2 diabetes mellitus (T2DM) has long been considered a risk factor for Alzheimer's disease (AD). However, the molecular links between T2DM and AD remain obscure. Here, we reported that serum-/glucocorticoid-regulated kinase 1 (SGK1) is activated by administering a chronic high-fat diet (HFD), which increases the risk of T2DM, and thus promotes Tau pathology via the phosphorylation of tau at Ser214 and the activation of a key tau kinase, namely, GSK-3ß, forming SGK1-GSK-3ß-tau complex. SGK1 was activated under conditions of elevated glucocorticoid and hyperglycemia associated with HFD, but not of fatty acid-mediated insulin resistance. Elevated expression of SGK1 in the mouse hippocampus led to neurodegeneration and impairments in learning and memory. Upregulation and activation of SGK1, SGK1-GSK-3ß-tau complex were also observed in the hippocampi of AD cases. Our results suggest that SGK1 is a key modifier of tau pathology in AD, linking AD to corticosteroid effects and T2DM.
MeSH term(s)	Alzheimer Disease/genetics ; Alzheimer Disease/metabolism ; Alzheimer Disease/pathology ; Animals ; Diabetes Mellitus, Type 2/genetics ; Diabetes Mellitus, Type 2/metabolism ; Diabetes Mellitus, Type 2/pathology ; Diet, High-Fat/adverse effects ; Enzyme Activation/genetics ; Glycogen Synthase Kinase 3 beta/genetics ; Glycogen Synthase Kinase 3 beta/metabolism ; Humans ; Immediate-Early Proteins/genetics ; Immediate-Early Proteins/metabolism ; Mice ; Mice, Transgenic ; Multiprotein Complexes/genetics ; Multiprotein Complexes/metabolism ; Protein Serine-Threonine Kinases/genetics ; Protein Serine-Threonine Kinases/metabolism ; Signal Transduction ; tau Proteins/genetics ; tau Proteins/metabolism
Chemical Substances	Immediate-Early Proteins ; Mapt protein, mouse ; Multiprotein Complexes ; tau Proteins ; Glycogen Synthase Kinase 3 beta (EC 2.7.11.1) ; Gsk3b protein, mouse (EC 2.7.11.1) ; Protein Serine-Threonine Kinases (EC 2.7.11.1) ; serum-glucocorticoid regulated kinase (EC 2.7.11.1)
Language	English
Publishing date	2021-04-21
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1108742-0
ISSN	1460-2083 ; 0964-6906
ISSN (online)	1460-2083
ISSN	0964-6906
DOI	10.1093/hmg/ddab115
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Article ; Online: Extensive leukoencephalopathy associated with idiopathic capillary leak syndrome: report of a case with neuropathology.

Ohira, Junichiro / Yoshimura, Hajime / Takanashi, Masashi / Yamashita, Daisuke / Hara, Shigeo / Ueno, Yuji / Hattori, Nobutaka / Kawamoto, Michi / Kohara, Nobuo

Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology

2021 Volume 42, Issue 5, Page(s) 2095–2098

Abstract: Introduction: Idiopathic systemic capillary leak syndrome (ISCLS) is a rare cryptogenic disorder characterized by recurrent hemoconcentration, hypoalbuminemia, edema, and hypotension due to extravascular fluid leakage. This is the first report that ... ...

Abstract	Introduction: Idiopathic systemic capillary leak syndrome (ISCLS) is a rare cryptogenic disorder characterized by recurrent hemoconcentration, hypoalbuminemia, edema, and hypotension due to extravascular fluid leakage. This is the first report that details uncommon extensive leukoencephalopathy caused by ISCLS upon a neuropathological investigation. Case report: A 68-year-old female had recurrent episodes of hemoconcentration, hypoalbuminemia, and generalized edema and was diagnosed with ISCLS. After 9 years, brain magnetic resonance imaging (MRI) incidentally revealed extensive leukoencephalopathy without neurological deficits. Thorough examinations ruled out other disorders, and the cerebral involvement due to ISCLS was finally diagnosed. Three years later, she developed an acute-onset coma and status epilepticus together with hypotension and hemoconcentration, which were compatible with ISCLS recurrence. Electroencephalogram and MRI were correlated with a seizure arising from the left hemisphere. Extensive leukoencephalopathy did not show notable changes for 3 years. Although treatment for ISCLS recurrence temporally improved hemoconcentration and consciousness, consciousness worsened again by marked edema of the left hemisphere, and she died of cerebral herniation. A brain autopsy revealed straggly perivascular plasma leakage around the small vessels of the deep white matter, which supported that the leukoencephalopathy was caused by ISCLS. Widespread myelin pallor and decreased axonal density with sparse astrogliosis and microgliosis were observed in the cerebral white matter and corresponded with a chronic change in the MRI. Conclusion: Current radiological and pathological observations revealed that frequent perivascular leakages could cause chronic leukoencephalopathy, were linked with the development of systemic capillary leakage in ISCLS, and provided insights into the mysterious pathophysiology.
MeSH term(s)	Aged ; Capillary Leak Syndrome/complications ; Capillary Leak Syndrome/diagnosis ; Female ; Humans ; Leukoencephalopathies/complications ; Leukoencephalopathies/diagnostic imaging ; Magnetic Resonance Imaging ; Recurrence
Language	English
Publishing date	2021-01-07
Publishing country	Italy
Document type	Case Reports ; Journal Article
ZDB-ID	2016546-8
ISSN	1590-3478 ; 1590-1874
ISSN (online)	1590-3478
ISSN	1590-1874
DOI	10.1007/s10072-020-05000-5
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